scholarly journals The Role of Mitochondrial DNA Variation in Drug Response: A Systematic Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Samantha W. Jones ◽  
Amy L. Ball ◽  
Amy E. Chadwick ◽  
Ana Alfirevic

Background: The triad of drug efficacy, toxicity and resistance underpins the risk-benefit balance of all therapeutics. The application of pharmacogenomics has the potential to improve the risk-benefit balance of a given therapeutic via the stratification of patient populations based on DNA variants. A growth in the understanding of the particulars of the mitochondrial genome, alongside the availability of techniques for its interrogation has resulted in a growing body of literature examining the impact of mitochondrial DNA (mtDNA) variation upon drug response.Objective: To critically evaluate and summarize the available literature, across a defined period, in a systematic fashion in order to map out the current landscape of the subject area and identify how the field may continue to advance.Methods: A systematic review of the literature published between January 2009 and December 2020 was conducted using the PubMed database with the following key inclusion criteria: reference to specific mtDNA polymorphisms or haplogroups, a core objective to examine associations between mtDNA variants and drug response, and research performed using human subjects or human in vitro models.Results: Review of the literature identified 24 articles reporting an investigation of the association between mtDNA variant(s) and drug efficacy, toxicity or resistance that met the key inclusion criteria. This included 10 articles examining mtDNA variations associated with antiretroviral therapy response, 4 articles examining mtDNA variants associated with anticancer agent response and 4 articles examining mtDNA variants associated with antimicrobial agent response. The remaining articles covered a wide breadth of medications and were therefore grouped together and referred to as “other.”Conclusions: Investigation of the impact of mtDNA variation upon drug response has been sporadic to-date. Collective assessment of the associations identified in the articles was inconclusive due to heterogeneous methods and outcomes, limited racial/ethnic groups, lack of replication and inadequate statistical power. There remains a high degree of idiosyncrasy in drug response and this area has the potential to explain variation in drug response in a clinical setting, therefore further research is likely to be of clinical benefit.

Pharmacy ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 80
Author(s):  
Jéssica José ◽  
Biljana Cvetkovski ◽  
Vicky Kritikos ◽  
Rachel Tan ◽  
Sinthia Bosnic-Anticevich ◽  
...  

Pharmacists have a valuable role in the management of allergic rhinitis (AR) at the community pharmacy level. This role has been reported extensively in numerous papers. However, a systematic review of the available literature and a comprehensive analysis of the outcomes has not been published. This systematic review aimed to evaluate the impact of interventions developed by pharmacists on clinical AR outcomes. A thorough search was performed in three electronic databases, including studies published between January 2000 and June 2019. After the selection process, only three articles met the inclusion criteria and were further analysed. Despite the scarcity of the available studies, in all of them was clear that the pharmacist plays a pivotal role in the management of AR, significantly improving the patients’ quality of life and symptom control. This systematic review also stresses the utmost importance to investigate and report practices and interventions developed by pharmacists using measurable outcomes.


2017 ◽  
Vol 42 (5) ◽  
pp. E2 ◽  
Author(s):  
Jacob R. Joseph ◽  
Brandon W. Smith ◽  
Xilin Liu ◽  
Paul Park

OBJECTIVESurgical robotics has demonstrated utility across the spectrum of surgery. Robotics in spine surgery, however, remains in its infancy. Here, the authors systematically review the evidence behind robotic applications in spinal instrumentation.METHODSThis systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Relevant studies (through October 2016) that reported the use of robotics in spinal instrumentation were identified from a search of the PubMed database. Data regarding the accuracy of screw placement, surgeon learning curve, radiation exposure, and reasons for robotic failure were extracted.RESULTSTwenty-five studies describing 2 unique robots met inclusion criteria. Of these, 22 studies evaluated accuracy of spinal instrumentation. Although grading of pedicle screw accuracy was variable, the most commonly used method was the Gertzbein and Robbins system of classification. In the studies using the Gertzbein and Robbins system, accuracy (Grades A and B) ranged from 85% to 100%. Ten studies evaluated radiation exposure during the procedure. In studies that detailed fluoroscopy usage, overall fluoroscopy times ranged from 1.3 to 34 seconds per screw. Nine studies examined the learning curve for the surgeon, and 12 studies described causes of robotic failure, which included registration failure, soft-tissue hindrance, and lateral skiving of the drill guide.CONCLUSIONSRobotics in spine surgery is an emerging technology that holds promise for future applications. Surgical accuracy in instrumentation implanted using robotics appears to be high. However, the impact of robotics on radiation exposure is not clear and seems to be dependent on technique and robot type.


