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.

Automated Interictal Epileptiform Discharge Detection from Scalp EEG Using Scalable Time-series Classification Approaches.

Deep learning for automated interictal epileptiform discharge (IED) detection has been topical with many published papers in recent years. All existing works viewed EEG signals as time-series and developed specific models for IED classification; however, general time-series classification (TSC) methods were not considered. Moreover, none of these methods were evaluated on any public datasets, making direct comparisons challenging. This paper explored two state-of-the-art convolutional-based TSC algorithms, InceptionTime and Minirocket, on IED detection. We fine-tuned and cross-evaluated them on a public (Temple University Events - TUEV) and two private datasets and provided ready metrics for benchmarking future work. We observed that the optimal parameters correlated with the clinical duration of an IED and achieved the best area under precision-recall curve (AUPRC) of 0.98 and F1 of 0.80 on the private datasets, respectively. The AUPRC and F1 on the TUEV dataset were 0.99 and 0.97, respectively. While algorithms trained on the private sets maintained their performance when tested on the TUEV data, those trained on TUEV could not generalize well to the private data. These results emerge from differences in the class distributions across datasets and indicate a need for public datasets with a better diversity of IED waveforms, background activities and artifacts to facilitate standardization and benchmarking of algorithms.

Ostracods as pollution indicators in Lap An Lagoon, central Vietnam.

Southeast Asia is particularly susceptible to the negative impacts of increasing coastal pollution as coastal populations and cities grow at unprecedented rates. Although water chemistry can be monitored, there are greater advantages in using bioindicators as reflectors of the combined effect of multiple pollution types on coastal ecosystem health and for early detection of the negative impacts of pollutants on biotic systems. This study explores the utility and application of ostracods as pollution bioindicators and examines the response of ostracod assemblages to variable pollution in Lap An Lagoon, central Vietnam. From 14 sites within the lagoon, 79 species of 46 genera were identified and sediment grain size, total organic carbon, organic matter and heavy metal concentration were measured. Cluster analysis, detrended correspondence analysis and canonical correspondence analysis identified four distinct ostracod biofacies that were highly correlated to the physical environmental variables (salinity, depth, sediment type, heavy metal concentrations, total organic carbon and organic matter) and are shown to be the main factors controlling ostracod biofacies. Low ostracod diversities were found in silty sediments with heavy metal concentrations likely toxic. Sinocytheridea impressa was indicative of a marginally polluted environment within the lagoon. This study provides evidence for the potential for Southeast Asian ostracods to be used in water quality assessments and the data collected can be used as a baseline for future pollution monitoring.

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.

Dimeric FcγR ectodomains detect pathogenic anti-platelet factor 4-heparin antibodies in heparin-induced thromobocytopenia.

Essentials FcγRIIa mediates life-threatening heparin-induced thrombocytopenia (HIT). Most anti-platelet factor (PF)4-heparin IgGs are not pathogenic so diagnosis of HIT is challenging. Dimeric rsFcγRIIa was used to quantify receptor-binding activity of anti-PF4-heparin antibodies. Dimeric rsFcγRIIa binding specifically correlated with occurrence of HIT. SUMMARY: Background Heparin-induced thrombocytopenia (HIT) is a major and potentially fatal consequence of antibodies produced against platelet factor 4 (PF4)-heparin complexes following heparin exposure. Not all anti-PF4-heparin antibodies are pathogenic, so overdiagnosis can occur, with resulting inappropriate use of alternative anticoagulation therapies that have associated risks of bleeding. However, definitive platelet functional assays are not widely available for routine analysis. Objectives To assess the utility of dimeric recombinant soluble FcγRIIa (rsFcγRIIa) ectodomains for detecting HIT antibodies. Patients/Methods Plasma from 27 suspected HIT patients were tested for pathogenic anti-PF4-heparin antibodies by binding of a novel dimeric FcγRIIa ectodomain probe. Plasmas were also tested by the use of PF4-heparin IgG ELISA, the HemosIL AcuStar HIT IgG-specific assay, and a serotonin release assay (SRA). Results The dimeric rsFcγRIIa test produced no false positives and excluded four samples that were positive by IgG ELISA. In this small patient cohort, the novel assay correctly assigned 93% of the suspected HIT patients, with two of the HIT patients being scored as false negatives. The improved discrimination of the novel assay over the IgG ELISA, which scored four false positives, supports the mechanistic interpretation that binding of dimeric rsFcγRIIa detects pairs of closely spaced IgG antibodies in PF4-heparin immune complexes. Conclusions This study found the cell-free, function-based dimeric rsFcγRIIa assay to be convenient, simple, and potentially predictive of HIT. The assay had improved specificity over the IgG ELISA, and correlated strongly with the AcuStar HIT IgG-specific assay, warranting further evaluation of its potential to identify HIT in larger patient cohorts.

