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The Cochrane Database of Systematic... Oct 2016People with thrombocytopenia due to bone marrow failure are vulnerable to bleeding. Platelet transfusions have limited efficacy in this setting and alternative agents... (Meta-Analysis)
Meta-Analysis Review
Alternative agents to prophylactic platelet transfusion for preventing bleeding in people with thrombocytopenia due to chronic bone marrow failure: a meta-analysis and systematic review.
BACKGROUND
People with thrombocytopenia due to bone marrow failure are vulnerable to bleeding. Platelet transfusions have limited efficacy in this setting and alternative agents that could replace, or reduce platelet transfusion, and are effective at reducing bleeding are needed.
OBJECTIVES
To compare the relative efficacy of different interventions for patients with thrombocytopenia due to chronic bone marrow failure and to derive a hierarchy of potential alternative treatments to platelet transfusions.
SEARCH METHODS
We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (the Cochrane Library 2016, Issue 3), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1980) and ongoing trial databases to 27 April 2016.
SELECTION CRITERIA
We included randomised controlled trials in people with thrombocytopenia due to chronic bone marrow failure who were allocated to either an alternative to platelet transfusion (artificial platelet substitutes, platelet-poor plasma, fibrinogen concentrate, recombinant activated factor VII (rFVIIa), desmopressin (DDAVP), recombinant factor XIII (rFXIII), recombinant interleukin (rIL)6 or rIL11, or thrombopoietin (TPO) mimetics) or a comparator (placebo, standard of care or platelet transfusion). We excluded people undergoing intensive chemotherapy or stem cell transfusion.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened search results, extracted data and assessed trial quality. We estimated summary risk ratios (RR) for dichotomous outcomes. We planned to use summary mean differences (MD) for continuous outcomes. All summary measures are presented with 95% confidence intervals (CI).We could not perform a network meta-analysis because the included studies had important differences in the baseline severity of disease for the participants and in the number of participants undergoing chemotherapy. This raised important concerns about the plausibility of the transitivity assumption in the final dataset and we could not evaluate transitivity statistically because of the small number of trials per comparison. Therefore, we could only perform direct pairwise meta-analyses of included interventions.We employed a random-effects model for all analyses. We assessed statistical heterogeneity using the I statistic and its 95% CI. The risk of bias of each study included was assessed using the Cochrane 'Risk of bias' tool. The quality of the evidence was assessed using GRADE methods.
MAIN RESULTS
We identified seven completed trials (472 participants), and four ongoing trials (recruiting 837 participants) which are due to be completed by December 2020. Of the seven completed trials, five trials (456 participants) compared a TPO mimetic versus placebo (four romiplostim trials, and one eltrombopag trial), one trial (eight participants) compared DDAVP with placebo and one trial (eight participants) compared tranexamic acid with placebo. In the DDAVP trial, the only outcome reported was the bleeding time. In the tranexamic acid trial there were methodological flaws and bleeding definitions were subject to significant bias. Consequently, these trials could not be incorporated into the quantitative synthesis. No randomised trial of artificial platelet substitutes, platelet-poor plasma, fibrinogen concentrate, rFVIIa, rFXIII, rIL6 or rIL11 was identified.We assessed all five trials of TPO mimetics included in this review to be at high risk of bias because the trials were funded by the manufacturers of the TPO mimetics and the authors had financial stakes in the sponsoring companies.The GRADE quality of the evidence was very low to moderate across the different outcomes.There was insufficient evidence to detect a difference in the number of participants with at least one bleeding episode between TPO mimetics and placebo (RR 0.86, 95% CI 0.56 to 1.31, four trials, 206 participants, low-quality evidence).There was insufficient evidence to detect a difference in the risk of a