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.

Obesity in women: anaesthetic implications for peri-operative and peripartum management.

The prevalence, healthcare and socio-economic impact of obesity (defined as having a body mass index of ≥ 30 kg.m-2 ) are disproportionately higher in women than men. A combination of biological and social factors, including the adaptation of energy homeostasis to the increased demands of pregnancy and lactation and poor access to healthy foods or exercise facilities, contribute to the increasing prevalence of obesity in women. Obesity-related physiological changes stem from mass loading and increased metabolism of adipose tissue, as well as secretion of bioactive substances from adipocytes leading to chronic low-grade inflammation. As a result, obesity is associated with increased risks of: infertility; malignancy; sleep-disordered breathing; cardiovascular disease; diabetes; and thromboembolism. Hence, obese women are at markedly increased risk of peri-operative morbidity and mortality and require comprehensive evaluation and targeted comorbidity optimisation by a multidisciplinary team. In addition to routine obstetric challenges, pregnancy in women with obesity further exacerbates the above risks, making multidisciplinary management starting at pre-conception even more important. Weight loss, lifestyle management and optimisation of comorbidity are the cornerstone of reducing obesity-related risks. The anaesthetist plays a vital role within the multidisciplinary team by emphasising weight loss as part of pre-operative comorbidity optimisation, formulation of individualised peri-operative management plans, supervising postoperative care in the high dependency or intensive care settings and providing safe labour analgesia and careful peripartum management for obese parturients.

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.

A risk score for postoperative nausea and/or vomiting in women undergoing cesarean delivery with intrathecal morphine.

BACKGROUND: Postoperative nausea and/or vomiting affects up to 80% of parturients undergoing cesarean delivery, but there is a lack of obstetric-specific risk-prediction models. We performed this study to identify postoperative nausea/vomiting risk factors in parturients undergoing cesarean delivery, formulate an obstetric-specific prediction model (Duke score), and compare its performance against the Apfel score. METHODS: A post-hoc analysis of data from two randomized controlled trials studying nausea/vomiting in women undergoing cesarean delivery with intrathecal morphine. Potential risk factors for postoperative nausea/vomiting within 24 h of surgery with univariate associations with P ≤0.20 were considered for inclusion in the multivariable analysis. After identifying the final multivariable model, we derived our Duke score by assigning points to the selected factors. We then tested the association of the Duke and Apfel scores with postoperative nausea and vomiting, and compared the area-under-the-receiver operating characteristic curve. RESULTS: Analysis included 260 parturients, of whom 146 (56.2%) experienced postoperative nausea/vomiting. Non-smoking during pregnancy (OR 2.29 [95% CI 1.12 to 4.67], P=0.023), and history of postoperative nausea/vomiting after cesarean delivery and/or morning sickness (2.09 [1.12 to 3.91], P=0.021) were independent predictors of postoperative nausea/vomiting and included in the Duke score. Both Duke and Apfel scores trended linearly with postoperative nausea/vomiting risk (Duke P=0.001; Apfel P=0.049) and had comparable areas-under-the-receiver operating characteristic curve (Duke 0.63 [0.57 to 0.70]; Apfel 0.59 [0.52 to 0.65], P=0.155). CONCLUSIONS: Both Duke and Apfel scores exhibited similar but poor predictive performance. Until better tools are developed, routine prophylactic anti-emetics appears to be a reasonable approach in this patient population.

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.

Saccadic delay in multiple sclerosis: A quantitative description.

