scholarly journals Orthostatic Hypotension and Antiparkinsonian Drugs: A Systematic Review and Meta-analysis

2021 ◽  
pp. 089198872110600
Author(s):  
Danielle, Nimmons ◽  
Cini Bhanu ◽  
Mine Orlu ◽  
Anette Schrag ◽  
Kate Walters

Background Orthostatic hypotension (OH) is multifactorial in Parkinson’s disease (PD). Antiparkinsonian medication can contribute to OH, leading to increased risk of falls, weakness and fatigue. Methods We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) of antiparkinsonian drugs associated with OH as an adverse effect, compared to placebo. We searched EMBASE, MEDLINE and Web of Science databases until November 2020. Analysis used fixed-effects models and the GRADE tool to rate quality of evidence. Meta-analysis was performed if 3 or more studies of a drug group were available. Results Twenty-one RCTs including 3783 patients were included comparing 6 PD drug groups to placebo (MAO-B inhibitors, dopamine agonists, levodopa, COMT inhibitors, levodopa and adenosine receptor antagonists). OH was recorded as an adverse event or measurement of vital signs, without further specification on how this was defined or operationalised. Meta-analysis was performed for MAO-B inhibitors and dopamine agonists, as there were 3 or more studies for these drug groups. In this analysis, compared with placebo, neither MAO-B inhibitors or dopamine agonists were associated with increased risk of OH, (OR 2.28 [95% CI:0.81–6.46]), (OR 1.39 [95% CI:0.97–1.98]). Conclusions Most studies did not specifically report OH, or reporting of OH was limited, including how and when it was measured. Furthermore, studies specifically reporting OH included participants that were younger than typical PD populations without multimorbidity. Future trials should address this, for example,, by including individuals over the age of 75, to improve estimations of how antiparkinsonian medications affect risk of OH.

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Martin L Campbell ◽  
John Larson ◽  
Talha Farid ◽  
Stacy Westerman ◽  
Michael S Lloyd ◽  
...  

Introduction: Women undergoing atrial fibrillation catheter ablation (AFCA) have higher rates of vascular complications and major bleeding. However, studies have been underpowered to detect differences in rare complications such as stroke/transient ischemic attack (TIA) and procedural mortality. Methods: We performed a systematic review of databases (PubMed, World of Science, Embase) to identify studies published since 2010 reporting AFCA complications by gender. Six complications of interest were: 1) vascular/groin complications; 2) pericardial effusion/tamponade; 3) stroke/TIA; 4) permanent phrenic nerve injury; 5) major bleeding & 6) procedural mortality. For meta-analysis, random effects models were used when heterogeneity between studies was ≥ 50% (vascular complications, major bleeding) and fixed effects models for other endpoints. Results: Of 5716 citations, 19 studies met inclusion criteria, comprising 244,353 patients undergoing AFCA, of whom 33% were women. Women were older (65.3 ± 11.2 vs. 60.4 ± 13.2 years), more likely hypertensive (60.6 vs. 55.5%) and diabetic (18.3 vs. 16.5%) and had higher CHA 2 DS 2 -VASc scores (3.0 ± 1.8 vs. 1.4 ± 1.4) (p<0.0001 for all comparisons). The rates of all 6 complications were significantly higher in women (Table). However, despite statistically significant differences, the overall incidences of major complications were very low in both genders: stroke/TIA (women 0.51 vs. men 0.39%) and procedural mortality (women 0.25 vs. men 0.18%). Conclusion: Women experience significantly higher rates of AFCA complications. However, the incidence of major procedural complications is very low in both genders. The higher rate of complications in women may be partially attributable to older age and a higher prevalence of comorbidities at the time of ablation. More detailed studies are needed to better define the mechanisms of increased risk in women and to identify strategies for closing the gender gap.


2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 71-71
Author(s):  
Zin Myint ◽  
Harry D. Momo ◽  
Danielle E. Otto ◽  
Donglin Yan ◽  
Robert S. DiPaola ◽  
...  

