Therapeutic high-dose vitamin D for vitamin D-deficient severe COVID-19 disease: randomized, double-blind, placebo-controlled study (SHADE-S).

BACKGROUND: efficacy of therapeutic cholecalciferol supplementation for severe COVID-19 is sparingly studied. OBJECTIVE: effect of single high-dose cholecalciferol supplementation on sequential organ failure assessment (SOFA) score in moderate-to-severe COVID-19. METHODS: participants with moderate to severe COVID-19 with PaO2/FiO2 ratio < 200 were randomized to 0.6 million IU cholecalciferol oral (intervention) or placebo. OUTCOMES: primary outcome was change in Day 7 SOFA score and pre-specified secondary outcomes were SOFA and 28-day all-cause mortality. RESULTS: in all, 90 patients (45 each group) were included for intention-to-treat analysis. 25(OH)D3 levels were 12 (10-16) and 13 (12-18) ng/ml (P = 0.06) at baseline; and 60 (55-65) ng/ml and 4 (1-7) ng/ml by Day 7 in vitamin D and placebo groups, respectively. The SOFA score on Day 7 was better in the vitamin D group [3 (95% CI, 2-5) versus 5 (95% CI, 3-7), P = 0.01, intergroup difference - 2 (95% CI, -4 to -0.01); r = 0.4]. A lower all-cause 28-day mortality [24% compared to 44% (P = 0.046)] was observed with vitamin D. CONCLUSIONS: single high-dose oral cholecalciferol supplementation on ICU admission can improve SOFA score at Day 7 and reduce in-hospital mortality in vitamin D-deficient COVID-19. ClinicalTrials.gov  id: NCT04952857 registered dated 7 July 2021. What is already known on this topic-vitamin D has immunomodulatory role. Observational and isolated intervention studies show some benefit in COVID-19. Targeted therapeutic vitamin D supplementation improve outcomes in severe COVID-19 is not studied in RCTs. What this study adds-high-dose vitamin D supplementation (0.6 Million IU) to increase 25(OH)D > 50 ng/ml is safe and reduces sequential organ failure assessment score, in-hospital mortality in moderate to severe COVID-19. How this study might affect research, practice or policy-vitamin D supplementation in vitamin D-deficient patients with severe COVID-19 is useful may be practiced.

Effect of Preoperative Carbohydrate Drink and Postoperative Chewing Gum on Postoperative Nausea and Vomiting in Patients Undergoing Day Care Laparoscopic Cholecystectomy: A Randomized Controlled Trial.

BACKGROUND: Postoperative nausea and vomiting (PONV) causes an unexpected prolonged hospital stay after ambulatory surgery. Novel measures such as preoperative loading of oral carbohydrates and postoperative chewing gum have recently gained momentum for postoperative recovery. This study evaluated the effects of preoperative carbohydrate loading and postoperative chewing gum (CG) on PONV after daycare laparoscopic cholecystectomy (LC). METHODS: A total of 100 patients were randomized to group A (preoperative carbohydrate loading with 200 ml of water with 25 g of carbohydrate and postoperative chewing gum (CG) when the patient responded to his/her name) and group B (standard care). The incidence of PONV and pain was assessed by using visual analogue scale. Quality of recovery (QoR-15) was assessed by using QoR15 questionnaire at 6 h, 24 h and 48 h after surgery. RESULTS: The incidence of PONV and pain was lower in group A; however, it was not significant (p > 0.05). The severity of PONV, pain and the need for rescue antiemetic was significantly lower in group A (p < 0.05). The episodes of PONV and required dose of antiemetic were less in group A. Group A also had a significantly higher QoR-15 score at all time points (p < 0.001). Preoperative dyspepsia was also noticed as a significant confounding predictor for postoperative vomiting. CONCLUSION: Preoperative carbohydrate drinks and early postoperative CG reduces the severity of PONV and requirement of antiemetics in patients undergoing LC. Hence, these simple measures can be used as a standard of care to optimize perioperative care in patients undergoing daycare surgery.

Transurethral lidocaine (100 mg) bladder irrigation (TULI100) reduces the incidence of catheter related bladder discomfort in transurethral resection of bladder tumors: A randomized, double blind, controlled trial.

