Calculation of effective dose of phenylephrine bolus for treatment of post-spinal hypotension in pre-eclamptic patients undergoing caesarean section - a non-randomised controlled trial.

BACKGROUND: Patients with pre-eclampsia require smaller vasopressor doses compared with those with normotension for management of post-spinal hypotension during caesarean section. However, the literature has little evidence as to the phenylephrine dose required for patients with pre-eclampsia. METHODS: Fifty patients, with either pre-eclampsia or normotension, and developing post-spinal hypotension during caesarean section under spinal anaesthesia, were studied. Women in both groups did not receive prophylactic vasopressors. The first patient in each group received phenylephrine 50 µg to treat the first episode of hypotension, defined as fall of systolic blood pressure ≥20% from baseline or an absolute value <100 mmHg. If hypotension was corrected within one minute it was considered a 'success'. The doses for the subsequent patients were determined by responses to all previous patients, according to a variation of Narayana's rule for the up-down sequential allocation method. RESULTS: The 95% effective dose (ED95) and 50% effective dose (ED50) of phenylephrine was 41.7 µg (95% CI 33.8 to 49.6 µg) and 29.1 µg (95% CI 26.0 to 32.2 µg) respectively in the pre-eclampsia group, and 64.9 µg (95% CI 54.1 to 75.7 µg) and 47.3 µg (95% CI 39.7 to 54.9 µg) respectively in the normotensive group. The proportionate reduction in phenylephrine dose ranged from 33% (95% CI 18 to 44%) to 40% (95% CI 19 to 52%). CONCLUSION: Patients with pre-eclampsia may need a 33% to 40% reduction in the first phenylephrine bolus dose, compared with patients with normotension, for the treatment of the first episode of post-spinal hypotension.

Patient perspectives on nipple-areola complex micropigmentation during the COVID-19 pandemic.

BACKGROUND: Micropigmentation is a well-recognised option for nipple-areola complex reconstruction, as part of the breast reconstruction pathway for patients following mastectomy. As a part of delayed breast reconstruction, this treatment was put on hold during the COVID-19 pandemic. AIMS: To assess the views of patients regarding micropigmentation in response to the COVID-19 pandemic, and whether their attitudes to seeking out this part of the reconstructive journey had been altered. METHODS: A questionnaire undertaken with 53 patients between August & September 2020 attending the Micropigmentation clinic. FINDINGS: 81.1% of patients reported COVID-19 had not impacted their decision, with a similar proportion happy to proceed with the treatment at the time of questioning. CONCLUSIONS: The results highlight the importance of nipple-areola complex to our patients' reconstructive journey.

Neonatal outcomes following phenylephrine or norepinephrine for treatment of spinal anaesthesia-induced hypotension at emergency caesarean section in women with fetal compromise: a randomised controlled study.

BACKGROUND: Norepinephrine is as effective as phenylephrine for management of spinal anaesthesia-induced hypotension. Most of the studies comparing these vasopressors have been conducted in healthy pregnant women undergoing elective caesarean section. In the current study, we tested the null hypothesis that there is no difference in neonatal outcome when phenylephrine or norepinephrine is used to treat spinal anaesthesia-induced hypotension in women undergoing emergency caesarean section for fetal compromise. METHODS: Patients undergoing caesarean section for fetal compromise who developed spinal anaesthesia-induced hypotension were randomised to receive phenylephrine 100 µg or norepinephrine 8 µg for treatment of each hypotensive episode, defined as systolic blood pressure <100 mmHg. Umbilical cord arterial and venous blood samples were obtained for blood gas analysis. The primary outcome measure was umbilical artery pH. RESULTS: One hundred patients (50 in each group) were studied. There was no significant difference in umbilical artery pH between the two groups (mean difference 0.001; 95% CI -0.032 to 0.034). The number of hypotensive episodes, vasopressor boluses required, the incidence of bradycardia, heart rate and blood pressure trends following vasopressor administration, and the incidence of nausea/vomiting were not significantly different between groups. CONCLUSION: Phenylephrine 100 µg and norepinephrine 8 µg were not significantly different in terms of neonatal outcome when administered as intravenous boluses for treatment of spinal anaesthesia-induced hypotension in parturients undergoing emergency caesarean sections for fetal compromise.

