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The Annals of Pharmacotherapy Jun 2024The objective was to evaluate the efficacy and safety of dexmedetomidine in the treatment and prophylaxis of paroxysmal sympathetic hyperactivity (PSH). (Review)
Review
OBJECTIVE
The objective was to evaluate the efficacy and safety of dexmedetomidine in the treatment and prophylaxis of paroxysmal sympathetic hyperactivity (PSH).
DATA SOURCES
A review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria and queried Embase, MEDLINE (PubMed), Cochrane CENTRAL, Web of Science, SciELO, Korean Journal Index (Clarivate), Global Index Medicus, and CINAHL Plus for results through June 2023.
STUDY SELECTION AND DATA EXTRACTION
Studies providing efficacy or safety data associated with dexmedetomidine with a reported diagnosis of PSH were included. Exclusion of studies in pediatric populations, without quantitative and qualitative outcome data, and not readily translatable to English was adhered to.
DATA SYNTHESIS
Thirteen observational studies of 178 patients were included in the qualitative analysis. Reductions in PSH frequency or symptom severity were reported in 44 of 48 patients who received dexmedetomidine for acute treatment. Prophylactic use of dexmedetomidine was associated with reductions in PSH-Assessment Measure (PSH-AM) scores in postsurgical patients with traumatic brain injuries (TBIs). Adverse events associated with dexmedetomidine were either absent or reported as none.
RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE
This review supports the safe and effective use of dexmedetomidine in the treatment and prophylaxis of PSH. Further investigation is required to determine optimal dosing strategies and the extent to which PSH etiology correlated to the efficacy of dexmedetomidine.
CONCLUSIONS
The use of dexmedetomidine appears to be both efficacious and safe for the treatment and prevention of PSH in patients experiencing a TBI. Additional research is needed to elucidate dosing strategies, titration parameters, and duration of therapy.
Topics: Dexmedetomidine; Humans; Autonomic Nervous System Diseases; Adrenergic alpha-2 Receptor Agonists; Observational Studies as Topic
PubMed: 37608463
DOI: 10.1177/10600280231194708 -
European Journal of Neurology Dec 2023Alpha-synuclein seed amplification assays (α-syn SAAs) are promising diagnostic methods for Parkinson's disease (PD) and other synucleinopathies. However, there is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND PURPOSE
Alpha-synuclein seed amplification assays (α-syn SAAs) are promising diagnostic methods for Parkinson's disease (PD) and other synucleinopathies. However, there is limited consensus regarding the diagnostic and differential diagnostic performance of α-syn SAAs on biofluids and peripheral tissues.
METHODS
A comprehensive research was performed in PubMed, Web of Science, Embase and Cochrane Library. Meta-analysis was performed using a random-effects model. A network meta-analysis based on an ANOVA model was conducted to compare the relative accuracy of α-syn SAAs with different specimens.
RESULTS
The pooled sensitivity and specificity of α-syn SAAs in distinguishing PD from healthy controls or non-neurodegenerative neurological controls were 0.91 (95% confidence interval [CI] 0.89-0.92) and 0.95 (95% CI 0.94-0.96) for cerebrospinal fluid (CSF); 0.91 (95% CI 0.86-0.94) and 0.92 (95% CI 0.87-0.95) for skin; 0.80 (95% CI 0.66-0.89) and 0.87 (95% CI 0.69-0.96) for submandibular gland; 0.44 (95% CI 0.30-0.59) and 0.92 (95% CI 0.79-0.98) for gastrointestinal tract; 0.79 (95% CI 0.70-0.86) and 0.88 (95% CI 0.77-0.95) for saliva; and 0.51 (95% CI 0.39-0.62) and 0.91 (95% CI 0.84-0.96) for olfactory mucosa (OM). The pooled sensitivity and specificity were 0.91 (95% CI 0.89-0.93) and 0.50 (95% CI 0.44-0.55) for CSF, 0.92 (95% CI 0.83-0.97) and 0.22 (95% CI 0.06-0.48) for skin, and 0.55 (95% CI 0.42-0.68) and 0.50 (95% CI 0.35-0.65) for OM in distinguishing PD from multiple system atrophy. The pooled sensitivity and specificity were 0.92 (95% CI 0.89-0.94) and 0.84 (95% CI 0.73-0.91) for CSF, 0.92 (95% CI 0.83-0.97) and 0.88 (95% CI 0.64-0.99) for skin and 0.63 (95% CI 0.52-0.73) and 0.86 (95% CI 0.64-0.97) for OM in distinguishing PD from progressive supranuclear palsy. The pooled sensitivity and specificity were 0.94 (95% CI 0.90-0.97) and 0.95 (95% CI 0.77-1.00) for CSF and 0.94 (95% CI 0.84-0.99) and 0.86 (95% CI 0.42-1.00) for skin in distinguishing PD from corticobasal degeneration.
