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1.
Saudi Pharm J ; 32(5): 102056, 2024 May.
Article in English | MEDLINE | ID: mdl-38577489

ABSTRACT

Background: Healthcare workers increasingly use Electronic Health Information Resources (EHIRs) to make evidence-based decisions. Our study was intended to assess the perception, attitude, and practice of healthcare professionals in medicine, pharmacy, and nursing regarding their perceived value and use of EHIRs. Methods: We conducted an observational cross-sectional study using a pre-validated questionnaire among healthcare professionals in Jazan province from September 2022 to February 2023. We included healthcare professionals and interns with medical, pharmacy, or nursing degrees and excluded those who refused informed consent. Results: We included fully completed data from 294 participants, with an actual response rate of just 80.1 %. Almost 87.41 % utilized the health information resources at their workplace, with UpToDate [39.45 %] and Medscape [67.01 %] being the most frequently used medical databases. The health facilities' access to electronic health resources significantly impacted healthcare professionals' [p = 0.04] and medical interns' [p = 0.02] roles. Faculty members felt the need to access electronic health information at their workplace [p = 0.00]. Lack of time to access electronic health information due to a busy schedule was a significant reason that impacted the attitude of medical professionals [p = 0.008] and nursing staff [p = 0.025]. An excessive amount of clinically unrelated data was the primary obstacle (181/294, p < 0.0001) in using electronic health information resources. Conclusion: Our study showed the pattern of healthcare professionals using EHIRs in the Jazan province, Saudi Arabia. We believe the study's outcome can help increase the calibre of electronic health information services available to healthcare professionals and raise awareness of different EHIRs in improving clinical care.

2.
Heliyon ; 9(11): e22197, 2023 Nov.
Article in English | MEDLINE | ID: mdl-38045149

ABSTRACT

Background: First aid during a seizure is critical, but many people in Jazan, Saudi Arabia may not know what to do. This is because epilepsy is often stigmatized in the region and regarded as a spiritual or mental disorder. This study investigated the awareness of seizure first aid among the population living in Jazan. Methods: An online survey was conducted. Healthcare workers and people who had never heard of epilepsy were excluded. Participants were asked to identify correct measures of seizure first aid from a list of 20 statements [9 correct and 11 incorrect]. A composite awareness score was calculated by subtracting the number of incorrect statements from the number of correct statements. Participants were classified into three groups: high, intermediate, and low awareness. Logistic regression was used to identify factors associated with high awareness. Results: Of the 1215 participants, 80.5 % had low awareness of seizure first aid. The most common correct responses were clearing the area of dangerous objects (91.3 %), putting a pillow under the neck (69.3 %), and timing the seizure (68.5 %). However, only 32.2 % knew to tell the person what happened after the seizure. The most common misconception was that an ambulance should be called immediately, regardless of the details (88.3 %). Other common misconceptions included putting something in the person's mouth (87.5 %), holding them down (83.0 %), taking out their contact lenses (79.9 %), and giving antiseizure medications orally (73.2 %). People who previously watched an educational video on seizure first aid (OR = 4.27, 95 % CI = 1.48-12.34, p = .007) or who knew someone with epilepsy (OR = 9.01, 95 % CI = 2.82-28.83, p < .001) were more likely to have a high awareness of seizure first aid. Conclusion: The study found that most people in Jazan, Saudi Arabia do not know how to provide first aid for seizures. The findings inform future research and highlight the need for increased education and training on seizure first aid in this region.

3.
J Med Life ; 16(7): 1050-1056, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37900062

ABSTRACT

In August 2022, the United States Food and Drug Administration issued marketing authorization for an orally administered vibrating colon-stimulating capsule for treating chronic idiopathic constipation. We aimed to review the literature systematically and synthesize evidence on the role of the vibrating capsule in chronic idiopathic constipation. A comprehensive search was conducted on PubMed, Embase, International Clinical Trials Registry Platform (World Health Organization), Cochrane Library databases, and two pre-print servers (medRxiv.org and Research Square) until 31 December 2022, to identify published pre-clinical and clinical original studies evaluating the role of the vibrating capsule in patients with chronic constipation. The studies were critically analyzed, and data were extracted. We identified thirty-three articles and five studies (one pre-clinical, one combined, and three clinical). The pre-clinical studies in dogs revealed no adverse effects of the vibrating capsule. In the clinical studies, there were significant findings observed. The number of spontaneous bowel movements per week and the proportion of patients experiencing an increase of at least one complete spontaneous bowel movement per week were both significantly higher in the group receiving the vibrating capsule compared to the group receiving the sham capsule. No treatment-related serious adverse event was noted. The mild adverse events were vibration sensation, diarrhea, and abdominal discomfort. The efficacy and safety profiles of the vibrating colon-stimulating capsule in treating patients with chronic constipation are promising. However, more robust evidence is required by conducting large randomized clinical trials before conclusively determining its wider use.


