Wide Range Of Estimates Research Articles

Estimation of groundwater recharge in a shallow sandy aquifer using unsaturated zone modeling and water table fluctuation method

Quantification of groundwater recharge is one of the most important issues in hydrogeology, especially in view of the ongoing changes in climate and land use. In this study, we use numerical models of 1D vertical flow in the vadose zone and the water table fluctuation (WTF) analysis to investigate local-scale recharge of a shallow sandy aquifer in the Brda outwash plain in northern Poland. We show that these two methods can be jointly used to improve confidence in recharge estimation. A set of preliminary numerical simulations based on soil water content measurements from 4 grassland and pine forest profiles provided a wide range of recharge estimates (263 mm to 839 mm for a 3-year period). Additional simulations were performed with the lower boundary condition specified as a functional relationship between the groundwater table elevation and the rate of groundwater outflow from the vertical profile (horizontal drains boundary condition). In this way, we could reproduce the water table fluctuations resulting from recharge and lateral discharge to nearby lakes. The agreement between simulated and observed groundwater levels differed depending on the specific set of parameters characterizing vadose zone flow, which allowed us to find the most representative parameter sets and refine the range of plausible recharge estimates (501 mm to 573 mm per 3 years). The recharge rates from WTF (410 mm to 606 mm per 3 years) were in good agreement with numerical simulations, providing that the effect of the natural recession of groundwater table due to lateral outflow was considered (master recession curve method). Our results show that: (i) the proposed approach combining 1D vadose zone modeling and WTF improves recharge estimation, (ii) multiple types of observations, including groundwater table positions, are needed to calibrate and validate vadose zone flow models, and (iii) extended periods of observations and simulations are necessary to capture year-to-year variability in the recharge rates.

Obesity and metabolic comorbidity in bipolar disorder: do patients on lithium comprise a subgroup? A naturalistic study

BackgroundBipolar disorders (BD) are associated with increased prevalence of obesity and metabolic syndrome (MetS). Nevertheless, there is a wide range in prevalence estimates, with little known about the contributions of pharmacotherapy. It has been suggested that lithium might have a more favorable metabolic profile. We hypothesized that lithium use is associated with less increased body mass index (BMI), MetS, and type II diabetes, when compared with non-lithium users (those on anticonvulsants, second-generation antipsychotics).MethodsCross-sectional study of 129 patients aged 18–85 with bipolar disorder, followed at tertiary care clinics in Montreal. Patients using lithium were compared with those not on lithium, for body mass index and metabolic syndrome.ResultsThe prevalence of obesity and metabolic syndrome in the sample of lithium-using patients with BD was 42.4 and 35.7% respectively, with an average BMI of 29.10 (+/− 6.70). Lithium and non-lithium groups did not differ in BMI or prevalence of MetS. However, compared to the non-lithium group, lithium users had lower hemoglobin A1C (5.24 +/− 0.53 versus 6.01 +/− 1.83, U = 753.5, p = 0.006) and lower triglycerides (1.46 +/− 0.88 versus 2.01 +/− 1.25, U = 947, p = 0.020).ConclusionsThere is a high prevalence of obesity and metabolic syndrome among patients with bipolar disorder. However, this did not appear to be associated with lithium use, when compared to those not on lithium. The lithium subgroup was also associated with lower prevalence of type II diabetes. Future prospective and intervention studies with larger sample sizes are necessary to further explore the association between lithium and insulin resistance, as well as its underlying mechanisms.

