Statin Selection in Qatar Based on Multi-indication Pharmacotherapeutic Multi-criteria Scoring Model, and Clinician Preference.

Purpose: Statin selection for the largest hospital formulary in Qatar is not systematic, not comparative, and does not consider the multi-indication nature of statins. There are no reports in the literature of multi-indication-based comparative scoring models of statins or of statin selection criteria weights that are based primarily on local clinicians' preferences and experiences. This study sought to comparatively evaluate statins for first-line therapy in Qatar, and to quantify the economic impact of this.

Longitudinal changes in cerebellar and subcortical volumes in adult-onset Niemann-Pick disease type C patients treated with miglustat.

Niemann-Pick disease type C (NPC) is a rare neurovisceral disorder resulting in impaired intracellular lipid trafficking. The only disease-modifying treatment available to date is miglustat, an iminosugar inhibiting the accumulation of lipid by-products in neurons. This study explored how changes in cerebellar grey and white matter volumes, and in subcortical volumes, related to patient treatment status and disability and ataxia ratings.

Isolated ventriculomegaly on prenatal ultrasound: what does fetal MRI add?

Introduction: Cerebral ventriculomegaly is one of the most commonly detected fetal anomalies at the midtrimester ultrasound. Current evidence suggests that magnetic resonance imaging (MRI) is indicated when the isolated ventriculomegaly (IVM) on ultrasound is severe (>15 mm), but there is less agreement when IVM is mild or moderate (10-15 mm). The current study aimed to determine the frequency and nature of additional findings on MRI in IVM and their relationship to the severity of VM and gestational age.

Design and nuclear magnetic resonance (NMR) structure determination of the second extracellular immunoglobulin tyrosine kinase A (TrkAIg2) domain construct for binding site elucidation in drug discovery.

The tyrosine kinase A (TrkA) receptor is a validated therapeutic intervention point for a wide range of conditions. TrkA activation by nerve growth factor (NGF) binding the second extracellular immunoglobulin (TrkAIg2) domain triggers intracellular signaling cascades. In the periphery, this promotes the pain phenotype and, in the brain, cell survival or differentiation.

Could cord blood cell therapy reduce preterm brain injury?

Major advances in neonatal care have led to significant improvements in survival rates for preterm infants, but this occurs at a cost, with a strong causal link between preterm birth and neurological deficits, including cerebral palsy (CP). Indeed, in high-income countries, up to 50% of children with CP were born preterm. The pathways that link preterm birth and brain injury are complex and multifactorial, but it is clear that preterm birth is strongly associated with damage to the white matter of the developing brain.

Correcting for the bias caused by exposure measurement error in epidemiological studies.

An important goal of many epidemiological studies is to estimate the magnitude of association between an exposure and an outcome. Exposure measurement error causes bias in such estimates of association and can be substantial. In this article, we describe the problem of exposure measurement error and its effects.

A study of up to 12 years of follow-up of Friedreich ataxia utilising four measurement tools.

Objective: To explore the progression of Friedreich ataxia by analysing the change in scores of four clinical measures (the Friedreich Ataxia Rating Scale (FARS), the International Cooperative Ataxia Rating Scale (ICARS), the Functional Independence Measure (FIM) and the Modified Barthel Index (MBI)) over a period of up to 12 years, to ascertain the effects of clinical variables on performance of these measures, and to determine the most sensitive rating scale for measuring disease progression.

Methods: We measured the disease progression of up to 147 individuals against disease duration grouped into 5-year intervals. Additional subgroups were created to study the effects of the size of the smaller FXN intron 1 GAA repeat size (GAA1) and onset age on rating scale performance.

Detecting brain injury in neonatal hypoxic ischemic encephalopathy: closing the gap between experimental and clinical research.

Moderate to severe neonatal hypoxic ischemic encephalopathy remains an important cause of infant death and childhood disability. Early and accurate diagnosis of encephalopathy is difficult but critical for timely intervention. Thus, we have utilized a clinically relevant large animal model of asphyxia in-utero, followed by immediate lamb delivery, resuscitation and clinical care over the next 72h for assessment of potential biomarkers of brain injury.

Alemtuzumab treatment of multiple sclerosis: long-term safety and efficacy.

Objectives: Alemtuzumab is a newly licensed treatment of active relapsing-remitting multiple sclerosis (RRMS) in Europe, which in phase II and III studies demonstrated superior efficacy over β-interferon in reducing disability progression over 2-3 years. In this observational cohort study, we sought to describe our longer-term experience of the efficacy and safety of alemtuzumab in active RRMS.

Methods: Clinical and laboratory data including serial Expanded Disability Status Scale (EDSS) assessments, from all 87 patients treated with alemtuzumab on investigator-led studies in Cambridge, UK, from 1999 to 2012, were collected.

Cobalamin E defect, a rare inborn error of vitamin B12 metabolism: value of early diagnosis and treatment.

Cobalamin and its metabolites play a crucial role in DNA synthesis and cellular energy metabolism. Disorders of cobalamin metabolism are rare, autosomal recessive, conditions that present with neurological dysfunction of varying severity. We report a child with cobalamin E defect presenting in early infancy with vertical nystagmus, developmental delay, deceleration in head growth, status epilepticus and leukoencephalopathy, with only mild haematological abnormalities.

