Nebulised amphotericin B to eradicate Candida colonisation from the respiratory tract in critically ill patients receiving selective digestive decontamination: a cohort study

INTRODUCTION: Colonisation of the lower respiratory tract with Candida species occurs in 25% of mechanically ventilated critically ill patients, and is associated with increased morbidity. Nebulised amphotericin B has been used to eradicate Candida as part of selective decontamination of the digestive tract (SDD) protocols, but its effectiveness is unknown. We aimed to determine the effectiveness of nebulised amphotericin B in eradicating Candida respiratory tract colonisation in patients receiving SDD. METHODS: We included consecutive mechanically ventilated patients during a four-year period. Microbiological screening was performed upon admission and twice weekly thereafter according to a standardised protocol. A colonisation episode was defined as the presence of Candida species in two consecutive sputum samples taken at least one day apart. To correct for time-varying bias and possible confounding, we used a multistate approach and performed time-varying Cox regression with adjustment for age, disease severity, Candida load at baseline and concurrent corticosteroid use. RESULTS: Among 1,819 patients, colonisation with Candida occurred 401 times in 363 patients; 333 of these events were included for analysis. Decolonisation occurred in 51 of 59 episodes (86%) and in 170 of 274 episodes (62%) in patients receiving and not receiving nebulised amphotericin B, respectively. Nebulised amphotericin B was associated with an increased rate of Candida eradication (crude HR 2.0; 95% CI 1.4 to 2.7, adjusted HR 2.2; 95% CI 1.6 to 3.0). Median times to decolonisation were six and nine days, respectively. The incidence rate of ventilator-associated pneumonia, length of stay and mortality did not differ between both groups. CONCLUSIONS: Nebulised amphotericin B reduces the duration of Candida colonisation in the lower respiratory tracts of mechanically ventilated critically ill patients receiving SDD, but data remain lacking that this is associated with a meaningful improvement in clinical outcomes. Until more evidence becomes available, nebulised amphotericin B should not be used routinely as part of the SDD protocol

Assessment of sensory neuropathy in patients with diabetic foot problems

Our aim of this study was to compare the accuracy of three different modalities for testing sensory neuropathy in diabetic patients with and without diabetic foot problems. The three devices used included the pin-prick testing using the Neurotip® (PPT), the Semmes–Weinstein 5.07/10 g monofilament testing (SWMT), and the rapid-current perception threshold (R-CPT) measurements using the Neurometer® testing. Our study population consisted of 54 patients (108 feet) with diabetic foot problems treated at the National University Hospital in Singapore by our multi-disciplinary diabetic foot care team. Our results showed no difference in sensory neuropathy detected by PPT and 5.07/10 g SWMT in both the pathological and normal foot. In the pathological foot, there was significant increase in sensory neuropathy detected by the Neurometer® device at both the big toe and ankle sites as compared to PPT and 5.07/10 g SWMT. In the normal foot, there was a significant increase in sensory neuropathy detected by the Neurometer® device at the big toe site only as compared to PPT and 5.07/10 g SWMT. Finally, the Neurometer® measurements detected a statistically higher proportion of feet with sensory neuropathy as compared to detection by the PPT or 5.07/10 g SWMT

Obesity-induced hypoadiponectinaemia: the opposite influences of central and peripheral fat compartments

