2,319 research outputs found

    Estimating the impact of tuberculosis anatomical classification on treatment outcomes: A patient and surveillance perspective analysis.

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    INTRODUCTION: Tuberculosis anatomical classification is inconsistent in the literature, which limits current tuberculosis knowledge and control. We aimed to evaluate whether tuberculosis classification impacts on treatment outcomes at patient and aggregate level. METHODS: We analyzed adults from São Paulo State, Brazil with newly diagnosed tuberculosis from 2010-2013. We used an extended clinical classification of tuberculosis, categorizing cases as pulmonary, pulmonary and extrapulmonary, extrapulmonary and miliary/disseminated. Our primary outcome was unsuccessful outcome of treatment. To investigate the reported treatment outcome at the aggregate level, we sampled 500 different "countries" from the dataset and compared the impact of pulmonary and extrapulmonary classifications on the reported treatment success. RESULTS: Of 62,178 patients, 49,999 (80.4%) were pulmonary, 9,026 (14.5%) extrapulmonary, 1,651 (2.7%) pulmonary-extrapulmonary and 1,502 (2.4%) miliary/disseminated. Pulmonary-extrapulmonary cases had similar unsuccessful outcome of treatment compared with pulmonary (adjusted-OR 1.00, 95%CI, 0.88-1.13, p = 0.941), while extrapulmonary were associated with better (adjusted-OR 0.65, 95%CI, 0.60-0.71, p<0.001) and miliary/disseminated with worse outcomes (adjusted-OR 1.51, 95%CI, 1.33-1.71, p<0.001). We found that 60 (12%) countries would report a difference ≥10% in treatment success depending on whether they reported all clinical forms together (current WHO recommendation) or pulmonary forms alone, overestimating the treatment success of pulmonary forms. CONCLUSIONS: The expanded anatomical classification of tuberculosis was strongly associated with treatment outcomes at the patient level. Remarkably, pulmonary with concomitant extrapulmonary forms had similar treatment outcomes compared with pulmonary forms after adjustment for potential confounders. At the aggregate level, reporting treatment success for all clinical forms together might hide differences in progress between pulmonary and extrapulmonary tuberculosis control

    The impact of being homeless on the unsuccessful outcome of treatment of pulmonary TB in São Paulo State, Brazil.

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    BACKGROUND: Tuberculosis (TB) is a major public health problem requiring complex treatment, the success of which depends on biological, social, and institutional factors. São Paulo State (SPS), in Brazil, has a high TB burden. Because of high socioeconomic heterogeneity and chaotic urbanisation, homelessness might play an important role in the TB burden in SPS. Our aim was to determine the association between homelessness and outcome of treatment of pulmonary TB (PTB) in SPS. METHODS: A historical cohort from the routine SPS TB database for 2009-2013 was analysed. The study population was newly diagnosed adult patients with PTB. Homelessness was ascertained at notification or when treatment started. Our outcome was unsuccessful outcome of treatment. We used logistic regression to adjust for potential confounders and multiple imputation for missing data. RESULTS: We analysed 61,817 patients; 1726 (2.8 %, 95%CI 2.7-2.9 %) were homeless. Homeless patients were concentrated in bigger cities, were more frequently middle-aged males, had black/brown skin colour, and had received less education (P < 0.001, for all). Alcohol and drug use was three times more frequent in homeless patients (43.2 % vs 14.4 %, 30.2 % vs. 9.4 %, P < 0.001, respectively). HIV testing was less common among the homeless, of whom 17.3 % were HIV positive compared with 8.5 % among the not homeless population (P < 0.001). Microbiologic confirmation was more frequent among the homeless (91.6 % vs. 84.8 %, P < 0.001). Unsuccessful outcome of treatment was 57.3 % among the homeless and 17.5 % among the not homeless (OR = 6.32, 95%CI 5.73-6.97, P < 0.001), mainly due to loss to follow-up (39 %) and death (10.5 %). After full-adjustment for potential confounders, homelessness remained strongly associated with lower treatment success (aOR = 4.96, 95 % CI 4.27-5.76, P < 0.001). HIV status interacted with homelessness: among HIV-infected patients, the aOR was 2.45 (95%CI 1.90-3.16, Pinteraction < 0.001). The population attributable fraction for the joint effect of homelessness, alcohol and drug use was almost 20 %. CONCLUSIONS: Confirming our hypothesis, homelessness led to a marked reduction in the successful treatment of newly diagnosed pulmonary tuberculosis. Homelessness and associated conditions were important contributors to lack of treatment success in pulmonary tuberculosis in São Paulo. A multifaceted intervention must be implemented to target this vulnerable population

    Digital health and inequalities in access to health services in Bangladesh: Mixed methods study

