Kinetic principles of ParA2-ATP cycling guide dynamic subcellular localizations in Vibrio cholerae.

Dynamic protein gradients are exploited for the spatial organization and segregation of replicated chromosomes. However, mechanisms of protein gradient formation and how that spatially organizes chromosomes remain poorly understood. Here, we have determined the kinetic principles of subcellular localizations of ParA2 ATPase, an essential spatial regulator of chromosome 2 segregation in the multichromosome bacterium, Vibrio cholerae. We found that ParA2 gradients self-organize in V. cholerae cells into dynamic pole-to-pole oscillations. We examined the ParA2 ATPase cycle and ParA2 interactions with ParB2 and DNA. In vitro, ParA2-ATP dimers undergo a rate-limiting conformational switch, catalysed by DNA to achieve DNA-binding competence. This active ParA2 state loads onto DNA cooperatively as higher order oligomers. Our results indicate that the midcell localization of ParB2-parS2 complexes stimulate ATP hydrolysis and ParA2 release from the nucleoid, generating an asymmetric ParA2 gradient with maximal concentration toward the poles. This rapid dissociation coupled with slow nucleotide exchange and conformational switch provides for a temporal lag that allows the redistribution of ParA2 to the opposite pole for nucleoid reattachment. Based on our data, we propose a 'Tug-of-war' model that uses dynamic oscillations of ParA2 to spatially regulate symmetric segregation and positioning of bacterial chromosomes.

Emergency Department Resuscitative Endovascular Balloon Occlusion of the Aorta in Trauma Patients With Exsanguinating Hemorrhage: The UK-REBOA Randomized Clinical Trial.

Importance: Bleeding is the most common cause of preventable death after trauma. Objective: To determine the effectiveness of resuscitative endovascular balloon occlusion of the aorta (REBOA) when used in the emergency department along with standard care vs standard care alone on mortality in trauma patients with exsanguinating hemorrhage. Design, Setting, and Participants: Pragmatic, bayesian, randomized clinical trial conducted at 16 major trauma centers in the UK. Patients aged 16 years or older with exsanguinating hemorrhage were enrolled between October 2017 and March 2022 and followed up for 90 days. Intervention: Patients were randomly assigned (1:1 allocation) to a strategy that included REBOA and standard care (n = 46) or standard care alone (n = 44). Main Outcomes and Measures: The primary outcome was all-cause mortality at 90 days. Ten secondary outcomes included mortality at 6 months, while in the hospital, and within 24 hours, 6 hours, or 3 hours; the need for definitive hemorrhage control procedures; time to commencement of definitive hemorrhage control procedures; complications; length of stay; blood product use; and cause of death. Results: Of the 90 patients (median age, 41 years [IQR, 31-59 years]; 62 [69%] were male; and the median Injury Severity Score was 41 [IQR, 29-50]) randomized, 89 were included in the primary outcome analysis because 1 patient in the standard care alone group declined to provide consent for continued participation and data collection 4 days after enrollment. At 90 days, 25 of 46 patients (54%) had experienced all-cause mortality in the REBOA and standard care group vs 18 of 43 patients (42%) in the standard care alone group (odds ratio [OR], 1.58 [95% credible interval, 0.72-3.52]; posterior probability of an OR >1 [indicating increased odds of death with REBOA], 86.9%). Among the 10 secondary outcomes, the ORs for mortality and the posterior probabilities of an OR greater than 1 for 6-month, in-hospital, and 24-, 6-, or 3-hour mortality were all increased in the REBOA and standard care group, and the ORs were increased with earlier mortality end points. There were more deaths due to bleeding in the REBOA and standard care group (8 of 25 patients [32%]) than in standard care alone group (3 of 18 patients [17%]), and most occurred within 24 hours. Conclusions and Relevance: In trauma patients with exsanguinating hemorrhage, a strategy of REBOA and standard care in the emergency department does not reduce, and may increase, mortality compared with standard care alone. Trial Registration: isrctn.org Identifier: ISRCTN16184981.

Injury by knife crime amongst children is associated with socioeconomic deprivation: an observational study.

