Lindsey Mulrooney

The American Society of Health System Pharmacists (ASHP) urged the US Department of Health and Human Services (HHS) to issue a Public Readiness and Emergency Preparedness (PREP) Act declaration to allow pharmacists to order and administer monkeypox 

vaccines in a letter addressed to HHS Secretary Xavier Becerra

The letter came in response to the HHS declaration of monkeypox as a public health emergency on August 4th, following a July 23rd announcement from the World Health Organization (WHO) declaring a global health emergency.

According to the letter, authored by Tom Kraus, MHS, JD, vice president of government relations at ASHP, there are over 6600 reported monkeypox cases in the United States, and the numbers are quickly rising. Kraus asserts that a PREP Act declaration allowing pharmacists to order and administer the vaccine would ensure timely access to vaccination and prevent virus infection in vulnerable populations.

“Pharmacists are well positioned to administer monkeypox vaccines for pre- and post-exposure prophylaxis of health care workers, patients, their close contacts, and populations at risk for severe disease from monkeypox virus (such as people with HIV or other immunocompromising conditions),” Kraus writes in the letter.

The CDC recommends the vaccine for monkeypox be given within 4 days from the date of exposure for the best chance to prevent onset of the disease and within 14 days to reduce symptoms of the disease.

Michael Ganio, PharmD, MS, BCPS, FASHP, senior director of pharmacy practice and quality at ASHP, explained that there are 2 current vaccines, but neither are available at pharmacies yet.

Referring to the Jynneos vaccine, fully approved for monkeypox, he said, “Currently, it's only available through the Strategic National Stockpile and it's being distributed to state and local territory health departments. From there, the state and territory health departments may work with a pharmacy or a health system or hospital to distribute the vaccine and help aid in immunization efforts.”

Ganio also discussed the role of pharmacists as a source of timely access to vaccines on a national scale, as demonstrated throughout the COVID-19 pandemic. This role could be key if pharmacists are authorized to administer vaccines for monkeypox.

“COVID-19 really put an emphasis on the role of pharmacists in public health. As we know, the pharmacist workforce and pharmacy technicians and interns have been at the forefront of vaccination efforts ever since,” Ganio said. “So, we know through the COVID-19 experience that pharmacists are in a place that we can leverage that patient accessibility.”

In the letter, Kraus suggested that proactive authorization allowing pharmacists to order and administer monkeypox vaccines would ensure that pharmacists are able to expand access as vaccine supplies increase and prevent delays in vaccination for individuals exposed to the virus.

“When patients access care from a pharmacist, directing the patient to another provider for vaccine administration would unnecessarily delay administration,” he wrote.

Additionally, the PREP Act declaration would improve access by making vaccine access uniform regardless of state.

“Currently, it's a patchwork from state to state of what vaccines pharmacists can administer,” Ganio noted in the interview with 

. “So, a PREP Act declaration and an amendment clarifying what pharmacists can administer would really streamline that access and make it uniform nationwide, and it could likely include technicians and pharmacy students, which really expands the workforce of available vaccinators.”

The ASHP letter also called for the HHS to proactively coordinate with payers, including Medicare and Medicaid, to ensure adequate reimbursement is available to support access to these services when provided by pharmacists.

“We welcome the opportunity to work with you to identify conditions under which pharmacists should administer monkeypox vaccines to our patients,” concluded Kraus.

American Society of Health-System Pharmacists Letter to HHS Secretary Xavier Becerra. ASHP; August 4, 2022. Accessed August 5, 2022. 

https://www.ashp.org/-/media/assets/advocacy-issues/docs/HHS-Letter-Monkeypox.pdf

Articles

The move would help ensure timely access to vaccination following the declaration of monkeypox as a public health emergency.

ASHP Urges HHS to Issue PREP Act Declaration Enabling Pharmacists to Administer Monkeypox Vaccines

The integration of patient-reported outcome measurements (PROMs) for pediatric patients with cancer in the clinical routine is possible and effective, according to a study published in 

PROMs were found to reflect daily symptoms in pediatric patients with cancer and assist in the clinical management and intervention of adverse events (AEs). Although PROMs are emerging as a vital component of adult cancer care, they have not been previously implemented for pediatric cancer care.

