Synthesis of Polysubstituted 2-Aminoimidazoles via Alkene-Diamination of Guanidine with Conjugated α-Bromoalkenones.

A step-economical access to polysubstituted aminoimidazoles has been accomplished via alkene vicinal C-N bonds formation of 2-bromo-2-alkenones with guanidine avoiding its NH-protection/derivatization prerequisite for electronic modulation. The approach has excellent substrate scope, is amenable to diverse guanidine-containing substrates, and introduces distinctive substitutions/functionalities into aminoimidazole core. It is also applicable to preparation of fused-imidazoles. The reaction involves a tandem pathway of aza-Michael addition, SN2, and a unique redox-neutral process, as evident by spectroscopic study and control experiments.

Developing technical support and strategic dialogue at the country level to achieve Primary Health Care-based health systems beyond the COVID-19 era.

This article is part of the Research Topic 'Health Systems Recovery in the Context of COVID-19 and Protracted Conflict'. Pursuing the objectives of the Declaration of Alma-Ata for Primary Health Care (PHC), the World Health Organization (WHO) and global health partners are supporting national authorities to improve governance to build resilient and integrated health systems, including recovery from public health stressors, through the long-term deployment of WHO country senior health policy advisers under the Universal Health Coverage Partnership (UHC Partnership). For over a decade, the UHC Partnership has progressively reinforced, via a flexible and bottom-up approach, the WHO's strategic and technical leadership on Universal Health Coverage, with more than 130 health policy advisers deployed in WHO Country and Regional Offices. This workforce has been described as a crucial asset by WHO Regional and Country Offices in the integration of health systems to enhance their resilience, enabling the WHO offices to strengthen their support of PHC and Universal Health Coverage to Ministries of Health and other national authorities as well as global health partners. Health policy advisers aim to build the technical capacities of national authorities, in order to lead health policy cycles and generate political commitment, evidence, and dialogue for policy-making processes, while creating synergies and harmonization between stakeholders. The policy dialogue at the country level has been instrumental in ensuring a whole-of-society and whole-of-government approach, beyond the health sector, through community engagement and multisectoral actions. Relying on the lessons learned during the 2014-2016 Ebola outbreak in West Africa and in fragile, conflict-affected, and vulnerable settings, health policy advisers played a key role during the COVID-19 pandemic to support countries in health systems response and early recovery. They brought together technical resources to contribute to the COVID-19 response and to ensure the continuity of essential health services, through a PHC approach in health emergencies. This policy and practice review, including from the following country experiences: Colombia, Islamic Republic of Iran, Lao PDR, South Sudan, Timor-Leste, and Ukraine, provides operational and inner perspectives on strategic and technical leadership provided by WHO to assist Member States in strengthening PHC and essential public health functions for resilient health systems. It aims to demonstrate and advise lessons and good practices for other countries in strengthening their health systems.

A Core-Linker-Polyamine (CLP) Strategy Enables Rapid Discovery of Antileishmanial Aminoalkylquinolinecarboxamides That Target Oxidative Stress Mechanism.

A Core-Linker-Polyamine (CLP) strategy has been exploited to develop new antileishmanial agents. It involves the linker-based assembly of alkyl-polyamine side chain as a potential pharmacophore motif with a privileged heterocyclic motif, 4-arylquinoline. A series of aminoalkyl 4-arylquinoline-2-carboxamides and their analogs were synthesized and tested against L. donovani promastigotes. Among all synthesized derivatives, 10 compounds showed significant antipromastigote activities with more efficacy (IC50 : 4.75-8 µM) than an antileishmanial oral drug Miltefosine (IC50 : 8.9±1.55 µM). Most active aminoalkyl-quinoline-carboxamides 9 a and 9 b, displayed negligible cytotoxicity towards human monocytic (THP-1) macrophages. The compounds show antileishmanial activity by generating mitochondrial superoxide radicals. However, they did not show interference with trypanothione reductase, a redox enzyme of Leishmania. Significant change in the morphology of the L. donovani promastigote by the compounds was observed. The Structure-activity relationship analysis suggest the pharmacophoric importance of alkylpolyamine and carboxamide motifs. In silico evaluation indicated that the investigated active molecules 9 a and 9 b possess important drug-likeness, physicochemical and pharmacokinetic-relevant properties.

Hepatitis Testing Performance of an Analyzer Integrated into Another Manufacturer's Automation System.

