Low-dose versus standard-dose olanzapine with triple antiemetic therapy for prevention of highly emetogenic chemotherapy-induced nausea and vomiting in patients with solid tumours: a single-centre, open-label, non-inferiority, randomised, controlled, phase 3 trial.

BACKGROUND: Olanzapine is an effective antiemetic agent but it results in substantial daytime somnolence when administered at the standard dose. Our aim was to compare the efficacy of low-dose versus standard-dose olanzapine after highly emetogenic chemotherapy in patients with solid tumours. METHODS: This was a single-centre, open-label, non-inferiority, randomised, controlled, phase 3 trial done in a tertiary care referral centre in India (Tata Memorial Centre, Homi Bhabha National Institute, Mumbai). Patients aged 13-75 years with an Eastern Cooperative Oncology Group performance status of 0-2, who were receiving doxorubicin-cyclophosphamide or high-dose cisplatin for a solid tumour were eligible. Patients were randomly assigned (1:1), with block randomisation (block sizes of 2 or 4) and stratified by sex, age (≥55 or <55 years), and chemotherapy regimen, to receive low-dose (2·5 mg) oral olanzapine or standard-dose (10·0 mg) oral olanzapine daily for 4 days, in combination with a triple antiemetic regimen. Study staff were masked to treatment allocation but patients were aware of their group assignment. The primary endpoint was complete control, defined as no emetic episodes, no rescue medications, and no or mild nausea in the overall phase (0-120 hours), assessed in the modified intention-to-treat (mITT) population (ie, all eligible patients who received protocol-specified treatment, excluding those who had eligibility violations and who withdrew consent after randomisation). Daytime somnolence was the safety endpoint of interest. Non-inferiority was shown if the upper limit of the one-sided 95% CI for the difference in the complete control proportions between the treatment groups excluded the non-inferiority margin of 10%. This study is registered with the Clinical Trial Registry India, CTRI/2021/01/030233, is closed to accrual, and this is the final data analysis. RESULTS: Between Feb 9, 2021, and May 30, 2023, 356 patients were pre-screened for eligibility, of whom 275 patients were enrolled and randomly assigned (134 to the 2·5 mg olanzapine group and 141 to the 10·0 mg olanzapine group). 267 patients (132 in the 2·5 mg group and 135 in the 10·0 mg group) were included in the mITT population, of whom 252 (94%) were female, 15 (6%) were male, and 242 (91%) had breast cancer. 59 (45%) of 132 patients in the 2·5 mg olanzapine group had complete control in the overall phase versus 59 (44%) of 135 in the 10·0 mg olanzapine group (difference -1·0% [one-sided 95% CI -100·0 to 9·0]; p=0·87). In the overall phase, there were significantly fewer patients in the 2·5 mg olanzapine group than in the 10·0 mg olanzapine group with daytime somnolence of any grade (86 [65%] of 132 vs 121 [90%] of 135; p<0·0001) and of severe grade on day 1 (six]5%] vs 54 [40%]; p<0·0001). INTERPRETATION: Our findings suggest that olanzapine 2·5 mg is non-inferior to 10·0 mg in antiemetic efficacy and results in reduced occurrence of daytime somnolence among patients receiving highly emetic chemotherapy and should be considered as a new standard of care. FUNDING: Progressive Ladies Welfare Association.

Salacia spp.: recent insights on biotechnological interventions and future perspectives.

The plants of the genus Salacia L. are the storehouse of several bioactive compounds, and are involved in treating human diseases and disorders. Hitherto, a number of reports have been published on in vitro biotechnology as well as microbial involvement in the improvement of Salacia spp. The present review provides comprehensive insights into biotechnological interventions such as tissue culture for plant propagation, in vitro cultures, and endophytic microbes for up-scaling the secondary metabolites and biological potential of Salacia spp. Other biotechnological interventions such as molecular markers and bio-nanomaterials for up-grading the prospective of Salacia spp. are also considered. The in vitro biotechnology of Salacia spp. is largely focused on plant regeneration, callus culture, cell suspension culture, somatic embryogenesis, and subsequent ex vitro establishment of the in vitro-raised plantlets. The compiled information on tissue cultural strategies, involvement of endophytes, molecular markers, and nanomaterials will assist the advanced research related to in vitro manipulation, domestication, and commercial cultivation of elite clones of Salacia spp. Moreover, the genetic diversity and other molecular-marker based assessments will aid in designing conservation policies as well as support upgrading and breeding initiatives for Salacia spp. KEY POINTS: • Salacia spp. plays a multifaceted role in human health and disease management. • Critical and updated assessment of tissue culture, endophytic microbes, metabolites, molecular markers, and bio-nanomaterials of Salacia spp. • Key shortcomings and future research directions for Salacia biotechnology.

