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Journal of Neurology, Neurosurgery, and... Nov 2020Evidence on preventing Alzheimer's disease (AD) is challenging to interpret due to varying study designs with heterogeneous endpoints and credibility. We completed a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Evidence on preventing Alzheimer's disease (AD) is challenging to interpret due to varying study designs with heterogeneous endpoints and credibility. We completed a systematic review and meta-analysis of current evidence with prospective designs to propose evidence-based suggestions on AD prevention.
METHODS
Electronic databases and relevant websites were searched from inception to 1 March 2019. Both observational prospective studies (OPSs) and randomised controlled trials (RCTs) were included. The multivariable-adjusted effect estimates were pooled by random-effects models, with credibility assessment according to its risk of bias, inconsistency and imprecision. Levels of evidence and classes of suggestions were summarised.
RESULTS
A total of 44 676 reports were identified, and 243 OPSs and 153 RCTs were eligible for analysis after exclusion based on pre-decided criteria, from which 104 modifiable factors and 11 interventions were included in the meta-analyses. Twenty-one suggestions are proposed based on the consolidated evidence, with Class I suggestions targeting 19 factors: 10 with Level A strong evidence (education, cognitive activity, high body mass index in latelife, hyperhomocysteinaemia, depression, stress, diabetes, head trauma, hypertension in midlife and orthostatic hypotension) and 9 with Level B weaker evidence (obesity in midlife, weight loss in late life, physical exercise, smoking, sleep, cerebrovascular disease, frailty, atrial fibrillation and vitamin C). In contrast, two interventions are not recommended: oestrogen replacement therapy (Level A2) and acetylcholinesterase inhibitors (Level B).
INTERPRETATION
Evidence-based suggestions are proposed, offering clinicians and stakeholders current guidance for the prevention of AD.
Topics: Alzheimer Disease; Antihypertensive Agents; Cognition; Craniocerebral Trauma; Depression; Diabetes Mellitus; Education; Evidence-Based Medicine; Exercise; Humans; Hyperhomocysteinemia; Hypertension; Hypotension, Orthostatic; Life Style; Obesity; Observational Studies as Topic; Randomized Controlled Trials as Topic; Risk Reduction Behavior; Stress, Psychological
PubMed: 32690803
DOI: 10.1136/jnnp-2019-321913 -
Journal of the American Medical... May 2019Orthostatic hypotension is a potential risk factor for falls in older adults, but existing evidence on this relationship is inconclusive. This study addresses the... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Orthostatic hypotension is a potential risk factor for falls in older adults, but existing evidence on this relationship is inconclusive. This study addresses the association between orthostatic hypotension and falls.
DESIGN
Systematic review and meta-analysis of the cross-sectional and longitudinal studies assessing the association between orthostatic hypotension and falls, as preregistered in the PROSPERO database (CRD42017060134).
SETTING AND PARTICIPANTS
A literature search was performed on February 20, 2017, in MEDLINE (from 1946), PubMed (from 1966), and EMBASE (from 1947) using the terms orthostatic hypotension, postural hypotension, and falls. References of included studies were screened for other eligible studies. Study selection was performed independently by 2 reviewers using the following inclusion criteria: published in English; mean/median age of the population ≥65 years; blood pressure measurement before and after postural change; and assessment of the association of orthostatic hypotension with falls. The following studies were excluded: conference abstracts, case reports, reviews, and editorials. Data extraction was performed independently by 2 reviewers.
MEASURES
Unadjusted odds ratios of the association between orthostatic hypotension and falls were used for pooling using a random effects model. Studies were rated as high, moderate, or low quality using the Newcastle-Ottawa Scale.
RESULTS
Out of 5646 studies, 63 studies (51,800 individuals) were included in the systematic review and 50 studies (49,164 individuals) in the meta-analysis. Out of 63 studies, 39 were cross-sectional and 24 were longitudinal. Orthostatic hypotension was positively associated with falls (odds ratio 1.73, 95% confidence interval 1.50-1.99). The result was independent of study population, study design, study quality, orthostatic hypotension definition, and blood pressure measurement method.
CONCLUSIONS AND IMPLICATIONS
Orthostatic hypotension is significantly positively associated with falls in older adults, underpinning the clinical relevance to test for an orthostatic blood pressure drop and highlighting the need to investigate orthostatic hypotension treatment to potentially reduce falls.