Acquired factor V deficiency in a patient with myeloma and amyloidosis.

INTRODUCTION: We describe our experience with managing an unusual case of acquired Factor V deficiency (aFVd) in a myeloma patient with demonstrated amyloidosis. METHODS: Following diagnosis, records of previous investigations were sought. Specific clotting factors and inhibitors were tested. The clinical progress and treatment response measured by serial factor V levels and coagulation parameters was then prospectively tracked. RESULTS: A 57 year-old woman presented with spontaneous right knee haemarthrosis in association with bilateral symmetrical polyneuropathy and proteinuria. Coagulation screen showed prolongation of both PT (18.6 s, normal range [9.9-11.4 s]) and aPTT (41.4 s, normal range [25.7-32.9 s]), which were both fully correctable following a mixing study. Liver function, fibrinogen, clotting factor II/VIII/X assays and disseminated intravascular coagulopathy screen was normal. FV level was reduced (19%, normal range [70-170%]). Inhibitor titer was undetectable. Congenital FVd was excluded as her previous coagulation screen was normal. Bone marrow investigation performed for suspected underlying plasma cell dyscrasia showed 60% neoplastic plasma cells. Congo red staining was positive for amyloid within vascular walls of the marrow trephine. She was diagnosed with light chain myeloma and aFVd. She received Bortezomib/Cyclophosphamide/Dexamethasone (VCD) chemotherapy. After one cycle of VCD, serum kappa free light chain (SFLC) was reduced from 6951 mg/L to 3354 mg/L with serial measurements of FV levels showing increment to 76% and normalization of PT/aPTT. CONCLUSION: Plasma cell dyscrasia with amyloidosis should be sought as a cause for aFVD, in particular one where bleeding manifestation is profound even with the absence of demonstrable inhibitors.

Safety and efficacy of warfarin in patients with moderate thrombocytopenia.

INTRODUCTION: Patients with moderate thrombocytopenia and comorbidities requiring anticoagulation are currently sub-optimally treated because of bleeding concerns. Guidance on anticoagulating such patients is currently lacking because of limited data on safety and efficacy of anticoagulation in such patients. METHODS: This retrospective study compared the incidence of bleeding and thrombosis in a cohort of warfarinized patients with sustained platelet counts below 100×109/L against a cohort with normal platelet counts (>140×109/L). Primary outcomes of safety and efficacy were determined by incidence rate ratios (IRR) of bleeding and thrombotic events. International normalized ratio (INR) and platelet counts during adverse events in thrombocytopenic arm were secondary outcomes. RESULTS: 137 thrombocytopenic patients (104,985 patient-exposure days) were compared against 939 normal patients (715,193 patient-exposure days). IRR of minor, major bleeding and thrombosis among thrombocytopenic patients were 3.03 (95% CI: 1.57-5.60), 1.48 (95% CI: 0.44-3.98), and 0.807 (95% CI: 0.09-3.43) respectively. Median INR and platelet count readings during minor and major bleeds were 3.60 (IQR: 2.70-4.12) and 3.12 (IQR: 2.82-4.22), and 99×109/L (IQR: 77.0-147.0×109/L) and 115×109/L (IQR: 107.5-169.5×109/L) respectively. CONCLUSION: Warfarinized thrombocytopenic patients are at higher risk of minor bleeding complications with a higher tendency for major bleeding but derive similar benefits against thrombotic events compared to normal patients. Bleeding events are associated with higher INRs. A narrow INR target with an upper limit below 2.5 together with closer anticoagulation monitoring may improve safety of patients.

