Protocol for a drugs exposure pregnancy registry for implementation in resource-limited settings

BACKGROUND: The absence of robust evidence of safety of medicines in pregnancy, particularly those for major diseases provided by public health programmes in developing countries, has resulted in cautious recommendations on their use. We describe a protocol for a Pregnancy Registry adapted to resource-limited settings aimed at providing evidence on the safety of medicines in pregnancy.METHODS/DESIGN:Sentinel health facilities are chosen where women come for prenatal care and are likely to come for delivery. Staff capacity is improved to provide better care during the pregnancy, to identify visible birth defects at delivery and refer infants with major anomalies for surgical or clinical evaluation and treatment. Consenting women are enrolled at their first antenatal visit and careful medical, obstetric and drug-exposure histories taken; medical record linkage is encouraged. Enrolled women are followed up prospectively and their histories are updated at each subsequent visit. The enrolled woman is encouraged to deliver at the facility, where she and her baby can be assessed.DISCUSSION:In addition to data pooling into a common WHO database, the WHO Pregnancy Registry has three important features: First is the inclusion of pregnant women coming for antenatal care, enabling comparison of birth outcomes of women who have been exposed to a medicine with those who have not. Second is its applicability to resource-poor settings regardless of drug or disease. Third is improvement of reproductive health care during pregnancies and at delivery. Facility delivery enables better health outcomes, timely evaluation and management of the newborn, and the collection of reliable clinical data. The Registry aims to improve maternal and neonatal care and also provide much needed information on the safety of medicines in pregnancy

Neurofilament light chain: A prognostic biomarker in amyotrophic lateral sclerosis.

OBJECTIVE: To test blood and CSF neurofilament light chain (NfL) levels in relation to disease progression and survival in amyotrophic lateral sclerosis (ALS). METHODS: Using an electrochemiluminescence immunoassay, NfL levels were measured in samples from 2 cohorts of patients with sporadic ALS and healthy controls, recruited in London (ALS/control, plasma: n = 103/42) and Oxford (ALS/control, serum: n = 64/36; paired CSF: n = 38/20). NfL levels in patients were measured at regular intervals for up to 3 years. Change in ALS Functional Rating Scale-Revised score was used to assess disease progression. Survival was evaluated using Cox regression and Kaplan-Meier analysis. RESULTS: CSF, serum, and plasma NfL discriminated patients with ALS from healthy controls with high sensitivity (97%, 89%, 90%, respectively) and specificity (95%, 75%, 71%, respectively). CSF NfL was highly correlated with serum levels (r = 0.78, p < 0.0001). Blood NfL levels were approximately 4 times as high in patients with ALS compared with controls in both cohorts, and maintained a relatively constant expression during follow-up. Blood NfL levels at recruitment were strong, independent predictors of survival. The highest tertile of blood NfL at baseline had a mortality hazard ratio of 3.91 (95% confidence interval 1.98-7.94, p < 0.001). CONCLUSION: Blood-derived NfL level is an easily accessible biomarker with prognostic value in ALS. The individually relatively stable levels longitudinally offer potential for NfL as a pharmacodynamic biomarker in future therapeutic trials. CLASSIFICATION OF EVIDENCE: This report provides Class III evidence that the NfL electrochemiluminescence immunoassay accurately distinguishes patients with sporadic ALS from healthy controls

Advancing diagnostics to address antibacterial resistance: The diagnostics and devices committee of the Antibacterial Resistance Leadership Group

Diagnostics are a cornerstone of the practice of infectious diseases. However, various limitations frequently lead to unmet clinical needs. In most other domains, diagnostics focus on narrowly defined questions, provide readily interpretable answers, and use true gold standards for development. In contrast, infectious diseases diagnostics must contend with scores of potential pathogens, dozens of clinical syndromes, emerging pathogens, rapid evolution of existing pathogens and their associated resistance mechanisms, and the absence of gold standards in many situations. In spite of these challenges, the importance and value of diagnostics cannot be underestimated. Therefore, the Antibacterial Resistance Leadership Group has identified diagnostics as 1 of 4 major areas of emphasis. Herein, we provide an overview of that development, highlighting several examples where innovation in study design, content, and execution is advancing the field of infectious diseases diagnostics