Topics: Accidental Falls; Aged; Blood Pressure; Blood Pressure Determination; Cross-Sectional Studies; Female; Geriatric Assessment; Humans; Hypotension, Orthostatic; Longitudinal Studies; Male; Risk Factors
PubMed: 30583909
DOI: 10.1016/j.jamda.2018.11.003 -
Clinical Obesity Dec 2021There have been increased reports of orthostatic intolerance post-bariatric surgery. However, the prevalence, pathophysiology and long-term outcomes have not been well... (Meta-Analysis)
Meta-Analysis
There have been increased reports of orthostatic intolerance post-bariatric surgery. However, the prevalence, pathophysiology and long-term outcomes have not been well described. Therefore, we sought to summarize evidence of orthostatic intolerance after bariatric surgery. We conducted a systematic review using PubMed, Scopus, CINAHL, Cochrane Database of Systematic Reviews and the Cochrane Central Register of Controlled Trials (CENTRAL) to identify relevant articles from the date of inception until 1st April 2020. Study selection, data extraction and quality assessment of the included studies were performed independently by two reviewers. The findings of the included studies were narratively reported. When feasible, a meta-analysis was done to summarize the relevant results. We included 20 studies (n = 19 843 participants) reporting findings of 12 prospective cohort studies, 5 retrospective cohort studies, 2 cross-sectional studies and one randomized controlled trial. The 5-year cumulative incidence of orthostatic intolerance was 4.2% (one study). Common clinical presentations of orthostatic intolerance were lightheadedness, dizziness, syncope and palpitation. The pooled data suggested improvement in overall cardiac autonomic function (sympathetic and parasympathetic) post-bariatric surgery. In addition, a significant systolic blood pressure drop may reflect a reset of the balance between the sympathetic and parasympathetic nervous systems after weight loss in the pooled analysis. Existing literature on orthostatic intolerance post-bariatric surgeries was limited or of low quality, and larger studies are needed to know the true incidence of orthostatic intolerance post-bariatric surgeries and the pathophysiology. We found one study reporting the 5-years cumulative incidence of orthostatic intolerance post-bariatric surgeries as only 4.2%. This could challenge the idea of increased orthostatic intolerance prevalence post-bariatric surgeries. Registration The review protocol was registered at the International Prospective Register of Systemic Reviews PROSPERO (CRD42020170877).
Topics: Bariatric Surgery; Cross-Sectional Studies; Humans; Orthostatic Intolerance; Prospective Studies; Retrospective Studies
PubMed: 34409762
DOI: 10.1111/cob.12483 -
JAMA Oct 2023There are ongoing concerns about the benefits of intensive vs standard blood pressure (BP) treatment among adults with orthostatic hypotension or standing hypotension. (Comparative Study)
Comparative Study Meta-Analysis
IMPORTANCE
There are ongoing concerns about the benefits of intensive vs standard blood pressure (BP) treatment among adults with orthostatic hypotension or standing hypotension.
OBJECTIVE
To determine the effect of a lower BP treatment goal or active therapy vs a standard BP treatment goal or placebo on cardiovascular disease (CVD) or all-cause mortality in strata of baseline orthostatic hypotension or baseline standing hypotension.
DATA SOURCES
Individual participant data meta-analysis based on a systematic review of MEDLINE, EMBASE, and CENTRAL databases through May 13, 2022.
STUDY SELECTION
Randomized trials of BP pharmacologic treatment (more intensive BP goal or active agent) with orthostatic hypotension assessments.
DATA EXTRACTION AND SYNTHESIS
Individual participant data meta-analysis extracted following PRISMA guidelines. Effects were determined using Cox proportional hazard models using a single-stage approach.
MAIN OUTCOMES AND MEASURES
Main outcomes were CVD or all-cause mortality. Orthostatic hypotension was defined as a decrease in systolic BP of at least 20 mm Hg and/or diastolic BP of at least 10 mm Hg after changing position from sitting to standing. Standing hypotension was defined as a standing systolic BP of 110 mm Hg or less or standing diastolic BP of 60 mm Hg or less.
RESULTS
The 9 trials included 29 235 participants followed up for a median of 4 years (mean age, 69.0 [SD, 10.9] years; 48% women). There were 9% with orthostatic hypotension and 5% with standing hypotension at baseline. More intensive BP treatment or active therapy lowered risk of CVD or all-cause mortality among those without baseline orthostatic hypotension (hazard ratio [HR], 0.81; 95% CI, 0.76-0.86) similarly to those with baseline orthostatic hypotension (HR, 0.83; 95% CI, 0.70-1.00; P = .68 for interaction of treatment with baseline orthostatic hypotension). More intensive BP treatment or active therapy lowered risk of CVD or all-cause mortality among those without baseline standing hypotension (HR, 0.80; 95% CI, 0.75-0.85), and nonsignificantly among those with baseline standing hypotension (HR, 0.94; 95% CI, 0.75-1.18). Effects did not differ by baseline standing hypotension (P = .16 for interaction of treatment with baseline standing hypotension).
