Multifocal stress fractures in a patient with rheumatoid arthritis.

Stress fractures are often associated to activities that requires repetitive stress such as running. However, insufficiency-type stress fractures can also occur in patients with risk factors such as rheumatoid arthritis. Diagnosis of stress fracture would require a thorough clinical evaluation along with radiological imaging. However, this may be difficult due to how it mimics other musculoskeletal problems. The case of a woman in her 60s presenting with 2 months of severe ipsilateral right knee and ankle pain is used as an example. Based on initial clinical assessment and plain radiograph, her provisional diagnosis was osteoarthritis or inflammatory arthritis secondary to rheumatoid disease. However, MRI scan revealed that she had multifocal stress fractures in her knee, ankle and foot. Hence, we hope that this case study can allow clinicians to consider multifocal stress fracture as a possible diagnosis in patients with risk factors and to have lower threshold in performing MRI scans.

Epidemiology and preventability of hospital-onset bacteremia and fungemia in 2 hospitals in India.

OBJECTIVE: Studies evaluating the incidence, source, and preventability of hospital-onset bacteremia and fungemia (HOB), defined as any positive blood culture obtained after 3 calendar days of hospital admission, are lacking in low- and middle-income countries (LMICs). DESIGN, SETTING, AND PARTICIPANTS: All consecutive blood cultures performed for 6 months during 2020-2021 in 2 hospitals in India were reviewed to assess HOB and National Healthcare Safety Network (NHSN) reportable central-line-associated bloodstream infection (CLABSI) events. Medical records of a convenience sample of 300 consecutive HOB events were retrospectively reviewed to determine source and preventability. Univariate and multivariable logistic regression analyses were performed to identify factors associated with HOB preventability. RESULTS: Among 6,733 blood cultures obtained from 3,558 hospitalized patients, there were 409 and 59 unique HOB and NHSN-reportable CLABSI events, respectively. CLABSIs accounted for 59 (14%) of 409 HOB events. There was a moderate but non-significant correlation (r = 0.51; P = .070) between HOB and CLABSI rates. Among 300 reviewed HOB cases, CLABSIs were identified as source in only 38 (13%). Although 157 (52%) of all 300 HOB cases were potentially preventable, CLABSIs accounted for only 22 (14%) of these 157 preventable HOB events. In multivariable analysis, neutropenia, and sepsis as an indication for blood culture were associated with decreased odds of HOB preventability, whereas hospital stay ≥7 days and presence of a urinary catheter were associated with increased likelihood of preventability. CONCLUSIONS: HOB may have utility as a healthcare-associated infection metric in LMIC settings because it captures preventable bloodstream infections beyond NHSN-reportable CLABSIs.

Prevalence of frailty and association with patient centered outcomes: A prospective registry-embedded cohort study from India.

PURPOSE: We aimed to study the prevalence of frailty, evaluate risk factors, and understand impact on outcomes in India. METHODS: This was a prospective registry-embedded cohort study across 7 intensive care units (ICUs) and included adult patients anticipated to stay for at least 48 h. Primary exposure was frailty, as defined by a score ≥ 5 on the Clinical Frailty Scale and primary outcome was ICU mortality. Secondary outcomes included in-hospital mortality and resource utilization. We used generalized linear models to evaluate risk factors and model association between frailty and outcomes. RESULTS: 838 patients were included, with median (IQR) age 57 (42,68) yrs.; 64.8% were male. Prevalence of frailty was 19.8%. Charlson comorbidity index (OR:1.73 (95%CI:1.39,2.15)), Subjective Global Assessment categories mild/moderate malnourishment (OR:1.90 (95%CI:1.29, 2.80)) and severe malnourishment (OR:4.76 (95% CI:2.10,10.77)) were associated with frailty. Frailty was associated with higher odds of ICU mortality (adjusted OR:2.04 (95% CI:1.25,3.33)), hospital mortality (adjusted OR:2.36 (95%CI:1.45,3.84)), development of stage2/3 AKI (unadjusted OR:2.35 (95%CI:1.60, 3.43)), receipt of non-invasive ventilation (unadjusted OR:2.68 (95%CI:1.77, 4.03)), receipt of vasopressors (unadjusted OR:1.47 (95%CI:1.04, 2.07)), and receipt of kidney replacement therapy (unadjusted OR:3.15 (95%CI:1.90, 5.17)). CONCLUSIONS: Frailty is common among critically ill patients in India and is associated with worse outcomes. STUDY REGISTRATION: CTRI/2021/02/031503.

