Exploring mechanisms and contexts in a Peer Education Project to improve mental health literacy in schools in England: a qualitative realist evaluation.

Poor adolescent mental health calls for universal prevention. The Mental Health Foundation's 'Peer Education Project' equips older students ('peer educators') to teach younger students ('peer learners') about mental health. The peer-led lessons cover defining good and bad mental health, risk and protective factors, self-care, help-seeking and looking after one another. While previous pre-post evaluations have suggested effectiveness, the mechanisms through which the intervention improves mental health literacy remain unclear. We purposively recruited seven secondary schools across England from 2020 to 2022 and collected data through five observations, 12 staff interviews and 15 student focus groups (totalling 134 students; 46 peer educators aged 14-18 years and 88 peer learners aged 11-13 years). Our realist analysis adopted retroductive logic, intertwining deductive and inductive approaches to test the initial programme theory against insights arising from the data. We developed Context-Mechanisms-Outcome configurations related to four themes: (i) modelling behaviours and forming supportive relationships, (ii) relevant and appropriate content, (iii) peer educators feeling empowered and (iV) a school culture that prioritises mental health support. Our refined programme theory highlights key mechanisms, contexts conducive to achieving the outcomes and ways to improve training, recruitment and delivery to maximise effectiveness for similar peer-led initiatives.

Shape-changing magnetic assemblies as high-sensitivity NMR-readable nanoprobes.

Fluorescent and plasmonic labels and sensors have revolutionized molecular biology, helping visualize cellular and biomolecular processes. Increasingly, such probes are now being designed to respond to wavelengths in the near-infrared region, where reduced tissue autofluorescence and photon attenuation enable subsurface in vivo sensing. But even in the near-infrared region, optical resolution and sensitivity decrease rapidly with increasing depth. Here we present a sensor design that obviates the need for optical addressability by operating in the nuclear magnetic resonance (NMR) radio-frequency spectrum, where signal attenuation and distortion by tissue and biological media are negligible, where background interferences vanish, and where sensors can be spatially located using standard magnetic resonance imaging (MRI) equipment. The radio-frequency-addressable sensor assemblies presented here comprise pairs of magnetic disks spaced by swellable hydrogel material; they reversibly reconfigure in rapid response to chosen stimuli, to give geometry-dependent, dynamic NMR spectral signatures. The sensors can be made from biocompatible materials, are themselves detectable down to low concentrations, and offer potential responsive NMR spectral shifts that are close to a million times greater than those of traditional magnetic resonance spectroscopies. Inherent adaptability should allow such shape-changing systems to measure numerous different environmental and physiological indicators, thus providing broadly generalizable, MRI-compatible, radio-frequency analogues to optically based probes for use in basic chemical, biological, medical and engineering research.

Interleukin-6 and total antioxidant capacity levels following N-acetylcysteine and a combination nutraceutical intervention in a randomised controlled trial for bipolar disorder.

OBJECTIVE: The aims of this study were to evaluate changes in inflammatory and oxidative stress levels following treatment with N-acetylcysteine (NAC) or mitochondrial-enhancing agents (CT), and to assess the how these changes may predict and/or moderate clinical outcomes primarily the Montgomery-Åsberg Depression Rating Scale (MADRS). METHODS: This study involved secondary analysis of a placebo-controlled randomised trial (n = 163). Serum samples were collected at baseline and week 16 of the clinical trial to determine changes in Interleukin-6 (IL-6) and total antioxidant capacity (TAC) following adjunctive CT and/or NAC treatment, and to explore the predictability of the outcome or moderator effects of these markers. RESULTS: In the NAC-treated group, no difference was observed in serum IL-6 and TAC levels after 16 weeks of treatment with NAC or CT. However, results from a moderator analysis showed that in the CT group, lower IL-6 levels at baseline was a significant moderator of MADRS χ2 (df) = 4.90, p = 0.027) and Clinical Global Impression-Improvement (CGI-I, χ2 (df) = 6.28 p = 0.012). In addition, IL-6 was a non-specific but significant predictor of functioning (based on the Social and Occupational Functioning Assessment Scale (SOFAS)), indicating that individuals with higher IL-6 levels at baseline had a greater improvement on SOFAS regardless of their treatment (p = 0.023). CONCLUSION: Participants with lower IL-6 levels at baseline had a better response to the adjunctive treatment with the mitochondrial-enhancing agents in terms of improvements in MADRS and CGI-I outcomes.

