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1.
Contemp Clin Trials ; 142: 107564, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38704119

ABSTRACT

INTRODUCTION: Women with atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS) have a significantly increased risk of breast cancer, which can be substantially reduced with antiestrogen therapy for chemoprevention. However, antiestrogen therapy for breast cancer risk reduction remains underutilized. Improving knowledge about breast cancer risk and chemoprevention among high-risk patients and their healthcare providers may enhance informed decision-making about this critical breast cancer risk reduction strategy. METHODS/DESIGN: We are conducting a cluster randomized controlled trial to evaluate the effectiveness and implementation of patient and provider decision support tools to improve informed choice about chemoprevention among women with AH or LCIS. We have cluster randomized 26 sites across the U.S. through the SWOG Cancer Research Network. A total of 415 patients and 200 healthcare providers are being recruited. They are assigned to standard educational materials alone or combined with the web-based decision support tools. Patient-reported and clinical outcomes are assessed at baseline, after a follow-up visit at 6 months, and yearly for 5 years. The primary outcome is chemoprevention informed choice after the follow-up visit. Secondary endpoints include other patient-reported outcomes, such as chemoprevention knowledge, decision conflict and regret, and self-reported chemoprevention usage. Barriers and facilitators to implementing decision support into clinic workflow are assessed through patient and provider interviews at baseline and mid-implementation. RESULTS/DISCUSSION: With this hybrid effectiveness/implementation study, we seek to evaluate if a multi-level intervention effectively promotes informed decision-making about chemoprevention and provide valuable insights on how the intervention is implemented in U.S. TRIAL REGISTRATION: NCT04496739.


Subject(s)
Breast Neoplasms , Chemoprevention , Humans , Female , Breast Neoplasms/prevention & control , Chemoprevention/methods , Patient Education as Topic/methods , Decision Support Techniques , Middle Aged , Adult , Decision Making , Health Knowledge, Attitudes, Practice , Risk Reduction Behavior , Research Design , Estrogen Antagonists/therapeutic use , Estrogen Antagonists/administration & dosage , Patient Reported Outcome Measures
3.
Telemed J E Health ; 30(4): e1110-e1118, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37883630

ABSTRACT

Background: Most of the Veterans Administration (VA) population is either overweight or obese, which is a serious health concern. Medical weight management visits have traditionally occurred through in-person clinics. However, the COVID-19 pandemic forced care delivery to virtual platforms. Methods: We compared weight loss with in-person versus telephone-based medical weight management (lifestyle counseling coupled with pharmacotherapy) delivered by physician and nurse practitioner visits during the pandemic. We designed a program evaluation utilizing a naturalistic (pragmatic) observational study structure, including both newly enrolled and previously established participants in the Minneapolis VA MOVE! program between 2017 and 2021. A "transition" cohort (n = 74) received in-person care from March 2019 to March 2020, and then transitioned to virtual care. A "new start" virtual care cohort (n = 149) enrolled after March 2020 was compared to a separate historical group (n = 180) that received in-person care between January 2017 and December 2019. Weight loss was accessed over a 9-month period in both cohorts. Results: Mean weight loss over 9 months was -6.5 ± 18.2 and -2.5 ± 13.3 lbs in the in-person and virtual phases of the transition cohort, respectively, without significant difference between the two phases (p = 0.22). Mean weight loss over 9 months in the new start (virtual) cohort was -14.4 ± 17.0 lbs compared to -16.7 ± 21.0 lbs in the historical cohort, without significant difference between groups (p = 0.44). Conclusions: In our naturalistic study in a single-site VA clinic setting, weight loss with telephone-based medical weight management during the pandemic was comparable to in-person care. These findings are important for veterans living in rural and/or underserved areas.


