Prediction of perinatal outcome in high-risk pregnancy by Doppler ultrasound: a prospective cohort study

Background: Doppler study of uterine and fetal vessels assesses the feto-maternal circulation. An abnormal Doppler study is a sign of placental dysfunction and fetal damage. This study aims to study the relationship of Doppler velocimetry of the uterine artery, umbilical artery, and middle cerebral artery to perinatal outcomes in normal and high-risk pregnancies.Methods: A prospective cohort study was conducted in a tertiary health care center. A total of 150 patients aged 18–35 years with the gestational age of 28 to 40 weeks in 2 cohorts, 75 in high risk and 75 in the non-high-risk cohort were included. Pregnant women with gestational hypertension, intrauterine growth restriction, preeclampsia, preeclampsia plus IUGR were included in high-risk cohort. Doppler study was carried out, data was collected, and was analyzed.Results: Doppler parameters and their association with perinatal outcome were measured. The sensitivity of umbilical artery index (79.4%) was found to be highly predictive of poor neonatal outcomes compared to middle cerebral artery Doppler (58.8%) and cerebroplacental ratio (41.2%) parameters. A high positive predictive value for unfavourable perinatal outcomes with an accuracy of 93% using umbilical artery indices, 95% using MCA Doppler, and 93% CPR was found in the study. Specificity of umbilical artery Doppler was 87.5%, MCA Doppler was 93.75% and CPR was 93.75%.Conclusions: When incorporated into evaluating high-risk pregnancies complicated by pregnancy-induced hypertension, preeclampsia, and IUGR in the third trimester, screening the fetuses for well-being with Doppler helps in timely intervention and improves the perinatal outcome

The NHS visitor and migrant cost recovery programme - a threat to health?

BACKGROUND: In April 2014 the UK government launched the 'NHS Visitor and Migrant Cost Recovery Programme Implementation Plan' which set out a series of policy changes to recoup costs from 'chargeable' (largely non-UK born) patients. In England, approximately 75% of tuberculosis (TB) cases occur in people born abroad. Delays in TB treatment increase risk of morbidity, mortality and transmission in the community. We investigated whether diagnostic delay has increased since the Cost Recovery Programme (CRP) was introduced. METHODS: There were 3342 adult TB cases notified on the London TB Register across Barts Health NHS Trust between 1st January 2011 and 31st December 2016. Cases with missing relevant information were excluded. The median time between symptom onset and treatment initiation before and after the CRP was calculated according to birthplace and compared using the Mann Whitney test. Delayed diagnosis was considered greater or equal to median time to treatment for all patients (79 days). Univariable logistic regression was used to manually select exposure variables for inclusion in a multivariable model to test the association between diagnostic delay and the implementation of the CRP. RESULTS: We included 2237 TB cases. Among non-UK born patients, median time-to-treatment increased from 69 days to 89 days following introduction of CRP (p < 0.001). Median time-to-treatment also increased for the UK-born population from 75.5 days to 89.5 days (p = 0.307). The multivariable logistic regression model showed non-UK born patients were more likely to have a delay in diagnosis after the CRP (adjOR 1.37, 95% CI 1.13-1.66, p value 0.001). CONCLUSION: Since the introduction of the CRP there has been a significant delay for TB treatment among non-UK born patients. Further research exploring the effect of policies restricting access to healthcare for migrants is urgently needed if we wish to eliminate TB nationally

Investigations on the creeks of Saurashtra

Gujarat has a rich estuarine system supported by run-off from five major rivers, viz., Narmada, Mahi, Tapti, Banas and Sabarmati. The branches of these rivers form several small creeks which act as outlets to the sea. These creeks are known to have supported traditional fisheries for a variety of shrimps and fishes over the years. However, these fisheries are now on a declining phase. With reduced rainfall in recent years, these creeks remain saline for a major part of the year. Natural flushing is further obstructed by the numerous check dams and small impoundments constructed across the rivers and rivulets flowing into these creeks

Unusal landings of large-sized Sepia pharaonis from the coastal waters of Saurashtra

Fishing grounds for cuttlefishes are beyond 50m depth zone, off Dwaraka. This report is on unsual landings of Sepia pharaonis from the coastal waters off Saurashtra. The total landing of S. pharaonis was estimated to be around 20 tonnes. It is revealed that minor upwelling has been the reason for this unusual catch