Diagnosis of human enterovirus A71 infection in Malaysia using a commercial IgM-capture enzyme-linked immunosorbent assay and an IgM-colloidal gold immunochromatographic assay.

Hand, foot and mouth disease (HFMD) is a common childhood infection caused by many enteroviruses, including enterovirus A71 (EV-A71). As EV-A71 is associated with severe neurological disease, early diagnosis is critical for clinical and public health management. In developing countries such as Malaysia, laboratory capacity to carry out EV-A71 IgM detection is greater than that of the gold standard methods of virus culture or molecular detection. This study evaluated two diagnostic kits, EV-A71 IgM-capture enzyme-linked immunosorbent (ELISA) and EV-A71 IgM-colloidal gold immunochromatographic assay (GICA), which had previously only been assessed in China. The assays were tested with 89 serum samples from patients with suspected HFMD. The sensitivity, specificity, positive predictive value, and negative predictive value rates were 78.4%, 80.8%, 74.4%, and 84.0%, respectively, for the IgM-capture ELISA, and 75.7%, 76.9%, 70.0%, and 81.6% for the IgM GICA. These performance measures were similar between the two assays. Concordance between the two assays was 91.1%. The sensitivity rates were lower than those previously reported, likely because the multiple circulating EV-A71 genotypes in Malaysia differ from the C4 subgenotype found in China and used in the assays. Both assays had low false positive rates (12.5% and 16.7% for ELISA and GICA, respectively) when tested on sera from patients confirmed to have enteroviruses. Both diagnostic kits are suitable for early diagnosis of HFMD caused by EVA71 in Malaysia, but confirmation with culture or PCR is still important.

Diagnosis of human enterovirus A71 infection in Malaysia using a commercial IgM-capture enzyme-linked immunosorbent assay and an IgM-colloidal gold immunochromatographic assay

Hand, foot and mouth disease (HFMD) is a common childhood infection caused by many enteroviruses, including enterovirus A71 (EV-A71). As EV-A71 is associated with severe neurological disease, early diagnosis is critical for clinical and public health management. In developing countries such as Malaysia, laboratory capacity to carry out EV-A71 IgM detection is greater than that of the gold standard methods of virus culture or molecular detection. This study evaluated two diagnostic kits, EV-A71 IgM-capture enzyme-linked immunosorbent (ELISA) and EV-A71 IgM-colloidal gold immunochromatographic assay (GICA), which had previously only been assessed in China. The assays were tested with 89 serum samples from patients with suspected HFMD. The sensitivity, specificity, positive predictive value, and negative predictive value rates were 78.4%, 80.8%, 74.4%, and 84.0%, respectively, for the IgM-capture ELISA, and 75.7%, 76.9%, 70.0%, and 81.6% for the IgM GICA. These performance measures were similar between the two assays. Concordance between the two assays was 91.1%. The sensitivity rates were lower than those previously reported, likely because the multiple circulating EV-A71 genotypes in Malaysia differ from the C4 subgenotype found in China and used in the assays. Both assays had low false positive rates (12.5% and 16.7% for ELISA and GICA, respectively) when tested on sera from patients confirmed to have enteroviruses. Both diagnostic kits are suitable for early diagnosis of HFMD caused by EV- A71 in Malaysia, but confirmation with culture or PCR is still important.

Sciatic nerve repair with tissue engineered nerve: Olfactory ensheathing cells seeded poly(lactic-co-glygolic acid) conduit in an animal model.