Ethnic differences in multimorbidity after accounting for social-economic factors, findings from The Health Survey for England.

BACKGROUND: Social-economic factors and health behaviours may be driving variation in ethnic health inequalities in multimorbidity including among distinct ethnic groups. METHODS: Using the cross-sectional nationally representative Health Surveys for England 2011-18 (N = 54 438, aged 16+), we performed multivariable logistic regression on the odds of having general multimorbidity (≥2 longstanding conditions) by ethnicity [British White (reference group), White Irish, Other White, Indian, Pakistani, Bangladeshi, Chinese, African, Caribbean, White mixed, Other Mixed], adjusting for age, sex, education, area deprivation, obesity, smoking status and survey year. This was repeated for cardiovascular multimorbidity (N = 37 148, aged 40+: having ≥2 of the following: self-reported diabetes, hypertension, heart attack or stroke) and multiple cardiometabolic risk biomarkers (HbA1c ≥6.5%, raised blood pressure, total cholesterol ≥5mmol/L). RESULTS: Twenty percent of adults had general multimorbidity. In fully adjusted models, compared with the White British majority, Other White [odds ratio (OR) = 0.63; 95% confidence interval (CI) 0.53-0.74], Chinese (OR = 0.58, 95% CI 0.36-0.93) and African adults (OR = 0.54, 95% CI 0.42-0.69), had lower odds of general multimorbidity. Among adults aged 40+, Pakistani (OR = 1.27, 95% CI 0.97-1.66; P = 0.080) and Bangladeshi (OR = 1.75, 95% CI 1.16-2.65) had increased odds, and African adults had decreased odds (OR = 0.63, 95% CI 0.47-0.83) of general multimorbidity. Risk of cardiovascular multimorbidity was higher among Indian (OR = 3.31, 95% CI 2.56-4.28), Pakistani (OR = 3.48, 95% CI 2.52-4.80), Bangladeshi (OR = 3.67, 95% CI 1.98-6.78), African (OR = 1.61, 95% CI 1.05-2.47), Caribbean (OR = 2.18, 95% CI 1.59-2.99) and White mixed (OR = 1.98, 95% CI 1.14-3.44) adults. Indian adults were also at risk of having multiple cardiometabolic risk biomarkers. CONCLUSION: Ethnic inequalities in multimorbidity are independent of social-economic factors. Ethnic minority groups are particularly at risk of cardiovascular multimorbidity, which may be exacerbated by poorer management of cardiometabolic risk requiring further investigation.

Topical delivery of mupirocin calcium nanostructured lipid carriers using a full-thickness excision wound healing model.

OBJECTIVE: Treatment of contaminated wounds represents a significant challenge in healthcare and there is a need to develop approaches maximising skin retention to maintain therapeutic concentrations of anti-infectives at the wound site. The objective of the present study was to develop and evaluate mupirocin calcium nanolipid emulgels to enhance wound healing performance and patient acceptability. METHODS: Nanostructured lipid carriers (NLCs) of mupirocin calcium were prepared by the phase inversion temperature method using Precirol ATO 5 (Gattefosse, India) and oleic acid as lipids and Kolliphor RH 40 (BASF, India) as surfactant and further incorporated into a gel base for topical delivery. RESULTS: The particle size, polydispersity index and zeta potential of mupirocin NLCs were found to be 128.8±1.25nm, 0.283±0.003 and -24.2±0.56mV, respectively. In vitro release studies from developed emulgel showed sustained drug release over 24 hours. Ex vivo drug permeation studies through excised rat abdominal skin showed better skin permeation (1712.38±15. 57µg/cm2) from developed emulgel compared to marketed ointment (827.92±21.42µg/cm2) after 8 hours, which was in agreement with in vitro antibacterial activity. Studies on Wistar rats indicated the nonirritant potential of developed emulgels. Further, mupirocin emulgels showed improved efficacy in percent wound contraction of acute contaminated open wounds in Wistar rats using a full-thickness excision wound healing model. CONCLUSION: The emulgels of mupirocin calcium NLCs appear to be effective in the treatment of contaminated wounds due to increased skin deposition and sustained release, thereby enhancing the wound healing potential of existing molecules.

Comparative evaluation of open tray impression technique: investigating the precision of four splinting materials in multiple implants.