BACKGROUND: The capacity to integrate platforms across vendors and disciplines has become an essential feature in the design of total laboratory automation (TLA) due space and test menu constraints. However, data on its performance are lacking. We aim to evaluate an integrated third-party immunoassay platform to the TLA system for the performance of hepatitis testing using turnaround time (TAT). METHODS: We use the Beckman Power Express (PE) system with linked 2 Beckman AU5800, 2 Beckman DxI 800, 2 Abbott Architect i2000, and other accessory components. The PE system is managed and interfaced to the laboratory information system (LIS) through Beckman Remisol (middleware) and Cennexus (track software). The hepatitis tests are performed on the Abbott Architect i2000 using Abbott Instrument Manager (middleware) for test results and this is interfaced with LIS and Cennexus. Using Viewics and Microsoft Excel, the test volumes and TAT of hepatitis results were analyzed before (February 2017 to January 2018) and after (February 2018 to January 2019) integration. RESULTS: The TAT for each hepatitis test has decreased significantly, ranging from 13 to 81-minute reductions (P value <0.0001 for all tests) after instrument integration. The standard deviations of the TAT also decreased for each test. In addition, savings in labor expenditure of around 2 hours per day were observed. There were no laboratory space savings identified. Instead, 47.6 square foot more of space was utilized by the track connection lines. CONCLUSIONS: Our findings show significant improvement of TAT of hepatitis testing with the integration of the third-party Abbott Architect i2000 to Beckman PE system. In addition, the synchronization of multiple middleware for specimen management and result reporting allow the laboratory to achieve new efficiencies handling reflex tests and managing human resources.

Techniques for cesarean section.

The effects of complete methods of cesarean section (CS) were compared. Metaanalysis of randomized controlled trials of intention to perform CS using different techniques was carried out. Joel-Cohen-based CS compared with Pfannenstiel CS was associated with reduced blood loss, operating time, time to oral intake, fever, duration of postoperative pain, analgesic injections, and time from skin incision to birth of the baby. Misgav-Ladach compared with the traditional method was associated with reduced blood loss, operating time, time to mobilization, and length of postoperative stay for the mother. Joel-Cohen-based methods have advantages compared with Pfannenstiel and traditional (lower midline) CS techniques. However, these trials do not provide information on serious and long-term outcomes.

Intracluster correlation coefficients from the 2005 WHO Global Survey on Maternal and Perinatal Health: implications for implementation research.

Cluster-based studies involving aggregate units such as hospitals or medical practices are increasingly being used in healthcare evaluation. An important characteristic of such studies is the presence of intracluster correlation, typically quantified by the intracluster correlation coefficient (ICC). Sample size calculations for cluster-based studies need to account for the ICC, or risk underestimating the sample size required to yield the desired levels of power and significance. In this article, we present values for ICCs that were obtained from data on 97,095 pregnancies and 98,072 births taking place in a representative sample of 120 hospitals in eight Latin American countries. We present ICCs for 86 variables measured on mothers and newborns from pregnancy to the time of hospital discharge, including 'process variables' representing actual medical care received for each mother and newborn. Process variables are of primary interest in the field of implementation research. We found that overall, ICCs ranged from a minimum of 0.0003 to a maximum of 0.563 (median 0.067). For maternal and newborn outcome variables, the median ICCs were 0.011 (interquartile range 0.007-0.037) and 0.054 (interquartile range 0.013-0.075) respectively; however, for process variables, the median was 0.161 (interquartile range 0.072-0.328). Thus, we confirm previous findings that process variables tend to have higher ICCs than outcome variables. We demonstrate that ICCs generally tend to increase with higher prevalences (close to 0.5). These results can help researchers calculate the required sample size for future research studies in maternal and perinatal health.

Caesarean delivery rates and pregnancy outcomes: the 2005 WHO global survey on maternal and perinatal health in Latin America.

BACKGROUND: Caesarean delivery rates continue to increase worldwide. Our aim was to assess the association between caesarean delivery and pregnancy outcome at the institutional level, adjusting for the pregnant population and institutional characteristics. METHODS: For the 2005 WHO global survey on maternal and perinatal health, we assessed a multistage stratified sample, comprising 24 geographic regions in eight countries in Latin America. We obtained individual data for all women admitted for delivery over 3 months to 120 institutions randomly selected from of 410 identified institutions. We also obtained institutional-level data. FINDINGS: We obtained data for 97,095 of 106,546 deliveries (91% coverage). The median rate of caesarean delivery was 33% (quartile range 24-43), with the highest rates of caesarean delivery noted in private hospitals (51%, 43-57). Institution-specific rates of caesarean delivery were affected by primiparity, previous caesarean delivery, and institutional complexity. Rate of caesarean delivery was positively associated with postpartum antibiotic treatment and severe maternal morbidity and mortality, even after adjustment for risk factors. Increase in the rate of caesarean delivery was associated with an increase in fetal mortality rates and higher numbers of babies admitted to intensive care for 7 days or longer even after adjustment for preterm delivery. Rates of preterm delivery and neonatal mortality both rose at rates of caesarean delivery of between 10% and 20%. INTERPRETATION: High rates of caesarean delivery do not necessarily indicate better perinatal care and can be associated with harm.

Determinants of perinatal mortality in Nigeria.

