Association of Individual Non-Steroidal Anti-Inflammatory Drugs and Chronic Kidney Disease: A Population-Based Case Control Study

Background

Non-steroidal anti-inflammatory agents (NSAIDs) are known to be associated with renal damage. No clear evidence exists regarding differential risk of chronic kidney disease (CKD), specifically, across various NSAIDs.

Aim

The aim of this population-based case-control study was to evaluate the association between use of individual NSAIDs and risk of CKD in a general population of Southern Italy.

Methods

A nested case-control study was carried out using the general practice Arianna database, identifying incident CKD patients as cases and matched controls from 2006 to 2011. The date of first CKD diagnosis was defined as the index date (ID). Conditional logistic regressions were performed to estimate the risk of CKD associated with NSAIDs by class and individual drugs as compared to non-use during different time windows (within one year, six or three months prior to ID), with the latter being defined as current users. Among current users, the effect of cumulative exposure to these drugs was evaluated.

Results

Overall, 1,989 CKD cases and 7,906 matched controls were identified. A statistically significant increase in the risk of CKD was found for current users of oxicams (adjusted OR: 1.68; 95% CI: 1.15-2.44) and concerning individual compounds, for ketorolac (adj. OR: 2.54; 95% CI: 1.45-4.44), meloxicam (adj. OR: 1.98; 95% CI: 1.01-3.87) and piroxicam (adj. OR: 1.95; 95% CI: 1.19-3.21).

Conclusions

The risk of CKD varies across individual NSAIDs. Increased risk has been found for ketorolac, which may precipitate subclinical CKD through acute renal damage, and long-term exposure to oxicams, especially meloxicam and piroxicam.     

Current Prevalence Pattern of Hypertension in Nigeria: A Systematic Review

BackgroundThe global burden of hypertension and other non-communicable diseases (NCDs) is rapidly increasing, and the African continent seems to be the most affected region in the world. The prevalence of hypertension in Nigeria forms a substantial portion of the total burden in Africa because of the large population of the country currently estimated to be over 170 million.ObjectiveThe purpose of this systematic review is to summarise up to date data on the prevalence and distribution of hypertension in Nigeria from prevalence studies.MethodsA search of the following databases: PubMed, EMBase and WHO cardiovascular InfoBase from 1968 till date was conducted to identify studies which provide estimates of prevalence of hypertension in Nigeria.ResultsThe search yielded a total of 1748 hits from which 45 relevant studies met the inclusion criteria for the review. The overall crude prevalence of hypertension ranged from 0.1% (95%CI:-0.1 to 0.3) to 17.5% (95% CI: 13.6 to 21.4) in children and 2.1% (95%CI: 1.4 to 2.8) to 47.2% (95%CI: 43.6 to 50.8) in adults depending on the benchmark used for diagnosis of hypertension, the setting in which the study was conducted, sex and ethnic group. The crude prevalence of hypertension ranged from 6.2% (95%CI: 4.0 to 8.4) to 48.9% (95%CI: 42.3 to 55.5) for men and 10% (95%CI: 8.1 to 12) to 47.3% (95%CI: 43 to 51.6%) for women. In most studies, prevalence of hypertension was higher in males than females. In addition, prevalence across urban and rural ranged from 9.5% (95%CI: 13.6 to 21.4) to 51.6% (95%CI: 49.8 to 53.4) and 4.8% (95%CI: 2.9 to 6.7) to 43% (95%CI: 42.1 to 43.9) respectively.ConclusionsThe prevalence of hypertension is high among the Nigerian population. Appropriate interventions need to be developed and implemented to reduce the preventable burden of hypertension especially at Primary Health Care Centres which is the first point of call for over 55% of the Nigerian population.     

Soil Methane Sink Capacity Response to a Long-Term Wildfire Chronosequence in Northern Sweden

Boreal forests occupy nearly one fifth of the terrestrial land surface and are recognised as globally important regulators of carbon (C) cycling and greenhouse gas emissions. Carbon sequestration processes in these forests include assimilation of CO₂ into biomass and subsequently into soil organic matter, and soil microbial oxidation of methane (CH₄). In this study we explored how ecosystem retrogression, which drives vegetation change, regulates the important process of soil CH₄ oxidation in boreal forests. We measured soil CH₄ oxidation processes on a group of 30 forested islands in northern Sweden differing greatly in fire history, and collectively representing a retrogressive chronosequence, spanning 5000 years. Across these islands the build-up of soil organic matter was observed to increase with time since fire disturbance, with a significant correlation between greater humus depth and increased net soil CH₄ oxidation rates. We suggest that this increase in net CH₄ oxidation rates, in the absence of disturbance, results as deeper humus stores accumulate and provide niches for methanotrophs to thrive. By using this gradient we have discovered important regulatory controls on the stability of soil CH₄ oxidation processes that could not have not been explored through shorter-term experiments. Our findings indicate that in the absence of human interventions such as fire suppression, and with increased wildfire frequency, the globally important boreal CH₄ sink could be diminished.     

