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Journal of Viral Hepatitis Jan 2024Pregnant mothers with chronic hepatitis B infection (CHB) need peri-partum antiviral prophylaxis (PAP) to reduce the risk of mother-to-child-transmission. Currently, PAP...
Pregnant mothers with chronic hepatitis B infection (CHB) need peri-partum antiviral prophylaxis (PAP) to reduce the risk of mother-to-child-transmission. Currently, PAP is recommended in those with high viral load (VL) that is, HBV DNA >200,000 IU/mL. Quantitative hepatitis B surface antigen (qHBsAg) >10,000 IU/mL, a cut-off derived primarily from hepatitis B e-antigen (HBeAg) positive antenatal cohorts in Chinese populations, is advocated as a surrogate marker of VL for guiding PAP. We investigated the utility of qHBsAg to predict high-VL in a multi-ethnic urban cohort with CHB. A consecutive cohort of women with CHB was identified from Barts Health NHS Trust databases in the United Kingdom. We included women with paired HBV DNA and qHBsAg during pregnancy. Women already on antiviral at conception were excluded. A total of 769 pregnancies in 678 CHB pregnant mothers (median age 31 years-old, 8.6% HBeAg+) were included. At median gestational age of 15.3 weeks, HBV DNA was 336 (IQR 44-2998) IU/mL, with 65 (8.5%) being high-VL. Serum qHBsAg was most useful in Black/Black-British/Caribbean/African (AUROC 0.946) with 100% sensitivity and 80.6% specificity to predict high-VL; but it performed less well for other ethnicities: Asian (AUROC 0.877), White (AUROC 0.797) and mixed ethnicities (AUROC 0.742). In conclusion, for settings where healthcare resources are not limited, HBV DNA remains the optimal marker to identify highly viraemic pregnancies for guiding PAP. For resource-limited settings where the prevailing cost is treatment, serum qHBsAg can be used in Black/Black British/Caribbean/African sub-cohorts, but not for other ethnicities.
Topics: Female; Humans; Pregnancy; Adult; Infant; Hepatitis B virus; Hepatitis B Surface Antigens; Hepatitis B e Antigens; DNA, Viral; Infectious Disease Transmission, Vertical; Hepatitis B, Chronic; Hepatitis B; Antiviral Agents
PubMed: 37881873
DOI: 10.1111/jvh.13893 -
Neuropsychiatric Disease and Treatment 2023The gene encodes the thyroid hormone (TH) transporter MCT8. Pathogenic variants result in a reduced TH uptake into the CNS despite high serum T3 concentrations....
INTRODUCTION
The gene encodes the thyroid hormone (TH) transporter MCT8. Pathogenic variants result in a reduced TH uptake into the CNS despite high serum T3 concentrations. Patients suffer from severe neurodevelopmental delay and require multidisciplinary care. Since a first compassionate use study in 2008, the development of therapies has recently gained momentum. Treatment strategies range from symptom-based approaches, supplementation with TH or TH-analogs, to gene therapy. All these studies have mainly used surrogate endpoints and clinical outcomes. However, the EMA and FDA strongly encourage researchers to involve patients and their advocacy groups in the design of clinical trials. This should strengthen the patients' perspective and identify clinical endpoints that are clinically relevant to their daily life.
METHODS
We involved patient families to define patient-relevant outcomes for MCT8 deficiency. In close collaboration with patient families, we designed a questionnaire asking for their five most preferred therapeutic goals, which, if achieved at least, make a difference in their lives. In addition, we performed a systematic review according to Cochrane recommendations of the published treatment trials.
RESULTS
We obtained results from 15 families with completed questionnaires from 14 mothers and 8 fathers. Improvement in development, especially in gross motor skills, was most important to the parents. 59% wished for head control and 50% for sitting ability. Another 36% wished for weight gain, 32% for improvement of expressive language skills, and 18% for a reduction of dystonia/spasticity, less dysphagia, and reflux. Paraclinical aspects were least important (5-9%). In a treatment trial (n=46) and compassionate use cases (n=83), the results were mainly inconclusive, partly due to a lack of predefined patient-centered clinical endpoints.
DISCUSSION
We recommend that future trials should define a relevant improvement in "development" and/or other patient-relevant outcomes compared to natural history as treatment goals.
