Publications by authors named "Rishab Gupta"

71 Publications

Proteomic Portraits Reveal Evolutionarily Conserved and Divergent Responses to Spinal Cord Injury.

Mol Cell Proteomics 2021 Jun 12;20:100096. Epub 2021 Jun 12.

Division of Neurosurgery, University of British Columbia, Vancouver, British Columbia, Canada.

Despite the emergence of promising therapeutic approaches in preclinical studies, the failure of large-scale clinical trials leaves clinicians without effective treatments for acute spinal cord injury (SCI). These trials are hindered by their reliance on detailed neurological examinations to establish outcomes, which inflate the time and resources required for completion. Moreover, therapeutic development takes place in animal models whose relevance to human injury remains unclear. Here, we address these challenges through targeted proteomic analyses of cerebrospinal fluid and serum samples from 111 patients with acute SCI and, in parallel, a large animal (porcine) model of SCI. We develop protein biomarkers of injury severity and recovery, including a prognostic model of neurological improvement at 6 months with an area under the receiver operating characteristic curve of 0.91, and validate these in an independent cohort. Through cross-species proteomic analyses, we dissect evolutionarily conserved and divergent aspects of the SCI response and establish the cerebrospinal fluid abundance of glial fibrillary acidic protein as a biochemical outcome measure in both humans and pigs. Our work opens up new avenues to catalyze translation by facilitating the evaluation of novel SCI therapies, while also providing a resource from which to direct future preclinical efforts.
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http://dx.doi.org/10.1016/j.mcpro.2021.100096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260874PMC
June 2021

Duraplasty in Traumatic Thoracic Spinal Cord Injury: Impact on Spinal Cord Hemodynamics, Tissue Metabolism, Histology, and Behavioral Recovery Using a Porcine Model.

J Neurotrauma 2021 Jun 18. Epub 2021 Jun 18.

International Collaboration on Repair Discoveries, University of British Columbia (UBC), Vancouver, British Columbia, Canada.

After acute traumatic spinal cord injury (SCI), the spinal cord can swell to fill the subarachnoid space and become compressed by the surrounding dura. In a porcine model of SCI, we performed a duraplasty to expand the subarachnoid space around the injured spinal cord and evaluated how this influenced acute intraparenchymal hemodynamic and metabolic responses, in addition to histological and behavioral recovery. Female Yucatan pigs underwent a T10 SCI, with or without duraplasty. Using microsensors implanted into the spinal cord parenchyma, changes in blood flow (ΔSCBF), oxygenation (ΔPO), and spinal cord pressure (ΔSCP) during and after SCI were monitored, alongside metabolic responses. Behavioral recovery was tested weekly using the Porcine Injury Behavior Scale (PTIBS). Thereafter, spinal cords were harvested for tissue sparing analyses. In both duraplasty and non-animals, the ΔSCP increased ∼5 mm Hg in the first 6 h post-injury. After this, the SCP appeared to be slightly reduced in the duraplasty animals, although the group differences were not statistically significant after controlling for injury severity in terms of impact force. During the first seven days post-SCI, the ΔSCBF or ΔPO values were not different between the duraplasty and control animals. Over 12 weeks, there was no improvement in hindlimb locomotion as assessed by PTIBS scores and no reduction in tissue damage at the injury site in the duraplasty animals. In our porcine model of SCI, duraplasty did not provide any clear evidence of long-term behavioral or tissue sparing benefit after SCI.
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http://dx.doi.org/10.1089/neu.2021.0084DOI Listing
June 2021

How many people with type 2 diabetes fulfil the eligibility criteria for randomized, controlled trials of insulin glargine 300 U/mL in a real-world setting?

Diabetes Obes Metab 2021 03 18;23(3):838-843. Epub 2020 Dec 18.

Department of Medicine, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.

Randomized controlled trial (RCT) populations often do not reflect those typically seen in clinical practice. This retrospective, observational cohort study analysed the real-world data of people with type 2 diabetes (T2DM) prescribed basal insulin analogues from electronic medical records (EMRs) in the Explorys database, which includes data from 39 integrated healthcare systems in the United States, to determine how representative selected RCTs investigating insulin glargine 300 U/mL (Gla-300) are of T2DM populations in a real-world setting. Applying eligibility criteria derived from the EDITION 1, 2 and 3 (Gla-300 vs. insulin glargine 100 U/mL [Gla-100]) and BRIGHT (Gla-300 vs. insulin degludec) RCTs, we observed that only 17% (33 345/191 218) of people captured in the real-world database would have been eligible for such trials. Those who were ineligible tended to be older, had more comorbidities and a higher baseline hypoglycaemia rate than the eligible group. Using another large US EMR database (Optum Humedica) as corroboration, we found that 15% (36 285/235 697) would have been eligible to participate in the EDITION/BRIGHT RCTs. Furthermore, only 7% (1734/24 547) would have been eligible for the CONCLUDE (insulin degludec vs. Gla-300) RCT. Our findings remind us of the value of real-world data studies, complementing the results of RCTs, and providing additional insights into groups who would typically be excluded from RCTs.
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http://dx.doi.org/10.1111/dom.14264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898683PMC
March 2021

Genome-Wide Association Studies of Schizophrenia and Bipolar Disorder in a Diverse Cohort of US Veterans.

Schizophr Bull 2021 03;47(2):517-529

Department of Psychiatry and Behavioral Sciences, SUNY Downstate Medical Center, Brooklyn, NY.

Background: Schizophrenia (SCZ) and bipolar disorder (BIP) are debilitating neuropsychiatric disorders, collectively affecting 2% of the world's population. Recognizing the major impact of these psychiatric disorders on the psychosocial function of more than 200 000 US Veterans, the Department of Veterans Affairs (VA) recently completed genotyping of more than 8000 veterans with SCZ and BIP in the Cooperative Studies Program (CSP) #572.