CONCLUSIONS AND RELEVANCE
In this population of hypertension trial participants, intensive therapy reduced risk of CVD or all-cause mortality regardless of orthostatic hypotension without evidence for different effects among those with standing hypotension.
Topics: Aged; Female; Humans; Male; Blood Pressure; Blood Pressure Determination; Cardiovascular Diseases; Hypertension; Hypotension, Orthostatic; Middle Aged
PubMed: 37847274
DOI: 10.1001/jama.2023.18497 -
International Journal of Cardiology.... Mar 2021Initial orthostatic hypotension is a clinically relevant syndrome in older adults which has been associated with symptoms of orthostatic intolerance. The aim of this... (Review)
Review
BACKGROUND
Initial orthostatic hypotension is a clinically relevant syndrome in older adults which has been associated with symptoms of orthostatic intolerance. The aim of this systematic review was to determine the prevalence of orthostatic intolerance symptoms in older adults with initial orthostatic hypotension.
METHODS
MEDLINE (from 1946), EMBASE (from 1974) and Cochrane were searched to December 6th 2019 using the terms "initial orthostatic hypotension", "postural hypotension" and "older adults". Study selection involved the following criteria: published in English; mean or median age 65 years and diagnosis of initial orthostatic hypotension encompassed a decrease in systolic blood pressure by ≥ 40 mmHg and/or diastolic blood pressure by ≥ 20 mmHg within a maximum of 1 min following a postural change.
RESULTS
Of 8311 articles, 12 articles reporting initial orthostatic hypotension prevalence in 3446 participants with a mean age of 75 (6 SD) years (56.5% female) were included. Five initial orthostatic hypotension definition variations were utilised and symptoms were reported in six articles (968 participants, mean age 73.4 (6.1 SD) years, 56% female). The prevalence of symptoms in older adults with initial orthostatic hypotension ranged from 24 to 100% and was dependent on variations in timing or the inclusion of symptoms in the initial orthostatic hypotension definition.
CONCLUSIONS
Where orthostatic intolerance symptoms were reported, a large proportion of older adults with a diagnosis of initial orthostatic hypotension were symptomatic. However, the literature on initial orthostatic hypotension and orthostatic intolerance symptoms is scarce and a variety of definitions of initial orthostatic hypotension are utilised.
PubMed: 33884364
DOI: 10.1016/j.ijchy.2020.100071 -
The Journal of Bone and Joint Surgery.... Feb 2023Orthostatic intolerance (OI)-type events following hip and knee arthroplasty increase the risk of falls, hospital length of stay, and health-care costs. There is a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Orthostatic intolerance (OI)-type events following hip and knee arthroplasty increase the risk of falls, hospital length of stay, and health-care costs. There is a limited understanding of the incidence of and risk factors for OI-type events in patients during the acute hospital stay. Our aim was to systematically review the incidence of and risk factors for OI-type events during the acute hospital stay following hip and knee arthroplasty.
METHODS
A systematic review and meta-analysis of studies that investigated the incidence of and risk factors for OI-type events was undertaken. A comprehensive search was performed in MEDLINE, Embase, and CINAHL from their inception to October 2021. The methodological quality of identified studies was assessed using the modified version of the Quality in Prognosis Studies (QUIPS) tool.
RESULTS
Twenty-one studies (14,055 patients) were included. The incidence was 2% to 52% for an OI event, 1% to 46% for orthostatic hypotension, and 0% to 18% for syncope/vasovagal events. Two studies reported female sex, high peak pain levels (>5 out of 10) during mobilization, postoperative use of gabapentin, and the absence of postoperative intravenous dexamethasone as risk factors. There was no consensus on the definition and assessment of an OI-type event.
CONCLUSIONS
OI-type events are common during the acute hospital stay following hip and knee arthroplasty, and 4 risk factors have been reported for OI-type events. High-quality prospective cohort studies are required to systematically and reliably determine the incidence of and risk factors for OI-type events.
