The single-cell epigenomic and transcriptional landscape of immunity to influenza vaccination.

Emerging evidence indicates a fundamental role for the epigenome in immunity. Here, we mapped the epigenomic and transcriptional landscape of immunity to influenza vaccination in humans at the single-cell level. Vaccination against seasonal influenza induced persistently diminished H3K27ac in monocytes and myeloid dendritic cells (mDCs), which was associated with impaired cytokine responses to Toll-like receptor stimulation. Single-cell ATAC-seq analysis revealed an epigenomically distinct subcluster of monocytes with reduced chromatin accessibility at AP-1-targeted loci after vaccination. Similar effects were observed in response to vaccination with the AS03-adjuvanted H5N1 pandemic influenza vaccine. However, this vaccine also stimulated persistently increased chromatin accessibility at interferon response factor (IRF) loci in monocytes and mDCs. This was associated with elevated expression of antiviral genes and heightened resistance to the unrelated Zika and Dengue viruses. These results demonstrate that vaccination stimulates persistent epigenomic remodeling of the innate immune system and reveal AS03's potential as an epigenetic adjuvant.

SREBP signaling is essential for effective B cell responses.

Our previous study using systems vaccinology identified an association between the sterol regulatory binding protein (SREBP) pathway and humoral immune response to vaccination in humans. To investigate the role of SREBP signaling in modulating immune responses, we generated mice with B cell- or CD11c+ antigen-presenting cell (APC)-specific deletion of SCAP, an essential regulator of SREBP signaling. Ablation of SCAP in CD11c+ APCs had no effect on immune responses. In contrast, SREBP signaling in B cells was critical for antibody responses, as well as the generation of germinal centers,memory B cells and bone marrow plasma cells. SREBP signaling was required for metabolic reprogramming in activated B cells. Upon mitogen stimulation, SCAP-deficient B cells could not proliferate and had decreased lipid rafts. Deletion of SCAP in germinal center B cells using AID-Cre decreased lipid raft content and cell cycle progression. These studies provide mechanistic insights coupling sterol metabolism with the quality and longevity of humoral immunity.

Adjuvanting a subunit COVID-19 vaccine to induce protective immunity.

The development of a portfolio of COVID-19 vaccines to vaccinate the global population remains an urgent public health imperative1. Here we demonstrate the capacity of a subunit vaccine, comprising the SARS-CoV-2 spike protein receptor-binding domain displayed on an I53-50 protein nanoparticle scaffold (hereafter designated RBD-NP), to stimulate robust and durable neutralizing-antibody responses and protection against SARS-CoV-2 in rhesus macaques. We evaluated five adjuvants including Essai O/W 1849101, a squalene-in-water emulsion; AS03, an α-tocopherol-containing oil-in-water emulsion; AS37, a Toll-like receptor 7 (TLR7) agonist adsorbed to alum; CpG1018-alum, a TLR9 agonist formulated in alum; and alum. RBD-NP immunization with AS03, CpG1018-alum, AS37 or alum induced substantial neutralizing-antibody and CD4 T cell responses, and conferred protection against SARS-CoV-2 infection in the pharynges, nares and bronchoalveolar lavage. The neutralizing-antibody response to live virus was maintained up to 180 days after vaccination with RBD-NP in AS03 (RBD-NP-AS03), and correlated with protection from infection. RBD-NP immunization cross-neutralized the B.1.1.7 SARS-CoV-2 variant efficiently but showed a reduced response against the B.1.351 variant. RBD-NP-AS03 produced a 4.5-fold reduction in neutralization of B.1.351 whereas the group immunized with RBD-NP-AS37 produced a 16-fold reduction in neutralization of B.1.351, suggesting differences in the breadth of the neutralizing-antibody response induced by these adjuvants. Furthermore, RBD-NP-AS03 was as immunogenic as a prefusion-stabilized spike immunogen (HexaPro) with AS03 adjuvant. These data highlight the efficacy of the adjuvanted RBD-NP vaccine in promoting protective immunity against SARS-CoV-2 and have led to phase I/II clinical trials of this vaccine (NCT04742738 and NCT04750343).