BACKGROUND: This study aimed to determine the relative positioning accuracy of multiple implants utilizing four distinct types of splinting materials. METHODS: The purpose of this in-vitro study was to compare the precision of four splinting materials in an open tray impression technique in multiple implant situations. Based on the material used for splinting, four groups were made (n = 40)- Group A: Conventional Method, Group B: Prefabricated Pattern Resin Framework, Group C: Prefabricated Metal Framework, Group D: Light Cured Pattern Resin, these groups were compared with the master model. A heat-cured clear acrylic resin and a master model were constructed. A pilot milling machine drill was used to drill four parallel holes in the anterior and premolar regions, which were later labeled as A, B, C, and D positions from right to left. Then, sequential drilling was carried out, and four 3.75­mm diameter and 13-mm long ADIN implant analogs with internal hex were placed in the acrylic model using a surveyor for proper orientation. The impression posts were then manually screwed to the implant analogs using an open tray, and they were secured to the implants using 10 mm flat head guide pins with a 15 N.cm torque. 10 Open tray polyether impressions were made, and casts were poured. Each splinting method's distortion values were measured using a coordinate measuring machine capable of recordings in the X-, Y-, and Z-axes. Comparison of mean distances for X1, X2, and X3 was made using the Kruskal-Wallis test, and Pairwise comparison was done using Post Hoc Tukey's Test. RESULTS: The differences between the groups were significant when assessing the distances X1, X2, and X3 (p < 0.05). The comparison of deviations between the groups revealed a statistically significant difference (p < 0.05) for the deviation distance X3 but not for the deviation distances X1 and X2. For distance Y1, the difference between the groups was statistically significant (p0.05), but it was not significant for distances Y2 and Y3. A statistically significant difference was seen in the comparison between the groups (p < 0.05) for the deviation distances Y1, Y2, and Y3. The results were statistically significant for the distance Z1 comparisons, namely, control vs. Group A (p = 0.012), control vs. Group B (p = 0.049), control vs. Group C (p = 0.048), and control vs. Group D (p = 0.021), and for distance Z3 comparison for control vs. Group A (p = 0.033). The results were statistically insignificant for the distance Z2 comparisons (p > 0.05). CONCLUSIONS: All splinting materials produced master casts with measurements in close proximity to the reference model. However, prefabricated pattern resin bars splinting showed the highest accuracy among the studied techniques. The most recent splinting techniques using prefabricated metal framework and light-cure pattern resin showed similar accuracy.

Preventing Risks of Infections and Medication Errors in IV therapy (PRIME): a patient safety initiative.

BACKGROUND: Two major avoidable reasons for adverse events in hospital are medication errors and intravenous therapy-induced infections or complications. Training for clinical staff and compliance to patient safety principles could address these. METHODS: Joint Commission International (JCI) consultants created a standardised, 6-month training programme for clinical staff in hospitals. Twenty-one tertiary care hospitals from across south-east Asia took part. JCI trained the clinical consultants, who trained hospital safety champions, who trained nursing staff. Compliance and knowledge were assessed, and monthly audits were conducted. RESULTS: There was an overall increase of 29% in compliance with parameters around medication preparation and vascular access device management. CONCLUSION: The programme improved safe practice around preparing medications management and managing vascular access devices. The approach could be employed as a continuous quality improvement initiative for the prevention of medication errors and infusion-associated complications.

Characterization of the wave phenomenon of flash-induced chlorophyll fluorescence in Chlamydomonas reinhardtii.

Flash-induced chlorophyll fluorescence relaxation is a powerful tool to monitor the reoxidation reactions of the reduced primary quinone acceptor, QA- by QB and the plastoquinone (PQ) pool, as well as the charge recombination reactions between the donor and acceptor side components of Photosystem II (PSII). Under certain conditions, when the PQ pool is highly reduced (e.g. in microaerobic conditions), a wave phenomenon appears in the fluorescence relaxation kinetics, which reflects the transient reoxidation and re-reduction of QA- by various electron transfer processes, which in cyanobacteria is mediated by NAD(P)H dehydrogenase (NDH-1). The wave phenomenon was also observed and assigned to the operation of type 2 NAD(P)H dehydrogenase (NDH-2) in the green alga Chlamydomonas reinhardtii under hydrogen-producing conditions, which required a long incubation of algae under sulphur deprivation (Krishna et al. J Exp Bot 70 (21):6321-6336, 2019). However, the conditions that induce the wave remained largely uncharacterized so far in microalgae. In this work, we investigated the wave phenomenon in Chlamydomonas reinhardtii under conditions that lead to a decrease of PSII activity by applying hydroxylamine treatment, which impacts the donor side of PSII in combination with a strongly reducing environment of the PQ pool (microaerobic conditions). A similar wave phenomenon could be induced by photoinhibitory conditions (illumination with strong light in the presence of the protein synthesis inhibitor lincomycin). These results indicate that the fluorescence wave phenomenon is activated in green algae when the PSII activity decreases relative to Photosystem I (PS I) activity and the PQ pool is strongly reduced. Therefore, the fluorescence wave could be used as a sensitive indicator of altered intersystem electron transfer processes, e.g. under stress conditions.

Characterization of the Wave Phenomenon in Flash-Induced Fluorescence Relaxation and Its Application to Study Cyclic Electron Pathways in Microalgae.

