See related AFP article, Top 20 Research Studies of 2023 for Primary Care Physicians.
Clinical question
Does bedtime administration of blood pressure medications improve outcomes?
Bottom line
Antihypertensive medication: Take it at a time that you are most likely to remember. In contrast with the problematic Hygia Chronotherapy Trial, this equally large TIME study found that it did not matter when patients took their blood pressure medications. Because medications are ineffective while still in the bottle, patients should take their antihypertensive medication when it suits them best.
Reference
Mackenzie IS, Rogers A, Poulter NR, et al.; TIME Study Group. Cardiovascular outcomes in adults with hypertension with evening versus morning dosing of usual antihypertensives in the UK (TIME study): a prospective, randomised, open-label, blinded-endpoint clinical trial. Lancet. 2022;400(10361):1417-1425.
Study design: Randomized controlled trial (single-blinded)
Funding source: Government
Allocation: Concealed
Setting: Outpatient (any)
Synopsis
The Hygia Chronotherapy Trial included more than 19,000 adults with hypertension and found that bedtime administration of antihypertensive medications decreased cardiovascular death and morbidity over more than 6 years of follow-up. However, it created a firestorm among hypertension researchers who thought the results were “too good to be true.” An independent review of the data confirmed the original study findings. In the Treatment in Morning vs. Evening (TIME) study, researchers randomly assigned adults with treated hypertension to take all their antihypertension medications either in the morning (6 AM to 10 AM; n = 10,601) or in the evening (8 PM to midnight; n = 10,503). The researchers instructed the evening-dose patients who were also taking a diuretic to take the diuretic earlier (6 PM) if they were troubled by nocturia or in the morning if the nocturia continued. The researchers used intention-to-treat analysis to compare the rate of the primary outcome—a composite of vascular death or hospitalization for nonfatal myocardial infarction or nonfatal stroke. The researchers used patient-submitted data supplemented by data from national registries. Adjudicators masked to allocation made the final outcome determinations. A total of 90.5% of participants were White, 42.5% were women, and 12.9% had preexisting cardiovascular disease. The mean baseline characteristics of each group were balanced. After a median follow-up of 5.2 years, 3.7% of the morning-dose patients and 3.4% of the evening-dose patients experienced the endpoint, and their time to first occurrence was similar. Additionally, there was no difference in the rate of any of the individual outcome components or in all-cause mortality (4.1% vs. 4.2%, respectively). The rate of adverse effects, including excessive visits to the toilet (day or night: 36.4% vs. 40.0%, respectively), were similar for both groups.
Henry C. Barry, MD, MS
Professor
Michigan State University
East Lansing, MI
Clinical question
Is a strategy of treat-to-target statin dosing noninferior to high-intensity dosing in adults with CAD?
Bottom line
Take a fixed-dose approach to lipid management. This study found that statin dosing based on a treat-to-target LDL cholesterol level of 50 to 70 mg per dL (1.29 to 1.81 mmol per L) is noninferior to a high-intensity strategy for reducing adverse events in adults with established CAD. Although the authors see this as an advantage that allows a tailored approach for individual dosing variability, it also serves as some of the best evidence yet that we can manage these patients with a high-intensity strategy and avoid the costs and burdens of repeated LDL cholesterol measurements.
Reference
Hong SJ, Lee YJ, Lee SJ, et al.; LODESTAR Investigators. Treat-to-target or high-intensity statin in patients with coronary artery disease: a randomized clinical trial. JAMA. 2023;329(13):1078-1087.
Study design: Randomized controlled trial (single-blinded)
Funding source: Industry
Allocation: Concealed
Setting: Outpatient (any)
Synopsis
There is minimal evidence supporting the superiority or noninferiority of a high-intensity strategy of statin dosing vs. a strategy of treating to a target low-density lipoprotein (LDL) level. These investigators identified 4,400 adults with coronary artery disease (CAD), including both stable ischemic heart disease and acute coronary syndrome. Eligible patients randomly received (concealed allocation assignment) a statin using either a strategy of treat-to-target an LDL level between 50 mg per dL and 70 mg per dL or a strategy of high-intensity therapy (20 mg rosuvastatin or 40 mg atorvastatin daily) without dose adjustment based on follow-up LDL levels. An independent committee masked to treatment group assignment assessed outcomes. Complete follow-up occurred for 98.7% of participants at 3 years.
Using both intention-to-treat and per-protocol analysis, the primary endpoint (a composite of all-cause death, myocardial infarction, stroke, and any coronary revascularization) occurred in 8.1% of the treat-to-target group and 8.7% in the high-intensity statin therapy group (nonsignificant difference; meeting the significance for noninferiority). No significant group differences occurred for multiple prespecified secondary end points, including new-onset diabetes, elevated liver enzymes, hospitalizations, end-stage kidney disease, or study drug discontinuation due to intolerance.
David C. Slawson, MD
Professor and Chair of Family Medicine Atrium Health
Charlotte, NC
Clinical question
Are ambulatory blood pressure readings better than clinic readings for predicting mortality?
Bottom line
Ambulatory blood pressure monitoring is better than office measurements. This study demonstrated that 24-hour ambulatory blood pressure monitoring was more informative than clinic readings for predicting mortality outcomes.
Reference
Staplin N, de la Sierra A, Ruilope LM, et al. Relationship between clinic and ambulatory blood pressure and mortality: an observational cohort study in 59 124 patients. Lancet. 2023;401(10393):2041-2050.
Study design: Cohort (retrospective)
Funding source: Other
Setting: Outpatient (any)
Synopsis
These authors, funded by government, foundations, and industry, linked data from the Spanish Ambulatory Blood Pressure Registry to the national vital statistics databases. The registry included 59,124 adults who met guideline-recommended indications for ambulatory blood pressure monitoring, which included suspected white-coat hypertension, refractory or resistant hypertension, assessment of drug treatment efficacy, high-risk hypertension, labile or borderline hypertension, and the study of circadian blood pressure patterns. Clinic blood pressures were based on the average of two readings recorded after 5 minutes of rest. The 24-hour ambulatory monitors measured blood pressure every 20 minutes during the day and every 30 minutes at night, and the researchers calculated the average for all valid readings.
