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Clinical Endocrinology Nov 2017The outcomes of patients with metastatic phaeochromocytoma (PHEO) and paraganglioma (PGL) are unclear. We performed a systematic review and meta-analysis of baseline... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The outcomes of patients with metastatic phaeochromocytoma (PHEO) and paraganglioma (PGL) are unclear. We performed a systematic review and meta-analysis of baseline characteristics and mortality rates of patients with metastatic PHEO and PGL (PPGL).
DESIGN
Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Scopus, Web of Science, and references of key articles were searched from inception to 2016.
PATIENTS
Studies comprised ≥20 patients with metastatic PPGL and reported baseline characteristics and follow-up data.
MEASUREMENTS
Reviewers extracted standardized data and assessed risk of bias using a modified Newcastle-Ottawa tool. Random-effects meta-analysis was used to pool event rates across studies.
RESULTS
Twenty retrospective noncomparative studies reported on 1338 patients with metastatic PHEO (685/1296, 52.9%) and PGL (611/1296, 47.1%), diagnosed at a mean age of 43.9 ± 5.2 years. Mean follow-up was 6.3 ± 3.2 years. Of 532 patients with reported data, 40.4% had synchronous metastases. Five-year (7 studies, n = 738) and 10-year (2 studies, n = 55) mortality rates for patients with metastatic PPGL were 37% (95% CI, 24%-51%) and 29% (95% CI, 17%-42%), respectively. Higher mortality was associated with male sex (RR 1.50; 95% CI, 1.11-2.02) and synchronous metastases (RR 2.43; 95% CI, 1.01-5.85).
CONCLUSIONS
Available low-quality evidence from heterogeneous studies suggests low mortality rates of patients with metastatic PPGL. Male sex and synchronous metastases correlated with increased mortality. The outcomes of patients with metastatic PPGL have been inadequately assessed, indicating the need for carefully planned prospective studies.
Topics: Adrenal Gland Neoplasms; Adult; Female; Humans; Male; Middle Aged; Mortality; Neoplasm Metastasis; Paraganglioma; Pheochromocytoma; Treatment Outcome
PubMed: 28746746
DOI: 10.1111/cen.13434 -
Journal of Traditional Chinese Medicine... Apr 2015To evaluate systematically the clinical efficacy and safety of potassium dehydroandrographolide succinate injection (PDS) in treatment of infantile pneumonia. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate systematically the clinical efficacy and safety of potassium dehydroandrographolide succinate injection (PDS) in treatment of infantile pneumonia.
METHODS
Randomized controlled trials (RCTs) of infantile pneumonia treated by PDS were searched in China National Knowledge Infrastructure Database, China Science and Technology Journal Database, Wanfang Database, Chinese Biomedical Literature Database, PubMed, and Cochrane Library, from January 1979 to July 2013. Two reviewers independently retrieved the RCTs and extracted the information. The quality of included studies was assessed by the Cochrane risk of bias, and a Meta-analysis was conducted with Review Manager 5.2 software.
RESULTS
A total of 9 studies with 1056 participants were included. The quality of the studies was generally no high, only one study mentioned the random method. The Meta-analysis indicated that PDS was significantly superior to the conventional therapy in the total effective rate [relative risk (RR) = 1.21, 95% CI (1.14, 1.27), P < 0.000 01], the time of temperature recovery [mean difference (MD) = -1.43, 95% CI (-1.75, -1.11), P < 0.000 01], rale disappeared and cough relieving [MD = -1.44, 95% CI (-1.93, -0.90), P < 0.000 01]. Six adverse drug reactions from five studies mainly represented rash and diarrhea, and no serious ADRs were reported.
CONCLUSION
Based on this systematic review, PDS was proved effective and relatively safe in treatment of infantile pneumonia. However the articles enrolled in the study were not high in quality, studies with higher quality should be conducted for assessment of efficacy and safety of PDS in treatment of infantile pneumonia.