PURPOSE: Children who live in areas of socioeconomic deprivation may be at higher risk of being victims of violent crime such as knife wounds. The current study investigated whether socioeconomic disparity was associated with higher risk of knife crime. METHODS: An observational study included patients aged ≤ 17 years at a UK Major Trauma Centre injured by knife trauma from 2016 to 2022. Indices of deprivation were recorded according to the zip code of residence and compared with those of all of England. These included Index of Multiple Deprivation (IMD); income; employment; education and skills; health and disability; crime; barriers to housing and services; living environment; and Income Deprivation Affecting Children Index (IDACI). RESULTS: There were 139 patients (96% male) with median age of 16 years. When compared with the whole of England, patients had worse indices of IMD (p = 0.021); income (p < 0.001); employment (p < 0.001); education and skills (p < 0.001); health and disability; and IDACI (p < 0.001). There were no significant differences in indices of crime, barriers to housing and services or living environment. CONCLUSIONS: Paediatric knife injury was associated with poor socioeconomic status in multiple domains. Focussed efforts to address socioeconomic disparities should be a priority as a public health measure for vulnerable children.

Poly(carboxypyrrole)s That Depolymerize from Head to Tail in the Solid State in Response to Specific Applied Signals.

This Article describes the design, synthesis, and analysis of a new class of polymer that is capable of depolymerizing continuously, completely, and cleanly from head to tail when a detection unit on the head of the polymer is exposed to a specific applied signal. The backbone of this polymer consists of 1,3-disubstituted pyrroles and carboxy linkages similar to polyurethanes. Diverse side chains or reactive end-groups can be introduced readily, which provides modular design of polymer structure. The designed depolymerization mechanism proceeds through spontaneous release of carbon dioxide and azafulvene in response to a single triggering reaction with the detection unit. These poly(carboxypyrrole)s depolymerize readily in nonpolar environments, and even in the bulk as solid-state plastics.

A study of outcomes of patients treated at a UK major trauma centre for moderate or severe injuries one to three years after injury.

OBJECTIVE: To assess return to work outcomes of major trauma patients treated at a level 1 UK major trauma centre and evaluate factors associated with improved outcomes. DESIGN: Cross-sectional cohort design. SUBJECTS: In total, 99 patients at one, two or three years post-discharge from a Major Trauma Centre with an injury severity score above 9, in full-time work or education prior to injury, aged 18-70 and discharged between April 2012 and June 2015. MAIN MEASURES: Self-report questionnaire including the Trauma Outcome Profile, the Multiple Sclerosis Neuropsychological Screening questionnaire and questions pertaining to work and education. RESULTS: Of the 99 patients in full-time work pre-injury, 65 made a complete return to work, 15 made an incomplete return to work and 19 did not return to work, where incomplete return to work was defined as working below 80% of previous working hours. In all, 25 participants scored below the cut-off point on physical disabilities, 46 below the cut-off point on mental functioning and 38 below the cut-off point on social interaction. Reduced anxiety and higher mental functioning were consistently associated with complete return to work. CONCLUSION: In all, 66% of patients with moderate to severe injuries made a complete return to work. A range of psycho-social, physical and functional health issues were persistent at long-term follow-up.

Metastasectomy of pancreatic and periampullary adenocarcinoma to solid organ: The current evidence.

PURPOSE: Pancreatic and periampullary adenocarcinoma have not generally been included in the tumour types considered for metastasectomy. However, there is an increasing interest that metastasectomy in well-selected patients can prolong survival. This review aims to establish the recent evidence on the surgical management of oligometastatic disease and survival outcome in patients who underwent metastasectomy focusing on isolated hepatic and pulmonary metastases. METHODS: A systematic search was performed in the PubMed database to identify all original articles on the role of metastasectomy for oligometastasis of pancreatic and periampullary adenocarcinoma. Data on methodologies used, 1,3,5 - year survival and median overall survival were summarized, and used to address relevant clinical questions related to the survival outcome in patients who underwent metastasectomy. RESULTS: Sixteen studies were included in this review. All the studies included were retrospective and heterogenous in nature and did not have a uniform reporting on survival outcomes. CONCLUSION: There is insufficient evidence to support a change of current practice in managing metastatic pancreatic and periampullary cancer. However, patients with ampullary cancer as the primary and any patients with first recurrence as isolated pulmonary metastases had better prognosis than patients with synchronous metastasis or metastases to the liver. This need to be explored in future studies.

Reconstitutions of plasmid partition systems and their mechanisms.

