Michael Raphael Salzberg | University of Melbourne (original) (raw)
Papers by Michael Raphael Salzberg
Internal medicine journal, Jan 8, 2018
Functional gastrointestinal disorders (FGIDs), are the commonest conditions observed in gastroint... more Functional gastrointestinal disorders (FGIDs), are the commonest conditions observed in gastrointestinal (GI) practice, yet the outcomes of their outpatient care are not known. We evaluated the outcome for patients with FGIDs attending a specialist GI clinic. Consecutive, newly referred patients with a FGID attending a specialist GI clinic in a tertiary hospital, over a one-year period were reviewed and then completed a phone survey to assess current symptoms. Of 102 patients 57% had IBS, 28% functional dyspepsia (FD) and 15% other functional disorders. At interview a median of 402 days after the last consultation 38% expressed symptom improvement, but 64% remained concerned about their condition despite 62% having been reassured. After treatment 50% of employed patients took time off work because of gut symptoms. FD patients were less likely to be symptomatically improved than other FGIDs (21% vs 45%, P=0.02). Patients given a low-FODMAP diet were more likely than others to achieve...
Inflammatory Bowel Diseases
Background: Patients with inflammatory bowel disease (IBD) often experience functional bowel symp... more Background: Patients with inflammatory bowel disease (IBD) often experience functional bowel symptoms despite achieving disease remission. Although behavioral treatment (bowel and pelvic floor muscle retraining) is effective for managing constipation or fecal incontinence in non-IBD patients, there is limited evidence for its efficacy in patients with quiescent inflammatory bowel disease. The aim of this study was to evaluate the outcome of gut-directed behavioral treatment, including pelvic floor muscle training, for symptoms of constipation or fecal incontinence in patients with IBD in disease remission. Methods: The outcome of consecutive patients with IBD in remission and symptoms of constipation or fecal incontinence was evaluated. Patients referred to a multidisciplinary gastroenterology clinic underwent gut-directed behavioral treatment, including pelvic floor muscle training. The primary outcome was patient-reported rating of change in symptoms on a 7-point Likert scale at the completion of treatment. Results: Forty IBD patients (median age, 35 years; 80% female; 24 Crohn's disease [CD], 12 ulcerative colitis [UC], 4 UC with ileoanal pouch) with ongoing symptoms of constipation (55%) or fecal incontinence (45%), despite drug therapy, were included. The median symptom duration at referral was 2 years. Thirty-five (87%) completed treatment with a median of 2 sessions. Improvement of "6 = much better" or "7 = very much better" was reported by 77% (17/22) with fecal incontinence and 83% (15/18) with constipation. Improvement occurred irrespective of IBD diagnosis, previous perianal fistulae, colorectal surgery, presence of an ileoanal pouch, or past obstetric trauma. Conclusions: Behavioral treatment effectively improves functional gut symptoms in a large majority of patients who are in IBD disease remission and who have not responded to drug therapy.
The American Journal of the Medical Sciences, 2016
The aim of this study was to explore the effect of kidney transplantation (KT) on psychological d... more The aim of this study was to explore the effect of kidney transplantation (KT) on psychological distress and quality of life (QoL) in patients with end-stage kidney disease using the Common Sense Model of illness adjustment. A total of 52 individuals (35 men and 17 women) with an average age of 53.54 years from a large metropolitan nephrology outpatient clinic participated. Poorer health status, illness perceptions and increased engagement in maladaptive coping were associated with psychological distress (specifically anxiety and depression) and poorer QoL. Hierarchical regression, after correcting for KT characteristics (years since most recent KT, number of transplants) indicated that poorer illness status and illness perception predicted QoL. After controlling for KT characteristics, poorer illness status and greater engagement in maladaptive coping predicted depression. In contrast, poorer illness perceptions and greater engagement in maladaptive coping predicted anxiety. Adaptive problem-focused and emotion-focused coping styles were not found to predict anxiety, depression or QoL. The finding of the present study emphasize on the importance of exploring and understanding the effect of illness status, illness perceptions and coping patterns in patients who have underwent KT.