Topics: Diterpenes; Drugs, Chinese Herbal; Humans; Infant, Newborn; Infant, Newborn, Diseases; Phytotherapy; Randomized Controlled Trials as Topic; Succinic Acid
PubMed: 25975044
DOI: 10.1016/s0254-6272(15)30019-4 -
Journal of Proteome Research Jul 2017Abdominal aortic aneurysm (AAA) is a complex disease posing diagnostic and therapeutic challenges. Metabonomics may aid in the diagnosis of AAA, determination of... (Review)
Review
Abdominal aortic aneurysm (AAA) is a complex disease posing diagnostic and therapeutic challenges. Metabonomics may aid in the diagnosis of AAA, determination of individualized risk, discovery of therapeutic targets, and improve understanding of pathogenesis. A systematic review of the diversity and outcomes of existing AAA metabonomic research has been performed. Original research studies applying metabonomics to human aneurysmal disease are included. Seven relevant articles were identified: four studies were based on plasma/serum metabolite profiling, and three studies examined aneurysmal tissue. Aminomalonic acid, guanidinosuccinic acid, and glycerol emerge as potential plasma biomarkers of large aneurysm. Lipid profiling improves predictive models of aneurysm presence. Patterns of metabolite variation associated with AAA relate to carbohydrate and lipid metabolism. Perioperative perturbations in metabolites suggest differential systemic inflammatory responses to surgery, generating hypotheses for adjunctive perioperative therapy. Significant limitations include small study sizes, lack of correction for multiple testing false discovery rates, and single time-point sampling. Metabolic profiling carries the potential to identify biomarkers of AAA and elucidate pathways underlying aneurysmal disease. Statistically and methodologically robust studies are required for validation, addressing the hiatus in understanding mechanisms of aneurysm growth and developing effective treatment strategies.
Topics: Aortic Aneurysm, Abdominal; Biomarkers; Disease Progression; Glycerol; Guanidines; Humans; Lipoxins; Malonates; Metabolome; Metabolomics; Prognosis; Succinates; Thromboxane B2
PubMed: 28287739
DOI: 10.1021/acs.jproteome.6b00894 -
The Cochrane Database of Systematic... Nov 2021Acute bacterial meningitis is a bacterial infection of the membranes that surround and protect the brain, known as the meninges. The primary therapy for bacterial... (Review)
Review
BACKGROUND
Acute bacterial meningitis is a bacterial infection of the membranes that surround and protect the brain, known as the meninges. The primary therapy for bacterial meningitis is antibiotics and corticosteroids. Although these therapies significantly improve outcomes, bacterial meningitis still has a high risk of death and a high risk of neurological sequelae in survivors. New adjuvant therapies are needed to further reduce the risk of death and neurological sequelae in bacterial meningitis.
OBJECTIVES
To assess the effects of non-corticosteroid adjuvant pharmacological therapies for mortality, hearing loss, and other neurological sequelae in people with acute bacterial meningitis.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, CINAHL, and LILACS databases and ClinicalTrials.gov and WHO ICTRP trials registers up to 30 September 2021, together with reference checking, citation searching, and contact with study authors to identify additional studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of any pharmacological adjuvant therapy for acute bacterial meningitis.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed and extracted data on methods, participants, interventions, and outcomes. We assessed risk of bias of studies with the Cochrane risk of bias tool and the certainty of the evidence using the GRADE approach. We presented results using risk ratios (RR) and 95% confidence intervals (CI) when meta-analysis was possible. All other results are presented in a narrative synthesis.