BACKGROUND: Transurethral resection of bladder tumors (TURBT) surgeries requires post-resection catheterization for continuous irrigation of the bladder. This indwelling catheter is associated with distressing catheter-related bladder discomfort (CRBD) and increases postoperative pain and agitation. OBJECTIVES: To prove the hypothesis that transurethral 100 mg lidocaine irrigation at the end of TURBT can reduce the frequency of moderate-to-severe postoperative CRBD. METHODS: 116 patients scheduled for TURBT were screened, 94 were recruited and completed the study. American Society of Anesthesiologists Physical Status I-II adult patients, 20-75 years of age undergoing elective TURBT surgery under general anesthesia were included. Transurethral normal saline with 0.01% lidocaine (100 mg in 1 L NS) was used for irrigation 30 min before the completion of surgery in group L, while only normal saline was used for transurethral irrigation in group N. The main outcomes were frequency of CRBD, pain and patient satisfaction at 0, 1, 2, and 6 h postoperatively. RESULTS: A total of 94 patients were analyzed in the study. The incidence of moderate-severe CRBD was significantly lower in group L as compared to group C at 0, 1, and 2 h (65.9% vs. 31.9%, p = 0.01; 31.9% vs. 10.6%, p = 0.012; 21.3% vs. 2.1%, p = 0.004, respectively). At the 6-h mark, the incidence of CRBD was lower in group L, although this did not achieve statistical significance (6.38% vs. 2.1%; p = 0.613). CONCLUSION: Irrigation with 0.01% lidocaine (100 mg) towards the end of TURBT reduces the incidence of moderate-severe CRBD by 52% and increases patient satisfaction.

Reporting adverse events of ChAdOx1 nCoV-19 coronavirus vaccine (Recombinant) among the vaccinated healthcare professionals: A cross-sectional survey.

Background & objectives: The safety of the ChAdOx1 nCoV-19 vaccine is a cause of concern for many who have been vaccinated. The people have multiple concerns and fear regarding the adverse events of the vaccine. Thus, this study was undertaken to establish the safety profile of ChAdOx1 nCoV-19 Corona Virus Vaccine (Recombinant) among the healthcare professionals. Methods: This was a descriptive cross-sectional survey. After taking clearance from the institutional ethics committee 1500 healthcare professionals, who had their vaccination in the past two weeks were selected. They were provided with an online survey proforma regarding adverse events following immunization (AEFIs) of COVID-19 vaccine developed using google forms with an informed consent form affixed to it. Results: A total of 1036 individuals participated in the study. The mean and median (inter quartile range) age of the participants was 37.7 ±11.25 and 35 (29-46) yr, respectively. Of these, 52.1 per cent were female, 29.3 per cent were doctors, 33.4 per cent were nurses and 9.5 per cent were paramedical staff. Forty six per cent participants experienced one or more minor AEFIs such as pain, tenderness, redness, etc. at the injection site. Fatigue (31.75%), generalized feeling of unwell (28.57%), muscle pain (23.16%) and fever (21.71%) were the most commonly reported systemic AEFIs followed by headache (20.07%), dizziness (10.03%) and joint pains (15.25%). Most of them experienced these AEFIs within 24 h of the first dose of administration. About 42 per cent of the participants took oral antipyretics/analgesics for managing the AEFIs. Interpretation & conclusions: ChAdOx1 nCoV-19 Corona Virus Vaccine was found to be associated with mild local and systemic AEFIs that were more common after the first dose as compared to the second dose. There adverse events could be dealt with oral over-the-counter medications, with no requirement of hospitalization.

Incidence & outcomes of clinically significant bleeding events in critically ill COVID-19 patients receiving Therapeutic dose AntiCoagulanTs: A retrospective cohort study (INTerACT study).

