scholarly journals Genetic Susceptibility to Drug Teratogenicity: A Systematic Literature Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Julia do Amaral Gomes ◽  
Emilie Willoch Olstad ◽  
Thayne Woycinck Kowalski ◽  
Kristina Gervin ◽  
Fernanda Sales Luiz Vianna ◽  
...  
Keyword(s):  
Genetic Susceptibility ◽  
Congenital Anomalies ◽  
Current Knowledge ◽  
Data Extraction ◽  
Extensive Literature ◽  
Clinical Implementation ◽  
Perinatal Complications ◽  
Neurodevelopmental Outcomes ◽  
Drug Classes ◽  
Sequencing Studies

Since the 1960s, drugs have been known to cause teratogenic effects in humans. Such teratogenicity has been postulated to be influenced by genetics. The aim of this review was to provide an overview of the current knowledge on genetic susceptibility to drug teratogenicity in humans and reflect on future directions within the field of genetic teratology. We focused on 12 drugs and drug classes with evidence of teratogenic action, as well as 29 drugs and drug classes with conflicting evidence of fetal safety in humans. An extensive literature search was performed in the PubMed and EMBASE databases using terms related to the drugs of interest, congenital anomalies and fetal development abnormalities, and genetic variation and susceptibility. A total of 29 studies were included in the final data extraction. The eligible studies were published between 1999 and 2020 in 10 different countries, and comprised 28 candidate gene and 1 whole-exome sequencing studies. The sample sizes ranged from 20 to 9,774 individuals. Several drugs were investigated, including antidepressants (nine studies), thalidomide (seven studies), antiepileptic drugs (five studies), glucocorticoids (four studies), acetaminophen (two studies), and sex hormones (estrogens, one study; 17-alpha hydroxyprogesterone caproate, one study). The main neonatal phenotypic outcomes included perinatal complications, cardiovascular congenital anomalies, and neurodevelopmental outcomes. The review demonstrated that studies on genetic teratology are generally small, heterogeneous, and exhibit inconsistent results. The most convincing findings were genetic variants in SLC6A4, MTHFR, and NR3C1, which were associated with drug teratogenicity by antidepressants, antiepileptics, and glucocorticoids, respectively. Notably, this review demonstrated the large knowledge gap regarding genetic susceptibility to drug teratogenicity, emphasizing the need for further efforts in the field. Future studies may be improved by increasing the sample size and applying genome-wide approaches to promote the interpretation of results. Such studies could support the clinical implementation of genetic screening to provide safer drug use in pregnant women in need of drugs.

scholarly journals Neonatal posthemorrhagic hydrocephalus from prematurity: pathophysiology and current treatment concepts

2012 ◽  
Vol 9 (3) ◽  
pp. 242-258 ◽  
Author(s):  
Shenandoah Robinson
Keyword(s):  
Preterm Infants ◽  
Current Knowledge ◽  
Perioperative Complications ◽  
Current Treatment ◽  
Neurosurgical Procedures ◽  
Perinatal Complications ◽  
Neurodevelopmental Outcomes ◽  
Posthemorrhagic Hydrocephalus ◽  
Multicenter Trials ◽  
Neonatal Icu

Object Preterm infants are at risk for perinatal complications, including germinal matrix–intraventricular hemorrhage (IVH) and subsequent posthemorrhagic hydrocephalus (PHH). This review summarizes the current understanding of the epidemiology, pathophysiology, management, and outcomes of IVH and PHH in preterm infants. Methods The MEDLINE database was systematically searched using terms related to IVH, PHH, and relevant neurosurgical procedures to identify publications in the English medical literature. To complement information from the systematic search, pertinent articles were selected from the references of articles identified in the initial search. Results This review summarizes the current knowledge regarding the epidemiology and pathophysiology of IVH and PHH, primarily using evidence-based studies. Advances in obstetrics and neonatology over the past few decades have contributed to a marked improvement in the survival of preterm infants, and neurological morbidity is also starting to decrease. The incidence of IVH is declining, and the incidence of PHH will likely follow. Currently, approximately 15% of preterm infants who suffer severe IVH will require permanent CSF diversion. The clinical presentation and surgical management of symptomatic PHH with temporary ventricular reservoirs (ventricular access devices) and ventriculosubgaleal shunts and permanent ventriculoperitoneal shunts are discussed. Preterm infants who develop PHH that requires surgical treatment remain at high risk for other related neurological problems, including cerebral palsy, epilepsy, and cognitive and behavioral delay. This review highlights numerous opportunities for further study to improve the care of these children. Conclusions A better grasp of the pathophysiology of IVH is beginning to impact the incidence of IVH and PHH. Neonatologists conduct rigorous Class I and II studies to advance the outcomes of preterm infants. The need for well-designed multicenter trials is essential because of the declining incidence of IVH and PHH, variations in referral patterns, and neonatal ICU and neurosurgical management. Well-designed multicenter trials will eventually produce evidence to enable neurosurgeons to provide their smallest, most vulnerable patients with the best practices to minimize perioperative complications and permanent shunt dependence, and most importantly, optimize long-term neurodevelopmental outcomes.

