Introduction: Based on the perceived risk to newborns and pregnancy outcomes associated with certain drugs, women may be hesitant to prescribe and take drugs during pregnancy. In cases like these, pregnant women may seek treatment using natural health products (NHPs) as alternatives to drugs. Unfortunately, evidence of safety in pregnancy and lactation is unknown for many NHPs. Objectives: To review the present state of evidence on the safety of NHPs during pregnancy and lactation. To create a new system to validate evidence on NHPs during pregnancy and lactation designed to affect medical decision. Methodology: NHPs were systematically reviewed and in some cases, meta-analyzed for evidence of safety during pregnancy and lactation. Results: In total, 79 NHPs were systematically reviewed and 2 NHPs were meta-analyzed in order to determine the evidence of safety in pregnancy and lactation. Despite the presence of data (72/79 NHPs in pregnancy and 53/77 NHPs in lactation), the quality of the data was generally poor. Using evidence-based medicine principles, a new system of evaluating evidence was established for studies involving NHPs in pregnancy and lactation. A number of NHPs were identified as being of potential risk in pregnancy. A number of NHPs were identified as potentially being apparently safe in pregnancy and lactation. Blue cohosh is of potential concern for harm in pregnancy given an apparent dose-dependant relationship. Conclusion: There is a large knowledge gap on the safety of NHPs in pregnancy, even more so in lactation. The new system for evaluating NHP safety in pregnancy and lactation will require validation. In order to improve the knowledge gap, future studies are proposed on NHPs in pregnancy and lactation as part of the newly formed MotherNature research network.

Introduction: Based on the perceived risk to newborns and pregnancy outcomes associated with certain drugs, women may be hesitant to prescribe and take drugs during pregnancy. In cases like these, pregnant women may seek treatment using natural health products (NHPs) as alternatives to drugs. Unfortunately, evidence of safety in pregnancy and lactation is unknown for many NHPs. Objectives: To review the present state of evidence on the safety of NHPs during pregnancy and lactation. To create a new system to validate evidence on NHPs during pregnancy and lactation designed to affect medical decision. Methodology: NHPs were systematically reviewed and in some cases, meta-analyzed for evidence of safety during pregnancy and lactation. Results: In total, 79 NHPs were systematically reviewed and 2 NHPs were meta-analyzed in order to determine the evidence of safety in pregnancy and lactation. Despite the presence of data (72/79 NHPs in pregnancy and 53/77 NHPs in lactation), the quality of the data was generally poor. Using evidence-based medicine principles, a new system of evaluating evidence was established for studies involving NHPs in pregnancy and lactation. A number of NHPs were identified as being of potential risk in pregnancy. A number of NHPs were identified as potentially being apparently safe in pregnancy and lactation. Blue cohosh is of potential concern for harm in pregnancy given an apparent dose-dependant relationship. Conclusion: There is a large knowledge gap on the safety of NHPs in pregnancy, even more so in lactation. The new system for evaluating NHP safety in pregnancy and lactation will require validation. In order to improve the knowledge gap, future studies are proposed on NHPs in pregnancy and lactation as part of the newly formed MotherNature research network.

Background: Laparoscopic surgery for colorectal cancer is a novel healthcare technology, for which much research evidence has been published. The objectives of this work were to compare the oncologic outcomes of this technology across different study types, and to define patterns of adoption on the basis of the literature. Methods: A comprehensive systematic review of the literature was conducted using 1) existing systematic reviews, 2) randomized controlled trials (RCTs), and 3) observational studies. Outcomes of interest were overall survival, and total lymph node harvest. Outcomes were compared for congruence. Adoption was evaluated by means of summary expert opinions in the literature. Results: 1) Existing systematic reviews were of low to moderate quality and displayed evidence of overlap and duplication. 2) Laparoscopy was not inferior to open surgery in terms of oncologic outcomes in any study type. 3) Oncologic outcomes from RCTs and observational studies were congruent. 4) Expert opinion in the literature has been supportive of this technology, paralleling the publication of large RCTs. Conclusions: The evaluation of laparoscopic surgery for colorectal cancer in RCTs and observational studies suggests that it is not inferior to open surgery. Adoption of this technology has paralleled RCT evidence.

