Failure of scabies treatment: a systematic review and meta-analysis.

BACKGROUND: Treatment failure is considered to be an important factor in relation to the increase in scabies incidence over the last decade. However, the regional and temporal differences, in addition to the predictors of therapy failure, are unclear. OBJECTIVES: We aimed to conduct a systematic review of the prevalence of treatment failure in patients with scabies and investigation of associated factors. METHODS: We searched MEDLINE, EMBASE, CINAHL, Web of Science, Scopus, Global Health and the Cochrane Central Register of Controlled Trials from inception to August 2021 for randomized and quasi-randomized trials, in addition to observational studies that enrolled children or adults diagnosed with confirmed or clinical scabies treated with permethrin, ivermectin, crotamiton, benzyl benzoate, malathion, sulfur or lindane, and measured treatment failure or factors associated with treatment failure. We performed a random effects meta-analysis for all outcomes reported by at least two studies. RESULTS: A total of 147 studies were eligible for inclusion in the systematic review. The overall prevalence of treatment failure was 15.2% [95% confidence interval (CI) 12.9-17.6; I2 = 95.3%, moderate-certainty evidence] with regional differences between World Health Organization regions (P = 0.003) being highest in the Western Pacific region (26.9%, 95% CI 14.5-41.2). Oral ivermectin (11.8%, 95% CI 8.4-15.4), topical ivermectin (9.3%, 95% CI 5.1-14.3) and permethrin (10.8%, 95% CI 7.5-14.5) had relatively lower failure prevalence compared with the overall prevalence. Failure prevalence was lower in patients treated with two doses of oral ivermectin (7.1%, 95% CI 3.1-12.3) compared with those treated with one dose (15.2%, 95% CI 10.8-20.2; P = 0.021). Overall and permethrin treatment failure prevalence in the included studies (1983-2021) increased by 0.27% and 0.58% per year, respectively. Only three studies conducted a multivariable risk factor analysis; no studies assessed resistance. CONCLUSIONS: A second dose of ivermectin showed lower failure prevalence than single-dose ivermectin, which should be considered in all guidelines. The increase in treatment failure over time hints at decreasing mite susceptibility for several drugs, but reasons for failure are rarely assessed. Ideally, scabicide susceptibility testing should be implemented in future studies.

Outcome prediction for symptomatic patients with fibroids who underwent uterine artery embolization.

PURPOSE: To predict the clinical outcome of symptomatic patients with uterine leiomyomas who underwent uterine artery embolization (UAE), based on clinical and radiological features. METHODS: Patients with symptomatic uterine leiomyomas who underwent UAE from March 2010 to September 2019 were consecutively included in this retrospective study. Patients with persistent or recurrent symptoms and those who needed repeated UAE, myomectomy, or hysterectomy following the initial treatment were considered to have a poor outcome after UAE. The total and enhancing volume of the dominant leiomyoma in each location and uterine volume were obtained before and after UAE. Univariate and multivariate Cox proportional hazard analyses were used to evaluate the parameters that could predict poor outcome. RESULTS: A total of 116 patients (mean age, 45 ± 5 years) were included. Forty-six patients (46/116, 39.7%) showed poor outcome. Cox regression analysis showed higher hazard of poor outcome for younger patients vs. older patients (HR: 0.92, p-value: 0.01), patients with adenomyosis vs. patients without adenomyosis (HR: 2.47, p-value < 0.01), patients with adenomyosis thickness > 2.5 cm before UAE vs. patients without adenomyosis (HR: 4.2, p-value < 0.01) and for patients with intramural fibroid enhancement volume > 440 cm3 compared to patients with no intramural fibroids (p-value: 0.06). Multivariate Cox regression analysis including age, the thickness of adenomyosis, and intramural leiomyoma volume of enhancement before UAE was chosen as the best model to predict the outcome. CONCLUSIONS: Pretreatment clinical and MRI features could identify patients with a higher risk for poor outcome after UAE.

Comparison between Gradient-Echo and Spin-Echo EPI MR Elastography at 3 T in quantifying liver stiffness of patients with and without iron overload; a prospective study.

