A Systematic Review and Meta-Analysis of Anti-Rheumatic Drugs and Pneumococcal Vaccine Immunogenicity in Inflammatory Arthritis.

BACKGROUND: Pneumococcal pneumonia is an important cause of morbidity and mortality amongst patients with inflammatory arthritis. Vaccination is recommended by the National Institute for Health and Care Excellence (NICE) but it remains unclear how vaccine efficacy is impacted by different immunosuppressive agents. Our objective was to compare the chance of a seroconversion following vaccination against pneumococcus in patients with inflammatory arthritis to that in the general population, as well as to compare the chance of seroconversion across different targeted therapies. METHODS: We searched MEDLINE, Embase and the Cochrane Library databases from inception until 20 June 2023. We included randomized controlled trials and observational studies. Aggregate data were used to undertake a pairwise meta-analysis. Our primary outcome of interest was vaccine seroconversion. We accepted the definition of serological response reported by the authors of each study. RESULTS: Twenty studies were identified in the systematic review (2807 patients) with ten reporting sufficient data to be included in the meta-analysis (1443 patients). The chance of seroconversion in patients receiving targeted therapies, relative to the general population, was 0.61 (95% CI 0.35 to 1.08). The reduced odds of response were skewed strongly by the effects of abatacept and rituximab with no difference between patients on TNF inhibitors (TNFis) or IL-6 inhibition and healthy controls. Within different inflammatory arthritis populations the findings remained consistent, with rituximab having the strongest negative impact on vaccine response. TNF inhibition monotherapy was associated with a greater chance of vaccine response compared with methotrexate (2.25 (95% CI 1.28 to 3.96)). JAK inhibitor (JAKi) studies were few in number and did not present comparable vaccine response endpoints to include in the meta-analysis. The information available does not suggest any significant detrimental effects of JAKi on vaccine response. CONCLUSION: This updated meta-analysis confirms that, for most patients with inflammatory arthritis, pneumococcal vaccine can be administered with confidence and that it will achieve comparable seroconversion rates to the healthy population. Patients on rituximab were the group least likely to achieve a response and further research is needed to explore the value of multiple-course pneumococcal vaccination schedules in this population.

Directive clinique no 443b : Opioïdes aux différentes étapes de la vie des femmes : Grossesse et allaitement.

OBJECTIF: Présenter aux professionnels de la santé les données probantes concernant l'utilisation des opioïdes et la santé des femmes. Les domaines d'intérêt sont la grossesse et les soins post-partum. POPULATION CIBLE: Toutes les femmes qui utilisent des opioïdes. RéSULTATS: Un dialogue ouvert et éclairé sur l'utilisation des opioïdes améliorera les soins aux patientes. BéNéFICES, RISQUES ET COûTS: L'exploration de l'utilisation d'opioïdes par une approche tenant compte des traumatismes antérieurs donne au professionnel de la santé et à la patiente l'occasion de bâtir une alliance solide, collaborative et thérapeutique. Cette alliance permet aux femmes de faire des choix éclairés. Elle favorise le diagnostic et le traitement possible du trouble lié à l'utilisation d'opioïdes. L'utilisation ne doit pas être stigmatisée, puisque la stigmatisation affaiblit le partenariat (le partenariat entre patiente et professionnel de la santé). Les professionnels de la santé ceus-ci doivent comprendre l'effet potentiel des opioïdes sur la santé les femmes enceintes et les aider à prendre des décisions éclairées sur leur santé. DONNéES PROBANTES: Une recherche a été conçue puis effectuée dans les bases de données PubMed et Cochrane Library pour la période d'août 2018 à mars 2023 des termes MeSH et mots clés suivants (et variantes) : opioids, opioid agonist therapy, illicit drugs, fertility, pregnancy, fetal development, neonatal abstinence syndrome et breastfeeding. MéTHODES DE VALIDATION: Les auteurs ont évalué la qualité des données probantes et la force des recommandations en utilisant le cadre méthodologique GRADE (Grading of Recommendations, Assessment, Development, and Evaluation). Voir l'annexe A en ligne (tableau A1 pour les définitions et tableau A2 pour l'interprétation des recommandations fortes et conditionnelles [faibles]). PROFESSIONNELS CONCERNéS: Tous les professionnels de la santé qui prodiguent des soins aux femmes et aux nouveaux-nés. RéSUMé POUR TWITTER: La consommation d'opioïdes pendant la grossesse coïncide souvent avec des problèmes de santé mentale et est associée à des conséquences néfastes pour la mère, le fœtus et le nouveau-né ; le traitement des troubles liés à la consommation d'opioïdes par agonistes peut être sûr pendant la grossesse lorsque les risques sont plus nombreux que les avantages. DÉCLARATIONS SOMMAIRES: RECOMMANDATIONS.