Modeling transcriptional regulation of the cell cycle using a novel cybernetic-inspired approach.

Quantitative understanding of cellular processes, such as cell cycle and differentiation, is impeded by various forms of complexity ranging from myriad molecular players and their multilevel regulatory interactions, cellular evolution with multiple intermediate stages, lack of elucidation of cause-effect relationships among the many system players, and the computational complexity associated with the profusion of variables and parameters. In this paper, we present a modeling framework based on the cybernetic concept that biological regulation is inspired by objectives embedding rational strategies for dimension reduction, process stage specification through the system dynamics, and innovative causal association of regulatory events with the ability to predict the evolution of the dynamical system. The elementary step of the modeling strategy involves stage-specific objective functions that are computationally determined from experiments, augmented with dynamical network computations involving endpoint objective functions, mutual information, change-point detection, and maximal clique centrality. We demonstrate the power of the method through application to the mammalian cell cycle, which involves thousands of biomolecules engaged in signaling, transcription, and regulation. Starting with a fine-grained transcriptional description obtained from RNA sequencing measurements, we develop an initial model, which is then dynamically modeled using the cybernetic-inspired method, based on the strategies described above. The cybernetic-inspired method is able to distill the most significant interactions from a multitude of possibilities. In addition to capturing the complexity of regulatory processes in a mechanistically causal and stage-specific manner, we identify the functional network modules, including novel cell cycle stages. Our model is able to predict future cell cycles consistent with experimental measurements. We posit that this innovative framework has the promise to extend to the dynamics of other biological processes, with a potential to provide novel mechanistic insights.

Modeling enzyme competition in Eicosanoid metabolism in macrophage cells using a cybernetic framework.

Cellular metabolism is a complex process involving the consumption and production of metabolites, as well as the regulation of enzyme synthesis and activity. Modeling of metabolic processes is important to understand the underlying mechanisms, with a wide range of applications in metabolic engineering and health sciences. Cybernetic modeling is a powerful technique that accounts for unknown intricate regulatory mechanisms in complex cellular processes. It models regulation as goal-oriented, where the levels and activities of enzymes are modulated by the cybernetic control variables to achieve the cybernetic objective. This study employed cybernetic model to study the enzyme competition between arachidonic acid (AA) and eicosapentaenoic acid (EPA) metabolism in murine macrophages. AA and EPA compete for the shared enzyme cyclooxygenase (COX). Upon external stimuli, AA produces pro-inflammatory 2-series prostaglandins (PGs) and EPA metabolizes to anti-inflammatory 3-series PGs, where pro- and anti- inflammatory responses are necessary for homeostasis. The cybernetic model adequately captured the experimental data for control and EPA-supplemented conditions. The model is validated by performing an F-test, conducting leave-one-out-metabolite cross-validation, and predicting an unseen experimental condition. The cybernetic variables provide insights into the competition between AA and EPA for the COX enzyme. Predictions from our model suggest that the system undergoes a switch from a predominantly pro-inflammatory state in the control to an anti-inflammatory state with EPA-supplementation. The model can also be used to analytically determine the AA and EPA concentrations required for the switch to occur. The quantitative outcomes enhance understanding of pro- and anti-inflammatory metabolism in RAW 264.7 macrophages.

Systems Analysis of Immunity to Influenza Vaccination across Multiple Years and in Diverse Populations Reveals Shared Molecular Signatures.

Systems approaches have been used to describe molecular signatures driving immunity to influenza vaccination in humans. Whether such signatures are similar across multiple seasons and in diverse populations is unknown. We applied systems approaches to study immune responses in young, elderly, and diabetic subjects vaccinated with the seasonal influenza vaccine across five consecutive seasons. Signatures of innate immunity and plasmablasts correlated with and predicted influenza antibody titers at 1 month after vaccination with >80% accuracy across multiple seasons but were not associated with the longevity of the response. Baseline signatures of lymphocyte and monocyte inflammation were positively and negatively correlated, respectively, with antibody responses at 1 month. Finally, integrative analysis of microRNAs and transcriptomic profiling revealed potential regulators of vaccine immunity. These results identify shared vaccine-induced signatures across multiple seasons and in diverse populations and might help guide the development of next-generation vaccines that provide persistent immunity against influenza.