OBJECTIVES: To compare the maximum axial area of the confidence mask and the calculated liver stiffness (LS) on gradient-echo (GRE) and spin-echo echo planar imaging (SE-EPI) MR elastography (MRE) in patients with and without iron deposition. METHODS: 104 patients underwent MRE by GRE and SE-EPI sequences at 3 T. R2* values >88 Hz in the liver were categorized in the iron overload group. The maximum axial area and the corresponding LS values were measured by manually contouring the whole area on one slice with the largest confidence mask at both GRE and SE-EPI sequences. RESULTS: In patients with iron overload, SE-EPI provided larger maximum axial confidence area in unfailed images (57.6 ± 41.7 cm2) compared to GRE (45.7 ± 29.1 cm2) (p-value = 0.007). In five patients with iron overload, imaging failed at GRE sequence, whereas at the SE-EPI sequence the maximum area of the confidence mask had a mean value of 33.5 ± 54.9 cm2. In livers without iron overload (R2*: 50.7 ± 13.1 Hz), the maximum area on the confidence mask was larger at SE-EPI (118.3 ± 41.2 cm2) than on GRE (105.1 ± 31.7 cm2) (P-value = 0.003). There was no significant difference in mean LS between SE-EPI (2.0 ± 0.3 kPa) and GRE (2.1 ± 0.5 kPa) in livers with iron overload (P value = 0.24). Similarly, in the group without iron overload, mean LS was 2.3 ± 0.7 kPa at SE-EPI and 2.4 ± 0.8 kPa at GRE sequences (P-value = 0.11). CONCLUSIONS: SE-EPI MRE can successfully provide similar LS measurements as GRE MRE. Furthermore, it provides a larger measurable area on the confidence mask in both groups with and without iron overload.

Hemodynamic Changes after Continuing or Omitting Regular Angiotensin Converting Enzyme Inhibitors before Cataract Surgery: A Comparative Study.

AIMS: In this study, we aimed to appraise the effects of interrupting (discontinuing) vs. continuing Angiotensin receptor blockers (ARBs) and Angiotensin-Converting Enzyme Inhibitors (ACEIs) on the hemodynamic changes of patients during and after cataract surgery. METHODS AND MATERIALS: Patients aged 40-70 years, American society of anesthesiologist (ASA) class II, taking ACEI/ARB medications, who were admitted to Khalili hospital (Shiraz, South of Iran) for cataract surgery, were enrolled in the study. Patients were randomly divided into two groups for continuing or withdrawing the use of ACEI/ARBs. Group 1 included the patients who continued ACEI/ARB administration, and group 2 included those who discontinued them before surgery. In the operating room, relevant demographic information was collected in addition to the data on patients' basic clinical status, including heart rate and blood pressure, before induction of anesthesia, during, and after that. The collected data were analyzed using SPSS 21, and p-values < 0.05 were considered statistically significant. RESULTS: Any significant differences were not revealed in demographic variables (age, sex, diabetes, hypertension, Myocardial infarction, Smoking, and duration of drug therapy) between the two groups. Time effect was significant (p<0.001) for systolic blood pressure, diastolic blood pressure, and heart rate, and interaction between time*group was not significant (p = 0.431, p = 0.566, and p = 0.355) for systolic blood pressure, diastolic blood pressure, and heart rate. However, the group effect wasn't significant (p=0.701, p=0.663, and p=0.669) for systolic blood pressure, diastolic blood pressure, and heart rate. CONCLUSION: It seems that in some minor surgeries, such as cataract surgery, withdrawal or continuation of ACEIs/ARBs have no significant effect on the hypotension and heart rate of patients during orafter an operation.

Instruments assessing risk of bias of randomized trials frequently included items that are not addressing risk of bias issues.

