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EBioMedicine Feb 2022Calcium plays a role in a wide range of biological functions. Here we conducted a phenome-wide Mendelian randomisation (MR-PheWAS) analysis and a systematic review for...
BACKGROUND
Calcium plays a role in a wide range of biological functions. Here we conducted a phenome-wide Mendelian randomisation (MR-PheWAS) analysis and a systematic review for MR studies to comprehensively investigate the health effects of serum calcium.
METHODS
One-hundred and thirty genetic variants strongly associated with serum calcium levels were used as instrumental variables. A phenome-wide association analysis (PheWAS) was conducted to examine the associations of genetically predicted serum calcium with 1473 distinct phenotypes in the UK Biobank including 339,197 individuals. Observed associations in PheWAS were further tested for replication in two-sample MR replication analysis. A systematic review for MR studies on serum calcium was performed to synthesize the published evidence and compare with the current MR-PheWAS findings.
FINDINGS
Higher genetically predicted calcium levels were associated with decreased risk of 5 diseases in dermatologic and musculoskeletal systems and increased risk of 17 diseases in circulatory, digestive, endocrine, genitourinary and immune systems. Eight associations were replicated in two-sample MR analysis. These included decreased risk of osteoarthritis and increased risk of coronary artery disease, myocardial infarction, coronary atherosclerosis, hyperparathyroidism, disorder of parathyroid gland, gout, and calculus of kidney and ureter with increased serum calcium. Systematic review of 25 MR studies provided supporting evidence on five out of the eight disease outcomes, while the increased risk of gout, hyperparathyroidism and disorder of parathyroid gland were novel findings.
INTERPRETATION
This study found wide-ranged health effects of high serum calcium, which suggests that the benefits and adversities of strategies promoting calcium intake should be assessed.
FUNDING
ET is supported by a CRUK Career Development Fellowship (C31250/A22804). XL is supported by the Natural Science Fund for Distinguished Young Scholars of Zhejiang Province. SCL acknowledges research funding from the Swedish Heart Lung Foundation (Hjärt-Lungfonden, 20210351), the Swedish Research Council (Vetenskapsrådet, 2019-00977), and the Swedish Cancer Society (Cancerfonden).
Topics: Calcium; Genome-Wide Association Study; Humans; Mendelian Randomization Analysis; Phenomics; Phenotype; Polymorphism, Single Nucleotide
PubMed: 35134646
DOI: 10.1016/j.ebiom.2022.103865 -
Andrology Feb 2023Type 2 diabetes mellitus and pre-diabetes are associated with reduced circulating testosterone levels. However, the role of testosterone replacement therapy in these... (Review)
Review
BACKGROUND
Type 2 diabetes mellitus and pre-diabetes are associated with reduced circulating testosterone levels. However, the role of testosterone replacement therapy in these patients is still conflicting.
OBJECTIVES
To summarize and critically analyze available data on the possible effect of testosterone administration in men with glucose abnormalities.
MATERIALS AND METHODS
A comprehensive systematic review was performed. When available, meta-analytic data were preferred. To better analyze the relationship between testosterone and the pre-diabetes condition, a systematic analysis was performed and the data obtained with the latter search were used for a meta-analytic approach. Finally, clinical data derived from a consecutive series of 4682 patients seeking medical care for sexual dysfunction at the University of Florence were also considered.
RESULTS
Patients with impaired fasting glucose were characterized by a 3 nmol/L lower level of total testosterone when compared to controls. Similarly, impaired fasting glucose was associated with a 1.8-fold increased risk of hypogonadism, when compared to subjects with normal glucose levels. Waist circumference and body mass index resulted as being the best predictors of reduced total testosterone levels. Secondary hypogonadism was two times higher in subjects with impaired fasting glucose when compared to rates observed in the general population. Testosterone replacement therapy was able to improve body composition, insulin resistance, and glucose profile both in impaired fasting glucose and type 2 diabetes mellitus whereas its role on body weight, lipid profile, and sexual function was less evident.
DISCUSSION AND CONCLUSION
Weight loss and physical activities are able to improve both metabolic profile and testosterone levels. The combined approach of testosterone replacement therapy and lifestyle modifications could be suggested in symptomatic hypogonadal men to better motivate patients to perform physical activity which can eventually result in weight loss as well as metabolic profile and sexual function improvement. Whether or not these approaches can prevent the development of type 2 diabetes mellitus from pre-clinical conditions requires more studies.
