Background The use of prophylactic antibiotics before endoscopic retrograde cholangiopancreatography (ERCP) is recommended by all major international gastroenterological societies, especially in the presence of an obstructed biliary system. Their use is intended to decrease or eliminate the incidence of complications following the procedure, namely cholangitis, cholecystitis, septicaemia, and pancreatitis. Objectives To assess the benefits and harms of antibiotics before elective ERCP in patients without evidence of acute or chronic cholecystitis, or acute or chronic cholangitis, or severe acute pancreatitis. Data collection and analysis We audited South African endoscopists who perform ERCPs in the form of a questionnaire. The review was conducted according to the recommendations of The Cochrane Collaboration as well as the Cochrane Hepato-Biliary Group. Review Manager 5 was used employing fixed-effect and random-effects model meta-analyses. Only randomised clinical trials were included in the analyses, irrespective of blinding, language, or publication status. Participants were patients that underwent elective ERCP that were not on antibiotics, without evidence of acute or chronic cholecystitis, cholangitis, or severe acute pancreatitis before the procedure. We compared patients that received prophylactic antibiotics before the procedure with patients that were given placebo or no intervention before the procedure. Results The audit revealed that no specific protocols were being implemented in South Africa, and there was a marked difference in the practice between surgical and medical gastroenterologists, with surgeons using antibiotics more often. There was also a wide spectrum of antibiotic types and combinations being used. Nine randomised clinical trials (1573 patients) were included into the review analyses. The majority of the trials had risks of bias. When all patients providing data for a certain outcome were included, the fixed-effect meta-analyses significantly favoured the use of prophylactic antibiotics in preventing cholangitis (relative risk (RR) 0.54, 95% CI 0.33 to 0.91), septicaemia (RR 0.35, 95% CI 0.11 to 1.11), bacteriaemia (RR 0.50, 95% CI 0.33 to 0.78), and pancreatitis (RR 0.54, 95% CI 0.29 to 1.00). In random-effects meta- analyses, only the effect on bacteriaemia remained significant. Overall mortality was not reduced (RR 1.33, 95% CI 0.32 to 5.44). If one selects patients in whom the ERCP resolved the biliary obstruction at the first procedure, there seem to be no significant benefit in using prophylactic antibiotics to prevent cholangitis (RR 0.98, 95% CI 0.35 to 2.69, only three trials). Conclusions Prophylactic antibiotics reduce bacteriaemia and seem to prevent cholangitis and septicaemia in patients undergoing elective ERCP. In the subgroup of patients with uncomplicated ERCP, the effect of antibiotics may be less evident. Further research is required to determine whether antibiotics can be given during or after an ERCP if it becomes apparent that biliary obstruction cannot be relieved during that procedure.

Introduction: During the last decade, our institution saw a 260% increase in bilateral breast reconstruction cases, consistent with national trends. We reported a drop in average age of prophylactic mastectomy from 57 to 51 years. There is limited data on the likelihood of histological abnormalities in this population. This study measures the prevalence of occult histological findings in prophylactic mastectomy patients. Given the current healthcare reform climate, we estimate the lifetime cost implications of prophylactic mastectomy with immediate reconstruction vs. surveillance. Methods: A retrospective database of breast reconstructions at the Massachusetts General Hospital was searched from 2004 to 2011 for prophylactic mastectomy patients. Breasts with prior biopsy-proven LCIS, DCIS, or cancer were excluded. Patient demographics, risk factors, and pathology reports were collected. Lifetime treatment reimbursements were estimated with 2013 rates from the Center for Medicare and Medicaid Services using Medicare billing codes. Reimbursements were estimated for 45-year-old patients undergoing contralateral prophylactic mastectomy and 40-year-old patients undergoing bilateral prophylactic mastectomies, and then were compared to women opting for surveillance. Conversion rates to cancer in these patients were used to estimate the percentage patients in the surveillance groups that would need therapeutic mastectomy. Sensitivity analyses were done to test the robustness of the models. Results: 495 prophylactic mastectomy specimens were identified, of which 2.0% had invasive cancer, 4.4% had ductal carcinoma in situ (DCIS), and 10.9% had lobular carcinoma in situ (LCIS) as the highest-risk lesion. Only age group was predictive of finding DCIS or cancer (P=0.02). The likelihood of finding LCIS, DCIS, or cancer increased with age group (P<0.001) and decreased with prior bilateral salpingo-oophorectomy (BSO)(P=0.02). In almost all scenarios, lifetime reimbursements were lower for pursuing either contralateral or bilateral prophylactic mastectomy, with immediate single-stage implant, expander, or abdominal perforator free flap (DIEP) reconstruction, as compared to surveillance. Conclusions: Prophylactic mastectomy patients have a significant rate of occult histological findings, increasing with age group and decreasing with prior BSO. Lifetime cost estimates suggest a cost-saving role in bilateral and contralateral prophylactic mastectomies. Ultimately, such a critical decision needs to be made individually, but should not be hindered by cost concerns. This study addresses a gap in knowledge with broad interest, contributing evidence of oncologic risk and cost to help guide decision-making in prophylactic mastectomy.

