Gynaecological cancer symptoms: influences on women’s awareness and medical help-seeking

This work stems from an increased effort to improve cancer survival rates through earlier diagnosis, which itself may be achieved through prompt medical help-seeking for symptoms. This thesis focuses on responses to symptoms potentially indicative of a gynaecological cancer; a group of cancers that pose a significant threat to women, and yet are under-represented in the literature. Four studies were conducted. Studies One and Two (n=1392 and n=1000, respectively) were population-based surveys of women, measuring awareness of cervical and ovarian cancer risk factors and symptoms, respectively. Study two also measured hypothetical help-seeking. Study three was a survey of a nationally-representative sample of women (n=911), which explored responses to real symptoms that were potentially indicative of a gynaecological cancer. Building on study three, study four explored responses to symptoms at a deeper level, through in-depth, one-to-one interviews with women who had recently, or were currently, experiencing a symptom potentially indicative of a gynaecological cancer. Awareness of symptom and risk factors for cervical and ovarian cancer was low overall. Women anticipated seeking help promptly for symptoms of ovarian cancer, however, when faced with real symptoms, outside of the context of cancer, help might not be sought as promptly. I found that women with symptoms respond in many different ways. Mapping my findings onto the Model of Pathways to Treatment, I identified a number of different influences which may be more important at the appraisal stage, including what can be expected as part of being a woman and those which may be more important at the help-seeking stage, such as feeling justified in seeking help. More education is needed about the symptoms and risk factors for gynaecological cancers. Further, campaigns encouraging women to seek help for symptoms should include messages which target those variables that may lead women to wait longer before seeking help, such as misattribution of symptoms

Ovarian cancer symptom awareness and anticipated time to help-seeking for symptoms among UK women.

OBJECTIVES: To determine levels of awareness of ovarian cancer symptoms and to identify barriers to help-seeking and predictors of a longer time to help-seeking in a UK female population-based sample. METHODS: A UK population-based sample of women [n=1000, including a subsample of women at higher risk due to their age (≥45 years, n=510)] completed the Ovarian Cancer Awareness Measure by telephone interview. Questions measured symptom awareness (using recall and recognition), barriers to medical help-seeking and anticipated time to help-seeking. Regression analyses identified predictors of a higher score on a scale of anticipated time to help-seeking. RESULTS: Most women (58% overall sample; 54% subgroup) were unable to recall any symptoms but 99% recognised at least one. Recognition was lowest for difficulty eating and persistently feeling full. In the sample overall, higher socio-economic status and higher endorsement of practical and service barriers independently predicted a longer anticipated time to help-seeking for more symptoms. White ethnicity was an additional predictor in the older subgroup. CONCLUSIONS: This study suggests awareness of ovarian cancer symptoms is low in the UK, and varies widely between symptoms. It identifies variables that may be involved in a longer time to help-seeking for possible ovarian cancer symptoms and highlights the need for more in-depth research into the factors related to time to help-seeking in real-world situations

Living with an Older Person Dying from Cancer, Lung Disease or Dementia: Health Outcomes from a General Practice Cohort Study

CONTEXT: Increasing numbers of people will die from chronic disease. Families contribute significantly to end-of-life care but their role may not be recognized. OBJECTIVES: To 1) establish the proportion of older cohabitees identified in primary care as "carers;" 2) describe demographic and lifestyle characteristics of cohabitees of people terminally ill with cancer, dementia, and chronic obstructive pulmonary disease (COPD); 3) describe their health a year before and after bereavement; and 5) compare health outcomes between cohabitees of people dying with cancer, COPD, or dementia. METHODS: Retrospective cohort study using a U.K. primary care database (The Health Improvement Network) of 13,693 bereaved cohabitees (a proxy marker for being a carer), aged 60 years or older of people dying from cancer, COPD, or dementia. Characteristics were described one year before and after bereavement. We compared cancer, COPD, and dementia cohabitee outcomes using incidence rate ratios one year before and after bereavement and calculated mortality risk post-bereavement. RESULTS: A total of 6.9% of cohabitees were recorded as carers. Health outcomes differed little between the three groups of cohabitees in the year prior to or after bereavement. The proportion of cohabitees with six or more consultations increased the year after bereavement (cancer cohabitees 16.0% to 18.8%, COPD cohabitees 17.8% to 20.4% and dementia cohabitees 15.5% to 17.5%). At post-bereavement (follow-up median 3 years, IQR 1.3-5.4), we found no mortality differences between the three groups. CONCLUSION: Recording of carers of terminally ill people was suboptimal. Cause of bereavement produced few differential effects on health outcomes or mortality

Social and structural conditions for the avoidance of advance care planning in neuro-oncology: a qualitative study