Topics: Male; Humans; Testosterone; Diabetes Mellitus, Type 2; Prediabetic State; Hypogonadism; Weight Loss; Glucose; Hormone Replacement Therapy
PubMed: 36542412
DOI: 10.1111/andr.13367 -
Quantitative Imaging in Medicine and... Mar 2023Accident and Emergency Department (AED) is the frontline of providing emergency care in a hospital and research focusing on improving decision-makings and service level... (Review)
Review
BACKGROUND
Accident and Emergency Department (AED) is the frontline of providing emergency care in a hospital and research focusing on improving decision-makings and service level around AED has been driving a rising number of attentions in recent years. A retrospective review among the published papers shows that related research can be classified according to six planning modules: demand forecasting, days-off scheduling, shift scheduling, line-of-work construction, task assignment and staff assignment. As patient arrivals demand forecasts enable smooth AED operational planning and help decision-making, this article conducted a systematic review on the statistical modelling approaches aimed at predicting the volume of AED patients' arrival.
METHODS
We carried out a systematic review of AED patient arrivals prediction studies from 2004 to 2021. The Medline, ScienceDirect, and Scopus databases were searched. A two-step screening process was carried out based on the title and abstract or full text, and 35 of 1,677 articles were selected. Our methods and results follow the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. We categorise AED methods for modelling patient arrivals into four main classes: regression, time series, artificial intelligence and time series regression. Choice of prediction model, selection of factors and model performance are compared. Finally, we discuss the advantages and limitations of the models and suggest future research directions.
RESULTS
A total of 1,677 papers that fulfilled the initial searching criteria was obtained from the three databases. Based on the first exclusion criteria, 1,603 articles were eliminated. The remaining 74 full text articles were evaluated based on the second exclusion criteria. Finally, 35 articles were selected for full review. We find that the use of artificial intelligence-based model has risen in recent years, from the view of predictive model selection. The calendar-based factors are most commonly used compared with other types of dependent variables, from the view of dependent variable selection.
CONCLUSIONS
All AEDs are inherently different and different covariables may have different effects on patient arrivals. Certain factors may play a key role in one AED but not others. Based on results of meta-analysis, when modelling patient arrivals, it is essential to understand the actual AED situation and carefully select relevant dominating factors and the most suitable modelling method. Local calibration is also important to ensure good estimates.
PubMed: 36915315
DOI: 10.21037/qims-22-268 -
Pain Physician Mar 2017Of all the postsurgical pain conditions, thoracotomy pain poses a particular therapeutic challenge in terms of its prevalence, severity, and ensuing postoperative... (Review)
Review
BACKGROUND
Of all the postsurgical pain conditions, thoracotomy pain poses a particular therapeutic challenge in terms of its prevalence, severity, and ensuing postoperative morbidity. Multiple pain generators contribute to the severity of post-thoracotomy pain, and therefore a multimodal analgesic therapy is considered to be a necessary strategy. Along with opioids, thoracic epidural analgesia, and paravertebral blocks, N-Methyl-D-Aspartate (NMDA) receptor antagonists such as ketamine have been used as adjuvants to improve analgesia.
OBJECTIVE
We reviewed the evidence for the efficacy of intravenous and epidural administration of ketamine in acute post-thoracotomy pain management, and its effectiveness in reducing chronic post-thoracotomy pain.
STUDY DESIGN
Systematic literature review and an analytic study of a data subset were performed.
METHODS
We searched PubMed, Embase, and Cochrane reviews using the key terms "ketamine," "neuropathic pain," "postoperative," and "post-thoracotomy pain syndrome." The search was limited to human trials and included all studies published before January 2015. Data from animal studies, abstracts, and letters were excluded. All studies not available in the English language were excluded. The manuscript bibliographies were reviewed for additional related articles. We included randomized controlled trials and retrospective studies, while excluding individual case reports.