The skeletal phenotype of chondroadherin deficient mice

Chondroadherin, a leucine rich repeat extracellular matrix protein with functions in cell to matrix interactions, binds cells via their a2b1 integrin as well as via cell surface proteoglycans, providing for different sets of signals to the cell. Additionally, the protein acts as an anchor to the matrix by binding tightly to collagens type I and II as well as type VI. We generated mice with inactivated chondroadherin gene to provide integrated studies of the role of the protein. The null mice presented distinct phenotypes with affected cartilage as well as bone. At 3–6 weeks of age the epiphyseal growth plate was widened most pronounced in the proliferative zone. The proteome of the femoral head articular cartilage at 4 months of age showed some distinct differences, with increased deposition of cartilage intermediate layer protein 1 and fibronectin in the chondroadherin deficient mice, more pronounced in the female. Other proteins show decreased levels in the deficient mice, particularly pronounced for matrilin-1, thrombospondin-1 and notably the members of the a1-antitrypsin family of proteinase inhibitors as well as for a member of the bone morphogenetic protein growth factor family. Thus, cartilage homeostasis is distinctly altered. The bone phenotype was expressed in several ways. The number of bone sialoprotein mRNA expressing cells in the proximal tibial metaphysic was decreased and the osteoid surface was increased possibly indicating a change in mineral metabolism. Micro-CT revealed lower cortical thickness and increased structure model index, i.e. the amount of plates and rods composing the bone trabeculas. The structural changes were paralleled by loss of function, where the null mice showed lower femoral neck failure load and tibial strength during mechanical testing at 4 months of age. The skeletal phenotype points at a role for chondroadherin in both bone and cartilage homeostasis, however, without leading to altered longitudinal growth

Decision heuristics in contexts integrating action selection and execution

Heuristics can inform human decision making in complex environments through a reduction of computational requirements (accuracy-resource trade-off) and a robustness to overparameterisation (less-is-more). However, tasks capturing the efficiency of heuristics typically ignore action proficiency in determining rewards. The requisite movement parameterisation in sensorimotor control questions whether heuristics preserve efficiency when actions are nontrivial. We developed a novel action selection-execution task requiring joint optimisation of action selection and spatio-temporal skillful execution. State-appropriate choices could be determined by a simple spatial heuristic, or by more complex planning. Computational models of action selection parsimoniously distinguished human participants who adopted the heuristic from those using a more complex planning strategy. Broader comparative analyses then revealed that participants using the heuristic showed combined decisional (selection) and skill (execution) advantages, consistent with a less-is-more framework. In addition, the skill advantage of the heuristic group was predominantly in the core spatial features that also shaped their decision policy, evidence that the dimensions of information guiding action selection might be yoked to salient features in skill learning

Assessment of midwifery care providers intrapartum care competencies, in four sub-Saharan countries: a mixed-method study protocol.

BACKGROUND: We aim to assess competencies (knowledge, skills and attitudes) of midwifery care providers as well as their experiences and perceptions of in-service training in the four study countries; Benin, Malawi, Tanzania and Uganda as part of the Action Leveraging Evidence to Reduce perinatal mortality and morbidity in sub-Saharan Africa project (ALERT). While today more women in low- and middle-income countries give birth in health care facilities, reductions in maternal and neonatal mortality have been less than expected. This paradox may be explained by the standard and quality of intrapartum care provision which depends on several factors such as health workforce capacity and the readiness of the health system as well as access to care. METHODS: Using an explanatory sequential mixed method design we will employ three methods (i) a survey will be conducted using self-administered questionnaires assessing knowledge, (ii) skills drills assessing basic intrapartum skills and attitudes, using an observation checklist and (iii) Focus Group Discussions (FGDs) to explore midwifery care providers' experiences and perceptions of in-service training. All midwifery care providers in the study facilities are eligible to participate in the study. For the skills drills a stratified sample of midwifery care providers will be selected in each hospital according to the number of providers and, professional titles and purposive sampling will be used for the FGDs. Descriptive summary statistics from the survey and skills drills will be presented by country. Conventional content analysis will be employed for data analysis of the FGDs. DISCUSSION: We envision comparative insight across hospitals and countries. The findings will be used to inform a targeted quality in-service training and quality improvement intervention related to provision of basic intrapartum care as part of the ALERT project. TRIAL REGISTRATION: PACTR202006793783148-June 17th, 2020