MAIN RESULTS
We found that five different adjuvant therapies have been tested in RCTs for bacterial meningitis. These include paracetamol (3 studies, 1274 participants who were children); immunoglobulins (2 studies, 49 participants; one study included children, and the other adults); heparin (1 study, 15 participants who were adults); pentoxifylline (1 study, 57 participants who were children); and a mixture of succinic acid, inosine, nicotinamide, and riboflavin mononucleotide (1 study, 30 participants who were children). Paracetamol may make little or no difference to mortality (paracetamol 35.2% versus placebo 37.4%, 95% CI 30.3% to 40.8%; RR 0.94, 95% CI 0.81 to 1.09; 3 studies, 1274 participants; I² = 0%; low certainty evidence); hearing loss (RR 1.04, 95% CI 0.80 to 1.34; 2 studies, 901 participants; I² = 0%; low certainty evidence); neurological sequelae other than hearing loss (RR 1.56, 95% CI 0.98 to 2.50; 3 studies, 1274 participants; I² = 60%; low certainty evidence); and severe hearing loss (RR 0.96, 95% CI 0.67 to 1.36; 2 studies, 901 participants; I² = 0%; low certainty evidence). Paracetamol may lead to slightly more short-term neurological sequelae other than hearing loss (RR 1.99, 95% CI 1.40 to 2.81; 2 studies, 1096 participants; I² = 0%; low certainty evidence) and slightly more long-term neurological sequelae other than hearing loss (RR 2.32, 95% CI 1.34 to 4.04; 2 studies, 901 participants; I² = 0%; low certainty evidence). No adverse events were reported in either group in any of the paracetamol studies (very low certainty evidence). Two paracetamol studies had a low risk of bias in most domains, and one had low or unclear risk of bias in all domains. We judged the certainty of evidence to be low for mortality due to limitations in study design (unclear risk of bias in at least one domain and imprecision (high level of uncertainty in absolute effects), and low for all other outcomes due to limitations in study design (unclear risk of bias in at least one domain), and imprecision (low sample size and few events) or inconsistency in effect estimates (heterogeneity). We were not able to perform meta-analysis for any of the other adjuvant therapies due to the limited number of included studies. It is uncertain whether immunoglobulins, heparin, or pentoxifylline improves mortality outcomes due to the very low certainty of the evidence. Zero adverse events were reported for immunoglobulins (very low certainty evidence), and allergic reactions occurred at a rate of 3.3% in participants receiving a mixture of succinic acid, inosine, nicotinamide, and riboflavin mononucleotide (intervention group) (very low certainty evidence). None of our other outcomes (hearing loss, neurological sequelae other than hearing loss, severe hearing loss, and short-term or long-term neurological sequelae other than hearing loss) were reported in these studies, and all of these studies were judged to have a high risk of bias. All reported outcomes for all included adjuvant therapies, other than paracetamol, were graded as very low certainty of evidence due to limitations in study design (unclear or high risk of bias in at least four domains) and imprecision (extremely low sample size and few events).
AUTHORS' CONCLUSIONS
Few adjuvant therapies for bacterial meningitis have been tested in RCTs. Paracetamol may make little or no difference to mortality, with a high level of uncertainty in the absolute effects (low certainty evidence). Paracetamol may make little or no difference to hearing loss, neurological sequelae other than hearing loss, and severe hearing loss (all low certainty evidence). Paracetamol may lead to slightly more short-term and long-term neurological sequelae other than hearing loss (both outcomes low certainty evidence). There is insufficient evidence to determine whether any of the adjuvant therapies included in this review (paracetamol, immunoglobulins, heparin, pentoxifylline, or a mixture of succinic acid, inosine, nicotinamide, and riboflavin mononucleotide) are beneficial or detrimental in acute bacterial meningitis.
Topics: Acetaminophen; Adrenal Cortex Hormones; Adult; Anti-Bacterial Agents; Child; Hearing Loss; Humans; Meningitis, Bacterial
PubMed: 34813078
DOI: 10.1002/14651858.CD013437.pub2 -
Journal of Traditional Chinese Medicine... Oct 2016To assess the effect and safety of Shengxuening (SXN), extract from excrement of bombyxin, in the treatment of renal anemia, compared to ferrous succinate and ferrous... (Review)
Review
OBJECTIVE
To assess the effect and safety of Shengxuening (SXN), extract from excrement of bombyxin, in the treatment of renal anemia, compared to ferrous succinate and ferrous sulfate.
METHODS
According to the participant, intervention, comparison, outcomes, study design (PICOS) principles, we searched the Chinese Biomedical Literature Database, China National Knowledge Infrastructure Database, Chinese Evidence-Based Medicine Database, Wanfang Database (From establishment to December 2014). Two reviewers selected articles independently according to the inclusion and exclusion criteria. The quality of included studies was assessed by using the Cochrane Handbook. All statistical analyses were conducted by using Revman (vision 5.2) software.
