This case-control study leveraged a large commercial insurance database and found increased rates of adverse outcomes over a 1-year period for a post-COVID-19 cohort surviving the acute phase of illness. Methods: An index month was set by adding 30 days to the COVID-19 diagnosis date (this study looked at outcomes starting one month after diagnosis).
This study used the data from the US Collaborative Network in TriNetX. From a cohort of more than 42 million records between 1 January 2019 and 31 March 2022, a total of 4,131,717 participants who underwent SARS-CoV-2 testing were recruited.
This article explains how generic and biosimilar companies have tried to navigate the ‘patent gamesmanship’ that brand-name manufacturers have used to delay competition for their products beyond the typical 20 years after an application is filed.
Key points from this article:
“The Hatch–Waxman Act, provided a partial solution by explicitly authorizing manufacturers to market generic drugs if they don’t claim any indications protected by active method-of-use patents.3 Such skinny labeling enables generics manufacturers to market their products for older, non–patent-protected indications without infringing later-issued method-of-use patents…43% of products that were the first available generic formulation of a brand-name drug included skinny labels”
The article delves into the GlaxoSmithKline v. Teva case which centers on the overlapping potential indications for the beta-blocker carvedilol. Teva had used skinny labeling to get approval for hypertension (HTN) but was sued by GlaxoSmithKline as carvedilol can be used for congestive heart failure (CHF).
Much of the case centers on the paradox that “by law, generics [& biosimilars] manufacturers are required to use very similar labels” as the labeling of original products even though the generic has requested approval for a much narrower approval. In this case, when the Teva generic was used for CHF, GlaxoSmithKline sued since the product was approved for HTN.
Another example: Humira has “more than 70 patents on inventions ranging from the active pharmaceutical ingredient and primary indications to the drug’s purity, various formulations, and secondary indications.” For a generic/biosimilar to address all of these (potentially-endless) patents is a huge barrier.
Based on this ruling, “brand-name manufacturers can thus now create labels that reference material related to new method-of-use patents and then sue generics manufacturers for patent infringement.”
“Lack of action by both the Supreme Court and Congress would allow brand-name drug manufacturers to wield a powerful new weapon to delay or deter the entry of generic and biosimilar drugs, which could have important implications for health care costs and patient welfare.”
My take: My prediction is that these tactics by drug manufacturers, despite their extensive financial connections with lawmakers, will eventually backfire and result in extensive changes to the regulations regarding exclusivity and pricing.
In an unrelated article in the same issue, Golda Grinberg provides a first-hand account of how families could benefit by the consideration of hospice in children with extensive medical problems. NEJM 2023; 388: 486-487. Please Look at My Baby — When Clinicians Should Say the Word “Hospice”
“To the surprise, perhaps even shock, of the SICU team, we tossed an option B onto the table: if we truly could not extubate, we suggested, maybe we should skip the trach and transition to comfort care….When presented with a child in whom previous extubation attempts had failed and who was becoming more deconditioned by the day, the SICU team had made the standard, safe, and familiar recommendation for an acute problem: place a trach… It would have been tremendously helpful if, from the beginning, we’d had an open conversation with our son’s medical team and discussed all the options.”
My take: Most parents are happy with their medical decisions for their children. However, it is not uncommon to hear parents say many years later that they wished that they had been informed of the long-term dire outlook of their children and the possibility of deescalation of care in children with severe medical conditions before embarking down the ‘standard’ path.
In 2021 a record48,000 Americans were killed by firearms, including suicides, homicides and accidents. So let’s try to bypass the culture wars and try a harm-reduction model familiar from public health efforts to reduce deaths from other dangerous products such as cars and cigarettes.
Harm reduction for guns would start by acknowledging the blunt reality that we’re not going to eliminate guns any more than we have eliminated vehicles or tobacco, not in a country that already has more guns than people.