Researchers conducted a single-cohort study to identify pediatric patients with cancer who are at risk of severe AEs of treatment and provide individualized supportive care using PROMs.

Researchers conducted the study from May 1, 2020, to November 15, 2021, at the Medical University of Innsbruck in Austria. The cohort included pediatric patients with a cancer diagnosis or their proxies. PROMs were implemented in daily clinical routine and patients were followed up until completion of therapy or through ongoing therapy until November 15, 2021.

Inclusion criteria for participants included treatment with chemotherapy and at least 30 days of active participation in ePROtect, the web-based approach for daily child self-reporting and parent-based proxy reporting used in the study.

Researchers analyzed the occurrence and severity of complications of cancer treatment, such as nausea, appetite loss, pain, sleep disturbance, and deterioration of physical functioning. They also identified early and appropriate clinical interventions based on detection of cancer-related symptoms via PROMs.

The cohort included 40 children, including 35 children aged 5 to 18 years and 5 proxies for children aged 1 to 4 years (median age, 9.1 [IQR, 6.3-12.2] years; 26 [65.0%] male). A total of 4410 daily PROMs and 7082 therapy days were analyzed for these children during a median follow up of 145.5 days. All study participants were White.

Researchers noted that most patients in this study could complete questionnaires on most days, regardless of age, diagnosis, and therapy; however, patient completion rates differed between modalities.

The overall median completion rate was 60.1% (IQR, 37.9%-81.0%). Completion rate was 57.5% during home stay, slightly lower than during inpatient stay (65.6%).

Patients were found to complete the monitoring on more than 50% of the days, even during unplanned inpatient stays. The researchers recommend conducting further in-depth analyses on the completion rates and are currently preparing to do so.

Severe symptoms were reported on 657 days (15.9%), with most symptoms associated with physical functioning followed by pain, sleep disturbance, and nausea and appetite loss.

A total of 321 AEs and cases of health deterioration were reported. PROMs were completed for 251 (78.2%) of these events. Given that most (56.4%) days are spent by the patient at home, researchers investigated whether the ePROtect reporting enabled early detection of health deterioration before clinical manifestation.

Mean scores for pain, nausea, physical activity, and sleep disturbance domains were found to be 15 to 20 points lower in cases of unplanned hospitalization compared with planned hospitalization 1 day before admission. Researchers found self-reported pain to be the most useful marker across all AEs, particularly when analyzed on the day before onset.

Collectively, these findings suggest that electronic symptom self-measuring with ePROtect is very well received for inpatient and outpatient use, according to the authors. They suggest that electronic symptom self-measuring can provide early detection of toxic effects and can anticipate necessary admissions or medical interventions.

Electronic symptom measuring also facilitates communication and awareness of symptoms for health care professionals, which can result in more effective treatment of patients.

“In the context of increasing demands regarding patient self-advocacy and self-management, symptom self-reporting allows patients to participate more actively in their therapy and may help improve their quality of life,” the authors concluded.

The study had some limitations, including the monocentric design with a small sample size. Additionally, randomization or cross-sectional study design with and without access to ePROtect was not currently possible, according to the authors.

However, they assert that their findings still contribute to the knowledge gap on the possibility of pediatric self-reporting and its integration into the clinical routine, highlighting the high adherence and participation rates in patients with diverse cancer seen in this cohort.

Meryk A, Kropshofer G, Hetzer B. Use of daily patient-reported outcome measurements in pediatric cancer care. 

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2794638

. Published July 26, 2022. Accessed July 27, 2022.

Electronic symptom self-measuring provided early detection of toxic effects and helped anticipate necessary medical interventions for pediatric patients with cancer.

Patient-Reported Outcome Measures Useful in Clinical Treatment of Pediatric Patients with Cancer

Opioid-involved overdose deaths rates steadily increased in counties of every urbanicity type during wave 4 of the US opioid crisis, which coincided with the COVID-19 pandemic, according to a research letter published in 

Though all counties experienced an increase in deaths, counties of different urbanicities experienced different timing of acceleration of opioid-involved overdose deaths.

