Hypothyroidism in Bangladesh: Is Autoimmunity the Next Big Threat?

In many low and middle-income countries, iodine-deficient hypothyroidism leads to complex public health consequences. However, increasing evidence from population-based studies has linked thyroid autoimmunity with excess iodine intake. The iodine supplementation program in Bangladesh was a success story. This cross-sectional study aims to assess the pattern and predictors of autoimmunity among Bangladeshi hypothyroid patients. In this study, 154 consecutive, newly detected, biochemically-confirmed patients with primary hypothyroidism were recruited from the Endocrinology outpatient department of Bangabandhu Sheikh Mujib Medical University and tested for anti-thyroid peroxidase and anti-thyroglobulin antibody levels from October 2015 and November 2016. Patterns of thyroid autoimmunity were assessed via descriptive statistics. Predictors of autoimmunity were assessed with multivariable mixed-effect logistic regression. The mean age of participants was 36.1±11.0 years, and 70.1% were female. The frequency of thyroid autoimmunity in the study subjects was very high, 89.0% were positive for either anti-TPO or anti-Tg antibodies and 48.7% were positive for both. More participants were positive for anti-TPO antibodies (82.5%) than anti-Tg antibodies (55.2%). The risk of autoimmunity was associated with the thyroid's structural abnormalities but not with functional status. Weight gain and hypertension were associated with autoimmunity, whereas diabetes was protective against autoimmunity.

Development and evaluation of a spiral model of assessing EBM competency using OSCEs in undergraduate medical education.

BACKGROUND: Medical students often struggle to understand the relevance of Evidence Based Medicine (EBM) to their clinical practice, yet it is a competence that all students must develop prior to graduation. Objective structured clinical examinations (OSCEs) are a valued assessment tool to assess critical components of EBM competency, particularly different levels of mastery as they progress through the course. This study developed and evaluated EBM based OSCE stations with an aim to establish a spiral approach for EBM OSCE stations for undergraduate medical students. METHODS: OSCE stations were developed with increasingly complex EBM tasks. OSCE stations were classified according to the classification rubric for EBP assessment tools (CREATE) framework and mapped against the recently published core competencies for evidence-based practice (EBP). Performance data evaluation was undertaken using Classical Test Theory analysing mean scores, pass rates, and station item total correlation (ITC) using SPSS. RESULTS: Six EBM based OSCE stations assessing various stages of EBM were created for use in high stakes summative OSCEs for different year groups across the undergraduate medical degree. All OSCE stations, except for one, had excellent correlation coefficients and hence a high reliability, ranging from 0.21-0.49. The domain mean score ranged from 13.33 to 16.83 out of 20. High reliability was demonstrated for the each of the summative OSCE circuits (Cronbach's alpha = 0.67-0.85). In the CREATE framework these stations assessed knowledge, skills, and behaviour of medical students in asking, searching, appraising, and integrating evidence in practice. The OSCE stations were useful in assessing six core evidence-based practice competencies, which are meant to be practiced with exercises. A spiral model of OSCEs of increasing complexity was proposed to assess EBM competency as students progressed through the MBChB course. CONCLUSIONS: The use of the OSCEs is a feasible method of authentically assessing leaner EBM performance and behaviour in a high stakes assessment setting. Use of valid and reliable EBM-based OSCE stations provide evidence for continued development of a hierarchy of assessing scaffolded learning and mastery of EBM competency. Further work is needed to assess their predictive validity.

"You can't always get what you want ": economic thinking, constrained optimization and health professions education.

Every choice we make in health professions education has a cost, whether it be financial or otherwise; by choosing one action (e.g., integrating more simulation, studying more for a summative examination) we lose the opportunity to take an alternative action (e.g., freeing up time for other teaching, leisure time). Economics significantly shapes the way we behave and think as educators and learners and so there is increasing interest in using economic ways of thinking and approaches to examine and understand how choices are made, the influence of constraints and boundaries in educational decision making, and how costs are felt. Thus, in this article, we provide a brief historical overview of modern economics, to illustrate how the core concepts of economics-scarcity (and desirability), rationality, and optimization-developed over time. We explain the important concept of bounded rationality, which explains how individual, meso-factors and contextual factors influence decision making. We then consider the opportunities that these concepts afford for health professions education and research. We conclude by proposing that embracing economic thinking opens up new questions and new ways of approaching old questions which can add knowledge about how choice is enacted in contemporary health professions education.

Influence of non-dipping pattern of blood pressure in gestational hypertension on maternal cardiac function, hemodynamics and intrauterine growth restriction.