Prophylactic and therapeutic antibiotic treatments have the potential to increase excretion of antibiotic resistance genes (ARGs) by dairy cattle through selection pressure on the gut microbiome. The objective of these studies was to evaluate the effect of cephapirin benzathine administered prophylactically at the end of lactation and pirlimycin hydrochloride administered therapeutically during a clinical mastitis infection on the abundance and relative abundance of ARGs in dairy cow feces. For prophylactic treatment using cephapirin benzathine, nineteen end-of-lactation cows were used. Treatment cows (n = 9) received cephapirin benzathine as an intramammary infusion prior to dry-off, and control cows (n =10) received no antibiotics. All cows received an internal non-antibiotic teat sealant. Fecal grab samples were collected for each cow on d -2 (baseline, used as covariate), d 1, 3, 5, 7, and once per week until d 49. Fecal samples were collected in sterile containers, then freeze-dried and subject to DNA extraction. The abundance of ampC, blaCMY-2, ermB, sul1, tetO, tetW, integrase-specific gene int1, and 16S rRNA were quantified using quantitative polymerase chain reaction (qPCR). The genes ampC and blaCMY-2 encode resistance to ß-lactam antibiotics, ermB to macrolides, sul1 to sulfonamides, tetO and tetW to tetracyclines, and int1 a class-1 integrase gene that facilitates horizontal transfer of ARGs across bacteria. The 16S rRNA gene was used as a representation of bacterial population. Absolute abundance was defined as number of ARG copies per gram of freeze-dried feces, while relative abundance was defined as ARG copy numbers per copy of 16S rRNA gene, which is indicative of the proportion of bacteria carrying ARGs. Non-normal data were logarithmically transformed and were statistically analyzed using PROC GLIMMIX in SAS 9.2. Abundance and relative abundance of sul1 and blaCMY-2 were below the limit of quantification in most samples and therefore not suitable for statistical comparisons. The int1 gene was not detectable in any sample. There were significant interactions between treatment and day for the abundance and relative abundance of ampC, tetO, and tetW. The abundance and relative abundance of ampC increased with time in control cows while remaining constant in antibiotic treated cows through the dry period. Antibiotics may act to stabilize the gut microbiome in response to diet and housing changes. There was a significant main effect of treatment for ermB with a significantly greater proportion of bacteria carrying ermB in control cows when compared to antibiotic treated cows. The tetracycline resistance genes tetO and tetW behaved similarly with a significant treatment by day interaction for the abundance and relative abundance of both genes. The relative abundance of both tetO and tetW were greater in control cows when compared to antibiotic treated cows on days 3, 5, 7, and 14. The abundance of both tetO and tetW resistance genes increased in antibiotic treated cows from day 1 to 49. There was also a significant increase in tetW relative abundance when comparing day 1 to 49. Administering long-acting antibiotics as intramammary dry treatment changed fecal bacteria composition during the dry period perhaps by stabilizing GI bacteria through dietary and housing changes. However, the use of prophylactic dry cow treatment does not uniformly or predictably lead to changes in fecal ARGs. In a second study, after clinical mastitis detection and identification, 6 lactating dairy cows received therapeutic mastitis treatment (pirlimycin hydrochloride as an intramammary infusion). Fecal grab samples were collected from each cow on d 0, 3, 9, and 12. Collection and analytical methods were as previously described. Abundance and relative abundance of sul1 and blaCMY-2 were again below the limit of quantification and therefore not suitable for statistical comparison. The int1 gene was not detected in any sample. The