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Neuromodulation : Journal of the... Jun 2024This review aims to assess the efficacy of transcutaneous electrical nerve stimulation (TENS) for neurogenic bladder after spinal cord injury (SCI). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
This review aims to assess the efficacy of transcutaneous electrical nerve stimulation (TENS) for neurogenic bladder after spinal cord injury (SCI).
MATERIALS AND METHODS
A systematic search was conducted of seven electronic data bases from inception to Dec 31, 2022, to identify randomized controlled trials that studied TENS for neurogenic bladder after SCI. The primary outcomes were maximum cystometric capacity (MCC) and residual urine volume (RUV). Secondary outcomes included maximum detrusor pressure, flow rate, and bladder diary. Random effects models were used in all analyses.
RESULTS
Eleven trials involving 881 participants were included. Meta-analysis showed that TENS in addition to conventional treatment had larger MCC (mean difference [MD] 50.55 ml, 95% CI 27.81-73.29, p<0.0001) and lower RUV (MD -22.96 ml, 95% CI -33.45 to -12.47, p<0.0001) than did conventional treatment only. Compared with magnetic stimulation, no differences were observed with TENS for MCC (MD -14.49 ml, 95% CI -48.97 to 19.98, p = 0.41) and RUV (MD 25 ml, 95% CI -61.79 to 111.79, p = 0.57). There also were no differences in MCC (MD -7.2 ml, 95% CI -14.56 to 0.16, p= 0.06) and (MD -5.2 ml, 95% CI -60.00 to 49.60, p = 0.851) when compared with solifenacin succinate and pelvic floor biofeedback, respectively.
CONCLUSIONS
TENS may be an effective treatment option for neurogenic bladder after SCI.
Topics: Spinal Cord Injuries; Humans; Urinary Bladder, Neurogenic; Transcutaneous Electric Nerve Stimulation; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 37642626
DOI: 10.1016/j.neurom.2023.06.002 -
The Cochrane Database of Systematic... Feb 2018Fibromyalgia is a clinically defined chronic condition of unknown etiology characterized by chronic widespread pain that often co-exists with sleep disturbances,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Fibromyalgia is a clinically defined chronic condition of unknown etiology characterized by chronic widespread pain that often co-exists with sleep disturbances, cognitive dysfunction and fatigue. People with fibromyalgia often report high disability levels and poor quality of life. Drug therapy, for example, with serotonin and noradrenaline reuptake inhibitors (SNRIs), focuses on reducing key symptoms and improving quality of life. This review updates and extends the 2013 version of this systematic review.
OBJECTIVES
To assess the efficacy, tolerability and safety of serotonin and noradrenaline reuptake inhibitors (SNRIs) compared with placebo or other active drug(s) in the treatment of fibromyalgia in adults.
SEARCH METHODS
For this update we searched CENTRAL, MEDLINE, Embase, the US National Institutes of Health and the World Health Organization (WHO) International Clinical Trials Registry Platform for published and ongoing trials and examined the reference lists of reviewed articles, to 8 August 2017.
SELECTION CRITERIA
We selected randomized, controlled trials of any formulation of SNRIs against placebo or any other active treatment of fibromyalgia in adults.
DATA COLLECTION AND ANALYSIS
Three review authors independently extracted data, examined study quality, and assessed risk of bias. For efficacy, we calculated the number needed to treat for an additional beneficial outcome (NNTB) for pain relief of 50% or greater and of 30% or greater, patient's global impression to be much or very much improved, dropout rates due to lack of efficacy, and the standardized mean differences (SMD) for fatigue, sleep problems, health-related quality of life, mean pain intensity, depression, anxiety, disability, sexual function, cognitive disturbances and tenderness. For tolerability we calculated number needed to treat for an additional harmful outcome (NNTH) for withdrawals due to adverse events and for nausea, insomnia and somnolence as specific adverse events. For safety we calculated NNTH for serious adverse events. We undertook meta-analysis using a random-effects model. We assessed the evidence using GRADE and created a 'Summary of findings' table.