The theory of 3 overlapping waves of opioid-involved overdose deaths based on supply and demand was posited by Daniel Ciccarone, MD, MPH, professor of Family Community Medicine at UCSF, in an earlier study. Supply factors included iatrogenic and new illicit sources, while demand included social, cultural, and technological factors.

In approximately 2000, the first wave was prompted by physicians overprescribing opioid painkillers associated with mass addiction. The second wave involved heroin. In 2007, opioid-involved overdose deaths from heroin escalated and surpassed those from prescription opioids by 2015. Wave 3 involved illicit synthetic opioids, such as fentanyl. The use of these escalated after 2013.

Further evidence suggests a fourth wave, complicated by the addition of stimulants and the COVID-19 pandemic. To inform prevention and mitigation strategies, researchers conducted a cross-sectional study examining trends in opioid-involved overdose death rates in urban and rural US counties during the 4 waves.

They sourced data on opioid-involved overdose deaths from January 1, 1999, to December 31, 2020, from the CDC’s WONDER Database. Opioid-involved overdose deaths included those from 3147 counties and county equivalents categorized on a 6-point urbanicity scale. Analyses were conducted to determine death rates.

The findings showed that counties of every urbanicity type experienced statistically significant annual opioid-involved overdose death rate growth, with the largest differences in opioid-involved overdose death rates by urbanicity observed at the start and end of the study period. The initial rank order, which identified urban counties as having the highest rates and rural counties the lowest, reemerged by 2020.

Opioid-involved overdose death rates were higher in most urban counties during waves 1 and 4; however, acceleration rates were higher in most rural counties. Before 2000, opioid-involved overdose deaths were rare in rural communities, which lacked resources to treat opioid use disorders.

Restrictions on synthetic and semisynthetic opioids were associated with increased heroin use, contributing to wave 2, beginning around 2013. Researchers found that wave 2 was characterized by accelerated growth in opioid-involved overdose death rates.

Diverse trends were observed across urbanicity. Linear growth shifted to nonlinear growth in wave 3.

Opioid-involved overdose deaths from fentanyl increased by a factor of 12 from 2013 to 2019. With 4 years of substantial acceleration across all urbanicity types, both urban and rural counties were substantially impacted by this wave.

During wave 4, which coincided with the COVID-19 pandemic, there was marked growth across all urbanicity types. The opioid crisis worsened in all county types. Overall, opioid-involved overdose death rates increased steadily in counties of every urbanicity type, with distinct temporal wave patterns by urbanicity.

“The varied timing of acceleration by urbanicity suggests that policy makers should consider resources and socioeconomic and treatment needs of rural and urban communities as the opioid crisis evolves, particularly because urban outreach and treatment approaches may not work in rural areas,” the authors wrote.

These findings were consistent with the wave theory posed by Ciccarone, according to the authors.

The study had limitations. As death investigation systems vary by state, the data may undercount opioid-involved overdose deaths. Not all individuals who die of opioid-involved overdose have opioid use disorder.

Additionally, deaths in wave 4 are often a function of multiple drug interactions or inclusion of stimulants with synthetic opioids in the nonregulated, nonopioid drug supply. Some opioid-involved overdose deaths are the result of drug interactions or recreational use that may require nonrehabilitative interventions.

Post L A, Lundberg A, Moss C B, et al. Geographic trends in opioid overdoses in the US from 1999 to 2020. 

2022;5(7):e2223631. doi:10.1001/jamanetworkopen.2022.23631

The suggested wave 4 of the opioid crisis saw high opioid-involved overdose death rates in urban counties and high acceleration of overdose deaths in rural counties, indicating that the opioid crisis worsened during the COVID-19 pandemic.