Investigating lipids as a source of chemical exchange-induced MRI frequency shifts.

While magnetic susceptibility is a major contributor to NMR resonance frequency variations in the human brain, a substantial contribution may come from the chemical exchange of protons between water and other molecules. Exchange-induced frequency shifts fe have been measured in tissue and protein solutions, but relatively lipid-rich white matter (WM) has a larger fe than gray matter, suggesting that lipids could contribute. Galactocerebrosides (GC) are a prime candidate as they are abundant in WM and susceptible to exchange. To investigate this, fe was measured in a model of WM lipid membranes in the form of multilamellar vesicles (MLVs), consisting of a 1:2 molar ratio of GC and phospholipids (POPC), and in MLVs with POPC only. Chemical shift imaging with 15% volume fraction of dioxane, an internal reference whose protons are assumed not to undergo chemical exchange, was used to remove susceptibility-induced frequency shifts in an attempt to measure fe in MLVs at several lipid concentrations. Initial analysis of these measurements indicated a necessity to correct for small unexpected variations in dioxane concentration due to its effect on the water frequency shift. To achieve this, the actual dioxane concentration was inferred from spectral analysis and its additional contribution to fe was removed through separate experiments which showed that the water-dioxane frequency shift depended linearly on the dioxane concentration at low concentrations with a proportionality constant of -0.021 ± 0.002 ppb/mM in agreement with published experiments. Contrary to expectations and uncorrected results, for GC + POPC vesicles, the dependence of the corrected fe on GC concentration was insignificant (0.023 ± 0.037 ppb/mM; r2 = 0.085, p > 0.57), whereas for the POPC-only vesicles a small but significant linear increase with POPC concentration was found: 0.044 ± 0.008 ppb/mM (r2 = 0.877, p < 0.01). These findings suggest that the exchange-induced contribution of lipids to frequency contrast in WM may be small. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Cognitive effects of adjunctive N-acetyl cysteine in psychosis.

BACKGROUND: Cognitive deficits are predictors of functional outcome in patients with psychosis. While conventional antipsychotics are relatively effective on positive symptoms, their impact on negative and cognitive symptoms is limited. Recent studies have established a link between oxidative stress and neurocognitive deficits in psychosis. N-acetylcysteine (NAC), a glutathione precursor with glutamatergic properties, has shown efficacy on negative symptoms and functioning in patients with schizophrenia and bipolar disorder, respectively. However, there are few evidence-based approaches for managing cognitive impairment in psychosis. The present study aims to examine the cognitive effects of adjunctive NAC treatment in a pooled subgroup of participants with psychosis who completed neuropsychological assessment in two trials of both schizophrenia and bipolar disorder. METHOD: A sample of 58 participants were randomized in a double fashion to receive 2 g/day of NAC (n = 27) or placebo (n = 31) for 24 weeks. Attention, working memory and executive function domains were assessed. Differences between cognitive performance at baseline and end point were examined using Wilcoxon's test. The Mann-Whitney test was used to examine the differences between the NAC and placebo groups at the end point. RESULTS: Participants treated with NAC had significantly higher working memory performance at week 24 compared with placebo (U = 98.5, p = 0.027). CONCLUSIONS: NAC may have an impact on cognitive performance in psychosis, as a significant improvement in working memory was observed in the NAC-treated group compared with placebo; however, these preliminary data require replication. Glutamatergic compounds such as NAC may constitute a step towards the development of useful therapies for cognitive impairment in psychosis.