Methods: We performed genome-wide association studies (GWAS) in CSP #572 and benchmarked the predictive value of polygenic risk scores (PRS) constructed from published findings. We combined our results with available summary statistics from several recent GWAS, realizing the largest and most diverse studies of these disorders to date.

Results: Our primary GWAS uncovered new associations between CHD7 variants and SCZ, and novel BIP associations with variants in Sortilin Related VPS10 Domain Containing Receptor 3 (SORCS3) and downstream of PCDH11X. Combining our results with published summary statistics for SCZ yielded 39 novel susceptibility loci including CRHR1, and we identified 10 additional findings for BIP (28 326 cases and 90 570 controls). PRS trained on published GWAS were significantly associated with case-control status among European American (P < 10-30) and African American (P < .0005) participants in CSP #572.

Conclusions: We have demonstrated that published findings for SCZ and BIP are robustly generalizable to a diverse cohort of US veterans. Leveraging available summary statistics from GWAS of global populations, we report 52 new susceptibility loci and improved fine-mapping resolution for dozens of previously reported associations.
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http://dx.doi.org/10.1093/schbul/sbaa133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7965063PMC
March 2021

Does Degarelix Hold Potential for the Treatment of Pedophilic Disorder?

JAMA Psychiatry 2020 10;77(10):1084-1085

State University of New York (SUNY) Downstate Health Sciences University, Brooklyn, New York.

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http://dx.doi.org/10.1001/jamapsychiatry.2020.2594DOI Listing
October 2020

Meditation-induced psychosis: a narrative review and individual patient data analysis.

Ir J Psychol Med 2019 Oct 31:1-7. Epub 2019 Oct 31.

Department of Psychiatry, SUNY Downstate Medical Center, Brooklyn, NY, USA.

Background: Meditation is associated with health benefits; however, there are reports that it may trigger or exacerbate psychotic states. In this review, we aim to collate case reports of psychotic disorders occurring in association with meditative practice and to discuss the relationship between psychosis and meditation.

Methodology: We performed case-based analysis of all the existing studies published in English language using PubMed, PsycINFO, Cochrane, Scopus, EMBASE, CINAHL and Google Scholar with the search terms; 'Psychosis' OR 'Psychotic Symptoms' OR 'Schizophrenia' AND 'Meditation.'

Results: A total of 19 studies and 28 cases were included in the review. The patients described had an age range of 18-57 years; there was equal distribution of males and females. The diagnoses included acute psychosis in 14 cases, schizophrenia in 7 cases, mania with psychotic symptoms in 3 cases, and schizoaffective disorder in 1 case. The types of meditation described were Transcendent, Mindfulness, Buddhist Meditation like Qigong, Zen, and Theraveda, and others like Bikram yoga, Pranic Healing, and Hindustan Type meditation. Of the 28 cases reported, 14 patients had certain precipitating factors like insomnia, lack of food intake, history of mental illness, stress, and psychoactive substance use.

Conclusion: There are case reports of psychotic disorder arising in association with meditative practice; however, it is difficult to attribute a causal relationship between the two. At the same time, there is a body of research describing the beneficial effect of meditative practice in clinical settings for patients with psychotic disorders. Appropriately designed studies are needed to further investigate the relationship between meditative practice and psychosis.
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http://dx.doi.org/10.1017/ipm.2019.47DOI Listing
October 2019

Cerebrospinal Fluid Proteomics For Identification Of α2-Macroglobulin As A Potential Biomarker To Monitor Pharmacological Therapeutic Efficacy In Dopamine Dictated Disease States Of Parkinson's Disease And Schizophrenia.

Neuropsychiatr Dis Treat 2019 2;15:2853-2867. Epub 2019 Oct 2.

Department of Biophysics.

Aim: Parkinson's disease and schizophrenia are clinical end points of dopaminergic deficit and excess, respectively, in the mid-brain. In accordance, current pharmacological interventions aim to restore normal dopamine levels, the overshooting of which culminates in adverse effects which results in psychotic symptoms in Parkinson's disease and extra-pyramidal symptoms in schizophrenia. Currently, there are no laboratory assays to assist treatment decisions or help foresee these drug side-effect outcomes. Therefore, the aim was to discover a protein biomarker that had a varying linear expression across the clinical dopaminergic spectrum.

Materials And Methods: iTRAQ-based proteomic experiments along with mass spectrometric analysis was used for comparative proteomics using cerebrospinal fluid (CSF). CSF fluid was collected from 36 patients with Parkinson's disease, 15 patients with urological diseases that served as neurological controls, and seven schizophrenic patients with hallucinations. Validation included ELISA and pathway analysis to highlight the varying expression and provide plausible molecular pathways for differentially expressed proteins in the three clinical phenotypes.

Results: Protein profiles were delineated in CSF from Parkinson's disease patients, neurological control and schizophrenia, respectively. Ten of the proteins that were identified had a linear relationship across the dopaminergic spectrum. α-2-Macroglobulin showed to be having high statistical significance on inter-group comparison on validation studies using ELISA.

Conclusions: Non-gel-based proteomic experiments are an ideal platform to discover potential biomarkers that can be used to monitor pharmaco-therapeutic efficacy in dopamine-dictated clinical scenarios. α-2 Macroglobulin is a potential biomarker to monitor pharmacological therapy in Parkinson's disease and schizophrenia.
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http://dx.doi.org/10.2147/NDT.S214217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6781638PMC
October 2019

Central Pontine/Extrapontine Myelinolysis Presenting with Manic and Catatonic Symptoms.

Indian J Psychol Med 2019 Sep-Oct;41(5):491-493. Epub 2019 Sep 5.

Department of Psychiatry, All India Institute of Medical Sciences, New Delhi, India.

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http://dx.doi.org/10.4103/IJPSYM.IJPSYM_58_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6753711PMC
September 2019

Effect of a Community Health Worker-Based Approach to Integrated Cardiovascular Risk Factor Control in India: A Cluster Randomized Controlled Trial.

Glob Heart 2019 12 12;14(4):355-365. Epub 2019 Sep 12.