Photosynthesis is a series of redox reactions, in which several electron transport processes operate to provide the energetic balance of light harvesting. In addition to linear electron flow, which ensures the basic functions of photosynthetic productivity and carbon fixation, alternative electron transport pathways operate, such as the cyclic electron flow (CEF), which play a role in the fine tuning of photosynthesis and balancing the ATP/NADPH ratio under stress conditions. In this work, we characterized the electron transport processes in microalgae species that have high relevance in applied research and industry (e.g., Chlorella sorokiniana, Haematococcus pluvialis, Dunaliella salina, Nannochloropsis sp.) by using flash-induced fluorescence relaxation kinetics. We found that a wave phenomenon appeared in the fluorescence relaxation profiles of microalgae to different extents; it was remarkable in the red cells of H. pluvialis, D. salina and C. sorokiniana, but it was absent in green cells of H. pluvialis and N. limnetica. Furthermore, in microalgae, unlike in cyanobacteria, the appearance of the wave required the partial decrease in the activity of Photosystem II, because the relatively high Photosystem II/Photosystem I ratio in microalgae prevented the enhanced oxidation of the plastoquinone pool. The wave phenomenon was shown to be related to the antimycin A-sensitive pathway of CEF in C. sorokiniana but not in other species. Therefore, the fluorescence wave phenomenon appears to be a species-specific indicator of the redox reactions of the plastoquinone pool and certain pathways of cyclic electron flow.

Comparative Study of Sofa, Apache Ii, Saps Ii, as a Predictor of Mortality in Patients of Sepsis Admitted in Medical ICU.

Sepsis is a life-threatening organ dysfunction with high mortality and morbidity. Various mortality prediction scores are currently in use for prediction of mortality. Although combination of various scores have not been used before. The aim of the study was to compare SOFA, APACHE II, SAPS II, as a predictor of mortality and to assess the usefulness of combination of different scores. MATERIAL: A one-year hospital based prospective study conducted from 1st January 2020 to 31st December 2020 in medical ICU, where 100 patients of sepsis admitted in ICU with evidence of organ dysfunction were included in the study and various scores like SOFA, APACHE II, and SAPS II were calculated at 24 and 48 hours of admission, using laboratory results and clinical examination. and an attempt to access for predictive accuracy of combination of scores was undertaken. OBSERVATION: Majority of the patients (37%) were in the age group of 60-79 years with maximum mortality in this age group of (39.22 %). Mortality rate was 51%, with higher mortality in the female group being 68.63%. Diabetes was most common comorbid in our study (41%). No significant difference was observed in physiological variable over 24 and 48 hours, however decrease in WBC and platelet count was noted at the end of 48 hours; Mean SOFA, APACHE II, SAPS II were significantly higher in the mortality group than the recovery group; All three scores had good diagnostic performance, with max sensitivity at 24 and 48 hours with APACHE II being 64.10% and 78.79% respectively, max specificity at 24 and 48 hours was noticed with SAPS II being 96.97% and 87.88% respectively. On further combination of scores, maximum sensitivity was seen with SOFA plus APACHE II at 48 hours of 74.36%, maximum specificity was seen at 24 hours with SOFA plus SAPS II of 93.94%. Upon application of Youden's index to the combination of scores, best diagnostic performance was seen with SOFA plus SAPS II at 48 hours. CONCLUSION: All the three scores showed good mortality prediction rate but among the scores higher sensitivity was seen with APACHE II score at 24 and 48 hours and higher specificity was seen with SAPS II at 24 and 48 hours. Combination of scores did show a slightly better predictability with combination of SAPS II and SOFA showing maximum Youden's index at 48 hours. Mortality was comparatively higher among the females and elderly group with most common risk factor being diabetes.

Identification of the AG afterglow thermoluminescence band in the cyanobacterium Synechocystis PCC 6803.

The so-called afterglow, AG, thermoluminescence (TL) band is a useful indicator of the presence of cyclic electron flow (CEF), which is mediated by the NADH dehydrogenase-like (NDH) complex in higher plants. Although NDH-dependent CEF occurs also in cyanobacteria, the AG band has previously not been found in these organisms. In the present study, we tested various experimental conditions and could identify a TL component with ca. +40°C peak temperature in Synechocystis PCC 6803 cells, which were illuminated by far-red (FR) light at around -10°C. The +40°C band could be observed when WT cells were grown under ambient air level CO2 , but was absent in the M55 mutant, which is deficient in the NDH-1 complex. These experimental observations match the characteristics of the AG band of higher plants. Therefore, we conclude that the newly identified +40°C TL component in Synechocystis PCC 6803 is the cyanobacterial counterpart of the plant AG band and originates from NDH-1-mediated CEF. The cyanobacterial AG band was most efficiently induced when FR illumination was applied at -10°C and its contribution to the total TL intensity declined when cells were illuminated above and below this temperature. Based on this phenomenon we also conclude that CEF is blocked by low temperatures at two different sites in Synechocystis PCC 6803: (1) Below -10°C at the level of NDH-1 and (2) below -30°C at the donor or acceptor side of Photosystem I.