Nurses report high rates of back pain with consequent disability, work absenteeism and attrition from the profession. In the current climate of an international nursing shortage, efficacious interventions to reduce the impact of back pain must be developed. It is uncertain what components a back pain preventive intervention should comprise. Appropriate and reliable means to assess back pain and disability in nurses is also undetermined. The first aim of this thesis was to undertake a mixed methods program of research to inform the development of an intervention to prevent back pain in nurses. The second aim of the thesis was to examine the psychometric and measurement properties of back pain and disability outcome instruments frequently applied in nursing samples. Epidemiological studies were undertaken to examine factors associated with back pain in nursing cohorts. In student nurses, a history of manual handling work was found to be significantly associated with neck and back pain outcomes. In a large population cohort study of nurses and midwives, pain characteristics (pain severity and radiation), pain-related cognitive and behavioural factors (kinesiophobia and passive pain coping), job characteristics (job classification and manual handling task frequency) as well as demographic interactions explained sick leave due to back pain. A systematic review was undertaken to determine the efficacy of interventions aiming to prevent back pain and back injury in nurses. Due to methodological heterogeneity, a qualitative synthesis of evidence was undertaken on the 16 studies that met inclusion criteria. The review identified moderate level evidence from multiple trials that manual handling training in isolation is not effective and multidimensional interventions are effective in preventing back pain and injury in nurses. Single trials provided moderate evidence that stress management programs do not prevent back pain and limited evidence that lumbar supports are effective in preventing back injury in nurses. There was conflicting evidence regarding the efficacy of exercise interventions and the provision of manual handling equipment and training. A qualitative description study was employed to explore the beliefs and perceptions of nursing stakeholders regarding risk factors for back pain and strategies to prevent back pain in nurses. Stakeholders identified individual, intrapersonal, organisational and environmental risk factors that were consistent with the social ecological view of health. They believed that interventions targeting the individual would be ineffective in the absence of workplace and other reforms. At the individual level, they recommended strategies that address physical, psychological and occupational preparedness for nursing work. In addition, they suggested ecological intervention strategies to induce change at the intrapersonal, organisational, community and policy levels. A mixed method synthesis of evidence was performed to develop an evidence-based and stakeholder-relevant intervention that aims to reduce the impact of back pain in nurses. The proposed intervention incorporates evidence-based multidimensional strategies that address individual and organisational level factors, and proposes ecological factors that may warrant inclusion once evidence of their causal association with back pain is established. Methodological studies examined the psychometric and measurement properties of key instruments used to assess back pain and disability in nursing populations. An extended version of the Nordic Musculoskeletal Questionnaire – that is frequently modified when applied in nursing cohorts - was developed and deemed to have acceptable test-retest reliability. The Oswestry Disability Index was found to have unacceptable measurement properties for application in nursing samples, and is therefore not recommended for future studies of back pain related disability in the nursing population. In summary, this program of research contributes novel insights that can meaningfully inform understanding of back pain prevention in nurses. Factors not previously assessed in nursing populations have been examined and shown to be significantly related to back pain outcomes. The strength of existing evidence for the prevention of back pain and injury in nurses has been established, and methodological advances regarding appropriate and reliable measurement of back pain and disability have been made. The views and perceptions of stakeholders from multiple levels and vantage points have been considered and integrated within the interpretation of evidence from multiple mixed method studies. In fact, stakeholders have played a crucial role in the identification of an appropriate theoretical framework – the social ecological paradigm - to conceptualise back pain causality in nurses and identify relevant solutions. A future research agenda of expanded scope is implicated to adequately address back pain prevention in nurses.

