Efficacy of clotrimazole for the management of oral candidiasis: A meta-analysis of randomized clinical trials

PurposeTo assess the efficacy and safety of topical application of clotrimazole versus others in the treatment of oropharyngeal candidiasis (OPC).MethodFour electronic databases, registries of ongoing trials, and manual search were used to identify randomized controlled trials (RCTs) that compared the efficacy of clotrimazole to other antifungal agents in patients who were clinically diagnosed with oral candidiasis up to November 1st, 2019. Primary outcomes were clinical response and mycological cure rates. Secondary outcomes include relapse rate, incidence of systemic infections, and compliance. Adverse effects were also evaluated.ResultsSixteen RCTs with a total of 1685 patients were included. Half of the eligible studies were considered at high risk of performance bias and more than a third, at high risk of reporting bias. Our analysis showed no significant difference in clinical response between clotrimazole and all other antifungal agents. However, clotrimazole was less effective in terms of mycologic cure and relapse rate. Sensitivity analysis comparing clotrimazole to other topical antifungal agents only showed no differences in clinical response, microbiologic cure or relapse. Further sensitivity analysis showed significant efficacy of fluconazole over clotrimazole.ConclusionThis meta-analysis indicated that clotrimazole is less effective than fluconazole but as effective as other topical therapies in treating OPC. Well-designed high-quality RCT is needed to validate these findings.     

Predictors of poor outcome in embolic stroke of undetermined source

Objectives:To identify the clinical predictors of death or disability at discharge.Methods:We retrospectively reviewed all ischemic stroke patients admitted to the stroke unit of King Abdulaziz Medical City, Riyadh, Saudi Arabia, from February 2016 - July 2018. We applied the Cryptogenic Stroke/ESUS International Working Group Embolic stroke of undetermined source (ESUS) criteria. We compared patients with poor outcomes (death or modified Rankin Scale [mRS] score >2) to those with favorable outcomes. Multivariate logistic regression was used to identify predictors of poor outcome. The regression model included age >60 years, gender, body mass index >25 kg/m², smoking history, comorbidities, previous ischemic/transient ischemic attack, pre-stroke mRS score >1, National Institutes of Health Stroke Scale (NIHSS) score at admission >5, pre-stroke antiplatelet use, and thrombolysis treatment.Results:Out of 147 patients who met the ESUS criteria, 28.8% had poor outcomes. Predictors of poor outcome were NIHSS score >5 (odds ratio [OR] 11.1, 95% confidence interval [CI] 4.4–28.2), pre-stroke mRS score >1 (OR 3.7, 95% CI 1.14–11.59), and age >60 years (OR 2.4, 95% CI 1.14–5.22).Conclusion:A significant proportion of ESUS patients were dead or disabled at discharge. Poor outcome was more in older patients with pre-stroke functional disability and moderate to severe stroke.

Embolic stroke of undetermined source (ESUS) is a subtype of cryptogenic ischemic stroke in which embolism is the most likely cause of stroke. According to the criteria proposed by the Cryptogenic Stroke/ESUS International Working Group, ESUS is defined as a non-lacunar infarct without (a) significant (≥50%) extracranial or intracranial atherosclerosis stenosis in arteries supplying the ischemia area, (b) major-risk cardioembolic source, and (c) any other specific etiology of stroke.1 Major sources of cardioembolic stroke are permanent or paroxysmal atrial fibrillation, intracardiac thrombus, presence of prosthetic cardiac valve, sustained atrial flutter, atrial myxoma, other cardiac tumors, mitral stenosis, recent myocardial infarction, ejection fraction <30%, valvular vegetation, and infective endocarditis.1In clinical practice, ESUS is common among patients with ischemic stroke (9–25%).2 It is associated with considerable mortality and morbidity. As many as a third of ESUS patients are either dead or lack independence after the stroke.3-6 Despite extensive literature on stroke prognosis in general, little is known about the predictors of death and disability in ESUS patients at discharge. Our aim was to identify the clinical predictors of poor outcome (death or disability) at discharge after ESUS.     