Overdose Deaths Increased in Wave 4 of the Opioid Crisis, Coinciding with the COVID-19 Pandemic

Individual patient factors, social determinants of health (SDOH), and COVID-19 severity and diagnosis date were associated with exacerbated health disparities in cancer treatment delays during the pandemic, according to a study published in 

As a result of the COVID-19 pandemic, cancer care has been frequently delayed or disrupted, resulting in amended care guidelines that helped clinicians prioritize patients with higher-risk disease to avoid treatment delays and suggested alternatives. However, much of the research on this topic focuses on patients with cancer who did not contract COVID-19 themselves.

To assess the associations of patient factors, SDOH, severity of COVID-19, and timing of COVID-19 diagnosis with the risk of treatment delay among patients with cancer, researchers conducted a prospective cohort study using the American Society of Clinical Oncology COVID-19 Oncology Data Registry.

The study was conducted from March 2020 through July 2021 at 60 academic and community medical practices in the United States. Participants included patients with any cancer diagnosis who were scheduled for treatment and contracted COVID-19. Researchers analyzed treatment delay, defined as more than 14 days between the date originally planned for treatment and the date of initiation of therapy, or discontinuation of therapy.

A total of 3028 patients were included in the registry, 2103 of whom had scheduled anticancer drug treatment.

Researchers found that 962 of these 2103 patients (46%) experienced anticancer drug delays or discontinuation. Delays were higher among Black patients compared to White patients (odds ratio [OR], 1.87; 95% CI, 1.40-2.51), and for Hispanic or Latino patients compared with non-Hispanic or Latino patients (OR, 1.91; 95% CI, 1.34-2.72).

These findings are in line with previous data showing persistent disparities in COVID-19–related outcomes in subgroups of disadvantaged and minority patients and populations.

Patients with 2 or more comorbidities experienced higher delays compared with patients with 0 to 1 comorbidities (OR, 1.23; 95% CI, 1.00-1.53), as did patients with metastatic disease rather than locoregional disease (OR, 1.63; 95% CI, 1.29-2.05).

Patients who experienced COVID-19 complications also had higher delays than those who did not (OR, 1.52; 95% CI, 1.24-1.86).

A lower likelihood of drug therapy delay was associated with living in an area with a higher proportion of residents reporting Hispanic or Latino ethnicity (OR, 0.76; 95% CI, 0.60-0.95) and contracting COVID-19 later in the pandemic (eg, January to March 2021: OR, 0.38; 95% CI, 0.26-0.53).

The authors suggest that that changes in COVID-19 management, and correspondingly, patient outcomes, emerged as clinicians developed an increasing understanding of the disease and made more nuanced accommodations to improve access to care as the pandemic progressed. COVID-19 vaccination was also associated with lower likelihood of anticancer drug delay, indicating that the vaccine can improve outcomes in this high-risk population.

A total of 95 of 202 patients (47%) experienced delay or discontinuation of radiation treatment, with having 2 or more comorbidities associated with delay (OR, 2.69; 95% CI, 1.20-6.20). Higher local-area median household income was associated with lower likelihood of radiation treatment delay (OR, 0.41; 95% CI, 0.17-0.94).

Of 125 patients who scheduled surgical treatment, 89 (71%) experienced delay. For surgical treatment, delays were higher among patients in the South compared with those in the Midwest (OR, 9.66; 95% CI, 2.14-52.3). The researchers noted an interesting finding that patients with 2 or more comorbidities experienced lower likelihoods of surgical treatment delay compared to patients with 0 to 1 (OR, 0.26; 95% CI, 0.07-0.88).

While an increased propensity for treatment delay was not observed among patients with hematologic malignant neoplasms compared with those with solid tumors overall, a greater association of hematologic malignant neoplasm with treatment delay was observed compared with the breast cancer group.

Overall, multiple patient factors, including race and ethnicity, underlying primary malignant neoplasms, multimorbidity, geographic location, receipt of COVID-19 vaccine, severity of COVID-19, and timing of COVID-19 diagnosis, were found to be associated with delays in cancer treatment.

“Quantification of the impact of COVID-19 on practice management can provide insight to health system leaders and public health authorities about the extent of disruptions in care, and differential impacts on vulnerable and/or disadvantaged populations,” the authors wrote.

They hope that their study can help inform proposals for well-targeted strategies to improve planning, preparation, patient support, and resource allocation during the ongoing COVID-19 pandemic and future national health emergencies.

