Chemotherapy alone versus chemotherapy plus radiotherapy for adults with early-stage Hodgkin's lymphoma.

Early-stage Hodgkin's lymphoma in adults is commonly treated with combined modality treatment of chemotherapy followed by radiotherapy. The role of radiotherapy has been questioned due to potential long-term adverse effects. To assess the effects of chemotherapy compared to chemotherapy plus radiotherapy in adults with early-stage Hodgkin's lymphoma. We updated all previous searches for randomised controlled trials (RCTs) on the databases Cochrane Central Register of Controlled Trial, MEDLINE and Embase, in trial registries and in relevant conference proceedings until November 2023. We included RCTs comparing chemotherapy alone with chemotherapy plus radiotherapy in adults with early-stage Hodgkin's lymphoma and excluded trials with more than 20% of participants with advanced Hodgkin's lymphoma. We considered immunotherapy in addition to chemotherapy eligible if both were applied similarly in the comparator groups, but did not identify such trials. For our comparisons, we separated RCTs with the same number of chemotherapy cycles in both arms and RCTs with a different number of cycles, when the chemotherapy regimens were the same. We separated RCTs which compared participants with a favourable, mixed or unfavourable risk profile. Two review authors independently screened search results, extracted data and assessed the quality of included trials. A third review author resolved discrepancies. We analysed time-to-event outcomes (overall survival, progression-free survival) as hazard ratios (HR) and binary outcomes (adverse events) as risk ratios (RR). We assessed the certainty of evidence using the GRADE approach. We included nine comparisons of eight RCTs involving 3840 participants in this updated review. Same number of chemotherapy cycles in both trial arms Favourable disease For overall survival in individuals with favourable Hodgkin's lymphoma, the evidence is uncertain and inconclusive (HR 0.92, 95% confidence interval (CI) 0.11 to 7.92; 2 RCTs, 1245 participants; very low-certainty evidence due to study limitations, inconsistency and imprecision). Additional radiotherapy to chemotherapy is likely to improve progression-free survival (HR 0.36, 95% CI 0.20 to 0.68; 2 RCTs, 1245 participants; moderate-certainty evidence due to study limitations). The evidence was uncertain and inconclusive for second-cancer-related mortality (RR 0.93, 95% CI 0.01 to 74.24; 2 RCTs, 1245 participants; very low-certainty evidence due to study limitations, inconsistency and substantial imprecision) and suggests little to no difference in cardiac disease-related mortality (RR 0.89, 95% CI 0.06 to 14.16; 1 RCT, 667 participants; low-certainty evidence due to substantial imprecision). There were no data on infection-related mortality or infertility. Mixed population For a population of mixed risk profile, the evidence on overall survival is uncertain and inconclusive (HR 0.79, 95% CI 0.13 to 4.80; 2 RCTs, 572 participants; very low-certainty evidence due to study limitations, inconsistency and imprecision). It indicates that additional radiotherapy may lead to an improvement in progression-free survival (HR 0.71, 95% CI 0.43 to 1.17; 2 RCTs, 572 participants; low-certainty evidence due to study limitations and imprecision). The evidence is uncertain and inconclusive for infection-related mortality (RR 1.35, 95% CI 0.17 to 10.87; 2 RCTs, 572 participants) and second-cancer-related mortality (RR 0.52, 95% CI 0.09 to 2.98; 2 RCTs, 572 participants) (both very low-certainty evidence due to study limitations and substantial imprecision), but suggests that additional radiotherapy may increase cardiac disease-related mortality (RR 3.03, 95% CI 0.12 to 73.92; 1 RCT, 420 participants; low-certainty evidence due to substantial imprecision). There were no data on infertility. Unfavourable disease For individuals with unfavourable disease, the evidence on overall survival is uncertain and inconclusive (HR 0.69, 95% CI 0.20 to 2.44; 2 RCTs, 688 participants; very low-certainty evidence due to study limitations and substantial imprecision), but additional radiotherapy probably improves progression-free survival (HR 0.55, 95% CI 0.19 to 1.60; 1 RCT, 651 participants; moderate-certainty evidence due to imprecision). The evidence was uncertain and inconclusive for cardiac disease-related mortality (RR 2.85, 95% CI 0.12 to 65.74; 1 RCT, 37 participants; very low-certainty evidence due to study limitations and substantial imprecision). There were no data on infection-related mortality, second-cancer related mortality or infertility. Different number of chemotherapy cycles in both trial arms Favourable disease The evidence for overall survival in individuals with favourable disease treated with different numbers of chemotherapy cycles in both arms is uncertain and inclusive (HR 0.36, 95% CI 0.04 to 3.38; 1 RCT, 357 participants; very low-certainty evidence due to study limitations and substantial imprecision), yet it suggests a likely improvement in progression-free survival with additional radiotherapy (HR 0.08, 95% CI 0.02 to 0.32; 1 RCT, 357 participants; moderate-certainty evidence due to study limitations). For second-cancer-related mortality, the evidence is uncertain and inconclusive (RR 0.21, 95% CI 0.01 to 4.34; 1 RCT, 465 participants; very low-certainty evidence due to study limitations and substantial imprecision). There were no data on infection-related mortality and infertility and data for cardiac disease-related mortality were not estimable (no events in either group). Unfavourable disease For individuals with an unfavourable risk profile, additional radiotherapy may decrease overall survival slightly (HR 1.66, 95% CI 0.95 to 2.90; 2 RCTs, 698 participants; low-certainty evidence due to study limitations and imprecision), but may slightly improve progression-free survival (HR 0.84, 95% CI 0.53 to 1.33; 2 RCTs, 698 participants; low-certainty evidence due to study limitations and imprecision). The evidence is uncertain and inconclusive for infection-related mortality (RR 6.90, 95% CI 0.36 to 132.34; 1 RCT, 276 participants), second-cancer-related mortality (RR 2.19, 95% CI 0.77 to 6.19; 2 RCTs, 870 participants) and cardiac disease-related mortality (RR 1.60, 95% CI 0.31 to 8.22; 2 RCTs, 870 participants) (all very low-certainty evidence due to study limitations and substantial imprecision). There were no data on infertility. The chemotherapy regimens in the trials differed and data for regimens commonly used today were limited. Additional radiotherapy may slightly improve progression-free survival. The available data for overall survival and adverse events were of low and very low certainty, and we were unable to draw conclusions about the effects of additional radiotherapy on these outcomes. No studies evaluated infertility. High-quality, longer-term follow-up data are required and data on fertility are needed.

