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The Cochrane Database of Systematic... Oct 2007The proportion of people living with and surviving cancer is growing. This has led to increased awareness of the importance of quality of life including sexual function... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The proportion of people living with and surviving cancer is growing. This has led to increased awareness of the importance of quality of life including sexual function in people with cancer. Sexual dysfunction (SD) is a potential long-term complication of cancer treatments.
OBJECTIVES
Evaluate effectiveness of interventions for SD following treatments for cancer and their adverse effects.
SEARCH STRATEGY
The Cochrane Pain, Palliative & Supportive Care Register, Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PsycInfo, AMED, CINAHL, Dissertation Abstracts and NHS Research Register were searched.
SELECTION CRITERIA
Randomised controlled trials (RCTs) were included that assessed the effectiveness of a treatment for SD. The trial population comprised of adults of either sex who at trial entry had developed SD as a consequence of cancer treatment.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted the data and assessed trial quality. Meta-analysis was considered for trials with comparable key characteristics.
MAIN RESULTS
Eleven RCTs with a total of 1743 participants were identified. The quality of the trials was poor. Ten trials explored interventions for SD in men following treatments for non-metastatic prostate cancer. One trial explored effectiveness in women of a lubricating vaginal cream following radiotherapy for cervical cancer. The strongest evidence (from four trials) was on oral phosphodiesterase type 5 (PDE5) inhibitors for erectile dysfunction (ED) following radiotherapy of the prostate or radical prostatectomy. The results using validated measures in all trials significantly favoured those in the PDE5 inhibitor group(s). The combined results of two trials indicated a significantly greater improvement in ED in the PDE5 inhibitor groups (odds ratio (OR) 10.09 95% confidence interval (CI) 6.20 to 16.43). Negative effects were few and usually mild to moderate headaches or flushing. One trial reported more clinically serious events including six events of tachycardia and six of chest pain. Following prostate cancer treatments there was some evidence that PDE5 inhibitors are more effective in combination with acetyl-L-carnitine and propionyl-L-carnitine and that sexual counselling improves self-administration of prostaglandin intra-cavernous injection for SD. There was some evidence following treatment for prostate cancer that transurethral alprostadil and vacuum constriction devices reduce SD, although in both trials negative effects were fairly common. There is some evidence that vaginal lubricating creams reduce SD.
AUTHORS' CONCLUSIONS
PDE5 inhibitors are an effective treatment for SD secondary to treatments for prostate cancer. Other interventions identified need to be tested in further RCTs. The SD interventions in this review are not representative of the range available for men and women. Further evaluations are needed for these interventions for SD following cancer treatments.
Topics: Administration, Intravaginal; Adult; Erectile Dysfunction; Female; Humans; Male; Neoplasms; Phosphodiesterase Inhibitors; Prostatic Neoplasms; Psychotherapy; Randomized Controlled Trials as Topic; Sexual Dysfunction, Physiological; Sexual Dysfunctions, Psychological; Uterine Cervical Neoplasms; Vacuum; Vaginal Creams, Foams, and Jellies
PubMed: 17943864
DOI: 10.1002/14651858.CD005540.pub2 -
The Cochrane Database of Systematic... Feb 2010Preparing the cervix prior to surgical abortion is intended to make the procedure both easier and safer. Options for cervical preparation include osmotic dilators and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Preparing the cervix prior to surgical abortion is intended to make the procedure both easier and safer. Options for cervical preparation include osmotic dilators and pharmacologic agents. Many formulations and regimens are available, and recommendations from professional organizations vary for the use of preparatory techniques in women of different ages, parity or gestational age of the pregnancy.
OBJECTIVES
To determine whether cervical preparation is necessary in the first trimester, and if so, which preparatory agent is preferred.
SEARCH STRATEGY
We searched Cochrane, Popline, Embase, Medline and Lilacs databases for randomised controlled trials investigating the use of cervical preparatory techniques prior to first trimester surgical abortion. In addition, we hand-searched key references and contacted authors to locate unpublished studies or studies not identified in the database searches.
