Diagnostic Efficacy of Enhanced Visual Assessment [Visual Check] for Triaging Cervical Cancer Screen Positive Women.

Introduction: Colposcopy is important for triaging any abnormal cervical screening test. Scarcity of trained colposcopists and colposcopy centers is a big hurdle to screening programs in low- and middle-income countries. Objectives of the Study: The objective was to assess the performance of the artificial intelligence incorporated into the mobile optical device technologies (ODT) Enhanced Visual Assessment (EVA visual check) against physician colposcopic diagnosis and the gold standard of histopathology. Materials and Methods: It was a cross-sectional observational study conducted on women referred to a colposcopy clinic following an abnormal screening test. Colposcopic examination was performed by colposcopists using the MobileODT EVA system. Physician's impression and Visual Check analysis were compared with the final histopathological analysis or cytology. Cases with normal cytology and normal colposcopy did not undergo biopsy, and these were considered normal. Results: A total of 2050 women were screened, and 147 screen-positive women were recruited in the study. EVA Visual Check had a sensitivity of 86.8% (75-95), specificity of 28.7% (20-39), positive predictive value (PPV) of 40.7% (32-50), negative predictive value (NPV) of 79.4% (62-91), and diagnostic accuracy of 49.7% (41-58) for diagnosing cervical intraepithelial neoplasia (CIN) 1+ lesions. EVA Visual Check has a sensitivity of 89.3% (72-98), specificity of 26.1% (18-35), PPV of 22.1% (15-31), NPV of 91.2% (76-98), and diagnostic accuracy of 38.1% (30-46) for CIN 2+ lesions. Conclusion: MobileODT EVA colposcope with AI has sensitivity comparable to physician's diagnosis, whereas specificity, PPV, and NPV were less than that of physician's diagnosis. It could prove valuable for triage of screen-positive women for further management.

Efficacy and Safety of Upadacitinib in Moderate-to-Severe Atopic Dermatitis: A Meta-Analysis.

Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disorder. Topical corticosteroids are the cornerstone of therapy in mild AD, whereas the JAK inhibitor upadacitinib is approved in the United States, Europe, and other countries for treating moderate-severe AD in adults and children over 12 years old whose disease is not adequately controlled with other systemic drugs, including biologics. The objective of this meta-analysis was to assess the overall efficacy and safety of upadacitinib in moderate to severe AD. All randomized controlled trials (RCTs) evaluating the efficacy and safety of upadacitinib in moderate to severe AD were included in the meta-analysis. The pooled analysis revealed a significant proportion of patients achieving Eczema Area and Severity Index-75 (EASI 75) (R.R. = 3.86; 95% CI = 3.12 to 4.78, p < 0.00001), EASI 100 (R.R. = 13.09; 95% CI = 7.40 to 23.17, p < 0.00001), Worst Pruritus Numerical Rating Score (WP-NRS) response (R.R. = 4.44; 95% CI = 3.72 to 5.29, p< 0.00001), and validated Investigator's Global Assessment (v-IGA) (RR = 5.96; 95% CI = 4.79 to 7.41, p < 0. 00001) in the upadacitinib arm compared to the placebo arm. Moreover, the pooled analysis also suggested that treatment-emergent adverse events (TAEs) were relatively higher with upadacitinib than with placebo, but were mild and easily manageable (R.R. = 1.15; 95% CI = 1.09 to 1.23, p<0.00001). This meta-analysis showed that upadacitinib had a significant beneficial effect and tolerable adverse effect profile in patients with moderate and severe AD. Dose regimens of 15 mg and 30 mg seemed to have similar benefits. However, further trials are needed to assess long-term efficacy and safety profile.

Pilot study comparing sleep logs to a commercial wearable device in describing the sleep patterns of physicians-in-training.

