How widespread is the Delta variant (B.1.617.2) in the US?

Centers for Disease Control and Prevention (CDC)

, as of October 9, 2021, the SARS-CoV-2 Delta variant made up 

The CDC estimates for the week ending on October 9, 2021, the 5 states with the highest unweighted proportion of new cases attributed to the SARS-CoV-2 Delta variant are:

How many people in the US have been vaccinated against COVID-19?

 as of today, October 21, 2021, at 2:11 PM, EDT:

The 5 states/territories with the highest percentage of population fully vaccinated are:

How many cases of COVID-19 have been confirmed in the US?

, as of today, October 21, 2021 at 4:21 PM, EDT, there have been:

The 5 states with the highest total confirmed cases are:

 California has the highest number of deaths due to COVID-19

 with 71 149 reported fatalities, followed by 

How many cases of COVID-19 have been confirmed globally?

Articles

Data from the CDC on the Delta variant and US vaccination rates and from the Johns Hopkins COVID-19 interactive map on cases and deaths in the US and worldwide.

COVID-19 Updates: Delta Variant, US Vaccinations, & Global Data as of October 21, 2021

The US Food and Drug Administration (FDA) authorized booster doses of the Moderna and Johnson & Johnson COVID-19 vaccine as well as a “mix and match” approach to boosters for all 3 available COVID-19 vaccines in the indicated populations, the agency announced Wednesday.

“As the pandemic continues to impact the country, science has shown that vaccination continues to be the safest and most effective way to prevent COVID-19, including the most serious consequences of the disease, such as hospitalization and death,” stated acting FDA Commissioner Janet Woodcock, MD, in a 

. “The available data suggest waning immunity in some populations who are fully vaccinated. The availability of these authorized boosters is important for continued protection against COVID-19 disease.”

The FDA amended emergency use authorizations (EUA) for COVID-19 vaccines to allow the following:

 that may be administered at least 6 months after completion of the primary series to adults aged ≥65 years, 18-64 years at high risk of severe COVID-19, and 18-64 years with frequent institutional or occupational exposure to SARS-CoV-2.

The use of a single booster dose of the J&J COVID-19 vaccine may be administered at least 2 months after completion of the single-dose primary regimen to adults aged ≥18 years.

The use of each of the available COVID-19 vaccines as a heterologous—or mix and match—booster dose in eligible persons after completion of primary vaccination with a different available COVID-19 vaccine.

 COVID-19 vaccine administered at least 6 months after completion of the primary series to adults aged 18-64 years with frequent institutional or occupational exposure to SARS-CoV-2.

The authorizations followed a 2-day meeting last week of the FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC), which 

 that the FDA authorize booster shots of the Moderna and J&J COVID-19 vaccines in eligible populations.

To support the authorization for emergency use of a single Moderna booster dose, the FDA analyzed data from a phase 2 trial, in which 149 adults who received the 2-dose 100-μg series, the dose authorized under EUA, plus the 50-μg booster dose were evaluated for immunogenicity. Results showed that the antibody response of the 149 participants against SARS-CoV-2 virus 29 days following

 a booster dose demonstrated a booster response, according to the FDA press release.

To support the single booster dose of the 

, the FDA analyzed immune response data in 39 participants from a study that included 24 participants aged between 18 and 55 years and 15 participants aged ≥ 65 years. Participants received a booster dose approximately 2 months after their first dose, and the results demonstrated a booster response, the agency noted in the press release.

For the mix and match EUA, the FDA cited data from a clinical trial conducted by the National Institute of Allergy and Infectious Diseases that showed heterologous boosters produced an immune response, with no new safety concerns.

“We will work to accrue additional data as quickly as possible to further assess the benefits and risks of the use of 

 in additional populations and plan to update the healthcare community and public with our determination in the coming weeks,” added Marks.

The FDA also urged clinicians to follow the recommendations that will be provided by the Centers for Disease Control and Prevention after a meeting of their Advisory Committee on Immunization Practices on Thursday, which are subject to approval by the CDC director.

CDC vaccine advisors will meet Thursday to discuss final approval of booster doses of Moderna and J&J vaccines and mix-and-match approach authorized by FDA. 

FDA Greenlights Mixing COVID-19 Boosters and Moderna, J&J Booster Shots

Advances in heart failure management, including inroads in treatment for HFpEF, are happening fast. Try 8 questions to find out how well you’ve been following the news.

Slideshows

A Heart Failure Research Roundup Quiz: 8 Questions 

 as of today, October 20, 2021, at 2:55 PM, EDT:

, as of today, October 20, 2021 at 3:21 PM, EDT, there have been:

 with 71 010 reported fatalities, followed by 

COVID-19 Updates: Delta Variant, US Vaccinations, & Global Data as of October 20, 2021

Among nearly 7500 patients in the Veterans Affairs (VA) health system who were identified as current or former smokers prior to undergoing lung cancer surgery, more than 4 in 10 (43%) continued to smoke—or had resumed smoking—one year later, according to findings presented at CHEST 2021, the American College of Chest Physicians' annual meeting held online October 17-20, 2021.

