Guideline No. 432a: Cervical Ripening and Induction of Labour - General Information.

OBJECTIVE: This guideline presents evidence and recommendations for cervical ripening and induction of labour. It aims to provide information to birth attendants and pregnant individuals on optimal perinatal care while avoiding unnecessary obstetrical intervention. TARGET POPULATION: All pregnant patients. BENEFITS, HARMS, AND COSTS: Consistent interprofessional use of the guideline, appropriate equipment, and trained professional staff enhance safe intrapartum care. Pregnant individuals and their support person(s) should be informed of the benefits and risks of induction of labour. EVIDENCE: Literature published to March 2022 was reviewed. PubMed, CINAHL, and the Cochrane Library were used to search for systematic reviews, randomized controlled trials, and observational studies on cervical ripening and induction of labour. Grey (unpublished) literature was identified by searching the websites of health technology assessment and health technology related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. 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 providers of obstetrical care.

Directive clinique no 432a : Maturation cervicale et déclenchement artificiel du travail - Information générale.

OBJECTIF: Présenter des données probantes et des recommandations sur la maturation cervicale et le déclenchement artificiel du travail. Fournir de l'information aux professionnels accoucheurs et aux personnes enceintes sur les soins périnataux optimaux et la prévention des interventions obstétricales inutiles. POPULATION CIBLE: Toutes les patientes enceintes. BéNéFICES, RISQUES ET COûTS: La mise en application interprofessionnelle et cohérente de la présente directive, l'équipement adéquat et le personnel compétent améliorent la sécurité des soins per partum. Les personnes enceintes et leurs personnes de soutien doivent être informées des risques et bénéfices du déclenchement artificiel du travail. DONNéES PROBANTES: La littérature publiée jusqu'en mars 2022 a été passée en revue. Une recherche a été effectuée dans les bases de données PubMed, CINAHL et Cochrane Library pour répertorier des revues systématiques, des essais cliniques randomisés et des études observationnelles sur la maturation cervicale et le déclenchement artificiel du travail. La littérature grise (non publiée) a été obtenue à l'aide de recherches menées dans des sites Web d'organismes s'intéressant à l'évaluation des technologies dans le domaine de la santé et d'organismes connexes, dans des collections de directives cliniques, des registres d'essais cliniques et des sites Web de sociétés de spécialité médicale nationales et internationales. 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 fournisseurs de soins obstétricaux.

Guideline No. 432b: Cervical Ripening.

OBJECTIVE: This guideline presents evidence and recommendations for cervical ripening and induction of labour. It aims to provide information to birth attendants and pregnant individuals on optimal perinatal care while avoiding unnecessary obstetrical intervention. TARGET POPULATION: All pregnant patients. BENEFITS, HARMS, AND COSTS: Consistent interprofessional use of the guideline, appropriate equipment, and trained professional staff enhance safe intrapartum care. Pregnant individuals and their support person(s) should be informed of the benefits and risks of induction of labour. EVIDENCE: Literature published to March 2022 was reviewed. PubMed, CINAHL, and the Cochrane Library were used to search for systematic reviews, randomized controlled trials, and observational studies on cervical ripening and induction of labour. Grey (unpublished) literature was identified by searching the websites of health technology assessment and health technology related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. 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 providers of obstetrical care.

Directive clinique no 432b : Maturation cervicale.

OBJECTIF: Présenter des données probantes et des recommandations sur la maturation cervicale et le déclenchement artificiel du travail. Fournir de l'information aux professionnels accoucheurs et aux personnes enceintes sur les soins périnataux optimaux et la prévention des interventions obstétricales inutiles. POPULATION CIBLE: Toutes les patientes enceintes. BéNéFICES, RISQUES ET COûTS: La mise en application interprofessionnelle et cohérente de la présente directive, l'équipement adéquat et le personnel compétent améliorent la sécurité des soins per partum. Les personnes enceintes et leurs personnes de soutien doivent être informées des risques et bénéfices du déclenchement artificiel du travail. DONNéES PROBANTES: La littérature publiée jusqu'en mars 2022 a été passée en revue. Une recherche a été effectuée dans les bases de données PubMed, CINAHL et Cochrane Library pour répertorier des revues systématiques, des essais cliniques randomisés et des études observationnelles sur la maturation cervicale et le déclenchement artificiel du travail. La littérature grise (non publiée) a été obtenue à l'aide de recherches menées dans des sites Web d'organismes s'intéressant à l'évaluation des technologies dans le domaine de la santé et d'organismes connexes, dans des collections de directives cliniques, des registres d'essais cliniques et des sites Web de sociétés de spécialité médicale nationales et internationales. 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 fournisseurs de soins obstétricaux.

