Efficacy of biological agents combined with oral immunotherapy (OIT) for food allergy: a protocol for a systematic review and meta-analysis.

INTRODUCTION: Food allergy affects a large population throughout the world. Recently, oral immunotherapy (OIT) has been reported as an effective treatment for severe food allergy. Although OIT was successful in numerous trials in desensitisation, adverse events including anaphylaxis during OIT frequently occur. Additionally, some patients fail to be desensitised after OIT and the response to treatment is often not sustained. As a further adjunctive therapy to facilitate OIT, the role of biological agents has been identified. For example, efficacy and safety of omalizumab as an adjuvant therapy of OIT has become apparent through some RCTs and observational studies. Interest towards this topic is growing worldwide, and ongoing trials will provide additional data on the biologics in food allergy.We aim to systematically analyse the efficacy and safety of OIT combined with biological agents for food allergy. METHODS AND ANALYSIS: This paper provides a protocol for a systematic review of the relevant published analytical studies using an aggregate approach following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. Two authors will perform a comprehensive search for studies on MEDLINE/PubMed, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) databases. Subsequently, two independent authors will perform abstract screening, full-text screening and data extraction. A meta-analysis will be conducted as appropriate. ETHICS AND DISSEMINATION: The protocol of this systematic review will be provided in a peer-reviewed journal. As the researchers will not identify the individual patients included in the studies, they do not need to acquire ethics approval. PROSPERO REGISTRATION NUMBER: CRD42022373015.

Pregnancy-related maternal deaths due to cardiovascular diseases in Japan from 2010 to 2019: an analysis of maternal death exploratory committee data.

OBJECTIVE: Cardiovascular disease (CVD) is the leading cause of maternal deaths in high-income countries. This study aimed to assess the characteristics of maternal deaths due to CVDs and the quality of care provided to patients, and to identify elements to improve maternal care in Japan. METHODS: This descriptive study used the maternal death registration data of the Maternal Deaths Exploratory Committee of Japan between 2010 and 2019. RESULTS: Of 445 eligible pregnancy-related maternal deaths, 44 (9.9%) were attributed to CVD. The most frequent cause was aortic dissection (18 patients, 40.9%), followed by peripartum cardiomyopathy (8 patients, 18.2%), and pulmonary hypertension (5 patients, 11.4%). In 31.8% of cases, cardiopulmonary arrest occurred within 30 min after initial symptoms. Frequent symptoms included pain (27.3%) and respiratory symptoms (27.3%), with 61.4% having initial symptoms during the prenatal period. 63.6% of the patients had known risk factors, with age ≥35 years (38.6％), hypertensive disorder (15.9%), and obesity (15.9%) being the most common. Quality of care was assessed as suboptimal in 16 (36.4%) patients. Cardiac risk assessment was insufficient in three patients with preexisting cardiac disease, while 13 patients had symptoms and risk factors warranting intensive monitoring and evaluation. CONCLUSION: Aortic dissection was the leading cause of maternal death due to CVDs. Obstetrics care providers need to be familiar with cardiac risk factors and clinical warning signs that may lead to impending fatal cardiac events. Timely risk assessment, patient awareness, and a multidisciplinary team approach are key to improving maternal care in Japan.

Regular weighing to prevent excessive gestational weight gain: a study protocol for a systematic review and meta-analysis.

BACKGROUND: Excessive weight gain during pregnancy results in maternal and fetal complications and could further impact offspring. The evidence regarding the association between regular weighing during the antenatal period and excessive weight gain is limited. METHODS: We will systematically review individual and cluster randomized controlled trials that evaluated regular weighing as an intervention compared to weighing only at the first booking of the antenatal visit. Trials that assessed the effectiveness of exercise, diet, or other behavioral interventions will be excluded. Pregnant women with a singleton pregnancy and no preexisting health complications are eligible for the review. The primary outcome will be the proportion of women at term who exceed the upper limit of the target range of weight as defined by the guidelines or recommendations for the population. We will search MEDLINE (via PubMed), Embase (via EMBASE.com ), Scopus, the Cumulative Index to Nursing and Allied Health Literature (CINAHL via EBSCO), The Cochrane Central Register of Controlled Trials (CENTRAL) and the trial protocol registers, ClinicalTrials.gov , and the International Clinical Trials Registry Platform (ICTRP) search portal. Full-text articles, unpublished studies, and ongoing trials reported in any language will be included. Two review authors will independently examine and screen for eligible studies and extract data for synthesis. DISCUSSION: We will discuss the effectiveness of regular weighing as a single intervention on reducing the proportion of women who have excessive gestational weight gain. This study will provide key information for countries to develop guidelines on antenatal care and strategies to tackle excessive gestational weight gain. We will create a "Summary of findings" table (Summary of findings table 1) according to the methods described in the Cochrane Handbook for Systematic Reviews of Interventions. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020212581.

Racial Disparities in Response to a US Food and Drug Administration Safety Communication Regarding the Use of Power Morcellation for the Treatment of Uterine Leiomyoma.

