Sampling time and indications appropriateness for therapeutically monitored drugs at a teaching university hospital in Oman.

OBJECTIVE: To evaluate prospectively the appropriateness of indications, sampling time and outcome of TDM requests at a teaching university hospital in Oman. METHODS: A prospective cross-sectional study was conducted over a four months period; October 2013-January 2014 at the Sultan Qaboos University Hospital (SQUH), an 855 bed university teaching hospital. Appropriateness criteria for indications and sampling time were defined a priori. The evaluated drug's requests were for carbamazepine, phenytoin, phenobarbital, valproic acid, digoxin, gentamicin, amikacin, vancomycin, tobramycin, theophylline, lithium, and cyclosporine. RESULTS: Of 733 evaluated TDM requisitions, the majority were for antibiotics (75.0%) followed by antiepileptics (10.5%) and cyclosporine (8.9%). Most of the requests had appropriate indication (78.2%), however, only 28.5% had appropriate sampling time. RESULTS were applied by dosage adjustments in 65.8% of requests and some of the inappropriately sampled requests (15.3%) were used as a basis for modifying the dosage regimen. Of all the reported plasma concentrations 42.3%, 41.2%, and 16.5% were within, below and above the reference range, respectively. CONCLUSION: TDM service is much less than optimal in SQUH. A lot of effort needs to be carried out to improve TDM use in the developing countries as adjusting the doses on results that are based on wrong sampling time might expose patients to toxicity or therapeutic failure.

Metabolic dysfunction-associated fatty liver disease: current therapeutic strategies.

The definition of "Metabolic Associated Fatty Liver Disease - MAFLD" has replaced the previous definition of Nonalcoholic Fatty Liver Disease (NAFLD), because cardiometabolic criteria have been added for the prevention of cardiological risk in these patients. This definition leads to an in-depth study of the bidirectional relationships between hepatic steatosis, Type 2 Diabetes Mellitus (T2DM), Cardiovascular Disease (CVD) and/or their complications. Lifestyle modification, which includes correct nutrition combined with regular physical activity, represents the therapeutic cornerstone of MAFLD. When therapy is required, there is not clear accord on how to proceed in an optimal way with nutraceutical or pharmacological therapy. Numerous studies have attempted to identify nutraceuticals with a significant benefit on metabolic alterations and which contribute to the improvement of hepatic steatosis. Several evidences are supporting the use of silymarin, berberine, curcumin, Nigella sativa, Ascophyllum nodosum, and Fucus vesiculosus, vitamin E, coenzyme Q10 and Omega-3. However, more evidence regarding the long-term efficacy and safety of these compounds are required. There is numerous evidence that highlights the use of therapies such as incretins or the use of Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) inhibitors or other similar therapies which, by assisting existing therapies for pathologies such as diabetes, hypertension, insulin resistance, have given a breakthrough in prevention and the reduction of cardiometabolic risk. This review gave an overview of the current therapeutic strategies that are expected to aid in the treatment and prevention of MAFLD.

The Gulf Achievement of Cholesterol Targets in Out-Patients Study (GULF ACTION): Design, Rationale, and Preliminary Results.

AIM: To assess the current dyslipidemia management in the Arabian Gulf region by describing the demographics, study design, and preliminary results of out-patients who achieved low-density lipoprotein cholesterol (LDL-C) goals at the time of the survey. BACKGROUND: The Arabian Gulf population is at high risk for atherosclerotic cardiovascular disease at younger ages. There is no up-to-date study regarding dyslipidemia management in this region, especially given the recent guideline-recommended LDL-C targets. OBJECTIVE: Up-to-date comprehensive assessment of the current dyslipidemia management in the Arabian Gulf region, particularly in view of the recent evidence of the additive beneficial effects of ezetimibe and proprotein convertase subtilisin/kexin-9 (PCSK-9) inhibitors on LDL-C levels and cardiovascular outcomes. METHODS: The Gulf Achievement of Cholesterol Targets in Out-Patients (GULF ACTION) is an ongoing national observational longitudinal registry of 3000 patients. In this study, adults ≥18 years on lipidlowering drugs for over three months from out-patients of five Gulf countries were enrolled between January 2020 and May 2022 with planned six-month and one-year follow-ups. RESULTS: Of the 1015 patients enrolled, 71% were male, aged 57.9±12 years. In addition, 68% had atherosclerotic cardiovascular disease (ASCVD), 25% of these patients achieved the LDL-C target, and 26% of the cohort were treated using combined lipid-lowering drugs, including statins. CONCLUSION: The preliminary results of this cohort revealed that only one-fourth of ASCVD patients achieved LDL-C targets. Therefore, GULF ACTION shall improve our understanding of current dyslipidemia management and "guideline gaps" in the Arabian Gulf region.

