Predicting the course of kidney disease in individuals with both type 1 and type 2 diabetes mellitus (DM) is a significant clinical and policy challenge. In several regions, DM is now the leading ...cause of end-stage renal disease. The aim of this study to identify both modifiable and non-modifiable risk factors, along with clinical markers and coexisting conditions, that increase the likelihood of stage 3-5 chronic kidney disease (CKD) development in individuals with type 2 DM in the United Arab Emirates (UAE). This was a single-center retrospective cohort study based on data derived from electronic medical records of UAE patients with DM who were registered at outpatient clinics at Tawam Hospital in Al Ain, UAE, between January 2011 and December 2021. Type 2 DM patients aged ≥ 18 years who had serum HbA1c levels ≥ 6.5% were included in the study. Patients with type 1 DM, who had undergone permanent renal replacement therapy, who had under 1 year of follow-up, or who had missing or incomplete data were excluded from the study. Factors associated with diabetic patients developing stage 3-5 CKD were identified through Cox regression analysis and a fine and gray competing risk model to account for competing events that could potentially hinder the development of CKD. A total of 1003 patients were recruited for the study. The mean age of the study cohort at baseline was 70.6 ± 28.2 years. Several factors were found to increase the risk of developing stage 3-5 CKD: advancing age (HR 1.005, 95% CI 1.002-1.009, p = 0.026), a history of hypertension (HR 1.69, 95% CI 1.032-2.8, p = 0.037), a history of heart disease (HR 1.49, 95% CI 1.16-1.92, p = 0.002), elevated levels of serum creatinine (HR 1.006, 95% CI 1.002-1.010, p = 0.003), decreased levels of estimated glomerular filtration rate (eGFR) (HR 0.943, 95% CI, 0.938-0.947; p < 0.001), and the use of beta-blockers (HR 139, 95% CI 112-173, p = 0.003). Implementing preventative measures, initiating early interventions, and developing personalized care plans tailored to address specific risk factors are imperative for reducing the impact of CKD. Additionally, the unforeseen findings related to eGFR highlight the ongoing need for research to deepen our understanding of the complexities of kidney disease.
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Background
Efficacy of clopidogrel may be diminished due to either co-administration of proton pump inhibitors or carrying
CYP2C19
loss-of-function alleles. However, patients may be at greater risk ...of major adverse cardiovascular events if taking clopidogrel together with proton pump inhibitors and also inherited the
CYP2C19
loss-of-function alleles which may cause further reduction of clopidogrel efficacy. This is due to the cumulative effects of drug-drug interactions and drug-gene interactions collectively referred to as multifactorial drug-gene interactions.
Aim of the review
The aim of this analysis was to estimate aggregated risk of major adverse cardiovascular events for either coronary heart disease or stroke patients with multifactorial drug-gene interactions versus clopidogrel alone with or without drug-gene interactions.
Methods
Literatures were searched using different resources based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Meta-analysis was performed using RevMan software following either fixed/random effects model based on the levels of heterogeneity. A
p
value < 0.05 (2-sided) was considered statistically significant.
Results
In total, five studies consisting 8,802 patients of coronary artery diseases or stroke were included in this meta-analysis in which 3,767 were prescribed clopidogrel alone, 1,931 were concomitantly taking clopidogrel and PPIs, 2,146 were carrying
CYP2C19
loss-of-function alleles and 958 were taking both clopidogrel and proton pump inhibitors while also carrying
CYP2C19
loss-of-function alleles. It was found that patients with multifactorial drug-gene interactions were associated with significantly increased risk of major adverse cardiovascular events compared to those taking clopidogrel alone without
CYP2C19
loss-of-function alleles (12% vs. 5.8%; RR 1.73; 95% CI 1.12–2.67;
p
= 0.01). Patients with multifactorial drug-gene interactions were also associated with significantly increased risk of major adverse cardiovascular events compared to drug-gene interactions (RR 1.63; 95% CI 1.31–2.03;
p
< 0.0001). Patients taking clopidogrel with proton pump inhibitors were also associated with 35% significantly increased risk of major adverse cardiovascular events compared to those taking only clopidogrel (RR 1.35; 95% CI 1.11–1.65;
p
= 0.003).
Conclusion
Patients inheriting
CYP2C19
loss-of-function alleles have significantly increased risk of major adverse cardiovascular events when taking clopidogrel and proton pump inhibitors concurrently.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Substantial efforts are currently focused on investigating and developing new multidrug-resistant tuberculosis (MDR-TB) drugs and diagnostic methods. In Yemen, however, the evaluation of ...health-related quality of life (HRQoL) and the effect of current MDR-TB treatment on the QoL are commonly ignored. This study evaluated the HRQoL during and after treatment and identified the risk factors that are predictive of HRQoL score differences.
