A Comparison Between the Transoral Endoscopic Thyroidectomy Vestibular Approach and the Transareolar Approach Regarding Perioperative Complications: A Systematic Review and Meta-Analysis.

The global adoption of remote thyroidectomy is increasing, with the transoral endoscopic thyroidectomy vestibular approach (TOETVA) and transareolar approach (TAA) emerging as predominant methods. However, existing meta-analyses comparing these approaches to operative surgeries and short-term postoperative complications have significant limitations. To address this gap, our meta-analysis provides a comprehensive comparison between the TOETVA and TAA, focusing on operation time, intraoperative blood loss, postoperative drainage, and hospital stay duration. It aims to offer robust insights into their relative efficacy and safety profiles. We searched SCOPUS, PubMed, Web of Science, MEDLINE, and Cochrane Library from June 2015 to January 2024 for studies comparing transoral endoscopic thyroidectomy with the vestibular approach and areolar thyroidectomy using keywords, including "transoral thyroidectomy" and "scarless thyroidectomy." Studies were included if they were randomized controlled trials, case-control studies, or prospective/retrospective cohort studies comparing the TOETVA and TAA. Exclusion criteria removed case series, cross-sectional studies, editorials, non-English language, animal studies, and irrelevant articles. Data on operative time, postoperative drainage, intraoperative blood loss, and hospital stay were extracted. The Newcastle-Ottawa Scale was used to assess study quality (all studies scored 7-8). The findings revealed that the operative time was longer among the TOETVA group, with less intraoperative blood loss (odds ratio (OR) = 13.31, 95% confidence interval (CI) = 4.44-22.19); OR = -1.61, 95% CI = -2.82 to -0.39, respectively). Regarding hospitalization duration and postoperative drainage, no discernible difference was observed between the endoscopic TAA (ETAA) and TOETVA (OR = -0.04, 95% CI = -0.24 to 0.16; OR = -6.74, 95% CI = -20.08 to 6.60, respectively). The TOETVA has advantages over the TAA in terms of intraoperative blood loss and shorter operation times. However, both approaches exhibited comparable outcomes in terms of hospital stay duration and postoperative drainage. Furthermore, extensive randomized trials are warranted.

Effects of Beta Lactams on Behavioral Outcomes of Substance Use Disorders: A Meta-Analysis of Preclinical Studies.

INTRODUCTION: Preclinical studies demonstrated that beta-lactams have neuroprotective effects in conditions involving glutamate neuroexcitotoxicity, including substance use disorders (SUDs). This meta-analysis aims to analyze the existing evidences on the effects of beta-lactams as glutamate transporter 1 (GLT-1) upregulators in animal models of SUDs, identification of gaps in the literature, and setting the stage for potential translation into clinical phases. METHODS: Meta-analysis was conducted on preclinical studies retrieved systematically from MEDLINE and ScienceDirect databases. Abused substances were identified by refereeing to the National Institute on Drug Abuse (NIDA). The results were quantitatively described with a focus on the behavioral outcomes. Treatment effect sizes were described using standardized mean difference, and they were pooled using random effect model. I2-statistic was used to assess heterogeneity, and Funnel plot and Egger's test were used for assessment of publication bias. RESULTS: Literature search yielded a total of 71 studies that were eligible to be included in the analysis. Through these studies, the effects of beta-lactams were evaluated in animal models of nicotine, cannabis, amphetamines, synthetic cathinone, opioids, ethanol, and cocaine use disorders as well as steroids-related aggressive behaviors. Meta-analysis showed that treatments with beta-lactams consistently reduced the pooled undesired effects of the abused substances in several paradigms, including drug-self administration, conditioned place preference, drug seeking behaviors, hyperlocomotion, withdrawal syndromes, tolerance to analgesic effects, hyperalgesia, and hyperthermia. CONCLUSION: This meta-analysis revealed that enhancing GLT-1 expression in the brain through beta-lactams seemed to be a promising treatment approach in the context of substance use disorders, as indicated by results in animal models.

A Physiologically Based Pharmacokinetic Model to Predict Systemic Ondansetron Concentration in Liver Cirrhosis Patients.

