Cochrane Db Syst Rev
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Cochrane Db Syst Rev · Nov 2022
ReviewDay 5 versus day 3 embryo biopsy for preimplantation genetic testing for monogenic/single gene defects.
Assisted reproductive technology (ART) has allowed couples with a family history of a monogenic genetic disease, or a disease-carrying gene, to reduce the chance of them having a child with the genetic disorder. This is achieved by genetically testing the embryos using an advanced process called preimplantation genetic testing for monogenic or single gene disorders (PGT-M), such as Huntington's disease or cystic fibrosis. This current terminology (PGT-M) has replaced the formerly-known preimplantation genetic diagnosis (PGD). During PGT-M, one or more embryo cells are biopsied and analysed for genetic or chromosomal anomalies before transferring the embryos to the endometrial cavity. Biopsy for PGT-M can be performed at day 3 of cleavage-stage embryo development when the embryo is at the six- to the eight-cell stage, with either one or two blastomeres being removed for analysis. Biopsy for PGT-M can also be performed on day 5 of the blastocyst stage of embryo development when the embryo has 80 to 100 cells, with five to six cells being removed for analysis. Day 5 biopsy has taken over from day 3 biopsy as the most widely-used biopsy technique; however, there is a lack of summarised evidence from randomised controlled trials (RCTs) that assesses the effectiveness and safety of day 5 biopsy compared to day 3 biopsy. Since biopsy is an invasive process, whether it is carried out at day 3 or day 5 of embryo development may have different impacts on further development, implantation, pregnancy, live birth and perinatal outcomes. ⋯ We are uncertain if there is a difference in live births and miscarriages, viable intrauterine pregnancies, ectopic pregnancies, stillbirths or termination of pregnancies between day 5 and day 3 embryo biopsy for PGT-M. There was insufficient evidence to draw any conclusions regarding other adverse outcomes. The results should be interpreted with caution, as the evidence was of very low certainty due to limited studies, high risk of bias in the included study, and an overall low level of precision.
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Cochrane Db Syst Rev · Nov 2022
ReviewAntipsychotic dose reduction compared to dose continuation for people with schizophrenia.
Antipsychotic drugs are the mainstay treatment for schizophrenia, yet they are associated with diverse and potentially dose-related side effects which can reduce quality of life. For this reason, the lowest possible doses of antipsychotics are generally recommended, but higher doses are often used in clinical practice. It is still unclear if and how antipsychotic doses could be reduced safely in order to minimise the adverse-effect burden without increasing the risk of relapse. ⋯ We included 25 RCTs, of which 22 studies provided data with 2635 participants (average age 38.4 years old). The median study sample size was 60 participants (ranging from 18 to 466 participants) and length was 37 weeks (ranging from 12 weeks to 2 years). There were variations in the dose reduction strategies in terms of speed of reduction (i.e. gradual in about half of the studies (within 2 to 16 weeks) and abrupt in the other half), and in terms of degree of reduction (i.e. median planned reduction of 66% of the dose up to complete withdrawal in three studies). We assessed risk of bias across outcomes predominantly as some concerns or high risk. No study reported data on the number of participants with a clinically important change in quality of life or functioning, and only eight studies reported continuous data on scales measuring quality of life or functioning. There was no difference between dose reduction and continuation on scales measuring quality of life (standardised mean difference (SMD) -0.01, 95% confidence interval (CI) -0.17 to 0.15, 6 RCTs, n = 719, I2 = 0%, moderate certainty evidence) and scales measuring functioning (SMD 0.03, 95% CI -0.10 to 0.17, 6 RCTs, n = 966, I2 = 0%, high certainty evidence). Dose reduction in comparison to continuation may increase the risk of rehospitalisation based on data from eight studies with estimable effect sizes; however, the 95% CI does not exclude the possibility of no difference (risk ratio (RR) 1.53, 95% CI 0.84 to 2.81, 8 RCTs, n = 1413, I2 = 59% (moderate heterogeneity), very low certainty evidence). Similarly, dose reduction increased the risk of relapse based on data from 20 studies (RR 2.16, 95% CI 1.52 to 3.06, 20 RCTs, n = 2481, I2 = 70% (substantial heterogeneity), low certainty evidence). More participants in the dose reduction group in comparison to the continuation group left the study early due to adverse effects (RR 2.20, 95% CI 1.39 to 3.49, 6 RCTs with estimable effect sizes, n = 1079, I2 = 0%, moderate certainty evidence) and for any reason (RR 1.38, 95% CI 1.05 to 1.81, 12 RCTs, n = 1551, I2 = 48% (moderate heterogeneity), moderate certainty evidence). Lastly, there was no difference between the dose reduction and continuation groups in the number of participants with at least one adverse effect based on data from four studies with estimable effect sizes (RR 1.03, 95% CI 0.94 to 1.12, 5 RCTs, n = 998 (4 RCTs, n = 980 with estimable effect sizes), I2 = 0%, moderate certainty evidence). AUTHORS' CONCLUSIONS: This review synthesised the latest evidence on the reduction of antipsychotic doses for stable individuals with schizophrenia. There was no difference between dose reduction and continuation groups in quality of life, functioning, and number of participants with at least one adverse effect. However, there was a higher risk for relapse and dropouts, and potentially for rehospitalisations, with dose reduction. Of note, the majority of the trials focused on relapse prevention rather potential beneficial outcomes on quality of life, functioning, and adverse effects, and in some studies there was rapid and substantial reduction of doses. Further well-designed RCTs are therefore needed to provide more definitive answers.