A Numerical Analysis of Resin Flow in Woven Fabrics: Effect of Local Tow Curvature on Dual-Scale Permeability

Permeability is a crucial flow parameter in liquid composite moulding (LCM), which is required to predict fibre impregnation, void formation and resin back flow. This work investigates the dual-scale (micro- and meso-) nature of permeability during resin infusion into woven fabric by incorporating the intra tow flow where the degree of local tow curvature (tow/yarn undulation) is taken into account. The mesoscopic permeability of a dual-scale porous media in a unit cell is estimated using Darcy’s law, where the Gebart analytical model is applied for the intra tow flow in longitudinal and transverse directions with respect to distinct fibre packing arrangements. The results suggest that for a low fibre volume fraction (≤42%), the degree of local curvature at the mesoscale can be neglected. However, for a high fibre volume fraction (>42%) and a higher fibre bundle curvature, the proposed model should be adopted, since the resin flow is affected by a mesoscopic tow curvature that could result in around 14% error in predicting permeability. It is shown that the permeability results of the current study are in good agreement with and in the range of the retrieved available experimental data from the literature.     

Electrocardiographic changes following intracranial haemorrhage: a retrospective cohort study

Objectives:To improve the understanding of the association between electrocardiographic (ECG) abnormalities and clinical outcomes of patients with all types of intracranial hemorrhage (ICH).Methods:A retrospective cohort study was conducted in a tertiary healthcare hospital on patients with ICH without cardiac disease or renal disease requiring dialysis. Demographic and clinical data were collected from hospital records. ECG record were obtained within 24 hours of presentation and prior to treatment. Records were interpreted for this study by a cardiologist blinded to other data.Results:Assessment of 291 patients (228 adults and 63 children) showed that subdural hemorrhage was the most common type of ICH (31.6%) followed by intraparenchymal hemorrhage (23.0%). ECG records were available for 98 patients. ECG abnormalities were most commonly nonspecific ST-segment changes (32.6%). In adults, history of neurological disease was associated with atrioventricular block (p=.004) and QTc prolongation (p=.041). Pediatric patients exhibited associations between ST-segment changes (p=.045) and sinus tachycardia (p=.027) and type of ICH. However, ECG changes were not statistically associated with clinical outcomes in adults or children.Conclusion:Significant ECG changes frequently occurred in patients with all types of ICH but did not consistently predict the outcome in this study. Close observation of patients is still recommended to detect ECG changes that could affect the treatment.

