Monday, June 28, 2021
Monday, June 21, 2021
- Jennifer Middleton, MD, MPH
Many prescribers discontinue patients' angiotension-converting enzyme inhibitors (ACE-Is) or angiotension receptor blockers (ARBs) as their estimated glomerular filtration rate (eGFR) worsens due to concerns about hyperkalemia, hypotension, and/or worsening chronic kidney disease (CKD). Slightly less than half of all persons with CKD stage 4 or 5 in the United States (US) are not currently prescribed an ACE-I or ARB. Two recent studies, however, demonstrate potential benefits of ACE-I and ARB use in patients with advanced CKD.
The first study reviewed the medical records in a large US health system of nearly 4,000 patients with CKD who were prescribed an ACE inhibitor or an ARB and whose CKD eventually worsened to an eGFR below 30 mL/min/1.73m2. Cohorts were divided into patients whose ACE-Is or ARBs were discontinued when their eGFR dropped below 30 mL/min/1.73m2 and those patients whose ACE-Is or ARBs were continued despite this lower eGFR. Researchers then tracked participants' outcomes for 5 years. They found that persons who had their ACE-I/ARB discontinued had a higher mortality risk than those whose ACE-Is/ARBs were continued (hazard ratio [HR] 1.39; 95% CI 1.20-1.60). The risk of adverse cardiac events was higher in persons who had stopped their ACE-I/ARB (HR 1.37; 95% CI 1.20-1.56). There was no difference in the rate of CKD progression to end-stage kidney disease (ESKD) between groups (HR 1.19; 95% CI 0.86-1.65).
The second study reviewed the medical records of nearly 5000 patients in Sweden with an eGFR below 30 mL/min/1.73m2 (but not receiving dialysis) who received a new prescription for either an ACE-I/ARB or a calcium channel blocker (CCB). After a median of 4.1 years, persons who received an ACE-I/ARB had a lower risk of needing to initiate dialysis compared to the persons who received a CCB (adjusted HR, 0.79 [95% CI, 0.69-0.89]). Mortality and risk of adverse cardiac events were similar in both groups (adjusted HR, 0.97 [95% CI, 0.88-1.07] and adjusted HR, 1.00 [95% CI, 0.88-1.15]), respectively).
These two studies examined different nuances of patients with advancing CKD: the first, persons whose previous ACE-I/ARB was continued despite worsening eGFR, the second, persons receiving new prescriptions for ACE-I/ARB at a lower eGFR. These differences may explain the studies' differing findings regarding mortality benefit of these medication classes (only found in the first study), adverse cardiac events benefit (the first study), and lowered risk of advancement to ESKD (the second study).
Cohort studies can only demonstrate correlation. Both studies' authors acknowledge the potential for unrecognized confounding factors; for example, it's possible that the persons in both studies who didn't receive ACE-Is/ARBs were somehow more ill than those who did. Until we see randomized controlled trials comparing these approaches, though, these current studies are the best evidence we have to date, and they suggest that continuing ACE-I/ARBs in persons with advanced CKD is likely safe and may have benefits.
If you'd like to read more, check out the AFP By Topic on Kidney Disease, which includes this article on "Chronic Kidney Disease: Detection and Evaluation" and this Cochrane for Clinicians on "ACE Inhibitors vs. ARBs for Patients with Diabetic Kidney Disease."
Monday, June 14, 2021
- Kenny Lin, MD, MPH
The need to restrict in-person office visits in 2020 to slow the spread of the COVID-19 pandemic affected prenatal care, as some in-person visits were transitioned to virtual or visit intervals were extended. But how did the traditional U.S. prenatal visit schedule - monthly until 28 weeks, biweekly until 36 weeks, and weekly until delivery - become established in the first place? According to a recent review article in the American Journal of Obstetrics & Gynecology, the present-day schedule of 12-14 visits over the course of one's pregnancy was codified in 1930 in a booklet published by the Federal Children's Bureau, during an era when the majority of births occurred in the home. In the intervening century, the only major effort to change the frequency of prenatal appointments came in 1989, when an expert panel commissioned by the Department of Health and Human Services recommended a flexible, risk-based schedule:
Their proposed schedule included 7 visits for low-risk multiparous patients and 9 visits for low-risk nulliparous patients, with additional visits added as needed for high-risk patients based on medical and social risk factors. Interestingly, they suggested a phone visit for multiparous patients at 10 week's gestation, perhaps a first step toward what we now see as telemedicine for prenatal care.
