Corneal Confocal Microscopy Identifies Parkinson's Disease with More Rapid Motor Progression

From Wiley via Jisc Publications RouterHistory: received 2020-12-15, rev-recd 2021-03-11, accepted 2021-03-12, pub-electronic 2021-04-07, pub-print 2021-08Article version: VoRPublication status: PublishedFunder: Michael J Fox Foundation Trust (Grant ID 12059); Id: http://dx.doi.org/10.13039/100010269ABSTRACT: Background: Corneal confocal microscopy (CCM) is a noninvasive, reproducible ophthalmic technique to quantify corneal small nerve fiber degeneration. CCM demonstrates small nerve fiber damage in Parkinson's disease (PD), but its role as a longitudinal biomarker of PD progression has not been explored. Objective: The aim of this study was to assess corneal nerve morphology using CCM in relation to disease progression in PD. Methods: Sixty‐four participants with PD were assessed at baseline and at 12‐month follow‐up. Participants underwent CCM with automated corneal nerve quantification and assessment of Movement Disorder Society Unified Parkinson's Disease Rating Scale, Hoehn and Yahr stage, and Montreal Cognitive Assessment. Results: Corneal nerve fiber density (CNFD), corneal nerve branch density, corneal nerve fiber length, corneal total branch density, and corneal nerve fiber area were significantly lower in participants with PD compared with healthy control subjects. Worsening of Movement Disorder Society Unified Parkinson's Disease Rating Scale part III score over 12 months was significantly greater in participants with a CNFD in the lowest compared with the highest quartile at baseline (mean difference: 6.0; 95% CI: 1.0–10.9; P = 0.019). There were no significant changes in CNFD, corneal nerve branch density, corneal nerve fiber length, corneal total branch density, corneal nerve fiber area, or corneal nerve fiber width between baseline and 12‐month follow‐up. Conclusions: CCM identifies neurodegeneration in patients with PD, especially those who show the greatest progression in neurological disability. CCM may be a useful tool to help enrich clinical trials with those likely to exhibit more rapid progression and reduce required sample size and cost of studies. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Societ

Effectiveness of a structured pharmacist-delivered intervention for patients post-acute coronary syndromes on all-cause hospitalizations and cardiac-related hospital readmissions: a prospective quasi-experimental study

Background: Acute coronary syndrome (ACS) is a leading cause of mortality and morbidity in Qatar and globally. Aim: The primary objective of the study was to evaluate the effectiveness of a structured clinical pharmacist-delivered intervention on all-cause hospitalizations and cardiac-related readmissions in patients with ACS. Method: A prospective quasi-experimental study was conducted at Heart Hospital in Qatar. Discharged ACS patients were allocated to one of three study arms: (1) an intervention group (received a structured clinical pharmacist-delivered medication reconciliation and counselling at discharge, and two follow-up sessions at 4 weeks and 8 weeks post-discharge), (2) a usual care group (received the general usual care at discharge by clinical pharmacists) or, (3) a control group (discharged during weekends or after clinical pharmacists' working hours). Follow-up sessions for the intervention group were designed to re-educate and counsel patients about their medications, remind them about the importance of medication adherence, and answer any questions they may have. At the hospital, patients were allocated into one of the three groups based on intrinsic and natural allocation procedures. Recruitment of patients took place between March 2016 and December 2017. Data were analyzed based on intention-to-treat principles. Results: Three hundred seventy-three patients were enrolled in the study (intervention = 111, usual care = 120, control = 142). Unadjusted results showed that the odds of 6-month all-cause hospitalizations were significantly higher among the usual care (OR 2.034; 95% CI: 1.103–3.748, p = 0.023) and the control arms (OR 2.704; 95% CI: 1.456–5.022, p = 0.002) when compared to the intervention arm. Similarly, patients in the usual care arm (OR 2.304; 95% CI: 1.122–4.730, p = 0.023) and the control arm (OR 3.678; 95% CI: 1.802–7.506, p ≤ 0.001) had greater likelihood of cardiac-related readmissions at 6 months. After adjustment, these reductions were only significant for cardiac-related readmissions between control and intervention groups (OR 2.428; 95% CI: 1.116–5.282, p = 0.025). Conclusion: This study demonstrated the impact of a structured intervention by clinical pharmacists on cardiac-related readmissions at 6 months post-discharge in patients post-ACS. The impact of the intervention on all-cause hospitalization was not significant after adjustment for potential confounders. Large cost‐effective studies are required to determine the sustained impact of structured clinical pharmacist-provided interventions in ACS setting. Trial registration: Clinical Trials: NCT02648243 Registration date: January 7, 2016.This work was supported by an internal grant (Grant Number QUUG-CPH-CPH-14\15-2) from Qatar University Office of Research and Graduate Studies. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of Qatar University

