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1.
J Med Internet Res ; 25: e41859, 2023 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-36645699

RESUMO

BACKGROUND: Adjusting to new or additional parenting responsibilities increases stress and affects parental well-being. Existing research has highlighted both parents' desire to receive more support. It has also been found that receiving sufficient social support enhances parenting outcomes. With the increasing popularity of mobile health apps, a Supportive Parenting App (SPA) intervention was developed to fulfill the support needs of parents during the perinatal period. OBJECTIVE: This study aimed to examine the effectiveness of the SPA on parental outcomes during the perinatal period. METHODS: A 2-group pretest and repeated posttest randomized controlled trial was conducted wherein 200 couples (N=400 mothers and fathers) were recruited from 2 public health care institutions in Singapore. Parents were randomly assigned to intervention (100/200, 50%) or control (100/200, 50%) groups. The SPA intervention consisted of a mobile app-based psychoeducation and peer support program to support parents from pregnancy to 6 months post partum. The outcome measures included postnatal depression, anxiety, parental bonding, parental self-efficacy, perceived social support, and parenting satisfaction. Data were collected at baseline (at >24 weeks of gestation-age of viability in Singapore) and at the first, second, fourth, sixth, ninth, and 12th month post partum. Linear mixed models were used to compare parental outcomes between the groups, and a linear mixed model for repeated measures was used to examine within-group changes. RESULTS: Parents in the intervention group mostly showed better outcomes compared with those in the control group. Parents in the intervention group had higher perceived social support than those in the control group at the first (effect size=1.59, 95% CI 0.38-2.80; Cohen standardized effect size=1.31; P=.01), second (effect size=1.98, 95% CI 1.09-2.88; Cohen standardized effect size=2.21; P=.003), and fourth (effect size=2.57, 95% CI 1.62-3.51; Cohen standardized effect size=2.72; P=.048) months post partum. However, parents in the intervention group showed significantly poorer parental bonding (effect size=1.67, 95% CI 0.24-3.11; Cohen standardized effect size=1.16; P=.02). The other parental outcomes did not differ significantly between groups. The scores of mothers and fathers also differed significantly for all outcomes except parental self-efficacy. CONCLUSIONS: Parents in the intervention group generally fared better, especially regarding perceived social support. However, the lack of statistical significance in most outcomes showed the limited effectiveness of the SPA intervention, which may be because of the COVID-19 pandemic. Parental differences in outcome scores suggest that mothers and fathers have different support needs; therefore, interventions should be tailored accordingly. Further improvements and evaluations are needed to examine the effectiveness of the SPA intervention in enhancing parental outcomes. Despite statistically insignificant results, limitations should be considered to further improve mobile health app-based interventions such as SPA, as they could serve as reliable and convenient sources of support for parents. TRIAL REGISTRATION: Clinicaltrails.gov NCT4706442; https://clinicaltrials.gov/ct2/show/NCT04706442.


Assuntos
COVID-19 , Aplicativos Móveis , Feminino , Gravidez , Humanos , Poder Familiar , Pandemias , Pais
2.
J Clin Nurs ; 32(13-14): 3528-3542, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35773956

RESUMO

AIMS AND OBJECTIVES: To explore the perspectives of parents during the perinatal period amid the COVID-19 pandemic and explore the experiences of Singaporean parents receiving perinatal support via the Supportive Parenting App (SPA). BACKGROUND: The stressors accompanying parenting responsibilities often affect the overall well-being of the family unit. With the emergence of the COVID-19 pandemic, Singaporean parents are forced to shoulder childcare responsibilities with minimal support due to safety restrictions. The Supportive Parenting Application (SPA) was introduced to parents during the start of the pandemic to offer timely additional support. It is a mobile health application-based educational support for parents across the perinatal period, consisting of features such as peer support, expert advice and discussion forums. DESIGN: Descriptive qualitative study. METHODS: Semi-structured one-to-one interviews were conducted with 33 parents (16 from the control group, 17 from the intervention group) in an ongoing randomised controlled trial between June 2021 and February 2022. The COREQ checklist was used to guide the reporting of the data. RESULTS: Four themes with 10 subthemes describing the perinatal experiences of parents were identified. The themes include 'Ups and downs' of parenting experiences; Perinatal care from 'best care' to 'flying blind'; What kept couples going and Use of technology-a way forward. CONCLUSION: Although COVID-19 negatively affected parents' availability of care and support, most could still access other support sources to help them. Additionally, the SPA was found to be a dependable information source for the intervention group parents. Future research could work on improving technology-based support based on the feedback given to offer better quality perinatal care for parents. RELEVANCE TO CLINICAL PRACTICE: Technology-based support provided by healthcare professionals helps provide reliable perinatal information and support for parents. More efforts should be directed towards developing quality informational resources and support to improve perinatal care. PATIENT OR PUBLIC CONTRIBUTION: Patients/members of the public contributed to the data collected and were involved in member checking to ensure the rigour of the study. CLINICAL TRIAL REGISTRATION NUMBER: NHG DSRB: 2019/00875.


