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1.
J Infect Chemother ; 29(1): 33-38, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36103949

RESUMO

BACKGROUND: Information regarding effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant strains on clinical manifestations and outcomes of coronavirus disease 2019 (COVID-19) in pregnant women is limited. METHODS: A retrospective observational study was conducted using the data from the nationwide COVID-19 registry in Japan. We identified pregnant patients with symptomatic COVID-19 hospitalized during the study period. The Delta and Omicron variants of concern (VOC) predominant periods were defined as August 1 to December 31, 2021 and January 1 to May 31, 2022, respectively. Clinical characteristics were compared between the patients in the Delta and Omicron VOC periods. In addition, logistic regression analysis was performed to identify risk factors for developing moderate-to-severe COVID-19. RESULTS: During the study period, 310 symptomatic COVID-19 cases of pregnant women were identified; 111 and 199 patients were hospitalized during the Delta and Omicron VOC periods, respectively. Runny nose and sore throat were more common, and fatigue, dysgeusia, and olfactory dysfunction were less common manifestations observed in the Omicron VOC period. In the multivariable logistic regression analysis, onset during the later stage of pregnancy (OR: 2.08 [1.24-3.71]) and onset during the Delta VOC period (OR: 2.25 [1.08-4.90]) were independently associated with moderate-to-severe COVID-19, whereas two doses of SARS-CoV-2 vaccine were protective against developing moderate-to-severe COVID-19 (OR: 0.34 [0.13-0.84]). CONCLUSIONS: Clinical manifestations of COVID-19 in pregnant women differed between the Delta and Omicron VOC periods. SARS-CoV-2 vaccination was still effective in preventing severe COVID-19 throughout the Delta and Omicron VOC periods.


Assuntos
COVID-19 , Complicações Infecciosas na Gravidez , Humanos , Feminino , Gravidez , Gestantes , COVID-19/epidemiologia , Vacinas contra COVID-19 , SARS-CoV-2 , Complicações Infecciosas na Gravidez/epidemiologia
2.
Soc Psychiatry Psychiatr Epidemiol ; 58(9): 1421-1429, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36928546

RESUMO

BACKGROUND: Discrimination is an important determinant of negative mental health outcomes. This study determined the association between the experience of COVID-19-related discrimination and psychological distress among healthcare workers (HCWs) in Japan. METHODS: This cross-sectional study conducted a health survey among 5703 HCWs of six national medical and research centers in Japan from October 2020 to March 2021. COVID-19-related discrimination was defined either when participants or their family members were badmouthed or when they felt discriminated against in some way. We used the Kessler Psychological Distress Scale (K6) to assess the presence of severe psychological distress (≥ 13 points). We used logistic regression models to examine the association between discrimination and psychological distress. We also identified factors associated with discrimination. RESULTS: Of the participants, 484 (8.4%) reported COVID-19-related discrimination and 486 (8.5%) had severe psychological distress. HCWs who were female vs. male (adjusted odds ratio [AOR] = 1.41, 95% confidence interval [CI] = 1.28-1.55), had high vs. low viral exposure (AOR = 2.31, 95% CI = 1.81-2.93), and worked for 11 or more hours/day vs. 8 or less hours/day (AOR = 1.42, 95% CI = 1.35-1.49) were more likely to have experienced COVID-19-related discrimination. The AOR (95% CI) of severe psychological distress was 1.83 (1.29-2.59) among those who experienced discrimination. In the stratified analysis by sociodemographic and job-related factors, all the interactions did not reach statistical significance (p for interaction > 0.20). CONCLUSION: Experience of COVID-19-related discrimination was associated with severe psychological distress among HCWs. During the pandemic, effective measures should be taken to prevent the development of negative mental health outcomes in HCWs who experience discrimination.