$\textbf{Background and Aims:}$ The substantial reduction in adiponectin concentration among obese individuals seems to depend on fat distribution and is a marker of metabolic and adipose tissue dysfunction. We aimed to: (i) address whether abdominal fat from different compartments (visceral, deep subcutaneous abdominal and superficial subcutaneous abdominal) and gluteofemoral fat are independently associated with blood adiponectin concentration; and (ii) investigate whether abdominal (proxied by waist circumference) and gluteofemoral fat (proxied by hip circumference) accumulation causally determine blood adiponectin concentration. $\textbf{Methods:}$ To investigate the independent association of abdominal and gluteofemoral fat with adiponectin concentration, we used multivariable regression and data from 30-year-old adults from the 1982 Pelotas Birth Cohort ($n$ = 2,743). To assess the causal role of abdominal and gluteofemoral fat accumulation on adiponectin concentration, we used Mendelian randomization and data from two consortia of genome-wide association studies—the GIANT ($n$ > 210 000) and ADIPOGen consortia ($n$ = 29 347). $\textbf{Results:}$ In the multivariable regression analysis, all abdominal fat depots were negatively associated with adiponectin concentration, specially visceral abdominal fat [men: $\beta$ = -0.24 standard unit of log adiponectin per standard unit increase in abdominal fat; 95% confidence interval (CI) = -0.31, -0.18; $P$ = 8*10$^{-13}$; women: $\beta$ = -0.31; 95% CI = -0.36, -0.25; $P$ = 7*10$^{-27}$), whereas gluteofemoral fat was positively associated with adiponectin concentration (men: $\beta$ = 0.13 standard unit of log adiponectin per standard unit increase in gluteofemoral fat; 95% CI = 0.03, 0.22; $P$ = 0.008; women: $\beta$ = 0.24; 95% CI = 0.17, 0.31; $P$ = 7*10$^{-11}$). In the Mendelian randomization analysis, genetically-predicted waist circumference was inversely related to blood adiponectin concentration ($\beta$ = -0.27 standard unit of log adiponectin per standard unit increase in waist circumference; 95% CI = -0.36, -0.19; $P$ = 2*10$^{-11}$), whereas genetically-predicted hip circumference was positively associated with blood adiponectin concentration ($\beta$ = 0.17 standard unit of log adiponectin per standard unit increase in hip circumference; 95% CI = 0.11, 0.24; $P$ = 1*10$^{-7}$). $\textbf{Conclusions:}$ These results support the hypotheses that there is a complex interplay between body fat distribution and circulating adiponectin concentration, and that whereas obesity-induced hypoadiponectinaemia seems to be primarily attributed to abdominal fat accumulation, gluteofemoral fat accumulation is likely to exert a protective effect.The study ‘Pelotas Birth Cohort, 1982’ is conducted by Postgraduate Program in Epidemiology at Universidade Federal de Pelotas with the collaboration of the Brazilian Public Health Association (ABRASCO). From 2004 to 2013, the Wellcome Trust supported the 1982 birth cohort study. The International Development Research Center, World Health Organization, Overseas Development Administration, European Union, National Support Program for Centers of Excellence (PRONEX), the Brazilian National Research Council (CNPq) and the Brazilian Ministry of Health supported previous phases of the study. M.C.B. receives financial support from the Brazilian National Research Council (CNPq) [144749/2014-9, 201498/2014-6 (Science Without Borders Program), and 163291/2015-2] and Coordenac¸~ao de Aperfeic¸oamento de Pessoal de Nıvel Superior (CAPES). K.K.O. is supported by the Medical Research Council [Unit Programme numbers MC_UU_12015/1 and MC_UU_12015/2]

Obesity-induced hypoadiponectinaemia: the opposite influences of central and peripheral fat compartments

$\textbf{Background and Aims:}$ The substantial reduction in adiponectin concentration among obese individuals seems to depend on fat distribution and is a marker of metabolic and adipose tissue dysfunction. We aimed to: (i) address whether abdominal fat from different compartments (visceral, deep subcutaneous abdominal and superficial subcutaneous abdominal) and gluteofemoral fat are independently associated with blood adiponectin concentration; and (ii) investigate whether abdominal (proxied by waist circumference) and gluteofemoral fat (proxied by hip circumference) accumulation causally determine blood adiponectin concentration. $\textbf{Methods:}$ To investigate the independent association of abdominal and gluteofemoral fat with adiponectin concentration, we used multivariable regression and data from 30-year-old adults from the 1982 Pelotas Birth Cohort ($n$ = 2,743). To assess the causal role of abdominal and gluteofemoral fat accumulation on adiponectin concentration, we used Mendelian randomization and data from two consortia of genome-wide association studies—the GIANT ($n$ > 210 000) and ADIPOGen consortia ($n$ = 29 347). $\textbf{Results:}$ In the multivariable regression analysis, all abdominal fat depots were negatively associated with adiponectin concentration, specially visceral abdominal fat [men: $\beta$ = -0.24 standard unit of log adiponectin per standard unit increase in abdominal fat; 95% confidence interval (CI) = -0.31, -0.18; $P$ = 8*10$^{-13}$; women: $\beta$ = -0.31; 95% CI = -0.36, -0.25; $P$ = 7*10$^{-27}$), whereas gluteofemoral fat was positively associated with adiponectin concentration (men: $\beta$ = 0.13 standard unit of log adiponectin per standard unit increase in gluteofemoral fat; 95% CI = 0.03, 0.22; $P$ = 0.008; women: $\beta$ = 0.24; 95% CI = 0.17, 0.31; $P$ = 7*10$^{-11}$). In the Mendelian randomization analysis, genetically-predicted waist circumference was inversely related to blood adiponectin concentration ($\beta$ = -0.27 standard unit of log adiponectin per standard unit increase in waist circumference; 95% CI = -0.36, -0.19; $P$ = 2*10$^{-11}$), whereas genetically-predicted hip circumference was positively associated with blood adiponectin concentration ($\beta$ = 0.17 standard unit of log adiponectin per standard unit increase in hip circumference; 95% CI = 0.11, 0.24; $P$ = 1*10$^{-7}$). $\textbf{Conclusions:}$ These results support the hypotheses that there is a complex interplay between body fat distribution and circulating adiponectin concentration, and that whereas obesity-induced hypoadiponectinaemia seems to be primarily attributed to abdominal fat accumulation, gluteofemoral fat accumulation is likely to exert a protective effect.The study ‘Pelotas Birth Cohort, 1982’ is conducted by Postgraduate Program in Epidemiology at Universidade Federal de Pelotas with the collaboration of the Brazilian Public Health Association (ABRASCO). From 2004 to 2013, the Wellcome Trust supported the 1982 birth cohort study. The International Development Research Center, World Health Organization, Overseas Development Administration, European Union, National Support Program for Centers of Excellence (PRONEX), the Brazilian National Research Council (CNPq) and the Brazilian Ministry of Health supported previous phases of the study. M.C.B. receives financial support from the Brazilian National Research Council (CNPq) [144749/2014-9, 201498/2014-6 (Science Without Borders Program), and 163291/2015-2] and Coordenac¸~ao de Aperfeic¸oamento de Pessoal de Nıvel Superior (CAPES). K.K.O. is supported by the Medical Research Council [Unit Programme numbers MC_UU_12015/1 and MC_UU_12015/2]