MAIN RESULTS
We added eight new studies with 1979 participants for a total of 18 included studies with 7903 participants. Seven studies investigated duloxetine and nine studies investigated milnacipran against placebo. One study compared desvenlafaxine with placebo and pregabalin. One study compared duloxetine with L-carnitine. The majority of studies were at unclear or high risk of bias in three to five domains.The quality of evidence of all comparisons of desvenlafaxine, duloxetine and milnacipran versus placebo in studies with a parallel design was low due to concerns about publication bias and indirectness, and very low for serious adverse events due to concerns about publication bias, imprecision and indirectness. The quality of evidence of all comparisons of duloxetine and desvenlafaxine with other active drugs was very low due to concerns about publication bias, imprecision and indirectness.Duloxetine and milnacipran had no clinically relevant benefit over placebo for pain relief of 50% or greater: 1274 of 4104 (31%) on duloxetine and milnacipran reported pain relief of 50% or greater compared to 591 of 2814 (21%) participants on placebo (risk difference (RD) 0.09, 95% confidence interval (CI) 0.07 to 0.11; NNTB 11, 95% CI 9 to 14). Duloxetine and milnacipran had a clinically relevant benefit over placebo in patient's global impression to be much or very much improved: 888 of 1710 (52%) on duloxetine and milnacipran (RD 0.19, 95% CI 0.12 to 0.26; NNTB 5, 95% CI 4 to 8) reported to be much or very much improved compared to 354 of 1208 (29%) of participants on placebo. Duloxetine and milnacipran had a clinically relevant benefit compared to placebo for pain relief of 30% or greater. RD was 0.10; 95% CI 0.08 to 0.12; NNTB 10, 95% CI 8 to 12. Duloxetine and milnacipran had no clinically relevant benefit for fatigue (SMD -0.13, 95% CI -0.18 to -0.08; NNTB 18, 95% CI 12 to 29), compared to placebo. There were no differences between either duloxetine or milnacipran and placebo in reducing sleep problems (SMD -0.07; 95 % CI -0.15 to 0.01). Duloxetine and milnacipran had no clinically relevant benefit compared to placebo in improving health-related quality of life (SMD -0.20, 95% CI -0.25 to -0.15; NNTB 11, 95% CI 8 to 14).There were 794 of 4166 (19%) participants on SNRIs who dropped out due to adverse events compared to 292 of 2863 (10%) of participants on placebo (RD 0.07, 95% CI 0.04 to 0.10; NNTH 14, 95% CI 10 to 25). There was no difference in serious adverse events between either duloxetine, milnacipran or desvenlafaxine and placebo (RD -0.00, 95% CI -0.01 to 0.00).There was no difference between desvenlafaxine and placebo in efficacy, tolerability and safety in one small trial.There was no difference between duloxetine and desvenlafaxine in efficacy, tolerability and safety in two trials with active comparators (L-carnitine, pregabalin).
AUTHORS' CONCLUSIONS
The update did not change the major findings of the previous review. Based on low- to very low-quality evidence, the SNRIs duloxetine and milnacipran provided no clinically relevant benefit over placebo in the frequency of pain relief of 50% or greater, but for patient's global impression to be much or very much improved and in the frequency of pain relief of 30% or greater there was a clinically relevant benefit. The SNRIs duloxetine and milnacipran provided no clinically relevant benefit over placebo in improving health-related quality of life and in reducing fatigue. Duloxetine and milnacipran did not significantly differ from placebo in reducing sleep problems. The dropout rates due to adverse events were higher for duloxetine and milnacipran than for placebo. On average, the potential benefits of duloxetine and milnacipran in fibromyalgia were outweighed by their potential harms. However, a minority of people with fibromyalgia might experience substantial symptom relief without clinically relevant adverse events with duloxetine or milnacipran.We did not find placebo-controlled studies with other SNRIs than desvenlafaxine, duloxetine and milnacipran.
Topics: Adrenergic Uptake Inhibitors; Adult; Carnitine; Cyclopropanes; Desvenlafaxine Succinate; Duloxetine Hydrochloride; Fibromyalgia; Humans; Milnacipran; Norepinephrine; Pregabalin; Quality of Life; Selective Serotonin Reuptake Inhibitors; Syndrome
PubMed: 29489029
DOI: 10.1002/14651858.CD010292.pub2 -
The Cochrane Database of Systematic... Dec 2016Several options exist for managing overactive bladder (OAB), including electrical stimulation (ES) with non-implanted devices, conservative treatment and drugs.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Several options exist for managing overactive bladder (OAB), including electrical stimulation (ES) with non-implanted devices, conservative treatment and drugs. Electrical stimulation with non-implanted devices aims to inhibit contractions of the detrusor muscle, potentially reducing urinary frequency and urgency.
