Hydroxyurea is a treatment option for young patients with sickle cell disease (SCD). Establishing the safety of hydroxyurea is of paramount importance. The effect of hydroxyurea on immune function and immunizations in SCD has not been studied previously.

Children with SCD receiving hydroxyurea have lower lymphocyte, CD4, and memory T-cell counts compared with those receiving placebo, but still in the range for healthy children. Despite slower response to measles vaccine, measles, mumps, and rubella and pneumococcal vaccines are effective. (Read the full article)

Direct antiglobulin titer (DAT) positive, blood group A or B newborns born to group O mothers have a high incidence of hyperbilirubinemia, attributable to increased hemolysis.

DAT ++ readings were associated with a higher incidence of hyperbilirubinemia and a greater degree of hemolysis than DAT ± or DAT + counterparts. DAT strength should be taken into consideration when planning treatment strategies or follow-up of ABO-heterospecific newborns. (Read the full article)

Guidelines for postdischarge monitoring of hyperbilirubinemia for neonates of white descent are available from the American Academy of Pediatrics; however, such information for healthy term and late preterm Chinese neonates is lacking.

A classification model for predicting the risk of significant hyperbilirubinemia in Chinese neonates was developed that combines a transcutaneous bilirubin–based nomogram with clinical risk factors. It classified newborns into 6 risk groups, which can guide clinicians in planning appropriate follow-up strategies. (Read the full article)

Source: www.nbcnews.com - Saturday, May 09, 2020
The U.S. unemployment rate reached 14.7 percent for April - the worst monthly rate since the Great Depression. The White House has projected optimism, saying they expect the economy to rocket upward once coronavirus restrictions are lifted. But many experts think that is not a realistic expectation.

Carbapenems are currently the preferred agents for the treatment of serious Acinetobacter infections. However, whether cefepime/cefpirome can be used to treat Acinetobacter bloodstream infection (BSI) if it is active against the causative pathogens is not clear. This study aimed to compare the efficacy of cefepime/cefpirome and carbapenem monotherapy in patients with Acinetobacter BSI. The population included 360 patients with monomicrobial Acinetobacter BSI receiving appropriate antimicrobial therapy admitted to four medical centres in Taiwan in 2012–2017. The predictors of 30-day mortality were determined by Cox regression analysis. The overall 30-day mortality rate in the appropriate antibiotic treatment group was 25.0% (90/360 patients), respectively. The crude 30-day mortality rates for cefepime/cefpirome and carbapenem therapy were 11.5% (7/61 patients) and 26.3% (21/80 patients), respectively. The patients receiving cefepime/cefpirome/carbapenem therapy were infected by Acinetobacter nosocomialis (51.8%), A. baumannii (18.4%) and A. pittii (12.1%). After adjusting for age, Sequential Organ Failure Assessment (SOFA) score, invasive procedures, and underlying diseases, cefepime/cefpirome therapy was not independently associated with a higher or lower 30-day mortality compared to the carbapenem therapy. SOFA score (hazard ratio [HR], 1.324; 95% confidence interval [CI], 1.137–1.543; P < 0.001) and neutropenia (HR, 7.060; 95% CI, 1.607–31.019; P = 0.010) were independent risk factors for 30-day mortality of patients receiving cefepime/cefpirome or carbapenem monotherapy. The incidence density of 30-day mortality for cefepime/cefpirome versus carbapenem therapy was 0.40% versus 1.04%. The therapeutic response of cefepime/cefpirome therapy was comparable to that of carbapenems among patients with Acinetobacter BSI receiving appropriate antimicrobial therapy.