Subject(s)
Colon , Constipation , United States , Humans , Animals , Dogs , Chronic Disease , Constipation/drug therapy
4.
Epilepsy Behav ; 138: 108960, 2023 01.
Article in English | MEDLINE | ID: mdl-36427450

ABSTRACT

OBJECTIVES: People with epilepsy have a higher prevalence of medical and psychiatric comorbidities compared to the general population. Comorbidities are associated with poor epilepsy outcomes, and there have been recommendations for screening and early identification to improve clinical management. Data from 'First Seizure Clinics' (FSCs) with expert epileptological review can inform about disorders already present at the point of diagnosis of epilepsy or unprovoked seizures. Here, we aimed to describe pre-existing conditions with a focus on psychiatric, substance use, cardiac, neurological, and cancer health domains. METHODS: We included 1383 adults who received a new diagnosis of epilepsy or unprovoked seizures at Austin Hospital (AH) or Royal Melbourne Hospital (RMH) (Australia) FSCs from 2000 to 2010. Data were audited from FSC records, primarily detailed interviews undertaken by epileptologists. Logistic regression examined age distribution and other risk factors. RESULTS: The median age at FSC presentation was 37 years (IQR 26-53, range 18-94). Pre-existing conditions were reported by 40 %; from 32 % in the youngest group (18-30 years) to 53 % in the oldest (65+ years). Psychiatric (18 %) and substance use (16 %) disorders were most common, with higher prevalence among patients 18 to 65 years of age compared to those older than 65 years (p < 0.001). Cardiac, neurological, or cancer conditions were reported by 3-6 %, most often amongst those older than 65 years (p < 0.01). Eight percent (n = 112) reported disorders in >1 health domain. The commonest combination was a psychiatric condition with substance use disorder. Of the sixty-two patients reporting this combination, 61 were ≤65 years of age. CONCLUSIONS: Pre-existing health conditions are present in a substantial proportion of patients diagnosed with epilepsy or unprovoked seizures. Disorders are highest amongst elders, but one-third of younger adults also reported positive histories. These are predominantly psychiatric and/or substance use disorders, conditions strongly associated with poor outcomes in the general population. These findings inform post-diagnosis planning and management, as well as research examining post-diagnostic outcomes and associations between comorbidities and epilepsy.


Subject(s)
Epilepsy , Mental Disorders , Adult , Humans , Aged , Preexisting Condition Coverage , Epilepsy/complications , Epilepsy/diagnosis , Epilepsy/epidemiology , Seizures/diagnosis , Comorbidity , Mental Disorders/diagnosis , Mental Disorders/epidemiology
5.
Clin Case Rep ; 10(5): e05894, 2022 May.
Article in English | MEDLINE | ID: mdl-35620259

ABSTRACT

Acute liver failure developed in a 48-year-old woman within days after she received adjuvant chemotherapy for breast cancer. On arrival at ED, she had severe encephalopathy and jaundice. Serum analyses demonstrated coagulopathy and markedly increased transaminases. She was admitted to the ICU for supportive treatment but died several days later.

6.
Neuropsychopharmacol Rep ; 42(2): 199-204, 2022 06.
Article in English | MEDLINE | ID: mdl-35318823

ABSTRACT

OBJECTIVES: Understanding how local "psychiatry clinic" characteristics shape research findings is essential for applying research into evolution, outcomes, and costs of mental health. However, a paucity of "psychiatry clinics" details has implications for the interpretation and utilization of this research. METHODS: We reviewed data of 746 patients with new-onset schizophrenia on antipsychotic monotherapy seen over four years in an "adult psychiatry clinic" at Jazan Health, Saudi Arabia. Protocol-driven interviews and investigations were recorded prospectively and extracted from the medical records for the study. Summary statistics and logistic regression analyses were applied to assess patients' characteristics and outcomes. RESULTS: The median patient age was 32 (IQR 27-39) years. Of patients, 589 (79.0%) were male, and 679 (91.0%) had a low-level education. The median follow-up duration was 51.4 (IQR 27.4-96.3) weeks. The most used initial antipsychotic drugs were olanzapine (48.8%), haloperidol (13.9%), and aripiprazole (11.3%). The numbers of patients who retained the initial drug at 24 and 52 weeks were 539 (72.3%) and 325 (43.6%), respectively. The initial drug was changed in 246 (33.0%) patients. The median time to initial drug change was 43.9 (IQR 14.8-85.0) weeks. The logistic regression demonstrated that male sex (P < 0.004), young adult age group (P < 0.027), predominant positive symptoms (P < 0.021), treatment with haloperidol (P < 0.024), and khat use (P < 0.006) were significant factors for drug change. CONCLUSIONS: This clinical records study demonstrated substantial individual variations in characteristics and in responding to initial antipsychotic medication. Insight into these findings will facilitate the planning for comprehensive research programs.