Assuntos
COVID-19 , Pandemias , Feminino , Gravidez , Humanos , COVID-19/epidemiologia , Pais , Poder Familiar , Pessoal de Saúde , Pesquisa Qualitativa
3.
J Perinat Med ; 49(2): 153-158, 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-32889795

RESUMO

OBJECTIVES: Pregnancy-associated venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE), is associated with increased risk of maternal mortality and morbidity. This study aimed to assess potential risk factors for pregnancy-associated VTE. METHODS: In this case-control study, women with pregnancy-associated VTE were identified via International Classification of Diseases codes and included if they had been objectively diagnosed with VTE during pregnancy or within six weeks postpartum, from 2004 to 2016, at KK Women's and Children's Hospital or Singapore General Hospital in Singapore. Controls, i.e. pregnant women without VTE, were selected from a prospective longitudinal study. The odds ratio (OR) for VTE was computed for a range of maternal and obstetric factors. RESULTS AND CONCLUSIONS: From 2004 to 2016, 89 cases of pregnancy-associated VTE and 926 controls were identifed and analysed using logistic regression. The most significant risk factors for pregnancy-associated VTE were smoking (OR 5.44, p=0.0002) and preterm delivery (OR 5.06, p=0.023). Malay race, multiparity, non-O blood group and caesarean section, were also identified to be of higher risk. These risk factors should be useful in the development of thromboprophylaxis strategies for pregnancy and the postpartum period, especially in Singapore.


Assuntos
Complicações Cardiovasculares na Gravidez/epidemiologia , Tromboembolia Venosa/epidemiologia , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Gravidez , Fatores de Risco , Singapura/epidemiologia , Adulto Jovem
4.
J Med Internet Res ; 23(12): e27033, 2021 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-36260376

RESUMO

BACKGROUND: The transition to parenthood can be challenging, and parents are vulnerable to psychological disorders during the perinatal period. This may have adverse long-term consequences on a child's development. Given the rise in technology and parents' preferences for mobile health apps, a supportive mobile health intervention is optimal. However, there is a lack of a theoretical framework and technology-based perinatal educational intervention for couples with healthy infants. OBJECTIVE: The aim of this study is to describe the Supportive Parenting App (SPA) development procedure and highlight the challenges and lessons learned. METHODS: The SPA development procedure was guided by the information systems research framework, which emphasizes a nonlinear, iterative, and user-centered process involving 3 research cycles-the relevance cycle, design cycle, and rigor cycle. Treatment fidelity was ensured, and team cohesiveness was maintained using strategies from the Tuckman model of team development. RESULTS: In the relevance cycle, end-user requirements were identified through focus groups and interviews. In the rigor cycle, the user engagement pyramid and well-established theories (social cognitive theory proposed by Bandura and attachment theory proposed by Bowlby) were used to inform and justify the features of the artifact. In the design cycle, the admin portal was developed using Microsoft Visual Studio 2017, whereas the SPA, which ran on both iOS and Android, was developed using hybrid development tools. The SPA featured knowledge-based content, informational videos and audio clips, a discussion forum, chat groups, and a frequently asked questions and expert advice section. The intervention underwent iterative testing by a small group of new parents and research team members. Qualitative feedback was obtained for further app enhancements before official implementation. Testing revealed user and technological issues, such as web browser and app incompatibility, a lack of notifications for both administrators and users, and limited search engine capability. CONCLUSIONS: The information systems research framework documented the technical details of the SPA but did not take into consideration the interpersonal and real-life challenges. Ineffective communication between the health care research team and the app developers, limited resources, and the COVID-19 pandemic were the main challenges faced during content development. Quick adaptability, team cohesion, and hindsight budgeting are crucial for intervention development. Although the effectiveness of the SPA in improving parental and infant outcomes is currently unknown, this detailed intervention development study highlights the key aspects that need to be considered for future app development.


Assuntos
COVID-19 , Aplicativos Móveis , Criança , Gravidez , Feminino , Humanos , Poder Familiar/psicologia , Pandemias , Pais
5.
J Obstet Gynaecol Res ; 47(1): 174-183, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32840028

RESUMO

OBJECTIVE: To determine the cumulative incidence, time of occurrence and risk factors of pregnancy-associated pulmonary embolism (PE) in Singapore, and to review the maternal mortality ratio of PE over the last four decades. STUDY DESIGN AND SETTING: In this retrospective epidemiology review, women with pregnancy-associated PE were identified via International Classification of Diseases codes and included if they had been objectively diagnosed on imaging with PE during pregnancy or within 6 weeks postpartum from 2004 to 2016 at KK Women's and Children's Hospital (KKH) and Singapore General Hospital (SGH) in Singapore. The medical records were reviewed and the time of occurrence of confirmed PE cases and risk factors for PE were noted. RESULTS: There were 18 PE cases out of 174 708 deliveries, of which two were fatal, giving a cumulative incidence of PE at 1.03 per 10 000 deliveries and a mortality rate of 11.1%. The maternal mortality ratio is 1.14 per 100 000 deliveries, the lowest compared to that of the previous three decades (2.5-4.9 per 100 000 deliveries). Majority of PE (66.7%) occurred during the first 2 weeks postpartum. Cumulative incidence of postpartum PE was four times more in caesarean section compared to vaginal delivery at 1.58 per 10 000 deliveries and 0.40 per 10 000 deliveries, respectively. CONCLUSION: Although the cumulative incidence of pregnancy-associated PE in Singapore is low, it is comparable to the United Kingdom (UK) and United States (US). Risk assessment and thromboprophylaxis have decreased PE mortality significantly during this period.