Evaluation of an intensive education program on the treatment of tobacco-use disorder for pharmacists: A study protocol for a randomized controlled trial

Background: Tobacco use is presently responsible for the death of over seven million people across the world. In Qatar, it is one of the main causes of premature deaths and preventable diseases. To reduce tobacco use, Qatar has ratified the World Health Organization (WHO)'s Framework Convention on Tobacco Control (FCTC) and has implemented many tobacco-control initiatives. In spite of these measures, tobacco use is still considered a public health threat in Qatar. Pharmacists practicing in retail/community pharmacy settings are often the first port of call for individuals requiring general health advice. Evidence has proven that they have a pivotal role in health promotion and disease prevention including tobacco cessation. However, pharmacists in Qatar are not actively involved in tobacco control and many have not received any education or training about smoking cessation counseling in the past. In an effort to build the capacity of pharmacists towards tobacco control in Qatar, the aim of the proposed study is to design, implement, and evaluate an intensive education program on tobacco dependence treatment for pharmacists in Qatar. Methods/design: The study will be a prospective randomized controlled trial comparing an intensive tobacco-related education program versus non-tobacco-related training on pharmacists' tobacco-use-related knowledge, attitudes, self-efficacy, and skills. Community pharmacists practicing in Qatar will be eligible for participation in the study. A random sample of pharmacists will be selected for participation. Consenting participants will be randomly allocated to intervention or control groups. Participants in the intervention group will receive an intensive education program delivered by a multi-disciplinary group of educators, researchers, and clinicians with expertise in tobacco cessation. A short didactic session on a non-tobacco-related topic will be delivered to pharmacists in the control group. The study has two primary outcomes: post-intervention tobacco-related knowledge and post-intervention skills for tobacco cessation assessed using a multiple-choice-based evaluation instrument and an Objective Structured Clinical Examination (OSCE), respectively. The secondary study outcomes are post-intervention attitudes towards tobacco cessation and self-efficacy in tobacco-cessation interventions assessed using a survey instrument. An additional secondary study outcome is the post-intervention performance difference in relation to tobacco-cessation skills in the practice setting assessed using the simulated client approach. Discussion: If demonstrated to be effective, this education program will be considered as a model that Qatar and the Middle East region can apply to overcome the burden of tobacco-use disorder. Trial registration: ClinicalTrials.gov, ID: NCT03518476. Registered on 8 May 2018. Version 1/22 June 2018. 2019 The Author(s).ASHP: American Society of Health-System Pharmacists; ATTUD: Association for the Treatment of Tobacco use and Dependence; CE: Continuous education; CPG: Clinical practice guidelines; FCTC: Framework Convention on Tobacco Control; FIP: International Pharmaceutical Federation; GATS: Global Adult Tobacco Survey; GYTS: Global Youth Tobacco Survey; HMC: Hamad Medical Corporation; MCQ: Multiple choice question; ME: Middle East; NRT: Nicotine replacement therapy; OSCE: Objective Structured Clinical Examination; PBL: Problem-based learning; QCHP: Qatar Council for Healthcare Practitioners; QU: Qatar University; SPIRIT: Standard Protocol Items: Recommendations for Interventional Trials; SPSS: Statistical Package of Social Sciences; TTM: Transtheoretical model; WHO: World Health OrganizationScopu

Prevalence and management of diabetic neuropathy in secondary care in Qatar

Aims Diabetic neuropathy (DN) is a “Cinderella” complication, particularly in the Middle East. A high prevalence of undiagnosed DN and those at risk of diabetic foot ulceration (DFU) is a major concern. We have determined the prevalence of DN and its risk factors, DFU and those at risk of (DFU) in patients with T2DM in secondary care in Qatar. Materials and methods Adults with T2DM were randomly selected from the two National Diabetes Centers in Qatar. DN was defined by the presence of neuropathic symptoms and a vibration perception threshold (VPT) ≥ 15 V. Participants with a VPT≥25 V were categorized as high risk for DFU. Painful DN was defined by a DN4 score ≥ 4. Logistic regression analysis was used to identify predictors of DN. Results In 1082 adults with T2DM (age 54 ± 11 years, duration of diabetes 10.0 ± 7.7 years, 60.6% males) the prevalence of DN was 23.0% (95% CI: 20.5%‐25.5%), of whom 33.7% (95% CI: 27.9%‐39.6%) were at high risk of DFU and 6.3% had DFU. 82.0% of the patients with DN were previously undiagnosed. The prevalence of DN increased with age and duration of diabetes and was associated with poor glycemic control (HbA1c ≥ 9%) AOR = 2.1 (95%CI: 1.3‐3.2), hyperlipidemia AOR = 2.7 (95%CI: 1.5‐5.0) and hypertension AOR = 2.0 (95%CI: 1.2‐3.4). Conclusions Despite, DN affecting 23% of adults with T2DM, 82% had not been previously diagnosed with 1/3 at high risk for DFU. This argues for annual screening and identification of patients with DN. Furthermore, we identify hyperglycemia, hyperlipidemia and hypertension as predictors of DN

