Glucagon-like peptide-1 receptor agonists in adolescents with overweight or obesity with or without type 2 diabetes multimorbidity-a systematic review and network meta-analysis.

AIM: To synthesize the evidence on the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in adolescents with overweight or obesity. MATERIALS AND METHODS: For this systematic review and network meta-analysis, we searched five databases and registries until 2 March 2024 for eligible randomized controlled trials (RCTs). The primary outcome was weight change. We did a pairwise meta-analysis to compare GLP-1RAs and placebo, followed by a drug-wise network meta-analysis (NMA) to compare GLP-1RAs against each other. RESULTS: We screened 770 records to include 12 RCTs with 883 participants. The evidence suggests that GLP-1RAs reduced weight (mean difference -4.21 kg, 95% confidence interval [CI] -7.08 to -1.35) and body mass index (BMI; mean difference -2.11 kg/m2, 95% CI -3.60 to -0.62). The evidence on waist circumference, body fat percentage and adverse events (AEs) was very uncertain. The results remained consistent with subgroup analyses for coexisting type 2 diabetes. Longer therapy duration led to a greater reduction in weight and BMI. In the NMA, semaglutide led to the greatest weight reduction, followed by exenatide, liraglutide and lixisenatide. CONCLUSIONS: The evidence suggests that GLP-1RAs reduce most weight-related outcomes in adolescents, with semaglutide being the most efficacious. There is uncertain evidence on body fat and serious AEs, probably due to fewer studies and low incidence, respectively. Larger RCTs with head-to-head comparisons, pragmatic design, adiposity-related outcomes, and economic evaluation can further guide the use and choice of GLP-1RAs.

Prenatal vitamin D levels and infant cognitive, motor, language and social-emotional development at 6 and 9 months of age.

AIM: Vitamin D is involved in several processes related to the development of neuronal and non-neuronal cells. There is a possible link between maternal vitamin D status in pregnancy and delayed neurocognitive development in the offspring. The aim of the study was to explore the association of maternal and cord blood vitamin D levels with infants' neurodevelopment at 6 and 9 months of age. METHODOLOGY: A cohort study was conducted in western Rajasthan, India. Maternal and cord blood samples were collected at the time of delivery. Serum 25(OH)-vitamin D levels were measured in both. Infant neurodevelopment was assessed at 6 and 9 months of age in six domains namely cognitive, receptive language, expressive language, fine motor, gross motor and social-emotional using the Bayley Scale of Infant Development- III (BSID-III). RESULTS: A total of 175 mother-child pairs were enrolled. Among the mothers taking part in this study, 7.3% had deficient and 59.09% had insufficient levels of serum 25(OH) vitamin D during the third trimester of their pregnancy. Maternal and cord blood serum 25-OH vitamin D levels were 18.86 ± 8.53 ng/mL and 17.39 ± 8.87 ng/mL, respectively, and there was a significant correlation (r = 0.9778, p = 0.000) between levels of vitamin D. Based on the repeated measures ANOVA, post hoc Tukey's HSD test, maternal vitamin D levels had a significant relationship (p = 0.047) to the cognitive development of infants at 6 months of age. Furthermore, cord serum vitamin D levels showed a significant association (p = 0.023 and p = 0.010) with the social-emotional development of the infant at the age of 6 and 9 months. CONCLUSION: Maternal and cord serum 25-OH vitamin D deficiency was significantly associated with the cognitive and social-emotional development of infants.

Evening versus morning dosing regimen drug therapy for hypertension.