abundance of 16S rRNA genes decreased with day and relative abundance ermB, tetO, and tetW increased with day. There was no significant effect of day on the relative abundance of ampC or the abundance of ampC, ermB, tetO, and tetW in feces of cows with clinical mastitis. Administering fast-acting antibiotics as therapeutic intramammary mastitis treatment to dairy cows increased the relative abundance (gene copies per 16S rRNA) of selected ARGs but not the total abundance of ARGs in feces. The use of antibiotics for prevention and treatment of bacterial infections does not uniformly or predictably increase ARGs. / Master of Science

This thesis presents a discursive analysis of accounts of breast cancer screening, risk and prevention. Breast cancer is currently the largest form of cancer death for women in Australia ( and many other Western nations ), but the causes are unknown. Consequently, health promotion has tended to focus on the early detection of the disease. Despite this focus, the currently available techniques for early detection of breast cancer continue to be subject to research and debate. For women at high risk of the disease due to a family history and, in some cases, a genetic predisposition, there is also discussion regarding the best course of preventative action. One option, prophylactic surgery ( or the removal of healthy breasts ), continues to be the topic of both medical and psychological research. In addition to the ongoing medical research and debate around the topics of breast cancer screening, risk and prevention, there has been extensive sociological theorising around the increased societal emphasis on risk more generally. This emphasis on risk has been argued to be one feature of governance in modern liberal democratic societies. Particularly with respect to health - care in such societies, there has been argued to be a shift towards increasing individual responsibility for health and the management of potential illness. A focus on individual responsibility is not necessarily a key feature of contemporary public health approaches. Nevertheless, it has been suggested that the emphasis on risk management, in combination with the prevalence of ' lifestyle ' diseases, has widened the gaze of public health, such that all aspects of individuals ' lives are open to scrutiny and regulation. An inevitable consequence of such shifts is the placing of increased responsibility for health on to individuals. The analysis in this thesis draws on a synthetic discursive approach to examine talk and text around the issues of breast cancer screening, risk and prevention, in light of these shifts in conceptualisations of health and health - care, and the medical debate surrounding detection and prevention techniques. In particular, three analytic chapters are concerned with three sets of data : media accounts of prophylactic mastectomy ; pamphlets promoting breast cancer screening ; and women ' s focus group talk. The analysis focuses on the discursive themes, ideological dilemmas, and subject positions deployed in the data. The following analytic findings are discussed : - the repeated positioning of individuals as ' patients without symptoms ', who are required to engage in risk management in order to prevent their ( inevitable ) future illness ; - the positioning of women in terms of traditional notions of femininity and mothering ; - the construction of a dilemmatic relationship between individuals and medical experts, whereby individuals are positioned as responsible for their own health and illness prevention, while simultaneously being reliant on medical experts who are sometimes wrong ; - the negotiation and flexible management of notions of responsibility, emotion and health behaviours in women ' s talk. The final chapter in the thesis considers implications of the analysis for public health and health promotion, and for a critical ( public ) health psychology. / Thesis (Ph.D.)--School of Psychology, 2006.

