Memory for pain: recalling the quality and intensity of expected acute pain.

This thesis reports a series of studies designed to assess the extent to which the intensity and qualitative nature of expected acute pain events can be recalled. The first preliminary study assessed recall of the intensity and quality of postoperative pain following day surgery for varicose vein removal. Twenty four participants reported their expectations of pain, their actual pain experiences and their retrospective ratings of pain using the Short Form McGill Pain Questionnaire (SF-MPQ) and a VAS to report pain intensity. In line with prior research, recollections of pain quality appeared to be less accurate than the retrospective ratings of pain intensity. In the second preliminary study, 50 participants who had never experienced vascular surgery were required to provide estimates of the likely nature of postoperative pain following varicose vein removal, based on the information provided in one of two patient information leaflets. Although both groups of non-patient participants overestimated the intensity of the pain, both provided estimates of the qualitative nature of the pain that were similar to the reports made by the patient participants. These preliminary studies highlighted the limitations of prior research which has inferred pain recall accuracy by simply by comparing descriptions of acute pain made whilst in pain with ratings made retrospectively, and demonstrated the need to employ a more direct method of assessing memory for pain. The preliminary studies also highlighted the need to consider the influence of the participants ’ expectations of the likely nature o f a forthcoming pain and levels of anxiety on memory for pain. Finally, investigating the relative extent to which pain can be recalled relative to another sensory experience was deemed to be necessary. The main study for this thesis assessed memory for experimentally induced acute pain using the remember/know research paradigm (see Tulving, 1985). In Part One of this study, Cold Pressor (CP) pain was induced in 97 participants who provided ratings of their expectations of the CP pain, followed by reports of their actual pain experiences using the MPQ and a VAS whilst using the CP. Participants also provided ratings of anxiety and used a list of 57 descriptors to report the taste of an unusual drink. In Part Two of the study, two weeks later, participants provided retrospective ratings of the CP pain using the MPQ and a VAS, ratings of anxiety, and the taste of the drink. Participants were then asked to make ‘remember’ or ‘know ’judgements about the MPQ pain and taste descriptors that they had selected, based on the level of conscious awareness accompanying their recollections. The findings indicate that memory for the intensity of expected acute pain was reliable for at least two weeks. In addition, the data suggest that recollections of the broad defining aspects of the quality of acute pain can also be reliable, but may be more appropriately assessed at a ‘type of pain’ level rather than the fine-grained level of individual MPQ descriptors. Central to this investigation was the finding that participants were readily able to distinguish between whether their recollections reflected ‘remembering’ and ‘knowing’ about their prior experiences of both pain and taste. It is concluded that the use of the remember/know distinction allows for a more direct assessment of the participants ’ reports of their memories than inferring the likely nature of these recollective experiences, and that recollections of pain and of other sensory experiences are broadly similar. Expectations and anxiety were not related to pain recall accuracy