Bacterial plasmid and chromosome segregation systems ensure that genetic material is efficiently transmitted to progeny cells. Cell-based studies have shed light on the dynamic nature and the molecular basis of plasmid partition systems. In vitro reconstitutions, on the other hand, have proved to be an invaluable tool for studying the minimal components required to elucidate the mechanism of DNA segregation. This allows us to gain insight into the biological and biophysical processes that enable bacterial cells to move and position DNA. Here, we review the reconstitutions of plasmid partition systems in cell-free reactions, and discuss recent work that has begun to challenge long standing models of DNA segregation in bacteria.

Design, Synthesis, and Characterization of Small-Molecule Reagents That Cooperatively Provide Dual Readouts for Triaging and, When Necessary, Quantifying Point-of-Need Enzyme Assays.

A newly designed small molecule reagent provides both qualitative and quantitative readouts in assays that detect enzyme biomarkers. The qualitative readout enables rapid triaging of samples so that only samples that contain relevant concentrations of the target analyte must be quantified. The reagent is accessible in essentially three steps and 34% overall yield, is stable as a solid when heated to 44 °C for >1 month, and does not produce background signal when used in an assay. This paper describes the design and synthesis of the reagent, characterizes its response properties, and establishes the scope of its reactivity.

Focal nodular hyperplasia: a review of current indications for and outcomes of hepatic resection.

BACKGROUND: Focal nodular hyperplasia (FNH) is a common benign disease of the liver with no recognized potential for malignant transformation. The term describes an entity of lobular proliferation of normally differentiated hepatocytes, frequently around a central fibrous scar. Two key issues influence surgical decision making in FNH: diagnostic certainty, and symptomatic assessment. METHODS: A systematic review of studies reporting hepatic resections of FNH was performed. Indications and outcomes in adult populations were examined with a focus on diagnostic workup, patient selection and operative mortality and morbidity. RESULTS: Diagnostic modalities in the majority of studies involved ultrasound and computed tomography. Fewer than half employed magnetic resonance imaging (MRI). In instances in which MRI was not available, diagnostic accuracy was inferior. CONCLUSIONS: Percutaneous biopsy should be avoided to prevent the risk for tumour seeding. Patients presenting with asymptomatic definitive FNH can be safely managed conservatively. In symptomatic patients surgical resection is a safe and effective treatment for which acceptable rates of morbidity (14%) and zero mortality are reported. However, evidence of symptom resolution is reported with conservative strategies. Diagnostic uncertainty remains the principal valid indication for FNH resection, but only in patients in whom contrast-enhanced MRI forms part of preoperative assessment.

Critical review of the prognostic significance of pathological variables in patients undergoing resection for colorectal liver metastases.

OBJECTIVE: The aim of this study was to identify prognostic factors, particularly pathological variables, that influence disease-free and overall survival following resection for colorectal liver metastases (CRLM). METHODS: Patients undergoing CRLM resection from January 2005 to December 2011 were included. Data analysed included information on demographics, laboratory results, operative findings, histopathological features and survival. RESULTS: A total of 259 patients were included. Of these, 138 (53.3%) patients developed recurrent disease, of which 95 died. The median length of follow-up in the remaining patients was 28 months (range: 12-96 months). There were significant associations between recurrence and higher tumour number (P = 0.002), presence of perineural invasion (P = 0.009) and positive margin (R1) resection (P = 0.002). Multivariate analysis showed all three prognostic factors to be independent predictors of disease-free survival. Significantly poorer overall survival after hepatic resection for CRLM was observed in patients undergoing hemi-hepatectomy or more radical resection (P = 0.021), patients with a higher number of tumours (P = 0.024) and patients with perineural invasion (P < 0.001). Multivariate analysis showed perineural invasion to be the only independent predictor of overall survival. CONCLUSIONS: The presence of perineural invasion, multiple tumours and an R1 margin were associated with recurrent disease. Perineural invasion was also an independent prognostic factor with respect to overall survival.

Novel Textbook Outcomes following emergency laparotomy: Delphi exercise.