OBJECTIVES: To establish whether items included in instruments published in the last decade assessing risk of bias of randomized controlled trials (RCTs) are indeed addressing risk of bias. STUDY DESIGN AND SETTING: We searched Medline, Embase, Web of Science, and Scopus from 2010 to October 2021 for instruments assessing risk of bias of RCTs. By extracting items and summarizing their essential content, we generated an item list. Items that two reviewers agreed clearly did not address risk of bias were excluded. We included the remaining items in a survey in which 13 experts judged the issue each item is addressing: risk of bias, applicability, random error, reporting quality, or none of the above. RESULTS: Seventeen eligible instruments included 127 unique items. After excluding 61 items deemed as clearly not addressing risk of bias, the item classification survey included 66 items, of which the majority of respondents deemed 20 items (30.3%) as addressing risk of bias; the majority deemed 11 (16.7%) as not addressing risk of bias; and there proved substantial disagreement for 35 (53.0%) items. CONCLUSION: Existing risk of bias instruments frequently include items that do not address risk of bias. For many items, experts disagree on whether or not they are addressing risk of bias.

Analgesic effect of ketorolac added to lidocaine in surgery of traumatic arm injuries: A double-blind, randomized clinical trial.

Acute pain after surgery can cause harmful effects. There are many ways to treat pain after surgery. Bier block technique is also a type of intravenous regional anesthesia that is suitable for short and minor surgeries of the arm, wrist, and fingers, so this study aims to compare the analgesic effect of Ketorolac in intravenous injection and when the lidocaine is added to Bier block. In surgery, traumatic injuries to the upper limbs. This study was a clinical trial, randomized and double-blind. The target population was candidates for upper limb orthopedic surgery. The patients selected based on the entry and exit criteria were randomly assigned to one of the 3 study groups. The intensity of pain, the amount of morphine consumed through the intravenous PCA pump, the incidence of side effects of morphine and ketorolac, as well as the overall patient satisfaction regarding the anesthesia method and pain control were compared between the groups. Data analysis, both descriptive and analytical, was done using SPSS statistical software version 21. The three studied groups were identical and had no differences in terms of quantitative and qualitative demographic variables. The median tourniquet closing time is different between the control group and the intravenous ketorolac and topical ketorolac groups with P=0.002 and P=0.001, respectively. There was no significant difference between the three groups in terms of the time of the first request to receive painkillers after deflating the tourniquet, but the amount of morphine received between the groups was significantly different (P=0.02). Comparison of pain intensity based on NRS, considering Taking the measurement repetition times indicated the significance of the effect of pain intensity between the groups (P=0.001). In terms of overall satisfaction with the quality of analgesia and anesthesia method, no significant difference was observed between the three study groups. In terms of the occurrence of complications related to the use of ketorolac, no complications were observed in any of the groups receiving this drug. In general, by conducting this study, it can be said that the administration of Ketorolac reduces the intensity of postoperative pain in the recovery room and transfer to the inpatient ward, and reduces the amount of morphine received by patients, but the time of the first request for pain relief by the patient It does not significantly delay and does not affect the overall satisfaction of patients with the quality of analgesia during and after the operation and their satisfaction with the anesthesia method they received.

Role of MRI-Derived Radiomics Features in Determining Degree of Tumor Differentiation of Hepatocellular Carcinoma.

Background: To investigate radiomics ability in predicting hepatocellular carcinoma histological degree of differentiation by using volumetric MR imaging parameters. Methods: Volumetric venous enhancement and apparent diffusion coefficient were calculated on baseline MRI of 171 lesions. Ninety-five radiomics features were extracted, then random forest classification identified the performance of the texture features in classifying tumor degree of differentiation based on their histopathological features. The Gini index was used for split criterion, and the random forest was optimized to have a minimum of nine participants per leaf node. Predictor importance was estimated based on the minimal depth of the maximal subtree. Results: Out of 95 radiomics features, four top performers were apparent diffusion coefficient (ADC) features. The mean ADC and venous enhancement map alone had an overall error rate of 39.8%. The error decreased to 32.8% with the addition of the radiomics features in the multi-class model. The area under the receiver-operator curve (AUC) improved from 75.2% to 83.2% with the addition of the radiomics features for distinguishing well- from moderately/poorly differentiated HCCs in the multi-class model. Conclusions: The addition of radiomics-based texture analysis improved classification over that of ADC or venous enhancement values alone. Radiomics help us move closer to non-invasive histologic tumor grading of HCC.

Magnetic Resonance Imaging Predictors of Hepatocellular Carcinoma Progression and Dropout in Patients in Liver Transplantation Waiting List.