Are midwives ready to provide quality evidence-based care after pre-service training? Curricula assessment in four countries-Benin, Malawi, Tanzania, and Uganda.

This research sought to map midwifery pre-service training curricula as part of the Action Leveraging Evidence to Reduce perinatal morTality and morbidity in sub-Saharan Africa (ALERT) project conducted in Benin, Malawi, Tanzania, and Uganda. We conducted the review in two phases. In the first phase, online interviews were performed with the lead project midwives in all four study countries to get an overview of midwifery care providers' pre-service training courses, registration, and licensing requirements. We performed a mapping review of midwifery care providers' pre-service training curricula from different training institutions in the four study countries during the second phase. Curricula were reviewed and mapped against the International Confederation of Midwives (ICM) Essential Competencies framework to assess whether these curricula included the minimum essential training components described in the ICM framework. We identified 10 different professional titles for midwifery care providers. The number of years spent in pre-service training varied from one and a half to four years. Ten pre-service curricula were obtained and the assessment revealed that none of the curricula included all ICM competencies. Main gaps identified in all curricula related to women-centred care, inclusion of women in decision making, provision of care to women with unintended or mistimed pregnancy, fundamental human rights of individuals and evidence-based learning. This review suggests that there are skills, knowledge and behaviour gaps in pre-service training curricula for midwifery care providers when mapped to the ICM Essential Competencies framework. These gaps are similar among the different training courses in participating countries. The review also draws attention to the plethora of professional titles and different pre-service training curricula within countries. Trial registration: PACTR202006793783148-June 17th, 2020

A framework for healthcare interventions to address maternal morbidity

© 2018 World Health Organization; licensed by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics. The maternal health agenda is undergoing a paradigm shift from preventing maternal deaths to promoting women's health and wellness. A critical focus of this trajectory includes addressing maternal morbidity and the increasing burden of chronic and noncommunicable diseases (NCD) among pregnant women. The WHO convened the Maternal Morbidity Working Group (MMWG) to improve the scientific basis for defining, measuring, and monitoring maternal morbidity. Based on the MMWG's work, we propose paradigms for conceptualizing maternal health and related interventions, and call for greater integration between maternal health and NCD programs. This integration can be synergistic, given the links between chronic conditions, morbidity in pregnancy, and long-term health. Pregnancy should be viewed as a window of opportunity into the current and future health of women, and offers critical entry points for women who may otherwise not seek or have access to care for chronic conditions. Maternal health services should move beyond the focus on emergency obstetric care, to a broader approach that encompasses preventive and early interventions, and integration with existing services. Health systems need to respond by prioritizing funding for developing integrated health programs, and workforce strengthening. The MMWG's efforts have highlighted the changing landscape of maternal health, and the need to expand the narrow focus of maternal health, moving beyond surviving to thriving

Malaria in HIV-Infected Children Receiving HIV Protease-Inhibitor- Compared with Non-Nucleoside Reverse Transcriptase Inhibitor-Based Antiretroviral Therapy, IMPAACT P1068s, Substudy to P1060

HIV and malaria geographically overlap. HIV protease inhibitors kill malaria parasites in vitro and in vivo, but further evaluation in clinical studies is needed