A prospective cohort study was conducted in four of the five main MDR-TB centres in Yemen. The patients confirmed with MDR-TB completed the SF-36 V2 survey at the beginning of treatment, end of treatment (continous phase) and at the 1 year follow-up after completing treatment. A total normal base score (NBS) of < 47 reflects impairment of functions, whereas a mental component summary (MCS) score of < 43 indicates a risk of depression.
At the beginning of treatment, the mean scores for all health domains were < 47 NBS points (PF = 40.7, RP = 16.1, BP = 21.6, GH = 28.3, VT = 14.55, SF = 25.9, RE = 13.7, and MH = 14.7). At the completion of treatment, all eight health domains increase compare to beginning of treatment (PF = 59.3, RP = 31.1, BP = 40.9, GH = 48.5, VT = 30.5, SF = 46.6, RE =26.6 & MH = 27.7), but a follow-up duration of 1 year after completing treatment showed decreased NBS points in all domains (PF = 51.5, RP = 30.6, BP = 39.1, GH = 47.8, VT = 30.2, SF = 43.7, RE =26.4 & MH = 27.2). Age, history of streptomycin use, baseline lung cavity, marital status and length of sickness before MDR-TB diagnosis were predictive of in PCS score differences, whereas, age, smoking, baseline lung cavity, stigma, residence, marital status and length of sickness before MDR-TB diagnosis were predictive of MCS scores differences.
The length of sickness before DR-TB diagnosis was found to be predictive of the trends in both PCS and MCS scores. Despite the positive outcome of MDR-TB treatment, the low HRQoL scores obtained for all heath domains and especially for mental health reflect a high depression status of patients even after 1 year of completing therapy. Moreover, the poor HRQoL, particularly regarding mental health, of study participants at the end of treatment demands the need for urgent attention from national tuberculosis control programme managers. Therefore, the Yemen Ministry of Health and the National Tuberculosis Control Programme should implement an intervention programme to enhance HRQoL at the end of treatment to avoid any further negative consequences of MDRTB in patients after treatment. Moreover, The HRQoL data of patients with MDR-TB must be collected at the different stages of MDR-TB treatment to provide an additional parameter for assessing the effectiveness of the treatment programme.
SNOYEM 1452. Registered 01 February 2013.
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The most effective antiplatelet treatments for acute coronary syndrome (ACS) patients carrying CYP2C19 loss-of-function (LoF) alleles undergoing percutaneous coronary intervention (PCI) is still ...debating and conflicting. It was aimed to compare the efficacy and safety endpoints for these patients treated with alternative P2Y12 receptor blockers (e.g. prasugrel or ticagrelor) against clopidogrel. Literature was searched in PubMed, Cochrane library, Synapse and 1000 Genomes databases following PRISMA guidelines for identifying relevant studies. Aggregated risk was estimated by RevMan software using either fixed/random-effects models where P values<0.05 (two-sided) were considered statistically significant. Nine studies comprising 16,132 ACS patients undergoing PCI were included in this analysis in which 2,746 and 2,640 patients were in the CYP2C19 LoF clopidogrel and alternatives treatment group, respectively. It was demonstrated that patients treated with prasugrel or ticagrelor significantly reduced the risk of MACEs (RR 0.58; 95% CI 0.45-0.76; P<0.0001) as compared to patients with clopidogrel where both groups carrying CYP2C19 LoF alleles. Subgroup analysis showed that prasugrel or ticagrelor significantly reduced the risk of cardiovascular death (RR 0.44; 95% CI: 0.25-0.74; P=0.002) and MI (RR 0.60; 95% CI: 0.44-0.81; P=0.0008) while other clinical outcomes were not found statistically significant between these two groups; stroke (RR 0.77; 95% CI: 0.43-1.38; P =0.39), stent thrombosis (RR 0.67; 95% CI: 0.38-1.18; P =0.17), unstable angina (RR 0.55; 95% CI: 0.13-2.33; P =0.42), revascularisation (RR 0.79; 95% CI: 0.
