Population-Level Incidence and Monitoring of Adverse Drug Reactions with Long-term Amiodarone Therapy

Introduction: Amiodarone is associated with significant long-lasting adverse drug reactions (ADRs). Guidelines recommend laboratory monitoring during long-term use. However, data of compliance with laboratory monitoring are lacking. Aims: The aim of this study was to assess laboratory monitoring of liver and thyroid function during amiodarone prescribing from 1989 to 2011 in the Tayside, UK, population (approximately 400 000) in relation to National Guidelines recommending laboratory monitoring every 6 months. We also report the population-level incidence of abnormal liver and thyroid function in relation to total exposure of amiodarone. Methods: Utilizing well-established record-linkage database, a longitudinal retrospective analysis of 1413 patients on long-term amiodarone was carried out, analyzing prescribing, biochemical, and clinical data. Results: Forty-six percent (46%), 28%, and 21% of patients underwent liver, thyroid, and combined testing, respectively, in accordance with guideline recommendations. Thirteen percent and 17% of patients did not have any ALT or TSH testing, respectively. During follow-up, 117 (9.5%) patients had an ALT 3×ULN and 16% patients had an abnormal TSH, (n=125, <0.4 mU/L and n=28, >10 mU/L). One hundred and forty patients (10%) required thyroxine replacement therapy, and 40 (3%) required on hyperthyroid medication. Total amiodarone exposure increased the likelihood of abnormal biochemical testing 2.5-fold after 4 years therapy for liver and thyroid function (P<.0005). Conclusion: In this population-based study, adherence to laboratory monitoring guidelines was suboptimal. There was a positive correlation with total amiodarone exposure and biochemical abnormalities and development of thyroid disease compared to the general population, highlighting the need for improvement and continued amiodarone monitoring

Cloud impacts on photochemistry: Building a climatology of photolysis rates from the Atmospheric Tomography mission

Abstract. Measurements from actinic flux spectroradiometers on board the NASA DC-8 during the Atmospheric Tomography (ATom) mission provide an extensive set of statistics on how clouds alter photolysis rates (J values) throughout the remote Pacific and Atlantic Ocean basins. J values control tropospheric ozone and methane abundances, and thus clouds have been included for more than three decades in tropospheric chemistry modeling. ATom made four profiling circumnavigations of the troposphere capturing each of the seasons during 2016–2018. This work examines J values from the Pacific Ocean flights of the first deployment, but publishes the complete Atom-1 data set (29 July to 23 August 2016). We compare the observed J values (every 3 s along flight track) with those calculated by nine global chemistry–climate/transport models (globally gridded, hourly, for a mid-August day). To compare these disparate data sets, we build a commensurate statistical picture of the impact of clouds on J values using the ratio of J-cloudy (standard, sometimes cloudy conditions) to J-clear (artificially cleared of clouds). The range of modeled cloud effects is inconsistently large but they fall into two distinct classes: (1) models with large cloud effects showing mostly enhanced J values aloft and or diminished at the surface and (2) models with small effects having nearly clear-sky J values much of the time. The ATom-1 measurements generally favor large cloud effects but are not precise or robust enough to point out the best cloud-modeling approach. The models here have resolutions of 50–200 km and thus reduce the occurrence of clear sky when averaging over grid cells. In situ measurements also average scattered sunlight over a mixed cloud field, but only out to scales of tens of kilometers. A primary uncertainty remains in the role of clouds in chemistry, in particular, how models average over cloud fields, and how such averages can simulate measurements. NERC ACSIS LTSM projec

Laboratory and Numerical Study of Saltwater Upconing in Fractured Coastal Aquifers

Supplementary Materials: The following are available online at https://www.mdpi.com/article/10.3390/w13233331/s1.Copyright: © 2021 by the authors. This study investigated the saltwater upconing mechanism in fractured coastal aquifers. Head-induced saline intrusion was initiated into three narrow sandbox aquifers containing individual horizontal discontinuities placed on different positions. Subsequently, using a peristaltic pump, freshwater was abstracted from the aquifers’ center, triggering saltwater upconing. Progressively larger pumping rates were applied until critical conditions, resulting in the wells’ salinization, were achieved. Advanced image analysis algorithms were utilized to recreate the saltwater concentration fields and quantify the extent of the saline wedges with a high accuracy. A numerical model was successfully employed to simulate the laboratory results and conduct a comprehensive sensitivity analysis, further expanding the findings of this investigation. The impact of the fractures’ length, permeability and position on the upconing mechanism was identified. It was established that the presence of high permeability discontinuities significantly affected aquifer hydrodynamics. The conclusions of this study could constitute a contribution towards the successful management of real-world fractured coastal aquifers.EPSRC Standard Research (Grant No. EP/R019258/1)

Meniscoplasty for stable osteochondritis dissecans of the lateral femoral condyle combined with a discoid lateral meniscus: a case report

<p>Abstract</p> <p>Introduction</p> <p>Osteochondritis dissecans of the lateral femoral condyle is relatively rare, and it is reported to often be combined with a discoid lateral meniscus. Given the potential for healing, conservative management is indicated for stable osteochondritis dissecans in patients who are skeletally immature. However, patients with osteochondritis dissecans of the lateral femoral condyle combined with a discoid lateral meniscus often have persistent symptoms despite conservative management.</p> <p>Case presentation</p> <p>We present the case of a seven-year-old Korean girl who had osteochondritis dissecans of the lateral femoral condyle combined with a discoid lateral meniscus, which healed after meniscoplasty for the symptomatic lateral discoid meniscus without surgical intervention for the osteochondritis dissecans. In addition, healing of the osteochondritis dissecans lesion was confirmed by an MRI scan five months after the operation.</p> <p>Conclusions</p> <p>Meniscoplasty can be recommended for symptomatic stable juvenile osteochondritis dissecans of the lateral femoral condyle combined with a discoid lateral meniscus when conservative treatment fails.</p