2021 ◽  
Vol 6 (2) ◽  
pp. 262-287
Author(s):  
Yvette D. Hyter

Purpose Maltreatment is a threat to child health and well-being and negatively influences all aspects of development, including language. Less seems to be known about the consequences that maltreatment has on social pragmatic communication. A systematic review of the literature was performed to summarize existing empirical research on complex trauma (the impact of maltreatment, including abuse and neglect, in the caregiving system) on social pragmatic communication of children and youth. The goal of this review article was to review the empirical evidence of the association between maltreatment and social pragmatic communication profiles of children. Method Research articles published between 1974, when the first comprehensive law of child protection was enacted, and 2020 were reviewed. Seven electronic databases were used to conduct the search for literature using several combined concepts related to social pragmatic communication and maltreatment. The inclusion criteria were that articles addressed any form of maltreatment, included participants aged 18 years or younger, and primarily focused on the impact of maltreatment on social pragmatic communication and that their method and findings were based on an experimental study. Studies were excluded if they were written in a language other than English, focused on adults, did not include the social pragmatic communication and maltreatment concepts, were a systematic review or meta-analysis, or were a theoretical rather than experimental study. A modified version of the Primary Research Appraisal Tool was used to determine key characteristics of each article. Results Thirty-eight articles met inclusion criteria for this study. Findings of these studies provide evidence that maltreatment has an impact on social pragmatic communication including social cognition, perspective taking, and belief attribution; executive functions including working memory; and pragmatic language including narrative discourse and the use of varied communicative functions. Conclusions The major findings have implications for knowledge and skills of speech-language and hearing professionals working with children and adolescents and for the type of assessment and intervention processes used to assess social pragmatic communication. Suggestions for future studies are provided.


2021 ◽  
Vol 10 (5) ◽  
pp. 1141
Author(s):  
Gianpaolo Marte ◽  
Andrea Tufo ◽  
Francesca Steccanella ◽  
Ester Marra ◽  
Piera Federico ◽  
...  

Background: In the last 10 years, the management of patients with gastric cancer liver metastases (GCLM) has changed from chemotherapy alone, towards a multidisciplinary treatment with liver surgery playing a leading role. The aim of this systematic review and meta-analysis is to assess the efficacy of hepatectomy for GCLM and to analyze the impact of related prognostic factors on long-term outcomes. Methods: The databases PubMed (Medline), EMBASE, and Google Scholar were searched for relevant articles from January 2010 to September 2020. We included prospective and retrospective studies that reported the outcomes after hepatectomy for GCLM. A systematic review of the literature and meta-analysis of prognostic factors was performed. Results: We included 40 studies, including 1573 participants who underwent hepatic resection for GCLM. Post-operative morbidity and 30-day mortality rates were 24.7% and 1.6%, respectively. One-year, 3-years, and 5-years overall survival (OS) were 72%, 37%, and 26%, respectively. The 1-year, 3-years, and 5-years disease-free survival (DFS) were 44%, 24%, and 22%, respectively. Well-moderately differentiated tumors, pT1–2 and pN0–1 adenocarcinoma, R0 resection, the presence of solitary metastasis, unilobar metastases, metachronous metastasis, and chemotherapy were all strongly positively associated to better OS and DFS. Conclusion: In the present study, we demonstrated that hepatectomy for GCLM is feasible and provides benefits in terms of long-term survival. Identification of patient subgroups that could benefit from surgical treatment is mandatory in a multidisciplinary setting.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Matteo Buda ◽  
Riccardo D’Ambrosi ◽  
Enrico Bellato ◽  
Davide Blonna ◽  
Alessandro Cappellari ◽  
...  

