AbstractClinical questionWhat are the benefits and harms of thyroid hormones for adults with subclinical hypothyroidism (SCH)? This guideline was triggered by a recent systematic review of randomised ...controlled trials, which could alter practice.Current practiceCurrent guidelines tend to recommend thyroid hormones for adults with thyroid stimulating hormone (TSH) levels >10 mIU/L and for people with lower TSH values who are young, symptomatic, or have specific indications for prescribing.RecommendationThe guideline panel issues a strong recommendation against thyroid hormones in adults with SCH (elevated TSH levels and normal free T4 (thyroxine) levels). It does not apply to women who are trying to become pregnant or patients with TSH >20 mIU/L. It may not apply to patients with severe symptoms or young adults (such as those ≤30 years old).How this guideline was createdA guideline panel including patients, clinicians, and methodologists produced this recommendation in adherence with standards for trustworthy guidelines using the GRADE approach.The evidenceThe systematic review included 21 trials with 2192 participants. For adults with SCH, thyroid hormones consistently demonstrate no clinically relevant benefits for quality of life or thyroid related symptoms, including depressive symptoms, fatigue, and body mass index (moderate to high quality evidence). Thyroid hormones may have little or no effect on cardiovascular events or mortality (low quality evidence), but harms were measured in only one trial with few events at two years’ follow-up.Understanding the recommendationThe panel concluded that almost all adults with SCH would not benefit from treatment with thyroid hormones. Other factors in the strong recommendation include the burden of lifelong management and uncertainty on potential harms. Instead, clinicians should monitor the progression or resolution of the thyroid dysfunction in these adults. Recommendations are made actionable for clinicians and their patients through visual overviews. These provide the relative and absolute benefits and harms of thyroid hormones in multilayered evidence summaries and decision aids available in MAGIC (https://app.magicapp.org/) to support shared decisions and adaptation of this guideline.
The current socio-economic, environmental and public health challenges that countries are facing clearly need common-defined strategies to inform and support our transition to a sustainable economy. ...Here, the technology-critical elements (which includes Ga, Ge, In, Te, Nb, Ta, Tl, the Platinum Group Elements and most of the rare-earth elements) are of great relevance in the development of emerging key technologies—including renewable energy, energy efficiency, electronics or the aerospace industry. In this context, the increasing use of technology-critical elements (TCEs) and associated environmental impacts (from mining to end-of-life waste products) is not restricted to a national level but covers most likely a global scale. Accordingly, the European COST Action TD1407: Network on Technology-Critical Elements (NOTICE)—from environmental processes to human health threats, has an overall objective for creating a network of scientists and practitioners interested in TCEs, from the evaluation of their environmental processes to understanding potential human health threats, with the aim of defining the current state of knowledge and gaps, proposing priority research lines/activities and acting as a platform for new collaborations and joint research projects. The Action is focused on three major scientific areas: (i) analytical chemistry, (ii) environmental biogeochemistry and (iii) human exposure and (eco)-toxicology.
Counseling for patients with primary hyperparathyroidism (PHPT) and mild hypercalcemia without indications for surgical intervention requires accurate estimates of the potential benefits of ...parathyroidectomy. We aim to summarize the available evidence regarding the benefits of parathyroidectomy that patients with mild PHPT without indications for surgery experience compared to observation. We searched multiple databases from inception to August 2015. We included randomized controlled trials (RCT) and observational studies that evaluated changes in bone health, quality of life or neuropsychiatric symptoms, or in the risk of nephrolithiasis, cardiovascular events, or death between patients undergoing parathyroidectomy or active surveillance. Eight studies were eligible. Risk differences were not significant, in part due to lack of events (fractures, nephrolithiasis, cardiovascular events, or deaths). No significant differences were observed across measures of bone health, quality of life, and neuropsychiatric symptoms. A single RCT evaluating bone mineral density (BMD) changes at 5 years found a small statistically significant effect favoring parathyroidectomy. Patients with mild PHPT without indications for surgery experience a limited number of adverse consequences during short-term follow-up limiting our ability to estimate the benefit of surgery during this timeframe. This information is helpful as these patients consider surgery versus active surveillance. Long-term data is warranted to determine who benefits in the long run from surgical intervention and the extent to which this benefit affects outcomes that matter to patients.
