Art Therapy in Advanced Cancer. A Mapping Review of the Evidence.

PURPOSE OF REVIEW: The benefits of arts in improving well-being in end-of-life patients have been stated by the WHO. To inspire clinical practice and future research, we performed a mapping review of the current evidence on the effectiveness of art therapy interventions in stage III and IV cancer patients and their relatives. RECENT FINDINGS: We identified 14 studies. Benefits reported by the authors were grouped as improved emotional and spiritual condition, symptom relief, perception of well-being, satisfaction, and helpfulness. As a body of evidence, notable limitations were observed: Only 1 study was a randomized controlled trial (RCT), and there was heterogeneity in the interventions and outcome measures. This mapping review highlights the evidence available on the effectiveness of art therapy in advanced cancer, which remains limited and presents specific challenges. It also provides a visual representation of the reported benefits, encouraging further and more rigorous investigation.

Effectiveness of medical nutrition therapy in adolescents with type 1 diabetes: a systematic review.

BACKGROUND: Medical nutrition therapy (MNT) has an integral role in overall diabetes management. During adolescence, consideration of physiological and psychosocial changes is essential for implementing an optimal diabetes treatment. OBJECTIVES: Our aim was to identify, summarize, and interpret the published literature about MNT in adolescents with type 1 diabetes. METHODS: The Medline (PubMed) and EMBASE databases were searched from January 1959 to December 2021. The inclusion criteria were interventional studies with MNT in adolescents with type 1 diabetes with a disease duration over 1 year, including the following outcomes: dietary intake and daily eating patterns (assessed with validated tools, two or more 24 h dietary recall or 3-day dietary records), the diabetes self-management education and support (DSMES), glycemic control, lipid profile and body mass index (BMI). The exclusion criteria were studies without a control group (except for pre-post studies), the lack of randomization and those studies that assessed only a single nutrient, food or meal consumption, as well as reviews, and in-vitro/in-vivo studies. The risk of bias assessment was performed using the Cochrane risk-of-bias tool for randomized trials. A narrative synthesis was performed to present the results. The quality of evidence was assessed with the GRADE guidance. RESULTS: From a total of 5377 records, 12 intervention studies (9 RCT and 3 pre-post intervention studies) were included. The data were assessed in order to perform a meta-analysis; however, the studies were too heterogeneous. The studies showed conflicting results about the effectiveness of MNT on dietary pattern, DSMES, glycemic control, lipid profile and BMI. CONCLUSIONS: Clinical research studies on the effectiveness of MNT in adolescents with type 1 diabetes are scarce. The limited number of studies with a high risk of bias precludes establishing robust conclusions on this issue. Further research is warranted.

Do manual therapies have a specific autonomic effect? An overview of systematic reviews.

BACKGROUND: The impact of manual therapy interventions on the autonomic nervous system have been largely assessed, but with heterogeneous findings regarding the direction of these effects. We conducted an overview of systematic reviews to describe if there is a specific autonomic effect elicited by manual therapy interventions, its relation with the type of technique used and the body region where the intervention was applied. METHODS: We conducted an overview according to a publicly registered protocol. We searched the Cochrane Database of Systematic Reviews, MEDLINE, EPISTEMONIKOS and SCOPUS, from their inception to march 2021. We included systematic reviews for which the primary aim of the intervention was to assess the autonomic effect elicited by a manual therapy intervention in either healthy or symptomatic individuals. Two authors independently applied the selection criteria, assessed risk of bias from the included reviews and extracted data. An established model of generalisation guided the data analysis and interpretation. RESULTS: We included 12 reviews (5 rated as low risk of bias according the ROBIS tool). The findings showed that manual therapies may have an effect on both sympathetic and parasympathetic systems. However, the results from included reviews were inconsistent due to differences in their methodological rigour and how the effects were measured. The reviews with a lower risk of bias could not discriminate the effects depending on the body region to which the technique was applied. CONCLUSION: The magnitude of the specific autonomic effect elicited by manual therapies and its clinical relevance is uncertain. We point out some specific recommendations in order to improve the quality and relevance of future research in this field.

Sample size, study length, and inadequate controls were the most common self-acknowledged limitations in manual therapy trials: A methodological review.

OBJECTIVES: The aim of this study was to quantify and analyze the presence and type of self-acknowledged limitations (SALs) in a sample of manual therapy (MT) randomized controlled trials. STUDY DESIGN AND SETTING: We randomly selected 120 MT trials. We extracted data related to SALs from the original reports and classified them into 12 categories. After data extraction, specific limitations within each category were identified. A descriptive analysis was performed using frequencies and percentages for qualitative variables. RESULTS: The number of SALs per trial article ranged from 0 to 8, and more than two-thirds of trials acknowledged at least two different limitations. Despite its small proportion, 9% of trials did not report SALs. The most common limitation declared, in almost half of our sample, related to sample size (47.5%) followed by limitations related to study length and follow-up (33.3%) and inadequate controls (32.5%). CONCLUSION: Our results indicate that at least two different limitations are consistently acknowledged in MT trial reports, the most common being those related to sample size, study length, follow-up, and inadequate controls. Analysis of the reasons behind the SALs gives some insights about the main difficulties in conducting research in this field and may help develop strategies to improve future research.

A methodological review revealed that reporting of trials in manual therapy has not improved over time.

