522 - Alcohol Use Disorder Rx, Actinic Keratosis Prognosis, Equanimity
From the Agency for Healthcare Research and Quality (AHRQ)
1) Medications for Alcohol Use Disorder
Alcohol use disorder (AUD) is an under-recognized cause of morbidity and mortality in the US affecting 28.3 million people older than 11 years and responsible for 140,000 deaths per year. Whereas medication treatment for opioid use disorder is well-recognized, only about 1% of people with AUD are prescribed medication-assisted treatment.
ARQH has newly updated a commissioned comparative effectiveness review from 2014 on medications for AUD. This systematic review used the same standard methodologies as the reviews performed for the US Preventive Services Task Force, with a comprehensive search for evidence, structured inclusion and exclusion criteria, critical appraisal of the included studies and an assessment for heterogeneity.
The review authors helpfully included drugs that are used off-label, if there was significant indication that they were used in the US. They also excluded trials with less than 12 weeks of follow up, since the short duration gives a skewed impression of effectiveness in this chronic disorder. All studies used medication in addition to behavioral therapies, such as counseling or group treatment.
The results, listed by the reviews’ Key Questions, are:
Effectiveness of the medications for reducing consumption of alcohol:
· Acamprosate reduced return to any drinking (relative risk (RR) 0.88, 95% confidence interval (CI) 0.83 to 0.93) and the percentage of heavy drinking days (-8.3 % of days, 95%CI -12.2 to -4.4), moderate strength of evidence (SOE).
· Naltrexone (50 mg dose) reduced return to any drinking (RR 0.93, 95%CI 0.87 to 1.00), return to heavy drinking (RR 0.81, 95%CI 0.72 to 0.90), percent of drinking days ( -5.10%, 95%CI -7.16 to -3.04) and percent of heavy drinking days (-4.26%, -7.61 to -0.91). Both the 100 mg dose and injectable naltrexone did not reduce return to drinking outcomes but did significantly decrease percentage of drinking days and heavy drinking days by 3-5 percent. SOE was moderate for return to drinking and low for drinking days outcomes.
· Disulfiram did not reduce return to any drinking (RR 1.03, 95% CI 0.90 to 1.17), low SOE.
· Baclofen reduced return to any drinking (RR 0.83, 95%CI 0.70 to 0.98), but improved no other outcomes, low SOE.
· Gabapentin reduced return to heavy drinking (RR 0.90, 95%CI 0.82 to 0.98), but improved no other outcomes, low SOE.
· Topiramate reduced percent drinking days (-7.2%, 95%CI -14.3 to -0.1), percent heavy drinking days (-6.2%, 95%CI -10.9 to -1.4) and number of drinks per drinking day (-2 drinks, 95%CI -3.1 to -1.0), moderate SOE.
· Varenicline had a low SOE of no benefit across all drinking outcomes.
· Evidence was insufficient or mixed for effects of ondansetron and prazosin.
A single study of injectable naltrexone was beneficial in reducing drinking days and heavy drinking days in people experiencing homelessness. The only available head-to-head comparison studies were included in the 2014 review and found no difference in outcomes between naltrexone and acamprosate (moderate SOE), naltrexone and topiramate, and disulfiram and naltrexone (both low/insufficient SOE).
Medications’ effect on health outcomes:
There was insufficient evidence for quality of life and any other health outcomes for all medications except: a low SOE for baclofen for no difference in quality of life and function and a low SOE for topiramate for injuries and quality of life.
Harms associated with medications:
There was no standard reporting of adverse events. Serious harm was rare; most were minor – diarrhea, dizziness, nausea, drowsiness, anxiety, etc. A head-to-head study found less headache and vomiting with acamprosate vs. naltrexone.
Medication use specifically in primary care:
There was only a single study conducted in a primary care setting, and it did not show a difference between acamprosate or placebo but had several methodological issues.
Medication effectiveness in specific subgroups of patients:
There was no evidence reported in subgroups of interest (gender, age, smoking status and comorbidity).
John’s Comments:
As many of you in Carilion know, we were part of a recent statewide study attempting to increase screening and treatment rates of AUD in primary care. We found, amongst other things, that not many primary care clinicians felt prepared to offer medication therapy. This review shows that we should offer naltrexone or acamprosate at a minimum and that we have some alternatives if these are not tolerated. For lots more quick information on AUD screening and management in primary care, including details about medications, head to our study website.
References:
· McPheeters M, O’Connor EA, Riley S, Kennedy SM, Voisin C, Kuznacic K, Coffey CP, Edlund M, Bobashev G, Jonas DE. Pharmacotherapy for Adults With Alcohol Use Disorder in Outpatient Settings: Systematic Review, Comparative Effectiveness Review No. 262. Agency for Healthcare Research and Quality; 2023. Link
From the Literature
2) The Clinical Significance of Actinic Keratoses
Actinic keratoses (AK) are common premalignant skin lesions with a small risk of progressing to cutaneous squamous cell carcinoma (SCC). Estimates indicate these lesions account for more than 10% of dermatology visits each year. Data have shown that somewhere between 0.06 – 0.6% of AKs advance to SCC per year. Lesions that do not progress to SCC may regress or persist as Aks with rates of regression estimated to be between 20-30%, though up to 50% of these may recur within a year.
There is some evidence that patients with AKs also have increased risks of other skin cancers beyond SCC due to the common denominator of cumulative ultraviolet (UV) light exposure, but this risk has not been well quantified.