Liver injury in hospitalized patients with COVID-19: An International observational cohort study.

BACKGROUND: Using a large dataset, we evaluated prevalence and severity of alterations in liver enzymes in COVID-19 and association with patient-centred outcomes. METHODS: We included hospitalized patients with confirmed or suspected SARS-CoV-2 infection from the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) database. Key exposure was baseline liver enzymes (AST, ALT, bilirubin). Patients were assigned Liver Injury Classification score based on 3 components of enzymes at admission: Normal; Stage I) Liver injury: any component between 1-3x upper limit of normal (ULN); Stage II) Severe liver injury: any component ≥3x ULN. Outcomes were hospital mortality, utilization of selected resources, complications, and durations of hospital and ICU stay. Analyses used logistic regression with associations expressed as adjusted odds ratios (OR) with 95% confidence intervals (CI). RESULTS: Of 17,531 included patients, 46.2% (8099) and 8.2% (1430) of patients had stage 1 and 2 liver injury respectively. Compared to normal, stages 1 and 2 were associated with higher odds of mortality (OR 1.53 [1.37-1.71]; OR 2.50 [2.10-2.96]), ICU admission (OR 1.63 [1.48-1.79]; OR 1.90 [1.62-2.23]), and invasive mechanical ventilation (OR 1.43 [1.27-1.70]; OR 1.95 (1.55-2.45). Stages 1 and 2 were also associated with higher odds of developing sepsis (OR 1.38 [1.27-1.50]; OR 1.46 [1.25-1.70]), acute kidney injury (OR 1.13 [1.00-1.27]; OR 1.59 [1.32-1.91]), and acute respiratory distress syndrome (OR 1.38 [1.22-1.55]; OR 1.80 [1.49-2.17]). CONCLUSIONS: Liver enzyme abnormalities are common among COVID-19 patients and associated with worse outcomes.

Prostaglandins for adult liver transplanted recipients.

BACKGROUND: Prostaglandins are naturally occurring lipids that are synthesised from arachidonic acid. Multiple studies have evaluated the benefits of prostaglandins in reducing ischaemia reperfusion injury after liver transplantation. New studies have been published since the previous review, and hence it was important to update the evidence for this intervention. OBJECTIVES: To evaluate the benefits and harms of prostaglandins in adults undergoing liver transplantation compared with placebo or standard care. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 27 December 2022. SELECTION CRITERIA: We included randomised clinical trials evaluating prostaglandins initiated in the perioperative period compared with placebo or standard care for adults undergoing liver transplantation. We included trials irrespective of reported outcomes. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. all-cause mortality, 2. serious adverse events, and 3. health-related quality of life. Our secondary outcomes were 4. liver retransplantation, 5. early allograft dysfunction, 6. primary non-function of the allograft, 7. acute kidney failure, 8. length of hospital stay, and 9. adverse events considered non-serious. We used GRADE to assess certainty of evidence. MAIN RESULTS: We included 11 randomised clinical trials with 771 adult liver transplant recipients (mean age 47.31 years, male 61.48%), of whom 378 people were randomised to receive prostaglandins and 393 people were randomised to either placebo (272 participants) or standard care (121 participants). All trials were published between 1993 and 2016. Ten trials were conducted in high- and upper-middle-income countries. Prostaglandins may reduce all-cause mortality up to one month (risk ratio (RR) 0.86, 95% confidence interval (CI) 0.61 to 1.23; risk difference (RD) 21 fewer per 1000, 95% CI 63 fewer to 36 more; 11 trials, 771 participants; low-certainty evidence). Prostaglandins may result in little to no difference in serious adverse events (RR 0.92, 95% CI 0.60 to 1.40; RD 81 fewer per 1000, 95% CI 148 fewer to 18 more; 6 trials, 568 participants; low-certainty evidence). None of the included trials reported health-related quality of life. Prostaglandins may result in little to no difference in liver retransplantation (RR 0.98, 95% CI 0.49 to 1.96; RD 1 fewer per 1000, 95% CI 33 fewer to 62 more; 6 trials, 468 participants; low-certainty evidence); early allograft dysfunction (RR 0.62, 95% CI 0.33 to 1.18; RD 137 fewer per 1000, 95% CI 241 fewer to 47 more; 1 trial, 99 participants; low-certainty evidence); primary non-function of the allograft (RR 0.58, 95% CI 0.26 to 1.32; RD 23 fewer per 1000, 95% CI 40 fewer to 16 more; 7 trials, 624 participants; low-certainty evidence); and length of hospital stay (mean difference (MD) -1.15 days, 95% CI -5.44 to 3.14; 4 trials, 369 participants; low-certainty evidence). Prostaglandins may result in a large reduction in the development of acute kidney failure requiring dialysis (RR 0.42, 95% CI 0.24 to 0.73; RD 100 fewer per 1000, 95% CI 132 fewer to 49 fewer; 5 trials, 477 participants; low-certainty evidence). The evidence is very uncertain about the effect of prostaglandins on adverse events considered non-serious (RR 1.19, 95% CI 0.42 to 3.36; RD 225 fewer per 1000, 95% CI 294 fewer to 65 fewer; 4 trials, 329 participants; very low-certainty evidence). Two trials reported receiving funding; one of these was with vested interests. We found one registered ongoing trial. AUTHORS' CONCLUSIONS: Eleven trials evaluated prostaglandins in adult liver transplanted recipients. Based on low-certainty evidence, prostaglandins may reduce all-cause mortality up to one month; may cause little to no difference in serious adverse events, liver retransplantation, early allograft dysfunction, primary non-function of the allograft, and length of hospital stay; and may have a large reduction in the development of acute kidney injury requiring dialysis. We do not know the effect of prostaglandins on adverse events considered non-serious. We lack adequately powered, high-quality trials evaluating the effects of prostaglandins for people undergoing liver transplantation.

