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Therapeutic Advances in... 2022Clozapine is the most effective medication for treatment-refractory schizophrenia but is associated with significant adverse drug effects, including hypotension and... (Review)
Review
BACKGROUND
Clozapine is the most effective medication for treatment-refractory schizophrenia but is associated with significant adverse drug effects, including hypotension and dizziness, which have a negative impact on quality of life and treatment compliance. Available evidence for the management of clozapine-induced hypotension is scant.
OBJECTIVES
Due to limited guidance on the safety and efficacy of pharmacological treatments for clozapine-induced hypotension, we set out to systematically review and assess the evidence for the management of clozapine-induced hypotension and provide guidance to clinicians, patients, and carers.
DESIGN
We undertook a systematic review of the safety and efficacy of interventions for clozapine-induced hypotension given the limited available evidence.
DATA SOURCES AND METHODS
PubMed, Embase, PsycINFO, CINAHL, and the Cochrane trial Registry were searched from inception to November 2021 for literature on the treatment strategies for clozapine-induced hypotension and dizziness using a PROSPERO pre-registered search strategy. For orthostatic hypotension, we developed a management framework to assist in the choice of intervention.
RESULTS
We identified nine case studies and four case series describing interventions in 15 patients. Hypotension interventions included temporary clozapine dose reduction, non-pharmacological treatments, and pharmacological treatments. Midodrine, fludrocortisone, moclobemide and Bovril combination, and etilefrine were associated with improvement in symptoms or reduction in orthostatic hypotension. Angiotensin II, arginine vasopressin, and noradrenaline successfully restored and maintained mean arterial pressure in critical care situations. A paradoxical reaction of severe hypotension was reported with adrenaline use.
CONCLUSION
Orthostatic hypotension is a common side effect during clozapine titration. Following an assessment of the titration schedule, salt and fluid intake, and review of hypertensive and nonselective α1-adrenergic agents, first-line treatment should be a temporary reduction in clozapine dose or non-pharmacological interventions. If orthostatic hypotension persists, fludrocortisone should be trialled with monitoring of potassium levels and sodium and fluid intake. Midodrine may be considered second-line or where fludrocortisone is contraindicated or poorly tolerated. For patients on clozapine with hypotension in critical care settings, the use of adrenaline to maintain mean arterial pressure should be avoided.
REGISTRATION
PROSPERO (Registration No. CRD42020191530).
PubMed: 35633931
DOI: 10.1177/20451253221092931 -
The Journals of Gerontology. Series A,... Feb 2024Falls are a common cause of injury, hospitalization, functional decline, and residential care admission among older adults. Cardiovascular disorders are recognized risk... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Falls are a common cause of injury, hospitalization, functional decline, and residential care admission among older adults. Cardiovascular disorders are recognized risk factors for falls. This systematic review assesses the association between cardiovascular disorders and falls in older adults.
METHODS
Systematic searches were conducted on MEDLINE and Embase, encompassing all literature published prior to December 31, 2022. Included studies addressed persons aged 50 years and older, and assessed the association between cardiovascular disorders and falls or the efficacy of cardiovascular-based interventions to reduce falls. Two reviewers independently extracted data and assessed study quality utilizing a modified Newcastle-Ottawa scale for observational studies, and the Cochrane Risk of Bias 2 tool for interventional studies. A systematic narrative analysis of all cardiovascular outcomes, and meta-analyses of unadjusted odds ratios (ORs) were performed.
RESULTS
One hundred and eighty-four studies were included: 181 observational and 3 interventional. Several cardiovascular disorders, including stroke, coronary artery disease, valvular heart disease, arterial stiffness, arrhythmia, orthostatic hypotension, and carotid sinus hypersensitivity, were consistently associated with falls. In meta-analysis of unadjusted ORs, the largest positive pooled associations with falls during a 12-month reporting interval were for stroke (OR: 1.90, 95% confidence interval [CI]: 1.70-2.11), peripheral arterial disease (OR: 1.82, 95% CI: 1.12-2.95), atrial fibrillation (OR: 1.52, 95% CI: 1.27-1.82), and orthostatic hypotension (OR: 1.39, 95% CI: 1.18-1.64).
CONCLUSIONS
Several cardiovascular disorders are associated with falls. These results suggest the need to incorporate cardiovascular assessments for patients with falls. This review informed the cardiovascular recommendations in the new World Guidelines for falls in older adults.Clinical Trials Registration Number: CRD42021272245.
