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》

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》

Exercise therapy for chronic fatigue syndrome.

Larun L ，Brurberg KG ，Odgaard-Jensen J ，Price JR ... -  《Cochrane Database of Systematic Reviews》

Exercise for osteoarthritis of the knee.

Knee osteoarthritis (OA) is a major public health issue causing chronic pain, impaired physical function, and reduced quality of life. As there is no cure, self-management of symptoms via exercise is recommended by all current international clinical guidelines. This review updates one published in 2015. We aimed to assess the effects of land-based exercise for people with knee osteoarthritis (OA) by comparing: 1) exercise versus attention control or placebo; 2) exercise versus no treatment, usual care, or limited education; 3) exercise added to another co-intervention versus the co-intervention alone. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and two trial registries (ClinicalTrials.gov and World Health Organisation International Clinical Trials Registry Platform), together with reference lists, from the date of the last search (1st May 2013) until 4 January 2024, unrestricted by language. We included randomised controlled trials (RCTs) that evaluated exercise for knee OA versus a comparator listed above. Our outcomes of interest were pain severity, physical function, quality of life, participant-reported treatment success, adverse events, and study withdrawals. We used the standard methodological procedures expected by Cochrane for systematic reviews of interventions. We included 139 trials (12,468 participants): 30 (3065 participants) compared exercise to attention control or placebo; 60 (4834 participants) compared exercise with usual care, no intervention or limited education; and 49 (4569 participants) evaluated exercise added to another intervention (e.g. weight loss diet, physical therapy, detailed education) versus that intervention alone. Interventions varied substantially in duration, ranging from 2 to 104 weeks. Most of the trials were at unclear or high risk of bias, in particular, performance bias (94% of trials), detection bias (94%), selective reporting bias (68%), selection bias (57%), and attrition bias (48%). Exercise versus attention control/placebo Compared with attention control/placebo, low-certainty evidence indicates exercise may result in a slight improvement in pain immediately post-intervention (mean 8.70 points better (on a scale of 0 to 100), 95% confidence interval (CI) 5.70 to 11.70; 28 studies, 2873 participants). Moderate-certainty evidence indicates exercise likely results in an improvement in physical function (mean 11.27 points better (on a scale of 0 to 100), 95% CI 7.64 to 15.09; 24 studies, 2536 participants), but little to no improvement in quality of life (mean 6.06 points better (on a scale of 0 to 100), 95% CI -0.13 to 12.26; 6 studies, 454 participants). There was moderate-certainty evidence that exercise likely increases participant-reported treatment success (risk ratio (RR) 1.46, 95% CI 1.11 to 1.92; 2 studies 364 participants), and likely does not increase study withdrawals (RR 1.08, 95% CI 0.92 to 1.26; 29 studies, 2907 participants). There was low-certainty evidence that exercise may not increase adverse events (RR 2.02, 95% CI 0.62 to 6.58; 11 studies, 1684 participants). Exercise versus no treatment/usual care/limited education Compared with no treatment/usual care/limited education, low-certainty evidence indicates exercise may result in an improvement in pain immediately post-intervention (mean 13.14 points better (on a scale of 0 to 100), 95% CI 10.36 to 15.91; 56 studies, 4184 participants). Moderate-certainty evidence indicates exercise likely results in an improvement in physical function (mean 12.53 points better (on a scale of 0 to 100), 95% CI 9.74 to 15.31; 54 studies, 4352 participants) and a slight improvement in quality of life (mean 5.37 points better (on a scale of to 100), 95% CI 3.19 to 7.54; 28 studies, 2328 participants). There was low-certainty evidence that exercise may result in no difference in participant-reported treatment success (RR 1.33, 95% CI 0.71 to 2.49; 3 studies, 405 participants). There was moderate-certainty evidence that exercise likely results in no difference in study withdrawals (RR 1.03, 95% CI 0.88 to 1.20; 53 studies, 4408 participants). There was low-certainty evidence that exercise may increase adverse events (RR 3.17, 95% CI 1.17 to 8.57; 18 studies, 1557 participants). Exercise added to another co-intervention versus the co-intervention alone Moderate-certainty evidence indicates that exercise when added to a co-intervention likely results in improvements in pain immediately post-intervention compared to the co-intervention alone (mean 10.43 points better (on a scale of 0 to 100), 95% CI 8.06 to 12.79; 47 studies, 4441 participants). It also likely results in a slight improvement in physical function (mean 9.66 points better, 95% CI 7.48 to 11.97 (on a 0 to 100 scale); 44 studies, 4381 participants) and quality of life (mean 4.22 points better (on a 0 to 100 scale), 95% CI 1.36 to 7.07; 12 studies, 1660 participants) immediately post-intervention. There was moderate-certainty evidence that exercise likely increases participant-reported treatment success (RR 1.63, 95% CI 1.18 to 2.24; 6 studies, 1139 participants), slightly reduces study withdrawals (RR 0.82, 95% CI 0.70 to 0.97; 41 studies, 3502 participants), and slightly increases adverse events (RR 1.72, 95% CI 1.07 to 2.76; 19 studies, 2187 participants). Subgroup analysis and meta-regression We did not find any differences in effects between different types of exercise, and we found no relationship between changes in pain or physical function and the total number of exercise sessions prescribed or the ratio (between exercise group and comparator) of real-time consultations with a healthcare provider. Clinical significance of the findings To determine whether the results found would make a clinically meaningful difference to someone with knee OA, we compared our results to established 'minimal important difference' (MID) scores for pain (12 points on a 0 to 100 scale), physical function (13 points), and quality of life (15 points). We found that the confidence intervals of mean differences either did not reach these thresholds or included both a clinically important and clinically unimportant improvement. We found low- to moderate-certainty evidence that exercise probably results in an improvement in pain, physical function, and quality of life in the short-term. However, based on the thresholds for minimal important differences that we used, these benefits were of uncertain clinical importance. Participants in most trials were not blinded and were therefore aware of their treatment, and this may have contributed to reported improvements.