Impact of surgery timing for craniosynostosis on neurodevelopmental outcomes: a systematic review

2019 ◽  
Vol 23 (4) ◽  
pp. 442-454 ◽  
Author(s):  
Rachel Mandela ◽  
Maggie Bellew ◽  
Paul Chumas ◽  
Hannah Nash
Keyword(s):  
Systematic Review ◽  
Beneficial Effect ◽  
Data Extraction ◽  
Sociodemographic Factors ◽  
Future Research ◽  
Neurodevelopmental Outcomes ◽  
Age At Surgery ◽  
Data Extraction Form ◽  
Surgery Timing ◽  
Anesthetic Exposure

OBJECTIVEThere are currently no guidelines for the optimum age for surgical treatment of craniosynostosis. This systematic review summarizes and assesses evidence on whether there is an optimal age for surgery in terms of neurodevelopmental outcomes.METHODSThe databases MEDLINE, PsycINFO, CINAHL, Embase + Embase Classic, and Web of Science were searched between October and November 2016 and searches were repeated in July 2017. According to PICO (participants, intervention, comparison, outcome) criteria, studies were included that focused on: children diagnosed with nonsyndromic craniosynostosis, aged ≤ 5 years at time of surgery; corrective surgery for nonsyndromic craniosynostosis; comparison of age-at-surgery groups; and tests of cognitive and neurodevelopmental postoperative outcomes. Studies that did not compare age-at-surgery groups (e.g., those employing a correlational design alone) were excluded. Data were double-extracted by 2 authors using a modified version of the Cochrane data extraction form.RESULTSTen studies met the specified criteria; 5 found a beneficial effect of earlier surgery, and 5 did not. No study found a beneficial effect of later surgery. No study collected data on length of anesthetic exposure and only 1 study collected data on sociodemographic factors.CONCLUSIONSIt was difficult to draw firm conclusions from the results due to multiple confounding factors. There is some inconclusive evidence that earlier surgery is beneficial for patients with sagittal synostosis. The picture is even more mixed for other subtypes. There is no evidence that later surgery is beneficial. The authors recommend that future research use agreed-upon parameters for: age-at-surgery cut-offs, follow-up times, and outcome measures.

scholarly journals Medical Students’ Knowledge and Perception of Deep Brain Stimulation

2021 ◽  
Vol 8 ◽  
pp. 238212052198997
Author(s):  
Brian F Saway ◽  
Sanaz Monjazeb ◽  
Kerilyn Godbe ◽  
Tessa Anwyll ◽  
Anita Kablinger ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Medical Students ◽  
Brain Stimulation ◽  
Treatment Modality ◽  
Current Knowledge ◽  
Clinical Implementation ◽  
Self Assessment ◽  
Clinical Exposure ◽  
Effective Treatment Modality ◽  
Deep Brain

