204 results on '"H. Kennedy"'
Search Results
2. Machine Learning and Causal Inference
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Paul N. Zivich, Alexander Breskin, and Edward H. Kennedy
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- 2022
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3. Nitrous oxide for the treatment of psychiatric disorders: A systematic review of the clinical trial landscape
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Helen Liu, Jaimie Kerzner, Ilya Demchenko, Duminda N. Wijeysundera, Sidney H. Kennedy, Karim S. Ladha, and Venkat Bhat
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Stress Disorders, Post-Traumatic ,Depressive Disorder, Major ,Psychiatry and Mental health ,Bipolar Disorder ,Nitrous Oxide ,Humans - Abstract
To systematically review published research studies and ongoing clinical trials investigating nitrous oxide (NA comprehensive literature search was conducted for studies published until June 2021 using the OVID databases (MEDLINE, Embase, APA PsycInfo) and the clinical trial registries (ClinicalTrials.gov, ICTRP).In total, five relevant published articles were identified, among which four investigated NPreliminary studies support the feasibility of administering N
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- 2022
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4. <scp> ABCB1 </scp> Gene Variants and Antidepressant Treatment Outcomes: A Systematic Review and Meta‐Analysis Including Results from the <scp>CAN‐BIND</scp> ‐1 Study
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Leen Magarbeh, Claudia Hassel, Maximilian Choi, Farhana Islam, Victoria S. Marshe, Clement C. Zai, Rayyan Zuberi, Roseann S. Gammal, Xiaoyu Men, Maike Scherf‐Clavel, Dietmar Enko, Benicio N. Frey, Roumen Milev, Claudio N. Soares, Sagar V. Parikh, Franca Placenza, Stephen C. Strother, Stefanie Hassel, Valerie H. Taylor, Francesco Leri, Pierre Blier, Faranak Farzan, Raymond W. Lam, Gustavo Turecki, Jane A. Foster, Susan Rotzinger, Stefan Kloiber, James L. Kennedy, Sidney H. Kennedy, Chad A. Bousman, and Daniel J. Müller
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Pharmacology ,Pharmacology (medical) - Published
- 2023
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5. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) recommendations for the management of patients with bipolar disorder with mixed presentations
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Claire O'Donovan, Joseph R. Calabrese, Ayal Schaffer, Roumen Milev, Eduard Vieta, Serge Beaulieu, Sagar V. Parikh, Gin S Malhi, Roger S. McIntyre, Raymond W. Lam, Michael Berk, David J. Bond, Sidney H. Kennedy, Benjamin I. Goldstein, Flávio Kapczinski, Benicio N. Frey, Martin Alda, Arun V. Ravindran, Márcia Kauer-Sant'Anna, Lakshmi N. Yatham, Trisha Chakrabarty, Jan-Marie Kozicky, Trisha Suppes, Verinder Sharma, Robert M. Post, Soham Rej, Valérie Tourjman, Shigenobu Kanba, and Gustavo Vazquez
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Divalproex ,Canada ,medicine.medical_specialty ,Bipolar Disorder ,Aripiprazole ,Cariprazine ,Anxiety ,chemistry.chemical_compound ,medicine ,Humans ,Asenapine ,Bipolar disorder ,Psychiatry ,Biological Psychiatry ,Lurasidone ,business.industry ,Valproic Acid ,medicine.disease ,Psychiatry and Mental health ,chemistry ,Olanzapine ,Quetiapine ,medicine.symptom ,business ,Mania ,Antipsychotic Agents ,medicine.drug - Abstract
Objectives The 2018 Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) guidelines provided clinicians with pragmatic treatment recommendations for bipolar disorder (BD). While these guidelines included commentary on how mixed features may direct treatment selection, specific recommendations were not provided- a critical gap which the current update aims to address. Method Overview of research regarding mixed presentations in BD, with treatment recommendations developed using a modified CANMAT/ISBD rating methodology. Limitations are discussed, including the dearth of high-quality data and reliance on expert opinion. Results No agents met threshold for first line treatment of DSM-5 manic or depressive episodes with mixed features. For mania + mixed features second line treatment options include asenapine, cariprazine, divalproex, and aripiprazole. In depression + mixed features, cariprazine and lurasidone are recommended as second line options. For DSM-IV defined mixed episodes, with a longer history of research, asenapine and aripiprazole are first line, and olanzapine (monotherapy or combination), carbamazepine, and divalproex are second line. Research on maintenance treatments following a DSM-5 mixed presentation is extremely limited, with third-line recommendations based on expert opinion. For maintenance treatment following a DSM-IV mixed episode, quetiapine (monotherapy or combination) is first line, and lithium and olanzapine identified as second line options. Conclusion The CANMAT and ISBD groups hope these guidelines provide valuable support for clinicians providing care to patients experiencing mixed presentations, as well as further influence investment in research to improve diagnosis and treatment of this common and complex clinical state.
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- 2021
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6. Brain age in mood and psychotic disorders: a systematic review and meta‐analysis
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Maria T. Romano, Sidney H. Kennedy, Taiane de Azevedo Cardoso, Stefanie Hassel, Benicio N. Frey, Stephen C. Strother, and Pedro Ballester
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medicine.medical_specialty ,Psychosis ,business.industry ,medicine.disease ,Psychiatry and Mental health ,Mood ,Neuroimaging ,Schizophrenia ,Meta-analysis ,medicine ,Major depressive disorder ,Bipolar disorder ,Psychiatry ,business ,Brain aging - Abstract
OBJECTIVE To evaluate whether accelerated brain aging occurs in individuals with mood or psychotic disorders. METHODS A systematic review following PRISMA guidelines was conducted. A meta-analysis was then performed to assess neuroimaging-derived brain age gap in three independent groups: (1) schizophrenia and first-episode psychosis, (2) major depressive disorder, and (3) bipolar disorder. RESULTS A total of 18 papers were included. The random-effects model meta-analysis showed a significantly increased neuroimaging-derived brain age gap relative to age-matched controls for the three major psychiatric disorders, with schizophrenia (3.08; 95%CI [2.32; 3.85]; p
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- 2021
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7. Effect of Body Size on Methylmercury Concentrations in Shoreline Spiders: Implications for Their Use as Sentinels
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Madeline P. Hannappel, Lexton P. Trauffler, Benjamin D. Barst, J. Margaret Castellini, Matthew M. Chumchal, Ray W. Drenner, Audrey R. Nolan, James H. Kennedy, and F. Manton Willoughby
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0106 biological sciences ,Health, Toxicology and Mutagenesis ,Zoology ,Schizocosa ,010501 environmental sciences ,Body size ,010603 evolutionary biology ,01 natural sciences ,chemistry.chemical_compound ,Animals ,Body Size ,Environmental Chemistry ,Methylmercury ,0105 earth and related environmental sciences ,Pardosa ,Shore ,Spider ,geography ,geography.geographical_feature_category ,biology ,Spiders ,Methylmercury Compounds ,biology.organism_classification ,Texas ,chemistry ,Bioaccumulation ,Tetragnatha - Abstract
Shoreline spiders have been proposed as sentinels to monitor aquatic contaminants including methylmercury (MeHg). The present study examined the effect of spider body size on MeHg concentrations in shoreline spiders. We collected 6 taxa of spiders belonging to 4 families (orb-weavers [Araneidae], long-jawed orb weavers [Tetragnathidae: Tetragnatha sp.], jumping spiders [Salticidae], and wolf spiders [Lycosidae: Pardosa sp., Rabidosa sp., and Schizocosa sp.]) from the shorelines of 14 human-made ponds at the Lyndon B. Johnson National Grasslands in north Texas (USA). As a proxy for body size, we measured leg length (tibia + patella) of each spider. Spider taxa differed by 3-fold in mean MeHg concentration, and MeHg concentrations in 4 of 6 spider taxa increased significantly with leg length. The present study is the first to demonstrate that shoreline spider MeHg concentrations increase as a function of spider body size. Because spider size may account for some within-taxa variation in MeHg concentrations, future studies that utilize spiders as sentinels of aquatic contamination by MeHg or other biomagnifying contaminants should take spider size into account. Environ Toxicol Chem 2021;40:1149-1154. © 2020 SETAC.
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- 2021
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8. Author response for 'Pregnancy vitamin D supplementation and childhood bone mass at age 4 years: Findings from the <scp>MAVIDOS</scp> Randomised Controlled Trial'
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null Elizabeth M Curtis, null Rebecca J Moon, null Stefania D'Angelo, null Sarah R Crozier, null Nicholas J Bishop, null Jaya Sujatha Gopal‐Kothandapani, null Stephen H Kennedy, null Aris T Papageorghiou, null Robert Fraser, null Saurabh V Gandhi, null Inez Schoenmakers, null Ann Prentice, null Hazel M Inskip, null Keith M Godfrey, null M Kassim Javaid, null Richard Eastell, null Cyrus Cooper, null Nicholas C Harvey, null Nigel K Arden, null Andrew Carr, null Elaine M Dennison, null Michael Clynes, null Stephen J Woolford, null M Zulf Mughal, and null the MAVIDOS Trial Group
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- 2022
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9. Functional imaging in youth at risk for transdiagnostic serious mental illness: Initial results from the <scp>PROCAN</scp> study
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Signe Bray, Benjamin I. Goldstein, Jean Addington, Bradley J. MacIntosh, Catherine Lebel, Paul D. Metzak, Stefanie Hassel, JianLi Wang, Sidney H. Kennedy, and Glenda MacQueen
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Canada ,Adolescent ,Brain activity and meditation ,Emotions ,Cognitive neuroscience ,Asymptomatic ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Family history ,Biological Psychiatry ,Motivation ,medicine.diagnostic_test ,Working memory ,business.industry ,Mental Disorders ,Mental illness ,medicine.disease ,Magnetic Resonance Imaging ,030227 psychiatry ,Functional imaging ,Psychiatry and Mental health ,Pshychiatric Mental Health ,medicine.symptom ,Functional magnetic resonance imaging ,business ,030217 neurology & neurosurgery ,Clinical psychology - Abstract
Background In their early stages, serious mental illnesses (SMIs) are often indistinguishable from one another, suggesting that studying alterations in brain activity in a transdiagnostic fashion could help to understand the neurophysiological origins of different SMI. The purpose of this study was to examine brain activity in youth at varying stages of risk for SMI using functional magnetic resonance imaging tasks (fMRI) that engage brain systems believed to be affected. Methods Two hundred and forty three participants at different stages of risk for SMI were recruited to the Canadian Psychiatric Risk and Outcome (PROCAN) study, however only 179 were scanned. Stages included asymptomatic participants at no elevated risk, asymptomatic participants at elevated risk due to family history, participants with undifferentiated general symptoms of mental illness, and those experiencing attenuated versions of diagnosable psychiatric illnesses. The fMRI tasks included: (1) a monetary incentive delay task; (2) an emotional Go-NoGo and (3) an n-back working memory task. Results Strong main effects with each of the tasks were found in brain regions previously described in the literature. However, there were no significant differences in brain activity between any of the stages of risk for SMI for any of the task contrasts, after accounting for site, sex and age. Furthermore, results indicated no significant differences even when participants were dichotomized as asymptomatic or symptomatic. Conclusions These results suggest that univariate BOLD responses during typical fMRI tasks are not sensitive markers of SMI risk and that further study, particularly longitudinal designs, will be necessary to understand brain changes underlying the early stages of SMI.