The study had some limitations. The study only enrolled patients who had test results positive for SARS-CoV-2, meaning that researchers had no information on control patients with cancer but without COVID-19 who were treated in the same practices and who may or may not have experienced delay.

Additionally, cause of delay could not be determined, making it difficult to determine whether delays were related to symptoms of COVID-19, isolation requirements, or structural factors.

The authors suggest that future analyses should be performed as the American Society of Clinical Oncology COVID-19 Oncology Data Registry continues to recruit patients and increase in size.

Mullangi S, Aviki E M, Chen Y, et al. Factors associated with cancer treatment delay among patients diagnosed with COVID-19. 

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2794732?utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_term=072822

Delays in anticancer drug therapy, radiation, and surgery were found to be associated with factors such as race and ethnicity, multimorbidity, COVID-19 vaccination, and severity of COVID-19, suggesting disparities in cancer care.

Treatment Delays for Patients with Cancer During Pandemic Linked to Social Factors, Vaccination Status

Maintaining high population immunity, preferably by booster uptake, is essential in determining appropriate quarantine duration for controlling the spread of SARS-CoV-2, according to a study recently published in 

The CDC’s reduction of the recommended 7-day quarantine for close contacts of a COVID-19 case to 5 days for the unvaccinated and no quarantine for the vaccinated may not effectively mitigate transmission, according to the authors. Quarantine and testing strategies were found to depend on the incubation period and the transmissibility and level of population immunity against infection.

Researchers compared the probability of post-quarantine transmission and the effective reproduction number with serial testing and isolation for the original SARS-CoV-2 strain and 3 variants of concern, Alpha, Delta, and Omicron, at different levels of vaccination. The comparison of the number of post-quarantine secondary infections between vaccinated and unvaccinated individuals demonstrated that the effect of vaccination status of an individual had only a limited effect on quarantine duration.

Vaccinated cases were less likely to exhibit symptoms than unvaccinated cases, which resulted in less frequent self-isolation. The decreases in case detection and self-isolation increased the probability of releasing an infectious case from quarantine.

Variants of concern produced increased transmission and earlier transmission in the disease time course than the original SARS-CoV-2 strain, challenging the effectiveness of current quarantine and testing strategies. The findings also suggested that determining optimal disease control strategies also depends on the level of population immunity.

Increasing population immunity through vaccine and booster uptake was found to mitigate transmission. Improving 2-dose vaccine uptake led to a substantial decrease in the probability of post-quarantine transmission during serial testing. Increasing uptake of 2-dose vaccines also notably reduced quarantine durations.

However, increasing booster uptake only provided substantive benefit to serial testing compared to quarantine. The decrease in probability of post-quarantine transmission concomitant with an increase in booster uptake was found to diminish as quarantine duration lengthened.

The effectiveness of serial testing in reducing transmission was greatly improved through an increase in booster uptake, according to the study.

Researchers found that scaling up vaccine-acquired immunity from no vaccination to 100% booster intake yielded a reduction in quarantine by 6 days for the original SARS-CoV-2 strain, but only yield a 2-day reduction in quarantine for the Omicron variant. In a population with 100% 2-dose vaccination, scaling up booster intake could justify a reduction of quarantine by as much as 3 days.

However, boosting only has a moderate impact of quarantine duration for Omicron, decreasing it by almost a day. Increasing booster uptake can result in significant differences in the required frequency of serial testing.

Increased 2-dose vaccine uptake also justified reduced surveillance through serial testing, according to the study. Additionally, the findings suggested that rapid antigen testing requires a frequency of every 6 days to curtail transmission within a population that is 100% boosted, encouraging booster uptake.

Overall, an individual’s vaccination status was found to have limited influence on post-quarantine transmission compared to vaccination coverage of the population. Increasing population immunity through vaccination not only decreases transmission, but can also allow for substantial relaxation of requirements for quarantine and testing.