life-threatening bleed between those treated with a TPO mimetic and placebo (RR 0.31, 95% CI 0.04 to 2.26, one trial, 39 participants, low-quality evidence).There was insufficient evidence to detect a difference in the risk of all-cause mortality between those treated with a TPO mimetic and placebo (RR 0.74, 95%CI 0.52 to 1.05, five trials, 456 participants, very low-quality evidence).There was a significant reduction in the number of participants receiving any platelet transfusion between those treated with TPO mimetics and placebo (RR 0.76, 95% CI 0.61 to 0.95, four trials, 206 participants, moderate-quality evidence).There was no evidence for a difference in the incidence of transfusion reactions between those treated with TPO mimetics and placebo (pOR 0.06, 95% CI 0.00 to 3.44, one trial, 98 participants, very low-quality evidence).There was no evidence for a difference in thromboembolic events between TPO mimetics and placebo (RR 1.41, 95%CI 0.39 to 5.01, five trials, 456 participants, very-low quality evidence).There was no evidence for a difference in drug reactions between TPO mimetics and placebo (RR 1.12, 95% CI 0.83 to 1.51, five trials, 455 participants, low-quality evidence).No trial reported the number of days of bleeding per participant, platelet transfusion episodes, mean red cell transfusions per participant, red cell transfusion episodes, transfusion-transmitted infections, formation of antiplatelet antibodies or platelet refractoriness.In order to demonstrate a reduction in bleeding events from 26 in 100 to 16 in 100 participants, a study would need to recruit 514 participants (80% power, 5% significance).
AUTHORS' CONCLUSIONS
There is insufficient evidence at present for thrombopoietin (TPO) mimetics for the prevention of bleeding for people with thrombocytopenia due to chronic bone marrow failure. There is no randomised controlled trial evidence for artificial platelet substitutes, platelet-poor plasma, fibrinogen concentrate, rFVIIa, rFXIII or rIL6 or rIL11, antifibrinolytics or DDAVP in this setting.
Topics: Benzoates; Bone Marrow Diseases; Chronic Disease; Deamino Arginine Vasopressin; Hemorrhage; Hemostatics; Humans; Hydrazines; Platelet Transfusion; Pyrazoles; Randomized Controlled Trials as Topic; Receptors, Fc; Recombinant Fusion Proteins; Thrombocytopenia; Thrombopoietin; Tranexamic Acid
PubMed: 27797129
DOI: 10.1002/14651858.CD012055.pub2 -
The Cochrane Database of Systematic... Aug 2016Platelet transfusions are used in modern clinical practice to prevent and treat bleeding in people with thrombocytopenia. Although considerable advances have been made... (Meta-Analysis)
Meta-Analysis Review
Alternatives, and adjuncts, to prophylactic platelet transfusion for people with haematological malignancies undergoing intensive chemotherapy or stem cell transplantation.
BACKGROUND
Platelet transfusions are used in modern clinical practice to prevent and treat bleeding in people with thrombocytopenia. Although considerable advances have been made in platelet transfusion therapy since the mid-1970s, some areas continue to provoke debate especially concerning the use of prophylactic platelet transfusions for the prevention of thrombocytopenic bleeding.
OBJECTIVES
To determine whether agents that can be used as alternatives, or adjuncts, to platelet transfusions for people with haematological malignancies undergoing intensive chemotherapy or stem cell transplantation are safe and effective at preventing bleeding.
SEARCH METHODS
We searched 11 bibliographic databases and four ongoing trials databases including the Cochrane Central Register of Controlled Trials (CENTRAL, 2016, Issue 4), MEDLINE (OvidSP, 1946 to 19 May 2016), Embase (OvidSP, 1974 to 19 May 2016), PubMed (e-publications only: searched 19 May 2016), ClinicalTrials.gov, World Health Organization (WHO) ICTRP and the ISRCTN Register (searched 19 May 2016).
SELECTION CRITERIA
We included randomised controlled trials in people with haematological malignancies undergoing intensive chemotherapy or stem cell transplantation who were allocated to either an alternative to platelet transfusion (artificial platelet substitutes, platelet-poor plasma, fibrinogen concentrate, recombinant activated factor VII, desmopressin (DDAVP), or thrombopoietin (TPO) mimetics) or a comparator (placebo, standard care or platelet transfusion). We excluded studies of antifibrinolytic drugs, as they were the focus of another review.