Intracranial hemorrhages (ICHs) are classified, depending on the cause, to traumatic and non-traumatic.1,2 Anatomical site further classifies ICHs into 4 main groups.1 Epidural hemorrhage (EDH) is defined as the blood collection between the bone and the dura mater.1 Subdural hemorrhages (SDH) are defined as the collection of blood beneath the dura and above the arachnoid membrane.1 Subarachnoid hemorrhages (SAH) are defined as bleeding into the space beneath the arachnoid membrane and above the pia mater.1 It commonly occurs after rupture of an aneurysm or an arteriovenous malformations in the brain.3 Non-traumatic, or spontaneous, ICHs usually involve the brain parenchyma and the subarachnoid space.2 Non-traumatic intraparenchymal hemorrhages (IPH) result from bleeding of small arteries, commonly due to hypertension; IPHs account for 10-20% of all strokes cases.4 Non-traumatic hemorrhages resulting from other causes are possible, such as hemorrhage associated with brain tumors and infections. It is well known that ICHs are associated with high mortality and morbidity rates on their own, but neurocardiac injuries following cerebrovascular events such as subarachnoid and cerebral hemorrhages worsen the clinical outcomes even more.5Stress on the nervous system can affect the heart functionally and structurally, a phenomenon known as neurogenic stress cardiomyopathy (NSC). The NSC occurs frequently in some types of ICHs such as non-traumatic SAH and non-traumatic IPH.6–8 Electrocardiographic (ECG) changes occur in 49% to 100% of patients following SAH.9,10 The most common ECG alterations following SAH and IPH are repolarization abnormalities such as QT interval prolongation, ST segment and T wave changes.11,12 Atrioventricular (AV) block, atrial flutter, and ventricular arrhythmia are the most common alterations associated with cardiac arrhythmias13 although the mechanisms are not yet fully uncovered. The catecholamine hypothesis, also known as catecholamine-mediated direct cardiac injury, is the most widely accepted proposed mechanism underlying the manifestation of NSC, whereby catecholamines directly damage cardiac tissue.6,14 The histopathological finding associated with excess catecholamine is myocardial contract band necrosis.15 A study by Naredi et al14 reported elevated levels of catecholamines in cases of SAH.The NSC may also be caused by traumatic brain injury though it has only been documented in a few case series, and no clear incidence has been reported. The standard biomarker used to diagnose NSC is serum troponin 1, which has a sensitivity of 100% and specificity of 91;6 elevated levels are associated with poor prognosis.13 New onset of ECG abnormalities have been found in 75% of patients following an acute cerebrovascular event without any previous history of heart disease.13 ECG abnormalities are associated with higher risk of poor outcomes in patients with NSC.5,7,8This study aimed to improve our understanding of the possible association between ECG abnormalities, different types of ICHs, and radiological findings. Furthermore, it aimed to identify the risk and prognostic factors associated with neurocardiac injury, which can be beneficial in identifying vulnerable patients and predicting possible adverse events.MethodsStudy design & parametersThis retrospective cohort study was conducted in a tertiary healthcare hospital and approved by the Research Ethics Committee and is in line with the principles of Helsinki Declaration. Considering the nature of this study, informed consent was not required.Search for prior related studies was done through PubMed database using the keywords “intracranial hemorrhage”, “epidural hemorrhage”, “subdural hemorrhage”, “subarachnoid hemorrhage”, “intracerebral hemorrhage”, “electrocardiographic changes”, “neurocardiac injury”, and “outcome”, separate and in combinations. Systematic reviews and meta analyses were prioritized when found, and studies as new as 2014 or newer were favored.This study was performed by reviewing the medical records of 384 patients diagnosed with ICH, admitted to the hospital between 2009 and 2017; the diagnosis was confirmed by computed tomography (CT) scans.All cases of traumatic and non-traumatic ICH were included in this study. Ninety-two patients were excluded from the study either due to unavailable clinical or radiological findings or due to a known history of heart disease, cardiac arrhythmia, or end-stage renal disease requiring dialysis. Cases of ICH related to infectious or oncological causes were excluded. Therefore, the statistical analysis included 292 patients in total; patients aged 0-18 accounted for 63 of the cases, and patients aged >18 years accounted for 229 cases.Data collected for analysis included demographic information, clinical presentations, laboratory results, and radiological data, including vital signs, electrolyte levels, concentration of serum creatinine, and blood urea nitrogen (BUN), all of which were recorded at the