The increasing consumption of pharmaceuticals, alongside their limited removal in wastewater treatment plants (WWTPs), have led to their ubiquitous occurrence in receiving aquatic environments. This ...study addresses the occurrence of 68 pharmaceuticals (PhACs) in the Ebro River Delta region (NE Spain), as well as their distribution in different environmental compartments, including surface water, sediments, biota (river biofilm and fish tissues), and field-collected plastic litter. In addition, their concentrations in serving WWTPs, as possible sources of environmental contamination, were also determined.
Our study confirmed the widespread occurrence of PhACs in riverine and, to a more limited extent, coastal environments. Most frequently detected PhACs belonged to analgesics/anti-inflammatories (e.g., ibuprofen) and psychiatric drugs (e.g., venlafaxine) therapeutic groups, followed by antihypertensives (e.g., valsartan) and antibiotics (e.g., azithromycin). Seasonal differences in cumulative levels of PhACs were reported for water and sediments (winter>summer). Despite spatial gradients were not clear along the river, a non-negligible contribution of upstream Ebro sites (reference area) was highlighted, which was unexpected based on the low anthropogenic pressure. Sediments represented a minor attenuation pathway for the selected PhACs, whereas they were more heavily accumulated in biota: fish liver (up to 166 ng/g dw), river biofilms (up to 108 ng/g dw), fish plasma (up to 63 ng/mL), and fish muscle (up to 31 ng/g dw).
These findings highlight the importance of biomonitoring in the characterization of polluted areas and prioritization of hazardous substances (e.g., psychiatric drugs) in aquatic systems, and a particular interest of fish plasma as non-destructive biomonitoring matrix. PhACs were also detected on plastic litter, demonstrating their role as environmental sinks for certain PhACs (e.g., analgesics/anti-inflammatories, psychiatric drugs). Overall, the widespread detection of PhACs in a variety of biotic and abiotic matrices from the lower Ebro River and Delta warns about their possible environmental implications.
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•No geographical variation in pharmaceutical pollution along lower Ebro River basin.•Analgesics/anti-inflammatories, psychiatric drugs and antihypertensives as most frequent in river water•Biomonitoring improves assessment of pharmaceutical contamination compared to grab water.•River biofilm, fish plasma (non-destructive) and liver more informative than fish muscle•Plastic litter as a passive sink of some pharmaceuticals
The recurrent nova (RN) V3890 Sgr was observed during the seventh day after the onset of its most recent outburst, with the Chandra ACIS-S camera and High Energy Transmission Gratings. A rich ...emission line spectrum was detected, due to transitions of Fe-L and K-shell ions ranging from neon to iron. The measured absorbed flux is 10−10 erg cm−2 s−1 in the 1.4-15 range (0.77-8.86 keV). The line profiles are asymmetric, blueshifted, and skewed toward the blue side, as if the ejecta moving toward us are less absorbed than the receding ejecta. The full width at half-maximum of most emission lines is 1000-1200 km s−1, with some extended blue wings. The spectrum is thermal and consistent with a plasma in collisional ionization equilibrium with column density 1.3 × 1022 cm−2 and at least two components at temperatures of about 1 and 4 keV, possibly a forward and a reverse shock, or regions with differently mixed ejecta and a red giant wind. The spectrum is remarkably similar to the symbiotic RNe V745 Sco and RS Oph, but we cannot distinguish whether the shocks occurred at a distance of a few au from the red giant, or near the giant's photosphere, in a high-density medium containing only a low mass. The ratios of the flux in lines of aluminum, magnesium, and neon relative to the flux in lines of silicon and iron probably indicate a carbon-oxygen white dwarf.
Summary
Background
In patients with multiple endocrine neoplasia type 1 (MEN‐1), pancreaticoduodenal (PD) neuroendocrine tumours (NETs) are associated with early mortality, yet the best treatment ...strategy remains uncertain.