OBJECTIVE: To determine risk factors for perinatal mortality among hospital-based deliveries in Nigeria. METHODS: The WHO Global Maternal and Perinatal Health Survey was implemented in Nigeria as a first step in establishing a global system for monitoring maternal and perinatal health. Twenty-one health facilities with more than 1000 deliveries annually were selected by a stratified multistage cluster sampling strategy. Information was recorded on all women who delivered and their neonates within a 3-month period. RESULTS: Overall, there were 9208 deliveries, comprising 8526 live births, 369 fresh stillbirths, 282 macerated stillbirths, 70 early neonatal deaths, and 721 perinatal deaths. The stillbirth and perinatal mortality rates were, respectively, 71 and 78 per 1000 deliveries; the early neonatal death rate was 8 per 1000 live births. Approximately 10% of all newborns weighed less than 2500 g, and 12.3% were born at less than 37 weeks of gestation. Predictors of perinatal mortality were mother's age, lack of prenatal care, unbooked status, prematurity, and birth asphyxia. CONCLUSION: The perinatal mortality rate remains unacceptably high in Nigeria. Fresh stillbirth accounted for most perinatal deaths. Interventions to improve the utilization and quality of prenatal care, in addition to the quality of intrapartum care, would considerably reduce perinatal death.

Cesarean delivery outcomes from the WHO global survey on maternal and perinatal health in Africa.

OBJECTIVE: To assess the association between cesarean delivery rates and pregnancy outcomes in African health facilities. METHODS: Data were obtained from all births over 2-3 months in 131 facilities. Outcomes included maternal deaths, severe maternal morbidity, fresh stillbirths, and neonatal deaths and morbidity. RESULTS: Median cesarean delivery rate was 8.8% among 83439 births. Cesarean deliveries were performed in only 95 (73%) facilities. Facility-specific cesarean delivery rates were influenced by previous cesarean, pre-eclampsia, induced labor, referral status, and higher health facility classification scores. Pre-eclampsia increased the risks of maternal death, fresh stillbirths, and severe neonatal morbidity. Adjusted emergency cesarean delivery rate was associated with more fresh stillbirths, neonatal deaths, and severe neonatal morbidity--probably related to prolonged labor, asphyxia, and sepsis. Adjusted elective cesarean delivery rate was associated with fewer perinatal deaths. CONCLUSION: Use of cesarean delivery is limited in the African health facilities surveyed. Emergency cesareans, when performed, are often too late to reduce perinatal deaths.

Methodological considerations in implementing the WHO Global Survey for Monitoring Maternal and Perinatal Health.

OBJECTIVE: To set up a global system for monitoring maternal and perinatal health in 54 countries worldwide. METHODS: The WHO Global Survey for Monitoring Maternal and Perinatal Health was implemented through a network of health institutions, selected using a stratified multistage cluster sampling design. Focused information on maternal and perinatal health was abstracted from hospital records and entered in a specially developed online data management system. Data were collected over a two- to three-month period in each institution. The project was coordinated by WHO and supported by WHO regional offices and country coordinators in Africa and the Americas. FINDINGS: The initial survey was implemented between September 2004 and March 2005 in the African and American regions. A total of 125 institutions in seven African countries and 119 institutions in eight Latin American countries participated. CONCLUSION: This project has created a technologically simple and scientifically sound system for large-scale data management, which can facilitate programme monitoring in countries.

Maternal and neonatal individual risks and benefits associated with caesarean delivery: multicentre prospective study.

OBJECTIVE: To assess the risks and benefits associated with caesarean delivery compared with vaginal delivery. DESIGN: Prospective cohort study within the 2005 WHO global survey on maternal and perinatal health. SETTING: 410 health facilities in 24 areas in eight randomly selected Latin American countries; 123 were randomly selected and 120 participated and provided data PARTICIPANTS: 106,546 deliveries reported during the three month study period, with data available for 97,095 (91% coverage). MAIN OUTCOME MEASURES: Maternal, fetal, and neonatal morbidity and mortality associated with intrapartum or elective caesarean delivery, adjusted for clinical, demographic, pregnancy, and institutional characteristics. RESULTS: Women undergoing caesarean delivery had an increased risk of severe maternal morbidity compared with women undergoing vaginal delivery (odds ratio 2.0 (95% confidence interval 1.6 to 2.5) for intrapartum caesarean and 2.3 (1.7 to 3.1) for elective caesarean). The risk of antibiotic treatment after delivery for women having either type of caesarean was five times that of women having vaginal deliveries. With cephalic presentation, there was a trend towards a reduced odds ratio for fetal death with elective caesarean, after adjustment for possible confounding variables and gestational age (0.7, 0.4 to 1.0). With breech presentation, caesarean delivery had a large protective effect for fetal death. With cephalic presentation, however, independent of possible confounding variables and gestational age, intrapartum and elective caesarean increased the risk for a stay of seven or more days in neonatal intensive care (2.1 (1.8 to 2.6) and 1.9 (1.6 to 2.3), respectively) and the risk of neonatal mortality up to hospital discharge (1.7 (1.3 to 2.2) and 1.9 (1.5 to 2.6), respectively), which remained higher even after exclusion of all caesarean deliveries for fetal distress. Such increased risk was not seen for breech presentation. Lack of labour was a risk factor for a stay of seven or more days in neonatal intensive care and neonatal mortality up to hospital discharge for babies delivered by elective caesarean delivery, but rupturing of membranes may be protective. CONCLUSIONS: Caesarean delivery independently reduces overall risk in breech presentations and risk of intrapartum fetal death in cephalic presentations but increases the risk of severe maternal and neonatal morbidity and mortality in cephalic presentations.