71 Background: Patients treated with androgen receptor inhibitors (ARIs) report a higher incidence of falls; although a potential mechanism of action is unknown. This systematic review evaluates the relative risk (RR) of fall and fracture in prostate cancer (PCa) patients that receive ARIs. Methods: We conducted a comprehensive literature search using Cochrane, Scopus and MedlinePlus databases from inception through August 2019, and evaluated all published prospective phase II, III and IV randomized controlled trials that treated PCa patients with ARIs. Reported fall and fractures as adverse events (AEs) were extracted for analysis. Retrospective, phase I, non-randomized phase II, and studies with control arms that used one of the ARIs were excluded. A mixed effects model was used to estimate effects of ARI on the RR, with the included studies treated as random effects and study arms treated as fixed effects in the pooled analysis. Sample size for each study was used to weight the mixed model. Results: Eleven studies met our inclusion criteria. The total population was 11,382; 6536 were in the ARI arm and 4846 in the control (CTL) arm. Study types were: 8 phase III; 2 phase II; 1 phase IV. Subjects in the ARI arm received enzalutamide, apalutamide or darolutamide in combination with androgen deprivation therapy or other enzalutamide combinations while in the CTL arm received placebo, bicalutamide or abiraterone. Treatment duration ranged from 5.4 to 20.5 mo for ARI vs. 5.4 to 18.3 mo for CTL. The reported incidence of fall was 481 (7.4%) in ARI and 201 (4.1%) for CTL. The incidence of fracture was 204 (3.1%) in ARI and 93 (1.9%) in control. The use of ARI was associated with an increased risk: all fall grades (RR 1.83; 95% CI 1.56-2.15; p <0.01); high grade fall (RR 1.69; 95% CI 1.09 – 2.62; p=0.019); all grade fracture (RR 1.56; 95% CI 1.23-1.97; p <0.01) and likely high grade fracture (RR 1.62; 95% CI 0.97 – 2.69; p=0.063). Conclusions: The use of ARI significantly increases falls and fractures in PCa patients as assessed by this meta-analysis study. Further studies would be warranted to identify and understand potential mechanisms and develop strategies to decrease falls and fractures associated with ARI use.


PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6737 ◽  
Author(s):  
Xin Sun ◽  
Li Lu ◽  
Yanbin Li ◽  
Rong Yang ◽  
Ling Shan ◽  
...  

Background Sjogren’s syndrome (SS) is a chronic autoimmune epithelitis characterized by disruption of epithelial cells, ensuing lymphoplasmocytic infiltration of exocrine glands, and subsequent dryness of the mouth and eyes. Individuals with SS are more likely to have the thyroid disease. However, this association remains controversial. This meta-analysis aimed to evaluate the risk of thyroid disease in patients with SS. Methods We performed this systematic review by searching both English and Chinese literature databases. Random- or fixed-effects models were used to summarize the association between thyroid disease and SS. The results were subjected to meta-analysis with odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Results The eight articles in this meta-analysis included 988 SS cases and 2,884 controls. Overall, the risk of thyroid disease in patients with SS was significantly increased compared with controls (OR, 3.29; 95% CI [2.08–5.21]). The risk of autoimmune thyroid disease (AITD) and non-AITD were also higher in patients with SS than in controls (OR, 3.48; 95% CI [1.59–7.63]; and OR, 2.90; 95% CI [1.51–5.57], respectively). Conclusions To the best of our knowledge, this systematic review is the first to demonstrate that the risk of thyroid disease was increased in SS compared to controls, suggesting that SS patients should be screened for thyroid disease.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e19624-e19624 ◽  
Author(s):  
Marigdalia K. Ramirez-Fort ◽  
Emily Christine Case ◽  
Alyx C. Rosen ◽  
Shenhong Wu ◽  
Mario E. Lacouture