The registry participants were, on average, 58.7 years of age, with a mean clinic blood pressure of 148/86.5 and a mean ambulatory blood pressure of 128.8/76.2. Slightly more than one-half (53%) were male. Over a median 9.7 years of follow-up, 7,174 (12.1%) of the participants died; 2,361 (4.0%) of those deaths were attributed to cardiovascular causes. Clinic and ambulatory pressures were only modestly correlated (0.43 and 0.52 for systolic pressure and diastolic pressure, respectively). After adjusting for many factors associated with mortality (age, sex, smoking status, body mass index, diabetes status, dyslipidemia, previous cardiovascular disease, number of antihypertensive drugs), the authors report that clinic systolic pressure was modestly associated with all-cause mortality (hazard ratio [HR] = 1.08) and cardiovascular mortality (HR = 1.11), whereas the associations with all-cause mortality and cardiovascular mortality were greater for ambulatory systolic pressure (HR = 1.30 and 1.41, respectively), daytime systolic pressure (HR = 1.25 and 1.35, respectively), and nocturnal systolic pressure (HR = 1.36 and 1.46, respectively).
Henry C. Barry, MD, MS
Professor
Michigan State University
East Lansing, MI
Clinical question
What is the optimal strategy for preventing strokes in adults 80 years or older who have atrial fibrillation?
Bottom line
In older adults with atrial fibrillation, DOACs have a better net clinical benefit compared with vitamin K antagonists. In this network meta-analysis that included lower-quality studies, DOACs provided a better balance of benefits (i.e., preventing stroke or systemic emboli) and harms (i.e., major bleeding) than vitamin K antagonists in adults 80 years or older with atrial fibrillation. The conclusions are consistent with findings from other analyses of DOACs that have demonstrated fewer harms and comparable benefits.
Reference
Lee KH, Chen YF, Yeh WY, et al. Optimal stroke preventive strategy for patients aged 80 years or older with atrial fibrillation: a systematic review with traditional and network meta-analysis [published correction appears in Age Ageing. 2023;52(1):afad002]. Age Ageing. 2022;51(12):afac292.
Study design: Meta-analysis (other)
Funding source: Government
Setting: Various (meta-analysis)
Synopsis
These authors searched multiple databases to identify studies that reported treatment outcomes of various anticoagulants to prevent stroke and other embolic events in adults with atrial fibrillation who were at least 80 years of age. The authors included 53 studies, 43 of which could be used for meta-analysis and 36 for network meta-analysis. Nine of the studies were randomized trials (12,461 participants) that had between 1 year and 2.8 years of follow-up. The 44 observational studies (383,630 participants) were both retrospective and prospective in nature and had up to 3.3 years of follow-up. The authors do not report the overall quality of the randomized or observational studies but report quality for the individual comparisons. For apixaban, dabigatran, rivaroxaban, and vitamin K antagonists, the overall quality was decent, and for edoxaban and aspirin the overall quality was low. The researchers' main interest was in comparing the direct oral anticoagulants (DOACs) with vitamin K antagonists. The rate of the composite of stroke or systemic emboli was slightly lower with the DOACs than with the vitamin K antagonists. Compared with placebo, the numbers needed to treat for the DOACs ranged from 19 to 22 compared with 23 for vitamin K antagonists. Compared with placebo, the DOACs also caused slightly fewer episodes of major bleeding (the number needed to treat to harm [NNTH] ranged from 7 to 24) than the vitamin K antagonists (NNTH = 9). Although aspirin was no more effective than placebo in preventing stroke or systemic emboli, it caused more major bleeding (NNTH = 9). The authors estimate that the net clinical benefit—a balance between benefits and harms—favored the DOACs in general and that edoxaban and apixaban had the best profiles. The inclusion of observational studies and the low-quality data for edoxaban likely overestimates its true effectiveness.
Henry C. Barry, MD, MS
Professor
Michigan State University
East Lansing, MI
Clinical question
In patients at high risk of cardiovascular disease, what is the effect of specific diets on mortality and cardiovascular events?
Bottom line
Mediterranean and low-fat diets minimally decrease mortality. This meta-analysis, which did not include low-carbohydrate/high-fat diets or intermittent fasting because of the lack of research, found that the Mediterranean diet (i.e., increased fish, fruit, vegetable, olive oil intake) and a low-fat diet were associated with a small benefit of reducing mortality and cardiovascular disease in patients with at least two risk factors. The small net benefit makes it unclear whether physicians should devote so much time to asking about and trying to affect diet, even in patients at high risk of adverse cardiovascular outcomes.
Reference
Karam G, Agarwal A, Sadeghirad B, et al. Comparison of seven popular structured dietary programmes and risk of mortality and major cardiovascular events in patients at increased cardiovascular risk: systematic review and network meta-analysis. BMJ. 2023;380:e072003.
Study design: Meta-analysis (randomized controlled trials)
Funding source: Self-funded or unfunded
Setting: Various (meta-analysis)
Synopsis
These investigators searched six databases, including Cochrane CENTRAL and a clinical trials database, and identified 40 English-language randomized studies that enrolled more than 35,000 participants across seven dietary programs: low fat, 18 studies; Mediterranean, 12; very low fat, six; modified fat, four; combined low fat and low sodium, three; Ornish, three; and Pritikin, one. All participants had at least two risk factors for cardiovascular disease. There were no studies of low-carbohydrate/high-fat diets or intermittent fasting included in this analysis because these have not been directly studied for their effects on cardiovascular disease and overall mortality. Two investigators independently selected studies for inclusion and extracted the data. The Mediterranean diet was associated with a small decrease in overall mortality (1.7%), as was a low-fat diet (0.9%). These diets were the most studied approaches in this analysis. The Mediterranean Diet also decreased, slightly, the risk of cardiovascular mortality (1.3%), stroke (0.7%), and nonfatal myocardial infarction (1.7%). The investigators rated the certainty of evidence as moderate for these approaches.
Allen F. Shaughnessy, PharmD, MMedEd
Professor of Family Medicine
Tufts University
Boston, MA
Clinical question
In the Omicron phase of the COVID-19 pandemic, is nirmatrelvir/ritonavir (Paxlovid) still effective at reducing hospitalizations and death in outpatients?