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- 2020
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10. Improving Identification of Patients at Low Risk for Major Cardiac Events After Noncardiac Surgery Using Intraoperative Data
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Amol S. Navathe, Mark D. Neuman, Victor J. Lei, Mark G. Weiner, Daniel Polsky, Peter W. Groeneveld, Xinwei Chen, Lee A. Fleisher, Edward H. Kennedy, ThaiBinh Luong, Kevin G. Volpp, and John H. Holmes
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medicine.medical_specialty ,Heart Diseases ,Leadership and Management ,Revised Cardiac Risk Index ,030204 cardiovascular system & hematology ,Assessment and Diagnosis ,Logistic regression ,Risk Assessment ,03 medical and health sciences ,Postoperative Complications ,0302 clinical medicine ,Risk Factors ,medicine ,Humans ,cardiovascular diseases ,030212 general & internal medicine ,Risk factor ,Care Planning ,Original Research ,Retrospective Studies ,Receiver operating characteristic ,business.industry ,Health Policy ,Retrospective cohort study ,General Medicine ,Guideline ,Perioperative ,United States ,Emergency medicine ,Female ,Fundamentals and skills ,business ,Mace - Abstract
BACKGROUND/OBJECTIVE: Risk-stratification tools for cardiac complications after noncardiac surgery based on preoperative risk factors are used to inform postoperative management. However, there is limited evidence on whether risk stratification can be improved by incorporating data collected intraoperatively, particularly for low-risk patients. METHODS: We conducted a retrospective cohort study of adults who underwent noncardiac surgery between 2014 and 2018 at four hospitals in the United States. Logistic regression with elastic net selection was used to classify in-hospital major adverse cardiovascular events (MACE) using preoperative and intraoperative data (“perioperative model”). We compared model performance to standard risk stratification tools and professional society guidelines that do not use intraoperative data. RESULTS: Of 72,909 patients, 558 (0.77%) experienced MACE. Those with MACE were older and less likely to be female. The perioperative model demonstrated an area under the receiver operating characteristic curve (AUC) of 0.88 (95% CI, 0.85-0.92). This was higher than the Lee Revised Cardiac Risk Index (RCRI) AUC of 0.79 (95% CI, 0.74-0.84; P < .001 for AUC comparison). There were more MACE complications in the top decile (n = 1,465) of the perioperative model’s predicted risk compared with that of the RCRI model (n = 58 vs 43). Additionally, the perioperative model identified 2,341 of 7,597 (31%) patients as low risk who did not experience MACE but were recommended to receive postoperative biomarker testing by a risk factor–based guideline algorithm. CONCLUSIONS: Addition of intraoperative data to preoperative data improved prediction of cardiovascular complication outcomes after noncardiac surgery and could potentially help reduce unnecessary postoperative testing.
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- 2020
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11. Facing the Giant: A Framework to Undo<scp>Sex‐Based</scp>Discrimination in Academia
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Alan H. Kennedy and Sebawit G. Bishu
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Marketing ,Public Administration ,Sociology and Political Science ,business.industry ,Internet privacy ,Undo ,Psychology ,business - Published
- 2020
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12. Reliability of a functional magnetic resonance imaging task of emotional conflict in healthy participants
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Glenda MacQueen, Benicio N. Frey, Stephen R. Arnott, Gulshan B. Sharma, Roumen Milev, Andrew D. Davis, Gésine L. Alders, Raymond W. Lam, Daniel J. Müller, Stephen C. Strother, Jacqueline K. Harris, Stefanie Hassel, Mojdeh Zamyadi, Susan Rotzinger, Geoffrey B. Hall, and Sidney H. Kennedy
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Male ,Emotions ,Audiology ,Task (project management) ,Conflict, Psychological ,Correlation ,0302 clinical medicine ,Image Processing, Computer-Assisted ,Emotional conflict ,Research Articles ,Reliability (statistics) ,Cerebral Cortex ,Brain Mapping ,Radiological and Ultrasound Technology ,medicine.diagnostic_test ,Depression ,fMRI ,05 social sciences ,Middle Aged ,Magnetic Resonance Imaging ,Healthy Volunteers ,Neurology ,emotional conflict ,Biomarker (medicine) ,Female ,CAN‐BIND ,Anatomy ,Psychology ,Research Article ,Adult ,medicine.medical_specialty ,Adolescent ,behavioral disciplines and activities ,050105 experimental psychology ,Young Adult ,03 medical and health sciences ,Predictive Value of Tests ,Functional neuroimaging ,test–retest reliability ,Reaction Time ,medicine ,Humans ,0501 psychology and cognitive sciences ,Radiology, Nuclear Medicine and imaging ,emotional Stroop ,Neural correlates of consciousness ,ICC ,Reproducibility of Results ,Oxygen ,Stroop Test ,Neurology (clinical) ,Functional magnetic resonance imaging ,Biomarkers ,Psychomotor Performance ,030217 neurology & neurosurgery - Abstract
Task‐based functional neuroimaging methods are increasingly being used to identify biomarkers of treatment response in psychiatric disorders. To facilitate meaningful interpretation of neural correlates of tasks and their potential changes with treatment over time, understanding the reliability of the blood‐oxygen‐level dependent (BOLD) signal of such tasks is essential. We assessed test–retest reliability of an emotional conflict task in healthy participants collected as part of the Canadian Biomarker Integration Network in Depression. Data for 36 participants, scanned at three time points (weeks 0, 2, and 8) were analyzed, and intra‐class correlation coefficients (ICC) were used to quantify reliability. We observed moderate reliability (median ICC values between 0.5 and 0.6), within occipital, parietal, and temporal regions, specifically for conditions of lower cognitive complexity, that is, face, congruent or incongruent trials. For these conditions, activation was also observed within frontal and sub‐cortical regions, however, their reliability was poor (median ICC
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- 2020
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13. Personality and risk for serious mental illness
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Catherine Lebel, Olga Santesteban-Echarri, Signe Bray, Benjamin I. Goldstein, Sidney H. Kennedy, Jean Addington, JianLi Wang, and Glenda MacQueen
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Adolescent ,Personality Inventory ,media_common.quotation_subject ,Anxiety ,Personality Disorders ,03 medical and health sciences ,0302 clinical medicine ,mental disorders ,medicine ,Humans ,Personality ,Big Five personality traits ,Biological Psychiatry ,media_common ,Neuroticism ,Extraversion and introversion ,business.industry ,Mental Disorders ,Conscientiousness ,Mental illness ,medicine.disease ,030227 psychiatry ,Psychiatry and Mental health ,Mood ,Pshychiatric Mental Health ,medicine.symptom ,business ,030217 neurology & neurosurgery ,Clinical psychology - Abstract
Aim Certain personality traits may be related to an increased risk of developing a severe mental illness (SMI). This study examined differences in personality characteristics in a sample of youth at-risk of SMI across different clinical stages compared to healthy controls (HCs). Method Personality characteristics were assessed with the NEO-Five-Factor Inventory-3 for 41 non-help seeking asymptomatic youth with risk factors for SMI (Stage 0), 52 youth with early mood and anxiety symptoms and distress (Stage 1a), 108 youth with an attenuated psychiatric syndrome (Stage 1b), and 42 HCs. Results Symptomatic participants scored significantly higher in neuroticism, and lower in extraversion, and conscientiousness compared to non-symptomatic participants. Compared to published norms, symptomatic participants had ratings of extraversion and conscientiousness in the low range and those with attenuated psychiatric syndromes scored high on neuroticism. Conclusion The observed personality profiles of the symptomatic stages were similar to reported profiles for discrete disorders. Early identification of this profile could aid identification of those at risk of SMI.
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- 2020
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14. Pretreatment anxious depression as a predictor of side effect frequency and severity in escitalopram and aripiprazole adjunctive therapy
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Caroline W, Espinola, Yuelee, Khoo, Roohie, Parmar, Ilya, Demchenko, Benicio N, Frey, Roumen V, Milev, Arun V, Ravindran, Sagar V, Parikh, Keith, Ho, Susan, Rotzinger, Wendy, Lou, Raymond W, Lam, Sidney H, Kennedy, and Venkat, Bhat
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Depressive Disorder, Major ,Behavioral Neuroscience ,Escitalopram ,Treatment Outcome ,Drug-Related Side Effects and Adverse Reactions ,Depression ,Aripiprazole ,Humans ,Drug Therapy, Combination - Abstract
To report side effect frequency and severity in patients with major depressive disorder (MDD) receiving escitalopram and aripiprazole adjunctive therapy and to examine whether pretreatment anxious depression is associated with the number and presence of specific side effects.188 of the 211 trial participants provided information on side effects during treatment with escitalopram (10-20 mg) for 8 weeks, and nonresponders received further augmentation on aripiprazole (2-10 mg) adjunctive therapy for another 8 weeks, whereas responders remained on escitalopram. Participants completed the Toronto Side Effects Scale at weeks 2, 4, 10, and 12. Covariate-adjusted negative binomial regression and Wilcoxon tests examined the association between anxious depression (GAD-7 ≥ 10) and number of side effects. Covariate-adjusted logistic regression and chi-square tests explored the association between anxious depression and specific side effects.For both therapies, the most frequent side effects were also the most severe. They mostly related to the central nervous system (CNS) (i.e., drowsiness and nervousness). Between baseline and week 2, the number of side effects participants experienced (incidence rate ratio [IRR] = 1.38, p = .010) or had trouble with (IRR = 1.34, p = .026) was significantly higher among those with anxious depression for escitalopram but not adjunctive aripiprazole. Further, odds of experiencing and having trouble with nervousness and agitation were also significantly higher in anxious depression for escitalopram only (p .05).Patients on escitalopram and aripiprazole adjunctive therapy may experience and have trouble with CNS side effects. Pretreatment anxious depression may predispose escitalopram recipients with MDD to developing side effects, especially those related to anxiety.
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- 2022
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15. Author response for 'Pretreatment anxious depression as a predictor of side effect frequency and severity in escitalopram and aripiprazole adjunctive therapy'
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null Caroline W. Espinola, null Yuelee Khoo, null Roohie Parmar, null Ilya Demchenko, null Benicio N. Frey, null Roumen V. Milev, null Arun V. Ravindran, null Sagar V. Parikh, null Keith Ho, null Susan Rotzinger, null Wendy Lou, null Raymond W. Lam, null Sidney H. Kennedy, null Venkat Bhat, and null the CAN‐BIND Investigator Team
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- 2022
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16. Functional analysis and intervention of perseverative speech in students with high‐functioning autism and related neurodevelopmental disabilities
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Abby V. Santos, Emily M. Kuntz, and Craig H. Kennedy
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Male ,050103 clinical psychology ,Adolescent ,Sociology and Political Science ,Psychological intervention ,Developmental psychology ,Applied Behavior Analysis ,Intervention (counseling) ,otorhinolaryngologic diseases ,medicine ,Humans ,Speech ,Attention ,0501 psychology and cognitive sciences ,Autistic Disorder ,Child ,Students ,Reinforcement ,Applied Psychology ,Verbal Behavior ,05 social sciences ,Extinction (psychology) ,medicine.disease ,Differential reinforcement ,High-functioning autism ,Philosophy ,Autism ,Female ,Psychology ,Reinforcement, Psychology ,Functional analysis (psychology) - Abstract
Although perseverative speech is a common characteristic of individuals with high-functioning neurodevelopmental disabilities, little is known about the operant functions of these verbalizations. We conducted analogue functional analyses of perseverative speech for 2 students using reinforcement contingencies that included alone, attention, control, escape, and tangible conditions. Results showed the following patterns: attention only (Charlotte) or multiply determined including an attention function (Paul). We then tested an intervention for perseverative speech maintained by social positive reinforcement that included differential reinforcement of alternative behavior and extinction of perseverative speech for 1 participant. The intervention reduced perseverative speech, but did not increase appropriate speech until we added a prompting component. We then replicated this three-component intervention with Paul. The results showed moderate to high decreases in levels of perseverative speech and increased appropriate verbalizations in both cases. The results systematically replicated the interventions of previous studies by adding a prompting component to the intervention.