e19624 Background: Everolimus is an mTOR inhibitor approved for treatment of renal cell carcinoma, subependymal giant cell astrocytoma, and progressive neuroendocrine tumors of pancreatic origin. Its use may be hindered due to adverse events, including rash. The reported incidence and risk of rash to everolimus varies widely and has not been closely investigated. Therefore, we conducted a systematic review and meta-analysis of the literature to determine the incidence and risk of developing rash. Methods: We searched PubMed and Web of Science databases and abstracts presented at the American Society of Clinical Oncology from 1998 to July 2011 using the keyword “everolimus” to identify relevant clinical trials. Eligible studies included prospective phase II and phase III clinical trials of cancer patients on 10 mg of everolimus daily with available data on incidence of rash. The summary incidence and relative risk (RR) of rash were calculated using either the random-effects or fixed-effects model, depending on the heterogeneity of the constituent studies. Results: A total of 2,242 patients with various malignancies from 13 clinical trials were included in the analysis. The summary incidences of all-grade and high-grade rash in patients on everolimus were28.6% (95% CI: 20.8 – 38.0) and 1.0% (95% CI: 0.6 – 1.7), respectively. Everolimus was associated with a statistically significant increased risk of all-grade rash (RR=3.853, 95% CI: 2.470 – 6.013, p=0.000), but the RR for high-grade rash (RR= 2.997, 95% CI: 0.633 – 14.185) was not statistically significant, with a p value of 0.166. Conclusions: Everolimus is associated with a significant risk of developing rash. Management of rash to everolimus is critical to prevent dose modifications and decreased quality of life, both of which can negatively affect clinical outcomes.


2014 ◽  
Vol 1 (2) ◽  
pp. 31-37 ◽  
Author(s):  
Khalid Bouti ◽  
Rajae Borki ◽  
Hicham Fenane ◽  
Laila Harrak

Background: Cannabis is the illicit psychoactive substance the most consumed in the world. Little is known about the association between the use of cannabis and the risk of lung cancer. Objective:The objective of this meta-analysis is to determine whether use of cannabis is a risk factor for lung cancer. Methods: We conducted a systematic review and meta-analyses of all languages articles using relevant computerised databases. MEDLINE (online PubMed), Web of knowledge, Embase, EBSCO CINAHL, ScienceDirect, Scopus, Cochrane Library, and Directory of Open Access Journals were searched to September 2014 for cohorts and case-control studies that assessed the risk of lung cancer associated with cannabis smoking. The literature search was performed with a combination of medical subject headings terms, "cannabis" and "lung neoplasms". Data extraction: Two investigators independently analysed and extracted results from eligible studies. Our study's registration number on PROSPERO is CRD42014008872. Results: The search strategy identified 2476 citations. 13 studies were eligible for inclusion: 2 pooled analysis of 9 case-control studies, one case-control study and 3 cohorts. The cumulative analysis for all the studies under a fixed-effects model showed that cannabis smoking determined an increased risk of developing lung cancer in the future (relative risk 1.22, 95% confidence interval 0.999–1.5; p=0.051), with no evidence of heterogeneity across the studies (I2: 34%; p¼0.01). Conclusions: The use of cannabis with or without tobacco smoking is associated with an increased risk for lung cancer


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 9088-9088
Author(s):  
Aaron Mark Drucker ◽  
Shenhong Wu ◽  
Ellin Berman ◽  
Mario E. Lacouture

9088 Background: Nilotinib is indicated for the treatment of chronic myelogenous leukemia (CML). The reported incidence and risk of rash from this medication vary widely and have been inconsistently reported in published trials. Therefore we conducted a systematic review and meta-analysis of the literature to determine the incidence and risk of developing rash. Methods: Relevant studies were identified from the PubMed database (1998-2012), abstracts presented at ASCO and ASH Conferences (2004-2011) and Web of Science database (1998-2012). Eligible studies were limited to prospective Phase II-III clinical trials in which patients received nilotinib at doses of either 300 mg or 400 mg twice daily. Incidence, relative risk (RR), and 95% confidence intervals (CI) were calculated using random-effects or fixed-effects models based on heterogeneity of included studies. Results: Data from a total of 3,186 patients receiving nilotinib in 16 clinical trials were available for analysis. The overall incidence of all-grade and high-grade (grade ≥3) rash were 33.1% (95% CI: 27.7-39.1) and 2.6% (95% CI: 2.1-3.4), respectively. Incidence of all-grade rash for patients with CML, gastrointestinal stromal tumor (GIST) and systemic mastocytosis were 33.2% (95% CI: 27.2-39.9), 25.7% (95% CI: 14.0-42.5) and 25.0% (95% CI: 15.7-37.4), respectively. Nilotinib was associated with increased risk of all-grade rash (RR=2.891, 95% CI: 2.079-4.020; P<0.001) when compared to patients treated with imatinib. Risk of high-grade rash was increased compared to imatinib (RR=1.823, 95% CI: 0.670-4.957), but this was not statistically significant (P=0.24). Conclusions: Patients with hematologic malignancies and GIST who are treated with nilotinib are at significant risk for developing a rash. Further studies for characterization, prevention and treatment of this untoward toxicity are needed in order to maintain patients’ quality of life and minimize the need for dose modification, which may impact clinical outcome.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12530-e12530
Author(s):  
Yan Mao ◽  
Janice Lu ◽  
Haibo Wang ◽  
Gang Nie