Assuntos
Embolia Pulmonar , Tromboembolia Venosa , Anticoagulantes , Cesárea , Criança , Feminino , Humanos , Gravidez , Embolia Pulmonar/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Singapura/epidemiologia
6.
Arch Gynecol Obstet ; 302(3): 679-683, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32535665

RESUMO

PURPOSE: Management of tubo-ovarian abscesses (TOA) is often complex and may include antibiotics, image-guided drainage via interventional radiology (IR) or surgery. We aim to (i) identify clinical factors that prognosticate primary drainage and (ii) compare outcomes of each treatment regimen. METHODS: This is a retrospective analysis on patients with TOA, admitted to KK Hospital, a tertiary women's hospital in Singapore from June 2016 to June 2017. Pregnant patients or patients who were discharged against medical advice were excluded. 102 patients were included in this study. RESULTS: 85.3% patients received antibiotics only, while 14.7% patients received antibiotics with IR drainage or surgery (primary drainage) as initial treatment. Subsequently, 20.7% failed antibiotic treatment and required IR drainage or surgery (secondary drainage). Patients aged above 40 years, TOA diameter of larger than 7 cm and presence of fever were found to be predictive of antibiotic failure, requiring secondary drainage. However, patients with primary drainage had a longer length of stay by 2.69 days (95% CI 1.44-3.94, p value < 0.001), compared to patients successfully managed conservatively. CONCLUSION: Patients who are above 40 years, febrile and have a larger TOA are at a higher risk of medical treatment failure, and should, therefore, be recommended for primary drainage at presentation. Further prospective studies should be conducted with a larger sample size to compare the outcomes of conservative management versus drainage of TOA.


Assuntos
Abscesso/cirurgia , Tratamento Conservador/métodos , Drenagem/métodos , Doenças Ovarianas/cirurgia , Adulto , Feminino , Humanos , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos
7.
Blood ; 130(18): 1995-2005, 2017 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-28851698

RESUMO

Many immune parameters show circadian rhythms during the 24-hour day in mammals. The most striking circadian oscillation is the number of circulating immune cells that display an opposite rhythm between humans and mice. The physiological roles and mechanisms of circadian variations in mouse leukocytes are well studied, whereas for humans they remain unclear because of the lack of a proper model. In this study, we found that consistent with their natural host species, mouse and human circulating leukocytes exhibited opposite circadian oscillations in humanized mice. This cyclic pattern of trafficking correlated well with the diurnal expression levels of C-X-C chemokine receptor 4, which were controlled by the intracellular hypoxia-inducible factor 1α/aryl hydrocarbon receptor nuclear translocator-like heterodimer. Furthermore, we also discovered that p38 mitogen-activated protein kinases/mitogen-activated 2 had opposite effects between mice and humans in generating intracellular reactive oxygen species, which subsequently regulated HIF-1α expression. In conclusion, we propose humanized mice as a robust model for human circadian studies and reveal insights on a novel molecular clock network in the human circadian rhythm.


Assuntos
Ritmo Circadiano/fisiologia , Leucócitos/fisiologia , Animais , Translocador Nuclear Receptor Aril Hidrocarboneto/metabolismo , Movimento Celular , Quimiocina CXCL12/metabolismo , Humanos , Síndrome do Jet Lag/fisiopatologia , Camundongos , Modelos Biológicos , Espécies Reativas de Oxigênio/metabolismo , Receptores CXCR4/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
8.
Eur J Nutr ; 58(3): 1081-1094, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29441408

RESUMO

PURPOSE: To examine the associations of energy, macronutrient and food intakes with GWG on 960 pregnant women from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) mother-offspring cohort. METHODS: Dietary intake was assessed at 26-28 weeks' gestation with a 24-hour recall and 3-day food diary. GWG z-scores were calculated from first (4-13 weeks' gestation) and last (30-40 weeks gestation) measured weights; inadequate and excessive GWG were defined using the Institute of Medicine recommendations based on weights between 15 and 35 weeks' gestation. Associations were examined using substitution models for macronutrient composition, with linear or multinomial logistic regressions. RESULTS: Mean ± SD daily energy intake was 1868 ± 598 kcal, and percentage energy intakes were 51.8 ± 8.9% from carbohydrate, 15.7 ± 3.9% from protein and 32.6 ± 7.7% from fat. Higher energy intake (per 500 kcal increment) was associated with 0.18 SD higher GWG. In isocaloric diets, higher-carbohydrate and lower-fat intakes (at 5% energy substitution) were associated with 0.07 SD higher GWG, and 14% higher likelihood of excessive GWG. Concordantly, the highest tertile of carbohydrate-rich foods intake was associated with 0.20 SD higher GWG, but the highest tertile of fruit and vegetable intake was independently associated with 60% lower likelihood of inadequate GWG. Additionally, the highest tertile of dairy intake was associated with 0.18 SD lower GWG; and the highest tertile of plant-based protein foods intake was associated with 60% and 34% lower likelihood of inadequate and excessive GWG. CONCLUSIONS: Balancing the proportions of carbohydrates and fat, and a higher intake of plant-based protein foods may be beneficial for achieving optimal GWG.