A Systematic Review of Household and Family Alcohol Use and Childhood Neurodevelopmental Outcomes in Low- and Middle-Income Countries.

Childhood exposure to alcohol misuse by household adults has been related to childhood developmental delay, cognitive impacts, mental illness, and problem behaviours. Most evidence comes from high income countries. This systematic review only included studies from low- and middle-income countries (LMICs). Five databases were searched from 1990-2020. Twenty-eight studies of children 0-12 years were included, with 42,599 participants from 11 LMICs. The most common outcome was behavioural problems/disorders (19 studies). Despite varying study designs, this review found that alcohol misuse by household members in LMICs is associated with adverse child neurodevelopmental outcomes, although casual inferences cannot be drawn in the absence of well conducted prospective studies. Statistically significant correlations were described between parental alcohol misuse and child emotional and behavioural difficulties, cognitive delay, and risky behaviours. In future, prospective cohort studies are recommended, with adjustment for confounders.

A Systematic Review of Household and Family Alcohol Use and Adolescent Behavioural Outcomes in Low- and Middle-Income Countries.

Exposure to alcohol misuse is considered an adverse childhood experience impacting on neurodevelopmental and behavioural outcomes in adolescents including substance use, mental illness, problem behaviours, suicidality, and teenage pregnancy. Most research on this issue has focussed on higher income countries, whereas patterns of alcohol use and related factors may be different in low- and middle-income countries (LMICs). This systematic review therefore seeks to collate all published studies from 1990-2020 on the topic set in LMICs. 43 studies were included, totalling 70,609 participants from 18 LMICs. Outcomes assessed included: substance use; depression/anxiety; suicidal ideation; problem behaviour; emotional dysfunction; teenage pregnancy; and self-harm. Despite heterogeneity in the studies identified, this review documented some association between exposure to household alcohol misuse and adverse adolescent outcomes in LMICs, including mental health problems, problem behaviours, and suicidality. The mechanisms leading to these outcomes are likely varied, and further research in different socio-economic and cultural contexts, particularly in the form of longitudinal studies, is called for.

Pathologic reporting practices for breast cancer specimens after neoadjuvant chemotherapy-a survey of pathologists in academic institutions across the United States.

Neoadjuvant chemotherapy is increasingly being used to treat primary invasive breast carcinoma. Response to neoadjuvant chemotherapy is an important determinant of prognosis. A multidisciplinary group published recommendations for standardization of pathologic reporting of postneoadjuvant chemotherapy specimens. Based on these recommendations, we sent a survey to 26 pathologists currently practicing breast pathology in academic centers across the United States. The survey consisted of six questions with yes/no answers. The pathologists were encouraged to add comments. We received responses from 23 breast pathologists from 19 centers. The questions and responses were as follows: 1. Do you grade tumors after neoadjuvant chemotherapy?-17 (74%) responded yes and 6 (26%) responded no. 2. Do you routinely repeat hormone receptors, HER2/Neu results after neoadjuvant chemotherapy?-15 (65%) responded yes and 8 (35%) responded no. 3. If there are features of tumor regression/tumor bed at the margin but no actual tumor at the margin do you report this?-11 (48%) responded yes and 8 (35%) responded no and 4 (17%) reported a variable practice. 4. Do you report number of nodes with fibrosis/changes of regression?-17 (74%) responded yes and 6 (26%) responded no. 5. Do you report residual cancer burden score on your report or at least provide information on your report so clinicians can calculate residual cancer burden?-17 (74%) responded yes and 6 (26%) responded no. 6. Do you have a specific synoptic for cases after neoadjuvant chemotherapy?-5 (22%) responded yes and 18 (78%) responded no. The major reasons provided for nonadherence to recommended guidelines included pathologists were unaware of prognostic importance of providing the information, reporting practices were clinician driven and some pathologists were unaware of the recommendation. We document that academic breast pathology practices show significant variability in reporting of postneoadjuvant chemotherapy cases. We document barriers to standard practice and provide recommendations we hope will contribute to a more uniform reporting practice for these complex specimens.

Association of Mean Platelet Volume with Acute Ischemic Cerebrovascular Accident Among Patients with Type 2 Diabetes Mellitus: A Hospital-Based Study.

