Oncology Practice Pays Over $1 Million to Settle Kickback Scheme

Physicians at a hematology and oncology practice in Texas have agreed to pay over $1.3 million to resolve alleged violations of the False Claims Act. The practice had entered into an unlawful kickback arrangement with a diagnostic reference laboratory, which provided in-office bone marrow biopsies and subsequent diagnostic testing. 

The practice received $115 for each biopsy referral, which the government contended constituted a kickback under the Anti-Kickback Statute. The settlement also resolves claims that the physicians at the practice provided medically unnecessary tests, services and treatments that were billed to federal health care programs. The lab has agreed to pay over $2.7 million to settle the False Claims Act allegations. 

Commenting on the case, Special Agent in Charge Jason E. Meadows with the US Department of Health and Human Services Office of Inspector General, said: “Violations of the Anti-Kickback Statute involving oncology services can waste scarce federal health care program funds and corrupt the medical decision-making process. Individuals who participate in the federal health care system are required to obey laws meant to preserve both the integrity of program funds and the provision of appropriate, quality services to patients.”

Hospital Nurse Steals Pain Medications From New Mothers 

A nurse working in the labor and delivery unit of an Iowa hospital was sentenced to federal prison for stealing pain medication from at least 50 new mothers. Rather than administering the medications to the patients, the nurse stole the Schedule II narcotics for herself and then documented that the drugs were administered to the mothers.

As a result of her actions, the mothers suffered in terrible pain and were delayed or denied further treatment because it was assumed they had already received a narcotic analgesic. It was revealed during the plea hearing that the nurse had also tampered with fentanyl vials, replacing the medication with saline and diverting it for her own use. She also admitted to routine drinking and marijuana use while working at the hospital. In order to pass the hospital’s drug test, the nurse used another person’s urine. As part of her plea deal, the nurse forfeited her nursing license and was sentenced to 1 year and 1 day in federal prison.

Anesthesiologist Serves Up Cocktail of Dangerous Drugs to Patients

An anesthesiologist from Texas was convicted of tampering with intravenous (IV) bags resulting in several patients suffering cardiac emergencies during routine medical procedures. The anesthesiologist would inject IV bags of saline with epinephrine, bupivacaine and other drugs and then place them into a warming bin for use. 

During the surgeries, patients would experience dangerous complications such as unexpected rises in blood pressure; the issues all occurred shortly after the IV bags had been hung. A month after these emergencies began, another anesthesiologist at the center died after treating herself for dehydration with an IV bag. Following this incident, an 18-year-old patient ended up in the intensive care unit after a routine sinus surgery. An analysis of the fluid in the IV bag used during the teenager’s surgery showed that it contained bupivacaine, epinephrine, and lidocaine. 

At trial, it was discovered that the anesthesiologist was facing disciplinary action for an alleged medical mistake and that he faced losing his medical license. He now faces a maximum penalty of 190 years in prison. 

Commenting on the case, US Attorney Leigha Simonton for the Northern District of Texas, said: “[The anesthesiologist] assembled ticking time bombs, then sat in wait as those medical time bombs went off one by one, toxic cocktails flowing into the veins of patients who were often at their most vulnerable, lying unconscious on the operating table. We saw the patients testify. Their pain, their fear and their trauma was palpable in that courtroom.”

Cardiologist Busted for Submitting Fake Claims for Office Visits

A NJ cardiologist has admitted to participating in a health care fraud scheme leading to over $1.9 million in insurance reimbursements for false claims. In one case, the doctor submitted a claim for office visits that lasted approximately 1675 minutes for 1 day’s worth of visits. He also billed for over $800,000 for office visits while he was out of the country. Additionally, claims for office visits were submitted when only prescriptions were being picked up for controlled substances at the front desk. 

According to the US Attorney’s Office, District of New Jersey, a charge of health care fraud carries a possible sentence of up to 10 years in prison and a fine of up to $250,000 or twice the gain or loss from the offense, whichever is greater. 

Physician Pays Hefty Fine for Poor Recordkeeping 

An Oklahoma doctor has agreed to pay $200,000 to settle civil penalty claims related to his failure to maintain controlled substance records as set forth in the Comprehensive Drug Abuse Prevention and Control Act of 1970. According to the Act, registrants seeking to purchase controlled substances need to fill out the purchaser portion of a DEA Form-222; the purchaser is then required to retain a copy of the form, which includes the date and quantity of the products received. Registrants who do not follow all the necessary steps related to the Act can face monetary penalties, as failure to comply can increase the potential for drug diversion. 

The Centers for Disease Control and Prevention’s (CDC) Advisory Committee on Immunization Practices (ACIP) discussed vaccinations for COVID-19, influenza, respiratory syncytial virus (RSV), pneumococcal infections, and other infectious diseases and made some related recommendations during their first 2024 meeting, held February 28 to 29.

COVID-19 Vaccine Recommendations

The ACIP now recommends that persons 65 years of age and older should receive an additional dose of the updated (2023-2024) COVID-19 vaccine.¹ The additional dose must be administered at least 4 months following the previous dose of the updated vaccine.

Adults aged 65 years and older have expressed a high level of concern about COVID-19, with 68.4% of individuals indicating they would definitely receive another vaccine dose should it become available.² The effectiveness of an additional dose of COVID-19 vaccine is demonstrated by past recommendations.

The need for the recommended 4-month COVID-19 booster vaccine for those age 65 and older is supported by both hospitalization data and scientific reasoning. An estimated 67% of COVID-19 hospitalizations were among patients age 65 years and older between October 2023 and January 2024, according to ACIP current respiratory season calculations made using data from COVID-NET, a population-based hospitalization surveillance program.³ Moreover, hospitalizations were 5 times higher for those age 65 years and older vs those aged 50 to 64 years.

The need for booster protection is also indicated by data showing that older adults may not be able to generate robust, long-lasting neutralizing antibody responses or good memory cytotoxic T-cells as there are fewer naive T-cells that respond to new pathogens.²

Vaccine formulations for the next COVID-19 season are already underway.²

Notably, members of the ACIP expressed concern that offering booster vaccinations for those age 65 and older at 4-month intervals could create vaccine fatigue as well as confusion for providers, given that immunocompromised patients may receive a booster dose following a 2-month interval.

In their June 2024 meeting, the ACIP plans to propose revised time frames for COVID-19 vaccine development and vaccination that will allow health care providers ample time to prepare for the COVID-19 viral season.

RSV Vaccine Developments

An ACIP work group on RSV vaccination in older adults presented its recommendation that providers and patients “consider timing of the RSV vaccination as part of shared clinical decision-making discussions,” noting that for most older adults, RSV vaccination is most beneficial when received in late summer or early fall, before the start of RSV season.⁴

Although shared decision-making between patient and provider is currently recommended for determining whether or not an adult patient should receive the RSV vaccine, this recommendation may be replaced by a universal recommendation that adults above a certain age receive the RSV vaccine, and a risk-based recommendation that adults over age 50 years receive the vaccine, according to the work group report, “RSV Vaccination in Older Adults: Work Group Interpretations.”⁴

The ACIP also expressed its intention to discuss the potential approval of the GSK RSV vaccine, AREXVY, for those aged 50 to 59 at “increased risk of RSV disease” at their June meeting.  AREXVY is currently approved for use in adults aged 60 and above.⁴

In anticipation of RSV-related actions set for June, the ACIP reviewed RSV vaccine data related to the Moderna mRNA vaccine.^4,5 The committee also discussed concerns over the potential connection between currently approved RSV vaccines and an increased incidence of Guillain-Barré Syndrome (GBS).

Moderna mRNA RSV Vaccine

Moderna has been conducting a clinical trial for their mRNA-based RSV vaccine for adults age 60 years and older (ClinicalTrials.gov Identifier: NCT05127434), which works by encoding the RSV fusion (F) glycoprotein.⁵ According to an ACIP report on trial findings that was presented at the February meeting, the vaccine has been generally well tolerated, efficacious through a median 8.6 months of follow-up, and presented no safety concerns (including no concern over GBS).

The trial enrolled a total of 26,550 healthy adults age 60 years and older, including those with chronic, stable health conditions. The primary endpoint was vaccine efficacy in preventing the first episode of RSV lower respiratory tract disease (LRTD) between 14 days and 12 months post-vaccination. The secondary endpoint was vaccine efficacy in preventing the first episode of RSV acute respiratory disease (ARD) and first hospitalization between 14 days and 12 months.

Trial investigators found that vaccine efficacy for RSV-LRTD with 2 or more symptoms reached 83.7%, whereas efficacy for RSV-LRTD with 3 or more symptoms was calculated as 82.4%.⁵ The efficacy threshold for RSV-ARD was set at 68.4%. Vaccine efficacy met lower bounds of confidence interval criteria to exceed 20%.

RSV Vaccines and GBS

For the February ACIP meeting, CDC’s Immunization Safety Office and the US Food and Drug Administration (FDA) shared preliminary data from multiple surveillance systems on the risk for GBS after RSV vaccination.⁴

An elevated but rare risk for GBS was observed following administration of the GSK’s AREXY and Pfizer’s ABRYSVO vaccines for RSV.  According to the work group report on RSV Vaccination in Older Adults, current surveillance data “support a potential increased risk for GBS after RSV vaccination among adults aged ≥60 years.”⁴

The report went on to note that “there is currently insufficient evidence to confirm whether RSV vaccination is associated with increased risk for GBS in older adults, or to estimate the magnitude of any increase in GBS risk after RSV vaccination.”⁴

Currently, clinical trials are underway evaluating the safety of these vaccines, examining the association between RSV vaccines and the incidence of GBS. More conclusive evidence of potential risks following RSV vaccination will be available following RSV monitoring using self-controlled case series designs.

Influenza Immunization in Children With Asthma

The ACIP also assessed evidence evaluating the safety of the live attenuated influenza vaccine (LAIV4) in children with asthma.⁶ The evidence indicated that LAIV4 may be a suitable option for children age 5 years and older with asthma.

Evidence presented included a study assessing whether LAIV4 is noninferior to IIV4. The study included 151 patients between the ages of 5 and 7 years with persistent asthma who were randomly assigned to 2 groups: one receiving LAIV4 FluMist and the other receiving IIV4 Fluzone. On days 15 and 43, the 2 groups were evaluated for symptoms following vaccination. The study investigators compared the proportion of patients using LAIV4 vs IIV4 who experienced an asthma exacerbation during the 42 days following vaccination.

Study findings showed that in the 14 days following vaccination, 3 exacerbations were reported among those receiving LAIV4 vs 4 exacerbations among those receiving IIV4 (3.9% vs. 5.7%, P =.74). In the 42-day symptom assessment, 8 asthma exacerbations were documented among those receiving LAIV4 and 10 among those receiving IIV4 (10.8% vs. 14.7%, p = 0.74). The upper bound for noninferiority was set at 10% with a difference in proportion of 3.9 (CI: 90%: -0.15, 0.07).⁶ Researchers rejected the null hypothesis and proved LAIV4 noninferiority to IIV4.

Limitations of the study include the enrollment of fewer participants than intended, setting the power at 79% and the enrollment of patients within 2 separate flu seasons, which may have led to slightly different products.

Further discussion of the suitability of LAIV4 for children age 5 years and older with asthma is anticipated at future ACIP meetings.

Pneumococcal Vaccination: PCV21 Considerations

The ACIP also discussed incorporating a recently developed pneumococcal vaccine, V116, a 21-valent pneumococcal conjugate vaccine (PCV21), into its roster of recommended pneumococcal vaccines. Toward that end, the committee reviewed phase 3 clinical trial results for V116 (ClinicalTrials.gov Identifier: NCT05425732).

The ACIP reported that the following policy questions are being actively considered by its work group:⁷

1. Should PCV21 be recommended for US adults aged 19 and older who currently have a recommendation to receive a PCV?
2. Should PCV21 be recommended for US adults aged 50 to 64 years who do not have risk-based indication for the pneumococcal vaccine?
3. Should PCV21 be recommended for US adults aged 19 to 49 years who do not have risk-based indication for the pneumococcal vaccine?

About 30% to 40% of adult invasive pneumococcal disease (IPD) cases are caused by serotypes that are not contained in currently available pneumococcal vaccines.⁸ The PCV21 vaccine contains most of these serotypes and provides broader coverage. In a phase 3, randomized, double-blind, active comparator-controlled clinical study of the V116 PCV21 vaccine, V116 was concluded to be superior to PCV20 for 10 out of the 11 of its unique strains.

The work group concluded that pneumococcal disease is of public health importance to adults currently recommended for PCV vaccination. While it may be appropriate to expand vaccination to patients between the ages of 50 to 64, committee members concluded that epidemiology does not support expanding vaccination to younger adults without indication.

At its June meeting, the ACIP plans to consider official draft policies on PCV21 use in US adults.⁷

More and more clinical trials of cancer drugs involve assessments of patients’ views on how treatments are affecting them. The US Food and Drug Administration (FDA) encourages the gathering and reporting of these patient-reported outcomes (PROs), which offer insight into the patient experience without biased interpretation by investigators. Still, PROs for cancer drugs are frequently absent from marketing approval requests submitted to the FDA, or they are inadequate. Recent studies have found that the FDA approves many novel cancer drugs without PROs, so these medications reach the market without patients’ perspectives on how these products influenced their quality of life.

A study presented at the American Society of Clinical Oncology’s 2023 annual meeting by investigators at Howard University in Washington, DC, revealed that less than half of 420 pivotal trials leading to FDA cancer drug approvals from 2006 to 2022 included PRO assessments.¹ Another study, published in 2023 in Supportive Care in Cancer,² showed that of 59 unique cancer drugs approved from 2013 to 2022 via the FDA’s accelerated approval pathway, only 59% included PRO assessments in the clinical trials. The investigators concluded that “PRO measurements are inconsistently utilized in trials leading to initial accelerated approvals of oncology drugs, and there seems to be a lack of harmonization of different PRO measurement tools across trials.”

In another study, investigators who reviewed transcripts from 27 meetings of the FDA’s Oncology Drugs Advisory Committee (ODAC) from 2016 to 2021 found that PRO-related topics were mentioned in only 12, according to a report in JCO Oncology Practice.³ Of those, ODAC reviewers were satisfied with PRO assessments in only 2.

“During ODAC meetings, committee members and FDA reviewers expressed frustration at the lack of PROs captured in clinical trials for cancer treatments,” authors Ari Gnanasakthy, MBA, MS, and colleagues concluded. “Less than half of evidence packages for cancer treatments submitted for FDA review included PROs. Even when PROs were included in evidence packages, the PROs were rarely deemed adequate for benefit-risk assessments.”

They added: “Lack of credible PRO data in oncology clinical trials prevents regulators from making comprehensive and accurate assessments of the benefits and risks of new cancer treatments. Clinicians and patients, therefore, are forced to choose among treatment options without understanding the experiences of patients who were treated with these options.”

