Rapid reviews for rapid decision-making during the coronavirus disease (COVID-19) pandemic, Norway, 2020.

In response to urgent needs for updated evidence for decision-making on various aspects related to coronavirus disease (COVID-19), the Norwegian Institute of Public Health established a rapid review team. Using simplified processes and shortcuts, this team produces summary reviews on request within 1-3 days that inform advice provided by the institute. All reviews are published with explicit messages about the risk of overlooking key evidence or making misguided judgements by using such rapid processes.

Carbohydrate quantity in the dietary management of type 2 diabetes: A systematic review and meta-analysis.

AIMS: This systematic review and meta-analysis (registration number: CRD42013005825) compares the effects of low carbohydrate diets (LCDs) on body weight, glycaemic control, lipid profile and blood pressure with the effects of higher carbohydrate diets (HCDs) in adults with type 2 diabetes. METHODS: MEDLINE, EMBASE, CENTRAL, CINAHL, Food Science Source and SweMed+ databases were systematically searched to identify randomized controlled trials (duration ≥3 months) investigating the effects of an LCD compared to an HCD in the management of type 2 diabetes. Data were extracted and pooled using a random effects model and were expressed as mean differences and risk ratio. Subgroup analyses were undertaken to examine the effects of duration of intervention, extent of carbohydrate restriction and risk of bias. The certainty of evidence was assessed using GRADE. RESULTS: Of the 1589 studies identified, 23, including 2178 participants, met inclusion criteria. Reductions were slightly greater with LCDs than with HCDs for HbA1c (-1.0 mmol/mol; CI, -1.9, -0.1 [-0.09%; CI, -0.17, -0.01]) and for triglycerides (-0.13 mmol/L; CI, -0.24, -0.02). Changes in weight, HDL- and LDL-cholesterol, total cholesterol and blood pressure did not differ significantly between groups. Subgroup analyses suggested that the difference in HbA1c was evident only in studies with a duration of ≤6 months and with a high risk of bias. CONCLUSIONS: The proportion of daily energy provided by carbohydrate intake is not an important determinant of response to dietary management, especially when considering longer term trials. A range of dietary patterns, including those traditional in Mediterranean countries, seems suitable for translating nutritional recommendations for individuals with diabetes into practical advice.

Interventions for ulceration and other skin changes caused by nerve damage in leprosy.

BACKGROUND: At the end of 2016, 145 countries reported to the World Health Organization (WHO) over 173,000 new cases of leprosy worldwide. In the past 20 years, over 16 million people have been treated for leprosy globally. The condition's main complications are injuries and ulceration caused by sensory loss from nerve damage. In this review we explored interventions to prevent or treat secondary damage to the skin in people affected by leprosy (Hansen's disease). This is an update of a Cochrane Review published in 2008. OBJECTIVES: To assess the effects of education, information, self-care programmes, dressings, skin care, footwear and other measures for preventing and healing secondary damage to the skin in persons affected by leprosy. SEARCH METHODS: We updated our searches of the following databases up to July 2018: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, AMED, LILACS, and CINAHL. We also searched five trial registers, three grey literature databases, and the reference lists of included studies for further references to relevant randomised controlled trials (RCTs). SELECTION CRITERIA: RCTs or quasi-RCTs or randomised cross-over trials involving anyone with leprosy and potential damage to peripheral nerves who was treated with any intervention designed to prevent damage, heal existing ulcers, and prevent development of new ulcers. Eligible comparisons were usual care, no interventions, or other interventions (e.g. other types of dressings or footwear). DATA COLLECTION AND ANALYSIS: We adhered to standard methodological procedures expected by Cochrane. Primary outcomes were prevention of ulcer(s), healing of existing ulcer(s) and adverse events. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We included 14 trials (854 participants). Eleven studies reported on gender (men: 472, women: 157). Participant age varied from 18 to 74 years. Most participants had a single, mainly non-infected, wound on one foot, which had been there for less than a year. Only seven studies reported whole study duration (there was no follow-up post-treatment), which was on average six months (range: 1 to 12 months). The studies were conducted in Brazil, Ethiopia, Egypt, Indonesia, Mexico, South Korea, and India. Many 'Risk of bias' assessments were rated as unclear risk due to limited information. Six studies had high risk of bias in at least one domain, including selection and attrition bias.Thirteen studies evaluated different interventions for treating existing ulcers, one of them also evaluated prevention of new ulcers. One study aimed to prevent skin changes, such as cracking and fissures. Investigated interventions included: laser therapy, light-emitting diode (LED), zinc tape, intralesional pentoxifylline, pulsed magnetic fields, wax therapy, ketanserin, human amniotic membrane gel, phenytoin, plaster shoes, and footwear.We are uncertain about the following key results, as the certainty of evidence is very low. All time points were measured from baseline.Three studies compared zinc tape versus other interventions and reported results in favour of zinc tape. One study compared zinc tape versus magnesium sulphate: at one month the number of healed ulcers and reduction in mean ulcer area was higher with zinc tape (risk ratio (RR) 2.00, 95% confidence interval (CI) 0.43 to 9.21, and mean difference (MD) -14.30 mm², 95% CI -26.51 to -2.09, respectively, 28 participants). Another study compared zinc tape and povidone iodine and found that even though there was a greater reduction in ulcer area after six weeks of treatment with zinc tape, there was no clear difference due to the wide 95% CI (MD 128.00 mm², 95% CI -110.01 to 366.01; 38 participants). The third study (90 participants) compared adhesive zinc tape with gauze soaked in Eusol, and found the healing time for deep ulcers was less compared to zinc tape: 17 days (95% CI 12 to 20) versus 30 days (95% CI 21 to 63). Adverse events were only collected in the study comparing zinc tape with gauze soaked in Eusol: there were no signs of skin sensitisation in either group at two months.Two studies compared topical phenytoin versus saline dressing and reported results in favour of phenytoin. One study reported a greater mean percentage reduction of ulcer area after four weeks with phenytoin 2% (MD 39.30%, 95% CI 25.82 to 52.78; 23 participants), and the other study reported a greater mean percentage reduction of ulcer volume (16.60%) after four weeks with phenytoin (95% CI 8.46 to 24.74; 100 participants). No adverse events were observed with either treatment during the four-month treatment period (2 studies, 123 participants). Prevention of ulcers was not evaluated in these nor the zinc studies, as the interventions were not for preventative use.Two studies compared protective footwear (with or without self-care) with either 1) polyvinyl chloride (PVC) boots, or 2) pulsed magnetic fields plus self-care and protective footwear. In the study comparing canvas shoes versus PVC boots, none of the 72 participants with scars at the start of the study developed new ulcers over one-year follow-up. Healing of ulcers was assessed in 38 participants from this study, but we are unclear if there is a difference between groups. In the study comparing pulsed magnetic fields (in addition to self-care and protective footwear) to only self-care and footwear in 33 participants, we are uncertain if the mean volume of ulcers at four to five weeks' follow-up was different between groups; this study did not evaluate the prevention of ulcers. Information for adverse events was only reported in the study comparing canvas shoes with PVC boots; the authors stated that the PVC boots could become hot in strong sunlight and possibly burn the feet. AUTHORS' CONCLUSIONS: Based on the available evidence, we could not draw firm conclusions about the effects of the included interventions. The main evidence limitations were high or unclear risk of bias, including selection, performance, detection, and attrition bias; imprecision due to few participants in the studies; and indirectness from poor outcome measurement and inapplicable interventions. Future research should clearly report important outcomes, such as adverse events, and assess widely available interventions, which should include treatments aimed at prevention. These trials should ensure allocation concealment, blinding, and an adequate sample size.

