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301. The role of abnormalities of lipoproteins and HDL functionality in small fibre dysfunction in people with severe obesity

Author

Azmi, Shazli, primary, Ferdousi, Maryam, additional, Liu, Yifen, additional, Adam, Safwaan, additional, Siahmansur, Tarza, additional, Ponirakis, Georgios, additional, Marshall, Andrew, additional, Petropoulos, Ioannis N., additional, Ho, Jan Hoong, additional, Syed, Akheel A., additional, Gibson, John M., additional, Ammori, Basil J., additional, Durrington, Paul N., additional, Malik, Rayaz A., additional, and Soran, Handrean, additional

Published
2021
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302. No evidence of improvement in neuropathy after renal transplantation in patients with end stage kidney disease

Author

Ferdousi, Maryam, primary, Azmi, Shazli, additional, Kalteniece, Alise, additional, Khan, Saif Ullah, additional, Petropoulos, Ioannis N., additional, Ponirakis, Georgios, additional, Alam, Uazman, additional, Asghar, Omar, additional, Marshall, Andrew, additional, Soran, Handrean, additional, Boulton, Andrew J. M., additional, Augustine, Titus, additional, and Malik, Rayaz A., additional

Published
2021
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303. Lipids and peripheral neuropathy

Author

Iqbal, Zohaib, primary, Bashir, Bilal, additional, Ferdousi, Maryam, additional, Kalteniece, Alise, additional, Alam, Uazman, additional, Malik, Rayaz A., additional, and Soran, Handrean, additional

Published
2021
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305. Corneal Nerve Loss in Patients with Acute Ischemic Stroke: A Surrogate Marker for Poor Pial Collaterals

Author

Khan, Adnan, primary, Menon, Ajay, additional, Akhtar, Naveed, additional, Kamran, Saadat, additional, Muhammad, Ahmad, additional, Ponirakis, Georgios, additional, Gad, Hoda, additional, Petropoulos, Ioannis, additional, Wadiwala, Faisal, additional, babu, Blessy, additional, Narangoli, Adeeb, additional, Bermejo, Pablo, additional, Hamad, Hanadi Al, additional, Ramadan, Marwan, additional, Woodruff, Peter, additional, Santos, Mark, additional, Saqqur, Maher, additional, Shuaib, Ashfaq, additional, and Malik, Rayaz A., additional

Published
2021
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307. Abnormal quantitative pupillary light responses following COVID-19.

Author

Bitirgen, Gulfidan, Korkmaz, Celalettin, Zamani, Adil, Iyisoy, Mehmet Sinan, Kerimoglu, Hurkan, and Malik, Rayaz A.

Abstract

Purpose: To characterize alterations in pupillary light reflex responses in subjects following coronavirus disease 2019 (COVID-19), especially those with long-COVID. Methods: Thirty-five subjects with previous COVID-19 and 30 healthy control participants were enrolled in this cross-sectional comparative study. An infrared dynamic pupillometry system (MonPack One; Metrovision, France) was used to quantify pupillary light responses. The National Institute for Health and Care Excellence (NICE) long-COVID questionnaire was used to identify persisting symptoms at least 4 weeks after acute COVID-19. Results: The median time after the diagnosis of acute COVID-19 was 4.0 (2.0–5.0) months. There was an increase in the latency of pupil contraction (P = 0.001) and a reduction in the duration of pupil contraction (P = 0.039) in post-COVID-19 subjects compared to healthy controls. No significant differences were observed in the initial pupil diameter, amplitude and velocity of pupil contraction or latency, velocity and duration of pupil dilation. Long-COVID was present in 25/35 (71%) subjects and their duration of pupil contraction was reduced compared to subjects without long-COVID (P = 0.009). The NICE long-COVID questionnaire total score (ρ = − 0.507; P = 0.002) and neurological score (ρ = − 0.412; P = 0.014) correlated with the duration of pupil contraction and the total score correlated with the latency of dilation (ρ = − 0.352; P = 0.038). Conclusion: Dynamic pupillometry reveals significant alterations in contractile pupillary light responses, indicative of parasympathetic dysfunction after COVID-19. [ABSTRACT FROM AUTHOR]

Published
2022
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309. Small Nerve Fiber Damage and Langerhans Cells in Type 1 and Type 2 Diabetes and LADA Measured by Corneal Confocal Microscopy

Author

D'Onofrio, Luca, primary, Kalteniece, Alise, additional, Ferdousi, Maryam, additional, Azmi, Shazli, additional, Petropoulos, Ioannis N., additional, Ponirakis, Georgios, additional, Alam, Uazman, additional, Asghar, Omar, additional, Marshall, Andrew, additional, Boulton, Andrew J.M., additional, Efron, Nathan, additional, Buzzetti, Raffaella, additional, Soran, Handrean, additional, and Malik, Rayaz A., additional

Published
2021
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310. Painful diabetic neuropathy is associated with increased nerve regeneration in patients with type 2 diabetes undergoing intensive glycemic control

Author

Ponirakis, Georgios, primary, Abdul‐Ghani, Muhammad A, additional, Jayyousi, Amin, additional, Zirie, Mahmoud A, additional, Qazi, Murtaza, additional, Almuhannadi, Hamad, additional, Petropoulos, Ioannis N, additional, Khan, Adnan, additional, Gad, Hoda, additional, Migahid, Osama, additional, Megahed, Ayman, additional, Al‐Mohannadi, Salma, additional, AlMarri, Fatema, additional, Al‐Khayat, Fatima, additional, Mahfoud, Ziyad, additional, Al Hamad, Hanadi, additional, Ramadan, Marwan, additional, DeFronzo, Ralph, additional, and Malik, Rayaz A, additional

Published
2021
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311. Prevalence of peripheral neuropathy in pre-diabetes: a systematic review

Author

Kirthi, Varo, primary, Perumbalath, Anugraha, additional, Brown, Emily, additional, Nevitt, Sarah, additional, Petropoulos, Ioannis N, additional, Burgess, Jamie, additional, Roylance, Rebecca, additional, Cuthbertson, Daniel J, additional, Jackson, Timothy L, additional, Malik, Rayaz A, additional, and Alam, Uazman, additional

Published
2021
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312. Bariatric Surgery-induced High-density Lipoprotein Functionality Enhancement Is Associated With Reduced Inflammation.

