Tag Archives: remain

Vadadustat for Anemia in Chronic Kidney Disease: Questions Remain

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This post originally appeared on Medscape Medical News Headlines

Oral vadadustat, one of a new class of hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs), is effective in the treatment of anemia in people with chronic kidney disease (CKD), but cardiovascular safety outcomes fall short of conventional injectable therapy among patients who are not dependent on dialysis, new data show.

“We found that, among patients with non–dialysis-dependent CKD, vadadustat was noninferior to darbepoetin alfa with regard to hematologic efficacy but did not meet the prespecified noninferiority criterion for cardiovascular safety, which was a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke,” say Glenn M. Chertow, MD, MPH, Stanford University School of Medicine, Palo Alto, California, and colleagues in their paper published this week in the New England Journal of Medicine.

In commenting on the research, Jay B. Wish, MD, medical director of the Out-Patient Dialysis Unit at Indiana University Hospital, Indianapolis, said the findings raise some concerns.

“There is little question regarding the efficacy of vadadustat — and HIF-PHIs in general, based on other studies, but there are still many questions to be answered regarding the safety of this new class of anemia agents,” he told Medscape Medical News.

“The lack of non-inferiority of vadadustat vs darbepoetin with regard to the time to a major adverse cardiovascular event (MACE) in the non-dialysis-dependent CKD population is of concern and may be a barrier to approval by the US Food and Drug Administration (FDA),” he added.

In an accompanying editorial, Adeera Levin, MD, head of the Division of Nephrology, University of British Columbia in Vancouver, Canada, agreed that the data offer pros — and notable cons.  

“The data are convincing that vadadustat is effective in increasing hemoglobin concentrations in both dialysis-dependent and non–dialysis-dependent populations but are less convincing with respect to safety,” she said.

Injectable Erythropoiesis-Stimulating Agents Have Safety Issues of Their Own

Anemia is a common concern among patients with CKD, affecting as many as 30% to 40% of patients who are not dependent on dialysis, and while injectable erythropoiesis-stimulating agents (ESAs) — along with iron deficiency correction — are recommended, ESAs carry a risk of cardiovascular events when treatment is targeted to near-normal levels of hemoglobin concentrations, resulting in a black-box warning requirement for the agents from the FDA.

The development of oral HIF-PHIs has meanwhile been greeted with excitement as potentially offering more convenience and adherence to treatment, and some agents in this class, including roxadustat, have already been approved in some countries.

To comprehensively compare the HIF-PHI vadadustat with the commonly used ESA, darbepoetin alfa (Aranesp), for safety and efficacy, researchers conducted two pooled analyses, each involving two open-label, noninferiority trials, with one analysis involving patients with CKD who did not require dialysis and another of patients who were undergoing dialysis.

In the first, Chertow and co-authors looked at the pooled data from two randomized, phase 3 noninferiority trials of patients with CKD who were not on dialysis, and who either were previously treated with an ESA (n = 1725) or were not previously treated with an ESA (n = 1751).

With a median follow-up of 1.63 and 1.80 years in the two studies, vadadustat did achieve noninferiority compared with darbepoetin alfa for hematologic efficacy, with least-squares mean changes in hemoglobin concentration from baseline to weeks 24 through 36 of 1.43±0.05 g per deciliter in the vadadustat group and 1.38±0.05 g per deciliter in the darbepoetin alfa group, falling withing the prespecified noninferiority margin.

However, in the primary safety endpoint of the time to first MACE — a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke — pooled across the two trials, a first MACE occurred in 22% in the vadadustat group and 19.9% in the darbepoetin alfa group, for a hazard ratio of 1.17, which failed to meet the prespecified noninferiority margin of 1.25.

The authors note that an analysis of events in the trials suggested that the higher risk in the vadadustat group was largely the result of an excess of nonfatal myocardial infarctions and a higher incidence of death from noncardiovascular causes; however, the causes of the higher noncardiovascular deaths could not be determined.