Guideline No. 443a: Opioid Use Throughout Women's Lifespan: Fertility, Contraception, Chronic Pain, and Menopause.

OBJECTIVE: To provide health care providers with the best evidence on opioid use and women's health. Areas of focus include general patterns of opioid use and safety of use; care of women who use opioids; stigma, screening, brief intervention, and referral to treatment; hormonal regulation; reproductive health, including contraception and fertility; sexual function; perimenopausal and menopausal symptoms; and chronic pelvic pain syndromes. TARGET POPULATION: The target population includes all women currently using or contemplating using opioids. OUTCOMES: Open, evidence-informed dialogue about opioid use will lead to improvements in patient care and overall health. BENEFITS, HARMS, AND COSTS: Exploring opioid use through a trauma-informed approach offers the health care provider and patient with an opportunity to build a strong, collaborative, and therapeutic alliance. This alliance empowers women to make informed choices about their own care. It also allows for the diagnosis and possible treatment of opioid use disorders. Use should not be stigmatized, as stigma leads to poor "partnered care" (i.e., the partnership between the patient and care provider). Therefore, health care providers and patients must understand the potential role of opioids in women's health (both positive and negative) to ensure informed decision-making. EVIDENCE: A literature search was designed and carried out in PubMed and the Cochrane Library databases from August 2018 until March 2023 using following MeSH terms and keywords (and variants): opioids, illicit drugs, fertility, pregnancy, breastfeeding, and aging. VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and weak recommendations). INTENDED AUDIENCE: All health care providers who care for women. TWEETABLE ABSTRACT: Opioid use can affect female reproductive function; health care providers and patients must understand the potential role of opioids in women's health to ensure informed decision-making. SUMMARY STATEMENTS: RECOMMENDATIONS.

Guideline No. 443b: Opioid Use Throughout Women's Lifespan: Opioid Use in Pregnancy and Breastfeeding.

OBJECTIVE: To provide health care providers the best evidence on opioid use and women's health. Areas of focus include pregnancy and postpartum care. TARGET POPULATION: The target population includes all women currently using or contemplating using opioids. OUTCOMES: Open, evidence-informed dialogue about opioid use will improve patient care. BENEFITS, HARMS, AND COSTS: Exploring opioid use through a trauma-informed approach provides the health care provider and patient with an opportunity to build a strong, collaborative, and therapeutic alliance. This alliance empowers women to make informed choices about their own care. It also allows for the diagnosis and possible treatment of opioid use disorders. Opioid use should not be stigmatized, as stigma leads to poor "partnered care" (i.e., the partnership between the patient and care provider). Health care providers need to understand the effect opioids can have on pregnant women and support them to make knowledgeable decisions about their health. EVIDENCE: A literature search was designed and carried out in PubMed and the Cochrane Library databases from August 2018 until March 2023 using following MeSH terms and keywords (and variants): opioids, opioid agonist therapy, illicit drugs, fertility, pregnancy, fetal development, neonatal abstinence syndrome, and breastfeeding. VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and conditional [weak] recommendations). INTENDED AUDIENCE: All health care providers who care for pregnant and/or post-partum women and their newborns. TWEETABLE ABSTRACT: Opioid use during pregnancy often co-occurs with mental health issues and is associated with adverse maternal, fetal, and neonatal outcomes; treatment of opioid use disorder with agonist therapy for pregnant women can be safe during pregnancy where the risks outnumber the benefits. SUMMARY STATEMENTS: RECOMMENDATIONS.

Validation of Ultrasound Dating Protocols Using Data From Twins Conceived Through In Vitro Fertilization in Nova Scotia: A Retrospective Cohort Study.