OBJECTIVES
To assess the effects of ES with non-implanted electrodes for OAB, with or without urgency urinary incontinence, compared with: placebo or any other active treatment; ES added to another intervention compared with the other intervention alone; different methods of ES compared with each other.
SEARCH METHODS
We searched the Cochrane Incontinence Specialised Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In-Process, ClinicalTrials.gov, WHO ICTRP and handsearching of journals and conference proceedings (searched 10 December 2015). We searched the reference lists of relevant articles and contacted specialists in the field. We imposed no language restrictions.
SELECTION CRITERIA
We included randomised or quasi-randomised controlled trials of ES with non-implanted devices compared with any other treatment for OAB in adults. Eligible trials included adults with OAB with or without urgency urinary incontinence (UUI). Trials whose participants had stress urinary incontinence (SUI) were excluded.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened search results, extracted data from eligible trials and assessed risk of bias, using the Cochrane 'Risk of bias' tool.
MAIN RESULTS
We identified 63 eligible trials (4424 randomised participants). Forty-four trials did not report the primary outcomes of perception of cure or improvement in OAB. The majority of trials were deemed to be at low or unclear risk of selection and attrition bias and unclear risk of performance and detection bias. Lack of clarity with regard to risk of bias was largely due to poor reporting.For perception of improvement in OAB symptoms, moderate-quality evidence indicated that ES was better than pelvic floor muscle training (PFMT) (risk ratio (RR) 1.60, 95% confidence interval (CI) 1.19 to 2.14; n = 195), drug treatment (RR 1.20, 95% 1.04 to 1.38; n = 439). and placebo or sham treatment (RR 2.26, 95% CI 1.85 to 2.77, n = 677) but it was unclear if ES was more effective than placebo/sham for urgency urinary incontinence (UUI) (RR 5.03, 95% CI 0.28 to 89.88; n = 242). Drug treatments included in the trials were oestrogen cream, oxybutynin, propantheline bromide, probanthine, solifenacin succinate, terodiline, tolterodine and trospium chloride.Low- or very low-quality evidence suggested no evidence of a difference in perception of improvement of UUI when ES was compared to PFMT with or without biofeedback.Low- quality evidence indicated that OAB symptoms were more likely to improve with ES than with no active treatment (RR 1.85, 95% CI 1.34 to 2.55; n = 121).Low- quality evidence suggested participants receiving ES plus PFMT, compared to those receiving PFMT only, were more than twice as likely to report improvement in UUI (RR 2.82, 95% CI 1.44 to 5.52; n = 51).There was inconclusive evidence, which was either low- or very low-quality, for OAB-related quality of life when ES was compared to no active treatment, placebo/sham or biofeedback-assisted PFMT, or when ES was added to PFMT compared to PFMT-only. There was very low-quality evidence from a single trial to suggest that ES may be better than PFMT in terms of OAB-related quality of life.There was a lower risk of adverse effects with ES than tolterodine (RR 0.12, 95% CI 0.05 to 0.27; n = 200) (moderate-quality evidence) and oxybutynin (RR 0.11, 95% CI 0.01 to 0.84; n = 79) (low-quality evidence).Due to the very low-quality evidence available, we could not be certain whether there were fewer adverse effects with ES compared to placebo/sham treatment, magnetic stimulation or solifenacin succinate. We were also very uncertain whether adding ES to PFMT or to drug therapy resulted in fewer adverse effects than PFMT or drug therapy alone Nor could we tell if there was any difference in risk of adverse effects between different types of ES.There was insufficient evidence to determine if one type of ES was more effective than another or if the benefits of ES persisted after the active treatment period stopped.
AUTHORS' CONCLUSIONS
Electrical stimulation shows promise in treating OAB, compared to no active treatment, placebo/sham treatment, PFMT and drug treatment. It is possible that adding ES to other treatments such as PFMT may be beneficial. However, the low quality of the evidence base overall means that we cannot have full confidence in these conclusions until adequately powered trials have been carried out, measuring subjective outcomes and adverse effects.