e12530 Background: Palbociclib is an oral small-molecule inhibitor of cyclin-dependent kinases 4 and 6 and has improved the progression-free survival of estrogen receptor positive, metastatic breast cancer (MBC). Its application in other cancers is also undergoing clinical evaluation. Neutropenia, especially high grade (grade 3 or 4), is one of the major side-effects of palbociclib, and the incidence was reported too vary in different studies. In order to better understand the overall risk of palbociclib associated neutropenia, we conducted a systematic review and meta-analysis. Methods: We conducted a systematic literature search (including Medline, Web of Science to November, 2016 and abstracts presented at the ASCO annual meetings from 2009 to 2016). Eligible studies include prospective clinical trials of patients with cancer treated with palbociclib on a 125mg daily 3/4 week schedule and have available data on neutropenia. The incidence and relative risk (RR) of neutropenia were calculated using a random-effects or fixed-effects model, depending on the heterogeneity of the included studies. Results: Eight studies published between 2012 and 2016 included a total of 1515 patients with cancer were eligible for analysis. For patients treated with palbociclib, the overall incidence of all-grade and high grade neutropenia were 77.4% (95% CI 70.9-82.8%) and 60.9% (57.8–63.8%), respectively. Surprisingly, the incidence of neutropenia was significantly different between MBC patients and non-MBC patients (all grade: RR 1.26 [95% CI 1.01–1.56], p = 0.041; high-grade: RR 1.57 [1.23–2.00], p = 0.000) who received palbociclib. Palbociclib was associated with a significantly increased risk of all-grade neutropenia in patients with cancer with an RR of 15.03 (10.17–22.21, p < 0.001) compared with controls. Conclusions: Patients with cancer who received palbociclib have a significant risk of developing neutropenia, especially MBC patients. It is strongly recommended to monitor these patients who are treated with palbociclib to adjust dose, treatment intervals, and avoid infections.


2019 ◽  
Vol 75 (5) ◽  
pp. 952-960 ◽  
Author(s):  
Silvia G R Neri ◽  
Juliana S Oliveira ◽  
Amabile B Dario ◽  
Ricardo M Lima ◽  
Anne Tiedemann

Abstract Background Recent investigations suggest that obesity may be associated with an increased risk of falls; however, this theory has yet to be definitively confirmed. This systematic review and meta-analysis examined the strength of the association between obesity and falls, multiple falls, fall-related injuries, and fall-related fractures among older adults. Methods MEDLINE, Embase, CINAHL, PsycINFO, SPORTDiscus, LILACS, and Web of Science databases were searched to identify observational studies that assessed the association between obesity and fall-related outcomes in participants aged 60 years and older. Two independent reviewers performed data extraction and quality assessment. Relative risks and 95% confidence intervals (CI) were pooled using random effect meta-analyses. Results Thirty-one studies including a total of 1,758,694 participants were selected from 7,815 references. Pooled estimates showed that obese older adults have an increased risk of falls compared with nonobese counterparts (24 studies; relative risk: 1.16; 95% CI: 1.07–1.26; I2: 90%). Obesity was also associated with an increased risk of multiple falls (four studies; relative risk: 1.18; 95% CI: 1.08–1.29; I2: 0%). There was no evidence, however, of an association between obesity and fall-related injuries (seven studies; relative risk: 1.04; 95% CI: 0.92–1.18; I2: 65%). Fall-related fractures were reported in only one study, which demonstrated a lower risk of hip fracture with obesity (odds ratio: 0.65; 95% CI: 0.63–0.68). Conclusions Obesity increases the risk of falls and multiple falls in people aged 60 years and older; however, there is insufficient evidence of an association with fall-related injuries or fractures. Prevention and treatment of obesity may play a role in preventing falls in older age.


