Life journeys with advanced breast cancer in Mauritania:A mixed methods case study

Background: Breast cancer is the most common cancer for women, globally. Social, religious and healthcare contexts have been shown to influence women’s experiences of advanced breast cancer; however, research has tended to focus on resource-rich nations. There is limited research from low-resource contexts, and little is known on the experiences of Arab, Muslim and African women with advanced breast cancer. Aim: To explore and understand the experiences of advanced breast cancer in the Islamic Republic of Mauritania, West Africa. Methods: Using a constructivist Stakian multi-case study approach, eight cases were constructed around women (n=8) with advanced breast cancer, family members (n=10) and health professionals (n=9). Data were collected longitudinally (up to nine months per case) and consisted of interviews, audio-journals, a patient reported outcome measurement scale and a performance status scale. Withincase and cross-case analysis was undertaken, with thematic analysis of qualitative data. Findings: Three key themes were identified: 1. Destiny, 2. Patience & Acceptance and 3. Journeying in search of a cure. Mauritanian women appreciate that Allah is all powerful and maintains control over their destinies and their breast cancer. A fear of causing offence to Allah influences how they express negative experiences of breast cancer and its treatments. The women’s access to information and treatment is controlled by health professionals and families. Women are, therefore, required to use their own observations and interpretations to understand their breast cancer and empower their pursuit of treatment and a cure. Conclusion: Maure women’s experiences of advanced breast cancer in Mauritania are influenced by power imbalances. Allah is all-powerful. Families and health professionals exert power over Maure women’s access to information, healthcare decisions and how they express negative experiences. This thesis demonstrates that Maure women are cognisant of these challenges and, either, accept them as reality or attempt to work around them

Response to David Freedman

As Jonathan Swift made mockingly clear, “modest proposals” that purport to solve previously unyielding problems can have horrible implications. Such proposals should be subjected to skeptical analysis. So we are pleased that our proposed random method of case selection for the qualitative component of multi-method research has attracted some skeptical commentary in the research community in political science. And we are very grateful to David Freedman for providing a perspective on our approach. He is especially qualified to do so, as he is a leading statistician who has long worried about inflated claims for statistical methods in the social sciences, and has been a champion of approaches that are sensitive to the particularities of each datapoint

Teaching A New Generation: The Differences Are Not Trivial

As organizational behavior learners apply managerial knowledge in classroom exercises or in the field, the hidden knowledge they hold of the cultural context of these applications works spontaneously to create meaning. This contextual knowledge is developed profoundly in our formative years; thus tacit experiential knowledge differs by generation. Today’s college-aged Millennials see organizational life and OB theory differently than yesterday’s Gen X, or Baby Boomer cohorts. These differences are revealed in an exercise using the vintage (1982) and current editions of the board game Trivial Pursuit. This activity asks learners to find the presence of generationally-cultivated knowledge in their daily lives and consider its effect on their use of OB theory. The experiential exercise is also linked to field interviews and other activities related to understanding generational differences in world view

Experiences of breast cancer in Arab countries:a thematic synthesis

Background Breast cancer is the most common cancer in women globally. Its negative effects on a woman's quality of life are related to the individual and socio-cultural factors. This review aimed to identify and synthesise the reported experiences and quality of life of women with breast cancer in Arab countries. Methods PubMed, Embase, Web of Science, SCOPUS, PsychInfo, CINAHL, Allied and Complementary Medicine Database, and Index Medicus for the Eastern Mediterranean Region were searched for articles published from start to March 2019 using PRISMA guidelines. These searches were complimented by citation tracking and hand searching of relevant journals. A thematic synthesis was carried out on the 'findings/results' sections from the identified papers. Results Of 5228 records identified, 19 were included in the review which represented 401 women from 11 Arab countries. All used qualitative methods of data collection to produce rich descriptions of experiences. Thematic synthesis of the extracted data identified three major themes, Perceptions and reactions, Coping or enduring and Changing roles. Conclusions This review provides a rich description of the reported quality of life and experiences of women with breast cancer in Arab countries. These are influenced by the women's and society's views of cancer, the women's role in society and family, religious faith and the healthcare context and access to treatment choices and information