BAWLD-CH<sub>4</sub>: a comprehensive dataset of methane fluxes from boreal and arctic ecosystems

Abstract. Methane (CH4) emissions from the boreal and arctic region are globally significant and highly sensitive to climate change. There is currently a wide range in estimates of high-latitude annual CH4 fluxes, where estimates based on land cover inventories and empirical CH4 flux data or process models (bottom-up approaches) generally are greater than atmospheric inversions (top-down approaches). A limitation of bottom-up approaches has been the lack of harmonization between inventories of site-level CH4 flux data and the land cover classes present in high-latitude spatial datasets. Here we present a comprehensive dataset of small-scale, surface CH4 flux data from 540 terrestrial sites (wetland and non-wetland) and 1247 aquatic sites (lakes and ponds), compiled from 189 studies. The Boreal–Arctic Wetland and Lake Methane Dataset (BAWLD-CH4) was constructed in parallel with a compatible land cover dataset, sharing the same land cover classes to enable refined bottom-up assessments. BAWLD-CH4 includes information on site-level CH4 fluxes but also on study design (measurement method, timing, and frequency) and site characteristics (vegetation, climate, hydrology, soil, and sediment types, permafrost conditions, lake size and depth, and our determination of land cover class). The different land cover classes had distinct CH4 fluxes, resulting from definitions that were either based on or co-varied with key environmental controls. Fluxes of CH4 from terrestrial ecosystems were primarily influenced by water table position, soil temperature, and vegetation composition, while CH4 fluxes from aquatic ecosystems were primarily influenced by water temperature, lake size, and lake genesis. Models could explain more of the between-site variability in CH4 fluxes for terrestrial than aquatic ecosystems, likely due to both less precise assessments of lake CH4 fluxes and fewer consistently reported lake site characteristics. Analysis of BAWLD-CH4 identified both land cover classes and regions within the boreal and arctic domain, where future studies should be focused, alongside methodological approaches. Overall, BAWLD-CH4 provides a comprehensive dataset of CH4 emissions from high-latitude ecosystems that are useful for identifying research opportunities, for comparison against new field data, and model parameterization or validation. BAWLD-CH4 can be downloaded from https://doi.org/10.18739/A2DN3ZX1R (Kuhn et al., 2021).

Prevalence of autism in Europe, North America and Oceania, 2000-2020: A systematic review

Abstract Background Since the first study of the prevalence of autism spectrum disorder (ASD) in 1966, several studies from across the world have reported increasing prevalence of ASD in children. This has led to a debate whether childhood ASD cases are increasing in real time or the increase is essentially due to improved accessibility/referral to health services or changes in diagnostic criteria and accuracy. Methods MEDLINE and PSYCINFO databases were searched for studies of ASD prevalence estimates in Europe, North America and Oceania published during 2000-2020 (including prevalence data for 1993-2019). Data including age at diagnosis, gender, ethnicity, diagnostic criteria/tools, method(s) of case detection and prevalence per 10,000 population were extracted. Results 75 studies, reporting a wide range of prevalence estimates, were included in the review. Overall, there was a steady and substantial increase in the prevalence of ASD in Europe, North America and Oceania during the last three decades. For Europe, the median prevalence was 59 per 10,000 population (range, 8 to 420; mean, 80). For North America, the median prevalence was 86 per 10,000 population (range, 11 to 247; mean, 95). For Oceania, the median prevalence was 47 per 10,000 population (range, 10 to 390; mean, 112). Overall, the prevalence was higher in White children compared to other ethnic groups. Conclusions It appears that several factors can be attributed to increasing prevalence of ASD in Europe, North America and Oceania. Some of the increase is likely due to increased case ascertainment, but other factors need further investigation to determine the reason(s) for increasing prevalence of ASD. Key messages There is a wide variation in the prevalence of ASD in populations of Europe, North America and Oceania. This is partly explained by differences in case ascertainment and sociodemographic factors. The differences in prevalence between ethnic groups need further investigation.

PH-ILD: Identification, Evaluation, and Monitoring: A Diagnostic View From Both Sides

PH-ILD: Identification, Evaluation, and Monitoring: A Diagnostic View From Both Sides

The Archean origin of oxygenic photosynthesis and extant cyanobacterial lineages.