RESULTS
A total of 14 randomized controlled trials (RCTs) were enrolled in the review. The results revealed that, when compared with blank group, SXN significantly improved the hemoglobin (P >) levels [MD = 6.29, 95% CI (1.65-10.94), P < 0.0008] and albumin (ALB) [MD = 10.98, 95% CI (6.97-14.99), P < 0.00001]. In addition, SXN could significantly increase the P > levels [MD = 10.98, 95% CI (6.97, 14.99), P < 0.00001]. Compared with other oral medicine SXN could improve the P > levels effectively [MD = 8.49, 95% CI (2.40, 14.58), P = 0.006]. And the subgroups analysis shown that compared with ferrous-sulfate there were significant differences [MD = 17.4, 95% CI (15.06, 19.73), P < 0.000 01] and the result of ferrous-succinate had significant differences [MD = 5.34, 95% CI (2.12, 8.56), P = 0.001] too. Compared with Intravenous iron groups, there were statistical differences [MD = - 5.04, 95% CI (- 9.59, - 0.50), P = 0.03]. In the safety analysis, the rate of adverse reactions in SXN groups and control groups were 19.3% and 3.7%, respectively (P < 0.000 01). Due to our studies were of poor methodological quality, and the sample size were small, the results were influenced by bias.
CONCLUSION
Our findings suggest that the SXN had better effect and was safer in the treatment of RA than ferrous succinate and ferrous sulfate.
Topics: Anemia; Animals; Bombyx; China; Drugs, Chinese Herbal; Humans; Neuropeptides; Randomized Controlled Trials as Topic
PubMed: 29932629
DOI: 10.1016/s0254-6272(16)30077-2 -
Investigative Ophthalmology & Visual... Aug 2021Diabetic retinopathy (DR), a common microvascular complication of diabetes, is the leading cause of acquired blindness in the working-age population. Individuals with...
PURPOSE
Diabetic retinopathy (DR), a common microvascular complication of diabetes, is the leading cause of acquired blindness in the working-age population. Individuals with diabetes still develop DR despite appropriate glycemic and blood pressure control, highlighting the pressing need to identify useful biomarkers for risk stratification. The purpose of this review is to systematically summarize potential metabolic biomarkers and pathways of DR, which could facilitate developing an understanding of the disease mechanisms, as well as new therapeutic measures.
METHODS
We searched PubMed and Web of Science for relevant metabolomics studies on humans published before September 30, 2020. Information regarding authors, title, publication date, study subjects, analytical platforms, methods of statistical analysis, biological samples, directions of change of potential metabolic biomarkers, and predictive values of metabolic biomarker panels was extracted, and the quality of the studies was assessed. Pathway analysis, including enrichment analysis and topology analysis, was derived from integrating differential metabolites using MetaboAnalyst 3.0, based on the Kyoto Encyclopedia of Genes and Genomes and Human Metabolome Database.
RESULTS
We found nine studies focused on the identification of potential biomarkers. Repeatedly identified metabolites including l-glutamine, l-lactic acid, pyruvic acid, acetic acid, l-glutamic acid, d-glucose, l-alanine, l-threonine, citrulline, l-lysine, and succinic acid were found to be potential biomarkers of DR. It was observed that l-glutamine and citrulline changed in all biological samples. Dysregulation of metabolic pathways involved amino acid and energy metabolism.
CONCLUSIONS
This review summarizes potential biomarkers and metabolic pathways, providing insights into new pathogenic pathways for this microvascular complication of diabetes.
Topics: Biomarkers; Diabetic Retinopathy; Humans; Metabolic Networks and Pathways; Metabolome; Metabolomics
PubMed: 34347011
DOI: 10.1167/iovs.62.10.4 -
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 -
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... Jul 2016There is considerable interest in detecting vesicoureteral reflux (VUR) because its presence, especially when severe, has been linked to an increased risk of urinary... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There is considerable interest in detecting vesicoureteral reflux (VUR) because its presence, especially when severe, has been linked to an increased risk of urinary tract infections and renal scarring. Voiding cystourethrography (VCUG), also known as micturating cystourethrography, is the gold standard for the diagnosis of VUR, and the grading of its severity. Because VCUG requires bladder catheterisation and exposes children to radiation, there has been a growing interest in other screening strategies that could identify at-risk children without the risks and discomfort associated with VCUG.
OBJECTIVES
The objective of this review is to evaluate the accuracy of two alternative imaging tests - the dimercaptosuccinic acid renal scan (DMSA) and renal-bladder ultrasound (RBUS) - in diagnosing VUR and high-grade VUR (Grade III-V VUR).
SEARCH METHODS
We searched MEDLINE, EMBASE, BIOSIS, and the Cochrane Register of Diagnostic Test Accuracy Studies from 1985 to 31 March 2016. The reference lists of relevant review articles were searched to identify additional studies not found through the electronic search.