No Increased Risk Seen in Dialysis-Dependent Patients

In the second study, by Kai-Uwe Eckardt, MD, of the Department of Nephrology and Medical Intensive Care, Charité–Universitätsmedizin, Berlin, Germany, and colleagues, also published in NEJM this week, the researchers looked at two trials with a combined 3923 patients who were dependent on dialysis. This also showed that vadadustat was noninferior to darbepoetin alfa in the correction and maintenance of hemoglobin concentration, with target hemoglobin concentrations achieved in both trials.

However, unlike the analysis of non–dialysis-dependent patients, the incidence of a first MACE event was similar between the two agents, therefore achieving noninferiority.

“The two international phase 3 clinical trials…met the prespecified noninferiority margins for cardiovascular safety, pooled across the two trials, and hematologic efficacy, assessed separately for each trial,” Eckardt and coauthors write.

Nevertheless, the possibility of safety issues that may exceed those already seen with ESAs is troublesome, Wish, the Indiana U. nephrologist, further commented.

“The FDA already considers ESAs to be dangerous enough to merit a black-box warning, and the restrictions regarding its use in non–dialysis-dependent patients (target Hb 10-10 g/dL) are even greater than those for dialysis-dependent patients (target Hb 10-11 g/dL),” he said. 

“So, an agent that may be even less safe than ESAs in the non–dialysis-dependent population may be considered by the FDA too toxic for approval.”

Higher Risk in Patients Not Dependent on Dialysis Seen Before

While the higher risk seen among patients who are not dependent on dialysis is puzzling, Wish noted that it’s not the first time this pattern has been observed.

Peginesatide (Omontys) [an erythropoiesis-stimulating agent that was recalled by the FDA in 2013 due to some cases of fatal anaphylaxis] had this exact same issue with demonstration of non-inferiority in dialysis-dependent patients, but lack of non-inferiority in non–dialysis-dependent patients,” he noted.

“The possible explanations are that there is an adverse cardiovascular risk property of vadadustat that is somehow blunted in the dialysis-dependent population, or that the adverse risk property of darbepoetin is greater in the dialysis-dependent population,” he explained.

Other considerations, in addition to MACE, include “long-term effects that may be due to off-target gene transcription induced by HIF-PHIs,” Wish added. 

“There may be off-target beneficial effects as well, which along with long-term adverse effects, may only be answered with long-term follow-up studies and registries following drug approval.”

In her editorial, Levin further underscored the need for more research into these unanswered questions.

“The issues raised in these trials should motivate us to answer critical questions regarding goals of therapy, risks, and benefits with trials specifically designed to do so,” she writes.

“To enable us to have informed discussions with our patients, many more questions need to be asked and answered,” she concludes.

The studies were supported by Akebia Therapeutics and Otsuka Pharmaceutical. Wish disclosed that he has been invited to a vadadustat virtual advisory board meeting in May 2021 by Otsuka and Akebia. Levin disclosed that she has provided educational seminars on the topic of anemia and HIF-PHIs, some of which were funded by AstraZeneca.

N Eng J Med. Published April 29, 2021.

Chertow et al study. Abstract
Eckardt et al study. Abstract
Editorial

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Medicaid expansion picks up bipartisan support in the Texas House, but hurdles remain

Author Karen Brooks Harper
This post originally appeared on The Texas Tribune: Main Feed

Medicaid expansion in Texas

“We exist, and we matter”

Renewables dominate the headlines, but oil and gas remain king

The transition to a global energy system that runs on renewable energy rather than finite and dirty coal, oil, and gas is arguably the number-one topic in the media, sometimes eclipsing even the pandemic.

Yet, for all the enthusiastic talk, it seems that we are nowhere near accomplishing the transition—and it may already be too late to do anything about climate change anyway, according to some climate scientists.

“Embedded power structures and support for a dying industry”: these are the factors that are keeping oil and gas as the world’s main sources of energy, according to the chief executive of one environmental nonprofit organization.