Calibrating the Human Mutation Rate via Ancestral Recombination Density in Diploid Genomes

The human mutation rate is an essential parameter for studying the evolution of our species, interpreting present-day genetic variation, and understanding the incidence of genetic disease. Nevertheless, our current estimates of the rate are uncertain. Most notably, recent approaches based on counting de novo mutations in family pedigrees have yielded significantly smaller values than classical methods based on sequence divergence. Here, we propose a new method that uses the fine-scale human recombination map to calibrate the rate of accumulation of mutations. By comparing local heterozygosity levels in diploid genomes to the genetic distance scale over which these levels change, we are able to estimate a long-term mutation rate averaged over hundreds or thousands of generations. We infer a rate of 1.61 ± 0.13 × 10⁻⁸ mutations per base per generation, which falls in between phylogenetic and pedigree-based estimates, and we suggest possible mechanisms to reconcile our estimate with previous studies. Our results support intermediate-age divergences among human populations and between humans and other great apes.     

Vascular Factors and Multiple Measures of Early Brain Health: CARDIA Brain MRI Study

Objective

To identify early changes in brain structure and function that are associated with cardiovascular risk factors (CVRF).

Design

Cross-sectional brain Magnetic Resonance I (MRI) study.

Setting

Community based cohort in three U.S. sites.

Participants

A Caucasian and African-American sub-sample (n= 680; mean age 50.3 yrs) attending the 25 year follow-up exam of the Coronary Artery Risk Development in Young Adults Study.

Primary and Secondary Outcomes

3T brain MR images processed for quantitative estimates of: total brain (TBV) and abnormal white matter (AWM) volume; white matter fractional anisotropy (WM-FA); and gray matter cerebral blood flow (GM-CBF). Total intracranial volume is TBV plus cerebral spinal fluid (TICV). A Global Cognitive Function (GCF) score was derived from tests of speed, memory and executive function.

Results

Adjusting for TICV and demographic factors, current smoking was significantly associated with lower GM-CBF and TBV, and more AWM (all <0.05); SA with lower GM-CBF, WM-FA and TBV (p=0.01); increasing BMI with decreasing GM-CBF (p<0003); hypertension with lower GM-CBF, WM-FA, and TBV and higher AWM (all <0.05); and diabetes with lower TBV (p=0.007). The GCS was lower as TBV decreased, AWM increased, and WM-FA (all p<0.01).

Conclusion

In middle age adults, CVRF are associated with brain health, reflected in MRI measures of structure and perfusion, and cognitive functioning. These findings suggest markers of mid-life cardiovascular and brain health should be considered as indication for early intervention and future risk of late-life cerebrovascular disease and dementia.     

A Systematic Review of Hospital-to-School Reintegration Interventions for Children and Youth with Acquired Brain Injury

Objectives

We reviewed the literature on interventions that aimed to improve hospital-to-school reintegration for children and youth with acquired brain injury (ABI). ABI is the leading cause of disability among children and youth. A successful hospital-to-school reintegration process is essential to the rehabilitative process. However, little is known about the effective components of of such interventions.

Methods and findings

Our research team conducted a systematic review, completing comprehensive searches of seven databases and selected reference lists for relevant articles published in a peer-reviewed journal between 1989 and June 2014. We selected articles for inclusion that report on studies involving: a clinical population with ABI; sample had an average age of 20 years or younger; an intentional structured intervention affecting hospital-to-school transitions or related components; an experimental design; and a statistically evaluated health outcome. Two independent reviewers applied our inclusion criteria, extracted data, and rated study quality. A meta-analysis was not feasible due to the heterogeneity of the studies reported. Of the 6933 articles identified in our initial search, 17 articles (reporting on 350 preadolescents and adolescents, aged 4–19, (average age 11.5 years, SD: 2.21) met our inclusion criteria. They reported on interventions varying in number of sessions (one to 119) and session length (20 minutes to 4 hours). The majority of interventions involved multiple one-to-one sessions conducted by a trained clinician or educator, homework activities, and parental involvement. The interventions were delivered through different settings and media, including hospitals, schools, and online. Although outcomes varied (with effect sizes ranging from small to large), 14 of the articles reported at least one significant improvement in cognitive, social, psychological, or behavioral functioning or knowledge of ABI.

Conclusions

Cognitive, behavioral, and problem-solving interventions have the potential to improve school reintegration for youth with ABI. However, more comprehensive interventions are needed to help link rehabilitation clinicians, educators, adolescents, and families.     