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- 2019
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17. Sleep disturbances in youth at‐risk for serious mental illness
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JianLi Wang, Kali Brummitt, Jacqueline Stowkowy, Dominique Bonneville, Catherine Lebel, Sidney H. Kennedy, Glenda MacQueen, Jean Addington, Benjamin I. Goldstein, and Signe Bray
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Adult ,Male ,Sleep Wake Disorders ,Psychosis ,medicine.medical_specialty ,Adolescent ,Asymptomatic ,Pittsburgh Sleep Quality Index ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Humans ,Medicine ,Child ,Psychiatry ,Biological Psychiatry ,Depression (differential diagnoses) ,business.industry ,Mental Disorders ,medicine.disease ,Mental illness ,Sleep in non-human animals ,030227 psychiatry ,Psychiatry and Mental health ,Distress ,Psychotic Disorders ,Subjective sleep ,Female ,Pshychiatric Mental Health ,medicine.symptom ,Sleep ,business ,030217 neurology & neurosurgery - Abstract
AIM To investigate sleep behaviours of youth at-risk for serious mental illness (SMI). METHODS This study included 243 youth, ages 12 to 25:42 healthy controls, 41 asymptomatic youth at-risk for mental illness (stage 0); 53 help-seeking youth experiencing distress (stage 1a) and 107 youth with attenuated syndromes (stage 1b). The Pittsburgh Sleep Quality Index was used to assess sleep dysfunction. RESULTS Stage 1b individuals indicated the greatest deficit in global sleep dysfunction (F = 26.18, P
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- 2019
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18. The symptom‐specific efficacy of antidepressant medication vs. cognitive behavioral therapy in the treatment of depression: results from an individual patient data meta‐analysis
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Robert J. DeRubeis, Ulrich Hegerl, Jeffrey R. Vittengl, Frank Petrak, Boadie W. Dunlop, Erica Weitz, Sona Dimidjian, Anne D. Simons, Robert A. Schoevers, David L. Dunner, Lynn Boschloo, Robin B. Jarrett, Ella Bekhuis, David C. Mohr, Gordon Parker, Mirjam Reijnders, Zindel V. Segal, Pim Cuijpers, Steven D. Hollon, Sidney H. Kennedy, Stephan Herpertz, Jeanne Miranda, A. John Rush, Lena C. Quilty, Clinical, Neuro- & Developmental Psychology, APH - Mental Health, APH - Global Health, Perceptual and Cognitive Neuroscience (PCN), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), and Clinical Cognitive Neuropsychiatry Research Program (CCNP)
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DISORDER ,medicine.medical_treatment ,psychic anxiety ,law.invention ,depressive symptoms ,0302 clinical medicine ,Randomized controlled trial ,law ,RATING-SCALE ,Depression (differential diagnoses) ,media_common ,OUTCOMES ,Depression ,general somatic symptoms ,Cognitive behavioral therapy ,Psychiatry and Mental health ,Feeling ,suicidal thoughts ,Meta-analysis ,RELIABILITY ,Anxiety ,Pshychiatric Mental Health ,medicine.symptom ,NETWORK STRUCTURE ,medicine.medical_specialty ,media_common.quotation_subject ,behavioral disciplines and activities ,feelings of guilt ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,Rating scale ,PSYCHOTHERAPY ,mental disorders ,precision psychiatry ,medicine ,DIFFERENTIAL CHANGE ,Psychiatry ,business.industry ,Hamilton Rating Scale for Depression ,PHARMACOTHERAPY ,Research Reports ,antidepressant medication ,RANDOMIZED-TRIAL ,cognitive behavioral therapy ,030227 psychiatry ,TREATING DEPRESSION ,depressed mood ,business ,030217 neurology & neurosurgery - Abstract
A recent individual patient data meta-analysis showed that antidepressant medication is slightly more efficacious than cognitive behavioral therapy (CBT) in reducing overall depression severity in patients with a DSM-defined depressive disorder. We used an update of that dataset, based on seventeen randomized clinical trials, to examine the comparative efficacy of antidepressant medication vs. CBT in more detail by focusing on individual depressive symptoms as assessed with the 17-item Hamilton Rating Scale for Depression. Five symptoms (i.e., "depressed mood" , "feelings of guilt" , "suicidal thoughts" , "psychic anxiety" and "general somatic symptoms") showed larger improvements in the medication compared to the CBT condition (effect sizes ranging from .13 to .16), whereas no differences were found for the twelve other symptoms. In addition, network estimation techniques revealed that all effects, except that on "depressed mood" , were direct and could not be explained by any of the other direct or indirect treatment effects. Exploratory analyses showed that information about the symptom-specific efficacy could help in identifying those patients who, based on their pre-treatment symptomatology, are likely to benefit more from antidepressant medication than from CBT (effect size of .30) versus those for whom both treatments are likely to be equally efficacious. Overall, our symptom-oriented approach results in a more thorough evaluation of the efficacy of antidepressant medication over CBT and shows potential in "precision psychiatry" .
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- 2019
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19. THE PATIENT AND CARER EXPERIENCE OF CHIMERIC ANTIGEN RECEPTOR T‐CELL THERAPY FOR RELAPSED/REFRACTORY B‐CELL LYMPHOMA AT A UK REGIONAL CENTRE
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J. Shaw, Tobias Menne, A. Publicover, F. Dewhurst, Wendy Osborne, H. Kennedy, R. Stocker, C. Stenson, and J. Vidrine
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Cancer Research ,medicine.medical_specialty ,Isolation (health care) ,business.industry ,Service delivery framework ,media_common.quotation_subject ,Hematology ,General Medicine ,Family life ,Patient satisfaction ,Oncology ,Feeling ,Family medicine ,medicine ,Anxiety ,Chimeric Antigen Receptor T-Cell Therapy ,Thematic analysis ,medicine.symptom ,business ,media_common - Abstract
Introduction: Chimeric Antigen Receptor T-cell therapy (CAR-T) is a potentially life-saving treatment for refractory haematological malignancies. Many UK CAR-T services are in their infancy. Patient perspectives on service delivery, treatment toxicity and impact on health related quality of life (HRQoL) are lacking. This qualitative evaluation aimed to explore the patient and carer experience of CAR-T and identify areas for service improvement. Methods: Patients who received CAR-T between April 2019 and March 2021 at the Freeman Hospital, Newcastle-upon-Tyne, who attended primary or follow-up appointments between December 2020 and March 2021 were asked if they wanted to take part in the evaluation. 16 semi-structured qualitative interviews were carried out with 10 patients and 4 carers at specific time points in the patient journey: hospital admission prior to CAR T-cell infusion, day 28 postinfusion and routine follow-up appointments after treatment (8, 9, 12 and 18 months). Five patients completed 2 interviews (pre-infusion and day 28). Results: The mean age of the patients was 54 and 60% were female. Nine patients had diffuse large B-cell lymphoma and one had primary mediastinal B-cell lymphoma. Inductive thematic analysis identified three main themes. The importance of the CAR-T nurse specialist as a point of contact was consistently identified by patients and carers as vital to navigating the treatment process. The continuity of care and approachability associated with this role were linked to patient satisfaction and perceived level of support received. Reported treatment toxicity centred on fatigue, poor appetite/weight loss and problems with memory and cognition. Patients and carers were well prepared for side effects in the acute treatment phase but some felt less prepared for prolonged impact on physical function and cognition after discharge. CAR-T therapy was viewed as a 'lifeline,' but the uncertainty of treatment outcome caused significant anxiety, disruption to employment and family life, and made it difficult to make future plans. Many responses were framed by the COVID-19 pandemic which increased feelings of isolation and vulnerability and had a significant, negative impact on HRQoL. Conclusions: To our knowledge this is the first qualitative work exploring the views of CAR-T patients and carers at multiple points in the patient journey, including perspectives on long-term treatment impact. Considerations for service creation and development nationally and internationally include: the importance of a dedicated nurse specialist, preparing patients for and supporting them with prolonged treatment side effects, and the psychological challenges associated with prognostic uncertainty. Expanding indications of CAR-T therapy mean there is an urgent need for multi-centre studies incorporating patient-reported outcome data to inform patient centred care and service delivery.
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- 2021
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20. Searching for tryptase in the RBL-2H3 mast cell model: Preparation for comparative mast cell toxicology studies with zebrafish
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Lisa M. Weatherly, Hina N. Hashmi, Juyoung Shim, Rachel H. Kennedy, Atefeh Rajaei, Julie A. Gosse, and Andrew V. Abovian
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0303 health sciences ,Cell type ,biology ,Chemistry ,Degranulation ,TPSB2 ,hemic and immune systems ,Tryptase ,010501 environmental sciences ,Toxicology ,Mast cell ,01 natural sciences ,TPSAB1 ,In vitro ,Cell biology ,03 medical and health sciences ,medicine.anatomical_structure ,Cell culture ,medicine ,biology.protein ,lipids (amino acids, peptides, and proteins) ,030304 developmental biology ,0105 earth and related environmental sciences - Abstract
Mast cells comprise a physiologically and toxicologically important cell type that is ubiquitous among species and tissues. Mast cells undergo degranulation, in which characteristic intracellular granules fuse with the plasma membrane and release many bioactive substances, such as enzymes β-hexosaminidase and tryptase. Activity of mast cells in the toxicology model organism, zebrafish, has been monitored via tryptase release and cleavage of substrate N-α-benzoyl-dl-Arg-p-nitroanilide (BAPNA). An extensively used in vitro mast cell model for studying toxicant mechanisms is the RBL-2H3 cell line. However, instead of tryptase, granule contents such as β-hexosaminidase have usually been employed as RBL-2H3 degranulation markers. To align RBL-2H3 cell toxicological studies to in vivo mast cell studies using zebrafish, we aimed to develop an RBL-2H3 tryptase assay. Unexpectedly, we discovered that tryptase release from RBL-2H3 cells is not detectable, using BAPNA substrate, despite optimized assay that can detect as little as 1 ng tryptase. Additional studies performed with another substrate, tosyl-Gly-Pro-Lys-pNA, and with an enzyme-linked immunosorbent assay, revealed a lack of tryptase protein released from stimulated RBL-2H3 cells. Furthermore, none of the eight rat tryptase genes (Tpsb2, Tpsab1, Tpsg1, Prss34, Gzmk, Gzma, Prss29, Prss41) is expressed in RBL-2H3 cells, even though all are found in RBL-2H3 genomic DNA and even though β-hexosaminidase mRNA is constitutively expressed. Therefore, mast cell researchers should utilize β-hexosaminidase or another reliable marker for RBL-2H3 degranulation studies, not tryptase. Comparative toxicity testing in RBL-2H3 cells in vitro and in zebrafish mast cells in vivo will require use of a degranulation reporter different from tryptase.
