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Introduction: There are conflicting reports on the effect of pregnancy on liver transaminase (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) levels. In this study, we sought to investigate the trajectories of AST and ALT levels during normal pregnancy and to compare them with AST and ALT levels of matched nonpregnant controls., Materials and Methods: Our multicenter retrospective study included 34,396 women who delivered at term at 12 primary maternity care units between January 2011 and December 2018 and 57,152 nonpregnant women younger than 45 years who received a medical checkup between 2016 and 2019. After matching at a ratio of 1:1 for adjustment of several factors (age, weight, and height), a total of 30,460 normal pregnant women and 30,460 nonpregnant women were selected for this study. We measured serum AST and ALT levels during each trimester and the postpartum period to compare with those of the nonpregnant women., Results: The ALT level began to decrease in the first half of the third trimester and was lowest in the second half of third trimester and at postpartum day 1 (median [interquartile range]: 8 [6-11] U/L, 8 [6-10] U/L, respectively). The decline reversed and returned to the level of a nonpregnant state by postpartum days 2-7. The AST level remained unchanged regardless of pregnancy. The prevalence of abnormal liver transaminases (AST >40 U/L and ALT >40 U/L) was <1% at third trimester; however, it increased to 3-5% on postpartum days 2-7., Conclusions: The ALT level was lower during pregnancy compared with nonpregnant women matched for several factors, whereas the AST level remained unchanged during pregnancy. Understanding the trajectories of AST and ALT levels during pregnancy may facilitate early recognition and diagnosis of impaired liver function, including liver disease and pregnancy complications that affect liver transaminases, such as pre-eclampsia and HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. more...

Background: A new voltage-gated Ca 2+ channel α 2 δ ligand, mirogabalin, was first approved for treating peripheral neuropathic pain in Japan in 2019. This is the first report on the prescription status of mirogabalin using a large-scale prescription database., Research Design and Methods: The authors analyzed the prescription data of 12,924 patients prescribed mirogabalin between 1 June and 31 August 2020. The endpoints were the number of patients prescribed, prescription days, prescription doses, dose changes, co-prescription patterns, medication possession ratio (MPR), and treatment discontinuation rates (TDRs)., Results: Mirogabalin was newly prescribed to 7,914 patients in the 3-month study period. Most patients were prescribed mirogabalin at about 10 mg/day during the study period, and 30.9% of patients were prescribed ≥ 20 mg/day on Day 90 after the first prescription. The most frequently prescribed concomitant drug was celecoxib. The MPR (80 to 110%) was 86.2%, indicating good treatment adherence. The cumulative TDRs during ≤ 7 Days, Days 31-60, and 61-90 were 14.0%, 70.0%, and 77.9%, respectively., Conclusions: Mirogabalin was prescribed to a considerable number of patients. These results may be useful for optimizing mirogabalin use for patients with peripheral neuropathic pain in daily clinical practice., Clinical Trial Registration Number: UMIN000042592. more...

Objective: To elucidate the efficacy and safety of MRgFUS in the treatment for refractory pain derived from medial knee OA., Methods: Twenty patients with medial knee OA eligible for total knee arthroplasty were included in this prospective, non-controlled study (UMIN000010193). MRgFUS treatment was provided at the site of most severe tenderness around the medial femorotibial joint of each patient under real-time monitoring of temperature. The goal temperature of the targeted bone surface was 55 °C. Numerical rating scale (NRS) worst pain scores, Western Ontario and McMaster Universities osteoarthritis index (WOMAC) scores, EuroQol 5 dimensions index (EQ-5D) scores and pressure pain threshold (PPT) were evaluated before treatment (baseline) and at 1 week and 1, 3, 6, and 12 months post-treatment, respectively. Complications and adverse events were also assessed clinically and radiographically., Results: Treatment response (a 50% or greater decrease in NRS score) was seen in 14 patients (14/19, 73.7%) at 12 months post-treatment. Mean NRS score rapidly decreased at 1 month after treatment and continued to decline through the following 12 months. At final follow-up, mean NRS score was 3.2 ± 1.9, significantly lower than at baseline ( p  = 0.0013). Mean WOMAC and EQ-5D scores also improved significantly from 1 month after treatment. Fifteen patients showed significant sustained increases in PPTs at the sites of most severe tenderness. No serious adverse events were observed during and after treatment., Conclusions: MRgFUS treatments were effective not only for managing refractory pain, but also for improving physical functions without adverse events in elderly patients with medial knee OA. more...

