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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., (© 2023 Association of Anaesthetists.)

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., (© 2023 Association of Anaesthetists.)

Purpose: Several studies found reduced retinal thickness on optical coherence tomography (OCT) in Alzheimer's disease (AD), even in preclinical stages, labelling this technique of interest as biomarker. In this study, we examine retinal thickness changes in preclinical AD, as defined by cognitively normal individuals with amyloid-beta (Aβ) on positron emission tomography (PET)., Methods: For this monocentre study, 145 cognitively healthy monozygotic twins aged ≥ 60 were included from the Netherlands Twin Register taking part in the EMIF-AD PreclinAD study. At baseline, participants underwent [ 18 F] flutemetamol PET that was visually rated for cortical Aβ. Binding potential was calculated as continuous measure for Aβ. Optical coherence tomography (OCT) was performed at baseline and after 22 months to assess changes in total and individual inner retinal layer thickness in the macular region (ETDRS circles) and peripapillary retinal nerve fibre layer thickness. Differences in rate of change between amyloid-beta positive and negative individuals and associations between binding potential and change in retinal thickness were evaluated., Results: Sixteen participants (11%) were positive for Aβ. Change in retinal thickness did not differ in any region between Aβ+ and Aβ- individuals. A positive association between binding potential and change in inner plexiform layer thickness was observed in the inner macular ring (beta = 1.708, CI = 0.575 to 2.841, p = 0.003)., Conclusion: Aβ+ individuals did not differ in rate of change of any retinal layer compared to controls, but higher binding potential at baseline was associated with less IPL thinning over time. Optical coherence tomography (OCT) as a longitudinal screening tool for preclinical AD seems limited, but IPL changes offer leads for further research., (© 2020 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

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., (© 2021 Association of Anaesthetists.)