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- 2018
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21. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder
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Sidney H. Kennedy, Gustavo Vazquez, Martin Alda, Gin S Malhi, Claire O'Donovan, Ayal Schaffer, David J. Bond, Jan Marie Kozicky, Trisha Suppes, Verinder Sharma, Eduard Vieta, Roger S. McIntyre, Serge Beaulieu, Raymond W. Lam, Shigenobu Kanba, Glenda MacQueen, Lakshmi N. Yatham, Soham Rej, Benicio N. Frey, Flávio Kapczinski, Arun V. Ravindran, Robert M. Post, Diane McIntosh, Sagar V. Parikh, Beny Lafer, Benjamin I. Goldstein, Roumen Milev, Michael Berk, and Joseph R. Calabrese
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Suicide Prevention ,Divalproex ,Bipolar Disorder ,Bipolar I disorder ,Anxiety ,Bipolar II disorder ,chemistry.chemical_compound ,0302 clinical medicine ,Asenapine ,Child ,Societies, Medical ,Research Articles ,Evidence-Based Medicine ,3. Good health ,Suicide ,Psychiatry and Mental health ,Olanzapine ,Lithium Compounds ,Female ,Original Article ,METABOLISMO ,Algorithms ,Antipsychotic Agents ,medicine.drug ,Canada ,medicine.medical_specialty ,Adolescent ,Cariprazine ,Lamotrigine ,Quetiapine Fumarate ,03 medical and health sciences ,medicine ,Humans ,Bipolar disorder ,Psychiatry ,Bupropion ,Biological Psychiatry ,Aged ,Lurasidone ,Mood Disorders ,business.industry ,Valproic Acid ,medicine.disease ,030227 psychiatry ,Editor's Choice ,Affect ,chemistry ,Quetiapine ,business ,030217 neurology & neurosurgery - Abstract
The Canadian Network for Mood and Anxiety Treatments (CANMAT) previously published treatment guidelines for bipolar disorder in 2005, along with international commentaries and subsequent updates in 2007, 2009, and 2013. The last two updates were published in collaboration with the International Society for Bipolar Disorders (ISBD). These 2018 CANMAT and ISBD Bipolar Treatment Guidelines represent the significant advances in the field since the last full edition was published in 2005, including updates to diagnosis and management as well as new research into pharmacological and psychological treatments. These advances have been translated into clear and easy to use recommendations for first, second, and third- line treatments, with consideration given to levels of evidence for efficacy, clinical support based on experience, and consensus ratings of safety, tolerability, and treatment-emergent switch risk. New to these guidelines, hierarchical rankings were created for first and second- line treatments recommended for acute mania, acute depression, and maintenance treatment in bipolar I disorder. Created by considering the impact of each treatment across all phases of illness, this hierarchy will further assist clinicians in making evidence-based treatment decisions. Lithium, quetiapine, divalproex, asenapine, aripiprazole, paliperidone, risperidone, and cariprazine alone or in combination are recommended as first-line treatments for acute mania. First-line options for bipolar I depression include quetiapine, lurasidone plus lithium or divalproex, lithium, lamotrigine, lurasidone, or adjunctive lamotrigine. While medications that have been shown to be effective for the acute phase should generally be continued for the maintenance phase in bipolar I disorder, there are some exceptions (such as with antidepressants); and available data suggest that lithium, quetiapine, divalproex, lamotrigine, asenapine, and aripiprazole monotherapy or combination treatments should be considered first-line for those initiating or switching treatment during the maintenance phase. In addition to addressing issues in bipolar I disorder, these guidelines also provide an overview of, and recommendations for, clinical management of bipolar II disorder, as well as advice on specific populations, such as women at various stages of the reproductive cycle, children and adolescents, and older adults. There are also discussions on the impact of specific psychiatric and medical comorbidities such as substance use, anxiety, and metabolic disorders. Finally, an overview of issues related to safety and monitoring is provided. The CANMAT and ISBD groups hope that these guidelines become a valuable tool for practitioners across the globe.
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- 2018
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22. Discussion of 'Data-driven confounder selection via Markov and Bayesian networks' by Jenny Häggström
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Sivaraman Balakrishnan and Edward H. Kennedy
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Statistics and Probability ,Computer science ,Machine learning ,computer.software_genre ,01 natural sciences ,General Biochemistry, Genetics and Molecular Biology ,Data-driven ,010104 statistics & probability ,0502 economics and business ,050207 economics ,0101 mathematics ,Unmeasured confounding ,Selection (genetic algorithm) ,General Immunology and Microbiology ,Markov chain ,business.industry ,Applied Mathematics ,05 social sciences ,Confounding ,Bayesian network ,General Medicine ,Doubly robust ,Causal inference ,Artificial intelligence ,General Agricultural and Biological Sciences ,business ,computer - Published
- 2017
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23. Seasonality of odonate-mediated methylmercury flux from permanent and semipermanent ponds and potential risk to red-winged blackbirds (Agelaius phoeniceus)
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James H. Kennedy, Matthew M. Chumchal, Edward B. Williams, and Ray W. Drenner
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0106 biological sciences ,Biomass (ecology) ,Potential risk ,Ecology ,Health, Toxicology and Mutagenesis ,Flux ,010501 environmental sciences ,Seasonality ,Biology ,medicine.disease ,biology.organism_classification ,010603 evolutionary biology ,01 natural sciences ,Predation ,chemistry.chemical_compound ,chemistry ,medicine ,Agelaius ,Environmental Chemistry ,Health risk ,Methylmercury ,0105 earth and related environmental sciences - Abstract
Methylmercury (MeHg) is an aquatic contaminant that can be transferred to terrestrial predators by emergent aquatic insects such as odonates (damselflies and dragonflies). We assessed the effects of month and pond permanence on odonate-mediated MeHg flux (calculated as emergent odonate biomass × MeHg concentration) in 10 experimental ponds and the potential risk to nestling red-winged blackbirds (Agelaius phoeniceus) posed by consuming MeHg-contaminated odonates. Emergent odonates were collected weekly from permanent ponds with bluegill (Lepomis macrochirus; n = 5) and semipermanent ponds without fish (n = 5) over an 8-mo period (January-August 2015). The MeHg flux from damselflies, aeshnid dragonflies, and libellulid dragonflies began in March and peaked in April, May, and June, respectively, and then declined throughout the rest of the summer. Odonate-mediated MeHg flux from semipermanent ponds without fish was greater than that from permanent ponds with fish. Nesting of red-winged blackbirds overlapped with peak odonate emergence and odonate-mediated MeHg flux. Because their diet can be dominated by damselflies and dragonflies, we tested the hypothesis that MeHg-contaminated odonates may pose a health risk to nestling red-winged blackbirds. Concentrations of MeHg in odonates exceeded wildlife values (the minimum odonate MeHg concentrations causing physiologically significant doses in consumers) for nestlings, suggesting that MeHg-contaminated odonates can pose a health risk to nestling red-winged blackbirds. Environ Toxicol Chem 2017;36:2833-2837. © 2017 SETAC.
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- 2017
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24. Recovery of aquatic insect-mediated methylmercury flux from ponds following drying disturbance
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Matthew M. Chumchal, Ashlyn E. Courville, James H. Kennedy, Frank M. Greenhill, Luke O. Lossau, Charlie A.A. Gober, and Ray W. Drenner
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010504 meteorology & atmospheric sciences ,biology ,Ecology ,Health, Toxicology and Mutagenesis ,Community structure ,Insectivore ,010501 environmental sciences ,biology.organism_classification ,Odonata ,01 natural sciences ,chemistry.chemical_compound ,Disturbance (ecology) ,chemistry ,Aquatic insect ,Environmental Chemistry ,Environmental science ,Terrestrial ecosystem ,Chaoboridae ,Methylmercury ,0105 earth and related environmental sciences - Abstract
Small ponds exist across a permanence gradient and pond permanence is hypothesized to be a primary determinant of insect community structure and insect-mediated methylmercury (MeHg) flux from ponds to the surrounding terrestrial landscape. Here we present the first experiment examining the recovery of insect-mediated MeHg flux following a drying disturbance that converted permanent ponds with insectivorous fish to semi-permanent ponds without fish. We used floating emergence traps to collect emergent insects for 10 weeks in the spring and summer from five ponds with fish (permanent) and five ponds that were drained to remove fish, dried and refilled with water (semi-permanent). During the 73 day period after semi-permanent ponds were refilled, total MeHg flux from semi-permanent ponds was not significantly different than total MeHg flux from permanent ponds, indicating that insect-mediated MeHg flux had rapidly recovered in semi-permanent ponds following the drying disturbance. Methylmercury fluxes from dragonflies (Odonata: Anisoptera) and phantom midges (Diptera: Chaoboridae) were significantly greater from newly refilled semi-permanent ponds than permanent ponds but the MeHg fluxes from other eight emergent insect taxa did not differ between treatments. The present study demonstrates the impact of drying disturbance and the effect of community structure on the cross-system transport of contaminants from aquatic to terrestrial ecosystems. This article is protected by copyright. All rights reserved
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- 2017
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25. A collaborative review of the current concepts and challenges of anastomotic leaks in colorectal surgery
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Neil Mortensen, Ronan A. Cahill, Robin H. Kennedy, R. W. Motson, P. R. O'Connell, A. C. Windsor, Brendan J. Moran, A Vallance, R. Novell, Mariana Berho, Timothy Rockall, N. Haboubi, Mark Coleman, Richard J. Heald, S. D. Wexner, Asha Senapati, David G. Jayne, and Frédéric Ris
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medicine.medical_specialty ,Fluorescence angiography ,business.industry ,Incidence (epidemiology) ,Enterostomy ,Gastroenterology ,MEDLINE ,Anastomotic Leak ,030230 surgery ,Delayed diagnosis ,United Kingdom ,Colorectal surgery ,Surgery ,03 medical and health sciences ,0302 clinical medicine ,Anastomotic leakage ,030220 oncology & carcinogenesis ,Anastomotic leaks ,medicine ,Humans ,Intensive care medicine ,business ,Colorectal Surgery ,Colorectal surgeons - Abstract
The reduction of the incidence, detection and treatment of anastomotic leakage (AL) continues to challenge the colorectal surgical community. AL is not consistently defined and reported in clinical studies, its occurrence is variably reported and its impact on longterm morbidity and health-care resources has received relatively little attention. Controversy continues regarding the best strategies to reduce the risk. Diagnostic tests lack sensitivity and specificity, resulting in delayed diagnosis and increased morbidity. Intra-operative fluorescence angiography has recently been introduced as a means of real-time assessment of anastomotic perfusion and preliminary evidence suggests that it may reduce the rate of AL. In addition, concepts are emerging about the role of the rectal mucosal microbiome in AL and the possible role of new prophylactic therapies. In January 2016 a meeting of expert colorectal surgeons and pathologists was held in London, UK, to identify the ongoing controversies surrounding AL in colorectal surgery. The outcome of the meeting is presented in the form of research challenges that need to be addressed.
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- 2017
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26. Arsenic inhibits mast cell degranulation via suppression of early tyrosine phosphorylation events
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Alejandro Velez, Jonathan H. Pelletier, Julie A. Gosse, Juyoung Shim, Rachel H. Kennedy, Lisa M. Weatherly, Lee M. Hutchinson, Hina N. Hashmi, and Kayla Blais
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0301 basic medicine ,Phosphoinositide 3-kinase ,Thapsigargin ,biology ,Cell Degranulation ,Chemistry ,Degranulation ,Tyrosine phosphorylation ,Toxicology ,Mast cell ,Cell biology ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,medicine ,biology.protein ,Phosphorylation ,030215 immunology ,Arsenite - Abstract
Exposure to arsenic is a global health concern. We previously documented an inhibitory effect of inorganic Arsenite on IgE-mediated degranulation of RBL-2H3 mast cells (Hutchinson et al., 2011; J. Appl. Toxicol. 31: 231-241). Mast cells are tissue-resident cells that are positioned at the host-environment interface, thereby serving vital roles in many physiological processes and disease states, in addition to their well-known roles in allergy and asthma. Upon activation, mast cells secrete several mediators from cytoplasmic granules, in degranulation. The present study is an investigation of Arsenite's molecular target(s) in the degranulation pathway. Here, we report that arsenic does not affect degranulation stimulated by either the Ca(2) (+) ionophore A23187 or thapsigargin, which both bypass early signaling events. Arsenic also does not alter degranulation initiated by another non-IgE-mediated mast cell stimulant, the G-protein activator compound 48/80. However, arsenic inhibits Ca(2) (+) influx into antigen-activated mast cells. These results indicate that the target of arsenic in the degranulation pathway is upstream of the Ca(2) (+) influx. Phospho-Syk and phospho-p85 phosphoinositide 3-kinase enzyme-linked immunosorbent assays data show that arsenic inhibits early phosphorylation events. Taken together, this evidence indicates that the mechanism underlying arsenic inhibition of mast cell degranulation occurs at the early tyrosine phosphorylation steps in the degranulation pathway. Copyright © 2016 John Wiley & Sons, Ltd.
