Therapeutic ultrasound for venous leg ulcers.

Cullum N ，Liu Z 《Cochrane Database of Systematic Reviews》

Honey as a topical treatment for wounds.

Jull AB ，Cullum N ，Dumville JC ，Westby MJ ，Deshpande S ，Walker N ... -  《Cochrane Database of Systematic Reviews》

Treatments for intractable constipation in childhood.

Constipation that is prolonged and does not resolve with conventional therapeutic measures is called intractable constipation. The treatment of intractable constipation is challenging, involving pharmacological or non-pharmacological therapies, as well as surgical approaches. Unresolved constipation can negatively impact quality of life, with additional implications for health systems. Consequently, there is an urgent need to identify treatments that are efficacious and safe. To evaluate the efficacy and safety of treatments used for intractable constipation in children. We searched CENTRAL, MEDLINE, Embase, and two trials registers up to 23 June 2023. We also searched reference lists of included studies for relevant studies. We included randomised controlled trials (RCTs) comparing any pharmacological, non-pharmacological, or surgical treatment to placebo or another active comparator, in participants aged between 0 and 18 years with functional constipation who had not responded to conventional medical therapy. We used standard Cochrane methods. Our primary outcomes were symptom resolution, frequency of defecation, treatment success, and adverse events; secondary outcomes were stool consistency, painful defecation, quality of life, faecal incontinence frequency, abdominal pain, hospital admission for disimpaction, and school absence. We used GRADE to assess the certainty of evidence for each primary outcome. This review included 10 RCTs with 1278 children who had intractable constipation. We assessed one study as at low risk of bias across all domains. There were serious concerns about risk of bias in six studies. One study compared the injection of 160 units botulinum toxin A (n = 44) to unspecified oral stool softeners (n = 44). We are very uncertain whether botulinum toxin A injection improves treatment success (risk ratio (RR) 37.00, 95% confidence interval (CI) 5.31 to 257.94; very low certainty evidence, downgraded due to serious concerns with risk of bias and imprecision). Frequency of defecation was reported only for the botulinum toxin A injection group (mean interval of 2.6 days). The study reported no data for the other primary outcomes. One study compared erythromycin estolate (n = 6) to placebo (n = 8). The only primary outcome reported was adverse events, which were 0 in both groups. The evidence is of very low certainty due to concerns with risk of bias and serious imprecision. One study compared 12 or 24 μg oral lubiprostone (n = 404) twice a day to placebo (n = 202) over 12 weeks. There may be little to no difference in treatment success (RR 1.29, 95% CI 0.87 to 1.92; low certainty evidence). We also found that lubiprostone probably results in little to no difference in adverse events (RR 1.05, 95% CI 0.91 to 1.21; moderate certainty evidence). The study reported no data for the other primary outcomes. One study compared three-weekly rectal sodium dioctyl sulfosuccinate and sorbitol enemas (n = 51) to 0.5 g/kg/day polyethylene glycol