Antimicrobial resistance in Indian isolates of non typhoidal Salmonella of livestock, poultry and environmental origin from 1990 to 2017.

A retrospective antimicrobial resistance study of nontyphoidal Salmonella enterica isolates from India during 1990-2017 was conducted to study the microbial susceptibility to antibiotics. A total of 271 Salmonella enterica isolates from poultry (n = 146), farm animals (n = 55) and environmental sources (n = 70) were tested for susceptibility using 15 antimicrobial drugs. The drug classes include aminoglycosides, phenicols, cephalosporins, penicillins, carbapenems, fluoroquinolones, and sulphonamide-trimethoprim. Study revealed that overall, 133 (49.08%) of 271 isolates were resistant to ≥ 1 antimicrobial drugs and 81 (29.89%) out of 271 isolates were multidrug resistant (resistance to ≥ 3 drugs). Majority (68.96%) of Typhimurium serovars (n = 87) were susceptible to all antibiotics tested, whereas only 5% Kentucky serovars (n = 40) were pan susceptible. All the drugs revealed decreasing trend of susceptibility from 1990 towards 2017 except cephalosporins and carbapenems. Statistical analysis of association between time period and antimicrobial resistance revealed a significance of < 0.05. Molecular detection of genetic determinants associated with antimicrobial resistance revealed the presence of genes like class I integrons, sul1, sul2, catIII, cmlA, dfrA, blaTEM, blaAmpC in the resistant isolates. Furthermore, plasmid mediated quinolone resistant determinants like qnrD and qnrS were also reported in the current study.

Knowledge assessment and outcomes of otolaryngology practice amidst the COVID-19 pandemic in a busy ENT department.

INTRODUCTION: Otolaryngology health personnel are at high risk of acquiring COVID-19 disease and, hence, are likely to have high stress levels. This study was designed to evaluate the feedback of otolaryngology healthcare workers in ENT departments who are managing patients in the coronavirus pandemic. METHODS: A questionnaire focused on all aspects of healthcare delivery was completed by otolaryngology healthcare workers. RESULTS: The findings, based on statistical analyses, included high stress levels and inadequate disease-related information in these workers. CONCLUSIONS: Healthcare authorities need to take care of issues related to mental health in healthcare professionals in addition to spreading awareness about safe practices. Further studies are needed to continuously monitor feedback from personnel as the coronavirus pandemic unravels in the future.

Stepwise interventions for improving hand hygiene compliance in a level 3 academic neonatal intensive care unit in north India.

OBJECTIVE: We evaluated effect of sequentially introducing four WHO-recommended interventions to promote hand-hygiene compliance in tertiary-care NICU. STUDY DESIGN: Four dedicated research nurses directly observed doctors and nurses to record success in hand-hygiene opportunities at randomly selected NICU beds and randomly sampled time-slots in four phases (of 4-weeks each): I-Baseline, II-Self-directed learning; III-Participatory learning; IV-Closed-Circuit Television (CCTV); and V-CCTV-plus (with feedback). FINDINGS: Hand-hygiene compliance changed from 61.8% (baseline) to 77% (end) with overall relative change: 24.6% (95% CI 18, 32; p value= 0.003); compared with preceding phase, relative changes of 21% (15, 28; <0.001), 4% (0, 8; 0.008), -10% (-13, -6; <0.001), and 10% (5, 15; <0.001) during phases II, III, IV, and V, respectively were observed. Rise in hand-hygiene compliance was higher for after-WHO-moments (12.7%; upto 2.5-folds for moment 5, <0.001) compared to before-WHO-moments (5.2%). Educational interventions, feedback and monitoring WHO moments can improve hand-hygiene compliance significantly among health-care providers in NICU.

On point identification of species origin of food animals by recombinase polymerase amplification-lateral flow (RPA-LF) assay targeting mitochondrial gene sequences.