Are Two- and Three-Dimensional Computed Tomographic Scan Measurements of Tibial Tubercle-Trochlear Groove Distance Equivalent? A Comparative Study.

Background: Accurate planning for patellar instability correction is important in obtaining good post-operative outcome. The main challenge in the current two-dimensional (2-D) computed tomographic (CT) scans method is the difficulty in choosing reliable bony landmarks. This study aimed to compare the reliabilities between the 2-D and three-dimensional (3-D) methods of measuring tibial tubercle-trochlear groove (TT-TG) distance. We hypothesize that the proposed 3-D method will result in measurements with narrower error margin, providing higher reliability and accuracy. Materials and Methods: We traced CT scans of 106 knees with no patellofemoral pathology from 59 subjects from the database system and converted all 2-D images into 3-D models to determine the values for each parameter. We compared the intra- and interobserver reliability of each method using intraclass correlation (ICC) and Bland-Altman method. Results: The values of TT-TG measured by 2-D and 3-D methods were 16.1 ± 4.6 mm and 16.2 ± 4.2 mm, respectively. The ICC values of both methods were comparable (95% limits of agreement between the same observer: - 3.3 to 3.8 mm versus - 2.4 to 2.7 mm and different observers: - 4.3 to 4.9 mm versus - 3.9 to 2.7 mm), with 3-D method results in narrower limits of agreement. Conclusion: TT-TG measurement is reliable using the 2-D method without using advanced radiographic software. The 3-D method of measuring TT-TG provides measurement with narrower variation when compared with the 2-D method. However, both TT-TG distances' measurement methods in the current study were comparable as the variations are not significant.

Colistin (Polymyxin E) Use in Abdominal Solid Organ Transplant Recipients.

Background: Patients undergoing solid organ transplantation are at a higher risk of multi-drug resistant (MDR) bacterial infections especially during the immediate post operative period. Objective: To audit the usage, dosage appropriateness and safety of colistin use in abdominal solid organ transplant recipients to treat immediate post-transplant bacterial infections. Methods: After completion of 1000 abdominal solid organ transplants at our institute, data of the transplant recipients who received colistin between October 2010 and December 2019 was extracted from the hospital health information system. Data of all microbiological culture isolates, the minimum inhibitory concentration (MIC) of colistin, appropriateness of colistin dosing and nephrotoxicity associated with colistin use was assessed. Results: Of the 1170 (732 liver and 438 renal) solid organ transplant recipients, 82 (66 liver and 16 renal) received colistin to treat posttransplant MDR bacterial infections. Nearly 60% received colistin as definitive therapy and 87.81% received colistin as combination. Mean duration of colistin therapy was found to be higher in renal than liver transplant recipients. Out of the total 89 bacterial isolates, there were 2 colistin resistant Klebsiella strains. Colistin in combination with meropenem (36.4%) was the most commonly used dual therapy. Out of the total 89 bacterial isolates, there were 2 colistin resistant Klebsiella strains. Overall in-hospital mortality of patients who received colistin was 43.9%. Renal impairment occurred in 28.8% of liver transplant recipients. Conclusion: Infection necessitating colistin use increases mortality by three folds in liver transplant recipients and by five percentage points in renal transplant recipients.

