Factors associated with hepatitis C testing, treatment, and current hepatitis C infection among men and women who inject drugs: The ETHOS engage study.

BACKGROUND: Evaluating gender-specific trends in hepatitis C virus (HCV) treatment uptake among men and women who inject drugs is crucial for ensuring equitable progress towards HCV elimination. This study aimed to quantify differences in testing, treatment, and current HCV infection between men and women who inject drugs. METHOD: ETHOS Engage is an observational cohort study of people who inject drugs attending drug treatment clinics and needle and syringe programs in Australia recruited from May 2018-September 2019 (wave 1) and November 2019-April 2021 (wave 2). Participants completed a questionnaire including self-reported HCV testing and treatment history and underwent point-of-care HCV RNA testing (Xpert® HCV Viral Load Fingerstick). Logistic regression was used to compare the factors associated with self-reported HCV testing and treatment and current HCV infection for men and women who inject drugs. RESULTS: Among 2,395 participants enrolled in ETHOS Engage, 66% (n = 1,591) were men, 33% (n = 786) women, and <1% (n = 18) did not identify as a man or woman. HCV testing history and current infection were similar among men and women. Among men or women ever eligible for HCV treatment (ever chronic HCV) (n = 1,242), women were less likely to report a history of HCV treatment compared to men (227/352, 64% vs. 631/890, 71%; p = 0.03). Among women, those aged <45 were less likely to report HCV testing (aOR: 0.57, 95%CI: 0.36, 0.90), treatment (aOR: 0.47, 95%CI: 0.29, 0.77), and more likely to have HCV infection (aOR: 1.48, 95%CI: 1.00, 2.20) CONCLUSION: Among women, those of childbearing age (<45) were less likely to report testing and treatment and were more likely to have current HCV infection. Women <45 years old should be a priority population for HCV care. Services that interface with these women should be optimised to enhance HCV testing and treatment.

Needle and syringe sharing among people who have recently injected drugs in Australia: The ETHOS Engage Study.

INTRODUCTION: Understanding needle/syringe sharing is crucial for reducing hepatitis C virus (HCV) infection and reinfection. This study aimed to assess the prevalence and factors associated with needle/syringe sharing among people who inject drugs in Australia, including those previously receiving HCV treatment. METHODS: The ETHOS Engage study was an observational cohort study which collected self-reported survey data on demographic and drug use information from people who inject drugs attending drug treatment clinics and needle and syringe programs over two waves between May 2018 and June 2021. Logistic regression was used to identify factors associated with needle/syringe sharing. RESULTS: Overall, 1555/2395 people enrolled in ETHOS Engage (65%) injected drugs in the past month. Among these, 432 (28%) reported needle/syringe sharing in the past month and 276 (18%) reported receptive sharing. Factors associated with receptive sharing included younger age (adjusted odds ratio [aOR] 1.72; 95% confidence interval [CI] 1.28-2.30), recent incarceration (aOR 2.04; 95% CI 1.40-2.94), more frequent injecting (≥daily vs. less than weekly; aOR 2.59; 95% CI 1.75-3.84) and unstable housing (aOR 1.78; 95% CI 1.26-2.52). Among 560 participants with prior HCV treatment, 87 (16%) reported receptive sharing with younger age (aOR 2.42; 95% CI 1.45-4.05) and daily or greater injection frequency (aOR 2.51; 95% CI 1.31-4.83) associated with receptive sharing. DISCUSSION AND CONCLUSIONS: Needle/syringe sharing was common among this population accessing harm reduction services. This study identifies high-risk populations with needle/syringe sharing. Research is needed to optimise HCV treatment to ensure people with ongoing risk behaviours receive adequate harm reduction following treatment to prevent reinfection.

Health-Related Quality of Life of People Who Inject Drugs: The Enhancing Treatment of Hepatitis C in Opioid Substitution Settings Engage Study.