Harrington Heart & Vascular Institute, University Hospitals, Case Western Reserve University, Cleveland, OH, USA; School of Public Health, Kent State University, Kent, OH, USA.

Background: Eighty percent of premature mortality from cardiovascular disease occurs in low- and middle-income countries. Hypertension, diabetes, and smoking are the top risk factors causing this disease burden.

Objectives: The study aimed to test the hypothesis that utilizing community health workers (CHWs) to manage hypertension, diabetes and smoking in an integrated manner would lead to improved control of these conditions.

Methods: This was a 2-year cluster (n = 12) randomized controlled trial of 3,556 adults (35 to 70 years of age) in a single town in India, who were screened at home for hypertension, diabetes, and smoking. Of these adults, 1,242 (35%) had at least 1 risk factor (hypertension = 650, diabetes = 317, smoking = 500) and were enrolled in the study. The intervention group had behavioral change communication through regular home visits from community health workers. The control group received usual care in the community. The primary outcomes were changes in systolic blood pressure, fasting blood glucose, and average number of cigarettes/bidis smoked daily among individuals with respective risk factors.

Results: The mean ± SD change in systolic blood pressure at 2 years was -12.2 ± 19.5 mm Hg in the intervention group as compared with -6.4 ± 26.1 mm Hg in the control group, resulting in an adjusted difference of -8.9 mm Hg (95% confidence interval [CI]: -3.5 to -14.4 mm Hg; p = 0.001). The change in fasting blood glucose was -43.0 ± 83.5 mg/dl in the intervention group and -16.3 ± 77.2 mg/dl in the control group, leading to an adjusted difference of -21.3 mg/dl (95% CI: 18.4 to -61 mg/dl; p = 0.29). The change in mean number of cigarettes/bidis smoked was nonsignificant at +0.2 cigarettes/bidis (95% CI: 5.6 to -5.2 cigarettes/bidis; p = 0.93).

Conclusions: A population-based strategy of integrated risk factor management through community health workers led to improved systolic blood pressure in hypertension, an inconclusive effect on fasting blood glucose in diabetes, and no demonstrable effect on smoking. (Study of a Community-Based Approach to Control Cardiovascular Risk Factors in India [SEHAT]; NCT02115711).
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http://dx.doi.org/10.1016/j.gheart.2019.08.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358973PMC
December 2019

Evaluation of α-synuclein and apolipoprotein E as potential biomarkers in cerebrospinal fluid to monitor pharmacotherapeutic efficacy in dopamine dictated disease states of Parkinson's disease and schizophrenia.

Neuropsychiatr Dis Treat 2019 19;15:2073-2085. Epub 2019 Jul 19.

Department of Biophysics.

Background And Objective: Dopamine plays an important role in the disease pathology of Parkinson's disease and schizophrenia. These two neuropsychiatric disorders represent disease end points of the dopaminergic spectrum where Parkinson's disease represents dopamine deficit and schizophrenia represents dopamine hyperactivity in the mid-brain. Therefore, current treatment strategies aim to restore normal dopamine levels. However, during treatment patients develop adverse effects due to overshooting of physiological levels of dopamine leading to psychosis in Parkinson's disease, and extrapyramidal symptoms in schizophrenia. Absence of any laboratory tests hampers modulation of pharmacotherapy. Apolipoprotein E and α-synuclein have an important role in the neuropathology of these two diseases. The objective of this study was to evaluate cerebrospinal fluid (CSF) concentrations of apolipoprotein E and α-synuclein in patients with these two diseases so that they may serve as biomarkers to monitor therapy in Parkinson's disease and schizophrenia.

Methods: Drug-naïve Parkinson's disease patients and Parkinson's disease patients treated with dopaminergic therapy, neurological controls, schizophrenic patients treated with antidopaminergic therapy, and drug-naïve schizophrenic patients were recruited for the study and CSF was collected. Enzyme-linked immunosorbent assays were carried out to estimate the concentrations of apolipoprotein E and α-synuclein. Pathway analysis was done to establish a possible role of these two proteins in various pathways in these two dopamine dictated diseases.

Results: Apolipoprotein E and α-synuclein CSF concentrations have an inverse correlation along the entire dopaminergic clinical spectrum. Pathway analysis convincingly establishes a plausible hypothesis for their co-regulation in the pathogenesis of Parkinson's disease and schizophrenia. Each protein by itself or as a combination has encouraging sensitivity and specificity values of more than 55%.

Conclusion: The dynamic variation of these two proteins along the spectrum is ideal for them to be pursued as pharmacotherapeutic biomarkers in CSF to monitor pharmacological efficacy in Parkinson's disease and schizophrenia.
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http://dx.doi.org/10.2147/NDT.S205550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6650621PMC
July 2019

Switching to insulin glargine 300 units/mL in real-world older patients with type 2 diabetes (DELIVER 3).

Diabetes Obes Metab 2019 11 18;21(11):2384-2393. Epub 2019 Jul 18.

Frank Riddick Diabetes Institute, Endocrinology Department, Ochsner Medical Center, New Orleans, Louisiana.

Aim: To compare the second-generation basal insulin glargine 300 units/mL (Gla-300) and first-generation basal insulins on glycaemic control and hypoglycaemia risk in older adults with type 2 diabetes (T2D).

Materials And Methods: DELIVER 3 was a retrospective observational cohort study of electronic medical records. A total of 1176 older adults (aged ≥ 65 years) with T2D and ≥1 HbA1c value during 6 month baseline and 3 to 6 month follow-up who switched from basal insulin to Gla-300 were propensity score-matched to 1176 older adults who switched to a first-generation basal insulin [insulin detemir (IDet) or insulin glargine 100 units/mL (Gla-100)]. Outcomes were follow-up HbA1c, achievement of HbA1c <7% and <8%, hypoglycaemia incidence and event rates, and healthcare resource utilization.