BACKGROUND: An association between gestational hypertension (GH) and changes of maternal cardiac function was previously reported. AIM: The study assessed the effect of non-dipping pattern of blood pressure (BP) in GH on haemodynamic function and intrauterine growth restriction (IUGR). METHODS: This study included 126 women (91 with GH and 35 normotensive controls). Based on the BP values measured by ambulatory blood pressure monitoring (ABPM), all hypertensive women were classified in dipper (46 women) or in non-dipper group (45 women). All participants underwent echocardiography and ABPM during the third trimester. RESULTS: Participants with GH and non-dipping pattern had significantly lower velocity of longitudinal systolic function (s') (p<0.0005), and cardiac output index (COi) compared to dippers (p<0.0005) and controls (p=0.002). Diastolic velocities at the mitral valve annulus were also lower in non-dippers e's (non-dippers vs dippers p=0.023; non-dippers vs controls p<0.0005) and e'l (non-dippers vs dippers p=0.048; non-dippers vs controls p<0.0005). There were significant differences in the index of the left ventricle filling pressure E/e' and myocardial mass index between women with GH and controls, but with no significant difference among dippers and non-dippers. Total vascular resistance was increased in non-dipping group compared to normotensives and dippers (p<0.0005). Multivariate regression analysis revealed that the peak night-time diastolic BP, left ventricular mass index and CO index were identified as independent predictors of IUGR. CONCLUSION: Changes in maternal hemodynamics, as well as IUGR, are strongly related to the non-dipping pattern of BP.

Acceptability of delivery modes for lifestyle advice in a large scale randomised controlled obesity prevention trial.

BACKGROUND: Preventing obesity is an international health priority and women living in rural communities are at an increased risk of weight gain. Lifestyle programs are needed as part of a comprehensive approach to prevent obesity. Evaluation provides a unique opportunity to investigate and inform improvements in lifestyle program implementation strategies. The Healthy Lifestyle Program for rural women (HeLP-her Rural) is a large scale, cluster randomized control trial, targeting the prevention of weight gain. This program utilises multiple delivery modes for simple lifestyle advice (group sessions, phone coaching, text messages, and an interactive program manual). Here, we describe the acceptability of these various delivery modes. METHODS: A mixed-method process evaluation was undertaken measuring program fidelity, recruitment strategies, dose delivered, program acceptability and contextual factors influencing program implementation. Data collection methodologies included qualitative semi-structured interviews for a sub-group of intervention participants [n = 28] via thematic analysis and quantitative methods (program checklists and questionnaires [n = 190]) analysed via chi square and t-tests. RESULTS: We recruited 649 women from 41 rural townships into the HeLP-her Rural program with high levels of program fidelity, dose delivered and acceptability. Participants were from low socioeconomic townships and no differences were detected between socioeconomic characteristics and the number of participants recruited across the towns (p = 0.15). A face-to-face group session was the most commonly reported preferred delivery mode for receiving lifestyle advice, followed by text messages and phone coaching. Multiple sub-themes emerged to support the value of group sessions which included: promoting of a sense of belonging, mutual support and a forum to share ideas. The value of various delivery modes was influenced by participant's various needs and learning styles. CONCLUSION: This comprehensive evaluation reveals strong implementation fidelity and high levels of dose delivery. We demonstrate reach to women from relatively low income rural townships and highlight the acceptability of low intensity healthy lifestyle programs with mixed face-to-face and remote delivery modes in this population. Group education sessions were the most highly valued component of the intervention, with at least one face-to-face session critical to successful program implementation. However, lifestyle advice via multiple delivery modes is recommended to optimise program acceptability and ultimately effectiveness. TRIAL REGISTRY: Australia & New Zealand Clinical Trial Registry. Trial number ACTRN12612000115831, date of registration 24/01/2012.

Stem cell therapies for recessive dystrophic epidermolysis bullosa.

Human epidermis is composed of a stratified squamous epithelium that provides a mechanical barrier against the external environment and which is renewed every 3-4 weeks by resident stem cells in the epidermis. However, in the inherited skin fragility disorder, recessive dystrophic epidermolysis bullosa (RDEB), there is recurrent trauma-induced subepidermal blistering that disrupts epidermal homeostasis and is likely to deplete the epidermal stem cell pool. This review article discusses the nature of epidermal stem cells and other stem cell populations in the skin, as well as other possible extracutaneous sources of stem cells, that might have physiological or therapeutic relevance to cell therapy approaches for RDEB. Strategies to identify, create and use cells with multipotent or pluripotent properties are explored and current clinical experience of stem cell therapy in RDEB is reviewed. There is currently no single optimal therapy for patients with RDEB, but cell therapy technologies are evolving and hold great potential for modifying disease severity and improving quality of life for people living with RDEB.