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    Background: Globally, the rapid growth of technology and its use as a development solution has generated much interest in digital health. In line with global trends, Bangladesh is also integrating technology into its health system to address disparities. Strong political endorsement and uptake of digital platforms by the government has influenced the rapid proliferation of such initiatives in the country. This paper aims to examine the implications of digital health on access to health care in Bangladesh, considering who uses electronic devices to access health information and services and why. Objective: This study aims to understand how access to health care and related information through electronic means (digital health) is affected by sociodemographic determinants (ie, age, gender, education, socioeconomic status, and personal and household ownership of mobile phones) in a semiurban community in Bangladesh. Methods: A cross-sectional survey of 854 households (between October 2013 and February 2014) and 20 focus group discussions (between February 2017 and March 2017) were conducted to understand (1) who owns electronic devices; (2) who, among the owners, uses these to access health information and services and why; (3) the awareness of electronic sources of health information; and (4) the role of intermediaries (family members or peers who helped to look for health information using electronic devices). Results: A total of 90.3% (771/854) of households (471/854, 55.2% of respondents) owned electronic devices, mostly mobile phones. Among these, 7.2% (34/471) used them to access health information or services. Middle-aged (35-54 years), female, less (or not) educated, and poorer people used these devices the least (α=.05, α is the level of significance). The lack of awareness, discomfort, differences with regular care-seeking habits, lack of understanding and skills, and proximity to a health facility were the main reasons for not using devices to access digital health. Conclusions: Although influenced by sociodemographic traits, access to digital health is not merely related to device ownership and technical skill. Rather, it is a combination of general health literacy, phone ownership, material resources, and technical skill as well as social recognition of health needs and inequity. This study’s findings should serve as a basis for better integrating technology within the health system and ensuring equitable access to health care

    E-health and M-health in Bangladesh: Opportunities and Challenges

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    There is growing enthusiasm amongst analysts of global health for the possibilities opened up by the rapid spread of mobile phone coverage. This includes substantially increasing access to health-related information and advice and to expert medical consultations. Some argue we are reaching a tipping point in the organisation of health systems in which new technology will drive new organisational arrangements (Christensen, Grossman and Hwang 2009; Bloom and Standing 2008). This is encouraging investment by foundations and bilateral aid agencies in the development of e-health and m-health as a way to improve access to health services in low- and middle-income countries. As with the introduction and spread of any new technology, there are a number of possible outcomes – or pathways – with different implications for the types of service provided and the distribution of benefits in the short and longer term. A recent STEPS Centre publication (2010) proposes the following characteristics of the way a technological innovation is spread: the direction of development and the way organisations incorporate the new technology into their operations; the distribution of benefits from the technology and the diversity of ways the technology is applied. It argues that the actual pathway of development is strongly influenced by political processes, involving a number of stakeholders with differing interests and understandings. A number of analysts argue that health systems are particularly path-dependent because of the importance that people give to arrangements they believe protect them from serious health problems (Bloom and Standing 2008). Lee and Lansky (2008), for example, suggest that resistance by stakeholders and complex regulatory barriers are substantially diminishing the impact of new technologies on the organisation of the American health system. Because of the path-dependent nature of the health sector, decisions made early in the emergence of a new technology are likely to have a strong and lasting influence (Bloom and Wolcott 2013). This report presents a snapshot of how information and communication technologies (ICTs) are influencing health system development in Bangladesh.UK Department for International Developmen

    dc readout experiment at the Caltech 40m prototype interferometer

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    The Laser Interferometer Gravitational Wave Observatory (LIGO) operates a 40m prototype interferometer on the Caltech campus. The primary mission of the prototype is to serve as an experimental testbed for upgrades to the LIGO interferometers and for gaining experience with advanced interferometric techniques, including detuned resonant sideband extraction (i.e. signal recycling) and dc readout (optical homodyne detection). The former technique will be employed in Advanced LIGO, and the latter in both Enhanced and Advanced LIGO. Using dc readout for gravitational wave signal extraction has several technical advantages, including reduced laser and oscillator noise couplings as well as reduced shot noise, when compared to the traditional rf readout technique (optical heterodyne detection) currently in use in large-scale ground-based interferometric gravitational wave detectors. The Caltech 40m laboratory is currently prototyping a dc readout system for a fully suspended interferometric gravitational wave detector. The system includes an optical filter cavity at the interferometer's output port, and the associated controls and optics to ensure that the filter cavity is optimally coupled to the interferometer. We present the results of measurements to characterize noise couplings in rf and dc readout using this system

    Management of incidental findings during imaging research in "healthy" volunteers: current UK practice

