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Respiratory Research Aug 2020The potential role of adjunctive anti-inflammatory therapy to enhance tuberculosis (TB) treatment has recently received increasing interest. There is, therefore, a need... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The potential role of adjunctive anti-inflammatory therapy to enhance tuberculosis (TB) treatment has recently received increasing interest. There is, therefore, a need to broadly examine current host-directed therapies (HDTs) that could accelerate treatment response and improve TB outcomes.
METHODS
This systematic review and meta-analysis included randomised controlled trials of vitamin D and other HDT agents in patients receiving antibiotic treatment for pulmonary TB. Sputum smear conversion rate at 4-8 weeks was the primary outcome. Secondary outcomes included blood indices associated with infectivity and inflammation, chest radiology and incidence of adverse events.
RESULTS
Fifty-five studies were screened for eligibility after the initial search, which yielded more than 1000 records. Of the 2540 participants in the 15 trials included in the meta-analysis, 1898 (74.7%) were male, and the age at entry ranged from 18 to 70 years. There was a 38% significantly (RR 1.38, 95% CI = 1.03-1.84) increased sputum smear negativity in patients administered with vitamin D in addition to standard TB treatment than those receiving only the TB treatment. Patients treated with other HDT anti-inflammatory agents in addition to TB treatment also had a 29% significantly increased sputum smear conversion rate (RR 1.29, 95% CI = 1.09-1.563). Lymphocyte to monocyte ratio was significantly higher in the vitamin D treatment groups compared to the controls (3.52 vs 2.70, 95% CI for difference 0.16-1.11, p = 0.009) and (adjusted mean difference 0.4, 95% CI 0.2 -- 0.6; p = 0.001); whilst tumour necrosis factor-alpha (TNF-α) showed a trend towards a reduction in prednisolone (p < 0.001) and pentoxifylline (p = 0.27) treatment groups. Vitamin D and N-acetylcysteine also accelerated radiographic resolution in treatment compared to placebo at 8 weeks. No differences were observed in the occurrence of adverse events among all HDT treatments.
CONCLUSIONS
Vitamin D and other anti-inflammatory HDT medications used as adjunct TB treatment may be well tolerated and effective. They significantly improved sputum smear conversion rate and chest radiological appearance, and also exhibited an inflammation resolution effect.
Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents; Drug Therapy, Combination; Humans; Randomized Controlled Trials as Topic; Treatment Outcome; Tuberculosis, Pulmonary; Vitamin D
PubMed: 32847532
DOI: 10.1186/s12931-020-01488-9 -
JHEP Reports : Innovation in Hepatology Oct 2020Granulocyte colony-stimulating factor (G-CSF) treatment has been proposed as a therapeutic option for patients with severe alcoholic hepatitis (AH). The aim of this...
BACKGROUND & AIMS
Granulocyte colony-stimulating factor (G-CSF) treatment has been proposed as a therapeutic option for patients with severe alcoholic hepatitis (AH). The aim of this study was to synthesise available evidence on the efficacy of G-CSF in AH.
METHODS
This is a meta-analysis of randomised controlled trials evaluating the risk of death at 90 days and the risk of infection.
RESULTS
Seven studies were included. Of a total of 396 patients, 336 had AH, 197 patients were treated with G-CSF, and 199 received placebo or pentoxifylline. In overall meta-analysis, G-CSF therapy was associated with a reduced risk of death at 90 days (odds ratio [OR] 0.28; 95% CI 0.09-0.88; = 0.03). There was high heterogeneity between studies ( <0.001; = 80%). Five studies were performed in Asia and 2 in Europe. In the subgroup analysis of studies performed in Asia, G-CSF was associated with a reduced risk of death (OR 0.15; 95% CI 0.08-0.28; <0.001; heterogeneity: = 0.5, = 0%). In European studies, G-CSF tended to increase mortality compared with controls, although the difference was not significant (OR 1.89; 95% CI 0.90-3.98; = 0.09; heterogeneity: = 0.8, = 0%). In Asian studies, occurrence of infection was less frequent in G-CSF patients than in controls (OR 0.12; 95% CI 0.06-0.23; <0.001; heterogeneity: = 0.7, = 0%), whilst in European studies, this occurrence was not statistically different (OR 0.92; 95% CI 0.50-1.68; = 0.78; heterogeneity: = 0.5, = 0%). In sensitivity analyses, excluding studies that included patients with acute-on-chronic liver failure (ACLF) other than AH, patients with less severe AH, or patients with non-response to corticosteroids, results were similar to those of overall analyses, both for mortality and occurrence of infection.
CONCLUSIONS
Granulocyte colony-stimulating factor therapy may improve the prognosis of patients with severe AH. However, owing to the high heterogeneity observed in the overall analysis caused by conflicting results between the Asian and European studies, G-CSF cannot currently be recommended for AH, particularly in Europe. Whether these differences can be explained by ethnic differences or disparities in patient selection and disease severity remains unclear.