OBJECTIVE: To study the association of MPV (mean platelet volume) and acute ischemic stroke in patients of type 2 diabetes mellitus (DM). MATERIAL: This was a 1-year cross-sectional hospital-based study involving 79 patients presented with acute ischemic stroke. Among them, 25 were diabetic and 54 were nondiabetic. Demographic data and history of the patients were recorded. Investigations such as haemoglobin estimation, platelet count, MPV, HbA1c, imaging studies were conducted and evaluated for acute ischemic brain stroke. All the patients underwent neurological examination according to National Institute of Health Stroke Scale (NIHSS) at the time of admission and MPV was noted. Outcome of stroke was assessed during discharge by modified Rankin morbidity (MRM) score. SPSS 20 was used to analyse the data. RESULTS: Among 79 them, 25 patients (31.6%) had history of diabetes which formed the diabetic subset and the remaining 54 (68.35%) were considered in non-diabetic subset. MPV in patients with DM was significantly high (10.16 ± 0.89 fL) compared to nondiabetic patients (8.25 ± 0.91 fL; p<0.001). The mean NIHSS scores were significantly high in patients with diabetes compared to nondiabetic patients (20.38±3.19 vs. 17.76±3.74; p=0.006). Also, the mean MRM scores were significantly high in diabetics than that of nondiabetics (4.12 ± 0.66 vs. 3.00 ± 0.61; p<0.001). History of stroke was present in 12% of patients with DM compared to 1.85% of the non-diabetic patients (p=0.091). CONCLUSION: Acute ischemic stroke in diabetic patients is significantly associated with raised MPV level, which is likely to be severe with high morbidity and mortality. Hence, MPV is an easily available blood parameter, which defines platelet reactivity and proves to be a good predictor of severity and outcome of stroke in diabetics. Also, higher percentile of patients showed history of recurrent stroke in diabetics as compared to non-diabetics in whom the MPV was considerably raised compared to other diabetic stroke cases.

Overnight 1-mg DST Serum Cortisol in Various Stages of Chronic Kidney Disease-Normative Data and Underlying Mechanisms.

Context: Data on the overnight 1 mg-dexamethasone suppression test (ONDST) in renal dysfunction are limited. Objective: We aim to determine the normative range of ONDST cortisol across chronic kidney disease (CKD) stages and reasons for its alteration. Methods: Prospectively, 180 CKD (30 each in G2-G5/5D) patients and 30 healthy controls underwent ONDST 8 Am serum cortisol (chemiluminescent immunoassay [CLIA]). In an exploratory cohort, 45 (15 each: G3b/G4, G5/G5D, and healthy controls) individuals' blood biochemistry for basal (8 Am) cortisol and adrenocorticotropin (ACTH), post-ONDST 8 Am dexamethasone, ACTH, cortisol (CLIA and liquid chromatography-tandem mass spectrometry), and 4 Pm cortisol was collected. Results: Post-ONDST cortisol (µg/dL) correlated inversely (r = 0.47; P < .005) with estimated glomerular filtration rate (eGFR) (mL/min/1.73 m2), with 95th percentile being 1.2 in controls, 3.0 in G2, 3.2 in G3a, 4.3 in G3b, 4.7 in G4, 5.7 in G5, and 7.1 in G5D. In the exploratory cohort, basal 8 Am cortisol and ACTH, and post-ONDST dexamethasone were similar among controls and CKD subgroups. ONDST ACTH (for evaluating the hypothalamo-pituitary-adrenal axis) was slightly higher in G5/5D vs controls (8.9 vs 6.1 pg/mL), while it was similar in G3b/G4 vs controls. Median 8 Am ONDST cortisol was similar on CLIA and LC-MS/MS in controls and higher on CLIA in G3b/4 (1.7 vs 1.1 µg/dL; P = .012) and G5/5D (2.4 vs 1.7 µg/dL; P = .002) than LC-MS/MS. Post-ONDST serum cortisol drop from 8 Am to 4 Pm was significant in controls (0.5-<0.2 µg/dL) and G3b/4 (1.7-1.2 µg/dL), but not in G5/5D (2.4-2.2 µg/dL). Conclusion: The normative data of ONDST serum cortisol with eGFR-based cutoffs are useful in evaluating Cushing syndrome in CKD. Prolonged cortisol half-life and immunoassay-related assay cross-reaction are likely contributors to higher ONDST cortisol.

International Nosocomial Infection Control Consortium (INICC) report of health care-associated infections, data summary of 25 countries for 2014 to 2023, Surgical Site Infections Module.