INTRODUCTION: Ondansetron is a drug that is routinely prescribed for the management of nausea and vomiting associated with cancer, radiation therapy, and surgical operations. It is mainly metabolized in the liver, and it might accumulate in patients with hepatic impairment and lead to unwanted adverse events. METHODS: A physiologically based pharmacokinetic (PBPK) model was developed to predict the exposure of ondansetron in healthy and liver cirrhosis populations. The population-based PBPK simulator PK-Sim was utilized for simulating ondansetron exposure in healthy and liver cirrhosis populations. RESULTS: The developed model successfully described the pharmacokinetics of ondansetron in healthy and liver cirrhosis populations. The predicted area under the curve, maximum systemic concentration, and clearance were within the allowed twofold range. The exposure of ondansetron in the population of Child-Pugh class C has doubled in comparison to Child-Pugh class A. The dose has to be adjusted for liver cirrhosis patients to ensure comparable exposure to a healthy population. CONCLUSION: In this study, the developed PBPK model has described the pharmacokinetics of ondansetron successfully. The PBPK model has been successfully evaluated to be used as a tool for dose adjustments in liver cirrhosis patients.

Arabic translation, cross cultural adaptation, and validation of Foot Health Status Questionnaire among Saudi individuals with plantar fasciitis.

BACKGROUND: Measuring quality of life (QoL) plays an essential role in enabling meaningful cross-cultural comparisons. The Foot Health Status Questionnaire (FHSQ) is a valid tool for assessing both foot-specific and general health-related quality of life (HrQoL), making it suitable for evaluating Plantar Fasciitis (PF) patients. METHODOLOGY: The aim of this study is to translate the FHSQ into Arabic following methodological assessments of the translation procedure. The translation was done using forward and back translation. A pre-test questionnaire was distributed among 50 patients, resulting in the final FHSQ-Ar version, which then underwent various psychometric evaluations among 87 persons with PF, including internal consistency, dimensionality, reliability, interpretability, and construct validity against the 100-mm Visual Analogue Scale (VAS). RESULTS: Internal consistency was adequate, ranging from 0.70 to 0.92. Reliability values ranged from 0.69 to 0.80, with a poor standard error of measurement (individual) but an acceptable standard error of measurement (group). Two domains exhibited floor effects, while one domain showed a ceiling effect. Regarding validity, three out of four hypothesized correlations with VAS scores were confirmed. Factor analysis revealed four dimensions, and confirmatory factor analysis demonstrated good fit (comparative fit index = 0.98, standardized root mean square = 0.06). CONCLUSION: The psychometric properties of the FHSQ-Ar were satisfactory. Further validation for other diseases may be warranted.

Impact of Plantar Fasciitis on Foot-Specific and Generic Health-Related Quality of Life in King Khalid University Hospital, Saudi Arabia.

Objectives The objective is to assess the extent of foot-specific and generic health-related quality of life (HRQoL) impairment among individuals diagnosed with plantar fasciitis (PF) at King Khalid University, Saudi Arabia, and to determine the influence of various sociodemographic and clinical factors. Methods In this cross-sectional study, we administered an online survey from March to June 2023 to patients with PF at King Khalid University Hospital. This questionnaire covered sociodemographic, and clinical characteristics, and included the translated Foot Health Status Questionnaire (FHSQ). Further, patient data were obtained from hospital records between 2016 and 2023 using the E-SIHI system. Results We recruited 209 patients for the study. Lower FHSQ scores were found in unemployed and low-income participants indicating a worse quality of life (QoL) in the Foot Pain domain, while those aged over 40 years and with low income showed greater impairment in the General Foot Health domain. No single factor influenced the Foot Function or Footwear domains. Worse General Health and Physical Activity scores were associated with low-education and low-income participants and those who did not exercise. Women exhibited a lower QoL than men in all domains except for General Health. Conclusion The QoL of Saudi women with PF was similar to that of women in other countries. However, the patients in the present study reported poorer footwear scores but better General Health scores. Therefore, focusing more on proper footwear-related treatments may help improve the QoL of patients with PF.

Liver Metabolomics and Inflammatory Profiles in Mouse Model of Fentanyl Overdose Treated with Beta-Lactams.