Epilepsia, Jan 14, 2016
To model the factors associated with depression in a community sample of people with epilepsy. Th... more To model the factors associated with depression in a community sample of people with epilepsy. The factors investigated were derived from proposed risk factors for depression from patients with epilepsy, other chronic illness, and the general population. Multivariate analysis using general linear regression models of factors associated with depression in the Tasmanian Epilepsy Register Mood Study (TERMS), a cross-sectional community sample of 440 patients with epilepsy. A model with acceptable fit was created that explained 66% of the variance of depression. Associated factors included in this model were neuroticism, physical functioning, social support, past history of depression, and stressful life events. In this cross-sectional study designed specifically to investigate depression in epilepsy, we showed that general risk factors for depression in other illness and in the general population are also important in patients with epilepsy, with little support for disease-related risk...
Aust N Z J Psychiat, 2002
The American Journal of the Medical Sciences, 2014
Journal of Wound, Ostomy and Continence Nursing, 2014
We employed the Common Sense Model (CSM) of illness perceptions to examine the relative contribut... more We employed the Common Sense Model (CSM) of illness perceptions to examine the relative contribution of illness perceptions, stoma self-efficacy, and coping strategies in explaining anxiety and depression symptoms in patients with a fecal ostomy. The CSM suggests that the consequences of illness activity, such as psychological distress, are influenced by an individual's illness perceptions as well as what coping strategies they engage in. Descriptive, cross-sectional questionnaire-based study. One hundred fifty adults with a stoma (54 males, and 96 females; mean age 44 years) completed an online survey. Several instruments were used to measure study outcomes, including the Health Perceptions Questionnaire, Brief Illness Perceptions Questionnaire, Carver Brief Coping Questionnaire, Stoma Self-Efficacy Scale, and the Hospital Anxiety and Depression Scale. Participants were advised of the study through online forums containing a link to the survey. Outcome measures used in the current study are valid and reliable and have been extensively used in medically ill patients. Using structural equation modeling, the final model provided an excellent fit to the data (χ23= 16.53, P = .22, χ/N = 1.27, SRMR < 0.03, RMSEA < 0.05, GFI > 0.97, CFI > 0.99). There was a direct pathway from health status to illness perceptions months since surgery directly influenced health status, illness beliefs, and adaptive emotion-focused coping (β= .81, P < .001). Several indirect (mediating) pathways were also identified. Illness perceptions mediated the relationship between health status and stoma self-efficacy and maladaptive and adaptive emotion-focused coping. Maladaptive coping mediated the relationship between illness perceptions and depression and anxiety, and adaptive emotion-focused coping mediated the relationship between illness perception and depression. The final model provided support for the CSM, in that illness perceptions were directly related to illness status, and that both illness perceptions and coping strategies directly influenced anxiety and depression. More specifically, maladaptive coping style (eg, ignore problems) exacerbated depression and anxiety symptoms, while self-efficacy and emotion-focused coping style (eg, seek advice) ameliorate depression, but not anxiety. Months since surgery was associated with improved health status, reduced poorer illness perceptions, and increased emotional-focused coping. Illness perceptions and coping were found to mediate anxiety and depression. The results confirm that how individuals perceive their illness and what coping strategies they engage in impacts their psychological well-being. Study findings support the need for designing targeting psychological interventions based on…
Epilepsy & Behavior, 2014
This study aimed to test whether a specific serotonin transporter (5HTT) gene polymorphism intera... more This study aimed to test whether a specific serotonin transporter (5HTT) gene polymorphism interacting with life stress increased the risk of depression in patients with epilepsy. The Tasmanian Epilepsy Register Mood Study (TERMS) used a cross-sectional study design of a community sample of patients with epilepsy previously recruited into the Tasmanian Epilepsy Register. It employed a mailed self-complete questionnaire and saliva DNA collection. Depression was assessed using the Center for Epidemiologic Studies Depression Scale. Environmental measures were selected to cover recent stressful events, epilepsy-related stress, current social support, and early life stress. Of 820 eligible participants, 553 (67%) participants completed the study. Experience of at least one stressful life event was very common, with a significant association between depression and the stressful life events (F=26.2, df=3, p<0.001). There was no association between serotonin transporter genotype and level of depressive symptoms reported (F=0.421, df=2, p=0.7). There was no evidence of any adverse life experiences interacting with serotonin transporter genotype to moderate the risk of depression. The failure to demonstrate a main effect of genotype on depression or a gene × environment interaction differs from several studies of patients with other chronic diseases. However, it is consistent with larger general population studies.