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations

<b>Background</b><p></p> Various tools exist for initial assessment of possible dementia with no consensus on the optimal assessment method. Instruments that use collateral sources to assess change in cognitive function over time may have particular utility. The most commonly used informant dementia assessment is the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE).<p></p> A synthesis of the available data regarding IQCODE accuracy will help inform cognitive assessment strategies for clinical practice, research and policy.<p></p> <b>Objectives</b><p></p> Our primary objective was to determine the diagnostic accuracy of the informant based questionnaire IQCODE, for detection of all cause (undifferentiated) dementia in community-dwelling adults with no previous cognitive assessment. We sought to describe the accuracy of IQCODE (the index test) against a clinical diagnosis of dementia (the reference standard).<p></p> Our secondary objective was to describe the effect of heterogeneity on the summary estimates. We were particularly interested in the traditional 26-item scale versus the 16-item short form; and language of administration. We explored the effect of varying the threshold IQCODE score used to define 'test positivity'.<p></p> <b>Search methods</b><p></p> We searched the following sources on 28 January 2013: ALOIS (Cochrane Dementia and Cognitive Improvement Group), MEDLINE (OvidSP), EMBASE (OvidSP), PsycINFO (OvidSP), BIOSIS Previews (ISI Web of Knowledge), Web of Science with Conference Proceedings (ISI Web of Knowledge), LILACS (BIREME). We also searched sources relevant or specific to diagnostic test accuracy: MEDION (Universities of Maastrict and Leuven); DARE (York University); ARIF (Birmingham University). We used sensitive search terms based on MeSH terms and other controlled vocabulary.<p></p> <b>Selection criteria</b><p></p> We selected those studies performed in community settings that used (not necessarily exclusively) the IQCODE to assess for presence of dementia and, where dementia diagnosis was confirmed, with clinical assessment. Our intention with limiting the search to a 'community' setting was to include those studies closest to population level assessment. Within our predefined community inclusion criteria, there were relevant papers that fulfilled our definition of community dwelling but represented a selected population, for example stroke survivors. We included these studies but performed sensitivity analyses to assess the effects of these less representative populations on the summary results.<p></p> <b>Data collection and analysis</b><p></p> We screened all titles generated by the electronic database searches and abstracts of all potentially relevant studies were reviewed. Full papers were assessed for eligibility and data extracted by two independent assessors. For quality assessment (risk of bias and applicability) we used the QUADAS 2 tool. We included test accuracy data on the IQCODE used at predefined diagnostic thresholds. Where data allowed, we performed meta-analyses to calculate summary values of sensitivity and specificity with corresponding 95% confidence intervals (CIs). We pre-specified analyses to describe the effect of IQCODE format (traditional or short form) and language of administration for the IQCODE.<p></p> <b>Main results</b><p></p> From 16,144 citations, 71 papers described IQCODE test accuracy. We included 10 papers (11 independent datasets) representing data from 2644 individuals (n = 379 (14%) with dementia). Using IQCODE cut-offs commonly employed in clinical practice (3.3, 3.4, 3.5, 3.6) the sensitivity and specificity of IQCODE for diagnosis of dementia across the studies were generally above 75%.<p></p> Taking an IQCODE threshold of 3.3 (or closest available) the sensitivity was 0.80 (95% CI 0.75 to 0.85); specificity was 0.84 (95% CI 0.78 to 0.90); positive likelihood ratio was 5.2 (95% CI 3.7 to 7.5) and the negative likelihood ratio was 0.23 (95% CI 0.19 to 0.29).<p></p> Comparative analysis suggested no significant difference in the test accuracy of the 16 and 26-item IQCODE tests and no significant difference in test accuracy by language of administration. There was little difference in sensitivity across our predefined diagnostic cut-points.<p></p> There was substantial heterogeneity in the included studies. Sensitivity analyses removing potentially unrepresentative populations in these studies made little difference to the pooled data estimates. The majority of included papers had potential for bias, particularly around participant selection and sampling. The quality of reporting was suboptimal particularly regarding timing of assessments and descriptors of reproducibility and inter-observer variability.<p></p> <b>Authors' conclusions</b><p></p> Published data suggest that if using the IQCODE for community dwelling older adults, the 16 item IQCODE may be preferable to the traditional scale due to lesser test burden and no obvious difference in accuracy. Although IQCODE test accuracy is in a range that many would consider 'reasonable', in the context of community or population settings the use of the IQCODE alone would result in substantial misdiagnosis and false reassurance. Across the included studies there were issues with heterogeneity, several potential biases and suboptimal reporting quality

The effect of resting ST segment depression on the diagnostic characteristics of the exercise treadmill test