DATA COLLECTION AND ANALYSIS
Two review authors screened all electronically derived citations and abstracts of papers identified by the review search strategy. Two review authors assessed risk of bias in the included studies and extracted data independently.
MAIN RESULTS
We identified 16 eligible trials. Four trials are ongoing and two have been completed but the results have not yet been published (trial completion dates: April 2012 to February 2017). Therefore, the review included 10 trials in eight references with 554 participants. Six trials (336 participants) only included participants with acute myeloid leukaemia undergoing intensive chemotherapy, two trials (38 participants) included participants with lymphoma undergoing intensive chemotherapy and two trials (180 participants) reported participants undergoing allogeneic stem cell transplantation. Men and women were equally well represented in the trials. The age range of participants included in the trials was from 16 years to 81 years. All trials took place in high-income countries. The manufacturers of the agent sponsored eight trials that were under investigation, and two trials did not report their source of funding.No trials assessed artificial platelet substitutes, fibrinogen concentrate, recombinant activated factor VII or desmopressin.Nine trials compared a TPO mimetic to placebo or standard care; seven of these used pegylated recombinant human megakaryocyte growth and differentiation factor (PEG-rHuMGDF) and two used recombinant human thrombopoietin (rhTPO).One trial compared platelet-poor plasma to platelet transfusion.We considered that all the trials included in this review were at high risk of bias and meta-analysis was not possible in seven trials due to problems with the way data were reported.We are very uncertain whether TPO mimetics reduce the number of participants with any bleeding episode (odds ratio (OR) 0.40, 95% confidence interval (CI) 0.10 to 1.62, one trial, 120 participants, very low quality evidence). We are very uncertain whether TPO mimetics reduce the risk of a life-threatening bleed after 30 days (OR 1.46, 95% CI 0.06 to 33.14, three trials, 209 participants, very low quality evidence); or after 90 days (OR 1.00, 95% CI 0.06 to 16.37, one trial, 120 participants, very low quality evidence). We are very uncertain whether TPO mimetics reduce platelet transfusion requirements after 30 days (mean difference -3.00 units, 95% CI -5.39 to -0.61, one trial, 120 participants, very low quality evidence). No deaths occurred in either group after 30 days (one trial, 120 participants, very low quality evidence). We are very uncertain whether TPO mimetics reduce all-cause mortality at 90 days (OR 1.00, 95% CI 0.24 to 4.20, one trial, 120 participants, very low quality evidence). No thromboembolic events occurred for participants treated with TPO mimetics or control at 30 days (two trials, 209 participants, very low quality evidence). We found no trials that looked at: number of days on which bleeding occurred, time from randomisation to first bleed or quality of life.One trial with 18 participants compared platelet-poor plasma transfusion with platelet transfusion. We are very uncertain whether platelet-poor plasma reduces the number of participants with any bleeding episode (OR 16.00, 95% CI 1.32 to 194.62, one trial, 18 participants, very low quality evidence). We are very uncertain whether platelet-poor plasma reduces the number of participants with severe or life-threatening bleeding (OR 4.00, 95% CI 0.56 to 28.40, one trial, 18 participants, very low quality evidence). We found no trials that looked at: number of days on which bleeding occurred, time from randomisation to first bleed, number of platelet transfusions, all-cause mortality, thromboembolic events or quality of life.
AUTHORS' CONCLUSIONS
There is insufficient evidence to determine if platelet-poor plasma or TPO mimetics reduce bleeding for participants with haematological malignancies undergoing intensive chemotherapy or stem cell transplantation. To detect a decrease in the proportion of participants with clinically significant bleeding from 12 in 100 to 6 in 100 would require a trial containing at least 708 participants (80% power, 5% significance). The six ongoing trials will provide additional information about the TPO mimetic comparison (424 participants) but this will still be underpowered to demonstrate this level of reduction in bleeding. None of the included or ongoing trials include children. There are no completed or ongoing trials assessing artificial platelet substitutes, fibrinogen concentrate, recombinant activated factor VII or desmopressin in people undergoing intensive chemotherapy or stem cell transplantation for haematological malignancies.