Exercise therapy for chronic fatigue syndrome.

Editorial Note: A statement from the Editor in Chief about this review and its planned update is available here: https://www.cochrane.org/news/cfs BACKGROUND: Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) is a serious disorder characterised by persistent postexertional fatigue and substantial symptoms related to cognitive, immune and autonomous dysfunction. There is no specific diagnostic test, therefore diagnostic criteria are used to diagnose CFS. The prevalence of CFS varies by type of diagnostic criteria used. Existing treatment strategies primarily aim to relieve symptoms and improve function. One treatment option is exercise therapy. OBJECTIVES: The objective of this review was to determine the effects of exercise therapy for adults with CFS compared with any other intervention or control on fatigue, adverse outcomes, pain, physical functioning, quality of life, mood disorders, sleep, self-perceived changes in overall health, health service resources use and dropout. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Group controlled trials register, CENTRAL, and SPORTDiscus up to May 2014, using a comprehensive list of free-text terms for CFS and exercise. We located unpublished and ongoing studies through the World Health Organization International Clinical Trials Registry Platform up to May 2014. We screened reference lists of retrieved articles and contacted experts in the field for additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) about adults with a primary diagnosis of CFS, from all diagnostic criteria, who were able to participate in exercise therapy. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, 'Risk of bias' assessments and data extraction. We combined continuous measures of outcomes using mean differences (MDs) or standardised mean differences (SMDs). To facilitate interpretation of SMDs, we re-expressed SMD estimates as MDs on more common measurement scales. We combined dichotomous outcomes using risk ratios (RRs). We assessed the certainty of evidence using GRADE. MAIN RESULTS: We included eight RCTs with data from 1518 participants.Exercise therapy lasted from 12 weeks to 26 weeks. The studies measured effect at the end of the treatment and at long-term follow-up, after 50 weeks or 72 weeks.Seven studies used aerobic exercise therapies such as walking, swimming, cycling or dancing, provided at mixed levels in terms of intensity of the aerobic exercise from very low to quite rigorous, and one study used anaerobic exercise. Control groups consisted of passive control, including treatment as usual, relaxation or flexibility (eight studies); cognitive behavioural therapy (CBT) (two studies); cognitive therapy (one study); supportive listening (one study); pacing (one study); pharmacological treatment (one study) and combination treatment (one study).Most studies had a low risk of selection bias. All had a high risk of performance and detection bias.Exercise therapy compared with 'passive' controlExercise therapy probably reduces fatigue at end of treatment (SMD -0.66, 95% CI -1.01 to -0.31; 7 studies, 840 participants; moderate-certainty evidence; re-expressed MD -3.4, 95% CI -5.3 to -1.6; scale 0 to 33). We are uncertain if fatigue is reduced in the long term because the certainty of the evidence is very low (SMD -0.62, 95 % CI -1.32 to 0.07; 4 studies, 670 participants; re-expressed MD -3.2, 95% CI -6.9 to 0.4; scale 0 to 33).We are uncertain about the risk of serious adverse reactions because the certainty of the evidence is very low (RR 0.99, 95% CI 0.14 to 6.97; 1 study, 319 participants).Exercise therapy may moderately improve physical functioning at end of treatment, but the long-term effect is uncertain because the certainty of the evidence is very low. Exercise therapy may also slightly improve sleep at end of treatment and at long term. The effect of exercise therapy on pain, quality of life and depression is uncertain because evidence is missing or of very low certainty.Exercise therapy compared with CBTExercise therapy may make little or no difference to fatigue at end of treatment (MD 0.20, 95% CI -1.49 to 1.89; 1 study, 298 participants; low-certainty evidence), or at long-term follow-up (SMD 0.07, 95% CI -0.13 to 0.28; 2 studies, 351 participants; moderate-certainty evidence).We are uncertain about the risk of serious adverse reactions because the certainty of the evidence is very low (RR 0.67, 95% CI 0.11 to 3.96; 1 study, 321 participants).The available evidence suggests that there may be little or no difference between exercise therapy and CBT in physical functioning or sleep (low-certainty evidence) and probably little or no difference in the effect on depression (moderate-certainty evidence). We are uncertain if exercise therapy compared to CBT improves quality of life or reduces pain because the evidence is of very low certainty.Exercise therapy compared with adaptive pacingExercise therapy may slightly reduce fatigue at end of treatment (MD -2.00, 95% CI -3.57 to -0.43; scale 0 to 33; 1 study, 305 participants; low-certainty evidence) and at long-term follow-up (MD -2.50, 95% CI -4.16 to -0.84; scale 0 to 33; 1 study, 307 participants; low-certainty evidence).We are uncertain about the risk of serious adverse reactions (RR 0.99, 95% CI 0.14 to 6.97; 1 study, 319 participants; very low-certainty evidence).The available evidence suggests that exercise therapy may slightly improve physical functioning, depression and sleep compared to adaptive pacing (low-certainty evidence). No studies reported quality of life or pain.Exercise therapy compared with antidepressantsWe are uncertain if exercise therapy, alone or in combination with antidepressants, reduces fatigue and depression more than antidepressant alone, as the certainty of the evidence is very low. The one included study did not report on adverse reactions, pain, physical functioning, quality of life, sleep or long-term results. AUTHORS' CONCLUSIONS: Exercise therapy probably has a positive effect on fatigue in adults with CFS compared to usual care or passive therapies. The evidence regarding adverse effects is uncertain. Due to limited evidence it is difficult to draw conclusions about the comparative effectiveness of CBT, adaptive pacing or other interventions. All studies were conducted with outpatients diagnosed with 1994 criteria of the Centers for Disease Control and Prevention or the Oxford criteria, or both. Patients diagnosed using other criteria may experience different effects.

Manipulation techniques for infant torticollis. / Manipulasjonsteknikker ved nakkeasymmetri hos spedbarn.