SELECTION CRITERIA
We considered published cross-sectional or cohort studies that compared the results of the index tests (DMSA scan or RBUS) with the results of radiographic VCUG in children less than 19 years of age with a culture-confirmed urinary tract infection.
DATA COLLECTION AND ANALYSIS
Two authors independently applied the selection criteria to all citations and independently abstracted data. We used the bivariate model to calculate summary sensitivity and specificity values.
MAIN RESULTS
A total of 42 studies met our inclusion criteria. Twenty studies reported data on the test performance of RBUS in detecting VUR; the summary sensitivity and specificity estimates were 0.44 (95% CI 0.34 to 0.54) and 0.78 (95% CI 0.68 to 0.86), respectively. A total of 11 studies reported data on the test performance of RBUS in detecting high-grade VUR; the summary sensitivity and specificity estimates were 0.59 (95% CI 0.45 to 0.72) and 0.79 (95% CI 0.65 to 0.87), respectively. A total of 19 studies reported data on the test performance of DMSA in detecting VUR; the summary sensitivity and specificity estimates were 0.75 (95% CI 0.67 to 0.81) and 0.48 (95% CI 0.38 to 0.57), respectively. A total of 10 studies reported data on the accuracy of DMSA in detecting high-grade VUR. The summary sensitivity and specificity estimates were 0.93 (95% CI 0.77 to 0.98) and 0.44 (95% CI 0.33 to 0.56), respectively.
AUTHORS' CONCLUSIONS
Neither the renal ultrasound nor the DMSA scan is accurate enough to detect VUR (of all grades). Although a child with a negative DMSA test has an < 1% probability of having high-grade VUR, performing a screening DMSA will result in a large number of children falsely labelled as being at risk for high-grade VUR. Accordingly, the usefulness of the DMSA as a screening test for high-grade VUR should be questioned.
Topics: Adolescent; Child; Child, Preschool; Cohort Studies; Cross-Sectional Studies; Humans; Infant; Infant, Newborn; ROC Curve; Radionuclide Imaging; Radiopharmaceuticals; Sensitivity and Specificity; Severity of Illness Index; Technetium Tc 99m Dimercaptosuccinic Acid; Ultrasonography; Urinary Tract Infections; Vesico-Ureteral Reflux; Young Adult
PubMed: 27378557
DOI: 10.1002/14651858.CD010657.pub2 -
Canadian Journal of Gastroenterology &... Nov 2014Constipation is an uncomfortable and common condition that affects many, irrespective of age. Since 1500 BC and before, health care practitioners have provided... (Review)
Review
BACKGROUND
Constipation is an uncomfortable and common condition that affects many, irrespective of age. Since 1500 BC and before, health care practitioners have provided treatments and prevention strategies to patients for chronic constipation despite the significant variation in both medical and personal perceptions of the condition.
OBJECTIVE
To review relevant research evidence from clinical studies investigating the efficacy and safety of commercially available pharmacological laxatives in Canada, with emphasis on studies adopting the Rome criteria for defining functional constipation.
SEARCH METHODS
PubMed, Medline, Embase and Evidence-Based Medicine Reviews databases were searched for blinded or randomized clinical trials and meta-analyses assessing the efficacy of nonstimulant and stimulant laxatives for the treatment of functional constipation.
RESULTS
A total of 19 clinical studies and four meta-analyses were retrieved and abstracted regarding study design, participants, interventions and outcomes. The majority of studies focused on polyethylene glycol compared with placebo. Both nonstimulant and stimulant laxatives provided better relief of constipation symptoms than placebo according to both objective and subjective measures. Only one study compared the efficacy of a nonstimulant versus a stimulant laxative, while only two reported changes in quality of life. All studies reported minor side effects due to laxative use, regardless of treatment duration, which ranged from one week to one year. Laxatives were well tolerated by both adults and children.
Topics: Bisacodyl; Canada; Citrates; Constipation; Dioctyl Sulfosuccinic Acid; Humans; Lactulose; Laxatives; Magnesium Oxide; Organometallic Compounds; Paraffin; Picolines; Polyethylene Glycols; Psyllium; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 25390617
DOI: 10.1155/2014/631740