Human autoimmunity after lymphocyte depletion is caused by homeostatic T-cell proliferation.

The association between lymphopenia and autoimmunity is recognized, but the underlying mechanisms are poorly understood and have not been studied systematically in humans. People with multiple sclerosis treated with the lymphocyte-depleting monoclonal antibody alemtuzumab offer a unique opportunity to study this phenomenon; one in three people develops clinical autoimmunity, and one in three people develops asymptomatic autoantibodies after treatment. Here, we show that T-cell recovery after alemtuzumab is driven by homeostatic proliferation, leading to the generation of chronically activated (CD28(-)CD57(+)), highly proliferative (Ki67(+)), oligoclonal, memory-like CD4 and CD8 T cells (CCR7(-)CD45RA(-) or CCR7(-)CD45RA(+)) capable of producing proinflammatory cytokines.

Small intragenic deletion in FOXP2 associated with childhood apraxia of speech and dysarthria.

Relatively little is known about the neurobiological basis of speech disorders although genetic determinants are increasingly recognized. The first gene for primary speech disorder was FOXP2, identified in a large, informative family with verbal and oral dyspraxia. Subsequently, many de novo and familial cases with a severe speech disorder associated with FOXP2 mutations have been reported.

Niemann-Pick type C Suspicion Index tool: analyses by age and association of manifestations.

Objective: The Suspicion Index (SI) screening tool was developed to identify patients suspected of having Niemann-Pick disease type C (NP-C). The SI provides a risk prediction score (RPS) based on NP-C manifestations within and across domains (visceral, neurological, and psychiatric). The aim of these subanalyses was to further examine the discriminatory power of the SI by age and manifestation-associations by NP-C suspicion-level and leading manifestations.

Australian Cerebral Palsy Child Study: protocol of a prospective population based study of motor and brain development of preschool aged children with cerebral palsy.

Background: Cerebral palsy (CP) results from a static brain lesion during pregnancy or early life and remains the most common cause of physical disability in children (1 in 500). While the brain lesion is static, the physical manifestations and medical issues may progress resulting in altered motor patterns. To date, there are no prospective longitudinal studies of CP that follow a birth cohort to track early gross and fine motor development and use Magnetic Resonance Imaging (MRI) to determine the anatomical pattern and likely timing of the brain lesion.

Evidence-based guideline for the written radiology report: methods, recommendations and implementation challenges.

The written radiology report is the dominant method by which radiologists communicate the results of diagnostic and interventional imaging procedures. It has an important impact on decisions about further investigation and management. Its form and content can be influential in reducing harm to patients and mitigating risk for practitioners but varies markedly with little standardisation in practice.

Cerebellar volume correlates with saccadic gain and ataxia in adult Niemann-Pick type C.

Background And Purpose: Cerebellar Purkinje cells are known to be highly vulnerable to neuronal pathology in Niemann-Pick type C (NPC), a disease where widespread white matter changes have also been reported. We sought to determine the relationship between white and grey matter cerebellar changes and clinical variables in NPC.

Materials And Methods: Ten adult patients with NPC were matched to control subjects (n=27) on age and gender.

Subcortical volumetric reductions in adult Niemann-Pick disease type C: a cross-sectional study.

Background And Purpose: Voxel-based analysis has suggested that deep gray matter rather than cortical regions is initially affected in adult Niemann-Pick type C. We sought to examine a range of deep gray matter structures in adults with NPC and relate these to clinical variables.

Materials And Methods: Ten adult patients with NPC (18-49 years of age) were compared with 27 age- and sex-matched controls, and subcortical structures were automatically segmented from normalized T1-weighted MR images.

Saccadic eye movement characteristics in adult Niemann-Pick Type C disease: relationships with disease severity and brain structural measures.

Niemann-Pick Type C disease (NPC) is a rare genetic disorder of lipid metabolism. A parameter related to horizontal saccadic peak velocity was one of the primary outcome measures in the clinical trial assessing miglustat as a treatment for NPC. Neuropathology is widespread in NPC, however, and could be expected to affect other saccadic parameters.

Reported eating ability of young children with cerebral palsy: is there an association with gross motor function?

Objective: To examine the association between parent-reported ability of young children with cerebral palsy (CP) to eat different food textures and gross motor functional abilities.

Design: Prospective, longitudinal, representative cohort study.

Setting: Community and tertiary pediatric hospital settings.

Pharmacy practice in Qatar: challenges and opportunities.

The State of Qatar is a small oil and gas-rich Gulf country that is experiencing rapid development in health care services, including pharmaceutical services. To date, there is no autonomous professional pharmacy association or society that regulates or promotes the practice of pharmacy in Qatar, and the challenges that face the profession of pharmacy in Qatar mirror the challenges facing the profession in all other Middle Eastern countries. However, a set of initiatives and projects that include pioneering educational initiatives, close alignment of practice with the educational providers, stronger leadership from a National Health Strategy, and the development of pharmacy leadership groups at the practice level all contribute in the fast development of the practice of pharmacy in this country.