BACKGROUND: Textbook outcomes are composite outcome measures that reflect the ideal overall experience for patients. There are many of these in the elective surgery literature but no textbook outcomes have been proposed for patients following emergency laparotomy. The aim was to achieve international consensus amongst experts and patients for the best Textbook Outcomes for non-trauma and trauma emergency laparotomy. METHODS: A modified Delphi exercise was undertaken with three planned rounds to achieve consensus regarding the best Textbook Outcomes based on the category, number and importance (Likert scale of 1-5) of individual outcome measures. There were separate questions for non-trauma and trauma. A patient engagement exercise was undertaken after round 2 to inform the final round. RESULTS: A total of 337 participants from 53 countries participated in all three rounds of the exercise. The final Textbook Outcomes were divided into 'early' and 'longer-term'. For non-trauma patients the proposed early Textbook Outcome was 'Discharged from hospital without serious postoperative complications (Clavien-Dindo ≥ grade III; including intra-abdominal sepsis, organ failure, unplanned re-operation or death). For trauma patients it was 'Discharged from hospital without unexpected transfusion after haemostasis, and no serious postoperative complications (adapted Clavien-Dindo for trauma ≥ grade III; including intra-abdominal sepsis, organ failure, unplanned re-operation on or death)'. The longer-term Textbook Outcome for both non-trauma and trauma was 'Achieved the early Textbook Outcome, and restoration of baseline quality of life at 1 year'. CONCLUSION: Early and longer-term Textbook Outcomes have been agreed by an international consensus of experts for non-trauma and trauma emergency laparotomy. These now require clinical validation with patient data.

Early vocational rehabilitation and psychological support for trauma patients to improve return to work (the ROWTATE trial): study protocol for an individually randomised controlled multicentre pragmatic trial.

BACKGROUND: Moderately severe or major trauma (injury severity score (ISS) > 8) is common, often resulting in physical and psychological problems and leading to difficulties in returning to work. Vocational rehabilitation (VR) can improve return to work/education in some injuries (e.g. traumatic brain and spinal cord injury), but evidence is lacking for other moderately severe or major trauma. METHODS: ROWTATE is an individually randomised controlled multicentre pragmatic trial of early VR and psychological support in trauma patients. It includes an internal pilot, economic evaluation, a process evaluation and an implementation study. Participants will be screened for eligibility and recruited within 12 weeks of admission to eight major trauma centres in England. A total of 722 participants with ISS > 8 will be randomised 1:1 to VR and psychological support (where needed, following psychological screening) plus usual care or to usual care alone. The ROWTATE VR intervention will be provided within 2 weeks of study recruitment by occupational therapists and where needed, by clinical psychologists. It will be individually tailored and provided for ≤ 12 months, dependent on participant need. Baseline assessment will collect data on demographics, injury details, work/education status, cognitive impairment, anxiety, depression, post-traumatic distress, disability, recovery expectations, financial stress and health-related quality of life. Participants will be followed up by postal/telephone/online questionnaires at 3, 6 and 12 months post-randomisation. The primary objective is to establish whether the ROWTATE VR intervention plus usual care is more effective than usual care alone for improving participants' self-reported return to work/education for at least 80% of pre-injury hours at 12 months post-randomisation. Secondary outcomes include other work outcomes (e.g. hours of work/education, time to return to work/education, sickness absence), depression, anxiety, post-traumatic distress, work self-efficacy, financial stress, purpose in life, health-related quality of life and healthcare/personal resource use. The process evaluation and implementation study will be described elsewhere. DISCUSSION: This trial will provide robust evidence regarding a VR intervention for a major trauma population. Evidence of a clinically and cost-effective VR intervention will be important for commissioners and providers to enable adoption of VR services for this large and important group of patients within the NHS. TRIAL REGISTRATION: ISRCTN: 43115471. Registered 27/07/2021.

Stage IV colorectal cancer: outcomes following the liver-first approach.

BACKGROUND: To date, there is limited data on the liver-first approach in the management of colorectal liver metastases (CRLM). The aim of the study was to assess the outcomes of the liver-first approach for patients with synchronous CRLM in two tertiary referral centers. METHODS: Patients with stage IV colorectal cancer selected for the liver-first approach from January 2009 to December 2012 in two tertiary referral centers were included. Data collated included demographics, chemotherapy, operative findings, histo-pathological features, and survival. RESULTS: Thirty-seven patients with synchronous CRLM were considered for the liver-first approach. Twenty-five patients had rectal cancer. All patients underwent induction chemotherapy. Thirty patients underwent hepatic resections with no post-operative deaths. Following liver resection, five patients failed to proceed to colorectal resection and one patient had complete response to chemo-radiotherapy. Of the 25 patients that completed the liver-first approach, 13 patients had recurrent disease, of which 12 patients died. The overall 1- and 3-year survival rates were 65.9% and 30.4%, respectively. CONCLUSION: The liver-first approach is a feasible strategy for patients with synchronous CRLM and may improve survival in selected patients. The selection of patients should be incorporated in a multidisciplinary approach to achieve the best possible outcomes.