This thesis presents a discursive analysis of accounts of breast cancer screening, risk and prevention. Breast cancer is currently the largest form of cancer death for women in Australia ( and many other Western nations ), but the causes are unknown. Consequently, health promotion has tended to focus on the early detection of the disease. Despite this focus, the currently available techniques for early detection of breast cancer continue to be subject to research and debate. For women at high risk of the disease due to a family history and, in some cases, a genetic predisposition, there is also discussion regarding the best course of preventative action. One option, prophylactic surgery ( or the removal of healthy breasts ), continues to be the topic of both medical and psychological research. In addition to the ongoing medical research and debate around the topics of breast cancer screening, risk and prevention, there has been extensive sociological theorising around the increased societal emphasis on risk more generally. This emphasis on risk has been argued to be one feature of governance in modern liberal democratic societies. Particularly with respect to health - care in such societies, there has been argued to be a shift towards increasing individual responsibility for health and the management of potential illness. A focus on individual responsibility is not necessarily a key feature of contemporary public health approaches. Nevertheless, it has been suggested that the emphasis on risk management, in combination with the prevalence of ' lifestyle ' diseases, has widened the gaze of public health, such that all aspects of individuals ' lives are open to scrutiny and regulation. An inevitable consequence of such shifts is the placing of increased responsibility for health on to individuals. The analysis in this thesis draws on a synthetic discursive approach to examine talk and text around the issues of breast cancer screening, risk and prevention, in light of these shifts in conceptualisations of health and health - care, and the medical debate surrounding detection and prevention techniques. In particular, three analytic chapters are concerned with three sets of data : media accounts of prophylactic mastectomy ; pamphlets promoting breast cancer screening ; and women ' s focus group talk. The analysis focuses on the discursive themes, ideological dilemmas, and subject positions deployed in the data. The following analytic findings are discussed : - the repeated positioning of individuals as ' patients without symptoms ', who are required to engage in risk management in order to prevent their ( inevitable ) future illness ; - the positioning of women in terms of traditional notions of femininity and mothering ; - the construction of a dilemmatic relationship between individuals and medical experts, whereby individuals are positioned as responsible for their own health and illness prevention, while simultaneously being reliant on medical experts who are sometimes wrong ; - the negotiation and flexible management of notions of responsibility, emotion and health behaviours in women ' s talk. The final chapter in the thesis considers implications of the analysis for public health and health promotion, and for a critical ( public ) health psychology. / Thesis (Ph.D.)--School of Psychology, 2006.

The development of a safe, effective prophylactic HIV vaccine remains a major global health priority. Stabilized, soluble trimers that mimic the native functional HIV trimer have been developed that elicit strain-specific neutralizing HIV antibodies in animal models, and are currently being evaluated in several human clinical trials. Identifying whether multiple immunogens could be administered to facilitate the broadening of responses represents a pivotal challenge. In this thesis, we characterized the antibody response in individuals infected with multiple HIV strains to inform the development of polyvalent and sequential HIV vaccine regimens. We found that conventional approaches to detect HIV co- and superinfection are confounded by recombination. Therefore, we developed an automated, Bayesian approach to detect superinfection explicitly accounting for recombination. Using simulated and real sequence data, we demonstrated that this approach is sensitive, highly specific, and robust to recombination. Furthermore, analyzing previously published sequence datasets, we identified cases of superinfection that previously went undetected, indicating that superinfection occurs more frequently than previously estimated. We characterized the development of antibodies in five superinfected individuals identified in the CAPRISA 002 acute infection cohort. Specifically, we evaluated whether superinfection re-engaged cross-reactive memory B cells, promoting the development of cross-neutralizing antibodies. By comparing the breadth of the neutralizing