A recently published retrospective cohort study attempted to answer this question. From a random sample of almost 5 million fee-for-service Medicare beneficiaries, a total of 555,945 patients with AKs with a mean age of 74 years (55% female, majority non-Hispanic white) were identified for the study. There were 481,024 patients with seborrheic keratoses (SKs) with a mean age of 73 years (72% female, majority non-Hispanic white) identified as a comparator group. All patients were required to have at least 1 year between data set entry and their first AK or SK. Patients with a history of skin cancer were excluded.
Outcomes were the first surgically treated skin cancer, including SCC, basal cell carcinoma (BCC) and melanoma. The researchers found the absolute risk of skin cancer after a first AK was 6.3% (95% CI, 6.3%-6.4%) at 1 year, 18.4% (95% CI, 18.3%-18.5%) at 3 years, and 28.5% (95% CI, 28.4%-28.7%) at 5 years. Patients with AKs also had an increased relative risk of all skin cancers compared with patients with SKs (adjusted hazard ratio [aHR], 2.17; 95% CI, 2.15-2.19).
The authors concluded that in older patients with AKs, there is a significant absolute risk of these patients developing a skin cancer in the next 5 years. They note that guidelines are lacking for follow-up skin cancer surveillance in patients with AKs and recommend that efforts to develop evidence-based recommendations for skin cancer surveillance in patients with AKs become a priority.
Mark’s Comments:
This Pointer became personal for me as I was treated with self-administered 5 fluorouracil (5 FU) for my own first AK over the past few weeks. Note that the study population of Medicare beneficiaries aged 65 years or older may not be a nationally representative sample, and surveillance bias may have contribute to the increased risk for skin cancer in patients with AKs. Interestingly, a study published in 2022 showed that for patients with multiple AKs treated with 5 FU, there was a 4-year risk of developing invasive cutaneous squamous cell carcinoma (cSCC) of 2.2%.
Once a patient is diagnosed with an AK, there is no reason we can’t treat them as well as follow them up for future surveillance. See the May 5,, 2023 Take 3 for more on skin cancer screening.
Reference:
· Mohr C et al. Skin Cancers in Medicare Beneficiaries with Actinic Keratoses. JAMA Dermatol. Published online November 8, 2023. Link
From PeerRxMed ( www.PeerRxMed.org )
3) Equanimity in the Midst of This Season’s “Surge”
“Let everything happen to you: beauty and terror. Just keep going. No feeling is final.” Rainer Maria Rilke (from the poem “Go to the Limits of Your Longing”) Full Poem
While here in southwest Virginia we have thus far been spared any unexpected surge of the many circulating seasonal viral illnesses, over the past few weeks I’ve been experiencing a “surge” of a different kind – that of an unusual amount of negatively charged and emotionally draining patient interactions, which have left me feeling frequently frustrated and quite weary. In this instance, I hope I’m alone in this experience, but in talking with some other colleagues, I fear that may not be the case. Since I know that our psyches are hardwired to overemphasize the “negative”, I have been consciously attempting to counter that tendency, but these interactions have often overwhelmed my emotional circuits.
It is in times like this that I find it helpful to revisit the psychological posture of “equanimity,” which is powerfully demonstrated by a favorite parable I have shared in this blog before and for my own sake, needed to revisit this week. Perhaps it will be a good reminder for you as well.
The Parable of the Farmer:
A farmer and his son had a beloved stallion who helped the family earn a living. One day, the horse ran away, and their neighbors exclaimed, “Your horse ran away, what terrible luck!” The farmer replied, “Maybe so, maybe not. We’ll see.”
A few days later, the horse returned home, leading a few wild mares back to the farm as well. The neighbors shouted out, “Your horse has returned, and brought several horses home with him. What great luck!” The farmer replied, “Maybe so, maybe not. We’ll see.”
Later that week, the farmer’s son was trying to break one of the mares and she threw him to the ground, breaking his leg. The villagers cried, “Your son broke his leg, what terrible luck!” The farmer replied, “Maybe so, maybe not. We’ll see.”
A few weeks later, soldiers from the national army marched through town, recruiting all the able-bodied boys for the army. They did not take the farmer’s son, who was still recovering from his injury. Friends shouted, “Your boy is spared, what tremendous luck!” To which the farmer replied, “Maybe so, maybe not. We’ll see.”
The word equanimity comes from the Latin aequanimitās, meaning “with an even mind; imperturbable.” It was during my residency training that I was first introduced to this concept when my department Chair shared Sir William Osler’s classic essay “Aequanimitās” with me. Dr. Osler considered equanimity as an essential quality for anyone in medicine but cautioned that it would only be attained with intentional practice. In the essay, he made it clear that equanimity was not a matter of denying our emotions (a common misperception), but rather in our consciously “owning” them and choosing when and how to express them rather than having them control us.
In reality, any circumstance we experience has the potential to elicit a wide spectrum of emotions. How we interpret and express them, however, is up to us, remembering that no feeling is final. After all, it’s our story, not theirs, as the parable so wisely demonstrates. How might the wisdom of the farmer inform the stories that you (and they) are telling right now? Are you ready to take ownership of any negative emotional surges that may arise from them? Well, we’ll see ….
Feel free to forward Take 3 to your colleagues. Glad to add them to the distribution list.
Mark and John
Carilion Clinic Department of Family and Community Medicine