Fentanyl is a highly potent opioid analgesic that is approved medically to treat acute and chronic pain. There is a high potential for overdose-induced organ toxicities, including liver toxicity, and this might be due to the increase of recreational use of opioids. Several preclinical studies have demonstrated the efficacy of beta-lactams in modulating the expression of glutamate transporter-1 (GLT-1) in different body organs, including the liver. The upregulation of GLT-1 by beta-lactams is associated with the attenuation of hyperglutamatergic state, which is a characteristic feature of opioid use disorders. A novel experimental beta-lactam compound with no antimicrobial properties, MC-100093, has been developed to attenuate dysregulation of glutamate transport, in part by normalizing GLT-1 expression. A previous study showed that MC-100093 modulated hepatic GLT-1 expression with subsequent attenuation of alcohol-increased fat droplet content in the liver. In this study, we investigated the effects of fentanyl overdose on liver metabolites, and determined the effects of MC-100093 and ceftriaxone in the liver of a fentanyl overdose mouse model. Liver samples from control, fentanyl overdose, and fentanyl overdose ceftriaxone- or MC-100093-treated mice were analyzed for metabolomics using gas chromatography-mass spectrometry. Heatmap analysis revealed that both MC-100093 and ceftriaxone attenuated the effects of fentanyl overdose on several metabolites, and MC-100093 showed superior effects. Statistical analysis showed that MC-100093 reversed the effects of fentanyl overdose in some metabolites. Moreover, enrichment analysis revealed that the altered metabolites were strongly linked to the glucose-alanine cycle, the Warburg effect, gluconeogenesis, glutamate metabolism, lactose degradation, and ketone body metabolism. The changes in liver metabolites induced by fentanyl overdose were associated with liver inflammation, an effect attenuated with ceftriaxone pre-treatments. Ceftriaxone normalized fentanyl-overdose-induced changes in liver interleukin-6 and cytochrome CYP3A11 (mouse homolog of human CYP3A4) expression. Our data indicate that fentanyl overdose impaired liver metabolites, and MC-100093 restored certain metabolites.

Physiologically-based pharmacokinetic modeling for single and multiple dosing regimens of ceftriaxone in healthy and chronic kidney disease populations: a tool for model-informed precision dosing.

Introduction: Ceftriaxone is one of commonly prescribed beta-lactam antibiotics with several label and off-label clinical indications. A high fraction of administered dose of ceftriaxone is excreted renally in an unchanged form, and it may accumulate significantly in patients with impaired renal functions, which may lead to toxicity. Methods: In this study, we employed a physiologically-based pharmacokinetic (PBPK) modeling, as a tool for precision dosing, to predict the biological exposure of ceftriaxone in a virtually-constructed healthy and chronic kidney disease patient populations, with subsequent dosing optimizations. We started developing the model by integrating the physicochemical properties of the drug with biological system information in a PBPK software platform. A PBPK model in an adult healthy population was developed and evaluated visually and numerically with respect to experimental pharmacokinetic data. The model performance was evaluated based on the fold error criteria of the predicted and reported values for different pharmacokinetic parameters. Then, the model was applied to predict drug exposure in CKD patient populations with various degrees of severity. Results: The developed PBPK model was able to precisely describe the pharmacokinetic behavior of ceftriaxone in adult healthy population and in mild, moderate, and severe CKD patient populations. Decreasing the dose by approximately 25% in mild and 50% in moderate to severe renal disease provided a comparable exposure to the healthy population. Based on the simulation of multiple dosing regimens in severe CKD population, it has been found that accumulation of 2 g every 24 h is lower than the accumulation of 1 g every 12 h dosing regimen. Discussion: In this study, the observed concentration time profiles and pharmacokinetic parameters for ceftriaxone were successfully reproduced by the developed PBPK model and it has been shown that PBPK modeling can be used as a tool for precision dosing to suggest treatment regimens in population with renal impairment.

Prevalence of Non-alcoholic Fatty Liver Disease (NAFLD) Among Diabetic Mellitus Patients in Saudi Arabia: Systematic Review and Meta-Analysis.