Topics: Adult; Electric Stimulation Therapy; Electrodes; Humans; Pelvic Floor; Randomized Controlled Trials as Topic; Urinary Bladder, Overactive; Urinary Incontinence, Urge
PubMed: 27935011
DOI: 10.1002/14651858.CD010098.pub4 -
Frontiers in Pharmacology 2022(AP) is a traditionally used herbaceous plant, whose main active constituent is andrographolide. Andrographolide derivative medications and herbal preparations of AP... (Review)
Review
Adverse Effects of Andrographolide Derivative Medications Compared to the Safe use of Herbal Preparations of : Results of a Systematic Review and Meta-Analysis of Clinical Studies.
(AP) is a traditionally used herbaceous plant, whose main active constituent is andrographolide. Andrographolide derivative medications and herbal preparations of AP are often used to treat respiratory tract infections. This study aims to systematically evaluate the safety of andrographolide derivative medications and herbal preparations of AP based on clinical studies. English and Chinese databases were searched for all types of clinical studies that reported adverse drug reactions (ADRs) and adverse events (AEs) of andrographolide derivative medications and herbal preparations of AP. The ADRs and AEs were classified according to manifestations, and graded according to severity. Single-rate meta-analysis was performed for ADR incidence using R software. A total of 262 studies were included, including 125 randomized controlled trials, 23 non-randomized controlled trials, 6 case series, and 108 case reports. In 9490 participants using andrographolide derivative injections, 383 (4.04%) reported ADRs. Meta-analysis showed that the ADR incidence of three most frequently used injections of andrographolide derivatives (andrographolide sulfonate, potassium sodium dehydroandrographolide succinate, and potassium dehydroandrographolide succinate) were 5.48% [95% CI (4.47%, 6.72%)], 3.69% [95% CI (2.59%, 4.94%)] and 5.33% [95% CI (3.68%, 7.72%)], respectively, which may be slightly higher than the actual ADR incidence, because only studies that reported the occurrence of ADRs or AEs were included, but studies without ADR and AE were not included. The ADRs of andrographolide derivative injections were mainly gastrointestinal, skin and subcutaneous tissue disorders, and anaphylaxis. Fifty-five patients experienced life-threatening anaphylactic shock, three patients died, and the causation attributed to the andrographolide derivative injection. Other ADRs were mild, moderate or medically significant. Nine herbal preparations of AP were tested in 10 studies, and the reported ADRs were mainly mild to moderate gastrointestinal, skin and subcutaneous tissue disorders. Except for five patients using andrographolide derivative injections eventually died, most of the ADRs were alleviated after drug withdrawal and symptomatic treatment. The ADRs of andrographolide derivative medications are few, but can be life-threatening, mainly gastrointestinal, skin and subcutaneous tissue disorders, and anaphylaxis. Injections of andrographolide derivatives should be used with caution. Herbal preparations of AP are essentially safe. : [website], identifier [registration number].
PubMed: 35153776
DOI: 10.3389/fphar.2022.773282 -
The Cochrane Database of Systematic... Jul 2018Ear wax (cerumen) is a normal bodily secretion that can become a problem when it obstructs the ear canal. Symptoms attributed to wax (such as deafness and pain) are... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Ear wax (cerumen) is a normal bodily secretion that can become a problem when it obstructs the ear canal. Symptoms attributed to wax (such as deafness and pain) are among the commonest reasons for patients to present to primary care with ear trouble.Wax is part of the ear's self-cleaning mechanism and is usually naturally expelled from the ear canal without causing problems. When this mechanism fails, wax is retained in the canal and may become impacted; interventions to encourage its removal may then be needed. Application of ear drops is one of these methods. Liquids used to remove and soften wax are of several kinds: oil-based compounds (e.g. olive or almond oil); water-based compounds (e.g. sodium bicarbonate or water itself); a combination of the above or non-water, non-oil-based solutions, such as carbamide peroxide (a hydrogen peroxide-urea compound) and glycerol.
OBJECTIVES
To assess the effects of ear drops (or sprays) to remove or aid the removal of ear wax in adults and children.
SEARCH METHODS
We searched the Cochrane ENT Trials Register; Cochrane Register of Studies; PubMed; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the most recent search was 23 March 2018.
SELECTION CRITERIA
Randomised controlled trials (RCTs) in which a 'cerumenolytic' was compared with no treatment, water or saline, an alternative liquid treatment (oil or almond oil) or another 'cerumenolytic' in adults or children with obstructing or impacted ear wax.