Epilepsy & Behavior, 2015
Depression is one of the most common psychiatric comorbidities in epilepsy; however, the factors ... more Depression is one of the most common psychiatric comorbidities in epilepsy; however, the factors contributing to this association remain unclear. There is a growing consensus that methodological limitations, particularly selection bias, affect many of the original studies. A systematic review focussed on community-based studies offers an alternative approach for the identification of the risk factors for depression. Searches were performed in MEDLINE (Ovid), 2000 to 31 December 2013, EMBASE, and Google Scholar to identify studies examining risk factors for depression in epilepsy. Community-based studies of adults with epilepsy that reported at least one risk factor for depression were included. The search identified 17 studies that met selection criteria, representing a combined total of 12,212 people with epilepsy with a mean sample size of 718. The most consistent risk factors for depression were sociodemographic factors, despite the fact that most studies focus on epilepsy-related factors. Most studies lacked a systematic conceptual approach to investigating depression, and few risk factors were consistently well studied. Future community-based studies require a detailed systematic approach to improve the ability to detect risk factors for depression in epilepsy. Psychological factors were rarely studied in community-based samples with epilepsy, although the consistent association with depression in the few studies that did suggests this warrants further examination.
Neurobiology of disease, Sep 13, 2016
The absence epilepsies are presumed to be caused by genetic factors, but the influence of environ... more The absence epilepsies are presumed to be caused by genetic factors, but the influence of environmental exposures on epilepsy development and severity, and whether this influence is transmitted to subsequent generations, is not well known. We assessed the effects of environmental enrichment on epilepsy and anxiety outcomes in multiple generations of GAERS - a genetic rat model of absence epilepsy that manifests comorbid elevated anxiety-like behaviour. GAERS were exposed to environmental enrichment or standard housing beginning either prior to, or after epilepsy onset, and underwent EEG recordings and anxiety testing. Then, we exposed male GAERS to early enrichment or standard housing and generated F1 progeny, which also underwent EEG recordings. Hippocampal CRH mRNA expression and DNA methylation were assessed using RT-PCR and pyrosequencing, respectively. Early environmental enrichment delayed the onset of epilepsy in GAERS, and resulted in fewer seizures in adulthood, compared wi...
Rheumatology (Oxford, England), Jan 8, 2016
The aim was to evaluate the utility of the common sense model (CSM) in characterizing contributor... more The aim was to evaluate the utility of the common sense model (CSM) in characterizing contributors to psychological well-being and quality of life (QoL) in patients with end-stage OA. One hundred and twenty patients [34 males, 86 females; mean (s.d.) age 65.52 (9.14) years] with end-stage OA (57.5% hip, 42.5% knee) were recruited. OA symptom severity was evaluated according to the WOMAC; coping styles were assessed with the Carver Brief COPE scale; illness perceptions were explored with the Brief Illness Perceptions Questionnaire; self-efficacy was assessed with the Arthritis Self-efficacy scale; anxiety, depression and overall distress were measured using the Hospital Anxiety and Depression Scale; and QoL was assessed using the WHO Quality of Life-short version. The CSM was used to explore the interrelationships between OA symptom severity, illness perceptions and coping strategies in patients. Two structural equation models were developed, with both found to have good fit. Consist...