Results: Following basal insulin switching, HbA1c reductions were greater/similar with Gla-300 versus IDet/Gla-100 (variable follow-up: -0.45% ± 1.40% vs. -0.29% ± 1.57%; P = .021; fixed follow-up: -0.48% ± 1.49% vs. -0.38% ± 1.59%; P = .114), while HbA1c goal attainment was similar in both cohorts. Gla-300 was associated with less hypoglycaemia [event rate: adjusted rate ratio (aRR): 0.63, 95% CI: 0.53-0.75; P < .001] and inpatient/emergency department-associated hypoglycaemia (adjusted hazard ratio: 0.58, 95% CI: 0.37-0.90; P = .016; aRR: 0.43, 95% CI: 0.31-0.60; P < .001) by variable follow-up. By fixed follow-up, hypoglycaemia results significantly or numerically favoured Gla-300.

Conclusion: Among older adults with T2D, switching to Gla-300 versus Gla-100/IDet was associated with greater/similar improvements in glycaemic control, and generally less hypoglycaemia.
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http://dx.doi.org/10.1111/dom.13818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6851991PMC
November 2019

Comparable glycaemic control and hypoglycaemia in adults with type 2 diabetes after initiating insulin glargine 300 units/mL or insulin degludec: The DELIVER Naïve D real-world study.

Diabetes Obes Metab 2019 09 21;21(9):2123-2132. Epub 2019 Jun 21.

AMCR Institute, Escondido, California.

Aim: To compare glycaemic control, hypoglycaemia and treatment discontinuation of insulin glargine 300 units/mL (Gla-300) and insulin degludec (IDeg) in a real-world study of insulin-naïve adults with type 2 diabetes (T2D).

Materials And Methods: DELIVER Naive D was a retrospective observational study that used electronic medical record data from the IBM Watson Health Explorys database. Insulin-naïve adults with T2D who started Gla-300 or IDeg between March 2015 and September 2017 were identified. Patients were active in the system for ≥12 months before and ≥6 months after starting Gla-300 or IDeg and had HbA1c measurements during 6-month baseline and 3- to 6-month follow-up. Outcomes were compared among 1:1 propensity score-matched cohorts.

Results: In the matched cohorts (n = 638 each), the mean age was 59 years, approximately 53% were male, and mean HbA1c was 9.67% (82 mmol/mol). Mean (SD) HbA1c decreases were comparable in the Gla-300 and IDeg cohorts (-1.67% [2.22] and -1.58% [2.20]; P = 0.51), as were HbA1c target attainment [<7% (53 mmol/mol): 23.8% and 27.4%; P = 0.20; <8% (64 mmol/mol): 55.0% and 57.1%; P = 0.63] and treatment discontinuation (29.2% and 32.6%; P = 0.14). Overall and inpatient/emergency department-associated hypoglycaemia incidences and event rates were similar in both cohorts using fixed 6-month or variable on-treatment follow-up.

Conclusions: Among real-world insulin-naïve adults with T2D, initiation of Gla-300 or IDeg resulted in comparable improvements in glycaemic control and similar rates of hypoglycaemia. These real-world data complement and confirm a randomized trial and other real-world studies.
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http://dx.doi.org/10.1111/dom.13793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771831PMC
September 2019

2D-DIGE as a strategy to identify serum protein biomarkers to monitor pharmacological efficacy in dopamine-dictated states of Parkinson's disease and schizophrenia.

Neuropsychiatr Dis Treat 2019 24;15:1031-1044. Epub 2019 Apr 24.

Department of Biophysics, All India Institute of Medical Sciences, New Delhi 110029, India,

Objectives: Parkinson's disease and schizophrenia are clinical scenarios that occur due to dopaminergic deficit and hyperactivity in the midbrain, respectively. Current pharmacological interventions for these two diseases therefore aim to restore normal dopamine levels in the midbrain. But during therapy, there is a overshooting of dopamine concentrations that result in hallucinations in Parkinson's disease patients and extra-pyramidal symptoms in schizophrenic patients. This causes a lot of inconvenience to the patents and the clinicians. There are no tests currently available to monitor drug efficacy in these two neuropsychiatric diseases.

Materials And Methods: Parkinson's disease and schizophrenic naïve patients were recruited. Serum proteins isolated from these two clinical phenotypes were labeled with fluorescent cyanine dyes and analyzed by two-dimensional difference in gel electrophoresis proteomic experiment. Differentially expressed spots that had consistent expression pattern across five sets of biological replicate gels were trypsin digested and subjected to mass spectrometric analysis for protein identification. Validation experiments were done for the identified proteins using antibody-based assay on a patient cohort that included naïve, treated, and those who had side effects.

Results: Serum α- and β-globin chains were identified as differentially expressed proteins having threefold higher expressions in Parkinson's patients as compared to schizophrenia. Interestingly, concentrations of these two proteins had an inverse correlation across clinical phenotypes in the dopaminergic spectrum. RBC contamination as a source for these proteins was ruled out.

Conclusion: There is a clear association of free serum globin with dopaminergic clinical states. This lays a platform for protein biomarker-based monitoring of pharmacological efficacy in Parkinson's disease and schizophrenia.
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http://dx.doi.org/10.2147/NDT.S198559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6488160PMC
April 2019

Glycaemic goal attainment and hypoglycaemia outcomes in type 2 diabetes patients initiating insulin glargine 300 units/mL or 100 units/mL: Real-world results from the DELIVER Naïve cohort study.

Diabetes Obes Metab 2019 07 5;21(7):1596-1605. Epub 2019 Apr 5.

Frank Riddick Diabetes Institute, Endocrinology Department, Ochsner Medical Center, New Orleans, Louisiana.

Aims: To compare HbA1c and hypoglycaemia in insulin-naïve patients with type 2 diabetes (T2D) who initiated insulin glargine 300 units/mL (Gla-300) or 100 units/mL (Gla-100).