With the rising incidence of hepatocellular carcinoma (HCC), more patients are now eligible for liver transplantation. Consequently, HCC progression and dropout from the waiting list are also anticipated to rise. We developed a predictive model based on radiographic features and alpha-fetoprotein to identify high-risk patients. Methods: This is a case-cohort retrospective study of 76 patients with HCC who were listed for liver transplantation with subsequent liver transplantation or delisting due to HCC progression. We analyzed imaging-based predictive variables including tumor margin (well- versus ill-defined), capsule bulging lesions, volumetric analysis and distance to portal vein, tumor numbers, and tumor diameter. Volumetric analysis of the index lesions was used to quantify index tumor total volume and volumetric enhancement, whereas logistic regression and receiver operating characteristic curve (ROC) analyses were used to predict the main outcome of disease progression. Results: In univariate analyses, the following baseline variables were significantly associated with disease progression: size and number of lesions, sum of lesion diameters, lesions bulging the capsule, and total and venous-enhancing (viable) tumor volumes. Based on multivariable analyses, a risk model including lesion numbers and diameter, capsule bulging, tumor margin (infiltrative versus well-defined), and alpha-fetoprotein was developed to predict HCC progression and dropout. The model has an area under the ROC of 82%, which was significantly higher than Milan criteria that has an area under the ROC of 67%. Conclusions: Our model has a high predictive test for patient dropout due to HCC progression. This model can identify high-risk patients who may benefit from more aggressive HCC treatment early after diagnosis to prevent dropout due to such disease progression.

Shorter versus longer durations of antibiotic treatment for patients with community-acquired pneumonia: a protocol for a systematic review and meta-analysis.

INTRODUCTION: Community-acquired pneumonia (CAP), frequently encountered in both outpatient and inpatient settings, is the leading cause of infectious disease-related mortality. While equipoise regarding the optimal duration of antimicrobial therapy to treat CAP remains, recent studies suggest shorter durations of therapy may achieve optimal outcomes. We have therefore planned a systematic review and meta-analysis evaluating the impact of shorter versus longer durations of antibiotic therapy for patients with CAP. METHODS AND ANALYSIS: We searched Ovid MEDLINE, Embase, CINAHL and Cochrane Central Register of Controlled Trials from inception to September 2021 for randomised controlled trials evaluating shorter versus longer duration of antibiotics. Eligible studies will compare durations with a minimum difference of two days of antibiotic therapy, irrespective of antibiotic agent, class, route, frequency or dosage, and will report on any patient-important outcome of benefit or harm. Paired reviewers working independently will conduct title and abstract screening, full-text screening, data extraction and risk of bias (RoB) evaluation using a modified Cochrane RoB 2.0 tool. We will perform random-effects modelling for meta-analyses, with study weights generated using the inverse variance method, and will assess certainty in effect estimates using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. The Instrument for assessing the Credibility of Effect Modification Analyses (ICEMAN) tool will inform assessments of credibility of subgroup effects based on severity of illness, drug class, duration of therapy, setting of CAP acquisition and RoB. ETHICS AND DISSEMINATION: The results will be of importance to general practitioners and internists managing CAP, and may directly inform international clinical guidance. Where concerns regarding antimicrobial resistance continue to grow internationally, this evidence summary may motivate new recommendations regarding shorter durations of therapy. We intend to disseminate our findings via national and international conferences, and publication in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42021283990.

Magnesium sulfate administration in difficult laryngoscopy: An effective and safe method.

PURPOSE: Difficult laryngeal exposure during laryngeal microsurgery and laser surgery is a major concern for otolaryngologists. This study evaluated the efficacy and safety of magnesium sulfate administration in difficult laryngeal exposure patients. STUDY DESIGN: Quasi-experimental design. MATERIALS AND METHODS: Forty adult patients scheduled for laryngeal microsurgery with difficult laryngeal exposure according to Cormack-Lehane (CL) classification were included. Magnesium sulfate 50% (20-30 mg/kg) was administered as a bolus injection. Laryngeal exposure and hemodynamic stability were evaluated before and after the intervention. RESULTS: CL grading was shown a statistically significant improvement after magnesium sulfate administration. There are no clinically significant changes in the mean arterial pressure, heart rate, and oxygen saturation levels in the patients who received magnesium sulfate for better laryngeal exposure. CONCLUSION: Magnesium sulfate is an effective and safe drug for better viewing in difficult laryngeal exposure patients.