C-reactive protein is increased in schizophrenia but is not altered by antipsychotics: meta-analysis and implications.

The inflammatory hypothesis of schizophrenia (SZ) posits that inflammatory processes and neural-immune interactions are involved in its pathogenesis, and may underpin some of its neurobiological correlates. SZ is the psychiatric disorder causing the most severe burden of illness, not just owing to its psychiatric impairment, but also owing to its significant medical comorbidity. C-reactive protein (CRP) is a commonly used biomarker of systemic inflammation worldwide. There are some conflicting results regarding the behaviour of CRP in SZ. The aims of this study were to verify whether peripheral CRP levels are indeed increased in SZ, whether different classes of antipsychotics divergently modulate CRP levels and whether its levels are correlated with positive and negative symptomatology. With that in mind, we performed a meta-analysis of all cross-sectional studies of serum and plasma CRP levels in SZ compared to healthy subjects. In addition, we evaluated longitudinal studies on CRP levels before and after antipsychotic use. Our meta-analyses of CRP in SZ included a total of 26 cross-sectional or longitudinal studies comprising 85 000 participants. CRP levels were moderately increased in persons with SZ regardless of the use of antipsychotics and did not change between the first episode of psychosis and with progression of SZ (g=0.66, 95% confidence interval (95% CI) 0.43 to 0.88, P<0.001, 24 between-group comparisons, n=82 962). The extent of the increase in peripheral CRP levels paralleled the increase in severity of positive symptoms, but was unrelated to the severity of negative symptoms. CRP levels were also aligned with an increased body mass index. Conversely, higher age correlated with a smaller difference in CRP levels between persons with SZ and controls. Furthermore, CRP levels did not increase after initiation of antipsychotic medication notwithstanding whether these were typical or atypical antipsychotics (g=0.01, 95% CI -0.20 to 0.22, P=0.803, 8 within-group comparisons, n=713). In summary, our study provides further evidence of the inflammatory hypothesis of SZ. Whether there is a causal relationship between higher CRP levels and the development of SZ and aggravation of psychotic symptoms, or whether they are solely a marker of systemic low-grade inflammation in SZ, remains to be clarified.

Citalopram and sertraline exposure compromises embryonic bone development.

Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed treatments for depression and, as a class of drugs, are among the most used medications in the world. Concern regarding possible effects of SSRI treatment on fetal development has arisen recently as studies have suggested a link between maternal SSRI use and an increase in birth defects such as persistent pulmonary hypertension, seizures and craniosynostosis. Furthermore, SSRI exposure in adults is associated with decreased bone mineral density and increased fracture risk, and serotonin receptors are expressed in human osteoblasts and osteoclasts. To determine possible effects of SSRI exposure on developing bone, we treated both zebrafish, during embryonic development, and human mesenchymal stem cells (MSCs), during differentiation into osteoblasts, with the two most prescribed SSRIs, citalopram and sertraline. SSRI treatment in zebrafish decreased bone mineralization, visualized by alizarin red staining and decreased the expression of mature osteoblast-specific markers during embryogenesis. Furthermore, we showed that this inhibition was not associated with increased apoptosis. In differentiating human MSCs, we observed a decrease in osteoblast activity that was associated with a decrease in expression of the osteoblast-specific genes Runx2, Sparc and Spp1, measured with quantitative real-time PCR (qRT-PCR). Similar to the developing zebrafish, no increase in expression of the apoptotic marker Caspase 3 was observed. Therefore, we propose that SSRIs inhibit bone development by affecting osteoblast maturation during embryonic development and MSC differentiation. These results highlight the need to further investigate the risks of SSRI use during pregnancy in exposing unborn babies to potential skeletal abnormalities.

Solar insolation in springtime influences age of onset of bipolar I disorder.