Leadership Development in Small and Medium Sized Enterprises: Phase 1 Report

Discussion with experts and a review of business and leadership literature reveals an urgent need to address leadership development issues in small and medium sized enterprises (SMEs). This research, based upon interviews with 20 SME directors, is the first part of a three phase programme and goes some way towards meeting this need by identifying the main challenges faced by SME leaders and a framework for the delivery of relevant training and support programmes. Qualitative analysis of the interviews revealed that SME leaders face a range of challenges arising out of the need to survive in an increasingly competitive, fast-changing environment with limited resources. Although many of the difficulties experienced appear to arise from factors external to the organisation, there is a general realisation that solutions must come from within and, more specifically, through the improved management of human resources and the freeing up the leader to focus on strategic development. The fact that SME organisational strategies tend to be driven largely by concerns for survival and operational needs, may often result in SME leaders placing a greater emphasis on the importance of leadership experience ‘in-situ’ and on-the-job training rather than formal education and qualifications. To this extent the SME director, him/herself, is rarely formally trained in management or leadership, rather learning through his or her own experience. Whilst this approach may well be effective for some, it may also pose a number of potential difficulties, most notably the effective development of future SME leaders and the diffusion of a congruous ‘leadership culture’ throughout the organisation. An exploration of the research findings in a group workshop environment revealed widespread agreement that one of the primary leadership concerns in SMEs is succession management and that any leadership development programme should address this issue. A discussion of possible approaches highlighted a need for two types of provision: firstly, help for current SME leaders in identifying and selecting potential candidates; and secondly, offering a fast-track scheme for selected individuals to help them rapidly develop their leadership skills. Such an approach would require a variety of methods matched to the different needs of participants, although likely elements would include in-house and external facilitated workshops and seminars for current and future leaders. In summary, the research has indicated a need for the provision of leadership development training/support tailored to the requirements and operating environment of SMEs. The Centre for Leadership Studies proposes piloting such a programme in the South West in early 2001 with a view to the eventual national implementation of outcomes.South West Regional Development Agency; Marchmont Observatory; Department for Education and Employmen

A rapid review of challenges faced by early-career international medical graduates in general practice and opportunities for supporting them.

BACKGROUND British General Practice is facing a workforce crisis against a backdrop of an ageing population experiencing increasingly complex health challenges. The National Health Service must increase the supply of General Practitioners (GPs), including International Medical Graduate (IMG) GPs, by increasing recruitment and retention. IMG GPs face distinct challenges during training and their early careers. Understanding these challenges as well as the help and support offered to early-career IMG GPs is crucial to building and sustaining the general practice workforce. AIM To understand the challenges facing early-career IMG GPs and the help and support they can access. DESIGN & SETTING Rapid review. METHOD Six databases and four websites were searched. Titles and abstracts were screened according to inclusion and exclusion criteria, followed by the full study where applicable. The included studies were analysed using a thematic synthesis approach to identify the challenges faced by early-career IMG GPs, as well as the help and support available. RESULTS The database search yielded 234 studies, with 38 additional studies identified via handsearching of websites. Twenty-one studies were included. Seven challenges were identified, as well as a range of help and support available. Early-career IMG GPs face a range of psychological, social, and practical challenges which may not be adequately addressed by the help and support currently offered by the NHS. CONCLUSION Further research is required to understand the extent to which early-career IMG GPs access the help and support offered, and if it adequately addresses the unique challenges they face

“Are you doing your pelvic floor?” An ethnographic exploration of the interaction between women and midwives about pelvic floor muscle exercises (PFME) during pregnancy

ObjectiveMany women experience urinary incontinence (UI) during and after pregnancy. Pelvic floor muscle exercises (PFME) can prevent and reduce the symptoms of UI. The objective of the study was to explore challenges, opportunities and concerns for women and health care professionals (HCPs), related to the implementation of PFME training for women in current antenatal care.DesignAn ethnographic study design was used. Researchers also formed and collaborated with a public advisory group, consisting of seven women with recent experiences of pregnancy, throughout the study.ParticipantsSeventeen midwife-woman interactions were observed in antenatal clinics. In addition, 23 midwives and 15 pregnant women were interviewed. Repeat interviews were carried out with 12 of the women postnatally. Interviews were also carried out with other HCPs; four physiotherapists, a linkworker/translator and two consultant obstetricians. Additional data sources included field notes, photographs, leaflets, policy and other relevant documents.SettingData were collected in three geographical areas of the UK spanning rural, urban and suburban areas. Data collection took place in antenatal clinics, in primary and secondary care settings, and the majority of women were interviewed in their homes.FindingsThree broad and inter-related themes of “ideological commitment”, “confidence” and “assumptions, stigma and normalisation” were identified. The challenges, opportunities and concerns regarding PFME implementation were explored within these themes.Conclusions and implications for practiceAlthough HCPs and some women knew that PFME were important, they were not prioritised and the significant benefits of doing PFME may not have been communicated by midwives or recognised by women. There was a lack of confidence amongst midwives to teach PFME and manage UI within the antenatal care pathway and amongst women to ask about PFME or UI. A perceived lack of consistent guidelines and policy at local and national levels may have impeded clear communication and prioritisation of PFME. Furthermore, assumptions made by both women and midwives, for example, women regarding UI as a normal outcome of pregnancy, or midwives’ perception that certain women were more likely to do PFME, may have exacerbated this situation. Training for midwives to help women in the antenatal period to engage in PFME could address challenges and concerns and to help prevent opportunities for women to learn about PFME from being missed