Longitudinal shear stress response in human endothelial cells to atheroprone and atheroprotective conditions.

The two main blood flow patterns, namely, pulsatile shear (PS) prevalent in straight segments of arteries and oscillatory shear (OS) observed at branch points, are associated with atheroprotective (healthy) and atheroprone (unhealthy) vascular phenotypes, respectively. The effects of blood flow-induced shear stress on endothelial cells (ECs) and vascular health have generally been studied using human umbilical vein endothelial cells (HUVECs). While there are a few studies comparing the differential roles of PS and OS across different types of ECs at a single time point, there is a paucity of studies comparing the temporal responses between different EC types. In the current study, we measured OS and PS transcriptomic responses in human aortic endothelial cells (HAECs) over 24 h and compared these temporal responses of HAECs with our previous findings on HUVECs. The measurements were made at 1, 4, and 24 h in order to capture the responses at early, mid, and late time points after shearing. The results indicate that the responses of HAECs and HUVECs are qualitatively similar for endothelial function-relevant genes and several important pathways with a few exceptions, thus demonstrating that HUVECs can be used as a model to investigate the effects of shear on arterial ECs, with consideration of the differences. Our findings show that HAECs exhibit an earlier response or faster kinetics as compared to HUVECs. The comparative analysis of HAECs and HUVECs presented here offers insights into the mechanisms of common and disparate shear stress responses across these two major endothelial cell types.

Impact of application of queuing theory on operational efficiency of patient registration.

Background: Hospital administrators are often challenged with overcrowding at hospitals. The study hospital receives referred patients; however, they have to wait in long queues even for getting registered. This was a cause of concern for hospital administrators. The study was undertaken to find an amicable solution to the queues at registration using Queuing Theory. Method: This observational and interventional study was carried out in a tertiary care ophthalmic hospital. In the first phase, data of service time and arrival rate was collected. The queuing model was built using the coefficient of variation (CoV) of the observed times. Server utilization for new patient registration was found to be 1.21 and was 0.63 for revisit patients. Scenario-based simulation carried out using free software for optimal utilization of both types of servers. Recommendations made to combine the registration process and to increase one server were implemented.In the second phase, after one year, patient registration data were collected and compared for the number of patients registered using SPSS 17. Results: Number of patients registered within the registration timings increased whereas the number of patients registered after the registration timings decreased significantly at 95% CI with a p-value of less than 0.001. Queues finished early and more number of patients were registered in the same time. Conclusion: Using queuing theory, the bottleneck of the systems can be identified. Scenario and software-based simulations provide solutions to the problem of queues. The study is an application of Queuing Theory with a focus on efficient resource utilization. It can be replicated in an organization with limited resources facing the challenge of queues.

Allocation scheduling leads to optimum utilization of operation theater time.

Background: Cancellation of surgeries is a regular phenomenon in any hospital, and reasons may vary from clinical to managerial ones. The aim of the study is to suggest scheduling to address the problem of time over run related cancellations. This is an observational and descriptive study conducted in a tertiary care hospital with ophthalmology facilities. The sample size is calculated with 95% confidence interval using Epi Info 6 from the total surgeries performed in the last 5 years (n = 380). Simple random sampling technique was used. Methods: Surgical time for all types of ophthalmic surgeries (n = 582) was observed. Allocation of listed cases to the available operating rooms (ORs) was carried out using the observed time using LEKIN software. Results: The time over-run of 2 h and 6 h was noted for two units, whereas idle OR time was observed in other units. An average idle time of 19% was noted on each day. Reallocation of the cases to the ORs was carried out taking all the planned cases (of both the operating units of the day) as the number of jobs and all the available ORs as parallel machines using LEKIN software. All the planned cases could be accommodated; still, an average of 17% of the total available operation theater (OT) time was found idle on each day. Conclusions: Planning of cases using procedure time and scheduling on a daily basis using allocation models with simple algorithms can provide optimal utilization of OTs and can address the time over-run and related cancellations.