SELECTION CRITERIA
Randomised controlled trials investigating any pharmacologic or mechanical method of cervical preparation, with the exception of nitric oxide donors (the subject of another Cochrane review), administered prior to first trimester surgical abortion were included. Outcome measures must have included the amount of cervical dilation achieved, the procedure duration or difficulty, side-effects, patient satisfaction or adverse events to be included in this review.
DATA COLLECTION AND ANALYSIS
Trials under consideration were evaluated by considering whether inclusion criteria were met as well as methodologic quality. Fifty-one studies were included, resulting in 24 different cervical preparation comparisons. Results are reported as odds ratios (OR) for dichotomous outcomes and weighted mean differences for continuous data.
MAIN RESULTS
When compared to placebo, misoprostol (400-600 microg given vaginally or sublingually), gemeprost, mifepristone (200 or 600 mg), prostaglandin E and F(2alpha) (2.5 mg administered intracervically) demonstrated larger cervical preparation effects. When misoprostol was compared to gemeprost, misoprostol was more effective in preparing the cervix and was associated with fewer gastrointestinal side-effects. For vaginal administration, administration 2 hours prior was less effective than administration 3 hours prior to the abortion. Compared to oral misoprostol administration, the vaginal route was associated with significantly greater initial cervical dilation and lower rates of side-effects; however, sublingual administration 2-3 hours prior to the procedure demonstrated cervical effects superior to vaginal administration.When misoprostol (600 microg oral or 800 microg vaginal) was compared to mifepristone (200 mg administered 24 hours prior to procedure), misoprostol had inferior cervical preparatory effects. Compared to day-prior laminaria tents, 200 or 400 microg vaginal misoprostol showed no differences in the need for further mechanical dilation or length of the procedure; similarly, the osmotic dilators Lamicel and Dilapan showed no differences in cervical ripening when compared to gemeprost, although gemeprost had cervical effects which were superior to laminaria tents. Older prostaglandin regimens (sulprostone, prostaglandin E(2) andF(2alpha)) were associated with high rates of gastrointestinal side-effects and unplanned pregnancy expulsions. Few studies reported women's satisfaction with cervical preparatory techniques.
AUTHORS' CONCLUSIONS
Modern methods of cervical ripening are generally safe, although efficacy and side-effects between methods vary. Reports of adverse events such as cervical laceration or uterine perforation are uncommon overall in this body of evidence and no published study has investigated whether cervical preparation impacts these rare outcomes. Cervical preparation decreases the length of the abortion procedure; this may become increasingly important with increasing gestational age, as mechanical dilation at later gestational ages takes longer and becomes more difficult. These data do not suggest a gestational age where the benefits of cervical dilation outweigh the side-effects, including pain, that women experience with cervical ripening procedures or the prolongation of the time interval before procedure completion. Mifepristone 200 mg, osmotic dilators and misoprostol, 400microg administered either vaginally or sublingually, are the most effective methods of cervical preparation.
Topics: Abortifacient Agents, Nonsteroidal; Abortion, Induced; Alprostadil; Cervical Ripening; Dinoprost; Dinoprostone; Female; Humans; Mifepristone; Misoprostol; Pregnancy; Pregnancy Trimester, First
PubMed: 20166091
DOI: 10.1002/14651858.CD007207.pub2 -
The Cochrane Database of Systematic... May 2010Diabetic kidney disease (DKD) is one of the major chronic microvascular complications in diabetes mellitus, and may progress to end-stage kidney disease (ESKD). There... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Diabetic kidney disease (DKD) is one of the major chronic microvascular complications in diabetes mellitus, and may progress to end-stage kidney disease (ESKD). There are no definitely effective approaches for preventing, delaying or treating DKD. Small studies have shown that Prostaglandin E1 (PGE1) can improve renal blood circulation and decrease proteinuria and albuminuria.
OBJECTIVES
To assess the benefits and harms of PGE1 for preventing the progression of DKD.