A Comprehensive Neuropsychological Study of Familial Hypercholesterolemia and Its Relationship with Psychosocial Functioning: A Biopsychosocial Approach.

BACKGROUND: Over the past few years, there has been an increasing interest in viewing the diagnosis of familial hypercholesterolemia (FH) through the lens of the biopsychosocial model. However, other than a few epidemiological surveys, there is a dearth of studies from emerging economies that have examined FH using the biological, psychological, and socio-environmental facets of the aforementioned model. AIM. The three aims of the current study were as follows: (i) to examine the psychosocial status among patients with genetically confirmed FH, (ii) to compare their intellectual capacity and cognitive outcomes with a reference group, and (iii) to examine the relationship between health literacy and cognitive functioning. METHOD: Consecutive FH patients referred to the lipid clinic at a tertiary care center for an expert opinion were recruited into this study conducted from September 2019 to March 2020. Information regarding psychosocial functioning, health literacy, quality of life, and affective ranges was surveyed. Indices of current reasoning ability and cognition (attention and concentration, memory, and executive functioning) were compared with a socio-demographically-matched reference group. The current hypothesis also explored the impact of FH on health literacy and cognition. RESULT: A total of 70 participants out of 106 (response rate: 66.0%) initially agreed to participate. However, 18 out of 70 dropped out of the study, yielding a final total of 52 FH patients. With 27 (51.9%) males and 25 (48.1%) females, the mean participant age stood at 37.2 years (SD = 9.2), ranging from 21 to 52 years of age. In the psychosocial data, thirty-two percent (n = 17) of them had anxiety (HADS ≥ 8), and twenty-five percent (n = 13) had depressive symptoms (HADS ≥ 8). The performance of the FH patients was significantly impaired compared to the control group on the indices of current reasoning ability and all domains of cognitive functioning. In the univariate analysis conducted to compare cognitive functioning with health literacy status, only indices of attention and concentration emerged as being significant. CONCLUSION: The current study indicates that the FH population is marked with impediments in biopsychosocial functioning, including indices tapping into the integrity of health literacy, quality of life, affective ranges, and higher functioning such as cognition and current reasoning ability when compared with a socio-demographically-matched reference group. The present results support the hypothesis that chronic diseases vis-à-vis the sequelae of coronary artery disease can potentially impede biopsychosocial functioning.

Consensus clinical recommendations for the management of plasma lipid disorders in the Middle East: 2021 update.

BACKGROUND AND AIMS: Disorders of plasma lipids remain key risk factors for the development of atherosclerotic cardiovascular disease (ASCVD) in the Middle East and are estimated to increase more dramatically in the next decade than in any other global region except Africa. This statement is an update to the 2016 consensus clinical recommendations for the management of plasma lipid disorders in the Middle East, following the evaluation of newer cholesterol-lowering agents in randomised controlled cardiovascular outcome trials, as well as the publication of revised international guidelines. METHODS: A multidisciplinary panel of regional experts was convened to update the consensus clinical recommendations for the management of plasma lipids in the Middle East. The recommendations constructed in 2016 were reviewed against emerging research since publication. RESULTS: Newly developed Middle East ASCVD risk categories were established using the multiple risk group categories from the recently updated international guidelines and the epidemiological evidence from the Gulf Region. These consensus recommendations support a more intensive reduction of LDL-C across cardiovascular risk categories. Alongside low-density lipoprotein cholesterol, we recommend non-high-density lipoprotein cholesterol as a primary treatment target. Lifestyle modifications remain the first-line treatment recommendation for all patients. The first-line pharmacological treatment in patients with dyslipidaemia is statin therapy, with a number of second-line agents available. The selection of a second lipid-lowering agent for combination therapy with statin should be based on the lipid-lowering target of the patient. Guidance is also provided on the management of underlying conditions and special populations; of particular pertinence in the region are familial hypercholesterolaemia, diabetes and metabolic dyslipidaemia. New therapies have emerged from research that found positive outcomes in reducing low-density lipoprotein cholesterol levels. The initial results of these newly researched drugs strongly indicate their inclusion as future therapies in dyslipidaemia management in the Middle East. CONCLUSIONS: These updated consensus clinical recommendations provide practicing clinicians with comprehensive, region-specific guidance to improve the detection and management of plasma lipid disorders in patients in the Middle East.