Carbapenem-resistant Gram-negative pathogens are a critical public health threat and there is an urgent need for new treatments. Carbapenemases (β-lactamases able to inactivate carbapenems) have been identified in both serine β-lactamase (SBL) and metallo β-lactamase (MBL) families. The recent introduction of SBL carbapenemase-inhibitors has provided alternative therapeutic options. Unfortunately, there are no approved inhibitors of MBL-mediated carbapenem-resistance and treatment options for infections caused by MBL-producing Gram-negatives are limited. Here, we present ZN148, a zinc-chelating MBL-inhibitor capable of restoring the bactericidal effect of meropenem and in vitro clinical susceptibility to carbapenems in >98% of a large international collection of MBL-producing clinical Enterobacterales strains (n=234). Moreover, ZN148 was able to potentiate the effect of meropenem against NDM-1-producing Klebsiella pneumoniae in a murine neutropenic peritonitis model. ZN148 showed no inhibition of the human zinc-containing enzyme glyoxylase II at 500 μM and no acute toxicity was observed in an in vivo mouse model with cumulative dosages up to 128 mg/kg. Biochemical analysis showed a time-dependent inhibition of MBLs by ZN148 and removal of zinc ions from the active site. Addition of exogenous zinc after ZN148 exposure only restored MBL activity by ~30%, suggesting an irreversible mechanism of inhibition. Mass-spectrometry and molecular modelling indicated potential oxidation of the active site Cys221 residue. Overall, these results demonstrate the therapeutic potential of a ZN148-carbapenem combination against MBL-producing Gram-negative pathogens and that ZN148 is a highly promising MBL inhibitor, capable of operating in a functional space not presently filled by any clinically approved compound.

Objectives: Carbapenemase-producing Enterobacterales and specifically KPC-producing Klebsiella pneumoniae (KPC-Kp) are rapidly spreading worldwide. The prognosis of ventilator-associated pneumonia (VAP) caused by KPC-producing Klebsiella pneumoniae (KPC-Kp) is not well known. Our study tries to assess whether ventilator-associated pneumonia caused by a KPC-Kp strain is associated with higher all-cause mortality than if caused by carbapenem-susceptible isolates.

Study design and methods: This is a retrospective cohort study of patients with VAP due to K. pneumoniae from a 35-bed polyvalent Intensive Care Unit in a university hospital (> 40,000 annual admissions) between January 2012 and December 2016. Adjusted multivariate analysis was used to study the association of KPC-Kp with 30-day all-cause mortality (Cox regression).

Results. We analyze 69 cases of K. pneumoniae VAP of which 39 were produced by a KPC-Kp strain with high-level resistance to meropenem (MIC > 16 mg/mL). All-cause mortality at 30 days was 41% in the KPC-Kp group (16/39) and 33.3% in the carbapenem-susceptible cases (10/30). KPC-Kp etiology was not associated with higher mortality when controlled for confounders (adjusted hazard ratio [lsqb]HR[rsqb] 1.25; 95% CI: 0.46–3.41). Adequate targeted therapy (HR 0.03; 95% CI: <0.01–0.23) was associated with all-cause mortality.

Conclussion. Assuming the limitations due to the available sample size, the prognosis of VAP caused by KPC-Kp is similar to VAPs caused by carbapenem-susceptible K. pneumoniae when appropriate treatment is used.

Mycobacterium abscessus lung infections remain difficult to treat. Recent studies have recognized the power of new combinations of antibiotics such as bedaquiline and imipenem although in vitro data have questioned this combination. We report that the efficacy of the bedaquiline plus imipenem treatment relies essentially on the activity of bedaquiline in a C3HeB/FeJ mice model of infection with a rough variant of M. abscessus. The addition of imipenem contributed at clearing the infection in the spleen.

Carbapenem pharmacokinetic profiles are significantly changed in critically ill patients because of the drastic variability of the patients' physiological parameters. Published population PK studies have mainly focused on specific diseases and the majority of these studies had small sample sizes. The aim of this study was to develop a population PK model of imipenem in critically ill patients that estimated the influence of various clinical and biological covariates and the use of Extracorporeal Membrane Oxygenation (ECMO) and Continuous Renal Replacement Therapy (CRRT). A two-compartment population PK model with Creatinine clearance (CrCL), body weight (WT), and ECMO as fixed effects was developed using the non-linear mixed effect model (NONMEM). A Monte Carlo simulation was performed to evaluate various dosing schemes and different levels of covariates based on the pharmacokinetic/pharmacodynamic index (f%T>MIC) for the range of clinically relevant minimum inhibitory concentrations(MICs). The results showed that there may be insufficient drug use in the clinical routine drug dose regimen, and 750mg Q6h could achieve a higher treatment success rate. The blood concentrations of imipenem in ECMO patients were lower than that of non-ECMO patients, therefore dosage may need to be increased. The dosage may need adjustment for patients with CrCL ≤ 70ml/min, but dose should be lowered carefully to avoid the insufficient drug exposure. Dose adjustment is not necessary for patients within the WT ranging from 50-80 kg. Due to the large variation in PK profile of imipenem in critically ill patients, TDM should be carried out to optimize drug regimens.