STUDY OBJECTIVE: To investigate whether the rate of increase in the performance of abdominal myomectomy over a laparoscopic approach after the US Food and Drug Administration (FDA) safety communication regarding morcellator use for myomectomy differs among races. DESIGN: Retrospective cohort study. SETTING: The American College of Surgeons National Surgical Quality Improvement data. PATIENTS: Patients aged 18 to 55 years who underwent either laparoscopic or abdominal myomectomy, excluding malignant cases, emergency cases, operations performed by nongynecologic specialists, and cases in which myomectomy was performed during cesarean section. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The odds ratios of abdominal myomectomy over laparoscopic myomectomy before and after the release of the FDA communication were calculated in 3 race categories: white, African American, and other races. In a logistic regression analysis adjusted for possible confounders, including all races, the odds ratio of abdominal myomectomy before and after the FDA communication was 1.30 (95% confidence interval [CI], 1.20-1.41; p <.001). In a logistic regression analysis with a product term of FDA communication exposure and race as a possible effect modifier, the African American population showed a significantly greater change in the odds of abdominal myomectomy over laparoscopic myomectomy in comparison with the white population (1.22; 95% CI, 1.02-1.47; p = .03). In contrast, other races showed no significant change (.83; 95% CI, .64-1.08; p = .17). CONCLUSION: After the FDA communication, the odds ratio of abdominal myomectomy was disproportionately increased in the African American population.

A three-step evaluation for safer curettage treatment of cesarean scar pregnancy.

Dilation and curettage is one of the treatment options for cesarean scar pregnancy, however, it sometimes requires a salvage therapy. Few reports discuss the methods of evaluating cesarean scar pregnancy before therapeutic procedures. We aimed to present a case study in which a three-step approach using a combination of preoperational sonohysterography, hysteroscopy, and laparoscopy was performed to evaluate cesarean scar pregnancy. A 33-year-old, G2P2, Japanese female with a history of two elective cesarean sections was diagnosed with viable cesarean scar pregnancy. We used the three-step approach right after undergoing bilateral uterine artery embolization and confirmed that there was a low possibility of fatal complications and we performed dilation and curettage. These steps could be done safely even if the cesarean scar pregnancy was viable. To perform safer curettage on cesarean scar pregnancy patients, these three steps seem to be useful.

Comparison of pharmacokinetics of mycophenolic acid and its glucuronide between patients with lupus nephritis and with kidney transplantation.

The pharmacokinetics of mycophenolic acid (MPA) and its glucuronide (mycophenolic acid phenolic glucuronide, MPAG) in lupus nephritis (LN) have not been fully characterized. The aim of this study was to evaluate the pharmacokinetics of MPA and MPAG in LN patients by comparing the pharmacokinetics with those of kidney transplant (KT) recipients. Six LN patients (World Health Organization class IV and V) and 24 KT recipients [8 recipients treated with tacrolimus (Tac) and 16 with cyclosporine (CyA)] during the early posttransplantation period were enrolled. Pharmacokinetic parameters of MPA and MPAG were compared between LN patients and Tac-treated or CyA-treated KT recipients. The area under the concentration-time curve (AUC0-12) of MPA normalized to mycophenolate mofetil (MMF) dose (mg/kg) was significantly lower in LN patients and CyA-treated KT recipients than in Tac-treated KT recipients [median (range), 2.19 (0.87-4.23), 2.36 (1.13-5.74), and 4.86 (3.25-6.75) microg x h/mL per mg/kg, P < 0.05 and P < 0.01, respectively]. Dose-normalized MPAG AUC0-12 was significantly lower in LN patients and slightly lower in Tac-treated KT recipients than in CyA-treated KT recipients [median (range), 35.0 (8.34-69.8), 51.6 (34.4-94.8), and 84.1 (34.7-152) microg x h/mL per mg/kg, P < 0.05 and P = 0.13, respectively]. The ratio of MPA AUC5-12 to AUC0-12, an estimate of MPA enterohepatic recirculation, was slightly higher in LN patients and Tac-treated KT recipients than in CyA-treated KT recipients [median (range), 0.44 (0.35-0.56), 0.45 (0.42-0.61), and 0.34 (0.22-0.55), P = 0.29 and P = 0.10, respectively]. Serum creatinine was significantly lower in LN patients than in Tac-treated and CyA-treated KT recipients. In conclusion, the pharmacokinetics of MPA in LN patients is characterized by high MPA clearance and in CyA-treated KT recipients. Despite this higher clearance of MPA, MPAG AUC0-12 was lower in LN patients most likely due to better renal function in LN patients.

Simultaneous determination of mycophenolic acid and its glucuronides in human plasma using isocratic ion pair high-performance liquid chromatography.

Therapeutic drug monitoring (TDM) of mycophenolic acid (MPA) following administration of mycophenolate mofetil (MMF) or the enteric-coated sodium salt of MPA formulations, seems beneficial because of the large intra- and inter-individual variability in MPA pharmacokinetics. MPA is an active component from these oral formulations and are further metabolised to inactive phenolic glucuronide (MPAG) and active acyl glucuronide (AcMPAG). This study aims to determine simultaneously these three metabolites of MMF using isocratic ion pair HPLC and to evaluate the short-term stability of AcMPAG in human plasma. Samples were prepared using solid phase extraction. Chromatographic separation was achieved over an RP column (TSKgel ODS-80Ts, 150 mm x 4.6 mm i.d., 5 microm particle size) with acetonitrile and 30 mM tetra-n-butylammonium bromide containing 5 mM ammonium acetate at pH 9.0 (33/67, v/v) as the mobile phase. The flow rate of the mobile phase was 1ml/min, and the wavelength of determination by UV detection was 250 nm (run time, 16 min). Calibration curves for MPA, MPAG and AcMPAG in human plasma were linear over a concentration range of 0.05-50, 0.1-400 and 0.08-8 microg/ml, respectively. Intra- and inter-assay R.S.D. were<6.5%. Extraction efficiencies were more than 85% for all analytes. Since AcMPAG was unstable in human plasma, plasma acidification was needed for the quantification of AcMPAG. Large interindividual variability was observed in the AcMPAG pharmacokinetics in the early period after renal transplantation. In conclusion, a simple, accurate and reproducible HPLC method to measure simultaneously these three MMF metabolites has been established. The method will be helpful in evaluating pharmacokinetics of MPA and its glucuronides.