Can Posttransarterial Chemoembolization Volumetric Oil Deposition on Computed Tomography Predict Treatment Response on Magnetic Resonance Imaging in Leiomyosarcoma Metastases to the Liver?

OBJECTIVE: To predict early tumor response to transarterial chemoembolization (TACE) based on volumetric oil deposition on posttreatment computed tomography (CT) in patients with leiomyosarcoma liver metastases. METHODS: This retrospective lesion-by-lesion based study included 32 lesions. The volumetric percent enhancing tumor on pre-TACE and 1-month post-TACE venous phase magnetic resonance imaging (MRI), and the percent oil deposition on CT 1 day after TACE were calculated. The predicted post-TACE enhanced percentage was computed by subtracting percent oil deposition from baseline percent enhanced. RESULTS: Mean percentage of viable tumor on pre-TACE MRI was 90.6% ± 9.3%. Mean oil deposition was calculated as 51.4% ± 26.2%. Mean percentage of measured residual tumor enhancement 1 month after TACE was 58.3% ± 27%, which correlates with predicted enhancement percentage of 43.9% ± 25.1% (r = 0.72, P < 0.001). A threshold of 35.5% for enhancement reduction was determined to predict tumor response with an accuracy of 78.1%. CONCLUSION: Volumetric oil deposition on CT can predict residual enhancement on post-TACE MRI.

Consistency of covid-19 trial preprints with published reports and impact for decision making: retrospective review.

Objective: To assess the trustworthiness (ie, complete and consistent reporting of key methods and results between preprint and published trial reports) and impact (ie, effects of preprints on meta-analytic estimates and the certainty of evidence) of preprint trial reports during the covid-19 pandemic. Design: Retrospective review. Data sources: World Health Organization covid-19 database and the Living Overview of the Evidence (L-OVE) covid-19 platform by the Epistemonikos Foundation (up to 3 August 2021). Main outcome measures: Comparison of characteristics of covid-19 trials with and without preprints, estimates of time to publication of covid-19 preprints, and description of differences in reporting of key methods and results between preprints and their later publications. For the effects of eight treatments on mortality and mechanical ventilation, the study comprised meta-analyses including preprints and excluding preprints at one, three, and six months after the first trial addressing the treatment became available either as a preprint or publication (120 meta-analyses in total, 60 of which included preprints and 60 of which excluded preprints) and assessed the certainty of evidence using the GRADE framework. Results: Of 356 trials included in the study, 101 were only available as preprints, 181 as journal publications, and 74 as preprints first and subsequently published in journals. The median time to publication of preprints was about six months. Key methods and results showed few important differences between trial preprints and their subsequent published reports. Apart from two (3.3%) of 60 comparisons, point estimates were consistent between meta-analyses including preprints versus those excluding preprints as to whether they indicated benefit, no appreciable effect, or harm. For nine (15%) of 60 comparisons, the rating of the certainty of evidence was different when preprints were included versus being excluded-the certainty of evidence including preprints was higher in four comparisons and lower in five comparisons. Conclusion: No compelling evidence indicates that preprints provide results that are inconsistent with published papers. Preprints remain the only source of findings of many trials for several months-an unsuitable length of time in a health emergency that is not conducive to treating patients with timely evidence. The inclusion of preprints could affect the results of meta-analyses and the certainty of evidence. Evidence users should be encouraged to consider data from preprints.

Dietary fish intake and the risk of multiple sclerosis: a systematic review and meta-analysis of observational studies.

