Feverfew for preventing migraine.

BACKGROUND: This review is an update of a previously published review in the Cochrane Database of Systematic Reviews on 'Feverfew for preventing migraine' (2004, Issue 1). Feverfew (Tanacetum parthenium L.) extract is a herbal remedy, which has been used for preventing attacks of migraine. OBJECTIVES: To systematically review the evidence from double-blind randomised controlled trials (RCTs) assessing the clinical efficacy and safety of feverfew monopreparations versus placebo for preventing migraine. SEARCH METHODS: For this updated version of the review we searched CENTRAL, MEDLINE, EMBASE and AMED to January 2015. We contacted manufacturers of feverfew and checked the bibliographies of identified articles for further trials. SELECTION CRITERIA: We included randomised, placebo-controlled, double-blind trials assessing the efficacy of feverfew monopreparations for preventing migraine in patients of any age. We included trials using clinical outcome measures, while we excluded trials focusing exclusively on physiological parameters. There were no restrictions regarding the language of publication. DATA COLLECTION AND ANALYSIS: We systematically extracted data on patients, interventions, methods, outcome measures, results and adverse events. We assessed risk of bias using the Cochrane 'Risk of bias' tool and evaluated methodological quality using the Oxford Quality Scale developed by Jadad and colleagues. Two review authors (BW and MHP for this update, MHP and EE for the original version) independently selected studies, assessed methodological quality and extracted data. We resolved disagreements concerning evaluation of individual trials through discussion. MAIN RESULTS: We identified one new study for this update, resulting in six trials (561 patients) meeting the inclusion criteria. Five of the six trials reported on the main outcome, migraine frequency. Although five of the trials were generally of good methodological quality, all studies were either of unclear or high risk of bias with regards to sample size. Pooled analysis of the results was not possible due to the lack of common outcome measures and heterogeneity between studies in terms of participants, interventions and designs.The most recent trial added to this version of the review is rigorous and larger (n = 218), using a stable feverfew extract at a dose determined by a previous dose-finding trial. It reports that feverfew reduced migraine frequency by 1.9 attacks from 4.8 to 2.9 and placebo by 1.3 from to 4.8 to 3.5 per month, resulting in a difference in effect between feverfew and placebo of 0.6 attacks per month. For the secondary outcome measures intensity and duration of migraine attacks, incidence and severity of nausea and vomiting, and global assessment no statistically significant differences were reported. Results of previous trials are not convincing: three trials reporting positive effects of feverfew are all of small sample size (17 to 60 participants), while two rigorous trials (n = 50, 147) did not find significant differences between feverfew and placebo. Only mild and transient adverse events, most commonly gastrointestinal complaints and mouth ulcers, were reported in the included trials. AUTHORS' CONCLUSIONS: Since the last version of this review, one larger rigorous study has been included, reporting a difference in effect between feverfew and placebo of 0.6 attacks per month. This adds some positive evidence to the mixed and inconclusive findings of the previous review. However, this constitutes low quality evidence, which needs to be confirmed in larger rigorous trials with stable feverfew extracts and clearly defined migraine populations before firm conclusions can be drawn. It appears from the data reviewed that feverfew is not associated with any major safety concerns.

Artichoke leaf extract for treating hypercholesterolaemia.