Bottom line
Nirmatrelvir/ritonavir is still effective for the Omicron phase of COVID-19. This well-done propensity score–matched study showed that nirmatrelvir/ritonavir continues to provide a clinically meaningful reduction in hospitalizations and death (number needed to treat = 62), especially in those who have received fewer vaccines and in adults older than 70 years. This is the third methodologically sound study with this conclusion. In the absence of randomized trials, this represents our best available evidence.
Reference
Schwartz KL, Wang J, Tadrous M, et al. Population-based evaluation of the effectiveness of nirmatrelvir-ritonavir for reducing hospital admissions and mortality from COVID-19. CMAJ. 2023;195(6):e220-e226.
Study design: Case-control
Funding source: Government
Setting: Outpatient (any)
Synopsis
The only published randomized trial of nirmatrelvir-ritonavir (Paxlovid) for outpatients with COVID-19 was completed in a relatively high-risk and unvaccinated population while the ancestral variant was predominant. Previous observational studies in Israel and Hong Kong found persistent benefit, especially in older adults. This Canadian study linked several databases (pharmacy, insurance, vaccination) to create a dataset with information on 177,545 patients with acute COVID-19, of whom 8876 had received Paxlovid. The patients' age range was 18 to 110 years, and the data were from April to August of 2022. The authors excluded those admitted to hospital, those with nosocomial infection, and non-Ontarians. Among the patients who received the medication, 72.5% were older than 70 years, 85% had three or more vaccines, and 57% had fewer than three comorbidities. The authors used propensity score matching to identify patients who were alike with regard to age, sex, vaccination status, and comorbidities but who differed with regard to whether they received Paxlovid. The groups who did and did not receive Paxlovid were quite different, but the propensity score matching is a good way to adjust for those differences. Overall, the use of Paxlovid reduced the likelihood of hospitalization or death in the weighted analysis (2.1% vs. 3.7%; odds ratio [OR] = 0.56; 95% CI, 0.47 to 0.67; number needed to treat [NNT] = 62). Mortality alone was also significantly lower (OR = 0.49; 0.40 to 0.60). Subgroup analyses found generally similar reductions in risk by age, vaccination, and the number of comorbidities. However, the absolute risk reduction and NNT were more favorable for patients older than 70 (NNT = 45) and for those who had fewer than 3 vaccinations (NNT = 28 to 30).
Mark H. Ebell, MD, MS
Professor
University of Georgia
Athens, GA
Clinical question
What is the optimal leukocyte cutoff for diagnosing UTI in older women?
Bottom line
Use a higher leukocyte cutoff to define pyuria in older women. For women 65 years and older, a much higher cutoff for pyuria should be used before diagnosing UTI to avoid overtreating asymptomatic bacteriuria. The optimal cutoff for automated microscopy was a leukocyte level of greater than 264 per μL (0.26 × 109 per L), which was 88% sensitive and 88% specific. A limitation of this diagnostic case-control design is that it tends to overestimate the accuracy of a test; therefore, a follow-up study using a cohort design that includes women with clinically suspected UTI should be done.
Reference
Bilsen MP, Aantjes MJ, van Andel E, et al. Current pyuria cutoffs promote inappropriate urinary tract infection diagnosis in older women. Clin Infect Dis. 2023;76(12):2070-2076.
Study design: Diagnostic test evaluation
Funding source: Government
Setting: Outpatient (any)
Synopsis
The usual cutoffs for diagnosing urinary tract infection (UTI) are greater than 10 leukocytes per microliter (mcl) or greater than 5 to 10 leukocytes/high-powered field. However, these cutoffs were derived from studies of premenopausal women. Approximately 20% of older women have asymptomatic bacteriuria (ASB), and 90% of them also have some degree of pyuria. To identify the optimal leukocyte cutoff for a diagnosis of UTI in older women, these researchers identified 63 women, 65 years and older, with UTI based on a positive urine culture for a uropathogen, at least two lower urinary tract symptoms (LUTS), and at least 10 leukocytes per mcl. The comparison group comprised 101 community-dwelling women, 65 years or older, without LUTS; 18 had ASB, 25 had a negative urine culture, and 58 had a culture with mixed flora. All urine samples underwent automated microscopy and urine flow cytometry. The area under the curve for leukocytes as a test for UTI was 0.93 for both methods. The optimal cutoff for automated microscopy was greater than 265 leukocytes per mcl, which was 88% sensitive and 88% specific (positive likelihood ratio [LR+] 7.2; negative likelihood ratio [LR-] 0.14). For flow cytometry, the optimal cutoff was greater than 231 leukocytes per mcl, which was 91% sensitive and 86% specific (LR+ 6.5; LR- 0.10). And what about the cutoff of greater than 10 leukocytes per mcl? It was 100% sensitive but only 36% specific.
Mark H. Ebell, MD, MS
Professor
University of Georgia
Athens, GA
Clinical question
What is the best oral monotherapy for toenail onychomycosis in adults?
Bottom line
Terbinafine for 12 weeks, followed by a period of no therapy, and then a 4-week booster is best for treating toenail onychomycosis. Based on effectiveness, safety, and cost, a regimen of terbinafine, 250 mg once daily for 12 weeks, followed by a 12-week period of no therapy, and then a 4-week booster of terbinafine, 250 mg, was preferred for onychomycosis in adults for the outcome of complete cure at 1 year. Terbinafine had fewer harms and a much lower cost than newer agents, such as oteseconazole (Vivjoa) and posaconazole (Noxafil), which can cost $1,000 or more.
Reference
Gupta AK, Venkataraman M, Bamimore MA. Relative impact of traditional vs. newer oral antifungals for dermatophyte toenail onychomycosis: a network meta-analysis study. Br J Dermatol. 2023;189(1):12-22.