We report the first clinical Escherichia. coli strain EC3000 with concomitant chromosomal colistin and carbapenem resistance. A novel in-frame deletion, 6-11(RPISLR), in pmrB contributing to colistin resistance was verified using recombinant DNA techniques. Although decreased fitness compared to the wild-type (WT) strain or EC3000 revertant (chromosomal replacement of WT pmrB in EC3000), a portion of serially passaged EC3000 strains preserving colistin resistance without selective pressure raises the concern for further spread.

Meropenem/vaborbactam resistance in Klebsiella pneumoniae is associated with loss of function mutations in the OmpK35 and OmpK36 porins. Here we identify two previously unknown loss of function mutations that confer cefuroxime resistance in K. pneumoniae. The proteins lost were NlpD and KvrA; the latter is a transcriptional repressor controlling capsule production. We demonstrate that KvrA loss reduces OmpK35 and OmpK36 porin production, which confers reduced susceptibility to meropenem/vaborbactam in a KPC-3 producing K. pneumoniae isolate.

Treatment of exacerbations of chronic Pseudomonas aeruginosa infections in patients with cystic fibrosis (CF) is highly challenging due to hypermutability, biofilm formation and an increased risk of resistance emergence. We evaluated the impact of ciprofloxacin and meropenem as monotherapy and in combination in the dynamic in vitro CDC biofilm reactor (CBR). Two hypermutable P. aeruginosa strains, PAOmutS (MIC_{ciprofloxacin} 0.25 mg/L, MIC_meropenem 2 mg/L) and CW44 (MIC_{ciprofloxacin} 0.5 mg/L, MIC_meropenem 4 mg/L), were investigated for 120h. Concentration-time profiles achievable in epithelial lining fluid (ELF) following FDA-approved doses were simulated in the CBR. Treatments were ciprofloxacin 0.4g every 8h as 1h-infusions (80% ELF penetration), meropenem 6 g/day as continuous infusion (CI; 30% and 60% ELF penetration) and their combinations. Counts of total and less-susceptible planktonic and biofilm bacteria and MICs were determined. Antibiotic concentrations were quantified by UHPLC-PDA. For both strains, all monotherapies failed with substantial regrowth and resistance of planktonic (≥8log₁₀ CFU/mL) and biofilm (>8log₁₀ CFU/cm²) bacteria at 120h (MIC_{ciprofloxacin} up to 8 mg/L, MIC_meropenem up to 64 mg/L). Both combination treatments demonstrated synergistic bacterial killing of planktonic and biofilm bacteria of both strains from ~48h onwards and suppressed regrowth to ≤4log₁₀ CFU/mL and ≤6log₁₀ CFU/cm² at 120h. Overall, both combination treatments suppressed amplification of resistance of planktonic bacteria for both strains, and biofilm bacteria for CW44. The combination with meropenem at 60% ELF penetration also suppressed amplification of resistance of biofilm bacteria for PAOmutS. Thus, combination treatment demonstrated synergistic bacterial killing and resistance suppression against difficult-to-treat hypermutable P. aeruginosa strains.

Background

Optimal concentrations of unbound antimicrobials are essential for maximum microbiological effect. Although hypoalbuminemia and albumin fluid resuscitation are common in critical care, the effects of different albumin concentrations on the unbound concentrations of highly protein-bound antimicrobials are not known. The aim of this study was to compare effects of different albumin states on total and unbound concentrations of ertapenem and ceftriaxone using an ovine model.

Methods

Design

Prospective, three phase intervention observational study.

Subjects

Healthy Merino sheep.

Interventions

Eight sheep were subject to three experimental phases; normoalbuminemia, hypoalbuminemia using plasmapheresis and albumin replacement using a 25% albumin solution. In each phase, ceftriaxone 40 mg/kg and ertapenem 15 mg/kg were given intravenously. Blood samples were collected at pre-defined intervals and analyzed using an ultra-high-performance liquid chromatography tandem mass spectrometry method. Pharmacokinetic parameters such as area under the curve (AUC_0-24), plasma clearance (CL) and apparent volume of distribution in the terminal phase (V_d) were estimated and compared between the phases.

