Effect of Domperidone on Insufficient Lactation in Puerperal Women: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background. There is a controversy within the medical community regarding the role of domperidone as a galactagogue and the drug has been removed from the US market owing to safety concerns. Objective. To perform a systematic review and meta-analysis of the available data assessing the effect of domperidone on breast milk production in women experiencing insufficient lactation. Study Selection. Randomized controlled trials (RCTs) examining the effect of domperidone on breast milk production of puerperal women were eligible for inclusion. Data Analysis. Absolute and relative changes from baseline were calculated for individual studies and pooled using a random effects model. Results. Three RCTs including 78 participants met the inclusion criteria. All showed a statistically significant increase in breast milk production following treatment with domperidone. The analysis of pooled data demonstrated a statistically significant relative increase of 74.72% (95%  CI = 54.57; 94.86, P < 0.00001) in daily milk production with domperidone treatment compared to placebo. No maternal or neonatal adverse events were observed in any of the trials. Conclusions. Evidence from a few small RCTs of moderate to high quality suggests that domperidone produces a greater increase in breast milk supply than placebo

The Fetal Safety of Angiotensin Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers

Angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are known to cause fetal renal damage in pregnancy. Due to conflicting reports in the literature, their safety after first trimester exposure has been debated. Our aim was to determine whether the use of ACE inhibitors or ARBs in the first trimester of pregnancy is associated with an increased risk for major malformations or other adverse outcomes. All subjects were prospectively enrolled from among women contacting a teratogen information service. At initial contact, details of maternal medical history and exposures were collected and follow-up interviews were conducted to ascertain pregnancy outcomes. Two comparator groups, women with hypertension treated with other antihypertensives, and healthy controls were also recruited. Baseline maternal characteristics were not different among the three groups. There were no differences in rates of major malformations. Both the ACE-ARBs and disease-matched groups exhibited significantly lower birth weight and gestational ages than the healthy controls (P < 0.001 for both variables). There was a significantly higher rate of miscarriage noted in the ACE/ARB group (P < 0.001). These results suggest that ACE inhibitors/ARBs are not major human teratogens; however, they may be associated with an increased risk for miscarriage

Pharmacokinetic Disposition and Clinical Outcomes in Infants and Children Receiving Intravenous Busulfan for Allogeneic Hematopoietic Stem Cell Transplantation

AbstractWe conducted a retrospective pharmacokinetic analysis of i.v. busulfan in children undergoing hematopoietic stem cell transplantation (HSCT) and describe its relation to transplantation outcomes. Forty-five children (median age, 3 yr) underwent HSCT at The Hospital for Sick Children from April 2003 through January 2006 and received i.v. busulfan every 6 h as part of their conditioning regimen. Initial busulfan doses were based on actual patient weight: <9 kg, 0.95 mg/kg per dose; 9-16 kg, 1.2 mg/kg per dose; 16-23 kg, 1.1 mg/kg per dose; 24-34 kg, 0.95 mg/kg per dose; >34 kg, 0.8 mg/kg per dose. Plasma busulfan concentrations were obtained after the first dose. The fourth and subsequent busulfan doses were adjusted to achieve an area under the concentration versus time curve (AUC) of 900-1500 μM·min. Development of hepatic venous occlusive disease (HVOD; modified Baltimore criteria) and engraftment (absolute neutrophil count ≥0.5 × 109/L) were evaluated. Busulfan pharmacokinetic parameters were calculated using 1-compartment methods. Mean busulfan pharmacokinetic parameters were maximum concentration (Cmax; 4.7 ± 0.75 μM), volume of distribution at steady state (0.68 ± 0.17 L/kg), elimination rate constant (0.0051 ± 0.0010 min−1), total body clearance (3.5 ± 1.23 mL/[min·kg]), and AUC (1271 ± 280 μM·min). Mean volume of distribution at steady state was larger in children <1 yr of age (0.77 ± 0.24 vs 0.64 ± 0.11 L/kg; P = .040) and children <4 yr of age (0.73 ± 0.18 vs 0.60 ± 0.11 L/kg; P = .001) than in older children. Compared with older children, mean weight-adjusted total body clearance was higher in children <4 yr of age (3.8 ± 1.40 versus 3.0 ± 0.76 mL/[min·kg]). HVOD was diagnosed in 8 children (18%), including 4 children <1 yr of age. Children who developed HVOD achieved a lower Cmax than did those without HVOD (4.2 ± 0.68 versus 4.8 ± 0.73 μM; P = .035). Other than Cmax, no association was observed between busulfan disposition and development of HVOD in children for whom i.v. busulfan doses were adjusted to achieve a target AUC. The influence of factors other than busulfan disposition on transplantation outcomes, such as genetic polymorphisms, should be evaluated

Self-reported perinatal depressive symptoms and postnatal symptom severity after treatment with antidepressants in pregnancy: a cross-sectional study in 12 European countries using the Edinburgh Postnatal Depression Scale