Author

Adam, Safwaan, Ho, Jan H., Yifen Liu, Siahmansur, Tarza, Siddals, Kirk, Iqbal, Zohaib, Azmi, Shazli, Senapati, Siba, New, John, Jeziorska, Maria, Ammori, Basil J., Syed, Akheel A., Donn, Rachelle, Malik, Rayaz A., Durrington, Paul N., and Soran, Handrean

Subjects
BARIATRIC surgery, HIGH density lipoproteins, INFLAMMATION
Abstract

Background: Emerging evidence suggests an association between impaired high-density lipoprotein (HDL) functionality and cardiovascular disease (CVD). HDL is essential for reverse cholesterol transport (RCT) and reduces inflammation and oxidative stress principally via paraoxonase-1 (PON1). RCT depends on HDL’s capacity to accept cholesterol (cholesterol efflux capacity [CEC]) and active transport through ATP-binding cassette (ABC) A1, G1, and scavenger receptor-B1 (SR-B1). We have studied the impact of Roux-en-Y gastric bypass (RYGB) in morbidly obese subjects on RCT and HDL functionality. Methods: Biomarkers associated with increased CVD risk including tumour necrosis factor-α (TNF-α), high-sensitivity C-reactive protein (hsCRP), myeloperoxidase mass (MPO), PON1 activity, and CEC in vitro were measured in 44 patients before and 6 and 12 months after RYGB. Overweight but otherwise healthy (mean body mass index [BMI] 28 kg/m² ) subjects acted as controls. Twelve participants also underwent gluteal subcutaneous adipose tissue biopsies before and 6 months after RYGB for targeted gene expression (ABCA1, ABCG1, SR-B1, TNF-α) and histological analysis (adipocyte size, macrophage density, TNF-α immunostaining). Results: Significant (P < 0.05) improvements in BMI, HDL-cholesterol, hsCRP, TNF-α, MPO mass, PON1 activity, and CEC in vitro were observed after RYGB. ABCG1 (fold-change, 2.24; P = 0.005) and ABCA1 gene expression increased significantly (fold-change, 1.34; P = 0.05). Gluteal fat adipocyte size (P < 0.0001), macrophage density (P = 0.0067), and TNF-α immunostaining (P = 0.0425) were reduced after RYBG and ABCG1 expression correlated inversely with TNF-α immunostaining (r = -0.71; P = 0.03). Conclusion: RYGB enhances HDL functionality in association with a reduction in adipose tissue and systemic inflammation. [ABSTRACT FROM AUTHOR]

Published
2022
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313. Early retinal functional alteration in relation to diabetes duration in patients with type 2 diabetes without diabetic retinopathy.

Author

Srinivasan, Sangeetha, Sivaprasad, Sobha, Rajalakshmi, Ramachandran, Anjana, Ranjit Mohan, Malik, Rayaz A., Kulothungan, Vaitheeswaran, Natarajan, Viswanathan, Raman, Rajiv, and Bhende, Muna

Subjects
DIABETIC retinopathy, TYPE 2 diabetes, PEOPLE with diabetes, OPTICAL coherence tomography, OUTDOOR photography, MACULAR edema
Abstract

To examine the retinal structure and function in relation to diabetes duration and glycemia in patients without diabetic retinopathy (DR). 85 adults with type 2 diabetes without DR or macular edema underwent dilated indirect ophthalmoscopy, optical coherence tomography (OCT), ultra-wide field fundus photography, multifocal electroretinography (mfERG) and HbA1C assessment. Patients were stratified as those with diabetes duration < 10 years and ≥ 10 years. Right eyes of all participants were analyzed. mfERG was analysed as ring 12, 34, 56. No significant differences were noted in OCT-derived retinal thickness measures between groups. mfERG P1 latencies were delayed, and amplitudes (nV/deg2) were reduced in all three rings in those with diabetes duration ≥ 10 years vs. < 10 years, with significant correlations to diabetes duration in all rings. Logistic regression showed that duration of diabetes ≥ 10 years was associated with greater age (odds ratio (OR) 1.081, 95% CI 1.022, 1.143) and lower P1 amplitudes in the middle ring (OR 0.924, 95% CI 0.854, 0.999). No significant correlations were observed between HbA1c and retinal measures. In the absence of DR, early retinal functional alterations are detectable on mfERG in patients with longer diabetes duration, but with no difference in OCT-derived retinal thickness. [ABSTRACT FROM AUTHOR]

Published
2022
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314. Corneal confocal microscopy identifies small nerve fibre damage in patients with hypertriglyceridemia.