Results

The protein and albumin concentrations were significantly different between phases. Hypoalbuminemia resulted in a significantly lower AUC_0-24 and higher CL of total and unbound concentrations of ceftriaxone compared to the other phases. Whereas albumin replacement led to higher AUC_0-24 and lower CL compared to other phases for both drugs. The V_d for total drug concentrations for both drugs were significantly lower with albumin replacement.

Conclusions

For highly protein-bound drugs such as ceftriaxone and ertapenem, both hypoalbuminemia and albumin replacement may affect unbound drug exposure.

Vinod K. Bhutani
Jan 1, 1999; 103:6-14
ARTICLES

Source: www.consumeraffairs.com - Friday, May 08, 2020
There are a couple of simple ways to stay ahead of the situation, and there's possible relief for those who can't By Gary Guthrie of ConsumerAffairs May 8, 2020 var myLink = "https://my.consumeraffairs.com/tax-relief/get-matched/"; var mySubTitle = "Get matched with an Accredited Tax Relief Partner"; window.onload = function changeLink(){var linkForm = document.getElementsByClassName("wzrd-wg__form")[0];var titleForm = document.getElementsByClassName("wzrd-wg__sbtl")[0];linkForm.setAttribute("action", myLink);if (mySubTitle != ""){titleForm.innerHTML = " " + mySubTitle + " ";}}; The hits keep on comin'! On Friday, the Bureau of Labor Statistics announced that the economy lost 20.5 million jobs in April, with the unemployment rate at 14.7 percent. Thank you, COVID-19. All told, upwards of 22 million Americans have lost their jobs during the pandemic, forcing many to collect unemployment to make ends meet. For some, a bonus of $600 each week in coronavirus relief is being added on. All that is fine and dandy for now, but most of those check recipients are unaware that they're going to have to pay taxes on that money because the IRS views it as "taxable income." Note: the "economic impact payment" Americans received is NOT taxable. "Most people don't realize it. They're thinking in the moment. They don't have much savings, credit is not great and then come April 15, 2021, you have a big tax bill you're not expecting," Ken Lin, the

Source: www.youtube.com - Monday, April 20, 2020

Source: www.youtube.com - Thursday, April 30, 2020

Javier Sotomayor talks to Sonam Saini about entering the hinterlands, rising ticket prices, and the threat from OTT players.

Four top Republican senators have urged US President Donald Trump to suspend all new guest worker visas for 60 days and some of its categories, including the H-1B visa, for at least the next year or...

The post-COVID era of movie-going will require collective efforts from audiences, production houses, cinema owners and the central and state governments; the revival of the movie-going experience to...

DOVER (January 3, 2020): As part of a systems-wide upgrade to State of Delaware banking processes, the Office of State Treasurer Colleen C. Davis and the Department of Labor have announced improvements to unemployment benefit payment distribution. By the end of this month, the state will move unemployment debit cards to the U.S. Bank ReliaCard®, […]

If you’re in state government, you're well aware of the unprecedented challenges that come with off-the-charts unemployment numbers due to COVID-19. Crashing websites at state unemployment insurance offices and multi-hour phone hold times for the millions of people who've lost their income due to the pandemic are only the most [...]

How analytics is helping state governments head off unemployment claims fraud was published on SAS Voices by Carl Hammersburg

In accordance with the Governor’s amended State of Emergency declaration, the Honorable Cerron Cade, Secretary of Labor for the State of Delaware has issued new guidelines to enhance the flexibility of Delaware’s unemployment insurance program to provide cash assistance to many Delaware workers whose employment has been impacted directly by coronavirus [COVID-19] and who would […]

The Coronavirus Aid, Relief, and Economic Security (CARES) Act recently passed by the United States Congress and signed into law on March 27th provides unemployment assistance to independent contractors and those self-employed who have been affected by the Coronavirus.

The federal Coronavirus Aid, Relief, and Economic Stability Act (CARES Act) created a new program called Pandemic Emergency Unemployment Compensation (PEUC), which provides 13 weeks of extended unemployment benefits to eligible workers.