Goldkuhle M ，Kreuzberger N ，von Tresckow B ，Eichenauer DA ，Specht L ，Monsef I ，Skoetz 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》

Effect and safety of intravenous iron compared to oral iron for treatment of iron deficiency anaemia in pregnancy.

Intravenous iron is increasingly used to treat iron-deficient anaemia (IDA) in pregnancy. A previous network meta-analysis suggested that intravenous irons have a greater effect on haematological parameters than oral irons; however, the impact on serious pregnancy complications such as postpartum haemorrhage (PPH) or the need for blood transfusion was unclear. Since then, several new randomised controlled trials (RCTs) have been conducted. To evaluate the effect and safety of intravenous versus oral iron preparations for treating IDA in pregnancy. We searched CENTRAL, MEDLINE, Embase, and two trial registries (ClinicalTrials.gov and the WHO ICTRP) for eligible studies. The latest search was performed on 19 March 2024. We included RCTs in pregnant women with confirmed IDA (haemoglobin (Hb) level < 11 g/dL as per World Health Organization (WHO) criteria) comparing intravenous (iron sucrose, ferric carboxymaltose, ferric derisomaltose, ferumoxytol) and oral (ferrous sulfate, ferrous fumarate, ferrous gluconate) iron preparations. Our outcomes were antenatal and postnatal Hb levels, antenatal and postnatal anaemia status, PPH, blood transfusion, maternal satisfaction, maternal well-being, breastfeeding, maternal mortality, maternal morbidity, and adverse events (AEs). We used the Cochrane RoB 1 tool to assess risk of bias in the included RCTs. We followed standard Cochrane methods. Two review authors independently assessed studies for eligibility and scientific rigour, evaluated the risk of bias of included studies, and extracted data. Where appropriate, we pooled data using a fixed-effect model in the first instance. We reported dichotomous data as risk ratios (RRs) with 95% confidence intervals (CIs) and continuous data as mean differences (MDs) with 95% CIs. We assessed the certainty of the evidence using the GRADE approach. We included 13 RCTs (3939 participants) mainly conducted in India and Africa (8/13). Gestational age at baseline ranged from 13 to 37 weeks, and Hb levels ranged from 5.0 to just below 11.0 g/dL. The most frequently compared preparations were intravenous iron sucrose versus oral ferrous sulfate (5/13). Most RCTs were at low risk of bias, and the certainty of evidence ranged from moderate to very low, mainly due to concerns over attrition bias, imprecision, and inconsistency. Antenatal outcomes Compared with oral iron, intravenous iron likely slightly increases Hb level three to six weeks after treatment start (MD 0.49, 95% CI 0.28 to 0.69; 11 RCTs; 2935 participants; moderate-certainty evidence) and likely reduces anaemia status three to six weeks after treatment start (RR 0.81, 95% CI 0.77 to 0.86; 5 RCTs; 2189 participants; moderate-certainty evidence). Compared with oral iron, intravenous iron likely slightly increases Hb level around birth (MD 0.55, 95% CI 0.33 to 0.77; 6 RCTs; 1574 participants; moderate-certainty evidence) and likely reduces anaemia status around birth (RR 0.85, 95% CI 0.77 to 0.93; 4 RCTs; 1240 participants; moderate-certainty evidence). Postpartum outcomes Compared with oral iron, intravenous iron may slightly increase Hb level postpartum (MD 0.54, 