Waiting until closer to the start of flu season offers greater immunity. However, there are risks with delay, especially if the flu comes early, or patients skip their flu shot.
Thousands of flu cases and hundreds of deaths could be avoided if older adults get their flu shots in October instead of August, new research suggests.
"There's controversy in the public health community over whether influenza vaccination should happen as soon as the vaccine becomes available in August, or if it's better to wait until later in the fall,” said study lead author Kenneth J. Smith, MD, professor of medicine and clinical and translational science at the University of Pittsburgh School of Medicine.
"What we've found is that it's a balancing act, but if a clinician believes a patient will return for vaccination in the fall, then our analysis shows that it is best if they advise that patient to wait," Smith said.
Smith pointed to a previous study which showed that flu vaccines are less potent as the flu season progresses and peaks in mid-winter.
Waiting until closer to the start of flu season ensures greater immunity.
However, if flu season arrives early or if delayed vaccination prompts more than one in 20 people who would otherwise be vaccinated to skip their flu shot, then the gains are negated, according to the Pitt study, published in the American Journal of Preventive Medicine.
Pitt researchers ran computer models to compare a "compressed" vaccination period that begins in October to the status quo, which typically begins in August, for people aged 65 or older.
The researchers focused on older adults because waning vaccine effectiveness is more of a threat to the elderly whose immune systems don't typically mount as strong of a defense to infections as younger people.
Older adults also have higher early vaccination rates than younger adults.
Using data from the 2013-2014 and 2014-2015 flu seasons, the researchers forecast the number of cases, hospitalizations and deaths for compressed and status quo vaccination scenarios if the flu season had peaked in December, February or April – early, normal or late, respectively. "Peak" refers to the period when the greatest number of people are sick that season.
In the projections for the normal and late flu seasons, compressed vaccination saved as many as 258 lives and prevented up to 22,062 cases of flu, compared to status quo vaccination timing.
But if flu season peaked early, as it does in about one of every four seasons, the model projected that dozens to hundreds of older adults would die because they wouldn't have been vaccinated in time.
In addition, the team found that if more than 5.5% of older adults who defer vaccination ultimately don't get the flu shot, then compressed vaccination will be a failure and will prevent fewer influenza cases than status quo vaccination.
Smith says these findings can help clinicians determine when to offer their patients flu immunizations – if the patients have multiple appointments each year and will be in the office in the fall or if they are in a senior community where flu immunization is offered through a scheduled clinic, then waiting is likely advisable.
However, if a patient comes in only for an annual check-up and is unlikely to seek out the flu vaccine in the fall, or if offering vaccinations during a compressed window will put overwhelming strain on the clinic, then getting vaccinated when convenient – even if that's in August – is best.
"In all scenarios, simply getting vaccinated is the best way to avoid the flu," said Smith. "If the choice is between getting the influenza immunization early or not getting it at all, getting it early is definitely better."
The former leader of Palo Pinto General Hospital and his coconspirators used the hospital's national provider ID to submit fraudulent claims for lab work.
The former CEO of a Texas community hospital has pleaded guilty to defrauding three health insurers in a pass-through billing scheme involving laboratory services, the Department of Justicesaid.
According to his plea papers, Palo Pinto General Hospital ex-CEO Harris Brooks and his co-conspirators, used the Mineral Wells, Texas hospital's in-network contracts with BlueCross BlueShield of Texas, CIGNA Texas, and United Healthcare to swindle the payers out of more than $9 million.
Using PPGH's national provider identification number, Brooks and his co-conspirators submitted claims to the insurance companies for allergy and genetic testing purportedly performed at PPGH.
In reality however, PPGH did not have the equipment on-site to perform the tests for which it submitted claims, and the patients for whom claims were submitted were receiving treatment at various spas and clinics throughout Texas and elsewhere, not PPGH, the plea agreement states.
The patients did not know about the pass-through charges using PPGH's insurance contracts.
Between September 2017 and June 2018, Brooks and his co-conspirators submitted claims totaling more than $55 million, the vast majority of which were fraudulent. As a result of these claims, the insurance companies paid PPGH more than $9 million.
Harris admitted that the purpose of the scheme was to receive higher reimbursements from the insurers.
According to his plea agreement, Brooks faces up to five years in prison and will be required to pay restitution to those he defrauded.