With the increasing burden of professional burnout in physicians, attention is being paid to optimizing sleep health, starting in training. The multiple dimensions of physicians' sleep are not well described due to obstacles to easily and reliably measuring sleep. This pilot study tested the feasibility of using commercial wearable devices and completing manual sleep logs to describe sleep patterns of medical students and residents. Prospective pilot study of 50 resident physicians and medical students during a single year of training. Participants completed a manual sleep log while concurrently wearing the Fitbit Inspire device for 14-consecutive days over three clinical rotations of varying work schedules: light, medium, and heavy clinical rotations. Study completion was achieved in 24/50 (48%) participants. Overall correlation coefficients between the sleep log and Fitbit were statistically low; however, the discrepancies were acceptable, i.e., Fitbit underestimated time in bed and total sleep time by 4.3 and 2.7 minutes, respectively. Sleep onset time and waketime were within 8 minutes, with good agreement. Treatment of sleep episodes during the day led to variance in the data. Average missingness of collected data did not vary between medical students or residents or by rotation type. When comparing the light to heavy rotations, hours slept went from 7.7 (±0.64) to 6.7 (±0.88), quality-of-life and sleep health decreased and stress, burnout, and medical errors increased. Burnout was significantly associated with worse sleep health, hours worked, and quality-of-life. Prospective data collection of sleep patterns using both sleep logs and commercial wearable devices is burdensome for physicians-in-training. Using commercial wearable devices may increase study success as long as attention is paid to daytime sleep. In future studies investigating the sleep of physicians, the timing of data collection should account for rotation type.

Efficacy and safety of monoamine reuptake inhibitors in attention deficit hyperactivity disorder: A Bayesian network meta-analysis.

The use of first-line drugs in clinical practice for attention deficit hyperactivity disorder (ADHD) is limited by their adverse effects. Many novel monoamine reuptake inhibitors (MRIs) with better safety profiles and comparable efficacy are also being tried for ADHD. This network meta-analysis (NMA) has evaluated the efficacy and safety of MRIs in ADHD. The data was extracted from 31 relevant clinical trials after a literature search on MEDLINE/PubMed, Embase, Scopus, Cochrane databases, and clinical trial registries. Quality assessment was performed using the risk of bias assessment tool (RoB2) by Cochrane Collaboration, and the random-effects model was used to estimate the effect size. Standardised mean difference (SMD) and 95% credible interval(95%CrI) were reported for the reduction in ADHD rating scale score. Network geometry was visualised, and node splitting was done for the closed triangles. Meta-regression was done for the duration of therapy. PRISMA-NMA guidelines were followed in selecting, analyzing, and reporting findings. The drugs showing significant reduction on the ADHD rating scale as compared to placebo are bupropion (SMD: 0.33; 95%CrI: 0.60,-0.059), dasotraline(SMD: 0.49; 95%CrI: 0.82,-0.16), venlafaxine(SMD: 0.71; 95%CrI: 1.3,-0.15), viloxazine(SMD: 0.45; 95%CrI: 0.77,-0.12). Other drugs (centanafadine, duloxetine, edivoxetine, reboxetine, tipepidine, vortioxetine) were no better than placebo in reducing symptom severity of ADHD. The efficacy of none of the drugs was found to be significantly different as compared to methylphenidate. Among all, duloxetine (OR:15; 95%CrI:1.8130) showed significantly more treatment-emergent adverse events than methylphenidate. In conclusion, venlafaxine, viloxazine, and bupropion are the most efficacious MRIs for ADHD symptom reduction as compared to placebo with high certainty of evidence.

Pharmacological interventions for antipsychotic-induced weight gain in schizophrenia: A network meta-analysis.