LAY SUMMARY
The main finding of this meta-analysis is that the use of granulocyte colony-stimulating factor (G-CSF) is associated with a mortality reduction of more than 70% at 3 months amongst patients with alcoholic hepatitis (AH) compared with controls who did not receive this therapy. However, owing to the high heterogeneity observed in the overall analysis caused by conflicting results between the Asian and European studies, G-CSF cannot currently be recommended for patients with AH, particularly in Europe. Whether these differences can be explained by ethnic differences or disparities in patient selection and disease severity remains unclear.
PubMed: 32775975
DOI: 10.1016/j.jhepr.2020.100139 -
The Cochrane Database of Systematic... May 2020Buerger's disease (thromboangiitis obliterans) is a non-atherosclerotic, segmental inflammatory pathology that most commonly affects the small and medium sized arteries,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Buerger's disease (thromboangiitis obliterans) is a non-atherosclerotic, segmental inflammatory pathology that most commonly affects the small and medium sized arteries, veins, and nerves in the upper and lower extremities. The aetiology is unknown, but involves hereditary susceptibility, tobacco exposure, immune and coagulation responses. In many cases, there is no possibility of revascularisation to improve the condition. Pharmacological treatment is an option for patients with severe complications, such as ischaemic ulcers or rest pain.This is an update of the review first published in 2016.
OBJECTIVES
To assess the effectiveness of any pharmacological agent (intravenous or oral) compared with placebo or any other pharmacological agent in patients with Buerger's disease.
SEARCH METHODS
The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL, AMED, the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials register to 15 October 2019. The review authors searched LILACS, ISRCTN, Australian New Zealand Clinical Trials Registry, EU Clinical Trials Register, clincialtrials.gov and the OpenGrey Database to 5 January 2020.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) involving pharmacological agents used in the treatment of Buerger's disease.
DATA COLLECTION AND ANALYSIS
Two review authors, independently assessed the studies, extracted data and performed data analysis.
MAIN RESULTS
No new studies were identified for this update. Five randomised controlled trials (total 602 participants) compared prostacyclin analogue with placebo, aspirin, or a prostaglandin analogue, and folic acid with placebo. No studies assessed other pharmacological agents such as cilostazol, clopidogrel and pentoxifylline or compared oral versus intravenous prostanoid. Compared with aspirin, intravenous prostacyclin analogue iloprost improved ulcer healing (risk ratio (RR) 2.65; 95% confidence interval (CI) 1.15 to 6.11; 98 participants; 1 study; moderate-certainty evidence), and helped to eradicate rest pain after 28 days (RR 2.28; 95% CI 1.48 to 3.52; 133 participants; 1 study; moderate-certainty evidence), although amputation rates were similar six months after treatment (RR 0.32; 95% CI 0.09 to 1.15; 95 participants; 1 study; moderate-certainty evidence). When comparing prostacyclin (iloprost and clinprost) with prostaglandin (alprostadil) analogues, ulcer healing was similar (RR 1.13; 95% CI 0.76 to 1.69; 89 participants; 2 studies; I² = 0%; very low-certainty evidence), as was the eradication of rest pain after 28 days (RR 1.57; 95% CI 0.72 to 3.44; 38 participants; 1 study; low-certainty evidence), while amputation rates were not measured. Compared with placebo, the effects of oral prostacyclin analogue iloprost were similar for: healing ischaemic ulcers (iloprost 200 mcg: RR 1.11; 95% CI 0.54 to 2.29; 133 participants; 1 study; moderate-certainty evidence, and iloprost 400 mcg: RR 0.90; 95% CI 0.42 to 1.93; 135 participants; 1 study; moderate-certainty evidence), eradication of rest pain after eight weeks (iloprost 200 mcg: RR 1.14; 95% CI 0.79 to 1.63; 207 participants; 1 study; moderate-certainty evidence, and iloprost 400 mcg: RR 1.11; 95% CI 0.77 to 1.59; 201 participants; 1 study; moderate-certainty evidence), and amputation rates after six months (iloprost 200 mcg: RR 0.54; 95% CI 0.19 to 1.56; 209 participants; 1 study, and iloprost 400 mcg: RR 0.42; 95% CI 0.13 to 1.31; 213 participants; 1 study). When comparing folic acid with placebo in patients with Buerger's disease and hyperhomocysteinaemia, pain scores were similar, there were no new cases of amputation in either group, and ulcer healing was not assessed (very low-certainty evidence). Treatment side effects such as headaches, flushing or nausea were not associated with treatment interruptions or more serious consequences. Outcomes such as amputation-free survival, walking distance or pain-free walking distance, and ankle brachial index were not assessed by any study. Overall, the certainty of the evidence was very low to moderate, with few studies, small numbers of participants, variation in severity of disease of participants between studies and missing information (for example regarding baseline tobacco exposure).