Speaking to CNBC, Carroll Muffett from the Institute for Environmental Law said, “It is not a matter of the absence of the technology or the inability to do it. If you actually look at what are the cheaper sources of the energy supply right now, it is not really even a matter of economics. It is much more about embedded power structures and continued support of dying industry.” 
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It is very likely that Muffett is referring to government subsidies for the oil and gas industry in countries such as the United States or the UK, as well as many developing nations. What he doesn’t mention in the above comment, however, is the fact that the US government—and many others—also have substantial subsidies for renewable power, and plans to boost these in a bid to encourage wider adoption. As Muffett puts it, the energy transition is “primarily a matter of political will and economic choices.”

Indeed, it is a matter of political choices. Virtually every reputable energy authority has repeatedly said that it is up to the politicians to make sure the transition occurs by encouraging renewables and discouraging oil and gas. This, however, begs one question and the question is this: if renewables were as economical as their proponents say, wouldn’t the private sector be embracing them on its own for the profit opportunities, rather than waiting for the subsidies to be granted before venturing into the field?

Read more on Oilprice.com: The most critical oil storage in the united states

There is also another question: if renewables are the economic choice, why are the emerging—meaning poorer—economies of Asia investing so heavily in fossil fuel generation capacity that demand for oil there could jump by as much as 25% by 2040, according to Wood Mackenzie? Even China, the indisputable global leader in renewable energy capacity, is building new coal power plants despite celebrations of solar becoming as cheap as coal two years ago. These are not questions that the most vocal advocates of renewable energy like to discuss. They interfere with the narrative that solar and wind are not only emission-free, but they are also as cheap as fossil fuels. If that were the case, it would certainly make fossil fuels irrelevant. After all, if two sources of energy cost the same, but one is renewable and the other one is finite, it would make the best economic sense to bet on the first and not the second, from a purely pragmatic point of view, even without factoring in emissions.

And yet, poorer economies are betting on fossil fuels while richer ones are investing billions in renewable energy generation and storage capacity, and in electric cars. It seems there is a disconnect in the logical sequence of arguments for the energy transition. On the one hand, solar and wind are cheaper—and hydrogen and EVs will soon get cheaper—so it would make sense for everyone to get on board with them. Yet on the other, wealthy nations are the ones being the most generous with wind and solar adoption, and support for hydrogen and EVs.
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“Human activity is driving climate change,” Colm Sweeney, the lead scientist for the Earth System Research Lab Aircraft Program of the US National Oceanic and Atmospheric Administration, told CNBC.

 “If we want to mitigate the worst impacts, it’s going to take a deliberate focus on reducing fossil fuels emissions to near zero — and even then, we’ll need to look for ways to further remove greenhouse gases from the atmosphere,” he said.

Fossil fuel emissions account for the vast majority of greenhouse gas emissions from human activity on the planet. The increase in their use reflects an increase in energy demand, and the world’s energy demand is expected to continue growing as the global population grows, driven, once again, by emerging economies. Growing energy demand appears to be incompatible with the Paris Agreement targets given the above factors regarding the cost of different energy sources and their relative reliability, which is motivating investment decisions.

Read more on Oilprice.com: Iraqi Kurdistan on the brink of collapse as oil prices crash

What this means is that the only way we could conceivably expect to progress towards limiting greenhouse gas emissions in any meaningful way is by curbing our energy demand. Indeed, one recent academic report from the UK calls for just that.

UK FIRES, a research program involving scientists from several reputable universities and businesses from resource-intensive sectors, said in the report that net zero was not enough and we should strive for absolute zero, to be achieved, among other measures, by people reducing their energy consumption to 60 percent of today’s levels.
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Voluntary energy consumption cuts are highly unlikely, so this, too, would require political action. Some are already calling political action for renewable energy a form of government abuse. Imagine what they would call policies forcing people to consume less energy than they are used to consuming.

This article was originally published on Oilprice.com

RT

This article originally appeared on RT Business News

Texas Senate approves a $250 billion state budget — but questions remain about how federal aid will be used

The Texas Senate unanimously signed off on a two-year, $ 250 billion state budget Tuesday, though there are still questions about how tens of billions of dollars in expected federal aid will be used — and whether it will arrive in time for lawmakers to use this legislative session.

“This budget … meets our essential needs in this growing state [and] it holds true to the principles of fiscal responsibility that make Texas strong and successful,” state Sen. Jane Nelson[2], the Flower Mound Republican who chairs the budget-writing Senate Finance Committee, told senators as the chamber took up Senate Bill 1[3].