Background: Deep brain stimulation (DBS) is a well-established neurosurgical procedure commonly used in movement and psychiatric disorders. Its widespread clinical implementation, however, may not be commensurate with medical education. No current assessment of medical student’s understanding of DBS as a treatment option for indicated conditions is available, potentially threatening the availability of DBS to future patients. The aim of the present study is to explore the current knowledge and attitudes of medical students toward DBS as a treatment modality. Methods: A total of 65 medical students at Virginia Tech Carilion School of Medicine were surveyed regarding their knowledge of DBS. The survey consisted of a 25-item questionnaire including a demographic section and 3 separate inventories designed to assess bias, knowledge, and self-assessment of knowledge specific to DBS therapy. Students in pre-clinical and clinical years were analyzed separately to describe changes in knowledge or attitude associated with clinical exposure to DBS. Comparisons were analyzed using t tests, ANOVA, and Pearson correlations. Results: Of surveyed students, 36% were unsure of the FDA approval status of DBS treatment; 65% of students believed they had not been adequately educated about DBS and its utility; and 10.6% of students believed that DBS is likely associated with severe adverse effects and/or brain damage. The overall baseline attitudes of students toward DBS were positive. There was no observed difference between surveyed pre-clinical and clinical students, highlighting a lack of exposure throughout the clinical years of medical school education. Conclusion: Although DBS is an effective treatment modality for various conditions, current education is non-commensurate with its application, which can negatively impact awareness and understanding for its implications by medical professionals. In order to better serve patients who may benefit from DBS, medical curricula must change to educate future physicians on the benefit of this intervention.

scholarly journals Genetic susceptibility, elevated blood pressure and risk of atrial fibrillation

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Nazarzadeh ◽  
A Pinho-Gomes ◽  
Z Bidel ◽  
D Canoy ◽  
A Dehghan ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Blood Pressure ◽  
Genetic Susceptibility ◽  
Genetic Risk ◽  
Funding Source ◽  
Individual Participant Data ◽  
Elevated Blood ◽  
Uk Biobank ◽  
Drug Classes ◽  
Individual Participant

Abstract Background Whether elevated blood pressure (BP) is a modifiable risk factor for atrial fibrillation (AF) is not established. Purpose We tested (1) whether the association between BP and risk of AF is causal, (2) whether it varies according to individual's genetic susceptibility for AF, and (3) the extent to which specific BP-lowering drugs are expected to reduce this risk. Methods First, causality of association was assessed through two-sample Mendelian Randomization (MR), using data from two independent genome-wide association studies that included a total of one million European population. Second, UK Biobank individual participant data of 329,237 participants at baseline was used to study the effect of BP on AF according to genetic susceptibility of developing AF. Third, a possible treatment effect with BP-lowering drug classes on AF risk was predicted through genetic variants in druggable genes that code proteins related to the function of each drug class. Estimated drug effects were compared with effects on incident coronary heart disease, for which direct trial evidence exists. Results The two-sample MR analysis indicated that on average each 10-mm Hg increment in systolic BP increased the risk of AF (odds ratio [OR]: 1.23 [1.11 to 1.36]). This association was replicated in the UK biobank using individual participant data. However, in a further genetic risk-stratified analysis, there was evidence for a linear gradient in the relative effects of systolic BP on AF; while there was no conclusive evidence of an effect in those with low genetic risk, a strong effect was observed among those with high genetic susceptibility for AF (Figure). The indirect comparison of predicted treatment effects using genetic proxies for three main drug classes (angiotensin-converting enzyme inhibitors, beta-blockers and calcium channel blockers) suggested similar average effects for prevention of atrial fibrillation and coronary heart disease. Conclusions The association between elevated BP and higher risk of AF is likely to be causal, suggesting that BP-lowering treatment may be effective in AF prevention. However, average effects masked clinically important variations, with a more pronounced effect in individuals with high genetic susceptibility. Figure 1 Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): British Heart Foundation

Drug-Induced Restless Legs Syndrome

2018 ◽  
Vol 52 (7) ◽  
pp. 662-672 ◽  
Author(s):  
Edna Patatanian ◽  
Melanie K. Claborn
Keyword(s):  
Restless Legs Syndrome ◽  
English Language ◽  
Case Reports ◽  
Data Extraction ◽  
Case Series ◽  
Predisposing Factors ◽  
Drug Induced ◽  
Restless Legs ◽  
Drug Classes ◽  
Study Selection

Objective: To review the literature on drug-induced restless legs syndrome (DI-RLS). Data Sources: The review included a search for English-language literature from 1966 to December 2017 in the MEDLINE, PubMed, and Ovid databases using the following search terms: restless legs syndrome (RLS), periodic limb movement, adverse effects, and drug-induced. In addition, background articles on the pathophysiology, etiology, and epidemiology of RLS were retrieved. Bibliographies of relevant articles were reviewed for additional citations. Study Selection and Data Extraction: All case reports, case series, and review articles of DI-RLS were identified and analyzed. There were only a small number of controlled clinical trials, and most data were from case reports and case series. Results: Several drugs and drug classes have been implicated in DI-RLS, with antidepressants, antipsychotics, and antiepileptics having the most evidence. In addition, RLS may be linked with a number of disorders or underlying predisposing factors as well. Conclusions: The prevalence of RLS is variable and ranges from 3% to 19% in the general population. There are many predisposing factors to RLS, but an emerging body of evidence suggests that there is an association between numerous drugs and RLS.

