scholarly journals The Influence of Beta-2 Adrenergic Receptor Gene Polymorphisms on Albuterol Therapy for Patients With Asthma: Protocol for a Systematic Review and Meta-Analysis

10.2196/14759 ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. e14759 ◽  
Author(s):  
Keiko Hikino ◽  
Shinobu Kobayashi ◽  
Erika Ota ◽  
Taisei Mushiroda ◽  
Tohru Kobayashi

Background Albuterol is one of the most frequently used medications in clinical practice and seeing varying responses to albuterol between individuals is not uncommon. Multiple studies have been conducted to investigate the associations of differing responses due to albuterol, particularly with regards to the two nonsynonymous single nucleotide polymorphisms (SNPs) at positions 16 (Arg16Gly: substitution of arginine to glycine at position 16; rs1042713) and 27 (Glu27Gln: substitution of glutamic acid to glutamine at position 27; rs1042714) on the β-2 adrenergic receptor (ADRB2) gene. However, the directions of the correlations are conflicting. Objective The objective of this systematic review and meta-analysis is to assess the effect of the two SNPs on the ADRB2 gene, in terms of the responses that present in asthmatic patients shortly after albuterol inhalation. Methods The primary outcome of this work is a detailed study of the associations of the two SNPs in the ADRB2 gene with treatment response and lung function testing shortly after administration of albuterol to asthmatic patients. A comprehensive literature search, using the OVID platform, MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials, will be conducted by a specialized librarian without language restrictions. We will include both prospective and retrospective original observational studies, and we will exclude nonhuman or in vitro studies. All abstracts will be reviewed by two authors who will also individually perform data extraction from each eligible study. Any arising disagreements will be resolved through discussion with a third party. Risk of bias for all included studies will be independently assessed using the quality of genetic association studies tool. We will report the systematic review and meta-analysis, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. A narrative synthesis of study results or meta-analyses will be undertaken when appropriate. Results At the moment of writing, we have already started the preliminary literature search and piloting of the study selection process. The anticipated completion date is September 30, 2019. Conclusions Our systematic review and meta-analysis aims to clarify the current evidence of associations between the two nonsynonymous SNPs in the ADRB2 gene and the responses that present in asthmatic patients shortly after albuterol inhalation. If positive correlations are found, this knowledge may be used to improve personalized pharmacotherapy of albuterol use. Trial Registration PROSPERO CRD42019074554; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=74554 International Registered Report Identifier (IRRID) PRR1-10.2196/14759

2019 ◽  
Author(s):  
Keiko Hikino ◽  
Shinobu Kobayashi ◽  
Erika Ota ◽  
Taisei Mushiroda ◽  
Tohru Kobayashi

BACKGROUND Albuterol is one of the most frequently used medications in clinical practice and seeing varying responses to albuterol between individuals is not uncommon. Multiple studies have been conducted to investigate the associations of differing responses due to albuterol, particularly with regards to the two nonsynonymous single nucleotide polymorphisms (SNPs) at positions 16 (Arg16Gly: substitution of arginine to glycine at position 16; rs1042713) and 27 (Glu27Gln: substitution of glutamic acid to glutamine at position 27; rs1042714) on the β-2 adrenergic receptor (ADRB2) gene. However, the directions of the correlations are conflicting. OBJECTIVE The objective of this systematic review and meta-analysis is to assess the effect of the two SNPs on the ADRB2 gene, in terms of the responses that present in asthmatic patients shortly after albuterol inhalation. METHODS The primary outcome of this work is a detailed study of the associations of the two SNPs in the ADRB2 gene with treatment response and lung function testing shortly after administration of albuterol to asthmatic patients. A comprehensive literature search, using the OVID platform, MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials, will be conducted by a specialized librarian without language restrictions. We will include both prospective and retrospective original observational studies, and we will exclude nonhuman or in vitro studies. All abstracts will be reviewed by two authors who will also individually perform data extraction from each eligible study. Any arising disagreements will be resolved through discussion with a third party. Risk of bias for all included studies will be independently assessed using the quality of genetic association studies tool. We will report the systematic review and meta-analysis, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. A narrative synthesis of study results or meta-analyses will be undertaken when appropriate. RESULTS At the moment of writing, we have already started the preliminary literature search and piloting of the study selection process. The anticipated completion date is September 30, 2019. CONCLUSIONS Our systematic review and meta-analysis aims to clarify the current evidence of associations between the two nonsynonymous SNPs in the ADRB2 gene and the responses that present in asthmatic patients shortly after albuterol inhalation. If positive correlations are found, this knowledge may be used to improve personalized pharmacotherapy of albuterol use. CLINICALTRIAL PROSPERO CRD42019074554; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=74554 INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID) PRR1-10.2196/14759