Study design: Meta-analysis (randomized controlled trials)
Funding source: Self-funded or unfunded
Setting: Outpatient (any)
Synopsis
The goal of this network meta-analysis was to compare individual oral antifungal regimens directly and indirectly for onychomycosis in adults. The surface under the cumulative ranking curve (SUCRA), a measure of the likelihood that a regimen was more likely to be effective or to cause harms, was calculated for each study and outcome. The researchers identified a total of 21 studies. The study quality was mixed, with many studies failing to mask participants and/or physicians. An overall assessment of the quality of each study was not provided, although by my review they were mostly at moderate to high risk of bias. The highest complete cure rates at one year were found for 250 mg terbinafine once daily for 12 weeks, followed by no treatment for 12 weeks, followed by 250 mg terbinafine once daily for another 4 weeks (SUCRA = 82.7%); the same regimen, but with an initial treatment period of 8 weeks (SUCRA = 80.4%); and 400 mg albaconazole once weekly for 36 weeks (SUCRA = 80.4%). Terbinafine 250 mg once daily for 24 weeks had the highest likelihood of mycological cure (SUCRA = 92.4%). In terms of adverse events, terbinafine 250 mg daily for 12 weeks was found to be significantly safer than albaconazole 400 mg weekly for 36 weeks; oteseconazole 600 mg daily for 2 weeks, then 600 mg weekly for 10 weeks; fluconazole 300 mg once weekly for 12 months; and posaconazole 200 mg daily for 24 weeks. Terbinafine costs pennies compared with $1,000 or more for the newer agents such as albaconazole and posaconazole.
Mark H. Ebell, MD, MS
Professor
University of Georgia
Athens, GA
Clinical question
Are dextromethorphan, honey, or inhaled ipratropium (Atrovent) better than usual care for symptom relief in patients with acute cough?
Bottom line
Antitussives, honey, and anticholinergics are ineffective for cough. Overall, patients had an additional 6.3 days of moderate or worse cough after enrollment, ranging from 5.9 to 7.1 days, with no significant difference between groups. This primary care study was underpowered but adds to the literature that fails to find significant benefit to these agents. If someone wants to avoid opioids, honey seems like the safest ineffective alternative (except for in children younger than 12 months).
Reference
Llor C, Moragas A, Ouchi D, et al. Effectiveness of antitussives, anticholinergics, and honey versus usual care in adults with uncomplicated acute bronchitis: a multiarm randomized clinical trial. Fam Pract. 2023;40(2):407-413.
Study design: Randomized controlled trial (nonblinded)
Funding source: Government
Setting: Outpatient (primary care)
Synopsis
It is good to know what works, but it is also good to know what probably doesn't. These Spanish investigators identified patients with less than 3 weeks of at least moderately severe acute cough (at least 4 on a 7-point Likert-type scale). The 194 participants were randomized to 1 of 4 groups: (1) usual care, (2) ipratropium bromide 2 x 20 μg puffs three times daily, (3) 1 tablespoon of honey three times daily, or (4) dextromethorphan 15 mg three times daily. The primary outcome was achieving a score of less than 3 for severity of cough on a 7-point Likert-type scale. Approximately one-half the patients completed the study, but about two-thirds in each group had some outcome data. Groups were similar at baseline: a mean age of 53 years, two-thirds were women, and a median of 5 days of cough at enrollment. Overall, patients had another 6.3 days of moderate or worse cough after enrollment, ranging from 5.9 to 7.1 days, with no significant difference between groups. The Kaplan-Meier analysis found no significant difference between groups. I would have appreciated an arm with 3 days of hydrocodone, which at least has the benefit of sedating someone with nighttime cough.
Mark H. Ebell, MD, MS
Professor
University of Georgia
Athens, GA
Clinical question
Which antidepressant classes are effective for pain syndromes?
Bottom line
Among antidepressants, only SNRIs are effective for some types of pain syndromes. This umbrella review summarized the results of the most comprehensive systematic reviews on the use of antidepressants for treatment of various pain syndromes. It found that the only good evidence supported the use of SNRIs (e.g., duloxetine [Cymbalta], venlafaxine) to treat some types of pain, including back, postoperative, and neuropathic pain and fibromyalgia. Based on moderate- and low-quality evidence, antidepressants in other classes were not effective for pain.
Reference
Ferreira GE, Abdel-Shaheed C, Underwood M, et al. Efficacy, safety, and tolerability of antidepressants for pain in adults: overview of systematic reviews. BMJ. 2023;380:e072415.
Study design: Meta-analysis (other)
Funding source: Self-funded or unfunded
Setting: Other
Synopsis
These investigators searched four databases, including Cochrane CENTRAL, and identified 26 systematic reviews that collectively analyzed 156 trials that enrolled more than 25,000 participants, including children. They had no language limitations. They eliminated duplicate reviews (i.e., those that covered the same question). Two investigators independently selected articles for inclusion and abstracted the data. The included reviews evaluated a total of eight antidepressant classes for 22 pain conditions. Based on moderate certainty evidence, serotonin-norepinephrine reuptake inhibitors (SNRIs) produce clinically relevant decreases for back pain, postoperative pain, neuropathic pain, and fibromyalgia. Based on moderate-to-low certainty evidence, no other antidepressant classes significantly improved the pain syndromes mentioned above, or chronic pain, knee osteoarthritis, functional dyspepsia, and others.
Allen F. Shaughnessy, PharmD, MMedEd
Professor of Family Medicine
Tufts University
Boston, MA
Clinical question
Are opioids effective in alleviating pain in adults with acute, nonspecific low back or neck pain?
Bottom line
Opioids are not more effective than placebo for acute back or neck pain. This rigorously conducted study showed that from week to week over a 6-week period, adults with acute, nonspecific low back or neck pain randomized to opioids had similar pain relief to those treated with placebo.
Reference
Jones CMP, Day RO, Koes BW, et al.; OPAL Investigators Coordinators. Opioid analgesia for acute low back pain and neck pain (the OPAL trial): a randomised placebo-controlled trial [published correction appears in Lancet. 2023;402(10402):612]. Lancet. 2023;402(10398):304-312.
Study design: Randomized controlled trial (double-blinded)
Funding source: Government
Allocation: Concealed
Setting: Outpatient (any)
Synopsis
These researchers recruited adults with less than 12 weeks of new onset low back or neck pain who sought care from their primary care physician or in an emergency department. The patients could have radicular symptoms, but no alarm symptoms, and they had to have pain of at least moderate severity. The authors randomized the patients to receive an opioid (twice daily 5 mg oxycodone and 2.5 mg naloxone, titratable to 10 mg oxycodone; n = 174) or placebo (n = 172). The patients were treated until their pain score was 0 or 1 out of 10 for 3 consecutive days or for a maximum of 6 weeks. Although the researchers assessed the participants at 2, 4, 6, 12, 26, and 52 weeks after enrollment, the primary outcome was pain on a 10-point visual analog scale at 6 weeks. At baseline, both groups had similar pain ratings (5.7 and 5.6, respectively). After 6 weeks, more participants dropped out of the opioid group (19%) than the placebo group (15%). The remaining participants in both groups improved by a similar degree (2.8 and 2.2, respectively). At no point during the 52-week follow-up did the opioid-treated patients experience more pain relief than the placebo-treated patients. Indeed, at a few points in time, the placebo-treated patients had greater pain relief. The masking of participants worked—roughly one-half in each group could not guess their treatment assignment. Approximately one-third of participants in each group experienced adverse events, but serious adverse events were infrequent (4% and 2%, respectively). In pain studies, a change of 2 points on a 10-point scale is generally considered to be clinically meaningful. This study reported only average changes and did not report the proportion of participants in each group who achieved this threshold, thereby leaving the question of whether some patients respond better to opioids than others unanswered.
Henry C. Barry, MD, MS
Professor
Michigan State University
East Lansing, MI
Clinical question
In patients with pain and function loss due to knee osteoarthritis, does high-dose medical exercise therapy improve pain and functioning scores more than low-dose exercise?
Bottom line
Exercise therapy improves pain and function in osteoarthritis. Tailored exercise therapy of at least 20 to 30 minutes three times per week improves pain and function scores in approximately one-half of patients with painful knee osteoarthritis. For patients interested in sports and recreation, high-dose exercise therapy (70 to 90 minutes three times per week) produces better results.
Reference
Torstensen TA, Østerås H, LoMartire R, et al. High- versus low-dose exercise therapy for knee osteoarthritis: a randomized controlled multicenter trial. Ann Intern Med. 2023;176(2):154-165.
Study design: Randomized controlled trial (single-blinded)
Funding source: Foundation
Setting: Outpatient (primary care)
Synopsis
For this study, conducted in Norway and Sweden, the researchers enrolled 189 patients between 45 and 85 years of age with knee osteoarthritis and a history of pain and decreased knee function. The patients did not have previous therapy. Using concealed allocation, the authors assigned participants to either 20 to 30 minutes of low-dose exercise therapy (two sets of 10 repetitions) or 70 to 90 minutes of high-dose exercise therapy (three sets of 30 repetitions), tailored to their specific needs by a physical therapist. Both groups were given instruction on how to perform the exercises and how to adjust the weight to perform without pain. The participants were asked to perform the exercises, on their own, three times a week for 12 weeks. Both groups improved over time to a similar extent for most outcomes of pain and function using the Knee Injury and Osteoarthritis Outcome Score, with approximately one-half the participants experiencing a clinically meaningful improvement in all outcome categories. High-dose exercise was associated with approximately 20% more participants achieving a clinically important improvement on the Function in Sport and Recreation score, which lasted for 3 months after the end of the study. A few quibbles: The study may have been underpowered to find the minimally clinically important difference between treatments, if one existed. As one might expect, 23% of participants dropped out of the study over the 3 months. Given a possible placebo response in this unmasked study, I would have suggested the authors include a "usual care" group as the third comparator.
Allen F. Shaughnessy, PharmD, MMedEd
Professor of Family Medicine
Tufts University
Boston, MA
Clinical question
Are healthful behaviors associated with a lower likelihood of developing type 2 diabetes?
Bottom line
Healthful behaviors reduce the risk of developing type 2 diabetes. Exhibiting healthful behaviors—maintaining a healthy body weight, eating a healthy diet, exercising regularly, smoking abstinence or cessation, and limiting alcohol consumption—is associated with a lower likelihood of developing type 2 diabetes. This is an association; it does not mean that counseling people to follow these behaviors will lessen their likelihood of developing type 2 diabetes. It simply gives motivation to people who are following these healthy habits to keep doing them.
Reference
Khan TA, Field D, Chen V, et al. Combination of multiple low-risk lifestyle behaviors and incident type 2 diabetes: a systematic reviewand dose-response meta-analysis of prospective cohort studies. Diabetes Care. 2023;46(3):643-656.
Study design: Meta-analysis (other)
Funding source: Foundation
Setting: Various (meta-analysis)
Synopsis
These authors identified cohort studies (but not randomized studies) by searching three databases, including Cochrane CENTRAL, as well as reference lists of retrieved articles and Google Scholar. Two researchers independently selected research for inclusion and abstracted the data. The research had to involve tracking the relationship between at least three behaviors (including healthy body weight, healthy diet, regular exercise, smoking abstinence or cessation, and light alcohol consumption) and the subsequent development of type 2 diabetes. They found 30 cohort comparisons enrolling a total of 1,693,753 people, of whom 75,669 (4.5%) developed type 2 diabetes. The risk of bias of the studies was low, and there was no evidence of publication bias. Adhering to at least three of these behaviors was associated with an 80% lower risk of type 2 diabetes (relative risk = 0.20; 95% CI, 0.17 to 0.23) when comparing the people with the highest adherence to the behaviors to those with the lowest adherence. There was no difference in outcomes when evaluated by sex, although the behaviors seemed to have a greater impact on people younger than 50 years.
Allen F. Shaughnessy, PharmD, MMedEd
Professor of Family Medicine
Tufts University
Boston, MA
Clinical question
What is the association between long-term glycemic control and dementia in adults with type 2 diabetes?
Bottom line
Very poor glycemic control is associated with dementia risk. In this large population-based cohort, adults 50 years and older with type 2 diabetes whose cumulative glycemic control was greater than 9% were at an increased risk of developing dementia over 6 years of follow-up (adjusted hazard ratio = 1.31 to 1.74).
Reference
Moran C, Lacy ME, Whitmer RA, et al. Glycemic control over multiple decades and dementia risk in people with type 2 diabetes. JAMA Neurol. 2023;80(6):597-604.