Detection and Isolation of Swine Influenza A Virus in Spiked Oral Fluid and Samples from Individually Housed,Experimentally Infected Pigs: Potential Role of Porcine Oral Fluid in Active Influenza A Virus Surveillance in Swine

Background

The lack of seasonality of swine influenza A virus (swIAV) in combination with the capacity of swine to harbor a large number of co-circulating IAV lineages, resulting in the risk for the emergence of influenza viruses with pandemic potential, stress the importance of swIAV surveillance. To date, active surveillance of swIAV worldwide is barely done because of the short detection period in nasal swab samples. Therefore, more sensitive diagnostic methods to monitor circulating virus strains are requisite.

Methods

qRT-PCR and virus isolations were performed on oral fluid and nasal swabs collected from individually housed pigs that were infected sequentially with H1N1 and H3N2 swIAV strains. The same methods were also applied to oral fluid samples spiked with H1N1 to study the influence of conservation time and temperature on swIAV infectivity and detectability in porcine oral fluid.

Results

All swIAV infected animals were found qRT-PCR positive in both nasal swabs and oral fluid. However, swIAV could be detected for a longer period in oral fluid than in nasal swabs. Despite the high detectability of swIAV in oral fluid, virus isolation from oral fluid collected from infected pigs was rare. These results are supported by laboratory studies showing that the PCR detectability of swIAV remains unaltered during a 24 h incubation period in oral fluid, while swIAV infectivity drops dramatically immediately upon contact with oral fluid (3 log titer reduction) and gets lost after 24 h conservation in oral fluid at ambient temperature.

Conclusions

Our data indicate that porcine oral fluid has the potential to replace nasal swabs for molecular diagnostic purposes. The difficulty to isolate swIAV from oral fluid could pose a drawback for its use in active surveillance programs.     

Detection of Hepatitis E Virus Antibodies in Dogs in the United Kingdom

Hepatitis E virus (HEV) genotypes 3 and 4 are zoonotic pathogens, with pigs predominantly implicated in disease transmission. The rapid rise in human cases in developed countries over the past decade indicates a change in epidemiology of HEV, and it has been suggested that additional animal species may be involved in transmission of infection. Multiple studies have identified contact with dogs as a risk factor for HEV infection in industrialised nations, and a low seroprevalence to HEV has previously been reported in dogs in low-income countries. In this study we aimed to evaluate the possibility that dogs are susceptible to HEV, and determine the frequency with which this occurs. Serum samples from UK dogs with and without hepatitis were screened for HEV-specific antibodies, and canine liver and stool samples were analysed by qPCR for the presence of HEV RNA. We describe evidence to show HEV infection occurs at low levels in dogs in the UK, but the strain of origin is undetermined. The low seroprevalence level of HEV in dogs implies the risk of zoonotic disease transmission is likely to be limited, but further investigations will be required to determine if HEV-infected dogs can transmit HEV to man.     

Different Stress-Induced Calcium Signatures Are Reported by Aequorin-Mediated Calcium Measurements in Living Cells of Aspergillus fumigatus

Aspergillus fumigatus is an inhaled fungal pathogen of human lungs, the developmental growth of which is reliant upon Ca²⁺-mediated signalling. Ca²⁺ signalling has regulatory significance in all eukaryotic cells but how A. fumigatus uses intracellular Ca²⁺ signals to respond to stresses imposed by the mammalian lung is poorly understood. In this work, A. fumigatus strains derived from the clinical isolate CEA10, and a non-homologous recombination mutant ΔakuB ^KU80, were engineered to express the bioluminescent Ca²⁺-reporter aequorin. An aequorin-mediated method for routine Ca²⁺ measurements during the early stages of colony initiation was successfully developed and dynamic changes in cytosolic free calcium ([Ca²⁺]_c) in response to extracellular stimuli were measured. The response to extracellular challenges (hypo- and hyper-osmotic shock, mechanical perturbation, high extracellular Ca²⁺, oxidative stress or exposure to human serum) that the fungus might be exposed to during infection, were analysed in living conidial germlings. The ‘signatures’ of the transient [Ca²⁺]_c responses to extracellular stimuli were found to be dose- and age-dependent. Moreover, Ca²⁺-signatures associated with each physico-chemical treatment were found to be unique, suggesting the involvement of heterogeneous combinations of Ca²⁺-signalling components in each stress response. Concordant with the involvement of Ca²⁺-calmodulin complexes in these Ca²⁺-mediated responses, the calmodulin inhibitor trifluoperazine (TFP) induced changes in the Ca²⁺-signatures to all the challenges. The Ca²⁺-chelator BAPTA potently inhibited the initial responses to most stressors in accordance with a critical role for extracellular Ca²⁺ in initiating the stress responses.