The association between epidural labour analgesia and postpartum depression: a randomised controlled trial.

There is conflicting evidence regarding the association between epidural labour analgesia and risk of postpartum depression. Most previous studies were observational trials with limited ability to account for confounders. We aimed to determine if epidural analgesia was associated with a significant change in the incidence of postpartum depression in this randomised controlled trial. We enrolled women aged 21-50 years old with a singleton fetus ≥ 36 weeks gestation. Patients were advised regarding available labour analgesic modalities during enrolment (epidural block; intramuscular pethidine; nitrous oxide; or intravenous remifentanil). On request for analgesia, patients were offered the modality that they had been allocated randomly to first. Blinded investigators recorded patient and obstetric characteristics within 24 h of delivery and assessed for postpartum depression at 6-10 weeks following delivery using the Edinburgh Postnatal Depression Scale (score ≥ 13 considered positive for postpartum depression). The modified intention-to-treat population consisted of all patients who received any form of labour analgesia, while per-protocol consisted of patients who received their randomised modality as their first form of labour analgesia. Of 881 parturients allocated randomly (epidural n = 441, non-epidural n = 440), we analysed 773 (epidural n = 389, non-epidural n = 384); 62 (15.9%) of women allocated to epidural group developed postpartum depression compared with 65 (16.9%) women allocate to the non-epidural group. There were no significant differences in the incidence of postpartum depression between the two groups (adjusted risk difference (95%CI) 1.6 (-3.0-6.3%), p = 0.49). Similar results were obtained with per-protocol analysis (adjusted risk difference (95%CI) -1.0 (-8.3-6.3%), p = 0.79). We found no significant difference in the risk of postpartum depression between patients who received epidural labour analgesia and those who utilised non-epidural analgesic modalities.

Risk factors for persistent pain after breast cancer surgery: a multicentre prospective cohort study.

Identifying factors associated with persistent pain after breast cancer surgery may facilitate risk stratification and individualised management. Single-population studies have limited generalisability as socio-economic and genetic factors contribute to persistent pain development. Therefore, this prospective multicentre cohort study aimed to develop a predictive model from a sample of Asian and American women. We enrolled women undergoing elective breast cancer surgery at KK Women's and Children's Hospital and Duke University Medical Center. Pre-operative patient and clinical characteristics and EQ-5D-3L health status were recorded. Pain catastrophising scale; central sensitisation inventory; coping strategies questionnaire-revised; brief symptom inventory-18; perceived stress scale; mechanical temporal summation; and pressure-pain threshold assessments were performed. Persistent pain was defined as pain score ≥ 3 or pain affecting activities of daily living 4 months after surgery. Univariate associations were generated using generalised estimating equations. Enrolment site was forced into the multivariable model, and risk factors with p < 0.2 in univariate analyses were considered for backwards selection. Of 210 patients, 135 (64.3%) developed persistent pain. The multivariable model attained AUC = 0.807, with five independent associations: age (OR 0.85 95%CI 0.74-0.98 per 5 years); diabetes (OR 4.68, 95%CI 1.03-21.22); pre-operative pain score at sites other than the breast (OR 1.48, 95%CI 1.11-1.96); previous mastitis (OR 4.90, 95%CI 1.31-18.34); and perceived stress scale (OR 1.35, 95%CI 1.01-1.80 per 5 points), after adjusting for: enrolment site; pre-operative pain score at the breast; pre-operative overall pain score at rest; postoperative non-steroidal anti-inflammatory drug use; and pain catastrophising scale. Future research should validate this model and evaluate pre-emptive interventions to reduce persistent pain risk.

Multiscale Analogue Modelling of Clinching Process to Investigate Thickness Tolerance and Tool Misalignment.