OBJECTIVE: Antipsychotic-induced weight gain (AIWG) is a significant but frequently neglected adverse effect of first- and second-generation antipsychotic therapy, which may lead to cardiovascular disturbances. The present network meta-analysis (NMA) was conducted to evaluate and compare the effects of available treatment options in antipsychotic-induced weight gain (AIWG). METHODS: The data was extracted from 68 relevant clinical trials after a literature search on MEDLINE/PubMed, Embase, Scopus, Cochrane databases and clinical trial registries. Random-effects Bayesian NMA was done to pool the effects across the interventions for the change in body weight from baseline. A network graph was built, a consistency model was run, node split analysis was performed, treatments were ranked as per the SUCRA score and meta-regression was done for the duration of therapy, baseline body weight and treatment strategy as the predictor variables. Finally, the results were sorted based on the certainty of evidence. RESULTS: The drugs showing significant reduction in body weight in order of magnitude of effect size include sibutramine 10 mg (-8.0 kg; -16. to -0.21), metformin 750 mg + lifestyle modification (-7.5 kg; -12 to -2.8), topiramate 200 mg (-7 kg; -10 to -3.4), metformin 750 mg (-5.7 kg; -9.3 to -2.1), topiramate 100 mg (-5.7 kg; -8.8 to -2.5), topiramate 50 mg (-5.2 kg; -10 to -0.57), liraglutide 1.8 mg (-5.2 kg; -10., -0.080), sibutramine 15 mg (-4.5 kg; -8.9 to -0.59), nizatidine 300 mg (-3.0 kg; -5.9 to -0.23) and metformin 1000 mg (-2.3 kg; -4.6 to -0.0046). There was no effect of duration of follow-up, baseline body weight and, preventive versus therapeutic strategy on weight reduction in AIWG. CONCLUSION: Metformin 750 mg with lifestyle modification was the most effective treatment for AIWG, followed by topiramate 200 mg, metformin 750 mg, and topiramate 100 mg with moderate certainty of evidence.

Evaluation of the pharmacodynamic interaction effect of augmentation agents with clozapine in patients with treatment-resistant schizophrenia: A simulation study of clinical data.

INTRODUCTION: The aim of the study was to evaluate interaction effect of various augmentation strategies with clozapine in patients with Treatment-resistant schizophrenia. METHODS: Data was extracted for change in positive and negative syndrome scale (PANSS) or brief psychiatric rating scale (BPRS) scores for monotherapy with various antipsychotic agents alone and their combination with clozapine. Individual patient data was generated using simulation of data (factorial trial framework) from published clinical trials for sample sizes from eight to 400 to evaluate interaction effect through linear modeling. Dose equivalents were calculated, and best fit models were determined for simulated data. RESULTS: The polynomial model was found to be the best fit for the simulated data to determine interaction effect of combination. The clozapine augmentation with risperidone and ziprasidone was found to be antagonistic, whereas it was additive for haloperidol, aripiprazole, and quetiapine. A synergistic effect was observed for ECT combined with clozapine (Interaction effect: -7.62; p <0.001). A sample size of 250-300 may be sufficient to demonstrate a clinically significant interaction in future trials. CONCLUSION: Clozapine may be augmented with electroconvulsive therapy, leading to the enhancement of antipsychotic effect. Though some antipsychotics like aripiprazole demonstrate additive effects, they may also add to the adverse effects.

Integration of Electrospun Scaffolds and Biological Polymers for Enhancing the Delivery and Efficacy of Mesenchymal Stem/Stromal Cell Therapies.

Mesenchymal stem/stromal cells (MSCs) have emerged as a promising therapeutic approach for a variety of diseases due to their immunomodulatory and tissue regeneration capabilities. Despite their potential, the clinical application of MSC therapies is hindered by limited cell retention and engraftment at the target sites. Electrospun scaffolds, with their high surface area-to-volume ratio and tunable physicochemical properties, can be used as platforms for MSC delivery. However, synthetic polymers often lack the bioactive cues necessary for optimal cell-scaffold interactions. Integrating electrospun scaffolds and biological polymers, such as polysaccharides, proteins, and composites, combines the mechanical integrity of synthetic materials with the bioactivity of natural polymers and represents a strategic approach to enhance cell-scaffold interactions. The molecular interactions between MSCs and blended or functionalized scaffolds have been examined in recent studies, and it has been shown that integration can enhance MSC adhesion, proliferation, and paracrine secretion through the activation of multiple signaling pathways, such as FAK/Src, MAPK, PI3K/Akt, Wnt/ß-catenin, and YAP/TAZ. Preclinical studies on small animals also reveal that the integration of electrospun scaffolds and natural polymers represents a promising approach to enhancing the delivery and efficacy of MSCs in the context of regenerating bone, cartilage, muscle, cardiac, vascular, and nervous tissues. Future research should concentrate on identifying the distinct characteristics of the MSC niche, investigating the processes involved in MSC-scaffold interactions, and applying new technologies in stem cell treatment and biofabrication to enhance scaffold design. Research on large animal models and collaboration among materials scientists, engineers, and physicians are crucial to translating these advancements into clinical use.