Subject(s)
COVID-19 , Telemedicine , Veterans , United States , Humans , United States Department of Veterans Affairs , Pandemics , COVID-19/epidemiology , Obesity/epidemiology , Obesity/therapy , Telephone , Weight Loss
4.
Public Health ; 225: 182-190, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37939459

ABSTRACT

OBJECTIVE: To evaluate the association of state-level lack of health insurance among women of reproductive age with variation in state low birth weight (LBW) rates. STUDY DESIGN: This cross-section study analyzes data from the 2016-2019 Pregnancy Risk Assessment Monitoring Survey for respondents with singleton, live births. METHODS: Respondents were divided into groups by state-level percent of uninsured women aged 19-44 years. Poisson regression was used to model the association between state percent uninsured and likelihood of LBW, controlling for individual sociodemographic and clinical risk factors. Sensitivity analyses were done for Medicaid and non-Hispanic Black subpopulations and alternative state characteristics, including Gini coefficients, total and public welfare expenditures, and state reproductive rights rankings. RESULTS: In adjusted multiple regression analyses, compared to respondents from states with <7% uninsured, respondents from states with 7% or more uninsured had an increased risk of LBW status (7-8.99% uninsured: adjusted incidence rate ratio [aIRR] 1.11, 95% confidence interval [CI] 1.04-1.18; 9-11.99% uninsured: aIRR 1.09, 95% CI 1.02-1.17; >11.99% uninsured: aIRR 1.15, 95% CI 1.08-1.22). However, there was no evident dose-response gradient. Sensitivity analyses produced virtually identical findings for subpopulations, and no other state characteristics were significant. CONCLUSION: States with the highest level of insurance coverage had a significantly lower LBW rate than other states. However, there was little evidence for greater odds of LBW with the highest levels of uninsured. Individual risk factors dominated LBW models, while state differences in income inequality, reproductive health policy, and per capita spending explained little of the variance in LBW.


Subject(s)
Insurance, Health , Medically Uninsured , Pregnancy , Infant, Newborn , United States/epidemiology , Humans , Female , Infant, Low Birth Weight , Medicaid , Risk Assessment
5.
J Paediatr Child Health ; 59(7): 879-884, 2023 07.
Article in English | MEDLINE | ID: mdl-37066819

ABSTRACT

AIMS: Knowledge on the spectrum of thyroid disorders amongst Turner syndrome (TS) patients in Southeast Asia is limited. This study aimed to evaluate the prevalence of thyroid autoimmunity, the spectrum of autoimmune thyroid disease and association with age and karyotype amongst Malaysian TS girls. METHODS: A cross-sectional study was conducted at 11 paediatric endocrine units in Malaysia. Blood samples for antithyroglobulin antibodies, antithyroid peroxidase antibodies and thyroid function test were obtained. In patients with pre-existing thyroid disease, information on clinical and biochemical thyroid status was obtained from medical records. RESULTS: Ninety-seven TS patients with a mean age of 13.4 ± 4.8 years were recruited. Thyroid autoimmunity was found in 43.8% of TS patients. Nineteen per cent of those with thyroid autoimmunity had autoimmune thyroid disease (Hashimoto thyroiditis in 7.3% and hyperthyroidism in 1% of total population). Patients with isochromosome X and patients with 45,X mosaicism or other X chromosomal abnormalities were more prone to have thyroid autoimmunity compared to those with 45,X karyotype (OR 5.09, 95% CI 1.54-16.88, P = 0.008 and OR 3.41, 95% CI 1.32-8.82, P = 0.01 respectively). The prevalence of thyroid autoimmunity increased with age (33.3% for age 0-9.9 years; 46.8% for age 10-19.9 years and 57.1% age for 20-29.9 years) with autoimmune thyroid disease detected in 14.3% during adulthood. CONCLUSION: Thyroid autoimmunity was significantly associated with the non 45,X karyotype group, particularly isochromosome X. Annual screening of thyroid function should be carried out upon diagnosis of TS until adulthood with more frequent monitoring recommended in the presence of thyroid autoimmunity.


Subject(s)
Hashimoto Disease , Isochromosomes , Thyroid Diseases , Turner Syndrome , Child , Female , Humans , Adult , Adolescent , Infant, Newborn , Infant , Child, Preschool , Young Adult , Hashimoto Disease/diagnosis , Hashimoto Disease/genetics , Autoimmunity , Turner Syndrome/complications , Turner Syndrome/diagnosis , Turner Syndrome/epidemiology , Cross-Sectional Studies , Autoantibodies/genetics , Thyroid Diseases/complications , Thyroid Diseases/diagnosis , Thyroid Diseases/epidemiology , Chromosome Aberrations
7.
Clin Transplant ; 36(10): e14703, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35538019