Assuntos
Dieta/métodos , Carboidratos da Dieta/administração & dosagem , Gorduras na Dieta/administração & dosagem , Proteínas Alimentares/administração & dosagem , Ingestão de Energia/fisiologia , Ganho de Peso na Gestação/fisiologia , Adulto , Estudos de Coortes , Registros de Dieta , Feminino , Humanos , Nutrientes/administração & dosagem , Gravidez , Singapura
9.
BMC Public Health ; 19(1): 890, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31277611

RESUMO

BACKGROUND: Pregnant women are at increased risk of influenza-related complications. The World Health Organisation recommends influenza vaccination to this high-risk population as highest priority. However, achieving high influenza vaccine coverage among pregnant women remains challenging. We conducted a cross-sectional survey to estimate the coverage and determinants of influenza vaccination among pregnant women in Singapore. METHODS: Between September and November 2017, pregnant women aged ≥21 years were recruited at two public hospitals in Singapore. Participants completed an anonymous, self-administered online questionnaire assessing participants' influenza vaccination uptake, knowledge of and attitudes towards influenza and the influenza vaccine, vaccination history, willingness to pay for the influenza vaccine, and external cues to vaccination. We estimated vaccine coverage and used multivariable Poisson models to identify factors associated with vaccine uptake. RESULTS: Response rate was 61% (500/814). Only 49 women (9.8, 95% Confidence Interval (CI): 7.3-12.7%) reported receiving the vaccine during their current pregnancy. A few misconceptions were identified among participants, such as the belief that influenza can be treated with antibiotics. The most frequent reason for not being vaccinated was lack of recommendation. Women who were personally advised to get vaccinated against influenza during pregnancy were 7 times more likely to be vaccinated (prevalence ratio (PR) = 7.11; 95% CI: 3.92-12.90). However, only 12% of women were personally advised to get vaccinated. Other factors associated with vaccine uptake were vaccination during a previous pregnancy (PR = 2.51; 95% CI: 1.54-4.11), having insurance to cover the cost of the vaccine (PR = 2.32; 95% CI: 1.43-3.76), and higher vaccine confidence (PR = 1.62; 95% CI: 1.30-2.01). CONCLUSIONS: Influenza vaccination uptake among pregnant women in Singapore is low. There is considerable scope for improving vaccination coverage in this high-risk population through vaccination recommendations from healthcare professionals, and public communication targeting common misconceptions about influenza and influenza vaccines.


Assuntos
Vacinas contra Influenza/administração & dosagem , Influenza Humana/prevenção & controle , Complicações Infecciosas na Gravidez/prevenção & controle , Gestantes/psicologia , Cobertura Vacinal/estatística & dados numéricos , Adulto , Estudos Transversais , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Hospitais Públicos , Humanos , Pessoa de Meia-Idade , Gravidez , Medição de Risco , Singapura , Inquéritos e Questionários , Adulto Jovem
10.
Gut ; 67(10): 1845-1854, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29602780

RESUMO

OBJECTIVE: As the current therapeutic strategies for human hepatocellular carcinoma (HCC) have been proven to have limited effectiveness, immunotherapy becomes a compelling way to tackle the disease. We aim to provide humanised mouse (humice) models for the understanding of the interaction between human cancer and immune system, particularly for human-specific drug testing. DESIGN: Patient-derived xenograft tumours are established with type I human leucocyte antigen matched human immune system in NOD-scid Il2rg-/- (NSG) mice. The longitudinal changes of the tumour and immune responses as well as the efficacy of immune checkpoint inhibitors are investigated. RESULTS: Similar to the clinical outcomes, the human immune system in our model is educated by the tumour and exhibits exhaustion phenotypes such as a significant declination of leucocyte numbers, upregulation of exhaustion markers and decreased the production of human proinflammatory cytokines. Notably, cytotoxic immune cells decreased more rapidly compared with other cell types. Tumour infiltrated T cells have much higher expression of exhaustion markers and lower cytokine production compared with peripheral T cells. In addition, tumour-associated macrophages and myeloid-derived suppressor cells are found to be highly enriched in the tumour microenvironment. Interestingly, the tumour also changes gene expression profiles in response to immune responses by upregulating immune checkpoint ligands. Most importantly, in contrast to the NSG model, our model demonstrates both therapeutic and side effects of immune checkpoint inhibitors pembrolizumab and ipilimumab. CONCLUSIONS: Our work provides a model for immune-oncology study and a useful parallel-to-human platform for anti-HCC drug testing, especially immunotherapy.


Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , Carcinoma Hepatocelular , Imunoterapia/métodos , Ipilimumab/farmacologia , Neoplasias Hepáticas , Microambiente Tumoral/imunologia , Animais , Antineoplásicos Imunológicos/farmacologia , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Citocinas/metabolismo , Modelos Animais de Doenças , Xenoenxertos/imunologia , Humanos , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Camundongos , Camundongos Endogâmicos NOD
11.
BMC Pregnancy Childbirth ; 18(1): 360, 2018 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-30185145

RESUMO

BACKGROUND: Progesterone is a critical hormone in early pregnancy. A low level of serum progesterone is associated with threatened miscarriage. We aim to establish the distribution of maternal serum progesterone in normal pregnancies compared to pregnancies complicated by threatened miscarriage from 5 to 13 weeks gestation. METHODS: This is a single centre, prospective cohort study of 929 patients. Women from the Normal Pregnancy [NP] cohort were recruited from antenatal clinics, and those in the Threatened Miscarriage [TM] cohort were recruited from emergency walk-in clinics. Women with multiple gestations, missed, incomplete or inevitable miscarriage were excluded from the study. Quantile regression was used to characterize serum progesterone levels in the NP and TM cohorts by estimating the 10th, 50th and 90th percentiles from 5 to 13 weeks gestation. Pregnancy outcome was determined at 16 weeks of gestation. Subgroup analysis within the TM group compared progesterone levels of women who subsequently miscarried with those who had ongoing pregnancies at 16 weeks of gestation. RESULTS: Median serum progesterone concentration demonstrated a linearly increasing trend from 57.5 nmol/L to 80.8 nmol/L from 5 to 13 weeks gestation in the NP cohort. In the TM cohort, median serum progesterone concentration increased from 41.7 nmol/L to 78.1 nmol/L. However, median progesterone levels were uniformly lower in the TM cohort by approximately 10 nmol/L at every gestation week. In the subgroup analysis, median serum progesterone concentration in women with ongoing pregnancy at 16 weeks gestation demonstrated a linearly increasing trend from 5 to 13 weeks gestation. There was a marginal and non-significant increase in serum progesterone from 19.0 to 30.3 nmol/L from 5 to 13 weeks gestation in women who eventually had a spontaneous miscarriage. CONCLUSIONS: Serum progesterone concentration increased linearly with gestational age from 5 to 13 weeks in women with normal pregnancies. Women with spontaneous miscarriage showed a marginal and non-significant increase in serum progesterone. This study highlights the pivotal role of progesterone in supporting an early pregnancy, with lower serum progesterone associated with threatened miscarriage and a subsequent complete miscarriage at 16 weeks gestation.


Assuntos
Ameaça de Aborto/sangue , Progesterona/sangue , Adulto , Estudos de Coortes , Feminino , Seguimentos , Idade Gestacional , Humanos , Gravidez , Resultado da Gravidez , Primeiro Trimestre da Gravidez/sangue , Estudos Prospectivos
12.
BMC Pregnancy Childbirth ; 17(1): 78, 2017 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-28264669

RESUMO

BACKGROUND: Our recent paper, based on a pilot cohort of 119 women, showed that serum progesterone <35 nmol/L was prognostic of spontaneous miscarriage by 16 weeks in women with threatened miscarriage in early pregnancy. Using a larger cohort of women from the same setting (validation cohort), we aim to assess the validity of serum progesterone <35 nmol/L with the outcome of spontaneous miscarriage by 16 weeks. METHODS: In a prospective cohort study, 360 pregnant women presenting with threatened miscarriage between gestation weeks 6-10 at a tertiary hospital emergency unit for women in Singapore were recruited for this study. The main outcome measure measured is spontaneous miscarriage prior to week 16 of gestation. Area under the ROC curve (AUC) and test characteristics (sensitivity, specificity, positive and negative predictive value) at a serum progesterone cutpoint of <35 nmol/L for predicting high and low risk of spontaneous miscarriage by 16 weeks were compared between the Pilot and Validation cohorts. RESULTS: Test characteristics and AUC values using serum progesterone <35 nmol/L in the validation cohort were not significantly different from those in the Pilot cohort, demonstrating excellent accuracy and reproducibility of the proposed serum progesterone cut-off level. CONCLUSIONS: The cut-off value for serum progesterone (35 nmol/L) demonstrated clinical relevance and allow clinicians to stratify patients into high and low risk groups for spontaneous miscarriage.