Assuntos
Pesquisa Biomédica , COVID-19 , Angústia Psicológica , Humanos , Masculino , Feminino , COVID-19/epidemiologia , Estudos Transversais , Japão/epidemiologia , Pessoal de Saúde/psicologia , Inquéritos Epidemiológicos
3.
Clin Infect Dis ; 75(1): e397-e402, 2022 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-35037051

RESUMO

BACKGROUND: Several studies have investigated whether pregnancy is a risk factor for developing severe coronavirus disease 2019 (COVID-19); however, the results remain controversial. In addition, the information regarding risk factors for developing severe COVID-19 in pregnant women is limited. METHODS: A retrospective cohort study analyzing the data from the nationwide COVID-19 registry in Japan was conducted. Propensity score-matched analysis was performed to compare COVID-19 severity between pregnant and nonpregnant women. Multivariate analysis was also conducted to evaluate risk factors for developing moderate-to-severe COVID-19 in pregnant women. RESULTS: During the study period, 254 pregnant and 3752 nonpregnant women of reproductive age were identified. After propensity score matching, 187 pregnant women and 935 nonpregnant women were selected. A composite outcome of moderate-to-severe COVID-19 was more frequently observed in pregnant women than that of nonpregnant women (n = 18 [9.6%] vs n = 46 [4.9%]; P = .0155). In multivariate analysis, the presence of underlying diseases and being in the second-to-third trimester of pregnancy were recognized as risk factors for moderate-to-severe COVID-19 in pregnant women (odds ratio [95% confidence interval]: 5.295 [1.21-23.069] and 3.871 [1.201-12.477], respectively). CONCLUSIONS: Pregnancy could be a risk factor for moderate-to-severe COVID-19 for women in Japan. In addition to the presence of comorbidities, advanced pregnancy stages may contribute to greater risks for developing moderate-to-severe COVID-19 in pregnant women.


Assuntos
COVID-19 , Complicações Infecciosas na Gravidez , COVID-19/epidemiologia , Feminino , Humanos , Japão/epidemiologia , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Resultado da Gravidez/epidemiologia , Gestantes , Pontuação de Propensão , Sistema de Registros , Estudos Retrospectivos , SARS-CoV-2
4.
Prev Med ; 161: 107123, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35787841

RESUMO

The effect of heated tobacco products (HTPs) use and moderate alcohol drinking on immunogenicity to coronavirus disease (COVID-19) vaccines remain elusive. This study aimed to examine the association of tobacco product use and alcohol consumption with anti-SARS-CoV-2 spike IgG antibody titers after the BNT162b2 vaccine. Participants were 3433 healthcare workers receiving two vaccine doses in the 4 national centers for advanced medical and research in Japan. Smoking status and alcohol consumption were assessed via a questionnaire, and anti-SARS-CoV-2 spike IgG titers were measured with chemiluminescent enzyme immunoassay using serum collected on the median of 64 days after the second vaccination. Multilevel linear regression models were used to estimate the geometric mean titers (GMT) and the ratios of means (RoM) between groups with adjustment for covariates. Compared with never-smokers (GMT = 118), IgG antibody titers were significantly lower among HTPs users (including those who also smoked cigarettes) (GMT = 105; RoM = 0.89 [95%CI: 0.78-0.99]) and exclusive cigarettes smokers (GMT = 98; RoM = 0.81 [95%CI: 0.71-0.92]). Compared with non-drinkers of alcohol (GMT = 123), alcohol drinkers consuming <1 go/day (GMT = 113; RoM = 0.93 [95%CI: 0.88-0.98]), 1-1.9 go/day (GMT = 104; RoM = 0.85 [95%CI: 0.78-0.93]), and ≥ 2 go/day (GMT = 103; RoM = 0.84 [95%CI: 0.74-0.96]) had significantly lower antibody titers (P for trend<0.01). Spline analysis showed a large reduction of antibody until around 1 go/day of alcohol consumption, and then they gradually decreased. Results suggest that in addition to conventional cigarette smoking and heavy alcohol drinking, HTPs use and moderate alcohol drinking may be predictors of lower immunological response to COVID-19 vaccine.


Assuntos
COVID-19 , Produtos do Tabaco , Consumo de Bebidas Alcoólicas , Vacina BNT162 , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Pessoal de Saúde , Humanos , Imunoglobulina G , Japão , Vacinação
5.
J Obstet Gynaecol Res ; 43(9): 1504-1508, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28691359

RESUMO

Chronic histiocytic intervillositis (CHI) is an extremely rare pathological condition but is strongly associated with severe obstetric complications and has a high recurrence rate. The management of this condition has not yet been established. We describe herein the occurrence of CHI in the late second-third trimester in each of three consecutive pregnancies in a single patient with four previous consecutive early miscarriages. In this patient, each of the three complicated pregnancies was managed with one of the following, respectively: low-dose aspirin; heparin plus low-dose aspirin; and prednisolone plus low-dose aspirin. CHI was histologically confirmed in all three pregnancies, but the clinical results and pathology (e.g. extent of histiocytic infiltration) in each pregnancy clearly differed with treatment. Both combination treatments eventuated in a live birth. Immunosuppressive therapy seemed to produce better clinical results by restricting the extent of the affected areas. The elevated alkaline phosphatase associated with the CHI was assumed to have no clinical prognostic value.


