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Due to the global SARS-CoV-2 pandemic, in-person laboratory medicine clerkships were converted to distance learning. The remote clerkship format provided advantages of allowing participation of students from more locations and greater scheduling flexibility but provided new challenges of maintaining learner engagement and providing experiential content of the laboratory environment. Gamification of educational content is one educational modality that has shown effectiveness in a multitude of different contexts to increase learner engagement and retention. Therefore, we created an interactive, educational 360° virtual reality walkthrough tour using off-the-shelf commercially available 360° cameras and software of the Transfusion service and Microbiology Laboratories. The process consists of taking multiple 360° still-images within the space, color-correction, blurring the faces of staff or sensitive information, adding navigation buttons, and other interactive elements. The virtual tours were used for both recruitment and education with further plans to integrate the learning modality into the curriculum. The clerkship is likely to remain as partially or fully as remote learning so such walkthrough tours will continue to remain relevant. This technology can be applied globally to other departments and institutions for education or recruitment.
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COVID-19 , Realidade Virtual , COVID-19/epidemiologia , Currículo , Humanos , Laboratórios , Pandemias , SARS-CoV-2RESUMO
Citrullination of arginine residues is a post-translational modification (PTM) found on myelin basic protein (MBP), which neutralizes MBPs positive charge, and is implicated in myelin damage and multiple sclerosis (MS). Here we identify lysine acetylation as another neutralizing PTM to MBP that may be involved in myelin damage. We quantify changes in lysine and arginine PTMs on MBP derived from mice induced with an experimental autoimmune encephalomyelitis (EAE) model of MS using liquid chromatography tandem mass spectrometry. The changes in PTMs are correlated to changes in neurological disability scoring (NDS), as a marker of myelin damage. We found that lysine acetylation increased by 2-fold on MBP during peak NDS post-EAE induction. We also found that mono- and dimethyl-lysine, as well as asymmetric dimethyl-arginine residues on MBP were elevated at peak EAE disability. These findings suggest that the acetylation and methylation of lysine on MBP are PTMs associated with the neurological disability produced by EAE. Since histone deacetylase (HDAC) inhibitors have been previously shown to improve neurological disability, we also show that treatment with trichostatin A (a HDAC inhibitor) improves the NDS of EAE mice but does not change MBP acetylation.
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Encefalomielite Autoimune Experimental/metabolismo , Lisina/metabolismo , Proteína Básica da Mielina/metabolismo , Doenças do Sistema Nervoso/etiologia , Acetilação , Animais , Inibidores de Histona Desacetilases/farmacologia , Ácidos Hidroxâmicos/farmacologia , Metilação , Camundongos , Esclerose Múltipla/metabolismo , Processamento de Proteína Pós-TraducionalAssuntos
Procedimentos Cirúrgicos Dermatológicos/métodos , Dermatopatias/cirurgia , Neoplasias Cutâneas/cirurgia , Contraindicações de Procedimentos , Procedimentos Cirúrgicos Dermatológicos/efeitos adversos , Procedimentos Cirúrgicos Dermatológicos/instrumentação , Humanos , Pele/anatomia & histologia , Dermatopatias/diagnósticoRESUMO
BACKGROUND: Discordant practice patterns may be a consequence of evidence-practice gaps or deficiencies in knowledge translation. We examined the current strategies used by hepato-pancreatico-biliary (HPB) surgeons in Canada for the perioperative management of pancreaticoduodenectomy (PD). METHODS: We generated a web-based survey that focused on the perioperative measures surrounding PD. The survey was distributed to all members of the Canadian Hepato-Pancreatico-Biliary Association. RESULTS: The survey was distributed to 74 surgeons and received a response rate of 50%. Many similarities in surgical techniques were reported; for example, most surgeons (86.5%) reconstruct the pancreas with pancreaticojejunostomy rather than pancreaticogastrostomy. In contrast, variable techniques regarding the use of peritoneal drainage tubes, anastomotic stents, octreotide and other intraoperative modalities were reported. Most surgeons (75.7%) reported that their patients frequently required preoperative biliary drainage, yet there was minimal agreement with the designated criteria. There was variability in postoperative care, including the use of epidural analgesia and timing of postoperative oral nutrition. CONCLUSION: We identified heterogeneity among Canadian HPB surgeons, suggesting a number of evidence-practice gaps within specific domains of pancreatic resections. Focused research in these areas may facilitate technical agreement and improve patient outcomes following PD.