Equal antipyretic effectiveness of oral and rectal acetaminophen: a randomized controlled trial [ISRCTN11886401]

BACKGROUND: The antipyretic effectiveness of rectal versus oral acetaminophen is not well established. This study is designed to compare the antipyretic effectiveness of two rectal acetaminophen doses (15 mg/kg) and (35 mg/kg), to the standard oral dose of 15 mg/kg. METHODS: This is a randomized, double-dummy, double-blind study of 51 febrile children, receiving one of three regimens of a single acetaminophen dose: 15 mg/kg orally, 15 mg/kg rectally, or 35 mg/kg rectally. Rectal temperature was monitored at baseline and hourly for a total of six hours. The primary outcome of the study, time to maximum antipyresis, and the secondary outcome of time to temperature reduction by at least 1°C were analyzed by one-way ANOVA. Two-way ANOVA with repeated measures over time was used to compare the secondary outcome: change in temperature from baseline at times1, 2, 3, 4, 5, and 6 hours among the three groups. Intent-to-treat analysis was planned. RESULTS: No significant differences were found among the three groups in the time to maximum antipyresis (overall mean = 3.6 hours; 95% CI: 3.2–4.0), time to fever reduction by 1°C or the mean hourly temperature from baseline to 6 hours following dose administration. Hypothermia (temperature < 36.5°C) occurred in 11(21.6%) subjects, with the highest proportion being in the rectal high-dose group. CONCLUSION: Standard (15 mg/kg) oral, (15 mg/kg) rectal, and high-dose (35 mg/kg) rectal acetaminophen have similar antipyretic effectiveness

Prevalence and risk factors for painful diabetic neuropathy in secondary health care in Qatar.

AIMS/INTRODUCTION:Painful diabetic peripheral neuropathy (PDPN) has a significant impact on the patient's quality of life. The prevalence of PDPN in the Middle East and North Africa (MENA) region has been reported to be almost double that of populations in the UK. We sought to determine the prevalence of PDPN and its associated factors in T2DM patients attending secondary care in Qatar. MATERIALS AND METHODS:This is a cross-sectional study of 1095 participants with T2DM attending Qatar's two national diabetes centers. PDPN and impaired vibration perception on the pulp of the large toes were assessed using the DN4 questionnaire with a cut-off ≥4 and the Neurothesiometer with a cut-off ≥15V, respectively. RESULTS:The prevalence of PDPN was 34.5% (95% CI: 31.7%-37.3%), but 80% of these patients had not previously been diagnosed or treated for this condition. Arabs had a higher prevalence of PDPN compared to South Asians (P<0.05). PDPN was associated with impaired vibration perception AOR=4.42 (95%CI: 2.92-6.70), smoking AOR=2.43 (95%CI: 1.43-4.15), obesity AOR=1.74 (95%CI: 1.13-2.66), being female AOR=1.65 (95%CI: 1.03-2.64) and duration of diabetes AOR=1.08 (95%CI: 1.05-1.11). Age, poor glycemic control, hypertension, physical activity and proteinuria showed no association with PDPN. CONCLUSIONS:PDPN occurs in 1/3 of T2DM patients attending secondary care in Qatar, but the majority have not been diagnosed. Arabs are at higher risk for PDPN. Impaired vibration perception, obesity and smoking are associated with PDPN in Qatar. This article is protected by copyright. All rights reserved