Recommendations from article:
We can try to keep firearms from people who are under 21 or who have a record of violent misdemeanors, alcohol abuse, domestic violence or some red flag that they may be a threat to themselves or others
To keep ineligible people from buying firearms, we need universal background checks
A pillar of harm reduction involving motor vehicles is the requirement of a license to drive a car. So why not a license to buy a gun?… In Massachusetts, which has one of the lowest gun mortality rates in the country, an applicant who wants to buy a gun must pay $100 for a license, be fingerprinted, undergo a background check and explain why he or she wants a gun. If the permit is granted, as it typically is after a few weeks, the bearer can then go to a gun store and buy the firearm. There is then an obligation to store it safely and report if it is stolen.
Smoking and alcohol cause more deaths in U.S. –both are regulated, not banned. “Because we’ve worked to reduce vehicle deaths and haven’t seriously attempted to curb gun violence, firearms now kill more people than cars.”
Background checks to purchase ammunition… this should be possible without creating burdens for gun owners who have already gone through background checks to buy weapons
Waiting periods and limits on how many guns one can purchase at a time may also help. We also need to crack down on untraceable ghost guns and on firearms made by 3-D printers; ghost guns are already a growing source of weapons for criminals
Warning labels: One proposed ammunition label has a photo of a bloody face and states that a gun increases the risk of someone in a home being killed
Increase costs of ownership to cover the damage associated with weapons: raise cost of guns through taxes/fees
This article proposes a lot of practical interventions that if implemented would likely reduce gun violence.
Related article: NPR Jan 24, 2023: Gun violence deaths: How the U.S. compares with the rest of the world The chart below shows how the U.S compares to gun violence in countries with low levels of gun violence. The U.S. compares favorably with Mexico, El Salvador, Guatemala, Venezuela, The Phillipines and Iraq. However, many violent places have lower gun violence than U.S. including Syria, Somalia, Afganistan, Iran, Pakistan, Yemen, and Libya.
This article details how AbbVie has perfected the use of patent protections to extend its monopoly over adalimumab; this has been to the detriment of many patients , employers and taxpayers who bear the additional costs. Key points:
In 2016, a blockbuster drug called Humira was poised to become a lot less valuable. The key patent on the best-selling anti-inflammatory medication, used to treat conditions like arthritis, was expiring at the end of the year…Through its savvy but legal exploitation of the U.S. patent system, Humira’s manufacturer, AbbVie, blocked competitors from entering the market.
Since the end of 2016, the drug’s list price has gone up 60 percent to over $80,000 a year, according to SSR Health, a research firm.
Patents are good for 20 years after an application is filed. Because they protect patent holders’ right to profit off their inventions, they are supposed to incentivize the expensive risk-taking that sometimes yields breakthrough innovations. But drug companies have turned patents into weapons to thwart competition. AbbVie and its affiliates have applied for 311 patents, of which 165 have been granted, related to Humira, according to the Initiative for Medicines, Access and Knowledge, which tracks drug patents. A vast majority were filed after Humira was on the market.
The article notes that one employer has been flying a patient receiving Humira to the Bahamas to pick up her medication.
AbbVie … will have a new way to make more money from the drug. Under the terms of the legal settlements… AbbVie will earn royalties from the knockoff products that it delayed.
In the longer run, though, AbbVie’s success with Humira may boomerang on the drug industry. Last year, the company’s tactics became a rallying cry for federal lawmakers as they successfully pushed for Medicare to have greater control over the price of widely used drugs that, like Humira, have been on the market for many years but still lack competition.
My take: It makes me mad when I read this article. First of all, there are a lot of patients harmed by this gaming. Second, it is outrageous that the cost of this expensive medication was raised 60% over the last 6 years (and going up 8% more in 2023). Third, I am disappointed to learn that AbbVie will still make money off biosimilars because I am looking forward to NOT using Humira because of these tactics. Lastly, I hope that this does prompt legislative/regulatory changes to limit this practice going forward.
Amjevita (adalimumab-atto) will be available in prefilled autoinjector pens (40 mg) and prefilled syringes (20 mg, 40 mg). Amjevita products will come in low-concentration forms, but they will be citrate-free. It’s expected to launch on January 31, 2023.