CONTEXTE: La discordance entre les modes de pratique pourrait être due à des lacunes au plan des pratiques fondées sur des preuves ou à une déficience du transfert des connaissances. Nous avons étudié les stratégies actuellement utilisées par les chirurgiens hépato-pancréato-biliaires (HPB) au Canada pour la prise en charge périopératoire de la pancréatoduodénectomie (PD). MÉTHODES: Nous avons préparé un questionnaire électronique sur les mesures périopératoires entourant la PD. Le questionnaire a été distribué à tous les membres de l'Association hépato-pancréato-biliaire canadienne. RÉSULTANTS: Le questionnaire a été distribué à 74 chirurgiens et a généré un taux de réponse de 50 %. De nombreuses similitudes dans les techniques chirurgicales ont été signalées : par exemple, la majorité des chirurgiens (86,5 %) reconstruisent le pancréas par pancréatojéjunostomie plutôt que par pancréatogastrostomie. En revanche, on a observé une variabilité dans les techniques d'utilisation des drains péritonéaux, des endoprothèses anastomotiques, des octréotides et autres modalités peropératoires. La majorité des chirurgiens (75,7 %) ont signalé que leurs patients avaient souvent besoin de drains biliaires préopératoires et pourtant, les critères désignés ne semblaient pas faire l'unanimité. On a aussi noté des différences dans les soins postopératoires, y compris en ce qui concerne le recours à l'analgésie péridurale et le moment de la reprise de l'alimentation orale après la chirurgie. CONCLUSION: Nous avons observé une hétérogénéité dans la pratique des chirurgiens HPB canadiens, ce qui donne à penser qu'il existe des lacunes au plan des pratiques fondées sur des preuves pour certains aspects précis des résections pancréatiques. Une recherche plus approfondie sur ces aspects pourrait favoriser le consensus technique et améliorer les résultats chez les patients après une PD.
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Pesquisas sobre Atenção à Saúde , Pancreaticoduodenectomia , Assistência Perioperatória , Analgesia Epidural/estatística & dados numéricos , Canadá , Fármacos Gastrointestinais/uso terapêutico , Humanos , Octreotida/uso terapêutico , Pancreaticoduodenectomia/métodos , StentsRESUMO
BACKGROUND: Heterogeneity in practice provides an opportunity for further study, as it may [IRT Rev 1] reflect deficiencies in knowledge translation or knowledge gaps. This survey aimed to assess practice patterns for the surgical treatment of malignancies of the liverwith the goal of identifying areas of variability. METHODS: We created a web-based survey focusing on scope of surgical practice, pre-and post-operative measures and practice patterns for liver and biliary surgery. We piloted the survey for clarity and made changes as needed. All members of the Canadian Hepato-Pancreatico-Biliary Association (CHPBA) were invited to participate. Descriptive statistics were used to analyze the results. RESULTS: The survey was sent to sixty-nine surgeons and thirty-six (52%) completed the survey in its entirety. Areas of agreement include defining the resectability of a tumourand in imaging modalities used to determine resectability. Variability surrounded utlilization of blood conservation strategies, withlow CVP anesthesia frequently used and all other strategies (autologous blood donation, acute normovolemic hemodilution, cell-saver, and tranexamic acid) rarely used. Post-operative analgesic technique was variable with epidural analgesia (50%) and IV-PCA (35.3%) nearly equally preferred. CONCLUSIONS: There is variability in some techniques and approaches used by hepatobiliary surgeons. Future research focusing on areas of uncertainty including techniques of blood conservation and post-operative analgesia are needed.
