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JAMA Network Open Apr 2023Thyroid storm is the most severe form of thyrotoxicosis, with high mortality, and is treated with propylthiouracil and methimazole. Some guidelines recommend...
IMPORTANCE
Thyroid storm is the most severe form of thyrotoxicosis, with high mortality, and is treated with propylthiouracil and methimazole. Some guidelines recommend propylthiouracil over methimazole, although the difference in outcomes associated with each treatment is unclear.
OBJECTIVE
To compare outcomes associated with use of propylthiouracil vs methimazole for the treatment of thyroid storm.
DESIGN, SETTING, AND PARTICIPANTS
This comparative effectiveness study comprised a large, multicenter, US-based cohort from the Premier Healthcare Database between January 1, 2016, and December 31, 2020. It included 1383 adult patients admitted to intensive or intermediate care units with a diagnosis of thyroid storm per International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes and treated with either propylthiouracil or methimazole. Analyses were conducted from July 2022 to February 2023.
EXPOSURE
Patients received either propylthiouracil or methimazole for treatment of thyroid storm. Exposure was assigned based on the initial thionamide administered.
MAIN OUTCOMES AND MEASURES
The primary outcome was the adjusted risk difference of in-hospital death or discharge to hospice between patients treated with propylthiouracil and those treated with methimazole, assessed by targeted maximum likelihood estimation.
RESULTS
A total of 1383 patients (656 [47.4%] treated with propylthiouracil; mean [SD] age, 45 [16] years; 473 women [72.1%]; and 727 [52.6%] treated with methimazole; mean [SD] age, 45 [16] years; 520 women [71.5%]) were included in the study. The standardized mean difference for age was 0.056, and the standardized mean difference for sex was 0.013. The primary composite outcome occurred in 7.4% of of patients (102 of 1383; 95% CI, 6.0%-8.8%). A total of 8.5% (56 of 656; 95% CI, 6.4%-10.7%) of patients who initiated propylthiouracil and 6.3% (46 of 727; 95% CI, 4.6%-8.1%) who initiated methimazole died in the hospital (adjusted risk difference, 0.6% [95% CI, -1.8% to 3.0%]; Pā=ā.64). There were no significant differences in duration of organ support, total hospitalization costs, or rates of adverse events between the 2 treatment groups.
CONCLUSION AND RELEVANCE
In this comparative effectiveness study of a multicenter cohort of adult patients with thyroid storm, no significant differences were found in mortality or adverse events in patients who were treated with propylthiouracil or methimazole. Thus, current guidelines recommending propylthiouracil over methimazole for treatment of thyroid storm may merit reevaluation.
Topics: Adult; Humans; Female; Middle Aged; Methimazole; Propylthiouracil; Thyroid Crisis; Antithyroid Agents; Critical Illness; Hospital Mortality
PubMed: 37067797
DOI: 10.1001/jamanetworkopen.2023.8655 -
British Medical Journal May 1972
Review
Topics: Adenoma; Carbimazole; Child; Eye Manifestations; Female; Graves Disease; Hot Temperature; Humans; Hyperkinesis; Hyperthyroidism; Iodides; Iodine Isotopes; Long-Acting Thyroid Stimulator; Pregnancy; Sweating; Thiouracil; Thyroid Function Tests; Thyroidectomy; Thyroxine; gamma-Globulins
PubMed: 4112238
DOI: 10.1136/bmj.2.5809.337 -
Medicine Jan 2020Cerebral palsy (CP) is a common disability in children featured with pathological gait and limb function limitation due to muscle weakness. Improving limb function and...
BACKGROUND
Cerebral palsy (CP) is a common disability in children featured with pathological gait and limb function limitation due to muscle weakness. Improving limb function and quality of life is currently considered to be highlighted. Physiotherapy is a chief component of rehabilitation for children with CP, correcting gait and improve walking capacity through muscle strength training. Standard rehabilitation programs for CP have not been determined. Core stability training (CST), which coordinates limb balance via trunk control, is widely used in sports competition. And it is gradually introduced into the rehabilitation of children with cerebral palsy with a positive impact on the patients' gait performance. By screening published literatures, this study aims to conduct a meta-analysis to systematically evaluate the effectiveness and safety of CST in gait of children with CP.
METHODS
Randomized controlled trials (RCTs) and controlled clinical trials (CCTs) on CST in the treatment of children with CP were searched from 6 databases. Moreover, the reference lists of conference papers and included literatures will be manually searched to avoid omissions. Literature screening and data extraction were performed independently by 2 researchers. RCTs carry out the risk of bias analysis evaluation from seven aspects through the Cochrane Collaboration's risk of bias tool. Fixed or random effect model will be performed to analyze the outcomes. When higher heterogeneity occurs (Iā>ā50%), the sensitivity or subgroup analysis will also be conducted to find potential factors. And the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach is used for assessing the quality of evidence.
RESULTS
The study will evaluate the effect of CST on gait of children with CP from multiple outcomes, including walking speed, endurance, stride length, and safety.