OBJECTIVES: Clinical practice guidelines recommend determining gestational age (GA) for twin pregnancies using the fetal crown rump length (CRL) of the larger fetus. This study investigated whether the CRL of the larger or smaller fetus at 11-14 weeks best predicted in vitro fertilization (IVF) assigned GA. METHODS: A retrospective cohort study of twin pregnancies conceived by IVF ± intracytoplasmic sperm injection, 2004-2022, generated GA estimations for each co-twin CRL at the 11-14 week ultrasound, to determine which fetus (smaller or larger) more consistently predicted IVF-assigned GA. Monoamniotic twins and twins with known structural or vascular abnormalities were excluded. Paired t tests evaluated the ability of CRL to predict GA, and logistic regression evaluated the predictive ability of each of the co-twin groups with increasing size differences. Statistical significance was set at P < 0.05. RESULTS: Viewpoint 6 identified 359 eligible twin pairs. CRL was closest with the smaller fetus (0.38 days); CRL for both the smaller (95% CI 0.16-0.61) and the larger (2.25 days, 95% CI 2.04-2.46) fetus showed deviation from IVF-assigned GA. As the absolute difference between the small and large fetus increased, the ultrasound-estimated GA of the smaller fetus was still consistently closer to IVF-assigned GA. CONCLUSIONS: In this selected population of twins with known GA, the CRL of the smaller fetus more accurately predicted IVF-assigned GA even with increasing differences in fetal size. These findings provide important information for appropriately dating pregnancies to facilitate adherence to national guidelines to monitor for pregnancy complications, and plan frequency and type of fetal surveillance, as well as timing of delivery.

Antenatal Corticosteroid Prophylaxis at Late Preterm Gestation: Clinical Guidelines Versus Clinical Practice.

OBJECTIVE: We investigated how the Antenatal Late Preterm Steroids (ALPS) trial findings have been translated into clinical practice in Canada and the United States (U.S.). METHODS: The study included all live births in Nova Scotia, Canada, and the U.S. from 2007 to 2020. Antenatal corticosteroids (ACS) administration within specific categories of gestational age was assessed by calculating rates per 100 live births, and temporal changes were quantified using odds ratio (OR) and 95% confidence intervals (CI). Temporal trends in optimal and suboptimal ACS use were also assessed. RESULTS: In Nova Scotia, the rate of any ACS administration increased significantly among women delivering at 350 to 366 weeks, from 15.2% in 2007-2016 to 19.6% in 2017-2020 (OR 1.36, 95% CI 1.14-1.62). Overall, the U.S. rates were lower than the rates in Nova Scotia. In the U.S., rates of any ACS administration increased significantly across all gestational age categories: among live births at 350 to 366 weeks gestation, any ACS use increased from 4.1% in 2007-2016 to 18.5% in 2017-2020 (OR 5.33, 95% CI 5.28-5.38). Among infants between 240 and 346 weeks gestation in Nova Scotia, 32% received optimally timed ACS, while 47% received ACS with suboptimal timing. Of the women who received ACS in 2020, 34% in Canada and 20% in the U.S. delivered at ≥37 weeks. CONCLUSION: Publication of the ALPS trial resulted in increased ACS administration at late preterm gestation in Nova Scotia, Canada, and the U.S. However, a significant fraction of women receiving ACS prophylaxis delivered at term gestation.

A Conversational, Virtual, Avatar-Led Cognitive Behavioral Therapy App Intervention for Improving the Quality of Life and Mental Health of People With Epilepsy: Protocol for a Randomized Controlled Trial.