The authors note that surveillance of the immunological status of the population is much more important than the status of the quarantined individual when determining effective quarantine durations. They recommend continued efforts to administer vaccines and booster doses to lessen the burden on health care systems and prevent large outbreaks with emerging variants of concern or their subvariants.

Wells C R, Pandey A, Gokcebel S, et al. Quarantine and serial testing for variants of SARS-CoV-2 with benefits of vaccination and boosting on consequent control of COVID-19. 

https://doi.org/10.1093/pnasnexus/pgac100

Increasing population immunity decreased transmission of COVID-19 and allowed for reductions in quarantine and testing, encouraging 2-dose vaccine and booster uptake. 

Study: Population Immunity More Important for Controlling Transmission of COVID-19 Than Individual Vaccination Status

White blood cells, known as gamma-delta T-cells, rein in early-stage tumors but undergo biochemical changes and begin strengthening tumors as colorectal cancer disease progresses, according to research published in 

“[Gamma-delta] T-cells that live in the gut act to prevent tumor formation,” said Bernardo Reis, a research associate in the laboratory of Daniel Mucida at The Rockefeller University, in a statement. “But once tumors form, gut [gamma-delta] T-cell populations change, enter the tumor, and promote tumor growth.”

This research clarifies the role of these cells in tumor growth for colorectal cancer, which had been previously debated, with some studies show that gamma-delta T-cells restrict tumor growth and others demonstrating that gamma-delta T-cells bolster tumors and help them spread.

“We had data showing [gamma-delta] T-cells were protective, but the literature suggested that they also promote tumor growth,” Reis said. “We wanted to understand what these [gamma-delta] T-cells were really up to.”

Researchers sought to determine whether gamma-delta T-cells help or hinder the growth of intestinal tumors using a mouse model of colorectal cancer. Researchers derived gamma-delta T-cells from the intestines of animals with early-stage tumors and from the tumors of mice with advanced cancer.

The researchers compared these 2 sources of supposedly identical cells. They were surprised to find vast molecular differences between them.

“The [gamma-delta] T-cells had completely changed,” Reis said in a statement.

The 2 categories of gamma-delta T-cells boasted different T-cell receptors. R2 T-cells that had entered the tumor produced interluekin-17, a cytokine that normally promotes inflammation in response to infection but promoted disease in the tumor microenvironment by spurring tumor growth and recruiting other cells to hide the tumor from the immune system, according to the investigators.

The researchers used CRISPR gene editing technology to confirm their findings. They selectively removed T-cell receptors from the white blood cells to change the cells from anti-tumor to pro-tumor, or vise versa. This allowed the researchers to increase the number and decrease the size of tumors in their mouse models.

“When we depleted the original [gamma-delta] T-cells, the mice became sicker,” Reis explained. “And when we depleted the tumor invading [gamma-delta] T-cells, the tumors shrank.”

Similar activity was observed in gamma-delta T-cells derived from human colorectal tumors and their environs. Cells inside the tumor resembled the renegade, late stage gamma-delta T-cells seen in mice, while cells hovering around the outside of the tumor looked more like the original cells.

“It almost looked like a fight between these two populations,” Reis said. “Regular cells were trying to contain the tumor while cells inside were promoting tumor growth.”

The Mucida lab plans to improve its understanding of what promotes gamma-delta T-cells’ shift from cells that hinder tumors to cells that help tumors. Researchers intend to delve deeper in future studies, examining whether it might be possible to modulate normal gamma-delta T-cells to curb the tumor and prevent the cancer-promoting T-cells from dominating the tumor.

Reis is also interested in exploring ways to manipulate the system by which altered gamma-delta T-cells enter the tumor.

“Perhaps we might one day fashion [gamma-delta] T-cells into Trojan horses that can act as anti-cancer cells right inside the tumor microenvironment,” he said.

The investigators hope this current research and potential future studies may open new paths toward colorectal cancer therapies.

Colorectal cancer tumors both helped and hindered by T-cells. Rockefeller University. News Release. July 22, 2022. Accessed July 25, 2022. 

https://www.eurekalert.org/news-releases/959668

Gamma-delta T-cells undergo a biochemical change that leads them to spur the growth of tumors that previously restricted.