AUTHORS' CONCLUSIONS
Moderate-certainty evidence suggests that intravenous iloprost (prostacyclin analogue) is more effective than aspirin for eradicating rest pain and healing ischaemic ulcers in Buerger's disease, but oral iloprost is not more effective than placebo. Very low and low-certainty evidence suggests there is no clear difference between prostacyclin (iloprost and clinprost) and the prostaglandin analogue alprostadil for healing ulcers and relieving pain respectively in severe Buerger's disease. Very low-certainty evidence suggests there is no clear difference in pain scores and amputation rates between folic acid and placebo, in people with Buerger's disease and hyperhomocysteinaemia. Further well designed RCTs assessing the effectiveness of pharmacological agents (intravenous or oral) in people with Buerger's disease are needed.
Topics: Adult; Alprostadil; Amputation, Surgical; Aspirin; Epoprostenol; Folic Acid; Hematinics; Humans; Iloprost; Male; Middle Aged; Pain; Placebos; Platelet Aggregation Inhibitors; Prostaglandins; Randomized Controlled Trials as Topic; Thromboangiitis Obliterans; Ulcer
PubMed: 32364620
DOI: 10.1002/14651858.CD011033.pub4 -
Italian Journal of Pediatrics Aug 2019Pentoxifylline may be an important approach to treat neonatal sepsis. However, its use has not been well established. We conduct a systematic review and meta-analysis to... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Pentoxifylline may be an important approach to treat neonatal sepsis. However, its use has not been well established. We conduct a systematic review and meta-analysis to evaluate the efficacy of pentoxifylline treatment for neonatal sepsis.
METHODS
PubMed, Embase, and the Cochrane Central Register of Controlled Trials are searched. Randomized controlled trials (RCTs) assessing the influence of pentoxifylline treatment on neonatal sepsis are included. Two investigators independently have searched articles, extracted data, and assessed the quality of included studies. This meta-analysis is performed using the random-effect model.
RESULTS
Seven RCTs involving 439 patients are included in the meta-analysis. Compared with control intervention for neonatal sepsis, pentoxifylline treatment is associated with reduced hospital stay (Std. MD = -0.61; 95% CI = -0.93 to - 0.29; P = 0.0002) and metabolic acidosis (RR = 0.38; 95% CI = 0.22 to 0.66; P = 0.0006), but has no remarkable impact on mortality (RR = 0.59; 95% CI = 0.30 to 1.16; P = 0.13), serum TNF-α (Std. MD = -0.38; 95% CI = -1.29 to 0.52; P = 0.41), serum CRP (Std. MD = -0.25; 95% CI = -0.92 to 0.42; P = 0.47), plasma IL-6 (Std. MD = -0.13; 95% CI = -0.41 to 0.15; P = 0.37), disseminated intravascular coagulopathy (RR = 0.55; 95% CI = 0.25 to 1.21; P = 0.14), and oliguria/anuria (RR = 0.77; 95% CI = 0.28 to 2.16; P = 0.62). In addition, pentoxifylline treatment can significantly reduce mortality (RR = 0.50; 95% CI = 0.29 to 0.88; P = 0.02) after excluding the study conducted by Akdag during the sensivity analysis.
CONCLUSIONS
Pentoxifylline treatment may be associated with reduced mortality and hospital stay in neonatal sepsis.
Topics: Humans; Infant; Infant, Newborn; Neonatal Sepsis; Pentoxifylline; Phosphodiesterase Inhibitors; Randomized Controlled Trials as Topic
PubMed: 31439016
DOI: 10.1186/s13052-019-0697-8 -
The Cochrane Database of Systematic... Jul 2019At the end of 2016, 145 countries reported to the World Health Organization (WHO) over 173,000 new cases of leprosy worldwide. In the past 20 years, over 16 million... (Review)
Review
BACKGROUND
At the end of 2016, 145 countries reported to the World Health Organization (WHO) over 173,000 new cases of leprosy worldwide. In the past 20 years, over 16 million people have been treated for leprosy globally. The condition's main complications are injuries and ulceration caused by sensory loss from nerve damage. In this review we explored interventions to prevent or treat secondary damage to the skin in people affected by leprosy (Hansen's disease). This is an update of a Cochrane Review published in 2008.
OBJECTIVES
To assess the effects of education, information, self-care programmes, dressings, skin care, footwear and other measures for preventing and healing secondary damage to the skin in persons affected by leprosy.
SEARCH METHODS
We updated our searches of the following databases up to July 2018: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, AMED, LILACS, and CINAHL. We also searched five trial registers, three grey literature databases, and the reference lists of included studies for further references to relevant randomised controlled trials (RCTs).
SELECTION CRITERIA
RCTs or quasi-RCTs or randomised cross-over trials involving anyone with leprosy and potential damage to peripheral nerves who was treated with any intervention designed to prevent damage, heal existing ulcers, and prevent development of new ulcers. Eligible comparisons were usual care, no interventions, or other interventions (e.g. other types of dressings or footwear).