Influence on Formularies

Lack of PROs could adversely affect decisions about which medications are placed on health plan formularies and thus covered by insurance. A survey of health plan representatives (90% pharmacists, 56% pharmacy administrators) found that 78% of the 106 respondents thought PRO evidence is useful for providing additional context for safety of oncology therapies. In addition, 47% suggested that formulary reviews would be at least somewhat influenced by a lack of PRO evidence from oncology clinical trials.

“US payers view PRO evidence from both clinical trials and real-world studies as useful for supplementing traditional clinical trial data when making oncology formulary decisions and for refining treatment pathways and care delivery models,” investigators Gary Oderda, PharmD, MPH, and coauthors concluded in a 2022 paper in the Journal of Managed Care & Specialty Pharmacy.⁴ “Manufacturers of oncology therapies should collect and consider leveraging PRO evidence from both settings when engaging with US payers.”

Primacy of Objective Data

Although PROs, which are subjective, can provide FDA reviewers with additional information to consider, objective data must be the foundation for evaluating a drug except in cases in which a drug’s effectiveness can only be evaluated using PROs, said Peter Lurie, MD, MPH, President and Executive Director at the Center for Science in the Public Interest in Washington, DC, and former Associate Commissioner for Public Health Strategy and Analysis at the FDA.

For example, in clinical trials of pain drugs, investigators have to rely on PROs to gauge effectiveness because changes in pain perception in response to treatment are subjective. This is not the case with diseases such as cancer for which objective measures are available, Dr Lurie said. Those measures, and not patient opinion, must provide the basis for approval. Cancer drugs “should not be coming onto the market because the majority of patients think the drugs work for them,” he said.

Dr Lurie asserted, “Encouraging assessment of PROs is definitely a good idea; making it a required part of the primary assessment of safety and efficacy probably is not.”

The American Society of Clinical Oncology said in an emailed statement that it “recommends that trialists consider including attributes of accessible and equitable research, such as patient-reported outcomes, in the design and conduct of all clinical trials, as understanding how patients are affected by a therapy is paramount.”

A recent federal cybersecurity advisory is urging health care providers to immediately adopt phishing-resistant multi-factor authentication (MFA) for all administrative access. Providers should put systems in place that verify implementation of new sign-in procedures, implement network segregation controls, and change and remove or deactivate all default credentials.

The advisory was issued by the Cybersecurity and Infrastructure Security Agency (CISA), which conducted a Risk and Vulnerability Assessment (RVA) last year to identify vulnerabilities and areas for improvement. An RVA is a 2-week penetration test of an entire organization, with 1 week spent on external testing and 1 week spent assessing the internal network. As part of the RVA, the CISA assessment team conducted web application, phishing, penetration, database, and wireless assessments. The team assessed a large organization deploying on-premises software.

During the 1-week external assessment, the team did not identify any significant or exploitable conditions in externally available systems. The assessment team was unable to gain initial access to the assessed organization through phishing. During internal penetration testing, however, the team exploited misconfigurations, weak passwords, and other issues through multiple attack paths to compromise the organization’s domain.

In coordination with the assessed organizations, CISA is releasing a new Cybersecurity Advisory (CSA) detailing the RVA team’s activities and key findings to provide network defenders and software manufacturers with recommendations to improve organizations’ and customers’ cyber posture.

“The threat is greater than ever,” said Tamer Baker, a specialist in cybersecurity and the Healthcare Chief Technology Officer at Zscaler, which has its headquarters in San Jose, California. More than 100 million people and 500 hospitals in the US alone have been impacted by breaches just in 2023, he said.

IT security equals patient security, Baker said. The average financial impact of a health care breach is now $11 million, which far exceeds the spending required to get proper security, according to Baker. “The advisory is long overdue; however, it is still not enough,” he said. “What’s needed is going to be more along the lines of what the state of New York has been leading the charge with. They are not only going to be putting in more regulations and requirements with some enforcement, but are also providing funding to help health systems achieve these goals.”

Impact on Patient Care

Cyberattacks adversely impact patient care in a serious way, and have been associated with extended hospital stays and increased mortality. “According to a national study conducted by Ponemon Institute, these cyberattacks have led to 56% longer hospital lengths of stay and 53% increase in mortality rate,” said Baker, who assists health care organizations, state and local governments, and educational institutions in their digital transformation efforts. Cyberattacks in just the last 12 months have caused thousands of patients to be transferred or diverted to other facilities. The attacks were associated with delays in procedures and tests, increased complications and poor outcomes.

From a user credential perspective, MFA is a good first step, but not enough, according to Baker. Bad actors have found several ways to get through MFA using vectors like MFA-bombing as an example. This is a social engineering cyberattack strategy whereby attackers repeatedly push second-factor authentication requests to the target victim’s email, phone, or registered devices. “We need to stop users from ever reaching phishing sites to begin with,” he said. “A big step will be to have security in place which blocks phishing attempts no matter if the user is on-network or off-network (working from anywhere).”

CISA encourages health care providers who are deploying on-premises software, as well as software manufacturers, to apply the recommendations in the mitigations section of the CSA in the new advisory. It is hoped that these recommendations can harden networks against malicious activity and reduce the likelihood of domain compromise.

Offline Security Systems

“A way to stop attacks directly on applications and infrastructure is to just remove them from the internet,” Baker said. “Hide these applications and infrastructure behind a security cloud so the bad actors can’t even find them on the internet. This same security cloud can connect your users to the applications securely.”

In addition to applying the newly listed mitigations, CISA recommends exercising, testing, and validating an organization’s security program against the threat behaviors mapped out in the advisory.

Frank Nydam, the CEO of Tausight, health care’s first AI-powered data security company, said health care providers remain a prime target of cybercriminals, and there is no sign of this trend abating. In the first 6-months of 2023 alone, he said, 325 covered entities reported data breaches to the US Department of Health and Human Services Office for Civil Rights (OCR). This represents an 86% increase from the same period in 2022. “Not only have cyberattacks become more frequent, but they have also become more costly, both from a financial perspective and a patient outcome perspective,” Nydam said.

Mostly Basic Cyber Hygiene

Many health care providers may think they need multiple layers of advanced tools, but Nydam said most of the time all about the fundamentals: “Basic cyber hygiene and understanding where your data are. That’s critical and often overlooked.” These strategies include regular patch updates for vulnerabilities, basic device encryption, monitoring business associates for their access to your data, and following strict access management practices like MFA. Common mistakes include failing to put a cyber response playbook in place,” Nydam said.

Other common oversights include not encrypting and patching machines, and not having proper data recovery systems in place. The most important items on a to-do list can be summarized simply. “Start cleaning up your house,” he said. This includes a data assessment to understand where your sensitive data lives. “House-cleaning steps like this can significantly reduce the attack surface, so that when a cyberattack does occur, it impacts far fewer patients.”

This month we look at a case that recently made headlines after a jury awarded the injured plaintiff almost 40 million dollars. 

Facts of the Case

Mr A was a 37-year-old landscaper who was married with two young children. He had been suffering from a cough with mucous and went to a pharmacy clinic for advice on what to take. At the pharmacy, his blood pressure reading was 132/82, and the clinic advised him to follow up with his primary care physician to rule out hypertension.

Mr A did not currently have a primary care physician, so he contacted his HMO who assigned Dr X as his primary care physician who would then be responsible for directing Mr A’s health care needs. Mr A made an appointment with the physician for the end of January.

At the appointment, Mr A complained of a persistent cough “for a couple of months” and difficulty breathing during the coughing fits. Mr A’s blood pressure reading was 190/102. Dr X examined the patient and noted in the chart that Mr A’s differential diagnosis included acute bronchitis, elevated blood pressure, tachycardia, and morbid obesity.

The doctor expressed concern about the patient’s blood pressure and noted in the chart that both the patient’s parents suffered from hypertension. The patient agreed to monitor his blood pressure at home using a home device for the next 2 weeks. Ultimately, the physician prescribed azithromycin, benzonatate perles, codeine/guaifenesin cough syrup, and a budesonide inhaler to treat the acute bronchitis. The physician did not order any medication to treat the hypertension.

At the end of day, in a follow-up call to the patient, Dr X expressed some concern that Mr A was possibly suffering from a pulmonary embolism and offered Mr A a referral for a CT scan. Mr A declined at that point, and the physician agreed with him. The physician documented this conversation in the patient’s chart.

A little over a week later, in early February, Mr A called the physician’s office and spoke to a nurse. Mr A complained of a sore throat, earache, and runny nose. In response, Dr X refilled Mr A’s antibiotic, but did not reevaluate him or ask him to return for a follow-up appointment.

About a month later, in early March, Mr A’s co-workers found him in his car in respiratory distress and called for an ambulance. First responders found Mr A sitting in his car, unable to speak, trying to move his right arm with his left. He was rushed to the hospital. On the way, his systolic blood pressure was as high as 290.

At the hospital, the stroke team sprung into action. Mr A was unable to speak or provide any medical history. An EKG revealed sinus tachycardia among other things. The emergency department team assessed Mr A as having had an acute intracerebral hemorrhage, likely secondary to hypertension. He was sent for a CT scan which confirmed that Mr A had suffered a devastating hemorrhagic stroke.

Ultimately, Mr A spent over a year in rehab undergoing physical, occupational, and speech therapy. He was left with hemiparesis, and is unable to walk long distances, drive, dress, bathe, or eat without assistance. His right hand is nonfunctional, and he suffers speech issues due to brain damage suffered from the stroke. He can no longer work and will require care for the rest of his life.

Mr A’s wife contacted a plaintiff’s attorney who hired a medical expert to review the records. The expert concluded that Dr X had been negligent in his treatment of the patient. Specifically, he faulted Dr X for failing to order blood or urine tests or any other diagnostic tests, failing to appreciate the significance of the patient’s hypertension, failing to send the patient to the emergency department or a cardiologist, and failing to appreciate the patient’s risk factors for stroke such as obesity, hypertension, and shortness of breath. 

The attorney filed a medical malpractice lawsuit against the HMO based on the negligence of Dr X, its employee.

Legal Background

It took almost 9 years for the case to make its way to a jury trial. The trial lasted 2 weeks and included the testimony of numerous medical experts. 

Mr A, who now suffers from aphasia, was unable to testify. According to his family, Mr A now must carry a card with him reading “I have aphasia, a loss for words not intelligence.”

The HMO defendant, rather than try to defend Dr X’s treatment of the patient, tried to defend itself by disassociating itself from the physician and denying that the physician was acting as the agent of the HMO, despite the fact that it was the one who assigned him. After the medical expert testimony, it was pretty much a given that Dr X was negligent, so the legal basis of the rest of the trial centered on whether he was acting as an agent of the HMO when he treated Mr A.

After 4 hours of deliberation, the jury determined that the HMO was responsible for the actions of its physician, and they awarded $39.9 million in damages to Mr A, a record-breaking verdict for a stroke victim.

Protecting Yourself

Why didn’t Dr X send the patient to the hospital, order diagnostic tests, or prescribe blood pressure medication? Without being in his head, we cannot know what was behind Dr X’s decisions, however, it is likely that the patient’s relatively young age played a role. It’s tempting to assume the best rather than the worst, and in most cases a 37-year-old with a cough might very well be someone with bronchitis. But as a medical professional it is essential to always consider the worst-case scenario in order to best prevent it. 

When the physician later called the patient to offer a CT scan because he had concerns about a potential pulmonary embolism, it is unclear if he advised the patient of the dangers of an embolism, or the urgency of the situation. Instead, he noted in the patient’s file that Mr A declined the referral and “I agreed with him.” The plaintiff’s medical expert rightly faulted Dr X for not instructing Mr A to call 911 or go to the emergency department for diagnostic testing. According to the medical expert, Dr X thoughtlessly assessed Mr A with acute bronchitis, but pulmonary embolism was in the differential diagnosis. “A doctor’s first duty is to protect his patient against serious and life-threatening disease,” concluded the medical expert.

While in most cases it will be the more common, less serious, diagnosis, it is remiss to not explore and rule out the most dangerous possibility.

Foot Bath Medication Scheme Lands Podiatrist in Hot Water

A podiatrist from Tennessee was convicted of 5 counts of health care fraud related to a scheme where he prescribed and dispensed medically unnecessary foot bath medications.  The podiatrist owned and operated a podiatry clinic and 2 in-house pharmacies; these pharmacies submitted nearly $4 million in claims to Medicare and TennCare for dispensing expensive antibiotic and antifungal drugs to be mixed into a tub of water for patients to soak their feet. These medications, which were dispensed as capsules, creams, and powders, were not even water soluble. The pharmacies were reimbursed over $3 million for these unnecessary treatments. The podiatrist faces up to 10 years in prison on each count of fraud.

Nurse Practitioner Trades Opioids for Money, Sex, and Fame 

A Tennessee nurse practitioner (NP) was sentenced to 20 years in prison for illegally prescribing medically unnecessary controlled substances to patients through his medical practice. Known locally as the “Rock Doc”, the NP prescribed more than 100,000 doses of hydrocodone, oxycodone, and fentanyl to his patients, including a pregnant woman. According to the US Attorney’s Office for the Western District of Tennessee, the NP maintained “a party-type atmosphere” at his medical practice and was known to engage in inappropriate physical relationships with some of his female patients. It is believed that part of the reason he prescribed these drugs was to improve his popularity on social media and promote a self-produced reality TV show pilot.

Drug Dealing Pharmacist Gets Prison Time for Unlawful Distribution

A Michigan pharmacist was sentenced to 8 years and 4 months in federal prison for filling fake prescriptions for controlled substances that totalled over 300,000 dosage units. These prescriptions were issued by a local doctor who was charged with unlawfully writing for controlled substances. The doctor pleaded guilty to the charge but died before sentencing. The pharmacist made over $780,000 from the distribution of these drugs from her pharmacy; the estimated street value was reported to be between $1.8 and $3.3 million. In addition to prison time, she was ordered to forfeit the proceeds of her drug dealing scheme.

Doctor Writes Undercover Agent Opioid Rx Without Legit Medical Purpose

A California doctor was sentenced to 1 year and 1 day in federal prison for distributing opioids outside the scope of medical practice. The internal medicine physician operated her practice from her home and was authorized to prescribe controlled substances. Concerning information obtained from a family member of one of the doctor’s former patients prompted an investigation into the doctor’s prescribing practices. An undercover agent was sent to her home complaining of leg pain and asking for hydrocodone 10mg tablets. The doctor prescribed the undercover agent 60 high dose hydrocodone tablets. No physical examination was conducted and no follow-up questions were asked; the doctor did not obtain medical records or provide an alternative treatment plan. In court, the doctor admitted that she knew she was prescribing an addictive medication outside the usual course of medical practice. According to the US Attorney’s Office of the Northern District of California, the doctor wrote these prescriptions in exchange for cash and street drugs, including cocaine and methamphetamine. In addition to her prison sentence, she was ordered to forfeit her medical license and pay a $4000 fine.

