Spatial Epidemiology: Current Approaches and Future Challenges

Spatial epidemiology is the description and analysis of geographic variations in disease with respect to demographic, environmental, behavioral, socioeconomic, genetic, and infectious risk factors. We focus on small-area analyses, encompassing disease mapping, geographic correlation studies, disease clusters, and clustering. Advances in geographic information systems, statistical methodology, and availability of high-resolution, geographically referenced health and environmental quality data have created unprecedented new opportunities to investigate environmental and other factors in explaining local geographic variations in disease. They also present new challenges. Problems include the large random component that may predominate disease rates across small areas. Though this can be dealt with appropriately using Bayesian statistics to provide smooth estimates of disease risks, sensitivity to detect areas at high risk is limited when expected numbers of cases are small. Potential biases and confounding, particularly due to socioeconomic factors, and a detailed understanding of data quality are important. Data errors can result in large apparent disease excess in a locality. Disease cluster reports often arise nonsystematically because of media, physician, or public concern. One ready means of investigating such concerns is the replication of analyses in different areas based on routine data, as is done in the United Kingdom through the Small Area Health Statistics Unit (and increasingly in other European countries, e.g., through the European Health and Environment Information System collaboration). In the future, developments in exposure modeling and mapping, enhanced study designs, and new methods of surveillance of large health databases promise to improve our ability to understand the complex relationships of environment to health

In vitro bioactivity of titanium-doped bioglass

Previous studies have suggested that incorporating relatively small quantities of titanium dioxide into bioactive glasses may result in an increase in bioactivity and hydroxyapatite formation. The present work therefore investigated the in vitro bioactivity of a titanium doped bioglass and compared the results with 45S5 bioglass. Apatite formation was evaluated for bioglass and Ti-bioglass in the presence and absence of foetal calf serum. Scanning electron microscopy (SEM) images were used to evaluate the surface development and energy dispersive X-ray measurements provided information on the elemental ratios. X-ray diffraction spectra confirmed the presence of apatite formation. Cell viability was assessed for bone marrow stromal cells under direct and indirect contact conditions and cell adhesion was assessed using SEM

Factors Associated With the Use of a Salt Substitute in Rural China.

Importance: Lowering sodium intake reduces blood pressure and may reduce the risk of cardiovascular diseases. The use of reduced-sodium salt (a salt substitute) may achieve sodium reduction, but its effectiveness may be associated with the context of its use. Objective: To identify factors associated with the use of salt substitutes in rural populations in China within the Salt Substitute and Stroke Study, a large-scale cluster randomized trial. Design, Setting, and Participants: This sequential mixed-methods qualitative evaluation, conducted from July 2 to August 28, 2018, in rural communities across 3 provinces in China, included a quantitative survey, collection of 24-hour urine samples, and face-to-face interviews. A random subsample of trial participants, selected from the 3 provinces, completed the quantitative survey (n = 1170) and provided urine samples (n = 1025). Interview respondents were purposively selected from the intervention group based on their different ranges of urinary sodium excretion levels. Statistical analysis was performed from September 18, 2018, to February 22, 2019. Exposures: The intervention group of the Salt Substitute and Stroke Study was provided with the free salt substitute while the control group continued to use regular salt. Main Outcomes and Measures: Knowledge, attitudes, and behaviors regarding the use of the salt substitute were measured using quantitative surveys, and urinary sodium levels were measured using 24-hour urine samples. Contextual factors were explored through semistructured interviews and integrated findings from surveys and interviews. Results: A total of 1170 individuals participated in the quantitative survey. Among the 1025 participants with successful urine samples, the mean (SD) age was 67.4 (7.5) years, and 502 (49.0%) were female. The estimated salt intake of participants who believed that high salt intake was good for health was higher; however, it was not significantly different (0.84 g/d [95% CI, -0.04 to 1.72 g/d]) from those who believed that high salt intake was bad for health. Thirty individuals participated in the qualitative interviews (18 women [60.0%]; mean [SD] age, 70.3 [6.0] years). Quantitative and qualitative data indicated high acceptability of and adherence to the salt substitute. Contextual factors negatively associated with the use of the salt substitute included a lack of knowledge about the benefits associated with salt reduction and consumption of high-sodium pickled foods. In addition, reduced antihypertensive medication was reported by a few participants using the salt substitute. Conclusions and Relevance: This study suggests that lack of comprehensive understanding of sodium reduction and salt substitutes and habitual consumption of high-sodium foods (such as pickled foods) were the main barriers to the use of salt substitutes to reduce sodium intake. These factors should be considered in future population-based, sodium-reduction interventions

Using a New Odour-Baited Device to Explore Options for Luring and Killing Outdoor-Biting Malaria Vectors: A Report on Design and Field Evaluation of the Mosquito Landing Box.