BACKGROUND: Professionals in fields including chiropractic, physiotherapy, manual therapy and osteopathy recommend manipulation techniques for the treatment of infant torticollis. This article summarises the research evaluating such treatment. MATERIAL AND METHOD: The article is based on a search in MEDLINE, EMBASE, CINAHL, Cochrane CENTRAL, AMED, PEDro, and the Index to Chiropractic Literature in August 2017. Controlled studies were included to assess efficacy, and observational studies to reveal the risk of harm. RESULTS: We reviewed 3 418 unique hits from the literature search. We included three randomised controlled studies on the efficacy of manual therapy or osteopathy and three observational studies on possible adverse effects. Two studies on manual therapy suggested that manipulation techniques do not have any greater effect on symmetry and motor outcomes than parental guidance, physiotherapy and home exercises. One study suggested that osteopathy may contribute to increased symmetry compared to placebo, but the clinical significance of this change is uncertain. Neither the three randomised studies nor a large patient series involving 695 infants found manipulation techniques to be associated with a risk of serious adverse events, but three patient histories demonstrated that manipulation techniques may cause harm if the observed asymmetry has serious underlying causes. INTERPRETATION: Manipulation techniques have not been shown to be efficacious in the treatment of infant torticollis, but the available evidence must be considered uncertain.

Exercise therapy for chronic fatigue syndrome.

BACKGROUND: Chronic fatigue syndrome (CFS) is characterised by persistent, medically unexplained fatigue, as well as symptoms such as musculoskeletal pain, sleep disturbance, headaches and impaired concentration and short-term memory. CFS presents as a common, debilitating and serious health problem. Treatment may include physical interventions, such as exercise therapy, which was last reviewed in 2004. OBJECTIVES: The objective of this review was to determine the effects of exercise therapy (ET) for patients with CFS as compared with any other intervention or control.• Exercise therapy versus 'passive control' (e.g. treatment as usual, waiting-list control, relaxation, flexibility).• Exercise therapy versus other active treatment (e.g. cognitive-behavioural therapy (CBT), cognitive treatment, supportive therapy, pacing, pharmacological therapy such as antidepressants).• Exercise therapy in combination with other specified treatment strategies versus other specified treatment strategies (e.g. exercise combined with pharmacological treatment vs pharmacological treatment alone). SEARCH METHODS: We searched The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR), the Cochrane Central Register of Controlled Trials (CENTRAL) and SPORTDiscus up to May 2014 using a comprehensive list of free-text terms for CFS and exercise. We located unpublished or ongoing trials through the World Health Organization (WHO) International Clinical Trials Registry Platform (to May 2014). We screened reference lists of retrieved articles and contacted experts in the field for additional studies SELECTION CRITERIA: Randomised controlled trials involving adults with a primary diagnosis of CFS who were able to participate in exercise therapy. Studies had to compare exercise therapy with passive control, psychological therapies, adaptive pacing therapy or pharmacological therapy. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, risk of bias assessments and data extraction. We combined continuous measures of outcomes using mean differences (MDs) and standardised mean differences (SMDs). We combined serious adverse reactions and drop-outs using risk ratios (RRs). We calculated an overall effect size with 95% confidence intervals (CIs) for each outcome. MAIN RESULTS: We have included eight randomised controlled studies and have reported data from 1518 participants in this review. Three studies diagnosed individuals with CFS using the 1994 criteria of the Centers for Disease Control and Prevention (CDC); five used the Oxford criteria. Exercise therapy lasted from 12 to 26 weeks. Seven studies used variations of aerobic exercise therapy such as walking, swimming, cycling or dancing provided at mixed levels in terms of intensity of the aerobic exercise from very low to quite rigorous, whilst one study used anaerobic exercise. Control groups consisted of passive control (eight studies; e.g. treatment as usual, relaxation, flexibility) or CBT (two studies), cognitive therapy (one study), supportive listening (one study), pacing (one study), pharmacological treatment (one study) and combination treatment (one study). Risk of bias varied across studies, but within each study, little variation was found in the risk of bias across our primary and secondary outcome measures.Investigators compared exercise therapy with 'passive' control in eight trials, which enrolled 971 participants. Seven studies consistently showed a reduction in fatigue following exercise therapy at end of treatment, even though the fatigue scales used different scoring systems: an 11-item scale with a scoring system of 0 to 11 points (MD -6.06, 95% CI -6.95 to -5.17; one study, 148 participants; low-quality evidence); the same 11-item scale with a scoring system of 0 to 33 points (MD -2.82, 95% CI -4.07 to -1.57; three studies, 540 participants; moderate-quality evidence); and a 14-item scale with a scoring system of 0 to 42 points (MD -6.80, 95% CI -10.31 to -3.28; three studies, 152 participants; moderate-quality evidence). Serious adverse reactions were rare in both groups (RR 0.99, 95% CI 0.14 to 6.97; one study, 319 participants; moderate-quality evidence), but sparse data made it impossible for review authors to draw conclusions. Study authors reported a positive effect of exercise therapy at end of treatment with respect to sleep (MD -1.49, 95% CI -2.95 to -0.02; two studies, 323 participants), physical functioning (MD 13.10, 95% CI 1.98 to 24.22; five studies, 725 participants) and self-perceived changes in overall health (RR 1.83, 95% CI 1.39 to 2.40; four studies, 489 participants). It was not possible for review authors to draw conclusions regarding the remaining outcomes.Investigators compared exercise therapy with CBT in two trials (351 participants). One trial (298 participants) reported little or no difference in fatigue at end of treatment between the two groups using an 11-item scale with a scoring system of 0 to 33 points (MD 0.20, 95% CI -1.49 to 1.89). Both studies measured differences in fatigue at follow-up, but neither found differences between the two groups using an 11-item fatigue scale with a scoring system of 0 to 33 points (MD 0.30, 95% CI -1.45 to 2.05) and a nine-item Fatigue Severity Scale with a scoring system of 1 to 7 points (MD 0.40, 95% CI -0.34 to 1.14). Serious adverse reactions were rare in both groups (RR 0.67, 95% CI 0.11 to 3.96). We observed little or no difference in physical functioning, depression, anxiety and sleep, and we were not able to draw any conclusions with regard to pain, self-perceived changes in overall health, use of health service resources and drop-out rate.With regard to other comparisons, one study (320 participants) suggested a general benefit of exercise over adaptive pacing, and another study (183 participants) a benefit of exercise over supportive listening. The available evidence was too sparse to draw conclusions about the effect of pharmaceutical interventions. AUTHORS' CONCLUSIONS: Patients with CFS may generally benefit and feel less fatigued following exercise therapy, and no evidence suggests that exercise therapy may worsen outcomes. A positive effect with respect to sleep, physical function and self-perceived general health has been observed, but no conclusions for the outcomes of pain, quality of life, anxiety, depression, drop-out rate and health service resources were possible. The effectiveness of exercise therapy seems greater than that of pacing but similar to that of CBT. Randomised trials with low risk of bias are needed to investigate the type, duration and intensity of the most beneficial exercise intervention.

Exercise therapy for chronic fatigue syndrome.