antibody response in superinfected individuals to those that typically develop in singly infected individuals, we showed that HIV superinfection was not sufficient to broaden responses. By characterizing the kinetics and specificity of autologous neutralizing antibody responses, we show that responses to the superinfecting viruses failed to efficiently recruit neutralizing memory B cells. Instead, the secondary infection elicited strain-specific, de novo responses. This occurred even though the superinfecting viruses were relatively closely related (from the same subtype). To determine whether the co-exposure to diverse Env antigens favours the development of cross-neutralizing antibodies better than sequential exposure, we characterized the development of neutralizing antibodies in HIV co-infected individuals where several divergent viruses were transmitted prior to seroconversion. We identified three cases of co-infection that encompassed immunological exposure to: (i) two diverse, unlinked Envs, (ii) two related Envs with diversity uniformly distributed over the trimer, and (iii) two diverse but recombined Envs such that clusters of high homology were preserved in the presence of high diversity elsewhere. We found that, like superinfection, co-infection was not sufficient to broaden neutralizing antibody responses. Co-exposure to two HIV Env antigens did not necessarily produce additive or cross-neutralizing antibody responses, and in some cases was subject to immunological interference. This was most evident in the case of co-infection with two related Envs where diversity was uniformly distributed across the Env trimer; in this case neutralizing antibody responses to one variant arose to the near exclusion of responses to the other. However, in the case of co-exposure to diverse Envs but where the trimer apex was conserved in both variants through recombination, potent neutralization of both variants was evident. This was the co-infected participant who developed the broadest neutralizing antibody response, and we show that cross-neutralization was mediated, in part, by trimer apextargeting neutralizing antibodies. In conclusion, we find that HIV superinfection fails to efficiently recruit neutralizing memory B cells and, at best, results in additive nAb responses rather than a synergistic effect leading to cross-neutralization; a distinction that is highly relevant for vaccine design. While sequential immunizations with heterologous Env immunogens may be able to improve the potency of elicited responses, alone, they are unlikely to promote the development of bnAbs. Our observations from cases of co-infection suggests that cocktails of divergent stabilized Env trimers are unlikely to drive the development of cross-neutralizing antibodies, and may be subject to interference. However, the rational design of more similar immunogen cocktails where conserved epitopes are preserved across immunogens may be able to facilitate neutralizing antibodies to these targets, as seen in one individual. Thus, the use of related, stabilized Env trimers with diversity introduced in key regions together with strategies to reduce the immunogenicity of immunodominant, strain-specific epitopes may represent one path to a cross-neutralizing antibody response to multiple Envs within a cocktail.

Objectives: Increasing knowledge of genetics has found that a mutation to the BRCA 1 or 2 genes are associated with a high risk of developing breast cancer throughout the lifespan. A woman with this genetic mutation may consider preventive surgery to reduce the risk of breast cancer. This involves a prophylactic bilateral mastectomy to remove the breasts when there is no cancer present and may be followed by breast reconstruction. This study aimed to explore the lived experience and psycho-social impact on women of this surgery. Design: Interpretative phenomenological analysis was employed in an in-depth study of a small sample of eleven female patients with BRCA 1/2 genetic mutations who had undergone preventive surgery of prophylactic bilateral mastectomy. Methods: Semi-structured interviews were carried out. The transcripts of those interviews served as the data for an interpretative phenomenological analysis. Results and conclusions: Three themes were identified from the Interpretative Phenomenological Analysis to convey the lived experience of participants. These were (1) focus on reduced risk of cancer; taking control, relief and benefit finding, (2) a focus on relationships; family life, medical professional and BRCA support group and other women with lived experience, and (3) Focus on experiencing surgery and impact on self; the importance of reconstruction, loss of sexual attractiveness, impact on self from negative reaction of others and adjusting to surgical results. The implications are discussed in relation to the current literature and clinical practice.

