Variation in methods, results and reporting in electronic health record-based studies evaluating routine care in gout: A systematic review

Objective: To perform a systematic review examining the variation in methods, results, reporting and risk of bias in electronic health record (EHR)-based studies evaluating management of a common musculoskeletal disease, gout. Methods: Two reviewers systematically searched MEDLINE, Scopus, Web of Science, CINAHL, PubMed, EMBASE and Google Scholar for all EHR-based studies published by February 2019 investigating gout pharmacological treatment. Information was extracted on study design, eligibility criteria, definitions, medication usage, effectiveness and safety data, comprehensiveness of reporting (RECORD), and Cochrane risk of bias (registered PROSPERO CRD42017065195). Results: We screened 5,603 titles/abstracts, 613 full-texts and selected 75 studies including 1.9M gout patients. Gout diagnosis was defined in 26 ways across the studies, most commonly using a single diagnostic code (n = 31, 41.3%). 48.4% did not specify a disease-free period before ‘incident’ diagnosis. Medication use was suboptimal and varied with disease definition while results regarding effectiveness and safety were broadly similar across studies despite variability in inclusion criteria. Comprehensiveness of reporting was variable, ranging from 73% (55/75) appropriately discussing the limitations of EHR data use, to 5% (4/75) reporting on key data cleaning steps. Risk of bias was generally low. Conclusion: The wide variation in case definitions and medication-related analysis among EHR-based studies has implications for reported medication use. This is amplified by variable reporting comprehensiveness and the limited consideration of EHR-relevant biases (e.g. data adequacy) in study assessment tools. We recommend accounting for these biases and performing a sensitivity analysis on case definitions, and suggest changes to assessment tools to foster this

Changes in the pharmacological management of rheumatoid arthritis over two decades

Objectives To assess whether modern management of RA has reduced the prescription of oral corticosteroids and NSAIDs and to evaluate use of pharmacological prophylaxis strategies. Methods Using the Clinical Practice Research Datalink, we explored long-term (≥3/12 months; ≥6/12 in sub-analyses) DMARD, corticosteroid and NSAID prescribing (annually, in the year post-diagnosis and across the patient’s life course to 15 years post-diagnosis), annual proportion with co-prescribing for prophylaxis of associated bone (corticosteroids, women only) and gastrointestinal (NSAIDs) comorbidity. Results Reported incidence of RA was 5.98 (0.37) per 10 000 person-years and prevalence was 0.91% (0.014) in 2017. In 71 411 RA patients, long-term DMARD prescribing initially rose post-diagnosis from 41.6% in 1998 to 67.9% in 2009. Corticosteroid prescribing changed little, overall [22.2% in 1998, 19.1% in 2016; incident risk ratio (IRR) 0.92, 95% CI: 0.82, 1.03] and across the life course from the first to fifteenth year (22.2% to 16.9%). NSAID prescribing declined from 57.7% in 1998, and significantly so from 2008, to 27.1% in 2016 (IRR 0.50, 95% CI: 0.44, 0.56). This continued across the life course (41.2% to 28.4%). Bone prophylaxis increased to 68.1% in 2008 before declining to 56.4% in 2017; gastrointestinal prophylaxis increased from 11.5% in 1998 to 62.6% in 2017. Sub-analyses showed consistent patterns. Conclusion Despite modern treatment strategies, corticosteroid prescribing in RA patients remains substantial and persists beyond 6 months once initiated. Rheumatologists need to determine causes and develop strategies to reduce corticosteroid use to minimize adverse event occurrence

Changes in ankylosing spondylitis incidence, prevalence and time to diagnosis over two decades

Objectives To assess changes in ankylosing spondylitis (AS) incidence, prevalence and time to diagnosis, between 1998 and 2017. Methods Using UK GP data from the Clinical Practice Research Datalink, we identified patients diagnosed with AS between 1998 and 2017. We estimated the annual AS incidence, prevalence and length of time from first recorded symptom of back pain to rheumatology referral and diagnosis. Results We identified 12 333 patients with AS. The incidence declined from 0.72 (±0.14) per 10 000 patient-years in 1998 to 0.39 (±0.06) in 2007, with this decline significant only in men, then incidence rose to 0.57 (±0.11) in 2017. By contrast, prevalence increased between 1998 and 2017 (from 0.13%±0.006 to 0.18%±0.006), rising steeply among women (from 0.06%±0.05 to 0.10%±0.06) and patients aged ≥60 (from 0.14%±0.01 to 0.26%±0.01). The overall median time from first symptom to rheumatology referral was 4.87 years (IQR=1.42–10.23). The median time from first symptom to diagnosis rose between 1998 and 2017 (from 3.62 years (IQR=1.14–7.07) to 8.31 (IQR=3.77–15.89)) and was longer in women (6.71 (IQR=2.30–12.36)) than men (5.65 (IQR=1.66–11.20)). Conclusion AS incidence declined significantly between 1998 and 2007, with an increase between 2007 and 2017 that may be explained by an improvement in the recognition of AS or confidence in diagnosing AS over time, stemming from increased awareness of inflammatory back pain and the importance of early treatment. The rising AS prevalence may indicate improved patient survival. The persisting delay in rheumatology referral and diagnosis remains of concern, particularly in women