A study on economic evaluation of an outreach health-care facility in Jhajjar District of Haryana: Service delivery model for increasing access to health care.

BACKGROUND: An outreach (OR) health-care facility providing broad specialty outpatient services was started by All India Institute of Medical Sciences (AIIMS), New Delhi, in rural area of district Jhajjar, Haryana. OBJECTIVES: This study aimed to ascertain the resource requirement for establishing an OR health-care facility and patient satisfaction with regard to the services being provided. METHODS: A cross-sectional study was conducted in 2017 at an OR Outpatient Department (OPD) of AIIMS, New Delhi, at Jhajjar. Service delivery model adopted for health-care delivery was hub and spoke. Traditional method of costing was used for economic evaluation. Feedback pro forma of 400 patients who attended OPD services was analyzed to measure health service accessibility. RESULTS: Capital expenditure to set up the facility was calculated to be approximately INR 17,57,49,074/- ($ 2,703,832) and operational cost per year was approximately INR 8,73,86,370/- ($ 1,344,406). Approximate per-patient cost for single OPD consultation was calculated to be INR 874 ($13.45) which included medicines and investigations. High scores for all domains of accessibility of health care were observed. CONCLUSION: The study provides a preliminary evidence that OR health-care facilities can be instrumental in increasing access to health-care delivery with lesser capital outlays, however, large-scale multicentric studies are needed to arrive at any conclusion. The services have been very well accepted by the local community members being quality medical care with highly subsidized health-care services.

Systems biology analysis of longitudinal functional response of endothelial cells to shear stress.

Blood flow and vascular shear stress patterns play a significant role in inducing and modulating physiological responses of endothelial cells (ECs). Pulsatile shear (PS) is associated with an atheroprotective endothelial phenotype, while oscillatory shear (OS) is associated with an atheroprone endothelial phenotype. Although mechanisms of endothelial shear response have been extensively studied, most studies focus on characterization of single molecular pathways, mainly at fixed time points after stress application. Here, we carried out a longitudinal time-series study to measure the transcriptome after the application of PS and OS. We performed systems analyses of transcriptional data of cultured human vascular ECs to elucidate the dynamics of endothelial responses in several functional pathways such as cell cycle, oxidative stress, and inflammation. By combining the temporal data on differentially expressed transcription factors and their targets with existing knowledge on relevant functional pathways, we infer the causal relationships between disparate endothelial functions through common transcriptional regulation mechanisms. Our study presents a comprehensive temporally longitudinal experimental study and mechanistic model of shear stress response. By comparing the relative endothelial expressions of genes between OS and PS, we provide insights and an integrated perspective into EC function in response to differential shear. This study has significant implications for the pathogenesis of vascular diseases.

Medical leadership competencies: A comparative study of physicians in public and private sector hospitals in India.

PURPOSE: Indian health care system comprising of public and private sectors needs enhancement of medical leadership capacity to face the growing challenges. Hence, this study was designed to evaluate medical leadership competencies of public and private sector doctors. FINDINGS: A survey questionnaire was developed to assess "self-assessed proficiency levels" as well as "perceived importance of competency levels," to which 532 doctors responded-290 (54.5%) from private sector and 242 (45.5%) from public sector hospitals. Statistically significant "leadership competency gap" was observed for all 30 leadership competencies in both sectors, more so in public sector. The 10 most deficient competencies were mainly in the NHS-MLCF domains of "working with others," "managing services," and "setting direction." The most low-rated competency among public sector doctors was "knowledge of HR, procurement, financial, and contract management" while "ability to influence key decision makers who determine future government policies" was most deficient among private sector physicians. Further, deficiencies related to "time and stress management" and "conducting need analysis, identifying and prioritizing requirements" were confined to public and private sector doctors, respectively. CONCLUSIONS: This study, first from India, highlights a critical need for medical leadership development programs in both sectors for enhancement of medical leadership capacity in the country.