Wilmington – Today, May 04, 2020, the Delaware Department of Labor is announcing the launch of a new unemployment insurance benefits system that will process claims for independent contractors, self-employed individuals, and others as detailed in the CARES Act. These individuals can file benefits claims for Pandemic Unemployment Assistance beginning the week of May 11, […]

2020 TVS Apache RR 310 Track Ride Review: After some laps of the MMRT in Chennai, we’re convinced that the 2020 edition RR 310 has come forth with a new personality. Sure, the ride dynamics remain the same but it is now definitely more refined than ever before transforming the ride experience for the better. […]

BS-VI Honda SP125 is a successor to the CB Shine and has been upgraded inside and out. It is powered by a new 124cc BS-VI engine and it gets new features like silent start, LED headlamp, new pass switch. Abhilasha Singh takes out for a ride around Mumbai to find out more.

Read Full Article at RT.com

The US Bureau of Labor Statistics (BLS) reported on Friday that the coronavirus shutdown has slashed a record number of jobs from nonfarm payrolls, sending the unemployment rate to record highs.
Read Full Article at RT.com

Clown Me In co-founder Sabine Choucair discusses the group’s new online workshop series, each Friday, ‘Happy Half-Hour’

If the Coronavirus goes on to postpone the Tokyo Olympics scheduled in July this year, it will hit yet another prominent sporting event after it delayed the Indian Premier League to April 15 from the scheduled March 29 start.

"Human lives take precedence over everything, including the staging of the Games." -- International Olympic Committee president Thomas Bach, announcing on Sunday that a postponement was under consideration.

Japan has asked for a one-year postponement of the Tokyo 2020 Games over the global coronavirus pandemic, and the International Olympic Committee has agreed, the country's prime minister said Tuesday.

The deadly COVID-19 pandemic caused an unprecedented postponement as the International Olympic Committee (IOC), the Japanese government and the athletes world over agreed that Olympics in July-August this year could not have gone ahead in the present circumstances.

The Covid-19 pandemic has not only affected the tech sector but also has given a massive blow to the world economy, resulting in massive layoffs and unemployment. Many companies in the US have started downsizing, due to the economic fallout of the coronavirus pandemic. Indians with H-1B Visas Getting Laid off Priya K, a techie […]

The post 65,000 Indians With H1B Visa Staring At Unemployment, Deportation, Uncertainty Over Visa Rules first appeared on Trak.in . Trak.in Mobile Apps: Android | iOS.

Sustainability is gaining traction in the creative industries, with the Italian region of Trentino designing a film production rating protocol that is being considered by the EU.

Between the infamous Peloton commercial, the wild Boyhood wannabe that ended up being a Subway ad, and the endless #girlboss marketing reminding you that even women can be part of the capitalist machine, 2019 was a year for advertising. 

But nothing quite tops this one, which was released in September but resurfaced in a viral tweet on Friday.  

The ad starts off with a bleak statistic: women hold just 10 percent of all patented inventions. Then, it pans over to a delightful montage of ambitious young women. Each one is filmed preparing for their career goals, from mixing delicate chemicals in a laboratory to carefully testing the consistency of soil.  Read more...

Suez Environnement, Europe’s second-biggest water company, and Chinese partners agreed to build an incinerator near Shanghai to treat hazardous and medical waste that will generate steam and supply energy.

Check here each week to keep up with the latest from John MacArthur's pulpit at Grace Community Church.

As part of the EU’s general clampdown on certain forms of aggressive tax planning, Directive 2011/16/EU (commonly known as DAC6) will soon require taxpayers and intermediaries across the EU to start reporting information in relation to certain...

The COVID-19 lockdown wiped out 20.5 million jobs in the United States in April, destroying nearly all the positions created in the prior decade in the world's largest economy, the Labor Department reported on Friday.

The youth unemployment rate has hit a record-high level in August since the Asian financial crisis. As for the number of net job increase, it fell to a low of 54 months. Even though the government is doing everything it can to create jobs, jobs-related figures won't budge. According to a report "August 2017 Employment Trend" published by the National Statistical Office on September 13, the jobless ratio of those aged between 15 and 29 was 9.4 percent, up 0.1 percentage point from a year ago. ...

La nouvelle sur la recrudescence des cas de contamination de Covid-19 a mis l'opinion en �moi et elle a m�me provoqu� des remous au plus haut sommet de l'Etat. ......