SEARCH STRATEGY
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Chinese Biomedicine Database (CBM) and reference lists of articles with no language restriction.
SELECTION CRITERIA
All randomised controlled trials (RCTs) or quasi-RCTs comparing any PGE1 agent used for preventing the progression of DKD, regardless of dosage, mode of administration, addition of cointerventions or duration of treatment.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed study quality and extracted data. For dichotomous outcomes (all-cause mortality, ESKD), results were expressed as relative risk (RR) with 95% confidence intervals (CI). Continuous outcomes (microalbuminuria, proteinuria, albuminuria, doubling of serum creatinine, serum creatinine) were expressed as mean difference (MD) with 95% CI.
MAIN RESULTS
Six studies (271 patients) were included. Five studies investigated PGE1 with or without fosinopril/losartan versus fosinopril/losartan or no treatment and one compared PGE1 versus Xueshuantong (a Chinese medicinal herb). There was a significant decrease in urinary albumin excretion rate (UAER) in patients treated with PGE1 (MD -48.28 microg/min, 95% CI -75.29 to -21.28), other outcomes also showed a significant decrease in the patients with PGE1 (albuminuria: MD -143.66 mg/24 h, 95% CI -221.48 to -65.84; proteinuria: MD -300 g/24 h, 95% CI -518.34 to -81.66). PGE1 had a positive effect on albuminuria (MD -660 mg/24 h, 95% CI -867.07 to -452.93) in clinical DKD (CDN, III stage of DN) compared with Xueshuantong. No data on incidence of ESKD, all-cause mortality or quality of life were available.
AUTHORS' CONCLUSIONS
PGE1 may have positive effects on DKD by reducing UAER, decreasing albuminuria and lessening proteinuria, with no obvious serious adverse events. However, limited by the poor methodological quality of the included studies and the small number of participants, there is currently insufficient evidence for determining if PGE1 could be used for preventing the progression of DKD. Large, properly randomised, placebo-controlled, double-blind studies are urgently needed.
Topics: Albuminuria; Alprostadil; Diabetic Nephropathies; Disease Progression; Drugs, Chinese Herbal; Fosinopril; Humans; Losartan; Proteinuria; Randomized Controlled Trials as Topic; Vasodilator Agents
PubMed: 20464745
DOI: 10.1002/14651858.CD006872.pub2 -
The Journal of Sexual Medicine Jan 2013Prostate cancer is common, and, thus, more men are being treated surgically. Long-term functional outcomes are of significant importance to the patient and their... (Review)
Review
INTRODUCTION
Prostate cancer is common, and, thus, more men are being treated surgically. Long-term functional outcomes are of significant importance to the patient and their partners. Erectile function (EF) preservation (rehabilitation) has gained significant traction worldwide, despite the absence of definitive evidence supporting its use.
AIM
To review the effectiveness of specific pharmacological therapies and other erectogenic aids in the treatment of post-radical prostatectomy (RP) erectile dysfunction.
METHODS
A systematic literature review of original peer-reviewed manuscripts and clinical trials reported in Medline.
MAIN OUTCOME MEASURE
This review focused on the evaluation of interventions that aimed to improve EF recovery following RP.
RESULTS
Although well documented in animal models, studies supporting the rehabilitation with phosphodiesterase type 5 inhibitors in humans are scarce. Daily sildenafil has been used in trials (only one randomized placebo-controlled trial) with a significant improvement in erection recovery when compared to placebo or no rehabilitation but with a low return to baseline rates (27% vs. 4% placebo). Nightly vardenafil vs. on demand vs. placebo has been studied in the Recovery of Erections: INtervention with Vardenafil Early Nightly Therapy trial with no difference in erection recovery following RP. Intracavernosal injections, although widely used and attractive from a rehabilitation standpoint, does not yet have definitive supporting its role in rehabilitation. Vacuum erection devices use following RP has been reported, but there are no data to support its role as monotherapy. Intraurethral alprostadil was also studied vs. sildenafil in a multicenter, randomized, open-label trial, and no superiority was found.