Physiotherapy for adults with joint hypermobility syndrome: A pilot randomised controlled trial

Background: Joint Hypermobility Syndrome (JHS) is a heritable disorder associated with laxity and pain in multiple joints. Physiotherapy is the mainstay of treatment but there is little research investigating its effectiveness. The aim of this study was therefore to conduct a pilot randomised controlled trial (RCT) to determine the feasibility of conducting a future definitive RCT. Methods: A comprehensive physiotherapy intervention was developed in conjunction with patients and healthcare professionals. It was then piloted and refined on the basis of patient and physiotherapist feedback. A parallel two-arm pilot RCT in two UK secondary care NHS Trusts compared 'Advice' against 'Advice & Physiotherapy'. Inclusion criteria were: >16 years, a diagnosis of JHS, and no other musculoskeletal conditions causing pain. The Advice intervention was a one-off session, supplemented by advice booklets from the Hypermobility Syndromes Association and Arthritis Research UK. All patients could ask questions specific to their circumstances and received tailored advice. Participants were then randomly allocated to 'Advice' (no further advice or physiotherapy) or 'Advice & Physiotherapy' (an additional six 30 minute sessions over 4 months). The Physiotherapy intervention was supported by a patient handbook and delivered on a one-to-one patient-therapist basis. It aimed to increase patients’ physical activity through developing knowledge, understanding and skills to better manage their condition. The primary outcome related to the feasibility of conducting a future definitive RCT. Qualitative interviews with patients and physiotherapists therefore formed a major component of data collection. Secondary outcomes included clinical measures (physical function, pain, global status, self-reported joint count, quality of life, exercise self-efficacy and adverse events); resource use (to estimate cost-effectiveness); and an estimate of the value of information from a future RCT. Outcomes were recorded at baseline, 4 months (at the end of physiotherapy) and 7 months (3 months following physiotherapy). Results: A total of n=29 participants were recruited to the pilot RCT. Recruitment was challenging, primarily due to a perceived lack of equipoise between Advice and Physiotherapy. The qualitative evaluation provided very clear guidance to inform a future RCT, including enhancement of the Advice intervention. Some patients reported that the Advice intervention was useful and the Physiotherapy intervention was evaluated very positively. The rate of return of questionnaires was low within the Advice group but reasonable in the Physiotherapy group. The Physiotherapy intervention showed evidence of promise in terms of primary and secondary clinical outcomes. The Advice arm experienced more adverse events. The value of information estimate indicated the potential for high value from a future RCT. Conclusion: A future definitive RCT of physiotherapy for JHS seems feasible, although the Advice intervention should be made more robust to address perceived equipoise and subsequent attrition

Implementing pelvic floor muscle training in women's childbearing years: A critical interpretive synthesis of individual, professional, and service issues