The 'strategic affiliation' will share management and administrative services with the aim of improving quality, lowering costs, and improving the consumer experience.
Cambia Health Solutions and Blue Cross and Blue Shield of North Carolina announced Tuesday that they will combine management and administrative services.
"We have to do something different to make health care better, simpler, and more affordable for the people we serve," Patrick Conway, president and CEO of Blue Cross NC, said in a media release.
"By sharing resources, innovations, and best-in-class services we can fundamentally transform the way individuals and families experience the health care system," Conway said.
Working under the Cambria Health Solutions name, the "strategic affiliation" will be governed by a board made up of 10 members from Blue Cross NC's board and nine members from Cambia's board.
Blue Cross NC will retain its own separate board and name, and the two companies will retain their separate, tax-paying, not-for-profit corporate structures.
"People and their families are hurting every day in the current health care system, longing for care focused on their needs,” said Mark Ganz, president and CEO of Cambia Health Solutions. "Together, we have the power to accelerate transformation, be a model for what is possible, and positively impact the lives of those we serve."
Under the affiliation, Ganz will be executive chair of Cambia's board, and Conway will be Cambia's new CEO. Conway also will remain CEO of Blue Cross NC, and the corporate headquarters will be in Durham, NC, and Portland, OR.
The strategic affiliation also will maintain the separate health plans in five states, all locally led and regulated.
The deal is subject to regulatory approval in North Carolina, Oregon, Washington, Idaho, and Utah.
While the two companies are calling the deal a "strategic affiliation," Nathan Ray, a senior principal in West Monroe’s healthcare & life sciences practice said "it appears to be like a merger."
"It will take the form of a long-term MSA with an agreement to share management, operations and administrative staffs, and the BCBSNC CEO becoming the CEO of Cambia," Ray said in an email exchange with HealthLeaders.
Ray said sharing management operations and administration makes sense because it provides cost synergies.
"They don't directly compete which probably allowed the executive teams to discuss such an opportunity," Ray said. "Geographic advantages including cheaper labor, or healthier membership may also be fringe benefits."
"In many cases consolidation of management, operations, administration of payers is an easy exercise to realize efficiencies and take advantage of unique opportunities sharing technology or strategy," he said.
Blue Cross NC and Cambia's health plans include Regence BlueCross BlueShield of Oregon, Regence BlueShield in Washington, Regence BlueShield of Idaho, and Regence BlueCross BlueShield of Utah.
The two companies said the affiliation builds on their existing Echo Health Ventures, a healthcare investment and development company launched in 2016.
Federal prosecutors said the illegal remuneration took the form of free or discounted medical practice and market development support for physicians.
Covidien LP will pay more than $17.4 million to settle whistleblower allegations that it provided illegal kickbacks to physicians to entice the use of its vein ablation products, the Department of Justice said.
The alleged kickbacks, violations of the False Claims Act and the Anti-Kickback Statute, took the form of free or discounted medical practice and market development support for physicians in California and Florida, DOJ said.
Assistant Attorney General Jody Hunt for DOJ's Civil Division said the settlement "serves as an important reminder to those in the healthcare community that unlawful kickbacks come in many forms and are not limited to monetary payments to providers."
"Providing free or discounted services to healthcare providers to induce the use of certain items or services can lead to excessive and unnecessary treatments, and drive up healthcare costs for everyone," Hunt said.
Federal prosecutors alleged that Covidien provided the illegal remuneration to physicians in California and Florida from Jan. 1, 2011, through Sept. 30, 2014, to induce them to buy Covidien's ClosureFAST radiofrequency ablation catheters that were billed to Medicare and to the California and Florida Medicaid programs.
The catheters are used to treat venous reflux disease, a disease often marked by the presence of varicose veins.
The illegal support allegedly provided by Covidien included customized marketing plans for specific vein practices; scheduling and conducting "lunch and learn" meetings and dinners with other physicians to drive referrals to specific vein practices; and providing assistance to specific vein practices in connection with planning, promoting, and conducting vein screening events to cultivate new patients for those practices.
"The government contended that Covidien provided discounted or free services to health providers – and so hoped to evade kickback charges," said Steven J. Ryan, Special Agent in Charge for the Office of Inspector General of the U.S. Department of Health and Human Services. "Companies seeking to buy clients through such arrangements can expect to pay a steep price."