BMJ Open ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. e046035
Author(s):  
Suparee Boonmanunt ◽  
Oraluck Pattanaprateep ◽  
Boonsong Ongphiphadhanakul ◽  
Gareth McKay ◽  
John Attia ◽  
...  

IntroductionObesity and being overweight are major risk factors for metabolic syndrome and non-communicable diseases. Despite the recommendation that a healthy diet and physical activity can reduce the severity of these diseases, many fail to adhere to these measures. From a behavioural economic perspective, adherence to such measures can be encouraged through financial incentives. However, additional related behavioural economic approaches may improve the effectiveness of an incentive programme. As such, we have developed a protocol for a systematic review and network meta-analysis to summarise the current evidence from financial incentive programmes with and without behavioural economic insights for promoting healthy diet and physical activity.Methods and analysisPrevious systematic reviews, meta-analyses and individual studies were identified from Medline and Scopus in June 2020 and will be updated until December 2020. Individual studies will be selected and data extracted by two reviewers. Disagreement will be resolved by consensus or adjudicated by a third reviewer. A descriptive analysis will summarise the effectiveness of behavioural economic incentive programmes for promoting healthy diet and physical activity. Moreover, individual studies will be pooled using network meta-analyses where possible. I2 statistics and Cochran’s Q test will be used to assess heterogeneity. Risk of bias and publication bias, if appropriate, will be evaluated, as well as the overall strength of the evidence.Ethics and disseminationEthics approval for a systematic review and meta-analysis is not required. The findings will be published in a peer-reviewed journal.PROSPERO registration numberCRD42020198024.


2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
M Oberndorfer ◽  
I Grabovac ◽  
S Haider ◽  
T E Dorner

Abstract Background Reports of the effectiveness of e-cigarettes (ECs) for smoking cessation vary across different studies making implementation recommendations hard to attain. We performed a systematic review and meta-analysis to synthesise the current evidence regarding the effectiveness of ECs for smoking cessation. Methods PubMed, PsycInfo and Embase databases were searched for randomized controlled trials comparing nicotine ECs with non-nicotine ECs or with established smoking cessation interventions (nicotine replacement therapy (NRT) and or counselling) published between 01/01/2014 and 01/05/2019. Data from eligible studies were extracted and used for random-effects meta-analyses. Results Our literature review yielded 13190 publications with 10 studies being identified as eligible for systematic review, covering 8362 participants, and 8 for meta-analyses (n = 30 - 6006). Using the last follow-up of eligible studies, the proportion of smokers achieving abstinence was 1.67 [95CI:0.99 - 2.81] times higher in nicotine EC users compared to non-nicotine EC users. The proportion of abstinent smokers was 1.69 [95CI:1.25 - 2.27] times higher in EC users compared to participants receiving NRT. EC users showed a 2.70 [95CI:1.15 - 6.30] times higher proportion of abstinent smokers in comparison to participants solely receiving counselling. Conclusions Our analysis showed modest effects of nicotine-ECs compared to non-nicotine ECs. When compared to NRT or counselling, results suggest that nicotine EC may be more effective for smoking cessation. As ECs also help maintaining routinized behaviour and social aspects of smoking, we hypothesise that this may explain their advantage as a tool for smoking cessation. However, given the small number of included studies, different populations, heterogeneous designs, and the overall moderate to low quality of evidence, it is not possible to offer clear recommendations. More comparable data is needed to strengthen confidence in the quality of evidence. Key messages The number of previous studies assessing the effectiveness of ECs for smoking cessation is limited. Further, comparability of these studies is restricted, weakening the quality of evidence. Although current evidence on the effectiveness of ECs for smoking cessation is inconclusive, our meta-analyses suggest that ECs could be a promising alternative tool in attempts to achieve abstinence.