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- 2016
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27. Physiological changes after colorectal surgery suggest anastomotic leakage is an early event: a retrospective cohort study
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John T. Jenkins, Kok‐Neang Tan, Omer Aziz, Filomena Liccardo, Robin H. Kennedy, Adam T. Stearns, and Emre Sivrikoz
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Adult ,Male ,medicine.medical_specialty ,Leak ,Time Factors ,Databases, Factual ,Respiratory rate ,Urology ,Anastomotic Leak ,Leukocyte Count ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Predictive Value of Tests ,Heart rate ,Humans ,Medicine ,Postoperative Period ,Prospective Studies ,Colectomy ,Aged ,Retrospective Studies ,Aged, 80 and over ,Creatinine ,Proctectomy ,biology ,business.industry ,C-reactive protein ,Gastroenterology ,Retrospective cohort study ,Middle Aged ,Colorectal surgery ,C-Reactive Protein ,chemistry ,Alanine transaminase ,Case-Control Studies ,030220 oncology & carcinogenesis ,biology.protein ,Female ,Laparoscopy ,030211 gastroenterology & hepatology ,Colorectal Neoplasms ,business - Abstract
Aim Anastomotic leakage (AL) is often identified 7-10 days after colorectal surgery. However, in retrospect, abnormalities may be evident much earlier. This study aims to identify the clinical time point when AL occurs. Method This is a retrospective case-matched cohort comparison study, assessing patients undergoing left-sided colorectal resection between 2006 and 2015 at a specialist colorectal unit. Patients who developed AL (LEAK) were case-matched to two CONTROL patients by procedure, gender, laparoscopic modality and diverting stoma. Case note review allowed the collection of basic observation data and blood tests (leukocyte count, C-reactive protein, bilirubin, alanine transaminase, creatinine) up to postoperative day (POD) 4. The cohorts were compared, with the main outcome measure being changes in basic observation data. Results Of 554 patients, 49 developed AL. These were matched to 98 CONTROL patients. Notes were available for 105 patients (32 LEAK/73 CONTROL). Groups were similar in demographics, tumour or nodal status, preoperative radiotherapy, intra-operative air-leak integrity and drain usage. AL was detected clinically at a median of 7.5 days postoperatively. There was a significantly increased heart rate by the evening on POD 1 in LEAK patients (82.8 ± 14.2/min vs 75.1 ± 12.7/min, P = 0.0081) which persisted for the rest of the study. By POD 3, there was a significant increase in respiratory rate (18.0 ± 4.2/min vs 16.5 ± 1.3/min, P = 0.0069) and temperature (37.0 ± 0.4C vs 36.7 ± 0.3C, P = 0.0006) in LEAK patients. C-reactive protein was significantly higher in LEAK patients from POD 2 (165 ± 95 mg/l vs 121 ± 75 mg/l, P = 0.023). Conclusions Physiological and biochemical changes associated with AL happen very early postoperatively, suggesting that AL may occur within 36 h after surgery, despite much later clinical detection.
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- 2018
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28. Zebrafish models of major depressive disorders
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Xiao-Yan Wen, Sidney H. Kennedy, Trehani M. Fonseka, and Jane A. Foster
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0301 basic medicine ,animal structures ,biology ,Pharmacological research ,fungi ,Danio ,Behavioral testing ,Translational research ,biology.organism_classification ,3. Good health ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,030104 developmental biology ,0302 clinical medicine ,Neurochemical ,Neuroscience ,Zebrafish ,030217 neurology & neurosurgery ,Genetic screen - Abstract
The zebrafish (Danio rerio) has emerged as a model species for translational research in various neuroscience areas, including depressive disorders. Because of their physiological (neuroanatomical, neuroendocrine, neurochemical) and genetic homology to mammals, robust phenotypes, and value in high-throughput genetic and chemical genetic screens, zebrafish are ideal for developing valid experimental models of major depression and discovering novel therapeutics. Behavioral testing approaches, such as approach-avoidance, cognitive, and social paradigms, are available in zebrafish and have utility in identifying depression-like indices in zebrafish in response to physiological, genetic, environmental, and/or psychopharmacological alterations. In addition, the high sensitivity of zebrafish to commonly prescribed psychotropic drugs supports the use of this model as an invaluable tool for pharmacological research and drug screening. This Review outlines the benefits of using the zebrafish model for depression studies and summarizes the current research in this field.
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- 2015
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29. Marginal Structural Models: An Application to Incarceration and Marriage During Young Adulthood
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Edward H. Kennedy and Valerio Baćak
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Estimation ,Mediation (statistics) ,Marginal structural model ,Regression analysis ,Family life ,Arts and Humanities (miscellaneous) ,Anthropology ,Econometrics ,Demographic economics ,National Longitudinal Surveys ,Psychology ,Social Sciences (miscellaneous) ,Criminal justice ,Panel data - Abstract
Advanced methods for panel data analysis are commonly used in research on family life and relationships, but the fundamental issue of simultaneous time-dependent confounding and mediation has received little attention. In this article the authors introduce inverse-probability-weighted estimation of marginal structural models, an approach to causal analysis that (unlike conventional regression modeling) appropriately adjusts for confounding variables on the causal pathway linking the treatment with the outcome. They discuss the need for marginal structural models in social science research and describe their estimation in detail. Substantively, the authors contribute to the ongoing debate on the effects of incarceration on marriage by applying a marginal structural model approach to panel data from the National Longitudinal Survey of Youth 1997 (N = 4,781). In line with the increasing evidence on the collateral consequences of contact with the criminal justice system, the authors find that incarceration is associated with reduced chances of entering marriage.
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- 2015
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30. A systematic review of patient preference elicitation methods in the treatment of colorectal cancer
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Nick Sevdalis, A Currie, Alan Askari, Robin H. Kennedy, Subramanian Nachiappan, and O D Faiz
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Risk ,medicine.medical_specialty ,Colorectal cancer ,business.industry ,Communication ,Decision Making ,Gastroenterology ,MEDLINE ,Patient Preference ,medicine.disease ,Neoadjuvant Therapy ,Preference ,Colorectal surgery ,Surgery ,Systematic review ,Quality of life ,Quality of Life ,medicine ,Adjuvant therapy ,Life expectancy ,Humans ,Colorectal Neoplasms ,business ,Intensive care medicine ,Colorectal Surgery - Abstract
Aim This systematic review aimed to assess the use of patient preference in colorectal cancer treatment. Eliciting patient preference is important for shared decision-making in colorectal cancer treatment. The introduction of newer treatments, which balance quality of life and overall survival, makes this an important future focus. Method A systematic search strategy of MEDLINE, Embase, PsycINFO, CINAHL and the Cochrane Database for Systematic Reviews was undertaken to obtain relevant articles. Information regarding the type of patients included, preference instruments, study settings, outcomes and limitations was extracted. Results The eight articles comprising this review each described an empirical study using a validated instrument to define patient preference for an aspect of colorectal cancer treatment. The evidence suggests that patients are prepared to trade significant reductions in life expectancy to avoid certain complications of colorectal surgery, particularly stoma formation. In the adjuvant setting, patients are prepared to risk significant treatment side effects to gain small potential increases in life expectancy and chance of survival. Where neoadjuvant or adjuvant treatment risks worsening function, however, patients generally forgo any potential increase in survival to improve bowel function and therefore quality of life. The only predictors of preference were tertiary education and previous cancer treatment. Conclusion Most patients judge a moderate survival benefit to be sufficient to make adjuvant therapy for colorectal cancer worthwhile, but they are willing to trade a potential reduction in life expectancy and survival to avoid certain unwanted surgical sequelae.
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- 2014
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31. Impact of chronic kidney disease on postoperative outcome following colorectal cancer surgery
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John T. Jenkins, P. Swift, Robin H. Kennedy, Omar Faiz, Alan Askari, George Malietzis, A Currie, and Subramanian Nachiappan
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Adult ,Male ,medicine.medical_specialty ,Population ,Adenocarcinoma ,urologic and male genital diseases ,Postoperative Complications ,Risk Factors ,Interquartile range ,Median follow-up ,Internal medicine ,medicine ,Humans ,Postoperative Period ,Renal Insufficiency, Chronic ,education ,Colectomy ,Survival analysis ,Aged ,Cause of death ,Aged, 80 and over ,education.field_of_study ,business.industry ,Proportional hazards model ,Hazard ratio ,Gastroenterology ,Middle Aged ,medicine.disease ,Survival Analysis ,Surgery ,Treatment Outcome ,Female ,Colorectal Neoplasms ,business ,Follow-Up Studies ,Kidney disease - Abstract
Aim Chronic kidney disease (CKD) is increasing in prevalence and is associated with cardiovascular events and mortality in asymptomatic and vascular surgery populations. This study aimed to determine the role of CKD in stratifying peri- and postoperative risk for colorectal cancer (CRC) patients with nonmetastatic disease undergoing elective curative resection. Method Patients diagnosed with nonmetastatic colorectal adenocarcinoma and undergoing surgical resection between 2006 and 2011 were identified from a prospectively collated database. Further information on survival and cause of death was gathered from a regional cancer registry. Estimated glomerular filtration rates were calculated using the Modification of Diet in Renal Disease (MDRD) equation. Kaplan–Meier survival curves were constructed for disease-free and overall survival. Multivariate Cox regression models were used to determine the role of CKD after stratification by several clinicopathological factors. Results Seven-hundred and eight colorectal resections were studied [median follow up: 45 (interquartile range, 21–65) months). Overall postoperative complications were similar, but patients with CKD were more likely to develop cardiovascular morbidity (P
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- 2014
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32. Ambient analysis of leachable compounds from single-use bioreactors with desorption electrospray ionization time-of-flight mass spectrometry
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Michael Ronk, Jian Liu, Liliana Marghitoiu, Yasser Nashed-Samuel, Joseph H. Kennedy, and Hans Lee
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chemistry.chemical_classification ,Desorption electrospray ionization ,Chromatography ,Chemistry ,Organic Chemistry ,Polymer ,Mass spectrometry ,High-performance liquid chromatography ,Analytical Chemistry ,Solvent ,Sample preparation ,Leaching (metallurgy) ,Time-of-flight mass spectrometry ,Spectroscopy - Abstract
RATIONALE Trace levels of bis(2,4-di-tert-butylphenyl)phosphate (BdtbPP) leaching from single-use bioreactors (SUBs) were recently found to be highly detrimental to mammalian cell growth. The traditional approach to detect the leachable requires time-consuming solvent extraction of SUBs. To assist the qualification of SUBs and/or their manufacturing raw materials in biopharmaceutical development and manufacturing, it is essential to develop a rapid and sensitive analytical approach for detecting this leachable and related compounds, which is described in this study. METHODS Native films from several commercially available SUBs were directly examined by desorption electrospray ionization (DESI) time-of-flight mass spectrometry (TOFMS) without sample preparation. As a comparison, the same SUBs were also analyzed by high-performance liquid chromatography (HPLC)/ultraviolet (UV) following the solvent extraction. RESULTS With a suitable spray solvent selected in this study, DESI-TOFMS enabled rapid and sensitive detection of leachable compounds directly from SUBs. Accurate mass measurement from TOFMS allowed ready identification of BdtbPP, its parent analog compound, and other polymer components in the SUBs from their protonated surrogates. The relative abundances of BdtbPP in different SUBs measured by DESI-TOFMS exhibited good correlation with those from the traditional extraction-based approach with HPLC/UV. CONCLUSIONS A rapid and sensitive approach was developed for direct detection of BdtbPP and other leachables from SUBs using DESI-TOFMS. The results are in high accordance with those from conventional approaches, which indicates the usefulness of the proposed method as a qualification tool for SUBs in biopharmaceutical development and also its great potential in the analysis of extractables/leachables in a wide variety of materials, process components, devices and containers used in the pharmaceutical industry. Copyright © 2014 John Wiley & Sons, Ltd.