Background & objectives: The high mortality associated with the thrombotic events in hospitalized COVID-19 patients resulted in the usage of anticoagulants in varying doses. Whether high-dose anticoagulants have led to better outcomes or higher incidence of clinically significant bleeding events is debatable. Thus, this study was conducted to find the incidence of clinically significant bleeding events in moderate-to-severe COVID-19 ARDS (acute respiratory distress syndrome) patients on therapeutic anticoagulation and their outcomes. Methods: In this retrospective, single-centre study of 155 critically ill COVID-19 patients, the incidence of clinically significant bleeding was observed. Multivariate regression models were used to evaluate the association between anticoagulant regimen, coagulation and inflammatory markers with the incidence of bleeding and thrombotic events. Results: The incidence of clinically relevant non-major bleeding was 33.54 per cent (26.17-41.46%) and major bleeding was 9.03 per cent (5.02-14.69%). The anticoagulation intensity at baseline had a high odds of major bleeding when enoxaparin and dual antiplatelet therapy were used together [adjusted odds ratio OR of 434.09 (3.81-49502.95), P<0.05]. At admission, bleeders had a poorer PaO2/FiO2 ratio with more patients on invasive ventilation. At the time of bleeding, the bleeders had a higher D-dimer, ferritin, C-reactive protein and procalcitonin compared to non-bleeders. The subhazard ratio for death in bleeders was 3.35 (95% confidence interval, 1.97-5.65; P<0.001). Interpretation & conclusions: The incidence of bleeding in critically ill COVID-19 patients on therapeutic anticoagulation may increase with the severity of the disease as well as with concurrent use of dual antiplatelets. Major bleeding may also contribute to higher mortality.

Neurological monitoring and sedation protocols in the Liver Intensive Care Unit.

Patients with liver disease often have alteration of neurological status which requires admission to an intensive care unit. Patients with acute liver failure (ALF), acute-on-chronic liver failure (ACLF) and rarely cirrhosis are at risk of cerebral edema. These patients require prompt assessment of neurological status including assessment of intra-cranial pressure (ICP) and monitoring metabolic parameters like arterial/venous ammonia levels, serum creatinine and serum electrolytes so that timely specific therapy for raised ICP can be instituted to prevent permanent neurological dysfunction. The overall aims of neuromonitoring and sedation protocols in a liver intensive care unit are to identify the level of multifactorial metabolic encephalopathy, individualize sedation and analgesia requirements for patients on mechanical ventilation, institute specific therapy to correct the neurological insult in ALF and ACLF, provide clear physiological data for guided therapy of drugs like muscle relaxants, antiepileptics, and cerebral edema reducing agents, and assist with overall prognostication. In this review article we will outline the clinical scenarios related to liver disease requiring intensive care and neuromonitoring, current techniques of neurological assessment, sedation protocols and point of care tests which enable the treating physician and intensivist guide therapy for raised ICP.

COVID-19 associated variations in liver function parameters: a retrospective study.

BACKGROUND: Characteristics of laboratory findings of COVID-19 patients are of great significance for diagnosis and treatment. Studies that have analysed the variations in hepatic profile in correlation with the inflammatory markers in SARS-CoV-2 are limited. METHODS: We retrospectively analysed liver function tests and inflammatory markers of 170 admitted patients with confirmed COVID-19 in the tertiary care centre, Post Graduate Institute of Medical Education and Research (PGIMER), India, using Roche Cobas Autoanalyzer. RESULTS: Number of patients with normal liver enzyme levels were 63 (41.5%), while with raised levels of any of the liver enzymes were 89 (58.5%), out of which 43 (48.31%) had liver injury which manifested as increased severity in terms of intensive care unit (ICU) requirement (p=0.0005). Significantly raised levels of liver enzymes and liver injury were observed with age (p<0.0001) and in males (p=0.004). Significantly decreased levels of albumin and total proteins and increased levels of total bilirubin (p<0.0001) were seen in patients with abnormal liver enzyme levels and liver injury as compared to patients with normal levels. Significant increase in the levels of alanine transaminase and gamma-glutamyl transferase was seen on the 7th day, CRP and ferritin (p<0.0001) peaks were observed on 2nd and 3rd day respectively. A significant positive correlation was found between the levels of these inflammatory markers and liver function parameters. CONCLUSIONS: More than half of patients admitted to the hospital with SARS-CoV-2 infection had an abnormal liver function which was found to be associated with raised levels of inflammatory markers. Significantly higher proportions of patients with abnormal liver function were elderly and males and were at higher risk of progressing to severe disease.

Demographic & clinical profile of patients with COVID-19 at a tertiary care hospital in north India.