Guideline No. 432c: Induction of Labour.

OBJECTIVES: This guideline presents evidence and recommendations for cervical ripening and induction of labour. It aims to provide information to birth attendants and pregnant individuals on optimal perinatal care while avoiding unnecessary obstetrical intervention. TARGET POPULATION: All pregnant patients. BENEFITS, RISKS, AND COSTS: Consistent interprofessional use of the guideline, appropriate equipment, and trained professional staff enhance safe intrapartum care. Pregnant individuals and their support person(s) should be informed of the benefits and risks of induction of labour. EVIDENCE: Literature published to March 2022 was reviewed. PubMed, CINAHL, and the Cochrane Library were used to search for systematic reviews, randomized control trials, and observational studies on cervical ripening and induction labour. Grey (unpublished) literature was identified by searching the websites of health technology assessment and health technology related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. 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 providers of obstetrical care. SUMMARY STATEMENTS: Misoprostol OXYTOCIN: RECOMMENDATIONS.

Directive clinique no 432c : Déclenchement artificiel du travail.

OBJECTIFS: Présenter des données probantes et des recommandations sur la maturation cervicale et le déclenchement artificiel du travail. Fournir de l'information aux professionnels accoucheurs et aux personnes enceintes sur les soins périnataux optimaux et la prévention des interventions obstétricales inutiles. POPULATION CIBLE: Toutes les patientes enceintes. BéNéFICES, RISQUES ET COûTS: La mise en application interprofessionnelle et cohérente de la présente directive, l'équipement adéquat et le personnel compétent améliorent la sécurité des soins per partum. Les personnes enceintes et leurs personnes de soutien doivent être informées des risques et bénéfices du déclenchement artificiel du travail. DONNéES PROBANTES: La littérature publiée jusqu'en mars 2022 a été passée en revue. Une recherche a été effectuée dans les bases de données PubMed, CINAHL et Cochrane Library pour répertorier des revues systématiques, des essais cliniques randomisés et des études observationnelles sur la maturation cervicale et le déclenchement artificiel du travail. La littérature grise (non publiée) a été obtenue à l'aide de recherches menées dans des sites Web d'organismes s'intéressant à l'évaluation des technologies dans le domaine de la santé et d'organismes connexes, dans des collections de directives cliniques, des registres d'essais cliniques et des sites Web de sociétés de spécialité médicale nationales et internationales. 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 fournisseurs de soins obstétricaux. DÉCLARATIONS SOMMAIRESMISOPROSTOL: OCYTOCINE: RECOMMANDATIONS.

Evaluation of a fit-for-purpose assay to monitor antigen-specific functional CD4+ T-cell subpopulations in rheumatoid arthritis using flow cytometry-based peptide-MHC class-II tetramer staining.

Antigen-specific T cells can serve as a response biomarker in non-clinical or clinical immunotherapy studies in autoimmune disease. There are protocols with optimized multimer staining methods to detect peptide (p)MHCII+ CD4+ T cells, and some qualified and validated protocols for pMHCI+ CD8+ T cells. However, no protocol is fully or partially qualified to enumerate and characterize antigen-specific pMHCII+ CD4+ T cells from patient samples. Implementing such an assay requires a desired level of specificity and precision, in terms of assay repeatability and reproducibility. In transgenic type II collagen (CII)-immunized HLA-DR1/DR4 humanized mouse models of collagen-induced arthritis (CIA), CII259-273-specific T cells dominantly expand. Therefore antigen-specific T cells recognizing this epitope presented by rheumatoid arthritis (RA)-associated risk HLA-DR allomorphs are of interest to understand disease progression and responses to immunotherapy in RA patients. Using HLA-DRB1∗04:01 or ∗01:01-collagen type II (CII)259-273 tetramers, we evaluated parameters influencing precision and reproducibility of an optimized flow cytometry-based method for antigen-specific CD4+ T cells and eight specific subpopulations with and without tetramer positivity. We evaluated specificity, precision, and reproducibility for research environments and non-regulated laboratories. The assay has excellent overall precision with %CV<25% for intra-assay repeatability, inter-analyst precision, and inter-assay reproducibility. The precision of the assay correlated negatively with the cell viability after thawing, indicating that post-thaw viability is a critical parameter for reproducibility. This assay is suitable for longitudinal analysis of treatment response and disease activity outcome in RA patients, and adaptable for translational or immunotherapy clinical trial settings.