Interferon regulatory factor 8-deficiency determines massive neutrophil recruitment but T cell defect in fast growing granulomas during tuberculosis

Following Mycobacterium tuberculosis (Mtb) infection, immune cell recruitment in lungs is pivotal in establishing protective immunity through granuloma formation and neogenesis of lymphoid structures (LS). Interferon regulatory factor-8 (IRF-8) plays an important role in host defense against Mtb, although the mechanisms driving anti-mycobacterial immunity remain unclear. In this study, IRF-8 deficient mice (IRF-8−/−) were aerogenously infected with a low-dose Mtb Erdman virulent strain and the course of infection was compared with that induced in wild-type (WT-B6) counterparts. Tuberculosis (TB) progression was examined in both groups using pathological, microbiological and immunological parameters. Following Mtb exposure, the bacterial load in lungs and spleens progressed comparably in the two groups for two weeks, after which IRF-8−/− mice developed a fatal acute TB whereas in WT-B6 the disease reached a chronic stage. In lungs of IRF-8−/−, uncontrolled growth of pulmonary granulomas and impaired development of LS were observed, associated with unbalanced homeostatic chemokines, progressive loss of infiltrating T lymphocytes and massive prevalence of neutrophils at late infection stages. Our data define IRF-8 as an essential factor for the maintenance of proper immune cell recruitment in granulomas and LS required to restrain Mtb infection. Moreover, IRF-8−/− mice, relying on a common human and mouse genetic mutation linked to susceptibility/severity of mycobacterial diseases, represent a valuable model of acute TB for comparative studies with chronically-infected congenic WT-B6 for dissecting protective and pathological immune reactions

A Systematic Review Comparing the Acceptability, Validity and Concordance of Discrete Choice Experiments and Best–Worst Scaling for Eliciting Preferences in Healthcare

Objective: The aim of this study was to compare the acceptability, validity and concordance of discrete choice experiment (DCE) and best–worst scaling (BWS) stated preference approaches in health. Methods: A systematic search of EMBASE, Medline, AMED, PubMed, CINAHL, Cochrane Library and EconLit databases was undertaken in October to December 2016 without date restriction. Studies were included if they were published in English, presented empirical data related to the administration or findings of traditional format DCE and object-, profile- or multiprofile-case BWS, and were related to health. Study quality was assessed using the PREFS checklist. Results: Fourteen articles describing 12 studies were included, comparing DCE with profile-case BWS (9 studies), DCE and multiprofile-case BWS (1 study), and profile- and multiprofile-case BWS (2 studies). Although limited and inconsistent, the balance of evidence suggests that preferences derived from DCE and profile-case BWS may not be concordant, regardless of the decision context. Preferences estimated from DCE and multiprofile-case BWS may be concordant (single study). Profile- and multiprofile-case BWS appear more statistically efficient than DCE, but no evidence is available to suggest they have a greater response efficiency. Little evidence suggests superior validity for one format over another. Participant acceptability may favour DCE, which had a lower self-reported task difficulty and was preferred over profile-case BWS in a priority setting but not necessarily in other decision contexts. Conclusion: DCE and profile-case BWS may be of equal validity but give different preference estimates regardless of the health context; thus, they may be measuring different constructs. Therefore, choice between methods is likely to be based on normative considerations related to coherence with theoretical frameworks and on pragmatic considerations related to ease of data collection

A novel design process for selection of attributes for inclusion in discrete choice experiments:Case study exploring variation in clinical decision-making about thrombolysis in the treatment of acute ischaemic stroke

On-line structured prioritisation exercise (SPE). Full survey used to collect data. (DOCX 42 kb

Thoracic costotransverse joint pain patterns: a study in normal volunteers

<p>Abstract</p> <p>Background</p> <p>Pain referral patterns of asymptomatic costotransverse joints have not been established. The objective of this study was to determine the pain referral patterns of asymptomatic costotransverse joints via provocative intra-articular injection.</p> <p>Methods</p> <p>Eight asymptomatic male volunteers received a combined total of 21 intra-articular costotransverse joint injections. Fluoroscopic imaging was used to identify and isolate each costotransverse joint and guide placement of a 25 gauge, 2.5 inch spinal needle into the costotransverse joint. Following contrast medium injection, the quality, intensity, and distribution of the resultant pain produced were recorded.</p> <p>Results</p> <p>Of the 21 costotransverse joint injections, 16 (76%) were classified as being intra-articular via arthrograms taken at the time of injection, and 14 of these injections produced a pain sensation distinctly different from that of needle placement. Average pain produced was 3.3/10 on a 0–10 verbal pain scale. Pain was described generally as a deep, dull ache, and pressure sensation. Pain patterns were located superficial to the injected joint, with only the right T2 injections showing referred pain 2 segments cranially and caudally. No chest wall, upper extremity or pseudovisceral pains were reported.</p> <p>Conclusion</p> <p>This study provides preliminary data of the pain referral patterns of costotransverse joints. Further research is needed to compare these findings with those elicited from symptomatic subjects.</p