Study design: Cohort (retrospective)
Funding source: Government
Setting: Population-based
Synopsis
These researchers used a diabetes registry from Kaiser Permanente Northern California and identified 253,211 adults with type 2 diabetes (T2DM) who were at least 50 years of age, had at least two glycated hemoglobin (HbA1c) readings and at least 3 years of follow-up, and did not have dementia at baseline. The registry included pharmacy and laboratory information, hospitalization records, and outpatient diagnoses. The authors grouped the HbA1c values into six groups (< 6%; 6% to < 7%; 7% to < 8%; 8% to < 9%; 9% to < 10%; 10% or more). Among the cohort, the researchers had more than 4.6 million HbA1c measurements and a median 5.9 years of follow-up. One-half the patients were White (50.6%), 9.9% were Black, 14.6% were Hispanic, and 17.5% were Asian. During the study time frame, 39,266 (15.5%) died, and 21,139 (8.3%) received a diagnosis of dementia. After multiple adjustments for factors potentially related to developing dementia or to degrees of glycemic control, the authors found a J-shaped relationship between glycemic control and the risk of developing dementia. The patients with cumulative HbA1cs of 9% to < 9.9% and those with cumulative HbA1cs greater than 10% had the greatest adjusted risk of dementia (hazard ratios [HRs] = 1.31 and 1.74, respectively). This study shows only associations, and many other factors the authors could not statistically manipulate could plausibly explain the association. To their credit, the authors state that their data support “relaxed glycemic targets for older people with type 2 diabetes.”
Henry C. Barry, MD, MS
Professor
Michigan State University
East Lansing, MI
Clinical question
What treatments for type 2 diabetes decrease the likelihood of adverse patient-oriented outcomes?
Bottom line
SGLT-2 inhibitors and GLP-1 receptor agonists are best at improving patient-oriented outcomes for type 2 diabetes. This study further separates the effect of diabetes treatments on blood glucose levels and important outcomes. SGLT-2 inhibitors and GLP-1 receptor agonists reduce all-cause and cardiovascular mortality and other cardiac-related problems. Older treatments, including insulin, do not affect long-term outcomes. Metformin was not found to be more effective than standard treatment to prevent important outcomes, which echoes previous findings.
Reference
Shi Q, Nong K, Vandvik PO, et al. Benefits and harms of drug treatment for type 2 diabetes: systematic review and network metaanalysis of randomised controlled trials. BMJ. 2023;381:e074068.
Study design: Meta-analysis (randomized controlled trials)
Funding source: Foundation
Setting: Various (meta-analysis)
Synopsis
These investigators searched three databases, including Cochrane Central, and identified 816 English-language randomized controlled studies (N = 471,038 participants) that compared two or more medications for type 2 diabetes. The researchers followed PRISMA criteria for reporting. Approximately one-quarter of the studies had a high risk of bias, usually due to lack of masking (62%). The researchers conducted a network meta-analysis, which compares all medications against one another by combining both direct and indirect evidence across all the studies. All the studies were short term, with a median duration of 6 months. Sodium glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists reduce all-cause mortality to a small extent compared with usual treatment. They also reduce death due to cardiovascular causes, the likelihood of nonfatal myocardial infarction, and admission for heart failure. They also have a demonstrated rate of adverse effects as compared with usual care. Finerenone (Kerendia) probably reduces, as compared with usual care, admissions for heart failure and end-stage kidney disease. Tirzepatide (Mounjaro) is associated with greatest amount of weight loss.
Just as important, this analysis clarifies which treatments do not have an overall benefit on patient-oriented outcomes. The older treatments, including insulin, do not affect mortality or hospitalizations, and the thiazolidinediones increase the likelihood of being admitted for heart failure. Metformin, the cornerstone of treatment in most guidelines, may not have a benefit over standard treatment.
Allen F. Shaughnessy, PharmD, MMedEd
Professor of Family Medicine
Tufts University
Boston, MA
Clinical question
Is mindfulness-based stress reduction noninferior to escitalopram for the treatment of anxiety disorders in adults?
Bottom line
Stress reduction training is a reasonable treatment option for adults with anxiety. This study found that standard mindfulness-based stress reduction is noninferior to pharmacotherapy with escitalopram for the treatment of anxiety disorders in adults. The primary outcome measurement occurred at 8 weeks from baseline. At 6 months, the anxiety scores remained improved, despite only 52% and 28% of patients in the escitalopram and mindfulness-based stress reduction groups, respectively, continuing treatment.
Reference
Hoge EA, Bui E, Mete M, et al. Mindfulness-based stress reduction vs escitalopram for the treatment of adults with anxiety disorders: a randomized clinical trial. JAMA Psychiatry. 2023;80(1):13-21.
Study design: Randomized controlled trial (single-blinded)
Funding source: Government
Allocation: Concealed
Setting: Outpatient (any)
Synopsis
Mindfulness-based stress reduction (MBSR) training is effective for decreasing anxiety symptoms in adults. It remains unclear how effective MBSR is compared with standard pharmacotherapy. These investigators identified adults, 18 to 75 years of age, with a primary diagnosis of generalized anxiety disorder, social anxiety disorder, panic disorder, or agoraphobia. Eligible patients (N = 276) randomly received assignment (concealed allocation) to either MBSR training (an 8-week protocol with weekly 2.5-hour long classes, a day-long weekend retreat class, and 45-minute daily home practice exercises) or escitalopram (10 mg daily orally, increased to 20 mg daily at week 2 if tolerated). Individuals masked to treatment group assignment assessed symptom severity using a standard validated anxiety scoring tool. Follow-up occurred for 95% of participants at 8 weeks.
Using both intention-to-treat and per-protocol analyses, at the primary endpoint of 8 weeks, MBSR therapy met the criteria for noninferiority compared with escitalopram. At 6 months of follow-up, 52% of patients were still taking escitalopram while only 28% of patients were still doing regular mindfulness meditation, yet the anxiety scores remained improved.
David C. Slawson, MD
Professor and Chair of Family Medicine Atrium Health
Charlotte, NC
Clinical question
Does framing depression as an adaptation to one’s environment, rather than a disease, result in better patient outcomes?
Bottom line
Framing depression as an adaptation can lead to better patient outcomes. Explaining to patients that their depressive symptoms are an adaptation to their current circumstances, rather than a disease, may produce less stigma and greater patient acceptance and self-efficacy. It may be time we start thinking of depression as a signal that something in a patient’s life needs more attention and not as something endogenous; this approach opens the toolbox. The chemical imbalance explanation of depression, if true at all, may be the effect and not the cause.
Reference
Schroder HS, Devendorf A, Zikmund-Fisher BJ. Framing depression as a functional signal, not a disease: rationale and initial randomized controlled trial. Soc Sci Med. 2023;328:115995.
Study design: Randomized controlled trial (nonblinded)
Funding source: Foundation
Allocation: Concealed
Setting: Outpatient (any)
Synopsis
"You have a chemical imbalance in your brain" is a common way to explain depression to patients. Although this explanation may decrease a patient's self-blame, it may also reduce their sense of hope for recovery, as well as stigmatize them or others with the "disease" of depression. It also may fail to get at the real explanation of depression for some—as an adaptation to the life situation in which they find themselves. This study enrolled 877 participants who had a history of depression (average Patient Health Questionnaire depression scale score 10.51) but had not been treated with psychotherapy or prescribed medication by a psychiatric specialist. The researchers' goal was to find people with depression who had not received the "depression is a disease" explanation, which is odd, because they allowed participation even if treated for depression by a primary care clinician (and what is even odder, they called these patients "treatment naive"). Using concealed allocation, participants were randomized to receive one of two descriptions of depression in a series of videos. One set of videos explained that depression is a disease caused by a variety of factors, including a chemical imbalance in the brain. The other set explained that depression was a functional signal that alerts the individual that something in his or her life needs more attention. There was a small benefit to the "depression as a signal" explanation in terms of participants' positive beliefs that they could overcome their depression (P = .02) and that depression is an adaptive response that can lead to new insights (P < .0001), and there was less stigma associated with mental illness in this group (P = .026). There was no difference in attitudes toward seeking help for depression, the participants feeling of responsibility for their symptoms, or indicators of a growth mindset toward depression. The effect sizes for the significant results were small, and it is possible that patients, either through their previous treatment experience or by consulting "Dr Google," were steeped in the depression-is-a-disease model.
Allen F. Shaughnessy, PharmD, MMedEd
Professor of Family Medicine
Tufts University
Boston, MA
Clinical question
Is an amoxicillin oral provocation challenge safe and accessible for distinguishing an erroneous penicillin allergy label from a true one in adults and children?
Bottom line
People labeled as penicillin allergic can be safely challenged in primary care. This study reports the outcome of an amoxicillin oral provocation challenge in 99 adults and children who were initially labeled as having a penicillin allergy and were subsequently identified by their history to be at low risk of a true allergy. A total of 96 patients (97%) completed the oral provocation challenge with no reaction, resulting in the removal of the erroneous allergy label. The three reactions were all mild and required minimal intervention (i.e., no epinephrine). Having primary care physicians use this method to identify the millions of adults and children who are incorrectly labeled as having a penicillin allergy may result in significant health care savings from the use of less effective, more expensive, or less safe alternative antibiotics.
Reference
Gateman DP, Rumble JE, Protudjer JLP, et al. Amoxicillin oral provocation challenge in a primary care clinic: a descriptive analysis. CMAJ Open. 2021;9(2):e394-e399.
Study design: Cohort (retrospective)
Funding source: Self-funded or unfunded
Setting: Outpatient (any)
Synopsis
Although approximately 10% of adults and children are labeled as having an allergy to penicillin, less than 20% of those are truly allergic. Referring the millions of adults labeled as allergic to penicillin for testing is not practical. However, an easy rule is available that can identify adults* at low risk of a true allergy. These investigators, using similar criteria as those in the decision tool, identified 99 adults and children, 18 months or older, considered at low risk (< 5%) of having a true penicillin allergy. Clinical settings were equipped with oral diphenhydramine elixir to manage mild reactions and epinephrine to manage anaphylactic reactions. Amoxicillin was given as an oral suspension (250 mg per 5 mL) with the first 10% of the challenge dose (50 mg or 4.5 mg per kg if the patient weighed < 10 kg) and the patients were observed for 20 minutes. If there was no reaction, patients received the remaining 90% of the remaining calculated dose (450 mg or 40.5 mg per kg) and were observed for an additional hour. A positive reaction was the development of objective findings, including urticaria, wheezing, or swelling, and did not include subjective symptoms such as pruritus without skin changes or dizziness. Patients were also instructed to report any delayed symptoms of rash, hives, wheezing, or swelling up to a week later.
Of the 99 eligible patients who completed the protocol, a mild reaction occurred in three patients (3%) and required the administration of oral diphenhydramine only. The remaining 96 patients (97%) had the penicillin allergy label removed from their medical record. No delayed reactions were reported.
*Note: Although the adult version is reliably accurate, the same is not true when using the same decision rule for children 12 years or younger.
David C. Slawson, MD
Professor and Chair of Family Medicine Atrium Health
Charlotte, NC
Clinical question
What is the rate of development of colorectal cancer in older patients with colon polyps?
Bottom line
Recommendations for a 5-year surveillance interval in older adults with previous polyps should trigger a discussion. In a population of older patients (65 years and older) with colon polyps identified by colonoscopy, few (0.2%) will develop colon cancer. It may be time to reevaluate the current recommendations for 5-year surveillance in older patients with previously identified polyps, especially for patients with a calculated shorter life expectancy.
Reference
Calderwood AH, Tosteson TD, Wang Q, et al. Association of life expectancy with surveillance colonoscopy findings and follow-up recommendations in older adults. JAMA Intern Med. 2023;183(5):426-434.
Study design: Cohort (prospective)
Funding source: Government
Setting: Population-based
Synopsis
These investigators used the registry from a single state in the United States to determine the outcome of surveillance colonoscopies performed on 9,831 people 65 years or older. Surveillance colonoscopies are performed on individuals with preexisting polyps. The participants were an average of 73.2 years of age, 46.2% were women, and 83.5% were White. Overall, 8% of patients were found to have advanced polyps and 0.2% had colorectal cancer.
Allen F. Shaughnessy, PharmD, MMedEd
Professor of Family Medicine
Tufts University
Boston, MA
Clinical question
Can nonprescription hearing aids be effective without a fitting by an audiologist?