Epilepsia, 2016
Environmental exposures impart powerful effects on vulnerability to many brain diseases, includin... more Environmental exposures impart powerful effects on vulnerability to many brain diseases, including epilepsy. Mesial temporal lobe epilepsy (MTLE) is a common form of epilepsy, and it is often accompanied by neuropsychiatric comorbidities. This study tests the hypothesis that environmental enrichment (EE) confers antiepileptogenic, psychoprotective, and neuroprotective effects in the amygdala kindling model of MTLE, and explores potential neurobiologic mechanisms. At weaning, male Wistar rats were allocated into either EE (large cages containing running wheels and toys; n = 43) or standard housing (SH; standard laboratory cages; n = 39) conditions. At P56, a bipolar electrode was implanted into the left amygdala, and rats underwent rapid amygdala kindling until experiencing five class V seizures (Racine scale, fully kindled). The elevated plus maze was used to assess anxiety. Postmortem histologic and molecular analyses investigated potential biologic mediators of effects. EE significantly delayed kindling epileptogenesis, with EE rats requiring a significantly greater number of kindling stimulations to reach a fully kindled state compared to SH rats (p < 0.05). EE and kindling both reduced anxiety (p < 0.05). Timm's staining revealed significant reductions in aberrant mossy fiber sprouting in EE rats (p < 0.05), and these effects of EE were accompanied by reduced expression of TrkB and CRH genes. We identify beneficial effects of EE on vulnerability to limbic epileptogenesis and anxiety, and identify reduced pathologic neuroplasticity and plasticity-related gene expression as potential underlying mechanisms. Enhanced environmental stimulation represents a potential antiepileptogenic strategy that might also mitigate the common psychiatric comorbidities of MTLE.
Clinical and Experimental Gastroenterology, 2015
ISRN Emergency Medicine, 2013
Objectives. To identify the proportion of adult emergency department (ED) patients who screen pos... more Objectives. To identify the proportion of adult emergency department (ED) patients who screen positive for depression. Secondary aims were to identify factors associated with a positive depression screen and determine predictors of a positive depression screen. Methods. This cross-sectional, prevalence survey of ED patients was conducted at two inner-city hospitals. 350 ED patients were screened for depression using the Patient Health Questionnaire-9 (PHQ-9). Clinical and demographic risk factors were examined through medical records and additional questionnaires. Results. Of 350 participants screened, 50 (14.3%; 95% CI = 11.0–18.4%) screened positive. Independent predictors of depression risk included self-reported depression and/or a previous diagnosis of depression (OR = 8.345; 95% CI = 3.524–19.762), seeing a mental health service provider in the past 6 months (OR = 4.518; 95% CI = 2.107–9.690), and previous discussion about mental health with a local doctor (OR = 2.369; 95% CI ...
Psychoneuroendocrinology, 2014
Oncology, 2007
Phase II/III trials have shown that capecitabine is an active, well-tolerated therapy for metasta... more Phase II/III trials have shown that capecitabine is an active, well-tolerated therapy for metastatic breast cancer (MBC). We report clinical findings from an expanded access program enabling patients ineligible for investigative trials to receive capecitabine before its approval and availability. Patients pretreated with at least two chemotherapy regimens, including a taxane, for MBC received oral capecitabine until disease progression or unacceptable toxicity. Six hundred and thirty-one patients received capecitabine (mean duration 3.8 months, range 0.1-24.7 months). The most common treatment-related grade 3/4 toxicities were diarrhea (9%) and hand-foot syndrome (8%). Grade 3/4 alopecia was absent and grade 3/4 myelosuppression was rare. Dose was modified in 172 patients (27%). Objective response rate in 349 evaluable patients was 35%. Median time to progression (n = 604) was 6.6 months (95% confidence interval, CI, 5.6-7.6) and median overall survival (n = 569) was 10.0 months (95% CI, 8.5-15.3). Our findings in a cohort of patients with pretreated progressive breast cancer confirm the high efficacy and tolerability of outpatient capecitabine.