Author

D'Onofrio, Luca, Ferdousi, Maryam, Kalteniece, Alise, Iqbal, Zohaib, Petropoulos, Ioannis N, Ponirakis, Georgios, Buzzetti, Raffaella, Malik, Rayaz A, and Soran, Handrean

Subjects
TRIGLYCERIDES, NEURONS, MICROSCOPY, HYPERLIPIDEMIA, OPTIC nerve, DESCRIPTIVE statistics, METABOLIC syndrome, DISEASE complications
Abstract

• Hypertriglyceridemia is a risk factor for the development of small fibre damage. • Patients with hypertriglyceridemia had a higher neuropathy disability score (NDS). • Patients with hypertriglyceridemia had lower of CCM parameters compared to control. • Subjects with metabolic syndrome showed lower CCM parameters compared to control. Hypertriglyceridemia has been identified as a risk factor for diabetic neuropathy. Patients with hypertriglyceridemia underwent assessment of neuropathy and corneal confocal microscopy. 24 patients with severe hypertriglyceridemia defined as a triglyceride level more than 5.5 mmol/L (485 mg/dL) with no history of diabetes and 19 age-matched controls underwent assessment of HbA1c, blood pressure, fasting lipid profile, neuropathy disability score (NDS) and corneal confocal microscopy (CCM). Patients with hypertriglyceridemia had a significantly higher NDS (P<0.001) and lower CNFD (no./mm2) (27.1 [25.0-29.9] Vs 35.9 [31.2-40.6], p<0.001), CNBD (no./mm2) (55.4±22.3 Vs 91.6±30.8, p<0.001), CNFL (mm/mm2) (19.2±4.3 Vs 26.7±4.4, p<0.001) and IWL (mm/mm2) (24.3±6.9 Vs 36.6±10.0, p<0.001) compared to control subjects. In subjects with hypertriglyceridemia serum triglyceride levels correlated with CNFD (rho= -0.473, p=0.002), CNBD (rho= -0.341, p=0.043), CNFL (rho= -0.446, p=0.006) and IWL (rho= -0.408, p=0.034), no correlation was found between triglycerides and CCM parameters in subjects without hypertriglyceridemia. Subjects with metabolic syndrome had a lower CNFD (32.3 [29.2-37.5] Vs 27.1 [20.8-30.2] no./mm2, p=0.003), CNBD (20.1±6.0 Vs 23.9±5.3 no./mm2, p=0.036), CNFL (57.7±26.9 Vs 79.2±32.6 mm/mm2, p=0.037) and IWL (25.4±7.1 Vs 32.9±11.2 mm/mm2, p=0.036) compared to subjects without metabolic syndrome. Hypertriglyceridemia and metabolic syndrome are associated with small nerve fibre damage and clinical neuropathy. Elevated serum triglycerides may be a potential therapeutic target for the treatment of peripheral neuropathy. [ABSTRACT FROM AUTHOR]

Published
2022
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315. Corneal confocal microscopy identifies a reduction in corneal keratocyte density and sub-basal nerves in children with type 1 diabetes mellitus

Author

Gad, Hoda, primary, Al-Jarrah, Bara, additional, Saraswathi, Saras, additional, Mohamed, Sara, additional, Kalteniece, Alise, additional, Petropoulos, Ioannis N, additional, Khan, Adnan, additional, Ponirakis, Georgios, additional, Singh, Parul, additional, Khodor, Souhaila Al, additional, Elawad, Mamoun, additional, Almasri, Wesam, additional, Hendaus, Mohamed A, additional, Akobeng, Anthony K, additional, Hussain, Khalid, additional, and Malik, Rayaz A, additional

Published
2021
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317. Corneal Immune Cells Are Increased in Patients With Multiple Sclerosis

Author

Khan, Adnan, primary, Li, Yi, additional, Ponirakis, Georgios, additional, Akhtar, Naveed, additional, Gad, Hoda, additional, George, Pooja, additional, Ibrahim, Faiza M., additional, Petropoulos, Ioannis N., additional, Canibano, Beatriz G., additional, Deleu, Dirk, additional, Shuaib, Ashfaq, additional, Kamran, Saadat, additional, and Malik, Rayaz A., additional

Published
2021
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322. Tau associated peripheral and central neurodegeneration: Identification of an early imaging marker for tauopathy

Author

Marquez, Alexandra, primary, Guernsey, Lucie S., additional, Frizzi, Katie E., additional, Cundiff, Morgan, additional, Constantino, Isabel, additional, Muttalib, Nabeel, additional, Arenas, Fernanda, additional, Zhou, Xiajun, additional, Lim, Sze Hway, additional, Ferdousi, Maryam, additional, Ponirakis, Georgios, additional, Silverdale, Monty, additional, Kobylecki, Christopher, additional, Jones, Matthew, additional, Marshall, Andrew, additional, Malik, Rayaz A., additional, and Jolivalt, Corinne G., additional

Published
2021
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323. Systemic Solutions for Addressing Non-Communicable Diseases in Low- and Middle-Income Countries

Author

Ganju,Aakash, Goulart,Alessandra C, Ray,Amrit, Majumdar,Anurita, Jeffers,Barrett W, Llamosa,Gloria, Cañizares,Henry, Ramos-Cañizares,Ianne Jireh, Fadhil,Ibtihal, Subramaniam,Kannan, Lim,Lee-Ling, El Bizri,Luna, Ramesh,M, Guilford,Mathew, Ali,Raghib, Devi,Ratna Duddi, Malik,Rayaz A, Potkar,Shekhar, and Wang,Yuan-Pang