BACKGROUND: Hypercholesterolaemia is directly associated with an increased risk for coronary heart disease and other sequelae of atherosclerosis. Artichoke leaf extract (ALE) has been implicated in lowering cholesterol levels. Whether ALE is truly effective for this indication is still a matter of debate. This is an update of a review first published in 2002 and last updated in 2009. OBJECTIVES: To assess the efficacy and safety of ALE in the treatment of hypercholesterolaemia., SEARCH METHODS: We updated searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library) (2012, Issue 5); MEDLINE Ovid (1966 to May Week 2, 2012); EMBASE Ovid (1980 to 2012 Week 19); and CINAHL Ebsco (1982 to May 2012) on 17 May 2012. CISCOM was last searched until June 2001, and AMED until June 2008. We checked reference lists of articles, and contacted manufacturers of preparations containing artichoke extract, and experts on the subject. No language restrictions were applied. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of ALE mono-preparations compared with placebo or reference medication for patients with hypercholesterolaemia. We excluded trials assessing ALE as one of several active components in a combination preparation or as a part of a combination treatment. DATA COLLECTION AND ANALYSIS: Data were extracted systematically and risk of bias was evaluated using the Cochrane 'Risk of bias' tool. Two authors independently performed the screening of studies, selection, data extraction and assessment of risk of bias. Disagreements in the evaluation of individual trials were resolved through discussion. MAIN RESULTS: We included three RCTs involving 262 participants. The trials were of adequate methodological quality but had some shortcomings. One trial was at low quality of risk, one at medium and one of unclear risk of bias. One trial is available as abstract only and includes a small sample. In the first trial the total cholesterol level in participants receiving ALE decreased by 4.2% from 7.16 (0.62) mmol/L to 6.86 (0.68) mmol/L after 12 weeks, and increased from 6.90 (0.49) mmol/L to 7.04 (0.61) mmol/L in patients receiving placebo, the total difference being statistically significant (P = 0.025). In the second trial ALE reduced total cholesterol levels by 18.5% from 7.74 mmol/L to 6.31 mmol/L after 42 ± 3 days of treatment, whereas placebo reduced cholesterol by 8.6% from 7.69 mmol/L to 7.03 mmol/L (P = 0.00001). The third trial, which is available as abstract only and provides limited data, stated that ALE significantly reduced blood cholesterol compared with placebo in a subgroup of patients with baseline total cholesterol levels of more than 230 mg/dL (P < 0.05). Trial reports indicate mild, transient and infrequent adverse events. AUTHORS' CONCLUSIONS: Data from three clinical trials assessing ALE for treating hypercholesterolaemia are available. Athough the trials are of adequate methodological quality they have some shortcomings and one is available as abstract only. There is an indication that ALE has potential in lowering cholesterol levels, but the evidence is, as yet, not convincing. The limited data on safety suggest only mild, transient and infrequent adverse events with the short term use of ALE.

Horse chestnut seed extract for chronic venous insufficiency.

BACKGROUND: Conservative therapy of chronic venous insufficiency (CVI) consists largely of compression treatment. However, this often causes discomfort and has been associated with poor compliance. Therefore, oral drug treatment is an attractive option. This is an update of a Cochrane review first published in 2002 and updated in 2004, 2006, 2008 and 2010. OBJECTIVES: To review the efficacy and safety of oral horse chestnut seed extract (HCSE) versus placebo, or reference therapy, for the treatment of CVI. SEARCH METHODS: For this update the Cochrane Peripheral Vascular Diseases Review Group searched their Specialised Register (last searched June 2012) and CENTRAL (Issue 5, 2012). For the previous versions of the review the authors searched AMED (inception to July 2005) and Phytobase (inception to January 2001) for randomised controlled trials (RCTs) of HCSE for CVI. Manufacturers of HCSE preparations and experts on the subject were contacted for published and unpublished material. There were no restrictions on language. SELECTION CRITERIA: RCTs comparing oral HCSE mono-preparations with placebo, or reference therapy, in people with CVI. Trials assessing HCSE as one of several active components in a combination preparation, or as a part of a combination treatment, were excluded. DATA COLLECTION AND ANALYSIS: Both authors independently selected the studies and, using a standard scoring system, assessed methodological quality and extracted data. Disagreements concerning evaluation of individual trials were resolved through discussion. MAIN RESULTS: Overall, there appeared to be an improvement in CVI related signs and symptoms with HCSE compared with placebo. Leg pain was assessed in seven placebo-controlled trials. Six reported a significant reduction of leg pain in the HCSE groups compared with the placebo groups, while another reported a statistically significant improvement compared with baseline. One trial suggested a weighted mean difference (WMD) of 42.4 mm (95% confidence interval (CI) 34.9 to 49.9) measured on a 100 mm visual analogue scale. Leg volume was assessed in seven placebo-controlled trials. Six trials (n = 502) suggested a WMD of 32.1ml (95% CI 13.49 to 50.72) in favour of HCSE compared with placebo. One trial indicated that HCSE may be as effective as treatment with compression stockings. Adverse events were usually mild and infrequent. AUTHORS' CONCLUSIONS: The evidence presented suggests that HCSE is an efficacious and safe short-term treatment for CVI. However, several caveats exist and larger, definitive RCTs are required to confirm the efficacy of this treatment option.