The cursed duet today: Tuberculosis and HIV-coinfection

The tuberculosis (TB) and HIV syndemic continues to rage and are a major public health concern worldwide. This deadly association raises complexity and represent a significant barrier towards TB elimination. TB continues to be the leading cause of death amongst HIV-infected people. This paper reports the challenges that lay ahead and outlines some of the current and future strategies that may be able to address this co-epidemic efficiently. Improved diagnostics, cheaper and more effective drugs, shorter treatment regimens for both drug-sensitive and drug-resistant TB are discussed. Also, special topics on drug interactions, TB-IRIS and TB relapse are also described. Notwithstanding the defeats and meagre investments, diagnosis and management of the two diseases have seen significant and unexpected improvements of late. On the HIV side, expansion of ART coverage, development of new updated guidelines aimed at the universal treatment of those infected, and the increasing availability of newer, more efficacious and less toxic drugs are an essential element to controlling the two epidemics. On the TB side, diagnosis of MDR-TB is becoming easier and faster thanks to the new PCR-based technologies, new anti-TB drugs active against both sensitive and resistant strains (i.e. bedaquiline and delamanid) have been developed and a few more are in the pipeline, new regimens (cheaper, shorter and/or more effective) have been introduced (such as the “Bangladesh regimen”) or are being tested for MDR-TB and drug-sensitive-TB. However, still more resources will be required to implement an integrated approach, install new diagnostic tests, and develop simpler and shorter treatment regimens

A comparison of electrochemical degradation of phenol on boron doped diamond and lead dioxide anodes

This work compares two electrode materials used to mineralize phenol contained in waste waters. Two disks covered with either boron doped diamond (BDD) or PbO2 were used as anodes in a one compartment flow cell under the same hydrodynamic conditions. Efficiencies of galvanostatic electrolyses are compared on the basis of measurements of Total Organic Carbon (TOC) and Chemical Oxygen Demand (COD). Galvanostatic electrolyses were monitored by analysis of phenol and of its oxidation derivatives to evaluate the operating time needed for complete elimination of toxic aromatics. The experimental current efficiency is close to the theoretical value for the BDD electrode. Other parameters being equal, phenol species disappeared at the same rate using the two electrode materials but the BDD anode showed better efficiency to eliminate TOC and COD. Moreover, during the electrolysis less intermediates are formed with BDD compared to PbO2 whatever the current density. A comparison of energy consumption is given based on the criterion of 99% removal of aromatic compounds

AT7519, a Novel Small Molecule Multi-Cyclin Dependent Kinase Inhibitor, Induces Apoptosis in Multiple Myeloma VIA GSK3 beta

Dysregulated cell cycling is a universal hallmark of cancer and is often mediated by abnormal activation of cyclin-dependent kinases (CDKs) and their cyclin partners. Overexpression of individual complexes are reported in multiple myeloma (MM), making them attractive therapeutic targets. In this study, we investigate the preclinical activity of a novel small-molecule multi-CDK inhibitor, AT7519, in MM. We show the anti-MM activity of AT7519 displaying potent cytotoxicity and apoptosis; associated with in vivo tumor growth inhibition and prolonged survival. At the molecular level, AT7519 inhibited RNA polymerase II (RNA pol II) phosphorylation, a CDK9, 7 substrate, associated with decreased RNA synthesis confirmed by [(3)H] Uridine incorporation. In addition, AT7519 inhibited glycogen synthase kinase 3beta (GSK-3beta) phosphorylation; conversely pretreatment with a selective GSK-3 inhibitor and shRNA GSK-3beta knockdown restored MM survival, suggesting the involvement of GSK-3beta in AT7519-induced apoptosis. GSK-3beta activation was independent of RNA pol II dephosphorylation confirmed by alpha-amanitin, a specific RNA pol II inihibitor, showing potent inhibition of RNA pol II phosphorylation without corresponding effects on GSK-3beta phosphorylation. These results offer new insights into the crucial, yet controversial role of GSK-3beta in MM and show significant anti-MM activity of AT7519, providing the rationale for its clinical evaluation in MM

Point of Care Nucleic Acid Testing for SARS-CoV-2 in Hospitalized Patients: A Clinical Validation Trial and Implementation Study