BACKGROUND: Primary brain tumours newly affect >260 000 people each year worldwide. In the UK, every year >10 000 people are diagnosed with a brain tumour while >5000 die annually from the disease. Prognoses are poor, cognitive deterioration common and patients have prolonged palliative needs. Advance care planning (ACP) may enable early discussion of future care decisions. Although a core commitment in the UK healthcare strategy, and the shared responsibility of clinical teams, ACP appears uncommon in practice. Evidence around ACP practice in neuro-oncology is limited. OBJECTIVES: We aimed to elicit key social and structural conditions contributing to the avoidance of ACP in neuro-oncology. DESIGN: A cross-sectional qualitative study design was used. SETTING: One tertiary care hospital in the UK. PARTICIPANTS: Fifteen healthcare professionals working in neuro-oncology participated in this study, including neuro-oncologists, neurosurgeons, clinical nurse specialists, allied healthcare professionals and a neurologist. METHOD: Semi-structured interviews were conducted with participants to explore their assumptions and experiences of ACP. Data were analysed thematically using the well-established framework method. RESULTS: Participants recognised the importance of ACP but few had ever completed formal ACP documentation. We identified eight key factors, which we suggest comprise three main conditions for avoidance: (1) difficulties being a highly emotive, time-intensive practice requiring the right 'window of opportunity' and (2) presence and availability of others; (3) ambiguities in ACP definition, purpose and practice. Combined, these created a 'culture of shared avoidance'. CONCLUSION: In busy clinical environments, 'shared responsibility' is interpreted as 'others' responsibility' laying the basis for a culture of avoidance. To address this, we suggest a 'generalists and specialists' model of ACP, wherein healthcare professionals undertake particular responsibilities. Healthcare professionals are already adopting this model informally, but without formalised structure it is likely to fail given a tendency for people to assume a generalist role

Analysis of a Series of Chlorogenic Acid Isomers using Differential Ion Mobility and Tandem Mass Spectrometry

Canada Foundation for InnovationChlorogenic acids are among the most abundant phenolics found in the human diet. Of these, the mono-caffeoylquinic acids are the predominant phenolics found in fruits, such as apples and pears, and products derived from them. In this research, a comprehensive study of the electrospray ionization (ESI) tandem mass spectrometric (MS/MS) dissociation behavior of the three most common mono-caffeoylquinic acids, namely 5-O-caffeoylquinic acid (5-CQA), 3-O-caffeoylquinic acid (3-CQA) and 4-O-caffeoylquinic acid (4-CQA), were determined using both positive and negative ionization. All proposed structures of the observed product ions were confirmed with second-generation MS3 experiments. Similarities and differences between the dissociation pathways in the positive and negative ion modes are discussed, confirming the proposed structures and the established MS/MS fingerprints. MS/MS dissociation was primarily driven via the cleavage of the ester bond linking the quinic acid moiety to the caffeic acid moiety within tested molecules. Despite being structural isomers with the same m/z values and dissociation behaviors, the MS/MS data in the negative ion mode was able to differentiate the three isomers based on ion intensity for the major product ions, observed at m/z 191, 178 and 171. This differentiation was consistent among various MS instruments. In addition, ESI coupled with high-field asymmetric waveform ion mobility spectrometry-mass spectrometry (ESI-FAIMS-MS) was employed for the separation of these compounds for the first time. By combining MS/MS data and differential ion mobility, a method for the separation and identification of mono-caffeoylquinic in apple/pear juice samples was developed with a run time of less than one minute. It is envisaged that this methodology could be used to identify pure juices based on their chlorogenic acid profile (i.e., metabolomics), and could also be used to detect juice-to-juice adulteration (e.g., apple juice addition to pear juice)

Scaling Up Towards International Targets for AIDS, Tuberculosis, and Malaria: Contribution of Global Fund-Supported Programs in 2011–2015

OBJECTIVE: The paper projects the contribution to 2011-2015 international targets of three major pandemics by programs in 140 countries funded by the Global Fund to Fight AIDS, Tuberculosis and Malaria, the largest external financier of tuberculosis and malaria programs and a major external funder of HIV programs in low and middle income countries. DESIGN: Estimates, using past trends, for the period 2011-2015 of the number of persons receiving antiretroviral (ARV) treatment, tuberculosis case detection using the internationally approved DOTS strategy, and insecticide-treated nets (ITNs) to be delivered by programs in low and middle income countries supported by the Global Fund compared to international targets established by UNAIDS, Stop TB Partnership, Roll Back Malaria Partnership and the World Health Organisation. RESULTS: Global Fund-supported programs are projected to provide ARV treatment to 5.5-5.8 million people, providing 30%-31% of the 2015 international target. Investments in tuberculosis and malaria control will enable reaching in 2015 60%-63% of the international target for tuberculosis case detection and 30%-35% of the ITN distribution target in sub-Saharan Africa. CONCLUSION: Global Fund investments will substantially contribute to the achievement by 2015 of international targets for HIV, TB and malaria. However, additional large scale international and domestic financing is needed if these targets are to be reached by 2015