First-line matched related donor hematopoietic stem cell transplantation compared to immunosuppressive therapy in acquired severe aplastic anemia.

INTRODUCTION: Acquired severe aplastic anemia (SAA) is a rare and progressive disease characterized by an immune-mediated functional impairment of hematopoietic stem cells. Transplantation of these cells is a first-line treatment option if HLA-matched related donors are available. First-line immunosuppressive therapy may be offered as alternative. The aim was to compare the outcome of these patients in controlled trials. METHODS: A systematic search was performed in the bibliographic databases MEDLINE, EMBASE, and The Cochrane Library. To show an overview of various outcomes by treatment group we conducted a meta-analysis on overall survival. We evaluated whether studies reported statistically significant factors for improved survival. RESULTS: 26 non-randomized controlled trials (7,955 patients enrolled from 1970 to 2001) were identified. We did not identify any RCTs. Risk of bias was high except in 4 studies. Young age and recent year of treatment were identified as factors for improved survival in the HSCT group. Advanced age, SAA without very severe aplastic anemia, and combination of anti-lymphocyte globulin with cyclosporine A were factors for improved survival in the IST group. In 19 studies (4,855 patients), summary statistics were sufficient to be included in meta-analysis. Considerable heterogeneity did not justify a pooled estimate. Adverse events were inconsistently reported and varied significantly across studies. CONCLUSIONS: Young age and recent year of treatment were identified as factors for improved survival in the transplant group. Advanced age, SAA without very severe aplastic anemia, and combination of anti-lymphocyte globulin with cyclosporine A were factors for improved survival in the immunosuppressive group. Considerable heterogeneity of non-randomized controlled studies did not justify a pooled estimate. Adverse events were inconsistently reported and varied significantly across studies.

Artichoke leaf extract for treating hypercholesterolaemia.

BACKGROUND: Hypercholesterolaemia is directly associated with an increased risk for coronary heart disease and other sequelae of atherosclerosis. Artichoke leaf extract (ALE) has been implicated in lowering cholesterol levels. Whether ALE is truly effective for this indication, however, is still a matter of debate. OBJECTIVES: To assess the evidence of ALE versus placebo or reference medication for treating hypercholesterolaemia defined as mean total cholesterol levels of at least 5.17 mmol/L (200 mg/dL). SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials 2008 Issue 2, MEDLINE, EMBASE, AMED and CINAHL from their respective inception until June 2008; CISCOM until June 2001. Reference lists of articles were checked. Manufacturers of preparations containing artichoke extract and experts on the subject were contacted. SELECTION CRITERIA: Randomised controlled trials (RCTs) of ALE mono-preparations compared with placebo or reference medication for patients with hypercholesterolaemia were included. Trials assessing ALE as one of several active components in a combination preparation or as a part of a combination treatment were excluded. DATA COLLECTION AND ANALYSIS: Data were extracted systematically and methodological quality was evaluated using a standard scoring system and the Cochrane risk of bias assessment. The screening of studies, selection, data extraction and assessment of methodological quality were performed independently by two reviewers. Disagreements in the evaluation of individual trials were resolved through discussion. MAIN RESULTS: Three RCTs (262 participants) met all inclusion criteria. In one trial the total cholesterol level in participants receiving ALE decreased by 4.2% from 7.16 (0.62) mmol/L to 6.86 (0.68) mmol/L after 12 weeks and increased from 6.90 (0.49) mmol/L to 7.04 (0.61) mmol/L in patients receiving placebo, the total difference being statistically significant (P = 0.025). In a further trial ALE reduced total cholesterol levels by 18.5% from 7.74 mmol/L to 6.31 mmol/L after 42 +/- 3 days of treatment whereas the placebo reduced cholesterol by 8.6% from 7.69 mmol/L to 7.03 mmol/L (P = 0.00001). Another trial did state that ALE significantly reduced blood cholesterol compared with placebo in a sub-group of patients with baseline total cholesterol levels of more than 230 mg/dL (P < 0.05). Trial reports indicate mild, transient and infrequent adverse events. AUTHORS' CONCLUSIONS: Some data from clinical trials assessing ALE for treating hypercholesterolaemia exist. There is an indication that ALE has potential in lowering cholesterol levels, the evidence is, however, as yet not convincing. The limited data on safety suggest only mild, transient and infrequent adverse events with the short term use of ALE.