BACKGROUND: Variation in blood pressure levels display circadian rhythms. Complete 24-hour blood pressure control is the primary goal of antihypertensive treatment and reducing adverse cardiovascular outcomes is the ultimate aim. This is an update of the review first published in 2011. OBJECTIVES: To evaluate the effectiveness of administration-time-related effects of once-daily evening versus conventional morning dosing antihypertensive drug therapy regimens on all-cause mortality, cardiovascular mortality and morbidity, total adverse events, withdrawals from treatment due to adverse effects, and reduction of systolic and diastolic blood pressure in people with primary hypertension. SEARCH METHODS: We searched the Cochrane Hypertension Specialised Register via Cochrane Register of Studies (17 June 2022), Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 6, 2022); MEDLINE, MEDLINE In-Process and MEDLINE Epub Ahead of Print (1 June 2022); Embase (1 June 2022); ClinicalTrials.gov (2 June 2022); Chinese Biomedical Literature Database (CBLD) (1978 to 2009); Chinese VIP (2009 to 7 August 2022); Chinese WANFANG DATA (2009 to 4 August 2022); China Academic Journal Network Publishing Database (CAJD) (2009 to 6 August 2022); Epistemonikos (3 September 2022) and the reference lists of relevant articles. We applied no language restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing the administration-time-related effects of evening with morning dosing monotherapy regimens in people with primary hypertension. We excluded people with known secondary hypertension, shift workers or people with white coat hypertension. DATA COLLECTION AND ANALYSIS: Two to four review authors independently extracted data and assessed trial quality. We resolved disagreements by discussion or with another review author. We performed data synthesis and analyses using Review Manager Web for all-cause mortality, cardiovascular mortality and morbidity, serious adverse events, overall adverse events, withdrawals due to adverse events, change in 24-hour blood pressure and change in morning blood pressure. We assessed the certainty of the evidence using GRADE. We conducted random-effects meta-analysis, fixed-effect meta-analysis, subgroup analysis and sensitivity analysis. MAIN RESULTS: We included 27 RCTs in this updated review, of which two RCTs were excluded from the meta-analyses for lack of data and number of groups not reported. The quantitative analysis included 25 RCTs with 3016 participants with primary hypertension. RCTs used angiotensin-converting enzyme inhibitors (six trials), calcium channel blockers (nine trials), angiotensin II receptor blockers (seven trials), diuretics (two trials), α-blockers (one trial), and ß-blockers (one trial). Fifteen trials were parallel designed, and 10 trials were cross-over designed. Most participants were white, and only two RCTs were conducted in Asia (China) and one in Africa (South Africa). All trials excluded people with risk factors of myocardial infarction and strokes. Most trials had high risk or unclear risk of bias in at least two of several key criteria, which was most prominent in allocation concealment (selection bias) and selective reporting (reporting bias). Meta-analysis showed significant heterogeneity across trials. No RCTs reported on cardiovascular mortality and cardiovascular morbidity. There may be little to no differences in all-cause mortality (after 26 weeks of active treatment: RR 0.49, 95% CI 0.04 to 5.42; RD 0, 95% CI -0.01 to 0.01; very low-certainty evidence), serious adverse events (after 8 to 26 weeks of active treatment: RR 1.17, 95% CI 0.53 to 2.57; RD 0, 95% CI -0.02 to 0.03; very low-certainty evidence), overall adverse events (after 6 to 26 weeks of active treatment: RR 0.89, 95% CI 0.67 to 1.20; I² = 37%; RD -0.02, 95% CI -0.07 to 0.02; I² = 38%; very low-certainty evidence) and withdrawals due to adverse events (after 6 to 26 weeks active treatment: RR 0.76, 95% CI 0.47 to 1.23; I² = 0%; RD -0.01, 95% CI -0.03 to 0; I² = 0%; very low-certainty evidence), but the evidence was very uncertain. AUTHORS' CONCLUSIONS: Due to the very limited data and the defects of the trials' designs, this systematic review did not find adequate evidence to determine which time dosing drug therapy regimen has more beneficial effects on cardiovascular outcomes or adverse events. We have very little confidence in the evidence showing that evening dosing of antihypertensive drugs is no more or less effective than morning administration to lower 24-hour blood pressure. The conclusions should not be assumed to apply to people receiving multiple antihypertensive drug regimens.

Growth dynamics of Rathke's Cleft cyst: a risk score system for surgical decision making.

OBJECTIVE: Rathke's cleft cysts (RCCs) exhibit variable growth patterns, thus posing a challenge in predicting progression. While some RCCs may not cause symptoms, others can insidiously cause pituitary dysfunction, which is often irreversible, even following surgery. Hence, it is crucial to identify asymptomatic RCCs that grow rapidly and pose a higher risk of causing endocrinologic dysfunction. This enables timely surgical intervention to prevent permanent damage. Our study examines the growth rate of RCCs, identifies factors that accelerate growth, and discusses the clinical implications of these findings. METHODS: A retrospective analysis of a prospectively maintained electronic database revealed 45 patients aged 18-80 years who underwent endoscopic endonasal surgery (EEA) for RCCs between 2010 and 2022 at our center. Of these, 20 required early operative intervention. The remaining 25 patients were followed closely clinically and radiologically before requiring surgery (initial conservative management group). We conducted an analysis of the factors predicting growth over time in this group. Using a regression model, we constructed a risk score system to predict RCC growth over time. RESULTS: Patients in the initial conservative group had smaller cysts and were generally older than those in the early surgery group. Patients with preoperative pituitary dysfunction showed a higher median growth of 1.0 mm in the longest diameter compared to those with normal pituitary function, with an increase of 0.5 mm. A sum of annual cyst growth of all (z, y, x) diameters, at a rate of 3 mm or greater, was associated with a clinically significant increase in the risk of pituitary dysfunction, exceeding 50%.The most significant factors predicting rapid growth in RCCs were smoking status, age, and T1-weighted magnetic resonance imaging (MRI) intensity of cysts. Smoking was the most critical risk factor for rapid cyst growth (p = < .001). Our risk score system accurately predicted RCC growth with a 74% accuracy rate, 73% sensitivity, and 75% specificity. CONCLUSION: Our analysis showed a strong link between active smoking and the rapid growth of RCC. This novel finding has significant preventive implications but needs validation by a large population database. Surgical intervention for RCC currently is often reserved for symptomatic cases. However, utilizing our risk-based scoring system to predict rapidly growing cysts may indicate early surgery in minimally symptomatic patients, thereby potentially preserving pituitary function.