OBJECTIVES: There is limited research on health-related quality of life (HRQoL) among people who inject drugs (PWID). We evaluated the HRQoL and associated factors among a cohort of PWID in Australia. METHODS: Participants were enrolled in an observational cohort study (the Enhancing Treatment of Hepatitis C in Opioid Substitution Settings Engage Study) from May 2018 to September 2019 (wave 1) and November 2019 to June 2021 (wave 2). Participants completed the EQ-5D-5L survey at enrolment. Two-part models were used to assess the association of clinical and socioeconomic characteristics with EQ-5D-5L scores. RESULTS: Among 2395 participants (median age, 43 years; 66% male), 65% reported injecting drug use in the past month, 20% had current hepatitis C virus (HCV) infection, and 68% had no/mild liver fibrosis (F0/F1). Overall, the mean EQ-5D-5L and EQ-visual analog scale scores were 0.78 and 57, respectively. In adjusted analysis, factors associated with significantly lower EQ-5D-5L scores include older ages, female (marginal effect = -0.03, P = .014), being homeless (marginal effect = -0.04, P = .040), and polysubstance use (marginal effect = -0.05, P < .001). Factors associated with significantly higher EQ-5D-5L scores were being Aboriginal/Torres Strait Islander (marginal effect = 0.03, P = .021) and recent injecting drug use in the past 12 months. Current HCV infection and liver fibrosis stage were not associated with reduced HRQoL among the study participants. CONCLUSIONS: PWID experienced a lower HRQoL compared with the general population. Further research is needed to understand HRQoL in this population to facilitate the development of multifaceted care models for PWID beyond HCV cure and inform health economic analyses for identifying optimal health strategies for PWID.

Evaluating the prevalence of current hepatitis C infection and treatment among Aboriginal and Torres Strait Islander peoples who inject drugs in Australia: The ETHOS engage study.

INTRODUCTION: Evaluating progress towards hepatitis C virus (HCV) elimination among Aboriginal and Torres Strait Islander peoples is critical given the disproportionate burden of infection. We examined factors associated with current HCV infection and self-reported treatment among Aboriginal and Torres Strait Islander (hereafter referred to as Aboriginal peoples) and non-Aboriginal peoples who inject drugs (PWID) in Australia. METHODS: ETHOS Engage is an observational cohort study of PWID attending drug treatment and needle and syringe programs in Australia. Participants underwent point-of-care HCV RNA testing (Xpert HCV RNA Viral Load Fingerstick) and completed a questionnaire including self-reported history of HCV treatment. RESULTS: Between May 2018 and June 2021, 2395 participants were enrolled and 555 (23%) identified as Aboriginal (median age 42 years, 58% were men, 63% injected drugs in last month, 76% ever incarcerated). HCV RNA prevalence was 23% among Aboriginal PWID (24% in 2018-2019 and 21% in 2019-2021; p = 0.44), and 21% among non-Aboriginal PWID (24% in 2018-2019 and 16% in 2019-2021; p < 0.001). Self-reported HCV treatment was 65% among Aboriginal PWID (63% in 2018-2019 and 69% in 2019-2021; p = 0.30), and 70% among non-Aboriginal PWID (67% in 2018-2019 and 75% in 2019-2021; p < 0.001). Among Aboriginal PWID, current HCV infection was associated with recently injecting drugs and receiving opioid agonist treatment, and self-reported HCV treatment was negatively associated with younger age, homelessness and recently injecting drugs. DISCUSSION AND CONCLUSIONS: Equitable access to HCV care and prevention is needed to ensure Australia meets its elimination targets among Aboriginal PWID.

Awareness of hepatitis C virus infection status among people who inject drugs in a setting of universal direct-acting antiviral therapy: The ETHOS Engage study.

BACKGROUND: Awareness of hepatitis C virus (HCV) infection status among people who inject drugs (PWID) can empower people with diagnosis, enable treatment uptake, and facilitate elimination. We aimed to evaluate awareness of HCV infection status among a large national cohort of PWID in an era of unrestricted HCV treatment. METHODS: ETHOS Engage is an observational cohort study of PWID attending drug treatment clinics and needle and syringe programs in Australia. Participants completed a questionnaire containing self-reported HCV data (including infection status: never tested, tested/unknown, no current HCV infection [HCV RNA not detectable], current HCV infection [HCV RNA detectable]) and underwent point-of-care HCV RNA testing (Xpert® HCV Viral Load Fingerstick). Awareness was defined as concordant self-reported HCV status and test result. Awareness was assessed among all participants, those with current HCV infection, and participants who reported a lifetime history of HCV treatment. Logistic regression was used to assess factors associated with awareness in these three populations. RESULTS: Among 2,305 PWID, 65% (n=1,506) were aware of their HCV infection status (self-reported HCV status matched HCV point-of-care result). Awareness of infection status was higher among those who were not currently infected (70%, n=1,281/1,818) compared to those with current HCV infection (46%, n=225/487). After adjusting, those with current HCV infection were less likely to be aware of infection status (aOR: 0.40, 95%CI: 0.30, 0.45). Among those who reported a lifetime history of HCV treatment, 71% (n=592/829) were aware of their HCV infection status. CONCLUSION: Among a large cohort of PWID in Australia, awareness of HCV infection status is sub-optimal, with particularly concerning levels among those with active infection. Increased and simplified testing, post-test counselling, and post-treatment monitoring is warranted.