BACKGROUND: Chronic fatigue syndrome (CFS) is characterised by persistent, medically unexplained fatigue, as well as symptoms such as musculoskeletal pain, sleep disturbance, headaches and impaired concentration and short-term memory. CFS presents as a common, debilitating and serious health problem. Treatment may include physical interventions, such as exercise therapy, which was last reviewed in 2004. OBJECTIVES: The objective of this review was to determine the effects of exercise therapy (ET) for patients with CFS as compared with any other intervention or control.• Exercise therapy versus 'passive control' (e.g. treatment as usual, waiting-list control, relaxation, flexibility).• Exercise therapy versus other active treatment (e.g. cognitive-behavioural therapy (CBT), cognitive treatment, supportive therapy, pacing, pharmacological therapy such as antidepressants).• Exercise therapy in combination with other specified treatment strategies versus other specified treatment strategies (e.g. exercise combined with pharmacological treatment vs pharmacological treatment alone). SEARCH METHODS: We searched The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR), the Cochrane Central Register of Controlled Trials (CENTRAL) and SPORTDiscus up to May 2014 using a comprehensive list of free-text terms for CFS and exercise. We located unpublished or ongoing trials through the World Health Organization (WHO) International Clinical Trials Registry Platform (to May 2014). We screened reference lists of retrieved articles and contacted experts in the field for additional studies SELECTION CRITERIA: Randomised controlled trials involving adults with a primary diagnosis of CFS who were able to participate in exercise therapy. Studies had to compare exercise therapy with passive control, psychological therapies, adaptive pacing therapy or pharmacological therapy. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, risk of bias assessments and data extraction. We combined continuous measures of outcomes using mean differences (MDs) and standardised mean differences (SMDs). We combined serious adverse reactions and drop-outs using risk ratios (RRs). We calculated an overall effect size with 95% confidence intervals (CIs) for each outcome. MAIN RESULTS: We have included eight randomised controlled studies and have reported data from 1518 participants in this review. Three studies diagnosed individuals with CFS using the 1994 criteria of the Centers for Disease Control and Prevention (CDC); five used the Oxford criteria. Exercise therapy lasted from 12 to 26 weeks. Seven studies used variations of aerobic exercise therapy such as walking, swimming, cycling or dancing provided at mixed levels in terms of intensity of the aerobic exercise from very low to quite rigorous, whilst one study used anaerobic exercise. Control groups consisted of passive control (eight studies; e.g. treatment as usual, relaxation, flexibility) or CBT (two studies), cognitive therapy (one study), supportive listening (one study), pacing (one study), pharmacological treatment (one study) and combination treatment (one study). Risk of bias varied across studies, but within each study, little variation was found in the risk of bias across our primary and secondary outcome measures.Investigators compared exercise therapy with 'passive' control in eight trials, which enrolled 971 participants. Seven studies consistently showed a reduction in fatigue following exercise therapy at end of treatment, even though the fatigue scales used different scoring systems: an 11-item scale with a scoring system of 0 to 11 points (MD -6.06, 95% CI -6.95 to -5.17; one study, 148 participants; low-quality evidence); the same 11-item scale with a scoring system of 0 to 33 points (MD -2.82, 95% CI -4.07 to -1.57; three studies, 540 participants; moderate-quality evidence); and a 14-item scale with a scoring system of 0 to 42 points (MD -6.80, 95% CI -10.31 to -3.28; three studies, 152 participants; moderate-quality evidence). Serious adverse reactions were rare in both groups (RR 0.99, 95% CI 0.14 to 6.97; one study, 319 participants; moderate-quality evidence), but sparse data made it impossible for review authors to draw conclusions. Study authors reported a positive effect of exercise therapy at end of treatment with respect to sleep (MD -1.49, 95% CI -2.95 to -0.02; two studies, 323 participants), physical functioning (MD 13.10, 95% CI 1.98 to 24.22; five studies, 725 participants) and self-perceived changes in overall health (RR 1.83, 95% CI 1.39 to 2.40; four studies, 489 participants). It was not possible for review authors to draw conclusions regarding the remaining outcomes.Investigators compared exercise therapy with CBT in two trials (351 participants). One trial (298 participants) reported little or no difference in fatigue at end of treatment between the two groups using an 11-item scale with a scoring system of 0 to 33 points (MD 0.20, 95% CI -1.49 to 1.89). Both studies measured differences in fatigue at follow-up, but neither found differences between the two groups using an 11-item fatigue scale with a scoring system of 0 to 33 points (MD 0.30, 95% CI -1.45 to 2.05) and a nine-item Fatigue Severity Scale with a scoring system of 1 to 7 points (MD 0.40, 95% CI -0.34 to 1.14). Serious adverse reactions were rare in both groups (RR 0.67, 95% CI 0.11 to 3.96). We observed little or no difference in physical functioning, depression, anxiety and sleep, and we were not able to draw any conclusions with regard to pain, self-perceived changes in overall health, use of health service resources and drop-out rate.With regard to other comparisons, one study (320 participants) suggested a general benefit of exercise over adaptive pacing, and another study (183 participants) a benefit of exercise over supportive listening. The available evidence was too sparse to draw conclusions about the effect of pharmaceutical interventions. AUTHORS' CONCLUSIONS: Patients with CFS may generally benefit and feel less fatigued following exercise therapy, and no evidence suggests that exercise therapy may worsen outcomes. A positive effect with respect to sleep, physical function and self-perceived general health has been observed, but no conclusions for the outcomes of pain, quality of life, anxiety, depression, drop-out rate and health service resources were possible. The effectiveness of exercise therapy seems greater than that of pacing but similar to that of CBT. Randomised trials with low risk of bias are needed to investigate the type, duration and intensity of the most beneficial exercise intervention.

Exercise therapy for chronic fatigue syndrome.