CONCLUSION
Based on evidence-based medicine, the conclusion of this study can demonstrate the effectiveness and safety of CST in gait correction for children with CP.
PROSPERO REGISTRATION NUMBER
PROSPERO CRD 42019134094.
Topics: Biomechanical Phenomena; Cerebral Palsy; Child; Clinical Trials as Topic; Exercise Therapy; Female; Humans; Male; Methylthiouracil; Muscle Strength; Research Design; Meta-Analysis as Topic; Systematic Review as Topic
PubMed: 31914039
DOI: 10.1097/MD.0000000000018609 -
Report on Carcinogens : Carcinogen... 2011
Topics: Animals; Antimetabolites; Antithyroid Agents; Carcinogens; Humans; Neoplasms; Propylthiouracil
PubMed: 21863091
DOI: No ID Found -
Canadian Family Physician Medecin de... Jul 2009I have a 33-year-old patient with hyperthyroidism who is 6 weeks pregnant. Her thyroid function is well controlled with a 5-mg dose of methimazole 3 times daily. She was... (Review)
Review
QUESTION
I have a 33-year-old patient with hyperthyroidism who is 6 weeks pregnant. Her thyroid function is well controlled with a 5-mg dose of methimazole 3 times daily. She was initially treated with propylthiouracil but was switched to methimazole owing to urticaria. I have heard about birth defects in infants whose mothers used methimazole during pregnancy. How safe is it?
ANSWER
In North America, propylthiouracil has been the drug of choice for hyperthyroidism during pregnancy. Methimazole is widely used in Europe, South America, and Asia, and is an alternative for patients who cannot tolerate propylthiouracil. Some case reports raised concern about fetal toxicity from methimazole, which is reportedly characterized by aplasia cutis, esophageal atresia, choanal atresia, facial abnormalities, and mental retardation. However, causality is unclear and the overall risk of congenital abnormalities in infants exposed to methimazole in utero was not higher than in those exposed to nonteratogenic drugs in cohort studies. It is important for a pregnant woman to continue methimazole, if necessary, because uncontrolled hyperthyroidism increases the risk of complications such as preterm labour and low birth weight.
Topics: Antithyroid Agents; Female; Fetal Diseases; Humans; Hyperthyroidism; Infant, Newborn; Lactation; Pregnancy; Pregnancy Complications; Propylthiouracil; Treatment Outcome
PubMed: 19602653
DOI: No ID Found -
Molecules (Basel, Switzerland) Oct 2021In this paper, we report X-ray absorption and core-level electron spectra of the nucleobase derivative 2-thiouracil at the sulfur L- and L-edges. We used soft X-rays...
In this paper, we report X-ray absorption and core-level electron spectra of the nucleobase derivative 2-thiouracil at the sulfur L- and L-edges. We used soft X-rays from the free-electron laser FLASH2 for the excitation of isolated molecules and dispersed the outgoing electrons with a magnetic bottle spectrometer. We identified photoelectrons from the 2p core orbital, accompanied by an electron correlation satellite, as well as resonant and non-resonant Coster-Kronig and Auger-Meitner emission at the L- and L-edges, respectively. We used the electron yield to construct X-ray absorption spectra at the two edges. The experimental data obtained are put in the context of the literature currently available on sulfur core-level and 2-thiouracil spectroscopy.
Topics: Electrons; Lasers; Photoelectron Spectroscopy; Sulfur; Thiouracil
PubMed: 34770877
DOI: 10.3390/molecules26216469 -
Physiology & Behavior Oct 2011Oral chemosensation can vary greatly across individuals, both in terms of the lowest concentration that can be detected (threshold) and in the magnitude of perceived... (Review)
Review
Oral chemosensation can vary greatly across individuals, both in terms of the lowest concentration that can be detected (threshold) and in the magnitude of perceived intensity for stimuli at higher concentrations (suprathreshold response). Individuals who experience greater taste intensity are often termed supertasters, and this phenotype has typically been measured via the suprathreshold bitterness of the tastant propylthiouracil (PROP). Notably, supertasting extends beyond bitterness and other tastants to include oral somatosensation and retronasal olfaction, and it may also include finer acuity as well. Here, we describe the evolution of the supertasting concept over the last 20 years, and summarize the current state of the field. Alternative phenotyping approaches that are not dependent on PROP are reviewed, and the molecular genetics of broadly tuned heightened taste and orosensory response are discussed. We conclude by initiating a conversation on nomenclature as we look toward the next 20 years of chemosensory research.
Topics: Humans; Phenotype; Propylthiouracil; Taste; Taste Threshold
PubMed: 21851828
DOI: 10.1016/j.physbeh.2011.08.003 -
Nature Protocols Aug 2019Analysis of cell-type-specific transcriptomes is vital for understanding the biology of tissues and organs in the context of multicellular organisms. In this Protocol...