95% CI 0.41 to 0.68; 3 RCTs; 1950 participants; low-certainty evidence). It may also reduce anaemia status (RR 0.66, 95% CI 0.59 to 0.73; 3 RCTs; 1950 participants; low-certainty evidence) and severe anaemia postpartum (RR 0.16, 95% CI 0.03 to 0.84; 2 RCTs; 1581 participants; very low-certainty evidence), although the evidence for the latter outcome is very uncertain. Compared with oral iron, intravenous iron may result in little to no difference in PPH (RR 1.44, 95% CI 0.50 to 4.20; 3 RCTs; 2251 participants; low-certainty evidence) and likely results in little to no difference in the need for blood transfusion (RR 0.97, 95% CI 0.58 to 1.60; 6 RCTs; 2592 participants; moderate-certainty evidence) or rates of breastfeeding (RR 1.04, 95% CI 0.97 to 1.12; 1 RCT; 404 participants; moderate-certainty evidence). No trials reported on maternal satisfaction or maternal well-being. Adverse outcomes Compared with oral iron, intravenous iron may have little to no effect on maternal mortality, but the evidence is very uncertain (RR 0.91, 95% CI 0.13 to 6.39; 4 RCTs; 2152 participants; very low-certainty evidence). Compared with oral iron, intravenous iron likely does not increase maternal morbidity: severe infections (RR 1.01, 95% CI 0.47 to 2.18; 1 RCT; 1881 participants; moderate-certainty evidence) and prolonged hospital stay (RR 0.86, 95% CI 0.62 to 1.21; 1 RCT; 1764 participants; moderate-certainty evidence) and may not increase admissions to the intensive care unit (ICU) (RR 1.99, 95% CI 0.18 to 21.87; 2 RCTs; 2069 participants; low-certainty evidence). Compared with oral iron, intravenous iron likely does not increase AEs (RR 1.05, 95% CI 0.82 to 1.35; 1 RCT; 349 participants; moderate-certainty evidence) and may not increase serious AEs (RR 1.25, 95% CI 0.61 to 2.59; 1 RCT; 1934 participants; low-certainty evidence). However, individual AEs were inconsistently reported across trials. Intravenous iron likely slightly increases Hb levels and likely reduces anaemia in pregnancy compared to oral iron. Hb levels postpartum may be slightly increased with intravenous iron, but the effect on postpartum severe anaemia status is very uncertain. Intravenous iron may result in little to no difference in PPH, and blood transfusion rates are likely unaffected by route of administration. Synthesis of adverse outcomes proved challenging due to their rarity and suboptimal reporting. The effects of intravenous iron on maternal mortality and admissions to the ICU are very uncertain, and there is likely little to no difference between groups in severe infections and prolonged hospital stay. Intravenous iron likely does not increase AEs and may not increase serious AEs; however, the 95% CIs in both cases include potential harm. Furthermore, this finding should be treated cautiously due to the varied adverse event profiles of both types of iron preparations. Data from the ongoing multicentre trials may address some of the identified evidence gaps. However, there is a clear need to strengthen the co-ordination of research efforts around clinically important time points of outcome measure, homogeneity of their definition, and safety reporting. This Cochrane Review was partially funded by the WHO and was supported by the UK Medical Research Council funding. Registration (2024): PROSPERO, CRD42024523791 via www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024523791.