LEVEL OF EVIDENCE
Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Topics: Humans; Female; Orthostatic Intolerance; Prospective Studies; Arthroplasty, Replacement, Knee; Arthroplasty, Replacement, Hip; Prognosis
PubMed: 36723468
DOI: 10.2106/JBJS.22.00600 -
PLoS Medicine Nov 2021Drug-induced orthostatic hypotension (OH) is common, and its resulting cerebral hypoperfusion is linked to adverse outcomes including falls, strokes, cognitive... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Drug-induced orthostatic hypotension (OH) is common, and its resulting cerebral hypoperfusion is linked to adverse outcomes including falls, strokes, cognitive impairment, and increased mortality. The extent to which specific medications are associated with OH remains unclear.
METHODS AND FINDINGS
We conducted a systematic review and meta-analysis to evaluate the extent to which specific drug groups are associated with OH. EMBASE, MEDLINE, and Web of Science databases were searched from inception through 23 November 2020. Placebo-controlled randomised controlled trials (RCTs) on any drug reporting on OH as an adverse effect in adults (≥18 years) were eligible. Three authors extracted data on the drug, OH, dose, participant characteristics, and study setting. The revised Cochrane risk-of-bias tool for randomised trials (RoB 2) was used to appraise evidence. Summary odds ratios (ORs) were estimated for OH using fixed effects Mantel-Haenszel statistics. We conducted subgroup analysis on validity of OH measurement, drug dose, risk of bias, age, and comorbidity. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool was used to summarise the certainty of evidence. Of 36,940 citations, 69 eligible RCTs were included in the meta-analysis comprising 27,079 participants. Compared with placebo, beta-blockers and tricyclic antidepressants were associated with increased odds of OH (OR 7.76 [95% CI 2.51, 24.03]; OR 6.30 [95% CI 2.86, 13.91]). Alpha-blockers, antipsychotics, and SGLT-2 inhibitors were associated with up to 2-fold increased odds of OH, compared to placebo. There was no statistically significant difference in odds of OH with vasodilators (CCBs, ACE inhibitors/ARBs, SSRIs), compared to placebo. Limitations of this study are as follows: data limited to placebo-controlled studies, (excluding head-to-head trials), many RCTs excluded older participants; therefore results may be amplified in older patients in the clinical setting. The study protocol is publicly available on PROSPERO (CRD42020168697).
CONCLUSIONS
Medications prescribed for common conditions (including depression, diabetes, and lower urinary tract symptoms) were associated with significantly increased odds of OH. Drugs causing sympathetic inhibition were associated with significantly increased odds of OH, while most vasodilators were associated with small nonsignificant differences in odds of OH, compared to placebo. Drugs targeting multiple parts of the orthostatic blood pressure (BP) reflex pathway (e.g. sympathetic inhibition, vasodilation, cardio-inhibitory effects) may carry cumulative risk, suggesting that individuals with polypharmacy could benefit from postural BP monitoring.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antidepressive Agents; Antipsychotic Agents; Humans; Hypotension, Orthostatic; Placebos; Randomized Controlled Trials as Topic; Vasodilator Agents
PubMed: 34752479
DOI: 10.1371/journal.pmed.1003821 -
The American Journal of Medicine Dec 2020Guidelines recommend increased salt intake as a first-line recommendation in the management of symptomatic orthostatic hypotension and recurrent syncope. There have been... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Guidelines recommend increased salt intake as a first-line recommendation in the management of symptomatic orthostatic hypotension and recurrent syncope. There have been no systematic reviews of this intervention. We sought to summarize the evidence for increased salt intake in patients with orthostatic intolerance syndromes.
METHODS
We conducted a systematic review and meta-analysis of studies in PubMed, EMBASE, and CINAHL. Interventional studies that increased salt intake in individuals with orthostatic intolerance syndromes were included. Primary outcome measures included incidence of falls and injuries, and rates of syncope and presyncope. Secondary outcome measures included other orthostatic intolerance symptoms, blood pressure, and heart rate.
RESULTS
A total of 14 studies were eligible, including participants with orthostatic hypotension, syncope, postural orthostatic tachycardia syndrome, and idiopathic orthostatic tachycardia (n = 391). Mean age was 35.6 (± 15) years. All studies were small and short-term (<60 mins-90 days). No study reported on the effect of increased salt intake on falls or injuries. Meta-analysis demonstrated that during head-up tilt, mean time to presyncope with salt intake increased by 1.57 minutes (95% confidence interval [CI], 1.26-1.88), mean systolic blood pressure increased by 12.27 mm Hg (95% CI, 10.86-13.68), and mean heart rate decreased by -3.97 beats per minute (95% CI, -4.08 to -3.86), compared with control. Increased salt increased supine blood pressure by 1.03 mm Hg (95% CI, 0.81 to 1.25). Increased salt intake resulted in an improvement or resolution of symptoms in 62.3% (95% CI, 51.6 to 72.6) of participants in short-term follow-up studies (mean follow-up of 44.3 days, 6 studies; n=91). Methodological quality of studies were low with high statistical heterogeneity in all meta-analyses.