DATA COLLECTION AND ANALYSIS
We used the standard methodological procedures expected by Cochrane. The primary outcomes were 1) the proportion of patients (or ears) with complete clearance of ear wax and 2) adverse effects (discomfort, irritation or pain). Secondary outcomes were: extent of wax clearance; proportion of people (or ears) with relief of symptoms due to wax; proportion of people (or ears) requiring further intervention to remove wax; success of mechanical removal of residual wax following treatment; any other adverse effects recorded and cost. We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics.
MAIN RESULTS
We included 10 studies, with 623 participants (900 ears). Interventions included: oil-based treatments (triethanolamine polypeptide, almond oil, benzocaine, chlorobutanol), water-based treatments (docusate sodium, carbamide peroxide, phenazone, choline salicylate, urea peroxide, potassium carbonate), other active comparators (e.g. saline or water alone) and no treatment. Nine of the studies were more than 15 years old.The overall risk of bias across the 10 included studies was low or unclear.
PRIMARY OUTCOME
proportion of patients (or ears) with complete clearance of ear waxSix studies (360 participants; 491 ears) contributed quantitative data and were included in our meta-analyses.Active treatment versus no treatmentOnly one study addressed this comparison. The proportion of ears with complete clearance of ear wax was higher in the active treatment group (22%) compared with the no treatment group (5%) after five days of treatment (risk ratio (RR) 4.09, 95% confidence interval (CI) 1.00 to 16.80); one study; 117 ears; NNTB = 8) (low-quality evidence).Active treatment versus water or salineWe found no evidence of a difference in the proportion of patients (or ears) with complete clearance of ear wax when the active treatment group was compared to the water or saline group (RR 1.47, 95% CI 0.79 to 2.75; three studies; 213 participants; 257 ears) (low-quality evidence). Two studies applied drops for five days, but one study only applied the drops for 15 minutes. When we excluded this study in a sensitivity analysis it did not change the result.Water or saline versus no treatmentThis comparison was only addressed in the single study cited above (active versus no treatment) and there was no evidence of a difference in the proportion of ears with complete wax clearance when comparing water or saline with no treatment after five days of treatment (RR 4.00, 95% CI 0.91 to 17.62; one study; 76 ears) (low-quality evidence).Active treatment A versus active treatment BSeveral single studies evaluated 'head-to-head' comparisons between two active treatments. We found no evidence to show that one was superior to any other.Subgroup analysis of oil-based active treatments versus non-oil based active treatmentsWe found no evidence of a difference in this outcome when oil-based treatments were compared with non-oil-based active treatments.
PRIMARY OUTCOME
adverse effects: discomfort, irritation or painOnly seven studies planned to measure and did report this outcome. Only two (141 participants;176 ears) provided useable data. There was no evidence of a significant difference in the number of adverse effects between the types of ear drops in these two studies. We summarised the remaining five studies narratively. All events were mild and reported in fewer than 30 participants across the seven studies (low-quality evidence).Secondary outcomesThree studies reported 'other' adverse effects (how many studies planned to report these is unclear). The available information was limited and included occasional reports of dizziness, unpleasant smell, tinnitus and hearing loss. No significant differences between groups were reported. There were no emergencies or serious adverse effects reported in any of the 10 studies.There was very limited or no information available on our remaining secondary outcomes.
AUTHORS' CONCLUSIONS
Although a number of studies aimed to evaluate whether or not one type of cerumenolytic is more effective than another, there is no high-quality evidence to allow a firm conclusion to be drawn and the answer remains uncertain.A single study suggests that applying ear drops for five days may result in a greater likelihood of complete wax clearance than no treatment at all. However, we cannot conclude whether one type of active treatment is more effective than another and there was no evidence of a difference in efficacy between oil-based and water-based active treatments.There is no evidence to show that using saline or water alone is better or worse than commercially produced cerumenolytics. Equally, there is also no evidence to show that using saline or water alone is better than no treatment.