CONCLUSIONS
At this time, we are unable to define what represents the optimal rehabilitation program in regard to strategies utilized, timing of intervention, or duration of treatment.
Topics: Clinical Protocols; Erectile Dysfunction; Humans; Male; Penile Erection; Phosphodiesterase 5 Inhibitors; Practice Guidelines as Topic; Prostatectomy
PubMed: 22970890
DOI: 10.1111/j.1743-6109.2012.02885.x -
The Cochrane Database of Systematic... Dec 2014Peripheral arterial disease is a major health problem, and in about 1% to 2% of patients the disease progresses to critical limb ischaemia (CLI). In a substantial number... (Review)
Review
BACKGROUND
Peripheral arterial disease is a major health problem, and in about 1% to 2% of patients the disease progresses to critical limb ischaemia (CLI). In a substantial number of patients with CLI, no effective treatment option other than amputation is available and around a quarter of these patients will require a major amputation during the following year. This is an update of the review first published in 2011.
OBJECTIVES
To determine the effectiveness and safety of local intramuscular transplantation of autologous adult bone marrow mononuclear cells (BMMNCs) as a treatment for critical limb ischaemia (CLI).
SEARCH METHODS
For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched February 2014) and the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 1).
SELECTION CRITERIA
We included all randomised controlled trials of CLI in which participants were randomly allocated to intramuscular administration of autologous adult BMMNCs or control (either no intervention or conventional conservative therapy). We excluded studies on patients with intermittent claudication.
DATA COLLECTION AND ANALYSIS
Two authors independently selected trials, assessed trials for eligibility and methodological quality, and extracted data. Disagreements were resolved by consensus or by the third author.
MAIN RESULTS
Only two small studies, with a combined total of 57 participants, met our inclusion criteria and were finally included. They were classified as having a moderate risk of bias with unclear issues regarding their methods, and according to the GRADE approach, the overall quality of the evidence would be considered as moderate. In one study the effects of intramuscular injections of BMMNCs in the ischaemic lower limbs of patients with CLI were compared with control (standard conservative treatment). No deaths were reported and no significant difference was observed between the two groups for either pain (P = 0.37) or the ankle brachial index (ABI) parameter. However, the treatment group showed a significantly smaller proportion of participants undergoing amputation compared with the control group (P = 0.026).In the other study, following subcutaneous injections of granulocyte colony-stimulating factor (G-CSF) for five days, peripheral blood derived mononuclear cells were collected and then transplanted by intramuscular injections into ischaemic lower limbs. The effects were compared with daily intravenous prostaglandin E1 injections (control group). No deaths were reported. Pain reduction was greater in the treatment group than in the control group (P < 0.001) as was increase in ABI (mean increase 0.13 versus 0.02, P < 0.01). The treatment group experienced a statistically significant increase in pain-free walking distance (PFWD) compared with the control group (mean increase 306.4 m versus 78.6 m, P = 0.007). A smaller proportion of participants underwent amputation in the treatment group compared with the control group (0% versus 36%, P = 0.007).
AUTHORS' CONCLUSIONS
The data from the published trials suggest that there is insufficient evidence to support this treatment. These results were based on only two trials which had a very small number of participants. Therefore evidence from larger randomised controlled trials is needed in order to provide adequate statistical power to assess the role of intramuscular mononuclear cell implantation in patients with CLI.
Topics: Adult; Alprostadil; Amputation, Surgical; Ankle Brachial Index; Bone Marrow Transplantation; Granulocyte Colony-Stimulating Factor; Humans; Injections, Intramuscular; Ischemia; Leg; Leukocytes, Mononuclear; Pain Measurement; Peripheral Vascular Diseases; Randomized Controlled Trials as Topic; Transplantation, Autologous; Vasodilator Agents
PubMed: 25525690
DOI: 10.1002/14651858.CD008347.pub3 -
Gastroenterology Dec 2018Several secretagogues have been approved for the treatment of irritable bowel syndrome with constipation (IBS-C). However, their relative efficacy is unclear because... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
Several secretagogues have been approved for the treatment of irritable bowel syndrome with constipation (IBS-C). However, their relative efficacy is unclear because there have been no head-to-head randomized controlled trials. We conducted a network meta-analysis to compare their efficacies in patients with IBS-C.