ABSTRACT

BACKGROUND: There are currently no guidelines pertaining to ERAS pathways in living donor hepatectomy. OBJECTIVES: The aim of this study was to identify whether surgical technique influences immediate and short-term outcomes after living liver donation surgery. DATA SOURCES: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. METHODS: Systematic review and meta-analysis following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel (CRD42021260707). Endpoints were mortality, overall complications, serious complications, bile eaks, pulmonary complications, estimated blood loss and length of stay. RESULTS: Of the 2410 screened articles, 21 articles were included for final analysis; three observational, 13 retrospective cohort, four prospective cohort studies, and one randomized trial. Overall complications were higher with right versus left hepatectomy (26.8% vs. 20.8%; OR 1.4, P = .010). Donors after left hepatectomy had shorter length of stay (MD 1.4 days) compared to right hepatectomy. There was no difference in outcomes after right donor hepatectomy with versus without middle hepatic vein. We had limited data on the influence of incision type and minimally invasive approaches on living donor outcomes, and no data on the effect of operative time on donor outcomes. CONCLUSIONS: Left donor hepatectomy should be preferred over right hepatectomy, as it is related to improved donor short-term outcomes (QOE; Moderate | Grade of Recommendation; Strong). Right donor hepatectomy with or without MHV has equivalent outcomes (QOE; Moderate | Grade of Recommendation; Strong); no preference is recommended, decision should be based on program's experience and expertise. No difference in outcomes was observed related to incision type, minimally invasive vs. open (QOE; Low | Grade of Recommendation; Weak); no preference can be recommended.


Subject(s)
Laparoscopy , Liver Transplantation , Humans , Retrospective Studies , Prospective Studies , Liver Transplantation/adverse effects , Laparoscopy/methods , Length of Stay , Postoperative Complications/etiology , Living Donors , Hepatectomy/methods , Liver/surgery
8.
Ann Oncol ; 32(12): 1626-1636, 2021 12.
Article in English | MEDLINE | ID: mdl-34606929

ABSTRACT

BACKGROUND: Tumor mutational burden (TMB) measurements aid in identifying patients who are likely to benefit from immunotherapy; however, there is empirical variability across panel assays and factors contributing to this variability have not been comprehensively investigated. Identifying sources of variability can help facilitate comparability across different panel assays, which may aid in broader adoption of panel assays and development of clinical applications. MATERIALS AND METHODS: Twenty-nine tumor samples and 10 human-derived cell lines were processed and distributed to 16 laboratories; each used their own bioinformatics pipelines to calculate TMB and compare to whole exome results. Additionally, theoretical positive percent agreement (PPA) and negative percent agreement (NPA) of TMB were estimated. The impact of filtering pathogenic and germline variants on TMB estimates was assessed. Calibration curves specific to each panel assay were developed to facilitate translation of panel TMB values to whole exome sequencing (WES) TMB values. RESULTS: Panel sizes >667 Kb are necessary to maintain adequate PPA and NPA for calling TMB high versus TMB low across the range of cut-offs used in practice. Failure to filter out pathogenic variants when estimating panel TMB resulted in overestimating TMB relative to WES for all assays. Filtering out potential germline variants at >0% population minor allele frequency resulted in the strongest correlation to WES TMB. Application of a calibration approach derived from The Cancer Genome Atlas data, tailored to each panel assay, reduced the spread of panel TMB values around the WES TMB as reflected in lower root mean squared error (RMSE) for 26/29 (90%) of the clinical samples. CONCLUSIONS: Estimation of TMB varies across different panels, with panel size, gene content, and bioinformatics pipelines contributing to empirical variability. Statistical calibration can achieve more consistent results across panels and allows for comparison of TMB values across various panel assays. To promote reproducibility and comparability across assays, a software tool was developed and made publicly available.


