Women's help seeking behaviour and the associated influencing factors on self discovery of a breast symptom

To investigate women’s help seeking behavior (HSB) following self discovery of a breast symptom and determine the associated influencing factors. A descriptive correlation design was used to ascertain the help seeking behavior (HSB) and the associated influencing factors of a sample of women (n = 449) with self discovered breast symptoms. The study was guided by the ‘Help Seeking Behaviour and Influencing Factors” conceptual framework (Facione et al., 2002; Meechan et al., 2003, 2002; Leventhal, Brissette and Leventhal, 2003 and O’Mahony and Hegarty, 2009b). Data was collected using a researcher developed multi-scale questionnaire package to ascertain women’s help seeking behavior on self discovery of a breast symptom and determine the factors most associated with HSB. Factors examined include: socio-demographics, knowledge and beliefs (regarding breast symptom; breast changes associated with breast cancer; use of alternative help seeking behaviours and presence or absence of a family history of breast cancer),emotional responses, social factors, health seeking habits and health service system utilization and help seeking behavior. A convenience sample (n = 449 was obtained by the researcher from amongst women attending the breast clinics of two large urban hospitals within the Republic of Ireland. All participants had self-discovered breast symptoms and no previous history of breast cancer. The study identified that while the majority of women (69.9%; n=314) sought help within one month, 30.1% (n=135) delayed help seeking for more than one month following self discovery of their breast symptom. The factors most significantly associated with HSB were the presenting symptom of ‘nipple indrawn/changes’ (p = 0.005), ‘ignoring the symptom and hoping it would go away’ (p < 0.001), the emotional response of being ‘afraid@ on symptom discovery (p = 0.005) and the perception/belief in longer symptom duration (p = 0.023). It was found that women who presented with an indrawn/changed nipple were more likely to delay (OR = 4.81) as were women who ‘ignored the symptoms and hoped it would go away’ (OR = 10.717). Additionally, the longer women perceived that their symptom would last, they more likely they were to delay (OR = 1.18). Conversely, being afraid following symptom discovery was associated with less delay (OR = 0.37; p=0.005). This study provides further insight into the HSB of women who self discovered breast symptoms. It highlights the complexity of the help seeking process, indicating that is not a linear event but is influenced by multiple factors which can have a significant impact on the outcomes in terms of whether women delay or seek help promptly. The study further demonstrates that delayed HSB persists amongst women with self discovered breast symptoms. This has important implications for continued emphasis on the promotion of breast awareness, prompt help seeking for self discovered breast symptoms and early detection and treatment of breast cancer, amongst women of all ages.

Issues in the prescribing of psychotropic and psychoactive medication for persons with learning disability: quantitative and qualitative perspectives

The administration of psychotropic and psychoactive medication for persons with learning disability and accompanying mental illness and/or challenging behaviour has undergone much critical review over the past two decades. Assessment and diagnosis of mental illness in this population continues to be psychopharmacological treatment include polypharmacy, irrational prescription procedures and frequent over-prescription. It is clear that all forms of treatment including non-pharmacological interventions need to be driven by accurate and appropriate diagnoses. Where a psychiatric diagnosis has been identified, it greatly aides the selection of appropriate medication, although a specific medication for each diagnosis, as was once hoped, is simply no longer a reality in practice. Part one of the present thesis seeks to address many of the current issues in mental health problems and pharmacological treatment to date. The author undertook a drug prevalence study within both residential and community facilities for persons with learning disability within the Mid-West region of Ireland in order to ascertain the current level of prescribing of psychotropic and psychoactive medications for this population. While many attempts have been made to account for the variation in prescribing, little systematic and empirical research has been undertaken to investigate the factors thought to influence such prescribing. While studies investigating the prescribing behaviours of General Practitioners (GP's) have illustrated the complex nature of the decision making process in the context of general practice, no similar efforts have yet been directed at examining the prescribing behaviours of Consultant Psychiatrists. Using The Critical Incident Technique, the author interviewed Consultant Psychiatrists in the Republic of Ireland to gather information relating not only to their patterns of prescribing for learning disabled populations, but also to examine reasons influencing their prescribing in addition to several related factors. Part two of this thesis presents the findings from this study and a number of issues are raised, not only in relation to attempting to account for the findings from part one of the thesis, but also with respect to implications for improved management and clinical practice.