Corneal nerve and brain imaging in mild cognitive impairment and dementia

Background: Visual rating of medial temporal lobe atrophy (MTA) is an accepted structural neuroimaging marker of Alzheimer's disease. Corneal confocal microscopy (CCM) is a non-invasive ophthalmic technique that detects neuronal loss in peripheral and central neurodegenerative disorders. Objective: To determine the diagnostic accuracy of CCM for mild cognitive impairment (MCI) and dementia compared to medial temporal lobe atrophy (MTA) rating on MRI. Methods: Subjects aged 60-85 with no cognitive impairment (NCI), MCI, and dementia based on the ICD-10 criteria were recruited. Subjects underwent cognitive screening, CCM, and MTA rating on MRI. Results: 182 subjects with NCI (n = 36), MCI (n = 80), and dementia (n = 66), including AD (n = 19, 28.8%), VaD (n = 13, 19.7%), and mixed AD (n = 34, 51.5%) were studied. CCM showed a progressive reduction in corneal nerve fiber density (CNFD, fibers/mm2) (32.0±7.5 versus 24.5±9.6 and 20.8±9.3, p < 0.0001), branch density (CNBD, branches/mm2) (90.9±46.5 versus 59.3±35.7 and 53.9±38.7, p < 0.0001), and fiber length (CNFL, mm/mm2) (22.9±6.1 versus 17.2±6.5 and 15.8±7.4, p < 0.0001) in subjects with MCI and dementia compared to NCI. The area under the ROC curve (95% CI) for the diagnostic accuracy of CNFD, CNBD, CNFL compared to MTA-right and MTA-left for MCI was 78% (67-90%), 82% (72-92%), 86% (77-95%) versus 53% (36-69%) and 40% (25-55%), respectively, and for dementia it was 85% (76-94%), 84% (75-93%), 85% (76-94%) versus 86% (76-96%) and 82% (72-92%), respectively. Conclusion: The diagnostic accuracy of CCM, a non-invasive ophthalmic biomarker of neurodegeneration, was high and comparable with MTA rating for dementia but was superior to MTA rating for MCI

Prevalence and risk factors for diabetic neuropathy and painful diabetic neuropathy in primary and secondary health care in Qatar.

AIMS/INTRODUCTION:This study determined the prevalence and risk factors for DPN and pDPN in patients with type 2 diabetes (T2D) in primary health care (PHC) and secondary health care (SHC) in Qatar. MATERIALS AND METHODS:This is a cross-sectional multi-center study. Adults with T2D were randomly enrolled from four PHC centres and two Diabetes Centres in SHC in Qatar. Subjects underwent assessment of clinical and metabolic parameters, DPN and pDPN. RESULTS:1,386 subjects with T2D (297 from PHC and 1,089 from SHC) were recruited. The prevalence of DPN (14.8% vs 23.9%, P=0.001) and pDPN (18.1% vs 37.5%, P<0.0001) was significantly lower in PHC compared to SHC, whilst those with DPN at high risk for DFU (31.8% vs 40.0%, P=0.3) was comparable. The prevalence of undiagnosed DPN (79.5% vs 82.3%, P=0.66) was comparably high but undiagnosed pDPN (24.1% vs 71.5%, P<0.0001) was lower in PHC compared to SHC. The odds of DPN and pDPN increased with age and diabetes duration and DPN increased with poor glycemic control, hyperlipidemia and hypertension, whilst pDPN increased with obesity and reduced physical activity. CONCLUSIONS:The prevalence of DPN and pDPN in T2D is lower in PHC compared to SHC and is attributed to overall better control of risk factors and referral bias due to patients with poorly managed complications being referred to SHC. However, ~80% of patients had not been previously diagnosed with DPN in PHC and SHC. Further, we identify a number of modifiable risk factors for PDN and pDPN

Association of Cerebral Ischemia With Corneal Nerve Loss and Brain Atrophy in MCI and Dementia

IntroductionThis study assessed the association of cerebral ischemia with neurodegeneration in mild cognitive impairment (MCI) and dementia.MethodsSubjects with MCI, dementia and controls underwent assessment of cognitive function, severity of brain ischemia, MRI brain volumetry and corneal confocal microscopy.ResultsOf 63 subjects with MCI (n = 44) and dementia (n = 19), 11 had no ischemia, 32 had subcortical ischemia and 20 had both subcortical and cortical ischemia. Brain volume and corneal nerve measures were comparable between subjects with subcortical ischemia and no ischemia. However, subjects with subcortical and cortical ischemia had a lower hippocampal volume (P &lt; 0.01), corneal nerve fiber length (P &lt; 0.05) and larger ventricular volume (P &lt; 0.05) compared to those with subcortical ischemia and lower corneal nerve fiber density (P &lt; 0.05) compared to those without ischemia.DiscussionCerebral ischemia was associated with cognitive impairment, brain atrophy and corneal nerve loss in MCI and dementia