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.

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.

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).

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.

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.

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.

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.

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.

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.

Cadmium and Zn hyperaccumulation provide efficient constitutive defense against Turnip yellow mosaic virus infection in Noccaea caerulescens.

To understand the role of Zn and Cd in anti-viral defence, Zn/Cd hyperaccumulator Noccaea caerulescens plants grown with deficient (0.3 µM), replete (10 µM) and excess (100 µM) Zn2+ and Cd (10 µM Zn2+ + 1 µM Cd2+) were infected with Turnip yellow mosaic virus (TYMV). Gas exchange and chlorophyll fluorescence kinetics analyses demonstrated direct TYMV effects on photosynthetic light reactions but N. caerulescens was more resistant against TYMV than the previously studied non-hyperaccumulator N. ochroleucum. Virus abundance and photosynthesis inhibition were the lowest in the high Zn and Cd treatments. RNAseq analysis of 10 µM Zn2+ plants revealed TYMV-induced upregulation of Ca transporters, chloroplastic ZTP29 and defence genes, but none of those that are known to be strongly involved in hyperaccumulation. Synchrotron µ-XRF tomography, however, showed that Zn hyperaccumulation remained strongest in vacuoles of epidermal storage cells regardless of infection. This was in contrast to N. ochroleucum, where apoplastic Zn drastically increased in response to TYMV. These results suggest that the antiviral response of N. caerulescens is less induced by the onset of this biotic stress, but it is rather a permanent resistant state of the plant. Real-time qPCR revealed upregulation of ferritin in Zn10 infected plants, suggesting Fe deprivation as a virus defence strategy under suboptimal Zn supply.

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.

Influence of Asafoetida Extract on the Virulence of the Entomopathogenic Nematode Steinernema carpocapsae and Its Symbiotic Bacterium Xenorhabdus nematophila in the Host Pyrrhocoris apterus.

Nematode-microbe symbiosis plays a key role in determining pathogenesis against pests. The modulation of symbiotic bacteria may affect the virulence of entomopathogenic nematodes (EPNs) and the biological management of pests. We tested the influence of asafoetida (ASF) extract on the virulence of Steinernema carpocapsae and its symbiotic bacterium, Xenorhabdus nematophila, in Pyrrhocoris apterus. A total of 100 mg of ASF killed 30% of EPNs in 48 h, while P. apterus remained unaffected. The EPNs pre-treated with 100 mg of ASF influenced P. apterus's mortality by 24-91.4% during a period of 24 to 72 h. The topical application of ASF acted as a deterrent to S. carpocapsae, lowering host invasion to 70% and delaying infectivity with 30% mortality for 168 h. Interestingly, Steinernema's symbiotic bacterium, Xenorhabdus, remained unaffected by ASF. An in vitro turbidity test containing 100 mg of ASF in a medium increased the growth rate of Xenorhabdus compared to a control. A disc diffusion assay confirmed the non-susceptibility of Xenorhabdus to ASF compared to a positive control, streptomycin. Pro-phenol oxidase (PPO) and phenol oxidase (PO) upregulation showed that ASF influences immunity, while EPN/ASF showed a combined immunomodulatory effect in P. apterus. We report that ASF modulated the virulence of S. carpocapsae but not that of its symbiotic bacterium, X. nematophila, against P. apterus.

Pharmacological augmentation of serotonin reuptake inhibitors in patients with obsessive-compulsive disorder: A network meta-analysis.

OBJECTIVES: The augmentation of serotonin reuptake inhibitors (SRIs) can be achieved by add-on therapy with different pharmacological agents in obsessive-compulsive disorder (OCD) for a better clinical outcome. This network meta-analysis (NMA) was conducted to evaluate and compare the effects of available augmentation agents for SRIs in OCD. METHOD: The data was extracted from 59 relevant clinical trials after a literature search on MEDLINE/PubMed, Scopus, Cochrane databases and clinical trial registries. PRISMA guidelines were followed in data extraction, analysis and reporting. Random effects Bayesian NMA was done to pool the effects across the interventions for the change in Yale-Brown Obsessive-Compulsive Scale (YBOCS) scoring from baseline to the end of the study. Network graph was built, consistency model was run, node splitting analysis was performed, treatments were ranked as per SUCRA score and meta-regression was done for refractoriness to SRIs and duration of augmentation therapy as the predictor variables. RESULTS: The drugs showing significant reduction in YBOCS scoring were pregabalin (MD:-8.1;95% CrI: -16, -0.43), memantine (MD:-6.2;95% CrI: -9.9, -2.3), lamotrigine (MD:-6;95% CrI: -12, -0.47), ondansetron (MD:-5.7;95% CrI: -11, -0.67), granisetron (MD:-5.6;95% CrI: -11, -0.44), aripiprazole (MD:-5.4;95% CrI:-9.1, -1.6), risperidone (MD:-3.3;95% CrI: -6.4, -0.20) and topiramate (MD:-5.3;95% CrI: -9.6, -0.97). The node-split analysis showed that direct and indirect pooled effect sizes for all comparisons were comparable. Meta-regression showed a statistically non-significant association between YBOCS score reduction with the duration of augmentation therapy, but significant with SRI-refractory status. Finally, the results were sorted based on certainty of evidence. CONCLUSION: Memantine was found to be most effective augmentation agent for SRIs in OCD, followed by lamotrigine, ondansetron and granisetron with moderate certainty of evidence. The augmentation agents showed better symptom reduction in patients with SRI-refractory OCD in comparison to non-refractory OCD. PROSPERO REGISTRATION: CRD42022360110.