Efficacy and safety of dasotraline in attention-deficit hyperactivity disorder: A systematic review and meta-analysis.

Background and Aim: Pharmacotherapeutic options for attention-deficit hyperactivity disorder (ADHD) are limited due to adverse effects and inadequate efficacy of existing drugs. Clinical trials were conducted on dasotraline in search of a safer and more efficacious alternatives to stimulant agents. This meta-analysis was conducted to evaluate the efficacy and safety of dasotraline in ADHD compared to placebo. Methods: The reviewers extracted data from five relevant clinical trials after a literature search on Medline/PubMed, Embase, Scopus, Google Scholar, and Cochrane databases and Clinical Trial Registries. Quality assessment was done using the risk of bias assessment tool, and the random-effects model was used to estimate the effect size. Sub-group analysis, meta-regression, and sensitivity analysis were done as applicable. PRISMA guidelines were followed in the selection, analysis, and reporting of findings. Results: Dasotraline significantly reduced the ADHD total symptom score (SMD: -0.35; 95% CI: -0.55 to -0.15; P < 0.001), hyperactivity/impulsivity subscale score (SMD: -0.27; 95% CI: -0.44 to -0.11; P = 0.001), inattentiveness sub-scale score (SMD: -0.33; 95% CI: -0.53 to -0.14; P < 0.001), and CGI-S (SMD: -0.25; 95% CI: -0.42 to -0.08; P = 0.003). Sub-group analysis showed a significant reduction of ADHD symptoms in both pediatric and adult age groups. Meta-regression showed a significant association between SMD of ADHD symptom score reduction and the duration of dasotraline therapy. The incidence of decreased appetite showed dose dependence but not the incidence of insomnia. Conclusions: Dasotraline 4 mg (in children) and 6 mg (in adults) can improve the clinical outcome in patients with ADHD by improving symptoms and global functioning with acceptable tolerability.PROSPERO Registration number: CRD42022321979.

Efficacy and safety of low-dose amisulpride versus olanzapine-fluoxetine combination in post-schizophrenic depression: A randomized controlled trial.

Post-schizophrenic depression (PSD) increases the morbidity, mortality, and health burden in patients with schizophrenia. However, treatment of PSD is challenging due to the lack of substantial evidence of standard clinical practice. This study was aimed at comparing the efficacy and safety of low-dose amisulpride versus olanzapine-fluoxetine combination (OFC) in PSD. This was a randomized controlled trial conducted in sixty patients with PSD fulfilling the eligibility criteria. Recruited patients were randomized to receive either amisulpride at low dose (i.e., 100-300 mg/day) or OFC (5/10 mg + 20 mg) for eight weeks. The Calgary Depression Scale for Schizophrenia (CDSS), the Clinical Global Impression-Severity (CGI-S) and serum BDNF levels were assessed at baseline and after eight weeks of treatment. The change in the CDSS scores from baseline over eight weeks was significant in both the amisulpride and OFC groups. However, the changes were not significant when compared between the groups. Similarly, the changes in CGI-S scores and serum BDNF levels were significant in each group; but non-significant between the groups. A significant negative correlation was found between the changes in the CDSS scores and the serum BDNF levels in each group. No significant adverse events were noted in either group. Thus, to conclude, low-dose amisulpride can be a potential monotherapy in PSD with a favourable clinical outcome and safety profile (ClinicalTrials.gov ID: NCT04876521).

Total valproate versus free valproate in therapeutic drug monitoring for bipolar disorder: A cross-sectional study.

