Corrigendum to "A narrative review of approved and emerging anti-obesity medications" [Saudi Pharm. J. 31(10) (2023) 101757].

[This corrects the article DOI: 10.1016/j.jsps.2023.101757.].

Association of level of adherence to Mediterranean diet with cognitive and dementia status in subjects with chronic diseases: a cross-sectional study.

Background: The Mediterranean diet has been linked to brain neuroprotection. Evidence from meta-analyses showed reduced risk of dementia with greater intake of vegetables and fruits, fish, and the Mediterranean diet. The current study raises important questions about the association between low risk dementia and Mediterranean diet.Objective: The objective was to evaluate the association between levels of adherence to the Mediterranean diet and dementia and cognitive status in subjects 50 years of age and older.Method: The Mediterranean Diet Adherence Screener (MEDAS), the modified 30-item 'Diagnostic and Statistical Manual of Mental Disorders Third Edition (DSM-III) risk of dementia, and the Standard Mini-Mental Status Examination (SMMSE) cognitive status scores were used to assess the levels of adherence to the Mediterranean diet'.Results: A total of 150 subjects were enrolled in the study. Forty-one (27.3%) had 'suspected or confirmed dementia, while 48 individuals (32%) were categorized as having moderate to severe cognitive decline. Subjects who reported moderate to high adherence to the Mediterranean diet (55, 36.7%) had significantly lower dementia scores (7.0 3.8 versus 17.6 5.1) and higher cognitive (25.4 3.8 versus 8.6 7.2) scores compared to those (38, 25.3%) who reported low adherence to the Mediterranean diet.Conclusion: Subjects who were highly or moderately adherent to the Mediterranean diet had significantly lower dementia scores and better cognitive status than those with low adherence.

The flavonoid luteolin reduces mutant huntingtin aggregation and cytotoxicity in huntingtin-mutated neuroblastoma cells.

Background: Huntington's disease is an inherited progressive neurodegenerative disorder caused by an expansion of the polyglutamine tract leading to malformation and aggregation of the mutant huntingtin protein in the cell cytoplasm and nucleus of affected brain regions. The development of neuroprotective agents from plants has received considerable research attention. Objective: Our study aims to investigate the neuroprotective effects of luteolin and the mechanisms that underline its potential mediated protection in the mutant htt neuroblastoma cells. Methods: The mutant htt neuroblastoma cells were transfected with 160Q, and the control wild-type neuroblastoma cells were transfected with 20Q htt for 24 h and later treated with luteolin. Cell viability was determined by MTT and PI staining in both groups, while western blotting was used to evaluate caspase 3 protein expression. Aggregation formation was assessed via immunofluorescence microscopy. Also, western blotting was utilized to measure the protein expression of mutant htt aggregated and soluble protein, Nrf2 and HO-1. The impact of Nrf2 on luteolin-treated neuroblastoma cells was assessed using small interfering RNAs. Results: Our study reports that luteolin can protect cultured cells from mutant huntingtin cytotoxicity, evidenced by increased viability and decreased apoptosis. Also, luteolin reduced the accumulation of soluble and insoluble mutant huntingtin aggregates in mutant htt neuroblastoma cells transfected with 160Q compared to the control wild-type. The mutant htt aggregate reduction mediated by luteolin appeared to be independent of the Nrf2 -HO-1 antioxidant pathway. Conclusion: Luteolin presents a new potential therapeutic and protective agent for the treatment and decreasing the cytotoxicity in neurodegenerative diseases such as Huntington's disease.

Aducanumab Therapy to Treat Alzheimer's Disease: A Narrative Review.

Background: Aducanumab, a new monoclonal antibody that targets ß-amyloid aggregates, has been granted conditional approval by the U.S. FDA for treatment of mild Alzheimer's disease (AD). The approval of this drug without a confirmed significant clinical impact has resulted in several debates. Objective: In this narrative review, aducanumab approval-related controversy, the drug's pharmacokinetics and pharmacodynamic characteristics, evidence from the efficacy and safety trials of aducanumab, implications of the drug approval, and the future directions in the management of patients with AD are summarized. Methods: Using relevant keywords, Google Scholar, Web of Science, and MEDLINE databases and manufacturer's website were searched. Results: Infusion of aducanumab at a higher dose resulted in a modest slowing of cognitive decline among patients with mild cognitive impairment or early-onset AD dementia. The drug however can cause amyloid-related imaging abnormalities. Due to modest impact on cognition, the use of this drug by patients with AD will most likely be limited. The manufacturer is required to run an extended phase IIIb trial to verify the benefit of this drug. Access to therapy requires a careful selection of patients and periodic monitoring to ensure the optimal use of the drug. Conclusion: Despite the limitations, aducanumab is the first disease-modifying therapy approved for the treatment of AD. Aducanumab addresses a part of the pathogenesis of AD; therefore, drugs that can act on multiple targets are needed. In addition, the search for preventive strategies, validated plasma-based assays, and newer drugs for AD, which are effective, safe, convenient, and affordable, is vital.

Umbrella Review on Non-Statin Lipid-Lowering Therapy.