Topics: Humans; Middle Aged; Aged; Hypotension, Orthostatic; Accidental Falls; Cardiovascular Diseases; Risk Factors; Stroke
PubMed: 37738307
DOI: 10.1093/gerona/glad221 -
Clinical Autonomic Research : Official... Jun 2022Orthostatic syncope (transient loss of conscious when standing-fainting) is common and negatively impacts quality of life. Many patients with syncope report experiencing... (Review)
Review
BACKGROUND
Orthostatic syncope (transient loss of conscious when standing-fainting) is common and negatively impacts quality of life. Many patients with syncope report experiencing fatigue, sometimes with "brain fog", which may further impact their quality of life, but the incidence and severity of fatigue in patients with syncope remain unclear. In this systematic review, we report evidence on the associations between fatigue and conditions of orthostatic syncope.
METHODS
We performed a comprehensive literature search of four academic databases to identify articles that evaluated the association between orthostatic syncope [postural orthostatic tachycardia syndrome (POTS), vasovagal syncope (VVS), orthostatic hypotension (OH)] and fatigue. Studies were independently screened using a multi-stage approach by two researchers to maintain consistency and limit bias.
RESULTS
Our initial search identified 2797 articles, of which 13 met our inclusion criteria (POTS n = 10; VVS n = 1; OH n = 1; VVS and POTS n = 1). Fatigue scores were significantly higher in patients with orthostatic syncope than healthy controls, and were particularly severe in those with POTS. Fatigue associated with orthostatic syncope disorders spanned multiple domains, with each dimension contributing equally to increased fatigue. "Brain fog" was an important symptom of POTS, negatively affecting productivity and cognition. Finally, fatigue was negatively associated with mental health in patients with POTS.
CONCLUSION
In conditions of orthostatic syncope, fatigue is prevalent and debilitating, especially in patients with POTS. The consideration of fatigue in patients with orthostatic disorders is essential to improve diagnosis and management of symptoms, thus improving quality of life for affected individuals.
Topics: Fatigue; Humans; Hypotension, Orthostatic; Postural Orthostatic Tachycardia Syndrome; Quality of Life; Syncope; Syncope, Vasovagal; Tilt-Table Test
PubMed: 35689118
DOI: 10.1007/s10286-022-00868-z -
The Journals of Gerontology. Series A,... Jan 2020Orthostatic hypotension (OH) is associated with increased risk of falls, cognitive impairment and death, as well as a reduced quality of life. Although it is presumed to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Orthostatic hypotension (OH) is associated with increased risk of falls, cognitive impairment and death, as well as a reduced quality of life. Although it is presumed to be common in older people, estimates of its prevalence vary widely. This study aims to address this by pooling the results of epidemiological studies.
METHODS
MEDLINE, EMBASE, PubMed, Web of Science, and ProQuest were searched. Studies were included if participants were more than 60 years, were set within the community or within long-term care and diagnosis was based on a postural drop in systolic blood pressure (BP) ≥20 mmHg or diastolic BP ≥10 mmHg. Data were extracted independently by two reviewers. Random and quality effects models were used for pooled analysis.
RESULTS
Of 23,090 identified records, 20 studies were included for community-dwelling older people (n = 24,967) and six were included for older people in long-term settings (n = 2,694). There was substantial variation in methods used to identify OH with differing supine rest duration, frequency and timing of standing BP, measurement device, use of standing and tilt-tables and interpretation of the diagnostic drop in BP. The pooled prevalence of OH in community-dwelling older people was 22.2% (95% CI = 17, 28) and 23.9% (95% CI = 18.2, 30.1) in long-term settings. There was significant heterogeneity in both pooled results (I2 > 90%).
CONCLUSIONS
OH is very common, affecting one in five community-dwelling older people and almost one in four older people in long-term care. There is great variability in methods used to identify OH.
Topics: Aged; Blood Pressure; Global Health; Humans; Hypotension, Orthostatic; Independent Living; Prevalence; Quality of Life; Risk Factors
PubMed: 30169579
DOI: 10.1093/gerona/gly188 -
Age and Ageing Sep 2021Initial orthostatic hypotension (OH) is a clinical syndrome of exaggerated transient orthostasis associated with higher risks of falls, frailty and syncope in older... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Initial orthostatic hypotension (OH) is a clinical syndrome of exaggerated transient orthostasis associated with higher risks of falls, frailty and syncope in older adults.
OBJECTIVE
To provide a prevalence estimate of initial OH in adults aged 65 years or older.