<b>Introduction:</b> Children's social, emotional, and behavioural difficulties are associated with reduced academic performance, stressed teacher-child relationships, and other negative academic and life outcomes. The Incredible Years Teacher Classroom Management (IY TCM) programme is one intervention developed to address problematic behaviours via training teachers to use positive and proactive management strategies. The overall aim of this DPhil is to use the Incredible Years Teacher Classroom Management programme as a case study for applying mixed methods at the systematic review level to ascertain what is known about both the programme's effectiveness and how people experience the course, and subsequently to use the systematic review's findings as a springboard (rather than as an end goal) for more exploratory research into 'for whom' the programme might work. <b>Method:</b> Study One is a mixed methods systematic review of IY TCM. It applied multilevel meta-analysis to RCT outcome data and grounded theory meta-synthesis to interview and focus group data on stakeholders' experiences of IY TCM. Quantitative and qualitative findings were cross-synthesised and mapped using an integrative grid. Study Two moves the field forward by filling a gap in the evidence base, as identified in Study One. Semi-structured telephone interviews were conducted with special educational needs coordinators (SENCos) across Devon, exploring the acceptability and appropriateness of expanding IY TCM to the subgroup of children with special educational needs (SEN) in mainstream schools. Data were analysed thematically and mapped onto IY TCM content. <b>Results:</b> In Study One, nine studies reported across 14 papers met inclusion criteria for either quantitative or qualitative strands of this systematic review. Multilevel meta-analysis of RCTs (n=4) indicated that the programme produced teacher- and child-level results in the desired directions. Clear trends across all measured outcomes favoured the intervention group over the treatment-as-usual comparison. Qualitative meta-synthesis (n=5) illuminated a cyclical learning process and broader conceptualisation of teacher and child outcomes than was evident in the quantitative evidence. Notably, RCT data on teacher outcomes were limited to self-reported or observed behaviours, while teachers described other benefits from IY TCM including increased knowledge and emotional well-being. Cross-synthesis of findings from the two review strands highlighted harmony across the RCT and qualitative evidence but also a number of areas in which constructs that were prioritised by one type of research were not integrated into the other. Study Two generated classroom management strategies from SENCos, which aligned closely with strategies taught in IY TCM, indicating that IY TCM would be both acceptable and applicable (if not sufficient) for use when working with children identified with SEN and behavioural difficulties in schools. <b>Discussion:</b> Based on the positive effects of implementing IY TCM despite very few studies to power analyses, the programme appears to offer tangible benefits to both teachers and children. It is possible that results are underestimated due to limited types of outcomes measured and absence of experiential data from additional stakeholders (e.g., parents). Depending on current provision of special educational needs services, schools operating inclusion models are likely to find these strategies beneficial for children identified with SEN, and this subgroup should be explicitly examined in future IY TCM studies.