Subject(s)
Antipsychotic Agents , Schizophrenia , Adult , Female , Haloperidol/adverse effects , Humans , Male , Saudi Arabia/epidemiology , Schizophrenia/diagnosis , Schizophrenia/drug therapy , Schizophrenia/epidemiology , Treatment Outcome
7.
Ther Adv Neurol Disord ; 14: 17562864211037430, 2021.
Article in English | MEDLINE | ID: mdl-34603506

ABSTRACT

Drug-resistant epilepsy occurs in 25-30% of patients. Furthermore, treatment with a first-generation antiseizure drug (ASD) fails in 30-40% of individuals because of their intolerable adverse effects. Over the past three decades, 20 newer- (second- and third-)generation ASDs with unique mechanisms of action and pharmacokinetic profiles have been introduced into clinical practice. This advent has expanded the therapeutic armamentarium of epilepsy and broadens the choices of ASDs to match the individual patient's characteristics. In recent years, research has been focused on defining the ASD of choice for different seizure types. In 2017, the International League Against Epilepsy published a new classification for seizure types and epilepsy syndrome. This classification has been of paramount importance to accurately classify the patient's seizure type(s) and prescribe the ASD that is appropriate. A year later, the American Academy of Neurology published a new guideline for ASD selection in adult and pediatric patients with new-onset and treatment-resistant epilepsy. The guideline primarily relied on studies that compare the first-generation and second-generation ASDs, with limited data for the efficacy of third-generation drugs. While researchers have been called for investigating those drugs in future research, epilepsy specialists may wish to share their personal experiences to support the treatment guidelines. Given the rapid advances in the development of ASDs in recent years and the continuous updates in definitions, classifications, and treatment guidelines for seizure types and epilepsy syndromes, this review aims to present a complete overview of the current state of the literature about the efficacy and tolerability of ASDs and provide guidance to clinicians about selecting appropriate ASDs for initial treatment of epilepsy according to different seizure types and epilepsy syndromes based on the current literature and recent US and UK practical guidelines.

8.
Neuropsychopharmacol Rep ; 41(3): 336-351, 2021 09.
Article in English | MEDLINE | ID: mdl-34296824

ABSTRACT

BACKGROUND: Antiseizure drugs (ASDs) are the primary therapy for epilepsy, with more than 20 drugs introduced into clinical practice to date. These drugs are typically grouped by their mechanisms of action and therapeutic spectrum. This article aims to educate non-neurologists and medical students about the new frontiers in the pharmacology of ASDs and presents the current state of the literature on the efficacy and tolerability of these agents. METHODS: Randomized controlled trials, observational studies, and evidence-based meta-analyses of ASD efficacy and tolerability as initial monotherapy for epileptic seizures and syndromes were identified in PubMed, EMBASE, the Cochrane Library, and Elsevier Clinical Pharmacology. RESULTS: The choice of ASD varies primarily according to the seizure type. Practical guidelines for ASD selection in patients with new-onset and drug-resistant epilepsy were recently published. The guidelines have shown that the newer-generation drugs, which have unique mechanistic and pharmacokinetic properties, are better tolerated but have similar efficacy compared with the older drugs. Several ASDs are effective as first-line monotherapy in focal seizures, including lamotrigine, carbamazepine, phenytoin, levetiracetam, and zonisamide. Valproate remains the first-line drug for many patients with generalized and unclassified epilepsies. However, valproate should be avoided, if possible, in women of childbearing potential because of teratogenicity. Toxicity profile precludes several drugs from use as first-line treatment, for example, vigabatrin, felbamate, and rufinamide. CONCLUSIONS: Antiseizure drugs have different pharmacologic profiles that should be considered when selecting and prescribing these agents for epilepsy. These include pharmacokinetic properties, propensity for drug-drug interactions, and adverse effects.