Abstract Background Revision surgery after the Latarjet procedure is a rare and challenging surgical problem, and various bony or capsular procedures have been proposed. This systematic review examines clinical and radiographic outcomes of different procedures for treating persistent pain or recurrent instability after a Latarjet procedure. Methods A systematic review of the literature was performed using the Medline, Cochrane, EMBASE, Google Scholar and Ovid databases with the combined keywords “failed”, “failure”, “revision”, “Latarjet”, “shoulder stabilization” and “shoulder instability” to identify articles published in English that deal with failed Latarjet procedures. Results A total of 11 studies (five retrospective and six case series investigations), all published between 2008 and 2020, fulfilled our inclusion criteria. For the study, 253 patients (254 shoulders, 79.8% male) with a mean age of 29.6 years (range: 16–54 years) were reviewed at an average follow-up of 51.5 months (range: 24–208 months). Conclusions Eden–Hybinette and arthroscopic capsuloplasty are the most popular and safe procedures to treat recurrent instability after a failed Latarjet procedure, and yield reasonable clinical outcomes. A bone graft procedure and capsuloplasty were proposed but there was no clear consensus on their efficacy and indication. Level of evidence Level IV Trial registration PROSPERO 2020 CRD42020185090—www.crd.york.ac.uk/prospero/


2021 ◽  
Vol 11 (4) ◽  
pp. 1903
Author(s):  
Adrian Kahn ◽  
Shlomo Matalon ◽  
Rahaf Bassam Salem ◽  
Lazar Kats ◽  
Liat Chaushu ◽  
...  

This study aimed to characterize the demographic and clinical features of underreported surgical ciliated cysts developing after sinus floor augmentation, based on a series of cases from our files and a systematic review of the literature. A series of five cases (four patients) of microscopically confirmed surgical ciliated cysts following sinus floor augmentation procedures from our files are described. A systematic literature search (1991–2020) with strict clinical-, radiological- and microscopic-based exclusion and inclusion criteria was performed to detect additional similar cases. The systematic review revealed only five cases that fulfilled the inclusion criteria. Altogether, surgical ciliated cysts associated with sinus floor augmentation have been rarely reported in the literature, and have not been characterized either demographically or clinically. Graft materials were diverse, implants were placed simultaneously, or up to two years post-augmentation. The associated surgical ciliated cysts developed between 0.5 and 10 years post-augmentation. Although limited in its extent, this study is the first series to characterize possible underreported sequelae of surgical ciliated cysts associated with sinus floor augmentation. It emphasizes the need for long post-operative follow-up and confirmation of lesion by microscopic examination.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
F Tenori. Lir. Neto ◽  
M Roque ◽  
S Esteves