Assuntos
Vilosidades Coriônicas/patologia , Histiocitose/patologia , Doenças Placentárias/tratamento farmacológico , Doenças Placentárias/patologia , Adulto , Feminino , Humanos , Nascido Vivo , Gravidez
6.
Reprod Med Biol ; 16(3): 297-301, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-29259481

RESUMO

Aim: An immune etiology for idiopathic recurrent miscarriage is an important issue because a fetus is allogenetically different from the mother. Type 1 T helper (Th1) and Type 2 (Th2) cells have important functions in immune responses and there is a general agreement that pregnancy is associated with Th2 cell dominance. The purpose of this case report is to establish the effectiveness of an immunosuppressive treatment for a patient who had 11 consecutive miscarriages despite several treatments, such as anticoagulation, that showed elevated Th1/Th2 cell ratios. Methods: This patient visited our clinic following 11 consecutive miscarriages between 2009 and 2014 that occurred between 5 and 8 weeks' gestation. The Th1/Th2 cell ratio was evaluated after the 12th conception and she received an immunosuppressive treatment (tacrolimus; 1 mg/d). Results: The Th1/Th2 cell ratio was elevated after the 12th conception, but the patient miscarried, with a normal karyotype of chorionic villi despite the immunosuppressive treatment. After the 13th conception, she began receiving treatment with 2 mg/d of tacrolimus at 4 weeks' gestation, which was continued until delivery. Conclusion: For recurrent miscarriage cases that show an elevated Th1/Th2 cell ratio after achieving pregnancy, immunosuppressive treatment with tacrolimus could be effective.

7.
Arch Gynecol Obstet ; 293(1): 197-202, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26246415

RESUMO

PURPOSE: Follicular fluid (FF) might reflect the environment during follicle and oocyte growth, and an evaluation of oxidative stress in the FF might be useful in predicting oocyte quality. In order to measure the oxidative stress (OS) in the FF from a single follicle of patients with endometrioma (EM), we evaluated whether an EM might affect the environment of follicular growth. METHODS: Between December 2011 and July 2013, 26 patients with a unilateral EM (EM group) and 29 without EM (control group) were enrolled in this study. The FF was obtained during the first puncture of follicular aspiration, and was stored at -30 °C until it was assayed. A Free Radical Elective Evaluator (WISMERLL, USA) was used to perform d-ROM and BAP tests to measure oxidative stress (U.CARR) and antioxidant power (µmol/L). RESULTS: The d-ROM values in the EMC and control groups were 328.7 ± 97.8 and 414.9 ± 84.2, respectively, and the BAP values for the two groups were 2474.3 ± 432.0 and 2552.8 ± 435.58, respectively. These values were similar between the two groups (mean ± SD). The number of patients with a modified BAP/d-ROM ratio of <1.0 in the EM group was similar to that for the control group at 16 and 15, respectively (61.5 and 51.7 %). CONCLUSIONS: The oxidative stress and antioxidant potential in the FF of the patients with unilateral EM showed values similar to those without an EM. Therefore, we concluded that EMs do not affect the environment for follicle growth during ART treatment.