Moreover, those whose smoking persisted or had resumed at the 1-year follow-up, study authors report, were approximately 30% more likely to die in the succeeding years.

The study also found that for those who did stop smoking after a diagnosis and before lung resection, seeing a primary care physician was a factor in being able to quit

As context for their research, investigators led by Brendan Heiden, MD, of Washington University in St Louis, observe that a significant proportion of patients diagnosed with lung cancer are smoking at the time of surgery but that cancer registries do not collect post-surgical data on the prevalence of persistent smoking. The result, they write in the study abstract, is a gap in knowledge about the relationship between continued smoking and outcomes in early-stage lung cancer.

The retrospective cohort study Heiden and colleagues pursued enrolled 7536 veterans with clinical stage 1 non-small-cell lung cancer undergoing surgery between 2006 and 2016. Mean patient age at surgery was 67 years, nearly all were men and 82% were white. For purposes of analysis researchers defined persistent cigarette smoking as individuals who continued to smoke 1 year after surgery. Sociodemographic and treatment-related factors associated with persistent smoking were assessed in multivariable modeling and the relationship between persistent smoking and all-cause mortality also was assessed.

At the time of lung cancer diagnosis, 68% (5142) of participants reported current smoking. Of those, 11.3% (580) reported they had stopped smoking between diagnosis date and surgical intervention. The researchers found that the interventions during the pre-operative period that were associated with smoking cessation were being prescribed cessation medication (odds ratio [OR] 1.466, 95% CI 1.213-1.771), more frequent medical encounters (OR 1.007, 95% CI 1.002-1.012), and seeing a primary care physician (OR 1.408, 95% CI 1.139-1.740). 

When they assessed persistent smoking at 1 year post-surgery, Heiden et al found more than half (56%) of participants who reported smoking when they were diagnosed continued to smoke with the strongest associations found for age (with older individuals less likely to smoke, OR 0.960, 95% CI 0.949-0.970), elevated Charlson comorbidity score (OR 1.049, 95% CI 1.011-1.089), and higher area deprivation index score (OR 1.007, 95% CI 1.002-1.011).

Patients who stopped smoking after diagnosis and before surgery were significantly less likely to be smoking 1-year post-surgery (OR 0.512, 95% CI 0.418-0.627). Median overall survival was significantly worse among participants who continued to smoke (73.1 months vs. 84.7 months, p<.001).

The authors urge health care providers, including surgeons, to “aggressively counsel patients regarding smoking cessation in the perioperative period,” suggesting that successful interventions can have a significant positive impact on early-stage lung cancer outcomes.

Association between persistent cigarette smoking and oncologic outcomes in stage 1 non-small cell lung cancer following surgery. 

CHEST 2021: Among >7000 veterans diagnosed with lung cancer and scheduled for surgery, seeing a primary care doctor was linked to pre-operative quitting. 

PCP Visits Associated with Smoking Cessation after Lung Cancer Diagnosis and Before Surgery

New research suggests the use of e-cigarettes increases the odds of developing asthma and chronic obstructive pulmonary disease (COPD), particularly in older adults, women, and Hispanic individuals.

 Annual Meeting, held in Orlando, Florida, and virtually between October 17-20, 2021.

 in recent years, few studies have examined the relationship between e-cigarette use and the development of obstructive pulmonary diseases. To help fill the knowledge gap, investigators analyzed pooled participant data from the Behavioral Risk Factor Surveillance System (BRFSS) from the years 2016, 2017, and 2018.

Researchers estimated the odds ratio (OR) between current e-cigarette use and 

 or COPD in crude analyses and analyses adjusted for confounding by age, sex, race, income, cigarette smoking, and body mass index, according to the study abstract.

A total of 741 870 BRFSS participants aged ≥18 years were included in the current analysis, of whom 32 114 (4.3%) were classified as current e-cigarette users and 709 756 (95.7%) as never users.

Results showed that current e-cigarette use was associated with higher odds of asthma and 

 in both the unadjusted (asthma: OR=1.37; 95% CI, 1.29-1.46; COPD: OR=1.69; 95% CI, 1.59-1.80) and adjusted analyses (asthma: OR=1.21; 95% CI, 1.13-1.29; COPD: OR=1.43; 95% CI, 1.34-1.54).

The odds of developing asthma with current e-cigarette use were highest in participants aged 55 to 64 years (OR=1.42; 95% CI, 1.22-1.64), women (OR=1.33; 95% CI, 1.22-1.45), and Hispanic individuals (OR=1.62; 95% CI, 1.28, 2.05), according to the abstract.