Mosquitoes that bite people outdoors can sustain malaria transmission even where effective indoor interventions such as bednets or indoor residual spraying are already widely used. Outdoor tools may therefore complement current indoor measures and improve control. We developed and evaluated a prototype mosquito control device, the 'Mosquito Landing Box' (MLB), which is baited with human odours and treated with mosquitocidal agents. The findings are used to explore technical options and challenges relevant to luring and killing outdoor-biting malaria vectors in endemic settings. Field experiments were conducted in Tanzania to assess if wild host-seeking mosquitoes 1) visited the MLBs, 2) stayed long or left shortly after arrival at the device, 3) visited the devices at times when humans were also outdoors, and 4) could be killed by contaminants applied on the devices. Odours suctioned from volunteer-occupied tents were also evaluated as a potential low-cost bait, by comparing baited and unbaited MLBs. There were significantly more Anopheles arabiensis, An. funestus, Culex and Mansonia mosquitoes visiting baited MLB than unbaited controls (P<=0.028). Increasing sampling frequency from every 120 min to 60 and 30 min led to an increase in vector catches of up to 3.6 fold (P<=0.002), indicating that many mosquitoes visited the device but left shortly afterwards. Outdoor host-seeking activity of malaria vectors peaked between 7:30 and 10:30pm, and between 4:30 and 6:00am, matching durations when locals were also outdoors. Maximum mortality of mosquitoes visiting MLBs sprayed or painted with formulations of candidate mosquitocidal agent (pirimiphos-methyl) was 51%. Odours from volunteer occupied tents attracted significantly more mosquitoes to MLBs than controls (P<0.001). While odour-baited devices such as the MLBs clearly have potential against outdoor-biting mosquitoes in communities where LLINs are used, candidate contaminants must be those that are effective at ultra-low doses even after short contact periods, since important vector species such as An. arabiensis make only brief visits to such devices. Natural human odours suctioned from occupied dwellings could constitute affordable sources of attractants to supplement odour baits for the devices. The killing agents used should be environmentally safe, long lasting, and have different modes of action (other than pyrethroids as used on LLINs), to curb the risk of physiological insecticide resistance

Cosmogenic neutron production at the Sudbury Neutrino Observatory

Neutrons produced in nuclear interactions initiated by cosmic-ray muons present an irreducible background to many rare-event searches, even in detectors located deep underground. Models for the production of these neutrons have been tested against previous experimental data, but the extrapolation to deeper sites is not well understood. Here we report results from an analysis of cosmogenically produced neutrons at the Sudbury Neutrino Observatory. A specific set of observables are presented, which can be used to benchmark the validity of geant4 physics models. In addition, the cosmogenic neutron yield, in units of 10-4 cm2/(g·μ), is measured to be 7.28±0.09(stat)-1.12+1.59(syst) in pure heavy water and 7.30±0.07(stat)-1.02+1.40(syst) in NaCl-loaded heavy water. These results provide unique insights into this potential background source for experiments at SNOLAB

Cost-Effectiveness of a Household Salt Substitution Intervention: Findings From 20 995 Participants of the Salt Substitute and Stroke Study

