Self-collection of samples for group B streptococcus testing during pregnancy: a systematic review and meta-analysis.

BACKGROUND: Sample self-collection for reproductive tract infection diagnosis has been found to offer greater convenience, privacy, autonomy, and expanded access to testing in non-pregnant adults. This review aimed to determine whether sample self-collection is as accurate as provider-collection for detection of group B streptococcus colonisation in pregnancy and whether a strategy of self-collection compared to provider-collection might improve maternal and neonatal health outcomes. METHODS: We searched CINAHL Plus, Medline, EMBASE, Maternity and Infant Care Database, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews in June 2022. Eligible studies compared self-collected and provider-collected samples taken from the same participants or participants randomised to either self-collection or provider-collection for reproductive tract infection testing using the same test and testing method in pregnant individuals. We included trials and observational studies. Reviewers assessed risk of bias using the QUADAS-2 checklist and independently extracted data. Sensitivity and specificity for group B streptococcus colonisation of self-collected compared to provider-collected samples were pooled using a bivariate, random-effects, meta-analytic model. This review was registered with PROSPERO (CRD42023396573). RESULTS: The search identified 5909 references, of which eleven diagnostic accuracy group B streptococcus studies were included (n = 3269 participants). No studies assessed the effects of self-collection in pregnancy on health outcomes. All studies had high or unclear risk of bias. Pooled sensitivities of self-collected samples for group B streptococcus detection were 82% (95% CI: 66-91%; I2 = 68.85%) in four trials (n = 1226) and 91% (95% CI: 83-96%; I2 = 37.38%) in seven non-randomised studies (n = 2043). Pooled specificities were 99% (95% CI: 98-99%; I2 = 12.08%) and 97% (95% CI: 94-99%; I2 = 72.50%), respectively. CONCLUSIONS: Self-collected samples for group B streptococcus detection in pregnancy had high specificity compared to provider-collection, but lower sensitivity, particularly for included trials. Studies investigating the effect of self-collection on health outcomes, and further higher quality trials comparing accuracy of self-collection to provider-collection, are required.

Antenatal corticosteroids in specific groups at risk of preterm birth: a systematic review.

OBJECTIVE: This study aimed to synthesise available evidence on the efficacy of antenatal corticosteroid (ACS) therapy among women at risk of imminent preterm birth with pregestational/gestational diabetes, chorioamnionitis or fetal growth restriction (FGR), or planned caesarean section (CS) in the late preterm period. METHODS: A systematic search of MEDLINE, EMBASE, CINAHL, Cochrane Library, Web of Science and Global Index Medicus was conducted for all comparative randomised or non-randomised interventional studies in the four subpopulations on 6 June 2021. Risk of Bias Assessment tool for Non-randomised Studies and the Cochrane Risk of Bias tool were used to assess the risk of bias. Grading of Recommendations Assessment, Development and Evaluations tool assessed the certainty of evidence. RESULTS: Thirty-two studies involving 5018 pregnant women and 10 819 neonates were included. Data on women with diabetes were limited, and evidence on women undergoing planned CS was inconclusive. ACS use was associated with possibly reduced odds of neonatal death (pooled OR: 0.51; 95% CI: 0.31 to 0.85, low certainty), intraventricular haemorrhage (pooled OR: 0.41; 95% CI: 0.23 to 0.72, low certainty) and respiratory distress syndrome (pooled OR: 0.59; 95% CI: 0.45 to 0.77, low certainty) in women with chorioamnionitis. Among women with FGR, the rates of surfactant use (pooled OR: 0.38; 95% CI: 0.23 to 0.62, moderate certainty), mechanical ventilation (pooled OR: 0.42; 95% CI: 0.26 to 0.66, moderate certainty) and oxygen therapy (pooled OR: 0.48; 95% CI: 0.30 to 0.77, moderate certainty) were probably reduced; however, the rate of hypoglycaemia probably increased (pooled OR: 2.06; 95% CI: 1.27 to 3.32, moderate certainty). CONCLUSIONS: There is a paucity of evidence on ACS for women who have diabetes. ACS therapy may have benefits in women with chorioamnionitis and is probably beneficial in FGR. There is limited direct trial evidence on ACS efficacy in women undergoing planned CS in the late preterm period, though the totality of evidence suggests it is probably beneficial. PROSPERO REGISTRATION NUMBER: CRD42021267816.