time of presentation. Other data associated with pathological findings including skull fractures, hydrocephalus, midline shift, neurogenic pulmonary edema, delayed cerebral ischemia, and hospital-acquired infections were also recorded. Level of consciousness was assessed by the Glasgow Coma Scale (GCS), which was documented at the time of presentation and before discharge or death. The site of hematoma was categorized as right or left hemisphere, or bilateral. Hematoma volume was calculated in cubic centimeters (cm³). Fisher grading scale and Hunt and Hess grading scale were utilized to predict the mortality and morbidity rates, vasospasm risk, and outcome in patients with SAH, for which a higher grade predicts a poorer outcome and a lower likelihood of survival. Patient outcome and the degree of neurological disability of patients recovering from ICH were measured by the Modified Rankin Scale (MRS) and length of stay until discharge or death.Electrocardiogram analysisThe ECG (12-lead) data were collected within 24 hours of patient presentation and before treatment and was obtained at a paper speed of 25 millimeters per second, with an amplitude calibration of 10 millimeters per millivolt. All ECGs were analyzed by an experienced cardiologist blinded to clinical and follow-up data. The ECG changes were documented if the abnormality was noted in at least 2 leads and were classified according to the modified Minnesota Code.16 ECG changes were assessed and classified based on the following parameters: (1) Rhythm: sinus rhythm, atrial fibrillation, or atrial flutter. (2) Rate: sinus bradycardia (less than 60 beats per minute) or sinus tachycardia (more than 100 beats per minute). (3) PR interval: normal (0.12 to 0.21 seconds) or prolonged (more than 0.21 seconds). (4) QRS complex width: prolonged if equal to or more than 0.12 seconds. (5) QTc prolongation (equal to or more than 440 milliseconds in men and 460 milliseconds in women). (6) Morphology (P wave, QRS complex, ST segment, T wave, Q wave, and U wave). (7) ST segment depression: down sloping or horizontal (more than 0.05 millivolts). (8) ST segment elevation: convexity of the ST segment upwards (more than 0.1 millivolts). (9) Prominent U wave: more than 25% of the largest T wave amplitude in precordial leads.Statistical analysisAll of the values were expressed as number (%) or mean±standard deviation (SD), as appropriate. Data were analyzed using Statistical Package for Social Sciences (SPSS Inc., version 22, Chicago, IL, USA). The data were analyzed by the Chi-Square test to compare between categorical variables and interdependent T-test or one-way analysis of variance (ANOVA) when involving numerical variables. A p-value less than or equal to 0.05 was considered statistically significant, with a 95% confidence interval. Missing data were dropped from the analysis.ResultsThe study included 291 participants with an average age of 59±34 years. Sixty-three (21.6%) participants were included in the pediatric group (below 18 years of age); 228 (78.4%) participants were included in the adult group (above 18 years of age). Two hundred and six (70.8%) participants were males; only 86 (29.2%) participants were females.Of the 291 research participants, 152 (52.2%) ICH cases were traumatic, while 140 (47.8%) cases were non-traumatic in origin. Overall, SDH was the most type of ICH. The death rate of the patients in this study was 18.9%. Although 76.3% of the participants were discharged from the hospital, they experienced complications such as hydrocephalus (10.7%), midline shift (7.6%), and intraventricular hemorrhage (IVH) (7.9%). One percent were in a vegetative state.Among the 291 study participants, ECGs were only available for 98 cases. Abnormalities were identified in 62.2% of the ECGs. Fifty percent of patients with neurological diseases for whom ECG records were available had 1st or 3rd degree AV blocks, which is significantly higher than those without neurological disease (p=.004). There were 4 patients with neurological diseases and ECG records; 3 had strokes, one of whom also had Alzheimer’s disease with 3rd degree AV block, and one with only trigeminal neuralgia with 1st degree AV block. All of them were adults. QTc prolongation was related to these neurological conditions (25% of those with neurological disease, trigeminal neuralgia vs 0% of those without QTc prolongation) (p=.041).Nevertheless, none of the ECG abnormalities were significantly associated with ICH outcomes (p>.05).Sociodemographic dimensions of the adult ICH groupThe subcategory “Adult ICH” was comprised of 228 participants with an average age of 56±19 years. One hundred and sixty-seven (73.2%) cases were male, whereas 61 (26.8%) were female. The prevalence of each ICH type with a traumatic or non-traumatic origin is shown in Table 1.Table 1Prevalence of ICH types of traumatic or non-traumatic origin in the ‘Adult ICH Group’. Nineteen cases were missing information about being traumatic or non-traumatic.