Physician Forks Over Thousands of Dollars for Genetic Testing Scheme

A Pennsylvania physician was ordered to pay a large sum of money for violating the False Claims Act by ordering unnecessary genetic testing for Medicare beneficiaries. The doctor referred more than 400 patients, with whom he had no medical relationship with, for these medically unnecessary genetic tests. Most referrals were done through brief telemedicine consultations and some were done without consultation at all. These genetic tests were reported to cost thousands of dollars per patient and were paid for by Medicare. According to the US Attorney’s Office for the Eastern District of Pennsylvania, the physician is responsible for paying $95,000 to resolve the allegations. Commenting on the case, Maureen R. Dixon, Special Agent in Charge for the US Department of Health and Human Services, Office of the Inspector General, Region III, said: “Accurately billing for services provided to Medicare beneficiaries is required of all health care providers. HHS-OIG and the US Attorney’s Office will continue to evaluate and pursue allegations of medically unnecessary services.”

Routine vaccine coverage in the United States (US) declined during the COVID-19 pandemic and has not rebounded to prepandemic levels. Vaccine hesitancy may in part be due to the uncomfortable process of vaccination. This article discusses strategies to help combat needle anxiety among children.

The rate of routine vaccination in the US has dropped below the 95% needed to protect the general population, putting large groups of children at risk for potentially life-threatening illnesses. Adding to the number of unvaccinated children has been an increase in the vaccine exception rate. During the 2022-23 school year, the exemption rate increased 0.4 percentage points to 3.0%. Exemptions increased in 41 states, exceeding 5% in 10 states.¹

The US Centers for Disease Control and Prevention (CDC) reported that among kindergarten-aged children in the 2022 to 2023 school year, vaccination rates for measles, mumps, and rubella (MMR); diphtheria, tetanus, and acellular pertussis (DTaP); poliovirus; and varicella were below the target level, ranging between 92.7% for DTaP to 93.1% for MMR and poliovirus.¹

Addressing pediatric needle pain has been repeatedly identified as a priority in pediatric medicine, however, it remains undermanaged in the clinical setting. In addition, recommended approaches to managing pediatric procedural pain do not address anxiety about needle pain, which is a key driver for noncooperation.

Evelyn Chan, MBBS, MSc, DCH of Monash Children’s Hospital and Royal Children’s Hospital in Australia has investigated strategies for reducing anxiety among children during painful procedures.

To prepare children for vaccination, they should be aware of what to expect, according to Dr Chan. Children should be encouraged to ask any questions or to voice concerns and their perspectives should be validated and listened to actively. During vaccination, the goal should be to distract and to relax. This could mean bringing a stuffed animal, looking at a tablet, or breathing deeply. Throughout the process, vaccination should be encouraged through positive reinforcement, by informing the child about the health benefits and that with vaccination they are protected from illness.

To minimize the pain of vaccination, Dr Chan recommends employing the 3 ‘P’s: physical numbing, positioning, and psychological techniques.²

• Some patients may benefit from using a numbing cream or cold pack to reduce procedural pain.
• Certain positions during the procedure may facilitate a more relaxed vaccination process, for example, sitting on their parent’s lap, facing the parent, etc.
• Patients may engage in conversation, play with a stress-relieving toy, practice deep breathing, or use medical virtual reality to distract them during the procedure.

To combat needle phobia, some children may benefit from role-playing, in which the child and guardian take turns playing doctor and patient, thereby familiarizing themselves with the procedure through play.

Adults should avoid minimizing or dismissing a child’s fears over vaccines, pretending that the child won’t be receiving a vaccine during an appointment, sharing negative experiences related to vaccines with the child, and using bribery or threats to try and force the child into compliance as these strategies can exacerbate anxiety and/or make the experience more distressing.

Significant changes are occurring in medical practice ownership, and the COVID-19 pandemic may have fueled some of the shift. The American Medical Association (AMA) has released a report showing that from 2012 to 2022 the share of physicians working in private practices fell 60.1% to 46.7%, a drop of 13 percentage points. In contrast, the proportion of physicians working in hospitals as direct employees or contractors increased from 5.6% in 2012 to 9.6% in 2022.

The analysis is part of the latest addition to the AMA’s Policy Research Perspective series that examines long–term changes in practice arrangements and payment methodologies. The AMA’s Physician Practice Benchmark Surveys are nationally representative surveys of post-residency physicians who provide at least 20 hours of patient care per week, are not employed by the federal government, and practice in the 50 states or the District of Columbia.

The latest survey was conducted from September to November 2022. Final data included 3500 physicians with a response rate of 31%.

The survey showed that the share of physicians working in practices at least partially owned by a hospital or health system increased from 23.4% in 2012 to 31.3% in 2022.

The proportion of physicians in small practices (10 or fewer physicians) shrank from 61.4 % in 2012 to 51.8% in 2022, the survey revealed. During that same period, the share of physicians in large practices (at least 50 physicians) grew from 12.2% to 18.3%. The proportion of physicians in midsized practices (11 to 49 physicians) remained relatively stable.

“In my opinion, the pandemic radically changed how physicians managed their practice because of the demands placed upon them by telemedicine, increased overhead costs, decreased reimbursement, and lack of staffing,” said Jason S. Greis, JD, a partner with the law firm of Benesch, Friedlander, Copland & Arnonoff LLP in Chicago, Illinois, where he is part of the firm’s Health Care & Life Sciences Practice Group. “Due to frustration, many physicians have accelerated the movement from privatized medicine to corporatized medicine backed by private equity and large hospital and health system acquirors.”

In 2022, single-specialty practices accounted for the largest share of physicians (41.8%), followed by multi-specialty group practices (26.7%), solo practices (12.9%), and a direct employment or contracting relationship with a hospital (9.6%). From 2012 to 2022, the number of physicians in multi-specialty practices and those with a direct employment or contracting relationship with a hospital grew by about 4%. The number of physicians in solo practices decreased 4%, and it was the same for single specialty group practices.

“I believe that physicians need to come together and merge into large multi-specialty practices to take advantage of cross-referrals in a way that complies with applicable federal and state fraud and abuse statutes,” Greis said.

In individual patients, an estimated glomerular filtration rate (eGFR) based on serum creatinine and/or cystatin C often differs substantially from measured GFR (mGFR), investigators reported in the Annals of Internal Medicine.

The individual-level difference between mGFR and eGFR is large, according to Tariq Shafi, MBBS, MHS, of The University of Mississippi Medical Center in Jackson, Mississippi, and colleagues. “Clinicians need to recognize that the eGFR is not an mGFR replacement and consider eGFR’s inaccuracy while managing individual patients.”

In analyses of data from 3223 participants across 4 studies, the investigators found that only 37% of eGFR results based on creatinine (eGFR_CR) fell within 10% of mGFR. For example, at an eGFR_CR of 45 mL/min/1.73 m², 15% of the participants had an mGFR outside of the range of 30-60 mL/min/1.73 m², 30% had an mGFR outside the range of 35-45 mL/min/1.73 m², and 57% had an mGFR outside the range of 40-50 mL/min/1.73 m². Such discrepancies between measured and estimated GFR were observed regardless of an individual’s race, age, or sex.

The agreement in chronic kidney disease (CKD) staging between mGFR and eGFR_CR was only 58% overall, Dr Shafi’s team reported. Among the 42% of patients who were misclassified, 22% were reclassified to a lower CKD stage and 20% to a higher stage. For 39%, the misclassification was by 1 CKD stage.

The eGFR equations incorporating cystatin C did not improve the probability of large errors and CKD stage misclassification. The investigators pointed out that non-GFR factors influence the serum concentration of creatinine and/or cystatin C, such as obesity, muscle mass, meat consumption, and fasting.

Findings Poised to Change Clinical Practice

The clinical implications of these findings are far-reaching. Underestimating GFR may exclude patients from receiving optimal therapies and overestimating GFR may leave patients vulnerable to drug adverse effects such as hyperkalemia from mineralocorticoid antagonists and toxicity from chemotherapy, Dr Shafi’s team pointed out.

In an interview with Renal & Urology News, Christine A. White, MD, MSc, of Queen’s University in Kingston, Ontario, Canada, who was not involved in the study, said the research by Dr Shafi and colleagues “exposes the substantial discrepancy that often exists between estimated GFR using creatinine or cystatin C and measured GFR in individuals. This discrepancy is not captured by the traditionally reported metric of overall population bias where individual positive and negative biases negate each other, leading to an erroneous impression of unbiased GFR estimation at the individual level.

“The discrepancy,” she continued, “has not been well appreciated by clinicians assessing patients’ kidney function who then make work-up and treatment decisions according to eGFR, nor is it explicitly addressed in many society clinical practice guidelines.”

Dr White said the study authors appropriately recommend that the uncertainty of eGFR be reported by laboratories alongside eGFR results and that GFR measurement should become more widespread. Dr White will be conducting a session on GFR measurement techniques at the American Society of Nephrology’s Kidney Week in November 2022.

“There are many ways to measure GFR using either renal or plasma clearance of a variety of exogenous markers with different sampling strategies,” she said. Few comparative studies have evaluated various protocols against the gold standard renal inulin clearance, which is no longer commercially available, she noted.

“Available studies indicate that GFR measurement protocols should be tailored according to specific patient characteristics such as level of eGFR and presence of edema,” Dr White said.

Iohexol has several advantages over other tracers, she explained. It is non-radioactive, inexpensive, and already in use worldwide as a contrast media, so it is “poised to become a preferred tracer.”

According to Dr White, “Studies such as this one may galvanize the development of GFR measurement protocols that are both accurate and logistically and economically feasible across the spectrum of GFR and clinical presentations.”

The study authors noted that advances in nonradiolabeled GFR measurement techniques have made it a “highly feasible” and safe outpatient procedure. Race, sex, age, and socioeconomic factors should not cause errors, although results may vary due to normal physiology and measurement errors, such as incomplete bladder emptying. It should be a “priority” and made “widely available,” they wrote.

The 4 cohorts in this study included GENOA (Genetic Epidemiology Network of Arteriopathy), ALTOLD (Assessing Long Term Outcomes in Living Kidney Donors), ECAC (Epidemiology of Coronary Artery Calcification), and CRIC (Chronic Renal Insufficiency Cohort). Overall, 58% of participants were White, 32% Black, 7% Hispanic, and 3% another race. The GFR was directly measured using urinary clearance of nonradiolabeled iothalamate in GENOA and ECAC, radiolabeled iothalamate in CRIC, and plasma clearance of iohexol in ALTOLD.

The investigators calculated eGFR_CR using the Chronic Kidney Disease Epidemiology (CKD-EPI) 2021 race-free equation, which is valid only in adults, and the European Kidney Function Consortium (EKFC) equation, which is valid in individuals aged 2 years or older. They calculated the eGFR from serum cystatin C (eGFR_CYS) and from serum creatinine and serum cystatin C combined (eGFR_CR-CYS) using the CKD-EPI 2012 and 2021 equations, respectively.

Reference

Shafi T, Zhu X, Lirette ST, et al. Quantifying individual-level inaccuracy in glomerular filtration rate estimation: a cross-sectional study. Ann Intern Med. Published online July 4, 2022. doi:10.7326/M22-0610

Researchers studied premature cancer death in 2020 among women from 185 countries who had 36 cancer types.^1,2 Of the 2.3 million women who died prematurely, an estimated 1.5 million could have avoided premature death via primary prevention or early detection strategies, and the remaining 800,000 deaths could have been prevented if women had equitable access to cancer care, according to researchers.

“[B]eing a woman impacts timely cancer care, more than being a man,” said Lancet report author Karla Unger-Saldaña, MD, of the National Cancer Institute of Mexico in Mexico City.

“[T]here are many mechanisms behind this starting with different access to education, health literacy, cancer awareness, and gender roles that interfere with women’s ability to seek care,” she added.

Women Experience Delays in Cancer Diagnosis

“[W]omen tend to be disadvantaged from first access to care for cancer, even starting from diagnosis,” said Lancet report author Verna Vanderpuye, MD, of Korle Bu Teaching Hospital in Accra, Ghana.

Studies have suggested that several cancers tend to be diagnosed later in women than in men. Women tend to have longer times from first presentation to diagnosis for gastrointestinal, genitourinary, lung, hematologic, and other cancers.^3-7

For example, in a UK study of 18,618 patients, women had delayed diagnoses of lymphoma, bladder cancer, colorectal cancer, gastric cancer, head and neck cancer, and lung cancer.⁷

Studies have also shown that women are more likely than men to first present with cancer symptoms at emergency rooms, with the greatest disparities seen for lung and gastrointestinal cancers.^8,9

These delays in diagnosis can mean that women are diagnosed with cancer at later stages than men. Research has shown that women are diagnosed with colon, rectal, and bladder cancer at later stages than men.^10-14

Delays in diagnosis may be partly explained by a lack of screening. For example, researchers found that health care providers are less likely to have discussions about lung cancer screening with women than with men.¹⁵ In addition, although screening has been shown to reduce the incidence of cervical cancer, many countries have not implemented widespread screening.^16,17    

How Sexism Impacts Access to Cancer Care

Sexism has been shown to impact women’s access to any type of health care, and this includes cancer care.¹

“Disrespectful or even discriminatory health care resulting from health care providers’ gender biases and stereotypes” affects women’s ability to receive the care they need, Dr Unger-Saldaña noted.

Studies have shown that women’s health concerns are less likely to be taken seriously and managed appropriately than men’s.^18,19 Women’s symptoms are more likely to be perceived as psychosocial, women are more likely to receive non-specific diagnoses, and they are more likely to be given prescriptions for psychoactive drugs.

A cancer-specific example of overlooking women’s health concerns is how physicians have delayed the diagnosis of breast cancer by inappropriately reassuring patients that a palpable mass is benign without performing a biopsy.²⁰

Research has also suggested that women with cancer are more likely than their male counterparts to experience adverse events related to cancer treatment, to report inadequate pain management, and to have their sexual health concerns overlooked.^21-23

“[I]n the area of breast and gynecologic cancers, only very recently have people focused on sexual health and sexual side effects of cancer treatment,” said Gita Suneja, MD, of the University of Utah in Salt Lake City, who was not involved in the Lancet report. “These are life-altering treatments that affect sexual health profoundly, yet we have long neglected women’s health and well-being.”

“Patriarchal ideas about women and women’s complaints often manifest in prevalent mistreatment, disrespect, negligence, and abuse of female patients by medical staff,” the authors of the Lancet report wrote. “These types of experiences can damage patients’ trust in health care providers and influence the patients’ willingness to participate in cancer screening or seek care for cancer symptoms.”

Another potential cause of suboptimal cancer care for women is the fact that they have been underrepresented in research, so cancers in women may not be as well understood as cancers in men.^24,25 The causes of breast cancer, for example, are not well understood, despite the fact that breast cancer was the most commonly diagnosed cancer worldwide in 2020.^1,26

“I think one of the key takeaways from our work was the degree to which sex and gender have not been adequately considered in cancer research, practice, and policy making,” said Lancet report author Ophira Ginsburg, MD, of the National Cancer Institute in Bethesda, Maryland. “We underestimated the massive role that gender-based and intersectional power dynamics play in the interactions of women with the cancer health system.”