Purpose: Management of chronic vision threatening auto-immune ocular diseases (AIOD, e.g. uveitis, scleritis) can be challenging. Guidelines recommend a multidisciplinary approach (MDA) with ophthalmologists and rheumatologists, to enhance the recognition of systemic diseases and guide the use of immunosuppressives. However, the indications and results of such an approach have not yet been studied., Methods: A monocentre, retrospective chart review of all patients treated in a MDA between ophthalmologists and rheumatologists, in a Dutch tertiary center. The collaboration was twofold: a combined multidisciplinary team meeting every 2 weeks, and an ophthalmology-dedicated rheumatology outpatient clinic. Primary endpoints of this descriptive study were as follows: indications for MDA, new diagnoses of systemic auto-immune diseases and changes in systemic immunosuppression and prednisone dosages., Results: In total, 157 adults (mean age 46 years, 57% female, median disease duration 19 months) were included, mainly with uveitis (74%) and scleritis (12%). Multidisciplinary approach (MDA)-indications included diagnostic workup (32%), treatment support (44%), diagnostic-and-treatment support (10%) and side effects (8%). A systemic disease was newly diagnosed in eight and already present in 34 patients. At baseline, 54 patients used oral prednisone at >7.5 mg/day. Non-corticoid immunosuppressives, mostly methotrexate, were started in 41% of the patients. During follow-up, systemic prednisone was lowered to ≤7.5 mg/day in 68% of the patients., Conclusion: This evaluation of an MDA-programme in the management of AIOD demonstrated its added value. Mainly, it addressed the high demand for support in managing systemic immunosuppression, resulting in significant corticosteroid tapering. In addition, it resulted in the recognition of underlying systemic diseases., (© 2020 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: There is urgent need for non-invasive diagnostic biomarkers in the preclinical phase of Alzheimer's Disease (AD). Several studies suggest that retinal thickness is reduced in AD. Here, we aim to test the diagnostic value of retinal thickness in preclinical AD, as defined by cognitively normal individuals with amyloid pathology on PET., Methods: One hundred and sixty five cognitively healthy monozygotic twins aged ≥ 60 were included from the Netherlands Twin Register taking part in the European Medical Information Framework for Alzheimer's Disease PreclinAD study. Participants underwent [ 18 F] flutemetamol PET that was visually rated for presence or absence of cortical amyloid beta (Aβ). Binding potential (BP ND ) was calculated as continuous measure for Aβ. Spectral Domain OCT was used to asses total and individual inner retinal layer thickness in the macular region (ETDRS circles) as well as peripapillary retinal nerve fibre layer (pRNFL) thickness. Differences between Aβ+ and Aβ- individuals and associations between BP ND and retinal thickness were analyzed., Results: No differences were found in retinal layer thickness in the macula or pRNFL between Aβ+ and Aβ- individuals. A positive associations between BP ND and macular total retinal thickness was observed in the inner ring (p = 0.018), but this was not statistically significant after correction for multiple testing (p = 0.144). Brain/eye parameters had moderate to high intra-twin correlations (p < 0.001) except visual rating score of Aβ, which did not correlate (r = 0.21, p = 0.068)., Conclusion: Variation in retinal thickness likely reflects genetic differences between individuals, but cannot discriminate between healthy and preclinical AD cases, making its use as biomarker in these early stages limited., (© 2019 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: To investigate causes, diagnostics and treatment modalities for persistent socket pain (PSP) after enucleation and evisceration., Methods: A systematic search was undertaken in accordance with the PRISMA Statement, in PubMed, Embase.com and Thomson Reuters/Web of Science. We searched for relevant papers until the 28th of July 2016. Inclusion criteria were (1) patients with a history of enucleation or evisceration, (2) PSP, (3) report of the cause and/or used diagnostics and/or treatment modality, (4) full text in English, Dutch or Spanish language. Excluded were (1) review articles, (2) comments, and publications concerning, (3) nonhumans, (4) exenterated patients, (5) acute postoperative pain, or (6) periorbital pain without pain in the socket. Given the lack of high quality evidence from randomized controlled trials, we examined all available evidence from primary observational studies and assessed quality within this lower level of evidence., Results: A total of 32 studies were included. Causes of PSP found were prosthesis-related (n = 5), dry socket (n = 2), trochleitis (n = 3), compression of the trigeminal nerve (n = 2), implant-related (n = unknown), inflammation (n = 5), surgery-related (n = 4), neuromas (n = 8), malignant tumours (n = 3), psychiatric/psychosocial (n = 2), phantom pain (n = 149), rarer entities (n = 3) or unknown (n = 14). Nonsurgical treatments suffice for conditions as trochleitis, prosthesis-related pain, dry socket and for phantom pain. Other causes of pain may require more invasive treatments such as implant removal., Conclusion: Careful history and examination can give some direction in the diagnostic procedure; however, PSP is probably multifactorial and the specific origin(s) may remain uncertain. Implant replacement can be an effective treatment. Studies to identifiy less invasive procedures are required., (© 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To report the cosmetic outcome and late effects of enucleation and/or irradiation for retinoblastoma and to evaluate the role of orbital implants., Methods: Patients (age >4 years) enucleated and/or irradiated for retinoblastoma, visiting the hospital for routine follow-up (April 2013 to May 2015), were included in our cross-sectional study. Data were obtained via clinical records, questionnaires, physical measurements and standardized photographs. Two independent observers scored the cosmetic features: upper eyelid position, lower eyelid position, volume deficiency, and prosthesis motility and overall cosmetic appearance., Results: A total of 195 patients participated. Ptosis was seen in 45 (28.3%) patients, lower lid sagging in 45 (28.3%). Both complications were associated with the orbital implant; ptosis being more common with increasing implant size (5.6% without implant, 16.7% with small implant, 37.1% with medium implant and 76.9% with large implant) and lower lid sagging being more common in patients without implant (20% with implant versus 37.5% without). Volume loss of the superior sulcus was seen in 107 sockets (66.9%), most frequent in additionally irradiated patients (χ 2 (2) = 42.7, p < 0.001) and in patients without implant (χ 2 (2) = 11.92, p = 0.003). Prosthesis motility was better in patients with orbital implant, regardless of the size., Conclusion: Minor late and potentially treatable effects were seen in patients with implant. Larger sized implants were associated with a higher incidence of ptosis; implant size did not affect subjective outcome with respect to volume or prosthetic motility. Treatment with EBRT had a less favourable outcome., (© 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To evaluate complications of different types of orbital implants following enucleation for retinoblastoma., Methods: We performed a retrospective chart study of all patients that underwent enucleation as treatment of retinoblastoma between April 1991 and June 2013. Events of implant exposure, extrusion (defined as a complete loss of the implant, or a major exposure that could not be closed) and socket abnormalities were analysed for association with implant type and influence of additional external beam radiation therapy (EBRT) and/or chemotherapy., Results: A total of 224 enucleations in 216 patients (eight bilateral) were identified. Mean age at surgery was 1.9 (median 1.5) years. Of the 219 included enucleated eyes, 20 were not replaced by a primary implant and 18 were replaced by an Allen implant. Scleral wrapped hydroxyapatite (HA) and acrylic implants (polymethylmethacrylate) were inserted in, respectively, 79 and 102 cases. In the total population, 29 treatment or implant-specific events (13.2%) were registered. Main complications were implant exposure n = 10 (4.6%) and extrusion n = 6 (2.7%). The acrylic/sclera group had less exposures or extrusions (5 of 102, 4.9%) compared to the HA/sclera group (10 of 79, 12.7%), although this difference did not quite reach statistical significance (p = 0.06). Additional treatment (chemotherapy and/or EBRT for the fellow eye) was administered in 78 cases (35.8%). The overall complication rate in the entire study population was significantly higher (16.7% versus 5.7%) in the group exposed to additional therapy (OR 3.3; 95% CI 1.30-8.36 p = 0.008). This negative effect of additional therapy was also significant in the combined acrylic/HA group (OR 2.9; 95% CI 0.97-8.46 p = 0.048)., Conclusion: Our results suggest a favourable outcome for acrylic implants compared to the HA implant. Additional treatment with chemotherapy and/or EBRT is associated with an increased risk of complications., (© 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