Serenoa repens (saw palmetto): a systematic review of adverse events.

Serenoa repens (W. Bartram) Small, also known as saw palmetto, is one of the most widely used herbal preparations for the treatment of lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH). Although a number of randomized controlled trials (RCTs) and systematic reviews of the efficacy of S. repens for the treatment of LUTS and BPH have been published, no systematic review on its drug interactions or adverse events currently exists. This review assesses all available human safety data of S. repens monopreparations. Systematic literature searches were conducted from date of inception to February 2008 in five electronic databases; reference lists and our departmental files were checked for further relevant publications. Information was requested from spontaneous reporting schemes of the WHO and national safety bodies. Twenty-four manufacturers/distributors of S. repens preparations and four herbalist organizations were contacted for additional information. No language restrictions were imposed. Only reports of adverse events in humans from monopreparations of S. repens were included. Data from all articles, regardless of study design, reporting adverse events or interactions were independently extracted by the first author and validated by the second. Forty articles (26 randomized controlled trials, 4 non-randomized controlled trials, 6 uncontrolled trials and 4 case reports/series) were included. They suggest that adverse events associated with the use of S. repens are mild and similar to those with placebo. The most frequently reported adverse events are abdominal pain, diarrhoea, nausea, fatigue, headache, decreased libido and rhinitis. More serious adverse events such as death and cerebral haemorrhage are reported in isolated case reports and data from spontaneous reporting schemes, but causality is questionable. No drug interactions were reported. Currently available data suggest that S. repens is well tolerated by most users and is not associated with serious adverse events. The majority of adverse events are mild, infrequent and reversible, and include abdominal pain, diarrhoea, nausea and fatigue, headache, decreased libido and rhinitis. We found no evidence for drug interactions with S. repens. However, higher quality reporting of adverse events is essential if safety assessments are to be improved in future.

Internal qigong for pain conditions: a systematic review.

UNLABELLED: The objective of this systematic review was to assess the evidence for the effectiveness of internal qigong as a treatment option for pain conditions. Nineteen databases were searched through to February 2009. Controlled clinical trials testing internal qigong in patients with pain of any origin assessing clinical outcome measures were considered. Trials using any type of internal qigong and control intervention were included. The selection of studies, data extraction, and validation were performed independently by 2 reviewers. Four randomized clinical trials (RCTs) and 3 controlled clinical trials met all inclusion criteria. One RCT suggested no significant difference for low back pain compared with electromyographic biofeedback. Two RCTs failed to show effects of internal qigong in neck pain compared with exercise therapy and waiting list control. One RCT suggested that qigong is inferior to aerobic exercise in patients with fibromyalgia. There are few RCTs testing the effectiveness of internal qigong in the management of pain conditions. Collectively, the existing trial evidence is not convincing enough to suggest that internal qigong is an effective modality for pain management. PERSPECTIVE: This review of controlled clinical trials focused on the effects of internal qigong, a self-directed energy healing intervention involving movement and meditation. Collectively, the existing trial evidence is not convincing enough to suggest that internal qigong is an effective modality for pain management. Future studies should be of high quality with particular emphasis on designing an adequate control intervention.

Acupuncture for allergic rhinitis: a systematic review.

OBJECTIVE: To systematically evaluate the effectiveness of acupuncture for treating or preventing allergic rhinitis (AR). DATA SOURCES: We retrieved data from 17 electronic databases, nonelectronic searches of conference proceedings, our own files of articles, and bibliographies of located articles. STUDY SELECTION: All randomized clinical trials (RCTs) of acupuncture for AR were considered for inclusion if they included placebo controls or were controlled against a comparator intervention. RESULTS: One hundred fifteen possibly relevant studies were identified and 12 RCTs met our inclusion criteria. The methodologic quality of the individual trials was variable. Our review includes 7 trials of high quality that met standards of methodologic rigor. All RCTs tested the effectiveness of acupuncture on AR symptoms and none on its curative value. Three RCTs failed to show superiority of acupuncture for treating or preventing symptoms for seasonal AR compared with placebo acupuncture. For perennial AR, 1 study reported favorable effects of acupuncture on a rhinitis symptoms score and 1 found positive results for a nasal symptoms score compared with placebo acupuncture (n = 152; standard mean difference, 0.45; 95% confidence interval, 0.13-0.78; P = .006; heterogeneity: chi2 = 0.45, P = .50, I2 = 0%). Two RCTs compared acupuncture with oral pharmacologic medications. Their results were in favor of acupuncture. CONCLUSIONS: The evidence for the effectiveness of acupuncture for the symptomatic treatment or prevention of AR is mixed. The results for seasonal AR failed to show specific effects of acupuncture. For perennial AR, results provide suggestive evidence of the effectiveness of acupuncture.