Novel insights into the role of the GABAB receptor in depression and anxiety

The GABAB receptor is a functional heterodimer comprising the GABAB1 and GABAB2 subunits, with the GABAB1 subunit displaying two major isoforms, GABAB(1a) and GABAB(1b). Preclinical findings have strongly implicated the GABAB receptor in stress-related psychiatric disorders, however, the precise contribution of the GABAB receptor in depression and anxiety disorders remains unknown. Emerging data suggest that the interaction between adverse environmental conditions, such as early life stress, and a specific genetic composition can increase the risk to develop psychiatric disorders in adulthood. This thesis investigated the role of the GABAB receptor alone or in combination with early-life stress (maternal separation), in modulating antidepressant like and anxiety-related behaviours. Pharmacological blockade of the GABAB receptor with CGP52432 had antidepressant-like behavioural effects. Moreover, mice lacking the GABAB(1b) receptor subunit isoform exhibited antidepressant-like behaviours in adulthood but anxiety-like behaviour in early-life. In response to maternal separation, GABAB(1a)-/- mice exhibited early-life stress-induced anhedonia, a core symptom of depression, while GABAB(1b)-/- mice exhibited a more resilient phenotype. Moreover, when compared with wildtype or GABAB(1a)-/- mice, GABAB(1b)-/- mice that underwent maternal separation exhibited enhanced stressinduced neuronal activation in the hippocampus and in the nucleus accumbens (NAcc), a critical area for anhedonia thus suggesting that enhanced stress-induced neuronal activation in the hippocampus and NAcc in GABAB(1b)-/- mice may be important for their antidepressant-like phenotype and their resilience to stress-induced anhedonia. Pharmacological blockade of GABAB receptor and GABAB(1b) receptor subunit isoform loss of function increased adult hippocampal cell proliferation, thus suggesting that increased hippocampal neurogenesis could be a potential mechanism for the antidepressant-like effects of GABAB receptor antagonists and GABAB(1b) receptor subunit isoform disruption. Finally, this thesis investigated whether the expression of several genes involved in hippocampal neurogenesis or the antidepressant response were altered in the mouse hippocampus following chronic treatment with a GABAB receptor antagonist.

The role of mitogen activated protein kinase phosphatase-1 in neurotoxic and inflammatory-induced changes in the development of midbrain dopaminergic neurons: relevance to Parkinson’s disease