NEED-The effect of dimensional variability of sheet thickness (tolerance) and tool misalignment is poorly understood for the clinching process. Finite element analysis (FEA) is valuable but requires a lot of and is difficult to verify in this situation due to the asymmetrical geometry and nonlinear plasticity. OBJECTIVE-The objective of this work was to determine the effect of thickness tolerance, tool misalignment and sheet placement (top vs. bottom) in the clinching process, by use of analogue modelling with plasticine. METHOD-Experiments used a scaled-up punch and die, with plasticine as the analogue. Thickness tolerances were represented by sheet thicknesses of 11 and 7 mm, 12 and 8 mm, 8 and 12 mm and 13 and 9 mm for upper and lower sheets, respectively. Two types of lubricant were tested between sheets: glycerine and silicone oil. Angular variability was also introduced. Measured parameters were interlock (also called undercut) and neck thickness. Analogue results for deformation were compared with microscopy of metal clinching. FINDINGS-The results reveal that the multiscale analogue model is an efficient tool for studying the effect of dimensional deviation on a clinch joint. Thickness tolerance showed a critical relationship with interlock, namely a reduction to about half that of the nominal, for both maximum and least material conditions. Increased angular misalignment also reduced the interlock. Compared with glycerine, silicone oil tests showed reduced interlock, possibly the result of a lower coefficient of friction. ORIGINALITY-This work demonstrates the usefulness of analogue modelling for exploring process variability in clinching. The results also show that significant effects for sheet placement are ductility, lubricant (friction), thickness of samples and tool misalignment.

The Effect of Transcranial Direct Current Stimulation Combined with Visual Cueing Training on Motor Function, Balance, and Gait Ability of Patients with Parkinson's Disease.

Background and Objectives: The purpose of this study was to investigate the effects of transcranial direct current stimulation (tDCS) on motor function, balance and gait ability in patients with Parkinson's disease (PD). Materials and Methods: For the experiment, 30 patients with PD were randomly assigned to the experimental group (n = 15) and the control group (n = 15). Visual cueing training was commonly applied to both groups, the experimental group applied tDCS simultaneously with visual training, and the control group applied sham tDCS simultaneously with visual training. All subjects were pre-tested before the first intervention, post-tested after completing all 4 weeks of intervention, and followed-up tested 2 weeks after the completing intervention. The tests used the Unified Parkinson's Disease Rating Scale (UPDRS) for motor function assessment, Functional Gait Assessment (FGA) for balance assessment, Freezing of Gait Questionnaire (FOG-Q) and the GAITRite system for gait ability assessment. Among the data obtained through the GAITRite system, gait velocity, cadence, step time, double support time, and stride length were analyzed. Results: The experimental group showed a significant decrease in UPDRS and a significant increase in FGA and cadence after the intervention. In addition, UPDRS and cadence showed a significant difference in the follow-up test compared to the pre-intervention test. Conclusions: This study suggests that the application of tDCS to the supplementary motor area of PD patients is useful as an adjuvant therapy for rehabilitation training of PD patients.

Intrathecal catheter use after accidental dural puncture in obstetric patients: literature review and clinical management recommendations.

If an accidental dural puncture occurs, one option is to insert a catheter and use it as an intrathecal catheter. This avoids the need for a further injection and can rapidly provide labour analgesia and anaesthesia for caesarean section. However, there are no recommendations for managing intrathecal catheters and, therefore, significant variation in clinical practice exists. Mismanagement of the intrathecal catheter can lead to increased motor block, high spinal anaesthesia, drug error, hypotension and fetal bradycardia. Care must be taken with an intrathecal catheter to adhere to strict aseptic technique, meticulous labelling, cautious administration of medications and good communication with the patient and other staff. Every institution considering the use of intrathecal catheters should establish a protocol. For labour analgesia, we recommend the use of dilute local anaesthetic agents and opioids. For caesarean section anaesthesia, gradual titration to the level of the fourth thoracic dermatome, with full monitoring, in a facility equipped to manage complications, should be performed using local anaesthetics combined with lipophilic opioids and morphine or diamorphine. Although evidence of the presence and duration of intrathecal catheters on the development of post-dural puncture headache and need for epidural blood patch is limited, we suggest considering leaving the intrathecal catheter in for 24 hours to reduce the chance of developing a post-dural puncture headache while maintaining precautions to avoid drug error and cerebrospinal fluid leakage. Injection of sterile normal saline into the intrathecal catheter may reduce post-dural puncture headache. The level of evidence for these recommendations was low.

Prediction of breakthrough pain during labour neuraxial analgesia: comparison of machine learning and multivariable regression approaches.