In addition, the odds of COPD with current e-cigarette use were higher for women (OR=1.57; 95% CI, 1.43-1.71) and Hispanic adults (OR=1.71; 95% CI, 1.28-2.28). Unlike asthma, however, participants aged ≥65 years had higher odds of developing COPD with e-cigarette use compared to younger adults (OR=2.09; 95% CI, 1.81-2.41).

In their conclusion, investigators emphasized the importance of regular follow-up and monitoring of signs and symptoms of asthma and COPD in patients who regularly use e-cigarettes, as well as early COPD prevention and prevention of asthma exacerbations in youth.

Researchers also highlighted the need for improved access to smoking cessation treatments for minority groups and for inclusion of information on e-cigarettes in guidance on smoking cessation.

The latter suggestion, they point out, is important because e-cigarettes have “been perceived to be a safer alternative to combustible tobacco use” despite their detrimental health effects.

Reference: Onaku E, Ajayi A, Babayale O, et al. 

The association between electronic cigarette use and obstructive pulmonary diseases

CHEST 2021: Study shows vaping raises the odds of developing asthma and COPD, especially in older adults, women, and Hispanic persons.

Study: Hispanic Adults, Women, and Older E-cigarette Users Face Higher Odds of Asthma and COPD

 Dr Sands, could you review our 2 newest agents, the JAK inhibitor tofacitinib and the S1P [sphingosine-1-phosphate] receptor modulator ozanimod?

 Sure. Both tofacitinib and ozanimod, in contrast with what Dr Ungaro and Dr Hanauer have been talking about, are oral agents. They’re small molecule agents. At this point, they’re approved for only ulcerative colitis within the realm of IBD [inflammatory bowel disease]. Tofacitinib is a Janus kinase inhibitor, or a JAK inhibitor. It’s a pan-JAK inhibitor. It works by basically inhibiting downstream inflammatory responses within inflammatory cells. It’s an orally available agent, and it’s effective in ulcerative colitis. But it’s positioned in its use after patients have failed anti-TNF [tumor necrosis factor] agents, so it’s a second-line agent.

Furthermore, it has recently had the addition of black box warnings for venous thromboembolism and increase in mortality. This comes from data out of the rheumatoid arthritis population, but has been generalized to its application with ulcerative colitis as well. It’s an effective agent. As with all agents, it’s somewhat less effective after patients have already failed an anti-TNF, which paradoxically is exactly the patient we would use it for.

Ozanimod is the newest one. It had already been on the market for treatment of multiple sclerosis. It works mechanistically in a different way. It’s an S1P receptor agonist, or sphingosine-1-phosphate receptor agonist. Without going into great detail about what it does or how it does it, it basically sequesters lymphocytes in lymph nodes and keeps them trapped in the lymph nodes and out of circulation. In a way, it’s another approach of targeting the trafficking of inflammatory cells and lymphocytes into the gut mucosa. But here it’s just trapping them in the lymph nodes and not killing them. Consequently, you can expect to see lymphopenia. But interestingly, you don’t see very much increased risk of infections. You see a slight uptick in herpes zoster, but not much else of note.

There are some other safety issues with ozanimod. It’s given in uptitrated dosing because it has cardiac conduction effects, which are easily titratable. You see rapid tachyphylaxis to that effect. But you want to use it with caution in patients who have cardiac conduction abnormalities. There are also rare cases of liver function abnormalities. I mentioned the lymphopenia. It can also cause macular edema—you don’t want patients who are susceptible to that to get it—and rare cases of pulmonary function abnormalities. You don’t necessarily have to monitor for that, but just be aware of that. But it’s effective in ulcerative colitis and provides another oral option for treatment.

Videos

What to know in terms of integrating new oral, small molecule targeted drugs into treatment plans for patients with ulcerative colitis.

Oral, Small Molecule Agents for Ulcerative Colitis

 We’d now like to focus on the biologic treatments and overall treatment response. Dr Hanauer, one of the older drugs that’s been available for years and used very often is mesalamine. What role does mesalamine play in disease management for ulcerative colitis and Crohn disease?

 Mesalamine has been a long-standing drug for mild to moderate ulcerative colitis. It’s more of a topical agent, and it’s more effective in ulcerative colitis than in Crohn disease because ulcerative colitis tends to be a more superficial inflammation of the colon. We have less evidence for the role of mesalamine as an inductive or maintenance agent in the setting of Crohn disease, where we have moved more toward biologic agents, as Dr Sands mentioned. Once the biologic agents have been utilized, mesalamine has a lesser role in both ulcerative colitis and Crohn disease. But it has been a standard agent for induction and maintenance of mild to moderate ulcerative colitis.