Recent Updates on Source, Biosynthesis, and Therapeutic Potential of Natural Flavonoid Luteolin: A Review.

Nature gives immense resources that are beneficial to humankind. The natural compounds present in plants provide primary nutritional values to our diet. Apart from food, plants also provide chemical compounds with therapeutic values. The importance of these plant secondary metabolites is increasing due to more studies revealing their beneficial properties in treating and managing various diseases and their symptoms. Among them, flavonoids are crucial secondary metabolite compounds present in most plants. Of the reported 8000 flavonoid compounds, luteolin is an essential dietary compound. This review discusses the source of the essential flavonoid luteolin in various plants and its biosynthesis. Furthermore, the potential health benefits of luteolins such as anti-cancer, anti-microbial, anti-inflammatory, antioxidant, and anti-diabetic effects and their mechanisms are discussed in detail. The activity of luteolin and its derivatives are diverse, as they help to prevent and control many diseases and their life-threatening effects. This review will enhance the knowledge and recent findings regarding luteolin and its therapeutic effects, which are certainly useful in potentially utilizing this natural metabolite.

Typical response of CD14++CD16- monocyte to knee synovial derived mediators as a key target to overcome the onset and progression of osteoarthritis.

Objective: Synovitis with increased infiltration of immune cells is observed in osteoarthritis (OA). Given the inflammatory condition of synovitis, we explored the protein profile of OA synovium (OAS) and its effect on circulating monocytes activation, migration, and functional commitments. Methods: Knee-synovium was acquired from end-stage OA (N = 8) and trauma patients (Trauma baseline control: TBC; N = 8) for characterization using H&E histology, IHC (iNOS), LCMS-QTOF, and MALDI-imaging. Response of peripheral blood monocytes to OAS conditioned-media (OACM) was observed using transwell (n = 6). The migrated cells were captured in SEM, quantified using phase-contrast microphotographs, and their activation receptors (CCR2, CXCR2, CX3CR1, and CD11b), pro-inflammatory genes, and phagocytic potential were studied using flow cytometry, gene expression array/qPCR, and latex beads (LB) phagocytosis assay, respectively. Results: The Venn diagram displayed 119 typical proteins in OAS, while 55 proteins in TBCS. The STRING protein network analysis indicated distinctive links between proteins and gene ontology (GO) and revealed proteins associated with leukocyte-mediated immunity in OAS as compared to TBC. The MALDI-imaging showed typical localized proteins at 2234.97, 2522.61, 2627.21, 3329.50, and 3539.69 m/z and IHC confirmed pro-inflammatory iNOS expression in OA synovium. CD14++CD16- classical monocytes significantly migrated in OACM and expressed CCR2, CXCR2, and CD11b receptors, TNFRSF11A, MAPK1, S100A8, HSPB1, ITGAL, NFATC1, IL13RA1, CD93, IL-1ß, TNF-α, and MYD88 genes and increased LB uptake as compared to SFM. Conclusion: Our findings suggest that the differential protein profile of OA synovium and the classical monocytes migrated, activated, and functionally committed in response to these mediators could be of therapeutic advantage.

Periprosthetic Femoral Fractures and Their Surgical Outcomes Between 2011 and 2021: A Single-Centre Observational Study.

Introduction Periprosthetic femoral fractures (PFFs) present a significant burden on the health service. The incidence continues to rise globally as a result of an ageing population and an increase in the number of primary hip and knee arthroplasties being performed. This is a 10-year, retrospective, observational study that aims to better understand the outcomes of PFF in our district general hospital. Materials and methods We identified the demographic information of patients who had a PFF and looked at how the American Society of Anesthesiologists (ASA) score, time to operation, length of stay, complications, and mortality data vary depending on where the fracture is sited and the operative management employed. Results During the period between January 2011 and March 2021, we identified 214 cases of PFF. The mean age was 82.5 years with a female preponderance of 76%. Between 2011-2016 and 2017-2021, the number of cases of PFF increased and patients with an ASA score of 3 or more increased from 43% to 73%. Length of stay was longer in the proximal PFF revision group than in the proximal PFF fixation group. Overall PFF mortality rates at 30 days, 90 days, and one year were 6%, 10%, and 15%, respectively. Conclusion Over the 10-year period, there was a significant increase in the incidence of patients presenting with PFF with multiple comorbidities. Mortality rates were lower in proximal PFF patients who underwent revision procedures rather than fixation. The patient demographics, complication rates, and mortality rates were comparable to similar studies across different countries.