Subjects
Journal of Multidisciplinary Healthcare
Abstract

Aakash Ganju,1 Alessandra C Goulart,2 Amrit Ray,3 Anurita Majumdar,4 Barrett W Jeffers,3 Gloria Llamosa,5 Henry Cañizares,6 Ianne Jireh Ramos-Cañizares,6 Ibtihal Fadhil,7 Kannan Subramaniam,8 Lee-Ling Lim,9 Luna El Bizri,10 M Ramesh,11 Mathew Guilford,12 Raghib Ali,13 Ratna Duddi Devi,14,15 Rayaz A Malik,16 Shekhar Potkar,17 Yuan-Pang Wang18 1Executive Office, Saathealth, Mumbai, India; 2Center for Clinical and Epidemiological Research, University Hospital, University of São Paulo, São Paulo, Brazil; 3Research, Development and Medical, Upjohn – a Pfizer Division, New York, NY, USA; 4Research, Development and Medical, Emerging Markets, Upjohn – a Pfizer Division, Singapore; 5Mexican Neurology and Psychiatry Society, Mexico City, Mexico; 6Vicente Sotto Memorial Medical Center, Cebu City, Philippines; 7Eastern Mediterranean NCD Alliance, Kuwait City, Kuwait; 8Research, Development and Medical, Upjohn – a Pfizer Division, Sydney, Australia; 9Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 10School of Pharmacy, Lebanese University, Hadath, Lebanon; 11Lee Kuan Yew School of Public Policy, National University of Singapore, Singapore; 12Executive Office, Common Health, Kuala Lumpur, Malaysia; 13Public Health Research Center, New York University, Abu Dhabi, United Arab Emirates; 14Executive Office, DakshamA Health and Education, Gurgaon, India; 15Board of Directors, International Alliance of Patient Organizations, London, England; 16Weill Cornell Medicine, Doha, Qatar; 17Research, Development and Medical, Upjohn – a Pfizer Division, Dubai, United Arab Emirates; 18Instituto de Psiquiatria (LIM-23), Hospital das Clinicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, BrazilCorrespondence: Kannan SubramaniamResearch, Development and Medical, Upjohn – a Pfizer Division, Sydney, NSW 2000, AustraliaTel +61 413 569 077Email Kannan.Subramaniam@pfizer.comAbstract: Non-communicable diseases (NCDs) have been on the rise in low- and middle-income countries (LMICs) over the last few decades and represent a significant healthcare concern. Over 85% of “premature” deaths worldwide due to NCDs occur in the LMICs. NCDs are an economic burden on these countries, increasing their healthcare expenditure. However, targeting NCDs in LMICs is challenging due to evolving health systems and an emphasis on acute illness. The major issues include limitations with universal health coverage, regulations, funding, distribution and availability of the healthcare workforce, and availability of health data. Experts from across the health sector in LMICs formed a Think Tank to understand and examine the issues, and to offer potential opportunities that may address the rising burden of NCDs in these countries. This review presents the evidence and posits pragmatic solutions to combat NCDs.Keywords: low- and middle-income countries, multisectoral, non-communicable diseases, public–private partnership, universal health coverage

Published
2020

324. Quality of diabetes care in patients with schizophrenia: a case-control study in Qatar

Author

Karim, Mustafa Abdul, Al-Baz, Nadeen, Ouanes, Sami, Khalil, Ali, Assar, Ahmed H., Alsiddiqi, Abdulkarim, Dabbous, Zeinab, Zirie, Mahmoud, Woodruff, Peter, Malik, Rayaz A., and Haddad, Peter M.

Subjects
Glycated Hemoglobin, Diabetes mellitus, Diabetes Mellitus, Type 2, lcsh:RC435-571, lcsh:Psychiatry, Case-Control Studies, Schizophrenia, Humans, Clinical sciences, Qatar, Retrospective Studies, Research Article, Diabetes care
Abstract

Background Patients with schizophrenia are at least twice as likely to develop diabetes mellitus compared to the general population. This is of significance in Qatar given the high prevalence of obesity and diabetes. Furthermore, the lifespan of people with schizophrenia is shortened by approximately 15 years, partly due to long-term microvascular and macrovascular complications. High quality diabetes care can significantly reduce morbidity and mortality. We assessed the level of diabetes care delivered to patients in Qatar with schizophrenia and diabetes compared to those with diabetes alone. Methods We performed a retrospective chart review of patients with diabetes mellitus with (n = 73) and without (n = 73) schizophrenia. Demographic information and electronic medical records were reviewed to determine adherence to American Diabetes Association standards of diabetes care in the last 6 and 12 months. Optimal diabetes care was defined as having completed glycated hemoglobin (HbA1c), lipid profile and retinal examination within 12 months. Results Optimal diabetes care was significantly lower in patients with schizophrenia and diabetes compared to diabetes alone [26.0% (n = 19/73) vs 52.1% (n = 38/73), p = 0.002]. Patients with diabetes and schizophrenia were also significantly less likely to have had body mass index recorded within 6 months (p = 0.008) and HbA1c (p = 0.006), lipid profile (p = 0.015), estimated glomerular filtration rate (eGFR) (p = 0.001) and order for retinal examination (p = 0.004) over 12 months. After adjusting for multiple comparisons, only assessment of eGFR (p = 0.01) and order for retinal examination (p = 0.04) remained significant. Conclusion Patients in Qatar with schizophrenia and diabetes, receive sub-optimal diabetes care compared to those with diabetes alone.Other Information Published in: BMC Psychiatry License: http://creativecommons.org/licenses/by/4.0/See article on publisher's website: http://dx.doi.org/10.1186/s12888-021-03121-5