PubMed: 37881807
DOI: 10.2147/NDT.S379703 -
JAMA Nov 2023
Topics: Female; Humans; Pregnancy; Fertilization in Vitro; Pregnancy Outcome; Reproductive Techniques, Assisted; Retrospective Studies; Surrogate Mothers
PubMed: 37851614
DOI: 10.1001/jama.2023.11023 -
Irish Journal of Medical Science Apr 2024Surrogacy is a form of assisted human reproduction whereby a surrogate woman carries a pregnancy for a commissioning couple or individual. There are two types of... (Review)
Review
BACKGROUND
Surrogacy is a form of assisted human reproduction whereby a surrogate woman carries a pregnancy for a commissioning couple or individual. There are two types of surrogacy, traditional and gestational. Worldwide we have seen a rapid increase in the use of surrogacy. Despite this, there is a lack of consensus internationally on the laws governing surrogacy. In Ireland, surrogacy remains largely unregulated. Currently, there is no specific legislation for surrogacy. This review aims to discuss its current regulatory status and associated ethical issues.
AIMS
On surrogacy from an Irish legal perspective, this study is to (i) demonstrate the lack of legislation, (ii) describe the Health Bill 2022 and (iii) examine the challenges surrounding surrogacy and Irish case law. On surrogacy from an Irish ethical perspective, this study is to (iv) discuss the ethical issues surrounding autonomy, (v) discuss the ethical issues surrounding non-maleficence, (vi) discuss the ethical issues surrounding justice and (vii) evaluate ethical issues specific to commercial surrogacy: (1) child welfare and (2) commodification and exploitation of children and women's bodies.
CONCLUSION
Surrogacy has raised several ethical issues. There are issues surrounding autonomy of the surrogate and commissioning couple, child welfare, exploitation and commodification, non-maleficence and justice. There are also significant legal concerns with surrogacy. It is neither legal nor illegal in Ireland. This creates challenges for the commissioning couple particularly in terms of custody of the child.
Topics: Pregnancy; Child; Female; Humans; Ireland; Surrogate Mothers; Uterus
PubMed: 37831359
DOI: 10.1007/s11845-023-03546-9 -
BMJ (Clinical Research Ed.) Oct 2023
Topics: Humans; Female; Pregnancy; Industry; Surrogate Mothers
PubMed: 37827543
DOI: 10.1136/bmj.p2003 -
Nature Communications Sep 2023Tumor recognition by T cells is essential for antitumor immunity. A comprehensive characterization of T cell diversity may be key to understanding the success of...
Tumor recognition by T cells is essential for antitumor immunity. A comprehensive characterization of T cell diversity may be key to understanding the success of immunomodulatory drugs and failure of PD-1 blockade in tumors such as multiple myeloma (MM). Here, we use single-cell RNA and T cell receptor sequencing to characterize bone marrow T cells from healthy adults (n = 4) and patients with precursor (n = 8) and full-blown MM (n = 10). Large T cell clones from patients with MM expressed multiple immune checkpoints, suggesting a potentially dysfunctional phenotype. Dual targeting of PD-1 + LAG3 or PD-1 + TIGIT partially restored their function in mice with MM. We identify phenotypic hallmarks of large intratumoral T cell clones, and demonstrate that the CD27 and CD27 T cell ratio, measured by flow cytometry, may serve as a surrogate of clonal T cell expansions and an independent prognostic factor in 543 patients with MM treated with lenalidomide-based treatment combinations.
Topics: Adult; Humans; Animals; Mice; Multiple Myeloma; T-Lymphocytes; Programmed Cell Death 1 Receptor; Lenalidomide; Clone Cells
PubMed: 37730678
DOI: 10.1038/s41467-023-41562-6 -
Journal of Assisted Reproduction and... Nov 2023In the last four decades, the assisted reproductive technology (ART) field has witnessed advances, resulting in improving pregnancy rates and diminishing complications,... (Review)
Review
In the last four decades, the assisted reproductive technology (ART) field has witnessed advances, resulting in improving pregnancy rates and diminishing complications, in particular reduced incidence of multiple births. These improvements are secondary to advanced knowledge on embryonic physiology and metabolism, resulting in the ability to design new and improved culture conditions. Indeed, the incubator represents only a surrogate of the oviduct and uterus, and the culture conditions are only imitating the physiological environment of the female reproductive tract. In vivo, the embryo travels through a dynamic and changing environment from the oviduct to the uterus, while in vitro, the embryo is cultured in a static fashion. Importantly, while culture media play a critical role in optimising embryo development, a large host of additional factors are equally important. Additional potential variables, including but not limited to pH, temperature, osmolality, gas concentrations and light exposure need to be carefully controlled to prevent stress and permit optimal implantation potential. This manuscript will provide an overview of how different current culture conditions may affect oocyte and embryo viability with particular focus on human literature.