Results of Surgical Treatment of Aneurysmal Subarachnoid Hemorrhage in a Single Institution Over 12 Years.

OBJECTIVE: For patients with aneurysmal subarachnoid hemorrhage (aSAH) in whom endovascular treatment is not the optimal treatment strategy, microsurgical clipping remains a viable option. We examined changes in morbidity and outcome over time in patients treated surgically and in relation to surgeon volume and experience. METHODS: All patients who underwent microsurgery for aSAH from 2007 to 2019 at our institution were included. We compared technical complication rates and surgical outcomes between experienced (≥50 independent cases) and inexperienced (<50 independent cases) surgeons and between high-volume (≥20 cases/year) and low-volume (<20 cases/year) surgeons. RESULTS: Most of the 1,003 aneurysms (970 patients, median age 56 years) were in the middle cerebral (41.4%), anterior communicating (27.6%), and posterior communicating (17.5%) arteries; 46.5% were <7 mm. The technical complication rate was 7%, resulting in postoperative infarct in 4.9% of patients. Nineteen patients (2%) died within 30 days of admission. There were no significant changes in rates of technical complication, postoperative infarct, or mortality over the study period. There were no differences in postoperative infarction and technical complication rates between experienced and inexperienced surgeons (P = 0.28 and P = 0.05, respectively), but there were differences when comparing high-volume and low-volume surgeons (P = 0.03 and P < 0.001, respectively). The independent predictors of postoperative infarctions were aneurysm size (P = 0.001), intraoperative large-vessel injury (P < 0.001), and low surgeon volume (P = 0.03). CONCLUSIONS: We present real-world data on surgical morbidity and outcomes after aSAH. We demonstrated a relationship between surgeon volume and outcome for surgical treatment of aSAH, which supports the benefit of subspecialization in cerebrovascular surgery.

Effect of antenatal corticosteroid administration-to-birth interval on maternal and newborn outcomes: a systematic review.

Background: Antenatal corticosteroids (ACS) are highly effective at improving outcomes for preterm newborns. Evidence suggests the benefits of ACS may vary with the time interval between administration-to-birth. However, the optimal ACS administration-to-birth interval is not yet known. In this systematic review, we synthesised available evidence on the relationship between ACS administration-to-birth interval and maternal and newborn outcomes. Methods: This review was registered with PROSPERO (CRD42021253379). We searched Medline, Embase, CINAHL, Cochrane Library, Global Index Medicus on 11 Nov 2022 with no date or language restrictions. Randomised and non-randomised studies of pregnant women receiving ACS for preterm birth where maternal and newborn outcomes were reported for different administration-to-birth intervals were eligible. Eligibility screening, data extraction and risk of bias assessment were performed by two authors independently. Fetal and neonatal outcomes included perinatal and neonatal mortality, preterm birth-related morbidity outcomes and mean birthweight. Maternal outcomes included chorioamnionitis, maternal mortality, endometritis, and maternal intensive care unit admission. Findings: Ten trials (4592 women; 5018 neonates), 45 cohort studies (at least 22,992 women; 30,974 neonates) and two case-control studies (355 women; 360 neonates) met the eligibility criteria. Across studies, 37 different time interval combinations were identified. There was considerable heterogeneity in included administration-to-birth intervals and populations. The odds of neonatal mortality, respiratory distress syndrome and intraventricular haemorrhage were associated with the ACS administration-to-birth interval. However, the interval associated with the greatest improvements in newborn outcomes was not consistent across studies. No reliable data were available for maternal outcomes, though odds of chorioamnionitis might be associated with longer intervals. Intepretation: An optimal ACS administration-to-birth interval likely exists, however variations in study design limit identification of this interval from available evidence. Future research should consider advanced analysis techniques such as individual patient data meta-analysis to identify which ACS administration-to-birth intervals are most beneficial, and how these benefits can be optimised for women and newborns. Funding: This study was conducted with funding support from the UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), Department of Sexual and Reproductive Health and Research (SRH), a co-sponsored programme executed by the World Health Organization.