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Neoplasias Colorretais/patologia , Hepatectomia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Procedimentos Médicos e Cirúrgicos sem Sangue , Canadá , Pressão Venosa Central , HumanosRESUMO
This is a case of a 35-year-old postpartum female presenting to the emergency department (ED) with acute onset chest pain and dyspnea with initial concern for acute ST-segment elevation myocardial infarct (STEMI). Her electrocardiogram (ECG) showed ST segment elevations in the lateral leads and inferior leads with depressions in the high lateral and septal leads. Given her post-partum status, spontaneous coronary artery dissection (SCAD) was part of the differential as well as other emergent processes. Upon cardiac catheterization, the patient was found to have 50% vasospasm in the left circumflex coronary artery. Her post-catheterization echocardiogram showed a normal ejection fraction (EF) without regional wall abnormalities. This is an interesting case of chest pain in a younger patient, without typical acute coronary syndrome (ACS) risk factors, presenting with a concerning ECG likely due to coronary vasospasm. We will discuss other atypical causes of STEMI patterns that should be considered in the differential and management of such patients. Topics: Sickle cell trait, STEMI, postpartum, vasospasm, ECG, cardiology.
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BACKGROUND: The surgical approach to the volar structures in the digits must be designed to provide adequate exposure of tendons, vessels and nerves but also in a way that prevents flexion contracture of the digit as the scar contracts. This is traditionally done using a zigzag 'Bruner' incision, first described by Dr Julian M Bruner in 1967. In this paper, we describe an alternative approach, the Volar Oblique incision, and present a single institutional cohort of patients who have undergone procedures beginning with this approach. METHODS: A retrospective cohort study was performed on eight cases that involved a Bruner incision and eight similar cases that involved a volar oblique incision. Charts were reviewed for demographic data. Patients were asked to return to clinic postoperatively for scar assessment using the Patient and Observer Scar Assessment Scale (POSAS), where lower scores correspond to more favourable scar characteristics. The average follow-up period was 22 months. While in clinic, standard joint measurements were taken to assess for any proximal interphalangeal joint contracture. Demographics and questionnaire data were analysed using the Mann-Whitney U test for non-parametric data and quantitative joint measurements were analysed using Student's t-test. RESULTS: There was no difference in flexion contracture between the two groups. The POSAS patient score for scar irregularity was lower in the volar oblique group compared to the Bruner group, but there was no difference in any of the other subcategories, the total patient score, nor the overall patient opinion. The total POSAS observer score was lower in the volar oblique group compared to the Bruner group, with lower scores in the scar thickness, observed relief and observed pliability subcategories as well as the overall observer opinion. CONCLUSION: The volar oblique incision appears to be satisfactory alternative to the classic Bruner incision in hand surgery that requires volar exposure of the digits. Future studies are needed to assess the validity of these findings on a larger scale. LAY SUMMARY: There are various types of incisions that surgeons use when they operate on fingers. When choosing an incision, it is important that the incision provides good exposure to the deeper structures but does not form a tight scar that limits movement of the finger (contracture).A commonly used incision for the palmar side of the finger is the zig-zag or 'Bruner' incision. Some people, however, find this zig-zag scar unappealing. We started using a single diagonal incision, which we have called the volar oblique, instead of the zig-zag Bruner for access to the middle joint of the finger. We wanted to describe the volar oblique technique and then compare the quality of these two scars and also assess if one limits movement of the finger more than the other.Our research found no differences in finger contracture between groups. We did, however, find that patients reported scar irregularity more favourably in the volar oblique group and that surgeons rated scar thickness, relief (roughness) and pliability of the volar oblique scar higher than that of the zig-zag Bruner scar.This research presents a novel surgical technique and compares its results with respect to scar quality and finger contracture to the more traditional zig-zag Bruner approach.