The American College of Obstetricians and Gynecologists (ACOG) decided to reject the new schedule based on insufficient supporting evidence, even though "these recommendations implied maintaining an existing visit structure that was also not evidence-based." Then, as now, supporting evidence for prenatal interventions was limited. For example, though long endorsed by ACOG, counseling for healthy weight and weight gain in pregnancy was not officially recognized by the U.S. Preventive Services Task Force as a beneficial preventive service until last month.
A research study of the Google Trends database suggested that interest in planned community birth in the U.S. and the United Kingdom rose during the pandemic: the frequency of online search queries related to home birth increased by 239% and 53%, respectively, from March through November 2020 compared to the preceding year. According to an article by Dr. Gregory Lang and colleagues in the June 1 issue of American Family Physician, out-of-hospital births increased by 75% from 2004 to 2017, and in 2018 one out of every 61 newborns was delivered outside of a hospital. Planned community births are associated with a lower risk of obstetric interventions, including cesarean delivery, and, in "low-risk, vertex, singleton, term pregnancies in patients who have not had a previous cesarean delivery," neonatal outcomes may be similar to those in hospital settings.
In an accompanying editorial, Drs. Lawrence Leeman and Jessica Goldstein discussed ways to promote safety in community-based birth settings, including "adequate birth attendant training, access to emergency obstetric care, and careful risk assessment throughout the prenatal and intrapartum periods." The authors noted that regardless of whether they personally provide maternity care services, "family physicians play an important role in improving the safety of community birthing by offering counseling on the choice of birth setting, consultation, and collaboration during prenatal care, and by facilitating the process of maternal or newborn transfer [to the hospital] when necessary."
Monday, June 7, 2021
- Jennifer Middleton, MD, MPH
The United States Preventive Services Task Force (USPSTF) updated its recommendations for colorectal cancer (CRC) screening last month; it is now a B recommendation for adults aged 45-49 to be screened. (The previous A recommendation for adults aged 50-75 is unchanged.) An increasing prevalence of CRC in younger adults, along with more outcome data from screening younger adults, led to the new recommendation for adults aged 45-49:
[T]he USPSTF determined that beginning screening at age 45 years and continuing to the age of 75 years, for the following screening strategies, yielded a reasonable balance of benefits (life-years gained) and burdens or harms (number of colonoscopies): annual FIT, sDNA-FIT every 1 to 3 years, CT colonography or flexible sigmoidoscopy every 5 years, colonoscopy every 10 years, or flexible sigmoidoscopy every 10 years with annual FIT.
The USPSTF's statement was supported by a systematic review and a modeling study. The systematic review sought to answer: 1) how effective is CRC screening to lower rates of CRC cancer and/or mortality, 2) how accurate are the available screening modalities, and 3) what are the harms of CRC screening. The researchers found that 1) screening via the modalities listed above* decreases cancer rates and improves mortality, 2) several modalities* have reasonable data to support their use, and 3) most harms are due to colonoscopy; since persons with a positive screening test then require colonoscopy, colonoscopy's harms were applied by researchers to the other testing modalities (the article's Table 4 reviews these in-depth). The modeling study used three sophisticated microsimulation models and found that "screening for colorectal cancer with stool tests, endoscopic tests, or computed tomography colonography starting at age 45 years provides an efficient balance of colonoscopy burden and life-years gained."