OBJECTIVE: To confirm prior findings that the larger the maximum monthly increase in solar insolation in springtime, the younger the age of onset of bipolar disorder. METHOD: Data were collected from 5536 patients at 50 sites in 32 countries on six continents. Onset occurred at 456 locations in 57 countries. Variables included solar insolation, birth-cohort, family history, polarity of first episode and country physician density. RESULTS: There was a significant, inverse association between the maximum monthly increase in solar insolation at the onset location, and the age of onset. This effect was reduced in those without a family history of mood disorders and with a first episode of mania rather than depression. The maximum monthly increase occurred in springtime. The youngest birth-cohort had the youngest age of onset. All prior relationships were confirmed using both the entire sample, and only the youngest birth-cohort (all estimated coefficients P < 0.001). CONCLUSION: A large increase in springtime solar insolation may impact the onset of bipolar disorder, especially with a family history of mood disorders. Recent societal changes that affect light exposure (LED lighting, mobile devices backlit with LEDs) may influence adaptability to a springtime circadian challenge.

Quality of life in bipolar and schizoaffective disorder--a naturalistic approach.

PURPOSE: The aim of this study was to evaluate the health-related quality of life (HRQoL) in bipolar type I (BD I) and schizoaffective (SQA) patients during a 2-year period in a naturalistic study. METHODS: This study was based on the data generated by the Bipolar Comprehensive Outcome Study, a prospective, non-interventional, observational study of participants with BD I and SQA disorder. Mixed-Model Repeated Measures Analysis was used to analyze changes in the SF-36 and EQ-5D. RESULTS: Participants exhibited low health status at baseline with SF-36 mean scores of 46.7±10.5 and 36.9±12.9 (best imaginable health=100, normal population≈50) for physical and mental components, respectively. No significant differences were found between the ratings of the BD I and SQA patients on HRQoL. The SF-36 SMC improved significantly over 24 months although SPC scores remained consistent across the study. On the whole, the lowest SMC score was observed among the depressed patients (38.20), followed by the patients with a mixed state (39.01) and the manic patients (39.83). LIMITATIONS: The observational design may have limited the causal relationships and the generalizability within the current findings. CONCLUSIONS: HRQoL was significantly impaired in all stages of BD and SQA when compared to the general population. The impairment of HRQoL was most pronounced in the depressed state, followed by the mixed state and then the manic state. The euthymic patients showed the least impairment. In addition, patients showed a global improvement in their mental health satisfaction over the 2 years follow up period.

Equal remission rates and reduced length of hospital stay with twice-daily repetitive transcranial magnetic stimulation (rTMS) for major depression - A large naturalistic retrospective cohort association study.

OBJECTIVES: Repetitive transcranial magnetic stimulation (rTMS) is a level 1a evidence-based treatment for major depression, but high cost of care and limited effectiveness in naturalistic cohorts have been lingering criticisms. This naturalistic, retrospective cohort analysis compares the effect of once and twice daily treatment protocols of rTMS using quality assurance data collected at an Australian private psychiatric hospital. METHODS: A total of 210 inpatients self-selected into two groups receiving up to 30 sessions of either daily (n = 101) or twice daily (n = 109) 10 Hz rTMS to the left dorsolateral prefrontal cortex (DLPFC). The a priori primary outcome measure was remission rate as measured by pre and post treatment HAMD-17 scores. Length of hospital stay was a secondary post hoc outcome adopted due to the importance to cost of acute psychiatric care. RESULTS: Remission rates were similar across groups, with 44.9% and 45.4% for twice daily and daily rTMS groups respectively, although these may be confounded by patient expectations, other treatments and medication changes given the naturalistic setting. The length of hospital stay was 10.11 days and 18.44 days for twice daily and daily rTMS respectively - the twice daily rTMS length of hospital stay was 45.1% shorter 95% CI [38.7% - 51.56%]. Dropout rates were high; Twenty-seven (24.77%) twice daily participants dropped out before 20 sessions were completed, and 35 (34.65%) of daily participants. CONCLUSIONS: Twice daily 10 Hz left sided rTMS remission outcomes were similar to traditional once daily rTMS but required a shorter length of hospital stay. This finding has substantial cost of care implications. If these findings are independently replicated, twice daily rTMS may become the standard of care for inpatient rTMS.