Materials And Methods: This retrospective cohort study examined electronic medical records of insulin-naïve adults with T2D who initiated Gla-300 or Gla-100 during March 2015 through to December 2016 with active records for ≥12 months before and ≥6 months after initiation, and ≥1 valid HbA1c value during 6-month baseline and 90-180-day follow-up. Outcomes included HbA1c and hypoglycaemia. Cohorts were propensity score-matched (1:2) on baseline demographic and clinical characteristics. Sensitivity analyses were conducted using broader inclusion criteria.

Results: The matched cohorts included 1004 Gla-300 and 2008 Gla-100 initiators (mean age 60.4 years; 53.2% male). During 6-month follow-up, Gla-300 versus Gla-100 initiators had a greater mean HbA1c decrease (-1.52 ± 2.08% vs. -1.30 ± 2.12%; P = 0.003) and more patients achieved HbA1c <7% (25.0% vs. 21.5%; P = 0.029) and <8% (55.0% vs. 49.2%; P = 0.002); and HbA1c <7% (21.9% vs. 17.4%; P = 0.003) and <8% (49.1% vs. 41.8%; P < 0.001) without hypoglycaemia. Gla-300 initiators were similarly or less likely to have any or inpatient/emergency department-associated hypoglycaemia during 3- and 6-month follow-up (e.g. any hypoglycaemia to 6 months: 9.7% vs. 12.5%; adjusted odds ratio 0.61; P = 0.057).

Conclusions: Among insulin-naïve adults with T2D, Gla-300 was associated with significantly better HbA1c reductions (latest value during 90-180-day follow-up) and similar or improved hypoglycaemia outcomes (3- and 6-month follow-up) than Gla-100.
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http://dx.doi.org/10.1111/dom.13693DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6618106PMC
July 2019

MicroRNA Biomarkers in Cerebrospinal Fluid and Serum Reflect Injury Severity in Human Acute Traumatic Spinal Cord Injury.

J Neurotrauma 2019 08 14;36(15):2358-2371. Epub 2019 May 14.

1International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, British Columbia, Canada.

Spinal cord injury (SCI) is a devastating condition with variability in injury mechanisms and neurologic recovery. Spinal cord impairment after SCI is measured and classified by a widely accepted standard neurological examination. In the very acute stages post-injury, however, this examination is extremely challenging (and often impossible) to conduct and has modest prognostic value in terms of neurological recovery. The lack of objective tools to classify injury severity and predict outcome is a barrier for clinical trials and thwarts development of therapies for those with SCI. Biological markers (biomarkers) represent a promising, complementary approach to these challenges because they represent an unbiased approach to classify injury severity and predict neurological outcome. Identification of a suitable panel of molecular biomarkers would comprise a fundamental shift in how patients with acute SCI are evaluated, stratified, and treated in clinical trials. MicroRNA are attractive biomarker candidates in neurological disorders for several reasons, including their stability in biological fluids, their conservation between humans and model mammals, and their tissue specificity. In this study, we used next-generation sequencing to identify microRNA associated with injury severity within the cerebrospinal fluid (CSF) and serum of human patients with acute SCI. The CSF and serum samples were obtained 1-5 days post-injury from 39 patients with acute SCI (24 American Spinal Injury Association Impairment Scale [AIS] A, 8 AIS B, 7 AIS C) and from five non-SCI controls. We identified a severity-dependent pattern of change in microRNA expression in CSF and identified a set of microRNA that are diagnostic of baseline AIS classification and prognostic of neurological outcome six months post-injury. The data presented here provide a comprehensive description of the CSF and serum microRNA expression changes that occur after acute human SCI. This data set reveals microRNA candidates that warrant further evaluation as biomarkers of injury severity after SCI and as key regulators in other neurological disorders.
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http://dx.doi.org/10.1089/neu.2018.6256DOI Listing
August 2019

A study of pathways to care among opioid dependent individuals seeking treatment at a community de-addiction clinic in India.

J Ethn Subst Abuse 2020 Jul-Sep;19(3):490-502. Epub 2019 Jan 11.

All India Institute of Medical Sciences, New Delhi, India.

Drug use, including opioid use disorder, is one of the rapidly rising and serious problems affecting populations globally. There is a treatment gap and delay in presentation of drug users to treatment centers. The present study aimed at assessing the pathways to care among opioid-dependent individuals seeking treatment from a community-based treatment center in India. In a cross-sectional observational study conducted at a community clinic of the National Drug Dependence Treatment Centre (NDDTC), New Delhi, India, a total of 100 treatment-seeking drug users (age 18-60 years) fulfilling DSM IV TR criteria for opioid dependence were recruited. The data were collected using a semistructured pro forma based on patient self-report and the encounter form used in the World Health Organization (WHO) Pathway Study. All participants were male, were mostly married, were employed, and belonged to nuclear families. Ninety-eight percent of participants has ever used heroin in a dependent fashion and 20% were using it currently. Mean age of the participants was 40.83 years (SD 12.7). Median age of onset of heroin use was 22 years (IQR 12). Median duration of heroin use was 138 months (IQR 132). Only 21% of participants visited the community deaddiction clinic at the first contact with care. The median time for first treatment-seeking attempt was 9.5 years (IQR 7). The study findings suggest significant delay between onset of drug-related problems and first treatment contact. There is a need to increase the availability and accessibility of treatment services to reduce the delay in treatment seeking.
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http://dx.doi.org/10.1080/15332640.2018.1542528DOI Listing
January 2019

Evaluation of Serum Apolipoprotein E as a Potential Biomarker for Pharmacological Therapeutic Efficacy Monitoring in Dopamine Dictated Disease Spectrum of Schizophrenia and Parkinson's disease: A Preliminary Study.

J Cent Nerv Syst Dis 2018 9;10:1179573518803585. Epub 2018 Oct 9.

Department of Biophysics, All India Institute of Medical Sciences, New Delhi, New Delhi, India.

Aim Of The Study: Parkinson's disease and schizophrenia are disease end points of dopaminergic deficit and hyperactivity, respectively, in the mid brain. Accordingly, current medications aim to restore normal dopamine levels, overshooting of which results in adverse effects of psychosis and extra-pyramidal symptoms, respectively. There are currently no available laboratory tests to guide treatment decisions or help predict adverse side effects of the drugs. The aim was to therefore explore the possibility of using apolipoprotein E as a biomarker to monitor pharmacological intervention in dopamine dictated states of Parkinson's disease and schizophrenia for optimum therapy.