Assuntos
Endometriose/metabolismo , Líquido Folicular/metabolismo , Infertilidade Feminina/metabolismo , Folículo Ovariano/metabolismo , Estresse Oxidativo , Adulto , Antioxidantes/metabolismo , Biomarcadores/sangue , Estudos de Casos e Controles , Endometriose/complicações , Endometriose/patologia , Estradiol/sangue , Feminino , Gonadotropinas/sangue , Humanos , Infertilidade Feminina/etiologia , Infertilidade Feminina/fisiopatologia , Infertilidade Feminina/terapia , Masculino , Oócitos/metabolismo , Oócitos/patologia , Folículo Ovariano/patologia , Folículo Ovariano/fisiologia , Resultado do Tratamento
8.
BMC Pregnancy Childbirth ; 15: 48, 2015 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-25884311

RESUMO

BACKGROUND: Corticosteroid or intravenous immunoglobulin is used in the management of idiopathic thrombocytopenic purpura during pregnancy. CASE PRESENTATION: A patient with idiopathic thrombocytopenic purpura had a previous history of interrupted pregnancy due to severe thrombocytopenia, and was unresponsive to high doses of corticosteroids and intravenous immunoglobulin. Immediately following pregnancy, our patient had a marked elevation in plasma levels of fibrinogen degradation products, D-dimer, and platelet factor 4, with a decrease in platelets, suggesting platelet activation and thrombogenesis. Combined treatment with an anticoagulant agent could prevent exacerbation of thrombocytopenia throughout pregnancy. Although the underlying causes leading to the series in her pregnancy course were uncertain, there were notable serological abnormalities, such as weakly positive antinuclear antibody and anti-U1-RNP antibody. CONCLUSION: When thrombocytopenia rapidly develops in patients with idiopathic thrombocytopenic purpura immediately following pregnancy, the possibility of a thrombogenic state and differential diagnosis, including antiphospholipid syndrome and collagen vascular disease, should be considered. Treatment with an anticoagulant agent might then be appropriate.


Assuntos
Heparina/administração & dosagem , Complicações Hematológicas na Gravidez , Púrpura Trombocitopênica Idiopática , Trombose/prevenção & controle , Adulto , Anticoagulantes/administração & dosagem , Monitoramento de Medicamentos/métodos , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Glucocorticoides/uso terapêutico , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Ativação Plaquetária/efeitos dos fármacos , Contagem de Plaquetas/métodos , Prednisolona/uso terapêutico , Gravidez , Complicações Hematológicas na Gravidez/sangue , Complicações Hematológicas na Gravidez/tratamento farmacológico , Complicações Hematológicas na Gravidez/fisiopatologia , Resultado da Gravidez , Púrpura Trombocitopênica Idiopática/sangue , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/fisiopatologia , História Reprodutiva , Trombose/sangue , Trombose/etiologia , Trombose/fisiopatologia
9.
J Infect Chemother ; 21(4): 238-46, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25708925

RESUMO

The current approach to protecting pregnant women from influenza infection and serious influenza-related complications is vaccination. It is, therefore, critical to evaluate the vaccine's safety, immunogenicity, and protection efficacy during pregnancy. However, because it is affected by previous influenza vaccination or infection, the efficacy of the seasonal trivalent inactivated influenza vaccine is difficult to evaluate in pregnant women. The A/H1N1pdm pandemic in 2009 provided us with the opportunity to evaluate the immunogenicity of the influenza vaccine unaffected by previous vaccinations or infections. Vaccination with inactivated influenza virus during pregnancy elicited neutralizing antibody titers that were sufficient and comparable to those of naturally infected individuals. Furthermore, post-pandemic surveys provided a wealth of definitive information on vaccine efficacy and safety. In addition, transplacental transfer of antibodies following vaccination protected newborn infants against influenza infection. With reports showing the effectiveness of influenza vaccine during pregnancy, it is suggested that influenza vaccination benefits both mothers and their young infants.


Assuntos
Imunidade Materno-Adquirida/imunologia , Vacinas contra Influenza , Influenza Humana , Complicações Infecciosas na Gravidez , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Feminino , Humanos , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/efeitos adversos , Vacinas contra Influenza/imunologia , Influenza Humana/imunologia , Influenza Humana/prevenção & controle , Gravidez , Complicações Infecciosas na Gravidez/imunologia , Complicações Infecciosas na Gravidez/prevenção & controle , Vacinação
10.
J Clin Apher ; 30(5): 305-7, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25413689