Published
2020

325. Stroke in the adult Qatari population (Q-stroke) a hospital-based retrospective cohort study

Author

Imam, Yahia Z., Kamran, Saadat, Saqqur, Maher, Ibrahim, Faisal, Chandra, Prem, Perkins, Jon D., Malik, Rayaz A., Akhtar, Naveed, Al-Jerdi, Salman, Deleu, Dirk, Elalamy, Osama, Osman, Yasir, Malikyan, Gayane, Elkhider, Hisham, Elmakki, Suha, ElSheikh, Lubna, Mhjob, Noha, Abdelmoneim, Mohamed S., Alkhawad, Nima, Own, Ahmed, and Shuaib, Ashfaq

Subjects
Adult, Male, Asia, Epidemiology, Endocrine Disorders, Cerebrovascular Diseases, Science, Cardiology, Hemorrhage, Vascular Medicine, Geographical Locations, Young Adult, Medical Conditions, Endocrinology, Signs and Symptoms, Risk Factors, Atrial Fibrillation, Medicine and Health Sciences, Diabetes Mellitus, Humans, Registries, Qatar, Ischemic Stroke, Aged, Retrospective Studies, Aged, 80 and over, Incidence, Middle Aged, Hospitals, Stroke, Hemorrhagic Stroke, Neurology, Metabolic Disorders, People and Places, Medicine, Female, Clinical Medicine, Arrhythmia, Research Article
Abstract

BackgroundStudies assessing the burden of stroke in Qataris are limited. We aim to study stroke in the Qatari population.MethodsA retrospective review was undertaken of all Qatari adults presenting with stroke to Hamad Medical Corporation over a 5-year period. Descriptive statistics were used to summarize demographic and all other clinical characteristics of the patients. The primary outcome was the incidence of stroke in the Qatari patients. Comparison was made between the sexes.Results862 patients were included, with 58.9% being male. The average incidence of stroke over the 5-year period was 92.04 per 100,000 adult Qatari population. The mean age of the cohort was 64.3±14.4 years, (range 19-105 years). The mean age of first ever cerebrovascular event was 63.2±14.5 years. The diagnosis was ischemic stroke in (73.7%), transient ischemic attack in (13.8%), intracerebral hemorrhage (ICH) in (11.6%), subarachnoid hemorrhage in (0.7%) and (0.2%) cerebral venous sinus thrombosis. Small vessel disease was the most common cause of ischemic stroke accounting for (46.5%), followed by large artery atherosclerosis (24.5%). Hypertension (82.7%) and diabetes (71.6%) were particularly prevalent in this cohort. Females were older (65.8±14.1 vs 63.4±14.5 years), had more hypertension and diabetes and more disability or death at 90 days (pConclusionStroke occurs at a significantly lower age in Qataris compared to the western population. This study has uncovered sex differences that need to be studied further.

Published
2020

326. A Spatially Constrained Deep Convolutional Neural Network for Nerve Fiber Segmentation in Corneal Confocal Microscopic Images using Inaccurate Annotations

Author

Zhang, Ning, Francis, Susan, Malik, Rayaz, and Chen, Xin

Subjects
FOS: Computer and information sciences, Computer Vision and Pattern Recognition (cs.CV), Computer Science - Computer Vision and Pattern Recognition, ComputingMethodologies_IMAGEPROCESSINGANDCOMPUTERVISION
Abstract

Semantic image segmentation is one of the most important tasks in medical image analysis. Most state-of-the-art deep learning methods require a large number of accurately annotated examples for model training. However, accurate annotation is difficult to obtain especially in medical applications. In this paper, we propose a spatially constrained deep convolutional neural network (DCNN) to achieve smooth and robust image segmentation using inaccurately annotated labels for training. In our proposed method, image segmentation is formulated as a graph optimization problem that is solved by a DCNN model learning process. The cost function to be optimized consists of a unary term that is calculated by cross entropy measurement and a pairwise term that is based on enforcing a local label consistency. The proposed method has been evaluated based on corneal confocal microscopic (CCM) images for nerve fiber segmentation, where accurate annotations are extremely difficult to be obtained. Based on both the quantitative result of a synthetic dataset and qualitative assessment of a real dataset, the proposed method has achieved superior performance in producing high quality segmentation results even with inaccurate labels for training., Comment: 4 pages, accepted for publication at IEEE International Symposium on Biomedical Imaging (ISBI) 2020

Published
2020
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327. An artificial intelligence-based deep learning algorithm for the diagnosis of diabetic neuropathy using corneal confocal microscopy:a development and validation study

Author

Williams, Bryan, Borroni, Davide, Liu, Rongjun, Zhao, Yitian, Zhang, Jiong, Lim, Jonathan, Ma, Baikai, Romano, Vito, Qi, Hong, Ferdousi, Maryam, Petropoulos, Ioannis, Ponirakis, Georgios, Kaye, Stephen, Malik, Rayaz, Alam, Uazman, Zheng, Yalin, Williams, Bryan, Borroni, Davide, Liu, Rongjun, Zhao, Yitian, Zhang, Jiong, Lim, Jonathan, Ma, Baikai, Romano, Vito, Qi, Hong, Ferdousi, Maryam, Petropoulos, Ioannis, Ponirakis, Georgios, Kaye, Stephen, Malik, Rayaz, Alam, Uazman, and Zheng, Yalin