Molecular Changes in the Dorsal Root Ganglion during the Late Phase of Peripheral Nerve Injury–induced Pain in Rodents: A Systematic Review

2021 ◽  
Author(s):  
Mehrman Chalaki ◽  
Luis J. Cruz ◽  
Sabien G. A. van Neerven ◽  
Joost Verhaagen ◽  
Albert Dahan ◽  
...  
Keyword(s):  
Dorsal Root Ganglion ◽  
Messenger Rna ◽  
Dorsal Root ◽  
Current Knowledge ◽  
Late Phase ◽  
Molecular Changes ◽  
Genomic Changes ◽  
Protein Levels ◽  
Fundamental Understanding ◽  
Sequencing Studies

The dorsal root ganglion is widely recognized as a potential target to treat chronic pain. A fundamental understanding of quantitative molecular and genomic changes during the late phase of pain is therefore indispensable. The authors performed a systematic literature review on injury-induced pain in rodent dorsal root ganglions at minimally 3 weeks after injury. So far, slightly more than 300 molecules were quantified on the protein or messenger RNA level, of which about 60 were in more than one study. Only nine individual sequencing studies were performed in which the most up- or downregulated genes varied due to heterogeneity in study design. Neuropeptide Y and galanin were found to be consistently upregulated on both the gene and protein levels. The current knowledge regarding molecular changes in the dorsal root ganglion during the late phase of pain is limited. General conclusions are difficult to draw, making it hard to select specific molecules as a focus for treatment.

scholarly journals P071: Artificial intelligence in emergency medicine: A scoping review

CJEM ◽  
2020 ◽  
Vol 22 (S1) ◽  
pp. S90-S90
Author(s):  
A. Kirubarajan ◽  
A. Taher ◽  
S. Khan ◽  
S. Masood
Keyword(s):  
Artificial Intelligence ◽  
Emergency Medicine ◽  
Language Processing ◽  
Scoping Review ◽  
Clinical Decision Making ◽  
Data Extraction ◽  
A Priori ◽  
Clinical Decision ◽  
Hospital Environment ◽  
Clinical Implementation

Introduction: The study of artificial intelligence (AI) in medicine has become increasingly popular over the last decade. The emergency department (ED) is uniquely situated to benefit from AI due to its power of diagnostic prediction, and its ability to continuously improve with time. However, there is a lack of understanding of the breadth and scope of AI applications in emergency medicine, and evidence supporting its use. Methods: Our scoping review was completed according to PRISMA-ScR guidelines and was published a priori on Open Science Forum. We systematically searched databases (Medline-OVID, EMBASE, CINAHL, and IEEE) for AI interventions relevant to the ED. Study selection and data extraction was performed independently by two investigators. We categorized studies based on type of AI model used, location of intervention, clinical focus, intervention sub-type, and type of comparator. Results: Of the 1483 original database citations, a total of 181 studies were included in the scoping review. Inter-rater reliability for study screening for titles and abstracts was 89.1%, and for full-text review was 77.8%. Overall, we found that 44 (24.3%) studies utilized supervised learning, 63 (34.8%) studies evaluated unsupervised learning, and 13 (7.2%) studies utilized natural language processing. 17 (9.4%) studies were conducted in the pre-hospital environment, with the remainder occurring either in the ED or the trauma bay. The majority of interventions centered around prediction (n = 73, 40.3%). 48 studies (25.5%) analyzed AI interventions for diagnosis. 23 (12.7%) interventions focused on diagnostic imaging. 89 (49.2%) studies did not have a comparator to their AI intervention. 63 (34.8%) studies used statistical models as a comparator, 19 (10.5%) of which were clinical decision making tools. 15 (8.3%) studies used humans as comparators, with 12 of the 15 (80%) studies showing superiority in favour of the AI intervention when compared to a human. Conclusion: AI-related research is rapidly increasing in emergency medicine. AI interventions are heterogeneous in both purpose and design, but primarily focus on predictive modeling. Most studies do not involve a human comparator and lack information on patient-oriented outcomes. While some studies show promising results for AI-based interventions, there remains uncertainty regarding their superiority over standard practice, and further research is needed prior to clinical implementation.