laxatives (n = 51) over a 52-week period. We are very uncertain whether rectal sodium dioctyl sulfosuccinate and sorbitol enemas improve treatment success (RR 1.33, 95% CI 0.83 to 2.14; very low certainty evidence, downgraded due to serious concerns with risk of bias and imprecision). Results of defecation frequency per week was reported only as modelled means using a linear mixed model. The study reported no data for the other primary outcomes. One study compared biofeedback therapy (n = 12) to no intervention (n = 12). We are very uncertain whether biofeedback therapy improves symptom resolution (RR 2.50, 95% CI 1.08 to 5.79; very low certainty evidence, downgraded due to serious concerns with risk of bias and imprecision). The study reported no data for the other primary outcomes. One study compared 20 minutes of intrarectal electromotive botulinum toxin A using 2800 Hz frequency and botulinum toxin A dose 10 international units/kg (n = 30) to 10 international units/kg botulinum toxin A injection (n = 30). We are very uncertain whether intrarectal electromotive botulinum toxin A improves symptom resolution (RR 0.96, 95% CI 0.76 to 1.22; very low certainty evidence) or if it increases the frequency of defecation (mean difference (MD) 0.00, 95% CI -1.87 to 1.87; very low certainty evidence). We are also very uncertain whether intrarectal electromotive botulinum toxin A has an improved safety profile (RR 0.20, 95% CI 0.01 to 4.00; very low certainty evidence). The evidence for these results is of very low certainty due to serious concerns with risk of bias and imprecision. The study did not report data on treatment success. One study compared the injection of 60 units botulinum toxin A (n = 21) to myectomy of the internal anal sphincter (n = 21). We are very uncertain whether botulinum toxin A injection improves treatment success (RR 1.00, 95% CI 0.75 to 1.34; very low certainty evidence). No adverse events were recorded. The study reported no data for the other primary outcomes. One study compared 0.04 mg/kg oral prucalopride (n = 107) once daily to placebo (n = 108) over eight weeks. Oral prucalopride probably results in little or no difference in defecation frequency (MD 0.50, 95% CI -0.06 to 1.06; moderate certainty evidence); treatment success (RR 0.96, 95% CI 0.53 to 1.72; moderate certainty evidence); and adverse events (RR 1.15, 95% CI 0.94 to 1.39; moderate certainty evidence). The study did not report data on symptom resolution. One study compared transcutaneous electrical stimulation to sham stimulation, and another study compared dietitian-prescribed Mediterranean diet with written instructions versus written instructions. These studies did not report any of our predefined primary outcomes. We identified low to moderate certainty evidence that oral lubiprostone may result in little to no difference in treatment success and adverse events compared to placebo. Based on moderate certainty evidence, there is probably little or no difference between oral prucalopride and placebo in defecation frequency, treatment success, or adverse events. For all other comparisons, the certainty of the evidence for our predefined primary outcomes is very low due to serious concerns with study limitations and imprecision. Consequently, no robust conclusions could be drawn.