Topics: Adult; Antipyrine; Benzocaine; Carbamide Peroxide; Carbonates; Cerumen; Child; Chlorobutanol; Choline; Dioctyl Sulfosuccinic Acid; Drug Combinations; Ear Canal; Ethanolamines; Humans; Hygiene; Peroxides; Pharmaceutical Solutions; Plant Oils; Potassium; Randomized Controlled Trials as Topic; Salicylates; Sodium Chloride; Surface-Active Agents; Urea; Water
PubMed: 30043448
DOI: 10.1002/14651858.CD012171.pub2 -
Current Medical Research and Opinion 2016Overactive bladder (OAB) is a particular challenge to treat in older adults with co-morbid conditions taking multiple medications. Antimuscarinics (e.g., solifenacin,... (Review)
Review
OBJECTIVE
Overactive bladder (OAB) is a particular challenge to treat in older adults with co-morbid conditions taking multiple medications. Antimuscarinics (e.g., solifenacin, fesoterodine) and β3-adrenergic receptor agonists (mirabegron) are similarly efficacious; however, antimuscarinics may be associated with side effects that result in poor persistence and contribute to anticholinergic burden, particularly in those taking other medications with anticholinergic properties. With a mechanism of action distinct from antimuscarinics, mirabegron has a different tolerability profile and does not contribute to anticholinergic burden. The objective of this review was to compare and contrast the tolerability profiles of antimuscarinics and mirabegron in older patients to inform practice.
METHODS
Prospective trials or retrospective subgroup analyses of antimuscarinics for the treatment of OAB in older patients were identified through a search of PubMed. Tolerability data and results of subgroup analyses of mirabegron in patients aged ≥65 and ≥75 years from a pooled analysis of three trials each of 12 weeks and a 1 year trial are described.
RESULTS
Anticholinergic adverse events (AEs) including dry mouth and constipation were more frequent with antimuscarinics versus mirabegron. In patients aged ≥65 years, dry mouth occurred with a six-fold higher incidence with tolterodine extended-release (ER) 4 mg than with mirabegron 25 mg or 50 mg over 12 weeks, and a three-fold higher incidence with tolterodine ER than mirabegron 50 mg over 1 year. Mirabegron had a low incidence of central nervous system effects. A systematic review of the cardiovascular safety profile of mirabegron has not identified any clinically significant effects on blood pressure or pulse rate at therapeutic doses amongst patients aged ≥65 years.
CONCLUSIONS
Mirabegron has a more favorable tolerability profile than antimuscarinics amongst older patients and may provide an improved benefit-to-risk ratio and therefore be considered as an alternative to antimuscarinics for older patients.
Topics: Acetanilides; Administration, Oral; Adrenergic beta-Antagonists; Aged; Benzhydryl Compounds; Blood Pressure; Clinical Trials as Topic; Constipation; Female; Heart Rate; Humans; Male; Middle Aged; Muscarinic Antagonists; Prospective Studies; Retrospective Studies; Solifenacin Succinate; Thiazoles; Tolterodine Tartrate; Urinary Bladder, Overactive
PubMed: 26828974
DOI: 10.1185/03007995.2016.1149806 -
Journal of Medical Genetics Apr 2020Pheochromocytoma and paraganglioma (PPGL) are tumours that arise from chromaffin cells. Some genetic mutations influence PPGL, among which, those in genes encoding... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pheochromocytoma and paraganglioma (PPGL) are tumours that arise from chromaffin cells. Some genetic mutations influence PPGL, among which, those in genes encoding subunits of succinate dehydrogenase (SDHA, SDHB, SDHC and SDHD) and assembly factor (SDHAF2) are the most relevant. However, the risk of metastasis posed by these mutations is not reported except for SDHB and SDHD mutations. This study aimed to update the metastatic risks, considering prevalence and incidence of each SDHx mutation, which were dealt formerly all together.
METHODS
We searched EMBASE and MEDLINE and selected 27 articles. The patients included in the studies were divided into three groups depending on the presence of PPGL. We checked the heterogeneity between studies and performed a meta-analysis using Hartung-Knapp-Sidik-Jonkman method based on a random effect model.
RESULTS
The highest PPGL prevalence was for SDHB mutation, ranging from 23% to 31%, and for SDHC mutation (23%), followed by that for SDHA mutation (16%). The lowest prevalence was for SDHD mutation, ranging from 6% to 8%. SDHAF2 mutation showed no metastatic events. The PPGL incidence showed a tendency similar to that of its prevalence with the highest risk of metastasis posed by SDHB mutation (12%-41%) and the lowest risk by SDHD mutation (~4%).