Metabolic Side Effects of Olanzapine in Patients With Psychotic Disorders in Oman: A Retrospective Cohort Study.

We evaluated the impact of olanzapine on metabolic changes in patients with psychotic disorders. This was a retrospective cohort study involving patients prescribed olanzapine and attending Sultan Qaboos University Hospital (Muscat, Oman). Patients were followed up retrospectively from March 2006 until April 2021. Cardiovascular treatment targets were evaluated as per the 2019 European Society of Cardiology guidelines. We enrolled 253 patients (mean age: 40±17 years). Olanzapine monotherapy was associated with increased body weight (+8 kg; 95% confidence interval (CI): 6-9; P < .001), body mass index (+3 kg/m2; 95% CI: 2-4; P < .001), total cholesterol (+.4 mmol/L; 95% CI: .3-.5; P < .001), low-density lipoprotein cholesterol (LDL-C) (+.3 mmol/L; 95% CI: .1-.4; P < .001), fasting triglycerides (+.2 mmol/L; 95% CI: .1-.3; P<.001), fasting glucose (+.6 mmol/L; 95% CI: .4-.7; P< .001), HbA1c (+.3%; 95% CI: .2-.4; P < .001), systolic blood pressure (BP) (+9 mmHg; 95% CI: 6-12; P < .001) and diastolic BP (+4 mmHg; 95% CI: 2-6; P < .001) levels. Cardiovascular therapeutic goals were attained in 38% (n = 97), 61% (n = 154), 71% (n = 180), and 59% (n = 150) for LDL-C, non-high-density lipoprotein cholesterol, triglycerides, and BP, respectively. Olanzapine was associated with adverse metabolic changes. Therefore, many patients were not at their target cardiovascular treatment goals.

The Genetic Spectrum of Familial Hypertriglyceridemia in Oman.

Familial hypertriglyceridemia (F-HTG) is an autosomal disorder that causes severe elevation of serum triglyceride levels. It is caused by genetic alterations in LPL, APOC2, APOA5, LMF1, and GPIHBP1 genes. The mutation spectrum of F-HTG in Arabic populations is limited. Here, we report the genetic spectrum of six families of F-HTG of Arab ancestry in Oman. Methods: six Omani families affected with triglyceride levels >11.2 mmol/L were included in this study. Ampli-Seq sequencing of the selected gene panels was performed. Whole-exome sequencing and copy number variant analysis were also performed in cases with negative exome results. Three novel pathogenic missense variants in the LPL gene were identified, p.M328T, p.H229L, and p.S286G, along with a novel splice variant c.1322+15T > G. The LPL p.H229L variant existed in double heterozygous mutation with the APOA5 gene p.V153M variant. One family had a homozygous mutation in the LMF1 gene (c.G107A; p.G36D) and a heterozygous mutation in the LPL gene (c.G106A; p.D36N). All affected subjects did not have a serum deficiency of LPL protein. Genetic analysis in one family did not show any pathogenic variants even after whole-exome sequencing. These novel LPL and APOA5 mutations are not reported in other ethnic groups. This suggests that patients with F-HTG in Oman have a founder effect and are genetically unique. This warrants further analysis of patients of F-HTG in the Middle East for preventative and counseling purposes to limit the spread of the disease in a population of high consanguinity.

Antihypertensive Drugs and Perinatal Outcomes in Hypertensive Women Attending a Specialized Tertiary Hospital.

Objectives: We sought to identify the most commonly used antihypertensive medications in pregnant women and to determine the impact of these medications on perinatal (maternal and fetal) outcomes. Methods: The medical records of 484 hypertensive pregnant women who attended a tertiary university hospital during the study period were retrospectively evaluated for eligibility. Singleton pregnancies of women on antihypertensive medications and who delivered in the hospital were included in the study. Results: A total of 210 women (mean age of 32.4±5.6 years and mean body mass index of 34.0±8.1 kg/m2) were eligible for inclusion in the study. The most prevalent subtype of hypertension was preeclampsia (41.4%). Low birth weight (LBW), preterm delivery (PTD), intrauterine growth restriction (IUGR), small for gestational age (SGA), respiratory distress syndrome, and neonatal care unit admissions were significantly higher in women with preeclampsia than in the women with other types of hypertension. Labetalol was the most commonly prescribed antihypertensive drug. There were 101 (48.1%) women on combined therapy. LBW, PTD, IUGR, SGA, respiratory distress syndrome, absent end diastolic flow, neonatal care unit admission, preeclampsia, and high dependency unit admissions of mothers were significantly higher in the women who received combined therapy. Conclusions: Labetalol was the most commonly prescribed antihypertensive drug in this cohort, and women on combined antihypertensive medications had significantly higher maternal and fetal complications. A larger prospective study including hypertensive women with or without antihypertensive medications in more than one center is needed to evaluate the effect of these drugs on perinatal outcomes.