Gordon M ，Grafton-Clarke C ，Rajindrajith S ，Benninga MA ，Sinopoulou V ，Akobeng AK ... -  《Cochrane Database of Systematic Reviews》

Compression for preventing recurrence of venous ulcers.

Up to 1% of adults will have a leg ulcer at some time. Most leg ulcers are venous in origin and are caused by high pressure in the veins due to blockage or damaged valves. Venous ulcer prevention and treatment typically involves the application of compression bandages/stockings to improve venous return and thus reduce pressure in the legs. Other treatment options involve removing or repairing veins. Most venous ulcers heal with compression therapy, but ulcer recurrence is common. For this reason, clinical guidelines recommend that people continue with compression treatment after their ulcer has healed. This is an update of a Cochrane review first published in 2000 and last updated in 2014. To assess the effects of compression (socks, stockings, tights, bandages) for preventing recurrence of venous leg ulcers. In August 2023, we searched the Cochrane Wounds Specialised Register, CENTRAL, MEDLINE, Embase, three other databases, and two ongoing trials registries. We also scanned the reference lists of included studies and relevant reviews and health technology reports. There were no restrictions on language, date of publication, or study setting. We included randomised controlled trials (RCTs) that evaluated compression bandages or hosiery for preventing the recurrence of venous ulcers. At least two review authors independently selected studies, assessed risk of bias, and extracted data. Our primary outcome was reulceration (ulcer recurrence anywhere on the treated leg). Our secondary outcomes included duration of reulceration episodes, proportion of follow-up without ulcers, ulceration on the contralateral leg, noncompliance with compression therapy, comfort, and adverse effects. We assessed the certainty of evidence using GRADE methodology. We included eight studies (1995 participants), which were published between 1995 and 2019. The median study sample size was 249 participants. The studies evaluated different classes of compression (UK class 2 or 3 and European (EU) class 1, 2, or 3). Duration of follow-up ranged from six months to 10 years. We downgraded the certainty of the evidence for risk of bias (lack of blinding), imprecision, and indirectness. EU class 3 compression stockings may reduce reulceration compared with no compression over six months (risk ratio (RR) 0.46, 95% confidence interval (CI) 0.27 to 0.76; 1 study, 153 participants; low-certainty evidence). EU class 1 compression stockings compared with EU class 2 compression stockings may have little or no effect on reulceration over 12 months (RR 1.70, 95% CI 0.67 to 4.32; 1 study, 99 participants; low-certainty evidence). There may be little or no difference in rates of noncompliance over 12 months between people using EU class 1 stockings and people using EU class 2 stockings (RR 1.22, 95% CI 0.40 to 3.75; 1 study, 99 participants; low-certainty evidence). UK class 2 hosiery compared with UK class 3 hosiery may be associated with a higher risk of reulceration over 18 months to 10 years (RR 1.55, 95% CI 1.26 to 1.91; 5 studies, 1314 participants; low-certainty evidence). People who use UK class 2 hosiery may be more compliant with compression treatment than people who use UK class 3 hosiery over 18 months to 10 years (RR for noncompliance 0.69, 95% CI 0.49 to 0.99; 5 studies, 1372 participants; low-certainty evidence). There may be little or no difference between Scholl UK class 2 compression stockings and Medi UK class 2 compression stockings in terms of reulceration (RR 0.77, 95% CI 0.47 to 1.28; 1 study, 166 participants; low-certainty evidence) and noncompliance (RR 0.97, 95% CI 0.84.1 to 12; 1 study, 166 participants; low-certainty evidence) over 18 months. No studies compared different lengths of compression (e.g. below-knee versus above-knee), and no studies measured duration of reulceration episodes, ulceration on the contralateral leg, proportion of follow-up without ulcers, comfort, or adverse effects. Compression with EU class 3 compression stockings may reduce reulceration compared with no compression over six months. Use of EU class 1 compression stockings compared with EU class 2 compression stockings may result in little or no difference in reulceration and noncompliance over 12 months. UK class 3 compression hosiery may reduce reulceration compared with UK class 2 compression hosiery; however, higher compression may lead to lower compliance. There may be little to no difference between Scholl and Medi UK class 2 compression stockings in terms of reulceration and noncompliance. There was no information on duration of reulceration episodes, ulceration on the contralateral leg, proportion of follow-up without ulcers, comfort, or adverse effects. More research is needed to investigate acceptable modes of long-term compression therapy for people at risk of recurrent venous ulceration. Future trials should consider interventions to improve compliance with compression treatment, as higher compression may result in lower rates of reulceration.

de Moraes Silva MA ，Nelson A ，Bell-Syer SE ，Jesus-Silva SG ，Miranda F Jr ... -  《Cochrane Database of Systematic Reviews》

Cryotherapy following total knee replacement.