OBJECTIVE: The aim of this review was to evaluate a selection of major reporting aspects in manual therapy (MT) trials, before and after the publication of the CONSORT extension for nonpharmacological trials (CONSORTnpt) STUDY DESIGN AND SETTING: We randomly selected 100 MT trials published between 2000 and 2015 and divided them into a pre-CONSORTnpt (n = 50) and a post-CONSORTnpt (n = 50) group. We extracted data on relevant issues of internal validity, reliability, and description of interventions. Two authors extracted data independently. Percentages were used for descriptive analyses, and Fisher's exact test and the chi-square test were used for group comparisons. RESULTS: Six different types of MT interventions with up to 20 controls were analyzed. The most common populations/conditions studied were healthy subjects and subjects with lower back or neck pain. Over 70% of studies included multi-session interventions, and 42% of studies reported long-term followup. The only significant differences between groups were the inclusion of a flowchart diagram, the estimated effect size, precision descriptions, and the description of intervention procedures. CONCLUSION: Our findings suggest that trials in MT show poor reporting even after the availability of standardized guidelines.

Homocysteine-lowering interventions for preventing cardiovascular events.

BACKGROUND: Cardiovascular disease, which includes coronary artery disease, stroke and peripheral vascular disease, is a leading cause of death worldwide. Homocysteine is an amino acid with biological functions in methionine metabolism. A postulated risk factor for cardiovascular disease is an elevated circulating total homocysteine level. The impact of homocysteine-lowering interventions, given to patients in the form of vitamins B6, B9 or B12 supplements, on cardiovascular events has been investigated. This is an update of a review previously published in 2009, 2013, and 2015. OBJECTIVES: To determine whether homocysteine-lowering interventions, provided to patients with and without pre-existing cardiovascular disease are effective in preventing cardiovascular events, as well as reducing all-cause mortality, and to evaluate their safety. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2017, Issue 5), MEDLINE (1946 to 1 June 2017), Embase (1980 to 2017 week 22) and LILACS (1986 to 1 June 2017). We also searched Web of Science (1970 to 1 June 2017). We handsearched the reference lists of included papers. We also contacted researchers in the field. There was no language restriction in the search. SELECTION CRITERIA: We included randomised controlled trials assessing the effects of homocysteine-lowering interventions for preventing cardiovascular events with a follow-up period of one year or longer. We considered myocardial infarction and stroke as the primary outcomes. We excluded studies in patients with end-stage renal disease. DATA COLLECTION AND ANALYSIS: We performed study selection, 'Risk of bias' assessment and data extraction in duplicate. We estimated risk ratios (RR) for dichotomous outcomes. We calculated the number needed to treat for an additional beneficial outcome (NNTB). We measured statistical heterogeneity using the I2 statistic. We used a random-effects model. We conducted trial sequential analyses, Bayes factor, and fragility indices where appropriate. MAIN RESULTS: In this third update, we identified three new randomised controlled trials, for a total of 15 randomised controlled trials involving 71,422 participants. Nine trials (60%) had low risk of bias, length of follow-up ranged from one to 7.3 years. Compared with placebo, there were no differences in effects of homocysteine-lowering interventions on myocardial infarction (homocysteine-lowering = 7.1% versus placebo = 6.0%; RR 1.02, 95% confidence interval (CI) 0.95 to 1.10, I2 = 0%, 12 trials; N = 46,699; Bayes factor 1.04, high-quality evidence), death from any cause (homocysteine-lowering = 11.7% versus placebo = 12.3%, RR 1.01, 95% CI 0.96 to 1.06, I2 = 0%, 11 trials, N = 44,817; Bayes factor = 1.05, high-quality evidence), or serious adverse events (homocysteine-lowering = 8.3% versus comparator = 8.5%, RR 1.07, 95% CI 1.00 to 1.14, I2 = 0%, eight trials, N = 35,788; high-quality evidence). Compared with placebo, homocysteine-lowering interventions were associated with reduced stroke outcome (homocysteine-lowering = 4.3% versus comparator = 5.1%, RR 0.90, 95% CI 0.82 to 0.99, I2 = 8%, 10 trials, N = 44,224; high-quality evidence). Compared with low doses, there were uncertain effects of high doses of homocysteine-lowering interventions on stroke (high = 10.8% versus low = 11.2%, RR 0.90, 95% CI 0.66 to 1.22, I2 = 72%, two trials, N = 3929; very low-quality evidence).We found no evidence of publication bias. AUTHORS' CONCLUSIONS: In this third update of the Cochrane review, there were no differences in effects of homocysteine-lowering interventions in the form of supplements of vitamins B6, B9 or B12 given alone or in combination comparing with placebo on myocardial infarction, death from any cause or adverse events. In terms of stroke, this review found a small difference in effect favouring to homocysteine-lowering interventions in the form of supplements of vitamins B6, B9 or B12 given alone or in combination comparing with placebo.There were uncertain effects of enalapril plus folic acid compared with enalapril on stroke; approximately 143 (95% CI 85 to 428) people would need to be treated for 5.4 years to prevent 1 stroke, this evidence emerged from one mega-trial.Trial sequential analyses showed that additional trials are unlikely to increase the certainty about the findings of this issue regarding homocysteine-lowering interventions versus placebo. There is a need for additional trials comparing homocysteine-lowering interventions combined with antihypertensive medication versus antihypertensive medication, and homocysteine-lowering interventions at high doses versus homocysteine-lowering interventions at low doses. Potential trials should be large and co-operative.

Autologous platelet-rich plasma for treating chronic wounds.

BACKGROUND: Autologous platelet-rich plasma (PRP) is a treatment that contains fibrin and high concentrations of growth factors with the potential to improve the healing of chronic wounds. This is the first update of a review first published in 2012. OBJECTIVES: To determine whether autologous PRP promotes the healing of chronic wounds. SEARCH METHODS: In June 2015, for this first update, we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library): Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. We also searched for ongoing and unpublished clinical trials in the WHO International Clinical Trials Registry Platform (ICTRP) (searched January 2015). We did not impose any restrictions with respect to language, date of publication, or study setting. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared autologous PRP with placebo or alternative treatments for any type of chronic wound in adults. We did not apply any date or language restrictions. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology, including two reviewers independently selecting studies for inclusion, extracting data, and assessing risk of bias. MAIN RESULTS: The search identified one new RCT, making a total of 10 included RCTs (442 participants, 42% women). The median number of participants per RCT was 29 (range 10 to 117). Four RCTs recruited people with a range of chronic wounds; three RCTs recruited people with venous leg ulcers, and three RCTs considered foot ulcers in people with diabetes. The median length of treatment was 12 weeks (range 8 to 40 weeks).It is unclear whether autologous PRP improves the healing of chronic wounds generally compared with standard treatment (with or without placebo) (risk ratio (RR) 1.19, 95% confidence interval (CI) 0.95 to 1.50; I(2) = 27%, low quality evidence, 8 RCTs, 391 participants). Autologous PRP may increase the healing of foot ulcers in people with diabetes compared with standard care (with or without placebo) (RR 1.22, 95% CI 1.01 to 1.49; I(2) = 0%, low quality evidence, 2 RCTs, 189 participants). It is unclear if autologous PRP affects the healing of venous leg ulcers (RR 1.02, 95% CI 0.81 to 1.27; I(2) = 0% ). It is unclear if there is a difference in the risk of adverse events in people treated with PRP or standard care (RR 1.05, 95% CI 0.29 to 3.88; I(2) = 0%, low quality evidence from 3 trials, 102 participants). AUTHORS' CONCLUSIONS: PRP may improve the healing of foot ulcers associated with diabetes, but this conclusion is based on low quality evidence from two small RCTs. It is unclear whether PRP influences the healing of other chronic wounds. The overall quality of evidence of autologous PRP for treating chronic wounds is low. There are very few RCTs evaluating PRP, they are underpowered to detect treatment effects, if they exist, and are generally at high or unclear risk of bias. Well designed and adequately powered clinical trials are needed.

Antifibrinolytic amino acids for upper gastrointestinal bleeding in people with acute or chronic liver disease.

BACKGROUND: Upper gastrointestinal bleeding is one of the most frequent causes of morbidity and mortality in the course of liver cirrhosis. People with liver disease frequently have haemostatic abnormalities such as hyperfibrinolysis. Therefore, antifibrinolytic amino acids have been proposed to be used as supplementary interventions alongside any of the primary treatments for upper gastrointestinal bleeding in people with liver diseases. This is an update of this Cochrane review. OBJECTIVES: To assess the beneficial and harmful effects of antifibrinolytic amino acids for upper gastrointestinal bleeding in people with acute or chronic liver disease. SEARCH METHODS: We searched The Cochrane Hepato-Biliary Controlled Trials Register (February 2015), Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2 of 12, 2015), MEDLINE (Ovid SP) (1946 to February 2015), EMBASE (Ovid SP) (1974 to February 2015), Science Citation Index EXPANDED (1900 to February 2015), LILACS (1982 to February 2015), World Health Organization Clinical Trials Search Portal (accessed 26 February 2015), and the metaRegister of Controlled Trials (accessed 26 February 2015). We scrutinised the reference lists of the retrieved publications. SELECTION CRITERIA: Randomised clinical trials irrespective of blinding, language, or publication status for assessment of benefits and harms. Observational studies for assessment of harms. DATA COLLECTION AND ANALYSIS: We planned to summarise data from randomised clinical trials using standard Cochrane methodologies and assessed according to the GRADE approach. MAIN RESULTS: We found no randomised clinical trials assessing antifibrinolytic amino acids for treating upper gastrointestinal bleeding in people with acute or chronic liver disease. We did not identify quasi-randomised, historically controlled, or observational studies in which we could assess harms. AUTHORS' CONCLUSIONS: This updated Cochrane review identified no randomised clinical trials assessing the benefits and harms of antifibrinolytic amino acids for upper gastrointestinal bleeding in people with acute or chronic liver disease. The benefits and harms of antifibrinolytic amino acids need to be tested in randomised clinical trials. Unless randomised clinical trials are conducted to assess the trade-off between benefits and harms, we cannot recommend or refute antifibrinolytic amino acids for upper gastrointestinal bleeding in people with acute or chronic liver diseases.

Homocysteine-lowering interventions for preventing cardiovascular events.

BACKGROUND: Cardiovascular disease, which includes coronary artery disease, stroke and congestive heart failure, is a leading cause of death worldwide. Homocysteine is an amino acid with biological functions in methionine metabolism. A postulated risk factor is an elevated circulating total homocysteine level, which is associated with cardiovascular events. The impact of homocysteine-lowering interventions, given to patients in the form of vitamins B6, B9 or B12 supplements, on cardiovascular events. This is an update of a review previously published in 2009 and 2013. OBJECTIVES: To determine whether homocysteine-lowering interventions, provided in patients with and without pre-existing cardiovascular disease are effective in preventing cardiovascular events, as well as all-cause mortality and evaluate their safety. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2014, Issue 1), MEDLINE (1950 to January week 5 2014), EMBASE (1980 to 2014 week 6) and LILACS (1986 to February 2014). We also searched Web of Science (1970 to 7 February 2014). We handsearched the reference lists of included papers. We also contacted researchers in the field. There was no language restriction in the search. SELECTION CRITERIA: We included randomised controlled trials assessing the effects of homocysteine-lowering interventions for preventing cardiovascular events with a follow-up period of one year or longer. We considered myocardial infarction and stroke as the primary outcomes. We excluded studies in patients with end-stage renal disease. DATA COLLECTION AND ANALYSIS: We performed study selection, 'Risk of bias' assessment and data extraction in duplicate. We estimated risk ratios (RR) for dichotomous outcomes. We measured statistical heterogeneity using the I(2) statistic. We used a random-effects model. MAIN RESULTS: In this second updated Cochrane Review, we identified no new randomised controlled trials. Therefore, this new version includes 12 randomised controlled trials involving 47,429 participants. In general terms, 75% (9/12) trials had a low risk of bias. Homocysteine-lowering interventions compared with placebo did not significantly affect non-fatal or fatal myocardial infarction (1743/23,590 (7.38%) versus 1247/20,190 (6.17%); RR 1.02, 95% confidence interval (CI) 0.95 to 1.10, I(2) = 0%, high quality evidence), stroke (968/22,348 (4.33%) versus 974/18,957 (5.13%); RR 0.91, 95% CI 0.82 to 1.0, I(2) = 11%, high quality evidence) or death from any cause (2784/22,648 (12.29%) versus 2502/19,250 (10.64%); RR 1.01, 95% CI 0.96 to 1.07, I(2) = 6%, high quality evidence). Homocysteine-lowering interventions compared with placebo did not significantly affect serious adverse events (cancer) (1558/18,130 (8.59%) versus 1334/14,739 (9.05%); RR 1.06, 95% CI 0.98 to 1.13; I(2) = 0%, high quality evidence). AUTHORS' CONCLUSIONS: This second update of this Cochrane Review found no evidence to suggest that homocysteine-lowering interventions in the form of supplements of vitamins B6, B9 or B12 given alone or in combination should be used for preventing cardiovascular events. Furthermore, there is no evidence to suggest that homocysteine-lowering interventions are associated with an increased risk of cancer.

Eculizumab for treating patients with paroxysmal nocturnal hemoglobinuria.

BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) is a chronic, not malignant, disease of the hematopoietic stem cells, associated with significant morbidity and mortality. It is a rare disease with an estimated incidence of 1.3 new cases per one million individuals per year. The treatment of PNH has been largely empirical and symptomatic, with blood transfusions, anticoagulation, and supplementation with folic acid or iron. Eculizumab, a biological agent that inhibits complement cascade, was developed for preventing hemolytic anemia and severe thrombotic episodes. OBJECTIVES: To assess the clinical benefits and harms of eculizumab for treating patients with paroxysmal nocturnal hemoglobinuria (PNH). SEARCH METHODS: We conducted a comprehensive search strategy. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2014, Issue 5), Ovid MEDLINE (from 1946 to 15 May 2014), EMBASE (from 1980 to 25 June 2014), and LILACS (from 1982 to 25 June 2014). We did not apply any language restrictions. SELECTION CRITERIA: We included randomized controlled trials (RCTs) irrespective of their publication status or language. No limits were applied with respect to period of follow-up. We excluded quasi-RCTs. We included trials comparing eculizumab with placebo or best available therapy. We included any patient with a confirmed diagnosis of PNH. Primary outcome was overall survival. DATA COLLECTION AND ANALYSIS: We independently performed a duplicate selection of eligible trials, risk of bias assessment, and data extraction. We estimated risk ratios (RRs) and 95% confidence interval (CIs) for dichotomous outcomes, and mean differences (MDs) and 95% CIs for continuous outcomes. We used a random-effects model for analysis. MAIN RESULTS: We identified one multicenter (34 sites) phase III RCT involving 87 participants. The trial compared eculizumab versus placebo, and was conducted in the US, Canada, Europe, and Australia with 26 weeks of follow-up. This small trial had high risk of bias in many domains (attrition and selective reporting). It was sponsored by a pharmaceutical company. No patients died during the study. By using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (scores can range from 0 to 100, with higher scores on the global health status and functioning scales indicating improvement), the trial showed improvement in health-related quality of life in patients treated with eculizumab (mean difference (MD) 19.4, 95% CI 8.25 to 30.55; P = 0.0007; low quality of evidence). By using the Functional Assessment of Chronic Illness Therapy Fatigue instrument (scores can range from 0 to 52, with higher scores indicating improvement in fatigue), the trial showed a reduction in fatigue (MD 10.4, 95% CI 9.97 to 10.83; P = 0.00001; moderate quality of evidence) in the eculizumab group compared with placebo. Eculizumab compared with placebo showed a greater proportion of patients with transfusion independence: 51% (22/43) versus 0% (0/44); risk ratio (RR) 46.02, 95% CI 2.88 to 735.53; P = 0.007; moderate quality of evidence; and withdrawal for any reason: 4.7% (2/43) versus 22.72% (10/44); RR 0.20, 95% CI 0.05 to 0.88; P = 0.03; moderate quality of evidence. Due to the low rate of events observed, the included trial did not show any difference between eculizumab and placebo in terms of serious adverse events: 9.3% (4/43) versus 20.4% (9/44); RR 0.15, 95% CI 0.15 to 1.37; P = 0.16; low quality of evidence. We did not observe any difference between intervention and placebo for the most frequent adverse events. One participant receiving placebo showed an episode of thrombosis. The trial did not assess overall survival, transformation to myelodysplastic syndrome and acute myelogenous leukemia, or development or recurrence of aplastic anemia on treatment. AUTHORS' CONCLUSIONS: This review has detected an absence of evidence for eculizumab compared with placebo for treating paroxysmal nocturnal hemoglobinuria (PNH), in terms of overall survival, nonfatal thrombotic events, transformation to myelodysplastic syndrome and acute myelogenous leukemia, and development and recurrence of aplastic anemia on treatment. Current evidence indicates that compared with placebo, eculizumab increases health-related quality of life and increases transfusion independence. During the execution of the included trial, no patients died. Furthermore, the intervention seems to reduce fatigue and withdrawals for any reason. The safety profile of eculizumab is unclear. These conclusions are based on one small trial with risk of attrition and selective reporting bias.Therefore, prescription of eculizumab for treating patients with PNH can neither be supported nor rejected, unless new evidence from a large high quality trial alters this conclusion. Therefore, we urge the reader to interpret the trial results with much caution. Future trials on this issue should be conducted according to the SPIRIT statement and reported according to the CONSORT statement by independent investigators, and using the Foundation of Patient-Centered Outcomes Research recommendations.

Coenzyme Q10 and male infertility: a meta-analysis.

OBJECTIVE: To evaluate the effect of coenzyme Q10 treatments in male infertility, specifically in these parameters: live birth and pregnancy rates, CoQ10 seminal concentration, sperm concentration, and sperm motility. MATERIALS AND METHODS: Systematic review and meta-analysis in male infertility patients with CoQ10 oral treatments. Three trials were included: 149 males in CoQ10 group and 147 males in placebo group. RESULTS: None of the included trials provided any data regarding live births. The results of this meta-analysis show that supplementing infertile men with CoQ10 does not increase pregnancy rates. The analysis showed, among patients receiving CoQ10 treatment, a statistically significant increase in: CoQ10 seminal concentration (RR 49.55, 95 % CI 46.44 to 52.66, I(2) = 17 %), sperm concentration (RR 5.33, 95 % CI 4.18 to 6.47, I(2) = 58 %), and sperm motility (RR 4.50, 95 % CI 3.92 to 5.08, I(2) = 0 %) CONCLUSION: There is no evidence in the literature that CoQ10 increases either live birth or pregnancy rates, but there is a global improvement in sperm parameters. Adequately powered, robust trials of individual and combination antioxidant therapies are required to guide clinical practice.

Homocysteine-lowering interventions for preventing cardiovascular events.

BACKGROUND: Cardiovascular disease (including coronary artery disease, stroke and congestive heart failure), is a leading cause of death worldwide. Homocysteine is an amino acid with biological functions in methionine metabolism. A postulated risk factor is elevated circulating total homocysteine levels, which are associated with cardiovascular events. This is an update of a review previously published in 2009. OBJECTIVES: To assess the clinical effectiveness of homocysteine-lowering interventions in people with or without pre-existing cardiovascular disease. SEARCH METHODS: We searched The Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (2012, Issue 2), MEDLINE (1950 to Feb week 2 2012), EMBASE (1980 to 2012 week 07), and LILACS (1986 to February 2012). We also searched ISI Web of Science (1970 to February 2012). We handsearched the reference lists of included papers. We also contacted researchers in the field. There was no language restriction in the search. SELECTION CRITERIA: We included randomised controlled trials assessing the effects of homocysteine-lowering interventions for preventing cardiovascular events with a follow-up period of one year or longer. We considered myocardial infarction and stroke as the primary outcomes. We excluded studies in patients with end-stage renal disease. DATA COLLECTION AND ANALYSIS: We performed study selection, 'Risk of bias' assessment and data extraction in duplicate. We estimated risk ratios (RR) for dichotomous outcomes. We measured statistical heterogeneity using I(2). We used a random-effects model. MAIN RESULTS: In this updated systematic review, we identified four new randomised trials, resulting in a total of 12 randomised controlled trials involving 47,429 participants. In general terms, the trials had a low risk of bias. Homocysteine-lowering interventions compared with placebo did not significantly affect non-fatal or fatal myocardial infarction (pooled RR 1.02, 95% CI 0.95 to 1.10, I(2) = 0%), stroke (pooled RR 0.91, 95% CI 0.82 to 1.0, I(2) = 11%) or death by any cause (pooled RR 1.01 (95% CI 0.96 to 1.07, I(2): 6%)). Homocysteine-lowering interventions compared with placebo did not significantly affect serious adverse events (cancer) (1 RR 1.06, 95% CI 0.98 to 1.13; I(2) = 0%). AUTHORS' CONCLUSIONS: This updated Cochrane review found no evidence to suggest that homocysteine-lowering interventions in the form of supplements of vitamins B6, B9 or B12 given alone or in combination should be used for preventing cardiovascular events. Furthermore, there is no evidence suggesting that homocysteine-lowering interventions are associated with an increased risk of cancer.

Efficacy and Safety of Needle Acupuncture for Treating Gynecologic and Obstetric Disorders: An Overview.

Background: Acupuncture is being used increasingly to treat gynecologic and obstetric disorders. Objective: The aim of this review was to determine the efficacy and safety of acupuncture for treating pelvic and low-back pain during pregnancy, pain during labor, primary dysmenorrhea, and menopausal symptoms. Design: This is an overview of systematic reviews (SRs) and randomized controlled trials (RCTs). Search strategy: A literature search was conducted, in July 2010, in MEDLINE,® the Cochrane Database of Systematic Reviews, CENTRAL, the Database of Abstracts of Reviews of Effects, and Tripdatabase. Selection criteria: Published SRs and RCTs found during the literature search were included as well as RCTs that were published after completion of the literature search. Analysis: Data from SRs and RCTs that provided quantitative information were pooled. Results: Eight SRs and nine RCTs were included. One SR and 4 RCTs showed that acupuncture reduced pelvic and low-back pain, compared to physiotherapy or usual prenatal care. Results were contradictory when interventions were compared with sham acupuncture. With respect to reduction of pain during labor, two SRs showed no differences between acupuncture and sham acupuncture. None of the three SRs included on primary dysmenorrhea produced conclusive results. Two SRs of studies on menopausal symptoms showed no differences between acupuncture and sham acupuncture. A meta-analysis of three additional RCTs identified a favorable effect of acupuncture for reducing frequency and intensity of hot flashes. Adverse effects were mild and infrequent. Conclusions: Evidence for the efficacy of needle acupuncture for treating the disorders evaluated remains inconclusive. The intervention showed promising results for reducing pelvic and back pain during pregnancy and climacteric vasomotor symptoms, although well-designed studies are needed to make the results more precise and reliable.

Autologous platelet-rich plasma for treating chronic wounds.

BACKGROUND: Autologous platelet-rich plasma (PRP) is a treatment that contains fibrin and high concentrations of growth factors and has the potential to aid wound healing. OBJECTIVES: To determine whether autologous PRP promotes the healing of chronic wounds. SEARCH METHODS: We searched the Cochrane Wounds Group Specialised Register (searched 15 August 2012); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 8); Ovid MEDLINE (1950 to August Week 1 2012); Ovid MEDLINE (In-Process & Other Non-Indexed Citations, August 14, 2012); Ovid EMBASE (1980 to 2012 Week 32); EBSCO CINAHL (1982 to 10 August 2012) and International Clinical Trials Registry Platform (ICTRP)(accessed 22 August 2012). No date or language restrictions were applied. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared autologous PRP with placebo or alternative treatments for any type of chronic wound in adults. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed each study against the inclusion criteria, extracted data and assessed risk of bias for all included trials. We calculated the risk ratio (RR) or the mean difference (MD) and time to wound healing was analysed as survival data using the hazard ratio (HR). We considered heterogeneity as significant when I(2) was >75%. MAIN RESULTS: Nine eligible RCTs were included, with a total of 325 participants of whom 44% were women. The median number of participants per RCT was 26 (range 10 to 86). Four RCTs recruited people with mixed chronic wounds (there were participants with wounds caused by more than one aetiology and participants who had wounds of several aetiologies in the same trial), three RCTs recruited people with venous leg ulcers and two RCTs considered foot ulcers in people with diabetes. The median length of treatment was 12 weeks (range eight to 40 weeks).One study was at low risk of bias, three studies were at high risk of bias with the remainder being at overall unclear risk of bias. The proportion of completely healed chronic wounds was reported in seven RCTs that compared PRP with standard treatment or placebo, with no statistically significant difference between the groups, in diabetic foot ulcers (RR 1.16; 95% CI 0.57 to 2.35), in venous leg ulcers (pooled RR 1.02; 95% CI 0.81 to 1.27; I(2)=0% ) and in mixed chronic wounds (pooled RR 1.85; 95% CI 0.76 to 4.51; I(2)=42%). The total area epithelialised at the end of the intervention was reported in three RCTs of mixed chronic wounds, there was no statistically significant difference between the groups (pooled MD -1.94 cm(2); 95% CI -4.74 to 0.86; I(2)=47%). The percentage of wound area healed was reported in two RCTs of mixed chronic wounds, and results were statistically significant in favour of the PRP group (RR 51.78%; 95% CI 32.70 to 70.86; I(2)= 0%). Wound complications like infection or necrosis were reported by three RCTs, and there was no statistically significant difference between groups (RR 1.08; 95% CI 0.31 to 3.73). Adverse effects were reported by three studies and there was no statistically significant difference between people treated with PRP and those not given PRP (pooled RR 1.07; 95% CI 0.32 to 3.58; I(2)=0%). AUTHORS' CONCLUSIONS: There is currently no evidence to suggest that autologous PRP is of value for treating chronic wounds. However, current evidence is based on a small number of RCTs, most of which are either at high or unclear risk of bias. Well-designed and adequately powered clinical trials are needed.

Antifibrinolytic amino acids for upper gastrointestinal bleeding in patients with acute or chronic liver disease.

BACKGROUND: Upper gastrointestinal bleeding is one of the most frequent causes of morbidity and mortality in the course of liver cirrhosis. Patients with liver disease frequently have haemostatic abnormalities like hyperfibrinolysis. Therefore, antifibrinolytic amino acids have been proposed to be used as supplementary interventions alongside any of the primary treatments for upper gastrointestinal bleeding in patients with liver diseases. OBJECTIVES: To assess the beneficial and harmful effects of antifibrinolytic amino acids for upper gastrointestinal bleeding in patients with acute or chronic liver disease. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register (11 June 2012), Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2012, Issue 5 of 12), MEDLINE (Ovid SP) (1946 to June 2012), EMBASE (Ovid SP) (1974 to June 2012), Science Citation Index EXPANDED (1900 to June 2012), LILACS (1982 to June 2012), Clinical Trials Search Portal of the WHO (accessed June 18, 2012), and the Metaregister of Controlled Trials (accessed June 18, 2012). We scrutinised the reference lists of the retrieved publications. SELECTION CRITERIA: Randomised clinical trials irrespective of blinding, language, or publication status for assessment of benefits and harms. Observational studies for assessment of harms. DATA COLLECTION AND ANALYSIS: Data from randomised clinical trials were to be summarised by standard Cochrane Collaboration methodologies. MAIN RESULTS: We could not find any randomised clinical trials assessing antifibrinolytic amino acids for treating upper gastrointestinal bleeding in patients with acute or chronic liver disease. We could not identify quasi-randomised, historically controlled, or observational studies in which we could assess harms. AUTHORS' CONCLUSIONS: No randomised clinical trials assessing the benefits and harms of antifibrinolytic amino acids for upper gastrointestinal bleeding in patients with acute or chronic liver disease were identified. The benefits and harms of antifibrinolytic amino acids need to be tested in randomised clinical trials. Unless randomised clinical trials are conducted to assess the trade off between benefits and harms, we cannot recommend nor refute antifibrinolytic amino acids for upper gastrointestinal bleeding in patients with acute or chronic liver diseases.

Non-invasive interventions for improving well-being and quality of life in patients with lung cancer.

BACKGROUND: This is an updated version of the original review published in Issue 4, 2004 of The Cochrane Library. Lung cancer is one of the leading causes of death globally. Despite advances in treatment, the outlook for the majority of patients remains grim and most face a pessimistic future accompanied by sometimes devastating effects on emotional and psychological health. Although chemotherapy is accepted as an effective treatment for advanced lung cancer, the high prevalence of treatment-related side effects as well the symptoms of disease progression highlight the need for high-quality palliative and supportive care to minimise symptom distress and to promote quality of life. OBJECTIVES: To assess the effectiveness of non-invasive interventions delivered by healthcare professionals in improving symptoms, psychological functioning and quality of life in patients with lung cancer. SEARCH STRATEGY: We ran a search in February 2011 to update the original completed review. We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2011, Issue 2), MEDLINE (accessed through PubMed), EMBASE, PsycINFO, AMED, British Nursing Index and Archive (accessed through Ovid) and reference lists of relevant articles; we also contacted authors. SELECTION CRITERIA: Randomised or quasi-randomised clinical trials assessing the effects of non-invasive interventions in improving well-being and quality of life in patients diagnosed with lung cancer. DATA COLLECTION AND ANALYSIS: Two authors independently assessed relevant studies for inclusion. Data extraction and risk of bias assessment of relevant studies was performed by one author and checked by a second author. MAIN RESULTS: Fifteen trials were included, six of which were added in this update. Three trials of a nursing intervention to manage breathlessness showed benefit in terms of symptom experience, performance status and emotional functioning. Four trials assessed structured nursing programmes and found positive effects on delay in clinical deterioration, dependency and symptom distress, and improvements in emotional functioning and satisfaction with care.Three trials assessed the effect of different psychotherapeutic, psychosocial and educational interventions in patients with lung cancer. One trial assessing counselling showed benefit for some emotional components of the illness but findings were not conclusive. One trial examined the effects of coaching sensory self monitoring and reporting on pain-related variables and found that although coaching increases the amount of pain data communicated to providers by patients with lung cancer, the magnitude of the effect is small and does not lead to improved efficacy of analgesics prescribed for each patient's pain level. One trial compared telephone-based sessions of either caregiver-assisted coping skills training (CST) or education/support involving the caregiver and found that patients in both treatment conditions showed improvements in pain, depression, quality of life and self efficacy.Two trials assessed exercise programmes; one found a beneficial effect on self empowerment and the other study showed an increase in quadriceps strength but no significant changes for any measure of quality of life. One trial of nutritional interventions found positive effects for increasing energy intake, but no improvement in quality of life. Two small trials of reflexology showed some positive but short-lasting effects on anxiety and pain intensity.The main limitations of the studies included were the variability of the interventions assessed and the approaches to measuring the considered outcomes, and the lack of data reported in the trials regarding allocation of patients to treatment groups and blinding. AUTHORS' CONCLUSIONS: Nurse follow-up programmes and interventions to manage breathlessness may produce beneficial effects. Counselling may help patients cope more effectively with emotional symptoms, but the evidence is not conclusive. Other psychotherapeutic, psychosocial and educational interventions can play some role in improving patients' quality of life. Exercise programmes and nutritional interventions have not shown relevant and lasting improvements of quality of life. Reflexology may have some beneficial effects in the short term.

Drug therapy for treating post-dural puncture headache.

BACKGROUND: Post-dural puncture headache (PDPH) is the most common complication of lumbar puncture, an invasive procedure frequently performed in the emergency room. Numerous pharmaceutical drugs have been proposed to treat PDPH but there are still some uncertainties about their clinical effectiveness. OBJECTIVES: To assess the effectiveness and safety of drugs for treating PDPH in adults and children. SEARCH STRATEGY: The search strategy included the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2011, Issue 2), MEDLINE (from 1950 to June 2011), EMBASE (from 1980 to June 2011) and CINAHL (from 1982 to June 2011). There was no language restriction. SELECTION CRITERIA: We considered randomised controlled trials (RCTs) assessing the effectiveness of any pharmacological drug used for treating PDPH. DATA COLLECTION AND ANALYSIS: Review authors independently selected studies, assessed risks of bias and extracted data. We estimated risk ratios (RR) for dichotomous data and mean differences (MD) for continuous outcomes. We calculated a 95% confidence interval (CI) for each RR and MD. We did not undertake meta-analysis because the included studies assessed different sorts of drugs or different outcomes. We performed an intention-to-treat (ITT) analysis. MAIN RESULTS: We included seven RCTs (200 participants) in this review (between 88% and 90.5% were women; mostly parturients (84% to 87%) after a lumbar puncture for a regional anaesthesia). Pharmacological drugs assessed were oral and intravenous caffeine, subcutaneous sumatriptan, oral gabapentin, oral theophylline, intravenous hydrocortisone and intramuscular adrenocorticotropic hormone (ACTH).One RCT reported data about PDPH persistence of any severity at follow up (primary outcome); caffeine reduced the number of participants with PDPH at one to two hours when compared to placebo. Treatment with caffeine also decreased the need for a conservative supplementary therapeutic option. Treatment with gabapentin versus placebo reported better visual analogue scale (VAS) scores after one, two, three and four days; treatment with hydrocortisone plus conventional treatment showed better VAS scores than conventional treatment alone at six, 24 and 48 hours and treatment with theophylline showed a lower mean "sum of pain" when compared with placebo. Sumatriptan and ACTH did not show any relevant effect for this outcome.There were no clinically significant drug adverse events.The rest of the outcomes were not reported by the RCTs or did not show any relevant effect. AUTHORS' CONCLUSIONS: Caffeine has shown effectiveness for treating PDPH, decreasing the proportion of participants with PDPH persistence and those requiring supplementary interventions, when compared with placebo. Gabapentin, theophylline and hydrocortisone have also shown a decrease in pain severity scores when compared with placebo or conventional care.There is a lack of conclusive evidence for the other drugs assessed (sumatriptan and ACTH).These conclusions should be interpreted with caution, due to the lack of information to allow correct appraisal of risk of bias, the small sample sizes of studies and also the limited generalisability, as most participants were post-partum women in their 30s.

Biofeedback for pain management during labour.

BACKGROUND: Labour is often associated with pain and discomfort caused by a complex and subjective interaction of multiple factors, and should be understood within a multi-dimensional and multi-disciplinary framework. Within the non-pharmacological approach, biofeedback has focused on the acquisition of control over some physiological responses with the aid of electronic devices, allowing individuals to regulate some physical processes (such as pain) which are not usually under conscious control. The role of this behavioural approach for the management of pain during labour, as an addition to the standard prenatal care, has been never assessed systematically. This review is one in a series of Cochrane reviews examining pain relief in labour, which will contribute to an overview of systematic reviews of pain relief for women in labour (in preparation). OBJECTIVES: To examine the effectiveness of the use of biofeedback in prenatal lessons for managing pain during labour. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 March 2011), CENTRAL (The Cochrane Library 2011, Issue 1), PubMed (1950 to 20 March 2011), EMBASE (via OVID) (1980 to 24 March 2011), CINAHL (EBSCOhost) (1982 to 24 March 2011), and PsycINFO (via Ovid) (1806 to 24 March 2011). We searched for further studies in the reference lists of identified articles. SELECTION CRITERIA: Randomised controlled trials of any form of prenatal classes which included biofeedback, in any modality, in women with low-risk pregnancies. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. MAIN RESULTS: The review included four trials (186 women) that hugely differed in terms of the diversity of the intervention modalities and outcomes measured. Most trials assessed the effects of electromyographic biofeedback in women who were pregnant for the first time. The trials were judged to be at a high risk of bias due to the lack of data describing the sources of bias assessed. There was no significant evidence of a difference between biofeedback and control groups in terms of assisted vaginal birth, caesarean section, augmentation of labour and the use of pharmacological pain relief. The results of the included trials showed that the use of biofeedback to reduce the pain in women during labour is unproven. Electromyographic biofeedback may have some positive effects early in labour, but as labour progresses there is a need for additional pharmacological analgesia. AUTHORS' CONCLUSIONS: Despite some positive results shown in the included trials, there is insufficient evidence that biofeedback is effective for the management of pain during labour.

Folic acid for fragile X syndrome.

BACKGROUND: It has been argued that individuals with fragile X syndrome could have low folate levels in their bodies and that supplementing their dietary intake might remediate the adverse developmental and behavioural effects of the condition. OBJECTIVES: To review the efficacy and safety of folic acid in the treatment of people with fragile X syndrome. SEARCH STRATEGY: We searched four databases in November 2010: CENTRAL, PubMed, EMBASE and PsycINFO. SELECTION CRITERIA: Randomised controlled trials. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed risk of bias using the Cochrane 'Risk of bias' tool. MAIN RESULTS: We included five trials, which were published between 1986 and 1992. Overall, they included 67 patients, all male, with ages ranging from one to 54 years. Intellectual disability in participants varied from borderline to severe and some studies included patients with an additional diagnosis of autism or autistic behaviour. Four of the studies were placebo-controlled cross-over trials and one study was a parallel design. The duration of follow-up ranged from two months to 12 months and the period on folic acid or placebo ranged from two to eight months. Doses of folic acid ranged from 10 mg to 250 mg per day, 10 mg per day being the most common. Most of the younger patients involved were also taking part in special education programmes (usually involving language and occupational therapy).We were not able to perform meta-analysis to combine results but none of the individual studies found evidence of clinical benefit with the use of folic acid medication in fragile X syndrome patients on any of the areas of interest, either psychological and learning capabilities or behaviour and social performance, as measured with standardised tools. Separate analysis of evidence for patients of different age groups, i.e. prepubertal children and postpubertal young people, found some statistically significant results, but did not show clear evidence of benefit for either group. Adverse effects of folic acid treatment were rare, not serious and transient.Studies were generally poorly reported and we classified only one study as being at low risk of bias. AUTHORS' CONCLUSIONS: The quality of available evidence is low and not suitable for drawing conclusions about the effect of folic acid on fragile X syndrome patients. It consists of few studies with small samples of patients, all of them male, with little statistical power to detect anything other than huge effects.