A Testing Campaign Intervention Consisting of Peer-Facilitated Engagement, Point-of-Care HCV RNA Testing, and Linkage to Nursing Support to Enhance Hepatitis C Treatment Uptake among People Who Inject Drugs: The ETHOS Engage Study.

This study evaluated HCV treatment initiation among people who inject drugs (PWID) following an intervention of campaign days involving peer connection, point-of-care HCV RNA testing, and linkage to nursing support. ETHOS Engage is an observational cohort study of PWID attending 25 drug treatment clinics and needle and syringe programs in Australia (May 2018-September 2019). Point-of-care results were provided to the nurse, facilitating confirmatory testing and treatment. The study aimed to evaluate treatment uptake and factors associated with treatment at 24 months post-enrolment. There were 317 people with current HCV infection and eligible for treatment (median age 43, 65% male, 15% homeless, 69% receiving opioid agonist treatment, 70% injected in last month). Overall, 15% (47/317), 27% (85/317), 38% (120/317), and 49% (155/317) of people with current HCV infection had initiated treatment at 3-, 6-, 12-, and 24-months following testing, respectively. Homelessness (adjusted hazard ratio (aHR): 0.40; 95% confidence interval: 0.23, 0.71) and incarceration in the past 12 months (vs. never, aHR:0.46; 0.28, 0.76) were associated with decreased treatment initiation in the 24 months post-enrolment. This testing campaign intervention facilitated HCV treatment uptake among PWID. Further interventions are needed to achieve HCV elimination among people experiencing homelessness or incarceration.

Prevalence and factors associated with hospitalisation for bacterial skin infections among people who inject drugs: The ETHOS Engage Study.

BACKGROUND: Injecting-related skin and soft tissue infections (SSTIs) are a preventable cause of inpatient hospitalisation among people who inject drugs (PWID). This study aimed to determine the prevalence of hospitalisation for SSTIs among PWID, and identify similarities and differences in factors associated with hospitalisation for SSTIs versus non-bacterial harms related to injecting drug use. METHODS: We performed cross-sectional analyses of baseline data from an observational cohort study of PWID attending drug treatment clinics and needle and syringe programs in Australia. Logistic regression models were used to identify factors associated with self-reported hospitalisation for (1) SSTIs (abscess and/or cellulitis), and (2) non-bacterial harms related to injecting drug use (e.g., non-fatal overdose; hereafter referred to as non-bacterial harms), both together and separately. RESULTS: 1851 participants who injected drugs in the previous six months were enrolled (67% male; 85% injected in the past month; 42% receiving opioid agonist treatment [OAT]). In the previous year, 40% (n = 737) had been hospitalised for drug-related causes: 20% (n = 377) and 29% (n = 528) of participants were admitted to hospital for an SSTI and non-bacterial harm, respectively. Participants who were female (adjusted odds ratio [aOR]: 1.53, 95% CI: 1.19-1.97) or homeless (aOR: 1.59, 95% CI: 1.16-2.19) were more likely to be hospitalised for an SSTI, but not a non-bacterial harm. Both types of hospitalisation were more likely among people recently released from prison. CONCLUSIONS: Hospitalisation for SSTIs is common among PWID. Community-based interventions to prevent SSTIs and subsequent hospitalisation among PWID will require targeting of at-risk groups, including women, people experiencing homelessness, and incarcerated people upon prison release.

Declining prevalence of current HCV infection and increased treatment uptake among people who inject drugs: The ETHOS Engage study.