Methods: Naïve and treated, Parkinson's disease and schizophrenic patients were recruited from neurology and psychiatry clinics. Serum of healthy volunteers was collected as controls. Serum concentrations of apolipoprotein E was estimated by enzyme-linked immunosorbent assay (ELISA). Pathway analysis was carried out to delineate the interactions of apolipoprotein E in Parkinson's disease and schizophrenia.

Results: Apolipoprotein E levels are higher in Parkinson's disease patients as compared with schizophrenic samples ( < .05). Also, post-treatment apolipoprotein E levels in both disease states were at par with levels seen in healthy controls. The interactions of apolipoprotein E validate the results and place the differential expression of the protein in Parkinson's disease and schizophrenia in the right perspective.

Conclusion: Apolipoprotein E concentration across the dopaminergic spectrum suggests that it can be pursued not only as a potential biomarker in schizophrenia and Parkinson's disease, but can also be an effective tool for clinicians to determine efficacy of drug-based therapy.
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http://dx.doi.org/10.1177/1179573518803585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6178121PMC
October 2018

A study of psychiatric comorbidity after traumatic limb amputation: A neglected entity.

Ind Psychiatry J 2017 Jul-Dec;26(2):228-232

Department of Psychiatry, All India Institute of Medical Sciences, New Delhi, India.

Background: Amputation following trauma is emerging as a major health burden on the medical services and on the families and the society as well. Loss of limbs causes inability to support self and the family that further leads to various psychiatric disorders in many patients. Therefore, the present study is planned to explore psychiatric comorbidity in patients with amputation following trauma.

Materials And Methods: Fifty-nine amputees were recruited by consecutive sampling within 6-month period from amputation clinic of a tertiary care hospital. All participants were interviewed on a semi-structured pro forma of sociodemographic and amputation-related parameters and assessed on psychiatric comorbidity using Mini-International Neuropsychiatric Interview scale.

Results: Majority of the patients were male (88.1%) and belonged to younger age group of 16-30 years (71.2%). Approximately, 97% of patients had single-limb amputation (96.6), predominantly right limb (55.9%). Lower limb amputation was noted in 79.7% of participants. Motor vehicle accident was the most common mode of injury followed by railway track injury and others. The most common psychiatric comorbidities in our sample were major depressive disorder (71.2%), suicidality (30.5%), and posttraumatic stress disorder (PTSD) (20.3%). PTSD was positively correlated with phantom sensation ( = 0.295, = 0.05) and phantom pain ( = 0.279, < 0.05).

Conclusion: A substantial proportion of amputees had alarming sign of depression, suicidal ideation, and PTSD. Thus, there is a need to form liaison between surgical treatment providers and psychiatrists and psychologists to manage psychiatric comorbidity in amputees.
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http://dx.doi.org/10.4103/ipj.ipj_80_16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6058428PMC
August 2018

Acute-onset Orofacial Dyskinesia with a Single Low Dose of Oral Flupentixol: A Case Report.

Indian J Psychol Med 2018 Mar-Apr;40(2):189-190

Department of Psychiatry and NDDTC, AIIMS, New Delhi, India.

Tardive dyskinesia are known to occur commonly among patients receiving neuroleptic drugs for prolonged periods. But, few reports of acute onset dyskinesia have also been reported in the literature. This report highlights one such case where the patient had dyskinetic movements with a single low dose of oral Flupentixol. Further, we examine the potential nosological status of acute onset dyskinesia associated with neuroleptic use.
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http://dx.doi.org/10.4103/IJPSYM.IJPSYM_170_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6008991PMC
July 2018

Use of opium containing herbal drug and associated mania.

Asian J Psychiatr 2018 Aug 21;36:36-37. Epub 2018 Jun 21.

Department of Psychiatry & National Drug Dependence Treatment Centre, All India Institute of Medical Sciences, New Delhi, India. Electronic address:

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http://dx.doi.org/10.1016/j.ajp.2018.06.006DOI Listing
August 2018

Clinical outcomes in real-world patients with type 2 diabetes switching from first- to second-generation basal insulin analogues: Comparative effectiveness of insulin glargine 300 units/mL and insulin degludec in the DELIVER D+ cohort study.

Diabetes Obes Metab 2018 09 25;20(9):2148-2158. Epub 2018 Jun 25.

Frank Riddick Diabetes Institute, Endocrinology Department, Ochsner Medical Center, New Orleans, Louisiana.

Aims: To compare clinical outcomes in patients with type 2 diabetes (T2D) switching from insulin glargine 100 units/mL (Gla-100) or insulin detemir (IDet) to insulin glargine 300 units/mL (Gla-300) or insulin degludec (IDeg).

Materials And Methods: We conducted a retrospective, observational study of electronic medical records for Gla-300/IDeg adult switchers (March 1, 2015 to January 31, 2017) with active records for 12-month baseline (glycated haemoglobin [HbA1c] used a 6-month baseline period) and 6-month follow-up periods. Gla-300 and IDeg switchers were propensity score-matched using baseline demographic and clinical characteristics. Outcomes were HbA1c change and goal attainment (among patients with HbA1c captured at follow-up), and hypoglycaemia with fixed follow-up (intention-to-treat [ITT]; 6 months) and variable follow-up (on-treatment [OT]; to discontinuation or 6 months).