2021 ◽  
Vol 15 ◽  
pp. 175346662110170
Author(s):  
Qianqian Chen ◽  
Ping Liu ◽  
Hong Zhou ◽  
Hui Kong ◽  
Weiping Xie

Background: Lung cancer is an important complication of combined pulmonary fibrosis and emphysema (CPFE). Whether the risk of lung cancer is higher in CPFE patients with usual interstitial pneumonia (UIP) than those with idiopathic pulmonary fibrosis (IPF) alone, remains controversial. We conducted this systematic review and meta-analysis to evaluate the prevalence of lung cancer in CPFE patients with UIP compared with IPF patients. Methods: We searched the PubMed, Embase, and Cochrane databases for studies that focused on the incidence of lung cancer in CPFE/UIP and IPF groups. We used a fixed-effects model to analyze the odds ratios (ORs) with 95% confidence intervals (CIs) according to data heterogeneity. The cumulative effects based on the publication year and sample size were assessed by cumulative meta-analysis. Results: A total of nine studies with 933 patients, including 374 CPFE patients with UIP, fulfilled the inclusion criteria. Overall, CPFE patients with UIP have a higher risk of lung cancer than those with IPF alone (OR = 2.69; 95% CI: 1.78–4.05). There were increased risks of lung cancer in CPFE/UIP patients with the presence of emphysema (OR = 2.93; 95% CI: 1.79–4.79) or emphysema in ⩾10% of the lung volume (OR = 2.22; 95% CI: 1.06–4.68). Conclusions: Our systematic review and meta-analysis indicated a significantly higher prevalence of lung cancer in CPFE patients with UIP than in patients with IPF alone. The reviews of this paper are available via the supplemental material section.


EP Europace ◽  
2020 ◽  
Vol 22 (7) ◽  
pp. 991-1000 ◽  
Author(s):  
Kit Engedal Kristensen ◽  
Cille Cederholm Knage ◽  
Liv Havgaard Nyhegn ◽  
Bart A Mulder ◽  
Michiel Rienstra ◽  
...  

Abstract Aims Coronary artery disease is an established risk factor for incident atrial fibrillation (AF), but it is unclear whether subclinical atherosclerosis also increases the risk of incident AF. Therefore, the aim was to assess the association between subclinical atherosclerosis, defined by increased carotid intima-media thickness (cIMT) or coronary artery calcium score (CACS), and incident AF. Methods and results A systematic review of MEDLINE, EMBASE, and Cochrane was done to find all cohort studies investigating the association between subclinical atherosclerosis, defined by increased cIMT or CACS, and incident AF. Eligible articles had to be available in an English full-text version; include adults over the age of 18 years; include ≥100 participants; and have a follow-up period ≥12 months. Data on cIMT were pooled using a fixed-effects model, while data on CACS (I2 &gt;25) were pooled using a random-effects model. Five studies on cIMT including 36 333 patients and two studies on CACS including 34 603 patients were identified. All studies investigating the association between increased cIMT and incident AF showed a significant association, with an overall hazard ratio (HR) of 1.43 [95% confidence interval (CI) 1.27–1.59]. The two studies investigating the association between increased CACS and AF also showed a significant association with an overall HR of 1.07 (95% CI 1.02–1.12). Conclusion Data from seven observational studies suggest that subclinical atherosclerosis defined by increased cIMT or CACS is associated with an increased risk of incident AF. These findings emphasize the need for further research investigating whether treatment of subclinical atherosclerosis should be a part of the initiatives to prevent AF.


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