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Background: While the benefits of levothyroxine are well‐established for overt hypothyroidism, they are unclear for subclinical hypothyroidism (SCH) among pregnant women. Objective: To estimate the effect of initiation of levothyroxine on pregnancy loss among women with SCH with an emulated target trial using observational data. Methods: We emulated a target trial using the United Kingdom's Clinical Practice Research Datalink to account for the staggered timing of diagnosis and treatment of SCH and the time of entry of women into prenatal care. We emulated multiple nested trials (at each gestational week) and used an intention‐to‐treat approach to define levothyroxine use (≥1 prescription in the 7 days prior to trial entry), with eligible users matched to non‐users (1:4) on time of diagnosis, gestational week of the first eligible trial and high‐dimensional propensity score. Pregnancy losses included spontaneous abortion and stillbirth. A pooled logistic regression model with bootstrap resampling was used to estimate the hazard ratios (HR) and 95% confidence intervals (CI). Results: Based on 159,177 eligible person‐trials (5781 women), the matched cohort included 181 initiators and 640 non‐initiators of levothyroxine, with 57 pregnancy losses occurring during follow‐up. Overall, the mean age of women was 32.2 years (SD 5.4), 25% were obese, 8% had type 2 diabetes and about 50% were nulliparous. After matching, women who initiated levothyroxine versus not had higher thyroid‐stimulating levels during pregnancy and were more likely to have a history of hypothyroidism. The cumulative incidence of pregnancy loss was lower in initiators versus non‐initiators of levothyroxine. The adjusted HR for pregnancy loss was 0.87 (95% CI 0.22, 1.56). Conclusions: Although our assessment of the effect of initiation of levothyroxine for SCH in pregnancy precludes any definitive conclusions due to wide confidence intervals, this study illustrates the feasibility of using the target trial emulation framework to examine the effectiveness of medication use in pregnancy. [ABSTRACT FROM AUTHOR]

BACKGROUND This article reviewed the research progress of pretreatment techniques for the analysis of precious metal elements in geological samples in recent years. The fire assay, alkali fusion, acid decomposition and adsorption methods used in the separation and enrichment of samples and absorption, tellurium co-precipitation, ion exchange, solvent extraction, distillation, and biosorption methods commonly used for sample decomposition were reviewed. The characteristics and deficiencies of each method were investigated, and the future development direction of the method is prospected. OBJECTIVES In order to make the analysis results accurate and reliable, it is necessary to select the appropriate means of sample decomposition and separation and enrichment to ensure complete sample decomposition, effectively eliminate the interference of co-existing ions and matrix effect, enhance the precious metal element test signal, and improve the signal-to-noise ratio. METHODS The fire assay method used for sample decomposition has been continuously explored and improved by analysts, and has become the best method to decompose precious metals. However, it still has the disadvantages of large reagent consumption, high cost, and long procedure. Although the alkali fusion method can decompose almost all geological samples, the resulted solution contained a large amount of sodium salt, which needed to be further purified. The acid decomposition method was mainly based on the high-pressure sealed Carius tube digestion, but it was limited by the nature of the sample. Different separation and enrichment methods were highly targeted. For example, the adsorption method was mostly used for the enrichment of Au, Pt, and Pd. The distillation method was only suitable for the analysis of Os and Ru. RESULTS Precious metal elements had features such as strong particle effects, complex and diverse forms, and ultra-trace amounts, so it was necessary to choose a suitable pretreatment method according to the type of samples. CONCLUSIONS Based on the existing precious metal decomposition methods, in combination with the current new experimental equipment and conditions, more efficient and rapid decomposition technologies should be sought and the background of the procedure and pollution problems in each step strictly controlled, realizing multi-technology and multi-method integration and meeting the requirements of precious metal analysis.

Black rock as an important carrier of platinum group elements was discovered in recent years. Due to the multiple origins and complex mineralization, the distribution and occurrence of platinum group elements in black rock are not clear, which is also the major reason why the analytical results of platinum group elements are unstable. According to the mineral properties and composition of black rock, the occurrences of Pt, Pd and Au in black rock could be divided into exchangeable phase, organic binding phase, sulfide bounding phase, and residue phase. The adsorption of Pt, Pd and Au from the organic carbon in black rocks was inhibited by adding potassium thiocyanate and sodium cyanide as desorbents. The distribution of Pt, Pd and Au in each phase was identified by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). The results show that: (1) The ratios of the total extraction of each phase to the total amount of the element are 94.4%-101.0% for Pt, 95.8%-101.0% for Pd, and 96.7%-102.0% for Au, indicating good accuracy and reproducibility. (2) The enrichment of Pt, Pd and Au in black rock minerals not only shows the chalcophile affinity, but also shows obvious correlation with the geological conditions and geological setting of organic carbon formation. The results provide important information for studying the geochemical environment and the metallogenic regularity of the platinum group elements in black rocks.

The prevalent new-user design includes a broader study population than the traditional new-user approach that is frequently used in pharmacoepidemiologic research. In an article appearing in this issue (Am J Epidemiol. 2021;190(7):1341–1348) , Webster-Clark et al. describe the treatment initiator types included in the prevalent new-user design and contrast the causal questions assessed using a prevalent new-user design versus a new-user design. They further applied a series of simulation studies showing the importance of accounting for treatment history in addition to time since initiation of the comparator in the prevalent new-user design. In this commentary, we put their findings in the broader context with a discussion of the strengths and limitations of the prevalent new-user design and settings where it would be most useful. The prevalent new-user design and new-user design both address unique questions of clinical and public health importance. Real-world evidence generated by pharmacoepidemiologic research is increasingly being used by regulators and other knowledge users to inform their decision-making. Understanding the causal questions addressed by different designs is crucial in this process; the study by Webster-Clark et al. represents an important step in addressing this issue. [ABSTRACT FROM AUTHOR]