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterised by the loss of midbrain dopaminergic neurons from the substantia nigra pars compacta(SNpc), which results in motor, cognitive and psychiatric symptoms. Evidence supports a role for the mitogen-activated protein kinase p38 in the demise of dopaminergic neurons, while mitogen-activated protein kinase phosphatase-1 (MKP-1), which negatively regulates p38 activity, has not yet been investigated in this context. Inflammation may also be associated with the neuropathology of PD due to evidence of increased levels of proinflammatory cytokines such as interleukin-1β (IL-1β) within the SNpc. Because of the specific loss of dopaminergic neurons in a discreet region of the brain, PD is considered a suitable candidate for cell replacement therapy but challenges remain to optimise dopaminergic cell survival and morphological development. The present thesis examined the role of MKP-1 in neurotoxic and inflammatory-induced changes in the development of midbrain dopaminergic neurons. We show that MKP-1 is expressed in dopaminergic neurons cultured from embryonic day (E) 14 rat ventral mesencephalon (VM). Inhibition of dopaminergic neurite growth induced by treatment of rat VM neurons with the dopaminergic neurotoxin 6- hydroxydopamine (6-OHDA) is mediated by p38, and is concomitant with a significant and selective decrease in MKP-1 expression in these neurons. Dopaminergic neurons transfected to overexpress MKP-1 displayed a more complex morphology and contributed to neuroprotection against the effects of 6-OHDA. Therefore, MKP-1 expression can promote the growth and elaboration of dopaminergic neuronal processes and can help protect them from the neurotoxic effects of 6-OHDA. Neural precursor cells (NPCs) have emerged as promising alternative candidates to fetal VM for cell replacement strategies in PD. Here we show that phosphorylated (and thus activated) p38 and MKP-1 are expressed at basal levels in untreated E14 rat VM NPCs (nestin, DCX, GFAP and DAT-positive cells) following proliferation as well as in their differentiated progeny (DCX, DAT, GFAP and βIII-tubulin) in vitro. Challenge with 6-OHDA or IL-1β changed the expression of endogenous phospho-p38 and MKP-1 in these cells in a time-dependent manner, and so the dynamic balance in expression may mediate the detrimental effects of neurotoxicity and inflammation in proliferating and differentiating NPCs. We demonstrate that there was an up-regulation in MKP-1 mRNA expression in adult rat midbrain tissue 4 days post lesion in two rat models of PD; the 6-OHDA medial forebrain bundle (MFB) model and the four-site 6-OHDA striatal lesion model. This was concomitant with a decrease in tyrosine hydroxylase (TH) mRNA expression at 4 and 10 days post-lesion in the MFB model and 10 and 28 days post-lesion in the striatal lesion model. There was no change in mRNA expression of the pro-apoptotic gene, bax and the anti-apoptotic gene, bcl-2 in the midbrain and striatum. These data suggest that the early and transient upregulation of MKP-1 mRNA in the midbrain at 4 days post-6-OHDA administration may be indicative of an attempt by dopaminergic neurons in the midbrain to protect against the neurotoxic effects of 6-OHDA at later time points. Collectively, these findings show that MKP-1 is expressed by developing and adult dopaminergic neurons in the midbrain, and can promote their morphological development. MKP-1 also exerts neuroprotective effects against dopaminergic neurotoxins in vitro, and its expression in dopaminergic neurons can be modulated by inflammatory and neurotoxic insults both in vitro and in vivo. Thus, these data contribute to the information needed to develop therapeutic strategies for protecting midbrain dopaminergic neurons in the context of PD.

An examination of the impact of dietary lipids on behaviour and neurochemistry

The molecular and cellular basis of stress pathology remains an important research question in biological science. A better understanding of this may enable the development of novel approaches for the treatment of stress-related disorders. There is a considerable body of scientific evidence suggesting that dietary lipids, phospholipids and omega-3 polyunsaturated fatty acids (n-3 PUFAs), have therapeutic potential for certain psychiatric disorders. Thus, we proposed n-3 PUFAs as a novel strategy for the prevention or amelioration of stress-related disorders. We hypothesised that these compounds would improve behavioural and neurobiological responses and alter gut microbial composition. Furthermore, we proposed a new mechanism of action exerted by n-3 PUFAs using an in vitro model of stress. Lastly, we explored the protective effects of both phospholipids and n-3 PUFAs against neuroinflammation, which has been shown to contribute to the development of stress-related disorders. We provide further evidence that glucocorticoids, inflammation and early-life stress induce vulnerability to psychopathologies. Specifically, we have demonstrated that corticosterone (CORT) alters cortical neuron and astrocyte percentage composition, reduces brain-derived-neuronal factor (BDNF) expression, and induces glucocorticoid receptor (GR) down-regulation in mixed cortical cultures. Interestingly, we found that lipopolysaccharide (LPS) treatment resulted in an over-expression of pro-inflammatory cytokines in cortical astrocyte cultures. Moreover, we demonstrate that early-life stress induces changes to the monoaminergic and immune systems as well as altered neuroendocrine response to stressors later in life. In addition, we found that early-life stress alters the gut microbiota in adulthood. These data demonstrate that n-3 PUFAs can attenuate CORT-induced cellular changes, but not those caused by LPS, within the cerebral cortex. Similarly, phospholipids were unable to reverse LPS-induced inflammation in cultured astrocytes. In addition, this thesis proposes that n-3 PUFAs may prevent the development or lessen the symptoms of mental illnesses, ameliorating anxiety- and depressive-like symptoms as well as cognitive effects, particularly when administered during neurodevelopment. Such effects may be mediated by GR activation as well as by modification of the gut microbiota composition. Taken together, our findings suggest that n-3 PUFAs have therapeutic potential for stress-related disorders and we provide evidence for the mechanisms by which they may exert these effects. These findings contribute to an exciting and growing body of research suggesting that nutritional interventions may have an important role to play in the treatment of stress-related psychiatric conditions.