The studies cited by the systematic review did not separately analyze their data for adults aged 45-49, and the modeling study is limited by the assumptions entered into the model by researchers. Criticism of the new recommendation for adults aged 45-49 centers around the lack of randomized controlled trials specifically examining this population. The capacity to accommodate this additional population segment is also of concern: "[r]eliance on colonoscopy for screening among individuals aged 45 to 49 years might crowd out approximately one-third of individuals aged 50 to 75 years whose [colorectal cancer] screening is not up-to-date, given limited endoscopy capacity in some communities." The new recommendations are also not an endorsement to ignore patients with concerning symptoms under the age of 45, since "[n]early half of patients with early onset CRC are diagnosed before age 45 years...as was the case for the actor Chadwick Boseman, who died from CRC at age 43 years. Symptoms of CRC...should be evaluated promptly with appropriate diagnostic tests."
As family physicians, we should both discuss the new recommendation with patients and also provide guidance regarding the choice of screening modality when appropriate. Although these 2020 AFP Practice Guidelines from the BMJ and the ACP refer to the 2016 USPSTF recommendation statement, their overviews of CRC screening options remain relevant and useful. The USPSTF's website also has this table reviewing the evidence base behind each screening modality.
* recommended screening modalities are annual Fecal Immunochemical Test (FIT), stool DNA-Fecal Immunochemical Test (sDNA-FIT) every 1-3 years, CT colonography or flexible sigmoidoscopy every 5 years, colonoscopy every 10 years, or flexible sigmoidoscopy every 10 years with annual FIT.
Tuesday, June 1, 2021
Few patients understand what the SARS-CoV-2 virus does to the human body or how a COVID-19 messenger RNA (mRNA) vaccine works. The following patient-centered explanation utilizes readily understood metaphors and two clear, simple illustrations that you may use in your vaccine counseling visits. When patients understand how the virus infects cells and how an mRNA vaccine works, most anti-vaccine myths are neutralized and vaccine hesitancy decreases.
Here is a sample conversation I've used to help persuade vaccine-hesitant and vaccine-resistant patients of the safety of the COVID-19 mRNA vaccines:
"Ms. Smith, can I explain to you how the COVID virus infects our body?
Here is a picture of the virus. You can see the spike proteins on the outside. These are like suction cups. They help the virus attach to the cells in our lungs. Inside the virus is RNA, which functions like a DVD because it stores all the information needed to make another virus. For this reason I've made it look like a DVD.
The mRNA then goes to the part of the cell that makes proteins. But instead of making a single COVID virus, the mRNA tricks the cell into making thousands of copies of the virus. This overwhelms the cell, causing it to explode, releasing all of those viruses to attack other lung cells. This process occurs until our immune system gets the outbreak under control. By then, in some patients with risk factors, too much damage has been done to the lungs, causing respiratory failure.
Now let me compare this to how an mRNA vaccine works. Imagine this book is the entire COVID RNA. To make the vaccine, a single page of this book with instructions for how to make a spike protein was photocopied. That information is all that is in the vaccine. When it gets inside a cell, the body sees it and says "Hey, these are instructions for making a protein!" Then the spike protein is made. At this point, the cell looks at the spike protein and says "Hey, you don't have ID!" Antibodies are made that fit the shape of the spike protein. The protein is quickly destroyed, as was the single page of mRNA instructions. So all you have left at this point are the antibodies against the spike protein, ready to attack the actual COVID virus.
You can see from this explanation that all of the mRNA in the COVID vaccine is actually present in a COVID infection. But instead of making cells explode, it just prepares the body to fight off the infection. So it makes no sense to downplay the risk of a COVID infection and exaggerate the risk of the mRNA vaccine when the complete set of COVID RNA and mRNA enter your body when you get infected. Every other time in your life you had a viral infection, your body had no problem getting rid of virus proteins and virus mRNA. It is no different with the mRNA of the COVID vaccines."
Dr. Porter is a staff physician at Waco Family Medicine in Waco, Texas.