Polyhydramnios and bone development: an unexplored relationship.

Immersion of a humans and Macaca mulatta into a pool with fluid whose specific weight is equal to their specific weight cause bone demineralization. Also, in professional scuba divers, bone mineral density is reduced. Because of water immersion, the apparent weight of scuba divers represents 10% of their actual weight. The aim of this paper was to point out a previously unexplored aspect of fetal bone development in an environment lacking adequate mechanical stress on fetal bone, such as polyhydramnios. In the first part of gestation, the human fetus develops under conditions similar to neutral floating and has an apparent weight which is approximately 5% of its actual weight. During the last trimester of gestation, the fetus overgrows the intrauterine cavity and its apparent body weight is 60-80% of its actual weight. Polyhydramnios represents an excess of amniotic fluid in the uterus during gestation and it can reduce the apparent weight of the fetus to 10-20% of its actual weight. Reduction of the mechanical stress on fetal bone caused by polyhydramnios may significantly affect bone development and ossification during the last trimester of gestation. It is necessary to direct further studies towards examining bone development and mineralization in newborns from gestations complicated by polyhydramnios. A complete lack of data and studies on fetal bone development and bone mineralization in pregnancies complicated by polyhydramnios is not surprising. There is still a misleading opinion that the fetus is in weightlessness condition in the intrauterine environment throughout the second half of gestation regardless of the amount of amniotic fluid.

The prognosis of highly active antiretroviral therapy (HAART) treated HIV infected patients in Serbia, related to the time of treatment initiation.

BACKGROUND: With the introduction of highly active antiretroviral treatment (HAART) an impressive improvement in patient survival and quality of life has bee observed. However, the optimal timing of initial HAART is still under consideration. OBJECTIVE: To investigate the prognosis of HAART treated patients in Serbia, related to the timing of HAART initiation. STUDY DESIGN: A series of 563 patients on HAART was retrospectively analyzed to investigate treatment response and survival. RESULTS: After a mean of 6 years (range 1-14) of treatment with PI-based and/or NNRTI-based regimens, a favorable response was achieved in 72.4%, treatment failure occurred in 7.9%, while 19.7% had a dissociative immunological/virological response. If treatment was initiated during primary HIV infection it took a shorter time to achieve a favorable response than in patients who began HAART in chronic HIV infection (2.7+/-2.2 years vs. 6.9+/-2.7 years, P<0.01). A higher proportion of patients with primary HIV infection then those treated in the chronic phase achieved a favorable response to HAART (88.4% vs. 71.9%, P=0.045). Patients who initiated HAART when their CD4 cell counts were below 200 cells/microL needed longer treatment for favorable response (8 years vs. 6 years, log rank P<0.01). Forty-seven (8.3%) patients died. The overall estimated survival was 13 years. Patients older then 40 and IVDU were more likely to die during HAART (OR 2.6, 95% CI 1.1-5.9, P=0.016, and OR 2.0, 95% CI 1.0-3.7, P=0.02, respectively). However, reaching and maintaining undetectable viremia was an independent predictor of longer survival (OR 11.3, 95% CI 4.6-27.7, P<0.01). CONCLUSION: Reaching and maintaining undetectable viremia during HAART predicted longer survival, even if sub-clinical immunodeficiency remained.

Influence of narrow band imaging (NBI) videobronchoscopy on the assessment of central lung cancer extension and therapeutic decision.

OBJECTIVES: Determination of specificity and sensitivity of narrow band imaging (NBI) in the assessment of tumor extension in centrally located lung cancer, when compared to white light bronchoscopy (WLB) alone, and evaluation of possible influence of NBI on therapeutic decision in patients with lung cancer. PATIENTS AND METHODS: We evaluated 36 patients with suspected lung cancer. All patients underwent WLB followed by NBI bronchoscopy. We were using videobronchoscope BF-1T180 and EVIS LUCERA SPECTRUM processor unit. RESULTS: Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for NBI in the assessment of tumor extension were 97.8, 85, 93.7, and 94.4%, respectively; and for WLB 92.3, 60, 69.6, and 88.9%, respectively. In 14 patients, NBI revealed more extensive tumor than WLB (p =.0057). In eight patients, NBI showed significant influence on therapeutic decision (p =.001). CONCLUSION: NBI videobronchoscopy had better specificity and sensitivity in the assessment of tumor extension in centrally located lung cancer, and it might play a significant role in the therapeutic decision.