Assuntos
Aborto Espontâneo/sangue , Ameaça de Aborto/sangue , Progesterona/sangue , Aborto Espontâneo/diagnóstico , Adulto , Área Sob a Curva , Estudos de Coortes , Técnicas de Apoio para a Decisão , Feminino , Humanos , Proteínas do Tecido Nervoso , Gravidez , Primeiro Trimestre da Gravidez , Prognóstico , Estudos Prospectivos , Curva ROC , Reprodutibilidade dos Testes , Medição de Risco , Adulto Jovem
13.
Proc Natl Acad Sci U S A ; 111(4): 1479-84, 2014 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-24474774

RESUMO

Immunodeficient mouse-human chimeras provide a powerful approach to study host-specific pathogens, such as Plasmodium falciparum that causes human malaria. Supplementation of immunodeficient mice with human RBCs supports infection by human Plasmodium parasites, but these mice lack the human immune system. By combining human RBC supplementation and humanized mice that are optimized for human immune cell reconstitution, we have developed RBC-supplemented, immune cell-optimized humanized (RICH) mice that support multiple cycles of P. falciparum infection. Depletion of human natural killer (NK) cells, but not macrophages, in RICH mice results in a significant increase in parasitemia. Further studies in vitro show that NK cells preferentially interact with infected RBCs (iRBCs), resulting in the activation of NK cells and the elimination of iRBCs in a contact-dependent manner. We show that the adhesion molecule lymphocyte-associated antigen 1 is required for NK cell interaction with and elimination of iRBCs. Development of RICH mice and validation of P. falciparum infection should facilitate the dissection of human immune responses to malaria parasite infection and the evaluation of therapeutics and vaccines.


Assuntos
Eritrócitos/parasitologia , Células Matadoras Naturais/imunologia , Malária Falciparum/imunologia , Plasmodium falciparum/imunologia , Animais , Adesão Celular , Humanos , Malária Falciparum/sangue , Camundongos , Parasitemia/imunologia
14.
Gut ; 65(10): 1744-53, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-26149491

RESUMO

OBJECTIVE: HCV infection affects millions of people worldwide, and many patients develop chronic infection leading to liver cancers. For decades, the lack of a small animal model that can recapitulate HCV infection, its immunopathogenesis and disease progression has impeded the development of an effective vaccine and therapeutics. We aim to provide a humanised mouse model for the understanding of HCV-specific human immune responses and HCV-associated disease pathologies. DESIGN: Recently, we have established human liver cells with a matched human immune system in NOD-scid Il2rg(-/-) (NSG) mice (HIL mice). These mice are infected with HCV by intravenous injection, and the pathologies are investigated. RESULTS: In this study, we demonstrate that HIL mouse is capable of supporting HCV infection and can present some of the clinical symptoms found in HCV-infected patients including hepatitis, robust virus-specific human immune cell and cytokine responses as well as liver fibrosis and cirrhosis. Similar to results obtained from the analysis of patient samples, the human immune cells, particularly T cells and macrophages, play critical roles during the HCV-associated liver disease development in the HIL mice. Furthermore, our model is demonstrated to be able to reproduce the therapeutic effects of human interferon alpha 2a antiviral treatment. CONCLUSIONS: The HIL mouse provides a model for the understanding of HCV-specific human immune responses and HCV-associated disease pathologies. It could also serve as a platform for antifibrosis and immune-modulatory drug testing.


Assuntos
Modelos Animais de Doenças , Hepatite C Crônica , Interferon-alfa/uso terapêutico , Camundongos Endogâmicos NOD , Animais , Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/imunologia , Hepatite C Crônica/fisiopatologia , Humanos , Imunidade Celular/imunologia , Interferon alfa-2 , Camundongos , Proteínas Recombinantes/uso terapêutico , Reprodutibilidade dos Testes
15.
J Immunol ; 191(6): 3192-9, 2013 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-23935193

RESUMO

Engraftment of human CD34⁺ hematopoietic stem/progenitor cells into immunodeficient mice leads to robust reconstitution of human T and B cells but not monocytes and macrophages. To identify the cause underlying the poor monocyte and macrophage reconstitution, we analyzed human myeloid cell development in humanized mice and found that it was blocked at the promonocyte stage in the bone marrow. Expression of human M-CSF or GM-CSF by hydrodynamic injection of cytokine-encoding plasmid completely abolished the accumulation of promonocytes in the bone marrow. M-CSF promoted the development of mature monocytes and tissue-resident macrophages whereas GM-CSF did not. Moreover, correlating with an increased human macrophages at the sites of infection, M-CSF-treated humanized mice exhibited an enhanced protection against influenza virus and Mycobacterium infection. Our study identifies the precise stage at which human monocyte/macrophage development is blocked in humanized mice and reveals overlapping and distinct functions of M-CSF and GM-CSF in human monocyte and macrophage development. The improved reconstitution and functionality of monocytes/macrophages in the humanized mice following M-CSF expression provide a superior in vivo system to investigate the role of macrophages in physiological and pathological processes.