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BACKGROUND: Radiofibrosis of breast tissue compromises breast reconstruction by interfering with tissue viability and healing. Autologous fat transfer may reduce radiotherapy-related tissue injury, but graft survival is compromised by the fibrotic microenvironment. Elevated expression of receptor for hyaluronan-mediated motility (RHAMM; also known as hyaluronan-mediated motility receptor, or HMMR) in wounds decreases adipogenesis and increases fibrosis. The authors therefore developed RHAMM peptide mimetics to block RHAMM profibrotic signaling following radiation. They propose that this blocking peptide will decrease radiofibrosis and establish a microenvironment favoring adipose-derived stem cell survival using a rat mammary fat pad model. METHODS: Rat mammary fat pads underwent a one-time radiation dose of 26 Gy. Irradiated (n = 10) and nonirradiated (n = 10) fat pads received a single intramammary injection of a sham injection or peptide NPI-110. Skin changes were examined clinically. Mammary fat pad tissue was processed for fibrotic and adipogenic markers using quantitative polymerase chain reaction and immunohistochemical analysis. RESULTS: Clinical assessments and molecular analysis confirmed radiation-induced acute skin changes and radiation-induced fibrosis in rat mammary fat pads. Peptide treatment reduced fibrosis, as detected by polarized microscopy of picrosirius red staining, increased collagen ratio of 3:1, reduced expression of collagen-1 crosslinking enzymes lysyl-oxidase, transglutaminase 2, and transforming growth factor ß1 protein, and increased adiponectin, an antifibrotic adipokine. RHAMM was expressed in stromal cell subsets and was downregulated by the RHAMM peptide mimetic. CONCLUSION: Results from this study predict that blocking RHAMM function in stromal cell subsets can provide a postradiotherapy microenvironment more suitable for fat grafting and breast reconstruction.
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Tecido Adiposo/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Fibrose/metabolismo , Receptores de Hialuronatos/metabolismo , Lesões Experimentais por Radiação/metabolismo , Adipogenia/efeitos dos fármacos , Adipogenia/fisiologia , Animais , Biomarcadores/metabolismo , Modelos Animais de Doenças , Fibrose/tratamento farmacológico , Peptídeos/farmacologia , Proteína 2 Glutamina gama-GlutamiltransferaseRESUMO
Malignant cylindroma is a rare and poorly understood cutaneous malignancy. There is a paucity of literature on these lesions, with only a select number of case reports and limited guidelines on management. We present a case of a 60-year old patient with a malignant cylindroma of the scalp treated surgically with staged perimeter excision and summarize our review of the literature with a focus on management of this potentially aggressive disease.
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BACKGROUND: Socioeconomic factors are known to affect outcomes for both medical and surgical conditions. The purpose of this systematic review was to assess the current evidence regarding the effect of socioeconomic factors such as income, geographic location, educational level, and occupation on clinical outcomes after distal radius fractures. METHODS: A systematic search strategy was performed to identify studies commenting on the effect of socioeconomic factors on clinical outcomes following open or closed distal radius fracture repair. Abstract and full-text screening was performed by 2 independent reviewers, and articles were evaluated by Structured Effectiveness Quality Evaluation Scale (SEQES). Treatment outcomes of interest included, but were not limited to, pain, function, range of motion, and grip strength. RESULTS: There were 1745 studies that met our inclusion and exclusion criteria for abstract screening. Of these, 48 studies met our inclusion criteria for full-text screening and 20 studies met our criteria for quality analysis with the SEQES score. There were 3 studies of high quality, 16 of moderate quality, and 1 of low quality. Meta-analyses were not possible due to the variability in outcomes of interest across papers. CONCLUSIONS: Patient factors indicative of socioeconomic status are relevant predictors of functional outcome after distal radius fractures. There is currently limited evidence in this area of research, and further examination should be considered to improve outcomes from a patient and system standpoint.
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Avaliação da Deficiência , Fraturas do Rádio/terapia , Escala Visual Analógica , Escolaridade , Emprego , Humanos , Renda , Ocupações , Fatores Raciais , Fatores SocioeconômicosRESUMO
After the initial responsiveness of triple-negative breast cancers (TNBCs) to chemotherapy, they often recur as chemotherapy-resistant tumors, and this has been associated with upregulated homology-directed repair (HDR). Thus, inhibitors of HDR could be a useful adjunct to chemotherapy treatment of these cancers. We performed a high-throughput chemical screen for inhibitors of HDR from which we obtained a number of hits that disrupted microtubule dynamics. We postulated that high levels of the target molecules of our screen in tumors would correlate with poor chemotherapy response. We found that inhibition or knockdown of dynamin 2 (DNM2), known for its role in endocytic cell trafficking and microtubule dynamics, impaired HDR and improved response to chemotherapy of cells and of tumors in mice. In a retrospective analysis, levels of DNM2 at the time of treatment strongly predicted chemotherapy outcome for estrogen receptor-negative and especially for TNBC patients. We propose that DNM2-associated DNA repair enzyme trafficking is important for HDR efficiency and is a powerful predictor of sensitivity to breast cancer chemotherapy and an important target for therapy.