Under the settlement agreement, Covidien will pay an additional $1.47 million to California and $1 million to Florida for claims settled by these state Medicaid programs.
The settlement resolves whistleblower lawsuits filed by two former sales managers for Covidien and a former employee of one of Covidien's customers. The whistleblowers will share more than $3.1 million of the settlement.
HealthLeaders' requests for comment from Covidien were not returned Tuesday morning.
"Medical errors are the third leading cause of death in the country," says Marcus Schabacker, MD, president and CEO, ECRI Institute. "This guidance can help healthcare leaders and clinicians save lives."
Healthcare providers rely on EHRs to help with clinical decision support and tracking test results. But that technology is just one tool in the diagnostic process, said William Marella, executive director of operations and analytics, at ECRI Institute PSO.
"We have to recognize the limits of current technology and ensure that we have processes in place to close the loop on diagnostic tests," Marella said. "This safety issue cuts across acute and ambulatory settings, requiring teamwork across the health system."
ECRI Institute’s 2019 list of concerns addresses systemic issues facing health systems, such as behavioral health concerns, clinician burnout, and skills development. Mobile health technology, number four on the list, opens up a world of opportunities by transporting healthcare to the home, but also presents potential risks.
The report also highlights ongoing clinical issues with infections from peripheral IV lines, sepsis, and anti-microbial stewardship. In the outpatient setting, at least 30% of antibiotic use is unnecessary.
The 2019 Top 10 Patient Safety Concerns are:
Diagnostic Stewardship and Test Result Management Using EHRs. "Providers have begun relying on the electronic health record (EHR) to help with clinical decision support, to track test results, and to flag issues. However, the EHR is only part of the solution."
Antimicrobial Stewardship in Physician Practices and Aging Services. "Perhaps the most significant challenge facing antibiotic stewardship is managing patient expectations. Moreover, unnecessary antibiotic administration puts patients at unnecessary risk of adverse drug reaction. And the broadest concern is that overprescribing leads to antimicrobial resistance."
Burnout and Its Impact on Patient Safety. " The electronic health record is a contributing factor, but burnout goes beyond providers’ oft-described frustrations with documentation. Healthcare is evolving rapidly and keeping up with the changes can be a challenge."
Patient Safety Concerns Involving Mobile Health. "Risks of mobile health technology include lack of regulation of new technologies, barriers to ensuring that providers are accurately receiving the data a device collects, and the possibility that a patient is not using the technology correctly or is not using it at all."
Reducing Discomfort with Behavioral Health. " In many healthcare settings, behavioral and physical health are siloed. But people with behavioral health needs are in every setting, and it is not always obvious when an individual has such needs."
Detecting Changes in a Patient’s Condition. " Sometimes staff are inadequately trained in recognizing changes in a patient’s condition or in responding to an alarm that is alerting caregivers to check on a patient.
Developing and Maintaining Skills. "Patient harm can occur if staff are uncomfortable using medical equipment or performing a procedure, or are unaccustomed to an organization or care area’s processes."
Early Recognition of Sepsis across the Continuum. "To facilitate timely diagnosis and management, healthcare organizations across the continuum should have protocols for response when sepsis is suspected, much as they do for chest pain."
Infections from Peripherally Inserted IV Lines. "Increased awareness of PIV-catheter-related infections, coupled with routine active surveillance and follow-up reporting, can help reduce the risk."
Standardizing Safety Efforts across Large Health Systems. "Regardless of organization size, the goal is to institute structures that effectively allow patient safety leaders to support organization leadership in engaging with patient safety priorities."
ECRI’s list does not necessarily represent the most frequently or most severe safety issues.
It identifies new risks, how existing concerns may be changing because of new technology or care delivery models, and persistent issues that need renewed attention or that might have additional solutions.
The nation's largest physicians' association warns that the proposed rules 'may lead to unintended consequences for patient privacy and physician burden.'
The American Medical Association is asking federal policy makers for an additional 30 days or more to review and comment on two proposed federal rules that address interoperability and information blocking.
The policy, published and detailed this month in the federal registry, comes from a mandate in the 21st Century Cures Act and Executive Order 13813 "to improve access to, and the quality of, information that Americans need to make informed health," the Centers for Medicare & Medicaid Services summarized.