This month we look at a case that took place in the emergency department (ED) of a hospital. The case looked at what the standard of proof is for a patient’s negligence claim against an ED physician. 

Just the Facts

Dr M was an emergency medicine physician working in the ED of a Texas hospital. In her position, she had handled all sorts of emergency situations, but this particular night brought something new.

The patient, a 13-year-old girl, Miss P, was brought to the ED by EMS at 9:15 pm. Miss P had been playing with her dog in her yard when she was bitten by a rattlesnake on her left foot. Her parents called paramedics who whisked her to the hospital. She was seen by Dr M at 9:20 pm.

The hospital had Snakebite Treatment Guidelines which were taken from recommendations of the American Academy of Family Practice and the manufacturer of the antivenom used by the hospital. Dr M reviewed the guidelines. According to the manufacturer, the antivenom was shown in clinical studies to be effective when given within 6 hours of snakebite, however, Dr M was concerned about the risks of the antivenom. She noted that the antivenom was contraindicated in patients with a known history of hypersensitivity to certain substances. Furthermore, 19 of 42 clinical trial participants experienced an adverse reaction, and 3 of those experienced a serious or severe adverse reaction. 

The Snakebite Treatment Guidelines set out a detailed, 7-part procedure for medical staff to follow when a patient is bitten by a viper. Part 1 is the initial assessment, including the patient’s vital signs and type of snakebite (if known). Part 2 lists initial lab tests to be ordered, and panels to be repeated 2 hours later. Part 3 deals with insertion of an IV and possible administration of a tetanus shot. Part 4, the antivenom decision tree, sets out the process that a doctor should use to determine whether (and when) to administer the antivenom. 

A patient’s severity score is assessed using several criteria, and the decision tree specifies that if the severity score is 3 or less and coagulation lab work is normal the patient should not be given antivenom, but rather be reassessed every 30 minutes for 8 hours. If the severity score is 4 or more, or coagulation lab work is abnormal, then the patient should be given the antivenom immediately. Parts 5 through 7 of the treatment guidelines cover dosing, adjunctive treatments that should and should not be administered, and follow-up once the patient is released. 

When Dr M initially assessed Miss P at 9:20 pm, the girl’s severity score was 2 and her coagulation lab work was normal. At 9:45 pm, the swelling had increased and the foot was discolored. By 10:15 pm, the swelling had progressed, but the patient’s severity score was still 2 based on the criteria. Dr M ordered morphine for the girl’s pain.

At 11:20 pm, Miss P told a nurse that she felt a burning pain in her toe. When the nurse reported this to Dr M, the physician added another point to Miss P’s severity score for paresthesia. Dr M also ordered that the girl’s coagulation workup be repeated on a stat basis. The lab results were returned at 11:39 pm and showed a drop in platelets and fibrinogen. These results increased the child’s severity score to 5.

Ten minutes later, at 11:50 pm, Dr M ordered 6 vials of antivenom be prepared. It was administered at 12:29 am, a little over 4 hours after the girl was bitten. The hospital did not admit children overnight, so Dr M arranged for Miss P’s transfer to a children’s hospital, which began its own antivenom protocol, and infused Miss P with more antivenom. Twenty-four hours after being transferred to the second hospital she was given her final dose of antivenom and was discharged on crutches the following afternoon after a physical therapy evaluation. 

Physician’s Unlawful Prescribing of Controlled Substances Leads to Patient Death 

A primary care physician from Pennsylvania has been sentenced to 22 years in prison for unlawfully prescribing oxycodone, fentanyl, and methadone to 3 patients. A jury found the doctor guilty on 71 counts of unlawful distribution of controlled substances, one of which resulted in the death of a 48-year old woman. The 3-week trial included testimony from the Drug Enforcement Administration (DEA)-Diversion Division, multiple pharmacists who refused to fill the doctor’s prescriptions, as well as experts in pain medicine, toxicology, and pathology. In addition to the prison term, the doctor was ordered to pay a fine of $50,000. Following his release from prison, he will be supervised by a probation officer for 3 years.

Prescription Drug Conspiracy Lands Nurse in Federal Prison

A Florida nurse has been sentenced to 3 years in federal prison for conspiring with another individual to distribute controlled substances in the names of individuals without lawful authority. Prior to forfeiting her licenses, the nurse was an advanced practice registered nurse, registered nurse, and DEA registrant, which gave her the authority to issue prescriptions for controlled substances. After her licensing became delinquent, she conspired with another individual who provided her with more than a dozen identifications and drivers licenses. She then proceeded to issue prescriptions for promethazine with codeine and oxycodone in exchange for payment. Thirty-four of these illegally issued prescriptions were for oxycodone and hydromorphone written for her deceased husband.

Psychiatrist Convicted of Money Laundering and Importing Illegal, Misbranded Drugs

A psychiatrist from Massachusetts has been convicted of international money laundering, illegally importing merchandise contrary to law and receiving and delivering misbranded drugs. For approximately 10 years, the physician purchased naltrexone pellet implants and disulfiram pellet implants and injections from Hong Kong. While both naltrexone and disulfiram have been approved by the Food and Drug Administration for the treatment of alcohol and opioid dependence and alcohol dependence, respectively, neither product is available in an implantable pellet formulation in the US. To conceal that the packages contained drugs, the doctor falsified shipping documents claiming that the packages contained “plastic beads in plastic tubes.” The psychiatrist then proceeded to implant these drugs into patients, who later testified that they experienced infections and complications related to the pellet implantation procedure. In addition to large fines, the charges of money laundering and importation of merchandise contrary to law each provide a sentence of up to 20 years in prison. 

NP Charged With Writing Amphetamine Rxs for No Legitimate Medical Reason

A New York psychiatric nurse practitioner (NP) has been arrested and charged with unlawful distribution of a controlled substance. He is being accused of prescribing amphetamine on 40 occasions to an individual who was never his patient. The charge of distributing controlled substances outside the course of professional practice and for no legitimate medical purpose carries a prison sentence of up to 20 years and a fine of up to $1 million.

Nurse Removes Fentanyl From IV Bag, Replaces With Saline 

A former nurse from Massachusetts has pleaded guilty to adulteration of a prescription drug. While working at a Massachusetts hospital, the nurse removed a bag of intravenous (IV) fentanyl solution from an automated dispensing machine and using a syringe, removed fentanyl from the bag. She then injected the bag with saline to replace the missing solution and returned the bag to its drawer in the machine. The bag was subsequently removed by a hospital employee before it was able to reach any patient. Testing confirmed that the bag contained less than the declared concentration of fentanyl and the nurse later admitted what she had done. Based on the charge, the nurse may face up to 3 years in prison, 1 year of supervised release, and a fine of up to $10,000. 

Respiratory syncytial virus (RSV) affects infants, young children, and older adults, particularly those with compromised respiratory or cardiovascular health. Every year RSV causes approximately 58,000 to 80,000 hospitalizations and 100 to 300 deaths in children aged less than 5 years, as well as 60,000 to 160,000 hospitalizations and 6,000 to 10,000 deaths among adults aged 65 years and older.¹

Most recent studies reveal a high threat of this infection in the southeastern region of the United States. A landmark study on patients under the age of 5 years suggested that RSV infection is the single greatest causative factor of pneumonia in this age group in the US.² In another study of adults aged 60 years and older hospitalized with RSV infection, 66% developed pneumonia.³ 

Risk Factors and Transmission for RSV

In children, risk factors for infection include prematurity at birth, low birthweight (<2500 g), underlying immunologic disorders (either natural or acquired), genetic and chromosomal abnormalities (eg, Down syndrome), the presence of other pulmonary disease processes, neoplasias, and defects of the heart and/or lung structures. In older adults, immunosuppression, chronic obstructive pulmonary disease (COPD), and heart failure increase susceptibility to RSV infection.⁴

Transmission of RSV takes place via droplets and contaminated surfaces. The virus can survive for many hours on hard surfaces such as tables and crib rails. Those infected with RSV are usually contagious for 3 to 8 days after showing symptoms. However, people can spread the disease in the prodromal phase, which is 1 to 2 days before demonstration of symptoms. Some infants and immunosuppressed adults can continue to spread the virus for as long as 4 weeks. Children are often exposed to and infected with RSV outside the home, such as in school or childcare centers.⁵

Clinical Manifestations of RSV

Symptoms of RSV infection include fever, cough, sneezing, and wheezing. Bronchiolitis is common in younger children with RSV. Clinically, bronchiolitis is characterized by expiratory breathing difficulty in infants. Other signs and symptoms include cough, tachypnea, hyperinflation, intercostal retractions, and wheezing.⁶ Pneumonia is a common sequela of RSV infection in both children and adults; it is most commonly evidenced by fever, cough, hypoxia, cyanosis, and pulmonary crackles. Infection can lead to complications that require supplemental oxygen, intensive care unit (ICU) admission, and mechanical ventilation. In older adults, particularly those over age 60 with underlying comorbidities, RSV can cause exacerbations of heart failure and COPD.^3,7

Pathophysiologic Mechanism of RSV

In children, particularly in premature infants, the immaturity of the pulmonary immune system is partly responsible for increased susceptibility to RSV infection. A genetic predisposition may also play a role in the development of severe lower respiratory infection and hyper-reactivity of the airway.  It is believed that the infant’s lungs are stimulated by a T-helper 2 cell inflammation reaction against RSV. There is a deficient response by interferons, which should naturally fight viruses, and increased response by the inflammatory mediators, interleukins. This results in goblet cell hyperplasia, increased mucus production, and bronchospasm.^8,9 

The mechanism by which RSV causes lower respiratory illness in older adults is less clear. Older adults are known to be less immunocompetent than younger adults and children. It is believed they possess lower RSV-specific serum immunoglobulin (Ig) and nasal IgA titers, which increases their susceptibility.¹⁰ Older patients with COPD have hyper-reactive airways and RSV, as well as other pathogens, can trigger an exacerbation. RSV infection causes mucous overproduction, reduced mucociliary clearance, and subsequent airway obstruction in those with COPD. Those with heart failure are in a precarious position where inflammation of the lungs can cause hypoxia, which can lead to decompensation of cardiac function.¹¹ Importantly, natural infection does not provide long-lasting immunity to RSV and reinfections with RSV can occur throughout life.¹² 

Diagnosis of RSV

Respiratory syncytial virus can be detected by rapid antigen detection tests (RADTs), direct fluorescent antibody (DFA), and polymerase chain reaction (PCR) testing on nasopharyngeal swabs and aspirates (Figure). Viral cultures can be done, however, turn-around time is up to 7 days. If RSV is the main concern, DFA testing or RADTs are most commonly recommended, particularly for infants and children. If other respiratory viruses are also of concern, PCR panels are available that test for a spectrum of respiratory viruses, including RSV. PCR testing is generally more reliable in adults and is recommended for all hospitalized or immunocompromised patients.¹³

Treatment of RSV

Treatment for RSV infection mainly includes supportive interventions to prevent dehydration, reduce fever, and manage airway obstruction. Intravenous fluids, bronchodilators, corticosteroids, and mucolytic agents can be used to relieve symptoms. Continual monitoring of oxygenation is necessary. Supplemental oxygen should be administered if needed. Mechanical ventilation may be required in severely affected individuals.

Prevention of RSV Infection

New prevention tools for RSV have become available according to the Centers for Disease Control and Prevention (CDC).¹⁴ These include monoclonal antibody agents and vaccines. Nirsevimab is a long-acting monoclonal antibody approved by the US Food and Drug Administration (FDA) to protect infants and young children at increased risk for severe RSV disease. Nirsevimab is safe and efficacious. In clinical trials, 1 dose of nirsevimab administered as an intramuscular injection protected infants for at least 5 months (the length of an average RSV season) and reduced the risk of severe RSV disease by about 80%.¹⁴

Another monoclonal antibody, palivizumab, is recommended by the American Academy of Pediatrics (AAP) for administration to infants and young children who are at increased risk of severe RSV disease. It is given in monthly intramuscular injections during RSV season.¹⁵

The FDA has approved two recombinant protein vaccines RSVPreF3 and RSVpreF that are approved by the FDA for use in adults aged 60 years and older to prevent RSV-associated lower respiratory tract disease. During the first RSV season after vaccination, each vaccine was more than 80% efficacious in preventing RSV-associated lower respiratory tract disease.¹⁶

On August 21, 2023, FDA approved the RSVpreF vaccine for use in pregnant women during weeks 32 through 36 of gestation for the prevention of RSV-associated lower respiratory tract disease in infants from birth through 6 months of age.¹⁷ 

Conclusion

Respiratory syncytial virus affects infants, young children, and older adults, particularly those with compromised respiratory or cardiovascular health. Most recent studies reveal a high threat of this infection in the southeastern region of the United States. Diagnosis of RSV is made by rapid antigen detection tests (RADTs), direct fluorescent antibody (DFA), and polymerase chain reaction (PCR) testing on nasopharyngeal swabs and aspirates. New prevention tools for RSV include monoclonal antibody agents and vaccines. These are proving to be highly efficacious and safe for children and adults.

A new real-world study has identified potentially nephrotoxic drug categories, both known and exploratory, contributing to acute kidney injury (AKI) risk in critically ill adults in the ICU.

Using electronic health record data from 92,616 ICU admissions at 13 Dutch hospitals, investigators found that 13,492 involved AKI (15%) based on serum creatinine criteria alone. After adjustment for confounding factors, 14 of 44 potentially nephrotoxic drug groups were significantly associated with higher AKI risk.

Among 19 drug categories known to be associated with AKI, 8 (42%) were confirmed as being nephrotoxic, Izak A.R. Yasrebi-de Kom, MSc, PhD, of the University of Amsterdam, in The Netherlands, and colleagues reported in Clinical Kidney Journal.¹ Opioids were significantly associated with a 1.4-fold increased risk of AKI after adjustment. Antimycotic antibiotics, glycopeptide antibiotics, sulfonamides, aminoglycosides, and penicillins were significantly associated with a 2.1-, 2.0-, 1.9-, 1.9-, and 1.6-fold increased AKI risk, respectively. Immunosuppressants and loop diuretics were both significantly associated with a 1.7-fold increased risk.

Among 25 other drugs that were explored, 6 (24%) were associated with AKI risk. Phosphodiesterase inhibitors, sympathomimetics α- and β-effect, antiarrhythmics, blood and plasma products, antihypertensives, plasma replacement products were significantly associated with a 1.8-, 1.7-, 1.6-, 1.4-, 1.3-, and 1.3-fold higher AKI risk, respectively.

Confounding by indication, specifically hypotension, may be responsible for the association observed with sympathomimetics with α- and β-effect, the investigators noted. After adjustment, nonsteroidal anti-inflammatory drugs (NSAID) excluding salicylates also were associated with AKI.

Across all analyses, 7 drug categories consistently showed an association with increased AKI risk: glycopeptide antibiotics (vancomycin and teicoplanin), sulfonamides (co-trimoxazole), aminoglycosides, penicillins, antiarrhythmics, loop diuretics, and immunosuppressants, the investigators reported.

