This May, Georgia Gov. Brian Kemp, a Republican, signed a law that boosts criminal penalties for assaults against hospital workers and allows health care facilities in the state to create independent police forces. The law is a response to that testimony as well as hospital lobbying and data documenting a rise in violence against health care workers. In enacting the law, Georgia joined other states attempting to reverse a rise in violence over the last several years through stiffer criminal penalties and enhanced law enforcement…
Health care workers are five times as likely to experience violence as employees in other industries, according to federal data. On May 3, the day after Kemp signed the Safer Hospitals Act into law, a person opened fire in a midtown Atlanta medical office, killing one woman and injuring four others, including workers at the medical practice…
Health centers say they are better able to retain workers and improve patient care when they can reduce the number of violent incidents,
Methods: The study used data from the Fragile Families and Child Wellbeing Study, a longitudinal birth cohort study of children born in 20 US cities. Study outcomes were “based on age-15 interviews with the focal children and their caregivers with sample sizes ranging from 2088 to 2327 across outcomes. The relationship between CPS contact and child wellbeing was estimated using the propensity score method of inverse probability of treatment weighting.”
Key findings:
“Despite a federal mandate to improve child wellbeing, we found no evidence that contact with the child welfare system improves child outcomes. Rather, CPS contact was associated with worse mental health and developmental outcomes” including associated increases in smoking (88% increase), in being expelled from school (18% increase), in depression (7.5% increase, and in anxiety (6.9% increase).
My take: While protecting children and reporting abuse/neglect are mandated, it is not clear that involvement of CPS results in better outcomes.
E Tobin-Tyler. NEJM 2023; 388: 1345-1347. Courts’ Disregard for Women’s Health and Safety — Intimate Partner Violence, Firearms, and “History and Tradition”
A few excerpts:
In June 2022, the Supreme Court issued its opinion in New York State Rifle & Pistol Association v. Bruen, which left the door open for constitutional challenges to virtually any state or federal firearm restriction. One of these restrictions is a federal law passed in 1994 as part of the Violence Against Women Act (VAWA) that makes it unlawful for people subject to certain domestic violence–related restraining orders to possess a firearm or ammunition for the duration of the order.
Writing for the majority in Bruen, Justice Clarence Thomas struck down New York’s restrictions on who may carry a firearm in public. In doing so, he declared that a government arguing in support of a restriction on firearm possession has the burden of showing that its regulation “is consistent with the Nation’s historical tradition of firearm regulation.”..
On the heels of the Supreme Court’s decision in Bruen, a federal district judge on November 10, 2022, held in United States v. Perez-Gallan that the VAWA’s restriction on firearm possession by people subject to restraining orders is unconstitutional…
Searching for relevant laws from the 18th and 19th centuries to justify current laws protecting people who have experienced IPV (intimate partner violence) obscures the fact that married women weren’t even considered legal subjects until the late 19th century. Instead, they were understood to be the property of their husbands.1 Black women who were enslaved, married or not, had no legal rights. “Wife beating” did not become illegal in some states until the late 19th century…
In Rahimi, the court applied Bruen’s “history and tradition” analysis to a case involving a person who not only was subject to a restraining order because he had allegedly assaulted his ex-girlfriend, but also had been involved in incidents in which he had fired a gun at people and at a constable’s car…The court determined that under Bruen’s analysis, there is no reason to consider the potential consequences for people experiencing IPV of permitting their abusers to possess guns.
My take: Deciding gun ownership laws solely on the basis of ‘history and tradition’ is incredibly stupid. Research shows that restriction of access to firearms by domestic abusers results in lower rates of gun deaths. This supreme court will allow anyone to possess a firearm, except those in their vicinity.
Related article: The Hill (5/11/23): Federal judge rules adults ages 18-20 cannot be blocked from purchasing handguns. “A federal judge in Virginia has ruled that federal laws prohibiting 18-to-20-year-olds from getting handguns at federally licensed firearms dealers are unconstitutional…The judge concluded that the Second Amendment’s “right of the people to keep and bear Arms” applies to people in that age group. “Because the statutes and regulations in question are not consistent with our Nation’s history and tradition, they, therefore, cannot stand,” Payne wrote.
Also, I want to give a shout out to Ajay Kaul (who completed his training in Cincy one year after I did) and his recent Bowel Sounds Podcast. Ajay is a terrific person. This was a good review on Achalasia and a reminder of the improvements in motility testing. A good clinical pearl was to ask anesthesiology to intubate patients with suspected achalasia to protect their airway.