Antenatal pelvic floor muscle training (PFMT) may be effective for the prevention and treatment of urinary and fecal incontinence both in pregnancy and postnatally, but it is not routinely implemented in practice despite guideline recommendations. This review synthesizes evidence that exposes challenges, opportunities, and concerns regarding the implementation of PFMT during the childbearing years, from the perspective of individuals, healthcare professionals (HCPs), and organizations.MethodsCritical interpretive synthesis of systematically identified primary quantitative or qualitative studies or research syntheses of women's and HCPs attitudes, beliefs, or experiences of implementing PFMT.ResultsFifty sources were included. These focused on experiences of postnatal urinary incontinence (UI) and perspectives of individual postnatal women, with limited evidence exploring the views of antenatal women and HCP or wider organizational and environmental issues. The concept of agency (people's ability to effect change through their interaction with other people, processes, and systems) provides an over?arching explanation of how PFMT can be implemented during childbearing years. This requires both individual and collective action of women, HCPs, maternity services and organizations, funders and policymakers.ConclusionNumerous factors constrain women's and HCPs capacity to implement PFMT. It is unrealistic to expect women and HCPs to implement PFMT without reforming policy and service delivery. The implementation of PFMT during pregnancy, as recommended by antenatal care and UI management guidelines, requires policymakers, organizations, HCPs, and women to value the prevention of incontinence throughout women's lives by using low?risk, low?cost, and proven strategies as part of women's reproductive health

Refined histopathological predictors of BRCA1 and BRCA2 mutation status: A large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia

Introduction: The distribution of histopathological features of invasive breast tumors in BRCA1 or BRCA2 germline mutation carriers differs from that of individuals with no known mutation. Histopathological features thus have utility for mutation prediction, including statistical modeling to assess pathogenicity of BRCA1 or BRCA2 variants of uncertain clinical significance. We analyzed large pathology datasets accrued by the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC) to reassess histopathological predictors of BRCA1 and BRCA2 mutation status, and provide robust likelihood ratio (LR) estimates for statistical modeling. Methods: Selection criteria for study/center inclusion were estrogen receptor (ER) status or grade data available for invasive breast cancer diagnosed younger than 70 years. The dataset included 4,477 BRCA1 mutation carriers, 2,565 BRCA2 mutation carriers, and 47,565 BCAC breast cancer cases. Country-stratified estimates of the

Germline HOXB13 mutations p.G84E and p.R217C do not confer an increased breast cancer risk

In breast cancer, high levels of homeobox protein Hox-B13 (HOXB13) have been associated with disease progression of ER-positive breast cancer patients and resistance to tamoxifen treatment. Since HOXB13 p.G84E is a prostate cancer risk allele, we evaluated the association between HOXB13 germline mutations and breast cancer risk in a previous study consisting of 3,270 familial non-BRCA1/2 breast cancer cases and 2,327 controls from the Netherlands. Although both recurrent HOXB13 mutations p.G84E and p.R217C were not associated with breast cancer risk, the risk estimation for p.R217C was not very precise. To provide more conclusive evidence regarding the role of HOXB13 in breast cancer susceptibility, we here evaluated the association between HOXB13 mutations and increased breast cancer risk within 81 studies of the international Breast Cancer Association Consortium containing 68,521 invasive breast cancer patients and 54,865 controls. Both HOXB13 p.G84E and p.R217C did not associate with the development of breast cancer in European women, neither in the overall analysis (OR = 1.035, 95% CI = 0.859-1.246, P = 0.718 and OR = 0.798, 95% CI = 0.482-1.322, P = 0.381 respectively), nor in specific high-risk subgroups or breast cancer subtypes. Thus, although involved in breast cancer progression, HOXB13 is not a material breast cancer susceptibility gene.Peer reviewe

Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes

Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57-1.65) with area under receiver-operator curve (AUC) = 0.630 (95%CI: 0.628-0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Goodness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs.NovartisEli Lilly and CompanyAstraZenecaAbbViePfizer UKCelgeneEisaiGenentechMerck Sharp and DohmeRocheCancer Research UKGovernment of CanadaArray BioPharmaGenome CanadaNational Institutes of HealthEuropean CommissionMinistère de l'Économie, de l’Innovation et des Exportations du QuébecSeventh Framework ProgrammeCanadian Institutes of Health Researc

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer.

Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM -/- patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors