Publications by authors named "Edina Mk da Silva"

13 Publications

  • Page 1 of 1

Enzyme replacement therapy with galsulfase for mucopolysaccharidosis type VI.

Cochrane Database Syst Rev 2021 09 17;9:CD009806. Epub 2021 Sep 17.

Emergency Medicine and Evidence Based Medicine, Universidade Federal de São Paulo, São Paulo, Brazil.

Background: Mucopolysaccharidosis type VI (MPS VI) or Maroteaux-Lamy syndrome is a rare genetic disorder caused by the deficiency of arylsulphatase B. The resultant accumulation of dermatan sulphate causes lysosomal damage. The clinical symptoms are related to skeletal dysplasia (i.e. short stature and degenerative joint disease). Other manifestations include cardiac disease, impaired pulmonary function, ophthalmological complications, hepatosplenomegaly, sinusitis, otitis, hearing loss and sleep apnea. Intellectual impairment is generally absent. Clinical manifestation is typically by two or three years of age; however, slowly progressive cases may not present until adulthood. Enzyme replacement therapy (ERT) with galsulfase is considered a new approach for treating MPS VI.

Objectives: To evaluate the effectiveness and safety of treating MPS VI by ERT with galsulfase compared to other interventions, placebo or no intervention.

Search Methods: Eletronic searches were performed on the Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Trials Register. Date of the latest search:  09 June 2021. Further searches of the following databases were also performed: CENTRAL, MEDLINE, LILACS, the Journal of Inherited Metabolic Disease, the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov. Date of the latest search: 20 August 2021.

Selection Criteria: Randomized and quasi-randomized controlled clinical studies of ERT with galsulfase compared to other interventions or placebo.

Data Collection And Analysis: Two authors independently screened the studies, assessed the risk of bias, extracted data and assessed the certainty of the the evidence using the GRADE criteria.

Main Results: One study was included involving 39 participants who received either ERT with galsulfase (recombinant human arylsulphatase B) or placebo. This small study was considered overall to have an unclear risk of bias in relation to the design and implementation of the study, since the authors did not report how both the allocation generation and concealment were performed. Given the very low certainty of the evidence, we are uncertain whether at 24 weeks there was a difference between groups in relation to the 12-minute walk test, mean difference (MD) of 92.00 meters (95% confidence interval (CI) 11.00 to 172.00), or the three-minute stair climb, MD 5.70 (95% CI -0.10 to 11.50). In relation to respiratory tests, we are uncertain whether galsulfase makes any difference as compared to placebo in forced vital capacity in litres (FVC (L) (absolute change in baseline), given the very low certainty of the evidence. Cardiac function was not reported in the included study. We found that galsulfase, as compared to placebo, may decrease urinary glycosaminoglycan levels at 24 weeks, MD -227.00 (95% CI -264.00 to -190.00) (low-certainty evidence). We are uncertain whether there are differences between the galsulfase and placebo groups in relation to adverse events (very low-certainty evidence). In general, the dose of galsulfase was well tolerated and there were no differences between groups. These events include drug-related adverse events, serious and severe adverse events, those during infusion, drug-related adverse events during infusion, and deaths. More infusion-related reactions were observed in the galsulfase group and were managed with interruption or slowing of infusion rate or administration of antihistamines or corticosteroids drugs. No deaths occurred during the study.   AUTHORS' CONCLUSIONS: The results of this review are based only on one small study (a 24-week randomised phase of the study and prior to the open-label extension). We are uncertain whether galsulfase is more effective than placebo, for treating people with MPS VI, in relation to the 12-minute walk test or the three-minute stair climb, as the certainty of the evidence has been assessed as very low. We found that galsulfase may reduce urinary glycosaminoglycans levels. We are also uncertain whether there are any differences between treatment groups in relation to cardiac or pulmonary functions, liver or spleen volume, overnight apnea-hypopnea, height and weight, quality of life and adverse effects. Further studies are needed to obtain more information on the long-term effectiveness and safety of ERT with galsulfase.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/14651858.CD009806.pub3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447860PMC
September 2021

Treatments for unruptured intracranial aneurysms.

Cochrane Database Syst Rev 2021 May 10;5:CD013312. Epub 2021 May 10.

Department of Surgery, Division of Vascular and Endovascular Surgery, Universidade Federal de São Paulo, São Paulo, Brazil.

Background: Unruptured intracranial aneurysms are relatively common lesions in the general population, with a prevalence of 3.2%, and are being diagnosed with greater frequency as non-invasive techniques for imaging of intracranial vessels have become increasingly available and used. If not treated, an intracranial aneurysm can be catastrophic. Morbidity and mortality in aneurysmal subarachnoid hemorrhage are substantial: in people with subarachnoid hemorrhage, 12% die immediately, more than 30% die within one month, 25% to 50% die within six months, and 30% of survivors remain dependent. However, most intracranial aneurysms do not bleed, and the best treatment approach is still a matter of debate.

Objectives: To assess the risks and benefits of interventions for people with unruptured intracranial aneurysms.

Search Methods: We searched CENTRAL (Cochrane Library 2020, Issue 5), MEDLINE Ovid, Embase Ovid, and Latin American and Caribbean Health Science Information database (LILACS). We also searched ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform from inception to 25 May 2020. There were no language restrictions. We contacted experts in the field to identify further studies and unpublished trials.

Selection Criteria: Unconfounded, truly randomized trials comparing conservative treatment versus interventional treatments (microsurgical clipping or endovascular coiling) and microsurgical clipping versus endovascular coiling for individuals with unruptured intracranial aneurysms.

Data Collection And Analysis: Two review authors independently selected trials for inclusion according to the above criteria, assessed trial quality and risk of bias, performed data extraction, and applied the GRADE approach to the evidence. We used an intention-to-treat analysis strategy.

Main Results: We included two trials in the review: one prospective randomized trial involving 80 participants that compared conservative treatment to endovascular coiling, and one randomized controlled trial involving 136 participants that compared microsurgical clipping to endovascular coiling for unruptured intracranial aneurysms. There was no difference in outcome events between conservative treatment and endovascular coiling groups. New perioperative neurological deficits were more common in participants treated surgically (16/65, 24.6%; 15.8% to 36.3%) versus 7/69 (10.1%; 5.0% to 19.5%); odds ratio (OR) 2.87 (95% confidence interval (CI) 1.02 to 8.93; P = 0.038). Hospitalization for more than five days was more common in surgical participants (30/65, 46.2%; 34.6% to 58.1%) versus 6/69 (8.7%; 4.0% to 17.7%); OR 8.85 (95% CI 3.22 to 28.59; P < 0.001). Clinical follow-up to one year showed 1/48 clipped versus 1/58 coiled participants had died, and 1/48 clipped versus 1/58 coiled participants had become disabled (modified Rankin Scale > 2). All the evidence is of very low quality.

Authors' Conclusions: There is currently insufficient good-quality evidence to support either conservative treatment or interventional treatments (microsurgical clipping or endovascular coiling) for individuals with unruptured intracranial aneurysms. Further randomized trials are required to establish if surgery is a better option than conservative management, and if so, which surgical approach is preferred for which patients. Future studies should include consideration of important characteristics such as participant age, gender, aneurysm size, aneurysm location (anterior circulation and posterior circulation), grade of ischemia (major stroke), and duration of hospitalizations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/14651858.CD013312.pub2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109849PMC
May 2021

Complementary and alternative therapies for post-caesarean pain.

Cochrane Database Syst Rev 2020 Sep 1;9:CD011216. Epub 2020 Sep 1.

Emergency Medicine and Evidence Based Medicine, Universidade Federal de São Paulo, São Paulo, Brazil.

Background: Pain after caesarean sections (CS) can affect the well-being of the mother and her ability with her newborn. Conventional pain-relieving strategies are often underused because of concerns about the adverse maternal and neonatal effects. Complementary alternative therapies (CAM) may offer an alternative for post-CS pain.

Objectives: To assess the effects of CAM for post-caesarean pain.

Search Methods: We searched Cochrane Pregnancy and Childbirth's Trials Register, LILACS, PEDro, CAMbase, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (6 September 2019), and checked the reference lists of retrieved articles.

Selection Criteria: Randomised controlled trials (RCTs), including quasi-RCTs and cluster-RCTs, comparing CAM, alone or associated with other forms of pain relief, versus other treatments or placebo or no treatment, for the treatment of post-CS pain.

Data Collection And Analysis: Two review authors independently performed study selection, extracted data, assessed risk of bias and assessed the certainty of evidence using GRADE.

Main Results: We included 37 studies (3076 women) which investigated eight different CAM therapies for post-CS pain relief. There is substantial heterogeneity among the trials. We downgraded the certainty of evidence due to small numbers of women participating in the trials and to risk of bias related to lack of blinding and inadequate reporting of randomisation processes. None of the trials reported pain at six weeks after discharge. Primary outcomes were pain and adverse effects, reported per intervention below. Secondary outcomes included vital signs, rescue analgesic requirement at six weeks after discharge; all of which were poorly reported, not reported, or we are uncertain as to the effect Acupuncture or acupressure We are very uncertain if acupuncture or acupressure (versus no treatment) or acupuncture or acupressure plus analgesia (versus placebo plus analgesia) has any effect on pain because the quality of evidence is very low. Acupuncture or acupressure plus analgesia (versus analgesia) may reduce pain at 12 hours (standardised mean difference (SMD) -0.28, 95% confidence interval (CI) -0.64 to 0.07; 130 women; 2 studies; low-certainty evidence) and 24 hours (SMD -0.63, 95% CI -0.99 to -0.26; 2 studies; 130 women; low-certainty evidence). It is uncertain whether acupuncture or acupressure (versus no treatment) or acupuncture or acupressure plus analgesia (versus analgesia) has any effect on the risk of adverse effects because the quality of evidence is very low. Aromatherapy Aromatherapy plus analgesia may reduce pain when compared with placebo plus analgesia at 12 hours (mean difference (MD) -2.63 visual analogue scale (VAS), 95% CI -3.48 to -1.77; 3 studies; 360 women; low-certainty evidence) and 24 hours (MD -3.38 VAS, 95% CI -3.85 to -2.91; 1 study; 200 women; low-certainty evidence). We are uncertain if aromatherapy plus analgesia has any effect on adverse effects (anxiety) compared with placebo plus analgesia. Electromagnetic therapy Electromagnetic therapy may reduce pain compared with placebo plus analgesia at 12 hours (MD -8.00, 95% CI -11.65 to -4.35; 1 study; 72 women; low-certainty evidence) and 24 hours (MD -13.00 VAS, 95% CI -17.13 to -8.87; 1 study; 72 women; low-certainty evidence). Massage We identified six studies (651 women), five of which were quasi-RCTs, comparing massage (foot and hand) plus analgesia versus analgesia. All the evidence relating to pain, adverse effects (anxiety), vital signs and rescue analgesic requirement was very low-certainty. Music Music plus analgesia may reduce pain when compared with placebo plus analgesia at one hour (SMD -0.84, 95% CI -1.23 to -0.46; participants = 115; studies = 2; I = 0%; low-certainty evidence), 24 hours (MD -1.79, 95% CI -2.67 to -0.91; 1 study; 38 women; low-certainty evidence), and also when compared with analgesia at one hour (MD -2.11, 95% CI -3.11 to -1.10; 1 study; 38 women; low-certainty evidence) and at 24 hours (MD -2.69, 95% CI -3.67 to -1.70; 1 study; 38 women; low-certainty evidence). It is uncertain whether music plus analgesia has any effect on adverse effects (anxiety), when compared with placebo plus analgesia because the quality of evidence is very low. Reiki We are uncertain if Reiki plus analgesia compared with analgesia alone has any effect on pain, adverse effects, vital signs or rescue analgesic requirement because the quality of evidence is very low (one study, 90 women). Relaxation Relaxation may reduce pain compared with standard care at 24 hours (MD -0.53 VAS, 95% CI -1.05 to -0.01; 1 study; 60 women; low-certainty evidence). Transcutaneous electrical nerve stimulation TENS (versus no treatment) may reduce pain at one hour (MD -2.26, 95% CI -3.35 to -1.17; 1 study; 40 women; low-certainty evidence). TENS plus analgesia (versus placebo plus analgesia) may reduce pain compared with placebo plus analgesia at one hour (SMD -1.10 VAS, 95% CI -1.37 to -0.82; 3 studies; 238 women; low-certainty evidence) and at 24 hours (MD -0.70 VAS, 95% CI -0.87 to -0.53; 108 women; 1 study; low-certainty evidence). TENS plus analgesia (versus placebo plus analgesia) may reduce heart rate (MD -7.00 bpm, 95% CI -7.63 to -6.37; 108 women; 1 study; low-certainty evidence) and respiratory rate (MD -1.10 brpm, 95% CI -1.26 to -0.94; 108 women; 1 study; low-certainty evidence). We are uncertain if TENS plus analgesia (versus analgesia) has any effect on pain at six hours or 24 hours, or vital signs because the quality of evidence is very low (two studies, 92 women).

Authors' Conclusions: Some CAM therapies may help reduce post-CS pain for up to 24 hours. The evidence on adverse events is too uncertain to make any judgements on safety and we have no evidence about the longer-term effects on pain. Since pain control is the most relevant outcome for post-CS women and their clinicians, it is important that future studies of CAM for post-CS pain measure pain as a primary outcome, preferably as the proportion of participants with at least moderate (30%) or substantial (50%) pain relief. Measuring pain as a dichotomous variable would improve the certainty of evidence and it is easy to understand for non-specialists. Future trials also need to be large enough to detect effects on clinical outcomes; measure other important outcomes as listed lin this review, and use validated scales.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/14651858.CD011216.pub2DOI Listing
September 2020

Cisplatin versus carboplatin in combination with third-generation drugs for advanced non-small cell lung cancer.

Cochrane Database Syst Rev 2020 01 13;1:CD009256. Epub 2020 Jan 13.

Centro de Estudos de Saúde Baseada em Evidências e Avaliação Tecnológica em Saúde, Cochrane Brazil, Rua Pedro de Toledo, 598, São Paulo, São Paulo, Brazil, 04039-001.

Background: Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer death in both sexes worldwide. Approximately 50% of those diagnosed with lung cancer will have locally advanced or metastatic disease and will be treated in a palliative setting. Platinum-based combination chemotherapy has benefits in terms of survival and symptom control when compared with best supportive care.

Objectives: To assess the effectiveness and safety of carboplatin-based chemotherapy when compared with cisplatin-based chemotherapy, both in combination with a third-generation drug, in people with advanced non-small cell lung cancer (NSCLC). To compare quality of life in people with advanced NSCLC receiving chemotherapy with cisplatin and carboplatin combined with a third-generation drug.

Search Methods: We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL; 13 January 2019), MEDLINE (via PubMed) (1966 to 13 January 2019), and Embase (via Ovid) (1974 to 13 January 2019). In addition, we handsearched the proceedings of the American Society of Clinical Oncology Meetings (January 1990 to September 2018) and reference lists from relevant resources.

Selection Criteria: Randomised clinical trials (RCTs) comparing regimens with carboplatin or cisplatin combined with a third-generation drug in people with locally advanced or metastatic NSCLC. We accepted any regimen and number of cycles that included these drugs, since there is no widely accepted standard regimen.

Data Collection And Analysis: Two review authors independently assessed the search results, and a third review author resolved any disagreements. The primary outcomes were overall survival and health-related quality of life. The secondary outcomes were one-year survival rate, objective response rate and toxicity.

Main Results: In this updated review, we located one additional RCT, for a total of 11 included RCTs (5088 participants, 4046 of whom were available for meta-analysis). There was no difference in overall survival (hazard ratio (HR) 0.99, 95% confidence interval (CI) 0.82 to 1.20; 10 RCTs; 2515 participants; high-quality evidence); one-year survival rate (risk ratio (RR) 0.98, 95% CI 0.89 to 1.08; I = 17%; 4004 participants; all 11 RCTs; high-quality evidence); or response rate (RR 0.89, 95% CI 0.79 to 1.00; I = 12%; all 11 RCTs; 4020 participants; high-quality evidence). A subgroup analysis comparing carboplatin with different doses of cisplatin found an overall survival benefit in favour of carboplatin-based regimens when compared to cisplatin at lower doses (40 to 80 mg/m) (HR 1.15, 95% CI 1.03 to 1.28; 6 RCTs; 2508 participants), although there was no overall survival benefit when carboplatin-based chemotherapy was compared to cisplatin at higher doses (80 to 100 mg/m) (HR 0.93, 95% CI 0.83 to 1.04; I = 0%; 4 RCTs; 1823 participants). Carboplatin caused more thrombocytopenia (RR 2.46, 95% CI 1.49 to 4.04; I = 68%; 10 RCTs; 3670 participants) and was associated with more neurotoxicity (RR 1.42, 95% CI 0.91 to 2.23; I = 0%, 5 RCTs; 1489 participants), although we believe this last finding is probably related to a confounding factor (higher dose of paclitaxel in the carboplatin-containing treatment arm of a large study included in the analysis). There was no statistically significant difference in renal toxicity (RR 0.52, 95% CI 0.19 to 1.45; I = 3%; 3 RCTs; 1272 participants); alopecia (RR 1.11, 95% CI 0.73 to 1.68; I = 0%; 2 RCTs; 300 participants); anaemia (RR 1.37, 95% CI 0.79 to 2.38; I2 = 77%; 10 RCTs; 3857 participants); and neutropenia (RR 1.18, 95% CI 0.85 to 1.63; I = 94%; 10 RCTs; 3857 participants) between cisplatin-based chemotherapy and carboplatin-based chemotherapy regimens. Two RCTs performed a health-related quality of life analysis; however, as they used different methods of measurement we were unable to perform a meta-analysis. One RCT reported comparative health-related quality of life data between cisplatin and carboplatin-containing arms but found no significant differences in global indices of quality of life, including global health status or functional scales. In this Cochrane review, we found that the quality of evidence was high for overall survival, one-year survival rate and response rate but moderate quality evidence for the other outcomes measured.

Authors' Conclusions: Advanced NSCL patients treated with carboplatin or cisplatin doublet with third-generation chemotherapy drugs showed equivalent overall survival, one-year survival, and response rate. Regarding adverse events, carboplatin caused more thrombocytopenia, and cisplatin caused more nausea/vomiting. Therefore, in this palliative therapeutic intent, the choice of the platin compound should take into account the expected toxicity profile, patient's comorbidities and preferences.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/14651858.CD009256.pub3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6956680PMC
January 2020

Acetyl-L-carnitine for the treatment of diabetic peripheral neuropathy.

Cochrane Database Syst Rev 2019 06 15;6:CD011265. Epub 2019 Jun 15.

Department of Internal Medicine, Universidade Federal de São Paulo, Rua Borges Lagoa, 1065/110, São Paulo, São Paulo, Brazil, 04038-032.

Background: Diabetic peripheral neuropathy (DPN) is a common and severe complication that affects 50% of people with diabetes. Painful DPN is reported to occur in 16% to 24% of people with diabetes. A complete and comprehensive management strategy for the prevention and treatment of DPN, whether painful or not, has not yet been defined.Research into treatment for DPN has been characterised by a series of failed clinical trials, with few noteworthy advances. Strategies that support peripheral nerve regeneration and restore neurological function in people with painful or painless DPN are needed. The amino acid acetyl-L-carnitine (ALC) plays a role in the transfer of long-chain fatty acids into mitochondria for β-oxidation. ALC supplementation also induces neuroprotective and neurotrophic effects in the peripheral nervous system. Therefore, ALC supplementation targets several mechanisms relevant to potential nerve repair and regeneration, and could have clinical therapeutic potential. There is a need for a systematic review of the evidence from clinical trials.

Objectives: To assess the effects of ALC for the treatment of DPN.

Search Methods: On 2 July 2018, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, LILACS, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform. We checked references, searched citations, and contacted study authors to identify additional studies.

Selection Criteria: We included randomised controlled trials (RCTs) and quasi-RCTs of ALC compared with placebo, other therapy, or no intervention in the treatment of DPN. Participants could be of any sex and age, and have type 1 or type 2 diabetes mellitus, of any severity, with painful or painless DPN. We accepted any definition of minimum criteria for DPN, in accordance with the Toronto Consensus. We imposed no language restriction.Pain was the primary outcome, measured as the proportion of participants with at least 30% (moderate) or 50% (substantial) decrease in pain over baseline, or as the score on a visual analogue scale (VAS) or Likert scale for pain.

Data Collection And Analysis: We followed standard Cochrane methods.

Main Results: We included four studies with 907 participants, which were reported in three publications. Three trials studied ALC versus placebo (675 participants); in one trial the dose of ALC was 2000 mg/day, and in the other two trials, it was 1500 mg/day or 3000 mg/day. The fourth trial studied ALC 1500 mg/day versus methylcobalamin 1.5 mg/day (232 participants). The risk of bias was high in both trials of different ALC doses and low in the other two trials.No included trial measured the proportion of participants with at least moderate (30%) or substantial (50%) pain relief. ALC reduced pain more than placebo, measured on a 0- to 100-mm VAS (MD -9.16, 95% CI -16.76 to -1.57; three studies; 540 participants; P = 0.02; I² = 56%; random-effects; very low-certainty evidence; a higher score indicating more pain). At doses of 1500 mg/day or less, the VAS score after ALC treatment was little different from placebo (MD -0.05, 95% CI -10.00 to 9.89; two studies; 159 participants; P = 0.99; I² = 0%), but at doses greater than 1500 mg/day, ALC reduced pain more than placebo (MD -14.93, 95% CI -19.16 to -10.70; three studies; 381 participants; P < 0.00001; I² = 0%). This subgroup analysis should be viewed with caution as the evidence was even less certain than the overall analysis, which was already of very low certainty.Two placebo-controlled studies reported that vibration perception improved after 12 months. We graded this evidence as very low certainty, due to inconsistency and a high risk of bias, as the trial authors did not provide any numerical data. The placebo-controlled studies did not measure functional impairment and disability scores. No study used validated symptom scales. One study performed sensory testing, but the evidence was very uncertain.The fourth included study compared ALC with methylcobalamin, but did not report effects on pain. There was a reduction from baseline to 24 weeks in functional impairment and disability, based on the change in mean Neuropathy Disability Score (NDS; scale from zero to 10), but there was no important difference between the ALC group (mean score 1.66 ± 1.90) and the methylcobalamin group (mean score 1.35 ± 1.65) groups (P = 0.23; low-certainty evidence).One placebo-controlled study reported that six of 147 participants in the ALC > 1500 mg/day group (4.1%) and two of 147 participants in the placebo group (1.4%) discontinued treatment because of adverse events (headache, facial paraesthesia, and gastrointestinal disorders) (P = 0.17). The other two placebo-controlled studies reported no dropouts due to adverse events, and more pain, paraesthesia, and hyperaesthesias in the placebo group than the 3000 mg/day ALC group, but provided no numerical data. The overall certainty of adverse event evidence for the comparison of ALC versus placebo was low.The study comparing ALC with methylcobalamin reported that 34/117 participants (29.1%) experienced adverse events in the ALC group versus 33/115 (28.7%) in the methylcobalamin group (P = 0.95). Nine participants discontinued treatment due to adverse events (ALC: 4 participants, methylcobalamin: 5 participants), which were most commonly gastrointestinal symptoms. The certainty of the adverse event evidence for ALC versus methylcobalamin was low.Two studies were funded by the manufacturer of ALC and the other two studies had at least one co-author who was a consultant for an ALC manufacturer.

Authors' Conclusions: We are very uncertain whether ALC causes a reduction in pain after 6 to 12 months' treatment in people with DPN, when compared with placebo, as the evidence is sparse and of low certainty. Data on functional and sensory impairment and symptoms are lacking, or of very low certainty. The evidence on adverse events is too uncertain to make any judgements on safety.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/14651858.CD011265.pub2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6953387PMC
June 2019

Oral isotretinoin for acne.

Cochrane Database Syst Rev 2018 Nov 24;11:CD009435. Epub 2018 Nov 24.

Emergency Medicine and Evidence Based Medicine, Universidade Federal de São Paulo, Rua Napoleão de Barros, 865, São Paulo, Sao Paulo, Brazil, 04024-002.

Background: Acne vulgaris, a chronic inflammatory disease of the pilosebaceous unit associated with socialisation and mental health problems, may affect more than 80% of teenagers. Isotretinoin is the only drug that targets all primary causal factors of acne; however, it may cause adverse effects.

Objectives: To assess efficacy and safety of oral isotretinoin for acne vulgaris.

Search Methods: We searched the following databases up to July 2017: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO and LILACS. We updated this search in March 2018, but these results have not yet been incorporated in the review. We also searched five trial registries, checked the reference lists of retrieved studies for further references to relevant trials, and handsearched dermatology conference proceedings. A separate search for adverse effects of oral isotretinoin was undertaken in MEDLINE and Embase up to September 2013.

Selection Criteria: Randomised clinical trials (RCTs) of oral isotretinoin in participants with clinically diagnosed acne compared against placebo, any other systemic or topical active therapy, and itself in different formulation, doses, regimens, or course duration.

Data Collection And Analysis: We used standard methodological procedures expected by Cochrane.

Main Results: We included 31 RCTs, involving 3836 participants (12 to 55 years) with mild to severe acne. There were twice as many male participants as females.Most studies were undertaken in Asia, Europe, and North America. Outcomes were generally measured between eight to 32 weeks (mean 19.7 weeks) of therapy.Assessed comparisons included oral isotretinoin versus placebo or other treatments such as antibiotics. In addition, different doses, regimens, or formulations of oral isotretinoin were assessed, as well as oral isotretinoin with the addition of topical agents.Pharmaceutical companies funded 12 included trials. All, except three studies, had high risk of bias in at least one domain.Oral isotretinoin compared with oral antibiotics plus topical agentsThese studies included participants with moderate or severe acne and assessed outcomes immediately after 20 to 24 weeks of treatment (short-term). Three studies (400 participants) showed isotretinoin makes no difference in terms of decreasing trial investigator-assessed inflammatory lesion count (RR 1.01 95% CI 0.96 to 1.06), with only one serious adverse effect found, which was Stevens-Johnson syndrome in the isotretinoin group (RR 3.00, 95% CI 0.12 to 72.98). However, we are uncertain about these results as they were based on very low-quality evidence.Isotretinoin may slightly improve (by 15%) acne severity, assessed by physician's global evaluation (RR 1.15, 95% CI 1.00 to 1.32; 351 participants; 2 studies), but resulted in more less serious adverse effects (67% higher risk) (RR 1.67, 95% CI 1.42 to 1.98; 351 participants; 2 studies), such as dry lips/skin, cheilitis, vomiting, nausea (both outcomes, low-quality evidence).Different doses/therapeutic regimens of oral isotretinoinFor our primary efficacy outcome, we found three RCTs, but heterogeneity precluded meta-analysis. One study (154 participants) reported 79%, 80% and 84% decrease in total inflammatory lesion count after 20 weeks of 0.05, 0.1, or 0.2 mg/kg/d of oral isotretinoin for severe acne (low-quality evidence). Another trial (150 participants, severe acne) compared 0.1, 0.5, and 1 mg/kg/d oral isotretinoin for 20 weeks and, respectively, 58%, 80% and 90% of participants achieved 95% decrease in total inflammatory lesion count. One RCT, of participants with moderate acne, compared isotretinoin for 24 weeks at (a) continuous low dose (0.25 to 0.4 mg/kg/day), (b) continuous conventional dose (0.5 to 0.7 mg/kg/day), and (c) intermittent regimen (0.5 to 0.7 mg/kg/day, for one week in a month). Continuous low dose (MD 3.72 lesions; 95% CI 2.13 to 5.31; 40 participants; one study) and conventional dose (MD 3.87 lesions; 95% CI 2.31 to 5.43; 40 participants; one study) had a greater decrease in inflammatory lesion counts compared to intermittent treatment (all outcomes, low-quality evidence).Fourteen RCTs (906 participants, severe and moderate acne) reported that no serious adverse events were observed when comparing different doses/therapeutic regimens of oral isotretinoin during treatment (from 12 to 32 weeks) or follow-up after end of treatment (up to 48 weeks). Thirteen RCTs (858 participants) analysed frequency of less serious adverse effects, which included skin dryness, hair loss, and itching, but heterogeneity regarding the assessment of the outcome precluded data pooling; hence, there is uncertainty about the results (low- to very-low quality evidence, where assessed).Improvement in acne severity, assessed by physician's global evaluation, was not measured for this comparison.None of the included RCTs reported birth defects.

Authors' Conclusions: Evidence was low-quality for most assessed outcomes.We are unsure if isotretinoin improves acne severity compared with standard oral antibiotic and topical treatment when assessed by a decrease in total inflammatory lesion count, but it may slightly improve physician-assessed acne severity. Only one serious adverse event was reported in the isotretinoin group, which means we are uncertain of the risk of serious adverse effects; however, isotretinoin may result in more minor adverse effects.Heterogeneity in the studies comparing different regimens, doses, or formulations of oral isotretinoin meant we were unable to undertake meta-analysis. Daily treatment may be more effective than treatment for one week each month. None of the studies in this comparison reported serious adverse effects, or measured improvement in acne severity assessed by physician's global evaluation. We are uncertain if there is a difference in number of minor adverse effects, such as skin dryness, between doses/regimens.Evidence quality was lessened due to imprecision and attrition bias. Further studies should ensure clearly reported long- and short-term standardised assessment of improvement in total inflammatory lesion counts, participant-reported outcomes, and full safety accounts. Oral isotretinoin for acne that has not responded to oral antibiotics plus topical agents needs further assessment, as well as different dose/regimens of oral isotretinoin in acne of all severities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/14651858.CD009435.pub2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6383843PMC
November 2018

Zinc supplementation for tinnitus.

Cochrane Database Syst Rev 2016 11 23;11:CD009832. Epub 2016 Nov 23.

Medicina, Medical School, Universidade Federal de São Paulo, Rua Pedro de Toledo, 598, São Paulo, São Paulo, Brazil, 04039-001.

Background: Tinnitus is the perception of sound without external acoustic stimuli. Patients with severe tinnitus may have physical and psychological complaints and their tinnitus can cause deterioration in their quality of life. At present no specific therapy for tinnitus has been found to be satisfactory in all patients. In recent decades, a number of reports have suggested that oral zinc supplementation may be effective in the management of tinnitus. Since zinc has a role in cochlear physiology and in the synapses of the auditory system, there is a plausible mechanism of action for this treatment.

Objectives: To evaluate the effectiveness and safety of oral zinc supplementation in the management of patients with tinnitus.

Search Methods: The Cochrane ENT Information Specialist searched the ENT Trials Register; Central Register of Controlled Trials (CENTRAL 2016, Issue 6); PubMed; EMBASE; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 14 July 2016.

Selection Criteria: Randomised controlled trials comparing zinc supplementation versus placebo in adults (18 years and over) with tinnitus.

Data Collection And Analysis: We used the standard methodological procedures recommended by Cochrane. Our primary outcome measures were improvement in tinnitus severity and disability, measured by a validated tinnitus-specific questionnaire, and adverse effects. Secondary outcomes were quality of life, change in socioeconomic impact associated with work, change in anxiety and depression disorders, change in psychoacoustic parameters, change in tinnitus loudness, change in overall severity of tinnitus and change in thresholds on pure tone audiometry. We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics.

Main Results: We included three trials involving a total of 209 participants. The studies were at moderate to high risk of bias. All included studies had differences in participant selection criteria, length of follow-up and outcome measurement, precluding a meta-analysis. The participants were all adults over 18 years with subjective tinnitus, but one study conducted in 2013 (n = 109) included only elderly patients. Improvement in tinnitus severity and disabilityOnly the study in elderly patients used a validated instrument (Tinnitus Handicap Questionnaire) for this primary outcome. The authors of this cross-over study did not report the results of the two phases separately and found no significant differences in the proportion of patients reporting tinnitus improvement at four months of follow-up: 5% (5/93) versus 2% (2/94) in the zinc and placebo groups, respectively (risk ratio (RR) 2.53, 95% confidence interval (CI) 0.50 to 12.70; very low-quality evidence).None of the included studies reported any significant adverse effects. Secondary outcomesFor the secondary outcome change in tinnitus loudness, one study reported no significant difference between the zinc and placebo groups after eight weeks: mean difference in tinnitus loudness -9.71 dB (95% CI -25.53 to 6.11; very low-quality evidence). Another study also measured tinnitus loudness but used a 0- to 100-point scale. The authors of this second study reported no significant difference between the zinc and placebo groups after four months: mean difference in tinnitus loudness rating scores 0.50 (95% CI -5.08 to 6.08; very low-quality evidence).Two studies used unvalidated instruments to assess tinnitus severity. One (with 50 participants) reported the severity of tinnitus using a non-validated scale (0 to 7 points) and found no significant difference in subjective tinnitus scores between the zinc and placebo groups at the end of eight weeks of follow-up (mean difference (MD) -1.41, 95% CI -2.97 to 0.15; very low-quality evidence). A third trial (n = 50) also evaluated the improvement of tinnitus using a non-validated instrument (a 0 to 10 scale: 10 = severe and unbearable tinnitus). In this study, after eight weeks there was no difference in the proportion of patients with improvement in their tinnitus, 8.7% (2/23) treated with zinc versus 8% (2/25) of those who received a placebo (RR 1.09, 95% CI 0.17 to 7.10, very low-quality evidence).None of the included studies reported any of our other secondary outcomes (quality of life, change in socioeconomic impact associated with work, change in anxiety and depression disorders, change in psychoacoustic parameters or change in thresholds on pure tone audiometry).

Authors' Conclusions: We found no evidence that the use of oral zinc supplementation improves symptoms in adults with tinnitus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/14651858.CD009832.pub2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6464312PMC
November 2016

Immediate versus delayed treatment for recently symptomatic carotid artery stenosis.

Cochrane Database Syst Rev 2016 Sep 9;9:CD011401. Epub 2016 Sep 9.

Department of Vascular Surgery, Universidade Federal de São Paulo, Rua Borges Lagoa, 754, São Paulo, Brazil, 04038-001.

Background: The timing of surgery for recently symptomatic carotid artery stenosis remains controversial. Early cerebral revascularization may prevent a disabling or fatal ischemic recurrence, but it may also increase the risk of hemorrhagic transformation, or of dislodging a thrombus. This review examined the randomized controlled evidence that addressed whether the increased risk of recurrent events outweighed the increased benefit of an earlier intervention.

Objectives: To assess the risks and benefits of performing very early cerebral revascularization (within two days) compared with delayed treatment (after two days) for people with recently symptomatic carotid artery stenosis.

Search Methods: We searched the Cochrane Stroke Group Trials Register in January 2016, the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library 2016, Issue 1), MEDLINE (1948 to 26 January 2016), EMBASE (1974 to 26 January 2016), LILACS (1982 to 26 January 2016), and trial registers (from inception to 26 January 2016). We also handsearched conference proceedings and journals, and searched reference lists. There were no language restrictions. We contacted colleagues and pharmaceutical companies to identify further studies and unpublished trials.

Selection Criteria: All completed, truly randomized trials (RCT) that compared very early cerebral revascularization (within two days) with delayed treatment (after two days) for people with recently symptomatic carotid artery stenosis.

Data Collection And Analysis: We independently selected trials for inclusion according to the above criteria, assessed risk of bias for each trial, and performed data extraction. We utilized an intention-to-treat analysis strategy.

Main Results: We identified one RCT that involved 40 participants, and addressed the timing of surgery for people with recently symptomatic carotid artery stenosis. It compared very early surgery with surgery performed after 14 days of the last symptomatic event. The overall quality of the evidence was very low, due to the small number of participants from only one trial, and missing outcome data. We found no statistically significant difference between the effects of very early or delayed surgery in reducing the combined risk of stroke and death within 30 days of surgery (risk ratio (RR) 3.32; confidence interval (CI) 0.38 to 29.23; very low-quality evidence), or the combined risk of perioperative death and stroke (RR 0.47; CI 0.14 to 1.58; very low-quality evidence). To date, no results are available to confirm the optimal timing for surgery.

Authors' Conclusions: There is currently no high-quality evidence available to support either very early or delayed cerebral revascularization after a recent ischemic stroke. Hence, further randomized trials to identify which patients should undergo very urgent revascularization are needed. Future studies should stratify participants by age group, sex, grade of ischemia, and degree of stenosis. Currently, there is one ongoing RCT that is examining the timing of cerebral revascularization.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/14651858.CD011401.pub2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457772PMC
September 2016

Enzyme replacement therapy with idursulfase for mucopolysaccharidosis type II (Hunter syndrome).

Cochrane Database Syst Rev 2011 Nov 9(11):CD008185. Epub 2011 Nov 9.

Emergency Medicine and Evidence Based Medicine, Universidade Federal de São Paulo, São Paulo, Brazil.

Background: Mucopolysaccharidosis II, also known as Hunter syndrome, is a rare, X-linked disease caused by a deficiency of the lysosomal enzyme iduronate-2-sulfatase, which catalyses a step in the catabolism of glycosaminoglycans. The glycosaminoglycans accumulate within tissues affecting multiple organs and physiologic systems. The clinical manifestations include neurologic involvement, severe airways obstruction, skeletal deformities and cardiomyopathy. The disease has a variable age of onset and variable rate of progression. In those with severe disease, death usually occurs in the second decade of life, whereas those patients with less severe disease may survive into adulthood. Enzyme replacement therapy with intravenous infusions of idursulfase has emerged as a new treatment for mucopolysaccharidosis type II.

Objectives: To evaluate the effectiveness and safety of enzyme replacement therapy with idursulfase compared to other interventions, placebo or no intervention, for treating mucopolysaccharidosis type II.

Search Methods: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register (date of last search 01 September 2011).We also searched EMBASE, PubMed and the Literature Latino-Americana e do Caribe em Ciências da Saúde (LILACS) (date of last search October 2009).

Selection Criteria: Randomised and quasi-randomised controlled trials of enzyme replacement therapy with idursulfase compared to no intervention, placebo or other options (e.g. behavioral strategies, transplantation).

Data Collection And Analysis: Two authors independently screened the trials identified, appraised quality of papers and extracted data.

Main Results: One study (96 patients) met the inclusion criteria, although the primary outcome of this review - z score for height and weight, was not assessed in the study. Following 53 weeks of treatment, patients in the weekly idursulfase 0.5 mg/kg group demonstrated a significant improvement rate compared with placebo for the primary outcome: distance walked in six minutes on the basis of the sum of ranks of change from baseline, mean difference 37.00 (95% confidence interval 6.52 to 67.48). The every-other-week idursulfase 0.5 mg/kg group also showed an improvement, which was not significant compared with placebo, mean difference 23.00 (95% confidence interval -4.49 to 50.49). After 53 weeks, there was no statistical significance difference in per cent predicted forced vital capacity between the three groups and absolute forced vital capacity was significantly increased from baseline in the weekly dosing group compared to placebo, mean difference 0.16 (95% confidence interval CI 0.05 to 0.27). No difference was observed between the every-other-week idursulfase 0.5 mg/kg group and placebo.In addition, liver and spleen volumes and urine glycosaminoglycan excretion were significantly reduced from baseline by both idursulfase dosing regimens. Idursulfase was generally well tolerated, but infusion reactions did occur. Idursulfase antibodies were detected in 31.7% of patients at the end of the study and they were related to a smaller reduction in urine glycosaminoglycan levels.

Authors' Conclusions: The current evidence is limited. While the randomised clinical trial identified was considered to be of good quality, it failed to describe important outcomes. It has been demonstrated that enzyme replacement therapy with idursulfase is effective in relation to functional capacity (distance walked in six minutes and forced vital capacity), liver and spleen volumes and urine glycosaminoglycan excretion in patients with mucopolysaccharidosis type II compared with placebo. There is no available evidence in the included study and in the literature on outcomes such as improvement in growth, sleep apnoea, cardiac function, quality of life and mortality. More studies are needed to obtain more information on the long-term effectiveness and safety of enzyme replacement therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/14651858.CD008185.pub2DOI Listing
November 2011

Surgery for stress urinary incontinence due to presumed sphincter deficiency after prostate surgery.

Cochrane Database Syst Rev 2011 Apr 13(4):CD008306. Epub 2011 Apr 13.

Urology, Universidade Federal de Sao Paulo - UNIFESP, Rua Doutor Nicolau de Sousa Queiros, 629 ap.130B, Sao Paulo, Sao Paulo, Brazil, 04105002.

Background: Incontinence after prostatectomy for benign or malignant disease is a well known and often a feared outcome. Although small degrees of incidental incontinence may go virtually unnoticed, larger degrees of incontinence can have a major impact on a man's quality of life.Conceptually, postprostatectomy incontinence may be caused by sphincter malfunction and/or bladder dysfunction. The majority of men with post-prostatectomy incontinence (60 to 100%) have stress urinary incontinence, which is the complaint of involuntary urinary leakage on effort or exertion, or on sneezing or coughing. This may be due to intrinsic sphincter deficiency and may be treated with surgery for optimal management of incontinence. Detrusor dysfunction is more common after surgery for benign prostatic disease.

Objectives: To determine the effects of surgical treatment for urinary incontinence related to presumed sphincter deficiency after prostate surgery for either benign LUTS secondary to BPH (transurethral resection of prostate (TURP), photo vaporization of the prostate, laser enucleation of the prostate and open prostatectomy) or radical prostatectomy for prostate cancer (retropubic, perineal, laparoscopic, or robotic).

Search Strategy: We searched the Cochrane Incontinence Group Specialised Register (searched 28 June 2010), MEDLINE (January 1966 to January 2010), EMBASE (January 1988 to January 2010), LILACS (January 1982 to January 2010) and the reference lists of relevant articles, handsearched conference proceedings and contacted investigators to locate studies.

Selection Criteria: Randomised or quasi-randomised trials that include surgical treatments of urinary incontinence after prostate surgery.

Data Collection And Analysis: Two authors independently screened the trials identified, appraised quality of papers and extracted data.

Main Results: Only one study with 45 participants met the inclusion criteria. Men were divided in two subgroups (minimal or total incontinence) and each group was randomized to artificial urethral sphincter (AUS) implantation or Macroplastique injection. Follow-up ranged from six to 120 months. In the trial as a whole, the men treated with AUS were more likely to be dry (18/20, 82%) than those who had the injectable treatment (11/23, 46%) (OR 5.67, 95% CI 1.28 to 25.10). However, this effect was only statistically significant for the men with more severe ('total') incontinence (OR 8.89, 95% CI 1.40 to 56.57) and the confidence intervals were wide. There were more severe complications in the group undergoing AUS, and the costs were higher.

Authors' Conclusions: The evidence available at present is limited because only one small randomised clinical trial was identified. Although the result is favourable for the implantation of AUS in the group with severe incontinence, this result should be considered with caution due to the small sample size and uncertain methodological quality of the study found.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/14651858.CD008306.pub2DOI Listing
April 2011

Aerobic exercise training programmes for improving physical and psychosocial health in adults with Down syndrome.

Cochrane Database Syst Rev 2010 May 12(5):CD005176. Epub 2010 May 12.

Emergency Medicine and Evidence Based Medicine, Universidade Federal de São Paulo, Rua Pedro de Toledo 598, São Paulo, Brazil, 04039-001.

Background: Although physical fitness has been suggested to improve physical and psychosocial health for a variety of population profiles, there is a lack of information about the safety and effectiveness of aerobic exercise for adults with Down syndrome.

Objectives: To evaluate the effectiveness and safety of aerobic exercise training programmes for physiological and psychosocial outcomes in adults with Down syndrome.

Search Strategy: The following electronic databases were searched: The Cochrane Central Register of Controlled Trials (CENTRAL) (2009, Issue 1); MEDLINE (1966 to August 2009); EMBASE (1980 to August 2009); CINAHL (1982 to August 2009); LILACS (1982 to August 2009); PsycINFO (1887 to August 2009); ERIC (1966 to August 2009); Current Controlled Trials (August 2009); and Campbell Collaboration's Social, Psychological, Educational and Criminological Register (C2- SPECTR) (to August 2009). Information about ongoing clinical trials was sought by searching ClinicalTrials.gov (http://clinicaltrials.gov) (accessed August 2009), and the National Research Register (NRR) (2009 Issue 1).

Selection Criteria: Randomised or quasi-randomised controlled trials using supervised aerobic exercise training programmes with behavioral components accepted as co-interventions.

Data Collection And Analysis: Two reviewers selected relevant trials, assessed methodological quality and extracted data. Where appropriate, data were pooled using meta-analysis with a random-effects model. Positive values favour the intervention group, while negative values favour the control group.

Main Results: Three studies included in this systematic review used different kinds of aerobic activity: walking/jogging and rowing training and included participants with a broad age range (17 to 65 years). They were conducted in the USA, Portugal and Israel. In the meta-analyses, only maximal treadmill grade was improved after aerobic exercise training programmes (4.26 grades (%) [95% CI 2.06, 6.45]). Other variables relative to work performance that could not be combined in a meta-analysis were also improved in the intervention group (maximal test time P=0.0003), total turns of fan wheel (P=0.02), resistance of ergometer (p=0.003), power knee extension and flexion (p<0.00001), and timed up and go test (p=0.008). Thirty other outcomes measured in this review including, oxidative stress and body composition variables, could not be combined in the meta-analysis. Apart from work performance, trials reported no statistically significant improvements.