Internal medicine journal, Jan 8, 2018
Functional gastrointestinal disorders (FGIDs), are the commonest conditions observed in gastroint... more Functional gastrointestinal disorders (FGIDs), are the commonest conditions observed in gastrointestinal (GI) practice, yet the outcomes of their outpatient care are not known. We evaluated the outcome for patients with FGIDs attending a specialist GI clinic. Consecutive, newly referred patients with a FGID attending a specialist GI clinic in a tertiary hospital, over a one-year period were reviewed and then completed a phone survey to assess current symptoms. Of 102 patients 57% had IBS, 28% functional dyspepsia (FD) and 15% other functional disorders. At interview a median of 402 days after the last consultation 38% expressed symptom improvement, but 64% remained concerned about their condition despite 62% having been reassured. After treatment 50% of employed patients took time off work because of gut symptoms. FD patients were less likely to be symptomatically improved than other FGIDs (21% vs 45%, P=0.02). Patients given a low-FODMAP diet were more likely than others to achieve...
Inflammatory Bowel Diseases
Background: Patients with inflammatory bowel disease (IBD) often experience functional bowel symp... more Background: Patients with inflammatory bowel disease (IBD) often experience functional bowel symptoms despite achieving disease remission. Although behavioral treatment (bowel and pelvic floor muscle retraining) is effective for managing constipation or fecal incontinence in non-IBD patients, there is limited evidence for its efficacy in patients with quiescent inflammatory bowel disease. The aim of this study was to evaluate the outcome of gut-directed behavioral treatment, including pelvic floor muscle training, for symptoms of constipation or fecal incontinence in patients with IBD in disease remission. Methods: The outcome of consecutive patients with IBD in remission and symptoms of constipation or fecal incontinence was evaluated. Patients referred to a multidisciplinary gastroenterology clinic underwent gut-directed behavioral treatment, including pelvic floor muscle training. The primary outcome was patient-reported rating of change in symptoms on a 7-point Likert scale at the completion of treatment. Results: Forty IBD patients (median age, 35 years; 80% female; 24 Crohn's disease [CD], 12 ulcerative colitis [UC], 4 UC with ileoanal pouch) with ongoing symptoms of constipation (55%) or fecal incontinence (45%), despite drug therapy, were included. The median symptom duration at referral was 2 years. Thirty-five (87%) completed treatment with a median of 2 sessions. Improvement of "6 = much better" or "7 = very much better" was reported by 77% (17/22) with fecal incontinence and 83% (15/18) with constipation. Improvement occurred irrespective of IBD diagnosis, previous perianal fistulae, colorectal surgery, presence of an ileoanal pouch, or past obstetric trauma. Conclusions: Behavioral treatment effectively improves functional gut symptoms in a large majority of patients who are in IBD disease remission and who have not responded to drug therapy.
The American Journal of the Medical Sciences, 2016
The aim of this study was to explore the effect of kidney transplantation (KT) on psychological d... more The aim of this study was to explore the effect of kidney transplantation (KT) on psychological distress and quality of life (QoL) in patients with end-stage kidney disease using the Common Sense Model of illness adjustment. A total of 52 individuals (35 men and 17 women) with an average age of 53.54 years from a large metropolitan nephrology outpatient clinic participated. Poorer health status, illness perceptions and increased engagement in maladaptive coping were associated with psychological distress (specifically anxiety and depression) and poorer QoL. Hierarchical regression, after correcting for KT characteristics (years since most recent KT, number of transplants) indicated that poorer illness status and illness perception predicted QoL. After controlling for KT characteristics, poorer illness status and greater engagement in maladaptive coping predicted depression. In contrast, poorer illness perceptions and greater engagement in maladaptive coping predicted anxiety. Adaptive problem-focused and emotion-focused coping styles were not found to predict anxiety, depression or QoL. The finding of the present study emphasize on the importance of exploring and understanding the effect of illness status, illness perceptions and coping patterns in patients who have underwent KT.