In multiple sclerosis (MS), eye movement disorders are common and can be quantified with infrared video-oculography. A well-known abnormality is internuclear ophthalmoplegia (INO). This study aims to describe saccadic abnormalities beyond INO and investigate their clinical relevance. A validated standardized infrared oculography protocol, DEMoNS, was used for quantifying saccadic eye movements in three different tasks in MS patients and healthy controls. The relationship between the saccadic parameters and disease characteristics was investigated. Furthermore, the association between saccadic parameters and visual functioning was analysed using logistic regression models, adjusted for possible confounders. This cross-sectional study included 218 subjects with MS and 58 healthy controls. The latency of all saccades was longer in MS patients than in healthy controls. This saccadic delay was larger in subjects with a longer disease duration and more disabled subjects. Furthermore, it was significantly related to presence of a lower vision-related quality of life. This study provided a comprehensive overview of performance of MS patients in different saccadic tasks, compared to healthy controls. Saccadic delay in MS patients was present in all saccadic tasks and was related to advancing disease and visual functioning in daily life.

Saccadic fatigability in the oculomotor system.

BACKGROUND: Fatigue is one of the most common and disabling symptoms in multiple sclerosis (MS), but challenging to quantify. This prospective study investigated if repeated saccadic eye movements enable measurement of oculomotor fatigability and can reflect on perceived fatigue in MS. METHODS: A standardized infrared oculography protocol (DEMoNS) was used for quantifying saccades in MS patients and healthy controls which included a first and a repeated pro-saccadic task (FPT and RPT). Saccadic peak velocity, latency, gain, area under the curve (AUC) and peak velocity divided by amplitude (Pv/Am) were calculated in both tasks. Perception based fatigue was assessed using the Checklist Individual Strength and the Neurological Fatigue Index (NFI). Linear regression models were used for assessing the relation between saccadic parameters and perceived fatigue. RESULTS: This study included 181 MS patients and 58 healthy controls subjects. From FPT to RPT, there were significant changes in saccadic parameters. Latency of both tasks was significantly related to NFI summary score (FPT: ß = 0.022, p = .049, RPT: ß 0.023, p = .021). These relationships were weakened after adjustment for Expanded Disability Status score (p > .05). There was however no significant group difference in changes in saccadic parameters. CONCLUSIONS: This study presents an objective and reproducible method for measuring saccadic fatigability. Saccadic fatigability was found to be of limited use in MS, and should be tested in conditions affecting ocular muscles or the neuromuscular junction.

Diagnosing and quantifying a common deficit in multiple sclerosis: Internuclear ophthalmoplegia.

OBJECTIVE: We present an objective and quantitative approach for diagnosing internuclear ophthalmoplegia (INO) in multiple sclerosis (MS). METHODS: A validated standardized infrared oculography protocol (DEMoNS [Demonstrate Eye Movement Networks with Saccades]) was used for quantifying prosaccades in patients with MS and healthy controls (HCs). The versional dysconjugacy index (VDI) was calculated, which describes the ratio between the abducting and adducting eye. The VDI was determined for peak velocity, peak acceleration, peak velocity divided by amplitude, and area under the curve (AUC) of the saccadic trajectory. We calculated the diagnostic accuracy for the several VDI parameters by a receiver operating characteristic analysis comparing HCs and patients with MS. The National Eye Institute Visual Function Questionnaire-25 was used to investigate vision-related quality of life of MS patients with INO. RESULTS: Two hundred ten patients with MS and 58 HCs were included. The highest diagnostic accuracy was achieved by the VDI AUC of 15° horizontal prosaccades. Based on a combined VDI AUC and peak velocity divided by amplitude detection, the prevalence of an INO in MS calculated to 34%. In the INO group, 35.2% of the patients with MS reported any complaints of double vision, compared to 18.4% in the non-INO group (p = 0.010). MS patients with an INO had a lower overall vision-related quality of life (median 89.9, interquartile range 12.8) compared to patients without an INO (median 91.8, interquartile range 9.3, p = 0.011). CONCLUSIONS: This study provides an accurate quantitative and clinically relevant definition of an INO in MS. This infrared oculography-based INO standard will require prospective validation. The high prevalence of INO in MS provides an anatomically well described and accurately quantifiable model for treatment trials in MS.

A standardized protocol for quantification of saccadic eye movements: DEMoNS.