Assuntos
Diferenciação Celular/imunologia , Fator Estimulador de Colônias de Macrófagos/metabolismo , Macrófagos/citologia , Células Precursoras de Monócitos e Macrófagos/citologia , Animais , Células da Medula Óssea/citologia , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/imunologia , Diferenciação Celular/efeitos dos fármacos , Separação Celular , Citometria de Fluxo , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/efeitos dos fármacos , Células-Tronco Hematopoéticas/imunologia , Humanos , Fator Estimulador de Colônias de Macrófagos/farmacologia , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Células Precursoras de Monócitos e Macrófagos/imunologia , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa
16.
Gynecol Endocrinol ; 31(8): 647-51, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26036717

RESUMO

This study seeks to establish progesterone and progesterone-induced blocking factor (PIBF) levels as predictors of subsequent completed miscarriage among women presenting with threatened miscarriage between 6 and 10 weeks of gestation. Our secondary objective was to assess the known maternal risk factors, toward development of a parsimonious and clinician-friendly risk assessment model for predicting completed miscarriage. In this article, we present a prospective cohort study of 119 patients presenting with threatened miscarriage from gestation weeks 6 to 10 at a tertiary women's hospital emergency unit in Singapore. Thirty (25.2%) women had a spontaneous miscarriage. Low progesterone and PIBF levels are similarly predictive of subsequent completed miscarriage. Study results (OR, 95% CI) showed that higher levels of progesterone (0.91, 95% CI 0.88-0.94) and PIBF (0.99, 95% CI 0.98-0.99) were associated with lower risk of miscarriage. Low progesterone level was a very strong predictor of miscarriage risk in our study despite previous concerns about its pulsatile secretion. Low serum progesterone and PIBF levels predicted spontaneous miscarriage among women presenting with threatened miscarriage between gestation weeks 6 to 10. Predictive models to calculate probability of spontaneous miscarriage based on serum progesterone, together with maternal BMI and fetal heart are proposed.


Assuntos
Aborto Espontâneo/diagnóstico , Ameaça de Aborto/sangue , Proteínas da Gravidez/sangue , Progesterona/sangue , Fatores Supressores Imunológicos/sangue , Aborto Espontâneo/sangue , Aborto Espontâneo/etiologia , Adulto , Biomarcadores/sangue , Feminino , Humanos , Gravidez , Primeiro Trimestre da Gravidez , Estudos Prospectivos , Risco , Medição de Risco , Adulto Jovem
17.
J Obstet Gynaecol Res ; 40(4): 1002-8, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24611987

RESUMO

AIM: To define the optimal gestational weight gain (GWG) for the multiethnic Singaporean population. METHODS: Data from 1529 live singleton deliveries was analyzed. A multinomial logistic regression analysis, with GWG as the predictor, was conducted to determine the lowest aggregated risk of a composite perinatal outcome, stratified by Asia-specific body mass index (BMI) categories. The composite perinatal outcome, based on a combination of delivery type (cesarean section [CS], vaginal delivery [VD]) and size for gestational age (small [SGA], appropriate [AGA], large [LGA]), had six categories: (i) VD with LGA; (ii) VD with SGA; (iii) CS with AGA; (iv) CS with SGA; (v) CS with LGA; (vi) and VD with AGA. The last was considered as the 'normal' reference category. In each BMI category, the GWG value corresponding to the lowest aggregated risk was defined as the optimal GWG, and the GWG values at which the aggregated risk did not exceed a 5% increase from the lowest aggregated risk were defined as the margins of the optimal GWG range. RESULTS: The optimal GWG by pre-pregnancy BMI category, was 19.5 kg (range, 12.9 to 23.9) for underweight, 13.7 kg (7.7 to 18.8) for normal weight, 7.9 kg (2.6 to 14.0) for overweight and 1.8 kg (-5.0 to 7.0) for obese. CONCLUSION: The results of this study, the first to determine optimal GWG in the multiethnic Singaporean population, concur with the Institute of Medicine (IOM) guidelines in that GWG among Asian women who are heavier prior to pregnancy, especially those who are obese, should be lower. However, the optimal GWG for underweight and obese women was outside the IOM recommended range.


Assuntos
Promoção da Saúde , Fenômenos Fisiológicos da Nutrição Materna , Política Nutricional , Gravidez/fisiologia , Adulto , Povo Asiático , Índice de Massa Corporal , China/etnologia , Feminino , Humanos , Peso Corporal Ideal/etnologia , Índia/etnologia , Malásia/etnologia , Fenômenos Fisiológicos da Nutrição Materna/etnologia , Prontuários Médicos , National Academies of Science, Engineering, and Medicine, U.S., Health and Medicine Division , Guias de Prática Clínica como Assunto , Gravidez/etnologia , Resultado da Gravidez , Medição de Risco , Singapura , Estados Unidos , Aumento de Peso/etnologia , Adulto Jovem
18.
West J Nurs Res ; 46(7): 517-524, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38822693