28
-2.24; P=0.66). Bleeding events were not found significantly different between these groups (RR 1.06; 95% CI: 0.88-1.28; P=0.55). Considering efficacy and safety, alternative antiplatelets (e.g. prasugrel or ticagrelor) may be regarded as better treatment option as compared to clopidogrel for ACS patients undergoing PCI.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background Cough is recognized as an important troublesome symptom in the diagnosis and monitoring of asthma. Asthma control is thought to be determined by the degree of airway inflammation and ...hyperresponsiveness but how these factors relate to cough frequency is unclear. The goal of this study was to investigate the relationships between objective cough frequency, disease control, airflow obstruction, and airway inflammation in asthma. Methods Participants with asthma underwent 24-h ambulatory cough monitoring and assessment of exhaled nitric oxide, spirometry, methacholine challenge, and sputum induction (cell counts and inflammatory mediator levels). Asthma control was assessed by using the Global Initiative for Asthma (GINA) classification and the Asthma Control Questionnaire (ACQ). The number of cough sounds was manually counted and expressed as coughs per hour (c/h). Results Eighty-nine subjects with asthma (mean ± SD age, 57 ± 12 years; 57% female) were recruited. According to GINA criteria, 18 (20.2%) patients were classified as controlled, 39 (43.8%) partly controlled, and 32 (36%) uncontrolled; the median ACQ score was 1 (range, 0.0-4.4). The 6-item ACQ correlated with 24-h cough frequency ( r = 0.40; P < .001), and patients with uncontrolled asthma (per GINA criteria) had higher median 24-h cough frequency (4.2 c/h; range, 0.3-27.6) compared with partially controlled asthma (1.8 c/h; range, 0.2-25.3; P = .01) and controlled asthma (1.7 c/h; range, 0.3-6.7; P = .002). Measures of airway inflammation were not significantly different between GINA categories and were not correlated with ACQ. In multivariate analyses, increasing cough frequency and worsening FEV1 independently predicted measures of asthma control. Conclusions Ambulatory cough frequency monitoring provides an objective assessment of asthma symptoms that correlates with standard measures of asthma control but not airflow obstruction or airway inflammation. Moreover, cough frequency and airflow obstruction represent independent dimensions of asthma control.
Asthma is a heterogeneous lung disease, usually characterised by chronic airway inflammation. Although evidence-based treatments are available in most countries, asthma control remains suboptimal, ...and asthma-related deaths continue to be an ongoing concern. Generally, it is believed that between 50 to 75% of patients with asthma can be considered as having mild asthma.Previous versions of Global Initiative for Asthma (GINA) suggested that mild asthma in adults can be well managed with either reliever medications, for example, short-acting beta
agonists (SABA) alone or with the additional use of controllers such as regular low-dose inhaled corticosteroids (ICS). Given the low frequency or non-bothersome nature of symptoms in mild asthma, patients' adherence towards their controller medications, especially to ICS is usually not satisfactory. Such patients often rely on SABA alone to relieve symptoms, which may contribute to SABA over-reliance. Overuse of relievers such as SABAs has been associated with poor asthma outcomes, such as exacerbations and even deaths. The new GINA 2019 asthma treatment recommendations represent significant shifts in asthma management at Steps 1 and 2 of the 5 treatment steps. The report acknowledges an emerging body of evidence suggesting the non-safety of SABAs overuse in the absence of concomitant controller medications, therefore does not support SABA-only therapy in mild asthma and has included new off-label recommendations such as symptom-driven (as-needed) low dose ICS-formoterol and "low dose ICS taken whenever SABA is taken".The GINA 2019 report highlights significant updates in mild asthma management and these recommendations represent a clear deviation from decades of clinical practice mandating the use of symptom-driven SABA treatment alone in those with mild asthma. While the new inclusions of strategies such as symptom-driven (as-needed) ICS-formoterol and "ICS taken whenever SABA is taken" are based on several key trials, data in this context are still only emergent data, with clear superiority of as needed ICS-formoterol combinations over maintenance ICS regimens yet to be established for valid endpoints. Nevertheless, current and emerging data position the clinical asthma realm at a watershed moment with imminent changes for the way we manage mild asthma likely in going forward.