AbstractOBJECTIVESThe aim of this study is to demonstrate the effect of resting ST segment depression on the diagnostic characteristics of the exercise treadmill test.BACKGROUNDPrevious studies evaluating the effect of resting ST segment depression on the diagnostic characteristics of exercise treadmill test have been conducted on relatively small patient groups and based only on visual electrocardiogram (ECG) analysis.METHODSA retrospective analysis of data collected prospectively was performed on consecutive patients referred for evaluation of chest pain. One thousand two hundred eighty-two patients without a prior myocardial infarction underwent standard exercise treadmill tests followed by coronary angiography, with coronary artery disease defined as a 50% narrowing in at least one major epicardial coronary artery. Sensitivity, specificity, predictive accuracy and area under the curve of the receiver operating characteristic (ROC) plots were calculated for patients with and without resting ST segment depression as determined by visual or computerized analysis of the baseline ECG.RESULTSSensitivity of the exercise treadmill test increased in 206 patients with resting ST segment depression determined by visual ECG analysis compared with patients without resting ST segment depression (77 ± 7% vs. 45 ± 4%) and specificity decreased (48 ± 12% vs. 84 ± 3%). With computerized analysis, sensitivity of the treadmill test increased in 349 patients with resting ST segment depression compared with patients without resting ST segment depression (71 ± 6% vs. 42 ± 4%) and specificity decreased (52 ± 9% vs. 87 ± 3%) (p < 0.0001 for all comparisons). There was no significant difference in the area under the curve of the ROC plots (0.66–0.69) or the predictive accuracy (62–68%) between the four subgroups.CONCLUSIONSThe diagnostic accuracy and high sensitivity of the exercise treadmill test in a large cohort of patients with resting ST segment depression and no prior myocardial infarction support the initial use of the test for diagnosis of coronary artery disease. The classification of resting ST segment depression by method of analysis (visual vs. computerized) did not affect the results

Tumour-derived leukaemia inhibitory factor is a major driver of cancer cachexia and morbidity in C26 tumour-bearing mice

BACKGROUND: Cancer cachexia is a metabolic wasting syndrome that is strongly associated with a poor prognosis. The initiating factors causing fat and muscle loss are largely unknown. Previously, we found that leukaemia inhibitory factor (LIF) secreted by C26 colon carcinoma cells was responsible for atrophy in treated myotubes. In the present study, we tested whether C26 tumour‐derived LIF is required for cancer cachexia in mice by knockout of Lif in C26 cells. METHODS: A C26 Lif null tumour cell line was made using CRISPR‐Cas9. Measurements of cachexia were compared in mice inoculated with C26 vs. C26^Lif−/− tumour cells, and atrophy was compared in myotubes treated with medium from C26 vs. C26^Lif−/− tumour cells. Levels of 25 cytokines/chemokines were compared in serum of mice bearing C26 vs. C26^Lif−/− tumours and in the medium from these tumour cell lines. RESULTS: At study endpoint, C26 mice showed outward signs of sickness while mice with C26^Lif−/− tumours appeared healthy. Mice with C26^Lif−/− tumours showed a 55–75% amelioration of body weight loss, muscle loss, fat loss, and splenomegaly compared with mice with C26 tumours (P < 0.05). The heart was not affected by LIF levels because the loss of cardiac mass was the same in C26 and C^26Lif−/− tumour‐bearing mice. LIF levels in mouse serum was entirely dependent on secretion from the tumour cells. Serum levels of interleukin‐6 and G‐CSF were increased by 79‐fold and 68‐fold, respectively, in C26 mice but only by five‐fold and two‐fold, respectively, in C26^Lif−/− mice, suggesting that interleukin‐6 and G‐CSF increases are dependent on tumour‐derived LIF. CONCLUSIONS: This study shows the first use of CRISPR‐Cas9 knockout of a candidate cachexia factor in tumour cells. The results provide direct evidence for LIF as a major cachexia initiating factor for the C26 tumour in vivo. Tumour‐derived LIF was also a regulator of multiple cytokines in C26 tumour cells and in C26 tumour‐bearing mice. The identification of tumour‐derived factors such as LIF that initiate the cachectic process is immediately applicable to the development of therapeutics to treat cachexia. This is a proof of principle for studies that when carried out in human cells, will make possible an understanding of the factors causing cachexia in a patient‐specific manner.This work was supported by NIAMS R01AR060217 to S. C. K. and R. W. J. and NIAMS R01 R01AR060209 to A. R. J., and by the Dudley Allen Sargent Research Fund. The authors certify that they comply with the ethical guidelines for publishing in the Journal of Cachexia, Sarcopenia and Muscle: update 2017.40 (R01AR060217 - NIAMS; R01 R01AR060209 - NIAMS; Dudley Allen Sargent Research Fund)Published versio