CONCLUSIONS
α-Synuclein SAAs of CSF, skin, saliva, submandibular gland, gastrointestinal tract and OM are promising diagnostic assays for PD, with CSF and skin α-syn SAAs demonstrating higher diagnostic performance.
Topics: Humans; Parkinson Disease; alpha-Synuclein; Network Meta-Analysis; Biomarkers; Multiple System Atrophy
PubMed: 37573472
DOI: 10.1111/ene.16041 -
Progress in Cardiovascular Diseases 2023With expanding commercial space programs, uncertainty remains about the cardiovascular effects of space environmental exposures including microgravity, confinement,... (Review)
Review
BACKGROUND
With expanding commercial space programs, uncertainty remains about the cardiovascular effects of space environmental exposures including microgravity, confinement, isolation, space radiation, and altered bacterial virulence. Current limited data suggests additional health threats compared to Earth.
METHODS
We systematically reviewed PubMed, CENTRAL, Web of Science, EMBASE and Cochrane databases for prospective studies on spaceflight and cardiovascular outcomes. Search terms combined cardiovascular disease topics with spaceflight concepts. No date or language restrictions were imposed.
RESULTS
35 studies representing 2696 space travelers met inclusion criteria. Studies were grouped into spaceflight associations with: atherosclerosis, mortality, cardiac function, orthostatic intolerance, and arrhythmias. Atherosclerosis evidence was limited, with animal studies linking space radiation to endothelial damage, oxidative stress, and inflammation. However, human data showed no significantly increased atherosclerotic disease in astronauts. Mortality studies demonstrated lower cardiovascular mortality in astronauts compared to the general population however there was conflicting data. Cardiac function studies revealed physiologic ventricular atrophy, increased arterial stiffness, and altered blood flow distribution attributed to microgravity exposure. Effects appeared transient and reversible post-flight. Orthostatic intolerance studies found astronauts experienced altered heart rate variability, baroreflex response, and blood pressure changes post-flight. Arrhythmia studies showed increased ventricular ectopy during spaceflight, but limited data on long term flights.
CONCLUSIONS
Environmental space hazards impact the cardiovascular system through multiple mechanisms. Microgravity causes cardiac atrophy and orthostatic intolerance while space radiation may potentially accelerate atherosclerosis. Further research is needed, especially regarding long-term spaceflights.
Topics: Humans; Cardiovascular Diseases; Orthostatic Intolerance; Prospective Studies; Space Flight; Hemodynamics; Arrhythmias, Cardiac; Atherosclerosis; Atrophy
PubMed: 37531984
DOI: 10.1016/j.pcad.2023.07.009 -
Journal of Human Hypertension Dec 2023Worldwide, raised blood pressure (BP) or hypertension is the global leading risk factor for the development of cardiovascular diseases and all-cause mortality, with the... (Meta-Analysis)
Meta-Analysis Review
Worldwide, raised blood pressure (BP) or hypertension is the global leading risk factor for the development of cardiovascular diseases and all-cause mortality, with the highest prevalence found in Asian and African origin populations. Post-exercise hypotension (PEH), defined as a sustained reduction in BP after a single bout of exercise is an important physiological phenomenon in BP management. However, little is known about the hypotensive effect of a single bout of exercise in non-Caucasian populations. We systematically summarized the acute effects of a single bout of aerobic exercise on BP in a population of African or Asian origin. We searched the MEDLINE database identifying randomized controlled trials investigating the effect of a single bout of aerobic exercise on BP in African or Asian populations with optimal BP, high normal BP or hypertension published in a peer reviewed journal up to August 2021. A subsequent meta-analysis was performed using random-effect models fitted to estimate effect sizes. We identified 10 aerobic exercise trials performed in individuals of Asian origin (n = 136; mean age: 29.51 (21.2-69) years: 78% male; baseline systolic BP/diastolic BP: 118.9 ± 9.64/68.9 ± 2.69 mmHg) and 11 aerobic exercise trials involving individuals of African origin (n = 157; mean age: 41.05 (29.9-49) years; 59% male; baseline systolic BP/diastolic BP: 134.5 ± 8.65 mmHg/82.2 ± 3.24 mmHg). Non-significant reductions in office systolic BP and diastolic BP at 30 min post exercise (-2.25 [-6.38, 1.88] mmHg, p = 0.28/-1.02 [-2.51, 0.47] mmHg, p = 0.18) and 60 min post exercise (-2.80 [-7.90, 2.28], p = 0.27/-1.95, [-5.66, 1.75], p = 0.3) were observed compared to the control intervention. No statistically significant differences were found between both ethnic groups (p > 0.05). Ambulatory BP was reported only in a few African groups. No effect was found on 24h-systolic BP post exercise, but 24h-diastolic BP was statistically significantly reduced (-1.89 [-3.47, -0.31] mmHg, p < 0.01) after a bout of aerobic exercise compared to the control intervention. The available evidence is insufficient to recommend a single session of aerobic exercise as an efficient tool to lower BP in African and Asian populations. Though, the paucity of data in non-Caucasian populations underscores the need for additional efforts to establish the efficacy of single bouts of exercise, including isometric and dynamic resistance exercise, as a potential non-pharmacological adjunct to help lowering BP in the daily life of descendants of Asian or African origin.