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Antineoplásicos/farmacologia , Dinaminas/metabolismo , Reparo de DNA por Recombinação , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/enzimologia , Animais , Células CHO , Cricetulus , Dinamina II , Dinaminas/genética , Feminino , Humanos , Camundongos , Camundongos Nus , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, which involves the progressive degeneration of motor neurons. ALS has long been considered a disease of the grey matter; however, pathological alterations of the white matter (WM), including axonal loss, axonal demyelination and oligodendrocyte death, have been reported in patients with ALS. The present review examined motor neuron death as the primary cause of ALS and evaluated the associated WM damage that is guided by neuronalglial interactions. Previous studies have suggested that WM damage may occur prior to the death of motor neurons, and thus may be considered an early indicator for the diagnosis and prognosis of ALS. However, the exact molecular mechanisms underlying earlyonset WM damage in ALS have yet to be elucidated. The present review explored the detailed anatomy of WM and identified several pathological mechanisms that may be implicated in WM damage in ALS. In addition, it associated the pathophysiological alterations of WM, which may contribute to motor neuron death in ALS, with similar mechanisms of WM damage that are involved in multiple sclerosis (MS). Furthermore, the early detection of WM damage in ALS, using neuroimaging techniques, may lead to earlier therapeutic intervention, using immunomodulatory treatment strategies similar to those used in relapsingremitting MS, aimed at delaying WM damage in ALS. Early therapeutic approaches may have the potential to delay motor neuron damage and thus prolong the survival of patients with ALS. The therapeutic interventions that are currently available for ALS are only marginally effective. However, early intervention with immunomodulatory drugs may slow the progression of WM damage in the early stages of ALS, thus delaying motor neuron death and increasing the life expectancy of patients with ALS.
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Esclerose Lateral Amiotrófica/patologia , Substância Branca/patologia , Esclerose Lateral Amiotrófica/tratamento farmacológico , Esclerose Lateral Amiotrófica/genética , Animais , Progressão da Doença , Humanos , Modelos BiológicosRESUMO
BACKGROUND: Perioperative red blood cell transfusions (RBCTs) are common in patients undergoing partial hepatectomy. We sought to explore the relationship between RBCTs and posthepatectomy perioperative outcomes in the contemporary surgical era. METHODS: We reviewed all patients undergoing partial hepatectomy from 2003 to 2012. Primary outcome was 30-day major morbidity (MM). We compared patients who did and received perioperative RBCT (defined as from time of operation until 30 days postoperatively. Multivariate analysis was performed to identify factors associated with MM and duration of stay, using logistic and negative binomial regression. RESULTS: Among 712 patients, 16.8% experienced MM, of whom 53.3% received RBCT. Patients who received RBCT experienced MM more commonly (30.8% vs 11.1%; P < .001). On multivariate analysis, the only factors associated with MM were age (relative risk [RR], 1.03; 95% CI, 1.00-1.06), greater operative time (RR, 1.29; 95% CI, 1.11-1.50), and RBCT (RR, 3.57; 95% CI, 1.81-7.04). RBCT was associated independently with a greater duration of stay (RR, 1.47; 95% CI, 1.13-1.91). CONCLUSION: Receipt of RBCT is associated independently with perioperative MM and prolonged hospitalization after partial hepatectomy. These findings further the rationale supporting the need for a strategy of blood management to decrease the use of RBCT after hepatectomy.