CONCLUSIONS
Our meta-analysis provides low-quality evidence of a short-term improvement in orthostatic intolerance with increased salt intake. There were no clinical trials demonstrating the efficacy and safety of increased salt intake on long-term clinical outcomes. Overall, there is a paucity of clinical trial evidence to support a cornerstone recommendation in the management of orthostatic intolerance syndromes.
Topics: Adult; Humans; Middle Aged; Orthostatic Intolerance; Sodium Chloride, Dietary; Young Adult
PubMed: 32603788
DOI: 10.1016/j.amjmed.2020.05.028 -
Cureus May 2023The literature on pharmacologic treatments for postural orthostatic tachycardia syndrome (POTS) is inconsistent and unstandardized. Therefore, we aimed to evaluate... (Review)
Review
The literature on pharmacologic treatments for postural orthostatic tachycardia syndrome (POTS) is inconsistent and unstandardized. Therefore, we aimed to evaluate choices in pharmacologic treatment options for POTS and the challenges encountered in the studies. We searched numerous databases like PubMed, Scopus, Embase, Web of Science, and Google Scholar for literature published before April 8, 2023. The search was done to retrieve potential peer-reviewed articles that explored drug therapy in POTS. Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines were used to conduct the systematic review. Of the 421 potential articles assessed, 17 met the inclusion criteria. Results demonstrated that pharmacologic treatment options for POTS were effective in reducing symptoms of POTS, but most of the studies were underpowered. Several were terminated due to various reasons. Midodrine ivabradine, bisoprolol, fludrocortisone, droxidopa, desmopressin, propranolol, modafinil, methylphenidate, and melatonin have been studied with positive impact but sample sizes that were low in the range of 10-50 subjects. Therefore, we concluded the treatment options effectively improve symptoms of POTS and increase orthostatic tolerance, but more evidence is needed as most studies had a low sample size and thus are underpowered.
PubMed: 37313107
DOI: 10.7759/cureus.38887 -
Heart Rhythm Nov 2022Cardioneuroablation (CNA) has emerged as promising therapy for patients with refractory vasovagal syncope (VVS). (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cardioneuroablation (CNA) has emerged as promising therapy for patients with refractory vasovagal syncope (VVS).
OBJECTIVE
The purpose of this study was to provide a freedom from syncope estimate for CNA, including subgroup analysis by method and target of ablation.
METHODS
A systematic search was performed in MEDLINE and EMBASE according to the PRISMA guidelines until February 14, 2022. Observational studies and clinical trials reporting freedom from syncope were included. Meta-analysis was performed with a random-effects model.
RESULTS
A total of 465 patients were included across 14 studies (mean age 39.8 ± 4.0 year; 53.5% female). Different techniques were used to guide CNA: 50 patients (10.8%) by mapping fractionated electrograms, 73 (15.7%) with the spectral method, 210 (45.2%) with high-frequency stimulation, 73 (15.7%) with a purely anatomically guided method, and 59 (12.6%) with a combination. The target was biatrial in 168 patients (36.1%), left atrium only in 259 (55.7%), and right atrium only in 38 (8.2%). The freedom from syncope was 91.9% (95% confidence interval [CI] 88.1%-94.6%; I = 6.9%; P = .376). CNA limited to right atrial ablation was associated with a significant lower freedom from syncope (81.5%; 95% CI 51.9%-94.7%; P <.0001) vs left atrial ablation only (94.0%; 95% CI 88.6%--6.9%) and biatrial ablation (92.7%; 95% CI 86.8%-96.1%). Subgroup analysis according to the technique used to identify ganglionated plexi did not show any significant difference in freedom from syncope (P = .206).
CONCLUSION
This meta-analysis suggests a high freedom from syncope after CNA in VVS. Well-designed, double-blind, multicenter, sham-controlled randomized clinical trials are needed to provide evidence for future guidelines.
Topics: Humans; Female; Adult; Male; Syncope, Vasovagal; Atrial Fibrillation; Heart Atria; Atrial Appendage; Catheter Ablation; Randomized Controlled Trials as Topic; Multicenter Studies as Topic
PubMed: 35716859
DOI: 10.1016/j.hrthm.2022.06.017