Topics: Cause of Death; Female; Hematologic Neoplasms; Hemorrhage; Humans; Leukemia, Myeloid, Acute; Lymphoma; Male; Plasma; Platelet Transfusion; Polyethylene Glycols; Recombinant Proteins; Remission Induction; Stem Cell Transplantation; Thrombocytopenia; Thrombopoietin
PubMed: 27548292
DOI: 10.1002/14651858.CD010982.pub2 -
The Cochrane Database of Systematic... Jan 2016Enuresis (bedwetting) affects up to 20% of five year-olds and 2% of adults. Although spontaneous remission often occurs, the social, emotional and psychological costs... (Review)
Review
BACKGROUND
Enuresis (bedwetting) affects up to 20% of five year-olds and 2% of adults. Although spontaneous remission often occurs, the social, emotional and psychological costs can be great. Tricyclics have been used to treat enuresis since the 1960s.
OBJECTIVES
To assess the effects of tricyclic and related drugs compared with other interventions for treating children with enuresis.
SEARCH METHODS
We searched the Cochrane Incontinence Group Specialised Trials Register (containing 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), on 30 November 2015, and reference lists of relevant articles.
SELECTION CRITERIA
We included all randomised and quasi-randomised trials comparing a tricyclic or related drug with another intervention for treating enuresis. We also included combination therapies that included tricyclics. We excluded trials for treating daytime wetting.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the quality of the eligible trials, and extracted data. We settled differences by discussion with a third review author.
MAIN RESULTS
Sixty-four trials met the inclusion criteria, involving 4071 children. The quality of many trials was poor, with comparisons addressed by single studies. Minor adverse effects were common, and reported in 30 trials. These included dizziness, headache, mood changes, gastrointestinal discomforts and neutropenia. More serious side-effects can occur but were not reported. Seven trials reported no adverse effects.Tricyclics are more effective than placebo, particularly for short-term outcomes. Compared to placebo, imipramine resulted in one fewer wet nights per week (mean difference (MD) -0.95, 95% confidence interval (CI) -1.40 to -0.50; 4 trials, 347 children), with fewer failing to achieve 14 consecutive dry nights (78% versus 95% for placebo, RR 0.74, 95% CI 0.61 to 0.90; 12 trials, 831 children). Amitriptyline and desipramine were more effective than placebo, but nortriptyline and mianserin showed no difference. Most tricyclics did not have a sustained effect after ceasing treatment, with 96% wetting at follow-up for imipramine versus 97% for placebo.Imipramine combined with oxybutynin is also more effective than placebo, with 33% failing to achieve 14 consecutive dry nights at the end of treatment versus 78% for placebo (RR 0.43, 95% CI 0.23 to 0.78; 1 trial, 47 children) and 45% wetting at follow-up versus 79% for placebo (RR 0.58, 95% CI 0.34 to 0.99; 1 trial, 36 children).There was insufficient evidence to judge the effect between different doses of tricyclics, and between different tricyclics. Treatment outcomes between tricyclic and desmopressin were similar, but were mixed when tricyclic was compared with an anticholinergic. However, when imipramine was compared with desmopressin plus oxybutynin (1 trial, 45 children), the combination therapy was more effective, with one fewer wet nights per week (MD 1.07, 95% CI 0.06 to 2.08) and 36% failing to achieve 14 consecutive dry nights versus 87% for imipramine (RR 2.39, 95% CI 1.35 to 4.25). Tricyclics were also more effective or showed no difference in response when compared to other drugs which are no longer used for enuresis.Tricyclics were less effective than alarms. Although there was no difference in the number of wet nights, 67% failed to achieve 14 consecutive dry nights for imipramine versus only 17% for alarms (RR 4.00, 95% CI 1.06 to 15.08; 1 trial, 24 children). Alarm therapy also had a more sustained effect after ceasing treatment with 100% on imipramine versus 58% on alarms wetting at follow-up (RR 