Abstract

Aims/hypothesis Corneal confocal microscopy is a rapid non-invasive ophthalmic imaging technique that identifies peripheral and central neurodegenerative disease. Quantification of corneal sub-basal nerve plexus morphology, however, requires either time-consuming manual annotation or a less-sensitive automated image analysis approach. We aimed to develop and validate an artificial intelligence-based, deep learning algorithm for the quantification of nerve fibre properties relevant to the diagnosis of diabetic neuropathy and to compare it with a validated automated analysis program, ACCMetrics. Methods Our deep learning algorithm, which employs a convolutional neural network with data augmentation, was developed for the automated quantification of the corneal sub-basal nerve plexus for the diagnosis of diabetic neuropathy. The algorithm was trained using a high-end graphics processor unit on 1698 corneal confocal microscopy images; for external validation, it was further tested on 2137 images. The algorithm was developed to identify total nerve fibre length, branch points, tail points, number and length of nerve segments, and fractal numbers. Sensitivity analyses were undertaken to determine the AUC for ACCMetrics and our algorithm for the diagnosis of diabetic neuropathy. Results The intraclass correlation coefficients for our algorithm were superior to those for ACCMetrics for total corneal nerve fibre length (0.933 vs 0.825), mean length per segment (0.656 vs 0.325), number of branch points (0.891 vs 0.570), number of tail points (0.623 vs 0.257), number of nerve segments (0.878 vs 0.504) and fractals (0.927 vs 0.758). In addition, our proposed algorithm achieved an AUC of 0.83, specificity of 0.87 and sensitivity of 0.68 for the classification of participants without (n = 90) and with (n = 132) neuropathy (defined by the Toronto criteria). Conclusions/interpretation These results demonstrated that our deep learning algorithm provides rapid and excellent localisat

Published
2020

328. Rapid corneal nerve fiber loss : A marker of diabetic neuropathy onset and progression

Author

Lewis, Evan J.H., Lovblom, Leif E., Ferdousi, Maryam, Halpern, Elise M., Jeziorska, Maria, Pacaud, Daniele, Pritchard, Nicola, Dehghani, Cirous, Edwards, Katie, Srinivasan, Sangeetha, Shtein, Roni Mintz, Efron, Nathan, Tavakoli, Mitra, Bril, Vera, Malik, Rayaz Ahmed, Perkins, Bruce A., Lewis, Evan J.H., Lovblom, Leif E., Ferdousi, Maryam, Halpern, Elise M., Jeziorska, Maria, Pacaud, Daniele, Pritchard, Nicola, Dehghani, Cirous, Edwards, Katie, Srinivasan, Sangeetha, Shtein, Roni Mintz, Efron, Nathan, Tavakoli, Mitra, Bril, Vera, Malik, Rayaz Ahmed, and Perkins, Bruce A.

Abstract

OBJECTIVE Corneal nerve fiber length (CNFL) represents a biomarker for diabetic distal symmetric polyneuropathy (DSP). We aimed to determine the reference distribution of annual CNFL change, the prevalence of abnormal change in diabetes, and its associated clinical variables. RESEARCH DESIGN AND METHODS We examined 590 participants with diabetes (399 with type 1 diabetes [T1D] and 191 with type 2 diabetes [T2D]) and 204 control patients without diabetes with at least 1 year of follow-up and classified them according to rapid corneal nerve fiber loss (RCNFL) if CNFL change was below the 5th percentile of the control patients without diabetes. RESULTS Control patients without diabetes were 37.9 6 19.8 years old, had median follow-up of three visits over 3.0 years, and mean annual change in CNFL was 20.1% (90% CI 25.9% to 5.0%). RCNFL was defined by values exceeding the 5th percentile of 6% loss. Participants with T1D were 39.9 6 18.7 years old, had median follow-up of three visits over 4.4 years, and mean annual change in CNFL was 20.8% (90% CI 214.0% to 9.9%). Participants with T2D were 60.4 6 8.2 years old, had median follow-up of three visits over 5.3 years, and mean annual change in CNFL was 20.2% (90% CI 214.1% to 14.3%). RCNFL prevalence was 17% overall and was similar by diabetes type (64 T1D [16.0%], 37 T2D [19.4%], P 5 0.31). RNCFL was more common in those with baseline DSP (47% vs. 30% in those without baseline DSP, P 5 0.001), which was associated with lower peroneal conduction velocity but not with baseline HbA1c or its change over follow-up. CONCLUSIONS An abnormally rapid loss of CNFL of 6% per year or more occurs in 17% of diabetes patients. RCNFL may identify patients at highest risk for the development and progression of DSP.

Published
2020

329. Prevalence and management of diabetic neuropathy in secondary care in Qatar

Author

Ponirakis, Georgios, Elhadd, Tarik, Chinnaiyan, Subitha, Dabbous, Zeinab, Siddiqui, Mashhood, Al‐muhannadi, Hamad, Petropoulos, Ioannis, Khan, Adnan, Ashawesh, Khaled AE, Dukhan, Khaled MO, Mahfoud, Ziyad R, Murgatroyd, Christopher, Slevin, Mark, Malik, Rayaz A, Ponirakis, Georgios, Elhadd, Tarik, Chinnaiyan, Subitha, Dabbous, Zeinab, Siddiqui, Mashhood, Al‐muhannadi, Hamad, Petropoulos, Ioannis, Khan, Adnan, Ashawesh, Khaled AE, Dukhan, Khaled MO, Mahfoud, Ziyad R, Murgatroyd, Christopher, Slevin, Mark, and Malik, Rayaz A

Abstract

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.