The new policy "would improve access to data about healthcare prices and outcomes, while minimizing reporting burdens on affected plans, health care providers, or payers," CMS said.
While supporting the policy, AMA Executive Vice President and CEO James Madara, MD, asked CMS to push back by one month the May 3 deadline for stakeholder input.
"Expediency should not take precedence over deliberation as we confront a true paradigm shift in healthcare. I therefore urge that the comment periods for both rules be extended by at least 30 days," Madara said in a one-page letter to CMS Administrator Seema Verma, and Donald Rucker, national coordinator for health information technology.
Madara did not raise specific concerns about the lengthy proposed rules, but noted that they are "interwoven, complex in nature, and include multiple detailed requests for information."
"To ensure that the rules are as successful as possible in meeting your goals, it is vital that stakeholders be given adequate time to provide comprehensive, thoughtful, and detailed comments," he said.
"I recognize and appreciate the desire for swift rulemaking. However, such rapid change in healthcare policy, technology, and business practices may lead to unintended consequences for patient privacy and physician burden."
While the reduction is impressive, it's still short of the 40% reduction goal set forward by the Utah-based health system when it announced the initiative in 2017.
Intermountain Healthcare reduced the number of opioid tablets prescribed to patients in acute pain by 3.8 million in 2018.
The 3.8 million fewer opioid pills prescribed by the health system in 2018 represents about a 30% reduction, falling short of the 40% reduction that Intermountain had targeted when it announced the initiative in 2017.
Intermountain executives say they're proud of the success, but will use 2019 to drill down into health system operations to identify opportunities to reduce opioid prescriptions by 5%.
"We knew these would be lofty goals and we're encouraged by the reduction in opioid tablets and the success of our other opioid-reduction efforts. We knew these were the right steps to take," said Intermountain CMO David Hasleton, MD.
"We're continuing our focus to implement appropriate evidence-based opioid treatments, provide alternative forms of pain control for our patients, and educate providers and the public about the safe use of opioid medications," Hasleton said.
Among the accomplishments touted by Intermountain:
Intermountain exceeded its goal to increase medically-assisted treatment for opioid use disorders by more than 10%.
Intermountain reduced by 29% the number of patients prescribed both opioids and benzodiazepines, the combination of which could suppress breathing.
Intermountain pharmacy drop-boxes have received over 26,000 pounds of medication since February 2015. Intermountain has also helped give out more than 2,644 naloxone kits.
Intermountain pharmacies offer naloxone kits for purchase without a prescription and the system has helped to fund additional kits for nonprofit Utah Naloxone.
Lisa Nichols, Intermountain Healthcare’s Community Health executive director, spoke with HealthLeaders about the health system's efforts to reduce opioid prescriptions. The following is an edited transcript.
HLM: How did you recognize that you had a problem with opioid prescriptions?
Nichols: We as a health system certainly watched the morbidity and mortality incidents and prevalence data in our community at the time we started our opioid initiatives. For several years, Utah was in the Top 10 in terms of overdose deaths and we're the largest health system in the state. If we've got a large number of overdose deaths, we understood that we have to intervene.
HLM: Initially you sought a 40% reduction in opioid prescriptions. How did you come to that number?
Nichols: We had surveyed about 16,000 patients post surgery around how many of the tablets they were given, did they use them and how did they dispose of their medication. We learned that most people were using 50% or less of the tablets that we were giving them. That really helped us feel comfortable that we could prescribe at least 40% less and still adequately manage people's needs.
HLM: You fell a little short of that goal. What happened?
Nichols: With each percentage reduction it became incrementally harder. We had some really good improvements at the beginning and then and then it just became harder. It's hard to find that balance between treating pain and ensuring people were safe.
HLM: Do you still consider the initiative a success?
Nichols: We're proud of where we got, but a lot of 2018 was also spent building the infrastructure to support this work. We put up digital dashboards and we did a lot of education with leaders and we have a continuous improvement huddling system for our goals.
We think that we can go further now that we have this incredible foundation set and we're able to drill down on who are high prescribers or are there geographic areas or facilities that are problematic. We think we can get at least another 5% reduction.
At least part of that 30% was the low-hanging fruit and that's why it got incrementally harder. But now we really can focus in, to the detail of are there specific procedures where they're prescribing more? It's not just focusing on prescribers. We continue to focus on our community and their awareness of the dangers of opioids, their understanding that over the counters are really effective.