Subject(s)
Mutation , Neoplasms , Biomarkers, Tumor , Humans , Neoplasms/diagnosis , Neoplasms/genetics , Reproducibility of Results , Tumor Burden
9.
J Paediatr Child Health ; 56(2): 272-275, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31410904

ABSTRACT

AIM: Perforated appendicitis has poorer clinical outcomes compared to non-perforated appendicitis. However, accurate outcome comparisons in research and clinical audits are challenged by its wide spectrum of manifestation. Previous attempts at the classification of severity have been complex and difficult to reproduce. In our study, we used another institution's (Jones et al., TX, USA) previously described simple classification system of peritoneal contamination and examined its usefulness in predicting outcomes. METHODS: With ethical approval, we retrospectively reviewed the records of all paediatric patients operated at our institution for perforated appendicitis from 2016 to 2017. Patient demographics, intra-operative and histological findings, post-operative outcomes and length of stay were collected. Patients were categorised into group 1 (purulence in right lower quadrant only) and group 2 (contamination in two or more quadrants). Post-operative complications were defined as procedure-related (e.g. post-operative ileus, intra-abdominal abscess, visceral injury) and non-procedure-related (e.g. bronchospasm). Statistical analysis using χ2 tests for categorical data and Mann-Whitney U-tests for non-parametric continuous variables was performed, with a significance of P < 0.05. RESULTS: There were 134 eligible patients. We excluded 19 with incomplete data, leaving 115 for analysis, of which 69 (60%) were in group 2. Those in group 2 had a longer stay (P = 0.005) and more post-operative complications (P = 0.001), particularly procedure-related events (P = 0.006). There were no differences in age (P = 0.182), gender (P = 0.876), readmission rate (P = 0.317) and non-procedure-related post-operative complications (0.152). CONCLUSION: This simple classification of perforated appendicitis appears to differentiate clinical outcomes well, particularly for iatrogenic morbidity, making it useful for operative preparation and outcomes research.


Subject(s)
Abdominal Abscess , Appendicitis , Appendectomy/adverse effects , Appendicitis/surgery , Child , Humans , Length of Stay , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Retrospective Studies
10.
Int J Dermatol ; 58(12): 1382-1387, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31286498

ABSTRACT

BACKGROUND: Reflectance confocal microscopy (RCM) is increasingly used for noninvasive in vivo diagnosis of skin cancers. We seek to determine if RCM is useful for the diagnosis and follow-up of squamous cell carcinoma in situ (SCCIS) posttreatment to document clearance. METHODS: A pilot prospective study enrolled 10 patients with a total of 11 SCCIS lesions. Clinical, confocal, histological features and fluorescence diagnosis (FD) were recorded pre- and posttreatment. RESULTS: Four SCCIS lesions underwent RCM imaging prior to biopsy, while 11 SCCIS lesions were followed up with RCM imaging. Clinical features of persistent SCCIS post-PDT in four out of 11 follow-up cases were confirmed with RCM and FD. There were no RCM features of SCCIS in seven lesions which were clinically cured. All eight (four new SCCIS and four follow-up) cases displayed atypical honeycomb pattern. Two cases (25%) showed numerous epidermal dendritic cells, while small bright refractive cells were present in the epidermis in two lesions (25%). Round blood vessels in the superficial dermis were seen in four lesions (50%), while three lesions (37.5%) showed dermal inflammatory cells. CONCLUSION: There was good correlation between histological and confocal features in patients who underwent RCM imaging prior to biopsy. RCM may be a complementary tool in diagnosing SCCIS and to monitor response to nonsurgical treatment by avoiding unnecessary biopsies especially in lesions with persistent residual postinflammatory erythema.


Subject(s)
Carcinoma, Squamous Cell/diagnosis , Epidermis/diagnostic imaging , Photochemotherapy/methods , Skin Neoplasms/diagnosis , Aftercare/methods , Aged , Aged, 80 and over , Aminolevulinic Acid/administration & dosage , Aminolevulinic Acid/analogs & derivatives , Biopsy , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/pathology , Epidermis/drug effects , Epidermis/pathology , Epidermis/radiation effects , Female , Follow-Up Studies , Humans , Male , Microscopy, Confocal/methods , Middle Aged , Pilot Projects , Prospective Studies , Skin Cream/administration & dosage , Skin Neoplasms/drug therapy , Skin Neoplasms/pathology , Treatment Outcome
11.
Article in English | MEDLINE | ID: mdl-30831468