DATA COLLECTION AND ANALYSIS
We adhered to standard methodological procedures expected by Cochrane. Primary outcomes were prevention of ulcer(s), healing of existing ulcer(s) and adverse events. We used GRADE to assess the certainty of evidence for each outcome.
MAIN RESULTS
We included 14 trials (854 participants). Eleven studies reported on gender (men: 472, women: 157). Participant age varied from 18 to 74 years. Most participants had a single, mainly non-infected, wound on one foot, which had been there for less than a year. Only seven studies reported whole study duration (there was no follow-up post-treatment), which was on average six months (range: 1 to 12 months). The studies were conducted in Brazil, Ethiopia, Egypt, Indonesia, Mexico, South Korea, and India. Many 'Risk of bias' assessments were rated as unclear risk due to limited information. Six studies had high risk of bias in at least one domain, including selection and attrition bias.Thirteen studies evaluated different interventions for treating existing ulcers, one of them also evaluated prevention of new ulcers. One study aimed to prevent skin changes, such as cracking and fissures. Investigated interventions included: laser therapy, light-emitting diode (LED), zinc tape, intralesional pentoxifylline, pulsed magnetic fields, wax therapy, ketanserin, human amniotic membrane gel, phenytoin, plaster shoes, and footwear.We are uncertain about the following key results, as the certainty of evidence is very low. All time points were measured from baseline.Three studies compared zinc tape versus other interventions and reported results in favour of zinc tape. One study compared zinc tape versus magnesium sulphate: at one month the number of healed ulcers and reduction in mean ulcer area was higher with zinc tape (risk ratio (RR) 2.00, 95% confidence interval (CI) 0.43 to 9.21, and mean difference (MD) -14.30 mm², 95% CI -26.51 to -2.09, respectively, 28 participants). Another study compared zinc tape and povidone iodine and found that even though there was a greater reduction in ulcer area after six weeks of treatment with zinc tape, there was no clear difference due to the wide 95% CI (MD 128.00 mm², 95% CI -110.01 to 366.01; 38 participants). The third study (90 participants) compared adhesive zinc tape with gauze soaked in Eusol, and found the healing time for deep ulcers was less compared to zinc tape: 17 days (95% CI 12 to 20) versus 30 days (95% CI 21 to 63). Adverse events were only collected in the study comparing zinc tape with gauze soaked in Eusol: there were no signs of skin sensitisation in either group at two months.Two studies compared topical phenytoin versus saline dressing and reported results in favour of phenytoin. One study reported a greater mean percentage reduction of ulcer area after four weeks with phenytoin 2% (MD 39.30%, 95% CI 25.82 to 52.78; 23 participants), and the other study reported a greater mean percentage reduction of ulcer volume (16.60%) after four weeks with phenytoin (95% CI 8.46 to 24.74; 100 participants). No adverse events were observed with either treatment during the four-month treatment period (2 studies, 123 participants). Prevention of ulcers was not evaluated in these nor the zinc studies, as the interventions were not for preventative use.Two studies compared protective footwear (with or without self-care) with either 1) polyvinyl chloride (PVC) boots, or 2) pulsed magnetic fields plus self-care and protective footwear. In the study comparing canvas shoes versus PVC boots, none of the 72 participants with scars at the start of the study developed new ulcers over one-year follow-up. Healing of ulcers was assessed in 38 participants from this study, but we are unclear if there is a difference between groups. In the study comparing pulsed magnetic fields (in addition to self-care and protective footwear) to only self-care and footwear in 33 participants, we are uncertain if the mean volume of ulcers at four to five weeks' follow-up was different between groups; this study did not evaluate the prevention of ulcers. Information for adverse events was only reported in the study comparing canvas shoes with PVC boots; the authors stated that the PVC boots could become hot in strong sunlight and possibly burn the feet.
AUTHORS' CONCLUSIONS
Based on the available evidence, we could not draw firm conclusions about the effects of the included interventions. The main evidence limitations were high or unclear risk of bias, including selection, performance, detection, and attrition bias; imprecision due to few participants in the studies; and indirectness from poor outcome measurement and inapplicable interventions. Future research should clearly report important outcomes, such as adverse events, and assess widely available interventions, which should include treatments aimed at prevention. These trials should ensure allocation concealment, blinding, and an adequate sample size.
PubMed: 31425632
DOI: 10.1002/14651858.CD012235.pub2 -
Fertility and Sterility Mar 2019Infertility due to nonobstructive azoospermia is treatable with the use of testicular sperm extraction and IVF. The optimal approach for sperm retrieval is...