2020 ◽  
Vol 64 (6) ◽  
pp. 547-555
Author(s):  
Vasilios Pergialiotis ◽  
Christina Nikolaou ◽  
Dimitrios Haidopoulos ◽  
Maximos Frountzas ◽  
Nikolaos Thomakos ◽  
...  

<b><i>Introduction:</i></b> Several studies have implicated the PIK3/AKT pathway in the pathophysiology of cancer progression as its activation seems to be aberrant in several forms of cancer. The purpose of the present systematic review is to evaluate the impact of PIK3CA mutations on survival outcomes of patients with cervical cancer. <b><i>Methods:</i></b> We used the Medline (1966–2020), Scopus (2004–2020), ClinicalTrials.gov (2008–2020), EMBASE (1980–2020), Cochrane Central Register of Controlled Trials (CENTRAL) (1999–2020), and Google Scholar (2004–2020) databases in our primary search along with the reference lists of electronically retrieved full-text papers. Statistical meta-analysis was performed with the RevMan 5.3 software. <b><i>Results:</i></b> Overall, 12 articles were included in the present study that comprised 2,196 women with cervical cancer. Of those, 3 studies did not report significant differences in survival outcomes among patients with mutated versus wild-type PIK3CA tumors, 5 studies reported decreased survival outcomes, and 3 studies revealed increased survival rates. The meta-analysis revealed that patients with the mutated PIK3CA genotypes had worse overall survival compared to patients with wild-type PIK3CA (HR 2.31; 95% CI: 1.51, 3.55; 95% PI: 0.54, 9.96; data from 3 studies) and the same was observed in the case of DFS rates (HR 1.82; 95% CI: 1.47, 2.25; 95% PI: 1.29, 2.56; data from 4 studies). <b><i>Conclusion:</i></b> Current evidence concerning the impact of PIK3CA mutations on survival outcomes of patients with cervical cancer is inconclusive, although the majority of included studies support a potential negative effect, primarily among those with squamous cell carcinoma tumors.


2020 ◽  
pp. bmjsrh-2019-200448
Author(s):  
Mia Schmidt-Hansen ◽  
Jonathan Lord ◽  
Elise Hasler ◽  
Sharon Cameron

BackgroundMedical abortion with mifepristone and misoprostol usually involves an interval of 36–48 hours between administering these drugs; however, it is possible that the clinical efficacy at early gestations may be maintained when the drugs are taken simultaneously. The objective of this systematic review was to determine the safety and effectiveness of simultaneous compared with interval administration of mifepristone and misoprostol for abortion up to 10+0 weeks’ gestation.MethodsWe searched Embase Classic, Embase; Ovid MEDLINE(R) including Daily, and Epub Ahead-of-Print, In-Process & Other Non-Indexed Citations; and Cochrane Library on 11 December 2019. We included randomised controlled trials (RCTs), published in English from 1985, comparing simultaneous to interval administration of mifepristone and misoprostol for early abortion. Risk of bias was assessed using the Cochrane Collaboration checklist for RCTs. Meta-analysis of risk ratios (RRs) using the Mantel-Haenszel method were performed. The quality of the evidence was assessed using GRADE.ResultsMeta-analyses of three RCTs (n=1280) showed no differences in ‘ongoing pregnancy’ (RR 1.78, 95% CI 0.38 to 8.36), ‘haemorrhage requiring transfusion or ≥500 mL blood loss’ (RR 0.11, 95% CI 0.01 to 2.03) and ‘incomplete abortion with the need for surgical intervention’ (RR 1.30, 95% CI 0.76 to 2.25) between the interventions. Individual study results showed no difference in patient satisfaction, or ‘need for repeat misoprostol’, although ‘time to onset of bleeding or cramping’ was longer after simultaneous than interval administration. The quality of evidence was very low to moderate.ConclusionThe published data support the use of simultaneous mifepristone and misoprostol for medical abortion up to 9+0 weeks in women who prefer this method of administration.


Author(s):  
Igor Grabovac ◽  
Moritz Oberndorfer ◽  
Jismy Fischer ◽  
Winfried Wiesinger ◽  
Sandra Haider ◽  
...  