Cyltezo (adalimumab-adbm) became the first biosimilar to be designated as interchangeable with Humira. Interchangeable biosimilars go through additional studies to determine whether you can switch back and forth between the biosimilar and the original product without issues. Biosimilars without this designation haven’t gone through these same studies.
Cyltezo will only be available in a prefilled syringe and will come in two doses: 20 mg and 40 mg. Both are low-concentration forms and citrate-free. Cyltezo is expected to launch in the U.S. as early as July 1, 2023.
Hyrimoz (adalimumab-adaz): a 40 mg dose will be available in both a pen and a syringe. A 10 mg syringe will also be available. Both are low-concentration forms. These products contain citric acid, which is closely related to citrate. Citric acid can also make injections more painful. A citrate-free high-concentration form of Hyrimoz is currently under FDA review. Hyrimoz is expected to launch in the U.S. on September 30, 2023.
Hadlima (adalimumab-bwwd) will be available in both an autoinjector and a syringe in a 40 mg dose. And it will come in both low- and high-concentration forms. The high-concentration form will be citrate-free. Hadlima is expected to launch in the U.S. on or after July 1, 2023.
Abrilada (adalimumab-afzb) will be available in a prefilled pen (40 mg) and in a syringe (10 mg, 20 mg, 40 mg). All Abrilada products will be low-concentration forms and citrate-free. Abrilada’s manufacturer has applied for interchangeable status with Humira. Abrilada is expected to launch in the U.S. as early as July 1, 2023.
Hulio (adalimumab-fkjp) will be available in a prefilled pen (40 mg) and in a syringe (20 mg and 40 mg). All forms are low-concentration and citrate-free. Hulio is expected to launch in the U.S. on or after July 1, 2023.
Yusimry (adalimumab-aqvh) will only be available in a 40 mg prefilled syringe. It will be in a low-concentration form and citrate-free. Yusimry is expected to launch in the U.S. on or after July 1, 2023.
Idacio (adalimumab-aacf) will be available in a 40 mg dose in both a pen and a syringe. Both forms will be low-concentration and citrate-free. Idacio is expected to launch in the U.S. as early as July 1, 2023.
My take: In high school, one of math teachers used to call me Hochman sub-1 and my twin brother Hochman sub-2. Perhaps, we can start designating biosimilars in a similar fashion?
“Gaming” U.S. Patent System by Big PharmaHumira, a rheumatoid arthritis drug from the Chicago-based biotech firm AbbVie, generated $17.3 billion in annual sales in 2021. There are 311 patent applications for the drug, 94% of which were sought after FDA approval. AbbVie’s original patent on the drug expired in 2016, but it won’t face competition until 2023
Two other important studies I wanted to cite -both studies have Benjamin Gold, one of my better-known partners, as one of the authors:
KA Chien, C Thomas, V Cooley, T Weinstein, KF Murray, L Muir, C Hayes, BD Gold, LM Gerber, CG Sauer, G Tomer. JPGN 2023; 76: 25-32. Physician Burnout in Pediatric Gastroenterology In this survey with 408 responses (23% response rate), the authors found 29% reported high risk for emotional exhaustion, 18% reported high risk for depersonalization, and 33% reported overall burnout.
The following information was provided by our coding advisor, Mary Suhr.
Time codes (when used) for inpatient visits have changed (see below). In 2023, when you share a service with an APP, you may bill on patient medical decision making or time spent. You can add the time together and whoever spends more total time on that date of service (including face to face and non-face to-face) gets to be the service provider for that charge.
Extra time code: 99418 for every 15 minutes increments above average inpatient code.
Observation codes are obsolete.
Specific requirements for documentation of History and Physical exam are NOT needed for coding. Good documentation is still important part of medical practice and for liability; patient still needs to be examined.
ALL outpatient and inpatient E/M visits will be leveled using the same methodology.
Coding is based on medical decision making or time code (whichever has higher complexity). When selecting a level of service for Medical Decision Making, there is still the concept of having three components/tables and the requirement that two of the three components are met. Tables 1, 2, and 3 outline the requirements.