Infertility due to nonobstructive azoospermia is treatable with the use of testicular sperm extraction and IVF. The optimal approach for sperm retrieval is microdissection testicular sperm extraction (mTESE). This systematic review summarizes and evaluates the literature pertaining to patient optimization before mTESE, mTESE technique, and post-mTESE testicular tissue processing. Preoperative patient optimization has been assessed in terms of adjuvant hormone therapy and varicocele repair. Limited data are available for adjuvant medical therapy, and although also limited, data for varicocele repair support increased sperm retrieval, pregnancy, and return of sperm to the ejaculate. Post-mTESE tissue processing has few comparative studies; however, most studies support the combination of mechanical mincing and use of type 4 collagenase for tissue disintegration along with pentoxifylline to assist in identifying motile and viable spermatozoa for intracytoplasmic sperm injection.
Topics: Azoospermia; Fertility; Humans; Infertility, Male; Male; Microdissection; Risk Factors; Sperm Injections, Intracytoplasmic; Sperm Retrieval; Spermatogenesis; Testis; Treatment Outcome; Urologic Surgical Procedures, Male
PubMed: 30827516
DOI: 10.1016/j.fertnstert.2019.01.003 -
Dermatology Research and Practice 2018The first choice drugs for the treatment of cutaneous and mucocutaneous leishmaniasis are pentavalent antimonials, sodium stibogluconate, or meglumine antimoniate.... (Review)
Review
The first choice drugs for the treatment of cutaneous and mucocutaneous leishmaniasis are pentavalent antimonials, sodium stibogluconate, or meglumine antimoniate. However, the treatment with these drugs is expensive, can cause serious adverse effects, and is not always effective. The combination of two drugs by different routes or the combination of an alternative therapy with systemic therapy can increase the efficacy and decrease the collateral effects caused by the reference drugs. In this systematic review we investigated publications that described a combination of nonconventional treatment for cutaneous and mucocutaneous with pentavalent antimonials. A literature review was performed in the databases Web of Knowledge and PubMed in the period from 01 of December 2004 to 01 of June 2017, according to Prisma statement. Only clinical trials involving the treatment for cutaneous or mucocutaneous leishmaniasis, in English, and with available abstract were added. Other types of publications, such as reviews, case reports, comments to the editor, letters, interviews, guidelines, and errata, were excluded. Sixteen articles were selected and the pentavalent antimonials were administered in combination with pentoxifylline, granulocyte macrophage colony-stimulating factor, imiquimod, intralesional sodium stibogluconate, ketoconazole, silver-containing polyester dressing, lyophilized LEISH-F1 protein, cryotherapy, topical honey, and omeprazole. In general, the combined therapy resulted in high rates of clinical cure and when relapse or recurrence was reported, it was higher in the groups treated with pentavalent antimonials alone. The majority of the articles included in this review showed that cure rate ranged from 70 to 100% in patients treated with the combinations. Serious adverse effects were not observed in patients treated with drugs combination. The combination of other drugs or treatment modalities with pentavalent antimonials has proved to be effective for cutaneous and mucocutaneous leishmaniasis and for most seemed to be safe. However, new randomized, controlled, and multicentric clinical trials with more robust samples should be performed, especially the combination with immunomodulators.
PubMed: 30675152
DOI: 10.1155/2018/9014726 -
The Cochrane Database of Systematic... Jan 2018Peripheral arterial occlusive disease (PAOD) is a common cause of morbidity and mortality due to cardiovascular disease in the general population. Although numerous... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Peripheral arterial occlusive disease (PAOD) is a common cause of morbidity and mortality due to cardiovascular disease in the general population. Although numerous treatments have been adopted for patients at different disease stages, no option other than amputation is available for patients presenting with critical limb ischaemia (CLI) unsuitable for rescue or reconstructive intervention. In this regard, prostanoids have been proposed as a therapeutic alternative, with the aim of increasing blood supply to the limb with occluded arteries through their vasodilatory, antithrombotic, and anti-inflammatory effects. This is an update of a review first published in 2010.
OBJECTIVES
To determine the effectiveness and safety of prostanoids in patients with CLI unsuitable for rescue or reconstructive intervention.
SEARCH METHODS
For this update, the Cochrane Vascular Information Specialist searched the Specialised Register (January 2017) and the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 1). In addition, we searched trials registries (January 2017) and contacted pharmaceutical manufacturers, in our efforts to identify unpublished data and ongoing trials.
SELECTION CRITERIA
Randomised controlled trials describing the efficacy and safety of prostanoids compared with placebo or other pharmacological control treatments for patients presenting with CLI without chance of rescue or reconstructive intervention.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials, assessed trials for eligibility and methodological quality, and extracted data. We resolved disagreements by consensus or by consultation with a third review author.