Pregabalin is one of the first-line treatments approved for the management of neuropathic pain (NeP). While many patients benefit from treatment with pregabalin, they are often treated with suboptimal doses, possibly due to unfamiliarity around prescribing the drug and/or side effects that can occur with up-titration. This narrative review discusses key aspects of initiating, titrating, and managing patients prescribed pregabalin therapy, and addresses concerns around driving and the potential for abuse, as well as when to seek specialist opinion. To ensure that patients derive maximum therapeutic benefit from the drug, we suggest a 'low and slow' dosing approach to limit common side effects and optimize tolerability alongside patients' expectations. When requiring titration to higher doses, we recommend initiating 'asymmetric dosing,' with the larger dose in the evening. Fully engaging patients in order for them to understand the expected timeline for efficacy and side effects (including their resolution), can also help determine the optimal titration tempo for each individual patient. The 'low and slow' approach also recognizes that patients with NeP are heterogeneous in terms of their optimal therapeutic dose of pregabalin. Hence, it is recommended that general practitioners closely monitor patients and up-titrate according to pain relief and side effects to limit suboptimal dosing or premature discontinuation. more...

Background: Chronic pain is often difficult to treat, and many patients are not satisfied with analgesic treatment. The authors assessed patient satisfaction with oral analgesics in patients with chronic pain in Japan., Research Design and Methods: This was an observational cross-sectional study conducted in dispensing pharmacies. A patient satisfaction questionnaire survey was conducted in 781 patients prescribed one nonsteroidal anti-inflammatory drug (NSAID) or neuropathic pain (NeP) drug for at least 90 consecutive days. The primary endpoint was patient satisfaction with analgesics. The secondary endpoints were pain relief, activity of daily living (ADL) improvement and doctor-patient communication., Results: The proportions of patients who answered 'satisfied if anything' or better for patient satisfaction in the NSAID and NeP drug groups were 70.0% and 65.2%, respectively, whereas those of patients who answered 'satisfied' were 43.3% and 29.4%, respectively. The proportions of patients with improved pain relief, ADL improvement, and good doctor-patient communication were numerically higher than those of patients who answered 'satisfied if anything' or better., Conclusions: Approximately two-thirds of the patients were satisfied with current analgesics. Patient satisfaction with oral analgesics could be influenced by multiple factors., Clinical Trial Registration Number: UMIN000036456. more...

Background : Information on prescriptions of oral analgesics for the treatment of pain is beneficial. However, there have been few reports on the prescription status of oral analgesics from a nation-wide, large-scale prescription database in Japan. Research design and methods : The authors analyzed the prescription data of 2,042,302 patients prescribed oral analgesics in 2017. The numbers/proportions of patients prescribed oral analgesics, adherence with approved doses, co-prescription patterns, dose changes, drug adherence, and treatment-discontinuation rates were evaluated. Results : Loxoprofen was prescribed to 32.5% of the patients, followed by celecoxib, prescribed to 16.0% of patients. Acetaminophen and pregabalin were prescribed to 10.5% and 9.4% of patients, respectively. Many analgesics were prescribed at lower doses than the approved doses. The most frequently used concomitant medication was pregabalin. For duloxetine and pregabalin, high proportions of patients were prescribed these drugs for > 90 days. Conclusions : Loxoprofen was the most prescribed of the non-steroidal anti-inflammatory drugs in Japan. The information obtained provides an overview of prescribed oral analgesics in Japan and could be useful for potential research into prescribed oral analgesics in the future. more...