Safety and effectiveness of Omnitrope® (somatropin) in PATRO Children: a multi-center, post-marketing surveillance study comparison of US and international cohort data.

There are known geographical differences in growth hormone deficiency (GHD) patient populations and treatment practices. Here, we present a comparison of safety and effectiveness data from patients treated with recombinant human growth hormone (rhGH) in the USA versus other countries. PAtients TReated with Omnitrope® (PATRO) Children is an international, non-interventional study with Omnitrope® (somatropin, Sandoz Inc.). All visits and assessments are carried out according to routine clinical practice, and doses of Omnitrope® are given according to country-specific prescribing information. By September 2018, 294 patients had been enrolled in the USA (53% rhGH-naïve) and 6206 patients had been enrolled across 13 other countries (international group; 86% rhGH-naïve). The most common indication in both groups was GHD. Overall, 194 US patients (66%) and 2977 international patients (48%) experienced adverse events (AEs; 886 and 11,716 events, respectively), most of which were of mild or moderate intensity. The AEs were suspected to be treatment-related in five US patients (1.7%) and 452 international patients (7.3%). All reported neoplasms were benign, non-serious, and considered unrelated to rhGH therapy. No cases of diabetes mellitus or hyperglycemia were reported. In rhGH-naïve GHD patients, after 3 years of rhGH therapy, the improvement in mean height SD score from baseline was + 1.25 and + 1.35 in US and international patients, respectively. CONCLUSION: Omnitrope® treatment appears to be well tolerated and effective in US patients and those from other countries. Across the pediatric indications included, there was no evidence of an increased risk of developing uncommon or unexpected AEs with rhGH. TRIAL REGISTRATION: NA. WHAT IS KNOWN: • Continued monitoring of patients treated with recombinant human growth hormone (rhGH) is important, particularly in terms of diabetogenic potential and the risk of malignancies. • The PAtients TReated with Omnitrope® (PATRO) Children study is a long-term, post-marketing surveillance program for the rhGH Omnitrope®. WHAT IS NEW: • Omnitrope® is well tolerated and effective in US patients, and those from other countries. • Across all indications included, there were no unexpected adverse events and there was no evidence of an increased risk of developing malignancies or diabetes.

No. 361-Caesarean Delivery on Maternal Request.

A maternal request for an elective CS in the absence of a maternal or fetal indication may raise risk-benefit considerations and ethical concerns for a health care provider. Appropriate counselling of the patient on the risks and benefits in proceeding with a CDMR without medical indication is essential. Providers should have a clear knowledge of the risks and benefits of providing an elective CS without medical indications compared to the risks and benefits of supporting an attempt at vaginal delivery, so that the patient may reach an informed decision. The principle of patient autonomy should be respected but other ethical principles (beneficence, non-maleficence and justice) need to be taken into consideration during the counselling process. There are no studies to estimate maternal and neonatal risks in CDMR. Often studies on CS before the onset of labour are used as surrogates to determine risks and benefits. After exploring the reasons behind the patient's request, and discussing the risks and benefits, if a patient insists on her choice a physician may pursue one of the following two options: 1) Agree to perform the CS after 39+0 weeks gestation; 2) Disagree and refer the patient for a second opinion.

Expanded access to cancer treatments from conversion to neutropenia prophylaxis with biosimilar filgrastim-sndz.

AIM: Biosimilar medicines offer significant cost-savings potential over their reference products, which can be re-allocated to provide access to other cancer treatments on a budget-neutral basis. METHODS: Simulation study using cost data for the USA under consideration of several prophylaxis patterns. RESULTS: Potential savings from conversion from reference filgrastim to biosimilar filgrastim-sndz are significant. These savings expand budget-neutral access to novel immunotherapies (obinutuzumab; pembrolizumab) or supportive care (filgrastim-sndz). CONCLUSION: The combination of biosimilar savings and expanded access increases the value of cancer care as the same supportive care is provided at lower cost, additional cancer care is enabled at no additional cost, and more patients will have access to cancer care.