MAIN RESULTS
For this update, 15 additional studies fulfilled selection criteria. We included in this review 33 randomised controlled trials with 4477 participants; 21 compared different prostanoids versus placebo, seven compared prostanoids versus other agents, and five conducted head-to-head comparisons using two different prostanoids.We found low-quality evidence that suggests no clear difference in the incidence of cardiovascular mortality between patients receiving prostanoids and those given placebo (risk ratio (RR) 0.81, 95% confidence interval (CI) 0.41 to 1.58). We found high-quality evidence showing that prostanoids have no effect on the incidence of total amputations when compared with placebo (RR 0.97, 95% CI 0.86 to 1.09). Adverse events were more frequent with prostanoids than with placebo (RR 2.11, 95% CI 1.79 to 2.50; moderate-quality evidence). The most commonly reported adverse events were headache, nausea, vomiting, diarrhoea, flushing, and hypotension. We found moderate-quality evidence showing that prostanoids reduced rest-pain (RR 1.30, 95% CI 1.06 to 1.59) and promoted ulcer healing (RR 1.24, 95% CI 1.04 to 1.48) when compared with placebo, although these small beneficial effects were diluted when we performed a sensitivity analysis that excluded studies at high risk of bias. Additionally, we found evidence of low to very low quality suggesting the effects of prostanoids versus other active agents or versus other prostanoids because studies conducting these comparisons were few and we judged them to be at high risk of bias. None of the included studies assessed quality of life.
AUTHORS' CONCLUSIONS
We found high-quality evidence showing that prostanoids have no effect on the incidence of total amputations when compared against placebo. Moderate-quality evidence showed small beneficial effects of prostanoids for rest-pain relief and ulcer healing when compared with placebo. Additionally, moderate-quality evidence showed a greater incidence of adverse effects with the use of prostanoids, and low-quality evidence suggests that prostanoids have no effect on cardiovascular mortality when compared with placebo. None of the included studies reported quality of life measurements. The balance between benefits and harms associated with use of prostanoids in patients with critical limb ischaemia with no chance of reconstructive intervention is uncertain; therefore careful assessment of therapeutic alternatives should be considered. Main reasons for downgrading the quality of evidence were high risk of attrition bias and imprecision of effect estimates.
Topics: Alprostadil; Amputation, Surgical; Epoprostenol; Humans; Iloprost; Ischemia; Leg; Leg Ulcer; Nafronyl; Nicotinic Acids; Pentoxifylline; Peripheral Vascular Diseases; Prostaglandins; Randomized Controlled Trials as Topic; Vasodilator Agents
PubMed: 29318581
DOI: 10.1002/14651858.CD006544.pub3 -
The Cochrane Database of Systematic... Dec 2017Exercise programmes are a relatively inexpensive, low-risk option compared with other, more invasive therapies for treatment of leg pain on walking (intermittent... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Exercise programmes are a relatively inexpensive, low-risk option compared with other, more invasive therapies for treatment of leg pain on walking (intermittent claudication (IC)). This is the fourth update of a review first published in 1998.
OBJECTIVES
Our goal was to determine whether an exercise programme was effective in alleviating symptoms and increasing walking treadmill distances and walking times in people with intermittent claudication. Secondary objectives were to determine whether exercise was effective in preventing deterioration of underlying disease, reducing cardiovascular events, and improving quality of life.
SEARCH METHODS
For this update, the Cochrane Vascular Information Specialist searched the Specialised Register (last searched 15 November 2016) and the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 10) via the Cochrane Register of Studies Online, along with trials registries.
SELECTION CRITERIA
Randomised controlled trials of an exercise regimen versus control or versus medical therapy for people with IC due to peripheral arterial disease (PAD). We included any exercise programme or regimen used for treatment of IC, such as walking, skipping, and running. Inclusion of trials was not affected by duration, frequency, or intensity of the exercise programme. Outcome measures collected included treadmill walking distance (time to onset of pain or pain-free walking distance and maximum walking time or maximum walking distance), ankle brachial index (ABI), quality of life, morbidity, or amputation; if none of these was reported, we did not include the trial in this review.
DATA COLLECTION AND ANALYSIS
For this update (2017), RAL and AH selected trials and extracted data independently. We assessed study quality by using the Cochrane 'Risk of bias' tool. We analysed continuous data by determining mean differences (MDs) and 95% confidence intervals (CIs), and dichotomous data by determining risk ratios (RRs) and 95% CIs. We pooled data using a fixed-effect model unless we identified significant heterogeneity, in which case we used a random-effects model. We used the GRADE approach to assess the overall quality of evidence supporting the outcomes assessed in this review.