ABSTRACT

New antimalarial agents are identified and developed after extensive testing on Plasmodium falciparum parasites that can be grown in vitro. These susceptibility studies are important to inform lead optimisation and support further drug development. Until recently, little was known about the susceptibility of non-falciparum species as these had not been adapted to in vitro culture. The recent culture adaptation of P. knowlesi has therefore offered an opportunity to routinely define the drug susceptibility of this species, which is phylogenetically closer to all other human malarias than is P. falciparum. We compared the in vitro susceptibility of P. knowlesi and P. falciparum to a range of established and novel antimalarial agents under identical assay conditions. We demonstrated that P. knowlesi is significantly less susceptible than P. falciparum to six of the compounds tested; and notably these include three ATP4 inhibitors currently under development as novel antimalarial agents, and one investigational antimalarial, AN13762, which is 67 fold less effective against P. knowlesi. For the other compounds there was a less than two-fold difference in susceptibility between species. We then compared the susceptibility of a recent P. knowlesi isolate, UM01, to that of the well-established, older A1-H.1 clone. This recent isolate showed similar in vitro drug susceptibility to the A1-H.1 clone, supporting the ongoing use of the better characterised clone to further study drug susceptibility. Lastly, we used isobologram analysis to explore the interaction of a selection of drug combinations and showed similar drug interactions across species. The species differences in drug susceptibility reported by us here and previously, support adding in vitro drug screens against P. knowlesi to those using P. falciparum strains to inform new drug discovery and lead optimisation.


Subject(s)
Antimalarials/pharmacology , Plasmodium falciparum/drug effects , Plasmodium knowlesi/drug effects , Artemisinins/pharmacology , Drug Combinations , Drug Discovery , Parasitic Sensitivity Tests
13.
Sci Total Environ ; 581-582: 782-793, 2017 Mar 01.
Article in English | MEDLINE | ID: mdl-28065542

ABSTRACT

Bio-accessibility and bioavailability of arsenic (As) in historically As-contaminated soils (cattle tick pesticide), and pristine soils were assessed using 3 different approaches. These approaches included human bio-accessibility using an extraction test replicating gastric conditions (in vitro physiologically-based extraction test); an operationally defined bioaccessibility extraction test - 1.0M HCl extraction; and a live organism bioaccumulation test using earthworms. A sequential extraction procedure revealed the soil As-pool that controls bio-accessibility and bioaccumulation of As. Findings show that As is strongly bound to historically contaminated soil with a lower degree of As bio-accessibility (<15%) and bioaccumulation (<9%) compared with freshly contaminated soil. Key to these lower degrees of bio-accessibility and bioaccumulation is the greater fraction of As associated with crystalline Fe/Al oxy-hydroxide and residual phases. The high bio-accessibility and bioaccumulation of freshly sorbed As in pristine soils were from the exchangeable and specifically sorbed As fractions. Arsenic bioaccumulation in earthworms correlates strongly with both the human bio-accessible, and the operationally defined bioavailable fractions. Hence, results suggest that indirect As bioavailability measures, such as accumulation by earthworm, can be used as complementary lines of evidence to reinforce site-wide trends in the bio-accessibility using in vitro physiologically-based extractions and/or operationally defined extraction test. Such detailed knowledge is useful for successful reclamation and management of the As contaminated soils.


Subject(s)
Arsenic/analysis , Pesticides/analysis , Soil Pollutants/analysis , Animals , Biological Availability , Environmental Pollution , Humans , Oligochaeta , Soil
14.
Chemosphere ; 168: 1324-1336, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27916260

ABSTRACT

Historic arsenic contamination of soils occurs throughout the world from mining, industrial and agricultural activities. In Australia, the control of cattle ticks using arsenicals from the late 19th to mid 20th century has led to some 1600 contaminated sites in northern New South Wales. The effect of aging in As-mobility in two dip-site soil types, ferralitic and sandy soils, are investigated utilizing isotopic exchange techniques, and synchrotron X-ray adsorption spectroscopy (XAS). Findings show that historic soil arsenic is highly bound to the soils with >90% irreversibly bound. However, freshly added As (either added to historically loaded soils or pristine soils) has a significantly higher degree of As-accessibility. XAS data indicates that historic soil arsenic is dominated as Ca- (svenekite, & weilite), Al-(mansfieldite), and Fe- (scorodite) like mineral precipitates, whereas freshly added As is dominated by mineral adsorption surfaces, particularly the iron oxy-hydroxides (goethite and hematite), but also gibbsite and kaolin surfaces. SEM data further confirmed the presence of scorodite and mansfieldite formation in the historic contaminated soils. These data suggest that aging of historic soil-As has allowed neoformational mineral recrystallisation from surface sorption processes, which greatly reduces As-mobility and accessibility.