Reduction of quantity smoked predicts future cessation among older smokers.

AIM: To examine whether smokers who reduce their quantity of cigarettes smoked between two periods are more or less likely to quit subsequently. STUDY DESIGN: Data come from the Health and Retirement Study, a nationally representative survey of older Americans aged 51-61 in 1991 followed every 2 years from 1992 to 1998. The 2064 participants smoking at baseline and the first follow-up comprise the main sample. MEASUREMENTS: Smoking cessation by 1996 is examined as the primary outcome. A secondary outcome is relapse by 1998. Spontaneous changes in smoking quantity between the first two waves make up the key predictor variables. Control variables include gender, age, education, race, marital status, alcohol use, psychiatric problems, acute or chronic health problems and smoking quantity. FINDINGS: Large (over 50%) and even moderate (25-50%) reductions in quantity smoked between 1992 and 1994 predict prospectively increased likelihood of cessation in 1996 compared to no change in quantity (OR 2.96, P<0.001 and OR 1.61, P<0.01, respectively). Additionally, those who reduced and then quit were somewhat less likely to relapse by 1998 than those who did not reduce in the 2 years prior to quitting. CONCLUSIONS: Reducing successfully the quantity of cigarettes smoked appears to have a beneficial effect on future cessation likelihood, even after controlling for initial smoking level and other variables known to impact smoking cessation. These results indicate that the harm reduction strategy of reduced smoking warrants further study.

A cross-site, comparative effectiveness study of an integrated HIV and substance use treatment program.

Co-occurrence of HIV and substance abuse is associated with poor outcomes for HIV-related health and substance use. Integration of substance use and medical care holds promise for HIV patients, yet few integrated treatment models have been reported. Most of the reported models lack data on treatment outcomes in diverse settings. This study examined the substance use outcomes of an integrated treatment model for patients with both HIV and substance use at three different clinics. Sites differed by type and degree of integration, with one integrated academic medical center, one co-located academic medical center, and one co-located community health center. Participants (n=286) received integrated substance use and HIV treatment for 12 months and were interviewed at 6-month intervals. We used linear generalized estimating equation regression analysis to examine changes in Addiction Severity Index (ASI) alcohol and drug severity scores. To test whether our treatment was differentially effective across sites, we compared a full model including site by time point interaction terms to a reduced model including only site fixed effects. Alcohol severity scores decreased significantly at 6 and 12 months. Drug severity scores decreased significantly at 12 months. Once baseline severity variation was incorporated into the model, there was no evidence of variation in alcohol or drug score changes by site. Substance use outcomes did not differ by age, gender, income, or race. This integrated treatment model offers an option for treating diverse patients with HIV and substance use in a variety of clinic settings. Studies with control groups are needed to confirm these findings.

Spatial distribution of bednet coverage under routine distribution through the public health sector in a rural district in Kenya.