<b>Background:</b> 'Competing risks' are events that either preclude or alter the probability of experiencing the primary study outcome(s). Many standard survival models fail to account for competing risks, introducing an unknown level of bias in their measures of absolute and relative risk. Individuals with type 2 diabetes mellitus (T2DM) and albuminuria are at increased risk of multiple competing causes of mortality, including cardiovascular disease (CVD), cancer and renal disease, yet studies to date have not implemented competing risks methodology. <b>Aim:</b> Using albuminuria in T2DM as a case study, this Thesis set out to quantify differences between standard- and competing-risks-adjusted survival analysis estimates of absolute and relative risk for the outcomes of cardiovascular and cancer mortality. <b>Methods:</b> 86,962 patients aged &ge;35 years with T2DM present on or before 2005 were identified in the Clinical Practice Research Datalink. To quantify differences in measures of absolute risk, cumulative risk estimates for cardiovascular and cancer mortality from standard survival analysis methods (Kaplan-Meier estimator) were compared to those from competing-risks-adjusted methods (cumulative incidence competing risk estimator). Cumulative risk estimates were stratified by patient albuminuria level (normoalbuminuria vs albuminuria). To quantify differences in measures of relative risk, estimates for the effect of albuminuria on the relative hazards of cardiovascular and cancer mortality were compared between standard cause-specific hazard (CSH) models (Cox-proportional-hazards regression), competing risk CSH models (unstratified Lunn-McNeil model), and competing risk subdistribution hazard (SDH) models (Fine-Gray model). <b>Results:</b> Patients with albuminuria, compared to those with normoalbuminuria, were older (p&LT;0.001), had higher systolic blood pressure (p&LT;0.001), had worse glycaemic control (p&LT;0.001), and were more likely to be current or ex-smokers (p&LT;0.001). Over the course of nine years of follow-up 22,512 patients died; 8,800 from CVD, 5,239 from cancer, and 8,473 from other causes. Median follow-up was 7.7 years. In patients with normoalbuminuria, nine-year standard and competing-risks-adjusted cumulative risk estimates for cardiovascular mortality were 11.1% (95% confidence interval (CI): 10.8-11.5%) and 10.2% (95% CI: 9.9-10.5%), respectively. For cancer mortality, these figures were 8.0% (95% CI: 7.7-8.3%) and 7.2% (95% CI: 6.9-7.5%). In patients with albuminuria, standard and competing-risks-adjusted estimates for cardiovascular mortality were 21.8% (95% CI: 20.9-22.7%) and 18.5% (95% CI: 17.8-19.3%), respectively. For cancer mortality, these figures were 10.7% (95% CI: 10.0-11.5%) and 8.6% (8.1-9.2%). For the effect of albuminuria on cardiovascular mortality, hazard ratios from multivariable standard CSH, competing risks CSH, and subdistribution hazard ratios from competing risks SDH models were 1.75 (95% CI: 1.63-1.87), 1.75 (95% CI: 1.64-1.87), and 1.58 (95% CI: 1.48-1.69), respectively. For the effect of albuminuria on cancer mortality, these values were 1.27 (95% CI: 1.16-1.39), 1.28 (95% CI: 1.17-1.40), and 1.11 (95% CI: 1.01-1.21). <b>Conclusions:</b> When evaluating measures of absolute risk, differences between standard and competing-risks-adjusted methods were small in absolute terms, but large in relative terms. For the investigation of epidemiological relationships using relative hazards models, standard survival analysis methods produced near-identical risk estimates to the CSH competing risks methods for the clinical associations evaluated in this Thesis. For the evaluation of risk prediction using relative hazards models, CSH models produced consistently higher risk estimates than SDH models, and their use may lead to over-estimation of the predictive effect of albuminuria on either outcome. Where outcomes are less common (like cancer) CSH models provide poor estimates of risk prediction, and SDH models should be used. This research demonstrates that differences can be present between risk estimates derived using CSH and SDH methods, and that the two are not necessarily interchangeable. Moreover, such differences may be present in other clinical areas.

