Zinc containing dental fixative causing copper deficiency myelopathy

A 62-year-old male, previously well, was referred to neurology clinic following 6 months history of worsening lower limbs instability, paraesthesia, pain and weakness rendering him housebound. Examination revealed upper motor neuron pattern of weakness of the lower limbs and loss of proprioception. Serum analysis revealed reduced caeruloplasmin and copper levels with raised zinc. Spinal imaging revealed subtle dorsal column intensity changes in C2-C7, confirmed with 3T MRI. A copper deficiency myeloneuropathy was diagnosed secondary to chronic use of a zinc-containing dental fixative paste. The paste was discontinued and a copper supplementation was started. Resolution of symptoms was not achieved with intensive physiotherapy. The patient remains a wheelchair user though progression of symptoms has halted. Prompt recognition and treatment of hyperzincaemia-induced hypocupraemia earlier in the disease course may have prevented any irreversible neurological deficit

Stroke and the heart: A focus on atrial fibrillation and heart failure

Cardio-embolic stroke accounts for nearly a third of all ischaemic strokes. The most clinically important cardio-embolic sources are non-valvular atrial fibrillation (AF) and chronic heart failure. Strokes due to these conditions are associated with greater disability and more mortality, as compared to stroke of other aetiology. This thesis is aimed at addressing some of the challenges faced by clinicians when dealing with stroke in patients with AF or heart failure, using an extensive range of historical data. Chapter 1 provides an introduction to stroke, AF and heart failure, including current prevalences, aetiology, and their complex intertwine relationship. The current acute stroke management in patients with AF or heart failure is also outlined within the chapter. In chapter 2, the data sources and statistical methods that were common to the studies in the thesis are outlined. The justifications of using historical data in the absence of evidence from robust clinical trials are also detailed. Chapter 3 explores the relevance of antithrombotic treatment on patterns and outcomes of acute stroke patients with AF. A non-randomised cohort analysis was conducted using data from the Virtual International Stroke Trials Archive (VISTA). The associations of antithrombotic treatment with the modified Rankin scale (mRS) outcome, and the occurrence of recurrent stroke and symptomatic intracerebral haemorrhage, at 90 days after stroke were described. Combined sequential antithrombotic therapy (i.e. oral anticoagulant and antiplatelet treatment), was associated with favourable outcome on ordinal mRS and significantly lower risk of recurrent stroke, symptomatic intracerebral haemorrhage and mortality by day 90, compared to the patients who did not receive any antithrombotic treatment. The relative-risk of recurrent stroke and symptomatic intracerebral haemorrhage appeared highest in the first 2 days after stroke before attenuating to become constant over time. Thus, early introduction of oral anticoagulant treatment (2-3 days after stroke), and to a lesser extent antiplatelet agents, was associated with substantially fewer recurrent stroke events over the following weeks but with no excess risk of symptomatic intracerebral haemorrhage. Chapter 4 seeks to describe the current prescribing patterns in stroke survivors with AF, with particular emphasis on socio-demographic associations. A cross-sectional analysis of city-wide Glasgow primary care data for the year 2010, was conducted. This chapter highlights that oral anticoagulant treatment was under-used in this high risk population, especially those of older age and affected by deprivation. Strategies need to be developed to improve prescription of oral anticoagulant treatment. Chapter 5 investigates the incidence of stroke within the available heart failure trials spanning a 30 year period, according to AF status at baseline. Individual patient data were pooled from 11 trials conducted in patients with heart failure and reduced ejection fraction (HF-REF); and, 3 trials performed in patients with heart failure and preserved ejection fraction (HF-PEF). Stroke incidence has not significantly declined over time in patients with HF-REF enrolled to trials, despite greater use of evidence-based heart failure and oral anticoagulant therapies. However, anticoagulation proportions remain under 70% among HF-REF patients with documented AF. Similar trends of stroke incidence were observed for patients enrolled in HF-PEF trials. Some patients with heart failure but without atrial fibrillation may be at high risk of stroke and may potentially benefit from oral anticoagulant treatment. Chapter 6 provides a comprehensive description of the current incidence of and risk factors for stroke in patients with HF-REF but without AF. Data from two large and contemporary heart failure trials, the Controlled Rosuvastatin in Multinational Trial Heart Failure (CORONA) and the Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza cardiac- Heart Failure trial (GISSI-HF), were pooled to enable the analysis. The new simple clinical predictive model for stroke showed that about one-third of patients without AF have a risk of stroke similar to patients with AF. The predictive model was also validated in an independent large data set. The high risk of stroke in patients without AF might be reduced by individualised and safer oral anticoagulant treatment. Correspondingly, Chapter 7 explores the risk-model for stroke in a contemporary cohort of patients with HF-PEF but without AF. Data were pooled from the Candesartan in Heart failure Assessment of Reduction in Mortality and Morbidity- Preserved trial (CHARM-Preserved) and the Irbesartan in Heart Failure with Preserved Systolic Function trial (I-Preserve), for patients with ejection fraction ≥45% only. The analysis showed that the simple clinical model developed in Chapter 6, for patients with HF-REF, is also applicable to patients with HF-PEF. There are concerns that systemic thrombolysis might not achieve clinically-important outcome among chronic heart failure patients with acute ischaemic stroke. Chapter 8 evaluates the relevance of chronic heart failure on the outcome of acute stroke patients who received thrombolysis. A non-randomised cohort analysis was conducted using data obtained from the Virtual International Stroke Trials Archive (VISTA). The associations of outcome among chronic heart failure patients with thrombolysis treatment using the mRS distribution at day 90, stratified by presence of AF, were evaluated. Chronic heart failure was associated with a worse outcome with or without thrombolysis. However, acute stroke patients who received thrombolysis had more favourable outcome regardless of heart failure status, compared to their untreated peers. The findings should reassure clinicians considering systemic thrombolysis treatment in hyper-acute ischaemic stroke patients with chronic heart failure. This thesis has summarised and extended our knowledge of the complex relationship between stroke and the heart, focusing on atrial fibrillation and heart failure. It has answered many questions and generated many more. The reported studies may assist clinicians who are dealing with stroke in patients with atrial fibrillation or heart failure. These conditions are common and each carry poor prognosis. Thus, even small advances in their treatment may have a useful societal impact

