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Annals of Internal Medicine Jan 2021Although intensive blood pressure (BP)-lowering treatment reduces risk for cardiovascular disease, there are concerns that it might cause orthostatic hypotension (OH). (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although intensive blood pressure (BP)-lowering treatment reduces risk for cardiovascular disease, there are concerns that it might cause orthostatic hypotension (OH).
PURPOSE
To examine the effects of intensive BP-lowering treatment on OH in hypertensive adults.
DATA SOURCES
MEDLINE, EMBASE, and Cochrane CENTRAL from inception through 7 October 2019, without language restrictions.
STUDY SELECTION
Randomized trials of BP pharmacologic treatment (more intensive BP goal or active agent) that involved more than 500 adults with hypertension or elevated BP and that were 6 months or longer in duration. Trial comparisons were groups assigned to either less intensive BP goals or placebo, and the outcome was measured OH, defined as a decrease of 20 mm Hg or more in systolic BP or 10 mm Hg or more in diastolic BP after changing position from seated to standing.
DATA EXTRACTION
2 investigators independently abstracted articles and rated risk of bias.
DATA SYNTHESIS
5 trials examined BP treatment goals, and 4 examined active agents versus placebo. Trials examining BP treatment goals included 18 466 participants with 127 882 follow-up visits. Trials were open-label, with minimal heterogeneity of effects across trials. Intensive BP treatment lowered risk for OH (odds ratio, 0.93 [95% CI, 0.86 to 0.99]). Effects did not differ by prerandomization OH ( for interaction = 0.80). In sensitivity analyses that included 4 additional placebo-controlled trials, overall and subgroup findings were unchanged.
LIMITATIONS
Assessments of OH were done while participants were seated (not supine) and did not include the first minute after standing. Data on falls and syncope were not available.
CONCLUSION
Intensive BP-lowering treatment decreases risk for OH. Orthostatic hypotension, before or in the setting of more intensive BP treatment, should not be viewed as a reason to avoid or de-escalate treatment for hypertension.
PRIMARY FUNDING SOURCE
National Heart, Lung, and Blood Institute, National Institutes of Health. (PROSPERO: CRD42020153753).
Topics: Antihypertensive Agents; Blood Pressure; Blood Pressure Determination; Humans; Hypertension; Hypotension, Orthostatic
PubMed: 32909814
DOI: 10.7326/M20-4298 -
Seminars in Neurology Oct 2020Acute-onset and severe sensory and autonomic deficits with no motor dysfunction, typically preceded by a febrile illness, with poor recovery, and often fatal outcome are...
Acute-onset and severe sensory and autonomic deficits with no motor dysfunction, typically preceded by a febrile illness, with poor recovery, and often fatal outcome are the hallmark features of acute sensory and autonomic neuronopathy (ASANN). Pathologically and electrophysiologically, ASANN is characterized by an extensive ganglionopathy affecting sensory and autonomic ganglia with preservation of motor neurons. Consequently, patients, usually children or young adult, develop acute-onset profound widespread loss of all sensory modalities resulting in automutilations, as well as autonomic failure causing neurogenic orthostatic hypotension, neurogenic underactive bladder, and gastroparesis and constipation. The diagnosis is clinical with support of nerve conduction studies and autonomic testing, as well as spinal cord magnetic resonance imaging showing characteristic posterior cord hyperintensities. Although the presumed etiology is immune-mediated, further studies are required to clarify the physiopathology of the disease. We here performed a systematic review of the epidemiology, pathophysiology, diagnosis, and management of ASANN, with three representative cases that recently presented at our clinic. All three patients had the typical clinical manifestations of ASANN but in different combinations, illustrating the variable phenotype of the disorder. Immunosuppression is seldom effective. Management options are limited to supportive and symptomatic care with the goal of minimizing complications and preventing death.
Topics: Autonomic Nervous System Diseases; Ganglia, Autonomic; Ganglia, Sensory; Humans
PubMed: 32906171
DOI: 10.1055/s-0040-1713843 -
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 -
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 -
Ultrasound (Leeds, England) May 2020It has long been suggested that ultrasound could be used to measure brain tissue pulsations in humans, but potential clinical applications are relatively unexplored. The...
INTRODUCTION
It has long been suggested that ultrasound could be used to measure brain tissue pulsations in humans, but potential clinical applications are relatively unexplored. The aim of this systematic review was to explore and synthesise available literature on ultrasound measurement of brain tissue motion in humans.
METHODS
Our systematic review was designed to include predefined study selection criteria, quality evaluation, and a data extraction , registered prospectively on PROSPERO (CRD42018114117). The systematic review was conducted by two independent reviewers.