The Senate’s budget as passed includes $ 117.9 billion in general revenue, which is roughly $ 5 billion over the amount[4] Texas Comptroller Glenn Hegar[5] projected lawmakers would have to work with. But it does not factor in over $ 35 billion in federal funding in coronavirus aid[6], much of which will go to the state government. Senators acknowledged during Tuesday’s debate that those funds may be a challenge to appropriate, depending on when they come in and what strings could be attached to them.

Nelson, asked by state Sen. Royce West[7], D-Dallas, whether those federal dollars would be appropriated before the end of the regular legislative session in May, said she “sure can’t say they definitely will be.” If those dollars arrived during the interim, Nelson said, there was language in the spending plan that would let lawmakers have input on how that money is appropriated.

The legislation now heads to the House, which filed its own two-year budget proposal[8] in January. The House’s proposed budget as filed would spend $ 119.7 in general revenue which is also over Hegar’s projection. The comptroller made that forecast in January, but cautioned that his projection was “clouded in uncertainty” due to the coronavirus pandemic’s impact on the state economy. He could modify his revenue estimate before the Legislature adjourns.

Still, the Legislature must pass a balanced budget before lawmakers gavel out. The two chambers will have to cut down their proposed spending plans or rely on accounting maneuvers, such as pushing off certain items or tapping into the state’s Economic Stabilization Fund, to help offset some of those expenses.

The Senate’s spending plan as passed would not pull dollars from the fund — also called the rainy day fund — which ended 2020 with a nearly $ 10 billion balance and is projected to end fiscal year 2023 at $ 11.6 billion if lawmakers do not use it, according to Hegar’s update in January.

The Senate’s budget continues to spend the most on public education and health care, with the plan fully funding the state’s public schools under a school finance system. The Legislature overhauled that financing system during the 2019 session by boosting funding, which included pay raises for teachers and slowing the growth of local property taxes. The current budget plan also adds $ 1 billion toward property tax cuts the Legislature spent over $ 5 billion on in 2019 and an additional $ 453 million to put toward retired teachers’ pensions.

State Sen. Eddie Lucio Jr[9]., a Brownsville Democrat who serves as vice chair of the Finance Committee, said his “worst-case scenario” this session would have been massive budget cuts to public schools like the cuts lawmakers made in 2011 after a recession.

“It was my dearest hope that we would not have to enact another cut so devastating 10 years later with the budget,” he said, referring to the economic fallout last year related to the pandemic. “I am pleased that we did not do so.”

On top of writing the 2022-2023 state budget, lawmakers will also have to pass legislation that covers expenses from the current budget. In January, Hegar projected the Legislature would face a nearly $ 1 billion deficit for the current budget — an improvement from the $ 4.6 billion projection he made in July 2020. Hegar’s estimate, he said, did not include savings from the 5% cuts to certain state agencies.

Before the Senate gave a final stamp of approval on its proposed spending plan, state Sen. Judith Zaffirini[10], D-Laredo, read a statement to the chamber explaining why she was voting for the legislation.

“After the year we’ve had,” she said, “it is miraculous we have produced a bill we can all support.”

And in a statement after the vote, Lt. Gov. Dan Patrick[11] applauded Nelson for her leadership, saying the lawmaker “has done a masterful job.”

“Like every budget passed by the Senate since I have been lieutenant governor, SB 1 is within the spending limit set by the Texas Constitution, and, once again, the growth rate does not exceed population times inflation,” Patrick said. “SB 1 will help ensure that the economic forecast for Texas will continue to be bright.”

References

  1. ^ Sign up for The Brief (www.texastribune.org)
  2. ^ Jane Nelson (www.texastribune.org)
  3. ^ Senate Bill 1 (capitol.texas.gov)
  4. ^ $ 5 billion over the amount (www.texastribune.org)
  5. ^ Glenn Hegar (www.texastribune.org)
  6. ^ in coronavirus aid (www.texastribune.org)
  7. ^ Royce West (www.texastribune.org)
  8. ^ filed its own two-year budget proposal (www.texastribune.org)
  9. ^ Eddie Lucio Jr (www.texastribune.org)
  10. ^ Judith Zaffirini (www.texastribune.org)
  11. ^ Dan Patrick (www.texastribune.org)

Cassandra Pollock

What happens when COVID-19 vaccine appointments remain unfilled?