BACKGROUND: Evaluating trends in HCV treatment and prevalence is crucial for monitoring elimination. We evaluated the change in current infection and treatment among people who inject drugs (PWID) between 2018-2019 and 2019-2021. METHODS: ETHOS Engage is an observational cohort study of PWID attending drug treatment clinics and needle and syringe programs in Australia. Participant enrolment occurred over two periods, Wave 1 (May 2018-September 2019, 25 sites) and Wave 2 (November 2019-June 2021, 21 sites), with baseline questionnaire completion and point-of-care HCV RNA testing (Xpert® HCV Viral Load Fingerstick). Logistic regression was used to identify factors associated with current HCV infection and historic HCV treatment. RESULTS: 2,395 individuals were enrolled across the two recruitment waves (66% male, median age 43, 72% current opioid agonist therapy, and 65% injecting in the previous month). HCV prevalence decreased from 24% to 17% between 2018-2019 and 2019-2021, respectively (p=0.003). HCV treatment increased from 66% to 74% between 2018-2019 and 2019-2021, respectively (p<0.001). After adjusting, there was a reduction in current HCV infection in 2019-2021 (adjusted odds ratio [aOR] 0.62; 95% CI, 0.50, 0.77) compared to 2018-2019. Other factors associated with current infection included homelessness (aOR, 1.70; 1.26, 2.30), incarceration (vs. never; historic: aOR 1.69; 95%CI 1.31, 2.19; recent: aOR 1.85; 95%CI, 1.35, 2.54), and recently injecting drugs (vs. >12 months ago; previous month

Willingness of people who inject drugs to participate in a randomised controlled trial involving financial incentives to initiate hepatitis C treatment.

BACKGROUND: Evidence regarding the acceptability of contingency management is limited. We investigated the willingness of people who inject drugs to participate in a randomised controlled trial (RCT) involving financial incentives to initiate HCV treatment. METHODS: ETHOS Engage is an observational cohort study of people with a history of injecting drug use who either injected in the past six months or receive opioid agonist therapy (OAT) in Australia. We assessed willingness to participate in a RCT with financial incentives and factors associated with preference for entire incentive ($60) at first clinic visit versus delayed incentive with logistic regression. RESULTS: 93% (593/635) of eligible participants agreed to participate in an RCT with financial incentives of which 24% were Aboriginal or Torres Strait Islander, 84% had completed secondary school, and 59% injected drugs in the prior month. Willingness to participate in an RCT increased by amount offered: unspecified (72%), $20 (75%), $60 (80%), and $100 (85%). The preferred incentive distribution method over three clinical visits was entire incentive at first clinical visit (32%). Among those with a preferred distribution method (n = 369), factors associated with entire incentive at first clinic visit were being Aboriginal or Torres Strait Islander (aOR 1.75; 95% CI 1.05-2.94), completion of secondary school (aOR 0.46; 95% CI 0.26-0.83) and mainly injected heroin in month prior (aOR 1.82; 95% CI 1.03-3.20). CONCLUSION: Most participants were willing to participate in an RCT involving financial incentives to initiate treatment but differed regarding distribution. Study findings inform implementation of incentives in clinical practice.

Progress Towards Elimination of Hepatitis C Infection Among People Who Inject Drugs in Australia: The ETHOS Engage Study.

BACKGROUND: Evaluating progress towards hepatitis C virus (HCV) elimination is critical. This study estimated prevalence of current HCV infection and HCV treatment uptake among people who inject drugs (PWID) in Australia. METHODS: The Enhancing Treatment of Hepatitis C in Opioid Substitution Settings Engage is an observational study of PWID attending drug treatment clinics and needle and syringe programs (NSPs). Participants completed a questionnaire including self-reported treatment history and underwent point-of-care HCV RNA testing (Xpert HCV Viral Load Fingerstick; Cepheid). RESULTS: Between May 2018 and September 2019, 1443 participants were enrolled (64% injected drugs in the last month, 74% receiving opioid agonist therapy [OAT]). HCV infection status was uninfected (28%), spontaneous clearance (16%), treatment-induced clearance (32%), and current infection (24%). Current HCV was more likely among people who were homeless (adjusted odds ratio, 1.47; 95% confidence interval, 1.00-2.16), incarcerated in the previous year (2.04; 1.38-3.02), and those injecting drugs daily or more (2.26; 1.43-2.42). Among those with previous chronic or current HCV, 66% (n = 520/788) reported HCV treatment. In adjusted analysis, HCV treatment was lower among females (.68; .48-.95), participants who were homeless (.59; .38-.96), and those injecting daily or more (.51; .31-.89). People aged ≥45 years (1.46; 1.06-2.01) and people receiving OAT (2.62; 1.52-4.51) were more likely to report HCV treatment. CONCLUSIONS: Unrestricted direct-acting antiviral therapy access in Australia has yielded high treatment uptake among PWID attending drug treatment and NSPs, with a marked decline in HCV prevalence. To achieve elimination, PWID with greater marginalization may require additional support and tailored strategies to enhance treatment.

Time to Detection of Hepatitis C Virus Infection With the Xpert HCV Viral Load Fingerstick Point-of-Care Assay: Facilitating a More Rapid Time to Diagnosis.