Topics: Humans; Male; Adult; Female; Post-Exercise Hypotension; Randomized Controlled Trials as Topic; Hypertension; Blood Pressure; Hypotension
PubMed: 37468543
DOI: 10.1038/s41371-023-00844-8 -
Neuromodulation : Journal of the... Oct 2023Falls in extrapyramidal disorders, particularly Parkinson's disease (PD), multisystem atrophy (MSA), and progressive supranuclear palsy (PSP), are key milestones... (Review)
Review
BACKGROUND
Falls in extrapyramidal disorders, particularly Parkinson's disease (PD), multisystem atrophy (MSA), and progressive supranuclear palsy (PSP), are key milestones affecting patients' quality of life, incurring increased morbidity/mortality and high healthcare costs. Unfortunately, gait and balance in parkinsonisms respond poorly to currently available treatments. A serendipitous observation of improved gait and balance in patients with PD receiving spinal cord stimulation (SCS) for back pain kindled an interest in using SCS to treat gait disorders in parkinsonisms.
OBJECTIVES
We reviewed preclinical and clinical studies of SCS to treat gait dysfunction in parkinsonisms, covering its putative mechanisms and efficacies.
MATERIALS AND METHODS
Preclinical studies in animal models of PD and clinical studies in patients with PD, PSP, and MSA who received SCS for gait disorders were included. The main outcome assessed was clinical improvement in gait, together with outcome measures used and possible mechanism of actions.
RESULTS
We identified 500 references, and 45 met the selection criteria and have been included in this study for analysis. Despite positive results in animal models, the outcomes in human studies are inconsistent.
CONCLUSIONS
The lack of blind and statistically powered studies, the heterogeneity in patient selection and study outcomes, and the poor understanding of the underlying mechanisms of action of SCS are some of the limiting factors in the field. Addressing these limitations will allow us to draw more reliable conclusions on the effects of SCS on gait and balance in extrapyramidal disorders.
Topics: Humans; Parkinson Disease; Spinal Cord Stimulation; Quality of Life; Parkinsonian Disorders; Multiple System Atrophy; Gait
PubMed: 37452800
DOI: 10.1016/j.neurom.2023.06.003 -
CNS Neuroscience & Therapeutics Dec 2023Parkinsonian disorders, such as Parkinson's disease (PD), multiple system atrophy (MSA), dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP) and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND & AIMS
Parkinsonian disorders, such as Parkinson's disease (PD), multiple system atrophy (MSA), dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), share early motor symptoms but have distinct pathophysiology. As a result, accurate premortem diagnosis is challenging for neurologists, hindering efforts for disease-modifying therapeutic discovery. Extracellular vesicles (EVs) contain cell-state-specific biomolecules and can cross the blood-brain barrier to the peripheral circulation, providing a unique central nervous system (CNS) insight. This meta-analysis evaluated blood-isolated neuronal and oligodendroglial EVs (nEVs and oEVs) α-synuclein levels in Parkinsonian disorders.
METHODS
Following PRISMA guidelines, the meta-analysis included 13 studies. An inverse-variance random-effects model quantified effect size (SMD), QUADAS-2 assessed risk of bias and publication bias was evaluated. Demographic and clinical variables were collected for meta-regression.