BACKGROUND: Chronic fatigue syndrome (CFS) is characterised by persistent, medically unexplained fatigue, as well as symptoms such as musculoskeletal pain, sleep disturbance, headaches and impaired concentration and short-term memory. CFS presents as a common, debilitating and serious health problem. Treatment may include physical interventions, such as exercise therapy, which was last reviewed in 2004. OBJECTIVES: The objective of this review was to determine the effects of exercise therapy (ET) for patients with CFS as compared with any other intervention or control.• Exercise therapy versus 'passive control' (e.g. treatment as usual, waiting-list control, relaxation, flexibility).• Exercise therapy versus other active treatment (e.g. cognitive-behavioural therapy (CBT), cognitive treatment, supportive therapy, pacing, pharmacological therapy such as antidepressants).• Exercise therapy in combination with other specified treatment strategies versus other specified treatment strategies (e.g. exercise combined with pharmacological treatment vs pharmacological treatment alone). SEARCH METHODS: We searched The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR), the Cochrane Central Register of Controlled Trials (CENTRAL) and SPORTDiscus up to May 2014 using a comprehensive list of free-text terms for CFS and exercise. We located unpublished or ongoing trials through the World Health Organization (WHO) International Clinical Trials Registry Platform (to May 2014). We screened reference lists of retrieved articles and contacted experts in the field for additional studies SELECTION CRITERIA: Randomised controlled trials involving adults with a primary diagnosis of CFS who were able to participate in exercise therapy. Studies had to compare exercise therapy with passive control, psychological therapies, adaptive pacing therapy or pharmacological therapy. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, risk of bias assessments and data extraction. We combined continuous measures of outcomes using mean differences (MDs) and standardised mean differences (SMDs). We combined serious adverse reactions and drop-outs using risk ratios (RRs). We calculated an overall effect size with 95% confidence intervals (CIs) for each outcome. MAIN RESULTS: We have included eight randomised controlled studies and have reported data from 1518 participants in this review. Three studies diagnosed individuals with CFS using the 1994 criteria of the Centers for Disease Control and Prevention (CDC); five used the Oxford criteria. Exercise therapy lasted from 12 to 26 weeks. Seven studies used variations of aerobic exercise therapy such as walking, swimming, cycling or dancing provided at mixed levels in terms of intensity of the aerobic exercise from very low to quite rigorous, whilst one study used anaerobic exercise. Control groups consisted of passive control (eight studies; e.g. treatment as usual, relaxation, flexibility) or CBT (two studies), cognitive therapy (one study), supportive listening (one study), pacing (one study), pharmacological treatment (one study) and combination treatment (one study). Risk of bias varied across studies, but within each study, little variation was found in the risk of bias across our primary and secondary outcome measures.Investigators compared exercise therapy with 'passive' control in eight trials, which enrolled 971 participants. Seven studies consistently showed a reduction in fatigue following exercise therapy at end of treatment, even though the fatigue scales used different scoring systems: an 11-item scale with a scoring system of 0 to 11 points (MD -6.06, 95% CI -6.95 to -5.17; one study, 148 participants; low-quality evidence); the same 11-item scale with a scoring system of 0 to 33 points (MD -2.82, 95% CI -4.07 to -1.57; three studies, 540 participants; moderate-quality evidence); and a 14-item scale with a scoring system of 0 to 42 points (MD -6.80, 95% CI -10.31 to -3.28; three studies, 152 participants; moderate-quality evidence). Serious adverse reactions were rare in both groups (RR 0.99, 95% CI 0.14 to 6.97; one study, 319 participants; moderate-quality evidence), but sparse data made it impossible for review authors to draw conclusions. Study authors reported a positive effect of exercise therapy at end of treatment with respect to sleep (MD -1.49, 95% CI -2.95 to -0.02; two studies, 323 participants), physical functioning (MD 13.10, 95% CI 1.98 to 24.22; five studies, 725 participants) and self-perceived changes in overall health (RR 1.83, 95% CI 1.39 to 2.40; four studies, 489 participants). It was not possible for review authors to draw conclusions regarding the remaining outcomes.Investigators compared exercise therapy with CBT in two trials (351 participants). One trial (298 participants) reported little or no difference in fatigue at end of treatment between the two groups using an 11-item scale with a scoring system of 0 to 33 points (MD 0.20, 95% CI -1.49 to 1.89). Both studies measured differences in fatigue at follow-up, but neither found differences between the two groups using an 11-item fatigue scale with a scoring system of 0 to 33 points (MD 0.30, 95% CI -1.45 to 2.05) and a nine-item Fatigue Severity Scale with a scoring system of 1 to 7 points (MD 0.40, 95% CI -0.34 to 1.14). Serious adverse reactions were rare in both groups (RR 0.67, 95% CI 0.11 to 3.96). We observed little or no difference in physical functioning, depression, anxiety and sleep, and we were not able to draw any conclusions with regard to pain, self-perceived changes in overall health, use of health service resources and drop-out rate.With regard to other comparisons, one study (320 participants) suggested a general benefit of exercise over adaptive pacing, and another study (183 participants) a benefit of exercise over supportive listening. The available evidence was too sparse to draw conclusions about the effect of pharmaceutical interventions. AUTHORS' CONCLUSIONS: Patients with CFS may generally benefit and feel less fatigued following exercise therapy, and no evidence suggests that exercise therapy may worsen outcomes. A positive effect with respect to sleep, physical function and self-perceived general health has been observed, but no conclusions for the outcomes of pain, quality of life, anxiety, depression, drop-out rate and health service resources were possible. The effectiveness of exercise therapy seems greater than that of pacing but similar to that of CBT. Randomised trials with low risk of bias are needed to investigate the type, duration and intensity of the most beneficial exercise intervention.

Exercise therapy for chronic fatigue syndrome.