Variation in Kaplan fiber insertion to the distal femur and surgical implications: A cadaveric anatomical study comparing Asian and Caucasian knees.

BACKGROUND: The iliotibial band together with its attachment to the distal femur, known eponymously as the Kaplan fibers, has been shown to contribute to anterolateral rotatory stability of the knee. However, there remains paucity of data regarding the detailed anatomy of the Kaplan fibers to aid us in anatomical-based surgical reconstruction of these structures. The aim of our study was to identify and compare the presence and quantitative anatomy of the Kaplan fibers in Caucasian and Asian cadavers. METHODS: Twenty paired fresh-frozen Asian and 20 unpaired embalmed Caucasian cadaveric knees were dissected using a standard outside-in technique. The presence, qualitative and quantitative measurements of any distal femoral attachments of the iliotibial band were recorded. Mean values of its dimensions were calculated and compared between the Caucasian and Asian groups. RESULTS: A consistent supracondylar attachment of the iliotibial band was found in all Caucasian knees and in 19 of 20 Asian knees. The fibers were noted to have two variations with regard to their insertion to the distal femur, either as a single limb or as a double limb attachment, averaging between 30 mm and 40 mm from the lateral femoral epicondyle. No statistically significant difference was noted in dimensions of the fibers between the Caucasian and Asian groups. CONCLUSIONS: The Kaplan fibers are a consistent attachment of the iliotibial band at the distal femur in both Caucasian and Asian knees with two different patterns of insertion. Surgical reconstructions should aim to recreate these attachments to be as anatomically based as possible.

A quality improvement initiative to improve the appropriateness of candidemia management by the implementation of a comprehensive candidemia care bundle at a tertiary care hospital in South India: Results of a quasi-experimental study.

ABSTRACT: Management of candidemia in developing countries like India encounters laxity in appropriate clinical management and challenges in terms of healthcare capacity, despite its association with high morbidity and mortality. Our study aims to evaluate the impact of a comprehensive candidemia care bundle implementation on appropriateness of therapy and major clinical outcomes.The single-center, quasi-experimental study conducted at a south Indian tertiary care center included adult patients diagnosed with candidemia. Following a retrospective review of candidemia patients of the pre-implementation period (January 2013-December 2015), the hospital antifungal stewardship team instituted a clinical pharmacist driven comprehensive candidemia care bundle for candidemia patients during the post-implementation period (October 2017-2019) and its impact on appropriateness of antifungal prescriptions and inpatient mortality was evaluated.The study included 175 patients with candidemia, comprising of 103 patients in the pre-implementation period and 72 patients in the post-implementation period. Appropriateness of antifungal prescriptions rose to 65% during post-implementation period from 30% observed in pre-implementation phase (P = .0005). The inhospital mortality rate reduced from 40% in the pre-implementation phase to 36% in the post-implementation phase, recording a 10% reduction over 2 years post-implementation (P = .26). No significant difference was observed in terms length of stay (P = .17).Our study demonstrates the successful implementation of an antifungal stewardship led comprehensive care bundle in a low middle income countries setting. The results of our study will have profound implications in improving the appropriateness of management of candidemia and feasibility of scaling up to wider settings could be explored.

Arthroscopically reduced, irreducible patella dislocation.

Acute patella dislocations account for approximately 2%-3% of knee injuries and are therefore a relatively common presentation in the accident and emergency department. The majority of patella dislocations can be reduced with simple manoeuvres or even spontaneously and can be managed conservatively by bracing and rehabilitation. The aim of this study is to identify and review the main causes of the unique and unexpected event of irreducible patella dislocation and their characteristic presentations. Irreducible patella dislocations can happen but are very rare. Currently, a limited number of case reports are available, prompting for a need for research on this topic. This case study can shed light on the possible pathogenesis and pathognomonic features of irreducible patella dislocations and provide insight on the available therapeutic approaches.