Subject(s)
Arsenic/chemistry , Minerals/chemistry , Soil Pollutants/chemistry , Soil/chemistry , Adsorption , Aluminum Compounds/chemistry , Calcium Compounds/chemistry , Iron Compounds/chemistry , Mining , New South Wales , Pesticides
15.
J Perinatol ; 37(3): 215-219, 2017 03.
Article in English | MEDLINE | ID: mdl-27735932

ABSTRACT

In our perinatal HIV cohort, we have observed difficulty swallowing pills as a frequent and significant barrier to adherence to highly active antiretroviral therapy. We refer to this problem as pill aversion and define it as difficulty swallowing pills with no persistent medical or structural cause as well as the anxiety and physical symptoms associated with pill swallowing. By applying cognitive behavioral theory to behavioral patterns within our pregnant HIV-infected population, we seek to better understand the development and reinforcement of pill aversion behavior. On the basis of this theory, our experience, and the pediatric pill-swallowing literature, we propose a conceptual framework for understanding the multiple causes of pill aversion and applying therapeutic interventions to a perinatal population. In a theoretical discussion, we address the roles of classical conditioning and cognitive theory in the development and experience of pill aversion in an HIV-infected pregnant population. We propose future steps for characterizing these behaviors and testing theories and interventions.


Subject(s)
Antiretroviral Therapy, Highly Active , Deglutition , HIV Infections/drug therapy , Medication Adherence/psychology , Pregnancy Complications, Infectious/drug therapy , Tablets/administration & dosage , Cohort Studies , Conditioning, Classical , Female , Humans , Infectious Disease Transmission, Vertical/prevention & control , Pregnancy/psychology , Psychoanalytic Theory
16.
J Perinatol ; 37(1): 21-26, 2017 01.
Article in English | MEDLINE | ID: mdl-27684420

ABSTRACT

OBJECTIVE: To characterize pregnant patients' knowledge, attitudes and preferences regarding antenatal HIV testing for themselves and their sexual partners. STUDY DESIGN: Observational, mixed methods study of HIV-negative pregnant women from a university-based urban clinic. Participants completed an anonymous survey about HIV testing for themselves and their partners. Descriptive statistics, bivariable analyses, multivariable logistic regression and qualitative thematic analysis were utilized. RESULTS: One hundred and forty-two patients (mean age 28.6±5.5 years) participated. A majority (57.7%) were married or partnered, and 92.9% reported having at least one current sexual partner. Although a majority (62.8%) reported their partner had a prior HIV test, and 93.0% of these women were aware of test results, only 20.7% reported partner testing had occurred in the past 6 months. Women who had a prior HIV test, who were older or who were non-white were more likely to be aware of their partner's HIV status. A majority (66.9%) of women desired knowledge of their partner's current status and 76.0% believed their partners would like to know his HIV status; in addition, 74% were interested in receiving partner testing at the site of prenatal care. Qualitative analysis demonstrated that health concerns and believing HIV knowledge is important to the relationship were motivators for desiring partner testing. CONCLUSIONS: In this urban community, a majority of pregnant women do not know HIV test results of their sexual partner during the current pregnancy. Women desired to know their partner's HIV status and were receptive to partner testing at the site of prenatal care or other locations. Partner testing may be a critical step toward elimination of seroconversion during pregnancy and maternal-to-child HIV transmission.