A nonlinear model of ionic wave propagation along microtubules.

Microtubules (MTs) are important cytoskeletal polymers engaged in a number of specific cellular activities including the traffic of organelles using motor proteins, cellular architecture and motility, cell division and a possible participation in information processing within neuronal functioning. How MTs operate and process electrical information is still largely unknown. In this paper we investigate the conditions enabling MTs to act as electrical transmission lines for ion flows along their lengths. We introduce a model in which each tubulin dimer is viewed as an electric element with a capacitive, inductive and resistive characteristics arising due to polyelectrolyte nature of MTs. Based on Kirchhoff's laws taken in the continuum limit, a nonlinear partial differential equation is derived and analyzed. We demonstrate that it can be used to describe the electrostatic potential coupled to the propagating localized ionic waves.

Screening for prostate cancer.

BACKGROUND: Any form of screening aims to reduce mortality and increase a person's quality of life. Screening for prostate cancer has generated considerable debate within the medical community, as demonstrated by the varying recommendations made by medical organizations and governed by national policies. Much of this debate is due to the limited availability of high quality research and the influence of false-positive or false-negative results generated by use of the diagnostic techniques such as the digital rectal examination (DRE) and prostate specific antigen (PSA) blood test. OBJECTIVES: To determine whether screening for prostate cancer reduces prostate cancer mortality and has an impact on quality of life. SEARCH STRATEGY: Electronic databases (PROSTATE register, CENTRAL the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CANCERLIT and the NHS EED) were searched electronically in addition to hand searching of specific journals and bibliographies in an effort to identify both published and unpublished trials. SELECTION CRITERIA: All randomised controlled trials of screening versus no screening or routine care for prostate cancer were eligible for inclusion in this review. DATA COLLECTION AND ANALYSIS: The search identified 99 potentially relevant articles that were selected for full text review. From these 99 citations, two randomised controlled trials were identified as meeting the review's inclusion criteria. Data from the trials were independently extracted by two authors. MAIN RESULTS: Two randomised controlled trials with a total of 55,512 participants were included; however, both trials had methodological weaknesses. Re-analysis using intention-to-screen and meta-analysis of results from the two randomised controlled trials indicated no statistically significant difference in prostate cancer mortality between men randomised for prostate cancer screening and controls (RR 1.01, 95% CI: 0.80-1.29). Neither study assessed the effect of prostate cancer screening on quality of life, all-cause mortality or cost effectiveness. AUTHORS' CONCLUSIONS: Given that only two randomised controlled trials were included, and the high risk of bias of both trials, there is insufficient evidence to either support or refute the routine use of mass, selective or opportunistic screening compared to no screening for reducing prostate cancer mortality. Currently, no robust evidence from randomised controlled trials is available regarding the impact of screening on quality of life, harms of screening, or its economic value. Results from two ongoing large scale multicentre randomised controlled trials that will be available in the next several years are required to make evidence-based decisions regarding prostate cancer screening.

Intrinsic FAK activity and Y925 phosphorylation facilitate an angiogenic switch in tumors.

Elevated focal adhesion kinase (FAK) expression occurs in advanced cancers, yet a signaling role for FAK in tumor progression remains undefined. Here, we suppressed FAK activity in 4T1 breast carcinoma cells resulting in reduced FAK Y925 phosphorylation, Grb2 adaptor protein binding to FAK, and signaling to mitogen-activated protein (MAP) kinase (MAPK). Loss of a FAK-Grb2-MAPK linkage did not affect 4T1 cell proliferation or survival in culture, yet FAK inhibition reduced vascular endothelial growth factor (VEGF) expression and resulted in small avascular tumors in mice. This FAK-Grb2-MAPK linkage was essential in promoting angiogenesis as reconstitution experiments using Src-transformed FAK-null fibroblasts revealed that point mutations affecting FAK catalytic activity (R454) or Y925 phosphorylation (F925) disrupted the ability of FAK to promote MAPK- and VEGF-associated tumor growth. Notably, in both FAK-inhibited 4T1 and Src-transformed FAK-null cells, constitutively activated (CA) mitogen-activated protein kinase kinase 1 (MEK1) restored VEGF production and CA-MEK1 or added VEGF rescued tumor growth and angiogenesis. These studies provide the first biological support for Y925 FAK phosphorylation and define a novel role for FAK activity in promoting a MAPK-associated angiogenic switch during tumor progression.

Hair cycle and wound healing in mice with a keratinocyte-restricted deletion of FAK.