A Case of Acute Intermittent Porphyria Leading to Severe Disability in a Young 21-Year-Old Female.

Acute intermittent porphyria (AIP) is a rare metabolic disorder that is challenging to diagnose and treat. Symptoms are nonspecific and severe acute attacks may be life-threatening. This is a case of a previously healthy 21-year-old woman diagnosed with an acute attack of AIP following recurrent hospitalizations with undiagnosed abdominal pain over a 12-month period with gradual onset of motor neuropathy which resulted in complete paralysis and respiratory failure. Through our case, we will highlight the challenges in AIP diagnosis and management, its potential severity, and how an early diagnosis could have prevented severe disability.

Tocolytic Therapy Inhibiting Preterm Birth in High-Risk Populations: A Systematic Review and Meta-Analysis.

This systematic review aimed to identify the benefits and possible harms of tocolytic therapy for preterm labour management in the context of pregnant women with extremely preterm birth, multiple gestations, or growth-restricted foetuses. A comprehensive search using MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, CINAHL, and the WHO Global Index Medicus databases was conducted from 10 to 15 July 2021. We included randomized controlled trials and non-randomized studies that assessed the effects of tocolysis compared with placebo or no treatment. We found 744 reports and, finally, nine studies (three randomized controlled trials and six cohort studies) pertaining to women with <28 weeks of gestation were included. No eligible studies were identified among women with a multiple pregnancy or a growth-restricted foetus. A meta-analysis of the trial data showed that there were no clear differences in perinatal death nor for a delay in birth. Non-randomized evidence showed that tocolysis delayed birth by 7 days, though there was no clear difference for preterm birth. In summary, it remains unclear whether tocolytic therapy for inhibiting preterm labour is beneficial for these subgroups of women and their newborns. Further well-designed randomized controlled trials and observational studies are needed to address the lack of evidence regarding tocolytic agents in these populations.

Access to, and experiences of, maternity care for women with physical disabilities: A scoping review.

OBJECTIVE: Women with physical disabilities face multiple barriers in accessing safe, respectful and acceptable healthcare. As the number of women with physical disabilities becoming pregnant rises, ensuring their access to acceptable and high-quality maternity care becomes increasingly important. This review aimed to explore the most recent evidence regarding access to, and experiences of, maternity care for women with physical disabilities in high-income countries. DESIGN: A scoping review was undertaken as guided by the Preferred Reporting Items for Systematic Reviews extension for scoping reviews (PRISMA-ScR). A systematic search of five online databases identified relevant articles published in English from 2000 to 2020. Reference lists of included studies were also screened, and quality was appraised using the Joanna Briggs Institute Checklists. A thematic synthesis was undertaken to develop descriptive and analytical themes. FINDINGS: After screening, 27 articles from eight high-income countries were included. All articles were identified as having moderate or high methodological rigour in the quality appraisal. Women with physical disabilities reported numerous barriers in accessing maternity care and described predominantly mixed and negative experiences of care. These findings were grouped under three major themes: women with physical disabilities want a "normal" pregnancy experience; the need to strengthen maternity provider's disability knowledge and skills; and promoting enabling environments for improved access to, and experiences of, maternity care. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: This review found that for women with physical disabilities access to, and experiences of, maternity care is suboptimal. Improving maternity providers disability knowledge and awareness, increasing the availability of support services for women, and increasing person-centred care through organisational policies and provider training may help to address the inequities women with disabilities face in accessing high-quality maternity care.