Exoplanet phase curves: observations and theory

Phase curves are the best technique to probe the three dimensional structure of exoplanets' atmospheres. In this chapter we first review current exoplanets phase curve observations and the particular challenges they face. We then describe the different physical mechanisms shaping the atmospheric phase curves of highly irradiated tidally locked exoplanets. Finally, we discuss the potential for future missions to further advance our understanding of these new worlds.Comment: Fig.5 has been updated. Table 1 and corresponding figures have been updated with new values for WASP-103b and WASP-18b. Contains a table sumarizing phase curve observation

A chemical survey of exoplanets with ARIEL

Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.Peer reviewedFinal Published versio

A sub-Neptune transiting the young field star HD 18599 at 40 pc

Transiting exoplanets orbiting young nearby stars are ideal laboratories for testing theories of planet formation and evolution. However, to date only a handful of stars with age <1 Gyr have been found to host transiting exoplanets. Here we present the discovery and validation of a sub-Neptune around HD 18599 , a young (300 Myr), nearby (d = 40 pc) K star. We validate the transiting planet candidate as a bona fide planet using data from the TESS , Spitzer , and Gaia  missions, ground-based photometry from IRSF , LCO , PEST , and NGTS , speckle imaging from Gemini, and spectroscopy from CHIRON , NRES , FEROS , and Minerva-Australis . The planet has an orbital period of 4.13 d , and a radius of 2.7 R⊕ . The RV data yields a 3-σ mass upper limit of 30.5 M⊕  which is explained by either a massive companion or the large observed jitter typical for a young star. The brightness of the host star (V∼9 mag) makes it conducive to detailed characterization via Doppler mass measurement which will provide a rare view into the interior structure of young planets

Toi-1235 b: A keystone super-earth for testing radius valley emergence models around early m dwarfs

Small planets on close-in orbits tend to exhibit envelope mass fractions of either effectively zero or up to a few percent depending on their size and orbital period. Models of thermally-driven atmospheric mass loss and of terrestrial planet formation in a gas-poor environment make distinct predictions regarding the location of this rocky/non-rocky transition in period-radius space. Here we present the confirmation of TOI-1235 b ($P=3.44$ days, $r_p=1.738^{+0.087}_{-0.076}$ R$_{\oplus}$), a planet whose size and period are intermediate between the competing model predictions, thus making the system an important test case for emergence models of the rocky/non-rocky transition around early M dwarfs ($R_s=0.630\pm 0.015$ R$_{\odot}$, $M_s=0.640\pm 0.016$ M$_{\odot}$). We confirm the TESS planet discovery using reconnaissance spectroscopy, ground-based photometry, high-resolution imaging, and a set of 38 precise radial-velocities from HARPS-N and HIRES. We measure a planet mass of $6.91^{+0.75}_{-0.85}$ M$_{\oplus}$ which implies an iron core mass fraction of $20^{+15}_{-12}$% in the absence of a gaseous envelope. The bulk composition of TOI-1235 b is therefore consistent with being Earth-like and we constrain a H/He envelope mass fraction to be $<0.5$% at 90% confidence. Our results are consistent with model predictions from thermally-driven atmospheric mass loss but not with gas-poor formation, which suggests that the former class of processes remain efficient at sculpting close-in planets around early M dwarfs. Our RV analysis also reveals a strong periodicity close to the first harmonic of the photometrically-determined stellar rotation period that we treat as stellar activity, despite other lines of evidence favoring a planetary origin ($P=21.8^{+0.9}_{-0.8}$ days, $m_p\sin{i}=13.0^{+3.8}_{-5.3}$ M$_{\oplus}$) that cannot be firmly ruled out by our data