Subject(s)
HIV Infections/prevention & control , Health Knowledge, Attitudes, Practice , Infectious Disease Transmission, Vertical/prevention & control , Pregnancy Complications, Infectious/prevention & control , Sexual Partners , Adult , Chicago , Female , HIV Infections/diagnosis , Hospitals, Urban , Humans , Logistic Models , Male , Mass Screening/methods , Multivariate Analysis , Needs Assessment , Pregnancy , Pregnancy, High-Risk , Prenatal Care , Prenatal Diagnosis/methods , Surveys and Questionnaires
17.
Aliment Pharmacol Ther ; 44(9): 957-966, 2016 11.
Article in English | MEDLINE | ID: mdl-27629859

ABSTRACT

BACKGROUND: In patients with chronic hepatitis B, tenofovir disoproxil fumarate (TDF) plus pegylated interferon (PEG-IFN) for 48-weeks results in higher rates of hepatitis B surface antigen (HBsAg) loss than either monotherapy. AIM: To identify baseline and on-treatment factors associated with HBsAg loss at Week 72 and provide a model for predicting HBsAg loss in patients receiving combination therapy for 48 weeks. METHODS: A secondary analysis of data from an open-label study where patients were randomised to TDF (300 mg/day, oral) plus PEG-IFN (PI, 180 µg/week, subcutaneous) for 48 weeks (TDF/PI-48w); TDF plus PEG-IFN for 16 weeks, TDF for 32 weeks (TDF/PI-16w+TDF-32w); TDF for 120 weeks (TDF-120w) or PEG-IFN for 48 weeks (PI-48w). Logistic regression methods were used to identify models that best predicted HBsAg loss at Week 72. RESULTS: Rates of HBsAg loss at Week 72 were significantly higher in the TDF/PI-48w group (6.5%) than in the TDF/PI-16w+TDF-32w (0.5%), TDF-120w (0%) and PI-48w (2.2%) groups (P = 0.09). The only baseline factor associated with response was genotype A. HBsAg decline at Week 12 or 24 of treatment was associated with HBsAg loss at Week 72 (P < 0.001). HBsAg decline >3.5 log10 IU/mL at Week 24 in the TDF/PI-48w group resulted in a positive predictive value of 85% and a negative predictive value of 99% for HBsAg loss at Week 72. CONCLUSIONS: HBsAg decline at Week 24 of TDF plus PEG-IFN combination therapy may identify patients who, after completing 48 weeks of treatment, have a better chance of achieving HBsAg loss at Week 72.


Subject(s)
Antiviral Agents/administration & dosage , Hepatitis B, Chronic/diagnosis , Hepatitis B, Chronic/drug therapy , Interferon-alpha/administration & dosage , Polyethylene Glycols/administration & dosage , Tenofovir/administration & dosage , Administration, Oral , Adult , DNA, Viral/blood , Drug Therapy, Combination , Female , Hepatitis B Surface Antigens/blood , Hepatitis B virus/drug effects , Hepatitis B virus/genetics , Humans , Injections, Subcutaneous , Male , Middle Aged , Predictive Value of Tests , Recombinant Proteins/administration & dosage , Treatment Outcome
18.
Front Microbiol ; 7: 808, 2016.
Article in English | MEDLINE | ID: mdl-27303390

ABSTRACT

Toxoplasma gondii is the causative agent for toxoplasmosis. The rhoptry protein 1 (ROP1) is secreted by rhoptry, an apical secretory organelle of the parasite. ROP1 plays an important role in host cell invasion. In this study, the efficacy of ROP1 as a vaccine candidate against toxoplasmosis was evaluated through intramuscular or subcutaneous injection of BALB/c mice followed by immunological characterization (humoral- and cellular-mediated) and lethal challenge against virulent T. gondii RH strain in BALB/c mice. Briefly, a recombinant DNA plasmid (pVAX1-GFP-ROP1) was expressed in CHO cells while expression of recombinant ROP1 protein (rROP1) was carried out in Escherichia coli expression system. Immunization study involved injection of the recombinant pVAX1-ROP1 and purified rROP1 into different group of mice. Empty vector and PBS served as two different types of negative controls. Results obtained demonstrated that ROP1 is an immunogenic antigen that induced humoral immune response whereby detection of a protein band with expected size of 43 kDa was observed against vaccinated mice sera through western blot analysis. ROP1 antigen was shown to elicit cellular-mediated immunity as well whereby stimulated splenocytes with total lysate antigen (TLA) and rROP1 from pVAX1-ROP1 and rROP1-immunized mice, respectively, readily proliferated and secreted large amount of IFN-γ (712 ± 28.1 pg/ml and 1457 ± 31.19 pg/ml, respectively) and relatively low IL-4 level (94 ± 14.5 pg/ml and 186 ± 14.17 pg/ml, respectively). These phenomena suggested that Th1-favored immunity was being induced. Vaccination with ROP1 antigen was able to provide partial protection in the vaccinated mice against lethal challenge with virulent RH strain of tachyzoites. These findings proposed that the ROP1 antigen is a potential candidate for the development of vaccine against toxoplasmosis.