Topics: Pregnancy; Humans; Female; Reproductive Techniques, Assisted; Embryo Implantation; Embryonic Development; Embryo, Mammalian; Culture Media; Embryo Culture Techniques; Fertilization in Vitro
PubMed: 37725178
DOI: 10.1007/s10815-023-02934-5 -
Medical Law Review Feb 2024For the court to grant a parental order recognising intended parents as legal parents of a surrogate-born child, the gametes of at least one of the intended parents must...
For the court to grant a parental order recognising intended parents as legal parents of a surrogate-born child, the gametes of at least one of the intended parents must have been used to create the embryo, under section 54(1)(b) and section 54A(1)(b) Human Fertilisation and Embryology Act 2008. In the Law Commission and Scottish Law Commission's consultation paper, there was a provisional proposal to remove the genetic link requirement in cases of medical necessity. However, this proposal was not included in the Law Commissions' Final Report, instead recommending the retention of the requirement for a genetic link in almost all circumstances. This article contends that the Law Commissions' recommendation should be reconsidered in light of the child's right to identity. By reviewing how identity has been used by the courts when determining whether to grant a parental order, as well as a developing interpretation of Article 8 of the United Nations Convention on the Rights of the Child and European Convention on Human Rights, it can be asserted that the identity of surrogate-born children necessitates recognition of the relationship between the child and intended parent(s), irrespective of a genetic link. On this basis, it is argued that there should be the possibility for intended parents to establish legal parenthood following surrogacy without the requirement for a genetic link.
Topics: Child; Humans; Female; Pregnancy; Parents; Human Rights; Surrogate Mothers
PubMed: 37717271
DOI: 10.1093/medlaw/fwad032 -
Journal of Clinical Epidemiology Oct 2023We operationalized a research usefulness tool identified through literature searches and consensus and examined if randomized controlled trials (RCTs) addressing preterm...
OBJECTIVES
We operationalized a research usefulness tool identified through literature searches and consensus and examined if randomized controlled trials (RCTs) addressing preterm birth prevention met predefined criteria for usefulness.
STUDY DESIGN AND SETTING
The usefulness tool included eight criteria combining 13 items. RCTs were evaluated for compliance with each item by multiple assessors (reviewer agreement 95-98%). Proportions of compliances with 95% confidence interval (CI) were calculated and change over time was assessed using ≧ 2010 as a cutoff.
RESULTS
Among 347 selected RCTs, published within 56 preterm birth Cochrane reviews, only 36 (10%, 95% CI = 7-14%) met more than half of the usefulness criteria. Compared to trials before 2010, recent trials used composite or surrogate (less informative) outcomes more often (13% vs. 25%, relative risk 1.91, 95% CI = 1.21-3.00). Only 16 trials reflected real practice (pragmatism) in design (5%, 95% CI = 3-7%), with no improvements over time. No trials reported involvement of mothers to reflect patients' research priorities and outcomes selection. Recent trials were more transparent.
CONCLUSION
Few preterm birth prevention RCTs met more than half of the usefulness criteria but most of usefulness criteria are improving after 2010. Use of informative outcomes, patient centeredness, pragmatism and transparency should be key targets for future research planning.
Topics: Infant, Newborn; Female; Humans; Premature Birth; Randomized Controlled Trials as Topic
PubMed: 37657614
DOI: 10.1016/j.jclinepi.2023.08.016 -
Fertility and Sterility Oct 2023Physicians involved in third-party assisted reproductive technology arrangements who discover material misconduct or other undisclosed information by a party to the...
Physicians involved in third-party assisted reproductive technology arrangements who discover material misconduct or other undisclosed information by a party to the arrangement (such as a gamete or embryo donor, gestational carrier, or intended parent) or by a nonmedical professional participant or entity (such as a recruiting program, gamete or embryo bank, or lawyer) should encourage that party or professional participant to disclose such misconduct or information. In some instances, it is ethically permissible for the physician to either disclose material information to the affected party or to decline to provide or continue to provide care. In all cases involving the legal status or rights of the parties, physicians should recommend that patients seek independent legal professional advice. This document replaces the document "Misconduct in third-party assisted reproduction," last published in 2018. The use of a physician's own gametes for the purpose of reproduction without the informed consent of the recipient(s) is unethical and illegal, as well as never permissible.
Topics: Humans; Female; Pregnancy; Embryo, Mammalian; Ethics Committees; Germ Cells; Reproductive Techniques, Assisted; Surrogate Mothers
PubMed: 37656092
DOI: 10.1016/j.fertnstert.2023.07.002