Non-alcoholic fatty liver disease (NAFLD) is a burgeoning global health concern, closely associated with the rising prevalence of type 2 diabetes mellitus (T2DM) and obesity. This systematic review and meta-analysis aim to comprehensively evaluate the prevalence of NAFLD in DM patients in Saudi Arabia, a country undergoing rapid socioeconomic changes. Our multifaceted search strategy identified four high-quality studies conducted between 2003 and 2022, covering hospital and community settings. The aggregate prevalence rate of NAFLD in DM patients was notably high, ranging from 47.8% to 72.8%. However, substantial heterogeneity (I² = 90.6%) was observed, indicating variability attributed to diverse study characteristics. The uniform application of ultrasound for diagnosis was noteworthy but raised concerns regarding sensitivity. This analysis underscores the urgency of public health measures for early detection and management of NAFLD in DM-prone populations in Saudi Arabia.

Development and Evaluation of a Physiologically Based Pharmacokinetic Model for Predicting Haloperidol Exposure in Healthy and Disease Populations.

The physiologically based pharmacokinetic (PBPK) approach can be used to develop mathematical models for predicting the absorption, distribution, metabolism, and elimination (ADME) of administered drugs in virtual human populations. Haloperidol is a typical antipsychotic drug with a narrow therapeutic index and is commonly used in the management of several medical conditions, including psychotic disorders. Due to the large interindividual variability among patients taking haloperidol, it is very likely for them to experience either toxic or subtherapeutic effects. We intend to develop a haloperidol PBPK model for identifying the potential sources of pharmacokinetic (PK) variability after intravenous and oral administration by using the population-based simulator, PK-Sim. The model was initially developed and evaluated to predict the PK of haloperidol and its reduced metabolite in adult healthy population after intravenous and oral administration. After evaluating the developed PBPK model in healthy adults, it was used to predict haloperidol-rifampicin drug-drug interaction and was extended to tuberculosis patients. The model evaluation was performed using visual assessments, prediction error, and mean fold error of the ratio of the observed-to-predicted values of the PK parameters. The predicted PK values were in good agreement with the corresponding reported values. The effects of the pathophysiological changes and enzyme induction associated with tuberculosis and its treatment, respectively, on haloperidol PK, have been predicted precisely. For all clinical scenarios that were evaluated, the predicted values were within the acceptable two-fold error range.

Zirconia Crowns for Primary Teeth: A Systematic Review and Meta-Analyses.

OBJECTIVE: The aim of this systematic review was to summarize the literature regarding the clinical performance of zirconia crowns for primary teeth. MATERIALS AND METHODS: Four electronic databases, Ovid, PubMed, Scopus, and Web of Science were searched. Clinical, observational, and laboratory studies were included. Studies that assessed the performance of zirconia crowns for primary teeth using outcomes such as gingival and periodontal health, parental satisfaction, color stability, crown retention, contour, fracture resistance, marginal integrity, surface roughness, and recurrent caries were included. Risk of bias was assessed using different assessment tools depending on the type of the assessed study. RESULTS: Out of the 2400 retrieved records, 73 full-text records were assessed for eligibility. Thirty-six studies were included for qualitative analysis. The included studies reported that zirconia crowns for primary teeth were associated with better gingival and periodontal health, good retention, high fracture resistance, color stability, high parental acceptance, good marginal adaptation, smooth cosmetic surface, and no recurrent caries. CONCLUSION: Zirconia crowns are promising alternative to other restorative materials and crowns in the field of pediatric dentistry. They showed higher properties and performance in different clinical aspects and great parental satisfaction.

Light Transmission of Various Aesthetic Posts at Different Depths and Its Effect on Push-Out Bond Strength, Microhardness of Luting Cement.

Background and Objectives: One requirement for the cemented post is the light transmittance on its entire length up to the deepest portion of a root canal to ensure the complete polymerization of resin cement. This study aimed to determine the light transmission ability in different aesthetic posts at different depths and its effect on the push-out bond strength and microhardness of luting cement at the corresponding interface. Materials and Methods: Twenty endodontic posts from glass fiber posts (GFP), zirconia ceramic posts (ZCP), and highly translucent zirconium oxide posts (HTZP) were sequentially sectioned into 12.8 and 4 mm lengths after recording the light intensity using a dental radiometer. Sixty single rooted premolar teeth root canals were treated and implanted vertically in a resin block. The post space was prepared and cemented with GFP, ZCP, and HTZP posts with twenty samples each. The root portion of teeth samples were sectioned into cervical, middle, and apical portion. A universal testing machine was utilized for the push-out bond strength test for the first ten samples from each group. The remaining ten samples from each group were used for the microhardness test using a micro-indenter instrument. The data were statistically analyzed using one-way Analysis of variance and Tukey HSD tests at p < 0.05. Results: The GFP endodontic postpresented with significant highest light translucency compared to HTZP, which was significantly higher than ZCP. GFP posts showed significantly higher bond strength per unit area compared to ZCP at analogous cross sections. The hardness of luting cement was also significantly higher amongst all tested endodontic posts. Conclusions: GFP high light translucency enhanced the curing of the luting resin cement that resulted in harder cement and a stronger bond supported by hardness and push-out tests. These findings suggest that GFP is preferred to be used with light-cured luting cements for restoration of endodontically treated teeth.