Focal adhesion kinase (FAK) is a critical component in transducing signals downstream of both integrins and growth factor receptors. To determine how the loss of FAK affects the epidermis in vivo, we have generated a mouse model with a keratinocyte-restricted deletion of fak (FAKK5 KO mice). FAK(K5 KO) mice displayed three major phenotypes--irregularities of hair cycle, sebaceous glands hypoplasia, and a thinner epidermis--pointing to defects in the proliferative capacity of multipotent stem cells found in the bulge. FAK-null keratinocytes in conventional primary culture undergo massive apoptosis hindering further analyses, whereas the defects observed in vivo do not shorten the mouse lifespan. These results suggest that the structure and the signaling environment of the native tissue may overcome the lack of signaling through FAK. Our findings point to the importance of in vivo and three-dimensional in vitro models in analyses of cell migration, proliferation, and survival. Surprisingly, the difference between FAKloxP/+ and FAKK5 KO mice in wound closure was not statistically significant, suggesting that in vivo loss of FAK does not affect migration/proliferation of basal keratinocytes in the same way as it affects multipotent stem cells of the skin.

Measurement of elastic properties of blood vessels.

This paper is related to the measurements of the modulus of elasticity of an artery by studying the deformations due to the inflation of an angioplasty balloon catheter used for Interventional Radiology (IR) procedures. Various types of balloons are studied in order to characterize and compare their behaviors at the time of inflation. A test bench, consisting of an angioplasty balloon, a Polyvinyl alcohol model and an actuator used to inflate a balloon, is developed for the realization of the experiments. The pressure-volume curve during the inflation of a balloon is observed. Elasticity modulus are derived with an analytical model of the measurement system. The results are then analyzed and compared to existing data from literature.

Measurement of internal constraints during an interventional radiology procedure.

This paper presents a novel method for measurements of internal constraints during an Interventional Radiology procedure. Fiber-optic strain gauge, operating as a Fabry-Perot interferometer, is inserted and navigated inside a polyvinyl alcohol (PVA) model. The information obtained from deformation of the Fabry-Perot cavity is analyzed and the results are then rescaled through a calibration procedure for catheters. The measures help to locate the maximum interaction forces between catheter and blood vessel wall at approximately 1.3 N and to observe the shape of dynamic interaction during manipulation.

Accessibility, nature and quality of health information on the Internet: a survey on osteoarthritis.

OBJECTIVES: This study aims to determine the quality and validity of information available on the Internet about osteoarthritis and to investigate the best way of sourcing this information. METHODS: Keywords relevant to osteoarthritis were searched across 15 search engines representing medical, general and meta-search engines. Search engine efficiency was defined as the percentage of unique and relevant websites from all websites returned by each search engine. The quality of relevant information was appraised using the DISCERN tool and the concordance of the information offered by the website with the available evidence about osteoarthritis determined. RESULTS: A total of 3443 websites were retrieved, of which 344 were identified as unique and providing information relevant to osteoarthritis. The overall quality of website information was poor. There was no significant difference between types of search engine in sourcing relevant information; however, the information retrieved from medical search engines was of a higher quality. Fewer than a third of the websites identified as offering relevant information cited evidence to support their recommendations. CONCLUSIONS: Although the overall quality of website information about osteoarthritis was poor, medical search engines may provide consumers with the opportunity to source high-quality health information on the Internet. In the era of evidence-based medicine, one of the main obstacles to the Internet reaching its potential as a medical resource is the failure of websites to incorporate and attribute evidence-based information.

Specialized medical search-engines are no better than general search-engines in sourcing consumer information about androgen deficiency.

BACKGROUND: The Internet provides consumers with access to online health information; however, identifying relevant and valid information can be problematic. Our objectives were firstly to investigate the efficiency of search-engines, and then to assess the quality of online information pertaining to androgen deficiency in the ageing male (ADAM). METHODS: Keyword searches were performed on nine search-engines (four general and five medical) to identify website information regarding ADAM. Search-engine efficiency was compared by percentage of relevant websites obtained via each search-engine. The quality of information published on each website was assessed using the DISCERN rating tool. RESULTS: Of 4927 websites searched, 47 (1.44%) and 10 (0.60%) relevant websites were identified by general and medical search-engines respectively. The overall quality of online information on ADAM was poor. The quality of websites retrieved using medical search-engines did not differ significantly from those retrieved by general search-engines. CONCLUSION: Despite the poor quality of online information relating to ADAM, it is evident that medical search-engines are no better than general search-engines in sourcing consumer information relevant to ADAM.