1.67, 95% CI 1.03 to 2.69; 1 trial, 24 children).Imipramine was more effective than simple behavioural therapies during treatment, with one fewer wet nights per week compared with star chart plus placebo (MD -0.80, 95% CI -1.33 to -0.27; 1 trial, 250 children). At follow-up 40% were wet with imipramine versus 80% with fluids and avoiding punishment (RR 0.50, 95% CI 0.28 to 0.89; 1 trial, 40 children). However, imipramine was less effective than complex behavioural therapies, with 61% failing to achieve 14 consecutive dry nights for imipramine versus 33% for the three-step programme (RR 1.83, 95% CI 1.08 to 3.12; 1 trial, 72 children) and 16% for the three-step programme combined with motivational therapy and computer-led education (RR 3.91, 95% CI 2.30 to 6.66; 1 trial, 132 children) at the end of treatment, with similar results at follow-up.Tricyclics were more effective than restricted diet, with 99% failing to achieve 14 consecutive dry nights versus 84% for imipramine (RR 0.84, 95% CI 0.75 to 0.93; 1 trial, 147 children).There was insufficient evidence to judge the effect of tricyclics compared to the other miscellaneous interventions studied.At the end of treatment there were about two fewer wet nights for imipramine plus oxybutynin compared with imipramine monotherapy (MD -2.10, 95% CI -2.99 to -1.21; 1 trial, 63 children) and 48% on imipramine plus oxybutynin failed to achieve 14 consecutive dry nights compared with 74% on imipramine monotherapy (RR 0.68, 95% CI 0.50 to 0.92; 2 trials, 101 children). At follow-up, 45% on imipramine plus oxybutynin were wetting versus 83% on imipramine monotherapy (RR 0.55, 95% CI 0.32 to 0.92; 1 trial, 36 children).When imipramine combined with desmopressin was compared with imipramine monotherapy, there was no difference in outcomes. However, when imipramine plus desmopressin was compared with desmopressin monotherapy, the combination was more effective, with 15% not achieving 14 consecutive dry nights at the end of treatment for imipramine plus desmopressin versus 40% for desmopressin monotherapy (RR 0.38, 95% CI 0.17 to 0.83; 1 trial, 86 children). Tricyclics combined with alarm therapy were not more effective than alarm monotherapy, alarm combined with desmopressin or alarm combined with nortriptyline. The addition of a tricyclic to other behavioural therapies did not alter treatment response.
AUTHORS' CONCLUSIONS
There was evidence that tricyclics are effective at reducing the number of wet nights during treatment, but do not have a sustained effect after treatment stops, with most children relapsing. In contrast, there was evidence that alarm therapy has better short- and long-term outcomes. There was some evidence that tricyclics combined with anticholinergics may be more effective that tricyclic monotherapy.
Topics: Antidepressive Agents, Tricyclic; Child; Child, Preschool; Clinical Alarms; Enuresis; Humans; Randomized Controlled Trials as Topic
PubMed: 26789925
DOI: 10.1002/14651858.CD002117.pub2 -
The Cochrane Database of Systematic... Dec 2012Enuresis (bedwetting) is a socially stigmatising and stressful condition which affects around 15% to 20% of five-year olds and up to 2% of young adults. Although there... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Enuresis (bedwetting) is a socially stigmatising and stressful condition which affects around 15% to 20% of five-year olds and up to 2% of young adults. Although there is a high rate of spontaneous remission, the social, emotional and psychological costs to the children can be great. Drugs (including desmopressin, tricyclics and other drugs) have often been tried to treat nocturnal enuresis.
OBJECTIVES
To assess the effects of drugs other than desmopressin and tricyclics on nocturnal enuresis in children and to compare them with other interventions.
SEARCH METHODS
We searched the Cochrane Incontinence Group Specialised Register of trials (searched 15 December 2011), which includes searches of MEDLINE and CENTRAL, to identify published and unpublished randomised and quasi-randomised trials. The reference lists of relevant articles were also searched.