The present study was aimed to develop and standardize Recombinase polymerase amplification-lateral flow (RPA-LF) assays for on point identification of species origin of food animals viz: cattle, buffalo and pig. Species specific RPA primers sets for cattle, buffalo and pig were designed by homology comparisons of the sequences of mitochondrial cytochrome b gene and d-loop region from common food species viz: cattle, buffalo, sheep, goat, pig and chicken. The RPA assays for designed primers sets were optimized using the reaction components from Twist Amp basic kit and instructions in its manual. Endpoint detection of species specific amplified RPA products were made by gel electrophoresis and designed species specific RPA-LFA strips. The developed assays were evaluated for their specificity, diagnostic sensitivity, and validated on coded samples and binary meat admixtures with relative percentage of 20, 10, 5 & 1% target species. The developed RPA assays resulted in amplification of DNA template exclusively of cattle, buffalo and pig origin to product sizes of 294, 405 and 283 bp respectively. The diagnostic sensitivities of developed assays were up to 10 pg of genomic DNA and highly correlated with species specific PCR assays taken as gold standard. Developed species specific RPA assays also identified the target species in coded samples and binary meat admixture up to 1%.

Paper-based loop-mediated isothermal amplification and lateral flow (LAMP-LF) assay for identification of tissues of cattle origin.

The present study was made with the objectives of development and standardization of cattle specific paper-based loop-mediated isothermal amplification cum lateral flow assay (LAMP-LFA), as a Point-of-care test (POCT) for identification of tissue of cattle origin. The components of standardized LAMP reaction utilizing cattle specific primer sets were lyophilized over paper buttons, identified best as the carrier of LAMP reagents. Based on probable LAMP amplicon, a pair of probes was designed, tagged and its hybridization with the amplified product of paper LAMP reaction was optimized. The components of lateral flow assay for detection of probe hybridized LAMP products were standardized. Analysis of successful amplification was made by using HNB dye, LAMP-LFA strip, and also by the typical ladder-like pattern on gel electrophoresis. The assay was found highly specific for cattle with an analytical sensitivity of 0.1 pg of absolute DNA. Laboratory validation carried out on samples from different individuals of cattle, coded samples, binary meat admixture, and heat-processed cattle tissues substantiated the accuracy of the assay. Comparison with pre-standardized species-specific PCR assay taken as gold standards revealed 100% conformity. The field utility of the developed assay was further established by its compatibility with the commercial kit eliminating the lengthy DNA extraction step and storage stability of LAMP reagent carrier buttons for 4 months under refrigeration. Thus, the developed assay capable of the result within 3 h in resource-limited settings can be used as POCT for identification of tissue of cattle origin.

ISAR Consensus Guidelines on Safety and Ethical Practices in In vitro Fertilization Clinics.

STUDY QUESTION: What are the Safe and Ethical practices for ART applicable in INDIA? WHAT IS ALREADY KNOWN: The Indian IVF industry is booming; with mushrooming of assisted reproductive technology (ART) clinics in the country, the need for regulation is immense. The ISAR has taken up this initiative to lead the way forward in establishing practice guidelines for the safe and ethical use of ARTs in our country. These guidelines discuss the points to consider before the starting of an IVF unit, to the designing of the laboratory, the staffing pattern and experience recommendations, laboratory safety guidelines, documentation and patient traceability, gamete traceability, handling biological material, the consumables and media, and different consents and checklists and also propose key performance indicators for the Indian scenario. STUDY DESIGN SIZE DURATION: This is the report of a 2-day consensus meeting where two moderators were assigned to a group of experts to collate information on safe and ethical ivf practices in INDIA. This meeting utilised surveys, available scientific evidence and personal laboratory experience into various presentations by experts on pre-decided specific topics. PARTICIPANTS/MATERIALS SETTING METHODS: Expert professionals from ISAR representing clinical and embryology fields. MAIN RESULTS AND THE ROLE OF CHANCE: The report is divided in various components including the regulations, the various requirements for an ART center, qualifications and trainings, recommendations on good practices and quality management: the report and recommendations of the expert panel reflect the discussion on each of the topics and try to lay down good practice points for labs to follow. LIMITATIONS REASONS FOR CAUTION: The recommendations are solely based on expert opinion. Future availability of data may warrant an update of the same. WIDER IMPLICATIONS OF THE FINDINGS: These guidelines can help labs across the country to standardise their ART services and improve clinical outcomes. STUDY FUNDING/COMPETING INTERESTS: The consensus meeting and writing of the paper was supported by funds from CooperSurgical India.