OBJECTIVES: The main aim of this review was to summarize current evidence on approved and emerging non-statin lipid-lowering therapies. METHODS AND MATERIALS: Recent literature on U.S. FDA approved non-statin lipid-lowering therapies and evolving lipid-lowering drugs currently under development was reviewed. RESULTS AND DISCUSSION: In the past 20 years, the emergence of non-statin cholesterol-lowering drugs has changed the landscape of dyslipidemia management. Food and Drug Administration approval of non-statin lipid-lowering therapies such as ezetimibe, proprotein convertase subtilisin/Kexin type 9 (PCSK9) inhibitors (evolocumab, alirocumab), bempedoic acid and combination of bempedoic acid and ezetimibe, evinacumab and other triglyceride-lowering agents (eg, icosapent ethyl) has emerged. The European Commission has also recently approved inclisiran for treatment of hypercholesterolemia and mixed hypercholesterolemia even though FDA has put the approval of this drug on hold. Recent guidelines have incorporated PCSK9 inhibitors to treat patients with primary hyperlipidemia and patients with very high-risk ASCVD, who could not achieve adequate lipid-lowering with combination therapy of maximally tolerated statin and ezetimibe. Icosapent ethyl use as an adjunct therapy to statins is also recommended to reduce the risk of ASCVD in patients with hypertriglyceridemia. CONCLUSION: Despite cost limitations, the uptake of PCSK9 inhibitors is increasing. Approval of bempedoic acid alone or in combination with ezetimibe has provided additional oral lipid-lowering drug alternatives to ezetimibe. Various lipid-lowering drug targets are under investigation.

Assessment of Predicted Rate and Associated Factors of Dabigatran-induced Bleeding Events in Malaysian Patients with Non-Valvular Atrial Fibrillation.

PURPOSE: To assess the predicted rate and the factors associated with bleeding events among patients with non-valvular atrial fibrillation (NVAF) receiving dabigatran therapy. METHODS: This retrospective cohort study includes adult patients of two tertiary hospitals in Malaysia. Potential study subjects were identified using pharmacy supply database or novel oral anticoagulant (NOAC) registry. Demographics, clinical data and laboratory test results were extracted from the medical records of the patients or electronic databases. The main outcome measure is the occurrence of a bleeding event. Bleeding events were classified into major bleeding, clinically relevant non-major bleeding, or minor bleeding, according to the International Society on Thrombosis and Haemostasis criteria. We consider clinically relevant non-major bleeding events or major bleeding events as clinically relevant bleeding events. An occurrence of any bleeding event was recorded from the initiation of NOAC therapy until the death of a patient, or the date of permanent discontinuation of NOAC use, or the last day of data collection. The predicted rate of dabigatran-induced bleeding events per 100 patient-years was estimated. RESULTS: During a median follow-up period of 18 months, 73 patients experienced 90 bleeding events. Among these patients, 25 including 4 fatal cases, experienced major bleeding events. The predicted rate per 100 patient-years of follow-up of any bleeding events was 9.0 [95% CI 6.9 to 11.1]; clinically relevant bleeding events 6.0 [95% CI 4.8 to 8.3], and major bleeding events 3.0 [95% CI 1.9 to 4.2]. The independent risk factor for clinically relevant bleeding events is prior bleeding. While prior bleeding or congestive heart failure is linked with major bleeding events. CONCLUSIONS: The predicted rate for dabigatran-induced major bleeding episodes is low but these adverse events carry a high fatality risk. Preventive measures should target older patients who have prior bleeding or congestive heart failure. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Factors associated with abrupt discontinuation of dabigatran therapy in patients with atrial fibrillation in Malaysia.

Background Oral anticoagulant therapy is indicated for the prevention of stroke or other thromboembolic events. Premature discontinuation of oral anticoagulants may increase the risk of thromboembolism resulting in adverse sequelae. There are sparse data on the prevalence and the predictors of dabigatran discontinuation in Malaysian patients with atrial fibrillation. Objectives Determine the reasons and identify associated factors for abrupt discontinuation of dabigatran, assess the switching pattern and the occurrence of thromboembolic events after dabigatran discontinuation. Setting A university-affiliated tertiary hospital in Kuala Lumpur, Malaysia. Methods The clinical and demographic data of a cohort who were initiated with dabigatran between 2010 and 2012 at the University of Malaya Medical Centre were reviewed until the date of death or on 31st December 2013. Those patients who discontinued dabigatran were further followed up until 31st December 2015 to determine the occurrence of any thromboembolic event. Main outcome measure Permanent discontinuation of dabigatran for more than 8 weeks. Results 26 (14 %) of a cohort of 192 patients discontinued dabigatran therapy during a median follow-up period of 20 (range 3-45) months. About one-half of the discontinuation occurred within the first 6 months of dabigatran use. The three most cited reasons for discontinuation are bleeding events (19 %), high out-of-pocket drug payment (19 %) and cardioversion (19 %). Heart failure [adjusted odds ratio 3.699 (95 % confidence interval 1.393-9.574)] or chronic kidney disease [adjusted odds ratio 5.211 (95 % confidence interval 1.068-23.475)] were found to be independent risk factors for abrupt dabigatran discontinuation. Patients who discontinued dabigatran received warfarin (38 %), antiplatelet agents (16 %) or no alternative antithrombotic therapy (46 %). Five of the 26 patients who discontinued dabigatran developed an ischaemic stroke within 3-34 months after discontinuation. Conclusion Abrupt dabigatran discontinuation without an alternative oral anticoagulant increases the risk of thromboembolic events. As adverse drug events and renal impairment contribute substantially to the premature discontinuation of dabigatran, it is important to identify and monitor patients at risk to reduce dabigatran discontinuation rate especially during the first six months of dabigatran therapy.