RESUMO

Fetal anemia is caused by Rhesus (RhD) sensitization as a result of RhD incompatibility during pregnancy. The severe form of this disease can cause hydrops fetalis leading to intrauterine death. We experienced a highly sensitized 39-year-old woman with B Rh-negative blood. She had a history of three induced abortions and experienced perinatal death associated with hydrops fetalis. During the pregnancy prior to her most recent one, she was treated with double-filtration plasmapheresis (DFPP), high dose γ-globulin and intrauterine fetal blood transfusion (IUT). For her most recent pregnancy, we performed only weekly or fortnightly DFPP from 13 weeks until delivery. Anti-D antibody titer was maintained between 32 and 256 without any signs of fetal anemia. IUT was not required at any stage of the pregnancy. No adverse events were observed. She successfully delivered a healthy male infant weighing 2,289 g by Cesarean section at 35 weeks. Repeated DFPP may be an effective and safe strategy to reduce antibody titers in highly sensitized women with RhD-incompatible pregnancy, avoiding the need for IUT.


Assuntos
Eritroblastose Fetal/prevenção & controle , Plasmaferese/métodos , Complicações na Gravidez/terapia , Isoimunização Rh/terapia , Imunoglobulina rho(D)/sangue , Adulto , Terapia Combinada , Eritroblastose Fetal/imunologia , Transfusão Total , Feminino , Humanos , Hiperbilirrubinemia Neonatal/etiologia , Hiperbilirrubinemia Neonatal/terapia , Recém-Nascido , Masculino , Fototerapia , Gravidez , Complicações na Gravidez/imunologia , Isoimunização Rh/sangue
11.
Mod Rheumatol ; 25(2): 215-8, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25146551

RESUMO

Abstract Objective. To clarify the clinical significance of antiphospholipid antibody (aPL) profile in patients with obstetric antiphospholipid syndrome (APS). Methods. Clinical records of 13 pregnant patients (15 pregnancies) with obstetrical APS were reviewed over 10 years. Patients who met the Sapporo Criteria fully were studied, whereas those with only early pregnancy loss were excluded. In addition to classical aPL: lupus anticoagulant (LA), anticardiolipin antibody (aCL), and anti-ß2-glycoprotein I (aß2GPI); phosphatidylserine-dependent anti-prothrombin antibody (aPS/PT) and kininogen-dependent anti-phosphatidylethanolamine antibody (aPE) were also examined in each case. Results. Cases were divided into two groups according to patient response to standard treatment: good and poor outcome groups. All cases with poor outcome presented LA, with IgG aß2GPI and IgG aPS/PT were also frequently observed. IgG aPE did not correlate with pregnancy outcome. Conclusion. aPL profile may predict pregnancy outcome in patients with this subset of obstetric APS.


Assuntos
Anticorpos Anticardiolipina/sangue , Anticorpos Antifosfolipídeos/sangue , Síndrome Antifosfolipídica/diagnóstico , Complicações na Gravidez/diagnóstico , Resultado da Gravidez , Adulto , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/imunologia , Feminino , Humanos , Gravidez , Complicações na Gravidez/sangue , Complicações na Gravidez/imunologia
12.
J Obstet Gynaecol Res ; 39(2): 500-3, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22925573

RESUMO

AIM: Measles during pregnancy has deleterious effects on both perinatal and maternal outcomes. In Japan, local epidemics of measles and cases of measles during pregnancy are still being reported; therefore, the seroprevalence of antibodies to measles is suspected to be still not sufficient. The aim of this study was to analyze the seroprevalence of antibodies to measles in Japanese pregnant women and estimate the percentage of these women who require vaccination or revaccination against measles. MATERIAL AND METHODS: We analyzed the seroprevalence of immunity to measles by the neutralization test in 10 349 pregnant women in the first trimester managed at the National Center for Child Health and Development between February 2004 and December 2010. The neutralization test titers were interpreted as follows: ≧1:8, seropositive; =4, low-positive; ≦4, seronegative. RESULTS: Of the total number of pregnant women tested, 7408 (71.6%) were seropositive, 1864 (18.0%) were low-positive, and 1079 (10.4%) were seronegative for measles antibodies, respectively. CONCLUSION: Our results revealed that 28% of our pregnant population was seronegative or low-positive for measles antibodies, and thought to require revaccination or vaccination. Screening for measles immunity might be advisable for women of childbearing age.