AUSTIN (KXAN) — Next week, the wait will be over for thousands of Central Texans in need of a COVID-19 vaccine. This comes as the state will see more than a million dose increase in supply.

The Department of State Health Services says there will be more doses from Johnson & Johnson and local pharmacies will see a big boost.

This is a welcomed relief for some of our viewers who tried to sign up for their first doses of the vaccine through Austin Public Health. On Thursday, many of them saw a tweet saying there were still thousands of appointments left.

Scheduling was closed and there were still appointments available. Austin Public Health told KXAN News almost all remaining appointments were for April 6. Those appointments will be included in its upcoming Monday release for next week’s appointments.

The department says all appointments for the week have still been filling up. However, staffers are seeing the appointments for that following Tuesday (which are available on Thursdays) are not quite filling up as fast and they aren’t quite sure why. Based on these last several appointments, APH is evaluating the release process to possibly expand eligibility within its system.

Currently, there are approximately 250,000 eligible accounts on APH who have not scheduled their first dose. APH believes there is a large number of people who have received a vaccination from a different provider. They launched a feature earlier in the week that allows individuals to update their profile with vaccination information if they received it from somewhere else.

APH says it has been working out a way to allow for the prioritization of groups within its system to ensure people are still able to access appointments when eligibility is expanded to all individuals.

Jennifer Sanders

Spain: FCDO removes some entry restrictions for UK arrivals but strict rules remain

The requirement applies to all passengers arriving by air or sea, regardless of their residence status in Spain or the length of time they intend on staying.

“A minimum fine of €3000 may be issued to anyone who arrives in Spanish airports or ports from ‘risk’ countries without adequate evidence of a negative PCR, TMA or LAMP test,” warns the FCDO

“While TMA and LAMP tests are not currently widely available in the UK, you should refer to testing facilities directly for specific information on the types of tests available to you, prior to booking an appointment.”

Britons are further warned not to use NHS testing to facilitate travel.

Texas state trooper not showing 'viable signs of brain activity' and will remain on life support, DPS says

MEXIA, Texas (KTRK) — A state trooper shot multiple times during a central Texas motorist assist call Friday night is no longer showing ‘viable brain activity,’ according to the Texas Department of Public Safety.DPS Trooper Chad Walker was shot multiple times as he answered a motorist assist call outside of Mexia, approximately 160 miles northwest of Houston, according to the Texas DPS Officers Association.

Walker suffered gunshot wounds to the head and abdomen during the shooting.Sunday night, DPS said Walker remained in critical condition. But by Monday afternoon, the agency posted an update on Twitter that Walker did not display signs of viable brain activity but remained on life support until he can become a donor.

“After extensive life-saving efforts conducted by the @bswhealth medical professionals, it has been determined that Trooper Chad Walker no longer displays signs of viable brain activity and he remains on life-support until he can share the gift of life as an organ donor,” DPS wrote. “This final sacrifice embodies Trooper Walker’s actions throughout his life and service as a Texas Highway Patrol Trooper. The Walker family is grateful for the continued support and prayers as they remain at Chad’s side.”

Family and friends created a GoFundMe to help Walker’s medical bills.
[2]

Trooper Walker, who is from Groesbeck, joined the Texas Department of Public Safety in 2015. Walker and his wife have a 15-year-old son, twin 7-year-old daughters and a 2-month-old daughter, according to the association.The suspect, identified as DeArthur Pinson Jr., 36, of Palestine, Texas, died by suicide on Saturday evening, Limestone County Judge Richard Duncan told KXXV-TV[3].

Soon after the shooting, around five miles outside of the city of 7,500, law enforcement from multiple agencies began an intense search for Pinson. Authorities said he took off into a wooded area and was on the run for several hours before his body was discovered.