Efficacy and safety of Risankizumab in moderate to severe psoriasis: A systematic review and meta-analysis.

Monoclonal antibodies are explored for their therapeutic potential in Psoriasis. To evaluate Risankizumab in the moderate to severe psoriasis with regard to efficacy, tolerability, and safety PubMed, Cochrane Central Register of Controlled Trials (CENTRAL) and clinicaltrials.gov, databases were searched for relevant RCTs. The reference lists of relevant publications were also scanned manually to identify any further studies not indexed in the searched databases. Only RCT aiming to evaluate the role of Risankizumab in the treatment of moderate to severe psoriasis were considered eligible for this systematic review. Intervention group was patients taking Risankizumab and placebo or other monoclonal antibody was considered as control group. Cochrane review manager 5 (RevMan) version 5.3 was used for data synthesis and meta-analysis. Quality assessment of included randomized controlled trials was done with Cochrane Collaboration risk of bias assessment tool, version 2.0 (ROB-2). Overall Grading of evidence for study objectives was performed with GRADE Pro GDT software. A total of seven studies were included in analysis with total of 1533 and 710 patients in Risankizumab and standard care groups, respectively. Statistically significant increase in percentage of individual achieving PASI90 (OR = 11.01 (95% CI = 8.67-13.99), DLQI-01 (OR = 6.95 (95% CI = 5.53-8.75), sPGA-01 (OR = 14.22 (95% CI = 11.10-18.22); sPGA-0 (OR = 6.39 (95% CI = 4.79-8.54) in risankizumab group as compared with control, with high quality of evidence. Increased risk of infections with risankizumab as compared with placebo (OR = 1.44 [95% CI = 1.13-1.83], high quality evidence), while no difference in SAE among two groups. Analysis of all outcome data from RCTs. In the light of evidence from systematic review on effectiveness of Risankizumab, we propose treatment with risankizumab for psoriasis patients not responding to available treatment.

Electronic-PRO Measures for adverse events Of Treatment In ONcology (E-PROMOTION).

PURPOSE: Cancer patients struggle with the trauma of the disease and its treatment. PRO-CTCAE was developed to improve the recording of underreported symptomatic toxicities. We evaluated the improvement and ease in reporting symptomatic adverse events through add-on PRO-CTCAE (via a mobile application) compared to standard clinician-reported outcomes in routine clinical practice. We also evaluated changes in the health-related quality of life (HRQoL). METHODS: 110 cancer patients were studied for three weeks between their first and second chemotherapy session. HRQoL was assessed using EORTC QLQ-c30. RESULTS: Fifty-three patients self-reported their symptomatic adverse events on the day 7th & day 14th after the first cycle of chemotherapy. For the other fifty-seven patients, recording of adverse events was done by standard clinician-reported outcomes. All the patients in the study group reported adverse events compared to only 21 % in the standard reporting group. All 15 domains of adverse events were reported in the self-reporting group compared to only 5 in the standard reporting group. The self-reporting group had a significantly better overall quality of life. CONCLUSIONS: Self-reporting of adverse events using mobile app-based PRO-CTCAE helps patients and clinicians with better documentation of symptomatic toxicities of chemotherapy, reducing the burden on physicians and improving patient satisfaction. Mobile app-based self-reporting empowers cancer patients undergoing treatment, improves their quality of life, and should be implemented in routine clinical practice. Wider implementation can lead to further optimised solutions.

Targeting self-care adherence for glycaemic control in multimorbid type 2 diabetes mellitus with depression using bupropion: a protocol for cross-over randomised controlled trial.

INTRODUCTION: Diabetes and depression are among the 10 biggest health burdens globally. They often coexist and exhibit a strong bidirectional relationship. Depression leads to decreased adherence to self-care activities. This impacts glycaemic control and worsens type 2 diabetes mellitus (T2D). Both conditions have a synergistic effect and lead to greater complications, hospitalisations, healthcare expenditure and a worse quality of life. There is no consensus on managing people with comorbid T2D and depression. Bupropion is an efficacious antidepressant with many properties suitable for T2D with depression, including a favourable metabolic profile, persistent weight loss and improvement in sexual dysfunction. We will assess the efficacy and safety of add-on bupropion compared with standard care in people with T2D and mild depression. This study can give valuable insights into managing the multimorbidity of T2D and depression. This can help mitigate the health, social and economic burden of both these diseases. RESEARCH DESIGN AND METHODS: This cross-over randomised controlled trial will recruit people with T2D (for 5 years or more) with mild depression. They will be randomised to add-on bupropion and standard care. After 3 months of treatment, there will be a washout period of 1 month (without add-on bupropion while standard treatment will continue). Following this, the two arms will be swapped. Participants will be assessed for glycosylated haemoglobin, adherence to diabetes self-care activities, lipid profile, urine albumin-to-creatinine ratio, autonomic function, sexual function, quality of life and adverse events. ETHICS AND DISSEMINATION: The Institutional Ethics Committee at All India Institute of Medical Sciences, Jodhpur has approved this study (AIIMS/IEC/2022/4172, 19 September 2022). We plan to disseminate the research findings via closed group discussions at the site of study, scientific conferences, peer-reviewed published manuscripts and social media. TRIAL REGISTRATION NUMBER: CTRI/2022/10/046411.