Health services received by individuals with duchenne/becker muscular dystrophy.

INTRODUCTION: Anecdotal reports from families and care providers suggest a wide variation in services received by individuals with Duchenne/Becker muscular dystrophy (DBMD). METHODS: We documented the type and frequency of health services received by individuals with DBMD using the Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet) interview data released in June 2012. Interviews with eligible caregivers from 5 sites (Arizona, Colorado, Georgia, Iowa, and western New York) were conducted from April 2007 to March 2012. RESULTS: Two hundred ninety-six caregivers (66% of those contactable) participated in the interview. There were significant differences among sites in the specialists seen and services received. Concurrence with cardiac recommendations was higher than that with respiratory recommendations. CONCLUSIONS: The results of this survey support and quantify the anecdotal reports from families and care providers regarding the disparities in services received by individuals with DBMD. It remains to be determined whether these differences affect outcomes.

The Management of Nausea and Vomiting of Pregnancy.

OBJECTIVES: To review the evidence-based management of nausea and vomiting of pregnancy and hyperemesis gravidarum. EVIDENCE: MEDLINE and Cochrane database searches were performed using the medical subject headings of treatment, nausea, vomiting, pregnancy, and hyperemesis gravidarum. The quality of evidence reported in these guidelines has been described using the Evaluation of Evidence criteria outlined in the Report of the Canadian Task Force on Preventative Health Care. BENEFITS: Nausea and vomiting of pregnancy has a profound effect on women's health and quality of life during pregnancy as well as a financial impact on the health care system, and its early recognition and management is recommended. COST: Costs, including hospitalizations, additional office visits, and time lost from work, may be reduced if nausea and vomiting in pregnancy is treated early.

Guselkumab (an IL-23-specific mAb) demonstrates clinical and molecular response in patients with moderate-to-severe psoriasis.

BACKGROUND: IL-23 expression is increased in psoriatic lesions and might regulate TH17 T-cell counts in patients with psoriasis. OBJECTIVES: We sought to test a novel IL-23-specific therapeutic agent for the treatment of psoriasis. METHODS: In this randomized, double-blind, placebo-controlled study the safety, tolerability, and clinical response of guselkumab, an anti-IL-23-specific mAb, were evaluated in patients with moderate-to-severe plaque psoriasis. A total of 24 patients were randomized to receive a single dose of placebo or 10, 30, 100, or 300 mg of guselkumab. Clinical response was assessed by using the Psoriasis Area and Severity Index (PASI). Additionally, histologic analysis and gene expression in skin biopsy specimens from guselkumab-treated patients were compared with those from placebo-treated patients. RESULTS: At week 12, 50% (10 mg), 60% (30 and 100 mg), and 100% (300 mg) of guselkumab-treated patients, respectively, achieved a 75% improvement in PASI scores from baseline compared with 0% of placebo-treated patients. Improvements in PASI scores were generally maintained through week 24 in all guselkumab-treated patients. The proportion of patients experiencing an adverse event was comparable between the combined guselkumab (13/20 [65.0%]) and placebo (2/4 [50.0%]) groups through week 24. Analysis of lesional and nonlesional skin biopsy specimens demonstrated decreases in epidermal thickness and T-cell and dendritic cell expression in guselkumab-treated patients compared with values seen in placebo-treated patients. At week 12, significant reductions in psoriasis gene expression and serum IL-17A levels were observed in guselkumab-treated patients. CONCLUSION: IL-23 inhibition with a single dose of guselkumab results in clinical responses in patients with moderate-to-severe psoriasis, suggesting that neutralization of IL-23 alone is a promising therapy for psoriasis.

Two-step delivery may avoid shoulder dystocia: head-to-body delivery interval is less important than we think.

A belief that prolonged head-to-body delivery interval endangers the newborn underpins the common obstetrical practice of delivering the baby's trunk immediately after the head is born. Without intervention, however, birth typically occurs in two steps: once the fetal head is delivered there is usually a pause, and the rest of the infant is born with the next contraction. Allowing a two-step delivery does not increase the risk of fetal harm, and may lower the incidence of shoulder dystocia. A two-step approach to delivery should be considered physiologically normal. This has implications for the definition of shoulder dystocia.