Outcome of Care Provided in Neonatal Surgery Intensive Care Unit of a Public Sector Tertiary Care Teaching Hospital of India.

AIMS: There is limited literature on the outcome of care in intensive care units (ICUs), especially when it comes to neonatal surgical units. Hence, this study was aimed to observe the outcome of care provided in the neonatal surgery ICU (NSICU) at an apex tertiary care teaching institute of North India. METHODS: A descriptive, observational study was carried out through retrospective medical record analysis of all the patients admitted in NSICU from January to June 2011. RESULTS: In NSICU, from January to June 2011, 85 patients were admitted. More than two-third (69.9%) patients were admitted through the emergency department. Of the total admitted patients, 69.9% were male. Mean and median age of the admitted patients were 6.31 and 2 days (range 0-153 days), respectively. The most common diagnosis was esophageal atresia with tracheoesophageal fistula (36.1%). Within a day of admission at NSICU, 88% patients underwent surgical intervention. Of the total admitted patients, 56.6% required mechanical ventilation with 3.57 days (range 0-31 days) of mean duration of mechanical ventilation. Reintubation rate (within 48 h of extubation) was observed to be 15.7%, and 27.7% (23) of the patients required vasopressor support during their NSICU stay. Patients who developed postoperative complications were 34.25%, with the most common being wound infection/discharge/dehiscence. Two patients were readmitted within 72 h of their discharge/transfer out from the NSICU. CONCLUSION: NSICU survival rate was 85.5% and net death rate was observed to be 14.5%. Sepsis was the major reason for mortality in NSICU.

Low reporting of violence against health-care workers in India in spite of high prevalence.

BACKGROUND: Violence against health-care workers has become a great issue in health-care organizations. This study was conceptualized with the aim to know the prevalence of violence and to identify gap between rate of reporting of an incident of violence at a tertiary care hospital in India. METHODS: The study was descriptive and cross-sectional; a validated questionnaire was used as a tool. Reported incidents of violence against workers were collected. P value <0.05 was considered statistically significant in the analysis. A Z test for proportion at 95% confidence interval was applied to analyze the level of difference between prevalence, rate of reporting, and their level of awareness. RESULTS: Of 394 respondents, 136(34.5%) workers had experienced workplace violence in the last 12 months. It was found that total 32 incidents of workplace violence were reported to the concerned authority. The reporting rate of violence is significantly low (23.5%), in spite of high prevalence (34.5%). Level of awareness regarding the reporting mechanism and regulations for the safeguard of health-care workers against workplace violence is only 24.6 %. CONCLUSION: This study concluded that the prevalence of violence among health-care workers is quite high, but the reporting rate is significantly low. The low rate of reporting is because of lack of awareness about the reporting mechanism of workplace violence. It is recommended that sensitizing workshops should be conducted to increase the level of awareness, which will result in reduction in the prevalence of violence and building a safe and secured workplace for health-care providers.

Krüppel-Like Factor 4 Regulation of Cholesterol-25-Hydroxylase and Liver X Receptor Mitigates Atherosclerosis Susceptibility.