OBJECTIVE: Quantitative saccadic testing is a non-invasive method of evaluating the neural networks involved in the control of eye movements. The aim of this study is to provide a standardized and reproducible protocol for infrared oculography measurements of eye movements and analysis, which can be applied for various diseases in a multicenter setting. METHODS: Development of a protocol to Demonstrate Eye Movement Networks with Saccades (DEMoNS) using infrared oculography. Automated analysis methods were used to calculate parameters describing the characteristics of the saccadic eye movements. The two measurements of the subjects were compared with descriptive and reproducibility statistics. RESULTS: Infrared oculography measurements of all subjects were performed using the DEMoNS protocol and various saccadic parameters were calculated automatically from 28 subjects. Saccadic parameters such as: peak velocity, latency and saccade pair ratios showed excellent reproducibility (intra-class correlation coefficients > 0.9). Parameters describing performance of more complex tasks showed moderate to good reproducibility (intra-class correlation coefficients 0.63-0.78). CONCLUSIONS: This study provides a standardized and transparent protocol for measuring and analyzing saccadic eye movements in a multicenter setting. The DEMoNS protocol details outcome measures for treatment trial which are of excellent reproducibility. The DEMoNS protocol can be applied to the study of saccadic eye movements in various neurodegenerative and motor diseases.

Closed-loop double-vasopressor automated system vs manual bolus vasopressor to treat hypotension during spinal anaesthesia for caesarean section: a randomised controlled trial.

Hypotension necessitating vasopressor administration occurs commonly during caesarean section under spinal anaesthesia. We developed a novel vasopressor delivery system that automatically administers phenylephrine or ephedrine based on continuous non-invasive arterial pressure monitoring. A phenylephrine bolus of 50 µg was given at 30-s intervals when systolic blood pressure fell < 90% of baseline; an ephedrine bolus of 4 mg was given instead if systolic pressure fell < 90% of baseline together with a heart rate < 60 beats.min(-1). The control group used manual boluses of either phenylephrine 100 µg or ephedrine 8 mg, administered at 1-min intervals based on the same thresholds for systolic pressure and heart rate. This randomised, controlled, double-blinded trial involved 213 healthy women who underwent elective caesarean delivery under spinal anaesthesia using 11 mg hyperbaric bupivacaine with 15 µg fentanyl and 100 µg morphine. The automated vasopressor group had better systolic pressure control, with 37/106 (34.9%) having any beat-to-beat systolic pressure reading < 80% of baseline compared with 63/107 (58.9%) in the control group (p < 0.001). There was no difference in the incidence of reactive hypertension, defined as systolic pressure > 120% of baseline, with 8/106 (7.5%) in the automated vasopressor group vs 14/107 (13.1%) in the control group, or total dose of vasopressors. The automated vasopressor group had lower median absolute performance error of 8.5% vs control of 9.8% (p = 0.013), and reduced incidence of nausea (1/106 (0.9%) vs 11/107 (10.3%), p = 0.005). Neonatal umbilical cord pH, umbilical lactate and Apgar scores were similar. Hence, our system afforded better control of maternal blood pressure and reduced nausea with no increase in reactive hypertension when compared with manual boluses.

Interactive technology in obstetric anaesthesia and analgesia: exploring seamless solutions to jagged problems.

Perioperative care often involves treating rapid changes in a patient's physiological profile that requires timely intervention by anaesthetists. Interactive technology and closed-loop systems are currently developed in obstetric anaesthesia and analgesia for maintaining parameters during caesarean section and epidural analgesia. This review discusses the principles of interactive systems and the use of patient feedback to integrate these interactive systems. The components of an interactive system such as the input sensor or device, microprocessor-based control unit and the effector are introduced. Developments in continuous, non-invasive blood pressure monitoring, control algorithms and smart pump technology would help to redefine how technology can assist obstetric anaesthetists to provide better care and improve clinical outcomes for pregnant women.

Closed-loop double-vasopressor automated system to treat hypotension during spinal anaesthesia for caesarean section: a preliminary study.