L'opinion selon laquelle la vie du nouveau-né est mise en danger lorsque l'intervalle entre l'accouchement de la tête fœtale et celui du reste du corps est prolongé est à l'origine de la pratique obstétricale courante qui cherche à accoucher le tronc fœtal immédiatement après l'accouchement de la tête. Toutefois, en l'absence d'intervention, l'accouchement se déroule généralement en deux étapes : une pause suit habituellement l'accouchement de la tête, puis le reste du corps est accouché au moment de la contraction suivante. Le fait de permettre un tel accouchement en deux étapes ne donne pas lieu à une hausse des risques auxquels le fœtus est exposé et pourrait même abaisser l'incidence de la dystocie de l'épaule. L'approche en deux étapes envers l'accouchement devrait être considérée comme étant physiologiquement normale; il en résulte donc des répercussions pour ce qui est de la définition de la dystocie de l'épaule.

Using a wearable patch to develop a digital monitoring biomarker of inflammation in response to LPS challenge.

Remote inflammation monitoring with digital health technologies (DHTs) would provide valuable information for both clinical research and care. Controlled perturbations of the immune system may reveal physiological signatures which could be used to develop a digital biomarker of inflammatory state. In this study, molecular and physiological profiling was performed following an in vivo lipopolysaccharide (LPS) challenge to develop a digital biomarker of inflammation. Ten healthy volunteers received an intravenous LPS challenge and were monitored for 24 h using the VitalConnect VitalPatch (VitalPatch). VitalPatch measurements included heart rate (HR), heart rate variability (HRV), respiratory rate (RR), and skin temperature (TEMP). Conventional episodic inpatient vital signs and serum proteins were measured pre- and post-LPS challenge. The VitalPatch provided vital signs that were comparable to conventional methods for assessing HR, RR, and TEMP. A pronounced increase was observed in HR, RR, and TEMP as well as a decrease in HRV 1-4 h post-LPS challenge. The ordering of participants by magnitude of inflammatory cytokine response 2 h post-LPS challenge was consistent with ordering of participants by change from baseline in vital signs when measured by VitalPatch (r = 0.73) but not when measured by conventional methods (r = -0.04). A machine learning model trained on VitalPatch data predicted change from baseline in inflammatory protein response (R2 = 0.67). DHTs, such as VitalPatch, can improve upon existing episodic measurements of vital signs by enabling continuous sensing and have the potential for future use as tools to remotely monitor inflammation.

Guselkumab Reduces Disease- and Mechanism-Related Biomarkers More Than Adalimumab in Patients with Psoriasis: A VOYAGE 1 Substudy.

Background: Psoriasis is an immune-mediated inflammatory disease characterized by activation of IL-23-driven IL-17-producing T cell and other IL-23 receptor-positive IL-17-producing cell responses. Selective blockade of IL-23p19 with guselkumab was superior to blockade of TNF-α with adalimumab (ADA) in treating moderate-to-severe psoriasis. Objective: Pharmacodynamic responses of guselkumab versus ADA were compared in patients with psoriasis in VOYAGE 1. Design: Inflammatory cytokine serum levels were assessed (n = 118), and lesional and nonlesional skin biopsies were collected (n = 38) in patient subsets at baseline and 4, 24, and 48 weeks after treatment to evaluate pharmacodynamic responses of guselkumab versus those of ADA. Results: Guselkumab provided rapid reductions in serum IL-17A, IL-17F, and IL-22 levels by week 4 versus at baseline, which were maintained through weeks 24 and 48 (P < .001). The magnitude of reduction of IL-17A and IL-22 at week 48 and IL-17F at weeks 4, 24, and 48 were greater with guselkumab than with ADA (all P < .05). In the skin, guselkumab reduced the expression of IL-23/IL-17 pathway-associated and psoriasis-associated genes. Conclusion: These data provide extensive characterization of pharmacodynamic anti-inflammatory responses to IL-23p19 and TNF-α inhibition in human blood and tissue over time with FDA-approved doses of guselkumab and ADA. Trial registration:ClinicalTrials.govClinicalTrials.gov (NCT02207231).