INTRODUCTION: Risk-prediction models for breakthrough pain facilitate interventions to forestall inadequate labour analgesia, but limited work has used machine learning to identify predictive factors. We compared the performance of machine learning and regression techniques in identifying parturients at increased risk of breakthrough pain during labour epidural analgesia. METHODS: A single-centre retrospective study involved parturients receiving patient-controlled epidural analgesia. The primary outcome was breakthrough pain. We randomly selected 80% of the cohort (training cohort) to develop three prediction models using random forest, XGBoost, and logistic regression, followed by validation against the remaining 20% of the cohort (validation cohort). Area-under-the-receiver operating characteristic curve (AUC), sensitivity, specificity, and positive and negative predictive values (PPV and NPV) were used to assess model performance. RESULTS: Data from 20 716 parturients were analysed. The incidence of breakthrough pain was 14.2%. Of 31 candidate variables, random forest, XGBoost and logistic regression models included 30, 23, and 15 variables, respectively. Unintended venous puncture, post-neuraxial analgesia highest pain score, number of dinoprostone suppositories, neuraxial technique, number of neuraxial attempts, depth to epidural space, body mass index, pre-neuraxial analgesia oxytocin infusion rate, maternal age, pre-neuraxial analgesia cervical dilation, anaesthesiologist rank, and multiparity, were identified in all three models. All three models performed similarly, with AUC 0.763-0.772, sensitivity 67.0-69.4%, specificity 70.9-76.2%, PPV 28.3-31.8%, and NPV 93.3-93.5%. CONCLUSIONS: Machine learning did not improve the prediction of breakthrough pain compared with multivariable regression. Larger population-wide studies are needed to improve predictive ability.

Association of renin-angiotensin-aldosterone system genetic polymorphisms with maternal hypotension during spinal anaesthesia for caesarean delivery: a retrospective cohort study.

BACKGROUND: Unless prevented, hypotension occurs in up to 80% of normotensive women undergoing spinal anaesthesia for caesarean delivery. Renin-angiotensin-aldosterone system genetic polymorphisms have been associated with hypertensive disease, but few studies investigated effects on blood pressure regulation under spinal anaesthesia. We postulated that these polymorphisms increased vasodilation and maternal hypotension during spinal anaesthesia. METHODS: A retrospective secondary analysis of data from four prospective trials with similar inclusion/exclusion criteria evaluating phenylephrine/ephedrine delivery systems during spinal anaesthesia for elective caesarean delivery. Angiotensin type-1 receptor (AT1R) (A1166C), angiotensin-converting enzyme (ACE) (I/D), and aldosterone synthase CYP11B2 (C344T) polymorphisms were identified from stored specimens. The associations between the polymorphisms and hypotension (systolic blood pressure <80% of baseline), and vasopressor use, were determined by univariable and multivariable regression. RESULTS: Of 556 patients, 378 (68.0%) had hypotension. The AC/CC genotypes of AT1R (A1166C) were associated with hypotension by univariable analysis (OR 2.70, 95% CI 1.38 to 5.28, P=0.004]) and multivariable analysis (OR 3.65, [95% CI 1.68 to 7.94, P=0.004]) after adjustment for age, race, intravenous fluid volume, and block height. No difference in vasopressor use or adverse maternal or fetal outcomes were noted. Baseline characteristics were similar, with the exception of higher baseline blood pressure, block height, and intravenous fluid volume in the hypotensive group. There was no significant association between ACE and CYP11B2 polymorphisms and hypotension. CONCLUSION: AC/CC genotypes of AT1R (A1166C) polymorphism were associated with maternal hypotension under spinal anaesthesia for caesarean delivery. An association with cardiovascular indices and high-risk parturients should be examined.

Incidence and risk factors for epidural re-siting in parturients with breakthrough pain during labour epidural analgesia: a cohort study.