Biomechanical comparison of new Achilles tendon rupture repair technique the "Giftbox" versus the Krackow technique in New Zealand white rabbits: An experimental animal study.

INTRODUCTION: To compare the strength between the Achilles tendons repaired with the "Giftbox" and the Krackow techniques in New Zealand white rabbits post six weeks of tendon healing. MATERIALS AND METHODS: Eight rabbits were randomized into Giftbox and Krackow groups. Tenotomy was performed on the Achilles tendon of one side of the lower limb and repaired with the respective techniques. The contralateral limb served as control. Subjects were euthanized six weeks post-operative, and both repaired and control Achilles tendons were harvested for biomechanical tensile test. RESULTS: The means of maximum load to rupture and tenacity in the Giftbox group (156.89 ± 38.49 N and 159.98 ± 39.25 gf/tex) were significantly different than Krackow's (103.55 ± 27.48 N and 104.91 ± 26.96 gf/tex, both p = 0.043). CONCLUSION: The tendons repaired with Giftbox technique were biomechanically stronger than those repaired with Krackow technique after six weeks of tendon healing.

Liver Transplantation Society of India Guidelines for the Management of Acute Liver Injury Secondary to Yellow Phosphorus-Containing Rodenticide Poisoning Using the Modified Delphi Technique of Consensus Development.

BACKGROUND: Acute liver failure caused by the ingestion of yellow phosphorus-containing rodenticide has been increasing in incidence over the last decade and is a common indication for emergency liver transplantation in Southern and Western India and other countries. Clear guidelines for its management are necessary, given its unpredictable course, potential for rapid deterioration and variation in clinical practice. METHODS: A modified Delphi approach was used for developing consensus guidelines under the aegis of the Liver Transplantation Society of India. A detailed review of the published literature was performed. Recommendations for three areas of clinical practice, assessment and initial management, intensive care unit (ICU) management and liver transplantation, were developed. RESULTS: The expert panel consisted of 16 clinicians, 3 nonclinical specialists and 5 senior advisory members from 11 centres. Thirty-one recommendations with regard to criteria for hospital admission and discharge, role of medical therapies, ICU management, evidence for extracorporeal therapies such as renal replacement therapy and therapeutic plasma exchange, early predictors of need for liver transplantation and perioperative care were developed based on published evidence and combined clinical experience. CONCLUSION: Development of these guidelines should help standardise care for patients with yellow phosphorus poisoning and identify areas for collaborative research.

Antimicrobial Stewardship and Its Impact on the Changing Epidemiology of Polymyxin Use in a South Indian Healthcare Setting.

Polymyxins being last resort drugs to treat infections triggered by multidrug-resistant pathogens necessitates the implementation of antimicrobial stewardship program (ASP) initiatives to support its rational prescription across healthcare settings. Our study aims to describe the change in the epidemiology of polymyxins and patient outcomes following the implementation of ASP at our institution. The antimicrobial stewardship program initiated in February 2016 at our 1300 bed tertiary care center involved post-prescriptive audits tracking polymyxin consumption and evaluating prescription appropriateness in terms of the right indication, right frequency, right drug, right duration of therapy and administration of the right loading dose (LD) and maintenance dose (MD). Among the 2442 polymyxin prescriptions tracked over the entire study period ranging from February 2016 to January 2020, the number of prescriptions dropped from 772 prescriptions in the pre-implementation period to an average of 417 per year during the post-implementation period, recording a 45% reduction. The quarterly patient survival rates had a significant positive correlation with the quarterly prescription appropriateness rates (r = 0.4774, p = 0.02), right loading dose (r = 0.5228, p = 0.015) and right duration (r = 0.4361, p = 0.04). Our study on the epidemiology of polymyxin use demonstrated favorable effects on the appropriateness of prescriptions and mortality benefits after successful implementation of antimicrobial stewardship in a real-world setting.

Mapping the Implementation of a Clinical Pharmacist-Driven Antimicrobial Stewardship Programme at a Tertiary Care Centre in South India.