Effects of metal-contaminated soils on the accumulation of heavy metals in gotu kola (Centella asiatica) and the potential health risks: a study in Peninsular Malaysia

Centella asiatica is a commonly used medicinal plant in Malaysia. As heavy metal accumulation in medicinal plants which are highly consumed by human is a serious issue, thus the assessment of heavy metals in C. asiatica is important for the safety of consumers. In this study, the heavy metal accumulation in C. asiatica and the potential health risks were investigated. Samples of C. asiatica and surface soils were collected from nine different sites around Peninsular Malaysia. The concentration of six heavy metals namely Cd, Cu, Ni, Fe, Pb and Zn were determined by air-acetylene flame atomic absorption spectrophotometer (AAS). The degree of anthropogenic influence was assessed by calculating the enrichment factor (EF) and index of geoaccumulation (Igeo). The heavy metal uptake into the plant was estimated through the calculation of translocation factor (TF), bioconcentration factor (BCF) and correlation study. Estimated daily intakes (EDI) and target hazard quotients (THQ) were used to determine the potential health risk of consuming C. asiatica. The results showed that the overall surface soil was polluted by Cd, Cu and Pb, while the uptake of Zn and Ni by the plants was high. The value of EDI and THQ showed that the potential of Pb toxicity in C. asiatica was high as well. As heavy metal accumulation was confirmed in C. asiatica, daily consumption of the plant derived from polluted sites in Malaysia was not recommended

The influence of 'significant others' on persistent back pain and work participation: a qualitative exploration of illness perceptions

Background Individual illness perceptions have been highlighted as important influences on clinical outcomes for back pain. However, the illness perceptions of 'significant others' (spouse/partner/close family member) are rarely explored, particularly in relation to persistent back pain and work participation. The aim of this study was to initiate qualitative research in this area in order to further understand these wider influences on outcome. Methods Semi-structured interviews based on the chronic pain version of the Illness Perceptions Questionnaire-Revised were conducted with a convenience sample of UK disability benefit claimants, along with their significant others (n=5 dyads). Data were analysed using template analysis. Results Significant others shared, and perhaps further reinforced, claimants' unhelpful illness beliefs including fear of pain/re-injury associated with certain types of work and activity, and pessimism about the likelihood of return to work. In some cases, significant others appeared more resigned to the permanence and negative inevitable consequences of the claimant's back pain condition on work participation, and were more sceptical about the availability of suitable work and sympathy from employers. In their pursuit of authenticity, claimants were keen to stress their desire to work whilst emphasising how the severity and physical limitations of their condition prevented them from doing so. In this vein, and seemingly based on their perceptions of what makes a 'good' significant other, significant others acted as a 'witness to pain', supporting claimants' self-limiting behaviour and statements of incapacity, often responding with empathy and assistance. The beliefs and responses of significant others may also have been influenced by their own experience of chronic illness, thus participants lives were often intertwined and defined by illness. Conclusions The findings from this exploratory study reveal how others and wider social circumstances might contribute both to the propensity of persistent back pain and to its consequences. This is an area that has received little attention to date, and wider support of these findings may usefully inform the design of future intervention programmes aimed at restoring work participation