Subject(s)
Epilepsies, Partial , Epilepsy, Generalized , Epilepsy , Pharmaceutical Preparations , Anticonvulsants/therapeutic use , Epilepsies, Partial/drug therapy , Epilepsy/drug therapy , Epilepsy, Generalized/drug therapy , Humans , Neuropharmacology , Seizures/drug therapy , Valproic Acid/therapeutic use
9.
Epilepsy Behav Rep ; 16: 100450, 2021.
Article in English | MEDLINE | ID: mdl-34142076

ABSTRACT

•We examined knowledge of and attitudes toward epilepsy among university students in Saudi Arabia.•Knowledge of and attitudes towards epilepsy were more favorable among students of health specialties.•One fifth linked epilepsy to spirits possession and mental disorders, but almost half prefer spiritual ritual treatment.•Social interactions with people with epilepsy were more favorable among women except toward marriage.•Universities should make efforts to correct misconceptions and reduce the social burden of epilepsy.

10.
East Mediterr Health J ; 27(4): 353-360, 2021 Apr 27.
Article in English | MEDLINE | ID: mdl-33955531

ABSTRACT

BACKGROUND: Khat contains the amphetamine-like cathinone, and can trigger onset of schizophrenia and exacerbate pre-existing psychosis. However, it remains unknown whether the use of khat complicates the outcome of schizophrenia treatment. AIMS: We tested the hypothesis that patients with schizophrenia who are using khat will fail to respond to standard antipsychotic treatment. METHODS: We retrospectively studied a consecutive series of patients who presented to an adult psychiatric clinic in Al-Amal Psychiatric Hospital in Jazan, Saudi Arabia, between January 1, 2013 and December 31, 2016. Patients with newly diagnosed schizophrenia on antipsychotic monotherapy (n = 1007, 817 men) were included and categorized into khat and non-khat users. A khat chewing index was developed to further categorize low, mild, moderate and heavy khat users. Antipsychotic medications were reviewed to determine their potential and the cause of substitution in association with khat use. RESULTS: There were 483 (48%) khat users. Olanzapine, haloperidol and aripiprazole were the most frequently used drugs (46.3%, 15.6% and 10%, respectively). The retention rate of the initial drug differed between the khat users and nonusers (53.8% and 78.4%, respectively). The proportion of moderate and heavy users (55% and 49%, respectively) who changed their initial drug was greater than that of low and mild users (35.6% and 44.7%, respectively). Lack of drug efficacy was the most appealing reason for switching the initial drug among moderate (51.7%) and heavy khat users (48.4%). CONCLUSIONS: Khat use hinders an individual's response to initial antipsychotic drug treatment for schizophrenia. Further studies are warranted to investigate the treatment decisions for this group of patients.


Subject(s)
Antipsychotic Agents , Schizophrenia , Adult , Antipsychotic Agents/adverse effects , Catha/adverse effects , Humans , Male , Retrospective Studies , Saudi Arabia , Schizophrenia/drug therapy
11.
Epilepsy Behav ; 121(Pt A): 108025, 2021 08.
Article in English | MEDLINE | ID: mdl-34022620

ABSTRACT

IMPORTANCE: Sudden unexpected death in epilepsy (SUDEP) may account for up to 17% of all deaths in epilepsy. However, it is unknown if neurologists discuss this risk with patients. OBJECTIVE: This study aimed to examine the understanding and practices of SUDEP by neurologists in Saudi Arabia. METHODS: An electronic web-based survey was sent to 125 neurologists using the mailing list of the Saudi Neurology Society. The survey questions included respondents' demographics, frequency of SUDEP discussion, reasons for discussing/not discussing SUDEP, and perceived patient reactions. Respondents' knowledge of the SUDEP risk factors was examined using 12 items from the currently available literature. Logistic regression analyses were applied to examine the factors that influence the frequency of SUDEP discussions and perceived patient reactions. PARTICIPANTS: The participants were neurologists who had completed postgraduate training, devoted >5% of their time to clinical care, and had at least one patient with epilepsy in their independent neurology clinic. RESULTS: A total of 60 respondents met the eligibility criteria and completed the surveys. Of them, 25% discussed SUDEP most of the time, 65% sometimes or rarely, and 10% never discussed it. Of those who discussed SUDEP with their patients, 63.3% did it if the patient was at high risk. Poor compliance with antiepileptic drugs (AEDs) was the most common patient factor highlighted (81.7%). The perceived patients' reactions were variable, with positive reactions (motivation to comply and appreciation) being the most frequent. The majority of respondents (78.3%) had incomplete understanding of the published SUDEP risk factors, with SUDEP knowledge scores ≤2.5 (≤50% of the possible total score). The most identified risk factors were frequent generalized tonic-clonic seizures (83.3%), long duration of epilepsy (53.3%), lack of use or sub-therapeutic levels of AEDs (50%), and AED polytherapy (50%). No association was found between how often SUDEP was discussed and other factors, including training in epilepsy, ≥10 years in practice, seeing ≥100 patients, and having SUDEP cases in the past two years. It was found that patients positively reacted to discussion on SUDEP if neurologists had a good understanding of the SUDEP risk factors (χ2 = 5.773, p = 0.016). CONCLUSIONS: Neurologists in Saudi Arabia do not often discuss SUDEP with patients that have epilepsy. Moreover, when they do, they stress a more individualized approach despite having only a limited understanding of the SUDEP risk factors. Our findings suggest that more guidance should be provided to practitioners on how best to counsel their patients about SUDEP.