Published
2020

330. Comparison of Surgical Site Infection Risk Between Warfarin, LMWH, and Aspirin for Venous Thromboprophylaxis in TKA or THA: A Systematic Review and Meta-Analysis

Author

Hughes, Luke D, Lum, Joann, Mahfoud, Ziyad, Malik, Rayaz Ahmed, Anand, Anoop, Charalambous, Charalambos P, Hughes, Luke D, Lum, Joann, Mahfoud, Ziyad, Malik, Rayaz Ahmed, Anand, Anoop, and Charalambous, Charalambos P

Abstract

Infection following arthroplasty can have devastating effects for the patient and necessitate further surgery. Venous thromboembolism (VTE) prophylaxis is required to minimize the risk of deep venous thrombosis and pulmonary embolism. Anticoagulation has been demonstrated to interfere with wound-healing and increase the risk of infection. We hypothesized that different anticoagulation regimes will have differing effects on rates of periprosthetic joint infection. The aim of this study was to compare the surgical site infection risk between the use of warfarin, low-molecular-weight heparin (LMWH), and aspirin for VTE prophylaxis following total knee or hip arthroplasty. A systematic literature search was conducted in November 2018 using the PubMed, CINAHL, and Cochrane Central Register of Controlled Trials (CENTRAL) databases to identify studies that compared warfarin, LMWH, and/or aspirin with regard to surgical site infection rates following hip or knee arthroplasty. Meta-analyses were performed to compare the infection and VTE risks between groups. Nine articles involving 184,037 patients met the inclusion criteria. Meta-analysis showed that warfarin prophylaxis was associated with a higher risk of deep infection (or infection requiring reoperation) (odds ratio [OR] = 1.929, 95% confidence interval [CI] = 1.197 to 3.109, p = 0.007) and surgical site infection overall (OR = 1.610, 95% CI = 1.028 to 2.522, p = 0.038) compared with aspirin in primary total joint arthroplasty, with similar findings also seen when primary and revision procedures were combined. There was no significant difference in infection risk between warfarin and LMWH and between LMWH and aspirin. There was a nonsignificant trend for VTE risk to be higher with warfarin compared with aspirin therapy for primary procedures (OR = 1.600, 95% CI = 0.875 to 2.926, p = 0.127), and this was significant when both primary and revision cases were included (OR = 2.674, 95% CI = 1.143 to 6.255, p = 0.023). Thes

Published
2020

331. Diabetic neuropathy is characterized by progressive corneal nerve fiber loss in the central and inferior whorl regions

Author

Ferdousi, Maryam, Kalteniece, Alise, Petropoulos, Ioannis, Azmi, Shazli, Dhage, Shaishav, Marshall, Andrew, Boulton, Andrew J.M., Efron, Nathan, Faber, Catharina G., Lauria, Giuseppe, Soran, Handrean, Malik, Rayaz A., Ferdousi, Maryam, Kalteniece, Alise, Petropoulos, Ioannis, Azmi, Shazli, Dhage, Shaishav, Marshall, Andrew, Boulton, Andrew J.M., Efron, Nathan, Faber, Catharina G., Lauria, Giuseppe, Soran, Handrean, and Malik, Rayaz A.

Abstract

PURPOSE. We hypothesized that longitudinal changes in corneal nerve morphology would differ between the central cornea and inferior whorl in relation to other measures of diabetic neuropathy. METHODS. Thirty patients with diabetes (age: 54.08 ± 15.86, duration: 23.95 ± 14.2, HbA1c: 7.51 ± 1.37) and 19 age-matched healthy controls (age: 49.47 ± 13.25) underwent assessment of neuropathy disability score (NDS), vibration perception threshold (VPT), cold (CPT) and warm (WPT) perception thresholds, peroneal motor nerve conduction velocity (PMNCV), corneal nerve fiber density (CNFD), branch density (CNBD), fiber length (CNFL), inferior whorl length (IWL), and the average of CNFL and IWL (ANFL) at baseline and after 1 to 8 years. RESULTS. In patients with diabetes, between baseline and follow-up, there was a significant reduction in CNBD (57.72 ± 30.08 vs. 44.04 ± 23.69; P = 0.02), CNFL (21.77 ± 5.19 vs. 15.65 ± 4.7; P < 0.0001), IWL (24.69 ± 8.67 vs. 14.23 ± 6.13; P < 0.0001), ANFL (23.26 ± 5.53 vs. 15.09 ± 4.48; P < 0.0001), and WPT (43.56 ± 4.43 vs. 40.78 ± 4.93; P = 0.01), and an increase in VPT (12.9 ± 8.96 vs. 13.78 ± 8.99; P = 0.02). There was no significant change in CNFD (27.12 ± 8.2 vs. 25.43 ± 7.11; P = 0.2), NDS (3.38 ± 3.35 vs. 2.61 ± 2.8; P = 0.08), CPT (17.7 ± 10.59 vs. 22.45 ± 9.23; P = 0.06), or PMNCV (42.4 ± 4.21 vs. 42.16 ± 6.3; P = 0.2). CONCLUSIONS. There is evidence of corneal nerve loss in patients with diabetes, particularly at the inferior whorl during follow-up.