Lawford BJ ，Hall M ，Hinman RS ，Van der Esch M ，Harmer AR ，Spiers L ，Kimp A ，Dell'Isola A ，Bennell KL ... -  《Cochrane Database of Systematic Reviews》

Tranexamic acid for preventing postpartum haemorrhage after caesarean section.

Postpartum haemorrhage (PPH) is common and potentially life-threatening. The antifibrinolytic drug tranexamic acid (TXA) is recommended for treating PPH; it reduces the risk of death from haemorrhage by one-third when given soon after bleeding onset, but not overall risk of death. Interest in whether TXA may be effective in preventing PPH is growing. Evidence indicates that TXA given more than three hours after injury to bleeding trauma patients increases mortality. Potential harm becomes critical in prophylactic use of TXA. Reliable evidence of the effect and safety profile of TXA is required before widespread prophylactic use can be considered. To assess the effects of TXA for preventing PPH compared to placebo or no treatment (with or without uterotonic co-treatment) in women during caesarean birth. We searched CENTRAL, MEDLINE, Embase, and WHO ICTRP to 20 February 2024 and searched reference lists of retrieved studies. We included randomised controlled trials (RCTs) evaluating the use of TXA alone or plus uterotonics during caesarean birth for preventing PPH. Trials needed to be prospectively registered (i.e. before starting recruitment). We applied a trustworthiness checklist. The critical outcome was blood loss ≥ 1000 mL, measured using estimated or calculated methods. Important outcomes included maternal death, severe morbidity, blood transfusion, the use of additional surgical interventions to control PPH, thromboembolic events, use of additional uterotonics, hysterectomy, maternal satisfaction, and breastfeeding at discharge. We assessed risk of bias in the included studies using Cochrane's RoB 1 tool. Two review authors independently selected trials, extracted data, and assessed risk of bias and trial trustworthiness. We pooled data using random-effects meta-analysis. We assessed the certainty of the evidence using GRADE. We included six RCTs with 15,981 participants. All 12 trials in the previous version of this review were not included after review of trial registrations and trustworthiness checklists. Most included studies involved women at low risk of PPH and were conducted in high-resource settings. Prophylactic TXA in addition to standard care compared to placebo in addition to standard care or standard care alone TXA results in little to no difference in estimated blood loss ≥ 1000 mL (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.79 to 1.11; 4 RCTs; n = 13,042; high certainty evidence), resulting in 8 fewer per 1000 women having estimated blood loss ≥ 1000 mL (from 30 fewer to 16 more). TXA likely results in a slight reduction in calculated blood loss ≥ 1000 mL (RR 0.83, 95% CI 0.76 to 0.92; 2 RCTs; n = 4327; moderate certainty evidence), resulting in 53 fewer per 1000 having calculated blood loss ≥ 1000 mL (from 75 fewer to 25 fewer). The evidence is very uncertain about the effect of TXA on maternal death (one event in placebo group, none in TXA group). No trials measured severe morbidity. TXA likely results in little to no