Insecticide-treated nets (ITNs) are one of the most important and cost-effective tools for malaria control. Maximizing individual and community benefit from ITNs requires high population-based coverage. Several mechanisms are used to distribute ITNs, including health facility-based targeted distribution to high-risk groups; community-based mass distribution; social marketing with or without private sector subsidies; and integrating ITN delivery with other public health interventions. The objective of this analysis is to describe bednet coverage in a district in western Kenya where the primary mechanism for distribution is to pregnant women and infants who attend antenatal and immunization clinics. We use data from a population-based census to examine the extent of, and factors correlated with, ownership of bednets. We use both multivariable logistic regression and spatial techniques to explore the relationship between household bednet ownership and sociodemographic and geographic variables. We show that only 21% of households own any bednets, far lower than the national average, and that ownership is not significantly higher amongst pregnant women attending antenatal clinic. We also show that coverage is spatially heterogeneous with less than 2% of the population residing in zones with adequate coverage to experience indirect effects of ITN protection.

The impact of structured support groups for pregnant South African women recently diagnosed HIV positive.

The authors of this study evaluated a structured 10-session psychosocial support group intervention for newly HIV-diagnosed pregnant South African women. Participants were expected to display increases in HIV disclosure, self-esteem, active coping and positive social support, and decreases in depression, avoidant coping, and negative social support. Three hundred sixty-one pregnant HIV-infected women were recruited from four antenatal clinics in Tshwane townships from April 2005 to September 2006. Using a quasi-experimental design, assessments were conducted at baseline and two and eight months post-intervention. A series of random effects regression analyses were conducted, with the three assessment points treated as a random effect of time. At both follow-ups, the rate of disclosure in the intervention group was significantly higher than that of the comparison group (p<0.001). Compared to the comparison group at the first follow-up, the intervention group displayed higher levels of active coping (t=2.68, p<0.05) and lower levels of avoidant coping (t=-2.02, p<0.05), and those who attended at least half of the intervention sessions exhibited improved self-esteem (t=2.11, p<0.05). Group interventions tailored for newly HIV positive pregnant women, implemented in resource-limited settings, may accelerate the process of adjusting to one's HIV status, but may not have sustainable benefits over time.

Preschool anxiety disorders predict different patterns of amygdala-prefrontal connectivity at school-age.

OBJECTIVE: In this prospective, longitudinal study of young children, we examined whether a history of preschool generalized anxiety, separation anxiety, and/or social phobia is associated with amygdala-prefrontal dysregulation at school-age. As an exploratory analysis, we investigated whether distinct anxiety disorders differ in the patterns of this amygdala-prefrontal dysregulation. METHODS: Participants were children taking part in a 5-year study of early childhood brain development and anxiety disorders. Preschool symptoms of generalized anxiety, separation anxiety, and social phobia were assessed with the Preschool Age Psychiatric Assessment (PAPA) in the first wave of the study when the children were between 2 and 5 years old. The PAPA was repeated at age 6. We conducted functional MRIs when the children were 5.5 to 9.5 year old to assess neural responses to viewing of angry and fearful faces. RESULTS: A history of preschool social phobia predicted less school-age functional connectivity between the amygdala and the ventral prefrontal cortices to angry faces. Preschool generalized anxiety predicted less functional connectivity between the amygdala and dorsal prefrontal cortices in response to fearful faces. Finally, a history of preschool separation anxiety predicted less school-age functional connectivity between the amygdala and the ventral prefrontal cortices to angry faces and greater school-age functional connectivity between the amygdala and dorsal prefrontal cortices to angry faces. CONCLUSIONS: Our results suggest that there are enduring neurobiological effects associated with a history of preschool anxiety, which occur over-and-above the effect of subsequent emotional symptoms. Our results also provide preliminary evidence for the neurobiological differentiation of specific preschool anxiety disorders.

When the library is located in prime real estate: a case study on the loss of space from the Duke University Medical Center Library and Archives.