BACKGROUND: Epilepsy is a common neurological disorder affecting about 1 in 100 people in the United Kingdom. Many individuals experience a lower quality of life as a result of their epilepsy diagnosis and are more likely to develop mental health problems, such as anxiety and depression. Medical interventions for this client group tend to focus on the treatment of seizures, whereas mental health disorders often remain undiagnosed and untreated. Early identification and treatment of mental health difficulties in people with epilepsy are vital to ensure better outcomes and improvements in quality of life. OBJECTIVE: The aim of this exploratory randomized controlled trial is to evaluate whether an 8-week cognitive behavioral therapy-based intervention delivered through a mobile app-ThinkNinja for Epilepsy-is a clinically effective tool to improve quality of life, mental health, and emotional well-being in a large sample of people with epilepsy and anxiety or comorbid anxiety and depression. METHODS: The study aims to recruit 184 individuals, 18 to 65 years of age, with a self-reported diagnosis of epilepsy and anxiety or comorbid anxiety and depression. Participants will be randomly assigned to the ThinkNinja for Epilepsy app condition (arm A) or the waiting-list control group (arm B). Participants in arm A will receive access to the ThinkNinja for Epilepsy app first. After 8 weeks, participants in arm B will receive the same full access to the ThinkNinja for Epilepsy app as the participants in arm A. This design will allow an initial between-subjects analysis between the two conditions as well as a within-subject analysis including all participants. The primary outcome is participants' quality of life, measured by the 10-item patient-weighted Quality of Life in Epilepsy questionnaire. The secondary outcomes include measures of anxiety, using the 7-item Generalized Anxiety Disorder assessment; depression, using the 9-item Patient Health Questionnaire; medication adherence, using the Medication Adherence Questionnaire; and impression of change, using the Patient Global Impression of Change questionnaire. RESULTS: Recruitment for this study began in March 2022 and was completed in October 2022. We expect data collection to be finalized by May 2023 and study results to be available within 12 months of the final data collection date. Results of the study will be written up as soon as possible thereafter, with the intention of publishing the outcomes in high-quality peer-reviewed journals. CONCLUSIONS: This study aims to determine the clinical efficacy and safety of the ThinkNinja for Epilepsy intervention at improving the quality of life, mental health, and emotional well-being of people with epilepsy. The findings from our study will hopefully contribute to addressing the critical gap in universal provision and accessibility of mental health and emotional well-being support for people with epilepsy. TRIAL REGISTRATION: ISRCTN Registry 16270209 (04/03/2022); https://www.isrctn.com/ISRCTN16270209. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/40261.

Guideline No. 425a: Cannabis Use Throughout Women's Lifespans - Part 1: Fertility, Contraception, Menopause, and Pelvic Pain.

OBJECTIVE: To provide health care providers with the best evidence on cannabis use with respect to women's health. Areas of focus include general patterns of cannabis use as well as safety of use; care for women who use cannabis; stigma; screening, brief intervention, and referral to treatment; impact on hormonal regulation; reproductive health, including contraception and fertility; sexual function; effects on perimenopausal and menopausal symptoms; and use in chronic pelvic pain syndromes. TARGET POPULATION: The target population includes all women currently using or contemplating using cannabis. OUTCOMES: Open, evidence-informed dialogue about cannabis use, which will lead to improvement in patient care. BENEFITS, HARMS, AND COSTS: Exploring cannabis use through a trauma-informed approach provides the health care provider and patient with an opportunity to build a strong, collaborative, therapeutic alliance. This alliance empowers women to make informed choices about their own care. It also allows for the diagnosis and possible treatment of cannabis use disorders. Use should not be stigmatized, as stigma leads to poor "partnered care" (i.e., the partnership between the patient and care provider). Multiple side effects of cannabis use may be mistaken for other disorders. Currently, use of cannabis to treat women's health issues is not covered by public funding; as a result, individual users must pay the direct cost. The indirect costs of cannabis use are unknown. Thus, health care providers and patients must understand the role of cannabis in women's health issues, so that women can make knowledgeable decisions. EVIDENCE: PubMed, EMBASE, and grey literature were searched to identify studies of "cannabis use and effect on infertility, contraception, perimenopause and menopausal symptoms, and pelvic pain" published between January 1, 2018 and February 18, 2021. All clinical trials, observational studies, reviews (including systematic reviews and meta-analyses), guidelines, and conference consensus statements were included. Publications were screened for relevance. The search terms were developed using the Medical Subject Headings (MeSH) terms and keywords (and variants), including cannabis, cannabinoids, marijuana, dexanabinol, dronabinol, tetrahydrocannabinol; the specific terms to capture women's health were estrogen, estradiol, medroxyprogesterone acetate, vaginal contraception, oral contraceptives, fertilization, amenorrhea, oligomenorrhea, pelvic pain, dysmenorrhea, endometriosis, interstitial cystitis, vulvodynia, and menopause. VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and weak recommendations). INTENDED AUDIENCE: All heath care providers who care for women. SUMMARY STATEMENTS: RECOMMENDATIONS.

Directive clinique no 425a : Le cannabis aux différentes périodes de la vie des femmes - Partie 1 : Fertilité, contraception, ménopause et douleur pelvienne.