Alginate-microencapsulation of human stem cell-derived ß cells with CXCL12 prolongs their survival and function in immunocompetent mice without systemic immunosuppression.

Pancreatic ß-cell replacement by islet transplantation for the treatment of type 1 diabetes (T1D) is currently limited by donor tissue scarcity and the requirement for lifelong immunosuppression. The advent of in vitro differentiation protocols for generating functional ß-like cells from human pluripotent stem cells, also referred to as SC-ß cells, could eliminate these obstacles. To avoid the need for immunosuppression, alginate-microencapsulation is widely investigated as a safe path to ß-cell replacement. Nonetheless, inflammatory foreign body responses leading to pericapsular fibrotic overgrowth often causes microencapsulated islet-cell death and graft failure. Here we used a novel approach to evade the pericapsular fibrotic response to alginate-microencapsulated SC-ß cells; an immunomodulatory chemokine, CXCL12, was incorporated into clinical grade sodium alginate to microencapsulate SC-ß cells. CXCL12 enhanced glucose-stimulated insulin secretion activity of SC-ß cells and induced expression of genes associated with ß-cell function in vitro. SC-ß cells co-encapsulated with CXCL12 showed enhanced insulin secretion in diabetic mice and accelerated the normalization of hyperglycemia. Additionally, SC-ß cells co-encapsulated with CXCL12 evaded the pericapsular fibrotic response, resulting in long-term functional competence and glycemic correction (>150 days) without systemic immunosuppression in immunocompetent C57BL/6 mice. These findings lay the groundwork for further preclinical translation of this approach into large animal models of T1D.

Harnessing CXCL12 signaling to protect and preserve functional ß-cell mass and for cell replacement in type 1 diabetes.

Type 1 diabetes (T1D) is a complex multifactorial disease characterized by autoimmune destruction of insulin-producing pancreatic ß cells. Our understanding of the pathogenic mechanisms and natural history of T1D has evolved significantly over the past two decades; we can efficiently predict high-risk individuals, early diagnose the disease and stage progression. Fortuitously, novel in vitro differentiation protocols for generating functional ß-like cells from human pluripotent stem cells have been developed. These advances provide a definitive roadmap to implement realistic preventive and ß-cell replacement therapies in T1D. Immunoprotection and preservation of functional ß-cell mass are a sine qua non for the success of these interventions. The chemokine, stromal cell-derived factor-1alpha, known as CXCL12-α, is an attractive therapeutic target molecule in this context. CXCL12-α signaling promotes ß-cell development, survival and regeneration and can mediate local immunomodulation in the pancreatic islets. Interestingly, CXCL12-α is robustly expressed in maturing insulin-producing ß cells and in adult ß cells during periods of injury and regeneration. However, under normal physiological settings, CXCL12-α is repressed in terminally differentiated mature ß cells and islets. Here, we provide a comprehensive overview of the role of CXCL12-α signaling in ß-cell biology, physiology and immune regulation. We discuss CXCL12-α signaling mechanisms that could be harnessed to modulate ß-cell autoimmunity, protect and preserve functional ß-cell mass and for cell replacement therapy in T1D.

Does neurogenesis relate to depression and do antidepressants affect neurogenesis?

Depression is characterized by atrophy in several brain structures, with the hippocampus seemingly particularly affected. A wide variety of cellular mechanisms have been proposed for these structural modifications, including the regression of dendritic branching. While neurogenesis alone appears inadequate to produce such marked changes, an altered rate is likely to affect hippocampal function. There is also strong evidence for neurotransmitter and glucocorticoid-mediated effects on neurogenesis, providing routes for the action of antidepressants. We aim to show how neurogenesis relates to the 'conventional monoaminergic theory of depression' and its modulation by antidepressants.