BACKGROUND & OBJECTIVES: The COVID-19 pandemic emerged as a major public health emergency affecting the healthcare services all over the world. It is essential to analyze the epidemiological and clinical characteristics of patients with COVID-19 in different parts of our country. This study highlights clinical experience in managing patients with COVID-19 at a tertiary care centre in northern India. METHODS: Clinical characteristics and outcomes of consecutive adults patients admitted to a tertiary care hospital at Chandigarh, India, from April 1 to May 25, 2020 were studied. The diagnosis of SARS-CoV-2 infection was confirmed by real-time reverse transcriptase polymerase chain reaction (RT-PCR) on throat and/or nasopharyngeal swabs. All patients were managed according to the institute's consensus protocol and in accordance with Indian Council of Medical Research guidelines. RESULTS: During the study period, 114 patients with SARS-CoV-2 infection were admitted. The history of contact with COVID-19-affected individuals was available in 75 (65.8%) patients. The median age of the patients was 33.5 yr (13-79 yr), and there were 66 (58%) males. Of the total enrolled patients, 48 (42%) were symptomatic. The common presenting complaints were fever (37, 77%), cough (26, 54%) and shortness of breath (10, 20.8%). Nineteen (17%) patients had hypoxia (SpO2<94%) at presentation and 36 (31%) had tachypnoea (RR >24). Thirty four (29.8%) patients had an accompanying comorbid illness. Age more than 60 yr and presence of diabetes and hypertension were significantly associated with severe COVID-19 disease. Admission to the intensive care unit (ICU) was needed in 18 patients (52%), with three (2.6%) patients requiring assisted ventilation. Mortality of 2.6 per cent (3 patients) was observed. INTERPRETATION & CONCLUSIONS: Majority of the patients with COVID-19 infection presenting to our hospital were young and asymptomatic. Fever was noted only in three-fourth of the patients and respiratory symptoms in half of them. Patients with comorbidities were more vulnerable to complications. Triaged classification of patients and protocol-based treatment resulted in good outcomes and low case fatality.

Combined Analysis of Anti SARS-CoV-2 IgG and IgM Responses in COVID19 Patients in India.

Coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a global health problem, India being the second most affected country. The kinetics of antibody response to SARS-CoV-2 in Indian population is not studied yet. To understand serological response in relation to age, gender, time period and severity of disease, Roche Elecsys anti-SARS-CoV-2 test was used which analysed both IgM and IgG. One hundred and three COVID-19 patients were enrolled. Seropositivity was seen in 64% of patients, with 33% at ≤ 7 days, 62% between 8 and 15 days and 81% at ≥ 16 days from the time of admission. Men (65%) showed higher antibody response than women (59%), whereas no difference was observed in seropositivity with respect to age of the patients. Dynamics of antibody responses revealed individual variations. Patients in ICU had higher antibody reactivity with 67% positivity as compared to 60% positivity in non-ICU patients. Kinetics of antibody response during COVID-19 disease varied in relation to gender, age, time period and severity and these factors might play an important role in treatment and control of COVID-19.

Tonic down-rolling and eccentric down-positioning of eyes under sevoflurane anesthesia without non-depolarizing muscle relaxant and its relationship with depth of anesthesia.

Purpose: To analyze the relationship between eccentric downward eye movement/eccentric downward eye-positioning (EDEM/EDEP) encountered in patients undergoing ophthalmic surgeries and its return to a centralized position under general anesthesia (GA) with the depth of anesthesia (DOA). Methods: Patients undergoing ophthalmic surgeries (6 months-12 years) under sevoflurane anesthesia without non-depolarizing muscle relaxant (NDMR) who witnessed a sudden tonic EDEM/EDEP were both retrospectively (R-group) and prospectively (P-group) enrolled (ambispective study). R-group included data-points after induction (AI) till the time surgery lasted while P-group compiled data both during induction (DI) and AI. DOA in terms of MAC (minimum alveolar concentration) at the time of EDEM/EDEP and centralization of eyeball and their timings were noted and compared for both AI and DI data-points. Also, vertical eccentric eye positions were scored and correlated with MAC. Results: AI data included 22 (14R+8P) events and their mean MAC of EDEM/EDEP and centralization were 1.60 ± 0.25 and 1.18 ± 0.17 respectively (p = 0.000). DI data included 62 (P) cases and its mean MAC of EDEM/EDEP and centralization was 2.19 ± 0.43 and 1.39 ± 0.26 respectively (p = 0.000). Median (IQR) eye positions during down-positioning in 84 events was -3 (-3.9 to -2.5). It was preceded by an eccentric upward drift of eyes in 10/22 (6R+4P) AI cases. A strong negative correlation was seen between DOA and eccentric eye positions (r = -0.77, p = 0.000). Conclusions: Tonic down-rolling of eyes is not uncommon in children seen without NDMR with higher depths of sevoflurane anesthesia compared to point of centralization and fluctuations in DOA should be avoided to circumvent inadvertent complications during ocular surgery.