BACKGROUND: Xpert HCV Viral Load Fingerstick assay (Xpert HCV VL FS) is a point-of-care test quantifying HCV RNA in <1 hour, enabling same-visit diagnosis and treatment. METHODS: This study evaluated time to HCV RNA detection using the Xpert HCV VL FS assay. Fingerstick whole-blood samples were collected from participants in an observational cohort in Australia. RESULTS: In May 2018-2019, 1468 participants were enrolled, 1426 had Xpert HCV VL FS testing performed, and 1386 had a valid result. HCV RNA was detected in 23% (325/1386). Among people with undetectable HCV RNA (n = 1061), median time to result was 57 minutes. Among people with detectable HCV RNA (n = 325), median time to HCV RNA detection was 32 minutes and 80% (261/325) had a detectable HCV RNA result in ≤40 minutes. Median time to HCV RNA detection was dependent on HCV RNA level. CONCLUSIONS: A quicker HCV diagnosis could be achieved by monitoring the time when HCV RNA is first detected with the Xpert HCV VL FS test, rather than HCV RNA quantification, although the current platform does not allow for this. These findings could facilitate new strategies to reduce waiting times for an HCV diagnosis and improve linkage to treatment.

Maraviroc, as a Switch Option, in HIV-1-infected Individuals With Stable, Well-controlled HIV Replication and R5-tropic Virus on Their First Nucleoside/Nucleotide Reverse Transcriptase Inhibitor Plus Ritonavir-boosted Protease Inhibitor Regimen: Week 48 Results of the Randomized, Multicenter MARCH Study.

BACKGROUND: Alternative combination antiretroviral therapies in virologically suppressed human immunodeficiency virus (HIV)-infected patients experiencing side effects and/or at ongoing risk of important comorbidities from current therapy are needed. Maraviroc (MVC), a chemokine receptor 5 antagonist, is a potential alternative component of therapy in those with R5-tropic virus. METHODS: The Maraviroc Switch Study is a randomized, multicenter, 96-week, open-label switch study in HIV type 1-infected adults with R5-tropic virus, virologically suppressed on a ritonavir-boosted protease inhibitor (PI/r) plus double nucleoside/nucleotide reverse transcriptase inhibitor (2 N(t)RTI) backbone. Participants were randomized 1:2:2 to current combination antiretroviral therapy (control), or replacing the protease inhibitor (MVC + 2 N(t)RTI arm) or the nucleoside reverse transcriptase inhibitor backbone (MVC + PI/r arm) with twice-daily MVC. The primary endpoint was the difference (switch minus control) in proportion with plasma viral load (VL) <200 copies/mL at 48 weeks. The switch arms were judged noninferior if the lower limit of the 95% confidence interval (CI) for the difference in the primary endpoint was < -12% in the intention-to-treat (ITT) population. RESULTS: The ITT population comprised 395 participants (control, n = 82; MVC + 2 N(t)RTI, n = 156; MVC + PI/r, n = 157). Baseline characteristics were well matched. At week 48, noninferior rates of virological suppression were observed in those switching away from a PI/r (93.6% [95% CI, -9.0% to 2.2%] and 91.7% [95% CI, -9.6% to 3.8%] with VL <200 and <50 copies/mL, respectively) compared to the control arm (97.6% and 95.1% with VL <200 and <50 copies/mL, respectively). In contrast, MVC + PI/r did not meet noninferiority bounds and was significantly inferior (84.1% [95% CI, -19.8% to -5.8%] and 77.7% [95% CI, -24.9% to -8.4%] with VL <200 and <50 copies/mL, respectively) to the control arm in the ITT analysis. CONCLUSIONS: These data support MVC as a switch option for ritonavir-boosted PIs when partnered with a 2-N(t)RTI backbone, but not as part of N(t)RTI-sparing regimens comprising MVC with PI/r. CLINICAL TRIALS REGISTRATION: NCT01384682.

Dual-Purpose Gastric Decompression and Enteral Feeding Tubes Rationale and Design of Novel Nasogastric and Nasogastrojejunal Tubes.