Aim
To assess patient important outcomes (mortality and metastasis) of PD‐NETs and predictors of outcomes in patients with MEN‐1.
Methods
Retrospective cohort of patients with MEN‐1 who attended the Mayo Clinic, Rochester, MN from 1997 to 2014.
Results
We identified 287 patients with MEN‐1; 199 (69%) patients had 217 PD‐NETs. Among those with a PD‐NETs, 129 (65%) had surgery of which 90 (70%) had their primary surgery performed at Mayo Clinic. The median postoperative follow‐up was 8 years during which 13 (14%) patients died. The mean (±standard deviation) age of death was 51 (±9) years. Tumour size, metastasis at surgery or tumour type were not predictive of mortality, but for every year older at surgery, the odds of metastasis increased by 6%. Surgery was not performed in 70 (35%) patients. Among those who were observed/medically managed without known metastatic disease, mean tumour growth was 0·02 cm/year (range, −0·13–0·4 cm/year). Four patients (7%) died at a median age of 77 (range, 51–89) years.
Conclusion
PD‐NETs are common in patients with MEN‐1 and are associated with early mortality even after surgical intervention. Active surveillance is a viable option in nonaggressive PD‐NETs, although definitive factors identifying such patients are lacking. Therefore, counselling regarding risks and benefits of current treatment options remains integral to the care of patients with MEN‐1.
Nova SMC 2016 has been the most luminous nova known in the direction of the Magellanic Clouds. It turned into a very luminous supersoft X-ray source between days 16 and 28 after the optical maximum. ...We observed it with Chandra, the HRC-S camera, and the Low Energy Transmission Grating on 2016 November and 2017 January (days 39 and 88 after optical maximum), and with XMM-Newton on 2016 December (day 75). We detected the compact white dwarf (WD) spectrum as a luminous supersoft X-ray continuum with deep absorption features of carbon, nitrogen, magnesium, calcium, probably argon, and sulfur on day 39, and oxygen, nitrogen, and carbon on days 75 and 88. The spectral features attributed to the WD atmosphere are all blueshifted, by about 1800 km s−1 on day 39 and up to 2100 km s−1 in the following observations. Spectral lines attributed to low-ionization potential transitions in the interstellar medium are also observed. Assuming the distance to the Small Magellanic Cloud, the bolometric luminosity exceeded the Eddington level for at least three months. A preliminary analysis with atmospheric models indicates an effective temperature of around 700,000 K on day 39, peaking at the later dates in the 850,000-900,000 K range, as expected for a 1.25 M WD. We suggest a possible classification as an oxygen-neon WD, but more precise modeling is needed to accurately determine the abundances. The X-ray light curves show a large, aperiodic flux variability, which is not associated with spectral variability. We detected red noise, but did not find periodic or quasiperiodic modulations.
The CALorimetric Electron Telescope (CALET)on the International Space Station consists of a high-energy cosmic-ray CALorimeter (CAL)and a lower-energy CALET Gamma-ray Burst Monitor (CGBM). CAL is ...sensitive to electrons up to 20 TeV, cosmic-ray nuclei from Z=1 throughZ∼40, and gamma rays over the range1 GeV–10 TeV. CGBM observes gamma rays from 7 keV to 20 MeV. The combined CAL-CGBM instrument has conducted a search for gamma-ray bursts (GRBs)since 2015 October. We report here on the results of a search for X-ray/gamma-ray counterparts to gravitational-wave events reported during the LIGO/Virgo observing run O3. No events have been detected that pass all acceptance criteria. We describe the components, performance, and triggering algorithms of the CGBM—the two Hard X-ray Monitors consisting of LaBr3(Ce)scintillators sensitive to 7 keV–1 MeV gamma rays and a Soft Gamma-ray Monitor BGO scintillator sensitive to 40 keV–20 MeV—and the high-energy CAL consisting of a charge detection module, imaging calorimeter, and the fully active total absorption calorimeter. The analysis procedure is described and upper limits to the time-averaged fluxes are presented.
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