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- 2014
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33. A prospective case controlled study of the short-term outcome following hemicolectomy for benign compared with malignant colonic polyps
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Ronan A. Cahill, A Brigic, Paul Bassett, Robin H. Kennedy, and Susan K. Clark
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Adenoma ,Male ,medicine.medical_specialty ,Colorectal cancer ,Colonic Polyps ,Resection ,Cohort Studies ,Postoperative Complications ,Interquartile range ,medicine ,Humans ,Prospective Studies ,Hemicolectomy ,Colectomy ,Aged ,business.industry ,Carcinoma ,Gastroenterology ,Case-control study ,Postoperative complication ,Length of Stay ,Middle Aged ,medicine.disease ,Surgery ,Logistic Models ,Treatment Outcome ,Case-Control Studies ,Colonic Neoplasms ,Linear Models ,Multilevel Analysis ,Female ,Full thickness ,business - Abstract
Aim The number of patients diagnosed with advanced colonic polyps has increased due to screening. The outcome of hemicolectomy for benign lesions is poorly documented. We present a case-matched study comparing the results of hemicolectomy for benign and malignant polyps performed in two institutions. Methods Data for consecutive patients undergoing surgery for benign colonic polyps (BCPs) were prospectively collected in two hospitals. Each patient was matched for age, sex, ASA grade, site and type of resection (laparoscopic, open and converted) with two controls who underwent surgery for colon cancer (CC). The length of stay (LOS) and 30-day outcome were analysed adjusting for potential confounders. Multilevel linear and logistic regression analyses were performed. Results Forty-six patients having hemicolectomy for BCP were matched with 81 patients with CC. The median size of BCP was 4 cm [interquartile range (IQR) 2.5–5.4 cm]. Patients with a BCP had a marginally longer LOS [median 5.5 (IQR 4–8) days and 5 (IQR 3–7) days (P = 0.04)]. Twenty-one (46%) of 46 patients with BCP had a postoperative complication compared with 25 (31%) of 81 CC patients (P = 0.12, OR = 2.11, 95% CI 0.82–5.41). Four (9%) of 46 patients with BCP underwent re-operation and a further three (7%) were readmitted compared with one (1%) and two (2%) of 81 patients with CC (P = 0.07 and 0.28). There was no mortality in either group. Conclusion Complications following hemicolectomy for BCP or CC are not significantly different. The results of the study provide further impetus to develop local full thickness colonic excision for benign colonic lesions as an alternative to major surgery.
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- 2014
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34. A systematic review of outcome reporting in colorectal cancer surgery
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Rachael O. Forsythe, Sara T Brookes, Angus G K McNair, R Hackett, Robin H. Kennedy, David G. Jayne, Susan J Dutton, Anne Pullyblank, Michael Thomas, Ann D. Russell, Kerry N L Avery, JE Jones, Richard Huxtable, Paul A. Sylvester, Alfred Oliver, Mark Coleman, Jane M Blazeby, Dion Morton, Robert N. Whistance, and Julia Brown
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Research Report ,medicine.medical_specialty ,Neoplasm, Residual ,Colorectal cancer ,business.industry ,Data synthesis ,Gastroenterology ,medicine.disease ,Wound infection ,Outcome (game theory) ,Surgery ,Outcome and Process Assessment, Health Care ,Postoperative Complications ,Outcome reporting ,Internal medicine ,Colorectal cancer surgery ,medicine ,Overall survival ,Humans ,Neoplasm Recurrence, Local ,Colorectal Neoplasms ,Prospective cohort study ,business - Abstract
Aim Evaluation of surgery for colorectal cancer (CRC) is necessary to inform clinical decision-making and healthcare policy. The standards of outcome reporting after CRC surgery have not previously been considered. Method Systematic literature searches identified randomized and nonrandomized prospective studies reporting clinical outcomes of CRC surgery. Outcomes were listed verbatim, categorized into broad groups (outcome domains) and examined for a definition (an appropriate textual explanation or a supporting citation). Outcome reporting was considered inconsistent if results of the outcome specified in the methods were not reported. Outcome reporting was compared between randomized and nonrandomized studies. Results Of 5644 abstracts, 194 articles (34 randomized and 160 nonrandomized studies) were included reporting 766 different clinical outcomes, categorized into seven domains. A mean of 14 ± 8 individual outcomes were reported per study. ‘Anastomotic leak’, ‘overall survival’ and ‘wound infection’ were the three most frequently reported outcomes in 72, 60 and 44 (37.1%, 30.9% and 22.7%) studies, respectively, and no single outcome was reported in every publication. Outcome definitions were significantly more often provided in randomized studies than in nonrandomized studies (19.0% vs 14.9%, P = 0.015). One-hundred and twenty-seven (65.5%) papers reported results of all outcomes specified in the methods (randomized studies, n = 21, 61.5%; nonrandomized studies, n = 106, 66.2%; P = 0.617). Conclusion Outcome reporting in CRC surgery lacks consistency and method. Improved standards of outcome measurement are recommended to permit data synthesis and transparent cross-study comparisons.
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- 2013
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35. The effect of lisdexamfetamine dimesylate on body weight, metabolic parameters, and attention deficit hyperactivity disorder symptomatology in adults with bipolar I/II disorder
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Joanna K. Soczynska, Sidney H. Kennedy, Isaac Szpindel, Doron Almagor, Timothy S. Bilkey, Hanna O. Woldeyohannes, Alissa M. Powell, Danielle S. Cha, Roger S. McIntyre, Laura Ashley Gallaugher, and Mohammad Alsuwaidan
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medicine.medical_specialty ,Adiponectin ,Lisdexamfetamine Dimesylate ,medicine.disease ,Psychiatry and Mental health ,Blood pressure ,Endocrinology ,Neurology ,Tolerability ,Internal medicine ,medicine ,Clinical Global Impression ,Attention deficit hyperactivity disorder ,Pharmacology (medical) ,Neurology (clinical) ,Bipolar disorder ,Psychology ,Body mass index - Abstract
Objectives We primarily sought to determine the effect of adjunctive lisdexamfetamine dimesylate (LDX) on anthropometric and metabolic parameters. Our secondary aim was to evaluate the effect of LDX on attention deficit hyperactivity disorder (ADHD) symptom severity in adults with bipolar I/II disorder. Methods Forty-five stable adults (i.e., non-rapid cycling, absence of clinically significant hypo/manic symptoms) with bipolar I/II disorder and comorbid ADHD were enrolled in a phase IV, 4-week, flexible dose, open-label study of adjunctive LDX. All subjects were initiated at 30 mg/day of adjunctive LDX for the first week with flexible dosing (i.e., 30–70 mg/day) between weeks 2 and 4. Results Of the 45 subjects enrolled, 40 received adjunctive LDX (mean dose = 60 ± 10 mg/day). A statistically significant decrease from baseline to endpoint was evident in weight (p
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- 2013
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36. Comparison of methods for estimating the effect of salvage therapy in prostate cancer when treatment is given by indication
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Jincheng Shen, Jeremy M. G. Taylor, Edward H. Kennedy, Douglas E. Schaubel, and Lu Wang
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Male ,Statistics and Probability ,Epidemiology ,medicine.medical_treatment ,Marginal structural model ,Salvage therapy ,Article ,law.invention ,Prostate cancer ,Randomized controlled trial ,law ,Statistics ,Humans ,Medicine ,Computer Simulation ,Survival analysis ,Randomized Controlled Trials as Topic ,Salvage Therapy ,Models, Statistical ,business.industry ,Proportional hazards model ,Prostatic Neoplasms ,Prostate-Specific Antigen ,medicine.disease ,Treatment Outcome ,Standard error ,Data Interpretation, Statistical ,Hormone therapy ,Neoplasm Recurrence, Local ,business - Abstract
For patients who were previously treated for prostate cancer, salvage hormone therapy is frequently given when the longitudinal marker prostate-specific antigen begins to rise during follow-up. Because the treatment is given by indication, estimating the effect of the hormone therapy is challenging. In a previous paper we described two methods for estimating the treatment effect, called two-stage and sequential stratification. The two-stage method involved modeling the longitudinal and survival data. The sequential stratification method involves contrasts within matched sets of people, where each matched set includes people who did and did not receive hormone therapy. In this paper, we evaluate the properties of these two methods and compare and contrast them with the marginal structural model methodology. The marginal structural model methodology involves a weighted survival analysis, where the weights are derived from models for the time of hormone therapy. We highlight the different conditional and marginal interpretations of the quantities being estimated by the three methods. Using simulations that mimic the prostate cancer setting, we evaluate bias, efficiency, and accuracy of estimated standard errors and robustness to modeling assumptions. The results show differences between the methods in terms of the quantities being estimated and in efficiency. We also demonstrate how the results of a randomized trial of salvage hormone therapy are strongly influenced by the design of the study and discuss how the findings from using the three methodologies can be used to infer the results of a trial. Copyright © 2013 John Wiley & Sons, Ltd.
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- 2013
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37. QUANTIFYING CONTINGENT RELATIONS FROM DIRECT OBSERVATION DATA: TRANSITIONAL PROBABILITY COMPARISONS VERSUS YULE'S Q
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Craig H. Kennedy, Blair P. Lloyd, and Paul J. Yoder
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Philosophy ,Sociology and Political Science ,Descriptive statistics ,Q-statistic ,Statistics ,Direct observation ,Range (statistics) ,Econometrics ,Contingency ,Psychology ,Applied Psychology ,Statistic - Abstract
Measuring contingencies or sequential associations may be applied to a broad range of response-stimulus, stimulus-stimulus, or response-response relations. Within behavior analysis, response-stimulus contingencies have been quantified by comparing 2 transitional probabilities and plotting them in contingency space. Within and outside behavior analysis, Yule's Q has become a recommended statistic used to quantify sequential associations between 2 events. In the current paper, we identify 2 methods of transitional probability comparisons used in the behavior-analytic literature to estimate contingencies in natural settings. We compare each of these methods to the more established Yule's Q statistic and evaluate relations between each pair of indices. Advantages and disadvantages of each method are identified, with recommendations as to which approach may be most appropriate for measuring contingencies.
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- 2013
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38. Towards the Prevention of Behavioural and Psychiatric Disorders in People with Intellectual Disabilities
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Paul Langthorne, Bruce J. Tonge, David Allen, Craig H. Kennedy, Eric Emerson, Robert J. Fletcher, Peter McGill, and Anton Dosen
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,Challenging behaviour ,Persons with Mental Disabilities ,Psychological intervention ,Public policy ,Comorbidity ,Education ,Young Adult ,Cost of Illness ,Risk Factors ,Intellectual Disability ,Intervention (counseling) ,Preventive Health Services ,Intellectual disability ,Developmental and Educational Psychology ,medicine ,Humans ,Child ,Psychiatry ,Mental Disorders ,Public health ,Models, Theoretical ,medicine.disease ,Mental health ,Additional research ,Caregivers ,Disease Susceptibility ,Public Health ,Psychology - Abstract
Intervention for behavioural and psychiatric disorders in people with intellectual disabilities often only takes place once these conditions are well established and more resistant to change. As an alternative, this paper promotes a public health prevention model and maps out opportunities for intervention at primary, secondary and tertiary levels. The resulting model is partly derived from generic research into these issues and partly on specific evidence on interventions for people with intellectual disabilities; it also contains more theoretical considerations. The additional research that is necessary to demonstrate the efficacy of the interventions identified is also considered. Central to this proposal is a greater integration of issues for people with intellectual disabilities within much broader policy and research agendas.