RESULTS
Ten studies were eligible for the evidence synthesis and qualitative evaluation. All eligible studies confirmed that brain tissue motion over the cardiac cycle could be measured using ultrasound; however, data acquisition, analysis, and outcomes varied. The majority of studies used tissue pulsatility imaging, with the right temporal window as the acquisition point. Currently available literature is largely exploratory, with measurements of brain tissue displacement over a narrow range of health conditions and ages. Explored health conditions include orthostatic hypotension and depression.
CONCLUSION
Further studies are needed to assess variability in brain tissue motion estimates across larger cohorts of healthy subjects and in patients with various medical conditions. This would be important for informing sample size estimates to ensure future studies are appropriately powered. Future research would also benefit from a consistent framework for data analysis and reporting, to facilitate comparative research and meta-analysis. Following standardisation and further healthy participant studies, future work should focus on assessing the clinical utility of brain tissue pulsation measurements in cerebrovascular disease states.
PubMed: 32528543
DOI: 10.1177/1742271X19894601 -
Indian Heart Journal 2019Orthostatic hypotension (OH) is common among elderly patients. Its presence may herald severe underlying comorbidities and be associated with a higher risk of mortality.... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Orthostatic hypotension (OH) is common among elderly patients. Its presence may herald severe underlying comorbidities and be associated with a higher risk of mortality. Interestingly, recent studies suggest that OH is associated with new-onset atrial fibrillation (AF). However, a systematic review and meta-analysis of the literature has not been performed. We assessed the association between AF and OH through a systematic review of the literature and a meta-analysis.
METHODS
We comprehensively searched the databases of MEDLINE and EMBASE from inception to November 2018. Published prospective or retrospective cohort studies that compared new-onset AF between male patients with and without OH were included. Data from each study were combined using the random-effects, generic inverse-variance method of DerSimonian and Laird to calculate risk ratios and 95% confidence intervals.
RESULTS
Four studies from October 2010 to March 2018 were included in the meta-analysis involving 76,963 subjects (of which 3318 were diagnosed with OH). The presence of OH was associated with new-onset AF (pooled risk ratio 1.48; 95% confidence interval [1.21, 1.81], p?< 0.001; I2 = 69.4%). In hypertensive patients, analysis revealed an association between OH and the occurrence of new-onset AF (OR 1.46; 95% CI [1.27, 1.68], p < 0.001 with I2 = 0).
CONCLUSIONS
OH was associated with new-onset AF up to 1.5-fold compared with those subjects without OH. The interplay between OH and AF is likely bidirectional.
Topics: Aged; Atrial Fibrillation; Humans; Hypotension, Orthostatic; Risk Factors
PubMed: 31779860
DOI: 10.1016/j.ihj.2019.07.009 -
Clinical Autonomic Research : Official... Sep 2019Autonomic dysfunction is a hallmark feature of hereditary ATTR amyloidosis. The aim of this study was to summarize the characteristics and natural history of autonomic...
BACKGROUND
Autonomic dysfunction is a hallmark feature of hereditary ATTR amyloidosis. The aim of this study was to summarize the characteristics and natural history of autonomic dysfunction in patients with hereditary ATTR amyloidosis.
METHODS
A systematic review of the natural history and clinical trials of patients with ATTR amyloidosis was performed. Alternative surrogate markers of autonomic function were analyzed to understand the prevalence and outcome of autonomic dysfunction.
RESULTS
Patients with early-onset disease displayed autonomic dysfunction more distinctively than those with late-onset disease. The nutritional status and some autonomic items in the quality-of-life questionnaires were used to assess the indirect progression of autonomic dysfunction in most studies. Gastrointestinal symptoms and orthostatic hypotension were resent earlier than urogenital complications. Once symptoms were present, their evolution was equivalent to the progression of the motor and sensory neuropathy impairment.
CONCLUSION
The development of autonomic dysfunction impacts morbidity, disease progression, and mortality in patients with hereditary ATTR amyloidosis.