Consensus and development of document for management of stabilized acute decompensated heart failure with reduced ejection fraction in India.

AIM: Ensuring adherence to guideline-directed medical therapy (GDMT) is an effective strategy to reduce mortality and readmission rates for heart failure (HF). Use of a checklist is one of the best tools to ensure GDMT. The aim was to develop a consensus document with a robust checklist for stabilized acute decompensated HF patients with reduced ejection fraction. While there are multiple checklists available, an India-specific checklist that is easy to fill and validated by regional and national subject matter experts (SMEs) is required. METHODOLOGY: A total of 25 Cardiology SMEs who consented to participate from India discussed data from literature, current evidence, international guidelines and practical experiences in two national and four regional meetings. RESULTS: Recommendations included HF management, treatment optimization, and patient education. The checklist should be filled at four time points- (a) transition from intensive care unit to ward, (b) at discharge, (c) 1st follow-up and (d) subsequent follow-up. The checklist is the responsibility of the consultant or the treating physician which can be delegated to a junior resident or a trained HF nurse. CONCLUSION: This checklist will ensure GDMT, simplify transition of care and can be used by all doctors across India. Institutions, associations, and societies should recommend this checklist for adaptability in public and private hospital. Hospital administrations should roll out policy for adoption of checklist by ensuring patient files have the checklist at the time of discharge and encourage practice of filling it diligently during follow-up visits.

Supercomputer-Based Ensemble Docking Drug Discovery Pipeline with Application to Covid-19.

We present a supercomputer-driven pipeline for in silico drug discovery using enhanced sampling molecular dynamics (MD) and ensemble docking. Ensemble docking makes use of MD results by docking compound databases into representative protein binding-site conformations, thus taking into account the dynamic properties of the binding sites. We also describe preliminary results obtained for 24 systems involving eight proteins of the proteome of SARS-CoV-2. The MD involves temperature replica exchange enhanced sampling, making use of massively parallel supercomputing to quickly sample the configurational space of protein drug targets. Using the Summit supercomputer at the Oak Ridge National Laboratory, more than 1 ms of enhanced sampling MD can be generated per day. We have ensemble docked repurposing databases to 10 configurations of each of the 24 SARS-CoV-2 systems using AutoDock Vina. Comparison to experiment demonstrates remarkably high hit rates for the top scoring tranches of compounds identified by our ensemble approach. We also demonstrate that, using Autodock-GPU on Summit, it is possible to perform exhaustive docking of one billion compounds in under 24 h. Finally, we discuss preliminary results and planned improvements to the pipeline, including the use of quantum mechanical (QM), machine learning, and artificial intelligence (AI) methods to cluster MD trajectories and rescore docking poses.

Supercomputer-Based Ensemble Docking Drug Discovery Pipeline with Application to Covid-19.

We present a supercomputer-driven pipeline for in-silico drug discovery using enhanced sampling molecular dynamics (MD) and ensemble docking. We also describe preliminary results obtained for 23 systems involving eight protein targets of the proteome of SARS CoV-2. THe MD performed is temperature replica-exchange enhanced sampling, making use of the massively parallel supercomputing on the SUMMIT supercomputer at Oak Ridge National Laboratory, with which more than 1ms of enhanced sampling MD can be generated per day. We have ensemble docked repurposing databases to ten configurations of each of the 23 SARS CoV-2 systems using AutoDock Vina. We also demonstrate that using Autodock-GPU on SUMMIT, it is possible to perform exhaustive docking of one billion compounds in under 24 hours. Finally, we discuss preliminary results and planned improvements to the pipeline, including the use of quantum mechanical (QM), machine learning, and AI methods to cluster MD trajectories and rescore docking poses.

Concomitant botanical medicine use among patients participating in commercial prostate cancer trials.