OBJECTIF: Fournir aux fournisseurs de soins de santé les meilleures données probantes sur l'utilisation de cannabis et la santé des femmes. Les domaines d'intérêt sont : les profils généraux d'utilisation du cannabis ainsi que la sécurité de la consommation; les soins aux femmes qui utilisent le cannabis; la stigmatisation; le dépistage, l'intervention brève et l'orientation vers le traitement; les effets sur la régulation hormonale; la santé reproductive, y compris la contraception et la fertilité; la fonction sexuelle; les effets sur les symptômes périménopausiques et postménopausiques; et l'utilisation dans le traitement des syndromes de douleur pelvienne chronique. POPULATION CIBLE: La population cible comprend toutes les femmes qui consomment ou utilisent du cannabis ou qui envisagent de le faire. RéSULTATS: Un dialogue ouvert et fondé sur des données probantes relativement à l'utilisation et la consommation de cannabis, dialogue qui mènera à l'amélioration des soins aux patientes. BéNéFICES, RISQUES ET COûTS: L'exploration de l'utilisation et de la consommation de cannabis par une approche basée sur la connaissance des traumatismes donne l'occasion au fournisseur de soins et à la patiente de créer une solide alliance thérapeutique collaborative. Cette alliance permet aux femmes de faire des choix éclairés sur leurs propres soins. Elle facilite également le diagnostic et le traitement possible des troubles de l'usage du cannabis. Il ne faut pas stigmatiser la consommation, car la stigmatisation nuit à l'alliance thérapeutique (c'est-à-dire le partenariat entre la patiente et le fournisseur de soins). Plusieurs effets indésirables de la consommation de cannabis peuvent être confondus avec d'autres problèmes de santé. À l'heure actuelle, l'utilisation du cannabis pour traiter les problèmes de santé féminine n'est pas financée par le secteur public; par conséquent, les utilisatrices doivent assumer les coûts directs. Les coûts indirects de l'utilisation de cannabis sont inconnus. Ainsi, les fournisseurs de soins et les patientes doivent comprendre le rôle du cannabis dans les problèmes de santé féminine de sorte que les femmes puissent prendre des décisions éclairées. DONNéES PROBANTES: Des recherches ont été effectuées dans PubMed, Embase et la littérature grise pour recenser des études publiées entre le 1er janvier 2018 et le 18 février 2021 concernant l'utilisation du cannabis et ses effets sur l'infertilité, la contraception, les symptômes périménopausiques et postménopausiques et la douleur pelvienne. Toutes les publications des types suivants ont été incluses : essais cliniques, études observationnelles, revues (y compris les revues systématiques et les méta-analyses), directives cliniques et déclarations de conférences de consensus. Un survol des publications a été effectué pour en confirmer la pertinence. Les termes de recherche ont été définis à l'aide des termes MeSH (Medical Subject Headings) et mots clés (et variantes) suivants : cannabis, cannabinoids, marijuana, dexanabinol, dronabinol et tetrahydrocannabinol. À ces termes ont été combinés les termes suivants afin de cerner la santé des femmes : estrogen, estradiol, medroxyprogesterone acetate, vaginal contraception, oral contraceptives, fertilization, amenorrhea, oligomenorrhea, pelvic pain, dysmenorrhea, endometriosis, interstitial cystitis, vulvodynia et menopause. MéTHODES DE VALIDATION: Les auteurs ont évalué la qualité des données probantes et la force des recommandations en utilisant l'approche d'évaluation, de développement et d'évaluation (GRADE). Voir l'annexe A en ligne (tableau A1 pour les définitions et tableau A2 pour l'interprétation des recommandations fortes et faibles). PROFESSIONNELS CONCERNéS: Tous les fournisseurs de soins de santé qui prodiguent des soins aux femmes. DÉCLARATIONS SOMMAIRES: RECOMMANDATIONS.

Guideline No. 425b: Cannabis Use Throughout Women's Lifespans - Part 2: Pregnancy, the Postnatal Period, and Breastfeeding.