Topics: Amyloid Neuropathies, Familial; Autonomic Nervous System Diseases; Humans
PubMed: 31473866
DOI: 10.1007/s10286-019-00630-y -
Journal of Clinical Hypertension... Aug 2019The relationships between orthostatic hypotension (OH) and some kinds of cardiovascular disease are inconsistent among studies. This updated meta-analysis was conducted... (Meta-Analysis)
Meta-Analysis
The relationships between orthostatic hypotension (OH) and some kinds of cardiovascular disease are inconsistent among studies. This updated meta-analysis was conducted in hopes of producing progress on this topic. A systematic database search was performed in electronic databases, including the Chinese Biomedical Database (CBM), PubMed, Web of Science, and the Cochrane Library. Summary hazard ratio (HR) estimates with 95% confidence intervals (CIs) were calculated by a random-effects model. Statistical heterogeneity was assessed with Cochran's Q test and the I statistic. From 1462 potentially eligible records, 15 studies met the inclusion criteria. Subjects with OH had a high risk of heart failure (HF) and atrial fibrillation (AF) (pooled HR 1.34, 95% CI 1.17-1.52, P < 0.001 and pooled HR 1.51, 95% CI 1.28-1.79, P < 0.001, respectively). This meta-analysis also showed significant associations between OH and the risks of developing coronary heart disease (CHD) (pooled HR 1.44, 95% CI 1.18-1.75, P < 0.001) and myocardial infarction (MI) (pooled HR 1.52, 95% CI 1.12-2.06, P = 0.008). Our study suggests that OH is positively associated with high risks of HF and AF. Moreover, it may be related to high risks of CHD and MI.
Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Cardiovascular Diseases; Coronary Disease; Female; Humans; Hypotension, Orthostatic; Male; Middle Aged; Myocardial Infarction; Prevalence; Prospective Studies; Risk Factors; Sensitivity and Specificity
PubMed: 31290595
DOI: 10.1111/jch.13613 -
Journal of Clinical Hypertension... Mar 2019Orthostatic hypertension (OHT), that is, sustained increase in blood pressure after standing, is an increasingly recognized cardiovascular disorder having been examined... (Comparative Study)
Comparative Study
Orthostatic hypertension (OHT), that is, sustained increase in blood pressure after standing, is an increasingly recognized cardiovascular disorder having been examined in much fewer studies compared with orthostatic hypotension (OH). However, in both OHT and OH, dysfunction of the autonomous nervous system is considered to be the primary pathophysiological disturbance, while significant associations with essential hypertension have been observed. Although in many studies OHT has been related to subclinical or clinical target organ damage, there is also evidence denying such an association. Because OHT is defined variably across different studies, the comparison of relevant outcomes is at least problematic. Since evidence about OHT treatment is exclusively based on limited non-randomized studies, no specific recommendations have been developed. Therefore, both the prognostic role and the clinical significance of OHT remain largely undefined. The aim of the present review is to summarize the available evidence regarding the definition, diagnosis, pathophysiology, prognostic role and treatment of OHT and highlight potential clinical implications of this underestimated condition.
Topics: Autonomic Nervous System Diseases; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Cardiovascular Diseases; Dizziness; Humans; Hypertension; Hypotension, Orthostatic; Non-Randomized Controlled Trials as Topic; Prognosis; Tilt-Table Test
PubMed: 30724451
DOI: 10.1111/jch.13491 -
The Cochrane Database of Systematic... Dec 2018Studies report that up to 80% of individuals with chronic obstructive pulmonary disease (COPD) may struggle with symptoms of depression. However, this major comorbidity... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Studies report that up to 80% of individuals with chronic obstructive pulmonary disease (COPD) may struggle with symptoms of depression. However, this major comorbidity in COPD is rarely managed effectively. A number of recent studies indicate that left untreated, COPD-related depression is associated with worse quality of life, worse compliance with COPD treatment plan, increased exacerbations, hospital admissions, and healthcare costs when compared to individuals with COPD without depression. Regrettably, COPD practice guidelines do not provide conclusive treatment recommendations for the use of antidepressants in patients with COPD, and base their guidelines on findings from trials in the general population. This may be problematic, as there is an elevated risk of respiratory issues associated with antidepressant treatment and COPD. Evaluating effectiveness and safety of pharmacological interventions specifically for patients with COPD and depression was therefore paramount.
OBJECTIVES
To assess the effectiveness and safety of pharmacological interventions for the treatment of depression in patients with COPD.
SEARCH METHODS
The last search was performed on 26 November 2018. We initially searched the following databases via the Specialised Trials Registers of the Cochrane Airways and Common Mental Disorders Groups (to June 2016): MEDLINE, Embase, PsycINFO, CINAHL, AMED, and the Cochrane Library trials register (CENTRAL). Searches from June 2016 to November 2018 were performed directly on Ovid MEDLINE, Embase, PsycINFO and the Cochrane Library (Issue 11, 2018). We searched ClinicalTrials.gov, the ISRCTN registry, and the World Health Organization International Clinical Trials Registry Platform to 26 November 2018. We searched the grey literature databases to identify studies not indexed in major databases and the reference lists of studies initially identified for full-text screening.