Authors' Conclusions: There is insufficient evidence to demonstrate that there is improvement in physical or psychosocial outcomes of aerobic exercise in adults with Down syndrome. Although evidence exists to support improvements in physiological and psychological aspects from strategies using mixed physical activity programmes, well-conducted research examining long-term physical outcomes, adverse effects, psychosocial outcomes and costs is required before informed practice decisions can be made.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/14651858.CD005176.pub4DOI Listing
May 2010

5-FU for genital warts in non-immunocompromised individuals.

Cochrane Database Syst Rev 2010 Apr 14(4):CD006562. Epub 2010 Apr 14.

Departament of Medicine, Urgency Medicine, Universidade Federal de São Paulo / Escola Paulista de Medicina, Rua Pedro de Toledo 598, São Paulo, SP, Brazil.

Background: Genital warts are common and usually are harmless but can be painful and psychologically burdensome. Several local treatments can be used, including topical 5-Fluorouracil (5-FU).

Objectives: To determine the effectiveness and safety of 5-FU topical treatment for genital warts in nonimmunocompromised individuals.

Search Strategy: Databases searched were Cochrane Central Register of Controlled Trials (The Cochrane Library 2009 Issue 3), MEDLINE (1966 to August 2009), EMBASE (until August 2009), LILACS (1982 to August 2009). The search had no language or publication restrictions.

Selection Criteria: The review included randomised controlled trials (RCTs) among women, men, or both sexes, aged 18 years and older, comparing: 5-FU versus placebo or no treatment; 5-FU in any dose versus other isolated treatment, topical or systemic; 5-FU in any dose associated with other treatment versus placebo; 5-FU in any dose associated with other treatment versus other isolated treatment, topical or systemic; 5-FU in any dose associated with other treatment versus other associated treatment, topical or systemic.

Data Collection And Analysis: Two authors independently assessed trial quality and extracted data from the original publications.

Main Results: Six trials involving 988 patients (645 women and 343 men) and reporting eight comparisons were found. Two studies reported withdrawals and dropouts, but none mentioned analysis by intention to treat (ITT). 5-FU presented better results for cure than placebo or no treatment (relative risk (RR) 0.39, 95% confidence interval (CI) 0.23 to 0.67), meta-cresol-sulfonic acid (MCSA) (RR 2.11, 95% CI 0.83 to 5.37), Podophylin 2%, 4% or 25% (RR 1.26, 95% CI 0.86 to 1.82). There were no statistical differences for treatment failure for 5-FU versus CO2 Laser (RR 0.69, 95% CI 0.43 to 1.11) versus 5-FU + INFalpha-2a (low dose) (RR 1.02, 95% CI 0.87 to 1.119). Worse results were found for 5-FU versus 5-FU + INFalpha-2a (high dose) (RR 10.78, 95% CI 1.50 to 77.36), and 5-FU + CO2 Laser INFalpha-2a (high dose) (RR 7.97, 95% CI 2.87 to 22.13).

Authors' Conclusions: The reviewed trials were highly variable in methods and quality, and the evidence provided by these studies was weak. Cure rates with several treatments were variable, and although 5-FU presents therapeutic results that are inferior to those seen with 5-FU + Inf alpha-2a (high dose) and 5-FU + CO2 Laser + Inf alpha-2a (high dose), the treatment should not be abandoned. Topical treatment with 5-FU has a therapeutic effect; however, the benefits and risks have not been determined clearly and further studies are needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/14651858.CD006562.pub2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7206224PMC
April 2010

WITHDRAWN: Aerobic exercise training programmes for improving physical and psychosocial health in adults with Down syndrome.

Cochrane Database Syst Rev 2009 Jul 8(3):CD005176. Epub 2009 Jul 8.

Emergency Medicine and Evidence Based Medicine, Universidade Federal de São Paulo, Rua Pedro de Toledo 598, São Paulo, Brazil, 04039-001.

Background: Although physical fitness has been suggested to improve physical and psychosocial health for a variety of population profiles, there is a lack of information about the safety and effectiveness of aerobic exercise for adults with Down syndrome.

Objectives: To evaluate the effectiveness and safety of aerobic exercise training programmes for physiological and psychosocial outcomes in adults with Down syndrome.

Search Strategy: Search terms and synonyms for "aerobic exercise" and "Down syndrome" were used within the following databases: CENTRAL (2007, Issue 1); MEDLINE via PUBMED (1966 to March 2007); EMBASE (2005 to April 2007); CINAHL (1982 to March 2007); LILACS (1982 to March 2007); PsycINFO (1887 to March 2007); ERIC (1966 to March 2007); CCT (March 2007); Academic Search Elite (to March 2007), C2- SPECTR (to March 2007 ), NRR (2007 Issue 1), ClinicalTrials.gov (accessed March 2007) and within supplements of Medicine and Science in Sports and Exercise.

Selection Criteria: Randomised or quasi-randomised controlled trials using supervised aerobic exercise training programmes with behavioral components accepted as co-interventions.

Data Collection And Analysis: Two reviewers selected relevant trials, assessed methodological quality and extracted data. Where appropriate, data was pooled using meta-analysis with a random effects model

Main Results: The two studies included in this trial used different kinds of aerobic activity: walking/jogging and rowing training. One included study was conducted in the USA, the other in Portugal. In the meta-analyses, only maximal treadmill grade, a work performance variable, was improved in the intervention group after aerobic exercise training programmes (-4.26 [95% CI -6.45, -2.06]) grade. The other outcomes in the meta-analysis showed no significant differences between intervention and control groups, as expressed by weighted mean difference: VO(2) peak -0.30 (95% CI -377, 3.17) mL.Kg.min(-1); peak heart rate, -2.84 (95% CI -10.73, 5.05) bpm; respiratory exchange ratio, 0.01 (95% CI -0.04, 0.06); pulmonary ventilation, -5.86 (95% CI -16.06, 4.34) L.min(-1). 30 other measures including work performance, oxidative stress and body composition variables could not be combined in the meta-analysis. Apart from work performance, trials reported no significant improvements in these measures.

Authors' Conclusions: There is insufficient evidence to support improvement in physical or psychosocial outcomes of aerobic exercise in adults with Down syndrome. Although evidence exists which supports improvements in physiological and psychological aspects from strategies using mixed physical activity programmes, well-conducted research which examines long-term physical outcomes, adverse effects, psychosocial outcomes and costs are required before informed practice decisions can be made.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/14651858.CD005176.pub3DOI Listing
July 2009
-->