The record of the coevolution of oxygenic phototrophs and the environment is preserved in three forms: genomes of modern organisms, diverse geochemical signals of surface oxidation and diagnostic Proterozoic microfossils. When calibrated by fossils, genomic data form the basis of molecular clock analyses. However, different interpretations of the geochemical record, fossil calibrations and evolutionary models produce a wide range of age estimates that are often conflicting. Here, we show that multiple interpretations of the cyanobacterial fossil record are consistent with an Archean origin of crown-group Cyanobacteria. We further show that incorporating relative dating information from horizontal gene transfers greatly improves the precision of these age estimates, by both providing a novel empirical criterion for selecting evolutionary models, and increasing the stringency of sampling of posterior age estimates. Independent of any geochemical evidence or hypotheses, these results support oxygenic photosynthesis evolving at least several hundred million years before the Great Oxygenation Event (GOE), a rapid diversification of major cyanobacterial lineages around the time of the GOE, and a post-Cryogenian origin of extant marine picocyanobacterial diversity.

Modelling the introduction and transmission of Campylobacter in a North American chicken flock.

Campylobacter is the second leading cause of foodborne illness in the United States. Although many food production animals carry Campylobacter as commensal bacteria, consumption of poultry is the main source of human infection. Previous research suggests that the biology of Campylobacter results in complete flock colonization within days. However, a recent systematic review found that the on-farm prevalence of Campylobacter varies widely, with some flocks reporting low prevalence. We hypothesized that the low prevalence of Campylobacter in some flocks may be driven by a delayed introduction of the pathogen. The objectives of this study were to (a) develop a deterministic compartmental model that represents the biology of Campylobacter, (b) identify the parameter values that best represent the natural history of the pathogen in poultry flocks and (c) examine the possibility that a delayed introduction of the pathogen is sufficient to replicate the observed low prevalence examples documented in the literature. A deterministic compartmental model was developed to examine the dynamics of Campylobacter in chicken flocks over a 56-day time period prior to movement to the abattoir. The model outcome of interest was the final population prevalence of Campylobacter at day 56. The resulting model that incorporated a high transmission rate (β=1.04) was able to reproduce the wide range of prevalence estimates observed in the literature when pathogen introduction time is varied. Overall, we established that the on-farm transmission rate of Campylobacter in chickens is likely high and can result in complete colonization of a flock when introduced early. However, delaying the time at which the pathogen enters the flock can reduce the prevalence observed at 56days. These results highlight the importance of enforcing strict biosecurity measures to prevent or delay the introduction of the bacteria to a flock.

Comparison of qSOFA and Hospital Early Warning Scores for prognosis in suspected sepsis in emergency department patients: a systematic review

BackgroundSepsis is a major cause of morbidity and mortality and many tools exist to facilitate early recognition. This review compares two tools: the quick Sequential Organ Failure Assessment (qSOFA) and...

Carbon pricing under uncertainty

Economists have adopted the Pigouvian approach to climate policy, which sets the carbon price to the social cost of carbon. We adjust this carbon price for macroeconomic uncertainty and disasters by deriving the risk-adjusted discount rate. We highlight ethics- versus market-based calibrations and discuss the effects of a falling term structure of the discount rate. Given the wide range of estimates used for marginal damages and the discount rate, it is unsurprising that negotiators and policy makers have rejected the Pigouvian approach and adopted a more pragmatic approach based on a temperature cap. The corresponding cap on cumulative emissions is lower if risk tolerance and temperature sensitivity are more uncertain. The carbon price then grows much faster than under the Pigouvian approach and discuss how this rate of growth is adjusted by economic and abatement cost risks. We then analyse how policy uncertainty and technological breakthrough can lead to the risk of stranded assets. Finally, we discuss various obstacles to successful carbon pricing.