SELECTION CRITERIA
All published and unpublished randomised controlled trials (RCTs) comparing the efficacy of pharmacological interventions with no intervention, placebo or co-intervention in adults with diagnosed COPD and depression were eligible for inclusion.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed articles identified by the search for eligibility. Our primary outcomes were change in depressive symptoms and adverse events. The secondary outcomes were: change in quality of life, change in dyspnoea, change in forced expiratory volume in one second (FEV), change in exercise tolerance, change in hospital utilisation (length of stay and readmission rates), and cost-effectiveness. For continuous outcomes, we calculated the pooled mean difference (MD) or standardised mean difference (SMD) with 95% confidence interval (CI) as appropriate. For dichotomous outcomes, we calculated the pooled odds ratio (OR) and corresponding 95% CI using a random-effects model. We assessed the quality of evidence using the GRADE framework.
MAIN RESULTS
Of the 1125 records screened for eligibility, four RCTs (N = 201 participants), and one on-going study, met the inclusion criteria. Two classes of antidepressants were investigated in two separate comparisons with placebo: a tricyclic antidepressant (TCA) and selective serotonin reuptake inhibitors (SSRIs).TCA versus placeboOnly one RCT (N = 30 participants) provided results for this comparison.Primary outcomesThe TCA (nortriptyline) reduced depressive symptoms post-treatment compared to placebo (MD -10.20, 95% CI -16.75 to -3.65; P = 0.007; very low-quality evidence), as measured by the Hamilton Depression Rating Scale (HAM-D). Three participants withdrew from the trial due to adverse events related to the tested antidepressant (dry mouth, sedation, orthostatic hypotension).Secondary outcomesThe overall results post-treatment indicated that nortriptyline was not effective in improving the quality of life of individuals with COPD, as measured by the Sickness Impact Profile (MD -2.80, 95% CI -11.02 to 5.42; P = 0.50; very low-quality evidence).The results for the change in dyspnoea for the domains examined (e.g. dyspnoea scores for 'most day-to-day activities') post-treatment showed no improvement in the intervention group (MD 9.80, 95% CI -6.20 to 25.80; P = 0.23; very low-quality evidence).No data were reported for change in FEV, change in exercise tolerance, change in hospital utilisation, or cost-effectiveness. The TCA study provided short-term results, with the last follow-up data collection at 12 weeks.The quality of the evidence for all the outcomes evaluated was very low due to a small sample size, imprecision, attrition, and selection and reporting bias.SSRIs versus placeboThree RCTs (N = 171 participants) provided results for this comparison.Primary outcomesThe pooled results for two studies showed no difference for the change in depressive symptoms post-intervention (SMD 0.75, 95% CI -1.14 to 2.64; 148 participants; 2 studies; P = 0.44; very low-quality evidence). High heterogeneity was observed (I² = 95%), limiting the reliability of these findings.While it was not possible to meta-analyse the total adverse events rates across the studies, it was possible to combine the results for two medication-specific adverse effects: nausea and dizziness. There were no significant post-treatment group differences for nausea (OR 2.32, 95% CI 0.66 to 8.12; 171 participants; 3 studies; P = 0.19; very low-quality evidence) or dizziness (OR 0.61, 95% CI 0.09 to 4.06; 143 participants; 2 studies; P = 0.61; very low-quality evidence).Secondary outcomesThe pooled analysis of two trials reporting data for the change in quality of life did not show improvement post-treatment in the intervention group compared to placebo (SMD 1.17, 95% CI -0.80 to 3.15; 148 participants; 2 studies; P = 0.25; very low-quality evidence).There was no difference between groups in change in FEV post-treatment (MD 0.01, 95% CI -0.03 to 0.05; 148 participants; 2 studies; P = 0.60; low-quality evidence). However, two trials reported improvement in exercise tolerance in the SSRI group versus the placebo group (MD 13.88, 95% CI 11.73 to 16.03; 148 participants; 2 studies; P < 0.001; very low-quality evidence).The trials included in this comparison did not report data related to the change in dyspnoea, hospital utilisation rates, or cost-effectiveness.
AUTHORS' CONCLUSIONS
There is insufficient evidence to make definitive statements about the efficacy or safety of antidepressants for treating COPD-related depression. New RCTs are needed; with better methodological quality and more accurate reporting of the methods used. Moreover, longer-term follow-up data collection is needed, including outcomes such as adverse events, hospital utilisation and cost-effectiveness.
Topics: Antidepressive Agents, Tricyclic; Depression; Dizziness; Dyspnea; Exercise Tolerance; Forced Expiratory Volume; Humans; Nausea; Nortriptyline; Paroxetine; Placebos; Pulmonary Disease, Chronic Obstructive; Quality of Life; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Sertraline
PubMed: 30566235
DOI: 10.1002/14651858.CD012346.pub2