Improving neonatal health with family-centered, early postnatal care: A quasi-experimental study in India.

Despite the global decline, neonatal mortality rates (NMR) remain high in India. Family members are often responsible for the postpartum care of neonates and mothers. Yet, low health literacy and varied beliefs can lead to poor health outcomes. Postpartum education for family caregivers, may improve the adoption of evidence-based neonatal care and health outcomes. The Care Companion Program (CCP) is a hospital-based, pre-discharge health training session where nurses teach key healthy behaviors to mothers and family members, including skills and an opportunity to practice them in the hospital. We conducted a quasi-experimental study to assess the effect of the CCP sessions on mortality outcomes among families seeking care in 28 public tertiary facilities across 4 Indian states. Neonatal mortality outcomes were reported post-discharge, collected via phone surveys at four weeks postpartum, between October 2018 to February 2020. Risk ratios (RR), adjusting for hospital-level clustering, were calculated by comparing mortality rates before and after CCP implementation. A total of 46,428 families participated in the pre-intervention group and 87,305 in the post-intervention group; 76% of families completed the phone survey. Among the 33,599 newborns born before the CCP implementation, there were 1386 deaths (NMR: 41.3 deaths per 1000 live births). After the intervention began, there were 2021 deaths out of 60,078 newborns born (crude NMR: 33.6 deaths per 1000 live births, RR = 0.82, 95% CI: 0.76, 0.87; cluster-adjusted RR = 0.82, 95% CI: 0.71, 0.94). There may be a substantial benefit to family-centered education in the early postnatal period to reduce neonatal mortality.

Long-Term Yogic Intervention Improves Symptomatic Scale and Quality of Life by Reducing Inflammatory Cytokines and Oxidative Stress in Breast Cancer Patients Undergoing Chemotherapy and/or Radiotherapy: A Randomized Control Study.

INTRODUCTION: Inflammation has been associated with tumor proliferation and metastasis in breast cancer. Yoga is an ancient therapy that helps in reducing inflammation and improves the patient's quality of life (QoL) and fatigue. In the current study, we investigated the effects of long-term yogic intervention at different time points on the level of inflammatory cytokines and oxidative stress, along with the symptomatic scale and QoL in stage II/III breast cancer patients. METHODS: Ninety-six stage II/III breast cancer patients receiving chemotherapy and/or radiotherapy were enrolled and divided into two groups, non-yoga (Group I) and yoga (Group II). Participants in Group II practiced yoga five days per week for 48 weeks. The European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC-QLQ30) was used to measure the QoL and symptomatic scale. Serum levels of pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-α), interferon-γ (IFN-γ) and granulocyte macrophage colony-stimulating factor (GM-CSF), and oxidative stress markers, superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and nitric oxide (NO) were measured at baseline, 16, 32, and 48 weeks in both groups. RESULTS: Yoga significantly (p<0.05) reduced the level of IFN-γ, TNF-α, and MDA and improved QoL (p<0.001) and symptomatic scale (p<0.05) in Group II patients compared to Group I. NO was upregulated in Group I whereas in Group II, it was neither decreased nor increased. CONCLUSION: These findings suggest that yoga may reduce levels of inflammatory cytokines and improve QoL and symptomatic scale in breast cancer patients receiving chemotherapy and/or radiotherapy. Yoga can be an important additional therapy during cancer treatments to cope with treatment side effects including fatigue, depression, and immunological profile, which directly affects the patient's quality of life.

Integrating an algorithmic and health systems thinking approach to improve the uptake of government antenatal nutrition services in Vidisha, Madhya Pradesh (India), 2018 to 2021.