BACKGROUND: Surgical site infection (SSI) rates are higher in low-resource countries (LRC) than in high-income counterparts. METHODS: Prospective cohort study using the INICC Surveillance Online System, from 116 hospitals in 75 cities across 25 Latin-American, Asian, Eastern-European, and Middle-Eastern countries: Argentina, Bahrain, Brazil, Colombia, Costa Rica, Dominican Republic, Ecuador, Egypt, Honduras, India, Kosovo, Kuwait, Lebanon, Mexico, Mongolia, Pakistan, Papua New Guinea, Philippines, Poland, Romania, Saudi Arabia, Thailand, Turkey, Venezuela, Vietnam. CDC/NHSN definitions were applied. Surgical procedures (SPs) were categorized according to the International Classification of Diseases criteria. RESULTS: From 2014 to 2023, we collected data on 1,251 SSIs associated with 56,617 SPs. SSI rates were significantly higher in SPs of INICC compared to CDC/NHSN data: hip prosthesis (3.68% vs 0.67%, relative risk [RR]=5.46, 95% confidence interval [CI]=3.71-8.03, P<.001), knee prosthesis (2.02% vs 0.58%, RR=3.49, 95% CI=1.87-6.49, P<.001), coronary artery bypass (4.16% vs 1.37%, RR=3.03, 95% CI=2.35-3.91, P<.001), peripheral vascular bypass (15.69% vs 2.93%, RR=5.35, 95% CI=2.30-12.48, P<.001), abdominal aortic aneurysm repair (8.51% vs 2.12%, RR=4.02, 95% CI=2.11-7.65, P<.001), spinal fusion (6.47% vs 0.70%, RR=9.27, 95% CI=6.21-13.84, P<.001), laminectomy (2.68% vs 0.72%, RR=3.75, 95% CI=2.36-5.95, P<.001), among others. CONCLUSIONS: Elevated SSI rates in LRCs emphasize the need for effective interventions.

Surveillance and epidemiology of Clostridioides difficile infection using the national health surveillance network criteria: A 7-year study from Mumbai, India.

INTRODUCTION: Clostridioides difficile (CD) is a significant cause of morbidity and mortality. While considerable data is available in the developed world regarding Clostridioides difficile infection (CDI), Indian data is sparse especially using the standardized surveillance systems. AIM AND OBJECTIVES OF THE STUDY: To identify the incidence, risk factors, and mortality rate associated with CDI in a tertiary care hospital based on the Laboratory-Identified (LabID) event criteria of the Centers for Disease Control and Prevention (CDC) National Health Surveillance Network (NHSN). MATERIALS AND METHODS: During a 7- year prospective observational study, CDI was diagnosed using CD polymerase chain reaction (PCR). CDI Laboratory-Identified (LabID) events were classified using the CDC NHSN surveillance definition, and CDI incidence was calculated per 10,000 Patient Days (PDs). Clinical details were collected as part of healthcare-associated infection (HCAI) surveillance. Healthcare Facility-Onset (HO) and Community-Onset Healthcare Facility-Associated (CO-HCFA) incident CDI events were analyzed further. RESULTS: Among 898 tested stool samples, 77 CDI LabID events were observed, with 68 being Incident events. Of 68 events, 76.5% (52/68), 19.1% (13/68), and 4.4% (3/68) were HO, Community-Onset (CO), and CO-HCFA CDI events respectively. The overall incidence of CDI events was 1.66 per 10,000 PDs. Risk factors observed were antibiotics exposure (100%), comorbidities (87.3%), antacids exposure (87.3%), age over 60 years (80%), and hospitalization within the past 6 months (67.3%). The crude mortality rate was 25.5% (14/55). CONCLUSION: These findings highlight the predominance of HO-CDI and the need for further investigation into CO-CDI in the Indian context to identify at-risk populations. Utilizing standardized surveillance methods such as NHSN definitions can facilitate accurate disease burden estimation, trend monitoring, and meaningful comparisons with global data.

Anti-Cholera toxin activity of selected polyphenols from Careya arborea, Punica granatum, and Psidium guajava.

Introduction: Careya arborea, Punica granatum, and Psidium guajava are traditionally used to treat diarrheal diseases in India and were reported to show anti-Cholera toxin activity from our earlier studies. As polyphenols are reported to neutralize Cholera toxin (CT), the present study investigated the inhibitory activity of selected polyphenols from these plants against CTB binding to GM1 receptor using in silico, in vitro, and in vivo approaches. Methods: Molecular modelling approach was used to investigate the intermolecular interactions of selected 20 polyphenolic compounds from three plants with CT using DOCK6. Based on intermolecular interactions, two phenolic acids, Ellagic acid (EA) and Chlorogenic acid (CHL); two flavonoids, Rutin (RTN) and Phloridzin (PHD) were selected along with their respective standards, Gallic acid (GA) and Quercetrin (QRTN). The stability of docked complexes was corroborated using molecular dynamics simulation. Furthermore, in vitro inhibitory activity of six compounds against CT was assessed using GM1 ELISA and cAMP assay. EA and CHL that showed prominent activity against CT in in vitro assays were investigated for their neutralizing activity against CT-induced fluid accumulation and histopathological changes in adult mouse. Results and discussion: The molecular modelling study revealed significant structural stability of the CT-EA, CT-CHL, and CT-PHD complexes compared to their respective controls. All the selected six compounds significantly reduced CT-induced cAMP levels, whereas EA, CHL, and PHD exhibited > 50% binding inhibition of CT to GM1. The EA and CHL that showed prominent neutralization activity against CT from in vitro studies, also significantly decreased CT-induced fluid accumulation and histopathological changes in adult mouse. Our study identified bioactive compounds from these three plants against CT-induced diarrhea.