Experience of symptoms indicative of gynaecological cancers in UK women

BACKGROUND: Gynaecological cancers account for ∼12% of female cancer incidence in the United Kingdom. Encouraging prompt help-seeking for potential symptoms could help improve outcomes. However, before developing help-seeking interventions, it is important to estimate the number of women with symptoms potentially indicative of a gynaecological cancer to help estimate the impact of such interventions on primary care. METHODS: As part of a face-to-face, population-based survey, women aged 16 (n=911) were shown a list of symptoms potentially indicative of a gynaecological cancer and were asked to indicate any experienced in the last 3 months. Those who reported symptoms were asked about their responses to one randomly selected index symptom. RESULTS: Just under half (44%) of the respondents reported a symptom, with 35% reporting a frequent and/or severe symptom. Younger (P<0.001), lower socioeconomic status (P<0.01) and non-White women (P<0.05) were significantly more likely to report symptoms. Few (14%) respondents were both older (45 years) and had a frequent and/or severe symptom. Of these women, 38% had seen a GP. CONCLUSION: Symptoms that potentially indicate a gynaecological cancer, even if limited to those that are frequent and/or severe, appear to be common. Consequently, encouraging prompt help-seeking may increase the burden on primary care. However, targeting those at increased risk (older women with frequent or severe symptoms) should avoid unmanageable increases in primary care consultations for gynaecological conditions

Theoretical Constraints on the Higgs Effective Couplings

We derive constraints on the sign of couplings in an effective Higgs Lagrangian using prime principles such as the naturalness principle, global symmetries, and unitarity. Specifically, we study four dimension-six operators, O_H, O_y, O_g, and O_gamma, which contribute to the production and decay of the Higgs boson at the Large Hadron Collider (LHC), among other things. Assuming the Higgs is a fundamental scalar, we find: 1) the coefficient of O_H is positive except when there are triplet scalars, resulting in a reduction in the Higgs on-shell coupling from their standard model (SM) expectations if no other operators contribute, 2) the linear combination of O_H and O_y controlling the overall Higgs coupling to fermion is always reduced, 3) the sign of O_g induced by a new colored fermion is such that it interferes destructively with the SM top contribution in the gluon fusion production of the Higgs, if the new fermion cancels the top quadratic divergence in the Higgs mass, and 4) the correlation between naturalness and the sign of O_gamma is similar to that of O_g, when there is a new set of heavy electroweak gauge bosons. Next considering a composite scalar for the Higgs, we find the reduction in the on-shell Higgs couplings persists. If further assuming a collective breaking mechanism as in little Higgs theories, the coefficient of O_H remains positive even in the presence of triplet scalars. In the end, we conclude that the gluon fusion production of the Higgs boson is reduced from the SM rate in all composite Higgs models. Our study suggests a wealth of information could be revealed by precise measurements of the Higgs couplings, providing strong motivations for both improving on measurements at the LHC and building a precision machine such as the linear collider.Comment: 37 pages, one figure; v2: improved discussion on dispersion relation and other minor modifications; version accepted for publication

Non-Invasive Cytology Brush PCR Diagnostic Testing in Mucosal Leishmaniasis: Superior Performance to Conventional Biopsy with Histopathology

Traditional methods of diagnosing mucosal leishmaniasis (ML), such as biopsy with histopathology, are insensitive and require collection of an invasive diagnostic specimen. species identification was performed by PCR-based assays of positive specimens. (n = 3).Use of commercial grade cytology brush PCR for diagnosis of ML is sensitive, rapid, well tolerated, and carries none of the risks of invasive diagnostic procedures such as biopsy. Further optimization is required for adequate species identification. Further evaluation of this method in field and other settings is warranted

Scaling clearance in paediatric pharmacokinetics: All models are wrong, which are useful?

AIM: When different models for weight and age are used in paediatric pharmacokinetic studies it is difficult to compare parameters between studies or perform model-based meta-analyses. This study aimed to compare published models with the proposed standard model (allometric weight(0.75) and sigmoidal maturation function). METHODS: A systematic literature search was undertaken to identify published clearance (CL) reports for gentamicin and midazolam and all published models for scaling clearance in children. Each model was fitted to the CL values for gentamicin and midazolam, and the results compared with the standard model (allometric weight exponent of 0.75, along with a sigmoidal maturation function estimating the time in weeks of postmenstrual age to reach half the mature value and a shape parameter). For comparison, we also looked at allometric size models with no age effect, the influence of estimating the allometric exponent in the standard model and, for gentamicin, using a fixed allometric exponent of 0.632 as per a study on glomerular filtration rate maturation. Akaike information criteria (AIC) and visual predictive checks were used for evaluation. RESULTS: No model gave an improved AIC in all age groups, but one model for gentamicin and three models for midazolam gave slightly improved global AIC fits albeit using more parameters: AIC drop (number of parameters), -4.1 (5), -9.2 (4), -10.8 (5) and -10.1 (5), respectively. The 95% confidence interval of estimated CL for all top performing models overlapped. CONCLUSION: No evidence to reject the standard model was found; given the benefits of standardised parameterisation, its use should therefore be recommended