Hypotension occurs in most caesarean sections under spinal anaesthesia, necessitating vasopressor administration. However, the optimal dosing regimen remains unclear. We have developed a novel vasopressor delivery system that automatically administers phenylephrine or ephedrine based on continuous non-invasive blood pressure monitoring. This prospective cohort study recruited 55 healthy women under standardised spinal anaesthesia with 2.2 ml hyperbaric bupivacaine 0.5%, 15 µg fentanyl and 100 µg morphine. A 50-µg phenylephrine bolus was given at 1-min intervals when systolic blood pressure fell below 90% of baseline, and a 4-mg ephedrine bolus was given when hypotension developed with bradycardia (heart rate <60 beats.min(-1) ). Systolic blood pressure was within 20% of baseline in 88% of all measurements. Six patients (11%) had one or more measurements above 120% of baseline (1% of all measurements), whereas 36 (65%) had at least one reading below 80% of baseline (11% of total measurements). The system maintained systolic blood pressure at a mean (SD) of -9.1 (7.0)% below baseline, with 5.4 (2.5)% fluctuation. Two patients (4%) experienced pre-delivery nausea. All 5-min Apgar scores were 9.

Silicone oil removal after rhegmatogenous retinal detachment: comparing techniques.

PURPOSE: To assess the outcome of silicone oil removal after rhegmatogenous retinal detachment (RRD) surgery, and to compare results of a two-port (infusion-extraction) versus a three-port (full vitrectomy) approach. METHODS: Primary outcome measure was the rate of redetachment. Secondary outcome measures were visual acuity, rate of intraoperative and postoperative epiretinal membrane removal and complications. RESULTS: We included 147 consecutive cases. There were 15 cases of giant retinal tear, 26 cases of RRD without proliferative vitreoretinopathy (PVR) and 106 cases of RRD with PVR. The overall redetachment rate after silicone oil removal was 17.7%. In the group treated with the two-port technique (n=95), the retina redetached in 16 cases (16.8%), and in the group treated with the three-port technique (n=52), redetachment occurred in 10 cases (19.2%). This difference was not statistically significant (P=0.717; χ (2)-test). There was a significantly higher redetachment rate in cases with a short oil tamponade duration of <2 months. CONCLUSION: We reconfirm a relatively high redetachment rate after silicone oil removal. The risk of redetachment is not lower with the three-port compared with the two-port approach.

Ministry of Health clinical practice guidelines: management of gambling disorders.

The Ministry of Health (MOH) has published clinical practice guidelines on Management of Gambling Disorders to provide doctors and patients in Singapore with evidence-based guidance on the management of gambling disorders. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the MOH clinical practice guidelines on Management of Gambling Disorders for the information of readers of the Singapore Medical Journal. Chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website (http://www.moh.gov.sg/mohcorp/publications.aspx?id=26136). The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines.

The additional value of blood culture bottles in the diagnosis of endophthalmitis.

PURPOSE: To assess the additional value of blood culture bottles (BCBs) in the diagnosis of endophthalmitis by comparing its culture yield with that of conventional media (CM). DESIGN: Retrospective consecutive case series. METHODS: We included patients who were treated between January 2001 and January 2010 for clinically suspected endophthalmitis of any etiology, and had vitreous specimens cultivated in both BCB and CM. RESULTS: Specimens from 85 eyes from 85 patients were included. The culture yield of BCB was 69%, and that of CM was 72% (difference not significant). Adding the results of BCB improved the yield of CM significantly by 13%, resulting in a combined yield of 81%. The sensitivity of detection of Haemophilus influenzae in BCB seemed lower compared with CM, possibly due to the lack of growth factors in the BCB. There was no difference in yield between specimens obtained by tap or by vitrectomy. CONCLUSION: In contrast with earlier reports, we did not find BCB superior to CM. The combined use of BCB and CM increased the pathogen detection rate significantly and should therefore be considered as the microbiological method of choice in the work-up of endophthalmitis.