Abstract Study question Does varicocelectomy improve sperm DNA quality in men with infertility and clinically detected varicoceles? Summary answer Varicocelectomy reduces sperm DNA fragmentation (SDF) rates in infertile men with clinical varicocele. What is known already Varicocele has been linked to male infertility through various non-mutually exclusive mechanisms, including an increase in reactive oxygen species (ROS) production that may lead to sperm DNA damage. Damage to sperm DNA may result in longer time-to-pregnancy, unexplained infertility, recurrent pregnancy loss, and failed intrauterine insemination or in vitro fertilization/intracytoplasmic sperm injection. Therefore, interventions aimed at decreasing SDF rates, including varicocele repair, have been explored to improve fertility and pregnancy outcomes potentially, either by natural conception or using medically assisted reproduction. Study design, size, duration Systematic review and meta-analysis Participants/materials, setting, methods We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Our systematic search included PubMed/Medline, EMBASE, Scielo, and Google Scholar to identify all relevant studies written in English and published from inception until October 2020. Inclusion criteria were studies comparing SDF rates before and after varicocelectomy in infertile men with clinical varicocele. Articles were included if the following SDF assays were utilized: SCSA, TUNEL, SCD test, or alkaline Comet. Main results and the role of chance Thirteen studies fulfilled the inclusion criteria and were selected for the analysis. The estimated weighted mean difference of SDF rates after varicocelectomy was –6.58% (13 studies, 95% CI –8.33%, –4.84%; I2=90% p < 0.0001). Subgroup analysis revealed a significant decrease in SDF rates using SCSA (eight studies, WMD –6.80%, 95% CI –9.31%, –4.28%; I2=89%, p < 0.0001), and TUNEL (three studies, WMD –4.86%, 95% CI –7.38%, –2.34%; I2=89%, p < 0.0001). The test for subgroup difference revealed that pooled results were conservative using the above SDF assays. Comet and SCD tests were used in only one study each; thus, a meta-analysis was not applicable. The studies were further categorized by the surgical technique (microsurgical versus non-microsurgical). This subgroup analysis showed a significant decrease in SDF rates using microsurgical technique (10 studies, WMD –6.70%, 95% CI –9.04%, –4.37%; I2=91%, p < 0.0001). After varicocelectomy, SDF rates were also decreased when non-microsurgical approaches were used, albeit the effect was not statistically significant (2 studies, WMD –6.84%, 95% CI –10.05%, 1.38%; I2=86%) (Figure 3). The heterogeneity was not materially affected by performing analyses by the above subgroups, suggesting that the SDF assay and surgical technique do not explain the inconsistency in the treatment effect across primary studies. Limitations, reasons for caution There were no randomized controlled trials comparing varicocelectomy to placebo for alleviating SDF levels. Heterogeneity was high, which may be explained by the low number of included studies. Pregnancy data are not available in most studies, thus the impact of reduced SDF after varicocelectomy on pregnancy rates unclear. Wider implications of the findings: Our study indicates a positive association between varicocelectomy and reduced postoperative SDF rates in men with clinical varicocele and infertility, independentetly of the assays used to measure SDF. These findings may help counsel and manage infertile men with varicocele and high SDF levels. Trial registration number Not applicable


2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Chloe Crompton ◽  
Bethany Duncan ◽  
Graham Simpson-Adkins

Purpose This paper aims to systematically review the available evidence that explores adverse childhood experiences (ACEs) in people with intellectual disabilities (PwID). It is important to systematically review this literature as, to date, there is little known about the number of studies in this area, despite the World Health Organization declaring ACE prevention and support as a global public health priority. Design/methodology/approach Published studies were identified from electronic database searches. Key journals and reference lists were also hand searched. Findings Two studies met the inclusion criteria and the prevalence and frequency of ACEs experienced by participants of these studies analysed. Overall, due to the small number of studies meeting the inclusion criteria, it is difficult to establish any meaningful conclusions. Originality/value This appears to be the first systematic review to try and identify a research base looking at the prevalence of ACEs within a PwID population. Findings suggest that this is a highly neglected area of research, and the authors hope to have identified that further evidence is required to draw clearer conclusions about the impact of ACEs on PwID.


Author(s):  
Jasmine Peters ◽  
Mariel S Bello ◽  
Leigh Spera ◽  
T Justin Gillenwater ◽  
Haig A Yenikomshian

Abstract Racial and ethnic disparities are endemic to the United States and are only beginning to attract the attention of researchers. With an increasingly diverse population, focused and tailored medicine to provide more equitable care is needed. For surgical trauma populations, this topic is a small but expanding field and still rarely mentioned in burn medicine. Disparities in prevention, treatment, and recovery outcomes between different racial and ethnic minorities who are burned are rarely discussed. The purpose of this study is to determine the current status of identified disparities of care in the burn population literature and areas of future research. A systematic review was conducted of literature utilizing PubMed for articles published between 2000-2020. Searches were used to identify articles that crossed the burn term (burn patient OR burn recovery OR burn survivor OR burn care) and a race/ethnicity and insurance status-related term (race/ethnicity OR African-American OR Black OR Asian OR Hispanic OR Latino OR Native American OR Indigenous OR Mixed race OR 2 or more races OR socioeconomic status OR insurance status). Inclusion criteria were English studies in the US that discussed disparities in burn injury outcomes or risk factors associated with race/ethnicity. 1,169 papers were populated, 55 were reviewed, and 36 articles met inclusion criteria. Most studies showed minorities had poorer inpatient and outpatient outcomes. While this is a concerning trend, there is a paucity of literature in this field and more research is needed to create culturally-tailored medical care and address the needs of disadvantaged burn survivors.


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