Objectives: There is some inconclusive evidence for the role of fish consumption in susceptibility to multiple sclerosis (MS). The present study aimed to systematically review and determine the association between dietary fish intake and risk of MS.Methods: A systematic search with related keywords was carried out in PubMed-MEDLIN, Scopus-EMBASE, and OVID-MEDLINE from inception up to September 2019 to find observational studies that evaluated the association between dietary fish intake and the risk of MS. Random effect and subgroup analyses were performed to calculate pooled estimates at 95% CIs.Results: Six articles met the inclusion criteria for systematic review and meta-analysis. The results of this study indicated that the consumption of fish decreases the risk of MS [OR (95% CIs): 0.77 (0.64, 0.92); p-value = 0.004; I2 = 54.7%] compared with controls.Discussion: Dietary intake of at least 0.5 servings of fish per week during adolescence and after might reduce the risk of MS; however, further studies are required to prove this preventive effect.

Imaging of Colorectal Liver Metastasis.

Colorectal cancer (CRC) is one of the most common cancers in the world. The most important determinant of survival and prognosis is the stage and presence of metastasis. The liver is the most common location for CRC metastasis. The only curative treatment for CRC liver metastasis (CRLM) is resection; however, many patients are ineligible for surgical resection of CRLM. Locoregional treatments such as ablation and intra-arterial therapy are also available for patients with CRLM. Assessment of response after chemotherapy is challenging due to anatomical and functional changes. Antiangiogenic agents such as bevacizumab that are used in the treatment of CRLM may show atypical patterns of response on imaging. It is vital to distinguish patterns of response in addition to toxicities to various treatments. Imaging plays a critical role in evaluating the characteristics of CRLM and the approach to treatment. CT is the modality of choice in the diagnosis and management of CRLM. MRI is best used for indeterminate lesions and to assess response to intra-arterial therapy. PET-CT is often utilized to detect extrahepatic metastasis. State-of-the-art imaging is critical to characterize patterns of response to various treatments. We herein review the imaging characteristics of CRLM with an emphasis on imaging changes following the most common CRLM treatments.

Current Treatments and Therapeutic Options for COVID-19 Patients: A Systematic Review.

INTRODUCTION: COVID-19 is the third rising epidemic in the 21st century that quickly turned into a worldwide pandemic. Many clinical studies have been achieved to investigate treatments to confront COVID-19. Therefore, we conducted a systematic review to describe the recent treatment strategies to treat COVID-19 patients. METHODS: A systematic search was performed in the databases of PubMed, Scopus, Embase, Science direct, Up to date, and Web of Science using the keywords of Coronavirus, COVID-19, SARS-CoV-2, Novel Coronavirus, 2019-nCoV, Treatment, Medicine, Therapy, Intervention, Drug, Medications, and Cure. All the relevant articles were collected from December 2019 to July 2020. RESULTS: We included 58 studies including 38 articles (eleven reviews, ten editorial documents, three case reports, one mix method, one cohort study), and 19 published clinical trials. Review of studies showed that Lopinavir/Ritonavir (n=16), Remdesivir (n=13), Convalescent plasma (n=11), Chloroquine (n=11), Ribavirin (n=9), Hydroxychloroquine sulfate (n=8), Traditional Chinese Medicine (TCM) (n=8), and Arbidol (n=7), were the most frequently therapies used to treat COVID-19 patients. CONCLUSION: In the absence of definitive treatment protocols, recently proposed approaches have appeared to be an effective therapy for accelerating the recovery of COVID-19 patients. Some of these treatments may have been in the early stages of testing. However, future preclinical and clinical trials are warranted to validate findings.

Noninvasive Risk Stratification for Nonalcoholic Fatty Liver Disease Among Living Liver Donor Candidates: A Proposed Algorithm.

To reduce waitlist mortality, living donor liver transplantation (LDLT) has increased over the past decade in the United States, but not at a rate sufficient to completely mitigate organ shortage. As a result, there are ongoing efforts to expand the living liver donor pool. Simultaneously, the prevalence of nonalcoholic fatty liver disease (NAFLD) in the general population has increased, which has significant implications on the pool of potential living liver donors. As such, a clinical assessment algorithm that exhaustively evaluates for NAFLD and fibrosis is critical to the safe expansion of LDLT. An ideal algorithm would employ safe and noninvasive methods, relying on liver biopsy only when necessary. While exclusion of NAFLD and fibrosis by noninvasive means is widely studied within the general population, there are no well-accepted guidelines for evaluation of living donors using these modalities. Here we review the current literature regarding noninvasive NALFD and fibrosis evaluation and propose a potential algorithm to apply these modalities for the selection of living liver donors.