Background: SSaSS (Salt Substitute and Stroke Study), a 5-year cluster randomized controlled trial, demonstrated that replacing regular salt with a reduced-sodium, added-potassium salt substitute reduced the risks of stroke, major adverse cardiovascular events, and premature death among individuals with previous stroke or uncontrolled high blood pressure living in rural China. This study assessed the cost-effectiveness profile of the intervention. Methods: A within-trial economic evaluation of SSaSS was conducted from the perspective of the health care system and consumers. The primary health outcome assessed was stroke. We also quantified the effect on quality-adjusted life-years (QALYs). Health care costs were identified from participant health insurance records and the literature. All costs (in Chinese yuan [¥]) and QALYs were discounted at 5% per annum. Incremental costs, stroke events averted, and QALYs gained were estimated using bivariate multilevel models. Results: Mean follow-up of the 20 995 participants was 4.7 years. Over this period, replacing regular salt with salt substitute reduced the risk of stroke by 14% (rate ratio, 0.86 [95% CI, 0.77-0.96]; P=0.006), and the salt substitute group had on average 0.054 more QALYs per person. The average costs (¥1538 for the intervention group and ¥1649 for the control group) were lower in the salt substitute group (¥110 less). The intervention was dominant (better outcomes at lower cost) for prevention of stroke as well as for QALYs gained. Sensitivity analyses showed that these conclusions were robust, except when the price of salt substitute was increased to the median and highest market prices identified in China. The salt substitute intervention had a 95.0% probability of being cost-saving and a >99.9% probability of being cost-effective. Conclusions: Replacing regular salt with salt substitute was a cost-saving intervention for the prevention of stroke and improvement of quality of life among SSaSS participants

The effects of a community-based sodium reduction program in rural china - a cluster-randomized trial

Background Average sodium intake and stroke mortality in northern China are both among the highest in the world. An effective, low-cost strategy to reduce sodium intake in this population is urgently needed. Objective We sought to determine the effects of a community-based sodium reduction program on salt consumption in rural northern China. Design This study was a cluster-randomized trial done over 18 months in 120 townships (one village from each township) from five provinces. Sixty control villages were compared to 60 intervention villages that were given access to a reduced-sodium, added-potassium salt substitute in conjunction with a community-based health education program focusing on sodium reduction. The primary outcome was the difference in 24-hour urinary sodium excretion between randomized groups. Results Among 1,903 people with valid 24-hour urine collections, mean urinary sodium excretion in intervention compared with control villages was reduced by 5.5% (-14mmol/day, 95% confidence interval -26 to -1; p = 0.03), potassium excretion was increased by 16% (+7mmol/day, +4 to +10; p<0.001), and sodium to potassium ratio declined by 15% (-0.9, -1.2 to -0.5; p<0.001). Mean blood pressure differences were -1.1 mm Hg systolic (-3.3 to +1.1; p = 0.33) and -0.7 mm Hg diastolic (-2.2 to +0.8, p = 0.35) and the difference in the proportion with hypertension was -1.3% (-5.1 to 2.5, p = 0.56). Conclusion There were clear differences in population sodium and potassium intake between villages that were most likely a consequence of increased use of salt substitute. The absence of effects on blood pressure reflects the moderate changes in sodium and potassium intake achieved. Trial Registration Clinicaltrials.gov identifier: NCT01259700

Overcoming the barriers of teaching physical examination at the bedside: More than just curriculum design

Background: Physicians in training must achieve a high degree of proficiency in performing physical examinations and must strive to become experts in the field. Concerns are emerging about physicians' abilities to perform these basic skills, essential for clinical decision making. Learning at the bedside has the potential to support skill acquisition through deliberate practice. Previous skills improvement programs, targeted at teaching physical examinations, have been successful at increasing the frequency of performing and teaching physical examinations. It remains unclear what barriers might persist after such program implementation. This study explores residents' and physicians' perceptions of physical examinations teaching at the bedside following the implementation of a new structured bedside curriculum: What are the potentially persisting barriers and proposed solutions for improvement? Methods: The study used a constructivist approach using a qualitative inductive thematic analysis that was oriented to construct an understanding of the barriers and facilitators of physical examination teaching in the context of a new bedside curriculum. Participants took part in individual interviews and subsequently focus groups. Transcripts were coded and themes were identified. Results: Data analyses yielded three main themes: (1) the culture of teaching physical examination at the bedside is shaped and threatened by the lack of hospital support, physicians' motivation and expertise, residents' attitudes and dependence on technology, (2) the hospital environment makes bedside teaching difficult because of its chaotic nature, time constraints and conflicting responsibilities, and finally (3) structured physical examination curricula create missed opportunities in being restrictive and pose difficulties in identifying patients with findings. Conclusions: Despite the implementation of a structured bedside curriculum for physical examination teaching, our study suggests that cultural, environmental and curriculum-related barriers remain important issues to be addressed. Institutions wishing to develop and implement similar bedside curricula should prioritize recruitment of expert clinical teachers, recognizing their time and efforts. Teaching should be delivered in a protected environment, away from clinical duties, and with patients with real findings. Physicians must value teaching and learning of physical examination skills, with multiple hands-on opportunities for direct role modeling, coaching, observation and deliberate practice. Ideally, clinical teachers should master the art of combining both patient care and educational activities