Epilepsia, Jan 14, 2016
To model the factors associated with depression in a community sample of people with epilepsy. Th... more To model the factors associated with depression in a community sample of people with epilepsy. The factors investigated were derived from proposed risk factors for depression from patients with epilepsy, other chronic illness, and the general population. Multivariate analysis using general linear regression models of factors associated with depression in the Tasmanian Epilepsy Register Mood Study (TERMS), a cross-sectional community sample of 440 patients with epilepsy. A model with acceptable fit was created that explained 66% of the variance of depression. Associated factors included in this model were neuroticism, physical functioning, social support, past history of depression, and stressful life events. In this cross-sectional study designed specifically to investigate depression in epilepsy, we showed that general risk factors for depression in other illness and in the general population are also important in patients with epilepsy, with little support for disease-related risk...
Aust N Z J Psychiat, 2002
The American Journal of the Medical Sciences, 2014
Journal of Wound, Ostomy and Continence Nursing, 2014
We employed the Common Sense Model (CSM) of illness perceptions to examine the relative contribut... more We employed the Common Sense Model (CSM) of illness perceptions to examine the relative contribution of illness perceptions, stoma self-efficacy, and coping strategies in explaining anxiety and depression symptoms in patients with a fecal ostomy. The CSM suggests that the consequences of illness activity, such as psychological distress, are influenced by an individual's illness perceptions as well as what coping strategies they engage in. Descriptive, cross-sectional questionnaire-based study. One hundred fifty adults with a stoma (54 males, and 96 females; mean age 44 years) completed an online survey. Several instruments were used to measure study outcomes, including the Health Perceptions Questionnaire, Brief Illness Perceptions Questionnaire, Carver Brief Coping Questionnaire, Stoma Self-Efficacy Scale, and the Hospital Anxiety and Depression Scale. Participants were advised of the study through online forums containing a link to the survey. Outcome measures used in the current study are valid and reliable and have been extensively used in medically ill patients. Using structural equation modeling, the final model provided an excellent fit to the data (χ23= 16.53, P = .22, χ/N = 1.27, SRMR < 0.03, RMSEA < 0.05, GFI > 0.97, CFI > 0.99). There was a direct pathway from health status to illness perceptions months since surgery directly influenced health status, illness beliefs, and adaptive emotion-focused coping (β= .81, P < .001). Several indirect (mediating) pathways were also identified. Illness perceptions mediated the relationship between health status and stoma self-efficacy and maladaptive and adaptive emotion-focused coping. Maladaptive coping mediated the relationship between illness perceptions and depression and anxiety, and adaptive emotion-focused coping mediated the relationship between illness perception and depression. The final model provided support for the CSM, in that illness perceptions were directly related to illness status, and that both illness perceptions and coping strategies directly influenced anxiety and depression. More specifically, maladaptive coping style (eg, ignore problems) exacerbated depression and anxiety symptoms, while self-efficacy and emotion-focused coping style (eg, seek advice) ameliorate depression, but not anxiety. Months since surgery was associated with improved health status, reduced poorer illness perceptions, and increased emotional-focused coping. Illness perceptions and coping were found to mediate anxiety and depression. The results confirm that how individuals perceive their illness and what coping strategies they engage in impacts their psychological well-being. Study findings support the need for designing targeting psychological interventions based on…
Epilepsy & Behavior, 2014
This study aimed to test whether a specific serotonin transporter (5HTT) gene polymorphism intera... more This study aimed to test whether a specific serotonin transporter (5HTT) gene polymorphism interacting with life stress increased the risk of depression in patients with epilepsy. The Tasmanian Epilepsy Register Mood Study (TERMS) used a cross-sectional study design of a community sample of patients with epilepsy previously recruited into the Tasmanian Epilepsy Register. It employed a mailed self-complete questionnaire and saliva DNA collection. Depression was assessed using the Center for Epidemiologic Studies Depression Scale. Environmental measures were selected to cover recent stressful events, epilepsy-related stress, current social support, and early life stress. Of 820 eligible participants, 553 (67%) participants completed the study. Experience of at least one stressful life event was very common, with a significant association between depression and the stressful life events (F=26.2, df=3, p<0.001). There was no association between serotonin transporter genotype and level of depressive symptoms reported (F=0.421, df=2, p=0.7). There was no evidence of any adverse life experiences interacting with serotonin transporter genotype to moderate the risk of depression. The failure to demonstrate a main effect of genotype on depression or a gene × environment interaction differs from several studies of patients with other chronic diseases. However, it is consistent with larger general population studies.