MAIN RESULTS
We included two new studies in this update and identified additional publications for previously included studies, bringing the total number of studies meeting the inclusion criteria to 32, and involving a total of 1835 participants with stable leg pain. The follow-up period ranged from two weeks to two years. Types of exercise varied from strength training to polestriding and upper or lower limb exercises; supervised sessions were generally held at least twice a week. Most trials used a treadmill walking test for one of the primary outcome measures. The methodological quality of included trials was moderate, mainly owing to absence of relevant information. Most trials were small and included 20 to 49 participants. Twenty-seven trials compared exercise versus usual care or placebo, and the five remaining trials compared exercise versus medication (pentoxifylline, iloprost, antiplatelet agents, and vitamin E) or pneumatic calf compression; we generally excluded people with various medical conditions or other pre-existing limitations to their exercise capacity.Meta-analysis from nine studies with 391 participants showed overall improvement in pain-free walking distance in the exercise group compared with the no exercise group (MD 82.11 m, 95% CI 71.73 to 92.48, P < 0.00001, high-quality evidence). Data also showed benefit from exercise in improved maximum walking distance (MD 120.36 m, 95% CI 50.79 to 189.92, P < 0.0007, high-quality evidence), as revealed by pooling data from 10 studies with 500 participants. Improvements were seen for up to two years.Exercise did not improve the ABI (MD 0.04, 95% CI 0.00 to 0.08, 13 trials, 570 participants, moderate-quality evidence). Limited data were available for the outcomes of mortality and amputation; trials provided no evidence of an effect of exercise, when compared with placebo or usual care, on mortality (RR 0.92, 95% CI 0.39 to 2.17, 5 trials, 540 participants, moderate-quality evidence) or amputation (RR 0.20, 95% CI 0.01 to 4.15, 1 trial, 177 participants, low-quality evidence).Researchers measured quality of life using Short Form (SF)-36 at three and six months. At three months, the domains 'physical function', 'vitality', and 'role physical' improved with exercise; however this was a limited finding, as it was reported by only two trials. At six months, meta-analysis showed improvement in 'physical summary score' (MD 2.15, 95% CI 1.26 to 3.04, P = 0.02, 5 trials, 429 participants, moderate-quality evidence) and in 'mental summary score' (MD 3.76, 95% CI 2.70 to 4.82, P < 0.01, 4 trials, 343 participants, moderate-quality evidence) secondary to exercise. Two trials reported the remaining domains of the SF-36. Data showed improvements secondary to exercise in 'physical function' and 'general health'. The other domains - 'role physical', 'bodily pain', 'vitality', 'social', 'role emotional', and 'mental health' - did not show improvement at six months.Evidence was generally limited in trials comparing exercise versus antiplatelet therapy, pentoxifylline, iloprost, vitamin E, and pneumatic foot and calf compression owing to small numbers of trials and participants.Review authors used GRADE to assess the evidence presented in this review and determined that quality was moderate to high. Although results showed significant heterogeneity between trials, populations and outcomes were comparable overall, with findings relevant to the claudicant population. Results were pooled for large sample sizes - over 300 participants for most outcomes - using reproducible methods.
AUTHORS' CONCLUSIONS
High-quality evidence shows that exercise programmes provided important benefit compared with placebo or usual care in improving both pain-free and maximum walking distance in people with leg pain from IC who were considered to be fit for exercise intervention. Exercise did not improve ABI, and we found no evidence of an effect of exercise on amputation or mortality. Exercise may improve quality of life when compared with placebo or usual care. As time has progressed, the trials undertaken have begun to include exercise versus exercise or other modalities; therefore we can include fewer of the new trials in this update.
Topics: Amputation, Surgical; Ankle Brachial Index; Exercise Therapy; Female; Humans; Intermittent Claudication; Male; Pain Management; Quality of Life; Randomized Controlled Trials as Topic; Time Factors; Walking
PubMed: 29278423
DOI: 10.1002/14651858.CD000990.pub4 -
The Cochrane Database of Systematic... Jul 2017A couple may be considered to have fertility problems if they have been trying to conceive for over a year with no success. This may affect up to a quarter of all... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A couple may be considered to have fertility problems if they have been trying to conceive for over a year with no success. This may affect up to a quarter of all couples planning a child. It is estimated that for 40% to 50% of couples, subfertility may result from factors affecting women. Antioxidants are thought to reduce the oxidative stress brought on by these conditions. Currently, limited evidence suggests that antioxidants improve fertility, and trials have explored this area with varied results. This review assesses the evidence for the effectiveness of different antioxidants in female subfertility.
OBJECTIVES
To determine whether supplementary oral antioxidants compared with placebo, no treatment/standard treatment or another antioxidant improve fertility outcomes for subfertile women.
SEARCH METHODS
We searched the following databases (from their inception to September 2016) with no language or date restriction: Cochrane Gynaecology and Fertility Group (CGFG) specialised register, the Cochrane Central Register of Studies (CENTRAL CRSO), MEDLINE, Embase, PsycINFO, CINAHL and AMED. We checked reference lists of appropriate studies and searched for ongoing trials in the clinical trials registers.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that compared any type, dose or combination of oral antioxidant supplement with placebo, no treatment or treatment with another antioxidant, among women attending a reproductive clinic. We excluded trials comparing antioxidants with fertility drugs alone and trials that only included fertile women attending a fertility clinic because of male partner infertility.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected eligible studies, extracted the data and assessed the risk of bias of the included studies. The primary review outcome was live birth; secondary outcomes included clinical pregnancy rates and adverse events. We pooled studies using a fixed-effect model, and calculated odds ratios (ORs) with 95% confidence intervals (CIs) for the dichotomous outcomes of live birth, clinical pregnancy and adverse events. We assessed the overall quality of the evidence by applying GRADE criteria.