SELECTION CRITERIA
All randomised trials of drugs (excluding desmopressin or tricyclics) for treating nocturnal enuresis in children up to the age of 16 years were included in the review. Trials were eligible for inclusion if children were randomised to receive drugs compared with placebo, other drugs or behavioral interventions for nocturnal enuresis. Studies which included children with daytime urinary incontinence or children with organic conditions were also included in this review if the focus of the study was on nocturnal enuresis. Trials focused solely on daytime wetting and trials of adults with nocturnal enuresis were excluded.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the quality of the eligible trials and extracted data. Differences between review authors were settled by discussion with a third review author.
MAIN RESULTS
A total of 40 randomised or quasi-randomised controlled trials (10 new in this update) met the inclusion criteria, with a total of 1780 out of 2440 children who enrolled receiving an active drug other than desmopressin or a tricyclic. In all, 31 different drugs or classes of drugs were tested. The trials were generally small or of poor methodological quality. There was an overall paucity of data regarding outcomes after treatment was withdrawn.For drugs versus placebo, when compared to placebo indomethacin (risk ratio [RR] 0.36, 95% CI 0.16 to 0.79), diazepam (RR 0.22, 95% CI 0.11 to 0.46), mestorelone (RR 0.32, 95% CI 0.17 to 0.62) and atomoxetine (RR 0.81, 95% CI 0.70 to 0.94) appeared to reduce the number of children failing to have 14 consecutive dry nights. Although indomethacin and diclofenac were better than placebo during treatment, they were not as effective as desmopressin and there was a higher chance of adverse effects. None of the medications were effective in reducing relapse rates, although this was only reported in five placebo controlled trials.For drugs versus drugs, combination therapy with imipramine and oxybutynin was more effective than imipramine monotherapy (RR 0.68, 95% CI 0.50 to 0.94) and also had significantly lower relapse rates than imipramine monotherapy (RR 0.35, 95% CI 0.16 to 0.77). There was an overall paucity of data regarding outcomes after treatment was withdrawn.For drugs versus behavioural therapy, bedwetting alarms were found to be better than amphetamine (RR 2.2, 95% CI 1.12 to 4.29), oxybutynin (RR 3.25, 95% CI 1.77 to 5.98), and oxybutynin plus holding exercises (RR 3.3, 95% CI 1.84 to 6.18) in reducing the number of children failing to achieve 14 consecutive dry nights.Adverse effects of drugs were seen in 19 trials while 17 trials did not adequately report the occurrence of side effects.
AUTHORS' CONCLUSIONS
There was not enough evidence to judge whether or not the included drugs cured bedwetting when used alone. There was limited evidence to suggest that desmopressin, imipramine and enuresis alarms therapy were better than the included drugs to which they were compared. In other reviews, desmopressin, tricyclics and alarm interventions have been shown to be effective during treatment. There was also evidence to suggest that combination therapy with anticholinergic therapy increased the efficacy of other established therapies such as imipramine, desmopressin and enuresis alarms by reducing the relapse rates, by about 20%, although it was not possible to identify the characteristics of children who would benefit from combination therapy. Future studies should evaluate the role of combination therapy against established treatments in rigorous and adequately powered trials.
Topics: Adolescent; Anti-Inflammatory Agents, Non-Steroidal; Antidiuretic Agents; Child; Child, Preschool; Cholinergic Antagonists; Clinical Alarms; Drug Therapy, Combination; Humans; Nocturnal Enuresis; Psychotropic Drugs; Randomized Controlled Trials as Topic
PubMed: 23235587
DOI: 10.1002/14651858.CD002238.pub2 -
Blood Transfusion = Trasfusione Del... Oct 2011
Review
Topics: Deamino Arginine Vasopressin; Hemophilia A; Hemostatics; Humans
PubMed: 21839010
DOI: 10.2450/2011.0113-10 -
BMJ Clinical Evidence Jan 2011Nocturnal enuresis affects 15% to 20% of 5-year-old children, 5% of 10-year-old children, and 1% to 2% of people aged 15 years and over. Without treatment, 15% of... (Review)
Review
INTRODUCTION
Nocturnal enuresis affects 15% to 20% of 5-year-old children, 5% of 10-year-old children, and 1% to 2% of people aged 15 years and over. Without treatment, 15% of affected children will become dry each year. Nocturnal enuresis is not diagnosed in children younger than 5 years, and treatment may be inappropriate for children younger than 7 years.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of interventions for relief of symptoms? We searched: Medline, Embase, The Cochrane Library, and other important databases up to February 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 19 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: acupuncture, anticholinergics (oxybutynin, tolterodine, hyoscyamine), desmopressin, dry bed training, enuresis alarm, hypnotherapy, standard home alarm clock, and tricyclics (imipramine, desipramine).