Protective effect of diosmin against doxorubicin-induced nephrotoxicity.

Doxorubicin (Dox) is an anthracycline antibiotic that is primarily used for treating various solid tumors including that of pulmonary, ovary, breast, uterine, cervix, and several blood cancers. However, nephrotoxicity associated with Dox treatment limits its clinical use. Administration of Dox in combination with compounds exhibiting antioxidant properties are being used to minimize the side effects of Dox. Diosmin is a flavonoid glycoside with numerous beneficial properties that is found in the pericarp of many citrus fruits. Diosmin has demonstrated antioxidant, anti-inflammatory, and anti-apoptotic effects in response to various insults, although the exact mechanism remains unknown. Therefore, this study was designed to evaluate the effect of diosmin in preventing kidney damage in response to Dox treatment. Male Wistar rats were randomly divided into four groups: control group, Dox group (20 mg/kg, i.p.), Dox plus low-dose diosmin group (100 mg/kg orally), and Dox plus high-dose diosmin group (200 mg/kg orally). A single intraperitoneal injection of Dox resulted in kidney damage as evidenced by significant alterations in kidney markers, histological abnormalities, and the attenuation of antioxidant defense mechanisms (GSH, SOD, and CAT). Moreover, Dox treatment significantly altered the expression of oxidative stress, inflammatory, and anti-apoptotic protein markers. Diosmin pretreatment alleviated Dox-induced nephrotoxicity by ameliorating the antioxidant mechanism, decreasing inflammation and apoptosis, and restoring kidney architecture. In conclusion, our results indicate that diosmin is a promising therapeutic agent for the prevention of nephrotoxicity associated with DOX.

Synthesis and Evaluation of Thiol-Conjugated Poloxamer and Its Pharmaceutical Applications.

The current study was designed to convert the poloxamer (PLX) into thiolated poloxamer (TPLX), followed by its physicochemical, biocompatibilities studies, and applications as a pharmaceutical excipient in the development of tacrolimus (TCM)-containing compressed tablets. Thiolation was accomplished by using thiourea as a thiol donor and hydrochloric acid (HCl) as a catalyst in the reaction. Both PLX and TPLX were evaluated for surface morphology based on SEM, the crystalline or amorphous nature of the particles, thiol contents, micromeritics, FTIR, and biocompatibility studies in albino rats. Furthermore, the polymers were used in the development of compressed tablets. Later, they were also characterized for thickness, diameter, hardness, weight variation, swelling index, disintegration time, mucoadhesion, and in vitro drug release. The outcomes of the study showed that the thiolation process was accomplished successfully, which was confirmed by FTIR, where a characteristic peak was noticed at 2695.9968 cm-1 in the FTIR scan of TPLX. Furthermore, the considerable concentration of the thiol constituents (20.625 µg/g of the polymer), which was present on the polymeric backbone, also strengthened the claim of successful thiolation. A mucoadhesion test illustrated the comparatively better mucoadhesion strength of TPLX compared to PLX. The in vitro drug release study exhibited that the TPLX-based formulation showed a more rapid (p < 0.05) release of the drug in 1 h compared to the PLX-based formulation. The in vivo toxicity studies confirmed that both PLX and TPLX were safe when they were administered to the albino rats. Conclusively, the thiolation of PLX made not only the polymer more mucoadhesive but also capable of improving the dissolution profile of TCM.

Transepithelial photorefractive keratectomy to treat mild myopia.