RESULTS
The meta-analysis included 1,565 patients with PD, 206 with MSA, 21 with DLB, 172 with PSP, 152 with CBS and 967 healthy controls (HCs). Findings suggest that combined concentrations of nEVs and oEVs α-syn is higher in patients with PD compared to HCs (SMD = 0.21, p = 0.021), while nEVs α-syn is lower in patients with PSP and CBS compared to patients with PD (SMD = -1.04, p = 0.0017) or HCs (SMD = -0.41, p < 0.001). Additionally, α-syn in nEVs and/or oEVs did not significantly differ in patients with PD vs. MSA, contradicting the literature. Meta-regressions show that demographic and clinical factors were not significant predictors of nEVs or oEVs α-syn concentrations.
CONCLUSION
The results highlight the need for standardized procedures and independent validations in biomarker studies and the development of improved biomarkers for distinguishing Parkinsonian disorders.
Topics: Humans; alpha-Synuclein; Biomarkers; Central Nervous System; Extracellular Vesicles; Multiple System Atrophy; Parkinson Disease; Parkinsonian Disorders
PubMed: 37416941
DOI: 10.1111/cns.14341 -
Journal of Clinical Monitoring and... Feb 2024Background- Subarachnoid hemorrhage (SAH) is one of the most devastating diseases with a high rate of morbidity and mortality. The heart rate variability (HRV) is a... (Review)
Review
Background- Subarachnoid hemorrhage (SAH) is one of the most devastating diseases with a high rate of morbidity and mortality. The heart rate variability (HRV) is a non-invasive method of monitoring various components of the autonomic nervous system activity that can be utilized to delineate autonomic dysfunctions associated with various physiological and pathological conditions. The reliability of HRV as a predictor of clinical outcome in aneurysmal subarachnoid hemorrhage (aSAH) is not yet well investigated in literature. Methods- A systematic review and in depth analysis of 10 articles on early HRV changes in SAH patients was performed. Results- This systematic review demonstrates a correlation between early changes in HRV indices (time and frequency domain) and the development of neuro-cardiogenic complications and poor neurologic outcome in patients with SAH. Conclusions- A correlation between absolute values or changes of the LF/HF ratio and neurologic and cardiovascular complications was found in multiple studies. Because of significant limitations of included studies, a large prospective study with proper handling of confounders is needed to generate high-quality recommendations regarding HRV as a predictor of post SAH complications and poor neurologic outcome.
Topics: Humans; Subarachnoid Hemorrhage; Heart Rate; Prospective Studies; Reproducibility of Results; Autonomic Nervous System
PubMed: 37335412
DOI: 10.1007/s10877-023-01043-z -
Anesthesia and Analgesia Aug 2023Chronic pain is a recognized complication of surgery, and it has been hypothesized that regional anesthesia might reduce the risk of development of chronic pain after...
BACKGROUND
Chronic pain is a recognized complication of surgery, and it has been hypothesized that regional anesthesia might reduce the risk of development of chronic pain after upper extremity surgery.
METHODS
A systematic literature review was performed to assess whether in patients undergoing elective upper extremity surgery (P), regional anesthesia (I), compared to general anesthesia (C), would result in lower long-term (>3 months) postoperative pain intensity (O). We included randomized and nonrandomized controlled trials (RCTs). Our primary outcome was numerical rating score or visual analogue scale for pain, at >3 months postoperatively. The Embase, Medline ALL, Web of Science Core Collections, Cochrane Central Register of Controlled Trials, and Google Scholar databases were searched for all reports assessing pain at >3 months after upper extremity surgery under general versus regional anesthesia. Secondary outcomes were: opioid prescription filling, complex regional pain syndrome (CRPS) incidence, the Mayo Wrist Score (MWS), and scores on the Disability of the Arm, Shoulder and Hand (DASH) questionnaire. Quality (or certainty) of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Risk-of-bias was assessed using the Cochrane tool for randomized trials (RoB 2.0) and nonrandomized trials (ROBINS-I).
RESULTS
This review included 14 studies, comprising 7 RCTs and 7 nonrandomized studies. Six of the 7 studies (4 RCTs, N = 273; 2 nonrandomized studies, N = 305) using a pain score, our primary outcome, report comparable long-term postoperative pain scores after regional and general anesthesia. Six of the 7 studies using our secondary outcomes report comparable long-term outcomes in terms of opioid prescription filling (2 retrospective cohort studies [RCSs], N = 89,256), CRPS incidence (1 RCT, N = 301), MWS (1 RCT and 1 RCS, N = 215), and DASH score (1 RCT, N = 36). Comparable outcomes were reported in all 7 RCTs (N = 778) and in 5 of the 7 nonrandomized studies, comprising 5 RCSs (N = 89,608). Two prospective observational studies (POSTs), comprising 279 patients, report a statistically significant difference in outcomes, with less pain and better DASH scores after brachial plexus anesthesia. All 14 studies provided moderate to very low certainty evidence, and there was a serious risk of bias due to confounding bias in 5 of the 7 nonrandomized studies (N = 631).