Topics: Antidiuretic Agents; Behavior Therapy; Double-Blind Method; Emotions; Humans; Hypnosis; Nocturnal Enuresis; Prospective Studies; United States Food and Drug Administration
PubMed: 21477399
DOI: No ID Found -
The Cochrane Database of Systematic... 2004Public concerns regarding the safety of transfused blood have prompted re-consideration of the use of allogeneic (from an unrelated donor) red blood cell (RBC)... (Review)
Review
BACKGROUND
Public concerns regarding the safety of transfused blood have prompted re-consideration of the use of allogeneic (from an unrelated donor) red blood cell (RBC) transfusion, and of a range of techniques designed to minimise transfusion requirements.
OBJECTIVES
To examine the evidence for the efficacy of desmopressin acetate (1-deamino-8-D-arginine-vasopressin; DDAVP), in reducing perioperative blood loss and the need for red cell transfusion in patients who do not have congenital bleeding disorders.
SEARCH STRATEGY
Articles were identified by: computer searches of MEDLINE, EMBASE, Current Contents (to May 2003), and the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library, Issue 1, 2003). References in the identified trials and review articles were searched and authors contacted to identify additional studies.
SELECTION CRITERIA
Controlled parallel group trials in which adult patients, scheduled for non-urgent surgery, were randomised to DDAVP, or to a control group, who did not receive the intervention.
DATA COLLECTION AND ANALYSIS
Trial quality was assessed using criteria proposed by Schulz et al. (Schulz 1995) and Jadad et al. (Jadad 1996). Main outcomes measured were: the number of patients exposed to allogeneic red cell transfusion, and the amount of blood transfused. Other outcomes measured were: re-operation for bleeding, blood loss, post-operative complications (thrombosis, infection, non-fatal myocardial infarction), mortality, and length of hospital stay (LOS).
MAIN RESULTS
Eighteen trials of DDAVP (n=1295) reported data on the number of patients transfused with allogeneic RBC transfusion. In subjects treated with DDAVP, the pooled relative risk of exposure to perioperative allogeneic RBC transfusion was 0.95 (95%CI = 0.86 to 1.06). The use of DDAVP did not significantly reduce blood loss; weighted mean difference (WMD) = -114.3ml: 95% confidence interval (95%CI) = -258.8 to 30.2ml per patient) or the volume of RBC transfused (WMD = -0.35 units: 95%CI = -0.70 to 0.01 units). In DDAVP-treated patients the relative risk of requiring re-operation due to bleeding was 0.69 (95%CI = 0.26 to 1.83). There was no statistically significant effect overall for mortality and non-fatal myocardial infarction in DDAVP-treated patients compared with control (RR = 1.72: 95%CI = 0.68 to 4.33) and (RR = 1.38: 95%CI = 0.77 to 2.50) respectively.
REVIEWER'S CONCLUSIONS
There is no convincing evidence that desmopressin minimises perioperative allogeneic RBC transfusion in patients who do not have congenital bleeding disorders. These data suggest that there is no benefit from using DDAVP as a means of minimising perioperative allogeneic RBC transfusion.