Rationale and design of Dapagliflozin vErsus SacubiTrIl-valsartaN therapY in Heart Failure with reduced ejection fraction (DESTINY-HF): a pragmatic randomised controlled trial protocol.

BACKGROUND: Heart failure affects almost 64 million people, with more than half of it constituting heart failure with reduced ejection fraction (HFrEF). Angiotensin receptor-neprilysin inhibitors (ARNI) and sodium-glucose cotransporter-2 (SGLT2) inhibitors (SGLT2i) are in the first line for HFrEF, but no head-to-head trials are available. Moreover, growth differentiation factor-15 (GDF-15) has been demonstrated as a promising prognostic marker, specifically for HFrEF, but has not been explored much. METHODS: This pragmatic randomised controlled trial recruits 100 patients with HFrEF (ejection fraction <40%) of New York Heart Association (NYHA) II-III and allocates them in a 1:1 ratio to the dapagliflozin and sacubitril/valsartan groups. The primary objective is to assess the difference in N-terminal pro-brain natriuretic peptide serum levels at the end of 16 weeks. The secondary efficacy objectives are to assess GDF-15, Kansas City Cardiomyopathy Questionnaire-overall summary score and estimated glomerular filtration rate. Patients will be assessed at baseline, fourth week and 16th week after randomisation. As health technology assessment practices widely differ in countries, cost assessment is a vital factor to consider. The cost needed to treat one cardiovascular event is also compared between both groups. The occurrence of safety events will also be evaluated at each follow-up point. CONCLUSION: This pragmatic study aims to compare the efficacy, safety and cost-effectiveness of dapagliflozin versus sacubitril/valsartan in patients with HFrEF in real-world settings. The study aims to provide clinicians with data to make informed decisions regarding the preferred drug class. Additionally, examining the impact of ARNI and SGLT2i on GDF-15 levels could offer better insights into prognosis among patients with HFrEF. ETHICS AND DISSEMINATION: This study involves human participants and was approved by Institutional Ethics Committee at AlIMS Jodhpur with reference number AIIMS/IEC/2023/5842 approved this study. Participants gave informed consent to participate in the study before taking part. The research findings will be disseminated via closed group discussions at the site of study, scientific conferences, peer-reviewed published manuscripts, and social media. TRIAL REGISTRATION NUMBER: CTRI/2023/12/060772.

PeRinatal, neOnatal, and Maternal OuTcomEs with azithromycin prophylaxis in pregnancy and labour (PROMOTE-PROPHYLAXIS): systematic review and meta-analysis.

Background: Initial randomised controlled trials (RCTs) showed that prophylactic azithromycin in pregnant women improved maternal and neonatal outcomes; however, the recent evidence did not show any benefit to neonatal survival. There is conflicting evidence over the role of azithromycin prophylaxis in antenatal and intrapartum periods. We explored whether azithromycin prophylaxis in pregnant women improves maternal and neonatal outcomes. Methods: For this systematic review and meta-analysis registered on PROSPERO [CRD42023411093], we searched seven databases (PubMed, Scopus, Embase, Cochrane Library, EBSCOHost, ProQuest, and Web of Science) and clinical trial registries until 04/23/2024, for RCTs evaluating antenatal/intrapartum azithromycin prophylaxis against placebo/routine care in pregnant women. The primary outcome was neonatal mortality. Intrapartum and antenatal administration were assessed separately. We used random-effects meta-analysis. The risk of bias was assessed using the Cochrane RoB 2 tool. The GRADE approach was used to evaluate the certainty of the evidence. Findings: Screening 2161 records retrieved 20 RCTs (56,381 participants). Intrapartum azithromycin may make little or no difference to neonatal mortality [5 RCTs, 44,436 participants; Risk Ratio (RR): 1.02, 95% CI 0.86-1.20, I 2  = 0%, very low certainty], and maternal mortality [3 RCTs, 44,131 participants, RR: 1.26, 0.65-2.42, I 2  = 0%, low certainty]. Similarly, antenatal azithromycin may have little or no effect on neonatal mortality [3 RCTs; 5304 participants; RR: 0.74, 0.35-1.56, I 2  = 43%, very-low certainty] and maternal mortality [3 RCTs; 8167 participants RR: 1.62, 0.67-3.91, I 2  = 0%, low certainty]. There is no data on long-term adverse outcomes and antimicrobial resistance. Interpretation: Low to very low certainty evidence suggests that intrapartum or antenatal azithromycin prophylaxis in pregnant women might not reduce maternal or neonatal mortality. Funding: None.