We want to continue to build that knowledge and empowerment of our patients to say to their prescribers. "Do I really need this?"
HLM: Where do you go from here in 2019?
Nichols: We have this 40% goal as a system and one of our improvements this year is we're now able to look at each clinical program and we can see where they are in their prescribing. If we want to get an additional 5%, how much would each clinical program need to reduce? So we're working much more granularly with each clinical program around "this is our expectation for your program. Is that realistic?" We're doing it in a much more targeted way.
HLM: What sort of patient metrics are you seeing that would indicate this initiative is working?
Nichols: Utah is one of only a handful of states that saw a decrease in opioid overdose deaths last year. We had a 12% decrease in overdose death. That's multifaceted. It's also because Naloxone has become much more available and treatment as become much more available. You need all of those components for this very complex problem.
The Trump administration says offering health insurance across state lines will enhance competition and lower premiums, but states may raise objections if their regulatory authority is challenged.
The Centers for Medicare & Medicaid Services wants suggestions on how to "eliminate regulatory, operational and financial barriers" that hinder the sale of health insurance plans across state lines.
"Americans are in desperate need of more affordable health insurance options," CMS Administrator Seema Verma said Wednesday in a media release announcing the request for information.
"Eliminating the barriers to selling health insurance coverage across state lines could help provide access to a more competitive and affordable health insurance market," she said.
In an October 2017 executive order, President Donald Trump mandated that CMS "facilitate the purchase of health insurance across state lines," which the administration said would "provide relief from rising premiums by increasing consumer choice and competition."
CMS said it wants feedback on how states can take advantage of Section 1333 of the Patient Protection and Affordable Care Act, which provides for a regulatory framework that allows two or more states to enter into a Health Care Choice Compact to facilitate the sale of health insurance coverage across state lines.
Specifically, federal policymakers are looking for input on how to expand access to health insurance coverage across state lines, effectively operationalize the sale of health insurance coverage across state lines, and understand the financial impacts of selling health insurance coverage across state lines, CMS said.
Trump's 2017 executive order also directs the Secretary of Labor "to consider expanding access to Association Health Plans, which could potentially allow American employers to form groups across State lines." That would allow health insurance providers to bypass state coverage requirements.
Health insurance oversight is left largely to the purview of states, which has created a regulatory patchwork that varies widely from state to state.
State and federal lawmakers, mostly Republican, have for the past decade pushed to sell health insurance across state lines, but the issue has proved to be nettlesome. The National Association of State Legislatures reportsthat at least 23 state legislatures have considered the idea over the past 10 years.
The National Association of Insurance Commissioners hasn't taken a firm stand on the idea, because it represents independent state insurance commissioners, many of whom may have varying levels of support for the idea.
In the past, however, state insurance commissioners have been reluctant to support any federal initiatives on the issue that weaken states' regulatory oversight.
A NAIC spokesman on Wednesday declined to comment, but said the association would respond to the RFI.
The RFI will be open for public comment for 60 days.
Healthcare information managers urge Congress to address a burdensome and costly healthcare regulatory environment that is driving up costs and diverting resources away from optimal patient care.
If Congress wants to stem rising healthcare costs, they could start by taking a look at expensive federal mandates.
That's one of several suggestions put forward by the College of Healthcare Information Management Executives in a six-page letter to Sen. Lamar Alexander, (R-TN) chairman of the Health, Education, Labor and Pensions Committee.
"Despite the infusion of nearly $40 billion for healthcare providers to adopt electronic health records, the costs to maintain those systems and ensure they are capable of enabling successful participation in federal programs comes with steep price tags," CHIME CEO Russell P. Branzell and CHIME Board Chair Shafiq Rab said in their joint letter.
"The 21st Century Cures Act recognized the need to bring transparency, especially around costs, to the EHR purchasing process, but there are many other financial burdens associated with participating in federal reporting programs," the letter said.
CHIME complained that while the Promoting Interoperability Program "altered the trajectory of EHR adoption… countless costs have continued to plague health systems to maintain compliance with the program mandates."
"The costs associated with new versions of certification, interface fees, quality reporting tools and patient engagement modules have forced health systems to choose between innovation or clinician requests and meeting federal mandates," CHIME said.