Quantification of solubility trapping in natural and engineered CO 2 reservoirs

Secure retention of CO 2 in geological reservoirs is essential for effective storage. Solubility trapping, the dissolution of CO 2 into formation water, is a major sink on geological timescales in natural CO 2 reservoirs. Observations during CO 2 injection, combined with models of CO 2 reservoirs, indicate the immediate onset of solubility trapping. There is uncertainty regarding the evolution of dissolution rates between the observable engineered timescale of years and decades, and the >10 kyr state represented by natural CO 2 reservoirs. A small number of studies have constrained dissolution rates within natural analogues. The studies show that solubility trapping is the principal storage mechanism after structural trapping, removing 10–50% of CO 2 across whole reservoirs. Natural analogues, engineered reservoirs and model studies produce a wide range of estimates on the fraction of CO 2 dissolved and the dissolution rate. Analogue and engineered reservoirs do not show the high fractions of dissolved CO 2 seen in several models. Evidence from natural analogues supports a model of most dissolution occurring during emplacement and migration, before the establishment of a stable gas–water contact. A rapid decline in CO 2 dissolution rate over time suggests that analogue reservoirs are in dissolution equilibrium for most of the CO 2 residence time. Supplementary material: Dissolution rate for all plots and exponential function curves for scenarios A and B are available at https://doi.org/10.6084/m9.figshare.c.5476199 Thematic collection: This article is part of the Geoscience for CO 2 storage collection available at: https://www.lyellcollection.org/cc/geoscience-for-co2-storage

Mini-Cog for the detection of dementia within a primary care setting.

Alzheimer's disease and other forms of dementia are becoming increasingly common with the aging of most populations. The majority of individuals with dementia will first present for care and assessment in primary care settings. There is a need for brief dementia screening instruments that can accurately detect dementia in primary care settings. The Mini-Cog is a brief, cognitive screening test that is frequently used to evaluate cognition in older adults in various settings. To determine the accuracy of the Mini-Cog for detecting dementia in a primary care setting. We searched the Cochrane Dementia and Cognitive Improvement Register of Diagnostic Test Accuracy Studies, MEDLINE, Embase and four other databases, initially to September 2012. Since then, four updates to the search were performed using the same search methods, and the most recent was January 2017. We used citation tracking (using the databases' 'related articles' feature, where available) as an additional search method and contacted authors of eligible studies for unpublished data. We only included studies that evaluated the Mini-Cog as an index test for the diagnosis of Alzheimer's disease dementia or related forms of dementia when compared to a reference standard using validated criteria for dementia. We only included studies that were conducted in primary care populations. We extracted and described information on the characteristics of the study participants and study setting. Using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) criteria we evaluated the quality of studies, and we assessed risk of bias and applicability of each study for each domain in QUADAS-2. Two review authors independently extracted information on the true positives, true negatives, false positives, and false negatives and entered the data into Review Manager 5 (RevMan 5). We then used RevMan 5 to determine the sensitivity, specificity, and 95% confidence intervals. We summarized the sensitivity and specificity of the Mini-Cog in the individual studies in forest plots and also plotted them in a receiver operating characteristic plot. We also created a 'Risk of bias' and applicability concerns graph to summarize information related to the quality of included studies. There were a total of four studies that met our inclusion criteria, including a total of 1517 total participants. The sensitivity of the Mini-Cog varied between 0.76 to 1.00 in studies while the specificity varied between 0.27 to 0.85. The included studies displayed significant heterogeneity in both methodologies and clinical populations, which did not allow for a meta-analysis to be completed. Only one study (Holsinger 2012) was found to be at low risk of bias on all methodological domains. The results of this study reported that the sensitivity of the Mini-Cog was 0.76 and the specificity was 0.73. We found the quality of all other included studies to be low due to a high risk of bias with methodological limitations primarily in their selection of participants. There is a limited number of studies evaluating the accuracy of the Mini-Cog for the diagnosis of dementia in primary care settings. Given the small number of studies, the wide range in estimates of the accuracy of the Mini-Cog, and methodological limitations identified in most of the studies, at the present time there is insufficient evidence to recommend that the Mini-Cog be used as a screening test for dementia in primary care. Further studies are required to determine the accuracy of Mini-Cog in primary care and whether this tool has sufficient diagnostic test accuracy to be useful as a screening test in this setting.