Computational and experimental pharmacology to decode the efficacy of Theobroma cacao L. against doxorubicin-induced organ toxicity in EAC-mediated solid tumor-induced mice.

Background and objective: Doxorubicin is extensively utilized chemotherapeutic drug, and it causes damage to the heart, liver, and kidneys through oxidative stress. Theobroma cacao L (cocoa) is reported to possess protective effects against several chemical-induced organ damages and also acts as an anticancer agent. The study aimed to determine whether the administration of cocoa bean extract reduces doxorubicin-induced organ damage in mice with Ehrlich ascites carcinoma (EAC) without compromising doxorubicin efficacy. Methodology: Multiple in vitro methods such as cell proliferation, colony formation, chemo-sensitivity, and scratch assay were carried out on cancer as well as normal cell lines to document the effect of cocoa extract (COE) on cellular physiology, followed by in vivo mouse survival analysis, and the organ-protective effect of COE on DOX-treated animals with EAC-induced solid tumors was then investigated. In silico studies were conducted on cocoa compounds with lipoxygenase and xanthine oxidase to provide possible molecular explanations for the experimental observations. Results: In vitro studies revealed potent selective cytotoxicity of COE on cancer cells compared to normal. Interestingly, COE enhanced DOX potency when used in combination. The in vivo results revealed reduction in EAC and DOX-induced toxicities in mice treated with COE, which also improved the mouse survival time; percentage of lifespan; antioxidant defense system; renal, hepatic, and cardiac function biomarkers; and also oxidative stress markers. COE reduced DOX-induced histopathological alterations. Through molecular docking and MD simulations, we observed chlorogenic acid and 8'8 methylenebiscatechin, present in cocoa, to have the highest binding affinity with lipoxygenase and xanthine oxidase, which lends support to their potential in ameliorating oxidative stress. Conclusion: The COE reduced DOX-induced organ damage in the EAC-induced tumor model and exhibited powerful anticancer and antioxidant effects. Therefore, COE might be useful as an adjuvant nutritional supplement in cancer therapy.

Nurture Early for Optimal Nutrition (NEON) participatory learning and action women's groups to improve infant feeding and practices in South Asian infants: pilot randomised trial study protocol.

INTRODUCTION: Feeding practices developed in early life can impact a child's nutrition, growth, dental health, cognitive development and lifetime risk of chronic diseases. Substantial evidence suggests ethnic health inequalities, and non-recommended complementary infant feeding practices among UK's South Asian (SA) population. Nurture Early for Optimal Nutrition aims to use women's group participatory learning and action (PLA) cycles to optimise infant feeding, care and dental hygiene practices in SA infants <2 years in East London. METHODS AND ANALYSIS: A three-arm pilot feasibility cluster randomised controlled trial will assess feasibility, acceptability, costs and explore preliminary effectiveness for proposed primary outcome (ie, reporting on body mass index (BMI) z-score). Multilingual SA community facilitators will deliver the intervention, group PLA Cycle, to mothers/carers in respective ethnic/language groups. 12 wards are randomised to face-to-face PLA, online PLA and usual care arms in 1:1:1 ratio. Primary outcomes are feasibility and process measures (ie, BMI z-score, study records, feedback questionnaires, direct observation of intervention and sustainability) for assessment against Go/Stop criteria. Secondary outcomes are cluster-level and economic outcomes (ie, eating behaviour, parental feeding practices, network diffusion, children development performance, level of dental caries, general practitioner utilisation, costs, staff time). Outcomes are measured at baseline, every 2 weeks during intervention, 14 weeks and at 6 months by blinded outcome assessors where possible. This study will use concurrent mixed-methods evaluation. Quantitative analyses include descriptive summary with 95% CI and sample size calculation for the definitive trial. The intervention effect with CI will be estimated for child BMI z-score. Implementation will be evaluated qualitatively using thematic framework analysis. ETHICS AND DISSEMINATION: Ethics approval was obtained from University College London (UCL), National Health Service (Health Research Authority (HRA) and Health and Care Research Wales (HRCW)). Results will be published in peer-reviewed journals, presented at scientific conferences/workshops with commissioners, partners and participating communities. Plain language summaries will be disseminated through community groups, websites and social media. TRIAL REGISTRATION NUMBER: IRAS-ID-296259 (ISRCTN10234623).