BACKGROUND: Atherosclerosis is a multifaceted inflammatory disease involving cells in the vascular wall (eg, endothelial cells [ECs]), as well as circulating and resident immunogenic cells (eg, monocytes/macrophages). Acting as a ligand for liver X receptor (LXR), but an inhibitor of SREBP2 (sterol regulatory element-binding protein 2), 25-hydroxycholesterol, and its catalyzing enzyme cholesterol-25-hydroxylase (Ch25h) are important in regulating cellular inflammatory status and cholesterol biosynthesis in both ECs and monocytes/macrophages. METHODS: Bioinformatic analyses were used to investigate RNA-sequencing data to identify cholesterol oxidation and efflux genes regulated by Krüppel-like factor 4 (KLF4). In vitro experiments involving cultured ECs and macrophages and in vivo methods involving mice with Ch25h ablation were then used to explore the atheroprotective role of KLF4-Ch25h/LXR. RESULTS: Vasoprotective stimuli increased the expression of Ch25h and LXR via KLF4. The KLF4-Ch25h/LXR homeostatic axis functions through suppressing inflammation, evidenced by the reduction of inflammasome activity in ECs and the promotion of M1 to M2 phenotypic transition in macrophages. The increased atherosclerosis in apolipoprotein E-/-/Ch25h-/- mice further demonstrates the beneficial role of the KLF4-Ch25h/LXR axis in vascular function and disease. CONCLUSIONS: KLF4 transactivates Ch25h and LXR, thereby promoting the synergistic effects between ECs and macrophages to protect against atherosclerosis susceptibility.

Systems Analysis of the Complement-Induced Priming Phase of Liver Regeneration.

Liver regeneration is a well-orchestrated process in the liver that allows mature hepatocytes to reenter the cell cycle to proliferate and replace lost or damaged cells. This process is often impaired in fatty or diseased livers, leading to cirrhosis and other deleterious phenotypes. Prior research has established the role of the complement system and its effector proteins in the progression of liver regeneration; however, a detailed mechanistic understanding of the involvement of complement in regeneration is yet to be established. In this study, we have examined the role of the complement system during the priming phase of liver regeneration through a systems level analysis using a combination of transcriptomic and metabolomic measurements. More specifically, we have performed partial hepatectomy on mice with genetic deficiency in C3, the major component of the complement cascade, and collected their livers at various time points. Based on our analysis, we show that the C3 cascade activates c-fos and promotes the TNF-α signaling pathway, which then activates acute-phase genes such as serum amyloid proteins and orosomucoids. The complement activation also regulates the efflux and the metabolism of cholesterol, an important metabolite for cell cycle and proliferation. Based on our systems level analysis, we provide an integrated model for the complement-induced priming phase of liver regeneration.

Serum microRNAs explain discordance of non-alcoholic fatty liver disease in monozygotic and dizygotic twins: a prospective study.

OBJECTIVE: In the setting where two individuals are genetically similar, epigenetic mechanisms could account for discordance in the presence or absence of non-alcoholic fatty liver disease (NAFLD). This study investigated if serum microRNAs (miRs) could explain discordance in NAFLD. DESIGN: This is a cross-sectional analysis of a prospective cohort study of 40 (n=80) twin-pairs residing in Southern California. All participants underwent a standardised research visit, liver MRI using proton-density fat fraction to quantify fat content and miR profiling of their serum. RESULTS: Among the 40 twin-pairs, there were 6 concordant for NAFLD, 28 were concordant for non-NAFLD and 6 were discordant for NAFLD. The prevalence of NAFLD was 22.5% (18/80). Within the six discordant twins, a panel of 10 miRs differentiated the twin with NAFLD from the one without. Two of these miRs, miR-331-3p and miR-30c, were also among the 21 miRs that were different between NAFLD and non-NAFLD groups (for miR-331-3p: 7.644±0.091 vs 8.057±0.071, respectively, p=0.004; for miR-30c: 10.013±0.126 vs 10.418±0.086, respectively, p=0.008). Both miRs were highly heritable (35.9% and 10.7%, respectively) and highly correlated with each other (R=0.90, p=2.2×10(-16)) suggesting involvement in a common mechanistic pathway. An interactome analysis of these two miRs showed seven common target genes. CONCLUSIONS: Using a novel human twin-study design, we demonstrate that discordancy in liver fat content between the twins can be explained by miRs, and that they are heritable.

Statistical insights into major human muscular diseases.