Total knee replacement (TKR) is a common intervention for people with end-stage symptomatic knee osteoarthritis, resulting in significant improvements in pain, function and quality of life within three to six months. It is, however, acutely associated with pain, local oedema and blood loss. Post-operative management may include cryotherapy. This is the application of low temperatures to the skin surrounding the surgical site, through ice or cooled water, often delivered using specialised devices. This is an update of a review published in 2012. To evaluate the effect of cryotherapy in the acute phase after TKR (within 48 hours after surgery) on blood loss, pain, transfusion rate, range of motion, knee function, adverse events and withdrawals due to adverse events. We searched CENTRAL, MEDLINE, Embase, six other databases and two trials registers, as well as reference lists, related links and conference proceedings on 27 May 2022. We included randomised controlled trials or controlled clinical trials comparing cryotherapy with or without other treatments (such as compression, regional nerve block or continuous passive motion) to no treatment, or the other treatment alone, following TKR for osteoarthritis. Two review authors independently selected studies for inclusion, extracted data and assessed risk of bias and certainty of evidence using GRADE. We discussed any disagreements and consulted another review author to resolve them, if required. Major outcomes were blood loss, pain, transfusion rate, knee range of motion, knee function, total adverse events and withdrawals from adverse events. Minor outcomes were analgesia use, knee swelling, length of stay, quality of life, activity level and participant-reported global assessment of success. We included 22 trials (20 randomised trials and two controlled clinical trials), with 1839 total participants. The mean ages reflected the TKR population, ranging from 64 to 74 years. Cryotherapy with compression was compared to no treatment in four studies, and to compression alone in nine studies. Cryotherapy without compression was compared to no treatment in eight studies. One study compared cryotherapy without compression to control with compression alone. We combined all control interventions in the primary analysis. Certainty of evidence was low for blood loss (downgraded for bias and inconsistency), pain (downgraded twice for bias) and range of motion (downgraded for bias and indirectness). It was very low for transfusion rate (downgraded for bias, inconsistency and imprecision), function (downgraded twice for bias and once for inconsistency), total adverse events (downgraded for bias, indirectness and imprecision) and withdrawals from adverse events (downgraded for bias, indirectness and imprecision). The nature of cryotherapy made blinding difficult and most studies had a high risk of performance and detection bias. Low-certainty evidence from 12 trials (956 participants) shows that cryotherapy may reduce blood loss at one to 13 days after surgery. Blood loss was 825 mL with no cryotherapy and 561 mL with cryotherapy: mean difference (MD) 264 mL less (95% confidence interval (CI) 7 mL less to 516 mL less). Low-certainty evidence from six trials (530 participants) shows that cryotherapy may slightly improve pain at 48 hours on a 0- to 10-point visual analogue scale (lower scores indicate less pain). Pain was 4.8 points with no cryotherapy and 3.16 points with cryotherapy: MD 1.6 points lower (95% CI 2.3 lower to 1.0 lower). We are uncertain whether cryotherapy improves transfusion rate at zero to 13 days after surgery. The transfusion rate was 37% with no cryotherapy and 79% with cryotherapy (risk ratio (RR) 2.13, 95% CI 0.04 to 109.63; 2 trials, 91 participants; very low-certainty evidence). Low-certainty evidence from three trials (174 participants) indicates cryotherapy may improve range of motion at discharge: it was 62.9 degrees with no cryotherapy and 71.2 degrees with cryotherapy: MD 8.3 degrees greater (95% CI 3.6 degrees more to 13.1 degrees more). We are uncertain whether cryotherapy improves function two weeks after surgery. Function was 75.4 points on the 0- to 100-point Dutch Western Ontario and McMaster Universities Arthritis Index (WOMAC) scale (lower score indicates worse function) in the control group and 88.6 points with cryotherapy (MD 13.2 points better, 95% CI 0.5 worse to 27.1 improved; 4 trials, 296 participants; very low-certainty evidence). We are uncertain whether cryotherapy reduces total adverse events: the risk ratio was 1.30 (95% CI 0.53 to 3.20; 16 trials, 1199 participants; very low-certainty evidence). Adverse events included discomfort, local skin reactions, superficial infections, cold-induced injuries and thrombolytic events. We are uncertain whether cryotherapy reduces withdrawals from adverse events (RR 2.71, 95% CI 0.42 to 17.38; 19 trials, 1347 participants; very low-certainty evidence). No significant benefit was found for secondary outcomes of analgesia use, length of stay, activity level or quality of life. Evidence from seven studies (403 participants) showed improved mid-patella swelling between two and six days after surgery (MD 7.32 mm less, 95% CI 11.79 to 2.84 lower), though not at six weeks and three months after surgery. The included studies did not assess participant-reported global assessment of success. The certainty of evidence was low for blood loss, pain and range of motion, and very low for transfusion rate, function, total adverse events and withdrawals from adverse events. We are uncertain whether cryotherapy improves transfusion rate, function, total adverse events or withdrawals from adverse events. We downgraded evidence for bias, indirectness, imprecision and inconsistency. Hence, the potential benefits of cryotherapy on blood loss, pain and range of motion may be too small to justify its use. More well-designed randomised controlled trials focusing especially on clinically meaningful outcomes, such as blood transfusion, and patient-reported outcomes, such as knee function, quality of life, activity level and participant-reported global assessment of success, are required.

Aggarwal A ，Adie S ，Harris IA ，Naylor J ... -  《Cochrane Database of Systematic Reviews》