INTRODUCTION: The debate about observing total versus free serum valproate levels for therapeutic drug monitoring (TDM) has been unresolved for decades. This study was planned to assess the agreement between the total versus free valproate levels and the advantage of one method over the other in TDM. METHODS: The present cross-sectional study was done on 93 patients with bipolar disorder. The intraclass correlation coefficient, Bland Altman analysis, and Lin's concordance analysis were done to assess the agreement between the total and free valproate concentrations. Linear and polynomial models were constructed to evaluate the relation between the two measurements. Receiver operating characteristics analysis was done to compare the accuracy for differentiating remission from non-remission on Young's mania rating scale (YMRS). RESULTS: The intraclass correlation coefficient and Lin's concordance correlation coefficient were 0.491 (p = .002) and 0.055 (95% CI:0.037, 0.073), respectively. Bland Altman's analysis showed proportional bias. A polynomial model of second order was found to be the best fit for the prediction of free valproate from the data for total valproate, and 81.4% of the variability in free valproate could be explained when adjusted for albumin levels. The area under the curve for total valproate was 0.60 when compared to free valproate 0.56 for differentiating between remission and non-remission, but the comparison between the two ROC analyses was not statistically significant. CONCLUSION: Free valproate does not provide any added advantage over the total valproate levels; hence, total valproate levels may continue to be used as the marker for drug monitoring.

Augmentation Strategies for Partial or Non-responders to Clozapine in Patients with Schizophrenia: A Bayesian Network Meta-analysis of Randomized Controlled Trials.

Clozapine is the only approved drug for treatment-resistant schizophrenia, but the response to the drug is often inadequate. Augmentation with other antipsychotics, anticonvulsants, and antidepressants is recommended for such patients, but there is a lack of evidence regarding the most effective therapy. This network meta-analysis was conducted to evaluate the efficacy of pharmacological agents used in the augmentation strategies in patients who were partial/ non-responders to clozapine. Relevant data were extracted from 30 randomized controlled trials through searches of electronic databases (MEDLINE/PubMed, Embase, Cochrane, clinical trial registries). PRISMA guidelines were followed for the extraction, management, analysis, and reporting of the data. The outcome measure in this study was a reduction in symptom severity according to total PANSS/BPRS and was reported as the standardized mean difference with a 95% credible interval. Bayesian network meta-analysis with random effects model and uninformative priors was conducted, and the ranking probability of each intervention was done. Meta-regression was done to assess the effect of duration on the reduction in symptom severity scores. Mirtazapine (-5.2 [95%CrI: -7.7, -2.7]) and memantine (-2.1 [95%CrI: -4.0, -0.19]] were more efficacious than placebo for augmentation of clozapine in partial/non-responders and were the most effective adjunctive agents as per SUCRA scores. Both drugs did not cause a significant increase in frequency of adverse events compared to placebo. There was a significant effect of duration on the reduction in symptom severity. There was no evident publication bias. Mirtazapine and memantine may prove beneficial for augmentation of clozapine in non/partial responders to monotherapy.

Medical Law and Medical School Curricula: A Systematic Review.

Health law plays a crucial role in the field of medicine, as it dictates appropriate practices, regulations, and rights and responsibilities for healthcare professionals and patients. Despite this undeniable relationship, there is a lack of focus on health law, and an outdated hidden curriculum in medical education has perpetuated long-standing negative perceptions of the legal system. PubMed was searched for articles related to medicolegal education that were published from January 1950 to December 2022. The following search terms were utilized: "(medical student) AND (law OR legal OR medico-legal) AND (education)". Literature that directly or indirectly discussed the relationship between law and medicine as well as the role of medical student education within the medicolegal nexus were reviewed. Additional literature was identified from reference lists of systematic and literature reviews. The authors manually reviewed each included publication to determine key details, study populations, and conclusions. The PubMed search revealed 3,592 papers that were sorted for relevance. Forty-four articles published between 1971 and 2022 were reviewed and analyzed. Three main themes consistently emerged from the discussions in these articles. The first theme concerns the sentiment among medical students that they were ill-prepared to manage the legal aspects of healthcare. The second theme concerns the negative perception of health law by medical students. The third theme details the benefits of including medicolegal courses in medical school curricula. This study sheds light on the notion that medical students feel ill-prepared to handle the legal aspects of healthcare due to limited medicolegal education. Furthermore, negative perceptions of the legal field continue to exist amongst medical students due to a plethora of factors, including an outdated hidden curriculum. Incorporating medicolegal courses into medical school curricula can foster positive attitudes toward the field of law and lead to enhanced professional ethics, increased patient advocacy, and potentially improved patient outcomes.