The Multiplanet System TOI-421*: A Warm Neptune and a Super Puffy Mini-Neptune Transiting a G9 V Star in a Visual Binary*

We report the discovery of a warm Neptune and a hot sub-Neptune transiting TOI-421 (BD-14 1137, TIC 94986319), a bright (V = 9.9) G9 dwarf star in a visual binary system observed by the Transiting Exoplanet Survey Satellite (TESS) space mission in Sectors 5 and 6. We performed ground-based follow-up observations—comprised of Las Cumbres Observatory Global Telescope transit photometry, NIRC2 adaptive optics imaging, and FIbre-fed Echellé Spectrograph, CORALIE, High Accuracy Radial velocity Planet Searcher, High Resolution Échelle Spectrometer, and Planet Finder Spectrograph high-precision Doppler measurements—and confirmed the planetary nature of the 16 day transiting candidate announced by the TESS team. We discovered an additional radial velocity signal with a period of five days induced by the presence of a second planet in the system, which we also found to transit its host star. We found that the inner mini-Neptune, TOI-421 b, has an orbital period of Pb = 5.19672 ± 0.00049 days, a mass of Mb = 7.17 ± 0.66 M⊕, and a radius of Rb = ${2.68}_{-0.18}^{+0.19}$ R⊕, whereas the outer warm Neptune, TOI-421 c, has a period of Pc = 16.06819 ± 0.00035 days, a mass of Mc = ${16.42}_{-1.04}^{+1.06}$ M⊕, a radius of Rc = ${5.09}_{-0.15}^{+0.16}$ R⊕, and a density of ρc = ${0.685}_{-0.072}^{+0.080}$ g cm−3. With its characteristics, the outer planet (ρc = ${0.685}_{-0.072}^{+0.080}$ g cm−3) is placed in the intriguing class of the super-puffy mini-Neptunes. TOI-421 b and TOI-421 c are found to be well-suited for atmospheric characterization. Our atmospheric simulations predict significant Lyα transit absorption, due to strong hydrogen escape in both planets, as well as the presence of detectable CH4 in the atmosphere of TOI-421 c if equilibrium chemistry is assumed

HD 183579b: a warm sub-Neptune transiting a solar twin detected by TESS

We report the discovery and characterization of a transiting warm sub-Neptune planet around the nearby bright (V = 8.75 mag, K = 7.15 mag) solar twin HD 183579, delivered by the Transiting Exoplanet Survey Satellite (TESS). The host star is located 56.8 ± 0.1 pc away with a radius of R* = 0.97 ± 0.02 R⊙ and a mass of M* = 1.03 ± 0.05 M⊙. We confirm the planetary nature by combining space and ground-based photometry, spectroscopy, and imaging. We find that HD 183579b (TOI-1055b) has a radius of Rp = 3.53 ± 0.13 R⊕ on a 17.47 d orbit with a mass of Mp = 11.2 ± 5.4 M⊕ (3σ mass upper limit of 27.4 M⊕). HD 183579b is the fifth brightest known sub-Neptune planet system in the sky, making it an excellent target for future studies of the interior structure and atmospheric properties. By performing a line-by-line differential analysis using the high-resolution and signal-to-noise ratio HARPS spectra, we find that HD 183579 joins the typical solar twin sample, without a statistically significant refractory element depletion

TESS Hunt for Young and Maturing Exoplanets (THYME). IV. Three Small Planets Orbiting a 120 Myr Old Star in the Pisces-Eridanus Stream

Young exoplanets can offer insight into the evolution of planetary atmospheres, compositions, and architectures. We present the discovery of the young planetary system TOI 451 (TIC 257605131, Gaia DR2 4844691297067063424). TOI 451 is a member of the 120 Myr old Pisces–Eridanus stream (Psc–Eri). We confirm membership in the stream with its kinematics, its lithium abundance, and the rotation and UV excesses of both TOI 451 and its wide-binary companion, TOI 451 B (itself likely an M-dwarf binary). We identified three candidate planets transiting in the Transiting Exoplanet Survey Satellite data and followed up the signals with photometry from Spitzer and ground-based telescopes. The system comprises three validated planets at periods of 1.9, 9.2, and 16 days, with radii of 1.9, 3.1, and 4.1 R ⨂, respectively. The host star is near-solar mass with V = 11.0 and H = 9.3 and displays an infrared excess indicative of a debris disk. The planets offer excellent prospects for transmission spectroscopy with the Hubble Space Telescope and the James Webb Space Telescope, providing the opportunity to study planetary atmospheres that may still be in the process of evolving