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Transfusão de Eritrócitos , Hepatectomia/efeitos adversos , Complicações Intraoperatórias/epidemiologia , Hepatopatias/cirurgia , Assistência Perioperatória , Complicações Pós-Operatórias/epidemiologia , Fatores Etários , Idoso , Feminino , Humanos , Tempo de Internação , Hepatopatias/mortalidade , Hepatopatias/patologia , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND: Pancreaticoduodenectomy remains a major undertaking with substantial perioperative morbidity and mortality. Previous studies in the colorectal population have noted a correlation between excessive postoperative fluid resuscitation and anastomotic complications. This study sought to assess the relationship between perioperative fluid management and clinical outcomes in patients undergoing pancreaticoduodenectomy. METHODS: Data from a single institution, prospective database over a 10-year period (2002 to 2012) were reviewed. Patients were compared for perioperative fluid balance and postoperative outcomes. Multivariable analysis was performed to assess the relationship between perioperative fluid administration and incidence of major adverse events. RESULTS: Higher positive fluid balance on postoperative day 0, postoperative day 1, and postoperative day 2 was associated with increased incidence of major adverse events, increased postoperative intensive care unit admission, and longer hospital stay. Higher positive fluid balance on postoperative day 0 was most strongly associated with postoperative morbidity (odds ratio 1.39, confidence interval 1.16 to 1.66, P = .0003). Fluid balance on postoperative day 3 was not associated with adverse events. CONCLUSIONS: Increased early perioperative fluid resuscitation is associated with major adverse events in patients undergoing pancreaticoduodenectomy. More restrictive fluid administration may improve postoperative outcomes; further prospective clinical trials focused on fluid resuscitation and goal-directed therapy are needed.
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Hidratação/efeitos adversos , Pancreaticoduodenectomia , Cuidados Pós-Operatórios , Idoso , Fístula Anastomótica/epidemiologia , Canadá/epidemiologia , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Análise Multivariada , Admissão do Paciente/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Equilíbrio HidroeletrolíticoRESUMO
OBJECTIVE: To investigate the impact of industry funding on reporting of subgroup analyses in randomised controlled trials. DESIGN: Systematic review. DATA SOURCES: Medline. STUDY SELECTION: Randomised controlled trials published in 118 core clinical journals (defined by the National Library of Medicine) in 2007. 1140 study reports in a 1:1 ratio by high (five general medicine journals with largest number of total citations in 2007) versus lower impact journals, were randomly sampled. Two reviewers, independently and in duplicate, used standardised, piloted forms to screen study reports for eligibility and to extract data. They also used explicit criteria to determine whether a randomised controlled trial reported subgroup analyses. Logistic regression was used to examine the association of prespecified study characteristics with reporting versus not reporting of subgroup analyses. RESULTS: 469 randomised controlled trials were included, of which 207 (44%) reported subgroup analyses. High impact journals (adjusted odds ratio 2.64, 95% confidence interval 1.62 to 4.33), non-surgical (versus surgical) trials (2.10, 1.26 to 3.50), and larger sample size (3.38, 1.64 to 6.99) were associated with more frequent reporting of subgroup analyses. The strength of association between trial funding and reporting of subgroups differed in trials with and without statistically significant primary outcomes (interaction P=0.02). In trials without statistically significant results for the primary outcome, industry funded trials were more likely to report subgroup analyses (2.29, 1.30 to 4.72) than non-industry funded trials. This was not true for trials with a statistically significant primary outcome (0.79, 0.46 to 1.36). Industry funded trials were associated with less frequent prespecification of subgroup hypotheses (31.3% v 38.0%, adjusted odds ratio 0.49, 0.26 to 0.94), and less use of the interaction test for analyses of subgroup effects (41.4% v 49.1%, 0.52, 0.28 to 0.97) than non-industry funded trials. CONCLUSION: Industry funded randomised controlled trials, in the absence of statistically significant primary outcomes, are more likely to report subgroup analyses than non-industry funded trials. Industry funded trials less frequently prespecify subgroup hypotheses and less frequently test for interaction than non-industry funded trials. Subgroup analyses from industry funded trials with negative results for the primary outcome should be viewed with caution.