BACKGROUND: The importance of early postoperative nutrition in surgical patients and early institution of enteral nutrition in intensive care unit (ICU) patients have recently been highlighted. Unfortunately, institution of enteral feeding in both groups of patients often has to be postponed due to delayed gastric emptying and the need for gastric decompression. The design of current polyvinylchloride (PVC) gastric decompression tubes (Salem Sump [Covidien, Mansfield, MA] in the United States; Ryles [Penine Health Care Ltd, Derby, UK] in the United Kingdom and Europe) make them unsuitable for their subsequent use as either nasogastric enteral feeding tubes or for continued gastric decompression during postpyloric enteral feeding. To overcome these problems, we have designed a range of polyurethane (PU) dual-purpose gastric decompression and enteral feeding tubes that include 2 nasogastric tubes (double lumen to replace Salem Sump; single lumen to replace Ryles). Two novel multilumen nasogastrojejunal tubes (triple lumen for the United States; double lumen for the United Kingdom and Europe) complete the range. By using PU, a given internal diameter (ID) and flow area can be incorporated into a lower outside diameter (OD) compared with that achieved with PVC. The ID and lumen and flow area of an 18Fr (OD 6.7 mm) PVC Salem Sump can be incorporated into a 14Fr (OD 4.7 mm) PU tube. The design of aspiration/infusion ports of current PVC and PU tubes invites occlusion by gastrointestinal mucosa and clogging by mucus and enteral feed. To overcome this, we have designed long, single, widened, smooth, and curved edge ports with no "dead space" to trap mucus or curdled diet. Involving up to 214° of the circumference, these ports have up to 11 times the flow areas of the aspiration ports of current PVC tubes. CONCLUSION: The proposed designs will lead to the development of dual-purpose nasogastric and nasojejunal tubes that will significantly improve the clinical and nutrition care of postoperative and ICU patients.

A meta-analysis of probiotic and synbiotic use in elective surgery: does nutrition modulation of the gut microbiome improve clinical outcome?

BACKGROUND: Perioperative nutrition modulation of gut microbiota is increasingly used as a strategy for reducing the infective complications of elective surgery. This meta-analysis assessed the effect of probiotic and synbiotic preparations on the incidence of postoperative sepsis. METHODS: Randomized controlled trials that compared preoperative dosing of probiotics and synbiotics in patients undergoing elective general surgical procedures were included. The primary outcome measure was the postoperative sepsis rate. Pooled outcome measures were determined using random effects models. RESULTS: Thirteen randomized controlled trials totaling 962 patients were included in this analysis (304 received synbiotics and 182 received probiotics). The incidence of postoperative sepsis was reduced in the probiotic group vs the control (pooled odds ratio [OR] = 0.42; 95% confidence interval [CI], 0.23-0.75; P = .003) and in the synbiotic group vs the control (pooled OR = 0.25; 95% CI, 0.1-0.6; P = .002). However, subgroup analysis failed to identify a significant reduction in the incidence of pneumonia, urinary tract infections, or wound infections in the postoperative phase for either treatment group. Synbiotics reduced the length of postoperative antibiotic use (weighted mean differences = -1.71; 95% CI, -3.2 to -0.21; P = .03). CONCLUSION: Probiotic and synbiotic nutrition strategies reduce the incidence of postoperative sepsis in the elective general surgery setting. These effects appear more pronounced with the use of synbiotics. High-powered, mechanistic studies are now required for the optimization of pro- and prebiotic regimens to further improve their efficacy.

Global metabolic phenotyping in an experimental laparotomy model of surgical trauma.

Surgical trauma initiates a complex series of metabolic host responses designed to maintain homeostasis and ensure survival. (1)H NMR spectroscopy was applied to intraoperative urine and plasma samples as part of a strategy to analyze the metabolic response of Wistar rats to a laparotomy model. Spectral data were analyzed by multivariate statistical analysis. Principal component analysis (PCA) confirmed that surgical injury is responsible for the majority of the metabolic variability demonstrated between animals (R² Urine = 81.2% R² plasma = 80%). Further statistical analysis by orthogonal projection to latent structure discriminant analysis (OPLS-DA) allowed the identification of novel urinary metabolic markers of surgical trauma. Urinary levels of taurine, glucose, urea, creatine, allantoin, and trimethylamine-N-oxide (TMAO) were significantly increased after surgery whereas citrate and 2-oxoglutarate (2-OG) negatively correlated with the intraoperative state as did plasma levels of betaine and tyrosine. Plasma levels of lipoproteins such as VLDL and LDL also rose with the duration of surgery. Moreover, the microbial cometabolites 3-hydroxyphenylpropionate, phenylacetylglycine, and hippurate correlated with the surgical insult, indicating that the gut microbiota are highly sensitive to the global homeostatic state of the host. Metabonomic profiling provides a global overview of surgical trauma that has the potential to provide novel biomarkers for personalized surgical optimization and outcome prediction.