INTRODUCTION: Epidural re-siting is one of the significant events during labour epidural analgesia that may result in decreased patient satisfaction. The aim of our study was to investigate the incidence of and factors associated with epidural re-siting in parturients using epidural analgesia, with an emphasis on those with breakthrough pain. METHODS: A retrospective cohort study of 10170 parturients who received labour epidural analgesia. The primary outcome was the incidence of epidural re-siting (binary data). Univariate and multivariate logistic regression analysis were performed to find associated risk factors for re-siting. RESULTS: Less than 1% (0.85%, 86/10170) of the women in the study had their epidural re-sited. Amongst the subset of women with breakthrough pain, the incidence of epidural re-siting was higher (4.7%, 68/1454). Most of the women who had their epidural re-sited had experienced breakthrough pain (79%, 68/86). Amongst all parturients, the presence of breakthrough pain (OR=21.31), hypotension (OR=4.18) and venous puncture (OR=2.74) were significantly associated with re-siting. Amongst the parturients with breakthrough pain who required epidural re-siting, lower cervical dilatation (OR=0.81), higher number of episodes of breakthrough pain (OR=1.83) and patchy block (OR=4.37) were significantly associated with re-siting. The areas-under-curves of two multivariate models were 0.894 and 0.806 respectively. CONCLUSION: In our institution, the incidence of epidural catheter re-siting was low in all patients. However, the majority of patients whose catheters were re-sited had exhibited breakthrough pain. The risk factors associated with the need for re-siting of catheters in all patients differed from those who had breakthrough pain.

Hyperbaric vs. isobaric bupivacaine for spinal anaesthesia for elective caesarean section: a Cochrane systematic review.

Both isobaric and hyperbaric bupivacaine have been used for spinal anaesthesia for elective caesarean section, but it is not clear if one is better than the other. The primary objective of this systematic review was to determine the effectiveness and safety of hyperbaric bupivacaine compared with isobaric bupivacaine administered during spinal anaesthesia for elective caesarean section. We included 10 studies with 614 subjects in the analysis. There was no evidence of differences either in the risk of conversion to general anaesthesia, with a relative risk (95%CI) of 0.33 (0.09-1.17) (very low quality of evidence), or in the need for supplemental analgesia, the relative risk (95%CI) being 0.61 (0.26-1.41) (very low quality of evidence). There was also no evidence of a difference in the use of ephedrine, the amount of ephedrine used, nausea and vomiting, or headache. Hyperbaric bupivacaine took less time to reach a sensory block height of T4, with a mean difference (95%CI) of -1.06 min (-1.80 to -0.31). Due to the rarity of some outcomes, dose variability, use of adjuvant drugs and spinal technique used, future clinical trials should look into using adequate sample size to investigate the primary outcome of the need for supplemental analgesia.

Comparison therapeutic efficacy of underwater and overground walking training on the healthy subjects balancing ability.

[Purpose] This study's working hypothesis is that underwater walking training is beneficial for healthy subjects balance. [Subjects and Methods] Forty eight subjects (Underwater walking group=25, Overground walking group=23) completed the experiment. Healthy subjects with no orthopedic history of lower extremity injuries were recruited. Gait training is performed using the underwater treadmill consisted of 30-minute walking sessions, five times per week for four weeks. [Results] After the intervention, the medial-lateral and anterior-posterior balance indices increased significantly. [Conclusion] This study conducted underwater walking training on the healthy subjects, with positive effects on balancing ability.

A case series of vital signs-controlled, patient-assisted intravenous analgesia (VPIA) using remifentanil for labour and delivery.

Intravenous remifentanil patient-controlled analgesia can be used during labour as an alternative to epidural analgesia. Adverse effects of opioids, including hypoxia and bradycardia, may lead to maternal morbidity and mortality. We devised an interactive feedback system based on a clinical proportional algorithm, to continuously monitor for adverse effects to enhance safety and better titrate analgesia. This vital signs-controlled, patient-assisted intravenous analgesia with remifentanil used a prototype delivery system linked to a pulse oximeter that evaluated maternal oxygen saturation and heart rate continuously. With this system, we detected oxygen saturation < 95% for more than 60 s in 15 of 29 subjects (52%); and heart rate < 60 min-1 for more than 60 s in 7 of 29 subjects (24%) during use. The system automatically responded appropriately by reducing the dosages and temporarily halting remifentanil administration, thus averting further hypoxia and bradycardia.

Underwater treadmill training and gait ability in the normal adult.

[Purpose] Our working hypothesis is that underwater treadmill training improves normal people's gait ability. [Subjects and Methods] Twenty-five healthy subjects with no orthopedic history of lower extremity were recruited. Gait training is performed using an underwater treadmill (HydroTrack® Underwater Treadmill System, Conray, Inc., Phoenix, AZ, USA), for twenty minutes per session, five sessions a week for four weeks. The water temperature was set at about 33 °C and the depth was fixed to reach between the subjects' xiphoid process and the navel. [Results] After the intervention, step length, velocity, and cadence increased significantly. [Conclusion] This study conducted underwater treadmill training with normal people, with positive effects on gait ability.