Orientador: Daniele Cristina Cataneo / Resumo: Introdução: a mitomicina C (MMC) é um antibiótico natural utilizado inicialmente como um agente anti neoplásico. Nas vias aéreas sua aplicação promove a inibição da proliferação de fibroblastos em áreas cicatriciais. Objetivo: avaliar a efetividade e segurança da MMC tópica no tratamento conservador das estenoses laringotraqueais. Método: revisão sistemática de estudos experimentais ou observacionais que tenham avaliado as intervenções conservadoras no tratamento das estenoses laringotraqueais com o uso da MMC tópica. Foram pesquisadas as bases de dados LILACS, Pubmed, Embase, Cochrane e Web of Science. Os desfechos avaliados foram: resolução completa ou parcial, caracterizada por tempo livre de sintomas maior ou igual um ano; número de procedimentos necessários com ou sem aplicações de MMC (um ou mais); e complicações decorrentes do procedimento. Resultados: foram selecionados 14 estudos, um prospectivo randomizado, um caso-controle e doze series de casos, envolvendo 365 pacientes. Em 10 estudos a intervenção sempre contou com a utilização de MMC e em quatro foram analisados dois grupos um com MMC, e outro sem. Com o uso da MMC a resolução avaliada em 11 estudos, foi de 69% (IC a 95% 61% a 77%, I2= 22,5%). Sem MMC a resolução avaliada em somente três estudos, foi de 43% (IC a 95% 17% a 70%, I2= 59,3%). Foi realizado um único procedimento em 55% dos pacientes (IC 95% 44 a 66%, I2= 52,3%), e em 45% dos pacientes foi realizado mais de um procedimento (IC 95% 34 a 56%, I2= 52,3%... (Resumo completo, clicar acesso eletrônico abaixo) / Mestre

Improving the effectiveness and efficiency of medication error reporting is key to enhancing patient safety. The aim of this research was to explore medication error reporting in the United Arab Emirates (UAE), examining the attitudes, beliefs, behaviors and experiences of health professionals. The first phase was a Joanna Briggs Institute registered systematic review of the beliefs, attitudes and experiences of health professionals relating to medication error reporting. Findings indicated the need for original research employing a mixed methods approach to quantify and generate in-depth information, grounded in theories of behaviour change. In the second phase, a cross-sectional survey of health professionals in the UAE was conducted to determine the behavioural determinants and facilitators and barriers of medication error reporting. Principal component analysis of responses from 294 health professionals identified six components: knowledge and skills related; feedback and support related; action and impact related; motivation related; effort related; and emotions. Responses were neutral for the motivation and effort related components, but negative for the emotions component. Comparison of component scores identified that, nurses, females, those with greater experience and being older were more likely to be positive in their responses (p<0.05). In terms of emotions, the component with the lowest scores, older respondents with greater experience gave more positive responses (p<0.05). In the final phase, face-to-face semi-structured interviews with 29 health professionals explored in-depth the behavioural determinants of medication errors reporting in the UAE. The theoretical domains framework was employed in constructing the interview schedule and interpreting the findings. ‘Goals’ and ‘intentions’ were determinants which acted as facilitators while ‘beliefs of the consequences’, ‘emotions’,’ ‘social influences and environmental context’ were barriers. This doctoral research has generated original findings which can support the development of interventions, based on behaviour change techniques, to enhance medication error reporting. These changes could impact at the levels of the organisation, health professional and patient.

Background: Links between later life depression (LLD) and adverse health outcomes are well-documented, with mental ill-health in rural older adults highlighted as a priority area for health care policy. In working age adults, models of depression show that specific psychological factors (e.g. hopelessness, neuroticism, extraversion and insecure attachment) interact with life stress to increase risk of depression. In older adults, however, the direct relationship between depression and hopelessness is inconsistently replicated. In addition, there is little evidence regarding how psychological factors interact with vulnerability to depression in older adults; and whether these factors act in the same manner as they do in working age adults. Objectives: A systematic review was carried out in order to determine the strength of the depression-hopelessness relationship, and the influence of personality traits (neuroticism/ extraversion) and insecure attachment (anxious/ avoidant) on this relationship. Next, an exploratory study was carried out to determine whether there was a direct relationship between depression and hopelessness in rural older adults living in the community and, secondly, whether this relationship was indirectly influenced by specific psychological factors (e.g. neuroticism, extraversion, and attachment styles). Methods: The systematic review was carried out using several databases (Psychinfo, Science Direct, EBCOS, Cohrane Library, PROSPERO, WEBCAT and Google Scholar). Studies relating to the variables of interest, meeting inclusion and exclusion criteria, were reviewed and evaluated for methodological biases. The pilot study asked older adults (N = 58) living in a remote and rural region to complete and return a packet of self-report questionnaires (Big Factor Inventory-10, Experiences in Close Relationships, Depression, Anxiety and Stress Scale, and the Beck Hopelessness Scale). Results: The systematic review identified twenty-one studies; four examining the depression-hopelessness relationship and seventeen investigating the effects of neuroticism, extraversion and insecure attachment styles on wellbeing, depression and/ or hopelessness. Findings from the pilot showed a direct relationship between depression and hopelessness in rural community dwelling older adults, with only neuroticism indirectly influencing this relationship. Conclusions: The systematic review suggests that it is not possible, as yet, to draw robust conclusions from the existing evidence base regarding the influence of psychological variables on depression and hopelessness in older adults. The findings were particularly sensitive to methodological limitations (e.g. variability between sampling methods and small effect sizes). Despite this, studies suggest some evidence for attachment and personality influencing on the depression-hopelessness relationship. Likewise, findings from the pilot study are limited by the small sample size and cross-sectional nature of the data. Preliminary findings, however, suggest that neuroticism, and not beliefs about insecure attachment, strengthens the relationship between depression and hopelessness in non-clinical, rural older adults. These findings are consistent with research on working age adults and could, potentially, represent an emerging relationship in non-clinical older adults. Further research, however, is required as to whether the same patterns are observed in clinical populations.