METHODS
We searched MEDLINE, EMBASE, EMBASE Classic, and the Cochrane Central Register of Controlled Trials through June 2018 to identify randomized controlled trials assessing the efficacy of secretagogues in adults with IBS-C. Trials included in the analysis reported a dichotomous assessment of overall response to therapy, and data were pooled using a random-effects model. Efficacy and safety of secretagogues were reported as a pooled relative risk with 95% confidence interval to summarize the effect of each comparison tested, and treatments were ranked according to their P score.
RESULTS
We identified 15 eligible randomized controlled trials of secretagogues that included 8462 patients. Linaclotide, lubiprostone, plecanatide, and tenapanor were superior to placebo for the treatment of IBS-C. Linaclotide (290 μg once daily) was ranked first in efficacy based on the end point recommended by the Food and Drug Administration for trials in IBS-C, the primary end point used in each trial, abdominal pain, and complete spontaneous bowel movements. Tenapanor (50 mg twice daily) was ranked first for decreasing bloating. Total numbers of adverse events were significantly larger with linaclotide (290 and 500 μg once daily) and plecanatide (3 mg once daily) compared with placebo. However, plecanatide 6 mg once daily ranked first for safety. Diarrhea was significantly more common with all drugs, except lubiprostone (8 μg twice daily). Nausea was significantly more common in patients who received lubiprostone.
CONCLUSIONS
In a network analysis of randomized controlled trials of secretagogues for IBS-C, we found all drugs to be superior to placebo. Efficacy was similar among individual drugs and dosages for most end points. However, data were extracted at the 12-week time point, so the long-term relative efficacy of these drugs is unknown.
Topics: Adult; Constipation; Female; Gastrointestinal Agents; Humans; Irritable Bowel Syndrome; Isoquinolines; Lubiprostone; Male; Middle Aged; Natriuretic Peptides; Network Meta-Analysis; Peptides; Randomized Controlled Trials as Topic; Secretagogues; Sulfonamides; Treatment Outcome
PubMed: 30144426
DOI: 10.1053/j.gastro.2018.08.021 -
World Journal of Urology Apr 2007As radical prostatectomy (RP) remains a commonly used procedure in the treatment of clinically localized prostate cancer, we critically analyzed the evidence suggesting... (Review)
Review
As radical prostatectomy (RP) remains a commonly used procedure in the treatment of clinically localized prostate cancer, we critically analyzed the evidence suggesting the role of pharmacological prophylaxis and treatment of erectile dysfunction (ED) after surgery. Systematic literature review using Medline and Cancerlit from January 1997 to December 2006. Abstracts published in the journals European Urology, The Journal of Urology, The International Journal of Impotence Research and The Journal of Sexual Medicine as official proceedings of internationally known scientific Societies held in the same time period were also assessed. Patient selection and surgical technique (i.e., preservation of neurovascular bundles) are the major determinants of post-operative erectile function. Pharmacological treatment of post-operative ED, using either oral or local approaches, is effective and safe. Moreover, recent studies have shown that pharmacological prophylaxis early after RP can significantly improve the rate of erectile function recovery after surgery. Use of on-demand treatments for treatment of ED in patients subjected to RP has been shown to be highly effective, especially in case of properly selected young patients treated with a bilateral nerve-sparing approach by experienced surgeons. In this context, pharmacological prophylaxis may potentially have a significant expanding role in future strategies aimed at preserving post-operative erectile function.