 Thank you. With that, before we go into how we might treat this patient specifically, I’d like to ask the panel to review for our audience the different classes of biologics that we often use to treat inflammatory bowel disease, and their advantages and disadvantages. Dr Ungaro, could you start off with the anti-TNF [tumor necrosis factor] drugs and your thoughts about these agents?

 Sure. The anti-TNF drugs, or anti–tumor necrosis factor agents, are our oldest class of biologic and the most tried-and-true agents. The main medications in this class are 3 injectables and 1 intravenous. The intravenous agent, the original anti-TNF, is infliximab. Then there are 3 subcutaneous formulations of anti-TNF: adalimumab, golimumab, and certolizumab, which patients are able to administer on their own. These are very efficacious and have a long track record of working well in both ulcerative colitis and Crohn disease. They tend to work fairly quickly. Compared with some of the other classes of agents, you can usually see response as soon as a couple weeks, and certainly within 6 to 12 weeks. The relative trade-offs between the different types of anti-TNF drugs often come down to patient convenience. Are they close to and able to get to an infusion center? You can use infliximab in that case. Or are they traveling a lot? Are they away at school or prefer the convenience of a subcutaneous injection? You can go for one of the injectables in that case.

 Thank you. Dr Hanauer, could you go over some of the relatively newer agents, the IL-12/23 inhibitor ustekinumab and the anti-integrin inhibitor vedolizumab?

 Similar to the TNF inhibitors that are effective in both ulcerative colitis and Crohn disease as Dr Ungaro mentioned, they’re also approved for other conditions: inflammatory diseases such as rheumatoid arthritis and psoriasis, and a number of less common immune diseases.

Ustekinumab, the IL-12/23 inhibitor, likewise has been effective for over a decade in the treatment of psoriatic arthritis. There’s a long safety experience in this with both psoriasis and psoriatic arthritis. Over the past several years, ustekinumab has also been demonstrated to be effective in both moderate to severe ulcerative colitis and Crohn disease, but as we’ve seen with the TNF inhibitors, at a somewhat higher dose than are used in other immune-mediated diseases, psoriasis in particular.

One of the advantages of ustekinumab is, No. 1, the ease of administration. In ulcerative colitis and Crohn disease, it begins with a single intravenous infusion and then 90 mg subcutaneously every 8 weeks, in contrast with some of the more frequent administration of the subcutaneous TNF inhibitors. In addition, I mentioned the safety, and TNF inhibitors are associated with risks for infections, such as pneumonia, and of course, tuberculosis [TB]. With ustekinumab, we also rule out TB exposure. But while there may be a slight increased risk of other infections, it appears to be less than that of the TNF inhibitors.

In contrast, vedolizumab is an agent that affects lymphocyte trafficking. In order for inflammation to occur in the bowel, inflammatory cells need to get into the intestine. Vedolizumab is an antagonist of alpha-4 beta-7 integrins, which are associated with about 3% of lymphocytes that are likely to be targeted into the intestine. Ustekinumab is a monoclonal antibody that blocks the interaction of the integrin on lymphocytes with the addressin, or the receptor on blood vessels within the intestine. Vedolizumab has been shown to be effective in moderate to severe ulcerative colitis and Crohn disease, is administered intravenously in maintenance every 8 weeks, and because of this gut selectivity, has seemed to be a very safe agent because it’s not associated with systemic inflammation. Likewise, it’s not as effective in patients who have systemic or extraintestinal manifestations that aren’t associated with gut inflammation.

A review of various classes of biologic therapies available to treat patients with ulcerative colitis or Crohn's disease.

Treatment Options for Ulcerative Colitis and Crohn's Disease

In the management of chronic pain, the primary goal is to maximize the patient’s level of functioning; usually the focus is on the ability to perform at work or school or to accomplish household chores.

One important area of life for many people, however, is often overlooked by healthcare professionals: sexual functioning.

A recent systematic review published in Pain Medicine examined the current research on how chronic musculoskeletal pain may affect sexual functioning.* The review included studies of patients with pain persisting for ≥3 months and sexual difficulty before any intervention. Studies were excluded if participants had other disorders, such as diabetes, that could impact sexual function or where the pain disorder was located in the sexual organs.

The slide show below offers the review's top-line findings. 

Sexual difficulties in the population with musculoskeletal chronic pain: a systematic review. 

The impact on sexual function of chronic pain conditions has received little research inquiry and requires much more focused clinical attention. 

Sexual Function & Chronic Pain: Results of a Systematic Review 

 as of today, October 19, 2021, at 3:15 PM, EDT:

, as of today, October 19, 2021 at 5:22 PM, EDT, there have been:

 with 70 870 reported fatalities, followed by 