Design, synthesis, and preliminary pharmacological evaluation of novel thiazolidinone derivatives as potential benzodiazepine agonists.

Thiazolidinones are well-known heterocycles that demonstrate promising biological effects such as anticonvulsant activity. Hybridization of these chemicals with scaffold, which has necessary pharmacophores for binding to the benzodiazepine receptors, can prompt a novel structure possessing extensive anticonvulsant effects. In this study, novel derivatives of thiazolidinone as new benzodiazepine agonists were designed, synthesized, and biologically evaluated. Compound 5h, 4-chloro-2-(2-fluorophenoxy)-N-(4-oxo-2-(p-tolyl)thiazolidin-3-yl)benzamide, exhibited considerable anticonvulsant activity, proper sedative-hypnotic effect, no memory impairment, and no muscle relaxant effect. The pharmacological effects of the designed compounds were antagonized by flumazenil, which confirmed the benzodiazepine receptors' involvement in their biological effects. Based on in silico calculations of ADME properties of our novel compounds, they could be active oral agents potentially. In this study, we designed novel structures by the hybridization of thiazolidinone moiety with scaffold which has necessary pharmacophores for binding to the benzodiazepine receptors. The results are very promising for developing new lead compounds as benzodiazepine agonists possess anticonvulsant effects.

What proportion of LI-RADS 5 observations reported in clinical practice do not meet LI-RADS 5 criteria?

OBJECTIVES: Liver Imaging Reporting and Data System (LI-RADS, LR) category 5 (definite hepatocellular carcinoma [HCC]) is assigned based on combinations of major imaging features (MFs): size, arterial-phase hyperenhancement (APHE), washout (WO), enhancing capsule, and threshold growth. The criteria were simplified in v2018 compared to v2017. The goal of this study is to assess the proportion of LR-5 observations reported in clinical practice with LI-RADS v2017 or v2018 that did not meet LR-5 criteria based on reported MFs. METHODS: All MR and CT reports using a standardized LI-RADS template between April 2017 and September 2020 were identified retrospectively. For each reported LR-5 observation, size, MFs, and LI-RADS version (v2017 or v2018) were extracted. Reported MFs were used to determine whether LR-5 criteria were met using the applied version of LI-RADS. The data was summarized descriptively. RESULTS: Three hundred eight observations in 234 patients (67.6% male, mean age 66.2 years) were reported as LR-5, including 136 (44.2%) with v2017 and 172 (55.8%) with v2018. 8/136 (6%) v2017 LR-5 observations and 6/172 (3%) v2018 LR-5 observations did not meet LR-5 criteria. Of 8 incorrectly categorized v2017 observations, 3 (43%) lacked APHE, 1 (14%) was a 16-mm new observation with APHE only, and 4 (43%) were 10-19 mm with APHE and WO. Of the 6 incorrectly categorized v2018 observations, 5 (83%) lacked APHE and 1 (17%) was < 10 mm. CONCLUSIONS: Depending on the LI-RADS version, 3-6% of LR-5 observations reported in clinical practice do not meet LR-5 criteria based on reported MFs. Key Points • Depending on the LI-RADS version, 3-6% of LR-5 observations in clinical practice do not meet LR-5 criteria based on reported major imaging features. • Assigning LR-5 category to observations without nonrim arterial-phase hyperenhancement was the most common error.

A systematic survey identified methodological issues in studies estimating anchor-based minimal important differences in patient-reported outcomes.