Efficacy and safety of sufentanil sublingual tablet system in postoperative pain management: a systematic review and meta-analysis.

BACKGROUND: Sufentanil sublingual tablet system (SSTS) is a recently approved formulation for postoperative pain management that has become popular due to its pharmacokinetic properties such as good bioavailability, rapid attainment of equilibrium and elimination without any metabolites, along with its pharmacodynamic properties such as rapid onset and effective pain reduction. It is also relatively well tolerated by patients. OBJECTIVE: This is a quantitative analysis of the efficacy and safety of SSTS in patients with moderate to severe postoperative pain. DESIGN: This is a systematic review and meta-analysis. Databases such as Cochrane Library, MEDLINE and EMBASE were searched for eligible articles. SETTINGS: Randomised controlled trials published after 2000 in English language and which assessed at least one of the outcome measures of interest with pain intensity difference between 12 hours and a maximum of 96 hours. PARTICIPANTS: Adults with moderate to severe postoperative pain and taking SSTS for pain management. METHODS: Data were analysed using Review Manager (RevMan) V.5.3. Risk of bias (RoB) assessment was done using RoB-2 scale, and overall grading of evidence of each outcome was done using GRADEpro Guideline Development Tool. RESULTS: Analysis of SSTS versus control indicates a statistically significant reduction in summed pain intensity difference at 12 hours (mean difference (MD)=-12.33 (95% CI -15.5 to -9.17), p<0.00001), summed pain intensity difference at 48 hours (MD=-43.57 (95% CI -58.65 to -28.48), p<0.00001), time-weighted total pain relief over 12 hours (MD=-4.77 (95% CI -6.28 to -3.27), p<0.00001) and pain intensity difference (MD=-0.73 (95% CI -1.00 to -0.46), p<0.00001) with SSTS, alongside high quality of evidence. Success of treatment as assessed by Patient Global Assessment (OR=4.01 (95% CI 2.74 to 5.89), p<0.00001) and Healthcare Professional Global Assessment (OR=4.46 (95% CI 3.03 to 6.56), p<0.00001) scoring at 72 hours was observed in a significantly high number of individuals using SSTS, with high quality of evidence. There was no difference in adverse events except for dizziness (RR=1.90, 95% CI 1.02 to 3.52). There was a significantly higher number of total adverse events in orthopaedic surgery in the SSTS group than in the comparator. CONCLUSION: SSTS is effective in postoperative pain management in patients with moderate to severe pain. It also has good tolerability and high patient satisfaction. PROSPERO REGISTRATION NUMBER: CRD42018115458.

COVISHIELD vaccine-induced thyroiditis: a case report.

BACKGROUND: The rapid development of coronavirus disease 2019 vaccines during the pandemic has left their long-term effects largely unknown. Instances of autoimmune and subacute thyroiditis showing features of autoimmune/inflammatory syndrome induced by adjuvants have been reported post-vaccination. This case report aims to highlight the autoimmune/inflammatory syndrome induced by adjuvants syndrome after coronavirus disease 2019 vaccination, drawing attention to a possible connection with thyroid dysfunction and urging for further thorough research. CASE PRESENTATION: We present a case of thyroiditis induced by the COVISHIELD vaccine in a 37-year-old Indian woman. An apparently normal and healthy adult woman developed neck pain and easy fatigability 2 weeks after the second dose of COVISHIELD, which gradually increased and was associated with irritability, decreased sleep, excessive sweating, tremor, palpitation, and weight loss. She presented to the outpatient department after 1 week of symptoms and was evaluated with laboratory tests and imaging. She was diagnosed with thyroiditis due to the coronavirus disease 2019 vaccine and was treated with propranolol. CONCLUSION: This case report adds to the growing evidence of coronavirus disease 2019 vaccine-related thyroid issues. The development of thyroiditis is rare and underreported post-coronavirus disease 2019 vaccination; hence, research to evaluate the association of coronavirus disease 2019 vaccines with thyroid dysfunction needs to be done in the future.

Are paid tools worth the cost? A prospective cross-over study to find the right tool for plagiarism detection.

Background: The increasing pressure to publish research has led to a rise in plagiarism incidents, creating a need for effective plagiarism detection software. The importance of this study lies in the high cost variation amongst the available options for plagiarism detection. By uncovering the advantages of these low-cost or free alternatives, researchers could access the appropriate tools for plagiarism detection. This is the first study to compare four plagiarism detection tools and assess factors impacting their effectiveness in identifying plagiarism in AI-generated articles. Methodology: A prospective cross-over study was conducted with the primary objective to compare Overall Similarity Index(OSI) of four plagiarism detection software(iThenticate, Grammarly, Small SEO Tools, and DupliChecker) on AI-generated articles. ChatGPT was used to generate 100 articles, ten from each of ten general domains affecting various aspects of life. These were run through four software, recording the OSI. Flesch Reading Ease Score(FRES), Gunning Fog Index(GFI), and Flesch-Kincaid Grade Level(FKGL) were used to assess how factors, such as article length and language complexity, impact plagiarism detection. Results: The study found significant variation in OSI(p < 0.001) among the four software, with Grammarly having the highest mean rank(3.56) and Small SEO Tools having the lowest(1.67). Pairwise analyses revealed significant differences(p < 0.001) between all pairs except for Small SEO Tools-DupliChecker. Number of words showed a significant correlation with OSI for iThenticate(p < 0.05) but not for the other three. FRES had a positive correlation, and GFI had a negative correlation with OSI by DupliChecker. FKGL negatively correlated with OSI by Small SEO Tools and DupliChecker. Conclusion: Grammarly is unexpectedly most effective in detecting plagiarism in AI-generated articles compared to the other tools. This could be due to different softwares using diverse data sources. This highlights the potential for lower-cost plagiarism detection tools to be utilized by researchers.