The treatment of impacted third molars that have neither symptoms nor disease is controversial. One school of thought is that these teeth should be extracted before they do become symptomatic and/or diseased. A second school of thought advocates retaining these teeth until such time when they show evidence of developing symptoms or disease. The purpose of this review is to present the reasoning behind the two opposing schools of thought. Studies involving both the risks and the benefits of extracting and retaining asymptomatic, disease-free third molars were examined. There are studies to support the proponents of each school of thought. Proponents of removal are of the belief that many asymptomatic and disease-free impacted third molars eventually do become symptomatic and/or diseased, and do so when the patient is older. The morbidity and incidence of complications common to the procedure increase with age, and therefore proponents of removal prefer that surgery be performed at a younger age when the complications are less likely to be as severe or permanent. Those in support of retaining and monitoring these teeth are of the opinion that the status of these asymptomatic and disease-free impacted third molars may never change and therefore never require surgical intervention. They believe the increased complication rate and morbidity experience by some of the older surgical patients do not justify the routine removal of all asymptomatic, disease-free impacted third molars at an early age. Both groups recognize that when surgical intervention is employed, complications such as pain, swelling, alveolar osteitis, periodontal problems, temporomandibular joint disorders, nerve involvement, sinus communication, and financial stress are not uncommon. Ultimately, the clinician must consider the information presented in this review, and combine it with his/her academic knowledge and personal clinical experience to inform the patient of the risks and benefits of both treatment options. That way, the clinician and the patient together can decide the strategy for management of an asymptomatic, disease-free third molar.

abstract: Prophylactic bilateral mastectomy (PBM) is the current recommended course of action for women with increased genetic risk for breast and ovarian cancer. Nevertheless, many receive negative feedback from family and friends surrounding the decision to undergo this surgery because they do not have cancer when the decision is made; this results in a limited support network for coping with their PBM. Low social support is associated with depression, negativity, and anxiety. Women who had a PBM, were currently undergoing or had completed reconstruction, and were in a committed romantic relationship at the time of the surgery were surveyed (N = 53). The hypotheses that women who received negative feedback about their decision to have a PBM would have poorer individual well-being, and that the use of a couples-based team approach would moderate these adverse effects were tested. Data analyses support the hypotheses that women in couples taking a team approach to PBM have better individual well-being. The effects of negative feedback from others about the decision to undergo a PBM on personal mental health were moderated by use of a couples-based team approach. Women who received negative feedback from multiple sources had better outcomes if they used a couples-based team approach. Many women have a preventative oophorectomy around the same time as their PBM. Menopause is associated with side effects such as increased vasomotor symptoms and decreased sexual functioning. The hypothesis that surgical menopause is related to declines in sexual satisfaction following PBM was also tested. Regression analysis revealed no relationship. This study indicates that women who experience social disapproval and lack collaborative support from their significant other may be at increased risk for poor individual well-being following PBM. / Dissertation/Thesis / Masters Thesis Psychology 2018

Class of 2015 Abstract / Objectives: The study aimed to increase EPS risk factor assessment when prescribers order prophylactic anticholinergics with antipsychotics. An evidence-based pharmacist checklist card was developed to aid in this decision making process. Methods: A retrospective chart review of patients admitted to the acute inpatient psychiatry units at an academic medical center was conducted to determine baseline prophylactic anticholinergic prescribing habits over a two-month period. Charts were included if the patient was at least 18 years old and ordered at least one scheduled antipsychotic during the admission. An educational intervention session introduced the pharmacist checklist card and shared baseline findings. Post-intervention data was collected during a two-month period following the intervention. The percentage of prophylactic anticholinergic orders based upon pharmacist checklist card parameters pre and post-intervention was analyzed using chi-square test. Results: There was a significant decrease in the total percentage of orders for prophylactic anticholinergics from 72.7% in the pre-intervention period to 50.8% in the post-intervention period (p<0.001). Significant changes in the percentage of orders for prophylactic anticholinergics were also found for patients at no-to-low risk for EPS (56.4% versus 31.8%, p=0.014) and at low-to-moderate risk for EPS (79.6% versus 50.8%, p=0.003). There were no significant changes observed in the percentage of orders for prophylactic anticholinergics for patients at moderate-to-high risk for EPS. A lower percentage of patients prescribed a prophylactic anticholinergic experienced adverse effects in the post versus the pre-intervention period (52.31% versus 75.27%, p=0.003). Conclusions: Significant differences were found between pre and post-intervention anticholinergic medication prescribing habits. This suggests that increased patient risk factor assessment in the form of a pharmacist checklist card is effective in decreasing orders for prophylactic anticholinergic medications not clinically indicated and reducing the incidence of adverse effects.