PURPOSE: To assess the safety and effectiveness of transepithelial photorefractive keratectomy (T-PRK) in patients with mild myopia using the Schwind Amaris 750 s Excimer laser system which take corneal epithelium variability in consideration during ablation. METHODS: A prospective case series study of patients with mild myopia with or without astigmatism (spherical equivalent ≤ -3 diopters), who underwent T-PRK as a single-step treatment, was carried out at King Abdulaziz University Hospital, Riyadh between May 2017 and January 2018. The main outcomes included postoperative uncorrected distance visual acuity (UDVA), residual refraction (manifest refraction) and complications. RESULTS: A total of 42 patients (84 eyes) underwent bilateral T-PRK with a preoperative spherical equivalent ranging from - 0.75 to - 3.00 D. Median spherical equivalent before Trans-PRK was - 1.75 (- 1.25to - 1.75). The spherical equivalent six months after Trans-PRK was 0.0 (- 0.25 to 0.5). All patients had a postoperative UDVA of 20/20 or better in the last follow-up. Transient postoperative corneal haze was observed in five eyes (6%). CONCLUSION: T-PRK appears to be safe and effective in patients who have mild myopia, with or without astigmatism. The normal variation in corneal epithelial thickness seems not to affect the outcomes.

Minimally invasive versus open surgery for the correction of adult degenerative scoliosis: a systematic review.

While open surgery has been the primary surgical approach for adult degenerative scoliosis, minimally invasive surgery (MIS) represents an alternative option and appears to be associated with reduced morbidity. Given the lack of consensus, we aimed to conduct a systematic review on available literature comparing MIS versus open surgery for adult degenerative scoliosis. PubMed, Embase, and Cochrane databases were searched through December 16, 2019, for studies that compared both MIS and open surgery in patients with degenerative scoliosis. Four cohort studies reporting on 350 patients met the inclusion criteria. In two studies, patients undergoing open surgery were younger and had more severe disease at baseline as compared with MIS. Patients who underwent MIS had less blood loss, shorter length of stay, and a reduced rate of complications and infections. Both MIS and open surgery resulted in a significant change in pain and disability scores and both approaches provided significant correction of deformity in all studies, although open surgery was associated with a greater change in pelvic incidence-lumbar lordosis mismatch (PI-LL) and sagittal vertical axis (SVA) in two and three studies, respectively. In patients with adult degenerative scoliosis undergoing surgery, both MIS and open approaches appeared to offer comparable improvements in pain and function. However, MIS was associated with better safety outcomes, while open surgery provided greater correction of spinal deformity. Further studies are needed to identify specific subset of patients who may benefit from one approach versus the other.

The Effectiveness of Antiepileptic Medications as Prophylaxis of Early Seizure in Patients with Traumatic Brain Injury Compared with Placebo or No Treatment: A Systematic Review and Meta-Analysis.

BACKGROUND: The use of antiepileptic drugs (AEDs) to prevent early posttraumatic seizure (PTS) for patients with severe traumatic brain injury (TBI) is currently recommended, although published studies present contradictory results concerning the protective effect of AEDs. OBJECTIVE: The purpose of this study was to quantify the association between the use of prophylactic AEDs, particularly of the 4 main drugs of interest (phenytoin, levetiracetam, valproate, or carbamazepine) versus placebo or no treatment, and risk of early seizures after TBI. METHODS: A comprehensive search was performed on PubMed, Embase, Cochrane Library, and ClinicalTrials.gov. The selection criteria were English written randomized controlled trials (RCTs) and observational studies, comparing AEDs with placebo or no treatment, for prevention of early PTS. Random-effects models were used to calculate pooled relative risk (RR). Subgroup analysis and meta-regression were used to assess heterogeneity sources. RESULTS: This research included 3 RCTs (750 patients) and 6 observational studies (3362 patients), analyzing the efficacy of phenytoin, levetiracetam, and valproate. The pooled RR estimate across RCTs trended toward a protective effect (RR, 0.58; 95% confidence interval, 0.20-1.72; I2 = 59.5%); a significant protective association was shown when pooling the results across all 6 observational studies (RR, 0.42; 95% confidence interval, 0.29-0.62; I2 = 0%). When stratifying the observational studies by drug, no significant difference was observed (P interaction = 0.73). Begg and Egger tests indicated no publication bias among observational studies. CONCLUSIONS: Only modest evidence suggested effectiveness of AEDs as prophylaxis of early PTS. Phenytoin was the most studied drug; more prospective studies are needed to assess the efficacy of other AEDs.