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Cochrane Db Syst Rev · Nov 2022
ReviewTiming of kidney replacement therapy initiation for acute kidney injury.
Acute kidney injury (AKI) is a common condition among patients in intensive care units (ICUs) and is associated with high numbers of deaths. Kidney replacement therapy (KRT) is a blood purification technique used to treat the most severe forms of AKI. The optimal time to initiate KRT so as to improve clinical outcomes remains uncertain. This is an update of a review first published in 2018. This review complements another Cochrane review by the same authors: Intensity of continuous renal replacement therapy for acute kidney injury. ⋯ Based on mainly low to moderate certainty of the evidence, early KRT has no beneficial effect on death and may increase the recovery of kidney function. Earlier KRT probably reduces the length of ICU and hospital stay but increases the risk of adverse events. Further adequate-powered RCTs using robust and validated tools that complement clinical judgement are needed to define the optimal time of KRT in critical patients with AKI in order to improve their outcomes. The surgical AKI population should be considered in future research.
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Cochrane Db Syst Rev · Nov 2022
Review Meta AnalysisPharmacological interventions for preventing venous thromboembolism in people undergoing bariatric surgery.
Venous thromboembolism (VTE), which comprises deep vein thrombosis (DVT) and pulmonary embolism (PE), is the leading cause of preventable death in hospitalised people and the third most common cause of mortality in surgical patients. People undergoing bariatric surgery have the additional risk factor of being overweight. Although VTE prophylaxis in surgical patients is well established, the best way to prevent VTE in those undergoing bariatric surgery is less clear. ⋯ Higher-dose heparin may make little or no difference to venous thromboembolism or major bleeding in people undergoing bariatric surgery when compared to standard-dose heparin. Heparin may make little or no difference to venous thromboembolism in people undergoing bariatric surgery when compared to pentasaccharide. There are inadequate data to draw conclusions about the effects of heparin compared to pentasaccharide on major bleeding. Starting prophylaxis with heparin 12 hours before bariatric surgery may make little or no difference to venous thromboembolism in people undergoing bariatric surgery when compared to starting heparin after bariatric surgery. There are inadequate data to draw conclusions about the effects of heparin started before versus after surgery on major bleeding. Combining mechanical and pharmacological prophylaxis (started 12 hours before surgery) may reduce VTE events in people undergoing bariatric surgery when compared to mechanical prophylaxis alone. No data are available relating to major bleeding. The certainty of the evidence is limited by small sample sizes, few or no events, and risk of bias concerns. Future trials must be sufficiently large to enable analysis of relevant clinical outcomes, and should standardise the time of treatment and follow-up. They should also address the effect of direct oral anticoagulants and antiplatelets, preferably grouping them according to the type of intervention.
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Cochrane Db Syst Rev · Nov 2022
ReviewFollicular flushing during oocyte retrieval in assisted reproductive techniques.
Follicular aspiration under transvaginal ultrasound guidance is routinely performed as part of assisted reproductive technology (ART) to retrieve oocytes for in vitro fertilisation (IVF). The process involves aspiration of the follicular fluid followed by the introduction of flush, typically culture media, back into the follicle followed by re-aspiration. However, there is a degree of controversy as to whether this intervention yields a larger number of oocytes and is hence associated with greater potential for pregnancy than aspiration only. ⋯ The effect of follicular flushing on both live birth and miscarriage rates compared with aspiration alone is uncertain. Although the evidence does not permit any firm conclusions on the impact of follicular flushing on oocyte yield, total number of embryos, number of cryopreserved embryos, or clinical pregnancy rate, it may be that the procedure itself takes longer than aspiration alone. The evidence was insufficient to permit any firm conclusions with respect to adverse events or safety.