The Optimal Management for People with Acute Stroke and Minor Deficits: Intravenous Thrombolysis or Medical Management

No abstract available

Strategi pengajaran Tafsir al-Quran dalam kalangan guru Pendidikan Islam

Kajian ini bertujuan untuk mengenal pasti strategi pengajaran Tafsir al-Quran dalam kalangan guru pendidikan Islam. Rekabentuk kajian adalah kajian kuantitatif dengan menggunakan kaedah tinjauan dalam mengumpul data yang melibatkan 254 orang pelajar tingkatan empat dan 34 orang guru Pendidikan Islam. Kajian ini melibatkan 5 buah Sekolah Menengah Kebangsaan Agama (SMKA) di Negeri Sabah. Data kajian telah dianalisis secara deskriptif menggunakan min, sisihan piawai dan peratus. Dapatan kajian mencatatkan tahap interpretasi amalan pengajaran tafsir dari aspek persediaan pengajaran, perkembangan pengajaran dan penutup pengajaran berada pada tahap sederhana tinggi. Dapatan kajian ini diharap dapat membantu pihak Kementerian Pelajaran Malaysia, sekolah, institusi-institusi pendidikan yang lain dalam menyusun dan merangka program yang bersesuaian dengan keperluan guru al-Quran serta dapat membantu guru dalam merancang pengajaran tafsir al-Quran yang lebih berkesan bagi meningkatkan penghayatan al-Quran dalam kalangan pelajar

Atrial Fibrillation and Stroke:State-of-the-art and future directions

Stroke is a major complication of atrial fibrillation (AF). About 25% of ischaemic stroke are cardio-embolic in origin; AF is the most common cause of those.1 Nonvalvular AF carries a 5-fold increased risk of stroke,2 while AF related to mitral stenosis increases the risk of stroke by 20-fold.3 The attributable risk of stroke for AF increases with age unlike other factors such as hypertension for instance.4When the AF is asymptomatic but detected on a cardiac implantable electronic device (CIED) or a wearable monitor, it is described as being subclinical. It is suspected that subclinical AF might be the cause of cryptogenic strokes (i.e., strokes of unknown aetiology).5 While previous studies showed that atrial high-rate events (AHREs) detected on a CIED were associated with increased risk of stroke,5,6 treating such episodes with anticoagulation has not been shown to reduce the risk of stroke. In fact, anticoagulation in these cases resulted in higher incidence of a composite of death or major bleeding, mainly driven by the increased risk of bleeding.7Not only that AF can cause stroke and vice versa,8 but stroke patients with AF were shown have higher stroke severity and mortality compared to those without.9 The effect of AF on mortality rate was primarily driven by stroke severity.9 The worse clinical and imaging outcome in AF-related strokes was attributed to bigger volumes of more severely hypo-perfused tissues, resulting in larger infarct size and higher risk of haemorrhagic transformation.10In this narrative review article, we provided an overview of the burden of AF and stroke, the complex interplay between the two conditions, as well as the treatment and secondary prevention of stroke in patients with AF. We comprehensively discussed the current evidence and the ongoing conundrums, and highlighted the future directions on the topic

A survey of opinion: When to start oral anticoagulants in patients with acute ischaemic stroke and atrial fibrillation?