Iodinated contrast media and proton pump inhibitors did not carry an increased AKI risk, according to the team.

Drug groups associated with a lower hazard of AKI included blood glucose-lowering agents, ACE inhibitors, and anti-epileptics.

These estimated risks reflect the average situation in clinical practice rather than intrinsic nephrotoxicity in the ICU population, the investigators pointed out.  Strategies for lowering AKI risk include dosage adjustments, therapeutic drug monitoring, or better hemodynamic monitoring and support, they noted.

“For many drug groups the nephrotoxicity has been firmly established and is in line with our results,” Dr Yasrebi-de Kom wrote. “For these groups ICUs should implement strategies to prevent or at least reduce severity of AKI due to nephrotoxicity. Clinical decision support systems, implementation of clinical pathways and nephrotoxin stewardship have all shown promising results to attain such improvements in kidney safety in ICU patients.”

A separate study published in Chest² examined 35,654 ICU admissions involving vancomycin combination treatment. Vancomycin and piperacillin-tazobactam were significantly associated with 1.4-fold increased odds of AKI and 1.3-fold increased odds of initiation of dialysis compared with vancomycin and cefepime and 1.3- and 1.6-fold increased odds of AKI and dialysis, respectively, compared with vancomycin and meropenem.

Managing AKI

The medical community is continuing to look for ways to improve AKI identification and management. In a recent Chinese trial (ClinicalTrials.gov Identifier: NCT03736304), investigators randomly assigned 2208 hospitalized patients to an AKI alert group or usual care group with no alert. Clinicians received automated messages to their mobile telephones alerting them to the potential for AKI along with general management measures. The primary outcome was maximum change in estimated glomerular filtration rate (eGFR) within 7 days.

At 7 days, the median absolute change in eGFR did not differ significantly between groups: 3.7 vs 2.9 mL/min/1.73m² in the AKI alert vs usual care group, Huijuan Mao, MD, PhD, of Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University in China, and colleagues reported in JAMA Network Open.³Patients in the alert group were significantly more likely to receive intravenous fluids within 2 days of randomization (82.6% vs 61.8%), less likely to be exposed to nonsteroidal anti-inflammatory drugs within 3 days after randomization (5.0% vs 11.0%), and more likely to have AKI documented in the discharge record (49.9% vs 27.3%), however.

In an accompanying editorial,⁴ Bourne L. Auguste, MD, MSc, of Sunnybrook Health Sciences Centre in Toronto, Ontario, Canada, and colleagues noted that electronic alerts “operate on the premise that real-time surveillance of declining kidney function paired with a prompt notification to the relevant health care practitioner have the potential to trigger timely interventions. Although the majority of literature in this area has attested to the ability of alerts to change physician behaviors in a way that favors earlier intervention as anticipated, most come up short in demonstrating any meaningful effect on patient outcomes.”

The editorialists pointed out that the premise of eGFR calculations “rests on stable serum creatinine levels, an assumption that is rarely met during the acute changes seen in AKI.” In the setting of AKI, “the kinetics of creatinine can lag its true clearance, misrepresenting the real-time state of kidney function and potentially affecting the timing and appropriateness of clinical interventions.”

Most critically ill patients with AKI, however, do not receive appropriate follow-up even once they’re discharged from the hospital. In a separate study of 29,732 ICU patients with AKI who survived to discharge, only 25% had both an outpatient serum creatinine and urinary protein measurement at 3 months, Ngan N. Lam, MD, MSc, of the University of Calgary in Canada, and colleagues reported in Kidney Medicine.⁵ Specifically, 64% had an outpatient creatinine measurement and 28% had a urinary protein measurement. Only 5% saw a nephrologist.

Liability in a medical malpractice case is not always clear-cut. Sometimes a patient is held partially liable for their own harm. Such was the situation in this month’s particularly tragic case, where the patient ultimately died by suicide. 

Facts of the Case

The patient, Mr P, was a 27-year-old man who had recently moved to a new state to take a job with a major airline company. The job proved to be very stressful, and Mr P began suffering from anxiety and panic attacks, leading him to seek help from a physician.

Mr P had no primary physician since his move, so in August he made a new patient appointment with a local primary care practice and was treated by Dr M. The patient explained to the physician that the move and new job had been more stressful than anticipated. He described symptoms including panic attacks, palpitations, shortness of breath, excessive worrying, and fear of losing control. He told the physician that he’d had the panic attacks for almost a year but they had been worsening in frequency and intensity.

Physically, the patient was healthy, with normal vitals. The physician noted that Mr P was a large-sized man, standing well over six foot three, and weighing close to 300 pounds. 

Dr M noted in the patient’s record that Mr P was suffering from an anxiety disorder and told the patient he was going to prescribe medication to help. The physician wrote prescriptions for citalopram (20mg daily, with 6 refills) and alprazolam (0.5mg, up to 3 times a day as needed for panic attacks, with 2 refills). 

The physician did not schedule a follow-up appointment with Mr P. Instead, he recommended that Mr P return in 3 months. Upon leaving the physician’s office, Mr P filled the prescriptions and began taking both medications. 

Less than a month later, in mid-September, Mr P went out for dinner and drinks with his fiancé. After several hours of drinking at the restaurant’s bar, Mr P and his fiancé had to be driven home by the restaurant’s manager because they were too intoxicated to drive. After arriving home, Mr P shot himself in the head with a handgun. He was transported to the closest hospital for emergency treatment, but he was not able to be resuscitated. 

After Mr P’s death, his parents sought counsel from a plaintiff’s attorney. The attorney hired an expert physician to go over Mr P’s records. The expert was critical of Dr M’s treatment of the patient and believed the physician had failed to treat the patient with the requisite standard of care. The attorney encouraged the parents to file a medical malpractice lawsuit against Dr M, and they did.

After Dr M was notified about the case against him, he met with the attorney provided by his medical malpractice insurance. While Dr M and the attorney both agreed that what happened to the patient was tragic, neither thought the physician should be liable for the patient’s action.

Pharmacist Gets Prison Time for Illegally Selling Prescription Cough Syrup

A Michigan pharmacist has been sentenced to 3 years in federal prison for illegally dispensing promethazine cough syrup. The pharmacist ordered more than $2.5 million dollars worth of the prescription syrup from various wholesale distributors and then sold it to drug dealers. When consumed at higher than recommended dosages, promethazine cough syrup can produce tranquilizing and euphoric effects. On the illegal street market, the drug is often referred to as “Green Drink” or “Purple Drink.” The pharmacist was ordered to forfeit approximately $9 million dollars of his earnings from these illegal transactions. 

Doctor Fraudulently Issues Over 500 Prescriptions for Opioids

A former doctor from Texas was sentenced to 30 months in federal prison for dispensing controlled substances without a legitimate medical purpose. The doctor admitted that he fraudulently issued more than 500 prescriptions, most of which were for opioids, in the names of family members (both living and deceased), former patients and other individuals after his medical license had expired and then been suspended. He then conspired with others to distribute the medications to unknown individuals.

Distributing Misbranded Drug Lands Clinician in Hot Water

A doctor from Louisiana was charged with distributing misbranded drugs, including medroxyprogesterone. According to the US Attorney’s Office, Eastern District of Louisiana, the physician had introduced the misbranded drugs, which lacked adequate directions for use, into interstate commerce between April 2018 and March 2023. A conviction could result in 1 year of prison time for the doctor and up to 1 year of supervised release.

Doctor Establishes Pain Management Clinic for Unlawful Purposes

A Florida doctor has been convicted of unlawfully dispensing and distributing controlled substances. The doctor established a pain management clinic from which he then issued prescriptions for controlled substances such as oxycodone, morphine, and alprazolam to patients without a legitimate medical need. Some prescriptions were even prewritten and handed to office managers to sell for cash payments of $250 to patients. Data from Florida’s prescription drug monitoring program showed that the doctor prescribed opioids to more than 1000 patients, almost a third of whom were found to have criminal records related to drug dealing.

Two Doctors Rack Up Multiple Charges for Illegal Ketamine Administration

Two Missouri doctors, a psychiatrist and an internal medicine specialist, were indicted and accused of illegally administering ketamine to patients. Though the psychiatrist was authorized by the Drug Enforcement Administration (DEA) to administer controlled substances, the clinic that was set up to provide the intravenous ketamine infusions for patients with serious mental health illnesses was not registered for this type of treatment. The indictment also alleges that the psychiatrist allowed the internal medicine specialist to use his DEA registration to administer ketamine infusions and esketamine nasal spray without direct supervision and that the ketamine and esketamine were unlawfully stored in the facility. The internal medicine specialist was also charged with Medicare fraud because he falsely used the psychiatrist’s name to bill for the services.

The hallucinogenic drug psilocybin, when used in combination with psychotherapy sessions, may reduce or eliminate depression in patients with cancer, new research suggests.^1,2

Prior research showed that depression reduces quality of life and increases the risk of death in patients with cancer, and common treatments for depression have generally produced poor results in cancer patients.¹

However, psilocybin and psychotherapy sessions provided a sustained improvement in depressive symptoms in a small trial of cancer patients with moderate to severe depression.^1,2

Though more research is needed, these findings “could have implications for helping millions of patients with cancer who are also struggling with the severe psychological impact of the disease,” study author Manish Agrawal MD, of Sunstone Therapies in Rockville, Maryland, said in a statement.³

Psilocybin had previously demonstrated benefits in patients with life-threatening illnesses and psychologic distress.¹ Psilocybin is a serotonergic agonist, found in many species of mushrooms, that interacts with 5-HT_2A receptors in the brain, resulting in altered perception, cognition, affect, and ego function. ^1,4

Because of a high potential for psilocybin misuse and production of an altered mental state, studies of psilocybin are typically designed with a 2:1 therapist‐to‐patient ratio.¹ To maximize safety for both patients and staff, most studies have been performed in psychiatric hospitals or academic centers.

For their phase 2 study (ClinicalTrials.gov Identifier: NCT04593563), Dr Agrawal and colleagues tested psilocybin in combination with psychotherapy in the outpatient setting and with a 1:1 therapist‐to‐patient ratio.¹

Study Details and Design

The study included 30 adult cancer patients who had moderate to severe depression and no psychotic features. The patients were referred by psychiatric and oncology services. They were required to be off antidepressant drugs, antipsychotic agents, and medical cannabis when screened for the study. 

About half of the patients (46.7%) had curable cancers. The most common cancers were breast cancer (33.3%) and leukemia/lymphoma (26.7%). Most patients (70%) had received at least 1 prior line of cancer therapy, and 50% had previously received antidepressants. The mean age of the patients was 56 years, 70% were women, and 80% were White.

After screening, each patient first met with their therapist alone for a preparatory session. In this session, patients received information about psilocybin treatment, had their medical history taken, and underwent some testing (physical exam, echocardiogram, etc.).

Patients had a second visit 1 day before receiving psilocybin treatment. In this visit, patients had group therapy for 75 minutes and individual therapy for 45 minutes. Patients received additional education during this visit, and any concerns they had were addressed.

At visit 3, patients received psilocybin at 25mg (five 5mg capsules). They were required to remain in the treatment facility for 8 hours after treatment. They were treated in groups of 3 or 4 people, but they were situated in adjacent rooms that were separated by sliding doors and open to a common area. Each patient was observed by their therapist, and 2 lead clinicians monitored the sessions via live video.

Visits 4 and 5 included both group and individual therapy sessions, exploring the significance, meaning, and impact of the experience. The researchers also assessed the safety and efficacy of treatment during visits 4 to 7.

Results: “Robust” and Sustained Benefit

The researchers measured changes in depression severity using the Montgomery-Asberg Depression Rating Scale (MADRS), which consists of 10 items, scored from 0 (normal) to 6 (severe).

Patients experienced rapid and “robust” reductions in MADRS scores from baseline, according to the researchers. The mean difference from baseline to week 8 was -19.1 points (P <.001). There was a mean difference of -17.8 points from baseline to week 1 and -19.2 points from baseline to week 3.

Overall, 80% of patients had a sustained response to psilocybin. Half of patients had a full remission of depressive symptoms (defined as a MADRS score below 10) at week 1, which persisted for at least 8 weeks.

Most patients had clinically meaningful reductions in their depressive symptoms from baseline to week 8, whether they had curable cancers (79.6%) or noncurable cancers (61.9%).

The researchers noted that there were no serious adverse events (AEs) related to psilocybin and no reports of suicidality. AEs were generally mild. The most common AEs of any severity were headache (80%), nausea (40%), crying (26.7%), and mood alteration (26.7%).

Patient Perceptions and Implications

In a companion study to the phase 2 trial, researchers evaluated patients’ reactions to the group therapy sessions.²

The researchers conducted interviews with 28 of the patients after the final psychotherapy session. Interviews were conducted an average of 2.9 months later, and the average duration of the interviews was 90 minutes.

Patients said the group therapy approach made them feel safe and prepared for psilocybin treatment and fostered feelings of connection, belonging, self-transcendence, and compassion.

“Many described an ongoing transformative impact on their lives and well-being more than 2 months after having received psilocybin, feeling better equipped to cope with cancer and, for some, end of life,” study author Yvan Beaussant MD, of the Dana-Farber Cancer Institute in Boston, said in a statement.³

The authors acknowledged that additional research is needed but concluded that these findings suggest psilocybin-assisted psychotherapy could potentially be integrated into cancer care.

“It’s really, really new, and there are a lot of kinks to work out, but it looks very, very promising from a research perspective and from what I see clinically,” said Larry Shapiro, PhD, of Quantum Behavioral LLC, in St Louis, Missouri, who was not involved in this research.

Disclosures: Dr Shapiro disclosed a relationship with Compass Pathways PLC. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original references for those disclosures.

Dr C was a cardiologist who worked in a mid-sized practice. He was well liked by his patients and had been seeing some of them for many years. One such patient was Ms P, aged 70. Ms P had a variety of cardiac issues, including atrial fibrillation, 2 mechanical heart valves, and a pacemaker. The patient was taking the anticoagulant medication warfarin to reduce her risk of stroke.

Ms P was on a schedule to have monthly blood work done to check her International Normalized Ratio (INR) level. In this way, her warfarin levels were being monitored regularly.    

There came a time when Dr C recommended that Ms P have elective surgery to have the battery in her pacemaker replaced. Ms P agreed, and the cardiologist stopped her warfarin 5 days before the surgery. Prior to the surgery, Ms P’s INR was normal. 

The procedure took place as planned and the battery was replaced without issue. Following the procedure, Dr C had the patient begin taking the blood thinner again, which she did. The following day, however, Ms P returned to the physician’s office with bleeding and a hematoma on the procedure site. Dr C, concerned about the possibility of an infection in the area, prescribed an antibiotic, sulfamethoxazole-trimethoprim, for 5 days. The physician also ordered an INR test for the patient for the following day.

The next day, Ms P went for her bloodwork which revealed an INR of 3.2. Dr C was satisfied with this number and advised the patient to go back for another INR in 1 month, as usual. This was the last conversation Dr C would ever have with his patient. 

Less than a month later, Ms P was brought to the emergency department with clear signs of bleeding. Hospital staff worked feverishly to save her. Her INR was 22.8 and she was grossly anemic. Ms P was given blood transfusions in an attempt to replace the blood loss but it was too late. She coded numerous times and died the following day.

After her funeral, her family sought the counsel of a plaintiff’s attorney. They did not understand why Ms P had not been monitored more closely following her procedure. The plaintiff’s attorney had a medical expert look over the records and the expert was critical of Dr C’s treatment of the patient, specifically of his failure to monitor the blood thinner more closely after restarting the medication following Ms P’s pacemaker battery replacement procedure. The attorney agreed to take the case and he filed the papers and served Dr C with notice of the lawsuit. 

Dr C was saddened and upset over the death of his patient, but he did not feel responsible for it, which is what he said after being notified about the lawsuit. Prior to going to the emergency department, her INR had been acceptable, if slightly high, he told his defense attorney. And if she had been in such bad shape before calling an ambulance, why had she not contacted him? 

The case moved forward through the discovery phase and although his attorney had told Dr C that cases are often dismissed or settled early on in the process, the case against him was still proceeding.

The American Medical Association officially recognized obesity as a disease in June 2013 after decades-long controversy.¹ Although lifestyle interventions are promoted as a first-line obesity treatment, the resultant short-term weight loss often fails to improve long-term outcomes.² In the search for other solutions, glucagon-like peptide-1 (GLP-1) receptor agonists such as tirzepatide (Mounjaro) and semaglutide (Wegovy^® or Ozempic^®) have greatly increased in popularity throughout the past year.

However, the media frenzy surrounding tirzepatide and semaglutide has raised concerns about this latest obesity treatment. Originally developed for diabetes, tirzepatide and semaglutide faced widespread drug shortages as celebrities such as Elon Musk and Chelsea Handler accredited the drugs for their weight loss. Resultant backlash attributed the anti-obesity medication boom to fatphobia.³

Still, the myriad of obesity’s biological and psychosocial obstacles can feel insurmountable after lifelong efforts to lose weight. But are GLP-1 receptor agonists the right solution for patients struggling to climb uphill to a “healthy weight”? Or do these injectables amplify disordered eating, weight stigma, and reliance on expensive pharmaceuticals? 

Perhaps it depends on who you ask.

For an insider’s view on this timely topic, we spoke with board-certified bariatric physician Kevin Huffman, DO and leading psychiatrist Michael Olla, MD, both of whom have decades of experience treating obesity and navigating its social implications.

Can BMI Justify Anti-Obesity Injections?

Although obesity is associated with higher risks for type 2 diabetes, certain cancers, mobility issues, and heart disease,¹ some experts feel that anthropometric measures such as body mass index (BMI) fail to reflect true health status.

A veteran in his field, Dr Huffman has treated more than 10,000 patients with obesity and trained and mentored hundreds of physicians and allied healthcare providers. He is also the CEO and founder of AmBari Nutrition and the founder and president of The American Bariatric Consultants. 

Dr Huffman admits that BMI does not tell the whole story about whether anti-obesity medication makes sense for an individual patient.

“BMI, a useful initial screening tool, necessitates more nuanced considerations when prescribing injectable weight loss medications,” he explains. “We acknowledge the uniqueness of each patient; body composition, fat distribution, metabolic health, and underlying medical conditions significantly influence our decision-making process.” 

He continues, “For instance, certain patients may present with central obesity despite having a lower BMI, this suggests an escalated risk for obesity-related complications. Diabetes or hypertension, obesity-related health issues, may still qualify individuals for intervention despite a slightly lower BMI than the conventional threshold.”

Providing Quality Care in a “Fatphobic” Environment

Medical professionals are far from immune to stigmatizing patients with obesity. Research findings show that over 50% of healthcare professionals attribute obesity to a lack of willpower.⁴

In addition, more than half of adults with overweight in Western countries report experiencing weight stigma. As a result of this stigma, patients with obesity and overweight are more likely to avoid healthcare.²

According to Dr Huffman, “Navigating through this deeply ingrained prejudice is crucial when prescribing injectable anti-obesity medications: potent tools in aiding patients on their weight loss journey. Unfortunately, many barriers arise due to the fear and stigma surrounding obesity, these factors tragically deter numerous individuals from pursuing these potentially life-altering treatments.”

He urges prescribers to approach these conversations with empathy, understanding, and a non-judgmental attitude to foster support and empower patients to access necessary, deserved care for a better quality of life.

Dr Olla is the medical director at Valley Spring Recovery Center. He is a leading authority figure in the field of psychiatric medicine who focuses on holistic healing, patient well-being, and evidence-based practices.

“Believe it or not, fatphobia or weight bias is a common issue in plenty of medical professionals,” Dr Olla explains. “Heavier patients tend to encounter lots of medical professionals with weight stigma. In these cases, doctors tend to focus so much on their weight that they ignore other symptoms these patients primarily come in for. This doesn’t just affect patients but also doctors who mean well.”

To address these biases, Dr Olla encourages medical professionals to have honest conversations with patients before prescribing anti-obesity medications. He suggests openly discussing fatphobia’s potential influence on the decision-making process and explaining the medication’s benefits and risks without pressuring patients to use medication unless medically justified.

According to Dr Olla, reviewing other treatment options respects a patient’s autonomy and right to make their own treatment decisions.

“The key is to focus on how the drug can help reverse or at least slow down the effects of obesity on the body,” he explains. “This can help the patient understand that their doctor is concerned about their overall health, rather than their weight.”

Human papillomavirus (HPV) remains the most common sexually transmitted infection and can be transmitted from one individual to another simply by skin-to-skin contact. This double-stranded virus invades cervical, cutaneous, and anogenital epithelium, causing cellular changes that may physically alter the appearance of tissues both microscopically and to the naked eye.¹ Over time, dysplasia associated with continued HPV infection may lead to cancer.² 

Primary care providers have a unique opportunity to improve outcomes by implementing screening for HPV, preventative measures against the virus (ie, vaccinations), and education regarding the significance of HPV infection and the risk of cancer development. Although most patients are unaware of infection with the virus because of clearance by a healthy immune system within 1 to 2 years^3,4 or regression to near-normal cytology after the initial infection, it is important to note that at least 18 strains of HPV are known to pose a high risk for cervical cancer.²  The majority of patients acquire an HPV infection between ages 15 and 25, and more than 4000 people die from cervical cancer each year.^3,5 From 2016 to 2020, cervical cancer was diagnosed at a rate of 7.7 cases per 100,000 women.⁶ Persistence of high-risk infection increases the likelihood of developing advanced, aggressive cancer.⁵ Therefore, the early detection of HPV infection is essential to control and treat the disease, maintain a patient’s quality of life, and slow or halt the progression of dysplasia to cancer development. 

There are multiple modifiable and nonmodifiable factors that lengthen the lifespan of infection (Figure 1).^2,7 These include smoking, having a compromised immune system, use of oral contraceptives, and/or a coexisting herpes infection.² Each of these factors weakens the body’s ability to fight off viral infections. Other risk factors for cervical cancer include engaging in practices or behaviors that increase the risk of sexually transmitted infections such as unprotected sex, multiple sexual partnerships over one’s lifetime, early age of sexual activity, and low socioeconomic status (the latter likely due to its negative effect on access to adequate health care).⁷ These risk factors should continue to be addressed by counseling in the primary care setting. 

Primary Prevention

Primary prevention of HPV infection begins with vaccination. Providers should recommend vaccination in all adolescents as vaccination decreases the risk of HPV infection and rates of cervical precancers.³ There is a 9-valent vaccine currently available that protects against the most common strains of HPV that lead to genital warts or cervical cancer: strains 6, 11, 16, 18, 31, 33, 45, 52, and 58.⁸ The vaccine is usually administered to males and females aged 11 to 12 years but can be administered to patients as young as age 9. ⁹ Primary care providers should prioritize educating themselves on the vaccine recommendations, side effects, and proper administration to bring comfort and understanding to young patients and their parents or guardians. Headache, syncope, injection-site reactions, erythema, and pain are some of the most common post-vaccination side effects to be aware of.

It is imperative to stress that vaccination should be completed before patients become sexually active. Unfortunately, vaccine effectiveness decreases with increased age.³ Herweijer et al conducted a population-based study in Sweden from 2006 to 2013 that followed the incidence of high-grade cervical lesions in girls and women aged 13 to 29 and compared outcomes based on the age when they initiated vaccination. Their research suggests that vaccination effectiveness may decline after a patient turns 17 years old (Figure 1).¹⁰ They found similar effectiveness of the vaccine between different classifications of cervical lesions. A systematic review by Ellingson et al also demonstrated that although still beneficial in older age groups, vaccination against HPV can significantly prevent the development of cervical abnormalities and cervical cancer when administered to patients at a younger age.¹¹ Of note, “catch-up” vaccinations for adults who did not receive them in adolescence are not recommended after a specific age threshold (26 years of age for women and 21 years of age for men).⁹

Screening with a pap smear in the medical setting is the first step in detecting precancerous cervical lesions in patients with HPV infection and no symptoms.³ During the procedure, a speculum is used to visualize the cervix and evaluate for any frank abnormalities such as drainage, polyps, or abrasions. Handheld tools are then used to scrape and collect cells from both the endocervix and the ectocervix. Collected cells are examined under a microscope by a cytopathologist to detect abnormal changes. This process of testing is called cervical cytology. Areas of high-grade cervical cell changes require excision to prevent progression.¹² 

Pap smears can be performed in both primary care and gynecologic settings. Preparation and completion of the screening pap smear procedure within the primary care setting can save time and avoid scheduling delays often seen at a specialist’s practice. This can also help eliminate barriers to care, including travel to additional offices, additional copays, and additional time that often deters patients from following through with referrals made by primary care providers.

As of 2018, the United States Preventative Services Task Force (USPSTF) recommends that women aged 21 to 29 should be screened every 3 years with cytology (Table 1). Women aged 30 to 65 are given 3 options: screening every 3 years with cytology, screening every 5 years with high-risk HPV (hrHPV) testing alone, or screening every 5 years with cytology and hrHPV testing at the same time. High-risk HPV testing involves the same sampling technique used for cytology during a regular pap smear, but the collection is then analyzed for HPV identification after undergoing many cycles of nucleic acid amplification such as polymerase chain reaction.¹³ Studies have shown that hrHPV testing detects at least 90% of precancers and cancers and is therefore superior to cytology in its ability to find more lesions per screen. When samples for cytology and hrHPV testing are collected during the same examination, a method called cotesting, the percentage of lesion detection is even greater.³ Providers must be mindful that these guidelines should be adjusted and personalized on a patient-to-patient basis to ensure each patient’s risks are adequately assessed. Annual screening examinations as previously recommended may not be appropriate for every individual.

Table 1. Recommendations for Screening for HPV¹³ 

When abnormal cytology is detected or HPV genotyping is positive, patients should be referred for colposcopy with or without a biopsy. The risk of cervical intraepithelial neoplasia (CIN) 2 or worse should be 4% or greater to indicate colposcopy.¹² 

Acetic acid (3% to 5%) solution aids in the visualization of abnormal cells on the cervix by causing a temporary color change from the normal pink of the cervical and vaginal tissue to white. After the acetic acid is applied, acetowhitening on the cervix can be visualized to differentiate classifications of CIN, if present (Figures 3-5).¹⁴ The degree of acetowhitening correlates with low and high-grade lesions.¹² Results of acetic acid application may range from no acetowhitening at all, to thin and translucent or thick and rapidly fading. Acetowhitening may or may not be present in the detection of cancer. Thus, the absence of acetowhitening does not rule out a possible cancer diagnosis. Acetowhitening is a tool that can be paired with the identification of other lesion characteristics and findings found on exam to assist in diagnosis.¹²

The terms high-grade squamous intraepithelial lesion (HSIL), moderate to severe dysplasia, and CIN 2 or 3 are used to classify precancerous lesions.³ The most common high-risk genotypes of HPV are 16, 18, 31, and 33.² These genotypes produce CIN 3 cellular changes, the classification that denotes the greatest severity of lesions and the final precursor before a lesion on the cervix becomes an invasive carcinoma.² In comparison to CIN 3, CIN 1 lesions have an 80% rate of regression to normal or less severe dysplasia.² In the United States, genotypes 16 and 33 are the most common found in women at risk for persistent HPV infection with progression.² A 2018 observational study by Bruno et al showed that HPV 16 infections are 5 times more likely than normal cells to progress to high-grade lesions.¹⁵ Closer monitoring of these patients is required to ensure worsening dysplasia receives early intervention. 

Studies have shown that cervical cancer develops more frequently in patients who do not undergo screening or who are not screened often enough.³ In a multivariate analysis of women from Puerto Rican with cervical cancer, Gómez-Vargas et al compared both localized tumor staging and 5-year survival between a group of women who underwent screening 3 years prior to their diagnosis and those who had not. Of the women, 43.5% of those who had been screened had a localized tumor, while only 33.1% of the unscreened group had the same staging. The 5-year survival rate was also higher among the screened women vs those who had not been screened within the specified timeframe (72% vs 54%).¹⁶ These findings further support the need for timely screening and its effect on more desirable outcomes in women at risk of developing HPV-related cancers. 

Barriers to Screening

It is the responsibility of primary care providers to do due diligence and provide care that falls within the appropriate scope of practice. Primary care providers who do opt to train and acquaint themselves with screening and treatment guidelines may face other difficulties not related to their ability to perform these duties. Practitioners may find themselves without support from gynecologists when telehealth consultations may be needed. Their offices may have staff shortages and their schedules may not allow them the time needed to commit to extensive gynecologic appointments. A lack of available chaperones may also pose a problem, compromising the security and confidence of everyone involved in these sensitive encounters. Primary care providers wishing to expand their scope to accommodate these patients must take these possibilities into account and find methods to address them.

As medical specialties become more complex and less accessible to patients, it becomes the responsibility of providers in primary care to offer opportunities for procedures such as cervical cancer screening in a timely manner. A cross-sectional study by Suk et al in 2022 proposed that 2 of the most modifiable barriers to up-to-date cervical cancer screening may be lack of a patient’s knowledge of the need to be screened and failure of health care professionals to recommend screening to their patients.¹⁷ 

Patients in rural areas are more likely to be without insurance, lack means for transportation, and have limited access to gynecologic specialists in their area, thus increasing their likelihood of being unscreened or under screened, further supporting the need for primary care providers to offer cervical cancer screening whenever possible. Providers may even find success in encouraging the use of HPV self-tests as a means for increasing the probability that a patient with positive results will then have a follow-up pap smear.¹⁸

Author Bios

Jazzlin Sharpe, MPA, PA-C, works as an orthopedic surgery PA in Augusta, Georgia. She graduated from the Physician Assistant program at Augusta University in 2023.