CPT 99251 (Straightforward Inpatient Consult) and CPT 99241 (Straightforward Outpatient Consult) are going away because the history and exam requirements for consults no longer apply and history/exam was the only difference between level 1 and level 2 consultation codes.
For consultations, you still need a requesting provider, a reason for the consult and a report back to the provider. CMS was explicit this year that assuming care of the problem is not considered a consult.
Consultationscannot be shared between two providers (e.g. physicians and APPs). If a consultation is shared between an APP and a MD, our advisor recommends the use admission codes for those. This is true for inpatient consultations as well as office-based consultations.
Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician. Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure. This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.
Why does Mississippi have the best childhood immunization rates (99%)? This is due to state policies. This article reviews the small but significant drops in childhood immunizations which is opening the door for highly contagious diseases like measles.
U.S. routine childhood vaccination rates have historically been among the world’s best. But within the first year of the pandemic, the nation’s children missed nine million vaccine doses for diseases like polio and measles. Rates for the three major childhood immunizations — for measles, mumps and rubella; chickenpox; and diphtheria, tetanus and pertussis — fell by an average of 1.3 percentage points, with the rates in seven states and many cities falling under 90 percent…
Measles should not be taken lightly. The virus is highly contagious; according to the C.D.C., if one person has it, up to 90 percent of the people close to that person who are not immune will also become infected. It can live up to two hours in the air. One to three of every 1,000 children who contract measles die of respiratory and neurological complications…
Covid vaccine acceptance and anti-vax attitudes do not fully explain differences among states. Neither do red-blue partisan affiliations or the strength of a state’s public health system. Instead, the decline is rooted in longstanding policies among some states that allow, for instance, for nonmedical exemptions, failures to rigorously enforce vaccination requirements and inadequate public health campaigns…
Vaccines are one of the few true cost savers in medicine. The routine immunizations of children born from 1994 to 2018 are projected to prevent nearly one million early deaths and save nearly $1.9 trillion in economic costs — more than $5,700 for each American, according to the C.D.C. For measles, a state might spend more than $2 million responding to a single outbreak, with each case costing nearly $50,000 on average, according to an analysis of a recent outbreak in Washington State.
To avoid dangerous and costly outbreaks, states should introduce enforceable solutions that give their children and communities the best protections against vaccine-preventable infectious diseases.
This article recommends medical schools stop participating in U.S. News & World Report’s (USNWR) ‘best medical school’ survey. I would advocate for eliminating USNWR’s reports more broadly including their ranking of hospitals and medical specialties.
The medical school rankings rely on the following:
Federal research dollars
Reputation – “assessed by a survey (with an abysmal response rate) of medical school deans, department chairs, and residency program directors”
Ratio of full-time faculty to students
Students’ median scores on the Medical College Admission Test and their undergraduate grade-point averages
“Yale and Harvard Law Schools recently announced they would no longer participate in U.S. News & World Report’s (USNWR) flawed ranking system, followed closely by additional schools. The nation’s medical schools need to follow their lead. Why? The USNWR ranking system is in direct opposition to medical schools’ goal of educating a well-trained, diverse, and culturally competent medical workforce..”
“It is hardly a secret among medical school deans that the USNWR rankings are based on data not directly related to educational process, quality, and outcomes. Nor can they trust the veracity of the data that are provided, given the recent scandals reported in other professional schools and colleges that manipulate the formula to their own advantage.”
“Comprehensive analyses of USNWR rankings have long demonstrated that the methodology is ill-conceived, that the response rate of those completing the questionnaires that feed into the ranking formula would not meet the standards of a peer-reviewed publication, and that the most important aspects of educational quality are largely ignored.”
“There is peer pressure to stay within the system and to compete for the top prize because it feels good to see your school on top, no matter how flawed the measuring stick.”
My take: It is difficult to measure quality. I do not trust USNWR’s rankings with regard to “best” medical school, “best” hospital or “best” subspecialty. I think medical care would be better off without these reports. Another option would be to focus on reporting hard data, rather than the current aggregate format. This data could include federal research dollars and reputational surveys; the latter would need to be transparent with regard to methodology.