Educating the next generation of cancer researchers: Evaluation of a cancer research partnership training program.

African American, American Indian and Alaska Native, Hispanic (or Latinx), Native Hawaiian, and other Pacific Islander groups are underrepresented in the biomedical workforce, which is one of the barriers to addressing cancer disparities among minority populations. The creation of a more inclusive biomedical workforce dedicated to reducing the burden of cancer health disparities requires structured, mentored research and cancer-related research exposure during the earlier stages of training. The Summer Cancer Research Institute (SCRI) is a multicomponent 8-week intensive summer program funded under the Partnership between a Minority Serving Institute and a National Institutes of Health-designated Comprehensive Cancer Center. In this survey study, we found that students who participated in the SCRI Program reported greater knowledge and interest in pursuing careers in cancer-related fields than their counterparts who did not participate in SCRI. Successes, challenges, and solutions in providing training in cancer and cancer health disparities research to improve diversity in the biomedical fields were also discussed.

Educating the Next Generation of Cancer Researchers: Evaluation of A Cancer Research Partnership Training Program.

African American, American Indian and Alaska Native, Hispanic (or Latinx), Native Hawaiian, and other Pacific Islander groups are underrepresented in the biomedical workforce, which is one of the barriers to addressing cancer disparities among minority populations. The creation of a more inclusive biomedical workforce dedicated to reducing the burden of cancer health disparities requires structured, mentored research and cancer-related research exposure during the earlier stages of training. The Summer Cancer Research Institute (SCRI), a multicomponent 8-week intensive summer program funded under the Partnership between a Minority Serving Institute and a National Institutes of Health-designated Comprehensive Cancer Center. This study assessed whether students who participated in the SCRI Program report greater knowledge and interest in pursuing careers in cancer-related fields than their counterparts who did not participate in SCRI. Successes, challenges, and solutions in providing training in cancer and cancer health disparities research to improve diversity in the biomedical fields were also discussed.

Illness burden and medical comorbidity in the Systematic Treatment Enhancement Program for Bipolar Disorder.

OBJECTIVE: Coexisting chronic medical conditions are common in bipolar disorder. Here, we report the prevalence and correlates of medical comorbidity in patients enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). We were particularly interested in associations between variables reflecting illness chronicity and burden with comorbid medical conditions. METHOD: We used intake data from the open-label component of the STEP-BD. History of medical comorbidity was obtained from the affective disorders evaluation, and its presence was the outcome of interest. The sample size in analyses varied from 3399 to 3534. We used multiple Poisson regression to obtain prevalence ratios. RESULTS: The prevalence of any medical comorbidity in the sample was 58.8%. In addition to demographic variable, several clinical characteristics were associated with the frequency of medical comorbidity. Having more than 10 previous mood episodes, childhood onset, smoking, lifetime comorbidity with anxiety, and substance use disorders were independently associated with having a medical comorbidity in the final multivariate model. CONCLUSION: The results presented here reveal strong associations between variables related to illness chronicity and medical burden in bipolar disorder. This lends further support to recent multidimensional models incorporating medical morbidity as a core feature of bipolar disorder.

The fabrication of uniform cylindrical nanoshells and their use as spectrally tunable MRI contrast agents.