Background: There is uncertainty regarding the optimal timing for initiation of oral anticoagulant treatment (OAC) in patients with recent ischaemic stroke and atrial fibrillation (AF). We surveyed the current UK practice and assessed clinician’s opinions of when to use OAC in recent stroke patients with AF. Methods: An online survey was sent to stroke physicians within the United Kingdom via their national societies. Results: One hundred and twenty-one clinicians responded to the survey. Ninety-five percent of responders agreed there was uncertainty regarding timing of OAC initiation after AF-related ischaemic stroke. Thirty-six percent of responders followed the ‘1-3-6-12’ European Society of Cardiology (ESC) guidelines recommendation. Uncertainty was greater in cases of moderate stroke than in cases of TIA, mild or severe stroke. Eighty-eight percent of responders would be willing to participate in a clinical trial of early vs. later initiation of OAC after stroke. Direct-acting oral anticoagulant (DOAC) were the preferred OAC of choice. Conclusion: There is a lack of consensus amongst stroke physicians for when to initiate OAC to prevent recurrence in stroke patients with AF. There is little uncertainty regarding TIA. A clinical trial assessing use of early vs. later initiation of DOAC in patients with recent ischaemic stroke and AF would be beneficial

Professional guideline versus product label selection for treatment with IV thrombolysis: an analysis from SITS registry

Introduction: Thrombolysis usage in ischaemic stroke varies across sites. Divergent advice from professional guidelines and product labels may contribute. Patients and methods: We analysed SITS-International registry patients enrolled January 2010 through June 2016. We grouped sites into organisational tertiles by number of patients arriving ≤2.5 h and treated ≤3 h, percentage arriving ≤2.5 h and treated ≤3 h, and numbers treated ≤3 h. We assigned scores of 1–3 (lower/middle/upper) per variable and 2 for onsite thrombectomy. We classified sites as lower efficiency (summed scores 3–5), medium efficiency (6–8) or higher efficiency (9–11). Sites were also grouped by adherence with European product label and ESO guideline: ‘label adherent’ (>95% on-label), ‘guideline adherent’ (≥5% off-label, ≥95% on-guideline) or ‘guideline non-adherent’ (>5% off-guideline). We cross-tabulated site-efficiency and adherence. We estimated the potential benefit of universally selecting by ESO guidance, using onset-to-treatment time-specific numbers needed to treat for day 90 mRS 0–1. Results: A total of 56,689 patients at 597 sites were included: 163 sites were higher efficiency, 204 medium efficiency and 230 lower efficiency. Fifty-six sites were ‘label adherent’, 204 ‘guideline adherent’ and 337 ‘guideline non-adherent’. There were strong associations between site-efficiency and adherence (P < 0.001). Almost all ‘label adherent’ sites (55, 98%) were lower efficiency. If all patients were treated by ESO guidelines, an additional 17,031 would receive alteplase, which translates into 1922 more patients with favourable three-month outcomes. Discussion: Adherence with product labels is highest in lower efficiency sites. Closer alignment with professional guidelines would increase patients treated and favourable outcomes. Conclusion: Product labels should be revised to allow treatment of patients ≤4.5 h from onset and aged ≥80 years

Risk of myocardial infarction and ischemic stroke in individuals with first-diagnosed paroxysmal vs. non-paroxysmal atrial fibrillation under anticoagulation

AimsThere is conflicting evidence on whether the type of atrial fibrillation (AF) is associated with risk of cardiovascular events, including acute myocardial infarction (MI) and ischemic stroke. The aim of the present study was to investigate whether the risk of MI and ischemic stroke differs between individuals with first-diagnosed paroxysmal vs. non-paroxysmal AF treated with anticoagulants.Methods and resultsDe-identified electronic medical records from the TriNetX federated research network were used. Individuals with a new diagnosis of paroxysmal AF who had no evidence of other types of AF in their records were 1:1 propensity score-matched with individuals with non-paroxysmal AF, defined as persistent or chronic AF, who had no evidence of other types of AF in their records. All patients were followed for three years for the outcomes of MI and ischemic stroke. Cox proportional hazard models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). In the propensity-matched cohort, among 24 848 well-matched AF individuals [mean age 74.4 ± 10.4; 10 101 (40.6%) female], 410 (1.7%) were diagnosed with acute MI and 875 (3.5%) with ischemic stroke during the three-year follow-up. Individuals with paroxysmal AF had significantly higher risk of acute MI (HR: 1.65, 95%CI: 1.35-2.01) compared to those with non-paroxysmal AF. First diagnosed paroxysmal AF was associated with higher risk of non-ST elevation MI (nSTEMI) (HR: 1.89, 95%CI: 1.44-2.46). No significant association was observed between the type of AF and risk of ischemic stroke (HR: 1.09, 95%CI: 0.95-1.25).ConclusionPatients with first-diagnosed paroxysmal AF had higher risk of acute MI compared to individuals with non-paroxysmal AF, attributed to the higher risk of nSTEMI among patients with first-diagnosed paroxysmal AF. There was no significant association between type of AF and risk of ischemic stroke