Subject(s)
Epilepsy , Sudden Unexpected Death in Epilepsy , Death, Sudden/epidemiology , Death, Sudden/etiology , Epilepsy/complications , Epilepsy/epidemiology , Humans , Neurologists , Risk Factors , Saudi Arabia/epidemiology
12.
Epilepsia Open ; 6(1): 171-180, 2021 03.
Article in English | MEDLINE | ID: mdl-33681660

ABSTRACT

Objective: 'First seizure' clinics (FSCs) aim to achieve early expert assessment for individuals with possible new-onset epilepsy. These clinics also have substantial potential for research into epilepsy evolution, outcomes, and costs. However, a paucity of FSCs details has implications for interpretation and utilization of this research. Methods: We reviewed investigation findings over 11 years (2000-2010) from two established independent FSCs at Austin Health (AH) and Royal Melbourne Hospital (RMH), Australia. These adult clinics are in major public hospitals and operate with similar levels of expertise. Organizational differences include screening and dedicated administration at AH. Included were N = 1555 patients diagnosed with new-onset unprovoked seizures/epilepsy (AH n = 901, RMH n = 654). Protocol-driven interviews and investigations had been recorded prospectively and were extracted from medical records for study. Results: Median patient age was 37 (IQR 26-52, range 18-94) years (AH 34 vs RMH 42 years; P < .001). Eighty-six percent of patients attended FSC within three weeks postindex seizure (median AH 12 vs RMH 25 days; P < .01). By their first appointment, 42% had experienced ≥2 seizures. An EEG was obtained within three weeks postindex seizure in 73% of patients, demonstrating epileptiform discharges in 25% (AH 33% vs RMH 15%). Seventy-six percent of patients had an MRI within 6 weeks. Of those with imaging (n = 1500), 19% had potentially epileptogenic abnormalities (RMH 28% vs AH 12%; P < .01). At both sites, changes due to previous stroke/hemorrhage were the commonest lesions, followed by traumatic brain injury. ≥WHO level 1 brain tumors diagnosed at presentation comprised a very small proportion (<1%) at each clinic. At both sites, epilepsy type could be determined in 60% of patients; RMH had more focal and AH more generalized epilepsy diagnoses. Significance: Differences between the clinics' administrative and screening practices may contribute to differences in investigation findings. Insight into these differences will facilitate interpretation and utilization, and planning of future research.


Subject(s)
Ambulatory Care Facilities/standards , Seizures/diagnosis , Adult , Ambulatory Care Facilities/organization & administration , Australia , Electroencephalography , Epilepsy/diagnosis , Female , Humans , Male , Outpatients/statistics & numerical data
13.
Can J Physiol Pharmacol ; 95(2): 140-150, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27901349