A new form of tunable magnetic resonance imaging agent based on precisely dimensioned cylindrical magnetic nanoshells is introduced. Using top-down prepatterned substrates, the nanoshells are fabricated by exploiting what is usually regarded as a detrimental processing side-effect, namely the redeposition of material back-sputtered during ion-milling. The well-resolved nuclear magnetic resonance peaks of the resulting nanostructures attest to the nanoscale fabrication control and the general feasibility of such sputter redeposition for fabrication of a variety of self-supporting, highly monodisperse nanoscale structures.

Numerical and experimental simulation of the effect of long bone fracture healing stages on ultrasound transmission across an idealized fracture.

The effect of various stages of fracture healing on the amplitude of 200 kHz ultrasonic waves propagating along cortical bone plates and across an idealized fracture has been modeled numerically and experimentally. A simple, water-filled, transverse fracture was used to simulate the inflammatory stage. Next, a symmetric external callus was added to represent the repair stage, while a callus of reducing size was used to simulate the remodeling stage. The variation in the first arrival signal amplitude across the fracture site was calculated and compared with data for an intact plate in order to calculate the fracture transmission loss (FTL) in decibels. The inclusion of the callus reduced the fracture loss. The most significant changes were calculated to occur from the initial inflammatory phase to the formation of a callus (with the FTL reducing from 6.3 to between 5.5 and 3.5 dB, depending on the properties of the callus) and in the remodeling phase where, after a 50% reduction in the size of the callus, the FTL reduced to between 2.0 and 1.3 dB. Qualitatively, the experimental results follow the model predictions. The change in signal amplitude with callus geometry and elastic properties could potentially be used to monitor the healing process.

EVALUATION OF A TRANSDISCIPLINARY CANCER RESEARCH TRAINING PROGRAM FOR UNDER-REPRESENTED MINORITY STUDENTS.

AIM/PURPOSE: This paper will describe the initial development of systems to evaluate research education activities of a U.S. academic Partnership to train minority students as cancer researchers and provide preliminary data from monitoring Partnership activities during the first six months. BACKGROUND: There is increased focus on multidisciplinary/transdisciplinary research training programs. However, few training programs have included detailed evaluations to assess their outcomes and effectiveness. METHODOLOGY: The Temple University/Fox Chase Cancer Center and Hunter College Regional Comprehensive Cancer Health Disparity Partnership (TUFCCC/HC Cancer Partnership, or the Partnership) is a recently-initiated center focused on training individuals from under-represented minorities (URMs) as cancer researchers. Evaluation of the training activities involves detailed specification of goals for each of the Partnership's Cores; objectives for addressing each goal; measures and indicators to determine progress towards each objective; and data sources to provide information for the measures/indicators. CONTRIBUTUION: This paper will provide important information for evaluation of training programs focused on students from URM populations and development of trans-disciplinary research education programs. FINDINGS: Goals, objectives, measures, and data sources for evaluation of the Partnership's Research Education Core (REC) were developed jointly by personnel from the REC and the Planning Evaluation Core (PEC) in an iterative process. These measures capture the training activities led by the REC (e.g., number of seminars and workshops), scientific output by trainees (e.g., papers and grants), and ability of the program to meet trainees' goals and expectations. RECOMMENDATIONS FOR PRACTITIONERS AND RESEARCHES: Evaluation plans for transdisciplinary training programs need to be developed prior to program initiation. Evaluation measures should be jointly specified by training and evaluation personnel, then reviewed and revised in an iterative process. IMPACT ON SOCIETY: This program is intended to enhance diversity among cancer researchers and increase studies to address disparities in cancer care. FUTURE RESEARCH: The PEC will oversee the evaluation of Partnership training activities over the five year period and assist Partnership leaders in ensuring successful outcomes.

ENACT: a protocol for a randomised placebo-controlled trial investigating the efficacy and mechanisms of action of adjunctive N-acetylcysteine for first-episode psychosis.