BACKGROUND: Chronic fatigue syndrome (CFS) is characterised by persistent, medically unexplained fatigue, as well as symptoms such as musculoskeletal pain, sleep disturbance, headaches and impaired concentration and short-term memory. CFS presents as a common, debilitating and serious health problem. Treatment may include physical interventions, such as exercise therapy, which was last reviewed in 2004. OBJECTIVES: The objective of this review was to determine the effects of exercise therapy (ET) for patients with CFS as compared with any other intervention or control.• Exercise therapy versus 'passive control' (e.g. treatment as usual, waiting-list control, relaxation, flexibility).• Exercise therapy versus other active treatment (e.g. cognitive-behavioural therapy (CBT), cognitive treatment, supportive therapy, pacing, pharmacological therapy such as antidepressants).• Exercise therapy in combination with other specified treatment strategies versus other specified treatment strategies (e.g. exercise combined with pharmacological treatment vs pharmacological treatment alone). SEARCH METHODS: We searched The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR), the Cochrane Central Register of Controlled Trials (CENTRAL) and SPORTDiscus up to May 2014 using a comprehensive list of free-text terms for CFS and exercise. We located unpublished or ongoing trials through the World Health Organization (WHO) International Clinical Trials Registry Platform (to May 2014). We screened reference lists of retrieved articles and contacted experts in the field for additional studies SELECTION CRITERIA: Randomised controlled trials involving adults with a primary diagnosis of CFS who were able to participate in exercise therapy. Studies had to compare exercise therapy with passive control, psychological therapies, adaptive pacing therapy or pharmacological therapy. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, risk of bias assessments and data extraction. We combined continuous measures of outcomes using mean differences (MDs) and standardised mean differences (SMDs). We combined serious adverse reactions and drop-outs using risk ratios (RRs). We calculated an overall effect size with 95% confidence intervals (CIs) for each outcome. MAIN RESULTS: We have included eight randomised controlled studies and have reported data from 1518 participants in this review. Three studies diagnosed individuals with CFS using the 1994 criteria of the Centers for Disease Control and Prevention (CDC); five used the Oxford criteria. Exercise therapy lasted from 12 to 26 weeks. Seven studies used variations of aerobic exercise therapy such as walking, swimming, cycling or dancing provided at mixed levels in terms of intensity of the aerobic exercise from very low to quite rigorous, whilst one study used anaerobic exercise. Control groups consisted of passive control (eight studies; e.g. treatment as usual, relaxation, flexibility) or CBT (two studies), cognitive therapy (one study), supportive listening (one study), pacing (one study), pharmacological treatment (one study) and combination treatment (one study). Risk of bias varied across studies, but within each study, little variation was found in the risk of bias across our primary and secondary outcome measures.Investigators compared exercise therapy with 'passive' control in eight trials, which enrolled 971 participants. Seven studies consistently showed a reduction in fatigue following exercise therapy at end of treatment, even though the fatigue scales used different scoring systems: an 11-item scale with a scoring system of 0 to 11 points (MD -6.06, 95% CI -6.95 to -5.17; one study, 148 participants; low-quality evidence); the same 11-item scale with a scoring system of 0 to 33 points (MD -2.82, 95% CI -4.07 to -1.57; three studies, 540 participants; moderate-quality evidence); and a 14-item scale with a scoring system of 0 to 42 points (MD -6.80, 95% CI -10.31 to -3.28; three studies, 152 participants; moderate-quality evidence). Serious adverse reactions were rare in both groups (RR 0.99, 95% CI 0.14 to 6.97; one study, 319 participants; moderate-quality evidence), but sparse data made it impossible for review authors to draw conclusions. Study authors reported a positive effect of exercise therapy at end of treatment with respect to sleep (MD -1.49, 95% CI -2.95 to -0.02; two studies, 323 participants), physical functioning (MD 13.10, 95% CI 1.98 to 24.22; five studies, 725 participants) and self-perceived changes in overall health (RR 1.83, 95% CI 1.39 to 2.40; four studies, 489 participants). It was not possible for review authors to draw conclusions regarding the remaining outcomes.Investigators compared exercise therapy with CBT in two trials (351 participants). One trial (298 participants) reported little or no difference in fatigue at end of treatment between the two groups using an 11-item scale with a scoring system of 0 to 33 points (MD 0.20, 95% CI -1.49 to 1.89). Both studies measured differences in fatigue at follow-up, but neither found differences between the two groups using an 11-item fatigue scale with a scoring system of 0 to 33 points (MD 0.30, 95% CI -1.45 to 2.05) and a nine-item Fatigue Severity Scale with a scoring system of 1 to 7 points (MD 0.40, 95% CI -0.34 to 1.14). Serious adverse reactions were rare in both groups (RR 0.67, 95% CI 0.11 to 3.96). We observed little or no difference in physical functioning, depression, anxiety and sleep, and we were not able to draw any conclusions with regard to pain, self-perceived changes in overall health, use of health service resources and drop-out rate.With regard to other comparisons, one study (320 participants) suggested a general benefit of exercise over adaptive pacing, and another study (183 participants) a benefit of exercise over supportive listening. The available evidence was too sparse to draw conclusions about the effect of pharmaceutical interventions. AUTHORS' CONCLUSIONS: Patients with CFS may generally benefit and feel less fatigued following exercise therapy, and no evidence suggests that exercise therapy may worsen outcomes. A positive effect with respect to sleep, physical function and self-perceived general health has been observed, but no conclusions for the outcomes of pain, quality of life, anxiety, depression, drop-out rate and health service resources were possible. The effectiveness of exercise therapy seems greater than that of pacing but similar to that of CBT. Randomised trials with low risk of bias are needed to investigate the type, duration and intensity of the most beneficial exercise intervention.

ST waveform analysis versus cardiotocography alone for intrapartum fetal monitoring: a systematic review and meta-analysis of randomized trials.

INTRODUCTION: ST waveform analysis was introduced to reduce metabolic acidosis at birth and avoid unnecessary operative deliveries relative to conventional cardiotocography. Our objective was to quantify the efficacy of ST waveform analysis vs. cardiotocography and assess the quality of the evidence using the Grading of Recommendations Assessment, Development and Evaluation tool. MATERIAL AND METHODS: We identified randomized controlled trials through systematic literature searches and assessed included studies for risk of bias. Meta-analyses were performed, calculating pooled risk ratio or peto odds ratio. We performed post hoc trial sequential analyses for selected outcomes to assess the risk of false-positive results and the need for additional studies. RESULTS: Six randomized controlled trials were included in the meta-analysis. ST waveform analysis was not associated with a reduction in operative deliveries due to fetal distress, but we observed a significantly lower rate of metabolic acidosis (peto odds ratio 0.64; 95% confidence interval 0.46-0.88). Accordingly, 401 women need to be monitored with ST waveform analysis to prevent one case of metabolic acidosis. No statistically significant effects were observed in other fetal or neonatal outcomes, except from fetal blood sampling (risk ratio 0.59; 95% confidence interval 0.45-0.79) and a minor reduction in the number of operative vaginal deliveries for all indications (risk ratio 0.92; 95% confidence interval 0.86-0.99). The quality of the evidence was high to moderate. CONCLUSIONS: Absolute effects of ST waveform analysis were minor, and the clinical significance of the observed reduction in metabolic acidosis is questioned. There is not enough evidence to justify the use of ST waveform analysis in contemporary obstetrics.

Use of forms for follow-up of diabetes in general practice.

BACKGROUND: The majority of patients with type 2 diabetes are followed up in general practice. We have investigated whether the use of forms by GPs for recording clinical data contributes to lower mortality and morbidity for this patient group. MATERIAL AND METHOD: This systematic review is based on literature searches in MEDLINE, EMBASE, ISI Web of Science, Cochrane CENTRAL and PubMed. We included studies that 1) dealt with adults over 18 years of age with diabetes who were followed up in the primary health service and 2) compared mortality and morbidity with and without the use of forms. We summarised the results qualitatively and using meta-analyses. RESULTS: Seven studies were included. One study (1262 participants) investigated the effect of the form on hard endpoints, without finding clear effects on mortality (HR 0.91; 95% CI 0.72-1.14), retinopathy (OR 0.90; 95% CI 0.53-1.52), peripheral nerve injury (OR 0.86; 95% CI 0.57-1.29), myocardial infarction (OR 0.65; 95% CI 0.31-1.35) or stroke (OR 0.89; 95% CI 0.39-2.01). Use of forms appears to have little or no effect on body weight (3 studies), and a small, positive effect on blood pressure (5 studies) and total cholesterol (2 studies). INTERPRETATION: Published data at present provide no clear answers, but shows that use of forms in the follow-up of patients with diabetes in general practice may tend to contribute to lower mortality and morbidity.

Exercise therapy for chronic fatigue syndrome.