Magnetic Resonance Tractography and Intraoperative Direct Electrical Stimulation in Eloquent Area Glioma Surgery for 102 Cases: A Tertiary Care Center Experience From Northwest India.

OBJECTIVE: Surgery of eloquent area gliomas is challenging and requires monitoring of the nearby white fiber tracts. In the present study, we analyzed 102 patients with eloquent region gliomas and discussed the concept of intraoperative dynamic white fiber tract navigation and monitoring. METHODS: A total of 102 patients with an eloquent area glioma (52 insular, 29 motor area, 21 temporoparietal) were evaluated. The position of the white fiber tracts (corticospinal tract [or motor fiber; CST], inferior fronto-occipital fasciculus [ventral language fiber; IFOF], superior longitudinal fasciculus [SLF], and arcuate fasciculus [dorsal language fiber; AF) was recorded. Awake mapping of the cortical and subcortical eloquent structures was performed for all 102 patients. The suction stimulator was coregistered and used as a dynamic stimulator navigator. RESULTS: Of the 102 patients, 60 were men and 42 were women, with an average age of 39.8 years. Most of the white fiber tracts were normal (CST, 31.3%; IFOF, 39.2%; SLF/AF, 40.19%) or displaced (CST, 59.8%; IFOF, 47.05%; AF/SLF, 44.11%). A few were disrupted (CST, 8.8%; IFOF, 13.7%; SLF/AF, 15.7%). The extent of tumor resection was 82.8%, 86.5%, and 94% for those with insular glioma, motor area glioma, and temporoparietal glioma, respectively. Of the 102 patients, 18 had developed transient speech and language disturbances with improvement, and 14 had developed motor deficits, of whom, all except for 2, had shown gradual improvement. When the dynamic suction stimulator navigator was used, the extent of resection was 96.5%, without any added deficits. CONCLUSIONS: The use of intraoperative neuronavigation and neurophysiological assessment can help achieve maximal tumor resection of eloquent area gliomas. Use of the integrated suction stimulator navigator provided dynamic navigation and mapping of the peritumoral eloquent fibers.

Effect of intraperitoneal magnesium sulfate in the prevention of postoperative pain in daycare laparoscopic cholecystectomy - A prospective randomized controlled trial.

This study evaluated the efficacy of intraperitoneal magnesium sulfate (MgSO4) in preventing postoperative pain after elective laparoscopic cholecystectomy (LC). It is a prospective, double-blinded, placebo-controlled, randomized trial which included 64 patients who underwent LC. Patients were equally randomized into Groups A and B. MgSO4 and normal saline were instilled in subdiaphragmatic space in Groups A and B, respectively, after creating pneumoperitoneum and before starting dissection. The Visual analogue Scale (VAS) was used to determine postoperative pain. Patients who received intraperitoneal MgSO4 had lower average VAS scores for the first 6 h postoperatively, and also, the time for the requirement of first analgesic was longer (3.6 ± 0.4 vs. 2.3 ± 1.0 h). The incidence of vomiting and the requirement for rescue antiemetic was also lower in Group A. Intraperitoneal instillation of MgSO4 reduces postoperative pain and vomiting following elective LC without incurring additional side effects.

Erratum: Addendum: Improved postoperative recovery profile in pediatric oral rehabilitation with low-dose dexmedetomidine as an opioid substitute for general anesthesia: a randomized double-blind clinical trial.

[This corrects the article on p. 357 in vol. 22, PMID: 36246035.].