There is an urgent need for rapid SARS-CoV-2 testing in hospitals to limit nosocomial spread. We report an evaluation of point of care (POC) nucleic acid amplification testing (NAAT) in 149 participants with parallel combined nasal and throat swabbing for POC versus standard lab RT-PCR testing. Median time to result is 2.6 (IQR 2.3–4.8) versus 26.4 h (IQR 21.4–31.4, p < 0.001), with 32 (21.5%) positive and 117 (78.5%) negative. Cohen’s κ correlation between tests is 0.96 (95% CI 0.91–1.00). When comparing nearly 1,000 tests pre- and post-implementation, the median time to definitive bed placement from admission is 23.4 (8.6-41.9) versus 17.1 h (9.0–28.8), p = 0.02. Mean length of stay on COVID-19 “holding” wards is 58.5 versus 29.9 h (p < 0.001). POC testing increases isolation room availability, avoids bed closures, allows discharge to care homes, and expedites access to hospital procedures. POC testing could mitigate the impact of COVID-19 on hospital systems

Exploring the views of infection consultants in England on a novel delinked funding model for antimicrobials: the SMASH study

OBJECTIVES: A novel ‘subscription-type’ funding model was launched in England in July 2022 for ceftazidime/avibactam and cefiderocol. We explored the views of infection consultants on important aspects of the delinked antimicrobial funding model. METHODS: An online survey was sent to all infection consultants in NHS acute hospitals in England. RESULTS: The response rate was 31.2% (235/753). Most consultants agreed the model is a welcome development (69.8%, 164/235), will improve treatment of drug-resistant infections (68.5%, 161/235) and will stimulate research and development of new antimicrobials (57.9%, 136/235). Consultants disagreed that the model would lead to reduced carbapenem use and reported increased use of cefiderocol post-implementation. The presence of an antimicrobial pharmacy team, requirement for preauthorization by infection specialists, antimicrobial stewardship ward rounds and education of infection specialists were considered the most effective antimicrobial stewardship interventions. Under the new model, 42.1% (99/235) of consultants would use these antimicrobials empirically, if risk factors for antimicrobial resistance were present (previous infection, colonization, treatment failure with carbapenems, ward outbreak, recent admission to a high-prevalence setting). Significantly higher insurance and diversity values were given to model antimicrobials compared with established treatments for carbapenem-resistant infections, while meropenem recorded the highest enablement value. Use of both ‘subscription-type’ model drugs for a wide range of infection sites was reported. Respondents prioritized ceftazidime/avibactam for infections by bacteria producing OXA-48 and KPC and cefiderocol for those producing MBLs and infections with Stenotrophomonas maltophilia, Acinetobacter spp. and Burkholderia cepacia. CONCLUSIONS: The ‘subscription-type’ model was viewed favourably by infection consultants in England

Exploring the views of infection consultants in England on a novel delinked funding model for antimicrobials: the SMASH study

OBJECTIVES: A novel 'subscription-type' funding model was launched in England in July 2022 for ceftazidime/avibactam and cefiderocol. We explored the views of infection consultants on important aspects of the delinked antimicrobial funding model. METHODS: An online survey was sent to all infection consultants in NHS acute hospitals in England. RESULTS: The response rate was 31.2% (235/753). Most consultants agreed the model is a welcome development (69.8%, 164/235), will improve treatment of drug-resistant infections (68.5%, 161/235) and will stimulate research and development of new antimicrobials (57.9%, 136/235). Consultants disagreed that the model would lead to reduced carbapenem use and reported increased use of cefiderocol post-implementation. The presence of an antimicrobial pharmacy team, requirement for preauthorization by infection specialists, antimicrobial stewardship ward rounds and education of infection specialists were considered the most effective antimicrobial stewardship interventions. Under the new model, 42.1% (99/235) of consultants would use these antimicrobials empirically, if risk factors for antimicrobial resistance were present (previous infection, colonization, treatment failure with carbapenems, ward outbreak, recent admission to a high-prevalence setting).Significantly higher insurance and diversity values were given to model antimicrobials compared with established treatments for carbapenem-resistant infections, while meropenem recorded the highest enablement value. Use of both 'subscription-type' model drugs for a wide range of infection sites was reported. Respondents prioritized ceftazidime/avibactam for infections by bacteria producing OXA-48 and KPC and cefiderocol for those producing MBLs and infections with Stenotrophomonas maltophilia, Acinetobacter spp. and Burkholderia cepacia. CONCLUSIONS: The 'subscription-type' model was viewed favourably by infection consultants in England