Analysis of cell-type-specific transcriptomes is vital for understanding the biology of tissues and organs in the context of multicellular organisms. In this Protocol Extension, we combine a previously developed cell-type-specific metabolic RNA labeling method (thiouracil (TU) tagging) and a pipeline to detect the labeled transcripts by a novel RNA sequencing (RNA-seq) method, SLAMseq (thiol (SH)-linked alkylation for the metabolic sequencing of RNA). By injecting a uracil analog, 4-thiouracil, into transgenic mice that express cell-type-specific uracil phosphoribosyltransferase (UPRT), an enzyme required for 4-thiouracil incorporation into newly synthesized RNA, only cells expressing UPRT synthesize thiol-containing RNA. Total RNA isolated from a tissue of interest is then sequenced with SLAMseq, which introduces thymine to cytosine (T>C) conversions at the sites of the incorporated 4-thiouracil. The resulting sequencing reads are then mapped with the T>C-aware alignment software, SLAM-DUNK, which allows mapping of reads containing T>C mismatches. The number of T>C conversions per transcript is further analyzed to identify which transcripts are synthesized in the UPRT-expressing cells. Thus, our method, SLAM-ITseq (SLAMseq in tissue), enables cell-specific transcriptomics without laborious FACS-based cell sorting or biochemical isolation of the labeled transcripts used in TU tagging. In the murine tissues we assessed previously, this method identified ~5,000 genes that are expressed in a cell type of interest from the total RNA pool from the tissue. Any laboratory with access to a high-throughput sequencer and high-power computing can adapt this protocol with ease, and the entire pipeline can be completed in <5 d.
Topics: Animals; Female; Gene Expression Profiling; High-Throughput Nucleotide Sequencing; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Organ Specificity; Pentosyltransferases; Sequence Analysis, RNA; Thiouracil; Transcriptome
PubMed: 31243395
DOI: 10.1038/s41596-019-0179-x -
The Cochrane Database of Systematic... Jun 2011Randomised clinical trials have addressed the question whether propylthiouracil has any beneficial effects in patients with alcoholic liver disease. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Randomised clinical trials have addressed the question whether propylthiouracil has any beneficial effects in patients with alcoholic liver disease.
OBJECTIVES
To assess the beneficial and harmful effects of propylthiouracil for patients with alcoholic liver disease.
SEARCH STRATEGY
We searched The Cochrane Hepato-Biliary Group Controlled Trials Register (April 2011), The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (April 2011), MEDLINE (1948 to April 2011), EMBASE (1980 to April 2011), and Science Citation Index Expanded (1900 to April 2011). These electronic searches were combined with full text searches. Manufacturers and researchers in the field were also contacted.
SELECTION CRITERIA
Randomised clinical trials studying patients with alcoholic steatosis, alcoholic fibrosis, alcoholic hepatitis, and/or alcoholic cirrhosis were included irrespective of blinding, publication status, or language. Interventions encompassed propylthiouracil at any dose versus placebo or no intervention.
DATA COLLECTION AND ANALYSIS
All analyses were performed according to the intention-to-treat method in RevMan Analyses. The risk of bias of the randomised clinical trials was evaluated by bias risk domains such as generation of allocation sequence, allocation concealment, blinding, incomplete outcome data, selective outcome reporting, academic bias, and source of funding.
MAIN RESULTS
Combining the results of six randomised clinical trials with high risk of bias which included 710 patients demonstrated no significant effects of propylthiouracil versus placebo on all-cause mortality (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.66 to 1.30), liver-related mortality (RR 0.90, 95% CI 0.58 to 1.40), or complications of the liver disease. Although propylthiouracil was not associated with a significant increased risk of non-serious adverse events, there were occasional instances of serious adverse events such as leukopenia and generalised bullous eruption.
AUTHORS' CONCLUSIONS
We could not demonstrate any significant beneficial effect of propylthiouracil on all-cause mortality, liver-related mortality, liver complications, or liver histology of patients with alcoholic liver disease. Propylthiouracil was associated with adverse events. Confidence intervals were wide. Thus, the risk of random errors and systematic errors was high. Accordingly, there is no evidence for using propylthiouracil for alcoholic liver disease outside randomised clinical trials.
Topics: Antimetabolites; Cause of Death; Humans; Liver Diseases, Alcoholic; Propylthiouracil; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 21678335
DOI: 10.1002/14651858.CD002800.pub3 -
Nutrients Nov 2017In the last several decades, the genetic ability to taste the bitter compound, 6--propyltiouracil (PROP) has attracted considerable attention as a model for... (Review)
Review
In the last several decades, the genetic ability to taste the bitter compound, 6--propyltiouracil (PROP) has attracted considerable attention as a model for understanding individual differences in taste perception, and as an oral marker for food preferences and eating behavior that ultimately impacts nutritional status and health. However, some studies do not support this role. This review describes common factors that can influence the characterization of this phenotype including: (1) changes in taste sensitivity with increasing age; (2) gender differences in taste perception; and (3) effects of smoking and obesity. We suggest that attention to these factors during PROP screening could strengthen the associations between this phenotype and a variety of health outcomes ranging from variation in body composition to oral health and cancer risk.
Topics: Food Preferences; Genetic Variation; Humans; Propylthiouracil; Taste Perception; Taste Threshold
PubMed: 29168731
DOI: 10.3390/nu9121275