Purpose: To explore the prevalence of self-reported antenatal and postnatal depressive symptoms by severity across multiple countries and the association between antidepressant treatment in pregnancy and postnatal symptom severity. Patients and methods: Multinational web-based study in 12 European countries (n=8069). Uniform data collection was ensured via an electronic questionnaire. Pregnant women at any gestational week and mothers of children with less than one year of age, could participate. We used the Edinburgh Postnatal Depression Scale (EPDS) to measure prevalence of antenatal and postnatal depressive symptoms according to severity, which were corrected by survey-weight adjustment (descriptive analysis). Within mothers with a psychiatric disorder (n=173), we estimated the association between antidepressant treatment in pregnancy and postnatal depressive symptom severity, as standardized EPDS mean scores, via inverse probability of treatment weight (association analysis). Results: In the descriptive analysis (n=8069), the period prevalence of moderate to very severe depressive symptoms was higher in the Western and Eastern regions relative to the Northern, both in the ante- (6.8-7.5% vs 4.3%) and postnatal period (7.6% vs 4.7%). One in two mothers with psychiatric disorders used antidepressant in pregnancy (86 out of 173). In the association analysis, women medicated at any time during pregnancy (adjusted β: -0.34, 95% CI: -0.66, -0.02) had a significant postnatal symptom severity reduction compared with the nonmedicated counterpart. This effect was larger (β: -0.74, 95% CI: -1.24, -0.24) when the analysis was restricted to mothers within six months after childbirth. Conclusions: The prevalence of self-reported antenatal and postnatal depressive symptoms differs across European countries. Among women with psychiatric disorders, those who had been on treatment with antidepressants during pregnancy were less likely to report postnatal depressive symptoms, particularly within the six-month period after childbirth, compared to the nonmedicated counterpart

Integrated collaborative care teams to enhance service delivery to youth with mental health and substance use challenges : Protocol for a pragmatic randomised controlled trial

Introduction: Among youth, the prevalence of mental health and addiction (MHA) disorders is roughly 20%, yet youth are challenged to access evidence-based services in a timely fashion. To address MHA system gaps, this study tests the benefits of an Integrated Collaborative Care Team (ICCT) model for youth with MHA challenges. A rapid, stepped-care approach geared to need in a youth-friendly environment is expected to result in better youth MHA outcomes. Moreover, the ICCT approach is expected to decrease service wait-times, be more youth-friendly and familyfriendly, and be more cost-effective, providing substantial public health benefits. Methods and analysis: In partnership with four community agencies, four adolescent psychiatry hospital departments, youth and family members with lived experience of MHA service use, and other stakeholders, we have developed an innovative model of collaborative, community-based service provision involving rapid access to needs-based MHA services. A total of 500 youth presenting for hospital-based, outpatient psychiatric service will be randomised to ICCT services or hospital-based treatment as usual, following a pragmatic randomised controlled trial design. The primary outcome variable will be the youth's functioning, assessed at intake, 6 months and 12 months. Secondary outcomes will include clinical change, youth/family satisfaction and perception of care, empowerment, engagement and the incremental cost-effectiveness ratio (ICER). Intent-to-treat analyses will be used on repeated-measures data, along with cost-effectiveness and cost-utility analyses, to determine intervention effectiveness. Ethics and dissemination: Research Ethics Board approval has been received from the Centre for Addiction and Mental Health, as well as institutional ethical approval from participating community sites. This study will be conducted according to Good Clinical Practice guidelines. Participants will provide informed consent prior to study participation and data confidentiality will be ensured. A data safety monitoring panel will monitor the study. Results will be disseminated through community and peer-reviewed academic channels

Pain Squad+ smartphone app to support real-time pain treatment for adolescents with cancer: protocol for a randomised controlled trial.

INTRODUCTION: Pain negatively affects the health-related quality of life (HRQL) of adolescents with cancer. The Pain Squad+ smartphone-based application (app), has been developed to provide adolescents with real-time pain self-management support. The app uses a validated pain assessment and personalised pain treatment advice with centralised decision support via a registered nurse to enable real-time pain treatment in all settings. The algorithm informing pain treatment advice is evidence-based and expert-vetted. This trial will longitudinally evaluate the impact of Pain Squad+, with or without the addition of nurse support, on adolescent health and cost outcomes. METHODS AND ANALYSIS: This will be a pragmatic, multicentre, waitlist controlled, 3-arm parallel-group superiority randomised trial with 1:1:1 allocation enrolling 74 adolescents with cancer per arm from nine cancer centres. Participants will be 12 to 18 years, English-speaking and with ≥3/10 pain. Exclusion criteria are significant comorbidities, end-of-life status or enrolment in a concurrent pain study. The primary aim is to determine the effect of Pain Squad+, with and without nurse support, on pain intensity in adolescents with cancer, when compared with a waitlist control group. The secondary aims are to determine the immediate and sustained effect over time of using Pain Squad+, with and without nurse support, as per prospective outcome measurements of pain interference, HRQL, pain self-efficacy and cost. Linear mixed models with baseline scores as a covariate will be used. Qualitative interviews with adolescents from all trial arms will be conducted and analysed. ETHICS AND DISSEMINATION: This trial is approved by the Hospital for Sick Children Research Ethics Board. Results will provide data to guide adolescents with cancer and healthcare teams in treating pain. Dissemination will occur through partnerships with stakeholder groups, scientific meetings, publications, mass media releases and consumer detailing. TRIAL REGISTRATION NUMBER: NCT03632343