Orientador: Antonio José Maria Cataneo / Resumo: Introdução: A paralisia de pregas vocais caracteriza-se como uma das principais complicações e sequelas após a tireoidectomia. A técnica convencional compreende a identificação visual do trajeto do nervo para sua preservação e a neuromonitorização do nervo laríngeo recorrente (NLR) durante a cirurgia de tireóide visa a redução do risco de paralisias por injúria ao NLR, porém sua utilidade ainda é discutível. Objetivos: Determinar através de revisão sistemática se o uso da neuromonitorização do NLR durante tireoidectomias realmente apresenta benefícios comparado á técnica convencional de identificação somente do nervo durante a cirurgia, especialmente em termos de redução do risco de paralisia de prega vocal, seja transitória ou permanente. Materiais e Métodos: A pesquisa nas principais bases de dados, MEDLINE via PUBMED, LILACS, SCOPUS, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL); clinicaltrials.gov e fontes adicionais foi realizada em Maio de 2018. Uma revisão sistemática e meta-análise foram feitas usando o modelo de efeitos fixos. O GRADE foi usado para classificar a qualidade das evidências. Os desfechos primários avaliados foram o total de paralisias do NLR por nervos em risco, paralisias transitórias e permanentes e o tempo de cirurgia comparando-se as duas técnicas. Como desfechos secundário avaliou-se o tempo de cirurgia. Foi realizada análise de subgrupos de pacientes de alto e baixo risco de injuria do NLR. Também avaliamos como análise de subgr... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Introduction: Vocal cord paralysis is characterized as one of the main complications and sequels after thyroidectomy. The conventional technique comprises the visual identification of the nerve path for its preservation and recurrent laryngeal nerve (RLN) neuromonitoring during thyroid surgery aims to reduce the risk of paralysis due to injury to the RLN, but its usefulness is still debatable. Objectives: To determine through systematic review if the use of neuromonitoring of the RLN during thyroidectomies actually presents benefits compared to the conventional technique of only identification of the nerve during surgery, especially in terms of reducing the risk of vocal fold paralysis, whether transient or permanent. Materials and Methods: The search in the main databases, MEDLINE, LILACS, SCOPUS, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL); clinicaltrials.gov and additional sources was performed in May 2018. A systematic review and meta-analysis was done using the fixed-effects model. GRADE was used to classify the quality of the evidence. The primary endpoints evaluated were the total nerve paralysis for nerves at risk, transient and permanent paralyzes, and surgery time comparing the two techniques. As secondary outcomes, the time of surgery was evaluated. We also evaluated as subgroup analysis the transient and permanent paralysis in a group of patients with high and low risk of RLN injury. Results: Four randomized clinical trials involving 1.379 pat... (Complete abstract click electronic access below) / Mestre