OBJECTIVE: To provide health care providers with the best evidence on cannabis use and women's health. Areas of focus include screening, dependence, and withdrawal; communication and documentation; pregnancy (including maternal and fetal outcomes); maternal pain control; postpartum care (including second-hand smoking and parenting); and breastfeeding. TARGET POPULATION: The target population includes women who are planning a pregnancy, pregnant, or breastfeeding. BENEFITS, HARMS, AND COSTS: Discussing cannabis use with women who are planning a pregnancy, pregnant, or breastfeeding allows them to make informed choices about their cannabis use. Based on the limited evidence, cannabis use in pregnancy or while breastfeeding should be avoided, or reduced as much as possible if abstaining is not feasible, given the absence of safety and long-term follow up data on cannabis-exposed pregnancies and infants. EVIDENCE: PubMed and Cochrane Library databases were searched for articles relevant to cannabis use during pregnancy and breastfeeding published between January 1, 2018, and February 5, 2021. The search terms were developed using the MeSH terms and keywords and their variants, including cannabis, cannabinoids, cannabidiol, CBD, THC, marijuana, edible, pregnancy, pregnant, prenatal, perinatal, postnatal, breastfeed, breastfed, lactation, nursing, fetus, fetal, neonatal, newborn, and child. In terms of publication type, all clinical trials, observational studies, reviews (including systematic reviews and meta-analyses), guidelines, and conference consensus statements were included. The main inclusion criteria were pregnant and breastfeeding women as the target population, and exposure to cannabis as the intervention of interest. VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and weak recommendations). INTENDED AUDIENCE: All health care providers who care for women of reproductive age. SUMMARY STATEMENTS: RECOMMENDATIONS.

Directive clinique no 425b : Le cannabis aux différentes périodes de la vie des femmes - Partie 2 : Grossesse, période postnatale et allaitement.

OBJECTIF: Fournir aux fournisseurs de soins les meilleures données probantes sur l'utilisation de cannabis et la santé des femmes. Les domaines d'intérêt sont le dépistage, la dépendance et le sevrage; la communication et la tenue de dossier; la grossesse (y compris les issues fœtales et maternelles); la gestion de la douleur maternelle; les soins postnataux (y compris la fumée secondaire et la parentalité); et l'allaitement. POPULATION CIBLE: Femmes enceintes, allaitantes ou qui planifient une grossesse. BéNéFICES, RISQUES ET COûTS: Discuter de l'utilisation de cannabis avec les femmes enceintes, allaitantes ou qui planifient une grossesse les aide à faire des choix éclairés. D'après des données probantes limitées, il faut éviter l'utilisation de cannabis pendant la grossesse ou l'allaitement, ou réduire la consommation au maximum si l'abstention n'est pas un objectif atteignable, étant donné l'absence de données sur l'innocuité et le suivi à long terme des grossesses et nourrissons exposés au cannabis. DONNéES PROBANTES: Les auteurs ont interrogé les bases de données PubMed et Cochrane Library pour extraire des articles sur l'utilisation de cannabis pendant la grossesse et l'allaitement publiés entre le 1er janvier 2018 et le 5 février 2021. Les termes de recherche ont été déterminés à partir de termes de recherche MeSH, de mots clés et de leurs variantes : cannabis, cannabinoids, cannabidiol, CBD, THC, marijuana, edible, pregnancy, pregnant, prenatal, perinatal, postnatal, breastfeed, breastfed, lactation, nursing, fetus, fetal, neonatal, newborn et child. Les auteurs ont inclus toutes les publications des types suivants : essais cliniques, études observationnelles, revues (y compris les revues systématiques et les méta-analyses), directives cliniques et déclarations de conférences de consensus. Les principaux critères d'inclusion étaient les femmes enceintes et allaitantes, comme population cible, et l'exposition au cannabis, comme intervention d'intérêt. MéTHODES DE VALIDATION: Les auteurs ont évalué la qualité des données probantes et la force des recommandations en utilisant le cadre méthodologique d'évaluation, de développement et d'évaluation (GRADE). Voir l'annexe A en ligne (tableau A1 pour les définitions et tableau A2 pour l'interprétation des recommandations fortes et faibles). PROFESSIONNELS CONCERNéS: Tous les fournisseurs de soins de santé qui prodiguent des soins aux femmes en âge de procréer. DÉCLARATIONS SOMMAIRES: RECOMMANDATIONS.

VIVA1: a more invasive subclone of MDA-MB-134VI invasive lobular carcinoma cells with increased metastatic potential in xenograft models.