Assuntos
Anticorpos Antivirais/análise , Vírus do Sarampo/imunologia , Vírus do Sarampo/isolamento & purificação , Sarampo/imunologia , Feminino , Humanos , Japão/epidemiologia , Sarampo/epidemiologia , Avaliação das Necessidades , Gravidez , Primeiro Trimestre da Gravidez , Estudos Soroepidemiológicos
13.
J Matern Fetal Neonatal Med ; 36(2): 2258254, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37705258

RESUMO

Some of obstetrical complications such as unexplained pregnancy loss and preeclampsia (PE) are associated with maternal-fetal immune abnormalities, leading to uteroplacental dysfunction, insufficient fetal immune tolerance, or fetal rejection. Immunosuppressants with calcineurin inhibitors could be useful for the prevention of these complications by modulating the cellular immune balance by directly inhibiting activated T-helper (Th) 1 and natural killer (NK)/NKT cells. We present our experience with the immunosuppressant tacrolimus in five pregnant women who had a previous pregnancy history of unexplained or preeclamptic stillbirth. Th1 and Th2 cell populations and NK cell activities in peripheral blood were measured as clinical parameters during pregnancy. Case 1-3 achieved suppressions of predominant Th1 immunity and live births without pregnancy-related complications. In case 4, increased tacrolimus dose after a miscarriage resulted in her first live birth; however, she developed PE and severe fetal growth restriction with elevated Th1/Th2 cell ratios at 26 weeks of gestation. Case 5 had a previous history of early onset PE and the hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome, and an emergency cesarean section was needed for maternal safety at 20 weeks of gestation. The course of the next pregnancy was stable under tacrolimus treatment; however, the HELLP syndrome recurred after PE at 33 weeks of gestation. Although an imbalance in the Th1/Th2 cell ratio was not observed during pregnancy, NK cell activity was markedly elevated before delivery. In conclusion, tacrolimus is a potential drug candidate for the prevention of unexplained or preeclamptic stillbirth with Th1-dominant immune states.


Assuntos
Aborto Espontâneo , Síndrome HELLP , Pré-Eclâmpsia , Humanos , Feminino , Gravidez , Tacrolimo/uso terapêutico , Natimorto , Pré-Eclâmpsia/tratamento farmacológico , Pré-Eclâmpsia/prevenção & controle , Preparações Farmacêuticas , Cesárea , Terapia de Imunossupressão , Imunossupressores/uso terapêutico , Síndrome HELLP/tratamento farmacológico , Síndrome HELLP/prevenção & controle
14.
Medicine (Baltimore) ; 102(32): e34317, 2023 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-37565878

RESUMO

INTRODUCTION: Infertility is estimated to affect 8% to 12% of reproductive-aged couples worldwide. While approximately 85% of infertile couples have an identified cause, the remaining 15% suffer physically and emotionally from unexplained intractable infertility. In recent years, maternal-to-fetal immunological abnormalities have attracted attention as mechanisms that differ from the conventional factors contributing to infertility and pregnancy loss. A T-helper 2 (Th2)-dominant immune state has been proposed as a maternal immune alteration to eliminate rejection and induce tolerance to a semi-allogeneic fetus. An imbalance in Th1 responses would not induce adequate maternal immune tolerance to the fetus or early embryos. Tacrolimus, widely used as an immunosuppressant agent in solid organ transplant recipients, is expected to suppress maternal rejection and promote tolerance to early embryos after assisted reproductive technology by modulating the immunological environment of the preimplantation endometrium. We planned an exploratory clinical trial to determine the efficacy, safety, and dosage of tacrolimus in women with intractable infertility. METHODS AND ANALYSIS: This is a multicenter, 2-dose, single-group controlled trial in infertile women who failed to achieve a chemical pregnancy despite multiple in vitro fertilization (IVF) and embryo transfer (ET) treatment cycles. The following 2 key selection criteria were set: no underlying factors of infertility despite appropriate evaluation and presence of Th1-dominant immune state, defined as a Th1/Th2 cell ratio ≥ 10.3 in the peripheral blood. A total of 26 eligible participants are randomly assigned (in a 2:1 ratio) to receive immunosuppressive therapy with oral tacrolimus at a daily dose of 2 mg or 4 mg. Tacrolimus is administered for 16 days starting from 2 days before ET. The primary endpoint is the presence of clinical pregnancy 3 weeks after IVF/ET treatment, and the secondary endpoint is the presence of biochemical pregnancy 2 weeks after IVF/ET treatment. Safety evaluation and biomarker discovery for tacrolimus treatment in infertile women will be conducted simultaneously. TRIAL REGISTRATION NUMBER: Japan Registry of Clinical Trials (jRCT; jRCTs031220235).