Minocycline in depression not responding to first-line therapy: A systematic review and meta-analysis.

BACKGROUND: Major depressive disorder is often resistant to first-line treatment, with around 30% failing to respond to traditional therapy. Treatment-resistant depression results in prolonged hospitalization and healthcare costs. Anti-inflammatory drugs have shown promising results in depression not responding to initial therapy. Minocycline has anti-inflammatory properties and crosses the blood-brain barrier. It has demonstrated varied results in several randomized controlled trials (RCTs). METHODS: We assessed the efficacy of minocycline compared to placebo in depression not responding to one first-line antidepressant via a systematic review and meta-analysis. We performed a comprehensive literature search across PubMed, Cochrane, and Scopus for RCTs. We visualized the results using forest plots and drapery plots. We assessed and explored heterogeneity using I2, prediction interval, and meta-regression. Then, we rated the certainty of the evidence. RESULTS: Four RCTs revealed a non-significant difference in depression severity [-3.93; 95% CI: -16.14 to 8.28], rate of response [1.15; 0.33-4.01], and rate of remission [0.94; 0.44-2.01]. However, the reduction in depression severity is significant at a trend of P < .1. The high between-study heterogeneity (I2 = 78%) for depression severity could be answered by meta-regression (P = .02) for the duration of therapy. CONCLUSION: There is no significant difference with minocycline compared to placebo for depression not responding to first-line antidepressant therapy. However, the treatment response varies with treatment duration and patients' neuroinflammatory state. Thus, larger and longer RCTs, especially in diverse disease subgroups, are needed for further insight. This is needed to allow greater precision medicine in depression and avoid elevated healthcare expenditure associated with hit-and-trial regimens. REGISTRATION: CRD42023398476 (PROSPERO).

Rationality, Efficacy, Tolerability of Empagliflozin Plus Linagliptin Combination for the Management of Type 2 Diabetes Mellitus: A Systematic Review of Randomized Controlled Trials and Observational Studies.

BACKGROUND: Treatment of diabetes mellitus includes more than one drug of different groups, which may lead to a high pill burden and non-adherence to drugs. We have aimed to systematically analyze the clinical efficacy, safety, and pharmacoeconomic cost-effectiveness of the fixed-dose combination of empagliflozin plus a linagliptin in Type-2 Diabetes mellitus (T2DM) patients. METHODS: A literature search of PubMed/MEDLINE, SCOPUS, Google Scholar, and EMBASE was performed using the MeSH terms and/or keywords"((Single-pill combination) OR ((Fixeddose combination) OR (Combination therapy)) AND (Empagliflozin add on-to Linagliptin) OR (Empagliflozin combined with Linagliptin) OR ((Combination of Empagliflozin and Linagliptin)" from the inception to February 2021. RESULTS: Search results were found in a total of 13 clinical studies. After removing duplicates and studies not according to inclusion criteria, a total of eight clinical studies (Randomized controlled trials: 7; Observational cohort studies: 1) were included (n=7491). A significant reduction in the primary endpoint, the mean changes in baseline HbA1c at the end of 24 weeks and/or 52 weeks was found in the empagliflozin plus a linagliptin combination group in all included studies. In addition, significant efficacy was seen in decreasing the secondary endpoints such as the mean change in the fasting plasma glucose, systolic and diastolic blood pressure (DBP), and body weight with fewer adverse events than the adverse effects with either drug alone. CONCLUSION: After reviewing findings from the available clinical studies of the combination of empagliflozin plus linagliptin, we conclude that the combination is effective, safe, tolerable, and rationale cost effective compared to placebo and either drug alone for the management of T2DM in patients with inadequate glycemic control with metformin alone, patients with intolerance to metformin, increased baseline HbA1c, patients with overweight or obesity and diabetic hypertensive, CHF, atherosclerotic cardiovascular disease, and renal dysfunction patients. Future randomized controlled trials in a larger number of T2DM patients with or without CHF and renal failure patients are recommended.

Toxicoepidemiology of poisoning exhibited in Indian population from 2010 to 2020: a systematic review and meta-analysis.