RESUMO

BACKGROUND: Postpartum depression (PPD) is highly prevalent and plagues a significant proportion of parents. Postpartum depression also exerts various negative consequences on infant development and parent-infant relationships. Social support is identified as an important factor influencing many parental predictors, and may affect the development of PPD. OBJECTIVE: This study aimed to investigate how perceived social support can indirectly influence PPD symptoms in parents at 6 months postpartum by influencing postpartum anxiety, parental satisfaction, and parental self-efficacy (PSE). METHODS: A secondary analysis of data from a randomized controlled trial was used with a cross-sectional exploratory design. A total of 400 Singaporean parents (200 couples) were included, and structural equation modeling was used to analyze the relationships between PPD and potential predictors. RESULTS: Findings revealed a less adequate fit between the hypothesized model and the data collected. Social support was found to be a significant predictor of postpartum anxiety, PSE, and parental satisfaction. Postpartum anxiety was a significant predictor of PPD, but PSE and parental satisfaction were not. CONCLUSION: This study provides an overview of how different parental predictors may be associated with PPD among Asian parents. Postpartum anxiety significantly predicted PPD, but social support had negative effects on postpartum anxiety, parenting satisfaction, and PSE. The findings provide further insight into how parents at risk of PPD can be identified and demonstrated how social support might negatively impact parental outcomes. More qualitative research with Asian parents is needed to further explain these findings and inform the development of future interventions.


Assuntos
Depressão Pós-Parto , Pais , Apoio Social , Humanos , Feminino , Depressão Pós-Parto/psicologia , Estudos Transversais , Adulto , Singapura , Pais/psicologia , Autoeficácia , Inquéritos e Questionários , Masculino , Poder Familiar/psicologia , Ansiedade/psicologia
19.
Autism Res ; 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38943428

RESUMO

This study aimed to document the safety and efficacy of a single infusion of autologous umbilical cord blood (UCB) in 20 autistic children aged 24-72 months. A pre-post treatment within-subjects open label design was used. At T = 0, 6, 12, and 18 months, participants underwent detailed and structured safety evaluations (via caregiver report), Vineland Adaptive Behavior Scale (Vineland-3), Stanford Binet Intelligence Scale (SB-5), Expressive One-Word Picture Vocabulary Test, Brief Observation of Social Communication Change (BOSCC), Pervasive Developmental Disorder-Behavior Inventory, Repetitive Behavior Scale-Revised, Sensory Experience Questionnaire (SEQ-2.1), Child Behavior Checklist, Clinical Global Impression-Severity and Improvement (CGI-I) Scales, and eye-gaze tracking. UCB infusion was conducted at T = 6 months, hence, 0-6 months was the control period, and 6-18 months the follow-up period. Of 20 children recruited, 19 completed the study and 1 was withdrawn due to UCB not meeting quality control criteria for infusion. There were 15 males and 4 females with an overall mean (SD) age of 4.15 (0.62) years. Mean (SD) cell dose administered was 38.16 (9.82) million cells/kg. None suffered serious adverse events although there were mild behavioral side effects and one unit grew coagulase negative staphylococcus from a post-thaw sample. There were no significant differences in Vineland-3, SB-5, BOSCC, and SEQ-2.1 scores at T = 12 and T = 18 months. Twelve participants had T = 18 CGI-I scores of 2-3 (minimally to much improved), seven participants had scores of 4 (no change). Autologous UCB infusion in autistic children is generally safe but not without risks, including that of infection. In this within-subjects study, some children showed global symptom improvements while others showed no change. Stem cell therapies for autism should only be conducted under strict clinical trial conditions with clear risk discussions.

20.
J Obstet Gynaecol Res ; 39(5): 905-13, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23379547

RESUMO

AIM: The aim of this study was to assess maternal characteristics as predictors of inadequate or excessive gestational weight gain (GWG) and to characterize maternal and neonatal outcomes associated with inadequate or excessive GWG in Asian women. MATERIAL AND METHODS: A study was conducted among 1166 Chinese, Malay, and Indian women who delivered a live singleton infant at KK Women's and Children's Hospital, Singapore. Logistic regression analysis was used to determine predictors and maternal and neonatal outcomes of inadequate or excessive GWG, relative to adequate (recommended) GWG. RESULTS: While maternal age less than 20 years, Malay ethnicity and underweight pre-pregnancy body mass index increased the risk of inadequate GWG, overweight pre-pregnancy body mass index decreased this risk. Tall stature and Malay ethnicity were associated with an increased risk of excessive GWG, while maternal age greater than 30 years was associated with a decreased risk. Inadequate GWG increased the risk of preterm birth and decreased the risk of delivery by cesarean section and postpartum weight retention at 6 months. Excessive GWG increased the risk of delivery by cesarean section, postpartum weight retention at 6, 12 and 24 months and having a high-birthweight baby. CONCLUSION: Maternal predictors and perinatal outcomes of GWG among Asian women are similar to those identified previously among Caucasian, African-American and Hispanic women.


Assuntos
Sobrepeso/fisiopatologia , Complicações na Gravidez/fisiopatologia , Magreza/fisiopatologia , Adolescente , Adulto , Peso ao Nascer , Índice de Massa Corporal , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Masculino , Sobrepeso/epidemiologia , Gravidez , Complicações na Gravidez/epidemiologia , Resultado da Gravidez , Gravidez na Adolescência , Estudos Retrospectivos , Fatores de Risco , Singapura , Magreza/epidemiologia , Aumento de Peso , Adulto Jovem
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