Efficacy and Safety of Fezolinetant for the Treatment of Menopause-Associated Vasomotor Symptoms: A Meta-analysis.

OBJECTIVE: To evaluate the efficacy and adverse events of fezolinetant for treating vasomotor symptoms (VMS) of menopause. DATA SOURCES: PubMed/MEDLINE, ClinicalTrials.gov , EMBASE, Cochrane Database, Scopus, and WHO International Clinical Trials Registry Platform were searched through June 2023 for publications and randomized controlled trials on fezolinetant compared with placebo in menopausal women who experienced moderate-to-severe VMS. METHODS OF STUDY SELECTION: Our literature search identified 330 articles, of which five studies with six reports were included in our meta-analysis per our eligibility criteria. TABULATION, INTEGRATION, AND RESULTS: The risk of bias was evaluated using Cochrane's RoB 2 (Risk of Bias version 2) tool, quality of evidence was graded using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach, and outcome measures data for effect size were pooled in random-effects model and rated. A total of 2,168 participants from five randomized clinical trials (six reports) were included. Fezolinetant significantly lowered VMS frequency, with pooled mean difference of 2.62 (95% CI, 1.84-3.41). The pooled mean difference for fezolinetant compared with placebo for the MENQOL (Menopause-Specific Quality of Life) measure was -0.60 (95% CI, -0.92 to -0.28), and the mean percentage improvement in VMS frequency was 22.51% (95% CI, 15.35-29.67). Fezolinetant was associated with improvement in sleep quality when compared with placebo. CONCLUSION: Fezolinetant is effective in lowering moderate-to-severe VMS frequency and sleep disturbances in postmenopausal women. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42023427616.

Efficacy of pharmacological agents for the management of treatment-resistant schizophrenia: a network meta-analysis.

OBJECTIVE: The present network meta-analysis (NMA) was conducted to compare and generate evidence for the most efficacious treatment among available pharmacological interventions for treatment-resistant schizophrenia (TRS). METHODS: Reviewers extracted data from 47 studies screened from PubMed/MEDLINE, Embase, Cochrane databases and clinical trial registries fulfilling the eligibility criteria. Random effects Bayesian NMA was done with non-informative priors. Network geometry was visualized, and node splitting was done for the closed triangles. Standardized mean difference and 95% credible interval(95%CrI) were reported for the reduction in symptom severity scores. The probability of each intervention for each rank was plotted. Meta-regression was done for the duration of the therapy. RESULTS: Augmentation of antipsychotics with escitalopram (SMD: -1.7[95%CrI: -2.8, -0.70]), glycine (SMD: -1.2 [95%CrI: -2.2, -0.28]) and Yokukansan (SMD: -1.3 [95%CrI: -2.4, -0.24]) shows a statistically significant reduction in symptom severity when compared to clozapine. As per surface under cumulative ranking curve analysis, escitalopram in combination with antipsychotics appeared to be the best intervention with moderate certainty of evidence. There was no significant effect of the duration of therapy on the treatment effects. CONCLUSION: Escitalopram augmentation of antipsychotics appears to be the most efficacious treatment with moderate certainty of evidence among the available pharmacological interventions. PROSPERO REGISTRATION: CRD42022380292.

Regio- and Stereocontrolled Hydrohalogenation of Ynamides with N-Halosuccinimides (NXS) as the Halogen Source: Synthesis of (E)-α-Haloenamides.

Presented herein is a facile stereoselective construction of synthetically versatile chiral and achiral (E)-α-haloenamides under mild conditions utilizing N-halosuccinimides and diphenylphosphine oxide. This reaction is metal-free, mild, efficient, very rapid, and practical and highlights the synthetic versatility of ynamides. The reaction has a broad substrate scope; both chiral and achiral ynamides have been transformed into the corresponding (E)-α-haloenamides within a very short period of time without compromising selectivity or complexity.