Engagement with a youth violence intervention programme is associated with lower re-attendance after violent injury: A UK major trauma network observational study.

The hospital based Redthread Youth Violence Intervention Programme (YVIP) utilises experienced youth workers to support 11-24 year olds following an episode of violent injury, assault or exploitation who present to the Emergency Department (ED) at the East Midlands Major Trauma Centre (MTC), Nottingham, UK. The YVIP aims to promote personal change with the aim of reducing the incidence of further similar events. We conducted a retrospective, observational, cohort study to examine the association between engagement with the YVIP and re-attendance rates to the ED following a referral to Redthread. We also examined factors associated with engagement with the full YVIP. We found that 573 eligible individuals were referred to the YVIP over two years. Assault with body parts 34.9% (n = 200) or a bladed object 29.8% (n = 171) were the commonest reason for referral. A prior event rate ratio (PERR) analysis was used to compare rates of attendance between those who did and did not engage with the full YVIP. Engagement was associated with a reduction in re-attendances of 51% compared to those who did not engage (PERR 0.49 [95% 0.28-0.64]). A previous attendance to the ED by an individual positively predicted engagement. (OR 2.82 [95% CI 1.07-7.42], P = 0.035). A weekend attendance (OR 0.26 [0.15-0.44], P<0.001) and a phone call approach (OR 0.25 [0.14-0.47], P = 0.001), rather than a face-to-face approach by a Redthread worker, negatively impacted engagement. In conclusion, assaults with or without a weapon contributed to a significant proportion of attendances among this age group. The Redthread YVIP was associated with reduced rates of re-attendance to the East Midlands MTC among young persons who engaged with the full programme.

Injuries among children attributed to violence and social funding: a 10-year observational study.

BACKGROUND: Mechanisms and patterns of injury in children are changing, with violent mechanisms becoming more prevalent over time. Government funding of services for children and young people has reduced nationally over the last decade. We aimed to investigate the trends in admissions of injured children to a Major Trauma Centre (MTC) and examine the relationship between injuries sustained by violent mechanisms and local authority funding of children and youth services within the same catchment area. METHODS: A 10-year observational study included all patients aged<18 years treated at a regional MTC between April 2012 and April 2022. Number of admissions with violent trauma, mechanism of injury, requirement for operative intervention and mortality were compared with published annual local authority expenditure reports. RESULTS: 1126 children were included; 71.3% were boys, with median age 11 years (IQR 3-16). There were 154/1126 (14%) children who were victims of violent trauma; they were more likely to be boys than children injured by non-violent mechanisms (84% vs 69%). The proportion of injuries attributed to violence increased over the study period at the same time as reductions in local authority funding of services for the early years, families and youth services. However, there were insufficient data to formally assess the interdependency between these factors. CONCLUSIONS: The proportion of injuries attributed to violence has increased over time, and government spending on specific children and young people's services has decreased over the same time period. Further work is needed to examine the interdependency between spending and violent injuries in children, and public health interventions to target violence-related injuries should take into account youth service funding.

Improvements over time for patients following liver trauma: A 17-year observational study.

Background: Centralisation of trauma care has been shown to be associated with improved patient outcomes. The establishment of Major Trauma Centres (MTC) and networks in England in 2012 allowed for centralisation of trauma services and specialties including hepatobiliary surgery. We aimed to investigate the outcomes for patients with hepatic injury over the last 17 years at a large MTC in England in relation to the MTC status of the centre. Methods: All patients who sustained liver trauma between 2005 and 2022 were identified using the Trauma Audit and Research Network database for a single MTC in the East Midlands. Mortality and complications were compared between patients before and after establishment of MTC status. Multivariable logistic regression models were used to determine the odds ratio (OR) and 95% confidence interval (95% CI) for complications according to MTC status, accounting for the potentially confounding variables of age, sex, severity of injuries and comorbidities for all patients, and the subgroup with severe liver trauma (AAST Grade IV and V). Results: There were 600 patients; the median age was 33 (IQR 22-52) years and 406/600 (68%) were male. There were no significant differences in 90-day mortality or length of stay between the pre- and post-MTC patients. Multivariable logistic regression models showed both lower overall complications [OR 0.24 (95% CI 0.14, 0.39); p < 0.001] and lower liver-specific complications [OR 0.21 (95% CI 0.11, 0.39); p < 0.001] in the post-MTC period. This was also the case in the severe liver injury subgroup (p = 0.008 and p = 0.002 respectively). Conclusions: Outcomes for liver trauma were superior in the post-MTC period even when adjusted for patient and injury characteristics. This was the case even though patients in this period were older with more comorbidities. These data support the centralisation of trauma services for those with liver injuries.