Bias and consistency in three-way gravity models

We study the incidental parameter problem for the “three-way” Poisson Pseudo-Maximum Likelihood (“PPML”) estimator recently recommended for identifying the effects of trade policies and in other panel data gravity settings. Despite the number and variety of fixed effects involved, we confirm PPML is consistent for fixed T and we show it is in fact the only estimator among a wide range of PML gravity estimators that is generally consistent in this context when T is fixed. At the same time, asymptotic confidence intervals in fixed-T panels are not correctly centered at the true parameter values, and cluster-robust variance estimates used to construct standard errors are generally biased as well. We characterize each of these biases analytically and show both numerically and empirically that they are salient even for real-data settings with a large number of countries. We also offer practical remedies that can be used to obtain more reliable inferences of the effects of trade policies and other time-varying gravity variables, which we make available via an accompanying Stata package called ppml_fe_bias.

A Scoping Review of Burnout in Neurosurgery.

Burnout is a negative workplace syndrome of emotional exhaustion, cynicism, and perceived professional inefficacy that risks the patient-provider relationship, patient care, and physician well-being. To assimilate the neurosurgical burnout literature in order to classify burnout among domestic and international neurosurgeons and trainees, identify contributory factors, and appraise the impact of wellness programs. A scoping review identified the available literature, which was reviewed for key factors related to burnout among neurosurgeons. Two researchers queriedPubMed, Embase, Google Scholar, Cochrane, and Web of Science for articles on burnout in neurosurgery and reduced 1610 results to 32 articles. A total of 32 studies examined burnout in neurosurgery. A total of 26 studies examined prevalence and 8 studies detailed impact of wellness programs. All were published after 2011. Burnout prevalence was measured mostly through the Maslach Burnout Inventory (n=21). In 4 studies, participants defined their own understanding of "burnout." Domestically, burnout prevalence was 11.2% to 67% among residents and 15% to 57% among attendings. Among trainees, poor operative experience, poor faculty relationships, and social stressors were burnout risks but not age, sex, or marital status. Among attendings, the literature identified financial or legal concerns, lack of intellectual stimulation, and poor work-life balance as risks. The impact of wellness programs on trainees is unclear but group exercises may offer the most benefit. Noticeable methodological differences in studies on trainee and attending burnout contribute to a wide range of neurosurgery burnout estimates and yield significant knowledge gaps. Environment may have greater impact on trainee burnout than demographics. Wellness programs should emphasize solidarity.

Comparative diagnostic performance of rapid antigen detection tests for COVID-19 in a hospital setting

BackgroundThe availability of accurate and rapid diagnostic tools for COVID-19 is essential for tackling the ongoing pandemic. Our study aimed to quantify the performance of available antigen-detecting rapid diagnostic tests (Ag-RDTs) in a real-world hospital setting. MethodsIn this retrospective analysis, the diagnostic performance of 7 Ag-RDTs was compared with real-time reverse transcription quantitative polymerase chain reaction assay in terms of sensitivity, specificity and expected predictive values. ResultsA total of 321 matched Ag-RDTreal-time reverse transcription quantitative polymerase chain reaction samples were analyzed retrospectively. The overall sensitivity and specificity of the Ag-RDTs was 78.7% and 100%, respectively. However, a wide range of sensitivity estimates by brand (66.0%–93.8%) and cycle threshold (Ct) cut-off values (Ct <25: 96.2%; Ct 30–35: 31.1%) was observed. The optimal Ct cut-off value that maximized sensitivity was 29. ConclusionsThe routine use of Ag-RDTs may be convenient in moderate-to-high intensity settings when high volumes of specimens are tested every day. However, the diagnostic performance of the commercially available tests may differ substantially.

Congenital malformations in sub-Saharan Africa—warnings of a silent epidemic?