CONCLUSION
There was no integrated evidence of how SDHx mutations are related to metastatic PPGL. However, these findings suggest that SDHA, SDHB and SDHC mutations are highly associated and should be tested as indicators of metastasis in patients with PPGL.
Topics: Adrenal Gland Neoplasms; Electron Transport Complex II; Germ-Line Mutation; Heterozygote; Humans; Membrane Proteins; Mitochondrial Proteins; Neoplasm Metastasis; Paraganglioma; Pheochromocytoma; Succinate Dehydrogenase
PubMed: 31649053
DOI: 10.1136/jmedgenet-2019-106324 -
American Journal of Therapeutics 2020Beta-blockers are one of the most important classes of cardiovascular agents and have been considered a cornerstone therapy in heart diseases, such as heart failure (HF)...
BACKGROUND
Beta-blockers are one of the most important classes of cardiovascular agents and have been considered a cornerstone therapy in heart diseases, such as heart failure (HF) and atrial fibrillation (AF). Among different beta-blockers, metoprolol is a selective beta1-adrenergic antagonist, which has been extensively used since the 1970s.
AREAS OF UNCERTAINTY
Although current guidelines include recommendations for the use of controlled-release metoprolol succinate in specific HF and AF indications, and despite extensive clinical experience with metoprolol, comparative evidence on the use of metoprolol succinate compared with other beta-blockers in these indications is limited.
DATA SOURCES
We systematically reviewed the data from head-to-head studies directly comparing this compound with other beta-blockers in the treatment of HF or AF. Only clinical trials and observational studies were considered; no other limits were applied. The quality and relevance of retrieved articles were reviewed.
RESULTS
A total of 18 articles of the 353 articles identified were selected for inclusion; 12 HF articles and 6 for AF. Additional references were identified from the bibliographies of retrieved articles. The studies show that oral prophylaxis with an appropriate dose of metoprolol may reduce new incidents of AF in high-risk patients. Furthermore, metoprolol succinate is associated with significant mortality and morbidity benefits in the treatment of HF.
CONCLUSIONS
Despite the introduction of newer beta-blockers with differing clinical characteristics since its introduction, metoprolol succinate remains a useful drug in both HF and AF.
Topics: Adrenergic alpha-1 Receptor Antagonists; Adrenergic beta-Antagonists; Atrial Fibrillation; Heart Failure; Humans; Metoprolol
PubMed: 31385823
DOI: 10.1097/MJT.0000000000001043 -
The Cochrane Database of Systematic... Apr 2016Several options exist for managing overactive bladder (OAB), including electrical stimulation (ES) with non-implanted devices, conservative treatment and drugs.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Several options exist for managing overactive bladder (OAB), including electrical stimulation (ES) with non-implanted devices, conservative treatment and drugs. Electrical stimulation with non-implanted devices aims to inhibit contractions of the detrusor muscle, potentially reducing urinary frequency and urgency.
OBJECTIVES
To determine the effectiveness of: ES with non-implanted electrodes compared with placebo or any other active treatment for OAB; ES added to another intervention compared with the other intervention alone; different methods of ES compared with each other.
SEARCH METHODS
We searched the Cochrane Incontinence Group Specialised Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In-Process, ClinicalTrials.gov, WHO ICTRP and handsearching of journals and conference proceedings (searched 10 December 2014). We searched the reference lists of relevant articles and contacted specialists in the field. We imposed no language restrictions.
SELECTION CRITERIA
We included randomised or quasi-randomised controlled trials of ES with non-implanted devices compared with any other treatment for OAB in adults. Eligible trials included adults with OAB with or without urgency urinary incontinence (UUI). Trials whose participants had stress urinary incontinence (SUI) were excluded.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened search results, extracted data from eligible trials and assessed risk of bias, using the Cochrane Collaboration's 'Risk of bias' tool.