OBJECTIVE: To determine the prevalence of pesticide, corrosive, drugs, venom and miscellaneous poisoning in India. SETTING: Systematic literature search was done in PubMed Central, Cochrane and Google Scholar databases for studies that satisfied the inclusion criteria. Systematic review and meta-analyses of all observational studies published in the English language from January 2010 to May 2020 were included in this review. PARTICIPANTS: Patients exposed to poisoning reported to hospitals were included. PRIMARY AND SECONDARY OUTCOME MEASURES: The prevalence of pesticide poisoning was analysed. The prevalence of poisoning due to corrosives, venom, drugs and miscellaneous agents, along with subgroup analysis based on age and region, was also determined. The percentage of persons with poisoning along with 95% CI was analysed. RESULTS: Pooled analysis of studies revealed that pesticides were the main cause of poisoning in adults, with an incidence of 63% (95% CI 63% to 64%), while miscellaneous agents were the main cause of poisoning in children, with an incidence of 45.0% (95% CI 43.1% to 46.9%), among those presenting to hospitals. Pesticide poisoning was the most prevalent in North India (79.1%, 95% CI 78.4% to 79.9%), followed by South (65.9%, 95% CI 65.3% to 66.6%), Central (59.2%, 95% CI 57.9% to 60.4%), West (53.1%, 95% CI 51.9% to 54.2%), North East (46.9%, 95% CI 41.5% to 52.4%) and East (38.5%, 95% CI 37.3% to 39.7%). The second most common cause of poisoning was miscellaneous agents (18%, 95% CI 18% to 19%), followed by drugs (10%, 95% CI 10% to 10%), venoms (6%, 95% CI 6% to 6%) and corrosives (2%, 95% CI 1% to 2%). CONCLUSIONS: Pesticide poisoning is the most common type of poisoning in adults, while miscellaneous agents remain the main cause of poisoning in children. PROSPERO REGISTRATION NUMBER: CRD42020199427.

Renal Histopathological Changes in Coronavirus Disease 2019 Patients: A Systematic Review and Meta-analysis of Individual Patient Data.

The major targets of coronavirus disease 2019 (COVID-19) are the respiratory and immune systems. However, a significant proportion of hospitalized patients had kidney dysfunction. The histopathological surveys have principally focused on respiratory, hematopoietic, and immune systems, whereas histopathologic data of kidney injury are lacking. Our study aimed to summarize the renal histopathological findings in COVID-19 from the published case report and case series. We conducted a systematic searching of databases such as MEDLINE, EMBASE, and Cochrane Library for published reports of COVID-19 patients with renal histopathological changes from autopsy studies and from "for cause" indication biopsies. Included in our study are case reports and case series with extractable quantitative data on patient demographics such as age, sex, ethnicity, as well as data on renal function tests, their comorbidities, and biopsy to study the histopathological changes. Data were analyzed with Microsoft Excel. To evaluate the methodological quality, we chose the framework for appraisal, synthesis, and application of evidence suggested by Murad et al. Systematic searches of literature found 31 studies that fulfilled the eligibility criteria. These studies included a total of 139 cases, where individual case details including clinical and histopathological findings were available. The median age of the cases was 62 years with a male:female ratio of 2.5:1. Associated comorbidities were noted in 78.4% of cases. The majority of the cases had renal dysfunction with proteinuria which was documented in more than two-thirds of the cases. The histopathological findings observed the frequent tubular involvement manifested by acute tubular injury. Regarding glomerular pathology, collapsing glomerulopathy emerged as a distinct lesion in these patients and was noted among 46.8% of cases with glomerular lesions. A small subset of cases (4.3%) had thrombotic microangiopathy. Collapsing glomerulopathy emerged as a hallmark of glomerular changes among COVID-19 patients. Tubular damage is common and is linked to multiple factors including ischemia, sepsis among others. In the form of thrombotic microangiopathy seen in a subset of patients, vascular damage hints toward the hyper-coagulable state associated with the infection. The demonstration of viral particles in renal tissue remains debatable and requires further study.

The Satisfaction Level of Undergraduate Medical and Nursing Students Regarding Distant Preclinical and Clinical Teaching Amidst COVID-19 Across India.

BACKGROUND: The COVID-19 pandemic has disrupted the educational system and led to a drastic shift of professional undergraduate teaching for medical and nursing students into online mode. METHODS: This was a cross-sectional, observational questionnaire-based study to assess the satisfaction level of the students. The questionnaire had 25 items of which 23 were questions with responses on the Likert scale and two items on views and suggestions were open-ended. The online questionnaire was shared through various messaging/mailing platforms. Overall satisfaction was assessed, and a satisfaction index was calculated for each item. Data are presented in frequencies and percentages, and SPSS was used to analyze the data. RESULTS: A total of 1068 students participated in the study. The majority were from the age group 21-23 years (54%) and there was almost the same number of participants from both genders. The majority of the students were medical undergraduates (n=919), were in their second year (n=669), belonged to a government institution (n=897) and used a mobile phone for their online classes (n = 871). The majority of the students were dissatisfied (42%) with no significant difference between medical and nursing students (p = 0.192). First-year students were significantly dissatisfied compared with other senior students (p = 0.005). The maximum satisfaction index (78.23%) was observed with faculties being supportive and responsive in resolving the queries and the minimum (46.39%) was observed with issues related to communication and discussion with peer students. There were 662 responses as views which mostly contained negative comments regarding interaction and focus, practical learning, teaching content, and technological/infrastructural flaws. There was major dissatisfaction regarding the practical and clinical learning. CONCLUSION: Online learning is essential at current times but is not an effective alternative for medical and nursing education. Face-to-face classes and practical sessions along with online learning can be a viable option.