Topics: Alprostadil; Erectile Dysfunction; Humans; Male; Phosphodiesterase Inhibitors; Prostatectomy; Prostatic Neoplasms; Vasodilator Agents
PubMed: 17340159
DOI: 10.1007/s00345-007-0148-9 -
European Journal of Obstetrics,... Dec 2011Medical regimens using mifepristone in combination with prostaglandins have been widely available for women undergoing termination of pregnancy (TOP) at 10-16 weeks'... (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVES
Medical regimens using mifepristone in combination with prostaglandins have been widely available for women undergoing termination of pregnancy (TOP) at 10-16 weeks' gestation in China. We undertook a systematic review to compare different regimens of mifepristone with prostaglandins for TOP at 10-16 weeks' gestation.
METHODS
We searched multiple electronic databases for English and Chinese language reports (1990-2007) including MEDLINE, the Cochrane Library and the Chinese Biomedical Literature Database. Included were trials comparing mifepristone with prostaglandins (misoprostol, gemeprost or carboprost (PG05)) to each other for women at 10-16 weeks' gestation. Outcomes were successful abortion rates, induction-to-expulsion time, blood loss and side effects. Data were processed with RevMan 5 software.
RESULTS
Nineteen trials comparing mifepristone with prostaglandin (misoprostol and PG05) were found of which 14 contributed to meta-analyses (4206 women). The quality of reports was poor. The effectiveness of vaginal mifepristone/misoprostol was super than mifepristone/PG05 (RR 1.14, 95%CI 1.05-1.22) as was induction-to-expulsion time, blood loss and side effects. When comparing misoprostol/mifepristone 150mg to misoprostol/mifepristone 200mg, no difference in TOP success rates were found (RR 0.98, 95%CI 0.96-1.01). Misoprostol vaginally compared to orally significantly increased the TOP success rate (RR 1.12, 95%CI 1.01-1.24). Gastrointestinal symptoms and fever occurred more often in misoprostol oral group (RR 1.67, 95%CI 1.46-1.91).
CONCLUSIONS
Medical regimens of mifepristone/prostaglandins were effective and safe for TOP at 10-16 weeks' gestation. Misoprostol was super than PG05, and misoprostol vaginally was found to have better effectiveness than misoprostol orally. Further research should evaluate the relative effectiveness of medical methods compared to surgery.
Topics: Abortifacient Agents, Nonsteroidal; Abortifacient Agents, Steroidal; Abortion, Induced; Alprostadil; Carboprost; Female; Humans; Mifepristone; Misoprostol; Pregnancy; Pregnancy Trimester, First; Pregnancy Trimester, Second; Prostaglandins; Randomized Controlled Trials as Topic
PubMed: 21741747
DOI: 10.1016/j.ejogrb.2011.06.034 -
Pharmacological Research Jul 2020Portal venous system thrombosis (PVST) is a life-threatening complication after splenectomy in cirrhotics patients with portal hypertension, while the application of... (Meta-Analysis)
Meta-Analysis
What intervention regimen is most effective prevention for Portal venous system thrombosis after splenectomy in cirrhotics patients with Portal hypertension? Systematic review and network meta-analysis.
Portal venous system thrombosis (PVST) is a life-threatening complication after splenectomy in cirrhotics patients with portal hypertension, while the application of intervention regimen may prevent the incidence of PVST. The aim of this network meta-analysis was to determine the most appropriate intervention regimen and application time. Several electronic databases were searched up to December 2019. We estimated summary odds ratios (OR) using pairwise and network meta-analyses with random effects for the outcome of occurrence of PVST. This work was registered with PROSPERO (CRD42019161406). The analysis was based on 19 researches, which included 1853 patients. The results drawn from the data in standard meta-analysis indicated that the application of intervention was better than no intervention use, and early application of interventions was better than delayed application in preventing the occurrence of PVST. Subsequent network meta-analysis was performed to determine the most suitable intervention regimen used early post-operation. For separate mono-therapy drug, alprostadil, antithrombin III, low molecular dextran were significantly more efficacious than others. However, mono-therapy analysis was not so close to clinical application. In the follow-up network meta-analysis, low molecular dextran combined with low molecular weight heparin exhibited the largest effect on the preventing the incidence of PVST (0.12, 0.03-0.49), followed by antithrombin III (0.12, 0.04-0.41) with low molecular dextran (0.14, 0.05-0.41). We could draw the conclusion that early application of low molecular weight heparin combined with low molecular dextran seems to be the most satisfactory treatment to prevent the incidence of PVST for patients with cirrhotic portal hypertension after splenectomy.