“Before Trooper Walker could stop his patrol unit (the suspect) immediately emerged from the driver’s seat of the disabled vehicle armed with a handgun and fired multiple rounds at Trooper Walker through the patrol unit’s windshield,” the officers association said Saturday.

On Saturday evening, members of the Fairfield Fire Department gathered together for a prayer vigil on behalf of Walker. Chaplain Andrew White and other local ministers led the crowd in prayer.

Another gathering 40 miles away took place in Waco near the hospital where Walker was being treated.

Pinson had a criminal history, including a 10-year prison sentence for armed robbery in Houston County, according to a 2007 edition of the Palestine Herald[4]. He was also in the U.S. Army and was arrested by Palestine police in 2003 for military desertion, the newspaper reported.

Copyright © 2021 KTRK-TV. All Rights Reserved.

References

  1. ^ March 29, 2021 (twitter.com)
  2. ^ GoFundMe (gofund.me)
  3. ^ KXXV-TV (www.kxxv.com)
  4. ^ according to a 2007 edition of the Palestine Herald (www.palestineherald.com)

KTRK

'Hello, friends': Jim Nantz agrees to remain with CBS Sports

Nantz’s contract was going to expire this spring. Some wondered if he’d leave CBS after his NFL partner Tony Romo signed a new contract worth $ 17.5 million a year.

Jim Nantz’s familiar introduction of “Hello friends” will continue to be heard on CBS for years to come.

Nantz and CBS Sports reached agreement on a new deal Thursday. The deal was first reported by the “Sports Business Journal”
CBS spokeswoman Jen Sabatelle confirmed the agreement but did not comment on the terms.
The 61-year old Nantz has been with CBS since 1985. He has been the lead announcer for the NCAA Tournament since 1991 and has worked the Masters since 1986. He has also been the lead voice for the network’s coverage of the NFL since 2002 and called his seventh Super Bowl last month.
Nantz’s contract, which was worth $ 6.5 million a year, was going to expire this spring. Some wondered if he would choose to leave CBS after his NFL partner Tony Romo signed a new contract worth $ 17.5 million a year, but that wasn’t the case.
A big reason for that is Nantz’s love of calling the Masters. He said last year that he would like to be calling the tournament until 2035 and possibly beyond. Nantz would turn 75 that year, and that would also be 50 Masters calls for him.
“I used to joke around in speaking engagements: I know my retirement date already. God willing, my health stays well, and CBS willing, that April 8, 2035, would be the way I would love to close out my career,” he said. “But here we are all of a sudden and that’s now well within sight. I’m feeling really young. Got a couple of young kids who are 4- and 6-years old. That date is way too close for me to be talking about retirement. So, I would like to push it out for another, who knows, several years at least.”
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TUI cruise line Marella set to offer UK cruises for 2021 but itineraries remain a mystery

Guests must be vaccinated in order to sail.

Viking Cruises is also offering its own range of UK holidays.

The cruise line has announced plans to resume sailing from May with the new domestic routes.

The England’s Scenic Shores sailings will span eight days.

Cruises are currently scheduled to depart from May 22, May 29 and June 5.

Further details on the holidays are anticipated to follow in the coming weeks and months.

Viking Cruises’ Chairman, Torstein Hagen, said: “We welcome the UK Government’s support for the return of safe domestic cruises as an important component in the travel industry’s recovery.

“In recognition of this support, and to celebrate the fact we have a British godmother—the esteemed broadcaster and journalist Anne Diamond—we have chosen to name our new ship, Viking Venus, in the UK on 17 May.

House prices: Properties in northern England to remain 'stamp duty free' for six months

The Midlands, northern England, Wales and Scotland have seen the most growth and are at an almost ten-year high.

Liverpool and Manchester have reportedly shown the strongest levels of growth and are up 6.6 percent and 6.4 percent respectively.

Manchester and Bristol have increased by almost £1,000 a month since the pandemic began a year ago.

Gráinne Gilmore, Head of Research, Zoopla, said: “The search for space is driving continued demand for family homes, which means prices for houses are rising faster than flats, and houses are also selling more quickly.