Urban biodiversity : State of the science and future directions

Since the 1990s, recognition of urban biodiversity research has increased steadily. Knowledge of how ecological communities respond to urban pressures can assist in addressing global questions related to biodiversity. To assess the state of this research field in meeting this aim, we conducted a systematic review of the urban biodiversity literature published since 1990. We obtained data from 1209 studies that sampled ecological communities representing 12 taxonomic groups. While advances have been made in the field over the last 30 years, we found that urban biodiversity research has primarily been conducted in single cities within the Palearctic and Nearctic realms, within forest remnants and residential locations, and predominantly surveys plants and birds, with significant gaps in research within the Global South and little integration of multi-species and multi-trophic interactions. Sample sizes remain limited in spatial and temporal scope, but citizen science and remote sensing resources have broadened these efforts. Analytical approaches still rely on taxonomic diversity to describe urban plant and animal communities, with increasing numbers of integrated phylogenetic and trait-based analyses. Despite the implementation of nature-based solutions across the world's cities, only 5% of studies link biodiversity to ecosystem function and services, pointing to substantial gaps in our understanding of such solutions. We advocate for future research that encompasses a greater diversity of taxonomic groups and urban systems, focusing on biodiversity hotspots. Implementing such research would enable researchers to move forward in an equitable and multidisciplinary way to tackle the complex issues facing global urban biodiversity.Peer reviewe

Urbanisation generates multiple trait syndromes for terrestrial animal taxa worldwide

Cities can host significant biological diversity. Yet, urbanisation leads to the loss of habitats, species, and functional groups. Understanding how multiple taxa respond to urbanisation globally is essential to promote and conserve biodiversity in cities. Using a dataset encompassing six terrestrial faunal taxa (amphibians, bats, bees, birds, carabid beetles and reptiles) across 379 cities on 6 continents, we show that urbanisation produces taxon-specific changes in trait composition, with traits related to reproductive strategy showing the strongest response. Our findings suggest that urbanisation results in four trait syndromes (mobile generalists, site specialists, central place foragers, and mobile specialists), with resources associated with reproduction and diet likely driving patterns in traits associated with mobility and body size. Functional diversity measures showed varied responses, leading to shifts in trait space likely driven by critical resource distribution and abundance, and taxon-specific trait syndromes. Maximising opportunities to support taxa with different urban trait syndromes should be pivotal in conservation and management programmes within and among cities. This will reduce the likelihood of biotic homogenisation and helps ensure that urban environments have the capacity to respond to future challenges. These actions are critical to reframe the role of cities in global biodiversity loss.info:eu-repo/semantics/publishedVersio

A Cost-effectiveness Analysis of Maternal Genotyping to Guide Treatment for Postpartum Pain and Avert Infant Adverse Events

BACKGROUND: The maternal and infant benefits of breastfeeding are numerous, however maternal exposure to medications during lactation raises concerns of infant exposure and may be an impediment to breastfeeding. Recent concerns about the safety of codeine, an analgesic commonly used after delivery, have arisen. Evidence suggests that mothers with an ultrarapid metabolizer phenotype may put their infants at risk for adverse events by producing more active metabolite, which is excreted into milk. Pharmacogenetic screening may be a valuable tool to identify such mothers, and avert adverse events. OBJECTIVES: The objective of the study was to determine the incremental costs of genotyping to averting neonatal adverse events during maternal pharmacotherapy. METHODS: A cost effectiveness analysis to determine the incremental costs of genotyping to guide codeine therapy compared to standard care to avert adverse events was performed. The base case was a prenatal patient whose metabolizer status was unknown, but who may require codeine analgesia after delivery. Parameter estimates and costs were ascertained from a concurrent clinical study, from the literature and expert opinion. RESULTS: Pharmacogenetic screening resulted in a cost of $9,997.43 per adverse event averted or$2,173.35 per infant symptom day averted, when compared to standard care. The results were not sensitive to most variables in one way analysis, with the exception of the costs of a hospital admission. This study was limited by a small number of trials from which parameter estimates could be extracted and the very small number of adverse events reported in infants in the literature. CONCLUSIONS: Although genotyping to guide pharmacotherapy was not cost saving, the cost to avert an infant adverse event may represent good value for money. It is not yet known whether implementation would be clinically viable, however these findings will have implications for new mothers and their health care providers world-wide.Ph.D