Topics: Dextrans; Drug Therapy, Combination; Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Humans; Hypertension, Portal; Liver Cirrhosis; Network Meta-Analysis; Portal Pressure; Portal Vein; Protective Factors; Risk Assessment; Risk Factors; Splenectomy; Treatment Outcome; Venous Thrombosis
PubMed: 32330553
DOI: 10.1016/j.phrs.2020.104825 -
The Cochrane Database of Systematic... Oct 2004Multiple pharmacologic treatments have been studied for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Multiple pharmacologic treatments have been studied for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS).
OBJECTIVES
Our objective was to determine the effects of pharmacologic treatments on clinical outcomes in adults with ALI or ARDS.
SEARCH STRATEGY
We searched OVID versions of CENTRAL (The Cochrane Library Issue 3, 2003), MEDLINE (1966 to week 2, January 2004), EMBASE (1980 to week 4, 2004), CINAHL (1982 to week 2, January 2004), and HEALTHSTAR (1995 to December 2003); proceedings from four conferences (1994 to 2003); and bibliographies of review articles and included studies.
SELECTION CRITERIA
Randomized controlled trials of pharmacologic treatments compared to no therapy or placebo for established ALI or ARDS in adults admitted to an intensive care unit, with measurement of early mortality (primary outcome), late mortality, duration of mechanical ventilation, ventilator-free days to day 28, or adverse events. We excluded trials of nitric oxide, partial liquid ventilation, fluid and nutritional interventions, oxygen, and trials in other populations reporting outcomes in subgroups of patients with ALI or ARDS.
DATA COLLECTION AND ANALYSIS
Two reviewers independently screened titles and abstracts, rated studies for inclusion, extracted data and assessed methodologic quality of included studies. Disagreements were resolved by consensus in consultation with a third reviewer. For each pharmacologic therapy, we quantitatively pooled the results of studies using random effects models where permitted by the available data. We contacted study authors when clarification of the primary outcome was required.
MAIN RESULTS
Thirty three trials randomizing 3272 patients met our inclusion criteria. Pooling of results showed no effect on early mortality of prostaglandin E1 (seven trials randomizing 697 patients; relative risk [RR] 0.95, 95% confidence interval [CI] 0.77 to 1.17), N-acetylcysteine (five trials randomizing 239 patients; RR 0.89, 95% CI 0.65 to 1.21), early high-dose corticosteroids (two trials randomizing 187 patients; RR 1.12, 95% CI 0.72 to 1.74), or surfactant (nine trials randomizing 1441 patients; RR 0.93, 95% CI 0.77 to 1.12). Two interventions were beneficial in single small trials; corticosteroids given for late phase ARDS reduced hospital mortality (24 patients; RR 0.20, 95% CI 0.05 to 0.81), and pentoxifylline reduced one-month mortality (RR 0.67, 95% CI 0.47 to 0.95) in 30 patients with metastatic cancer and ARDS. Individual trials of nine additional interventions failed to show a beneficial effect on prespecified outcomes.
REVIEWERS' CONCLUSIONS
Effective pharmacotherapy for ALI and ARDS is extremely limited, with insufficient evidence to support any specific intervention.
Topics: Acetylcysteine; Adrenal Cortex Hormones; Alprostadil; Humans; Pulmonary Surfactants; Randomized Controlled Trials as Topic; Respiratory Distress Syndrome
PubMed: 15495113
DOI: 10.1002/14651858.CD004477.pub2