Methylphenidate significantly improves declarative memory functioning of adults with ADHD

Contains fulltext : 87790.pdf (publisher's version ) (Closed access)BACKGROUND: Declarative memory deficits are common in untreated adults with attention-deficit hyperactivity disorder (ADHD), but limited evidence exists to support improvement after treatment with methylphenidate. The objective of this study was to examine the effects of methylphenidate on memory functioning of adults with ADHD. METHODS: Eighteen adults with ADHD who were clinical responders to methylphenidate participated in this randomized crossover trial. After 3 days of no treatment, patients received in random order either their usual methylphenidate dose (mean: 14.7 mg; range: 10-30 mg) or placebo, separated by a 6-7-day washout period. Patients performed an immediate word recall test 1 h after treatment administration. Three hours after intake, patients performed the second part of the memory test (delayed word recall and a recognition test). RESULTS: Delayed recognition and immediate recall was similar on treatment and on placebo. Delayed word recall was significantly better in the methylphenidate than in the placebo condition (F (1, 17) = 7.0, p < 0.017). A significant correlation was found between prestudy CES-D depression scores and difference scores on delayed recall (r = 0.602, p < 0.008). CONCLUSION: Methylphenidate improves declarative memory functioning in patients with ADHD. New studies should further examine whether subclinical depressive symptoms mediate the effect of methylphenidate on declarative memory.1 oktober 201

Saposin C Coupled Lipid Nanovesicles Specifically Target Arthritic Mouse Joints for Optical Imaging of Disease Severity

Rheumatoid arthritis is a chronic inflammatory disease affecting approximately 1% of the population and is characterized by cartilage and bone destruction ultimately leading to loss of joint function. Early detection and intervention of disease provides the best hope for successful treatment and preservation of joint mobility and function. Reliable and non-invasive techniques that accurately measure arthritic disease onset and progression are lacking. We recently developed a novel agent, SapC-DOPS, which is composed of the membrane-associated lysosomal protein saposin C (SapC) incorporated into 1,2-dioleoyl-sn-glycero-3-phospho-L-serine (DOPS) lipid nanovesicles. SapC-DOPS has a high fusogenic affinity for phosphatidylserine-enriched microdomains on surfaces of target cell membranes. Incorporation of a far-red fluorophore, CellVue Maroon (CVM), into the nanovesicles allows for in vivo non-invasive visualization of the agent in targeted tissue. Given that phosphatidylserine is present only on the inner leaflet of healthy plasma membranes but is “flipped” to the outer leaflet upon cell damage, we hypothesized that SapC-DOPS would target tissue damage associated with inflammatory arthritis due to local surface-exposure of phosphatidylserine. Optical imaging with SapC-DOPS-CVM in two distinct models of arthritis, serum-transfer arthritis (e.g., K/BxN) and collagen-induced arthritis (CIA) revealed robust SapC-DOPS-CVM specific localization to arthritic paws and joints in live animals. Importantly, intensity of localized fluorescent signal correlated with macroscopic arthritic disease severity and increased with disease progression. Flow cytometry of cells extracted from arthritic joints demonstrated that SapC-DOPS-CVM localized to an average of 7–8% of total joint cells and primarily to CD11b+Gr-1+ cells. Results from the current studies strongly support the application of SapC-DOPS-CVM for advanced clinical and research applications including: detecting early arthritis onset, assessing disease progression real-time in live subjects, and providing novel information regarding cell types that may mediate arthritis progression within joints