SARS-CoV-2 has tragically shown the cost of a global pandemic. Only a few years earlier, the outbreak of Zika virus in Brazil and elsewhere in South America caught the international community by surprise. There was no epidemiological surveillance for Zika virus established at the time, since the African-origin virus was previously endemic in Africa and Asia only; clinicians either failed to notify authorities of suspected cases, or reported Zika, dengue, and chikungunya infections in parallel, with limited diagnostic facilities available to differentiate between them. 1 Fischer C Drosten C Drexler JF The difficulties in obtaining reliable Zika virus diagnostics. Lancet Infect Dis. 2019; 19: 240-241 Summary Full Text Full Text PDF PubMed Scopus (8) Google Scholar A lack of common understanding about diagnosis and symptoms produced different case definitions and a wide range of case estimates; 2 Victora CG Schuler-Faccini L Matijasevich A Ribeiro E Pessoa A Barros FC Microcephaly in Brazil: how to interpret reported numbers?. Lancet. 2016; 387: 621-624 Summary Full Text Full Text PDF PubMed Scopus (165) Google Scholar early estimates of the risk of microcephaly varied across Brazil. 3 Jaenisch T Rosenberger KD Brito C Brady O Brasil P Marques ET Risk of microcephaly after Zika virus infection in Brazil, 2015 to 2016. Bull World Health Organ. 2017; 95: 191-198 Crossref PubMed Scopus (60) Google Scholar These challenges delayed meaningful epidemiological interpretations and probably contributed to an increase in unsafe abortions 4 Aiken AR Scott JG Gomperts R Trussell J Worrell M Aiken CE Requests for abortion in Latin America related to concern about Zika Virus exposure. N Engl J Med. 2016; 375: 396-398 Crossref PubMed Scopus (1) Google Scholar and pregnancy delays 5 Castro MC Han QC Carvalho LR Victora CG França GVA Implications of Zika virus and congenital Zika syndrome for the number of live births in Brazil. Proc Natl Acad Sci USA. 2018; 115: 6177-6182 Crossref PubMed Scopus (49) Google Scholar throughout Latin America for fear of the Zika-associated complications.

Measuring human capital using global learning data

Human capital—that is, resources associated with the knowledge and skills of individuals—is a critical component of economic development1,2. Learning metrics that are comparable for countries globally are necessary to understand and track the formation of human capital. The increasing use of international achievement tests is an important step in this direction3. However, such tests are administered primarily in developed countries4, limiting our ability to analyse learning patterns in developing countries that may have the most to gain from the formation of human capital. Here we bridge this gap by constructing a globally comparable database of 164 countries from 2000 to 2017. The data represent 98% of the global population and developing economies comprise two-thirds of the included countries. Using this dataset, we show that global progress in learning—a priority Sustainable Development Goal—has been limited, despite increasing enrolment in primary and secondary education. Using an accounting exercise that includes a direct measure of schooling quality, we estimate that the role of human capital in explaining income differences across countries ranges from a fifth to half; this result has an intermediate position in the wide range of estimates provided in earlier papers in the literature5–13. Moreover, we show that average estimates mask considerable heterogeneity associated with income grouping across countries and regions. This heterogeneity highlights the importance of including countries at various stages of economic development when analysing the role of human capital in economic development. Finally, we show that our database provides a measure of human capital that is more closely associated with economic growth than current measures that are included in the Penn world tables version 9.014 and the human development index of the United Nations15.

In Vitro Susceptibility of Plasmodium falciparum Isolates from the China-Myanmar Border Area to Piperaquine and Association with Candidate Markers.