METHODS
Literature search of MEDLINE (from 1946), Embase (from 1947) and Cochrane Central Register of Controlled Trials was performed until 6 December 2019, using the terms 'initial orthostatic hypotension', 'postural hypotension' and 'older adults'. Articles were included if published in English and participants were 65 years or older. Random effects models were used for pooled analysis.
RESULTS
Of 5,136 articles screened, 13 articles (10 cross-sectional; 3 longitudinal) reporting data of 5,465 individuals (54.5% female) from the general (n = 4,157), geriatric outpatient (n = 1,136), institutionalised (n = 55) and mixed (n = 117) population were included. Blood pressure was measured continuously and intermittently in 11 and 2 studies, respectively. Pooled prevalence of continuously measured initial OH was 29.0% (95% CI: 22.1-36.9%, I2 = 94.6%); 27.8% in the general population (95% CI: 17.9-40.5%, I2 = 96.1%), 35.2% in geriatric outpatients (95% CI: 24.2-48.1%, I2 = 95.3%), 10.0% in institutionalised individuals (95% CI: 2.4-33.1%, I2 = 0%) and 21.4% in the mixed population (95% CI: 7.0-49.6, I2 = 0%). Pooled prevalence of intermittently measured initial OH was 5.6% (95% CI: 1.5-18.9%, I2 = 81.1%); 1.0% in the general population (95% CI: 0.0-23.9%, I2 = 0%) and 7.7% in geriatric outpatients (95% CI: 1.8-27.0%, I2 = 86.7%).
CONCLUSION
The prevalence of initial OH is high in older adults, especially in geriatric outpatients. Proper assessment of initial OH requires continuous blood pressure measurements.
Topics: Accidental Falls; Aged; Blood Pressure; Cross-Sectional Studies; Female; Frailty; Humans; Hypotension, Orthostatic; Male; Prevalence
PubMed: 34260686
DOI: 10.1093/ageing/afab090 -
Clinical Parkinsonism & Related... 2021Frailty and Parkinson's disease (PD) are common conditions that increase with age. Independently, frailty and PD lead to increased morbidity and mortality for patients.... (Review)
Review
INTRODUCTION
Frailty and Parkinson's disease (PD) are common conditions that increase with age. Independently, frailty and PD lead to increased morbidity and mortality for patients. Few studies report on frailty in patients with PD. We performed a systematic review and -analysis of the prevalence, associations and outcomes of frailty in persons with PD.
METHODS
We searched four electronic databases and grey literature from inception to May 19, 2020, for articles which reported the prevalence, associations and outcomes of frailty in persons with PD.
RESULTS
One-thousand and sixty-three citations were identified, of which 127 articles were reviewed. Thirty studies were included. Twenty-eight studies were observational and the settings varied including 25 community and 5 inpatient studies.The most common frailty screening measures were the frailty phenotype and clinical frailty scale. The prevalence of frailty in PD using the FP was 0.38 (0.24-0.55) with I = 92.6% (p < 0.01). Frailty was associated with recurrent falls, cognitive impairment, dementia, orthostatic hypotension, fatigue, hallucinations, nursing home placement, dependency in activities of daily living and in-patient mortality. PD disease duration, motor impairment, non-tremor dominant PD (postural instability/gait difficulty dominant phenotype) and total daily levodopa dose were associated with frailty.
CONCLUSION
Frailty is common in PD. There is no agreed upon tool for identifying frailty, however, the importance of its identification is apparent given the high prevalence and the association between frailty and adverse outcomes in persons with PD. Future studies are required to guide clinicians in how best to identify and manage frail patients with PD.
PubMed: 34316672
DOI: 10.1016/j.prdoa.2021.100095 -
Cardiology 2023Space travel imposes significant gravitational and radiation stress on both cellular and systemic physiology, resulting in myriad cardiovascular changes that have not...
INTRODUCTION
Space travel imposes significant gravitational and radiation stress on both cellular and systemic physiology, resulting in myriad cardiovascular changes that have not been fully characterized.
METHODS
We conducted a systematic review of the cellular and clinical adaptations of the cardiovascular system after exposure to real or simulated space travel in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The PubMed and Cochrane databases were searched in June 2021 for all peer-reviewed articles published since 1950 related to the following search terms entered in separate pairs: "cardiology and space" and "cardiology and astronaut." Only cellular and clinical studies in English concerning the investigation of cardiology and space were included.