The Achievement of Non-high-density Lipoprotein Cholesterol Target in Patients with Very High Atherosclerotic Cardiovascular Disease Risk Stratified by Triglyceride Levels Despite Statin-controlled Low-density Lipoprotein Cholesterol.

Objectives: We sought to estimate the percentage achievements of non-high-density lipoprotein cholesterol (non-HDL-C) target in patients with very high atheroscleroticcardiovascular diseases (ASCVD) risk stratified by triglyceride (TG) levels despite statin-controlled low-density lipoprotein cholesterol (LDL-C) in the Centralized Pan-Middle East Survey on the under treatment of hypercholesterolemia. Methods: The non-HDL-C target achievement in patients with diabetes mellites (DM) and patients with established ASCVD was defined according to European Society of Cardiology and European Atherosclerosis Society 2019 guidelines for managing dyslipidemia. Patients were stratified to controlled LDL-C defined as < 70 mg/dL (< 1.8 mmol/L) with normal TG < 150 mg/dL (< 1.7 mmol/L) and high TG between 150-400 mg/dL (1.7-4.5 mmol/L). Results: The mean age of our cohort was 58.0±11.0 years, 6.8% (n = 717) were male, 9.7% (104) were smokers, and 48.4% (n = 518) had body mass index of ≥ 30 kg/m2. Those with high TG levels male (76.5% vs. 63.8%; p < 0.001), smokers (16.1% vs. 7.7%; p < 0.001), have metabolic syndrome (77.6% vs. 17.1%; p < 0.001), and low HDL-C levels (79.2% vs. 49.4%; p < 0.001). The majority (93.9%, n = 1008) were on statins (atorvastatin and rosuvastatin) with only 2.2% (n = 24) on the combined statins plus fenofibrate/gemfibrozil. Only 27.4% (n = 294) of patients had non-HDL-C goal attainment. Goal attainment rates in patients with diabetes (3.1% vs. 34,4%; p < 0.001), coronary artery disease (CAD) (2.4% vs. 37.9%; p < 0.001), diabetes plus CAD (0% vs. 40.0%; p < 0.001), and CVD (0% vs. 30.0%; p = 0.048) were significantly lower in those with higher TG levels. Conclusions: A large proportion of statin-controlled LDL-C diabetic patients and patients with established ASCVD with high TGs did not achieve the non-HDL-C target. Our study did not demonstrate an association between ASCVD and high TG levels; and therefore, a follow-up study is highly required to assess long-term ASCVD outcomes in this cohort.

Familial Hypercholesterolemia in the Arabian Gulf Region: Clinical results of the Gulf FH Registry.

BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is a common autosomal dominant disorder that can result in premature atherosclerotic cardiovascular disease (ASCVD). Limited data are available worldwide about the prevalence and management of FH. Here, we aimed to estimate the prevalence and management of patients with FH in five Arabian Gulf countries (Saudi Arabia, Oman, United Arab Emirates, Kuwait, and Bahrain). METHODS: The multicentre, multinational Gulf FH registry included adults (≥18 years old) recruited from outpatient clinics in 14 tertiary-care centres across five Arabian Gulf countries over the last five years. The Gulf FH registry had four phases: 1- screening, 2- classification based on the Dutch Lipid Clinic Network, 3- genetic testing, and 4- follow-up. RESULTS: Among 34,366 screened patient records, 3713 patients had suspected FH (mean age: 49±15 years; 52% women) and 306 patients had definite or probable FH. Thus, the estimated FH prevalence was 0.9% (1:112). Treatments included high-intensity statin therapy (34%), ezetimibe (10%), and proprotein convertase subtilisin/kexin type 9 inhibitors (0.4%). Targets for low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol were achieved by 12% and 30%, respectively, of patients at high ASCVD risk, and by 3% and 6%, respectively, of patients at very high ASCVD risk (p <0.001; for both comparisons). CONCLUSIONS: This snap-shot study was the first to show the high estimated prevalence of FH in the Arabian Gulf region (about 3-fold the estimated prevalence worldwide), and is a "call-to-action" for further confirmation in future population studies. The small proportions of patients that achieved target LDL-C values implied that health care policies need to implement nation-wide screening, raise FH awareness, and improve management strategies for FH.