One- and two-year outcomes and predictors of mortality following emergency laparotomy: a consecutive series from a United Kingdom teaching hospital.

BACKGROUND: Data on outcomes of patients who underwent emergency laparotomy (EML) are limited. This prospective observational study examined aspects of inpatient care and outcomes following EML with a view to identifying predictors of mortality. METHODS: Data collected from consecutive inpatients who underwent EML in a UK teaching hospital over a 3-month period included perioperative physiology, treatment, morbidity, and mortality (30-day, in-hospital, 12-month, and 24-month). Univariate and multiple logistic regression analyses were used to identify predictors of mortality. RESULTS: Eighty-five patients (44 male) with a mean ± SD age of 61 ± 18 years were studied. Postoperatively, 51 % of patients were admitted to the intensive care (ICU) or the high-dependency unit (HDU). 30-day, in-hospital, 12-month, and 24-month mortality was 14, 16.5, 22.4, and 25.9 %, respectively. After adjusting for confounding variables, age ≥70 years (odds ratio [OR] = 9.2, P = 0.004) and a need for postoperative ICU/HDU (OR = 15.0, P = 0.014) were independent predictors of 30-day mortality. Independent predictors of in-hospital mortality were age ≥70 years (OR = 18.2, P = 0.016), ASA ≥III (OR = 22.1, P = 0.034), preoperative sepsis (OR = 20.6, P = 0.045), and need for postoperative ICU/HDU (OR = 21.5, P = 0.038). Independent predictors of 12-month mortality were preoperative urea >7.5 mmol/L (OR = 3.5, P = 0.038) and need for postoperative ICU/HDU (OR = 3.7, P = 0.044). Age ≥70 years was the only independent predictor of 24-month mortality (OR = 4.5, P = 0.014). Almost all deaths recorded in the 24 months following surgery resulted from disseminated malignancy. CONCLUSION: Patients who underwent EML had favourable outcomes, with 2-year survival close to 75 %. Age ≥70 years and the need for postoperative ICU/HDU care were independent predictors of mortality.

Study protocol: a randomized controlled trial of a computer-based depression and substance abuse intervention for people attending residential substance abuse treatment.

BACKGROUND: A large proportion of people attending residential alcohol and other substance abuse treatment have a co-occurring mental illness. Empirical evidence suggests that it is important to treat both the substance abuse problem and co-occurring mental illness concurrently and in an integrated fashion. However, the majority of residential alcohol and other substance abuse services do not address mental illness in a systematic way. It is likely that computer delivered interventions could improve the ability of substance abuse services to address co-occurring mental illness. This protocol describes a study in which we will assess the effectiveness of adding a computer delivered depression and substance abuse intervention for people who are attending residential alcohol and other substance abuse treatment. METHODS/DESIGN: Participants will be recruited from residential rehabilitation programs operated by the Australian Salvation Army. All participants who satisfy the diagnostic criteria for an alcohol or other substance dependence disorder will be asked to participate in the study. After completion of a baseline assessment, participants will be randomly assigned to either a computer delivered substance abuse and depression intervention (treatment condition) or to a computer-delivered typing tutorial (active control condition). All participants will continue to complete The Salvation Army residential program, a predominantly 12-step based treatment facility. Randomisation will be stratified by gender (Male, Female), length of time the participant has been in the program at the commencement of the study (4 weeks or less, 4 weeks or more), and use of anti-depressant medication (currently prescribed medication, not prescribed medication). Participants in both conditions will complete computer sessions twice per week, over a five-week period. Research staff blind to treatment allocation will complete the assessments at baseline, and then 3, 6, 9, and 12 months post intervention. Participants will also complete weekly self-report measures during the treatment period. DISCUSSION: This study will provide comprehensive data on the effect of introducing a computer delivered, cognitive behavioral therapy based co-morbidity treatment program within a residential substance abuse setting. If shown to be effective, this intervention can be disseminated within other residential substance abuse programs. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12611000618954.