Results: Each matched cohort comprised 1592 patients. The mean decrease in HbA1c and HbA1c goal (<7.0% [53 mmol/mol] and <8.0% [64 mmol/mol]) attainment rates were similar for Gla-300 (n = 742) and IDeg (n = 727) switchers. Using fixed follow-up (ITT method), hypoglycaemia incidence decreased significantly from baseline with Gla-300 (all hypoglycaemia: 15.6% to 12.7%; P = .006; hypoglycaemia associated with inpatient/emergency department [ED] encounter: 5.3% to 3.5%; P = .007), but not with IDeg. After adjusting for baseline hypoglycaemia, no significant differences in hypoglycaemia incidence and event rate were found at follow-up (ITT) for Gla-300 vs IDeg. Using variable follow-up (OT), hypoglycaemia incidence was similar in both groups, but Gla-300 switchers had a lower inpatient/ED hypoglycaemia event rate at follow-up (adjusted rate ratio 0.56; P = .016).

Conclusions: In a real-world setting, switching from Gla-100 or IDet to Gla-300 or IDeg was associated with similar improvements in glycaemic control and hypoglycaemia in adult patients with T2D.
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http://dx.doi.org/10.1111/dom.13345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6099352PMC
September 2018

Multinational comparative cross-sectional survey of views of medical students about acceptable terminology and subgroups in schizophrenia.

BMJ Open 2018 06 7;8(6):e021461. Epub 2018 Jun 7.

Clinical Trials Facility, Tom Rudd Unit, Southern Health NHS Foundation Trust, Hampshire, UK.

Aim: The aim of this study was to inform thinking around the terminology for 'schizophrenia' in different countries.

Objectives: The objective of this study was to investigate: (1) whether medical students view alternative terminology (psychosis subgroups), derived from vulnerability-stress models of schizophrenia, as acceptable and less stigmatising than the term schizophrenia; (2) if there are differences in attitudes to the different terminology across countries with different cultures and (3) whether clinical training has an impact in reducing stigma.

Design: This is a cross-sectional survey that examined the attitudes of medical students towards schizophrenia and the alternative subgroups.

Setting: The study was conducted across eight sites: (1) University of Southampton, UK; (2) All India Institute of Medical Science, India; (3) Rowan University, USA; (4) Peshawar Medical College, Pakistan; (5) Capital Medical University, China; (6) College of Medicine and Medical sciences, Bahrain; (7) Queens University, Kingston, Canada and (8) University of Cape Town, South Africa.

Method: This study extended an initial pilot conducted by the Royal College of Psychiatrists on the term schizophrenia and psychosis subgroups to assess whether the subgroup terminology might have an effect on the attitudes of a convenience sample of medical students from eight different countries and potentially play a role in reducing stigmatisation.

Results: 1873 medical students completed a questionnaire recording their attitudes to schizophrenia and the psychosis subgroups. A reduction in negative perceptions were found for the psychosis subgroups, especially for the stress sensitivity psychosis and anxiety psychosis subgroups. Negative perceptions were found for drug-related psychosis. Participants who had undergone clinical training had overall positive attitudes. Differences across different countries were found.

Conclusion: The attitudes towards psychosis subgroups used in this study have shown mixed results and variation across countries. Further research is warranted to investigate acceptability of terminology. Methods of reducing stigma are discussed in line with the findings.

Ethics: The study received ethical approval from ERGO (Ethics and Research Governance Online; ID: 15972) and subsequently from the ethics committee at each site.
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http://dx.doi.org/10.1136/bmjopen-2017-021461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6009566PMC
June 2018

Effect of a bisphosphonate and selective estrogen receptor modulator on bone remodeling in streptozotocin-induced diabetes and ovariectomized rat model.

Spine J 2018 10 21;18(10):1877-1887. Epub 2018 May 21.

Department of Neurosurgery, Kyungpook National University, Kyungpook National University Hospital, 130 Dongdeok-ro, Jung-gu, Daegu 700-721, Republic of Korea. Electronic address:

Background Context: Diabetes and menopause can cause severe osteoporosis. In general, menopause and diabetes can lead to an imbalance in bone turnover, which results in secondary osteoporosis. However, the efficacy of antiresorptive drugs against this form of osteoporosis has not been extensively evaluated.

Objective: The aim of this study was to determine the changes in vertebral bone remodeling when postmenopausal osteoporosis is accompanied by diabetes and to compare the efficacy of bisphosphonates and selective estrogen-receptor modulators (SERMs) against these outcomes.

Study Design: Streptozotocin-induced diabetic, ovariectomized Sprague-Dawley rats were used as the disease model. Alendronate and raloxifene were used as the bisphosphonate and SERM, respectively.

Methods: We divided 62 female rats into five groups: (1) control (n=14), (2) DM (diabetes) (n=12), (3) DM+OVX (diabetes+ovariectomy) (n=12), (4) DM+OVX+A (diabetes+ovariectomy+alendronate) (n=12), and (5) DM+OVX+R (diabetes+ovariectomy+raloxifene) (n=12). Serum biochemical markers of bone turnover, including osteocalcin and the C-telopeptide of type I collagen (CTX-1), were analyzed. We measured histomorphometric parameters of the fourth lumbar vertebrae using microcomputed tomography. Mechanical strength was evaluated by a compression test.

Results: In the DM and DM+OVX group, only the levels of osteocalcin significantly decreased compared with those of the control group at 8 weeks after OVX. At 12 weeks, the serum CTX-1 levels in the DM+OVX+A and DM+OVX+R groups were significantly lower than those of the DM+OVX group, but there were no changes in the levels of osteocalcin. Bone mineral density and mechanical strength were higher in the DM+OVX+A and DM+OVX+R groups than in the DM and DM+OVX groups (p<.05).

Conclusions: Even if postmenopausal osteoporosis is accompanied by diabetes in this animal model, both alendronate and raloxifene seem to show antiresorptive effects, decreased bone turnover rates, and improved bone mechanical strength. Therefore, alendronate and raloxifene are effective in the treatment of osteoporosis even for bone loss caused by DM and postmenopausal osteoporosis.
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http://dx.doi.org/10.1016/j.spinee.2018.05.020DOI Listing
October 2018

Injection Butorphanol dependence: A case report.

Asian J Psychiatr 2018 Jun 14;35:45-46. Epub 2018 May 14.