MAIN RESULTS
We included 50 trials involving 6510 women. Investigators compared oral antioxidants, including combinations of antioxidants, N-acetyl-cysteine, melatonin, L-arginine, myo-inositol, D-chiro-inositol, carnitine, selenium, vitamin E, vitamin B complex, vitamin C, vitamin D+calcium, CoQ10, pentoxifylline and omega-3-polyunsaturated fatty acids versus placebo, no treatment/standard treatment or another antioxidant.Very low-quality evidence suggests that antioxidants may be associated with an increased live birth rate compared with placebo or no treatment/standard treatment (OR 2.13, 95% CI 1.45 to 3.12, P > 0.001, 8 RCTs, 651 women, I = 47%). This suggests that among subfertile women with an expected live birth rate of 20%, the rate among women using antioxidants would be between 26% and 43%.Very low-quality evidence suggests that antioxidants may be associated with an increased clinical pregnancy rate compared with placebo or no treatment/standard treatment (OR 1.52, 95% CI 1.31 to 1.76, P < 0.001, 26 RCTs, 4271 women, I = 66%). This suggests that among subfertile women with an expected clinical pregnancy rate of 22%, the rate among women using antioxidants would be between 27% and 33%. Heterogeneity was moderately high.There was insufficient evidence to determine whether there was a difference between the groups in rates of miscarriage (OR 0.79, 95% CI 0.58 to 1.08, P = 0.14, 18 RCTs, 2834 women, I = 23%, very low quality evidence). This suggests that, among subfertile women with an expected miscarriage rate of 7%, use of antioxidants would be expected to result in a miscarriage rate of between 4% and 7%. There was also insufficient evidence to determine whether there was a difference between the groups in rates of multiple pregnancy (OR 1.00, 95% CI 0.73 to 1.38, P = 0.98, 8 RCTs, 2163 women, I = 4%, very low quality evidence). This suggests that among subfertile women with an expected multiple pregnancy rate of 8%, use of antioxidants would be expected to result in a multiple pregnancy rate between 6% and 11%. Likewise, there was insufficient evidence to determine whether there was a difference between the groups in rates of gastrointestinal disturbances (OR 1.55, 95% CI 0.47 to 5.10, P = 0.47, 3 RCTs, 343 women, I = 0%, very low quality evidence). This suggests that among subfertile women with an expected gastrointestinal disturbance rate of 2%, use of antioxidants would be expected to result in a rate between 1% and 11%. Overall adverse events were reported by 35 trials in the meta-analysis, but there was insufficient evidence to draw any conclusions.Only one trial reported on live birth, clinical pregnancy or adverse effects in the antioxidant versus antioxidant comparison, and no conclusions could be drawn.Very low-quality evidence suggests that pentoxifylline may be associated with an increased clinical pregnancy rate compared with placebo or no treatment (OR 2.07, 95% CI 1.20 to 3.56, P = 0.009, 3 RCTs, 276 women, I = 0%). This suggests that among subfertile women with an expected clinical pregnancy rate of 25%, the rate among women using pentoxifylline would be between 28% and 53%.There was insufficient evidence to determine whether there was a difference between the groups in rates of miscarriage (OR 1.34, 95% CI 0.46 to 3.90, P = 0.58, 3 RCTs, 276 women, I = 0%) or multiple pregnancy (OR 0.78, 95% CI 0.20 to 3.09, one RCT, 112 women, very low quality evidence). This suggests that among subfertile women with an expected miscarriage rate of 4%, the rate among women using pentoxifylline would be between 2% and 15%. For multiple pregnancy, the data suggest that among subfertile women with an expected multiple pregnancy rate of 9%, the rate among women using pentoxifylline would be between 2% and 23%.The overall quality of evidence was limited by serious risk of bias associated with poor reporting of methods, imprecision and inconsistency.
AUTHORS' CONCLUSIONS
In this review, there was very low-quality evidence to show that taking an antioxidant may provide benefit for subfertile women, but insufficient evidence to draw any conclusions about adverse events. At this time, there is limited evidence in support of supplemental oral antioxidants for subfertile women.
Topics: Abortion, Spontaneous; Administration, Oral; Antioxidants; Female; Humans; Infertility, Female; Live Birth; Oxidative Stress; Pentoxifylline; Pregnancy; Pregnancy Rate; Pregnancy, Multiple; Randomized Controlled Trials as Topic
PubMed: 28752910
DOI: 10.1002/14651858.CD007807.pub3