BACKGROUND AND AIM: Synthetic nerve conduits have been sought for repair of nerve defects as the autologous nerve grafts causes donor site morbidity and possess other drawbacks. Many strategies have been investigated to improve nerve regeneration through synthetic nerve guided conduits. Olfactory ensheathing cells (OECs) that share both Schwann cell and astrocytic characteristics have been shown to promote axonal regeneration after transplantation. The present study was driven by the hypothesis that tissue-engineered poly(lactic-co-glycolic acid) (PLGA) seeded with OECs would improve peripheral nerve regeneration in a long sciatic nerve defect. MATERIALS AND METHODS: Sciatic nerve gap of 15 mm was created in six adult female Sprague-Dawley rats and implanted with PLGA seeded with OECs. The nerve regeneration was assessed electrophysiologically at 2, 4 and 6 weeks following implantation. Histopathological examination, scanning electron microscopic (SEM) examination and immunohistochemical analysis were performed at the end of the study. RESULTS: Nerve conduction studies revealed a significant improvement of nerve conduction velocities whereby the mean nerve conduction velocity increases from 4.2 ΁ 0.4 m/s at week 2 to 27.3 ΁ 5.7 m/s at week 6 post-implantation (P < 0.0001). Histological analysis revealed presence of spindle-shaped cells. Immunohistochemical analysis further demonstrated the expression of S100 protein in both cell nucleus and the cytoplasm in these cells, hence confirming their Schwann-cell-like property. Under SEM, these cells were found to be actively secreting extracellular matrix. CONCLUSION: Tissue-engineered PLGA conduit seeded with OECs provided a permissive environment to facilitate nerve regeneration in a small animal model.

Re-ordering chaotic carbon: origins and application of textured carbon.

Formation of nanocrystals with preferred orientation within the amorphous carbon matrix has attracted lots of theoretical and experimental attentions recently. Interesting properties of this films, easy fabrication methods and practical problems associated with the growth of other carbon nanomaterials such as carbon nanotubes (CNTs) and graphene gives this new class of carbon nanostructure a potential to be considered as a replacement for some applications such as thermal management at nanoscale and interconnects. In this short review paper, the fabrication techniques and associated formation mechanisms of these nanostructured films have been discussed. Besides, electrical and thermal properties of these nanostructured films have been compared with CNTs and graphene.

Heparin-induced thrombocytopenia: evaluation of IgG and IgGAM ELISA assays.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a rare complication of heparin therapy resulting from antibody production to platelet factor 4 and heparin complexes (H-PF4). METHODS: We have evaluated four enzyme-linked immunosorbent assay (ELISA)-based screening tests to identify the best assay(s) with the highest specificity but without underdiagnosis of HIT. As functional assays are difficult to perform, ELISAs are useful to provide clinicians with a timely answer. Over a 10-month period, all samples (N=107) referred to our laboratory were tested for HIT antibodies using four commercially available ELISA kits, two detecting IgG/A/M anti-H-PF4 antibodies and the other two IgG specific. RESULTS: Twenty-eight samples were positive by at least one assay; IgGAM ELISAs were found to be more sensitive with 24 samples positive by Asserachrom IgGAM and 23 by Zymutest IgGAM. Only 18 samples were positive by GTI-PF4-IgG and Zymutest IgG. The gold standard serotonin release assay (SRA) was used as a confirmation assay, and 11/28 samples tested positive. All these SRA-positive samples were positive by all four assays. None of the IgGAM-only-positive samples was found to be positive by SRA suggesting a better specificity for the IgG-only assays. CONCLUSION: Our data strongly support the use of IgG-only assays for the detection of HIT antibodies.

Femtosecond laser induced surface nanostructuring and simultaneous crystallization of amorphous thin silicon film.

Ultrafast pulsed laser irradiation is demonstrated to be able to produce surface nano-structuring and simultaneous crystallization of amorphous silicon thin film in one step laser processing. After fs laser irradiation on 80 nm-thick a-Si deposited on Corning 1737 glass substrate, the color change from light yellow to dark brown was observed on the sample surface. AFM images show that the surface nano-spike pattern was produced on amorphous-Si:H film by fs laser irradiation. Furthermore, micro-Raman results indicate that the a-Si has been crystallized into nanocrystalline Si. Also, the absorptance of the fs laser treated Si thin film was found to increase in the spectrum range of below bandgap compared to original untreated a-Si. The developed process has a potential application in fabrication of high efficiency Si thin film solar cells.