Objective: The objective of this study is to identify any correlation between the maternal protein S (PS) activity, which decreases spontaneously during normal pregnancy, and the pregnancy outcome, especially the amount of bleeding during caesarean section (CS)., Materials and Methods: We analyzed 129 pregnant women who received elective CS at our hospital which is a tertiary perinatal center. The relationship between the amount of intraoperative hemorrhage and PS activity was estimated by simple linear regression. Univariate and multivariate analyses were also performed to determine whether or not the maternal PS activity was associated with massive hemorrhage (>1000 g)., Results: The maternal PS activity correlated with the amount of intraoperative hemorrhage (p = .048, r = 0.175) and could be an independent predictor of massive hemorrhage (odds ratio 1.06; 95% confidence interval 1.01-1.12; p = .013)., Conclusions: Maternal PS activity was associated with the amount of hemorrhage during CS and the occurrence of massive hemorrhage. PS activity reduction naturally occurring during pregnancy could contribute to alleviation of massive hemorrhage. more...

Postpartum haemorrhage (PPH) is a potentially life-threatening condition. Women undergoing caesarean section (CS) are at particular risk, and improvements in the management of PPH during CS are required. We investigated the use of a tissue hardness metre to quantify uterine contractions during CS with a view to its application for obstetric bleeding management. Fifty pregnant women at term who underwent elective CS were recruited. Using a tissue hardness metre, we measured uterine hardness twice during CS: after placental removal and before peritoneum closure. Each measurement was conducted at two standardised points: fundus and corpus uteri. Concurrently, obstetricians subjectively graded uterine contractions as weak, medium, or strong. The hardness metre accurately quantified the degree of uterine contraction assessed by the obstetricians, and could be an effective clinical tool for early recognition of intra-operative massive bleeding. IMPACT STATEMENT What is already known on this subject? Maintaining adequate uterine contraction leads to prevention of excessive blood loss, which decreases the incidence and severity of PPH. However, the assessment of uterine contraction is currently judged by obstetricians, who manually and subjectively evaluate uterine contraction according to uterine hardness. Therefore, uterine atony remains a clinical diagnosis without a universal definition. What do the results of this study add? The present study investigated the use of a tissue hardness metre to quantify uterine contractions during CS with a view to its application for obstetric bleeding management. The hardness metre was able to quantify the degree of uterine contraction perceived by obstetricians. Quantifying uterine hardness during CS correlates with the amount of intra-operative bleeding and is useful for early recognition of massive haemorrhage. What are the implications of these findings for clinical practice and/or further research? To improve the management of atonic PPH and avoid serious complications, the tissue hardness metre should be considered as a potential clinical tool during CS. more...

Maternal inflammation is associated with spontaneous preterm birth and respiratory impairment among premature infants. Recently, molecular hydrogen (H2) has been reported to have a suppressive effect on oxidative stress and inflammation. The aim of this study was to evaluate the effects of H2 on fetal lung injury caused by maternal inflammation. Cell viability and the production of interleukin-6 (IL-6) and reactive oxygen species (ROS) were examined by treatment with lipopolysaccharide (LPS) contained in ordinal or H2-rich medium (HM) using a human lung epithelial cell line, A549. Pregnant Sprague Dawley rats were divided into three groups: Control, LPS, and HW + LPS groups. Rats were injected with phosphate-buffered saline (Control) or LPS intraperitoneally (LPS) on gestational day 19 and provided H2 water (HW) ad libitum for 24 h before LPS injection (HW + LPS). Fetal lung samples were collected on day 20, and the levels of apoptosis, oxidative damage, IL-6, and vascular endothelial growth factor (VEGF) were evaluated using immunohistochemistry. The number of apoptotic cells, and levels of ROS and IL-6 were significantly increased by LPS treatment, and repressed following cultured with HM in A549 cells. In the rat models, the population positive for cleaved caspase-3, 8-hydroxy-2'-deoxyguanosine, IL-6, and VEGF was significantly increased in the LPS group compared with that observed in the Control group and significantly decreased in the HW + LPS group. In this study, LPS administration induced apoptosis and oxidative damage in fetal lung cells that was ameliorated by maternal H2 intake. Antenatal H2 administration may decrease the pulmonary mobility associated with inflammation in premature infants. more...