Department of Psychiatry & National Drug Dependence Treatment Center, All India Institute of Medical Sciences, New Delhi, India. Electronic address:

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http://dx.doi.org/10.1016/j.ajp.2018.05.008DOI Listing
June 2018

Prescribing Patterns of Proprotein Convertase Subtilisin-Kexin Type 9 Inhibitors in Eligible Patients With Clinical Atherosclerotic Cardiovascular Disease or Heterozygous Familial Hypercholesterolemia.

Am J Cardiol 2018 05 12;121(10):1155-1161. Epub 2018 Feb 12.

Regeneron Pharmaceuticals, Inc., Tarrytown, New York.

Two proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors are approved for patients with atherosclerotic cardiovascular disease or heterozygous familial hypercholesterolemia who require additional low-density lipoprotein cholesterol (LDL-C) lowering. This retrospective study sought to determine differences between eligible patients who were prescribed and those who were not prescribed a PCSK9 inhibitor. Patients from an electronic medical record database were included in the analysis, and their demographic, clinical, and treatment characteristics were evaluated. Of 368,624 PCSK9 inhibitor-eligible patients, 1,752 (<0.5%) received a PCSK9 inhibitor prescription. Patients who received a PCSK9 inhibitor were more frequently associated with a higher cardiovascular disease risk category and a higher baseline LDL-C level (139.4 vs 103.5 mg/dl; p <0.0001) compared with those who did not. Patients with a PCSK9 inhibitor prescription were significantly more likely to be on ezetimibe, alone or in combination with a statin, at baseline compared with those without (29% vs 5%; p <0.0001). The use of a PCSK9 inhibitor was very low in the 2 groups of patients identified as PCSK9 inhibitor-eligible based on the American College of Cardiology Expert Consensus Decision Pathway. In conclusion, this study demonstrates that most PCSK9 inhibitor-eligible patients do not receive a PCSK9 inhibitor prescription, highlighting that many high-risk patients could benefit from additional LDL-C lowering with a PCSK9 inhibitor.
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http://dx.doi.org/10.1016/j.amjcard.2018.02.002DOI Listing
May 2018

Prevalence and pattern of cardiovascular risk factors in a population in India.

Heart Asia 2017 14;9(2):e010931. Epub 2017 Sep 14.

Harrington Heart & Vascular Institute, University Hospitals Cleveland Medical Centre, Case Western Reserve University, Cleveland, Ohio, USA.

Background: Cardiovascular disease is the leading cause of mortality in India. Since it is largely driven by risk factors such as hypertension, diabetes and smoking, it is important to study the treatment cascade for these conditions and identify areas for improvement.

Methods: This is a cross-sectional study from Project SEHAT (Study to Enhance Heart Associated Treatments), an ongoing cluster randomised controlled trial testing the hypothesis that a community health worker-led intervention can improve the control of cardiovascular risk factors in a community in West Bengal, India. For the baseline data, 3556 adults, between the ages of 35 and 70, were screened for hypertension, diabetes and smoking. For hypertension and diabetes, an elevated reading was confirmed on a repeat visit.

Results: 18.3% (n=650), 9.0% (n=317) and 14.1% (n=500) of adults were diagnosed with hypertension, diabetes and smoking, respectively. Overall, 35.0% (n=1242) adults had at least one of the three risk factors. 55.1% (n=358) of participants with hypertension and 40.4% (n=128) of participants with diabetes were unaware of their respective condition. 36.6% (n=238) of those with hypertension and 58.0% (n=184) of diabetics were on treatment. 8.2% (n=53) hypertensives were controlled (blood pressure <140/90 mm Hg) while 13.6% (n=43) diabetics were controlled (defined as fasting blood sugar <126 mg/dL). Less than 1% diabetics were on insulin, and average number of medications for a patient with hypertension was 1.2.

Conclusions: In our population in semiurban India, one in three adults have a major cardiovascular risk factor, with low control rates. There is a large burden of undiagnosed cardiovascular risk factors and a large gap between treatment and control, which may be explained by lack of treatment intensification.
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http://dx.doi.org/10.1136/heartasia-2017-010931DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5818042PMC
September 2017

Real-world evidence concerning clinical and economic outcomes of switching to insulin glargine 300 units/mL vs other basal insulins in patients with type 2 diabetes using basal insulin.

Diabetes Obes Metab 2018 05 24;20(5):1293-1297. Epub 2018 Jan 24.

Ochsner Medical Center, New Orleans, Louisiana.

This retrospective cohort study compared real-world clinical and healthcare-resource utilization (HCRU) data in patients with type 2 diabetes using basal insulin (BI) who switched to insulin glargine 300 units/mL (Gla-300) or another BI. Data from the Predictive Health Intelligence Environment database 12 months before (baseline) and 6 months after (follow-up) the switch date (index date, March 1, 2015 to May 31, 2016) included glycated haemoglobin A1c (HbA1c), hypoglycaemia, HCRU and associated costs. Baseline characteristics were balanced using propensity score matching. Change in HbA1c from baseline was similar in both matched cohorts (n = 1819 in each). Hypoglycaemia incidence and adjusted event rate were significantly lower with Gla-300. Patients switching to Gla-300 had a significantly lower incidence of HCRU related to hypoglycaemia. All-cause and diabetes-related hospitalization and emergency-department HCRU were also favourable for Gla-300. Lower HCRU translated to lower costs in patients using Gla-300. In this real-world study, switching to Gla-300 reduced the risk of hypoglycaemia in patients with type 2 diabetes when compared with those switching to another BI, resulting in less HCRU and potential savings of associated costs.
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http://dx.doi.org/10.1111/dom.13199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5947830PMC
May 2018

Letter to the Editor. Symptomatic degenerative lumbar disease and obesity.

J Neurosurg Spine 2018 01 3;28(1):129. Epub 2017 Nov 3.

2SUNY Downstate Medical Center, Brooklyn, NY.

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http://dx.doi.org/10.3171/2017.6.SPINE17654DOI Listing
January 2018
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