RESULTS
Eighteen studies were identified, comprising 14 clinical and 4 cellular investigations. On the genetic level, pluripotent stem cells in humans and cardiomyocytes in mice displayed increased beat irregularity, with clinical studies revealing a persistent increase in heart rate after space travel. Further cardiovascular adaptations included a higher frequency of orthostatic tachycardia but no evidence of orthostatic hypotension, after return to sea level. Hemoglobin concentration was also consistently decreased after return to Earth. No consistent change in systolic or diastolic blood pressure or any clinically significant arrhythmias were observed during or after space travel.
CONCLUSION
Changes in oxygen carrying capacity, blood pressure, and post-flight orthostatic tachycardia may serve as reasons to further screen for pre-existing anemic and hypotensive conditions among astronauts.
Topics: Humans; Animals; Mice; Space Flight; Astronauts; Heart; Blood Pressure; Tachycardia
PubMed: 37302388
DOI: 10.1159/000531466 -
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 -
Clinical Autonomic Research : Official... Aug 2021To systematically review the evidence base for the effectiveness and safety of caffeine for the treatment of neurogenic orthostatic hypotension in adults.
PURPOSE
To systematically review the evidence base for the effectiveness and safety of caffeine for the treatment of neurogenic orthostatic hypotension in adults.
METHODS
Eight electronic databases were searched in January 2021. Original research studies or case reports involving adults with neurogenic orthostatic hypotension were included if caffeine was an intervention and outcomes included symptoms, blood pressure or adverse effects. Relevant studies were screened and underwent qualitative analysis. Insufficient reporting precluded meta-analysis.
RESULTS
Five studies were identified: four crossover studies and one case report summation. Study size ranged from 5 to 16 participants. Participants had neurogenic orthostatic hypotension, with a mean standing systolic blood pressure of 86 mmHg. Two studies evaluated caffeine alone. Three studies administered caffeine in combination with ergotamine. Caffeine dose ranged from 100 to 300 mg. Nature and timing of outcomes measured varied between studies, with measurements being recorded from 30 to 480 min after intervention. Caffeine/ergotamine improved symptoms in one study and reduced orthostatic blood pressure drop in two studies. Caffeine/ergotamine increased seated blood pressure in three studies, whilst the results for caffeine alone were inconsistent. No serious adverse events were reported. All studies demonstrated high risk of bias.
CONCLUSION
Caffeine should only be considered as a treatment for adults with neurogenic orthostatic hypotension when evidence-based treatments have been exhausted.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO ID: CRD42020124589. Date of registration: 30/10/2020.
Topics: Adult; Blood Pressure; Caffeine; Databases, Factual; Humans; Hypotension, Orthostatic
PubMed: 34143333
DOI: 10.1007/s10286-021-00814-5 -
Frontiers in Cardiovascular Medicine 2022Syncope (transient loss of consciousness and postural tone) and presyncope are common manifestations of autonomic dysfunction that are usually triggered by orthostasis....
PURPOSE
Syncope (transient loss of consciousness and postural tone) and presyncope are common manifestations of autonomic dysfunction that are usually triggered by orthostasis. The global impact of syncope on quality of life (QoL) is unclear. In this systematic review, we report evidence on the impact of syncope and presyncope on QoL and QoL domains, identify key factors influencing QoL in patients with syncopal disorders, and combine available data to compare QoL between syncopal disorders and to population normative data.
METHODS
A comprehensive literature search of academic databases (MEDLINE (PubMed), Web of Science, CINAHL, PsycINFO, and Embase) was conducted (February 2021) to identify peer-reviewed publications that evaluated the impact of vasovagal syncope (VVS), postural orthostatic tachycardia syndrome (POTS), or orthostatic hypotension (OH) on QoL. Two team members independently screened records for inclusion and extracted data relevant to the study objectives.
RESULTS
From 12,258 unique records identified by the search, 36 studies met the inclusion criteria (VVS: = 20; POTS: = 13; VVS and POTS: = 1; OH: = 2); 12 distinct QoL instruments were used. Comparisons of QoL scores between patients with syncope/presyncope and a control group were performed in 16 studies; significant QoL impairments in patients with syncope/presyncope were observed in all studies. Increased syncopal event frequency, increased autonomic symptom severity, and the presence of mental health disorders and/or comorbidities were associated with lower QoL scores.
CONCLUSION
This review synthesizes the negative impact of syncope/presyncope on QoL and identifies research priorities to reduce the burden of these debilitating disorders and improve patient QoL.
PubMed: 35224062
DOI: 10.3389/fcvm.2022.834879