The Duke University Medical Center Library and Archives is located in the heart of the Duke Medicine campus, surrounded by Duke Hospital, ambulatory clinics, and numerous research facilities. Its location is considered prime real estate, given its adjacency to patient care, research, and educational activities. In 2005, the Duke University Library Space Planning Committee had recommended creating a learning center in the library that would support a variety of educational activities. However, the health system needed to convert the library's top floor into office space to make way for expansion of the hospital and cancer center. The library had only five months to plan the storage and consolidation of its journal and book collections, while working with the facilities design office and architect on the replacement of key user spaces on the top floor. Library staff worked together to develop plans for storing, weeding, and consolidating the collections and provided input into renovation plans for users spaces on its mezzanine level. The library lost 15,238 square feet (29%) of its net assignable square footage and a total of 16,897 (30%) gross square feet. This included 50% of the total space allotted to collections and over 15% of user spaces. The top-floor space now houses offices for Duke Medicine oncology faculty and staff. By storing a large portion of its collection off-site, the library was able to remove more stacks on the remaining stack level and convert them to user spaces, a long-term goal for the library. Additional space on the mezzanine level had to be converted to replace lost study and conference room spaces. While this project did not match the recommended space plans for the library, it underscored the need for the library to think creatively about the future of its facility and to work toward a more cohesive master plan.

Involuntary Memories and Dissociative Amnesia: Assessing Key Assumptions in PTSD Research.

Autobiographical memories of trauma victims are often described as disturbed in two ways. First, the trauma is frequently re-experienced in the form of involuntary, intrusive recollections. Second, the trauma is difficult to recall voluntarily (strategically); important parts may be totally or partially inaccessible-a feature known as dissociative amnesia. These characteristics are often mentioned by PTSD researchers and are included as PTSD symptoms in the DSM-IV-TR (American Psychiatric Association, 2000). In contrast, we show that both involuntary and voluntary recall are enhanced by emotional stress during encoding. We also show that the PTSD symptom in the diagnosis addressing dissociative amnesia, trouble remembering important aspects of the trauma is less well correlated with the remaining PTSD symptoms than the conceptual reversal of having trouble forgetting important aspects of the trauma. Our findings contradict key assumptions that have shaped PTSD research over the last 40 years.

Differential predictability of four dimensions of affect intensity.

Individual differences in affect intensity are typically assessed with the Affect Intensity Measure (AIM). Previous factor analyses suggest that the AIM is comprised of four weakly correlated factors: Positive Affectivity, Negative Reactivity, Negative Intensity and Positive Intensity or Serenity. However, little data exist to show whether its four factors relate to other measures differently enough to preclude use of the total scale score. The present study replicated the four-factor solution and found that subscales derived from the four factors correlated differently with criterion variables that assess personality domains, affective dispositions, and cognitive patterns that are associated with emotional reactions. The results show that use of the total AIM score can obscure relationships between specific features of affect intensity and other variables and suggest that researchers should examine the individual AIM subscales.

A memory-based model of posttraumatic stress disorder: evaluating basic assumptions underlying the PTSD diagnosis.

In the mnemonic model of posttraumatic stress disorder (PTSD), the current memory of a negative event, not the event itself, determines symptoms. The model is an alternative to the current event-based etiology of PTSD represented in the Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; American Psychiatric Association, 2000). The model accounts for important and reliable findings that are often inconsistent with the current diagnostic view and that have been neglected by theoretical accounts of the disorder, including the following observations. The diagnosis needs objective information about the trauma and peritraumatic emotions but uses retrospective memory reports that can have substantial biases. Negative events and emotions that do not satisfy the current diagnostic criteria for a trauma can be followed by symptoms that would otherwise qualify for PTSD. Predisposing factors that affect the current memory have large effects on symptoms. The inability-to-recall-an-important-aspect-of-the-trauma symptom does not correlate with other symptoms. Loss or enhancement of the trauma memory affects PTSD symptoms in predictable ways. Special mechanisms that apply only to traumatic memories are not needed, increasing parsimony and the knowledge that can be applied to understanding PTSD.