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background and Objective. Clozapine is a second-generation antipsychotic drug that is considered the most effective treatment for refractory schizophrenia. Several clozapine population ...pharmacokinetic models have been introduced in the last decades. Thus, a systematic review was performed (i) to compare published pharmacokinetics models and (ii) to summarize and explore identified covariates influencing the clozapine pharmacokinetics models. Methods. A search of publications for population pharmacokinetic analyses of clozapine either in healthy volunteers or patients from inception to April 2019 was conducted in PubMed and SCOPUS databases. Reviews, methodology articles, in vitro and animal studies, and noncompartmental analysis were excluded. Results. Twelve studies were included in this review. Clozapine pharmacokinetics was described as one-compartment with first-order absorption and elimination in most of the studies. Significant interindividual variations of clozapine pharmacokinetic parameters were found in most of the included studies. Age, sex, smoking status, and cytochrome P450 1A2 were found to be the most common identified covariates affecting these parameters. External validation was only performed in one study to determine the predictive performance of the models. Conclusions. Large pharmacokinetic variability remains despite the inclusion of several covariates. This can be improved by including other potential factors such as genetic polymorphisms, metabolic factors, and significant drug-drug interactions in a well-designed population pharmacokinetic model in the future, taking into account the incorporation of larger sample size and more stringent sampling strategy. External validation should also be performed to the previously published models to compare their predictive performances.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Clopidogrel is a widely-used antiplatelet drug. It is important for the treatment and prevention of coronary heart disease. Clopidogrel can effectively reduce platelet activity and therefore reduce ...stent thrombosis. However, some patients still have ischemic events despite taking the clopidogrel due to the alteration in clopidogrel metabolism attributable to various genetic and non-genetic factors. This review aims to summarise the mechanisms and causes of clopidogrel resistance (CR) and potential strategies to overcome it. This review summarised the possible effects of genetic polymorphism on CR among the Asian population, especially
, where the prevalence rate among Asians was 23.00%, 4.61%, 15.18%, respectively. The review also studied the effects of other factors and appropriate strategies used to overcome CR. Generally, CR among the Asian population was estimated at 17.2-81.6%. Therefore, our overview provides valuable insight into the causes of RC. In conclusion, understanding the prevalence of drug metabolism-related genetic polymorphism, especially
alleles, will enhance clinical understanding of racial differences in drug reactions, contributing to the development of personalised medicine in Asia.
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The World Health Organization (WHO) has reported that Yemen has a high burden of drug resistance and a worrying shortage of implemented diagnostic methods and drug treatment regimens. Therefore, in ...this study, we evaluated the risk factors associated with multidrug-resistant tuberculosis (MDR-TB) and explored the poor TB management in Yemen.
Between January 2014 and December 2016, we enrolled 135 patients with MDR-TB from drug resistance programmes at four major TB centres in Yemen for this prospective study. After exclusion of 20 patients, treatment outcomes were reported for 115 patients who attended a series of follow-ups.
A total of 115 patients with MDR-TB were analysed from the four main TB centres in Yemen. Most patients (35.2%) were from the Aden TB centre. A success rate of 77.4% was reported for TB treatment. Of the 115 patients, 69.6% were resistant to two drugs, 18.3% were resistant to three drugs, and 12.2% were resistant to four drugs. During the intensive phase of treatment, 19 patients (16.5%) reported one or more adverse events. A multivariate logistic regression analysis revealed that a baseline body weight of ≤40 kg p = 0.016; adjusted odds ratio (AOR) = 25.09, comorbidity (p = 0.049; AOR = 4.73), baseline lung cavities (p = 0.004; AOR = 15.32), and positive culture at the end of the intensive phase (p = 0.009; AOR = 8.83) were associated with the unsuccessful treatment outcomes in drug-resistant TB patients.
The success rate achieved after treatment was below the levels established by the WHO End TB Strategy (90%) and the United Nations Sustainable Development Goals (80%). Identification of risk factors associated with MDR-TB in Yemen is essential because it allows health workers to identify high-risk patients, especially in the absence of a second-line treatment or a laboratory diagnostic method. The Yemen National Tuberculosis Control Program should formulate new strategies for early detection of MDR-TB and invest in new programmes for MDR-TB management.
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This paper reports an important investigation and quantification of adulteration of sexual enhancement supplements with prescription medicines available in United Arab Emirates (UAE): tadalafil, ...sildenafil and vardenafil. A total of 158 sexual enhancement supplements were collected and analyzed in the current study. The samples were screened using REVERSE-phase liquid chromatography tandem high-resolution mass spectrometry/mass spectrometry (RP-HPLC-MS/MS). Of all sexual enhancements, 12.7% (95% CI: 7.4–18) contained undeclared sildenafil, 3.8% (95% CI: 0.78–6.81) contained undeclared tadalafil and 1.9% (95% CI: 0.25–4.05) contained undeclared vardenafil. Of all sexual enhancement supplements, 13.9% (95% CI: 8.5–19.4) contained significant concentrations of sildenafil, tadalafil or vardenafil. While the study found relatively low levels of undeclared pharmaceutical ingredients in the sexual enhancement dietary supplements available on the UAE market, it is likely that patients with ED tend to consume multiple such supplements daily, thereby exposing themselves to highly elevated cumulative levels.
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