Effect of Virgin Coconut Oil (VCO) on Cardiometabolic Parameters in Patients with Dyslipidemia: A Randomized, Add-on Placebo-Controlled Clinical Trial.

OBJECTIVE: Statin monotherapy for dyslipidemia is limited by adverse effects and limited effectiveness in certain subgroups like metabolic syndrome. Add-on therapy with an agent with a known safety profile may improve clinical outcomes, and virgin coconut oil (VCO) may be the candidate agent for improving the cardiometabolic profile. The present study was conducted to evaluate the effect of add-on VCO with atorvastatin in dyslipidemia in adults. METHODS: A randomized, double-blind clinical trial was conducted on 150 patients with dyslipidemia who were randomized into control and test groups. The control group received atorvastatin monotherapy, whereas the test group received add-on VCO with atorvastatin for 8 weeks. At baseline, demographic, clinical, and biochemical parameters were assessed and repeated after 8 weeks of therapy. The main outcome measures were lipid profile, cardiovascular risk indices, 10-year cardiovascular risk, body fat compositions, and thiobarbituric acid reactive substances (TBARS). RESULTS: The increase in HDL in the test group was significantly greater than in the control group (MD: 2.76; 95%CI: 2.43-3.08; p < 0.001). The changes in the atherogenic index (p = 0.003), coronary risk index (p < 0.001), cardiovascular risk index (p = 0.001), and TBARS (p < 0.001) were significantly greater in the test group. The decrease in LDL, total cholesterol and lipoprotein(a), were significantly higher in the control group. There were no significant differences between the groups with respect to the changes in triglyceride, VLDL, and 10-year cardiovascular risk. CONCLUSIONS: Add-on VCO (1000 mg/day) with atorvastatin (10 mg/day) can achieve a better clinical outcome in patients with dyslipidemia by increasing HDL and improving oxidative stress cardiovascular risk indices.

Association between sleep health and rates of self-reported medical errors in intern physicians: an ancillary analysis of the Intern Health Study.

STUDY OBJECTIVES: Reduced sleep duration and work hour variability contribute to medical error and physician burnout. This study assesses the relationships between physician performance, burnout, and the dimensions of sleep beyond hours slept. METHODS: This was an ancillary analysis of 3 years of data from an international prospective cohort study: the Intern Health Study. Actigraphy data from 3,654 intern physicians capturing sleep timing, regularity, efficiency, and duration were used individually and combined as a composite sleep health index to measure the association of multidimensional sleep patterns on self-reported medical errors and burnout. RESULTS: From 2017-2019, interns' work hours decreased by 4 hours per week and total sleep time also decreased (6.7 to 5.99 hours), and sleep efficiency, timing, and regularity all worsened (all P < .05). In the 21.2% of participants who committed an error, there was no difference in sleep duration, timing, or regularity. Lower sleep efficiency was associated with higher odds of committing an error (P = .003) and higher burnout scores (P < .001). Although overall sleep quality was poor in the entire cohort, interns in the lowest quintile of sleep duration, regularity, and efficiency had higher burnout scores than those in the best quintile. CONCLUSIONS: Sleep efficiency, not duration, was associated with increased self-reported medical errors and burnout in intern physicians. Overall sleep quality and duration worsened despite fewer hours worked. Future studies on physician burnout should measure all aspects of sleep health. CITATION: Hassinger AB, Velez C, Wang J, Mador MJ, Wilding GE, Mishra A. Association between sleep health and rates of self-reported medical errors in intern physicians: an ancillary analysis of the Intern Health Study. J Clin Sleep Med. 2024;20(2):221-227.

Antigen loss following CAR-T cell therapy: Mechanisms, implications, and potential solutions.