RESULTS
This systematic literature search yielded 15 randomized control trials evaluating the efficacy of ketamine in the treatment of acute post-thoracotomy pain; fewer studies assessed its effect on attenuating chronic post-thoracotomy pain. The majority of reviewed studies demonstrated that ketamine has efficacy in reduction of acute pain, but the evidence is limited on the long-term benefits of ketamine to prevent post-thoracotomy pain syndrome, regardless of the route of administration. A nested analytical study found there is a statistically significant reduction in acute post-thoracotomy pain with IV or epidural ketamine. However currently, the evidence for a role of ketamine as a preventative agent for chronic post-thoracotomy pain is insufficient due to the heterogeneity of the studies reviewed with regard to the route of administration, dosage, and outcome measures.
LIMITATIONS
The evidence for a role of ketamine as a preventative agent for chronic post-thoracotomy pain is insufficient due to the heterogeneity of the studies reviewed.
CONCLUSION
The majority of randomized controlled trials reviewed show no role for ketamine in attenuating or preventing post-thoracotomy pain syndrome at variable follow-up lengths. Therefore, additional research is warranted with consideration of risk factors and long-term follow-up for chronic post-thoracotomy pain though the evidence for benefit appears clear for acute post-thoracotomy pain.Key words: Ketamine, postoperative, thoracotomy pain, post thoracotomy pain syndrome, neuropathic pain.
Topics: Humans; Ketamine; Pain, Postoperative; Randomized Controlled Trials as Topic; Thoracotomy
PubMed: 28339431
DOI: No ID Found -
Translational Psychiatry Sep 2022Hyperthyroidism and clinical depression are common, and there is preliminary evidence of substantial comorbidity. The extent of the association in the general... (Meta-Analysis)
Meta-Analysis
Hyperthyroidism and clinical depression are common, and there is preliminary evidence of substantial comorbidity. The extent of the association in the general population, however, has not yet been estimated meta-analytically. Therefore we conducted this systematic review and meta-analysis (registered in PROSPERO: CRD42020164791). Until May 2020, Medline (via PubMed), PsycINFO, and Embase databases were systematically searched for studies on the association of hyperthyroidism and clinical depression, without language or date restrictions. Two reviewers independently selected epidemiological studies providing laboratory or ICD-based diagnoses of hyperthyroidism and diagnoses of depression according to operationalized criteria (e.g. DSM) or to cut-offs in established rating scales. All data, including study quality based on the Newcastle-Ottawa Scale, were independently extracted by two authors. Odds ratios for the association of clinical depression and hyperthyroidism were calculated in a DerSimonian-Laird random-effects meta-analysis. Out of 3372 papers screened we selected 15 studies on 239 608 subjects, with 61% women and a mean age of 50. Relative to euthyroid individuals, patients with hyperthyroidism had a higher chance of being diagnosed with clinical depression: OR 1.67 ([95% CI: 1.49; 1.87], I: 6%; prediction interval: 1.40 to 1.99), a result supported in a number of sensitivity and subgroup analyses. The OR was slightly less pronounced for subclinical as opposed to overt hyperthyroidism (1.36 [1.06; 1.74] vs. 1.70 [1.49; 1.93]). This comorbidity calls for clinical awareness and its reasons need investigation and may include neurobiological mechanisms, common genetic vulnerability and a generally heightened risk for clinical depression in patients with chronic somatic disorders.
Topics: Comorbidity; Depression; Depressive Disorder, Major; Female; Humans; Hyperthyroidism; Male; Middle Aged
PubMed: 36064836
DOI: 10.1038/s41398-022-02121-7 -
International Journal of Molecular... May 2023Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with unknown etiology. Many metabolic alterations occur during ALS progress and can be used as a... (Meta-Analysis)
Meta-Analysis Review
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with unknown etiology. Many metabolic alterations occur during ALS progress and can be used as a method of pre-diagnostic and early diagnosis. Dyslipidemia is one of the physiological changes observed in numerous ALS patients. The aim of this study is to analyze the possible relationship between the rate of disease progression (functional rating scale (ALS-FRS)) and the plasma lipid levels at the early stage of ALS. A systematic review was carried out in July 2022. The search equation was "Triglycerides AND amyotrophic lateral sclerosis" and its variants. Four meta-analyses were performed. Four studies were included in the meta-analysis. No significant differences were observed between the lipid levels (total cholesterol, triglycerides, HDL cholesterol, and LDL cholesterol) and the ALS-FRS score at the onset of the disease. Although the number of studies included in this research was low, the results of this meta-analytic study suggest that there is no clear relationship between the symptoms observed in ALS patients and the plasma lipid levels. An increase in research, as well as an expansion of the geographical area, would be of interest.