ABSTRACT

This study aimed to investigate effects of curcumin on high fructose diet (HFD)-induced metabolic syndrome (MetS) in rats and the possible mechanisms involved. MetS was induced in male albino rats (n = 20), over 8 weeks, by 65% HFD. For 8-week experiment period, rats were assigned to 2 equal groups: curcumin-treated rats received curcumin (200 mg/kg, p.o, once daily) along with HFD, and untreated rats were fed with HFD only. We evaluated body mass (BM), systolic blood pressure (SBP), homeostasis model assessment of insulin resistance (HOMA-IR), and serum levels of glucose, insulin, leptin, total cholesterol (TC), triglycerides (TGs), uric acid, malondialdehyde (MDA; lipid peroxidation product), and tumor necrosis factor-α (TNF-α; inflammatory cytokine), and serum catalase (endogenous antioxidant) activity and immunohistochemical expression of nuclear factor κB (NF-κB; inflammation-related transcription factor) in hepatocytes. HFD produced increases in BM, SBP, HOMA-IR, and serum levels of glucose, insulin, leptin, TC, TGs, uric acid, MDA, and TNF-α, a decrease in catalase activity, and strong positive expression of NF-κB in hepatocytes. Curcumin, in presence of HFD, produced significant improvements in all glucose and fat metabolism parameters, and in oxidative stress and inflammation biomarkers. Curcumin may potentially be useful in the treatment of MetS through its ability to modulate oxidation stress status and inflammation cascades.


Subject(s)
Curcumin/therapeutic use , Fructose/adverse effects , Metabolic Syndrome/drug therapy , Metabolic Syndrome/metabolism , NF-kappa B/metabolism , Oxidative Stress/drug effects , Tumor Necrosis Factor-alpha/metabolism , Animals , Blood Glucose , Blood Pressure/drug effects , Body Weight/drug effects , Catalase/blood , Cholesterol/blood , Curcumin/pharmacology , Hepatocytes/metabolism , Insulin/blood , Leptin/blood , Liver/pathology , Male , Malondialdehyde/blood , Metabolic Syndrome/chemically induced , Metabolic Syndrome/pathology , Rats , Tumor Necrosis Factor-alpha/blood , Uric Acid/blood
14.
Pharmacology ; 98(5-6): 242-250, 2016.
Article in English | MEDLINE | ID: mdl-27449930

ABSTRACT

AIMS: The present study evaluated the effects of sitagliptin-insulin against type 2 diabetes mellitus with neuropathy in rats and possible neuroprotective mechanisms. METHODS: Diabetes was induced in 32 adult male albino rats by 6-week high-fat high-sugar diet followed by streptozotocin 30 mg/kg intraperitoneal injection. For 4 weeks thereafter, diabetic rats were divided into 4 groups, each group receiving one of the following daily: vehicle (untreated diabetic), insulin 10 IU/kg SC, sitagliptin 30 mg/kg PO or sitagliptin-insulin. We assessed systolic blood pressure (SBP), blood glucose, serum insulin and advanced glycation end-products (AGEs), thermal hyperalgesia and sciatic nerve tumor necrosis factor-alpha (TNF-α), superoxide dismutase (SOD) and malondialdehyde (MDA) and sciatic histopathology. RESULTS: Compared to untreated and insulin-treated groups, sitagliptin decreased SBP, serum AGEs and sciatic MDA and TNF-α, and increased serum insulin and sciatic SOD, but insulin decreased blood glucose more. Sitagliptin-insulin (greater than sitagliptin or insulin alone) superiorly decreased and increased the above respective parameters, and ameliorated hyperalgesia and sciatic histopathological changes, but was similar to insulin in decreasing blood glucose, and similar to sitagliptin in rising serum insulin. CONCLUSIONS: Sitagliptin-insulin combination produced hypoglycemic and neuroprotective effect and ameliorated hyperalgesia, oxidative stress and inflammation more than either drug alone. This combination might have clinical efficacy in uncontrolled type 2 diabetes with neuropathy.


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Diabetic Neuropathies/drug therapy , Insulin/administration & dosage , Neuroprotection/drug effects , Oxidative Stress/drug effects , Sitagliptin Phosphate/administration & dosage , Animals , Blood Glucose/drug effects , Blood Glucose/metabolism , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/pathology , Diabetic Neuropathies/blood , Diabetic Neuropathies/pathology , Drug Therapy, Combination , Hypoglycemic Agents/administration & dosage , Inflammation/blood , Inflammation/drug therapy , Male , Neuroprotection/physiology , Oxidative Stress/physiology , Rats , Rats, Sprague-Dawley
15.
Calcif Tissue Int ; 98(6): 556-65, 2016 06.
Article in English | MEDLINE | ID: mdl-26842957