Assuntos
Aborto Espontâneo , Infertilidade Feminina , Gravidez , Humanos , Feminino , Adulto , Infertilidade Feminina/tratamento farmacológico , Tacrolimo/uso terapêutico , Fertilização in vitro , Transferência Embrionária/métodos , Técnicas de Reprodução Assistida , Taxa de Gravidez
15.
J Psychiatr Res ; 159: 153-158, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36731380

RESUMO

Previous cross-sectional studies showed that COVID-19-related discrimination against healthcare workers was linked to depression. However, no study has examined the longitudinal association that allows causal interpretations. This prospective cohort study aimed to examine whether COVID-19-related discrimination at baseline is associated with depression and suicidal ideation several months later. Data were collected from October 2020 to July 2021. Multivariable logistic regression was performed. Fixed effects models were used to control for the effect of hospitals (Level 2 variable). Adjustments also included age, sex, living alone, alcohol consumption, exercise, BMI, working hours, comorbidity, and frontline worker status (Level 1 variables). Multiple sensitivity analyses were conducted to examine if the results substantially changed and were robust to unmeasured confounding. Multiple imputation for missing data was conducted via chained equations. As the final sample, 2862 healthcare workers without depression at baseline were studied. A total of 269 individuals (9.4%) experienced COVID-19-related discrimination. Depression was suggested in 205 participants (7.2%), and suicidal ideation in 108 participants (3.8%). In the adjusted models, COVID-19-related discrimination was significantly associated with subsequent depression (OR = 2.18, 95% CI = 1.39 to 2.90) and suicidal ideation (OR = 2.07, 95% CI = 1.22 to 3.50). Multiple sensitivity analyses verified the results. COVID-19-related discrimination results in depression and suicidal ideation in healthcare workers. Interventions to prevent such discrimination against healthcare workers, e.g., anti-discrimination campaigns, are crucial during the COVID-19 pandemic.


Assuntos
COVID-19 , Ideação Suicida , Humanos , Depressão , Estudos Prospectivos , Pandemias
16.
PLoS One ; 18(4): e0283658, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37023035

RESUMO

Patients with underlying medical conditions are at high risk of developing serious symptoms of the coronavirus disease 2019 than healthy individuals; therefore, it is necessary to evaluate the immune response to vaccination among them to formulate precision and personalized vaccination strategies. However, inconsistent evidence exists regarding whether patients with underlying medical conditions have lower anti-SARS-CoV-2 spike IgG antibody titers. We performed a cross-sectional study enrolling 2762 healthcare workers who received second doses of BNT162b2 vaccination from three medical and research institutes between June and July, 2021. Medical conditions were surveyed by a questionnaire, and spike IgG antibody titers were measured with chemiluminescent enzyme immunoassay using serum collected on the median of 62 days after the second vaccination. Multilevel linear regression model was used to estimate geometric mean and ratio of mean (95% confidence interval, CI) for the presence and absence of medical conditions and treatments. Among all participants (median age, 40 years [interquartile range, 30-50]; male proportion, 29.4%), the prevalence of hypertension, diabetes, chronic lung disease, cardiovascular disease, and cancer was 7.5%, 2.3%, 3.8%, 1.8%, and 1.3%, respectively. Patients with treated hypertension had lower antibody titers than those without hypertension; the multivariable-adjusted ratio of mean (95% CI) was 0.86 (0.76-0.98). Patients with untreated and treated diabetes had lower antibody titers than those without diabetes; the multivariable-adjusted ratio of mean (95% CI) was 0.63 (0.42-0.95) and 0.77 (0.63-0.95), respectively. No substantial difference was observed between the presence or absence of chronic lung disease, cardiovascular disease, or cancer. Patients with untreated hypertension and patients with untreated and treated diabetes had lower spike IgG antibody titers than participants without those medical conditions, suggesting that continuous monitoring of antibody titers and further booster shots could be necessary to maintain adaptive immunity in patients with hypertension or diabetes.