OBJECTIVE: To systematically survey the literature addressing the reporting of studies estimating anchor-based minimal important differences (MIDs) and choice of optimal MIDs. STUDY DESIGN AND SETTING: We searched Medline, Embase and PsycINFO from 1987 to March 2020. Teams of two reviewers independently identified eligible publications and extracted quotations addressing relevant issues for reporting and/or selecting anchor-based MIDs. Using a coding list, we assigned the same code to quotations capturing similar or related issues. For each code, we generated an 'item', i.e., a specific phrase or sentence capturing the underlying concept. When multiple concepts existed under a single code, the team created multiple items for that code. We clustered codes addressing a broader methodological issue into a 'category' and classified items as relevant for reporting, relevant for selecting an anchor-based MID, or both. RESULTS: We identified 136 eligible publications that provided 6 categories (MID definition, anchors, patient-reported outcome measures, generalizability and statistics) and 24 codes. These codes contained 34 items related to reporting MID studies, of which 29 were also related to selecting MIDs. CONCLUSION: The systematic survey identified items related to reporting of anchor-based MID studies and selecting optimal MIDs. These provide a conceptual framework to inform the design of studies related to MIDs, and a basis for developing a reporting standard and a selection approach for MIDs.

Antibody and cellular therapies for treatment of covid-19: a living systematic review and network meta-analysis.

OBJECTIVE: To evaluate the efficacy and safety of antiviral antibody therapies and blood products for the treatment of novel coronavirus disease 2019 (covid-19). DESIGN: Living systematic review and network meta-analysis, with pairwise meta-analysis for outcomes with insufficient data. DATA SOURCES: WHO covid-19 database, a comprehensive multilingual source of global covid-19 literature, and six Chinese databases (up to 21 July 2021). STUDY SELECTION: Trials randomising people with suspected, probable, or confirmed covid-19 to antiviral antibody therapies, blood products, or standard care or placebo. Paired reviewers determined eligibility of trials independently and in duplicate. METHODS: After duplicate data abstraction, we performed random effects bayesian meta-analysis, including network meta-analysis for outcomes with sufficient data. We assessed risk of bias using a modification of the Cochrane risk of bias 2.0 tool. The certainty of the evidence was assessed using the grading of recommendations assessment, development, and evaluation (GRADE) approach. We meta-analysed interventions with ≥100 patients randomised or ≥20 events per treatment arm. RESULTS: As of 21 July 2021, we identified 47 trials evaluating convalescent plasma (21 trials), intravenous immunoglobulin (IVIg) (5 trials), umbilical cord mesenchymal stem cells (5 trials), bamlanivimab (4 trials), casirivimab-imdevimab (4 trials), bamlanivimab-etesevimab (2 trials), control plasma (2 trials), peripheral blood non-haematopoietic enriched stem cells (2 trials), sotrovimab (1 trial), anti-SARS-CoV-2 IVIg (1 trial), therapeutic plasma exchange (1 trial), XAV-19 polyclonal antibody (1 trial), CT-P59 monoclonal antibody (1 trial) and INM005 polyclonal antibody (1 trial) for the treatment of covid-19. Patients with non-severe disease randomised to antiviral monoclonal antibodies had lower risk of hospitalisation than those who received placebo: casirivimab-imdevimab (odds ratio (OR) 0.29 (95% CI 0.17 to 0.47); risk difference (RD) -4.2%; moderate certainty), bamlanivimab (OR 0.24 (0.06 to 0.86); RD -4.1%; low certainty), bamlanivimab-etesevimab (OR 0.31 (0.11 to 0.81); RD -3.8%; low certainty), and sotrovimab (OR 0.17 (0.04 to 0.57); RD -4.8%; low certainty). They did not have an important impact on any other outcome. There was no notable difference between monoclonal antibodies. No other intervention had any meaningful effect on any outcome in patients with non-severe covid-19. No intervention, including antiviral antibodies, had an important impact on any outcome in patients with severe or critical covid-19, except casirivimab-imdevimab, which may reduce mortality in patients who are seronegative. CONCLUSION: In patients with non-severe covid-19, casirivimab-imdevimab probably reduces hospitalisation; bamlanivimab-etesevimab, bamlanivimab, and sotrovimab may reduce hospitalisation. Convalescent plasma, IVIg, and other antibody and cellular interventions may not confer any meaningful benefit. SYSTEMATIC REVIEW REGISTRATION: This review was not registered. The protocol established a priori is included as a data supplement. FUNDING: This study was supported by the Canadian Institutes of Health Research (grant CIHR- IRSC:0579001321). READERS' NOTE: This article is a living systematic review that will be updated to reflect emerging evidence. Interim updates and additional study data will be posted on our website (www.covid19lnma.com).