ABSTRACT

Long-term anti-epileptic drug (AED) therapy is associated with increased fracture risk. This study tested whether substituting the newer AED levetiracetam has less adverse effects on bone than older AEDs. An open-label randomized comparative trial. Participants had "failed" initial monotherapy for partial epilepsy and were randomized to substitution monotherapy with levetiracetam or an older AED (carbamazepine or valproate sodium). Bone health assessments, performed at 3 and 15 months, included areal bone mineral density (aBMD) and content at lumbar spine (LS), total hip (TH), forearm (FA), and femoral neck (FN), radial and tibial peripheral quantitative computed tomography and serum bone turnover markers. Main outcomes were changes by treatment group in aBMD at LS, TH, and FA, radial and tibial trabecular BMD and cortical thickness. 70/84 patients completed assessments (40 in levetiracetam- and 30 in older AED group). Within-group analyses showed decreases in both groups in LS (-9.0 %; p < 0.001 in levetiracetam vs. -9.8 %; p < 0.001 in older AED group), FA (-1.46 %; p < 0.001 vs. -0.96 %; p < 0.001, respectively) and radial trabecular BMD (-1.46 %; p = 0.048 and -2.31 %; p = 0.013, respectively). C-terminal telopeptides of type I collagen (ßCTX; bone resorption marker) decreased in both groups (-16.1 %; p = 0.021 vs. -15.2 %; p = 0.028, respectively) whereas procollagen Ι N-terminal peptide (PΙNP; bone formation marker) decreased in older AED group (-27.3 %; p = 0.008). The treatment groups did not differ in any of these measures. In conclusion, use of both levetiracetam and older AEDs was associated with bone loss over 1 year at clinically relevant fracture sites and a reduction in bone turnover.


Subject(s)
Anticonvulsants/adverse effects , Bone Remodeling/drug effects , Bone and Bones/drug effects , Epilepsy/drug therapy , Piracetam/analogs & derivatives , Absorptiometry, Photon , Adult , Aged , Bone Density/drug effects , Carbamazepine/adverse effects , Female , Humans , Levetiracetam , Male , Middle Aged , Piracetam/adverse effects , Tomography, X-Ray Computed , Valproic Acid/adverse effects
16.
Article in English | MEDLINE | ID: mdl-26180775

ABSTRACT

Nephropathy is one of the major complications of diabetes often leading to chronic kidney disease (CKD). Inflammation and oxidative stress are associated with pathogenesis of diabetic nephropathy (DN) and found to be regulated by nuclear receptors such as vitamin D receptors (VDR). Vitamin D and its analogues have been effectively used in patients with CKD. The review attempts to summarize the available evidence on the role of vitamin D in DN. Electronic databases (MEDLINE, EMBASE, and Cochrane Library) were searched for studies assessing the role of vitamin D or its analogues on kidney function in type 2 diabetic patients. Studies evaluating kidney functions (urinary albumin/protein creatinine ratio, albuminuria and eGFR) were included and quality and risk of bias assessment performed. Additionally effect on 25 (OH) vitamin D, calcium and HbA1c were evaluated. The mean or its % change along with their standard deviation (SD) was used for reporting our results. RevMan (V5.2) was used for data analysis. Six studies included in this review evaluated the role of cholecalciferol, calcitriol and paricalcitol in patients with DN. Study designs differed (three randomized, one non-randomized and two uncontrolled trials) with varying degree of quality and risk of biases. Vitamin D analogues showed significant improvement in kidney function in two randomized studies. None of the studies reported significant incidences of hypercalcemia. Vitamin D analogues show significant improvement of kidney function in DN. Randomized controlled trials with longer duration, comparing the efficacy of vitamin D and its analogues are needed.

17.
Neurology ; 81(10): 920-7, 2013 Sep 03.
Article in English | MEDLINE | ID: mdl-23925763

ABSTRACT

OBJECTIVE: To determine the frequency and nature of potentially epileptogenic lesions on MRI in adults with new-onset seizures. METHODS: We prospectively studied a consecutive series of 993 patients (597 males [61%]; mean [SD] age: 42.2 [18.8] years, range 14.3-94.3 years) who presented to an adult First Seizure Clinic over a 10-year period. The MRI scans, performed clinically on 3- and 1.5-tesla scanners, were reviewed for their diagnostic yield, nature of abnormalities, and their association with abnormal electrical activity on EEG. RESULTS: MRI scans were acquired in 764 patients (77%); potentially epileptogenic lesions were detected in 177 (23%). The frequency of potentially epileptogenic lesions was higher in patients who were diagnosed as having an epileptic seizure (28%) than in those with a nonepileptic event (8%) (p < 0.001), and highest in those who had focal-onset seizures (53%) (p < 0.001). The most common lesion type in patients with focal seizures was gliosis or encephalomalacia (49%). Other common lesion types were tumors (15%), cavernomas (9%), and mesial temporal sclerosis (9%). Abnormal MRI and EEG were concordant in 18% of patients, with EEG being normal in 55% of patients with epileptogenic lesions. CONCLUSIONS: MRI reveals potentially epileptogenic lesions in a minority of patients with a newly diagnosed seizure disorder. Lesions are most common in patients who have experienced focal seizures. The presence of a potentially epileptogenic MRI lesion did not influence the chance of having an abnormal EEG.