Nicholson L ，Axon E ，Daru J ，Rogozińska E ... -  《Cochrane Database of Systematic Reviews》

Perineal techniques during the second stage of labour for reducing perineal trauma and postpartum complications.

Postpartum haemorrhage (PPH) is responsible for around 27% of global maternal deaths. Perineal tears are common in vaginal births and a significant contributor to excessive blood loss. A diversity of perineal techniques are utilised to prevent perineal trauma and reduce the incidence of PPH; however, they lack evidence-based comparisons to understand their effects. To assess the effect of perineal techniques during the second stage of labour on the incidence of and morbidity associated with perineal trauma to prevent postpartum complications. We searched four databases and two trial registers up to 16 April 2024. We checked references, searched citations and contacted study authors to identify additional studies. We included randomised controlled trials (RCTs) of women in the second stage of labour who intended to give birth vaginally, comparing any perineal techniques with control or another perineal technique. We excluded studies that performed perineal techniques outside the second stage of labour. Our critical outcomes were second-, third- and fourth-degree tears measured immediately after birth, and PPH ≥ 500 mL measured within 24 hours after birth. We used the Cochrane risk of bias 2 tool to assess bias in the included RCTs. We synthesised results for each outcome within each comparison using meta-analysis where possible. Where this was not possible due to the nature of the data, we synthesised results narratively. We used GRADE to assess the certainty of evidence for each outcome. We included a total of 17 studies with 13,695 participants. Hands off (or poised) versus hands on Hands off (poised) may result in little to no difference in second-degree tears (risk ratio (RR) 0.73, 95% confidence interval (CI) 0.32 to 1.64; 2 studies; low-certainty evidence) and third- or fourth-degree tears when data are combined (RR 1.27, 95% CI 0.81 to 1.99; 2 studies; low-certainty evidence). The evidence is very uncertain about the effect of hands off (poised) on third-degree tears and fourth-degree tears when reported separately (RR 0.50, 95% CI 0.05 to 5.27; 1 study; very low-certainty evidence and RR 3.00, 95% CI 0.13 to 71.22; 1 study; very low-certainty evidence). Hands off (poised) may result in little to no difference in PPH ≥ 500 mL (RR 1.16, 95% CI 0.92 to 1.47; 1 study; low-certainty evidence). Hands off (poised) probably results in little to no difference in breastfeeding two days after birth (RR 1.02, 95% CI 0.99 to 1.06; 1 study; moderate-certainty evidence) and perineal pain (RR 0.98, 95% CI 0.94 to 1.01; 1 study; moderate-certainty evidence). Vocalisation versus control Vocalisation may result in a reduction in second-degree tears (RR 0.56, 95% CI 0.23 to 1.38; 1 study; low-certainty evidence) and third-degree tears (RR 0.13, 95% CI 0.01 to 2.32; 1 study; low-certainty evidence), but the CIs are wide and include the possibility of no effect. No events were reported for fourth-degree tears (low-certainty evidence). Vocalisation may increase maternal satisfaction (RR 1.19, 95% CI 0.93 to 1.51; 1 study; low-certainty evidence). The evidence is very uncertain about the effect of vocalisation on perineal pain (RR 1.44, 95% CI 0.81 to 2.58; 1 study; very low-certainty evidence). Warm compress on the perineum versus control (hands off or no warm compress) Warm compress on the perineum may result in little to no difference in second-degree tears (RR 0.94, 95% CI 0.72 to 1.21; 2 studies; low-certainty evidence), but likely results in a reduction in third- or fourth-degree tears (RR 0.46, 95% CI 0.27 to 0.79; 3 studies; moderate-certainty evidence). Evidence from two smaller studies is very uncertain about the effect of warm compress on the perineum on third-degree tears (RR 0.51, 95% CI 0.04 to 7.05; 2 studies; very low-certainty evidence) or fourth-degree tears (RR 0.11, 95% CI 0.01 to 2.06; 2 studies; very low-certainty evidence) when reported separately. Warm compress likely results in a large reduction in perineal pain (mean difference (MD) -0.81, 95% CI -1.18 to -0.44; 1 study; moderate-certainty evidence). The evidence is very uncertain about the effect of warm compress on the perineum on maternal satisfaction and PPH ≥ 500 mL. Massage of the perineum versus control (hands off or no usual care) Massage of the perineum may have little to no effect on second-degree tears (RR 1.04, 95% CI 0.89 to 1.21; 4 studies; low-certainty evidence). The evidence is very uncertain about the effect of massage of the perineum on third-degree tears (RR 0.57, 95% CI 0.16 to 2.02; 4 studies; very low-certainty evidence). Massage of the perineum may reduce fourth-degree tears but the CIs are wide and include the possibility of no effect (RR 0.26, 95% CI 0.04 to 1.61; 4 studies; low-certainty evidence). The evidence suggests that massage likely results in little to no difference in perineal pain (RR 0.97, 95% CI 0.90, 1.05; 1 study; moderate-certainty evidence). One study reported 10 participants with postpartum haemorrhage across three interventions (warm compress, massage, control). Combined warm compress and massage of the perineum versus control Combined warm compress and massage of the perineum likely results in a reduction in second-degree tears when compared to a control (RR 0.63, 95% CI 0.46 to 0.86; 1 study; moderate-certainty evidence), but the evidence is very uncertain about the effect on third-degree tears (RR 2.92, 95% CI 0.12 to 70.72; 1 study; very low-certainty evidence). The intervention may result in a reduction in PPH ≥ 500 mL but the CIs are wide and include the possibility of no effect (RR 0.43, 95% CI 0.14 to 1.35; 1 study; low-certainty evidence). Combined warm compress and massage likely results in an increase in maternal satisfaction (MD 0.4, 95% CI -0.01 to 0.81; 1 study; moderate-certainty evidence). Combined warm compress and massage of the perineum versus massage alone Combined warm compress and massage of the perineum may result in little to no difference in second-degree tears (RR 0.95, 95% CI 0.86 to 1.06; 1 study; low-certainty evidence) when compared to massage alone, but the evidence is very uncertain about the effect on third- or fourth-degree tears (RR 0.98, 95% CI 0.06 to 15.49; 1 study; very low-certainty evidence). It may also result in little to no difference in PPH ≥ 500 mL (RR 1.10, 95% CI 0.59 to 2.07; 1 study; low-certainty evidence). The evidence suggests that combined warm compress and massage may result in little to no difference in maternal satisfaction (1 study; low-certainty evidence). Other perineal techniques We also assessed evidence on the following comparisons, but since they are used less frequently in global clinical practice to optimise birth outcomes, we have not presented the results summary here: Ritgen's manoeuvre versus standard care; primary delivery of posterior versus anterior shoulder; massage with enriched oil on the perineum versus massage with liquid wax; petroleum jelly on the perineum versus control; and perineal protection device versus control. Overall, the evidence for the effectiveness of perineal techniques to reduce perineal trauma and postpartum haemorrhage is very uncertain. Very few studies reported rates of postpartum haemorrhage, adverse events, women's or health workers' experience or other important outcomes that allow us to understand the effectiveness and acceptability of perineal techniques to reduce perineal trauma. Prior to any further large trials, research is needed to clarify the types of interventions, including a clear description of the process of development and involvement of relevant stakeholders. There is a need to clarify how the intervention is proposed to achieve its effects. Trials would benefit from process evaluation alongside, to explore context, mechanisms and effects. This Cochrane review was funded (in part) by WHO (APW 2024/1475460). TF, VL and the CIDG editorial base are funded by UK aid from the UK government for the benefit of low- and middle-income countries (project number 300342-104). The views expressed do not necessarily reflect the UK government's official policies. Registration and protocol: PROSPERO, CRD42024537252. Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024537252.