BACKGROUND: First-episode psychosis (FEP) may lead to a progressive, potentially disabling and lifelong chronic illness; however, evidence suggests that the illness course can be improved if appropriate treatments are given at the early stages. Nonetheless, the efficacy of antipsychotic medications is suboptimal, particularly for negative and cognitive symptoms, and more efficacious and benign treatments are needed. Previous studies have shown that the antioxidant amino acid N-acetylcysteine (NAC) reduces negative symptoms and improves functioning in chronic schizophrenia and bipolar disorder. Research is scarce as to whether NAC is beneficial earlier in the course of illness. The primary aim of this study is to determine the efficacy of treatment with adjunctive NAC (2 g/day for 26 weeks) compared with placebo to improve psychiatric symptoms in young people experiencing FEP. Secondary aims are to explore the neurobiological mechanisms underpinning NAC and how they relate to various clinical and functional outcomes at 26- and 52-week follow-ups. METHODS/DESIGN: ENACT is a 26-week, randomised controlled trial of adjunctive NAC versus placebo, with a 26-week non-treatment follow-up period, for FEP. We will be recruiting 162 young people aged 15-25 years who have recently presented to, and are being treated at, the Early Psychosis Prevention and Intervention Centre, Melbourne, Australia. The primary outcome is the Total Score on the Positive and Negative Syndrome Scale which will be administered at baseline, and weeks 4, 8, 12, 26 (primary endpoint), and 52 (end of study). Secondary outcomes include: symptomatology, functioning, quality of life, neurocognition, blood-derived measures of: inflammation, oxidative and nitrosative stress, and magnetic resonance spectroscopy measures of glutathione concentration. DISCUSSION: Targeted drug development for FEP to date has generally not involved the exploration of neuroprotective agents. This study has the potential to offer a new, safe, and efficacious treatment for people with FEP, leading to better treatment outcomes. Additionally, the neuroprotective dimension of this study may lead to a better long-term prognosis for people with FEP. It has the potential to uncover a novel treatment that targets the neurobiological mechanisms of FEP and, if successful, will be a major advance for psychiatry. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ID: ACTRN12618000413224. Registered on 21 March 2018.

Preoperative resolution of jaundice following biliary stenting predicts more favourable early survival in resected pancreatic ductal adenocarcinoma.

INTRODUCTION: Despite the widespread use of endoscopic biliary stenting in patients presenting with potentially resectable pancreatic cancer, there is no general consensus regarding whether this represents a superior management approach over expeditious surgical intervention. The objective of this study was to investigate the influence of preoperative biliary stenting and resolution of jaundice on subsequent postoperative survival following resection for pancreatic cancer. METHODS: 155 patients undergoing partial pancreatoduodenectomy for pancreatic ductal adenocarcinoma between January 1997 and August 2007 were identified from a prospectively maintained database. RESULTS: There was no survival difference when comparing patients undergoing preoperative biliary drainage (n = 130) with those who did not (n = 25) (log rank, P = 0.981). When analysing individual prognostic factors as continuous variables in univariate Cox analysis, lower albumin levels (P = 0.016), elevated alkaline phosphatase levels (P = 0.011) and elevated CRP levels (P = 0.021) were associated with poorer overall survival. Multivariable Cox regression demonstrated that both albumin (P = 0.008) and CRP (P = 0.038) remained significant independent predictors of overall survival alongside lymph node ratio (P = 0.018). Although preoperative bilirubin levels were not associated with overall survival when analysed as a continuous variable (Cox, P = 0.786), the presence of jaundice (i.e., bilirubin >35 micromol/l) at the time of surgery was a significant adverse predictor of early survival in patients undergoing preoperative biliary drainage (Breslow-Gehan-Wilcoxon, P = 0.013) and remained a significant predictor of early survival when included in a further Cox analysis with censoring of cases who survived beyond 6 months (Cox, P = 0.017). CONCLUSION: These results suggest that the presence of jaundice at the time of resection has an adverse impact on early, but not overall, postoperative survival in pancreatic cancer patients undergoing preoperative biliary drainage.