Abstract Introduction Reports of the effectiveness of e-cigarettes (ECs) for smoking cessation vary across different studies making implementation recommendations hard to attain. We performed a systematic review and meta-analysis to assess the current evidence regarding effectiveness of ECs for smoking cessation. Methods PubMed, PsycInfo, and Embase databases were searched for randomized controlled trials comparing nicotine ECs with non-nicotine ECs or with established smoking cessation interventions (nicotine replacement therapy [NRT] and or counseling) published between 1 January 2014 and 27 June 2020. Data from eligible studies were extracted and used for random-effects meta-analyses (PROSPERO registration number: CRD42019141414). Results The search yielded 13 950 publications with 12 studies being identified as eligible for systematic review (N = 8362) and 9 studies for random-effects meta-analyses (range: 30–6006 participants). The proportion of smokers achieving abstinence was 1.71 (95 CI: 1.02–2.84) times higher in nicotine EC users compared with non-nicotine EC users. The proportion of abstinent smokers was 1.69 (95 CI: 1.25–2.27) times higher in EC users compared with participants receiving NRT. EC users showed a 2.04 (95 CI: 0.90–4.64) times higher proportion of abstinent smokers in comparison with participants solely receiving counseling. Conclusions Our results suggest that nicotine ECs may be more effective in smoking cessation when compared with placebo ECs or NRT. When compared with counseling alone, nicotine ECs are more effective short term, but its effectiveness appears to diminish with later follow-ups. Given the small number of studies, heterogeneous design, and the overall moderate to low quality of evidence, it is not possible to offer clear recommendations. Implications The results of this study do not allow for a conclusive argument. However, pooling current evidence points toward a potential for ECs as a smoking cessation tool. Though, given the overall quality of evidence, future studies should aim for more clarity in terms of interventions and larger study populations.


2020 ◽  
pp. 026921552095193
Author(s):  
Alberto Saavedra-García ◽  
Jose A Moral-Munoz ◽  
David Lucena-Anton

Objective: To evaluate the current evidence on the effectiveness of simultaneous combination of mirror therapy and electrical stimulation in the recovery of upper limb motor function after stroke, compared with conventional therapy, mirror therapy or electrical stimulation isolated. Data sources: Articles published in PubMed, Web of Science, Scopus, Physiotherapy Evidence Database (PEDro), Cochrane Central register of controlled trials and ScienceDirect up to July 2020. Review methods: The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed. Methodological quality was assessed using the PEDro tool. The RevMan 5.4 statistical software was used to obtain the meta-analysis, through the standardized mean difference and 95% confidence intervals (CI), and to evaluate the risk of bias. The GRADE approach was employed to assess the certainty of evidence. Results: Eight articles were included in this systematic review, seven were included in the meta-analysis. A total of 314 participants were analyzed. The overall quality of the articles included in this review was good. There was no overall significant mean difference on upper limb motor function after stroke using the Upper-Extremity Fugl-Meyer Assessment by 1.56 (95% CI = –2.08, 5.20; P = 0.40; moderate-certainty evidence) and the Box and Block Test results by 1.39 (95% CI = –2.14, 4.92; P = 0.44; high-certainty evidence). There was overall significant difference in the Action Research Arm Test by 3.54 (95% CI = 0.18, 6.90; P = 0.04; high-certainty evidence). Conclusion: Direct scientific evidence about the effectiveness of the combined therapy of mirror therapy and electrical stimulation simultaneously for the improvement of the upper limb motor function after stroke is lacking. Further high-quality and well-designed research is needed.


Neurosurgery ◽  
2017 ◽  
Vol 80 (5) ◽  
pp. 701-715 ◽  
Author(s):  
Daniel Yavin ◽  
Steven Casha ◽  
Samuel Wiebe ◽  
Thomas E Feasby ◽  
Callie Clark ◽  
...  