Complementary therapies for neuropathic and neuralgic pain: systematic review.

OBJECTIVE: To assess the evidence from rigorous clinical trials, systematic reviews, and meta-analyses of complementary and alternative therapies for treating neuropathic and neuralgic pain. METHODS: Systematic searches were carried out in the databases Medline, Embase, Amed, Scopus, the Cochrane Database of Systematic Reviews, Natural Standard, and the Natural Medicines Comprehensive Database. Each database was searched from its respective inception until March 2006. To be included, trials were required to state that they were randomized. Systematic reviews and meta-analyses were included if based on the results of randomized trials. No language restrictions were imposed. RESULTS: Five relevant systematic reviews and meta-analyses and 15 additional trials met the inclusion criteria and were reviewed. Data on the following complementary and alternative medicine treatments were identified: acupuncture, electrostimulation, herbal medicine, magnets, dietary supplements, imagery, and spiritual healing. CONCLUSIONS: On the basis of our findings, the evidence is not fully convincing for most complementary and alternative medicine modalities in relieving neuropathic or neuralgic pain. However, for topically applied capsaicin there is evidence of effectiveness beyond placebo. The evidence can be classified as encouraging and warrants further study for cannabis extract, magnets, carnitine, and electrostimulation.

Bee venom acupuncture for musculoskeletal pain: a review.

UNLABELLED: Bee venom (BV) acupuncture (BVA) involves injecting diluted BV into acupoints and is used for arthritis, pain, and rheumatoid diseases. The objective of this systematic review was to evaluate the evidence for the effectiveness of BVA in the treatment of musculoskeletal pain. Seventeen electronic databases were systematically searched up to September 2007 with no language restrictions. All randomized clinical trials (RCTs) of BVA for patients with musculoskeletal pain were considered for inclusion if they included placebo controls or were controlled against a comparator intervention. Methodology quality was assessed and, where possible, statistical pooling of data was performed. A total of 626 possibly relevant articles were identified, of which 11 RCTs met our inclusion criteria. Four RCTs that tested the effects of BVA plus classic acupuncture compared with saline injection plus classic acupuncture were included in the main meta-analysis. Pain was significantly lower with BVA plus classic acupuncture than with saline injection plus classic acupuncture (weighted mean difference: 100-mm visual analog scale, 14.0 mm, 95% CI = 9.5-18.6, P < .001, n = 112; heterogeneity: tau(2) = 0, chi(2) = 1.92, P = .59, I(2) = 0%). Our results provide suggestive evidence for the effectiveness of BVA in treating musculoskeletal pain. However, the total number of RCTs included in the analysis and the total sample size were too small to draw definitive conclusions. Future RCTs should assess larger patient samples for longer treatment periods and include appropriate controls. PERSPECTIVE: Bee venom acupuncture involves injecting diluted BV into acupoints and is used for arthritis, pain, and rheumatoid diseases. A meta-analysis produced suggestive evidence for the effectiveness of BVA in musculoskeletal pain management. However, primary data were scarce. Future RCTs should assess larger patient samples for longer treatment periods and include appropriate controls.

Tai chi for osteoarthritis: a systematic review.