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    OBJECTIVES: Incidental findings (IF) are becoming increasingly common due to the proliferation of imaging research. IFs can be life-changing for “healthy” volunteers. This study examined variation in IF management in UK research studies of healthy volunteers, including comparison with ethical and legal guidelines, thus providing baseline data and informing future practice. METHODS: Questionnaire of participant background [medical/non-medical; radiologist/non-radiologist; years as principal investigator (PI)], type of research (involving children or not), institutional policy, volunteer information, radiologist involvement in reporting scans and IF disclosure mechanisms. Investigator's current and perceived “ideal” practice was examined. Participants were PIs performing imaging research of healthy volunteers approved by UK ethics committees (2006–2009). RESULTS: 63/146 (43%) surveys completed. 54/61 (88.5%) had site-specific guidelines. Information commonly provided to volunteers should IF be found: personal data (51/62; 82%), contingency plans (54/62; 87%) and disclosure to general practitioner (GP)/treating physician (47/62; 76%). PIs used different strategies for image review. Commonest: radiologist reports research scans only when researcher suspicious of IF [15/57 (26%) compared with 5/28 (16%) in ideal practice]. Commonest ideal reporting strategy: routine reporting by specialist radiologists [9/28 (29%) compared with 8/57 (14%) in current practice]. 49/56 (87.5%) have a standardised disclosure contingency plan, usually involving GP. PIs most commonly disclosed IFs to volunteers when judged relevant (27/58; 47%), most commonly face to face (22/54; 41%), by volunteer's GP (26/60; 43%). Background of PI influenced consent, reporting and disclosure practice. CONCLUSION: There is wide variation in handling IFs in UK imaging research. Much of the current practice contravenes the vague existing legal and ethical guidelines, and is unlikely to be in the best interests of volunteers or researchers

    Molecular dynamics simulation of the order-disorder phase transition in solid NaNO2_2

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    We present molecular dynamics simulations of solid NaNO2_2 using pair potentials with the rigid-ion model. The crystal potential surface is calculated by using an \emph{a priori} method which integrates the \emph{ab initio} calculations with the Gordon-Kim electron gas theory. This approach is carefully examined by using different population analysis methods and comparing the intermolecular interactions resulting from this approach with those from the \emph{ab initio} Hartree-Fock calculations. Our numerics shows that the ferroelectric-paraelectric phase transition in solid NaNO2_2 is triggered by rotation of the nitrite ions around the crystallographical c axis, in agreement with recent X-ray experiments [Gohda \textit{et al.}, Phys. Rev. B \textbf{63}, 14101 (2000)]. The crystal-field effects on the nitrite ion are also addressed. Remarkable internal charge-transfer effect is found.Comment: RevTeX 4.0, 11 figure

    Incidental findings found in "healthy" volunteers during imaging performed for research: current legal and ethical implications

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    Incidental findings found in “healthy” volunteers during research imaging are common and have important implications for study design and performance, particularly in the areas of informed consent, subjects' rights, clinical image analysis and disclosure. In this study, we aimed to determine current practice and regulations concerning information that should be given to research subjects when obtaining consent, reporting of research images, who should be informed about any incidental findings and the method of disclosure. We reviewed all UK, European and international humanitarian, legal and ethical agencies' guidance. We found that the guidance on what constitutes incidental pathology, how to recognise it and what to do about it is inconsistent between agencies, difficult to find and less complete in the UK than elsewhere. Where given, guidance states that volunteers should be informed during the consent process about how research images will be managed, whether a mechanism exists for identifying incidental findings, arrangements for their disclosure, the potential benefit or harm and therapeutic options. The effects of incidentally discovered pathology on the individual can be complex and far-reaching. Radiologist involvement in analysis of research images varies widely; many incidental findings might therefore go unrecognised. In conclusion, guidance on the management of research imaging is inconsistent, limited and does not address the interests of volunteers. Improved standards to guide management of research images and incidental findings are urgently required

    Synthetic Lethality of Chk1 Inhibition Combined with p53 and/or p21 Loss During a DNA Damage Response in Normal and Tumor Cells

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    Cell cycle checkpoints ensure genome integrity and are frequently compromised in human cancers. A therapeutic strategy being explored takes advantage of checkpoint defects in p53-deficient tumors in order to sensitize them to DNA-damaging agents by eliminating Chk1-mediated checkpoint responses. Using mouse models, we demonstrated that p21 is a key determinant of how cells respond to the combination of DNA damage and Chk1 inhibition (combination therapy) in normal cells as well as in tumors. Loss of p21 sensitized normal cells to the combination therapy much more than did p53 loss and the enhanced lethality was partially blocked by CDK inhibition. In addition, basal pools of p21 (p53 independent) provided p53 null cells with protection from the combination therapy. Our results uncover a novel p53-independent function for p21 in protecting cells from the lethal effects of DNA damage followed by Chk1 inhibition. As p21 levels are low in a significant fraction of colorectal tumors, they are predicted to be particularly sensitive to the combination therapy. Results reported in this study support this prediction
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