Abstract BACKGROUND: Due to uncertain evidence, lumbar fusion for degenerative indications is associated with the greatest measured practice variation of any surgical procedure. OBJECTIVE: To summarize the current evidence on the comparative safety and efficacy of lumbar fusion, decompression-alone, or nonoperative care for degenerative indications. METHODS: A systematic review was conducted using PubMed, MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (up to June 30, 2016). Comparative studies reporting validated measures of safety or efficacy were included. Treatment effects were calculated through DerSimonian and Laird random effects models. RESULTS: The literature search yielded 65 studies (19 randomized controlled trials, 16 prospective cohort studies, 15 retrospective cohort studies, and 15 registries) enrolling a total of 302 620 patients. Disability, pain, and patient satisfaction following fusion, decompression-alone, or nonoperative care were dependent on surgical indications and study methodology. Relative to decompression-alone, the risk of reoperation following fusion was increased for spinal stenosis (relative risk [RR] 1.17, 95% confidence interval [CI] 1.06-1.28) and decreased for spondylolisthesis (RR 0.75, 95% CI 0.68-0.83). Among patients with spinal stenosis, complications were more frequent following fusion (RR 1.87, 95% CI 1.18-2.96). Mortality was not significantly associated with any treatment modality. CONCLUSION: Positive clinical change was greatest in patients undergoing fusion for spondylolisthesis while complications and the risk of reoperation limited the benefit of fusion for spinal stenosis. The relative safety and efficacy of fusion for chronic low back pain suggests careful patient selection is required (PROSPERO International Prospective Register of Systematic Reviews number, CRD42015020153).


2020 ◽  
pp. 106002802094912
Author(s):  
Anum Saqib Zaidi ◽  
Gregory M. Peterson ◽  
Luke R.E. Bereznicki ◽  
Colin M. Curtain ◽  
Mohammed Salahudeen

Objective: To investigate mortality and hospitalization outcomes associated with medication misadventure (including medication errors [MEs], such as the use of potentially inappropriate medications [PIMs], and adverse drug events [ADEs]) among people with cognitive impairment or dementia. Data Sources: Ovid MEDLINE, Ovid EMBASE, Ovid International Pharmaceutical Abstracts, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Central Register of Controlled Trials were searched from inception to December 2019. Study Selection and Data Extraction: Relevant studies using any study design were included. Reviewers independently performed critical appraisal and extracted relevant data. Data Synthesis: The systematic review included 10 studies that reported the outcomes of mortality or hospitalization associated with medication misadventure, including PIMs (n=5), ADEs (n=2), a combination of MEs and ADEs (n=2), and drug interactions (n=1). Five studies examining the association between PIMs and mortality/hospitalization were included in the meta-analyses. Exposure to PIMs was not associated with either mortality (odds ratio [OR]=1.36; 95%CI=0.79-2.35) or hospitalization (OR=1.02; 95%CI=0.83-1.26). In contrast, single studies indicated that ADEs with cholinesterase inhibitors were associated with mortality and hospitalization. Relevance to Patient Care and Clinical Practice: Individuals with cognitive impairment or dementia are at increased risk of medication misadventure; based on relatively limited published data, this does not necessarily translate to increased mortality and hospitalization. Conclusions: Overall, medication misadventure was not associated with mortality or hospitalization in people with cognitive impairment or dementia, noting the limited number of studies, difficulty in controlling potential confounding variables, and that most studies focus on PIMs.


2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Wei Jiang ◽  
Shaojun Liao ◽  
Xiankun Chen ◽  
Cecilia Stålsby Lundborg ◽  
Gaetano Marrone ◽  
...  

Background. Depression is a debilitating comorbidity of heart failure (HF) that needs assessment and management. Along with mind-body exercise to deal with HF with depression, the use of TaiChi and/or Qigong practices (TQPs) has increased. Therefore, this systematic review assesses the effects of TQPs on depression among patients with HF. Methods. Randomized controlled trials (RCTs) that examined the effect of TQPs on depression in patients with HF were searched by five databases (PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, CINAHL, and China National Knowledge Infrastructure (CNKI)). With standardized mean difference (SMD) and 95% confidence intervals (95% CI), random-effects meta-analyses of the effect of TQPs on depressive symptoms were performed. Results. Of eight included RCTs, seven (481 patients) provided data for the meta-analysis. The pooling revealed that TQPs contribute to depression remission in HF (SMD −0.66; 95% CI −0.98 to −0.33, P < 0.0001 ; I2 = 64%). Its antidepressive effect was not influenced by intervention duration or exercise setting, but rather by ejection fraction subtype, depressive severity, and depression instruments. The beneficial effects were preserved when the study with the largest effect was removed. Conclusion. This study suggests that TQPs might be a good strategy for alleviating depressive symptoms in patients with HF. And rigorous-design RCTs, which focus on the identified research gaps, are needed to further establish the therapeutic effects of TQPs for depression in HF.


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