Assuntos
COVID-19 , Doenças Cardiovasculares , Hipertensão , Humanos , Masculino , Adulto , Vacina BNT162 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Estudos Transversais , Anticorpos Antivirais , Imunoglobulina G , Vacinação
18.
Vaccines (Basel) ; 10(9)2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36146559

RESUMO

Vaccine literacy of healthcare workers (HCWs) may affect the COVID-19 vaccine uptake of the general population. This study aimed to clarify the vaccine literacy level of HCWs in Japan and its impacts on their concerns about vaccines and intention to recommend that others receive vaccines. This cross-sectional survey was conducted in July 2021 based on the recruitment of HCWs in a pediatric and maternity hospital and research center in Tokyo, Japan. All HCWs in this center had the chance to receive the COVID-19 vaccine before the survey, and their vaccine coverage was relatively high, at 95%. A total of 1519 workers answered the questionnaire. The results showed that HCWs with lower functional vaccine literacy had 1.5 times as many concerns about the efficacy of vaccines and 1.6 times as many concerns about the future side effects compared with those with higher literacy. Further, HCWs with higher vaccine literacy were more likely to recommend that older people, people with comorbidities, and pregnant women receive vaccines. Our findings suggest that high vaccine literacy alleviates concerns about COVID-19 vaccines and raised the intention to recommend vaccines to others. To achieve high vaccine coverage, countermeasures such as personalized education are essential.

19.
Front Psychiatry ; 13: 774919, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35370822

RESUMO

Background: Although higher rates of burnout have been reported during the COVID-19 pandemic, the contribution of the modifiable factors is lesser-known. We investigated how the risk of emotional exhaustion was associated with mindfulness skills and social support in a single medical center in Japan. Methods: We conducted a cross-sectional web survey on mental health for all staff of a national medical hospital from February to March 2021. We examined the association between self-rated emotional exhaustion and levels of mindfulness and social support using multivariate logistic regression. Results: Of the 830 participants, signs of emotional exhaustion were observed in 261 (31%) individuals. Among those highly exposed to the virus at work, individuals with low levels of mindfulness and social support had significantly higher odds of emotional exhaustion [OR 3.46 (95% CI; 1.48-8.09), OR; 3.08 (95% CI; 1.33-7.13), respectively] compared to those with high levels. However, among those not highly exposed to the virus, individuals with both low and moderate levels of mindfulness had significantly higher odds of emotional exhaustion. [OR 3.33 (95% CI; 2.22-5.00), OR; 2.61 (95% CI; 1.73-3.94), respectively]. Conclusion: We found that factors associated with emotional exhaustion differed by exposure to SARS-CoV-2. Building mindfulness skills can help reduce the high burden placed on the staff. Additionally, increasing social support may be useful especially for workers highly exposed to SARS-CoV-2.

20.
Hum Fertil (Camb) ; 25(5): 975-982, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34304683

RESUMO

Tacrolimus has received considerable attention as a treatment approach for infertility associated with maternal-foetal immune abnormalities, such as repeated implantation failure (RIF) and recurrent pregnancy loss (RPL). This study examined the changes in T-helper (Th) 1 and 2 cell populations during pregnancy in peripheral blood of tacrolimus-treated RIF patients who delivered a liveborn infant from August 2012 to February 2020 at the National Centre for Child Health and Development. A total of 58 eligible study subjects were divided into two groups according to the presence of a history of RPL: (i) RIF-alone group (n = 31); and (ii) RIF-plus-RPL group (n = 27). In a flow cytometric analysis, the Th1/Th2 cell ratios were significantly higher before pregnancy than after pregnancy, and during the first trimester than the second trimester in the RIF-alone group (p = 0.0071 and p = 0.0087, respectively). However, no significant differences were present in the RIF-plus-RPL group. Although the Th1 immunity was suppressed under tacrolimus treatment in both groups, a delayed reduction in the Th1 cell percentage after initiation of treatment was observed in the RIF-plus-RPL group. In conclusion, the cellular immune alterations in tacrolimus-treated patients with RIF were different depending on the presence or absence of a history of RPL.


Assuntos
Aborto Habitual , Infertilidade Feminina , Gravidez , Criança , Humanos , Feminino , Tacrolimo/uso terapêutico , Aborto Habitual/tratamento farmacológico , Implantação do Embrião
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