In 2018, the Government of Madhya Pradesh initiated the feasibility testing of integrating an algorithmic approach (assess, give, counsel, treat) to strengthen antenatal nutrition services in routine government-funded programmes coupled with a health system thinking approach to strengthen the health service delivery platform. Implementation phases included (1) an evidence review and stakeholder consultations (April 2018) and (2) a health systems strengthening preparedness phase (May-December 2018), including pilot testing in Vidisha district (January-December 2019) covering ∼54 100 pregnant women with 237 antenatal contact points through 241 government auxiliary nurse midwives/staff nurses. During 2020-21, feasibility testing was expanded to an additional 7 districts. We used programme registers of the Auxiliary Nurse Midwives Registers (2019-21) and National Family Health Survey data for 2016 and 2021 to show changes in the Vidisha district and 7 expansion districts. We compare the performance of Vidisha district with Ashok Nagar district, where no such intervention occurred. Comparing 2016 and 2021 data, the Vidisha district showed improvements in receipt of antenatal care in the first trimester (29 to 85%) and in four antenatal visits (17 to 54%). Using the difference-in-difference approach, a 42% net increase in first-trimester antenatal check-ups in Vidisha as compared to Ashok Nagar is observed. There was also an improvement in the maternal nutrition budget of the state from USD 8.5 million to USD 17.8 million during this period. The Vidisha initiative offers several lessons in time-effective workflow to deliver all constituents of nutrition services at various antenatal contact points through and via routine government health systems. Continued execution of the algorithm for screening, with longitudinal data on the management of all nutrition risks, will be critical to show its long-term impact on maternal morbidities and birth outcomes.

Levothyroxine Therapy and Predictors of Cardiovascular Risk in Clinical Hypothyroidism: A Prospective Cohort Study.

Background Hypothyroidism is associated with hypoadiponectinemia, insulin resistance, and increased cardiovascular risk. The association of adiponectin, insulin resistance, and future cardiovascular risk in clinical hypothyroidism and the effect of levothyroxine are non-conclusive because of the contradictory results. The present prospective cohort study has been conducted to evaluate the effect of levothyroxine on serum adiponectin, insulin resistance, and cardiovascular risk in patients with clinical hypothyroidism. Methods Sixty patients with clinical hypothyroidism who were prescribed levothyroxine were recruited following selection criteria and changes in Zulewski's score, glycemic parameters, homeostatic model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), lipid profile, serum adiponectin, serum high-sensitivity C-reactive protein (hs-CRP), cardiovascular risk indices, and Framingham risk score were assessed 12 weeks post-levothyroxine therapy. Receiver operating characteristic (ROC) analysis was done to detect the cut-off for adiponectin levels to differentiate between responders and non-responders. Neural network models were created to predict the risk of cardiovascular morbidity. Results Post-levothyroxine therapy, there was a significant improvement in body mass index (BMI) (p = 0.025), diastolic blood pressure (p = 0.021), Zulewski's score (p < 0.001), serum insulin (p = 0.005), fasting sugar (p < 0.001), serum adiponectin (p < 0.001), thyroid profile (p < 0.001), total cholesterol (p < 0.001), low-density lipoprotein (p < 0.001), high-density lipoprotein (p = 0.007), triglycerides (p = 0.002), and subcutaneous fat (p = 0.015). Serum adiponectin showed significant improvement in hypothyroid patients compared to euthyroid individuals (mean difference: -2.21; 95% CI: -2.52 to -1.91; p < 0.001). Mean difference in insulin resistance (HOMA-IR: 0.3, p < 0.001; QUICKI: -0.002, p < 0.001) and cardiovascular risk (atherogenic index: 0.12, p = 0.04; coronary risk index: 0.14, p = 0.038; Framingham risk score: 0.65, p = 0.041) also showed improvement. Serum adiponectin and thyroid-stimulating hormone levels were directly correlated with insulin resistance and cardiovascular risk scores. Conclusion The reduced serum adiponectin level and increased cardiovascular risk in clinical hypothyroidism were improved with hormone replacement, and serum adiponectin level was found to be a good prognostic marker for the treatment response.

The Attending of the Day ("The Pretending"): An Exercise in Autonomy.

Background As regulations governing appropriate resident supervision increase, it has become increasingly difficult to provide residents with the appropriate level of autonomy during their training years. The "Attending of the Day" describes an experiential teaching method that provides a balance between learners' autonomy and appropriate supervision. Methodology Each day one member of the inpatient team is selected as the "Attending of the Day," or "The Pretending." She or he then performs the typical duties of the teaching faculty, from medical decision-making regarding patient care to educating other team members during rounds. "The Pretending" is directly supervised by the clinical faculty. Results Using the grounded theory methodology, we analyzed 935 anonymous evaluations from students and residents over 14 years, leading to the identification of the following three major themes: created an enabling learning environment, provided autonomy, and improved confidence. These results led to the inclusion of the technique as part of the Back to Bedside initiative, which was rated as an essential tool in building confidence and autonomy by 75% of the participants in the 2018 Accreditation Council for Graduate Medical Education's Back to Bedside residents' well-being survey. Recently, the Jacobs School of Medicine launched the Moments of Excellence in Education: Recognition and Inspiration (MEE:RI) program which gives students a way to recognize exemplary moments of teaching they encounter. The "Attending of the Day" method received recognition as a transformative experience in students' medical education. Conclusions The "Attending of the Day" is the first innovative experiential learning technique that allows learners of all levels in both Undergraduate Medical Education (UME) and Graduate Medical Education (GME) to practice and assess autonomy. This innovation suggests that residents and students are looking for opportunities to challenge themselves. "The Pretending" allows them to experience those challenges in an empowering learning environment while they gradually build their confidence on the path to achieving progressive autonomy.