Epilepsy & Behavior, 2015
Depression is one of the most common psychiatric comorbidities in epilepsy; however, the factors ... more Depression is one of the most common psychiatric comorbidities in epilepsy; however, the factors contributing to this association remain unclear. There is a growing consensus that methodological limitations, particularly selection bias, affect many of the original studies. A systematic review focussed on community-based studies offers an alternative approach for the identification of the risk factors for depression. Searches were performed in MEDLINE (Ovid), 2000 to 31 December 2013, EMBASE, and Google Scholar to identify studies examining risk factors for depression in epilepsy. Community-based studies of adults with epilepsy that reported at least one risk factor for depression were included. The search identified 17 studies that met selection criteria, representing a combined total of 12,212 people with epilepsy with a mean sample size of 718. The most consistent risk factors for depression were sociodemographic factors, despite the fact that most studies focus on epilepsy-related factors. Most studies lacked a systematic conceptual approach to investigating depression, and few risk factors were consistently well studied. Future community-based studies require a detailed systematic approach to improve the ability to detect risk factors for depression in epilepsy. Psychological factors were rarely studied in community-based samples with epilepsy, although the consistent association with depression in the few studies that did suggests this warrants further examination.
Neurobiology of disease, Sep 13, 2016
The absence epilepsies are presumed to be caused by genetic factors, but the influence of environ... more The absence epilepsies are presumed to be caused by genetic factors, but the influence of environmental exposures on epilepsy development and severity, and whether this influence is transmitted to subsequent generations, is not well known. We assessed the effects of environmental enrichment on epilepsy and anxiety outcomes in multiple generations of GAERS - a genetic rat model of absence epilepsy that manifests comorbid elevated anxiety-like behaviour. GAERS were exposed to environmental enrichment or standard housing beginning either prior to, or after epilepsy onset, and underwent EEG recordings and anxiety testing. Then, we exposed male GAERS to early enrichment or standard housing and generated F1 progeny, which also underwent EEG recordings. Hippocampal CRH mRNA expression and DNA methylation were assessed using RT-PCR and pyrosequencing, respectively. Early environmental enrichment delayed the onset of epilepsy in GAERS, and resulted in fewer seizures in adulthood, compared wi...
Rheumatology (Oxford, England), Jan 8, 2016
The aim was to evaluate the utility of the common sense model (CSM) in characterizing contributor... more The aim was to evaluate the utility of the common sense model (CSM) in characterizing contributors to psychological well-being and quality of life (QoL) in patients with end-stage OA. One hundred and twenty patients [34 males, 86 females; mean (s.d.) age 65.52 (9.14) years] with end-stage OA (57.5% hip, 42.5% knee) were recruited. OA symptom severity was evaluated according to the WOMAC; coping styles were assessed with the Carver Brief COPE scale; illness perceptions were explored with the Brief Illness Perceptions Questionnaire; self-efficacy was assessed with the Arthritis Self-efficacy scale; anxiety, depression and overall distress were measured using the Hospital Anxiety and Depression Scale; and QoL was assessed using the WHO Quality of Life-short version. The CSM was used to explore the interrelationships between OA symptom severity, illness perceptions and coping strategies in patients. Two structural equation models were developed, with both found to have good fit. Consist...