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., (© 2013 The Association of Anaesthetists of Great Britain and Ireland.)

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., (Anaesthesia © 2012 The Association of Anaesthetists of Great Britain and Ireland.)

Objective: Human mesenchymal stem cells (hMSCs) represent one of the most promising stem cell therapies for traumatic injury and age-related degenerative diseases involving cartilage. However, few genetic factors regulating chondrogenesis of MSCs have been identified. One study showed that zinc-finger protein 145 (ZNF145), a transcription factor, was up-regulated during 3-lineage differentiation of hMSCs. The present study was undertaken to validate whether this novel transcription factor is useful for the repair and regeneration of cartilage., Methods: Human MSCs were transfected with lentiviral short hairpin RNA (for small interfering RNA knockdown of ZNF145) and a lentiviral vector for overexpression of ZNF145, and the effects of ZNF145 on chondrogenesis were studied using quantitative polymerase chain reaction and immunostaining. Microarray and transient expression analyses were used to determine whether ZNF145 is a factor operating upstream of SOX9. Allogeneic transplantation of hMSCs into osteochondral defects in rats was performed to determine the effects of ZNF145 on repair of cartilage in vivo., Results: Small interfering RNA-mediated gene silencing of ZNF145 slowed down chondrogenesis, whereas overexpression of ZNF145 enhanced chondrogenesis. Global gene expression profiling showed up-regulated gene expression in ZNF145-overexpressing MSCs, and transient overexpression of ZNF145 enhanced the expression of SOX9, suggesting that ZNF145 acts as a factor upstream of SOX9, the master regulator of chondrogenesis. Moreover, allogeneic transplantation of hMSCs into osteochondral defects of rat knees showed that ZNF145-overexpressing MSCs repaired cartilage defects better and earlier than empty control MSCs., Conclusion: These findings suggest that ZNF145 gene therapy may be a very useful strategy for improving the quality of cartilage regeneration and repair., (Copyright © 2011 by the American College of Rheumatology.)