BACKGROUND: Invasive lobular carcinoma (ILC) is the second most common type of breast cancer. As few tools exist to study ILC metastasis, we isolated ILC cells with increased invasive properties to establish a spontaneously metastasising xenograft model. METHODS: MDA-MB-134VI ILC cells were placed in transwells for 7 days. Migrated cells were isolated and expanded to create the VIVA1 cell line. VIVA1 cells were compared to parental MDA-MB-134VI cells in vitro for ILC marker expression and relative proliferative and invasive ability. An intraductally injected orthotopic xenograft model was used to assess primary and metastatic tumour growth in vivo. RESULTS: Similar to MDA-MB-134VI, VIVA1 cells retained expression of oestrogen receptor (ER) and lacked expression of E-cadherin, however showed increased invasion in vitro. Following intraductal injection, VIVA1 and MDA-MB-134VI cells had similar primary tumour growth and survival kinetics. However, macrometastases were apparent in 7/10 VIVA1-injected animals. Cells from a primary orthotopic tumour (VIVA-LIG43) were isolated and showed similar proliferative rates but were also more invasive than parental cells. Upon re-injection intraductally, VIVA-LIG43 cells had more rapid tumour growth with similar metastatic incidence and location. CONCLUSIONS: We generated a new orthotopic spontaneously metastasising xenograft model for ER+ ILC amenable for the study of ILC metastasis.

Maternal cannabis use during pregnancy and maternal and neonatal outcomes: A retrospective cohort study.

OBJECTIVE: To examine the relationship between reported prenatal cannabis use and neonatal and maternal outcomes and whether the legalisation of cannabis in Canada affected the rates of reported use or the association with maternal and neonatal outcomes. DESIGN: Population-based retrospective cohort study. SETTING: Routinely collected data in a real-world setting. POPULATION: All women in the Canadian province of Nova Scotia with singleton births between 1 January 2004 and 30 June 2021. METHODS: The association between cannabis use and maternal and neonatal outcomes was examined using generalised linear models with inverse probability weighting. MAIN OUTCOME MEASURES: Maternal and neonatal outcomes in the peripartum and postpartum period. RESULTS: Rates of reported cannabis use in pregnancy increased from 1.3% to 7.5% over the study period with no appreciable change in slope after legalisation in 2018. Infants of mothers reporting cannabis use in pregnancy were more likely to have major anomalies and a 5-minute Apgar score ≤7, require neonatal intensive care unit admission, and had lower birthweight, head circumference and birth length than infants of mothers not reporting cannabis use. These associations did not differ before and after legalisation. CONCLUSIONS: Reported cannabis use during pregnancy is associated with early postnatal complications and reduced fetal growth, even after taking into account a range of confounding factors. Rates of reported cannabis use during pregnancy increased over the past 5 years in Nova Scotia with no apparent additional effect of legalisation.

Tidal Flushing Rather Than Non-Point Source Nitrogen Pollution Drives Nutrient Dynamics in A Putatively Eutrophic Estuary.

The effects of nonpoint source nutrients on estuaries can be difficult to pinpoint, with researchers often using indicator species, monitoring, and models to detect influence and change. Here, we made stable isotope measurements of nitrogen and carbon in sediment, water column particulates, primary producers, and consumers at 35 stations in the reportedly eutrophic Barnegat Bay (New Jersey) to assess N sources and processing pathways. Combined with water quality and hydrological data, our C and N isoscapes revealed four distinct geographic zones with diverging isotopic baselines, indicating variable nutrient sources and processing pathways. Overall, the carbon stable isotopes δ13C) reflected the terrestrial-marine gradient with the most depleted values in the urban and poorly flushed north of the estuary to the most enriched values in the salt marsh-dominated south. In contrast, the nitrogen stable isotope values δ15N) were most enriched near the oceanic inlets and were consistent with offshore δ15N values in particulate organic matter. Several biogeochemical processes likely alter δ15N, but the relatively lower δ15N values associated with the most urbanized area indicate that anthropogenic runoff is not a dominant N source to this area. Our findings stand in contrast to previous studies of similar estuaries, as δ15N signatures of biota in this system are inversely correlated to population density and nutrient concentrations. Further, our analyses of archival plant (Spartina sp., Phragmites australis) and shell (Geukensia demissa, Ilyanassa obsoleta) samples collected between 1880 and 2020 indicated that δ15N values have decreased over time, particularly in the consumers. Overall, we find that water quality issues appear to be most acute in the poorly flushed parts of Barnegat Bay and emphasize the important role that oceanic exchange plays in water quality and associated estuarine food webs in the lagoon.