The Florida Surgeon General’s recommendation that young men shouldn’t get the COVID-19 vaccine was made “despite the state having contradictory data,” according to the Tampa Bay Times.
In October, Florida Surgeon General Joseph Ladapo, MD, PhD, announced that young men shouldn’t get the COVID-19 vaccine, countering CDC guidance. His recommendation was based on an analysis that purported to show an increased risk of cardiac-related death for men ages 18 to 39.
However, draft versions of the analysis obtained by the Tampa Bay Times show that “catching COVID-19 could increase the chances of a cardiac-related death much more than getting the vaccine,” the article stated.
“That data was included in anearlier version of the state’s analysis but was missing from the final version compiled and posted online by the Florida Department of Health,” the Times reported. “Ladapo did not reference the contradictory data in a release posted by the state.”
My take: The approach taken by Florida’s “surgeon general” is one of making sure the facts don’t get in the way of a perfectly good narrative.
FDA has approved Daybue (trofinetide) oral solution as the first treatment for Rett syndrome, a rare, genetic neurological disorder. Daybue is approved for the treatment of Rett syndrome in adults and children 2 years of age and older.
Patients take Daybue either orally or via gastrostomy tube. The recommended dose is based on patient weight. Daybue is taken twice daily, morning and evening, with or without food.
Disease or Condition
Rett syndrome is a rare, genetic neurological and developmental disorder that affects the way the brain develops. Patients with Rett syndrome experience a progressive loss of motor skills and language. Most babies with Rett syndrome seem to develop as expected for the first six months of life. These babies then lose skills they previously had attained at approximately six to 18 months of age — such as the ability to crawl, walk, communicate, or use their hands. The hallmark of Rett syndrome is near constant repetitive hand movements, such as rubbing or clapping. Rett syndrome leads to severe impairments affecting nearly every aspect of life, including the ability to speak, walk, eat, and breathe.
The syndrome primarily affects females (1 in 10,000) and even more rarely affects males.
Effectiveness
The efficacy and safety of Daybue was evaluated in a randomized, double-blind, placebo-controlled, 12-week study (Study 1; NCT04181723) of patients with Rett syndrome five to 20 years of age. Patients were randomized to receive Daybue (N=93) or matching placebo (N=94) for 12 weeks. The dose of Daybue was based on patient weight to achieve similar exposure in all patients.
The co-primary efficacy measures were change from baseline in the Rett Syndrome Behavior Questionnaire (RSBQ) total score and the Clinical Global Impression-Improvement (CGI-I) score at week 12. The RSBQ is a 45-item rating scale completed by the caregiver that assesses a range of signs and symptoms of Rett syndrome. Lower scores represented lesser severity in signs and symptoms of Rett syndrome. The CGI-I is a 7-point scale rated by clinicians to assess how much a patient’s illness has improved or worsened. A decrease in CGI-I score indicates improvement.
Patients treated with Daybue demonstrated a statistically significant difference compared to placebo on the co-primary efficacy endpoints, as measured by the change from baseline in the RSBQ total score and the CGI-I score at week 12.
Safety Information
Most common adverse reactions, occurring in at least 10% of Daybue-treated patients and twice the rate of placebo, included diarrhea (81%) and vomiting (27%).
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.
My take: Many detractors of vaccination have focused on potential cardiac adverse events. These studies indicate that COVID vaccination provides protection against major cardiovascular outcomes
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.
No Exaggeration: Too Many Children Are Dying in the U.S. “The sad fact is that a child or adolescent in the United States is 57% more likely to die by the age of 19 years than those in other wealthy nations.” This is due mainly to more deaths from MVAs and from gun violence.
Aslo, gun violence is widespread and is more common in ‘red’ states than ‘blue’ states despite the widely-held notion that gun violence occurs mainly in large urban centers.
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.
2. Cyltezo
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.
3. Hyrimoz
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.
4. Hadlima
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.
5. Abrilada
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.
6. Hulio
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.
7. Yusimry
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.
8. Idacio
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.
VC Cohran, BD Gold, DJ Spencer, CR Cole. JPGN 2022; 75: 689-691. Health Care Disparities in Gastroenterology: The Pediatric Gastroenterology Perspective This commentary reviewed survey results highlighting healthcare disparities which have been identified in IBD, NALFD, and liver transplantation. The authors outline some of the steps that NASPGHAN has taken as well as some of the work that is needed.
gutsandgrowth 