Subject(s)
Magnetic Resonance Imaging/methods , Seizures/diagnosis , Seizures/epidemiology , Adolescent , Adult , Age of Onset , Aged , Aged, 80 and over , Child , Cohort Studies , Female , Humans , Male , Middle Aged , Prospective Studies , Seizures/pathology , Young Adult
19.
Arch Neurol ; 69(12): 1563-71, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22945760

ABSTRACT

OBJECTIVE To determine whether patients who fail their first antiepileptic drug (AED) have better neuropsychiatric and quality-of-life (QOL) outcomes if substituted to levetiracetam monotherapy compared with a second older AED. DESIGN Randomized comparative trial. Participants with partial epilepsy who had failed monotherapy with phenytoin sodium, carbamazepine, or valproate sodium were randomized to substitution monotherapy with levetiracetam or a different older AED. Assessments were performed at baseline, 3 months, and 12 months using questionnaires measuring neuropsychiatric, QOL, seizure control, AED adverse effects, and neurocognitive outcomes. SETTING Epilepsy service of a teaching hospital. PATIENTS Fifty-one patients were randomized to levetiracetam and 48 were randomized to a second older AED (25 to valproate and 23 to carbamazepine). MAIN OUTCOME MEASURES Proportions showing improvements in depression (on the Hospital Anxiety and Depression Scale) and QOL scores (on the 89-item Quality of Life in Epilepsy Inventory) at 3 months. RESULTS There were no differences between the groups in depression scores at 3 months (improvement in 17 of 43 patients [39.5%] in the levetiracetam group and 15 of 44 patients [34.1%] in the older AED group; P = .60), but a greater proportion of the older AED group improved on the 89-item Quality of Life in Epilepsy Inventory compared with the levetiracetam group (27 of 38 patients [71.1%] vs 21 of 43 patients [48.8%], respectively; P = .04). The QOL, anxiety, and AED adverse effects scores were improved in both groups at 3 and 12 months after randomization. CONCLUSIONS Substitution monotherapy in a patient experiencing ongoing seizures or tolerability issues is associated with sustained improvements in measures of QOL, psychiatric, and adverse events outcomes. Patients switched to levetiracetam do not have better outcomes than those switched to a second older AED. TRIAL REGISTRATION anzctr.org.au Identifier: ACTRN12606000102572.

20.
Neurobiol Dis ; 39(1): 116-25, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20153428

ABSTRACT

The incidence of psychosis is increased in people with epilepsy, including idiopathic generalized epilepsies. To study the biological basis for this co-morbidity, we compared GAERS, a genetic rat model of absence epilepsy, to non-epileptic control rats (NEC). Mature, 14-week old GAERS showed enhanced amphetamine-induced locomotor hyperactivity - a feature also present in young (6-week old) GAERS prior to epilepsy onset. Prepulse inhibition and its disruption by psychotropic drugs did not differ between strains, although GAERS displayed elevated startle responses at both epileptic and pre-epileptic ages. The frontoparietal cortex of GAERS displayed a twofold increase in the power of gamma (30-80 Hz) oscillations, a proposed neurophysiological correlate of psychosis. Radioligand binding autoradiography demonstrated reduced densities of dopamine transporters in the caudate nucleus and nucleus accumbens core and of dopamine D2 receptors in the caudate nucleus. GAERS provide an opportunity to study the neurodevelopmental, genetic and therapeutic aspects of psychiatric comorbidities associated with epilepsy.


Subject(s)
Disease Models, Animal , Epilepsy/genetics , Epilepsy/psychology , Phenotype , Psychotic Disorders/genetics , Animals , Comorbidity , Dopamine Uptake Inhibitors/administration & dosage , Environment , Epilepsy/metabolism , Female , Genetic Predisposition to Disease/genetics , Habituation, Psychophysiologic/physiology , Hyperkinesis/chemically induced , Hyperkinesis/genetics , Hyperkinesis/metabolism , Male , Psychotic Disorders/classification , Psychotic Disorders/metabolism , Rats , Rats, Mutant Strains , Rats, Wistar , Species Specificity
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