Assessment of Caregiving Burden of Family Caregivers of Advanced Cancer Patients and Their Satisfaction with the Dedicated Inpatient Palliative Care Provided to Their Patients: A Cross-Sectional Study from a Tertiary Care Centre in South Asia.

BACKGROUND AND OBJECTIVES: Family Caregivers (FCs) of advanced cancer patients often suffer from caregiving burden due to stress arising from the responsibility of caregiving. During the course of their patients palliative therapy, FCs quality of life seems to be influenced by their satisfaction with the quality of patient care. In this study, caregiving burden of FCs and their satisfaction with dedicate Inpatient palliative care (IPC) services provided to their patients  were studied. MATERIAL AND METHODS: This cross-sectional study assessed 211 FCs of advanced cancer patients. Caregiving burden of FCs and their satisfaction with IPC were studied through Zarith Burden Interview (ZBI-12 version) and Family Carer Satisfaction with Palliative Care scale (FAMCARE-2)  questionnaires, respectively. Descriptive and correlation analyses were deployed for data analysis. RESULTS: The summative mean ZBI-12 score for FCs was 20.26±5.92, suggesting moderate to high caregiving burden among FCs. Significantly higher scores were observed among FCs who belonged to below poverty line (BPL) families(p=0.025), revealing higher caregiving burden among this lower income group. FCs who were male, unmarried, unemployed, and residing in rural experienced higher caregiving burden. However, it did not lead to a statistically significant difference. The summative mean FAMCARE-2 scale scores was 74.01±4.34, which suggested FCs high satisfaction with the palliative care services provided to their patients. FAMCARE-2 scale scores were lower for BPL families, but it was not statistically significant. CONCLUSION: FCs from lower-income groups experienced higher caregiving burden. It seems that IPC unit provided satisfactory services to advanced cancer patients, leading to enhancement of FCs satisfaction and consequently quality of life. 
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Efficacy of green tea, its polyphenols and nanoformulation in experimental colitis and the role of non-canonical and canonical nuclear factor kappa beta (NF-kB) pathway: a preclinical in-vivo and in-silico exploratory study.

NF-kB plays a major role in the aetiopathogenesis of inflammatory-colitis. In this study, we evaluated the efficacy of green tea and its polyphenols and their nanoformulation in Tri-Nitro Benzene Sulfonic acid (TNBS) induced colitis in in-vivo system (Rat) and the involvement of non-canonical and canonical NF-kB pathway in green tea mediated protection (in-silico platform). We used the Wister rat model of TNBS-induced colitis. Rats were grouped into eleven groups (six animals each) and administered vehicle (ethanol), TNBS, Epicatechin (EC), Epigallocatechin (EGC), Epicatechin-gallate (ECG), Epigallocatechin-gallate (EGCG), sulfasalazine, green tea, EGCG + sulfasalazine, nano-EGCG and nano-EGCG + sulfasalazine for 14 days after induction of colitis. Colonic tissue was evaluated for the level of malondialdehyde, myeloperoxidase activity, catalase, reduced glutathione, glutathione peroxidase, IL-6, TNF-α, IL-1ß, NF-κB and morphological and histopathological evidence of damage. In the in-silico part, molecular docking and dynamic simulation study of EGCG was done against different targets in NF-kB for detailed evaluation of the role of non-canonical and canonical NF-KB pathway. In our study, EGCG reduced colonic inflammation, markers of oxidative stress, TNF-α, NF-κB, IL-1ß and IL-6. Nano-EGCG + sulfasalazine was more efficacious when compared to EGCG + sulfasalazine. In molecular docking and molecular dynamic simulation studies, EGCG showed a good binding profile to the inhibitor binding sites of IKK-beta, IKK-alpha and NIK. Thus, it can be concluded that EGCG showed protective action in experimental colitis acting through both non-canonical and canonical NF-kB pathway. Nano-EGCG + sulfasalazine combination showed better protection than nano-EGCG alone. Communicated by Ramaswamy H. Sarma.

Target/therapies for chronic recurrent erythema nodosum leprosum.

A Type 2 lepra reaction or erythema nodosum leprosum is an anticipated complication in the lepromatous spectrum of leprosy cases. It is an example of an immune complex-mediated complement activated disease (Type III hypersensitivity reaction). Hence, we tried to target the inflammatory mediators and the mental stressors for the possible management strategies.