BACKGROUND: Chronic fatigue syndrome (CFS) is characterised by persistent, medically unexplained fatigue, as well as symptoms such as musculoskeletal pain, sleep disturbance, headaches and impaired concentration and short-term memory. CFS presents as a common, debilitating and serious health problem. Treatment may include physical interventions, such as exercise therapy, which was last reviewed in 2004. OBJECTIVES: The objective of this review was to determine the effects of exercise therapy (ET) for patients with CFS as compared with any other intervention or control.• Exercise therapy versus 'passive control' (e.g. treatment as usual, waiting-list control, relaxation, flexibility).• Exercise therapy versus other active treatment (e.g. cognitive-behavioural therapy (CBT), cognitive treatment, supportive therapy, pacing, pharmacological therapy such as antidepressants).• Exercise therapy in combination with other specified treatment strategies versus other specified treatment strategies (e.g. exercise combined with pharmacological treatment vs pharmacological treatment alone). SEARCH METHODS: We searched The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR), the Cochrane Central Register of Controlled Trials (CENTRAL) and SPORTDiscus up to May 2014 using a comprehensive list of free-text terms for CFS and exercise. We located unpublished or ongoing trials through the World Health Organization (WHO) International Clinical Trials Registry Platform (to May 2014). We screened reference lists of retrieved articles and contacted experts in the field for additional studies SELECTION CRITERIA: Randomised controlled trials involving adults with a primary diagnosis of CFS who were able to participate in exercise therapy. Studies had to compare exercise therapy with passive control, psychological therapies, adaptive pacing therapy or pharmacological therapy. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, risk of bias assessments and data extraction. We combined continuous measures of outcomes using mean differences (MDs) and standardised mean differences (SMDs). We combined serious adverse reactions and drop-outs using risk ratios (RRs). We calculated an overall effect size with 95% confidence intervals (CIs) for each outcome. MAIN RESULTS: We have included eight randomised controlled studies and have reported data from 1518 participants in this review. Three studies diagnosed individuals with CFS using the 1994 criteria of the Centers for Disease Control and Prevention (CDC); five used the Oxford criteria. Exercise therapy lasted from 12 to 26 weeks. Seven studies used variations of aerobic exercise therapy such as walking, swimming, cycling or dancing provided at mixed levels in terms of intensity of the aerobic exercise from very low to quite rigorous, whilst one study used anaerobic exercise. Control groups consisted of passive control (eight studies; e.g. treatment as usual, relaxation, flexibility) or CBT (two studies), cognitive therapy (one study), supportive listening (one study), pacing (one study), pharmacological treatment (one study) and combination treatment (one study). Risk of bias varied across studies, but within each study, little variation was found in the risk of bias across our primary and secondary outcome measures.Investigators compared exercise therapy with 'passive' control in eight trials, which enrolled 971 participants. Seven studies consistently showed a reduction in fatigue following exercise therapy at end of treatment, even though the fatigue scales used different scoring systems: an 11-item scale with a scoring system of 0 to 11 points (MD -6.06, 95% CI -6.95 to -5.17; one study, 148 participants; low-quality evidence); the same 11-item scale with a scoring system of 0 to 33 points (MD -2.82, 95% CI -4.07 to -1.57; three studies, 540 participants; moderate-quality evidence); and a 14-item scale with a scoring system of 0 to 42 points (MD -6.80, 95% CI -10.31 to -3.28; three studies, 152 participants; moderate-quality evidence). Serious adverse reactions were rare in both groups (RR 0.99, 95% CI 0.14 to 6.97; one study, 319 participants; moderate-quality evidence), but sparse data made it impossible for review authors to draw conclusions. Study authors reported a positive effect of exercise therapy at end of treatment with respect to sleep (MD -1.49, 95% CI -2.95 to -0.02; two studies, 323 participants), physical functioning (MD 13.10, 95% CI 1.98 to 24.22; five studies, 725 participants) and self-perceived changes in overall health (RR 1.83, 95% CI 1.39 to 2.40; four studies, 489 participants). It was not possible for review authors to draw conclusions regarding the remaining outcomes.Investigators compared exercise therapy with CBT in two trials (351 participants). One trial (298 participants) reported little or no difference in fatigue at end of treatment between the two groups using an 11-item scale with a scoring system of 0 to 33 points (MD 0.20, 95% CI -1.49 to 1.89). Both studies measured differences in fatigue at follow-up, but neither found differences between the two groups using an 11-item fatigue scale with a scoring system of 0 to 33 points (MD 0.30, 95% CI -1.45 to 2.05) and a nine-item Fatigue Severity Scale with a scoring system of 1 to 7 points (MD 0.40, 95% CI -0.34 to 1.14). Serious adverse reactions were rare in both groups (RR 0.67, 95% CI 0.11 to 3.96). We observed little or no difference in physical functioning, depression, anxiety and sleep, and we were not able to draw any conclusions with regard to pain, self-perceived changes in overall health, use of health service resources and drop-out rate.With regard to other comparisons, one study (320 participants) suggested a general benefit of exercise over adaptive pacing, and another study (183 participants) a benefit of exercise over supportive listening. The available evidence was too sparse to draw conclusions about the effect of pharmaceutical interventions. AUTHORS' CONCLUSIONS: Patients with CFS may generally benefit and feel less fatigued following exercise therapy, and no evidence suggests that exercise therapy may worsen outcomes. A positive effect with respect to sleep, physical function and self-perceived general health has been observed, but no conclusions for the outcomes of pain, quality of life, anxiety, depression, drop-out rate and health service resources were possible. The effectiveness of exercise therapy seems greater than that of pacing but similar to that of CBT. Randomised trials with low risk of bias are needed to investigate the type, duration and intensity of the most beneficial exercise intervention.

Hospital at home for acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Hospital at home schemes are a recently adopted method of service delivery for the management of acute exacerbations of chronic obstructive pulmonary disease (COPD) aimed at reducing demand for acute hospital inpatient beds and promoting a patient-centred approach through admission avoidance. However, evidence in support of such a service is contradictory. OBJECTIVES: To evaluate the efficacy of hospital at home compared to hospital inpatient care in acute exacerbations of COPD. SEARCH METHODS: Trials were identified from searches of electronic databases, including CENTRAL, MEDLINE, EMBASE, and the Cochrane Airways Group Register (CAGR). The review authors checked the reference lists of included trials. The CAGR was searched up to February 2012. The additional databases were searched up to October 2010. SELECTION CRITERIA: We considered randomised controlled trials where patients presented to the emergency department with an exacerbation of their COPD. Studies must not have recruited patients for whom treatment at home is usually not viewed as an responsible option (e.g. patients with an impaired level of consciousness, acute confusion, acute changes on the radiograph or electrocardiogram, arterial pH less than 7.35, concomitant medical conditions). DATA COLLECTION AND ANALYSIS: Two review authors independently selected articles for inclusion, assessed the risk of bias and extracted data for each of the included trials. MAIN RESULTS: Eight trials with 870 patients were included in the review and showed a significant reduction in readmission rates for hospital at home compared with hospital inpatient care of acute exacerbations of COPD (risk ratio (RR)0.76; 95% confidence interval (CI) from 0.59 to 0.99; P=0.04). Moreover, we observed a trend towards lower mortality in the hospital at home group, but the pooled effect estimate did not reach statistical significance (RR 0.65, 95% CI 0.40 to 1.04, P = 0.07). For health-related quality of life, lung function (FEV1) and direct costs, the quality of the available evidence is in general too weak to make firm conclusions. AUTHORS' CONCLUSIONS: Selected patients presenting to hospital emergency departments with acute exacerbations of COPD can be safely and successfully treated at home with support from respiratory nurses. We found evidence of moderate quality that hospital at home may be advantageous with respect to readmission rates in these patients. Treatment of acute exacerbation of COPD in hospital at home also show a trend towards reduced mortality rate when compared with conventional inpatient treatment, but these results did not reach statistical significance (moderate quality evidence). For other outcomes than readmission and mortality rate, we assessed the evidence to be of low or very low quality.