Robot-assisted intersphincteric resection facilitates an efficient sphincter-saving in patients with low rectal cancer

Purpose

Few investigations of robot-assisted intersphincteric resection (ISR) are presently available to support this procedure as a safe and efficient procedure. We aimed to evaluate the utility of robot-assisted ISR by comparison between ISR and abdominoperineal resection (APR) using both robot-assisted and open approaches.

Methods

The 558 patients with lower rectal cancer (LRC) who underwent curative operation was enrolled between July 2010 and June 2015 to perform either by robot-assisted (ISR vs. APR = 310 vs. 34) or open approaches (144 vs. 70). Perioperative and functional outcomes including urogenital and anorectal dysfunctions were measured. Recurrence and survival were examined in 216 patients in which >3 years had elapsed after the operation.

Results

The robot-assisted approach was the most significant parameter to determine ISR achievement among potent parameters (OR = 3.467, 95% CI = 2.095–5.738, p < 0.001). Early surgical complications occurred more frequently in the open ISR group (16 vs. 7.7%, p = 0.01). The voiding and male sexual dysfunctions were significantly more frequent in the open ISR (p < 0.05). The fecal incontinence and lifestyle alteration score was greater in the open ISR than in the robot-assisted ISR at 12 and 24 months, respectively (p < 0.05). However, the 3-year cumulative rates of local recurrence and survival did not differ between the two groups.

Conclusions

The current procedure of robot-assisted ISR replaced a significant portion of APR to achieve successful SSO via mostly transabdominal approach and double-stapled anastomosis. The robot-assisted ISR with minimal invasiveness might be a help to reduce anorectal and urogenital dysfunctions.

     

Levels of Evidence within Cardiovascular Medicine Research in Saudi Arabia: A Systematic Review

International commitments to reduce the prevalence of non-communicable disease have led the Government of Saudi Arabia to invest more in research related to cardiovascular disease. However, the strength of evidence derived from these research activities remains unclear. The aim of our study was to examine the level of evidence within clinical Cardiovascular Medicine research in Saudi Arabia. We conducted a systematic review of published articles that included a population from Saudi Arabia. Electronic databases EMBASE and MEDLINE (Ovid) were searched up to 25^th of April 2021, supplemented by a second search in CENTRAL (Cochrane Central Register of Controlled Trials) and www.clinicaltrials.gov. In addition, the Snowball- and Pearl-growing methods of search were conducted for finding additional eligible articles. Finally, a search was conducted in PubMed database for all eligible articles published by Journal of the Saudi Heart Association from the first indexed issue up to April 2021. Level of evidence of reviewed articles was determined using the Oxford Level of Evidence 2 scale. We calculated the mean level of evidence over 5-year periods, and explored evidence for a time trend for number of published articles and LOE using linear regression. Of the 1113 records identified, 418 met the inclusion criteria for analysis. The articles were published between September 1986 and March 2021. More than half of the included articles were level IV studies (n = 242, 57.8%). Furthermore, we observed no trend over the years for increased mean of level of evidence (β = −0.07, 95% CI [−0.20, −0.06], p = 0.236). Overall, the level of evidence produced by the articles in clinical Cardiovascular Medicine in Saudi Arabia is very low. Prioritizing higher-quality research is critical to produce the clinical practices and policies necessary to reduce the burden of cardiovascular diseases in Saudi Arabia.     

Expanding the phenotype of SLC25A42‐associated mitochondrial encephalomyopathy

SLC25A42 gene encodes an inner mitochondrial membrane protein that imports Coenzyme A into the mitochondrial matrix. A mutation in this gene was recently reported in a subject born to consanguineous parents who presented with mitochondrial myopathy with muscle weakness and lactic acidosis. In this report, we present 12 additional individuals with the same founder mutation who presented with variable manifestations ranging from asymptomatic lactic acidosis to a severe phenotype characterized by developmental regression and epilepsy. Our report confirms the link between SLC25A42 and mitochondrial disease in humans, and suggests that pathogenic variants in SLC25A42 should be interpreted with the understanding that the associated phenotype may be highly variable.