CONCLUSIONS
The results of this review indicate that upper extremity regional anesthesia, compared to general anesthesia, is unlikely to change pain intensity at >3 months postoperatively.
Topics: Humans; Chronic Pain; Analgesics, Opioid; Retrospective Studies; Anesthesia, Conduction; Hand; Complex Regional Pain Syndromes; Pain, Postoperative; Observational Studies as Topic
PubMed: 37227939
DOI: 10.1213/ANE.0000000000006529 -
Neurochemical Research Aug 2023Peripheral neuropathies caused by the peripheral nervous system (PNS) damage can occur due to trauma and other disorders. They present as altered sensation, weakness,... (Meta-Analysis)
Meta-Analysis Review
Peripheral neuropathies caused by the peripheral nervous system (PNS) damage can occur due to trauma and other disorders. They present as altered sensation, weakness, autonomic symptoms, and debilitating pain syndrome with a wide range of clinical signs. Acetyl-L-Carnitine (ALCAR) is a biological compound with essential roles in mitochondrial oxidative metabolism and anti-oxidant effects that protects mitochondria from oxidative damage and inhibits apoptosis caused by mitochondrial damage. This study is a systematic review and meta-analysis of the effects of ALCAR on peripheral nerve injuries. This review examines studies on treating traumatic peripheral neuropathies in which ALCAR is administered to rats with sciatic nerve injury with an appropriate control group. The articles were divided based on the mode of ALCAR administration. If one method was used in more than one article, their results were entered in the "Revman5.4" software and were meta-analyzed. Studies were selected from 1994 to 2018 on rats with varying physical injuries to their sciatic nerves. In one study, ALCAR was provided to rats in their drinking water, while in other studies, ALCAR was injected intra-peritoneally. Different mechanisms of ALCAR actions have been suggested in this study, but the underpinnings of the neuroprotective effects of ALCAR are still unclear. Further studies are mandatory to clarify the actual mechanisms of the neuroprotective activity of ALCAR. Based on the results of existing studies, ALCAR effectively increases the tolerance threshold of thermal and mechanical stimuli, reduces latency, and reduces apoptosis; finally, adjusting the dose and duration of administration may increase the dose and duration axon diameter.
Topics: Animals; Rats; Acetylcarnitine; Nerve Regeneration; Peripheral Nerve Injuries; Sciatic Nerve
PubMed: 37037995
DOI: 10.1007/s11064-023-03911-1 -
European Journal of Pain (London,... Aug 2023The aim of this systematic review was to appraise and analyse the knowledge on bone-related biochemical and histological biomarkers in complex regional pain syndrome 1... (Review)
Review
OBJECTIVE
The aim of this systematic review was to appraise and analyse the knowledge on bone-related biochemical and histological biomarkers in complex regional pain syndrome 1 (CRPS 1).
DATABASE
A total of 7 studies were included in the analysis (biochemical analyses n = 3, animal study n = 1, histological examination n = 3).
RESULTS
Two studies were classified as having a low risk of bias and five studies with a moderate risk of bias. Biochemical analysis indicated an increased bone turnover with increased bone resorption (elevated urinary levels of deoxypyridinoline) and bone formation (increased serum levels of calcitonin, osteoprotegerin and alkaline phosphatase). The animal study reported an increased signalling of proinflammatory tumour necrosis factor 4 weeks postfracture, which did, however, not contribute to local bone loss. Histological examination from biopsies revealed thinning and resorption of cortical bone, rarefication and reduction in trabecular bone and vascular modification in the bone marrow in acute CRPS 1, and replacement of the bone marrow by dystrophic vessels in chronic CRPS 1.
CONCLUSION
The limited data reviewed revealed certain potential bone-related biomarkers in CRPS. Biomarkers hold the potential to identify patients who may benefit from treatments that influence bone turnover. Thus, this review identifies important areas for future research in CRPS1 patients.
Topics: Animals; Reflex Sympathetic Dystrophy; Biomarkers; Complex Regional Pain Syndromes
PubMed: 36999437
DOI: 10.1002/ejp.2116