Topics: Adult; Blood Loss, Surgical; Deamino Arginine Vasopressin; Erythrocyte Transfusion; Hemostatics; Humans; Randomized Controlled Trials as Topic; Transplantation, Homologous
PubMed: 14973974
DOI: 10.1002/14651858.CD001884.pub2 -
The Cochrane Database of Systematic... 2000Enuresis (bedwetting) is a socially disruptive and stressful condition which affects around 15-20% of five year olds, and up to 2% of young adults. Although there is a... (Review)
Review
BACKGROUND
Enuresis (bedwetting) is a socially disruptive and stressful condition which affects around 15-20% of five year olds, and up to 2% of young adults. Although there is a high rate of spontaneous remission, the social, emotional and psychological costs to the children can be great.
OBJECTIVES
To assess the effects of desmopressin on nocturnal enuresis in children, and to compare desmopressin with other interventions.
SEARCH STRATEGY
The following electronic databases were searched: MEDLINE to June 1997; AMED; ASSIA; BIDS; BIOSIS Previews (1985-1996); CINAHL; DHSS Data; EMBASE (1974 to June 1997); PsycLIT and SIGLE. Organisations, manufacturers, researchers and health professionals concerned with enuresis were contacted for information. The reference sections of obtained studies were also checked for further trials. Date of the most recent search: July 1997.
SELECTION CRITERIA
All randomised trials of desmopressin for nocturnal enuresis in children were included in the review. Trials were eligible for inclusion if: children were randomised to receive desmopressin compared with placebo, other drugs or other conservative interventions for nocturnal bedwetting; participants with organic causes for their bedwetting were excluded; and baseline assessments of the level of bedwetting were reported. Trials focused solely on daytime wetting were excluded.
DATA COLLECTION AND ANALYSIS
Two reviewers independently assessed the quality of the eligible trials, and extracted data.
MAIN RESULTS
Twenty one randomised trials involving 948 children treated with desmopressin, met the inclusion criteria. The quality of many of the trials was poor. Desmopressin was compared with a tricyclic drug in two trials, and with alarms in one. Desmopressin was effective in reducing bedwetting in a variety of doses and forms. Each dose of desmopressin reduced bedwetting by at least one night per week during treatment (eg 20microg: 1.56 fewer wet nights per week, 95% CI -1.94 to -1.19). Participants on desmopressin were 4.6 times more likely to achieve 14 consecutive dry nights (95% CI 1.38 to 15.02) compared with placebo. However, there was no difference after treatment was finished. There was no apparent dose-related effect of desmopressin, but the evidence was limited. Data which compared oral and nasal administration were too few to be conclusive. Desmopressin and imipramine (a tricyclic drug) were equally effective in one small trial. Amitriptyline (another tricyclic) was not consistently better than desmopressin either alone or when used as a supplement. In a single trial, desmopressin was initially superior to using an alarm in reducing the number of wet nights per week: WMD -1.7 (95% CI: -2.96 to -0.45), but this result was not sustained; after three months of treatment, patients using the alarm had 1.4 fewer wet nights per week than with desmopressin: (95% CI: 0.14 to 2.65). Participants receiving the alarm intervention were also nine times less likely to relapse than those given desmopressin: RR 9.2 (95% CI: 1.28 to 65.9). Combining alarm and drug therapy was found to be superior to alarm treatment alone. The addition of desmopressin to an alarm schedule resulted in one less wet night per week: (95% CI: -1.55 to -0.45).
REVIEWER'S CONCLUSIONS
Desmopressin rapidly reduced the number of wet nights per week, but there was some evidence that this was not sustained after treatment stopped. Comparison with alternative treatments suggested that desmopressin and tricyclics had similar clinical effects, but that alarms produced more sustained benefits. However, based on the available evidence, these conclusions can only be tentative. There was some evidence of minor side effects of desmopressin in the included trials, such as nasal irritation and nose bleeds. However, the risk of water intoxication associated with over-drinking before bedtime has been reported. Patients and their families need to be warned of potential adverse effects and advise
Topics: Child; Deamino Arginine Vasopressin; Enuresis; Humans; Renal Agents
PubMed: 10796860
DOI: 10.1002/14651858.CD002112