Epilepsia, 2016
Environmental exposures impart powerful effects on vulnerability to many brain diseases, includin... more Environmental exposures impart powerful effects on vulnerability to many brain diseases, including epilepsy. Mesial temporal lobe epilepsy (MTLE) is a common form of epilepsy, and it is often accompanied by neuropsychiatric comorbidities. This study tests the hypothesis that environmental enrichment (EE) confers antiepileptogenic, psychoprotective, and neuroprotective effects in the amygdala kindling model of MTLE, and explores potential neurobiologic mechanisms. At weaning, male Wistar rats were allocated into either EE (large cages containing running wheels and toys; n = 43) or standard housing (SH; standard laboratory cages; n = 39) conditions. At P56, a bipolar electrode was implanted into the left amygdala, and rats underwent rapid amygdala kindling until experiencing five class V seizures (Racine scale, fully kindled). The elevated plus maze was used to assess anxiety. Postmortem histologic and molecular analyses investigated potential biologic mediators of effects. EE significantly delayed kindling epileptogenesis, with EE rats requiring a significantly greater number of kindling stimulations to reach a fully kindled state compared to SH rats (p < 0.05). EE and kindling both reduced anxiety (p < 0.05). Timm's staining revealed significant reductions in aberrant mossy fiber sprouting in EE rats (p < 0.05), and these effects of EE were accompanied by reduced expression of TrkB and CRH genes. We identify beneficial effects of EE on vulnerability to limbic epileptogenesis and anxiety, and identify reduced pathologic neuroplasticity and plasticity-related gene expression as potential underlying mechanisms. Enhanced environmental stimulation represents a potential antiepileptogenic strategy that might also mitigate the common psychiatric comorbidities of MTLE.
Clinical and Experimental Gastroenterology, 2015
ISRN Emergency Medicine, 2013
Objectives. To identify the proportion of adult emergency department (ED) patients who screen pos... more Objectives. To identify the proportion of adult emergency department (ED) patients who screen positive for depression. Secondary aims were to identify factors associated with a positive depression screen and determine predictors of a positive depression screen. Methods. This cross-sectional, prevalence survey of ED patients was conducted at two inner-city hospitals. 350 ED patients were screened for depression using the Patient Health Questionnaire-9 (PHQ-9). Clinical and demographic risk factors were examined through medical records and additional questionnaires. Results. Of 350 participants screened, 50 (14.3%; 95% CI = 11.0–18.4%) screened positive. Independent predictors of depression risk included self-reported depression and/or a previous diagnosis of depression (OR = 8.345; 95% CI = 3.524–19.762), seeing a mental health service provider in the past 6 months (OR = 4.518; 95% CI = 2.107–9.690), and previous discussion about mental health with a local doctor (OR = 2.369; 95% CI ...
Psychoneuroendocrinology, 2014
Oncology, 2007
Phase II/III trials have shown that capecitabine is an active, well-tolerated therapy for metasta... more Phase II/III trials have shown that capecitabine is an active, well-tolerated therapy for metastatic breast cancer (MBC). We report clinical findings from an expanded access program enabling patients ineligible for investigative trials to receive capecitabine before its approval and availability. Patients pretreated with at least two chemotherapy regimens, including a taxane, for MBC received oral capecitabine until disease progression or unacceptable toxicity. Six hundred and thirty-one patients received capecitabine (mean duration 3.8 months, range 0.1-24.7 months). The most common treatment-related grade 3/4 toxicities were diarrhea (9%) and hand-foot syndrome (8%). Grade 3/4 alopecia was absent and grade 3/4 myelosuppression was rare. Dose was modified in 172 patients (27%). Objective response rate in 349 evaluable patients was 35%. Median time to progression (n = 604) was 6.6 months (95% confidence interval, CI, 5.6-7.6) and median overall survival (n = 569) was 10.0 months (95% CI, 8.5-15.3). Our findings in a cohort of patients with pretreated progressive breast cancer confirm the high efficacy and tolerability of outpatient capecitabine.