Dwan K ，Fox T ，Lutje V ，Lavender T ，Mills TA ... -  《Cochrane Database of Systematic Reviews》

Infliximab for maintenance of medically-induced remission in Crohn's disease.

Infliximab is a monoclonal antibody that binds and neutralises tumour necrosis factor-alpha (TNF-α) which is present in high levels in the blood serum, mucosa and stool of patients with Crohn's disease. To determine the efficacy and safety of infliximab for maintaining remission in patients with Crohn's disease. On 31 August, 2021 and 23 June, 2023, we searched CENTRAL, Embase, MEDLINE, ClinicalTrials.gov, and WHO ICTRP. Randomised controlled trials (RCTs) in which infliximab was compared to placebo or another active comparator for maintenance, remission, or response in patients with Crohn's disease. Pairs of review authors independently selected studies and conducted data extraction and risk of bias assessment. We expressed outcomes as risk ratios and mean differences with 95% confidence intervals. We assessed the certainty of the evidence using GRADE. Our primary outcome was clinical relapse. Secondary outcomes were loss of clinical response, endoscopic relapse, and withdrawal due to serious and adverse events. Nine RCTs with 1257 participants were included. They were conducted between 1999 and 2022; seven RCTs included biologically-naive patients, and the remaining two included a mix of naive/not naive patients. Three studies included patients in clinical remission, five included patients with a mix of activity scores, and one study included biologic responders with active disease at baseline. All studies allowed some form of concomitant medication during their duration. One study exclusively included patients with fistulating disease. The age of the participants ranged from 18 to 69 years old. All but one single-centre RCT were multicentre RCTs. Four studies were funded by pharmaceutical companies, two had a mix of commercial and public funding, and two had public funding. Infliximab is probably superior to placebo in preventing clinical relapse in patients who have mixed levels of clinical disease activity at baseline, and are not naive to biologics (56% vs 75%, RR 0.73, 95% CI 0.63 to 0.84, NNTB = 5, moderate-certainty evidence). We cannot draw any conclusions on loss of clinical response (RR 0.59, 95% CI 0.37 to 0.96), withdrawals due to adverse events (RR 0.66, 95% CI 0.37 to 1.19), or serious adverse events (RR 0.60, 95% CI 0.36 to 1.00) because the evidence is very low certainty. Infliximab combined with purine analogues is probably superior to purine analogues for clinical relapse (12% vs 59%, RR 0.20, 95% CI 0.10 to 0.42, NNTB = 2, moderate-certainty evidence), for patients in remission, and who are not naive to biologics. We cannot draw any conclusions on withdrawals due to adverse events (RR 0.47, 95% CI 0.15 to 1.49), and serious adverse events (RR 1.19, 95% CI 0.54 to 2.64) because the evidence is very low certainty. We cannot draw any conclusions about the effects of infliximab on serious adverse events compared to purine analogues (RR 0.79, 95% CI 0.37 to 1.68) for a population in remission at baseline because the evidence is very low certainty. There was no evidence available for the outcomes of clinical relapse, loss of clinical response, and withdrawal due to adverse events. Infliximab may be equivalent to biosimilar for clinical relapse (47% vs 40% RR 1.18, 95% CI 0.82 to 1.69), and it may be slightly less effective in averting loss of clinical response (49% vs 32%, RR 1.50, 95% CI 1.01 to 2.23, low-certainty evidence), for a population with mixed/low disease activity at baseline. Infliximab may be less effective than biosimilar in averting withdrawals due to adverse events (27% vs 0%, RR 20.73, 95% CI 2.86 to 150.33, low-certainty evidence). Infliximab may be equivalent to biosimilar for serious adverse events (10% vs 10%, RR 0.99, 95% CI 0.39 to 2.50, low-certainty evidence). We cannot draw any conclusions on the effects of subcutaneous biosimilar compared with intravenous biosimilar on clinical relapse (RR 1.01, 95% CI 0.65 to 1.57), loss of clinical response (RR 0.94, 95% CI 0.70 to 1.25), and withdrawals due to adverse events (RR 0.77, 95% CI 0.30 to 1.97) for an active disease population with clinical response at baseline because the evidence is of very low certainty. We cannot draw any conclusions on the effects of infliximab compared to adalimumab on loss of clinical response (RR 0.68, 95% CI 0.29 to 1.59), withdrawals due to adverse events (RR 0.10, 95% CI 0.01 to 0.72), serious adverse events (RR 0.09, 95% CI 0.01 to 1.54) for an active disease population with clinical response at baseline because the evidence is of very low certainty. There was no evidence available for the outcome of clinical relapse. Infliximab is probably more effective in preventing clinical relapse than placebo (moderate-certainty evidence). Infliximab in combination with purine analogues is probably more effective in preventing clinical and endoscopic relapse than purine analogues alone (moderate-certainty evidence). No conclusions can be drawn regarding prevention of loss of clinical response, occurrence of withdrawals due to adverse events, or total adverse events due to very low-certainty evidence for both of these comparisons. There may be little or no difference in prevention of clinical relapse, withdrawal due to adverse events or total adverse events between infliximab and a biosimilar (low-certainty evidence). Infliximab may lead to more loss of clinical response than a biosimilar (low-certainty evidence). We were unable to draw meaningful conclusions about other comparisons and outcomes related to missing data or very low-certainty evidence due to serious concerns about imprecision and risk of bias. Further research should focus on comparisons with other active therapies for maintaining remission, as well as ensuring adequate power calculations and reporting of methods.

Gordon M ，Sinopoulou V ，Akobeng AK ，Sarian A ，Moran GW ... -  《-》