Topics: Humans; Amyotrophic Lateral Sclerosis; Neurodegenerative Diseases; Triglycerides; Cholesterol, HDL; Cholesterol, LDL
PubMed: 37240018
DOI: 10.3390/ijms24108675 -
Environmental Health : a Global Access... May 2023Per- and polyfluoroalkyl substances (PFAS) are used for their properties such as stain and water resistance. The substances have been associated with adverse health... (Review)
Review
Per- and polyfluoroalkyl substances (PFAS) are used for their properties such as stain and water resistance. The substances have been associated with adverse health outcomes in both pregnant mothers and infants, including pre-eclampsia and low birthweight. A growing body of research suggests that PFAS are transferred from mother to fetus through the placenta, leading to in utero exposure. A systematic review was performed using the PubMed database to search for studies evaluating determinants of PFAS concentrations in blood matrices of pregnant mothers and neonates shortly after birth. Studies were included in this review if an observational study design was utilized, exposure to at least one PFAS analyte was measured, PFAS were measured in maternal or neonatal matrices, at least one determinant of PFAS concentrations was assessed, and results such as beta estimates were provided. We identified 35 studies for inclusion in the review and evaluated the PFAS and determinant relationships among the factors collected in these studies. Parity, breastfeeding history, maternal race and country of origin, and household income had the strongest and most consistent evidence to support their roles as determinants of certain PFAS concentrations in pregnant mothers. Reported study findings on smoking status, alcohol consumption, and pre-pregnancy body mass index (BMI) suggest that these factors are not important determinants of PFAS concentrations in pregnant mothers or neonates. Further study into informative factors such as consumer product use, detailed dietary information, and consumed water sources as potential determinants of maternal or neonatal PFAS concentrations is needed. Research on determinants of maternal or neonatal PFAS concentrations is critical to estimate past PFAS exposure, build improved exposure models, and further our understanding on dose-response relationships, which can influence epidemiological studies and risk assessment evaluations. Given the potential for adverse outcomes in pregnant mothers and neonates exposed to PFAS, it is important to identify and understand determinants of maternal and neonatal PFAS concentrations to better implement public health interventions in these populations.
Topics: Female; Pregnancy; Infant; Infant, Newborn; Humans; Body Mass Index; Fetus; Mothers; Placenta; Fluorocarbons; Observational Studies as Topic
PubMed: 37161484
DOI: 10.1186/s12940-023-00992-x -
Sports Medicine (Auckland, N.Z.) Aug 2022Carbohydrates are an important fuel for optimal exercise performance during moderate- and high-intensity exercise; however, carbohydrate ingestion during high-intensity... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Carbohydrates are an important fuel for optimal exercise performance during moderate- and high-intensity exercise; however, carbohydrate ingestion during high-intensity exercise may cause gastrointestinal upset. A carbohydrate oral rinse is an alternative method to improve exercise performance in moderate- to high-intensity exercise with a duration of 30-75 min. This is the first systematic review and meta-analysis to comprehensively examine the isolated effect of maltodextrin-based rinsing on exercise performance.
OBJECTIVE
The objective of this review was to establish the effect of a maltodextrin-based carbohydrate oral rinse on exercise performance across various modes of exercise. Furthermore, a secondary objective was to determine the effects of moderators [(1) participant characteristics; (2) oral rinse protocols; (3) exercise protocol (i.e. cycling, running etc.) and (4) fasting] on exercise performance while using a maltodextrin-based, carbohydrate oral rinse.
METHODS
Five databases (MEDLINE, PsycINFO, Embase, SPORTDiscus and Global Health) were systematically searched for articles up to March 2021 and screened using Covidence (a systematic review management tool). A random effects robust meta-analysis and subgroup analyses were performed using Stata Statistical Software: Release 16.