Infections in immunosuppressed travellers with autoimmune inflammatory diseases-a narrative review and advice for clinical practice.

The management of autoimmune, inflammatory diseases has been revolutionized by biologic therapies. A beneficial consequence of better disease control is that more patients are well enough to travel the world. There is now a class of traveller, the significantly immunosuppressed person with autoimmune disease, with specific risks and requirements. This review introduces the concept of the pre-travel risk assessment and discusses the major vaccine-preventable and non-vaccine-preventable travel-associated infections. The challenges and controversies around vaccination and immunosuppression are reviewed with advice for clinical practice.

A systematic review and network meta-analysis of the safety of early interventional treatments in rheumatoid arthritis.

OBJECTIVES: To evaluate the safety of treatment strategies in patients with early RA. METHODS: Systematic searches of MEDLINE, EMBASE and PubMed were conducted up to September 2020. Double-blind randomized controlled trials (RCTs) of licensed treatments conducted on completely naïve or MTX-naïve RA patients were included. Long-term extension studies, post-hoc and pooled analyses and RCTs with no comparator arm were excluded. Serious adverse events, serious infections and non-serious adverse events were extracted from all RCTs, and event rates in intervention and comparator arms were compared using meta-analysis and network meta-analysis (NMA). RESULTS: From an initial search of 3423 studies, 20 were included, involving 9202 patients. From the meta-analysis, the pooled incidence rates per 1000 patient-years for serious adverse events were 69.8 (95% CI: 64.9, 74.8), serious infections 18.9 (95% CI: 16.2, 21.6) and non-serious adverse events 1048.2 (95% CI: 1027.5, 1068.9). NMA showed that serious adverse event rates were higher with biologic monotherapy than with MTX monotherapy, rate ratio 1.39 (95% CI: 1.12, 1.73). Biologic monotherapy rates were higher than those for MTX and steroid therapy, rate ratio 3.22 (95% CI: 1.47, 7.07). Biologic monotherapy had a higher adverse event rate than biologic combination therapy, rate ratio 1.26 (95% CI: 1.02, 1.54). NMA showed no significant difference between strategies with respect to serious infections and non-serious adverse events rates. CONCLUSION: The study revealed the different risk profiles for various early RA treatment strategies. Observed differences were overall small, and in contrast to the findings of established RA studies, steroid-based regimens did not emerge as more harmful.

IL-6 inhibition in the treatment of COVID-19: A meta-analysis and meta-regression.

OBJECTIVES: Multiple RCTs of interleukin-6 (IL-6) inhibitors in COVID-19 have been published, with conflicting conclusions. We performed a meta-analysis to assess the impact of IL-6 inhibition on mortality from COVID-19, utilising meta-regression to explore differences in study results. METHODS: Systematic database searches were performed to identify RCTs comparing IL-6 inhibitors (tocilizumab and sarilumab) to placebo or standard of care in adults with COVID-19. Meta-analysis was used to estimate the relative risk of mortality at 28 days between arms, expressed as a risk ratio. Within-study mortality rates were compared, and meta-regression was used to investigate treatment effect modification. RESULTS: Data from nine RCTs were included. The combined mortality rate across studies was 19% (95% CI: 18, 20%), ranging from 2% to 31%. The overall risk ratio for 28-day mortality was 0.90 (95% CI: 0.81, 0.99), in favour of benefit for IL-6 inhibition over placebo or standard of care, with low treatment effect heterogeneity: I2 0% (95% CI: 0, 53%). Meta-regression showed no evidence of treatment effect modification by patient characteristics. Trial-specific mortality rates were explained by known patient-level predictors of COVID-19 outcome (male sex, CRP, hypertension), and country-level COVID-19 incidence. CONCLUSIONS: IL-6 inhibition is associated with clinically meaningful improvements in outcomes for patients admitted with COVID-19. Long-term benefits of IL-6 inhibition, its effectiveness across healthcare systems, and implications for differing standards of care are currently unknown.