Amber Casado, MPAS, PA-C, is an Assistant Professor at Augusta University in the Physician Assistant Department. She also practices clinically in hospital medicine. She graduated with her Master of Physician Assistant from Augusta University in 2017.

References

1. Manini I, Montomoli E. Epidemiology and prevention of Human Papillomavirus. Ann Ig. 2018;30(4 Supple 1):28-32. doi:10.7416/ai.2018.2231

2. Bruno MT, Cassaro N, Bica F, Boemi S. Progression of CIN1/LSIL HPV persistent of the cervix: actual progression or CIN3 coexistence. Infect Dis Obstet Gynecol. 2021;2021:6627531. doi:10.1155/2021/6627531

3. Eun TJ, Perkins RB. Screening for cervical cancer. Med Clin North Am. 2020;104(6):1063-1078. doi:10.1016/j.mcna.2020.08.006

4. de Sanjosé S, Brotons M, Pavón MA. The natural history of human papillomavirus infection. Best Pract Res Clin Obstet Gynaecol. 2018;47:2-13. doi:10.1016/j.bpobgyn.2017.08.015

5. Surveillance, Epidemiology, and End Results Program (SEER). National Cancer Institute; 2023. Accessed October 30, 2023. https://seer.cancer.gov/statfacts/html/cervix.html#incidence-mortality

6. SEER*Explorer: An interactive website for SEER cancer statistics [Internet]. Surveillance Research Program, National Cancer Institute; 2023 Apr 19. [updated: 2023 Jun 8]. Accessed October 30, 2023. https://seer.cancer.gov/statistics-network/explorer/

7. Balasubramaniam SD, Balakrishnan V, Oon CE, Kaur G. Key molecular events in cervical cancer development. Medicina (Kaunas). 2019;55(7):384. doi:10.3390/medicina55070384

8. Giuliano AR, Joura EA, Garland SM, et al. Nine-valent HPV vaccine efficacy against related diseases and definitive therapy: comparison with historic placebo population. Gynecol Oncol. 2019;154(1):110-117. doi:10.1016/j.ygyno.2019.03.253

9. Laprise JF, Chesson HW, Markowitz LE, et al. Effectiveness and cost-effectiveness of human papillomavirus vaccination through age 45 years in the United States. Ann Intern Med. 2020;172(1):22-29. doi:10.7326/M19-1182

10. Herweijer E, Sundström K, Ploner A, Uhnoo I, Sparén P, Arnheim-Dahlström L. Quadrivalent HPV vaccine effectiveness against high-grade cervical lesions by age at vaccination: A population-based study [published correction appears in Int J Cancer. 2017 Jul 1;141(1):E1-E4]. Int J Cancer. 2016;138(12):2867-2874. doi:10.1002/ijc.30035

11. Ellingson MK, Sheikha H, Nyhan K, Oliveira CR, Niccolai LM. Human papillomavirus vaccine effectiveness by age at vaccination: A systematic review. Hum Vaccin Immunother. 2023;19(2):2239085. doi:10.1080/21645515.2023.2239085

12. Burness JV, Schroeder JM, Warren JB. Cervical Colposcopy: Indications and Risk Assessment. Am Fam Physician. 2020;102(1):39-48.

13. US Preventive Services Task Force, Curry SJ, Krist AH, et al. Screening for Cervical Cancer: US Preventive Services Task Force Recommendation Statement. JAMA. 2018;320(7):674-686. doi:10.1001/jama.2018.10897

14. Sellors JW, Sankaranaravanan R. Chapter 7: Colposcopic assessment of cervical intraepithelial neoplasia. In: Sellors JW, Sankaranaravanan R, eds. Colposcopy and Treatment of Cervical Intraepithelial Neoplasia: A Beginner’s Manual. World Health Organization; 2003:62-63.

15. Bruno MT, Ferrara M, Fava V, Rapisarda A, Coco A. HPV genotype determination and E6/E7 mRNA detection for management of HPV positive women. Virol J. 2018;15(1):52. doi:10.1186/s12985-018-0957-z

16. Gómez-Vargas V, Ortiz-Ortiz KJ, Almodóvar-Rivera I, Torres-Cintrón CR, Deshmukh AA, Ortiz AP. Screening history and survival among women with cervical cancer in Puerto Rico. J Low Genit Tract Dis. 2023;27(1):19-23. doi:10.1097/LGT.0000000000000709

17. Suk R, Hong YR, Rajan SS, Xie Z, Zhu Y, Spencer JC. Assessment of US Preventive Services Task Force guideline-concordant cervical cancer screening rates and reasons for underscreening by age, race and ethnicity, sexual orientation, rurality, and insurance, 2005 to 2019. JAMA Netw Open. 2022;5(1):e2143582. doi:10.1001/jamanetworkopen.2021.43582
18. Lea CS, Perez-Heydrich C, Des Marais AC, et al. Predictors of cervical cancer screening among infrequently screened women completing human papillomavirus self-collection: My body my test-1. J Womens Health (Larchmt). 2019;28(8):1094-1104. doi:10.1089/jwh.2018.7141

Across the often insufferable world of social media platforms such as TikTok, occasionally, a healthcare-related trend deserves a second look. One of these trends is a group of young people who felt that the period coinciding with the global pandemic from 2020 to 2022 went by as a blur; it appeared that they remembered who they were prepandemic and post, but little else in between.

This phenomenon has been coined “Covid amnesia.” It appears to be the result of the world having moved on so quickly from the pandemic (ie, quickly returning to large-scale concerts and tourism) that hardly anyone seems to have the appetite to discuss the suffocating years between 2020 and 2022.

Some psychiatrists see this phenomenon as a means to avoid talking about traumatic events. In a rushed bid to return to normalcy, public discourse on the pandemic has largely vanished from view. Having been held back for years, many have chosen to leave the chaos and the heartbreak behind and forge a new path forward. 

Nevertheless, the academic dissection of the worst pandemic in a century has animated researchers; this is evidenced by the considerable quantity of academic work being published in the period that followed. In stark contrast with the general public, researchers feel that the cooled-down atmosphere of today is perfect for picking apart various aspects of the pandemic and to advocate for evidence-based policy changes slowly. 

COVID-19 and NMOSD 

The general strategy during the pandemic was to shield vulnerable/elderly populations from any possible contact with COVID-19; this was seen as necessary to preserve life. At the top of the list of vulnerable individuals are patients suffering from chronic neuro-inflammatory disorders such as multiple sclerosis and neuromyelitis optica spectrum disorder (NMOSD). 

Read more about NMOSD etiology 

Statistical studies seem to lend validity to these concerns; patients with these disorders had higher hospitalization rates, and patients with greater disability scores were likely to suffer from severe COVID-19. Vaccines, however, have tremendously altered the medical landscape for the better. Nevertheless, anomalies remained among patients with these disorders compared with the general population. 

Eisler and colleagues conducted a study about how the various treatments for multiple sclerosis and NMOSD come together in influencing outcomes during the pandemic. They carried out a single-center, observational study in a multiple sclerosis center in Switzerland and published their findings in the Journal of Clinical Medicine. For this study, they collected extensive clinical information from participants, including vaccination status. 

Among 352 patients with multiple sclerosis/NMOSD, 315 were vaccinated with mRNA vaccines. Overall, 134 had at least 1 experience of COVID-19. Researchers found that patients who were older, had a higher Expanded Disability Status Scale score, and a positive vaccination status had a lower risk of contracting COVID-19; inversely, individuals treated with antiCD20 appear to be at an increased risk of contracting COVID-19. 

NMOSD Complicating Vaccinations 

Although the medical community is overwhelmingly in favor of vaccines due to the benefit it confers to society as a whole, including to those who choose to remain unvaccinated, we should be clear-eyed about how certain negative factors are associated with COVID-19 vaccines.

In a letter to the editor of Multiple Sclerosis and Related Disorders, Josef Finsterer of the Neurology and Neurophysiology Center in Vienna, Austria, contends that there are considerable case studies documenting patients with newly developed NMOSD after a SARS-CoV-2 vaccination. He cites examples of patients who seemingly develop NMOSD out of the blue after receiving various COVID-19 vaccinations. 

“It is well known that SARS-CoV-2 vaccinations can trigger relapses of NMOSD,” he wrote. “In a study of 30 patients with aquaporin (AQP)-IgG positive NMOSD, 1 of 26 patients (4%) experienced a relapse within 1 month of the SARS-CoV-2 vaccination.” 

However, public information campaigns in many parts of the world appeared to direct all individuals to receive a COVID-19 vaccine, regardless of preexisting vulnerabilities. In fact, a digital COVID-19 vaccine passport was almost a prerequisite entry pass for most facilities in Malaysia, where I reside; conscientious objectors would find themselves unable to maneuver freely in their own country for months until vaccine mandates were relaxed.

All individuals were encouraged to get the vaccine, even those deemed vulnerable because the potential benefits outweighed any risks. Whether this statement can bear the intense academic scrutiny coming its way is yet to be seen. 

Read more about NMOSD treatment 

Because a lot of evidence for and against COVID-19 vaccines appear anecdotal in nature, much more research is needed to separate fact from fiction. Public health policies implemented during the pandemic will doubtlessly be discussed for years to come.

Granted, the COVID-19 pandemic caught the world unprepared. However, its relationship to autoimmune disorders deserve full exploration. Only then can we devise better guidelines if the next pandemic arrives and provide the public with solid, science-backed data about how to prevent infection and protect vulnerable individuals at the same time. 

Data from several recent phase 3 trials support changes to standard care for non-small cell lung cancer (NSCLC), according to researchers.

Results from the MARIPOSA trial suggest that amivantamab plus lazertinib represents a new first-line standard of care for patients with advanced, EGFR-mutant NSCLC.¹

The MARIPOSA-2 trial suggests that amivantamab plus chemotherapy should be considered a new standard of care for patients with advanced, EGFR-mutant NSCLC who have disease progression on or after osimertinib.²

Results from the PAPILLON trial suggest that amivantamab plus chemotherapy represents a new standard of care for the first-line treatment of patients with NSCLC who have EGFR exon 20 insertion mutations.³

The LIBRETTO-431 trial suggests that selpercatinib should be considered a first-line standard of care for RET fusion-positive, advanced NSCLC.⁴

And results from the KEYNOTE-167 trial suggest that neoadjuvant pembrolizumab plus chemotherapy, followed by adjuvant pembrolizumab, should be standard care for early-stage NSCLC.⁵ Results from all of these trials were recently presented at the ESMO Congress 2023.

MARIPOSA: Amivantamab Plus Lazertinib vs Osimertinib

In the MARIPOSA trial, amivantamab plus lazertinib significantly improved progression-free survival (PFS) when compared to osimertinib monotherapy in patients with previously untreated, advanced EGFR-mutant NSCLC.¹

The trial (ClinicalTrials.gov Identifier: NCT04487080) enrolled 1074 patients with treatment-naïve, EGFR-mutant, locally advanced or metastatic NSCLC. Patients were randomly assigned to receive amivantamabplus lazertinib (n=429), osimertinib alone (n=429), or lazertinib alone (n=216).

The median follow-up was 22.0 months. The study’s primary endpoint was PFS by blinded independent central review (BICR). The median PFS was 23.7 months with amivantamab plus lazertinib and 16.6 months with osimertinib (hazard ratio [HR], 0.70; 95% CI, 0.58-0.85; P <.001). The 12-month PFS rate was 73% and 65%, respectively. The 24-month PFS rate was 48% and 34%, respectively.

The median extracranial PFS was 27.5 months with amivantamab plus lazertinib and 18.5 months with osimertinib (HR, 0.68; 95% CI, 0.56-0.83; P <.001). The 24-month extracranial PFS rate was 53% and 38%, respectively. The overall response rate (ORR) was 86% with amivantamab plus lazertinib and 85% with osimertinib. The median duration of response was 25.8 months and 16.8 months, respectively.

The 24-month rate of PFS after first subsequent therapy (PFS2) was 72% with amivantamab plus lazertinib and 64% with osimertinib (HR, 0.75; 95% CI, 0.58-0.98; P =.03). Overall survival (OS) data were immature, but there was a trend toward improved OS with amivantamab plus lazertinib. The 24-month OS rate was 74% with amivantamab plus lazertinib and 69% with osimertinib (HR, 0.80; 95% CI, 0.61-1.05; P =.11).

These results suggest that amivantamab plus lazertinib represents a new first-line standard of care for patients with advanced EGFR-mutant NSCLC, according to study presenter Byoung Chul Cho, MD, PhD, of Yonsei University in Seoul, Republic of Korea.

Dr Cho noted, however, that grade 3 or higher treatment-emergent adverse events (AEs) were more common in the amivantamab-lazertinib arm than in the osimertinib arm — 75% and 43%, respectively.

Treatment-related AEs leading to discontinuation occurred in 10% of patients in the combination arm and 3% of those in the osimertinib arm. Diarrhea was more frequent in patients receiving osimertinib, but paronychia, rash, and hypoalbuminemia were more common with amivantamab plus lazertinib.

An AE of special interest was venous thromboembolism (VTE), which occurred in 37% of patients in the amivantamab-lazertinib arm and 9% of those in the osimertinib arm. The rate of treatment discontinuation due to VTE was 3% in the combination arm and 0.5% in the osimertinib arm.

Only 1% of patients in the amivantamab-lazertinib arm and none in the osimertinib arm were on anticoagulants during the study, and most VTEs in the amivantamab-lazertinib arm occurred within the first 4 months of treatment.

“Therefore, prophylactic dose anticoagulation is now recommended for the first 4 months of treatment in the ongoing trials of the amivantamab plus lazertinib,” Dr Cho said. “We need a better understanding of the impact of this new therapy on patient quality of life, particularly given a long treatment duration,” said study discussant Zosia Piotrowska, MD, of Massachusetts General Hospital in Boston.

She noted that there was a higher discontinuation rate for amivantamab plus lazertinib. “What is the impact of early amivantamab discontinuation?” she asked. “I think this will be important to evaluate to understand better whether patients need to continue amivantamab for the duration of first-line therapy.”

This month we look at a cautionary tale involving a physician’s use of social media in her practice. This fairly shocking story made it to the mainstream media. The physician, now permanently unlicensed, is currently facing over a dozen lawsuits from former patients.

Just the Facts

Dr G was a plastic surgeon whose practice specialized in cosmetic surgery of the face, breast and body. She received her degree in 2005, was in residencies through 2010, and was licensed to practice medicine in her state in 2009. Earlier in her career, she had performed reconstructive surgery for breast reconstruction and maxillofacial reconstruction after trauma and was medical director of breast services at a hospital. In 2012, as a mom of 3 children under 5 years old, she started her own practice, Roxy Plastic Surgery. The practice originally consisted of an office manager and patient coordinators, but by 2022 the staff had expanded to 20 people, including 2 social media staff. 

Starting in 2017, she discontinued accepting insurance and focused on cosmetic surgery. Her practice primarily specialized on surgery of the breast, abdomen, buttocks, thighs, and arms, including Brazilian butt lifts. She also performed fat grafting on breasts as well as breast augmentation, mastopexy, breast reductions, abdominoplasty, upper blepharoplasty, and labiaplasty, among other procedures.