Muscular diseases lead to muscle fiber degeneration, impairment of mobility, and in some cases premature death. Many of these muscular diseases are largely idiopathic. The goal of this study was to identify biomarkers based on their functional role and possible mechanisms of pathogenesis, specific to individual muscular disease. We analyzed the muscle transcriptome from five major muscular diseases: acute quadriplegic myopathy (AQM), amyotrophic lateral sclerosis (ALS), mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), dermatomyositis (DM) and polymyositis (PM) using pairwise statistical comparison to identify uniquely regulated genes in each muscular disease. The genome-wide information encoded in the transcriptome provided biomarkers and functional insights into dysregulation in each muscular disease. The analysis showed that the dysregulation of genes in forward membrane pathway, responsible for transmitting action potential from neural excitation, is unique to AQM, while the dysregulation of myofibril genes, determinant of the mechanical properties of muscle, is unique to ALS, dysregulation of ER protein processing, responsible for correct protein folding, is unique to DM, and upregulation of immune response genes is unique to PM. We have identified biomarkers specific to each muscular disease which can be used for diagnostic purposes.

Healthcare associated infections in Paediatric Intensive Care Unit of a tertiary care hospital in India: Hospital stay & extra costs.

BACKGROUND & OBJECTIVES: Healthcare associated infections (HAIs) increase the length of stay in the hospital and consequently costs as reported from studies done in developed countries. The current study was undertaken to evaluate the impact of HAIs on length of stay and costs of health care in children admitted to Paediatric Intensive Care Unit (PICU) of a tertiary care hospital in north India. METHODS: This prospective study was done in the seven bedded PICU of a large multi-specialty tertiary care hospital in New Delhi, India. A total of 20 children with HAI (cases) and 35 children without HAI (controls), admitted to the PICU during the study period (January 2012 to June 2012), were matched for gender, age, and average severity of illness score. Each patient's length of stay was obtained prospectively. Costs of healthcare were estimated according to traditional and time driven activity based costing methods approach. RESULTS: The median extra length of PICU stay for children with HAI (cases), compared with children with no HAI (controls), was seven days (IQR 3-16). The mean total costs of patients with and without HAI were ' 2,04,787 (US$ 3,413) and ' 56,587 (US$ 943), respectively and the mean difference in the total cost between cases and controls was ' 1,48,200 (95% CI 55,716 to 2,40,685, p<0.01). INTERPRETATION & CONCLUSIONS: This study highlights the effect of HAI on costs for PICU patients, especially costs due to prolongation of hospital stay, and suggests the need to develop effective strategies for prevention of HAI to reduce costs of health care.

A comparative cost analysis of polytrauma and neurosurgery Intensive Care Units at an apex trauma care facility in India.

CONTEXT: Although Intensive Care Units (ICUs) only account for 10% of the hospital beds, they consume nearly 22% of the hospital resources. Few definitive costing studies have been conducted in Indian settings that would help determine appropriate resource allocation. AIM: The aim of this study was to evaluate and compare the cost of intensive care delivery between multispecialty and neurosurgery ICUs at an apex trauma care facility in India. MATERIALS AND METHODS: The study was conducted in a polytrauma and neurosurgery ICU at a 203-bedded Level IV trauma care facility in New Delhi, India, from May 1, 2012 to June 30, 2012. The study was cross-sectional, retrospective, and record-based. Traditional costing was used to arrive at the cost for both direct and indirect cost estimates. The cost centers included in the study were building cost, equipment cost, human resources, materials and supplies, clinical and nonclinical support services, engineering maintenance cost, and biomedical waste management. STATISTICAL ANALYSIS: Statistical analysis was performed by Fisher's two tailed t-test. RESULTS: Total cost/bed/day for the multispecialty ICU was Rs. 14,976.9/- and for the neurosurgery ICU, it was Rs. 14,306.7/-, workforce constituting nearly half of the expenditure in both ICUs. The cost center wise and overall difference in the cost among the ICUs were statistically significant. CONCLUSIONS: Quantification of expenditure in running an ICU in a trauma center would assist health-care decision makers in better allocation of resources. Although multispecialty ICUs are more cost-effective, other factors will also play a role in defining the kind of ICU that needs to be designed.