19.
Front Microbiol ; 7: 609, 2016.
Article in English | MEDLINE | ID: mdl-27199938

ABSTRACT

Toxoplasmosis is a foodborne disease caused by Toxoplasma gondii, an obligate intracellular parasite. Severe symptoms occur in the immunocompromised patients and pregnant women leading to fatality and abortions respectively. Vaccination development is essential to control the disease. The T. gondii dense granule antigen 2 and 5 (GRA2 and GRA5) have been targeted in this study because these proteins are essential to the development of parasitophorous vacuole (PV), a specialized compartment formed within the infected host cell. PV is resistance to host cell endosomes and lysosomes thereby protecting the invaded parasite. Recombinant dense granular proteins, GRA2 (rGRA2) and GRA5 (rGRA5) were cloned, expressed, and purified in Escherichia coli, BL21 (DE3) pLysS. The potential of these purified antigens as subunit vaccine candidates against toxoplasmosis were evaluated through subcutaneous injection of BALB/c mice followed by immunological characterization (humoral- and cellular-mediated) and lethal challenge against virulent T. gondii RH strain in BALB/c mice. Results obtained demonstrated that rGRA2 and rGRA5 elicited humoral and cellular-mediated immunity in the mice. High level of IgG antibody was produced with the isotype IgG2a/IgG1 ratio of ≈0.87 (p < 0.001). Significant increase (p < 0.05) in the level of four cytokines (IFN-γ, IL-2, IL-4, and IL-10) was obtained. The antibody and cytokine results suggest that a mix mode of Th1/Th2-immunity was elicited with predominant Th1-immune response inducing partial protection against T. gondii acute infection in BALB/c mice. Our findings indicated that both GRA2 and GRA5 are potential candidates for vaccine development against T. gondii acute infection.

20.
J Perinatol ; 36(8): 593-7, 2016 08.
Article in English | MEDLINE | ID: mdl-27031319

ABSTRACT

OBJECTIVE: The objective of this study was to investigate the association between interdelivery interval (IDI) and subsequent perinatal outcomes in a large population-based cohort. STUDY DESIGN: Retrospective cohort study of primiparous women with singleton gestations giving birth in the US in 2011 to 2012. IDI was defined as the time between last live birth and index live birth. IDI was categorized as 4 to 17 months, 18 to 36 months (referent), 37 to 60 months and >60 months. Statistical comparisons were made using chi-square tests and multivariable logistic regression models to control for confounding. Covariates included maternal age, prior preterm birth, prior cesarean and medical comorbidities. RESULTS: Of the 1 964 523 women meeting study criteria, 9.0% had an IDI of 4 to 17 months, 39.7% 18 to 36 months, 26.8% 37 to 60 months and 24.5% >60 months. Short IDI was associated with preterm delivery (<37 weeks; 13.8 vs 8.8%, (adjusted odds ratio (aOR) 1.51, 95% confidence interval (CI) 1.48 to 1.53)) and adverse perinatal outcomes including low 5-min Apgar, small for gestational age (SGA) status and neonatal intensive care unit (NICU) admission. Women with long IDI had a higher risk of induction of labor, cesarean delivery, chorioamnionitis, maternal ICU admission, preterm delivery and SGA status, 5-min Apgar score <4, and NICU admission. CONCLUSIONS: Compared with women with 18 to 36 month IDIs, women with either shorter or very long IDIs were at an increased risk of adverse maternal and neonatal outcomes.


Subject(s)
Birth Intervals/statistics & numerical data , Cesarean Section/statistics & numerical data , Pregnancy Outcome/epidemiology , Premature Birth/epidemiology , Adult , Apgar Score , Confounding Factors, Epidemiologic , Female , Humans , Infant, Newborn , Infant, Small for Gestational Age , Logistic Models , Male , Maternal Age , Multivariate Analysis , Pregnancy , Registries , Retrospective Studies , United States/epidemiology , Young Adult
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