Dr G’s practice was busy. In 2022, there was a 2-year wait list for her surgical practice, and she was performing 2 to 5 surgeries per day. Dr G understood the power of social media and started using it in her practice from the beginning. Believing that people might be getting unrealistic expectations about plastic surgery from television, she originally set up a Facebook account to educate people and prepare them, realistically, for recovery. She also wanted to demystify the surgical process and give patients and their families a “peek behind the curtain to be able to see what was going on back there.” She branched out to other social media platforms, including Instagram, Snapchat, and eventually TikTok. Dr G began posting (with patient consent) before and after pictures of patients on her social media streams.

Starting around 2014, Dr G began using Snapchat to show videos of surgeries. These were not livestreamed but were rather videotaped and posted afterwards. Later on, however, when the video-streaming social media site TikTok became popular, Dr G began using it to livestream surgeries in real time. To livestream the procedures, Dr G would have an employee filming and streaming to TikTok while Dr G performed the surgery. Her TikTok account grew in popularity, and the doctor would actively ask viewers to ‘follow’ or ‘like’ her social media. She gained a tremendous social media following over the next few years, with her patients referring to her as Dr Roxy, and themselves as “Roxy’s Foxies.” Her practice sold merchandise on its website, such as t-shirts, that she advertised via social media.

While livestreaming surgeries, Dr G would interact with the social media audience, which numbered up to 300,000 people, and answer questions and comments which were read to her by the camera operator. Dr G believed she was being the ‘most transparent surgeon that ever existed’ because she showed what she was doing and wasn’t trying to hide anything. But, starting in 2018, she began receiving cautions from the state Medical Board.

Almost 30 million Americans take aspirin for primary or secondary prevention of cardiovascular disease (CVD) or colorectal cancer (CRC).¹ For decades, aspirin has been recommended as primary prevention for patients at risk for CVD, despite the attendant increased risk of major bleeding.² However, the results of recent clinical trials have challenged the clinical risk-to-benefit trade-off of daily aspirin use.

The most recent recommendations from the US Preventive Services Task Force (USPSTF) have abandoned the routine recommendation for daily aspirin use for primary prevention of CVD.³ Continue reading to learn more about the potential benefits and harms of daily aspirin use.

What Are the Potential Benefits of Daily Aspirin?

Aspirin has been used for its antipyretic and analgesic properties long before it came into use to prevent or treat CVD. After the discovery of aspirin’s antiplatelet and antithrombotic effects, researchers began to explore the possibility of using it to prevent and treat acute coronary syndrome and stroke.²

At low doses, aspirin is an irreversible inhibitor of cyclo-oxygenase-1 (COX-1), which inhibits platelet function.³ In patients with pre-existing CVD, aspirin can reduce the risk of experiencing a CVD event by 21% and all-cause mortality by 13%. However, the benefit of daily low-dose aspirin use in patients without pre-existing CVD (primary prevention) is less clear.^1,3 

Although the systematic review commissioned by the USPSTF found that daily low-dose aspirin is associated with a clinically significant reduction in absolute risk of CVD events, it is a modest reduction, with an odds ratio (OR) of 0.9.⁴

Daily Aspirin Use: Current USPSTF Recommendations to Prevent Cardiovascular Disease

New studies have highlighted the potential for daily aspirin to cause harm. In 2022, the USPSTF released new recommendations on the use of aspirin for the primary prevention of CVD.³ The new recommendations are as follows⁵:

• For adults between 40 and 59 years of age with a 10% or greater 10-year CVD risk, the Task Force recommends that the decision to start aspirin therapy be an individual one. This recommendation is offered as a grade C recommendation, with moderate certainty of a small benefit.⁵ 

• For adults older than 60 years, the Task Force recommends against starting low-dose aspirin therapy. This recommendation is offered as a grade D recommendation, which recommends against using aspirin for this population.⁵ 

These recommendations apply to adults older than 40 years of age without signs or symptoms of CVD and not at increased risk for bleeding.

What Changed From the Previous USPSTF Recommendations?

The 2016 USPSTF recommendations had stronger recommendations for the use of aspirin to prevent CVD and CRC. The new recommendations concluded that there was insufficient evidence that low-dose daily aspirin reduces the incidence of or mortality from CRC.³ Therefore, the new recommendations only address daily aspirin use for the primary prevention of CVD.  

The previous recommendations advised initiating daily aspirin use for adults aged 50 to 59 years with a 10% or greater 10-year CVD risk without increased risk for bleeding, who have a life expectancy of 10 years or greater, and who are willing to take daily low-dose aspirin for at least 10 years. This recommendation was also a higher grade (Grade B — high certainty of a moderate benefit) compared with the updated recommendations.⁶ 

In the 2016 USPSTF recommendations, the Task Force recommended an individual decision for initiating aspirin use for adults aged 60 to 69 years with a 10% or greater 10-year CVD risk. This recommendation was offered as a grade C recommendation.⁶ 

The previous recommendations cited insufficient evidence for daily aspirin use in adults younger than 50 years and older than 70 years.⁶ The updated recommendations have addressed patients as young as 40 years.³ 

Why Did the USPSTF Recommendations Change?

New data on the potential risk of aspirin have prompted the change in the USPSTF recommendations on daily aspirin use for primary prevention of CVD. The primary risk of daily aspirin use is an increased risk of major bleeding such as gastrointestinal bleeding, intracranial bleeding, and hemorrhagic stroke.⁴ 

The factor contributing to the increased risk of bleeding is aspirin’s inhibition of platelet activity. Additionally, by inhibiting COX-1, aspirin may promote gastrointestinal bleeding by inhibiting the production of several prostaglandins that protect the gastrointestinal mucosa.³ 

Since the 2016 USPSTF recommendations, 3 trials have been published with a focus on special populations of patients, including those with older age, diabetes, and additional CVD risk factors.^7-9

Aspirin Use in Older Adults

A randomized, placebo-controlled clinical trial (ASPREE; ClinicalTrials.gov Identifier: 01038583) of more than 19,000 adults older than 70 years in Australia and the United States found that, compared with placebo, enteric-coated aspirin 100 mg resulted in a significantly higher risk of major bleeding. Additionally, aspirin 100 mg/d was not associated with a significantly lower risk of CVD compared with placebo.⁷ 

Aspirin Use in Adults With Diabetes 

A randomized, placebo-controlled trial (ASCEND; ClinicalTrials.gov Identifier: NCT00135226) of more than 15,000 adults with diabetes but without CVD found that, compared with placebo, aspirin 100 mg/d significantly reduced the risk of CV events (8.5% in the aspirin group vs 9.6% in the placebo group; P=.01). However, the authors concluded that these benefits were counterbalanced by the increased risk of bleeding (4.1% in the aspirin group vs 3.2% in the placebo group; P=.003).⁸  

Aspirin Use in Adults at Moderate Risk for CVD

The Aspirin to Reduce Risk of Initial Vascular Events (ARRIVE; ClinicalTrials.gov Identifier: NCT00501059) study was a randomized, placebo-controlled trial of more than 12,000 adults at moderate risk for CVD (defined as a 10% to 20% 10-year risk). Due to a lower-than-expected event rate, the authors were unable to address the role of aspirin in the primary prevention of CVD in a moderate-risk population. However, the results were consistent with the results from other trials with a low-risk population.⁹ 

Updated Evidence Report and Systematic Review for the USPSTF

The systematic review commissioned by the USPSTF included 11 randomized controlled trials (including the studies discussed above) and 1 pilot trial with more than 134,000 patients. The authors of this systematic review found that although low-dose aspirin was associated with a small reduction in CV events, it was also associated with small increases in major bleeding events.⁴ 

The results for aspirin use for the prevention of CRC were not as robust as those for primary CVD prevention and were highly variable.⁴ 

Authors of another systematic review and meta-analysis from 2019 on the association of aspirin use with CV events and bleeding events found that the absolute risk reduction of CV events (0.41%) did not outweigh the increased risk of major bleeding (0.47%).¹⁰ 

Implementing USPSTF Daily Aspirin Recommendations Into Practice 

The 2022 USPSTF recommendations align with the position of other professional organizations and guidelines, including^11-13:

• 2019 American College of Cardiology/American Heart Association (ACC/AHA) Guideline on the Primary Prevention of Cardiovascular Disease — available here¹¹; and
• 2021 European Society of Cardiology (ESC) Guidelines on Cardiovascular Disease Prevention in Clinical Practice — available here.¹²

The American Academy of Family Physicians (AAFP) has also released a statement supporting the USPSTF recommendations on aspirin use for the primary prevention of CVD.¹³ 

Shared Decision-Making

Aspirin use is no longer routinely recommended for any patient. Initiating daily aspirin use should be based on shared decision-making between patients and their health care providers. It is important to determine what factors are most important for patients when making this treatment decision.³ 

Patients who choose to initiate aspirin may place a higher value on aspirin’s benefit of decreasing the risk of CV events and stroke than the increased risk of bleeding. For these patients, clinicians can recommend low-dose aspirin (< 100 mg/d). The most common aspirin dosage for this purpose is 81 mg/d.³

Patients who choose not to initiate aspirin may place a higher value on the increased risk of bleeding and the increased pill burden of daily aspirin.³

Clinicians should educate patients about the increased risk of bleeding, including signs and symptoms to watch for, such as^3,14,15:

• Severe headache;
• Dizziness;
• Nausea and vomiting;
• Seizures; 
• Weakness on 1 or both sides;
• Fatigue; 
• Aphasia;
• Black, tarry stool;
• Coffee ground vomit;
• Abdominal cramping; and 
• Pallor. 

Re-evaluating Patients Taking Daily Aspirin

Patients currently taking aspirin daily should be regularly evaluated to ensure the benefit of treatment still outweighs the risk. The risk of serious bleeding increases with age. Modeling data from the USPSTF shows that it may be reasonable to stop daily aspirin use at the age of 75 years.³

Alternative Approaches to Primary CVD Prevention

Other approaches to the primary prevention of CVD should also be considered. Other therapies with a more favorable safety profile than aspirin include antihypertensive agents and statin therapy.¹

In the future, it may be possible to identify distinct populations of patients that may benefit from aspirin therapy, such as those with hyperactive platelets. However, more research is needed to determine the potential benefit to these patients.¹

This article originally appeared on The Cardiology Advisor

There is an interesting term describing some patients’ experiences with health care that is gaining significant traction in social and print media: “medical gaslighting.” It refers to a situation in which a patient’s concerns or symptoms are ignored or dismissed by a health care professional.¹ This might result from delayed or missed diagnoses, failed efforts to obtain a more extensive workup of unexplained symptoms, or ignored pain concerns.

Because this problem may be more common among women and racial minorities, the behavior is hypothesized to be a reflection of existing entrenched societal power imbalances. The term was appropriated from the successful movie adaptation of the 1940 play “Gaslight” where a husband psychologically manipulates his spouse into doubting her sanity. When he dims the gaslights in the home and then denies doing so and blames his wife’s perception on her overactive imagination, she begins to increasingly doubt her own judgment.²

Thus, medical gaslighting is a term rooted in malevolence and psychological abuse. Understanding this would be a reasonable starting point for discussing communication problems between patients and physicians. From an ethics perspective, the words medical professionals choose matter as much as the words patients use to describe their concerns. The ethical practice of health care, enhanced through evidence-based, relationship-centered communication techniques, requires specificity, empathy, and clarity in language. A term like gaslighting, which implies a deliberate attempt at manipulation for one’s own gain, is not likely to engage health care professionals in problem solving.

Miscommunication

For sure, patients’ experiences matter regardless of the good intent of the health care professional. If a patient feels dismissed because they believe their persistent symptoms are being ignored by their provider, that miscommunication deserves more attention in the treatment relationship. If a patient has had to see 4 different physicians before getting a definitive diagnosis, the patient’s feelings of frustration and anger should not be unexpected.  But these situations do not necessarily mean that the physician is at fault. Even if they’re not displaying deliberate ill will and manipulation, health care professionals can still fail in their best efforts to convey empathy, concern, or due diligence when addressing patient’s concerns.

Those on the other side of the stethoscope have important perspectives that can help understand this problem and hopefully direct patients and physicians to some solutions. Some physicians may share a patient’s frustration about their persistent symptoms but also realize (and maybe inadequately communicate) that further testing or procedures is low-value care without a role in elucidating the patient’s concerns.

Some physicians lack the robust communication skills needed to manage patients with unique needs. Other physicians may be subject to bias by not considering diagnoses in patient populations with a lower probability of disease. Medical students are still advised that “when they hear hoofbeats, think horses, not zebras” because pattern recognition makes for rapid accurate diagnoses and treatments. Errors in clinical reasoning and misappreciation of distribution of disease are always potential sources of bias, but it stems from the error in applying epidemiology to the patient’s case, not individual malice.   

A Problem of Equity

Health care professionals should neither remain blameless when patients are feeling dismissed, nor should they be considered the sole etiology of the problem. From a population health perspective, when these events occur more frequently in certain minority populations and are associated with health disparities, action is required on the part of individual health care professionals and the health care system in which they work. 

Such unwarranted variation in health care practice is a problem of equity that has a direct effect on the quality of care. We will arrive at better and more directed solutions when we begin to understand the physician and health system factors, patient demographics, and patient diagnoses, among other variables that may contribute to lower patient satisfaction in certain patient populations.³  

What Physicians Can Do

What can and should physicians do to address these challenges? First, when they sense a patient’s dissatisfaction, they can acknowledge this to the patient. Physicians can share what may be their own frustration with the challenge, and openly commit to work together to figure it out. Patients who feel heard are more likely to believe their physician is empathic and trying to be helpful. Second, physicians should recognize the potential for implicit bias in clinical reasoning and when automatic pattern recognition in diagnosis may be leading them to premature closure. Third, they should share their thinking with patients. Transparency in clinical reasoning goes a long way to helping patients appreciate and agree with a diagnostic and treatment plan. Physicians should consider “thinking out loud” with patients as they explain their recommendations. When patients realize all that is being considered in the physician’s clinical reasoning, what has been ruled out and why, they are more likely to trust the physician’s judgment and that they are being adequately cared for.

Finally, health care professionals should push back against the concept of gaslighting if they are accused of deliberately misleading and manipulating patients to advance their own agenda. Such an unsubstantiated claim undermines medical professionalism and the public’s trust in health care. It is time to call medical gaslighting what it likely is: patient dissatisfaction with their health care. Physicians should make a greater effort to understand why and improve how they communicate with patients.

References

1. Wenner MM.  Women are calling out ‘medical gaslighting’. New York Times. March 28, 2022.
2. Hoberman J. Why ‘gaslight’ hasn’t lost its glow. New York Times. Aug 21, 2019. 
3. Durbhakula S, Fortin AH. Turning down the flame on medical gaslighting. J Gen Intern Med. Published online July 5, 2023. doi:10.1007/s11606-023-08302-4