Stroke aetiological classification reliability and effect on trial sample size: systematic review, meta-analysis and statistical modelling

Background: Inter-observer variability in stroke aetiological classification may have an effect on trial power and estimation of treatment effect. We modelled the effect of misclassification on required sample size in a hypothetical cardioembolic (CE) stroke trial. Methods: We performed a systematic review to quantify the reliability (inter-observer variability) of various stroke aetiological classification systems. We then modelled the effect of this misclassification in a hypothetical trial of anticoagulant in CE stroke contaminated by patients with non-cardioembolic (non-CE) stroke aetiology. Rates of misclassification were based on the summary reliability estimates from our systematic review. We randomly sampled data from previous acute trials in CE and non-CE participants, using the Virtual International Stroke Trials Archive. We used bootstrapping to model the effect of varying misclassification rates on sample size required to detect a between-group treatment effect across 5000 permutations. We described outcomes in terms of survival and stroke recurrence censored at 90 days. Results: From 4655 titles, we found 14 articles describing three stroke classification systems. The inter-observer reliability of the classification systems varied from ‘fair’ to ‘very good’ and suggested misclassification rates of 5% and 20% for our modelling. The hypothetical trial, with 80% power and alpha 0.05, was able to show a difference in survival between anticoagulant and antiplatelet in CE with a sample size of 198 in both trial arms. Contamination of both arms with 5% misclassified participants inflated the required sample size to 237 and with 20% misclassification inflated the required sample size to 352, for equivalent trial power. For an outcome of stroke recurrence using the same data, base-case estimated sample size for 80% power and alpha 0.05 was n = 502 in each arm, increasing to 605 at 5% contamination and 973 at 20% contamination. Conclusions: Stroke aetiological classification systems suffer from inter-observer variability, and the resulting misclassification may limit trial power. Trial registration: Protocol available at reviewregistry540

Derivation and validation of a novel prognostic scale (modified–stroke subtype, Oxfordshire Community Stroke Project classification, age, and prestroke modified Rankin) to predict early mortality in acute stroke

Background and Purpose The stroke subtype, Oxfordshire Community Stroke Project classification, age, and prestroke modified Rankin (SOAR) score is a prognostic scale proposed for early mortality prediction after acute stroke. We aimed to evaluate whether including a measure of initial stroke severity (National Institutes of Health Stroke Scale and modified-SOAR [mSOAR] scores) would improve the prognostic accuracy. Methods Using Anglia Stroke and Heart Clinical Network data, 2008 to 2011, we assessed the performance of SOAR and mSOAR against in-hospital mortality using area under the receiver operating curve statistics. We externally validated the prognostic utility of SOAR and mSOAR using an independent cohort data set from Glasgow. We described calibration using Hosmer–Lemeshow goodness-of-fit test. Results A total of 1002 patients were included in the derivation cohort, and 105 (10.5%) died as inpatients. The area under the receiver operating curves for outcome of early mortality derived from the SOAR and mSOAR scores were 0.79 (95% confidence interval, 0.75–0.84) and 0.83 (95% confidence interval, 0.79–0.86), respectively (P=0.001). The external validation data set contained 1012 patients with stroke; of which, 121 (12.0%) patients died within 90 days. The mSOAR scores identified the risk of early mortality ranging from 3% to 42%. External validation of mSOAR score yielded an area under the receiver operating curve of 0.84 (95% confidence interval, 0.82–0.88) for outcome of early mortality. Calibration was good (P=0.70 for the Hosmer–Lemeshow test). Conclusions—Adding National Institutes of Health Stroke Scale data to create a modified-SOAR score improved prognostic utility in both derivation and validation data sets. The mSOAR may have clinical utility by using easily available data to predict mortality