In many parts of the world, including in India, pharmacist roles in antimicrobial stewardship (AMS) programmes remain unexplored. We describe the evolution and effect of the role of adding clinical pharmacists to a multidisciplinary AMS at a tertiary care teaching hospital in Kerala, India. Through effective leadership, multidisciplinary AMS (February 2016) and antitubercular therapy (ATT) stewardship programmes (June 2017) were established. Clinical pharmacists were introduced as core members of the programmes, responsible for the operational delivery of key stewardship interventions. Pharmacy-led audit and feedback monitored the appropriateness of antimicrobial prescriptions and compliance to AMS/ATT recommendations. Between February 2016 and January 2017, 56% (742/1326) of antimicrobial prescriptions were appropriate, and 54% (318/584) of recommendations showed compliance. By the third year of the AMS, appropriateness increased to 80% (1752/2190), and compliance to the AMS recommendations to 70% (227/325). The appropriateness of ATT prescriptions increased from a baseline of 61% (95/157) in the first year, to 72% (62/86, June 2018-February 2019). The compliance to ATT recommendations increased from 42% (25/60) to 58% (14/24). Such a model can be effective in implementing sustainable change in low- and middle-income countries (LMICs) such as India, where the shortage of infectious disease physicians is a major impediment to the implementation and sustainability of AMS programmes.

Vitamin C Therapy for Routine Care in Septic Shock (ViCTOR) Trial: Effect of Intravenous Vitamin C, Thiamine, and Hydrocortisone Administration on Inpatient Mortality among Patients with Septic Shock.

BACKGROUND: Sepsis remains a leading cause of death worldwide despite advances in management strategies. Preclinical and observational studies have found mortality benefit with high-dose vitamin C in sepsis. Our study aims to prospectively evaluate the effect of intravenous hydrocortisone, vitamin C [ascorbic acid (AA)], and thiamine (HAT) administration in reducing inpatient all-cause mortality among patients with septic shock. MATERIALS AND METHODS: Our single-center, prospective, open-label, randomized controlled trial recruited patients with admitting diagnosis of septic shock and assigned eligible patients (1:1) into either intervention (HAT) or control group (routine). The HAT group received intravenous combination of vitamin C (1.5 g every 6 hours), thiamine (200 mg every 12 hours), and hydrocortisone (50 mg every 6 hours) within 6 hours of onset of septic shock admission. The treatment was continued for at least 4 days, in addition to the routine standard of care provided to the control group. Thiamine and hydrocortisone use in control arm was not restricted. Vitamin C levels were estimated at baseline and at the end of the 4 days of treatment for both groups. The primary outcome evaluated was mortality during inpatient stay. RESULTS: Among 90 patients enrolled, 88 patients completed the study protocol. The baseline characteristics between the HAT (n = 45) and the routine (n = 43) groups were comparable. The all-cause mortality in the HAT cohort was 57% (26/45) compared to 53% (23/43) in the routine care group (p = 0.4, OR 1.19, 95% CI 0.51-2.76). The time to reversal of septic shock was significantly lower in the HAT (34.58 ± 22.63 hours) in comparison to the routine care (45.42 ± 24.4 hours) (p = 0.03, mean difference -10.84, 95% CI -20.8 to -0.87). No significant difference was observed between the HAT and the routine care with respect to changes in sequential organ failure assessment (SOFA) scores at 72 hours (2.23 ± 2.4 vs 1.38 ± 3.1), the use of mechanical ventilation (48% vs 46%), and mean Vasoactive Inotropic Score (7.77 ± 12.12 vs 8.86 ± 12.5). CONCLUSION: Intravenous administration of vitamin C, thiamine, and hydrocortisone did not significantly improve the inpatient all-cause mortality among patients with septic shock. CLINICAL SIGNIFICANCE: HAT protocol does not reduce hospital mortality but decreases time to shock reversal in septic shock. HOW TO CITE THIS ARTICLE: Mohamed ZU, Prasannan P, Moni M, Edathadathil F, Prasanna P, Menon A, et al. Vitamin C Therapy for Routine Care in Septic Shock (ViCTOR) Trial: Effect of Intravenous Vitamin C, Thiamine, and Hydrocortisone Administration on Inpatient Mortality among Patients with Septic Shock. Indian J Crit Care Med 2020;24(8):653-661.

Dilatational Percutaneous vs Surgical TracheoStomy in IntEnsive Care UniT: A Practice Pattern Observational Multicenter Study (DISSECT).