RESULTS
Thirty-five articles met the inclusion criteria and were included in the systematic review; 34 of these articles were included in the meta-analysis. When using a conventional meta-analytic approach, overall, a carbohydrate oral rinse improved exercise performance in comparison with a placebo (SMD = 0.15, 95% CI 0.04, 0.27; p = 0.01). Furthermore, when implementing an adjusted, conservative, random effects meta-regression model using robust variance estimation, overall, compared with placebo, a carbohydrate oral rinse demonstrated evidence of improving exercise performance with a small effect size (SMD = 0.17, 95% CI - 0.01, 0.34; p = 0.051).
CONCLUSION
This systematic review and meta-analysis demonstrates that a maltodextrin-based carbohydrate oral rinse can improve exercise performance. When comparing the two meta-analytic approaches, although non-significant, the more robust, adjusted, random effects meta-regression model demonstrated some evidence of a maltodextrin-based carbohydrate oral rinse improving exercise performance overall.
Topics: Bicycling; Exercise; Humans; Mouthwashes; Polysaccharides
PubMed: 35239154
DOI: 10.1007/s40279-022-01658-3 -
Ageing Research Reviews Dec 2023Alterations in nitric oxide (NO) synthesis have been reported in Alzheimer's disease and vascular dementia. However, as the measurement of NO in biological samples is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Alterations in nitric oxide (NO) synthesis have been reported in Alzheimer's disease and vascular dementia. However, as the measurement of NO in biological samples is analytically challenging, alternative, stable circulatory biomarkers of NO synthesis may be useful to unravel new pathophysiological mechanisms and treatment targets in dementia.
METHODS
We conducted a systematic review and meta-analysis of the circulating concentrations of arginine metabolites linked to NO synthesis, arginine, citrulline, asymmetric (ADMA) and symmetric (SDMA) dimethylarginine, and ornithine, in Alzheimer's disease and vascular dementia. We searched for relevant studies in PubMed, Scopus, and Web of Science from inception to the 31st of May 2023. The JBI checklist and GRADE were used to assess the risk of bias and the certainty of evidence, respectively.
RESULTS
In 14 selected studies, there were no significant between-group differences in arginine and ornithine concentrations. By contrast, compared to controls, patients with dementia had significantly higher ADMA (standard mean difference, SMD=0.62, 95% CI 0.06-1.19, p = 0.029), SDMA (SMD=0.70, 95% CI 0.34-1.35, p<0.001), and citrulline concentrations (SMD=0.50, 95% CI 0.08-0.91, p = 0.018). In subgroup analysis, the effect size was significantly associated with treatment with cholinesterase inhibitors and/or antipsychotics for ADMA, and underlying disorder (Alzheimer's disease), study continent, and analytical method for citrulline.
CONCLUSION
Alterations in ADMA, SDMA, and citrulline, biomarkers of NO synthesis, may be useful to investigate the pathophysiology of different forms of dementia and identify novel therapeutic strategies. (PROSPERO registration number: CRD42023439528).
Topics: Humans; Alzheimer Disease; Dementia, Vascular; Citrulline; Arginine; Biomarkers; Ornithine
PubMed: 38007048
DOI: 10.1016/j.arr.2023.102139 -
Life (Basel, Switzerland) Dec 2022Metagenomic Next Generation Sequencing (mNGS) allows the evaluation of complex microbial communities, avoiding isolation and cultivation of each microbial species, and... (Review)
Review
Metagenomic Next Generation Sequencing (mNGS) allows the evaluation of complex microbial communities, avoiding isolation and cultivation of each microbial species, and does not require prior knowledge of the microbial sequences present in the sample. Applications of mNGS include virome characterization, new virus discovery and full-length viral genome reconstruction, either from virus preparations enriched in culture or directly from clinical and environmental specimens. Here, we systematically reviewed studies that describe novel virus identification through mNGS from samples of different origin (plant, animal and environment). Without imposing time limits to the search, 379 publications were identified that met the search parameters. Sample types, geographical origin, enrichment and nucleic acid extraction methods, sequencing platforms, bioinformatic analytical steps and identified viral families were described. The review highlights mNGS as a feasible method for novel virus discovery from samples of different origins, describes which kind of heterogeneous experimental and analytical protocols are currently used and provides useful information such as the different commercial kits used for the purification of nucleic acids and bioinformatics analytical pipelines.
PubMed: 36556413
DOI: 10.3390/life12122048