Advice to rest in bed versus advice to stay active for acute low-back pain and sciatica.

BACKGROUND: Acute low-back pain (LBP) is a common reason to consult a general practitioner. Debate continues on the comparative effectiveness of advice on bed rest and staying active as part of the primary care management. OBJECTIVES: To determine the effects of advice to rest in bed or stay active for patients with acute low-back pain or sciatica. SEARCH STRATEGY: We searched the Cochrane Back Review Group Trials Register, CENTRAL, MEDLINE, EMBASE, Sport, and SCISEARCH to May 2009, reference lists of relevant articles, and contacted authors of relevant articles. SELECTION CRITERIA: Randomised trials of the effectiveness of advice to stay active or rest in bed for patients with acute LBP or sciatica. The main outcomes were pain, functional status, recovery and return to work. DATA COLLECTION AND ANALYSIS: Two authors independently selected trials, assessed the risk of bias and extracted data. The trials were combined qualitatively or statistically, depending on data availability and presentation. MAIN RESULTS: We included ten RCTs with varying risk of bias. For patients with acute LBP, results from two trials (N = 401) suggest small improvements in pain relief (SMD 0.22 (95% CI: 0.02 to 0.41) and functional status (SMD 0.29 (95% CI: 0.09 to 0.49) in favour of advice to stay active. For patients with sciatica, there is moderate quality evidence of little or no difference in pain relief (SMD -0.03 (95% CI: -0.24 to 0.18)) or functional status (SMD 0.19 (95% CI: -0.02 to 0.41)), between advice to rest in bed or stay active.Low quality evidence (3 RCTs, N = 931) suggests little or no difference between exercises, advice to rest in bed or stay active for patients with acute LBP. Low quality evidence (1 RCT, N = 250) suggests little or no difference between physiotherapy, advice to rest in bed or stay active for patients with sciatica. No trials that compared different ways of delivering advice. AUTHORS' CONCLUSIONS: Moderate quality evidence shows that patients with acute LBP may experience small benefits in pain relief and functional improvement from advice to stay active compared to advice to rest in bed; patients with sciatica experience little or no difference between the two approaches. Low quality evidence suggests little or no difference between those who received advice to stay active, exercises or physiotherapy. Further research is very likely to have an important impact on the estimate of effect and is likely to change our confidence in it.

Dynamic contrast-enhanced magnetic resonance imaging of tumor interstitial fluid pressure.

BACKGROUND AND PURPOSE: High interstitial fluid pressure (IFP) in the primary tumor has been shown to promote metastasis in melanoma xenografts and to predict for poor survival in cervical cancer patients. The potential usefulness of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA)-based dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for assessing tumor IFP noninvasively was investigated in the present study. MATERIALS AND METHODS: A-07 and R-18 melanoma xenografts with and without necrotic regions were subjected to DCE-MRI and subsequent measurement of IFP. Tumor images of E.F (E is the initial extraction fraction of Gd-DTPA and F is blood perfusion) and lambda (lambda is proportional to extracellular volume fraction) were produced by Kety analysis of DCE-MRI series. RESULTS: In tumors without necrosis, significant inverse correlations were found between E.F and IFP, both for A-07 and R-18 tumors, and between lambda and IFP for A-07 tumors. Significant correlations between E.F and IFP or between lambda and IFP could not be detected for tumors with necrotic regions. CONCLUSIONS: DCE-MRI may be developed to be a useful noninvasive method for assessing IFP in tumors without necrosis. This possibility warrants further studies involving several physiologically different experimental tumor lines, as well as human tumors.

Assessment of extravascular extracellular space fraction in human melanoma xenografts by DCE-MRI and kinetic modeling.

Tumor aggressiveness and response to therapy are influenced by the extravascular extracellular space fraction (EESF) of the malignant tissue. The EESF may, therefore, be an important prognostic parameter for cancer patients. The aim of this study was to investigate whether gadopentetate dimeglumine (Gd-DTPA)-based dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can be used to assess the EESF of tumors. Amelanotic human melanoma xenografts (A-07, R-18) were used as preclinical models of human cancer. Images of E.F (E is the initial extraction fraction of Gd-DTPA and F is perfusion) and lambda (the partition coefficient of Gd-DTPA) were obtained by Kety analysis of DCE-MRI data. Our study was based on the hypothesis that lambda is governed by the EESF and is not influenced significantly by microvascular density (MVD) or blood perfusion. To test this hypothesis, we searched for correlations between lambda and E.F, MVD or EESF by comparing lambda images with E.F images, histological preparations from the imaged tissue and the radial heterogeneity in EESF obtained by invasive imaging. Positive correlations were found between lambda and EESF. Thus, median lambda was larger in A-07 tumors than in R-18 tumors by a factor of 4.2 (P<.00001), consistent with the histological observation that EESF is approximately fourfold larger in A-07 tumors than in R-18 tumors. The radial heterogeneity in lambda in A-07 and R-18 tumors was almost identical to the radial heterogeneity in EESF. Moreover, lambda was larger in tissue regions with high EESF than in tissue regions with low EESF in A-07 tumors (P=.048). On the other hand, significant correlations between lambda and MVD or E.F could not be detected. Consequently, Kety analysis of Gd-DTPA-based DCE-MRI series of xenografted tumors provides lambda images that primarily reflect the EESF of the tissue.

Fluctuations in pO2 in irradiated human melanoma xenografts.

Several studies have demonstrated that untreated tumors may show significant fluctuations in tissue oxygen tension (pO(2)). Radiation treatment may induce changes in the tumor microenvironment that alter the pO(2) fluctuation pattern. The purpose of the present study was to investigate whether pO(2) fluctuations may also occur in irradiated tumors. A-07 human melanoma xenografts were irradiated with single doses of 0, 5 or 10 Gy. Fluctuations in pO(2) were recorded with OxyLite probes prior to irradiation and 24 and 72 h after the radiation exposure. Radiation-induced changes in the tumor microenvironment (i.e. blood perfusion and extracellular volume fraction) were assessed by dynamic contrast-enhanced magnetic resonance imaging. Seventy-two hours after 10 Gy, tumor blood perfusion had decreased to approximately 40% of that prior to irradiation, whereas the extracellular volume fraction had increased by approximately 25%. Fluctuations in pO(2) were seen in most tumors, irrespective of radiation dose and time after irradiation. The mean pO(2), the number of fluctuations around the mean pO(2), the number of fluctuations around threshold pO(2) values of 1, 2, 3, 5, 7 and 10 mmHg, and the amplitude of the fluctuations were determined for each pO(2) trace. No significant differences were detected between irradiated and unirradiated tumors. The results showed that pO(2) fluctuations may occur in irradiated tumors and that the pO(2) fluctuation pattern in A-07 tumors exposed to 5 or 10 Gy is similar to that in untreated tumors. Consequently, these doses did not induce changes in the tumor microenvironment that were sufficient to cause detectable alterations in the pO(2) fluctuation pattern.