Common variants of catechol-O-methyltransferase influence patient-controlled analgesia usage and postoperative pain in patients undergoing total hysterectomy.

Catechol-O-methyltransferase (COMT) gene polymorphisms and haplotypes have been associated with both experimental and clinical pain phenotypes. In this prospective study, we investigated the association of three common polymorphisms with experimentally induced pressure pain, postoperative pain and amount of self-administered morphine in 973 patients who underwent scheduled total hysterectomy. DNA extracted from peripheral blood was genotyped for three COMT polymorphisms by Taqman assay or a PCR-based method. In the overall sample, rs4633 and rs4680 were significantly associated with morphine use, whereas rs4818 was associated with time-averaged pain scores. Statistically significant associations were found between COMT rs4633 and rs4680 genotypes and the amount of morphine self-administered through a patient-controlled analgesia pump. For rs4818, the only statistically significant association was with time-averaged pain scores. Haplotype analysis showed statistically significant association of the low pain sensitivity haplotype with time-averaged pain scores; and average pain sensitivity haplotype with total morphine and weight-adjusted morphine.

Methylnaltrexone to prevent intrathecal morphine-induced pruritus after Caesarean delivery: a multicentre, randomized clinical trial.

BACKGROUND: Intrathecal morphine-induced pruritus is a very common side-effect that is difficult to prevent or treat. Central and peripheral mechanisms are believed to be involved. The aim of this study was to determine if a peripherally acting, µ-opioid antagonist would reduce morphine-induced pruritus. METHODS: We conducted a multicentre, randomized, blinded, placebo-controlled trial of women having elective Caesarean section under spinal anaesthesia with intrathecal morphine 100 µg. After delivery, participants received either subcutaneous methylnatrexone bromide 12 mg (MNTX group, n=69) or saline (placebo group, n=68). Pruritus, nausea, pain, analgesic use, and side-effects were assessed at 2, 4, 8, and 24 h. The primary outcome was the severity of pruritus (0-10 score). RESULTS: One hundred and thirty-seven women completed the study, with five major protocol violations. There was no statistically significant difference between the MNTX and placebo groups for the median (IQR) pruritus AUC scores [24 (9-47) vs 36 (11-68), median difference 8.5, 95% confidence interval (CI) 0-20, P=0.09] or the worst pruritus score [3 (2-7) vs 5 (2-6), median difference 1, 95% CI 0-2, P=0.24]. The incidence of pruritus was 84% in the MNTX group and 88% in the placebo group (P=0.48). Analgesic and gastrointestinal outcomes did not significantly differ between the groups. CONCLUSIONS: A single dose of subcutaneous methylnaltrexone bromide 12 mg did not reduce the overall severity or incidence of pruritus. In this study, treatment with a peripherally acting µ-opioid antagonist was generally ineffective against intrathecal morphine-induced pruritus, but a small clinical effect cannot be excluded. CLINICAL TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ACTRN12611000345987).

Assessment of an updated double-vasopressor automated system using Nexfin for the maintenance of haemodynamic stability to improve peri-operative outcome during spinal anaesthesia for caesarean section.

Hypotension occurs commonly during spinal anaesthesia for caesarean section, associated with maternal and fetal adverse effects. We developed a double-vasopressor automated system with a two-step algorithm and continuous non-invasive haemodynamic monitoring using the Nexfin device. The system delivered 25 µg phenylephrine every 30 s when systolic blood pressure was between 90% and 100% of baseline, or 2 mg ephedrine at this blood pressure range and heart rate < 60 beats.min(-1) ; and 50 µg phenylephrine or 4 mg ephedrine when systolic blood pressure was < 90% of baseline with the same heart rate criterion. Fifty-seven women received standardised spinal anaesthesia. Twenty-seven (47.4%) had at least one reading of hypotension defined as systolic blood pressure < 80% baseline. Systolic blood pressure was within 20% of the baseline in a mean (SD) of 79.8 (20.9)% of measurements. Fifty-three (93.0%) women required phenylephrine before delivery while 10 (17.5%) required ephedrine. Six women (10.5%) experienced nausea and three (5.3%) vomited. The system was able to achieve a low incidence of maternal hypotension with good maternal and fetal outcomes.