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- 2013
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39. Efficacy of the novel antidepressant agomelatine for anxiety symptoms in major depression
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Sidney H. Kennedy, F. Picarel-Blanchot, and Dan J. Stein
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medicine.medical_specialty ,Sertraline ,Generalized anxiety disorder ,Hamilton Anxiety Rating Scale ,medicine.drug_class ,Venlafaxine ,medicine.disease ,Anxiolytic ,Psychiatry and Mental health ,Neurology ,medicine ,Agomelatine ,Anxiety ,Antidepressant ,Pharmacology (medical) ,Neurology (clinical) ,medicine.symptom ,Psychology ,Psychiatry ,medicine.drug - Abstract
Objectives Anxiety in major depression is associated with increased morbidity. The antidepressant, agomelatine, which acts as an agonist at melatonin MT1 and MT2 receptors and as an antagonist at serotonin 5-HT2C receptors, has demonstrated efficacy and safety in both major depression and generalized anxiety disorder. Here, we investigated the efficacy of agomelatine in anxious depression. Methods Data from three placebo-controlled short-term trials of agomelatine and three comparative studies of agomelatine versus fluoxetine, sertraline, and venlafaxine were pooled. Effects of agomelatine on anxiety symptoms were assessed with the Hamilton Anxiety Rating Scale in four studies (one vs placebo and three vs active comparator) and with the Hamilton Depression Rating Scale (HAMD) anxiety subscore in all six studies. Anxiolytic and antidepressant efficacies of agomelatine were assessed in patients with more severe anxiety symptoms at baseline (score ≥5 on HAMD anxiety subscore). Results Agomelatine had a significantly greater effect on anxiety symptoms than both placebo and a number of comparator antidepressants. In more anxious depressed patients, agomelatine had a significantly greater effect on anxiety and depressive symptoms than both placebo and comparator antidepressants. Conclusion Once-a-day oral agomelatine is a new, efficacious alternative option for the treatment of anxiety in patients with major depression. Copyright © 2013 John Wiley & Sons, Ltd.
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- 2013
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40. Requirement for postoperative imaging in an enhanced recovery programme
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John T. Jenkins, Robin H. Kennedy, J. Burch, Jennifer C E Lane, and David Burling
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medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Gastroenterology ,Interventional radiology ,Retrospective cohort study ,Colorectal surgery ,Surgery ,medicine.anatomical_structure ,Interquartile range ,Cohort ,Medicine ,Abdomen ,business ,Adverse effect ,Laparoscopy - Abstract
Aim Enhanced recovery after surgery (ERAS) produces benefits to patients by reducing the length of hospital stay and morbidity. Its effect on nursing and physiotherapy workload has been studied, but the demand upon radiology is unclear. We aimed to determine radiology use to understand possible hidden expenditure not included in existing ERAS cost-effectiveness analyses. Method Two-hundred and sixty-five patients from a prospective multidimensional ERAS database were retrospectively assessed for postoperative radiology use. All had undergone colorectal surgery within an established ERAS programme from 2008 to 2009, with all data prospectively recorded. Laparoscopy was offered for all primary colon and rectal resections. All adverse events, including gut dysfunction, surgical site infection and reoperation, were assessed. All radiology within 30 days of surgery was recorded. Results Radiology data were absent in 12 patients, leaving 253 for analysis. Postoperative radiology was used in 71 (28%) patients, and 41 (16%) had CT of the abdomen and pelvis (A/P) within 30 days of surgery. In 33 (13%) patients this was required during the primary admission, including 30% of patients with any postoperative adverse event. Nine (27%; 3.6% of the whole cohort) of the 33 patients required reoperation. No patient required interventional radiology. The median time to CT (A/P) during primary admission was 5 (interquartile range, 3–8) days. Eight (3%) patients had CT (A/P) after readmission with one reoperation. Forty (16%) patients underwent plain radiology (chest or abdominal) and six (2%) had abdominal ultrasound. Using general estimates of CT and plain radiology total costs, these data suggest an overall radiology cost of over £22 000, amounting to a radiology cost of £90 per ERAS patient. Conclusion Postoperative radiology is required in a significant proportion of ERAS patients, potentially reflecting a low threshold to investigate in the presence of an adverse event. Very few require subsequent intervention. Radiology costs incurred with ERAS should be considered in future economic analyses.
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- 2013
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41. Early prediction of adverse events in enhanced recovery based upon the host systemic inflammatory response
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J. Burch, Jennifer C E Lane, S. Wright, Robin H. Kennedy, and John T. Jenkins
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Univariate analysis ,medicine.medical_specialty ,biology ,Receiver operating characteristic ,business.industry ,C-reactive protein ,Organ dysfunction ,Gastroenterology ,Area under the curve ,Context (language use) ,Colorectal surgery ,Surgery ,Internal medicine ,biology.protein ,medicine ,medicine.symptom ,business ,Adverse effect - Abstract
Aim Early identification of patients experiencing postoperative complications is imperative for successful management. C-reactive protein (CRP) is a nonspecific marker of inflammation used in many specialties to monitor patient condition. The role of CRP measurement early in the elective postoperative colorectal patient is unclear, particularly in the context of enhanced recovery (ERAS). Methods Five hundred and thirty-three consecutive patients who underwent elective colorectal surgery between October 2008 and October 2010 within an established ERAS programme were studied. Patients were separated into a development group of 265 patients and a validation group of 268 patients by chronological order. CRP and white cell count were added to a prospectively maintained ERAS database. The primary outcome of the study was all adverse events (including infective complications, postoperative organ dysfunction and prolonged length of stay) during the initial hospital admission. Significant predictors for adverse events on univariate analysis were submitted to multivariate regression analysis and the resulting model applied to the validation group. The validity and predictive accuracy of the regression model was assessed using receiver operating characteristic curve/area under the curve (AUC) analysis. Results CRP levels > 150 mg/l on postoperative day 2 and a rising CRP on day 3 were independently associated with all adverse events during the hospital admission. A weighted model was applied to the validation group yielding an AUC of 0.65 (95% CI 0.58–0.73) indicating, at best, modest discrimination and predictive accuracy for adverse events. Conclusion Measurement of CRP in patients after elective colorectal surgery in the first few days after surgery within ERAS can assist in identifying those at risk of adverse events and a prolonged hospital stay. A CRP value of > 150 mg/l on day 2 and a rising CRP on day 3 should alert the surgeon to an increased likelihood of such events.
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- 2013
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42. Deviation and failure of enhanced recovery after surgery following laparoscopic colorectal surgery: early prediction model
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Jonathan Ockrim, Neil J. Smart, Nader K. Francis, A. S. Allison, Robin H. Kennedy, and Paul D. White
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Retrospective review ,medicine.medical_specialty ,Scoring system ,business.industry ,Gastroenterology ,Colorectal surgery ,Resection ,Surgery ,Anesthesia ,Early prediction ,Vomiting ,Medicine ,medicine.symptom ,business ,Enhanced recovery after surgery ,Delayed discharge - Abstract
Aim Enhanced recovery after surgery (ERAS) pro-grammes are well established, but deviation from thepostoperative elements may result in delayed discharge.Early identification of such patients may allow remedialaction to be taken. The aims of this study were toinvestigate factors associated with delayed discharge andto produce a predictive scoring system for ERAS failure.Method A retrospective review was carried out of casenotes of patients who underwent elective laparoscopiccolorectal resection and ERAS at Yeovil District Hospitalbetween 2002 and 2009. Univariate and multivariateanalyses were performed and binary logistic regressionwas used to model a predictive scoring system.Results In all, 385 patient records were reviewed with amedian length of stay of 6 days; 122 (31%) patientsstayed longer than 1 week (delayed discharge) and 159(41%) deviated in up to two postoperative ERAS factors.Patient demographic factors were not predictive ofdelayed discharge. Deviation from ERAS factors at theend of the first postoperative day, including continuedintravenous fluid infusion, lack of functioning epidural,inability to mobilize, vomiting requiring nasogastric tubeinsertion and re-insertion of urinary catheter, werestrongly associated with delayed discharge. A five-elementpredictive scoring system for ERAS failure and delayeddischarge was formulated.Conclusion Enhanced recovery failure and delayed dis-charge after laparoscopic colorectal surgery can bepredicted by the early deviation from postoperativefactors of an ERAS programme.Keywords Enhanced recovery after surgery (ERAS),laparoscopic, colorectalWhat is new in this paper?The paper demonstrates a method of weighted predictionof deviation and failure in enhanced recovery afterlaparoscopic colorectal surgery.
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- 2012
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43. ‘Trainee’ evaluation of the English National Training Programme for laparoscopic colorectal surgery
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Susannah M. Wyles, Mark Coleman, Robin H. Kennedy, Danilo Miskovic, George B. Hanna, and Melody Ni
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Response rate (survey) ,medicine.medical_specialty ,Trainer ,business.industry ,Gastroenterology ,Questionnaire ,Computer-assisted web interviewing ,Colorectal surgery ,Likert scale ,Outreach ,Family medicine ,Physical therapy ,medicine ,business ,Training programme - Abstract
Aim The aim of this study was to review trainees’opinions of the training they had received through theNational Training Programme (NTP).Method An online questionnaire was distributed to NTPtrainees who hadcompleted five or more training episodeswithin the programme. Demographic data were collected.Opinion was given using a five-point Likert scale (1 =stronglydisagree,2 = disagree,3 = undecided,4 = agree,5 = stronglyagree).Percentages,meanvaluesandSDwerepresented. ANOVA and Mann–Whitney U-tests wereused to examine the impact of different factors on ratingsand the difference between ratings, respectively.Results Fifty-four registered trainees fulfilled the inclu-sion criteria, and 37 (69% response rate) completed thequestionnaire. Teaching sessions were organized using aninreach (11%), in-house (11%), outreach (27%) or com-bination (51%) system of training. Trainees felt that theirtrainers seldom cancelled sessions (93%), that it was easyto organize (92%) and consent (100%) the patient, andthat their hospital was supportive of training (97%).Trainees stated that overall their trainers were excellentat training (Likert scale = 4.71 ± 0.46) and that theyreceived regular feedback (87%). The only variable tohave a significant impact on the level of NTP approvalwas whether the trainee was able to choose his or hertrainer (supportive of NTP, chose trainer P = 0.050;critical of NTP, chose trainer P = 0.020).Conclusion The large majority of trainees was highlysatisfied with the training received in this innovativeprogramme, irrespective of region or training structureused, thus demonstrating acceptability of the programmein its current form.Keywords Training, surgery, laparoscopic, colorectal,programme, mentoringWhat is new in this paper?The National Training Programme for laparoscopiccolorectal surgery in England (Lapco) was set up toprovide structured training to consultant surgeons and isthe first such development internationally. This paperdescribes the results of a questionnaire survey to assessthe quality of training provided within the NationalTraining Programme.