"Capital budgets are limited and as federal mandates amp up expectations, more and more resources continue to be dedicated to the Centers for Medicare and Medicaid Services or the Office of the National Coordinator's wishes, rather than those of the patient or clinician," the letter said, adding that "Congress must work with the administration to continue to infuse flexibility into the PI program, so it better aligns with patient and clinician needs."
CHIME highlighted other areas of concern, including:
Quality Measurement: "The burden of quality measurement that our members shoulder to meet reporting requirements levied by CMS is significant. Hours of work and expertise are required to comply with these reporting demands and such burdens are exacerbated by a lack of technical harmonization."
HIPAA Compliance: "The complexities with meeting HHS privacy and security requirements can be staggering. Audits by the Office for Civil Rights are perceived as being punitive and not assisting the organization to recover and learn from a breach. It is vital that Congress and HHS identify a pathway for ensuring providers do not unduly shoulder the burden of protecting PHI in situations outside their control."
Harmonizing Privacy and Consent Laws: "The exchange of data among providers in various locations and settings will require the harmonization of state and federal privacy laws. As an example, consent policy varies by jurisdiction and personal health information type, and similar to most privacy policy, there is no national consent policy."
Rethinking Telehealth policies: "Whether public and private payers cover telehealth services and adequately reimburse hospitals and other healthcare providers for providing those services, is a complex and evolving issue and, as a result, a possible barrier to standardizing the provision of these valuable services."
Researchers looked at the time to first breast cancer diagnostic testing, diagnosis, and chemotherapy among a group of women whose employers switched from low-deductible to high-deductible health plans.
Low-income women enrolled in high-deductible health plans delay chemotherapy treatments for breast cancer by nearly nine months, compared with low-income women enrolled in low-deductible plans, a new study shows.
Delays also occurred at the diagnosis and testing stages, including a 1.6 months delay to initial breast imaging, a 2.7 months delay to first biopsy, and a 6.6 months delay to early-stage breast cancer diagnosis, according to the research published this week in Health Affairs.
"The most likely reason that women delay these events along the path towards breast cancer diagnosis and treatment would be the barrier of high out-of-pocket costs that women face when they join high-deductible health plans," said study chief author J. Frank Wharam, MD, with the Harvard Pilgrim Health Care Institute.
Wharam says that cancer screenings, diagnosis, and treatment often go through stages, and this is where the delays mount.
"What we found was that in between the stages—from screenings to diagnostic tests to a biopsy to a diagnosis of cancer to chemotherapy—there were some delays and those delays added up to be quite substantial by the time you compared time to chemotherapy," he says.
"And again, this is likely related to fear of out-of-pocket costs," he says. "We do know that people tend to put off care towards the end of the year when there's a high-deductible health plan because their cost sharing goes down once they hit the deductible, so that's possibly another factor."
The researchers looked at the time to first breast cancer diagnostic testing, diagnosis, and chemotherapy among a group of women whose employers switched their insurance coverage from health plans with low deductibles ($500 or less) to plans with high deductibles ($1,000 or more) between 2004 and 2014.
The research group included 54,403 low-income and 76,776 high-income women who were continuously enrolled in low-deductible plans for a year and then up to four years in HDHPs.
Low-income women in HDHPs experienced relative delays of 1.6 months to first breast imaging, 2.7 months to first biopsy, 6.6 months to incident early-stage breast cancer diagnosis, and 8.7 months to first chemotherapy.
High-income HDHP members had shorter delays that did not differ significantly from those of their low-income counterparts.
HDHP members living in metropolitan, nonmetropolitan, predominantly white, and predominantly nonwhite areas also experienced delayed breast cancer care.
The researchers recommend developing policies to reduce out-of-pocket spending obligations to encourage prompt screening and treatment.
Wharam says further study is needed to determine if the treatment delays were detrimental.
"There's not great evidence about whether longer delays are associated with worse outcomes," he says. "There have been a few studies that indicate that delays of three to four months between diagnosis and surgery are associated with worse outcomes such as survival. But those studies are a bit challenging in the sense that the delays might be related to other illnesses."
"We're not completely sure, but if it was a two- or three-month delay to chemotherapy, I don't think there'd be as much great concern as if it were, say, a two-year delay," Wharam says. "We're in this in-between area where I'm not sure of the downstream impact on health outcomes like death and survival and progression to metastatic disease."