Trends in worldwide nanotechnology patent applications: 1991 to 2008

Nanotechnology patent applications published during 1991–2008 have been examined using the “title–abstract” keyword search on esp@cenet “worldwide” database. The longitudinal evolution of the number of patent applications, their topics, and their respective patent families have been evaluated for 15 national patent offices covering 98% of the total global activity. The patent offices of the United States (USA), People’s Republic of China (PRC), Japan, and South Korea have published the largest number of nanotechnology patent applications, and experienced significant but different growth rates after 2000. In most repositories, the largest numbers of nanotechnology patent applications originated from their own countries/regions, indicating a significant “home advantage.” The top applicant institutions are from different sectors in different countries (e.g., from industry in the US and Canada patent offices, and from academe or government agencies at the PRC office). As compared to 2000, the year before the establishment of the US National Nanotechnology Initiative (NNI), numerous new invention topics appeared in 2008, in all 15 patent repositories. This is more pronounced in the USA and PRC. Patent families have increased among the 15 patent offices, particularly after 2005. Overlapping patent applications increased from none in 1991 to about 4% in 2000 and to about 27% in 2008. The largest share of equivalent nanotechnology patent applications (1,258) between two repositories was identified between the US and Japan patent offices

Compromise or Capitulation? US Food and Drug Administration Jurisdiction Over Tobacco Products

Stanton Glantz and colleagues critique the recent policy decision in the United States to grant the FDA regulatory authority over tobacco products, a decision that has broad but not unanimous support among health care professionals

Trends for nanotechnology development in China, Russia, and India

China, Russia, and India are playing an increasingly important role in global nanotechnology research and development (R&D). This paper comparatively inspects the paper and patent publications by these three countries in the Thomson Science Citation Index Expanded (SCI) database and United States Patent and Trademark Office (USPTO) database (1976–2007). Bibliographic, content map, and citation network analyses are used to evaluate country productivity, dominant research topics, and knowledge diffusion patterns. Significant and consistent growth in nanotechnology papers are noted in the three countries. Between 2000 and 2007, the average annual growth rate was 31.43% in China, 11.88% in Russia, and 33.51% in India. During the same time, the growth patterns were less consistent in patent publications: the corresponding average rates are 31.13, 10.41, and 5.96%. The three countries’ paper impact measured by the average number of citations has been lower than the world average. However, from 2000 to 2007, it experienced rapid increases of about 12.8 times in China, 8 times in India, and 1.6 times in Russia. The Chinese Academy of Sciences (CAS), the Russian Academy of Sciences (RAS), and the Indian Institutes of Technology (IIT) were the most productive institutions in paper publication, with 12,334, 6,773, and 1,831 papers, respectively. The three countries emphasized some common research topics such as “Quantum dots,” “Carbon nanotubes,” “Atomic force microscopy,” and “Scanning electron microscopy,” while Russia and India reported more research on nano-devices as compared with China. CAS, RAS, and IIT played key roles in the respective domestic knowledge diffusion

Nano Mapper: an Internet knowledge mapping system for nanotechnology development

Nanotechnology research has experienced rapid growth in recent years. Advances in information technology enable efficient investigation of publications, their contents, and relationships for large sets of nanotechnology-related documents in order to assess the status of the field. This paper presents the development of a new knowledge mapping system, called Nano Mapper (http://nanomapper.eller.arizona.edu), which integrates the analysis of nanotechnology patents and research grants into a Web-based platform. The Nano Mapper system currently contains nanotechnology-related patents for 1976–2006 from the United States Patent and Trademark Office (USPTO), European Patent Office (EPO), and Japan Patent Office (JPO), as well as grant documents from the U.S. National Science Foundation (NSF) for the same time period. The system provides complex search functionalities, and makes available a set of analysis and visualization tools (statistics, trend graphs, citation networks, and content maps) that can be applied to different levels of analytical units (countries, institutions, technical fields) and for different time intervals. The paper shows important nanotechnology patenting activities at USPTO for 2005–2006 identified through the Nano Mapper system