Chimeric Antigen Receptor T-cell (CAR-T cell) therapy has emerged as a groundbreaking immunotherapeutic approach for treating various hematological malignancies. CAR-T cells are engineered to express synthetic receptors that target specific antigens on cancer cells, leading to their eradication. While the therapy has shown remarkable efficacy, a significant challenge that has been observed in 30%-70% of patients showing recurrent disease is antigen loss or downregulation. We searched PubMed/MEDLINE, EMBASE, and Google scholar for articles on antigen loss/escape following Chimeric antigen receptor T-cell therapy in malignancies. Antigen loss refers to the loss or reduction in the expression of the target antigen on cancer cells, rendering CAR-T cells ineffective. This phenomenon poses a significant clinical concern, as it can lead to disease relapse and limited treatment options. This review explores the mechanisms underlying antigen loss following CAR-T cell therapy, its implications on treatment outcomes, and potential strategies to overcome the problem.

Cervical Cancer Screening Coverage at Tertiary Care Institutes Across India.

OBJECTIVES: The 70% screening coverage target proposed in the global cervical cancer elimination strategy is not achieved even at tertiary centres in India. A situational analysis was done to assess the currently existing facilities and barriers in tertiary care institutes. METHODS: This cross sectional multicentric study was conducted from August to September 2021 in six tertiary care institutes across India. Women aged 30-49 years attending outpatient services (OPD) were invited for cervical screening. Women and health care professionals (HCPs) were administered structured questionnaires to assess knowledge, attitude and practices regarding cervical cancer screening services. RESULTS: Out of 6709 eligible women who attended OPD, 1666 (24.8%; range:19-57%) received screening. Availability of screening kits was limited to 10-25 Pap/HPV tests per day. Visual inspection with acetic acid (VIA) and HPV testing were offered only at certain centres. Colposcopy and treatment facilities were optimal at all centres. Knowledge, attitude and practices were analysed for 1800 women: 45.7% had heard of cervical cancer, 78.0% did not know that it is preventable, 75.8% never heard about screening. Common symptoms correctly identified included postmenopausal bleeding (4.8%), postcoital bleeding (5.7%), intermenstrual bleeding (5.8%) and vaginal discharge (12.4%). Risk factors were identified by minority: poor menstrual hygiene (6.6%), oral contraceptive pill use (6.4%), multiparity (4.4%), and HPV infection (3.0%). Out of 21, mean total knowledge score (MTKS) was 2.07± 2.67. Out of 317 HCPs, 96.5% knew that cervical cancer is caused by HPV infection, is preceded by premalignant stage, and that it is preventable by screening and treatment (80.1%). Knowledge about screening modalities was present in 87.4% for cytology, 75.1% for VIA, 68.8% for HPV test. MTKS of HCPs was 20.88±6.61 out of 32. CONCLUSION: Even at tertiary centres, limited availability of HPV tests, reluctance to implement VIA and lack of awareness among women remain the major barriers.

Automated Assessment of Digital Images of Uterine Cervix Captured Using Transvaginal Device-A Pilot Study.

In low-resource settings, a point-of-care test for cervical cancer screening that can give an immediate result to guide management is urgently needed. A transvaginal digital device, "Smart Scope®" (SS), with an artificial intelligence-enabled auto-image-assessment (SS-AI) feature, was developed. In a single-arm observational study, eligible consenting women underwent a Smart Scope®-aided VIA-VILI test. Images of the cervix were captured using SS and categorized by SS-AI in four groups (green, amber, high-risk amber (HRA), red) based on risk assessment. Green and amber were classified as SS-AI negative while HRA and red were classified as SS-AI positive. The SS-AI-positive women were advised colposcopy and guided biopsy. The cervix images of SS-AI-negative cases were evaluated by an expert colposcopist (SS-M); those suspected of being positive were also recommended colposcopy and guided biopsy. Histopathology was considered a gold standard. Data on 877 SS-AI, 485 colposcopy, and 213 histopathology were available for analysis. The SS-AI showed high sensitivity (90.3%), specificity (75.3%), accuracy (84.04%), and correlation coefficient (0.670, p = 0.0) in comparison with histology at the CINI+ cutoff. In conclusion, the AI-enabled Smart Scope® test is a good alternative to the existing screening tests as it gives a real-time accurate assessment of cervical health and an opportunity for immediate triaging with visual evidence.