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- 2012
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44. Laparoscopic total colectomy and ileorectal anastomosis (IRA), supported by an enhanced recovery programme in cases of familial adenomatous polyposis
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Susan K. Clark, F. J. McNicol, R. K. S. Phillips, and R. H. Kennedy
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Laparoscopic surgery ,medicine.medical_specialty ,Colorectal cancer ,business.industry ,General surgery ,medicine.medical_treatment ,Gastroenterology ,Retrospective cohort study ,Anastomosis ,medicine.disease ,Familial adenomatous polyposis ,Surgery ,Ileorectal anastomosis ,medicine ,Young adult ,business ,Colectomy - Abstract
Aim Familial adenomatous polyposis (FAP) is associated with an almost 100% chance of colorectal cancer by the age of 50 years. Surgery is the only prophylaxis. The study compared the outcome of prophylactic laparoscopic colectomy and ileorectal anastomosis (IRA) with conventional open surgery. Method A case–control study was carried out including all cases of proven FAP undergoing prophylactic laparoscopic colectomy with IRA between 1 April 2006 and 31 March 2008 using a standardized technique within an enhanced recovery programme (ERAS). All data were collected prospectively. Controls were identified retrospectively from patients who underwent open prophylactic IRA before 31 March 2008 and were matched for age, gender, BMI and ASA. Outcomes included duration of surgery, complications, length of stay, readmission and mortality. Results During the study period 25 patients underwent laparoscopic IRA. The median operating time was longer in the laparoscopic group (235 vs 180 mins, P
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- 2012
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45. The first 3 years of national bowel cancer screening at a single UK tertiary centre
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Brian P. Saunders, Siwan Thomas-Gibson, S. Marshall, Noriko Suzuki, Ana Ignjatovic, Chris H. Fraser, Sachin Gupta, Margaret Vance, Robin H. Kennedy, and S. Sala
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medicine.medical_specialty ,medicine.diagnostic_test ,Colorectal cancer ,business.industry ,medicine.medical_treatment ,Perforation (oil well) ,Gastroenterology ,Colonoscopy ,Sigmoidoscopy ,medicine.disease ,Comorbidity ,digestive system diseases ,Polypectomy ,Surgery ,Internal medicine ,medicine ,Adverse effect ,business ,Index Colonoscopy - Abstract
Aim St Mark’s Bowel Cancer Screening Centre commenced screening in October 2006 as a contributor to the national programme. The first 35 months’ experience is reported. Method Individuals with a positive faecal occult blood test (FOBT) were offered colonoscopy or alternatives if they had significant comorbidity. All screening data were collected prospectively. Results Of the 98 815 FOBT kits issued, 42 523 were returned (43% uptake; 20.79% men). In total, 1339/1488 (90%) FOBT-positive participants attended the nurse clinic (57% men). Of these, 1057 had an index colonoscopy, 115 had a computed tomography colonoscopy (CTC) and eight had a flexible sigmoidoscopy. Five hundred and seventeen (44%) procedures were ‘normal’ (no polyps/cancers). Eighty (6%) individuals had colorectal cancer. The polyp detection rate in index procedures, including colonoscopy, CTC and flexible sigmoidoscopy, was 50%. The adenoma detection rate of all colonoscopies was 62.8%. The median polyp size was 5 (1–80) mm. In total, 1200 colonoscopies were performed by five accredited colonoscopists (96% completion rate). There were 13 (1%) adverse events with
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- 2012
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46. The genetic ghost of an invasion past: colonization and extinction revealed by historical hybridization inSenecio
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Rubén Barone, Michael Möller, Joachim W. Kadereit, Mark E. Looseley, Aaron H. Kennedy, Pieter B. Pelser, Linda E. Watson, Hans Peter Comes, Julie F. Barcelona, Glynis V. Cron, Richard J. Abbott, Fabián Hernández, and Joseph J. Milton
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Extinction ,biology ,Phylogenetics ,Lineage (evolution) ,Genetics ,Zoology ,Colonization ,Senecioneae ,Internal transcribed spacer ,Senecio ,biology.organism_classification ,Ecology, Evolution, Behavior and Systematics ,Invasive species - Abstract
Hybridization is an important evolutionary factor in the diversification of many plant and animal species. Of particular interest is that historical hybridization resulting in the origin of new species or introgressants has occurred between species now geographically separated by great distances. Here, we report that Senecio massaicus, a tetraploid species native to Morocco and the Canary Islands, contains genetic material of two distinct, geographically separated lineages: a Mediterranean lineage and a mainly southern African lineage. A time-calibrated internal transcribed spacer phylogeny indicates that the hybridization event took place up to 6.18 Ma. Because the southern African lineage has never been recorded from Morocco or the Canary Islands, we hypothesize that it reached this area in the distant past, but never became permanently established. Interestingly, the southern African lineage includes S. inaequidens, a highly invasive species that has recently become widespread throughout Europe and was introduced at the end of the 19th century as a ‘wool alien’. Our results suggest that this more recent invasion of Europe by S. inaequidens represents the second arrival of this lineage into the region.
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- 2011
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47. The effects of agomelatine on sexual function in depressed patients and healthy volunteers
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Sakina J. Rizvi, Sidney H. Kennedy, Susana Majadas, and Angel L. Montejo
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medicine.medical_specialty ,Serotonin reuptake inhibitor ,Venlafaxine ,Placebo ,Gastroenterology ,Paroxetine ,Psychiatry and Mental health ,Sexual dysfunction ,Neurology ,Norepinephrine reuptake inhibitor ,Internal medicine ,Anesthesia ,medicine ,Agomelatine ,Pharmacology (medical) ,Neurology (clinical) ,medicine.symptom ,Sexual function ,Psychology ,medicine.drug - Abstract
Background Selective serotonin reuptake inhibitor (SSRI) and serotonin and norepinephrine reuptake inhibitor antidepressants are associated with high rates of treatment-emergent sexual dysfunction (TESD) due to stimulation of serotonin receptors. Objective The objective is to evaluate the effect of agomelatine on sexual function in depressed patients. Methods This paper reviews published and unpublished data on sexual function with agomelatine in depressed patients and healthy volunteers. Results Agomelatine, an agonist of melatonergic MT1 and MT2 receptors and antagonist of 5-HT2 receptors, is associated with similar rates of sexual dysfunction compared with placebo and lower rates compared with other antidepressants. Twice as many sexually active depressed patients (n = 193) reported a deterioration of sexual function during 12 weeks of treatment with venlafaxine compared with agomelatine (15.2% vs. 8.2%, p
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- 2011
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48. Individualization of surgical management for early-stage colonic cancer
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A Brigic, P. Sibbons, Ronan A. Cahill, Robin H. Kennedy, and C. Fraser
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education.field_of_study ,medicine.medical_specialty ,medicine.diagnostic_test ,Colorectal cancer ,business.industry ,General surgery ,Population ,Gastroenterology ,medicine.disease ,Screening programme ,Colonic cancer ,Segmental colectomy ,medicine ,Stage (cooking) ,education ,Laparoscopy ,Surgical treatment ,business - Abstract
A significant number of patients each year undergo radical segmental colectomy for node-negative colonic cancer in the UK. They are likely to represent 50% of our colonic cancer population in the future due to the implementation of the National Bowel Cancer Screening Programme. Short-term morbidity rates of up to 40% are associated with the current surgical treatment and need serious consideration. In this article, we discuss a combination of two techniques that will allow minimally invasive treatment in an increasing number of patients with early colonic cancer.
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- 2011
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49. Higher-tier assessment of the potential for groundwater issues due to the use of 1,3-D soil fumigant; evaluation of the active ingredient, metabolites and potentially related chlorinated compounds
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Luna Greco, Marco Trevisan, Lucrezia Lamastra, Gabriella Fait, Federico Ferrari, Ettore Capri, and Steve H. Kennedy
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Abiotic component ,Active ingredient ,chemistry.chemical_compound ,1,3-Dichloropropene ,chemistry ,Manufacturing process ,Insect Science ,Environmental chemistry ,Environmental science ,General Medicine ,Contamination ,Agronomy and Crop Science ,Groundwater - Abstract
BACKGROUND: 1,3-Dichloropropene (1,3-D, CAS No. 542-75-6) is a broad-spectrum soil fumigant used to control numerous species of soilborne plant-parasitic nematodes. 1,3-D consists of two isomers, (Z)- and (E)-1,3-D. There are a number of low-level chlorinated compounds that could potentially be produced as a part of the 1,3-D manufacturing process. 1,3-D and its metabolites, as well as potentially related chlorinated compounds, represent potential groundwater contaminants. RESULTS: This study has investigated the hydrolytic stability, under biotic and abiotic conditions in the laboratory, of an extensive representative list of 1,3-D and potentially related chlorinated compounds in order to predict their environmental fate. All of these compounds showed intrinsic hydrolytic instability under both abiotic and biotic test conditions. Furthermore, a monitoring programme was carried out. Twenty-five wells were monitored in five Italian regions characterised by historical and existing use of 1,3-D. The parent compound, its two major metabolites and potentially related chlorinated compounds were not detected in the well water at > 0.1 µg L−1 at any sampling location. CONCLUSION: The soil fumigant (E,Z)-1,3-D, its metabolites and potentially related chlorinated compounds constitute a low risk to groundwater. Copyright © 2011 Society of Chemical Industry
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- 2011
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50. Relationships between benthic macroinvertebrate community structure and geospatial habitat, in-stream water chemistry, and surfactants in the effluent-dominated Trinity River, Texas, USA
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James H. Kennedy, Scott D. Dyer, Bradford B. Price, Allen M. Nielsen, Jaime L. Slye, Kathleen Stanton, Hans Sanderson, Sam F. Atkinson, Michael Ciarlo, and David R. Johnson
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Aquatic Organisms ,Watershed ,Ecology ,Health, Toxicology and Mutagenesis ,Aquatic ecosystem ,Community structure ,Household Products ,Biodiversity ,Invertebrates ,Texas ,Surface-Active Agents ,Rivers ,Habitat ,Benthic zone ,Water Pollution, Chemical ,Animals ,Regression Analysis ,Environmental Chemistry ,Environmental science ,Water quality ,Species richness ,Surface water ,Ecosystem ,Water Pollutants, Chemical ,Environmental Monitoring - Abstract
Over the past 20 years, benthic macroinvertebrate community structure studies have been conducted on the upper Trinity River, Texas, USA, which is dominated by municipal wastewater treatment plant (WWTP) and industrial effluents. The Trinity River is located in the Dallas—Fort Worth metropolitan area, and is the most highly populated and industrialized watershed in Texas. As such, the Trinity River represents a near-worst-case scenario to examine the environmental effects of domestic–municipal and industrial effluents on aquatic life. A 1987 to 1988 study concluded that many stretches of the river supported a diverse benthic community structure; however, a decline in taxa richness occurred immediately downstream of WWTPs. A 2005 study designed to parallel the 1987 to 1988 efforts evaluated how changes in water quality, habitat, and increased urbanization impacted benthic community structure. Physicochemical measurements, habitat quality, geospatial variables, and benthic macroinvertebrates were collected from 10 sites. Surfactants were measured and toxic units (TUs) were calculated for surface water and pore water as indicators of domestic/household use of cleaning products. Total TUs indicated a low potential for biological impacts. Toxic unit distribution was not dependent on WWTP location and did not correlate with any benthic variable. Eight environmental parameters were determined to be useful for predicting changes in benthic macroinvertebrate community structure: surfactant surface water TUs (SWTU), in-stream habitat cover, and surface water total organic carbon were the top three parameters. Abundance, taxa richness, and taxa similarity in 2005 had increased since the earlier study throughout the immediate vicinity of the metropolitan area. Environ. Toxicol. Chem. 2011; 30:1127–1138. © 2011 SETAC
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- 2011
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