OBJECTIVES: Patients with cancer frequently use botanical medications. The concomitant use of such medications by patients on commercial trials has not been well-described, despite the importance of these trials for evaluating the safety and efficacy of new agents. We sought to describe the use of botanical medications taken by patients with prostate cancer enrolled on global commercial trials. DESIGN: Retrospective study. SETTING: Regulatory repository of commercial clinical trial data. INTERVENTIONS: Anti-cancer therapy. MAIN OUTCOME MEASURES: Botanical and medication use data were pooled across six international commercial randomized trials for metastatic prostate cancer with detailed information on medication and indications. Botanical products were considered to have potential for drug interaction if they led to a change in drug exposure in human trials. Potential for interaction was ascertained by PubMed review. Descriptive statistics were used for analysis. RESULTS: Of 7318 enrolled patients, 700 (10 %) reported botanical use at any time and 653 (9%) reported use of botanical products while on trial. Nearly half of botanical product types were not classified by plant (43 %). The highest proportion of botanical use was among patients in Asian countries (32 %), followed by patients in North America (13 %). Eighty-six different types of botanical products were used; of these, nineteen had a patient-reported anti-cancer indication. CONCLUSIONS: Botanical medicine use among patients with prostate cancer in commercial trials is moderate, although it varies by region. Practitioners should be aware of the use of botanical interventions in a clinical trial context.

A multicentre observational study on the epidemiology, risk factors, management and outcomes of mucormycosis in India.

OBJECTIVES: To describe the epidemiology, management and outcome of individuals with mucormycosis; and to evaluate the risk factors associated with mortality. METHODS: We conducted a prospective observational study involving consecutive individuals with proven mucormycosis across 12 centres from India. The demographic profile, microbiology, predisposing factors, management and 90-day mortality were recorded; risk factors for mortality were analysed. RESULTS: We included 465 patients. Rhino-orbital mucormycosis was the most common (315/465, 67.7%) presentation followed by pulmonary (62/465, 13.3%), cutaneous (49/465, 10.5%), and others. The predisposing factors included diabetes mellitus (342/465, 73.5%), malignancy (42/465, 9.0%), transplant (36/465, 7.7%), and others. Rhizopus species (231/290, 79.7%) were the most common followed by Apophysomyces variabilis (23/290, 7.9%), and several rare Mucorales. Surgical treatment was performed in 62.2% (289/465) of the participants. Amphotericin B was the primary therapy in 81.9% (381/465), and posaconazole was used as combination therapy in 53 (11.4%) individuals. Antifungal therapy was inappropriate in 7.6% (30/394) of the individuals. The 90-day mortality rate was 52% (242/465). On multivariate analysis, disseminated and rhino-orbital (with cerebral extension) mucormycosis, shorter duration of symptoms, shorter duration of antifungal therapy, and treatment with amphotericin B deoxycholate (versus liposomal) were independent risk factors of mortality. A combined medical and surgical management was associated with a better survival. CONCLUSIONS: Diabetes mellitus was the dominant predisposing factor in all forms of mucormycosis. Combined surgical and medical management was associated with better outcomes. Several gaps surfaced in the management of mucormycosis. The rarer Mucorales identified in the study warrant further evaluation.

Thromboinflammatory changes in plasma proteome of pregnant women with PCOS detected by quantitative label-free proteomics.

Polycystic ovary syndrome (PCOS) is the most common endocrinological disorder of fertile-aged women. Several adverse pregnancy outcomes and abnormalities of the placenta have been associated with PCOS. By using quantitative label-free proteomics we investigated whether changes in the plasma proteome of pregnant women with PCOS could elucidate the mechanisms behind the pathologies observed in PCOS pregnancies. A total of 169 proteins with ≥2 unique peptides were detected to be differentially expressed between women with PCOS (n = 7) and matched controls (n = 20) at term of pregnancy, out of which 35 were significant (p-value < 0.05). A pathway analysis revealed that networks related to humoral immune responses, inflammatory responses, cardiovascular disease and cellular growth and proliferation were affected by PCOS. Classification of cases and controls was carried out using principal component analysis, orthogonal projections on latent structure-discriminant analysis (OPLS-DA), hierarchical clustering, self-organising maps and ROC-curve analysis. The most significantly enriched proteins in PCOS were properdin and insulin-like growth factor II. In the dataset, properdin had the best predictive accuracy for PCOS (AUC = 1). Additionally, properdin abundances correlated with AMH levels in pregnant women.