Plasmodium falciparum from the Greater Mekong subregion has evolved resistance to the artemisinin-based combination therapy dihydroartemisinin and the partner drug piperaquine. To monitor the potential westward spread or independent evolution of piperaquine resistance, we evaluated the in vitro susceptibility of 120 P. falciparum isolates collected at the China-Myanmar border during 2007-2016. The parasite isolates displayed a relatively wide range of piperaquine susceptibility estimates. While 56.7% of the parasites showed bimodal drug response curves, all but five generated area-under-the-curve (AUC) estimates consistent with a susceptible phenotype. Using the piperaquine survival assay (PSA), 5.6% parasites showed reduced susceptibility. Of note, parasites from 2014-2016 showed the highest AUC value and the highest proportion with a bimodal curve, suggesting falling effectiveness in these later years. Unsupervised K-mean analysis of the combined data assigned parasites into three clusters and identified significant correlations between IC50, IC90, and AUC values. No parasites carried the E415G mutation in a putative exo-nuclease, new mutations in PfCRT, or amplification of the plasmepsin 2/3 genes, suggesting mechanisms of reduced piperaquine susceptibility that differ from those described in other countries of the region. The association of increased AUC, IC50, and IC90 values with major PfK13 mutations (F446I and G533S) suggests that piperaquine resistance may evolve in these PfK13 genetic backgrounds. Additionally, the Pfmdr1 F1226Y mutation was associated with significantly higher PSA values. Further elucidation of piperaquine resistance mechanisms and continuous surveillance are warranted.

Measurement and prognosis of frail patients undergoing transcatheter aortic valve implantation: a systematic review and meta-analysis

ObjectivesOur objectives were to review the literature to identify frailty instruments in use for transcatheter aortic valve implantation (TAVI) recipients and synthesise prognostic data from these studies, in order to...

How common is primary aldosteronism?

Primary aldosteronism, characterized by renin-independent aldosterone secretion from one or both adrenal glands, is the most common and modifiable form of secondary hypertension. The prevalence of primary aldosteronism is increasingly recognized to be much higher than previously thought with many cases still undetected. Prior prevalence studies on primary aldosteronism have reported a wide range of estimates due to heterogeneity of both disease definitions and study populations such that it is difficult to claim a single point estimate. More recent evidence demonstrates that primary aldosteronism, as defined by conventional biochemical diagnostic criteria, is highly prevalent within populations where it is not typically considered such as mild-to-moderate hypertension, prehypertension, and even normotension. Yet, our current screening approach fails to capture many cases. Furthermore, there is mounting evidence that renin-independent aldosteronism exists as a continuum of disease that extends below the current biochemical diagnostic thresholds used to define primary aldosteronsim and has clinically relevant treatment and outcome implications for a much broader patient population. Indeed, much of what we current label as 'essential hypertension' is, in fact, renin-independent aldosterone-mediated hypertension. Primary aldosteronism and milder forms of renin-independent aldosteronism are highly prevalent, yet vastly under-recognized, in the general population.

Rheumatoid arthritis-associated interstitial lung disease: epidemiology, risk/prognostic factors, and treatment landscape.

To summarise the epidemiology, risk and prognostic factors, and treatment landscape of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Targeted and systematic literature reviews were conducted to characterise the epidemiology and treatment landscape associated with RA-ILD, respectively. MEDLINE®, Embase, and CENTRAL were searched via OvidSP in March 2019 and December 2018. The results were narratively summarised. A total of 24 and 20 publications were captured through targeted and systematic literature review, respectively. No randomised controlled trials were identified; publications were observational cohort studies, cross-sectional, or case-control. Unadjusted incidence of interstitial lung disease (ILD) ranged from 1.3/1,000 person-years for interstitial pneumonia-type ILD to 5.0/1,000 person-years for 'probable or definite ILD'. Prevalence of ILD ranged from 1.8% to 67% (median: 24.9%) and varied with case definition and sample size. Few publications identified the same risk and prognostic factors; age, male sex, duration of disease, and antibodies to cyclic citrullinated peptides were the most frequently reported risk factors for development of RA-ILD, and age was the most common predictor of mortality. Despite identification of a variety of pharmacotherapeutic interventions, assessment of the comparative efficacy and safety of the available treatments were difficult due to heterogenous reporting of outcomes and small sample size. A wide range of estimates were identified for incidence and prevalence of RA-ILD. Further, there was no consensus on risk and prognostic factors. Sufficiently powered clinical trials are needed to confirm the findings of the observational studies with respect to efficacy and safety of current treatments.