MAIN RESULTS
We identified 51 eligible trials (3443 randomised participants). Thirty-three trials did not report the primary outcomes of subjective change in OAB symptoms. The majority of trials were deemed to be at low or unclear risk of selection and attrition bias and unclear risk of performance and detection bias. Lack of clarity with regard to risk of bias was largely due to poor reporting.Twenty-three trials (1654 participants) compared ES with no active treatment, placebo or sham treatment. Moderate-quality evidence indicated that OAB symptoms were more likely to improve in people receiving ES than with no active treatment, placebo or sham treatment (relative risk (RR) for no improvement 0.54, 95% confidence interval (CI) 0.47 to 0.63). Moderate-quality evidence indicated that similar numbers of people receiving ES and no active treatment, placebo or sham treatment experienced adverse effects.Eight trials (542 participants) compared ES with conservative treatment. Very low-quality evidence suggested no evidence of a difference between ES and PFMT or PFMT plus biofeedback in OAB symptoms (RR for no improvement 0.79, 95% CI 0.51 to 1.21 and 0.97, 95% CI 0.60 to 1.57 respectively). There was no evidence of a difference between ES and conservative treatment with regard to adverse effects.Sixteen trials (894 participants) compared ES with drug treatment (probanthine, tolterodine, oxybutynin, propantheline bromide, solifenacin succinate, terodiline, trospium chloride, terodiline). Moderate-quality evidence indicated that OAB symptoms were more likely to improve with ES than drug treatment (RR for no improvement 0.66, 95% CI 0.48 to 0.90). Low-quality evidence suggested a greater risk of adverse effects with oxybutynin (RR 1.26, 95% CI 1.07 to 1.49) and with tolterodine (RR 1.51, 95% CI 1.21 to 1.89) than with ES. There was insufficient evidence of a difference between ES and trospium hydrochloride (RR 0.73, 95% CI 0.43 to 1.25).Eight trials (252 participants) compared ES combined with another treatment versus the other treatment alone, two trials (48 participants) compared ES plus conservative treatment with no active treatment, placebo or sham treatment and six trials (361 participants) compared different types of ES. None of these comparisons had sufficient evidence to indicate any differences between the treatment groups in terms of OAB or adverse effects.Moderate-quality evidence suggested that ES improved OAB-related quality of life more than no active treatment, placebo or sham treatment. There was insufficient evidence of any difference between ES and any other treatment with regard to quality of life.There was insufficient evidence to determine if the benefits of ES persisted after the active treatment period stopped.
AUTHORS' CONCLUSIONS
Electrical stimulation appeared to be more effective than both no treatment and drug treatment for OAB. There was insufficient evidence to determine if ES was more effective than conservative treatment or which type of ES was more effective. This review underlines the need to conduct well-designed trials in this field measuring subjective outcomes and adverse effects.
Topics: Adult; Electric Stimulation Therapy; Electrodes; Humans; Randomized Controlled Trials as Topic; Urinary Bladder, Overactive
PubMed: 27037009
DOI: 10.1002/14651858.CD010098.pub3 -
International Journal of Molecular... Oct 2022Mitochondria dysfunction is implicated in the pathogenesis of cardiovascular diseases (CVD). Exercise training is potentially an effective non-pharmacological strategy... (Meta-Analysis)
Meta-Analysis Review
Mitochondria dysfunction is implicated in the pathogenesis of cardiovascular diseases (CVD). Exercise training is potentially an effective non-pharmacological strategy to restore mitochondrial health in CVD. However, how exercise modifies mitochondrial functionality is inconclusive. We conducted a systematic review using the PubMed; Scopus and Web of Science databases to investigate the effect of exercise training on mitochondrial function in CVD patients. Search terms included “mitochondria”, “exercise”, “aerobic capacity”, and “cardiovascular disease” in varied combination. The search yielded 821 records for abstract screening, of which 20 articles met the inclusion criteria. We summarized the effect of exercise training on mitochondrial morphology, biogenesis, dynamics, oxidative capacity, antioxidant capacity, and quality. Amongst these parameters, only oxidative capacity was suitable for a meta-analysis, which demonstrated a significant effect size of exercise in improving mitochondrial oxidative capacity in CVD patients (SMD = 4.78; CI = 2.99 to 6.57; p < 0.01), but with high heterogeneity among the studies (I2 = 75%, p = 0.003). Notably, aerobic exercise enhanced succinate-involved oxidative phosphorylation. The majority of the results suggested that exercise improves morphology and biogenesis, whereas findings on dynamic, antioxidant capacity, and quality, were inadequate or inconclusive. A further randomized controlled trial is clearly required to explain how exercise modifies the pathway of mitochondrial quantity and quality in CVD patients.
Topics: Humans; Antioxidants; Exercise; Cardiovascular Diseases; Mitochondria; Succinates
PubMed: 36293409
DOI: 10.3390/ijms232012559