scholarly journals BARIATRIC SURGERY AND BINGE EATING DISORDER: SHOULD SURGEONS CARE ABOUT IT? A LITERATURE REVIEW OF PREVALENCE AND ASSESSMENT TOOLS

2019 ◽  
Vol 56 (1) ◽  
pp. 55-60 ◽  
Author(s):  
Beatriz H TESS ◽  
Letícia MAXIMIANO-FERREIRA ◽  
Denis PAJECKI ◽  
Yuan-Pang WANG
Keyword(s):  
Bariatric Surgery ◽  
Eating Disorder ◽  
Binge Eating ◽  
Binge Eating Disorder ◽  
Current Knowledge ◽  
Data Extraction ◽  
Patient Characteristics ◽  
Assessment Tools ◽  
Clinical Interviews ◽  
Study Heterogeneity

ABSTRACT BACKGROUND: Eating pathologies among bariatric surgery candidates are common and associated with adverse surgical outcomes, including weight regain and low quality of life. However, their assessment is made difficult by the great variety and inconsistent use of standardized measures. OBJECTIVE: The purpose of this review was to synthesize current knowledge on the prevalence of binge eating disorder (BED) in presurgical patients and to make a critical appraisal of assessment tools for BED. METHODS: A search was conducted on PubMed, Scopus, and Web of Science databases from January 1994 to March 2017. Data were extracted, tabulated and summarized using a narrative approach. RESULTS: A total of 21 observational studies were reviewed for data extraction and analysis. Prevalence of BED in bariatric populations ranged from 2% to 53%. Considerable variation in patient characteristics and in BED assessment measures was evident among the studies. In addition, several methodological weaknesses were recognized in most of the studies. Ten different psychometric instruments were used to assess BED. Clinical interviews were used in only 12 studies, though this is the preferred tool to diagnose BED. CONCLUSION: Study heterogeneity accounted for the variability of the results from different centers and methodological flaws such as insufficient sample size and selection bias impaired the evidence on the magnitude of BED in surgical settings. For the sake of comparability and generalizability of the findings in future studies, researchers must recruit representative samples of treatment-seeking candidates for bariatric surgery and systematically apply standard instruments for the assessment of BED.

Corticosteroids in Tuberculosis

1996 ◽  
Vol 30 (11) ◽  
pp. 1298-1303 ◽  
Author(s):  
Jennifer R Cisneros ◽  
Kim M Murray
Keyword(s):  
Literature Review ◽  
Corticosteroid Therapy ◽  
Case Reports ◽  
Data Extraction ◽  
Individual Case ◽  
Extensive Literature ◽  
Concomitant Disease ◽  
Rapid Reduction ◽  
Medline Search ◽  
Additional Information

OBJECTIVE: TO examine the effects of corticosteroids used for concomitant disease states in patients with latent or active tuberculosis (TB). The role of corticosteroids in the treatment of extrapulmonary TB is also discussed. DATA SOURCES: A MEDLINE search was conducted for the years 1953-1995. The International Pharmaceutical Abstracts service was also used to conduct an extensive literature review. In addition, relevant articles were cross-referenced to screen for additional information. STUDY SELECTION/DATA EXTRACTION: During the literature review, emphasis was placed on human studies and individual case reports. DATA SYNTHESIS: The resurgence of TB in this decade has affected many populations, especially immunocompromised patients. These patients may need corticosteroid therapy for various concomitant diseases that might predispose a patient to develop primary TB infection or reactivate latent TB infection. In appropriate patients, prophylaxis with isoniazid is recommended. Corticosteroid therapy may benefit patients with some forms of extrapulmonary TB. After steroid therapy, improved survival and more rapid reduction of tuberculous symptoms have been noted in cases of tuberculous pleurisy, endobronchial TB, tuberculous meningitis, and tuberculous pericarditis. Corticosteroids may also be useful in controlling both fever and hypersensitivity reactions in pulmonary and extrapulmonary TB, although not routinely used for this purpose. CONCLUSIONS: Corticosteroids may play an important role in TB infection by promoting reactivation of latent infection. Corticosteroids may modify symptoms of some forms of extrapulmonary TB, although randomized, placebo-controlled studies are needed before corticosteroids will have a definitive place in the standard therapy of TB.

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