difference in blood transfusion (RR 0.88, 95% CI 0.72 to 1.08; 5 RCTs; n = 15,740; moderate certainty evidence), resulting in 4 fewer per 1000 women requiring a blood transfusion (from 10 fewer to 3 more). TXA results in little to no difference in additional surgical interventions to control PPH (RR 1.02, 95% CI 0.86 to 1.22; 4 RCTs; n = 15,631; high certainty evidence), resulting in 1 more per 1000 women requiring additional surgical intervention (from 4 fewer to 7 more). The evidence is very uncertain about the effect of TXA on thromboembolic events (RR 1.40, 95% CI 0.22 to 8.90; 4 RCTs; n = 14,480; very low certainty evidence), resulting in 1 more per 1000 women having a thromboembolic event (from 2 fewer to 17 more). TXA results in little to no difference in the need for additional uterotonics (RR 0.88, 95% CI 0.78 to 1.00; 4 RCTs; n = 15,728; high certainty evidence), resulting in 15 fewer per 1000 women requiring additional uterotonics (from 27 fewer to 0 fewer). The evidence is very uncertain about the effect of TXA on hysterectomy (RR 0.80, 95% CI 0.20 to 3.29; 2 RCTs; n = 4546; very low certainty evidence), resulting in 3 fewer per 10,000 women requiring a hysterectomy (from 11 fewer to 31 more). One trial measuring maternal satisfaction reported no difference between groups at day two postpartum. No data were available on breastfeeding. Overall, studies had low risk of bias. We downgraded the certainty of evidence mainly for imprecision. Prophylactic TXA in addition to standard care during caesarean birth results in little to no difference in estimated blood loss ≥ 1000 mL and likely results in a slight reduction in calculated blood loss ≥ 1000 mL compared to placebo. There were no data for severe morbidity due to PPH. Event rates for further interventions to control PPH were low and similar across groups. Prophylactic TXA thus results in little to no difference between groups for additional surgical interventions (32 versus 31 per 1000), and likely results in little to no difference between groups for blood transfusions (31 versus 36 per 1000) and use of additional uterotonics (107 versus 121 per 1000). There were very few events for the outcomes maternal death (1 in placebo group), thromboembolic events (2 versus 3 per 1000), and hysterectomy (1 per 1000 in each group). Evidence for these serious adverse events is therefore very uncertain. Decisions about implementing routine prophylactic TXA during caesarean birth should not only consider outcomes related to blood loss, but also the relatively low rates of PPH morbidity and uncertainty of serious adverse events. Most studies included women at low risk of PPH, thereby precluding any conclusions about women at high risk of PPH. Cost associated with routine use of an additional drug for all caesarean births needs to be considered. This Cochrane review was funded in part by the World Health Organization. The published protocol and updates to the review can be accessed: Protocol (2009) DOI: 10.1002/14651858.CD007872 Original Review (2010) DOI: 10.1002/14651858.CD007872.pub2 Review Update (2015) DOI: 10.1002/14651858.CD007872.pub3.

Rohwer C ，Rohwer A ，Cluver C ，Ker K ，Hofmeyr GJ ... -  《Cochrane Database of Systematic Reviews》