The aim of this study was to evaluate data from controlled clinical trials testing the effectiveness of tai chi for treating osteoarthritis. Systematic searches were conducted on MEDLINE, AMED, British Nursing Index, CINAHL, EMBASE, PsycInfo, The Cochrane Library 2007, Issue 2, the UK National Research Register and ClinicalTrials.gov, Korean medical databases, the Qigong and Energy database and Chinese medical databases (until June 2007). Hand searches included conference proceedings and our own files. There were no restrictions regarding the language of publication. All controlled trials of tai chi for patients with osteoarthritis were considered for inclusion. Methodological quality was assessed using the Jadad score. Five randomised clinical trials (RCTs) and seven non-randomised controlled clinical trials (CCTs) met all inclusion criteria. Five RCTs assessed the effectiveness of tai chi on pain of osteoarthritis (OA). Two RCTs suggested significant pain reduction on visual analog scale or Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) compared to routine treatment and an attention control program in knee OA. Three RCTs did not report significant pain reduction on multiple sites pain. Four RCTs tested tai chi for physical functions. Two of these RCTs suggested improvement of physical function on activity of daily living or WOMAC compared to routine treatment or wait-list control, whilst two other RCTs failed to do so. In conclusion, there is some encouraging evidence suggesting that tai chi may be effective for pain control in patients with knee OA. However, the evidence is not convincing for pain reduction or improvement of physical function. Future RCTs should assess larger patient samples for longer treatment periods and use appropriate controls.

Complementary medicine for treating or preventing influenza or influenza-like illness.

The objective of this review was to assess the evidence for the effectiveness of complementary and alternative therapies for preventing or treating influenza or influenza-like illness, including avian influenza. Systematic literature searches were conducted in 5 databases until June 2006; other data sources included bibliographies of located articles, manufacturers of commercially available preparations, and experts in the field. Randomized clinical trials, controlled against placebo or active comparator, were included. Decisions on inclusion, data extraction, and methodological quality assessment were performed independently by 2 reviewers. Fourteen randomized controlled trials testing 7 preparations were included. For Oscillococcinum, P. quinquefolium extract, Sambucus nigra, and the herbal combination Kan Jang, 2 or more trials reporting some encouraging data were identified. In conclusion, the effectiveness of any complementary and alternative therapy for treating or preventing seasonal influenza is not established beyond reasonable doubt. Current evidence from randomized controlled trials is sparse and limited by small sample sizes, low methodological quality, or clinically irrelevant effect sizes. For avian influenza, no data are currently available. These results strengthen conventional approaches for seasonal influenza.

Clinical effectiveness of garlic (Allium sativum).

The objective of this review is to update and assess the clinical evidence based on rigorous trials of the effectiveness of garlic (A. sativum). Systematic searches were carried out in Medline, Embase, Amed, the Cochrane Database of Systematic Reviews, Natural Standard, and the Natural Medicines Comprehensive Database (search date December 2006). Our own files, the bibliographies of relevant papers and the contents pages of all issues of the review journal FACT were searched for further studies. No language restrictions were imposed. To be included, trials were required to state that they were randomized and double blind. Systematic reviews and meta-analyses of garlic were included if based on the results of randomized, double-blind trials. The literature searches identified six relevant systematic reviews and meta-analysis and double-blind randomized trials (RCT) that were published subsequently. These relate to cancer, common cold, hypercholesterolemia, hypertension, peripheral arterial disease and pre-eclampsia. The evidence based on rigorous clinical trials of garlic is not convincing. For hypercholesterolemia, the reported effects are small and may therefore not be of clinical relevance. For reducing blood pressure, few studies are available and the reported effects are too small to be clinically meaningful. For all other conditions not enough data are available for clinical recommendations.

Mind-body therapies: are the trial data getting stronger?

The effectiveness of mind-body therapies is sometimes doubted. The aim of this article is to evaluate trends in the development of the evidence base for autogenic training, hypnotherapy, and relaxation therapy. For this purpose, a comparison of 2 series of systematic reviews was conducted. The first is related to the evidence base in 2000, the second to that in 2005. Both employed virtually the same methodology and criteria for evaluation. The results of our comparisons show considerable changes during the observation period. The weight of the evidence has become stronger for several indications, and the direction of the evidence has been altered in a positive sense in several conditions. Applying the rules of evidence-based medicine, the following mind-body therapies are now supported by strong evidence: hypnotherapy for labor pain and relaxation therapy for anxiety and insomnia, as well as for nausea and vomiting induced by chemotherapy. It is concluded that an evidence-based approach for mind-body therapies is constructive and can generate positive results.