INTRODUCTION: Tracheostomy is among the common procedures performed in the intensive care unit (ICU), with percutaneous dilatational tracheostomy (PDT) being the preferred technique. We sought to understand the current practice of tracheostomy in Indian ICUs. MATERIALS AND METHODS: A pan-India multicenter prospective observational study, endorsed and peer-reviewed by the Indian Society of Critical Care Medicine (ISCCM), on various aspects of tracheostomy performed in critically ill patients was conducted between September 1, 2019 and December 31, 2019. The SPSS software was used for the statistical analysis. Cross tables were generated and the chi-square test was used for testing of association. The p value < 0.05 was considered statistically significant. RESULTS: Out of 67 ICUs that participated, 88.1% were from private sector hospitals. A total of 923 tracheostomies were performed during the study period; out of which, 666 were PDT and 257 were surgical tracheostomy (ST). Coagulopathic patients received more platelet transfusion [p = 0.037 with platelet count (PC) < 50 × 109, p = 0.021 with PC 50-100 × 109] and fresh frozen plasma transfusion in the ST group (p = 0.0001). The performance of PDT vs ST by day 7 of admission was 28.4% vs 21% (p = 0.023). The single dilator technique (60.4%) was the preferred technique for PDT followed by the Grigg's forceps and then the multiple dilator technique. Fiberoptic bronchoscope (FOB) and ultrasonography (USG) were used in 29.3% and 16.8%, respectively, for guidance during tracheostomy. Most of the PDTs were performed by a trained intensivist (74.2%), whereas ST was mostly done by an ENT surgeon (56.8%). Percutaneous dilatational tracheostomy resulted in less hemorrhagic (2.6% vs 7%, p = 0.002) and desaturation complications (2.3% vs 6.6%, p = 0.001) as compared to ST. The duration of procedure was shorter in the PDT group (average shortening by 9.2 minutes) and the ventilator-free days (VFD) were higher in the PDT group. The cost was less in PDT by approximately Rs. 13,104. CONCLUSION: Percutaneous dilatational tracheostomy, especially the single dilator technique, is preferred by clinicians in Indian ICUs. The incidence of minor complications like hemorrhagic episodes is lower with PDT. Percutaneous dilatational tracheostomy was found to be cheaper on cost per patient basis as compared to ST (with or without complications). HOW TO CITE THIS ARTICLE: Gupta S, Tomar DS, Dixit S, Zirpe K, Choudhry D, Govil D, et al. Dilatational Percutaneous vs Surgical TracheoStomy in IntEnsive Care UniT: A Practice Pattern Observational Multicenter Study (DISSECT). Indian J Crit Care Med 2020;24(7):514-526.

Clinical efficacy and pharmacokinetics of colistimethate sodium and colistin in critically ill patients in an Indian hospital with high endemic rates of multidrug-resistant Gram-negative bacterial infections: A prospective observational study.

BACKGROUND: Safe and effective use of colistin requires robust pharmacokinetic (PK) and pharmacodynamic (PD) data to guide dosing. AIM: To evaluate the pharmacokinetics of colistimethate sodium and colistin in critically ill patients and correlate with clinical efficacy and renal function. MATERIALS AND METHODS: Twenty critically ill adult patients with colistin-susceptible multidrug-resistant (MDR) infections and normal renal function treated with intravenous colistimethate sodium - at a 9 million units (270 mg CBA) loading dose followed by maintenance (MD) of 3 million units t.i.d, 24 hours later - were evaluated for clinical cure (CC) at the end of therapy. Patient characteristics and plasma colistin levels at 0, 0.5, 1, 2, 4, 8 and 12 hours after the loading dose and at 1, 2 and 8 hours after the eighth and ninth infusion of MD were evaluated. Colistimethate sodium and colistin levels were measured by high-performance liquid chromatography and tandem mass spectrometry (HPLC-MS/MS). RESULTS: Among the 20 patients who were evaluated, 60% had pneumonia. Predominant pathogens were Klebsiella pneumoniae and Acinetobacter spp. Clinical cure was 50% (10/20). Mean peak loading dose concentrations were 3 ± 1.1 mg/L (1.75-5.14) and 2.37 ± 1.2 mg/L (1.52-5.54) for 'cure' and 'failure' groups, respectively (p = 0.13), while mean steady-state (Cssavg) concentrations were 2.25 ± 1.3 mg/L and 1.78 ± 1.1 mg/L in 'cure' and 'failure' groups, respectively (p = 0.19). Nephrotoxicity was 5% on day 7 of therapy. However, bacteriological cure could not be correlated with PK/PD. CONCLUSIONS: Subtherapeutic Cssavg with clinical failure and lower efficacy without significant nephrotoxicity highlights the need for therapeutic drug monitoring to guide colistin dosing.