Published
2020

336. Effect of bariatric surgery on plasma levels of oxidised phospholipids, biomarkers of oxidised LDL and lipoprotein(a)

Author

Ho, Jan Hoong, primary, Adam, Safwaan, additional, Liu, Yifen, additional, Azmi, Shazli, additional, Dhage, Shaishav, additional, Syed, Akheel A., additional, Ammori, Basil J., additional, Donn, Rachelle, additional, Heald, Adrian, additional, Gibson, Martin J., additional, Malik, Rayaz A., additional, Yang, Xiaohong, additional, Durrington, Paul N., additional, Tsimikas, Sotirios, additional, and Soran, Handrean, additional

Published
2021
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338. Greater small nerve fibre damage in the skin and cornea of type 1 diabetic patients with painful compared to painless diabetic neuropathy

Author

Ferdousi, Maryam, primary, Azmi, Shazli, additional, Kalteniece, Alise, additional, Petropoulos, Ioannis Nikolaos, additional, Ponirakis, Georgios, additional, Asghar, Omar, additional, Alam, Uazman, additional, Marshall, Andrew, additional, Boulton, Andrew J. M., additional, Efron, Nathan, additional, Soran, Handrean, additional, Jeziorska, Maria, additional, and Malik, Rayaz A., additional

Published
2021
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339. Distinctive Microbial Signatures and Gut-Brain Crosstalk in Pediatric Patients with Coeliac Disease and Type 1 Diabetes Mellitus

Author

Singh, Parul, primary, Rawat, Arun, additional, Al-Jarrah, Bara, additional, Saraswathi, Saras, additional, Gad, Hoda, additional, Elawad, Mamoun, additional, Hussain, Khalid, additional, Hendaus, Mohammed A., additional, Al-Masri, Wesam, additional, Malik, Rayaz A., additional, Al Khodor, Souhaila, additional, and Akobeng, Anthony K., additional

Published
2021
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341. Mitigation of hypoglycemia during Ramadan using the flash glucose monitoring system following dose adjustment of insulin and sulphonylurea in patients taking multiple glucose-lowering therapies (The PROFAST-IT Study)

Author

Elhadd, Tarik, primary, Bashir, Mohamed, additional, Baager, Khaled A., additional, Ali, Hamda A., additional, Almohannadi, Dabia H.S., additional, Dabbous, Zainab, additional, Malik, Rayaz A., additional, and Abou-Samra, Abdul-Badie, additional

Published
2021
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342. Widespread sensory neuropathy in diabetic patients hospitalized with severe COVID-19 infection

Author

Odriozola, Ariel, primary, Ortega, Lucía, additional, Martinez, Lidia, additional, Odriozola, Samantha, additional, Torrens, Ainhoa, additional, Corroleu, David, additional, Martínez, Silvia, additional, Ponce, Meritxell, additional, Meije, Yolanda, additional, Presas, Mercedes, additional, Duarte, Alejandra, additional, Belén Odriozola, M., additional, and Malik, Rayaz A., additional

Published
2021
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343. Bariatric surgery leads to an improvement in small nerve fibre damage in subjects with obesity

Author

Azmi, Shazli, primary, Ferdousi, Maryam, additional, Liu, Yifen, additional, Adam, Safwaan, additional, Iqbal, Zohaib, additional, Dhage, Shaishav, additional, Ponirakis, Georgios, additional, Siahmansur, Tarza, additional, Marshall, Andrew, additional, Petropoulos, Ioannis, additional, Kalteniece, Alise, additional, Ho, Jan Hoong, additional, Syed, Akheel, additional, Gibson, John M., additional, Ammori, Basil J., additional, Durrington, Paul N., additional, Malik, Rayaz A., additional, and Soran, Handrean, additional

Published
2021
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345. Corneal confocal microscopy identifies small fibre damage and progression of diabetic neuropathy

Author

Dhage, Shaishav, primary, Ferdousi, Maryam, additional, Adam, Safwaan, additional, Ho, Jan Hoong, additional, Kalteniece, Alise, additional, Azmi, Shazli, additional, Alam, Uazman, additional, Ponirakis, Georgios, additional, Petropoulos, Ioannis, additional, Atkinson, Andrew J., additional, Marshall, Andrew, additional, Jeziorska, Maria, additional, Soran, Handrean, additional, and Malik, Rayaz A., additional

Published
2021
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346. Corneal Keratocyte Density and Corneal Nerves Are Reduced in Patients With Severe Obesity and Improve After Bariatric Surgery

Author

Iqbal, Zohaib, primary, Kalteniece, Alise, additional, Ferdousi, Maryam, additional, Adam, Safwaan, additional, D'Onofrio, Luca, additional, Ho, Jan H., additional, Rao, Anoop Prasanna, additional, Dhage, Shaishav, additional, Azmi, Shazli, additional, Liu, Yifen, additional, Donn, Rachelle, additional, Malik, Rayaz A., additional, and Soran, Handrean, additional

Published
2021
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348. Pregabalin for neuropathic pain in primary care settings: recommendations for dosing and titration

Author

Freynhagen, Rainer, primary, Baron, Ralf, additional, Kawaguchi, Yoshiharu, additional, Malik, Rayaz A., additional, Martire, Diane L., additional, Parsons, Bruce, additional, Rey, Roberto D., additional, Schug, Stephan A., additional, Jensen, Troels Staehelin, additional, Tölle, Thomas R., additional, Ushida, Takahiro, additional, and Whalen, Ed, additional

Published
2021
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349. Diagnosing small fiber neuropathy in clinical practice: a deep phenotyping study

Author

Egenolf, Nadine, primary, Altenschildesche, Caren Meyer zu, additional, Kreß, Luisa, additional, Eggermann, Katja, additional, Namer, Barbara, additional, Gross, Franziska, additional, Klitsch, Alexander, additional, Malzacher, Tobias, additional, Kampik, Daniel, additional, Malik, Rayaz A., additional, Kurth, Ingo, additional, Sommer, Claudia, additional, and Üçeyler, Nurcan, additional

Published
2021
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