Bottom line
Consider a do-it-yourself approach for hearing loss. Hearing aids are now available in many countries without the need for a fitting by an audiologist. This study found that participants reported a higher benefit with a self-fitted nonprescription hearing aid than with a hearing aid fitted by an audiologist. The hearing aid used in the study requires the use of a smartphone app.
Reference
De Sousa KC, Manchaiah V, Moore DR, et al. Effectiveness of an over-the-counter self-fitting hearing aid compared with an audiologist-fitted hearing aid: a randomized clinical trial. JAMA Otolaryngol Head Neck Surg. 2023;149(6):522-530.
Study design: Randomized controlled trial (nonblinded)
Funding source: Government
Allocation: Concealed
Setting: Outpatient (specialty)
Synopsis
These researchers recruited 64 adult participants, average age 63.6 years, who answered an advertisement regarding hearing loss. After bilateral hearing loss was verified, all participants received a nonprescription hearing aid (Lexie Lumen). The participants were then randomized, using concealed allocation, to be fitted by an audiologist or to self-fit the aid using the accompanying smartphone application. Rather than audiologic measurement, the primary outcome of this study was self-reported hearing aid benefit. Two weeks after receiving the hearing aid, self-reported hearing aid benefit was statistically higher (medium effect size), on average, in the self-fitting group. Speech recognition in noise was similar in both groups. At the end of the 6-week study, there were no differences between groups on any measure. The researchers did not comment on study power or sample size.
Allen F. Shaughnessy, PharmD, MMedEd
Professor of Family Medicine
Tufts University
Boston, MA
Clinical question
What are the current recommendations from American and European professional societies for the treatment of type 2 diabetes mellitus?
Bottom line
The management of type 2 diabetes continues to move away from glycemic goal chasing to a more holistic approach to patient care that also considers medications, weight management, attention to cardiovascular risk factors, and kidney protection. Metformin is recommended for most patients, although new classes of medications that affect the heart and kidneys should be considered for many patients. Sulfonylureas, thiazolidinediones, and insulin have little effect except to lower blood glucose levels and are distinctly de-emphasized.
Reference
Davies MJ, Aroda VR, Collins BS, et al. Management of hyperglycemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2022;45(11):2753-2786.
Study design: Practice guideline
Funding source: Foundation
Setting: Various (guideline)
Synopsis
These guidelines were developed by a working group comprising members from two professional societies and included endocrinologists and researchers (i.e., no patients or primary care clinicians). Most of the working group members had substantial relationships with the pharmaceutical industry. The group systematically reviewed the evidence and assessed its quality. Rather than strict guidelines ("do this, don’t do that"), these guidelines continue to move away from an emphasis on markers of glucose control and toward an emphasis on modifiable risk factors to prevent complications and optimize quality of life. However, they also recommend an HbA1c goal of less than 7% (53 mmol per mol) in most adults with a life expectancy of 10 years or more. The authors also suggest principles of care that are much more holistic, including emphasis on social determinants, psychosocial factors, and shared decision-making. The four buckets of care include weight management, medications for glycemia management, attention to cardiovascular risk factors, and kidney protection. Metformin remains a mainstay of treatment, although the authors also suggest treatment that controls glycemia and offers cardiorenal protection—that is, a sodium–glucose cotransporter 2 inhibitor (SGLT2i) and glucagon-like peptide 1 receptor agonist (GLP-1 RA) medication, alone or in combination. Insulin is pushed to the back of the line, to be used when needed to provide further control of blood sugar.
Allen F. Shaughnessy, PharmD, MMedEd
Professor of Family Medicine
Tufts University
Boston, Mass.
Clinical question
What are the updated guidelines from the ACP for the treatment of acute depression?
Bottom line
For patients in the acute phase of major depressive disorder, the ACP continues the trend away from drug therapy to talk therapy. CBT is recommended as first-line treatment for patients with moderate symptoms (conditional recommendation). The group recommends offering CBT, medication therapy, or a combination to patients with more profound symptoms based on evidence that up to 70% of patients with moderate to severe depression will not respond to a second-generation antidepressant.
Reference
Qaseem A, Owens DK, Etxeandia-Ikobaltzeta I, et al. Nonpharmacologic and pharmacologic treatments of adults in the acute phase of major depressive disorder: a living clinical guideline from the American College of Physicians [published correction appears in Ann Intern Med. 2023;176(8):1143-1144]. Ann Intern Med. 2023;176(2):239-252.
Study design: Practice guideline
Funding source: Foundation
Setting: Various (guideline)
Synopsis
This report updates the guidelines last issued by the American College of Physicians (ACP) in 2016. It is based on a separate systematic review that focused on patient-oriented outcomes; it specifically reviewed patient values and preferences. No guideline development members had conflicts of interest. The evidence was graded. For mild depression, the group recommends cognitive behavior therapy (CBT) and not medication (conditional recommendation; low-certainty evidence). For moderate to severe symptom scores, the guidelines recommend, based on patient preference, either CBT or a second-generation antidepressant (i.e., not a tricyclic antidepressant) without recommending a specific one (strong recommendation; moderate-certainty evidence). The combination of psychotherapy and medication is also an option for moderate to severe depression (conditional recommendation; low-certainty evidence). Patients who do not respond to initial drug treatment should be switched to or augmented with CBT (conditional recommendation; low-certainty evidence), switched to a different medication, or treated with an additional antidepressant (conditional recommendation; low-certainty evidence).
Allen F. Shaughnessy, PharmD, MMedEd
Professor of Family Medicine
Tufts University
Boston, Mass.
Clinical question
When should screening for colorectal cancer begin, and how should it be done?
Bottom line
This ACP guideline updates recommendations from a 2019 ACP guideline, based on the publication of two new guidelines from other groups. There are two new recommendations: (1) consider not screening for colorectal cancer in patients 45 to 49 years of age, and (2) do not use stool DNA, computed tomography colonography, capsule endoscopy, urine, or serum tests to screen for colorectal cancer.
Reference
Qaseem A, Harrod CS, Crandall CJ, et al. Screening for colorectal cancer in asymptomatic average-risk adults: a guidance statement from the American College of Physicians (version 2). Ann Intern Med. 2023;176(8):1092-1100.
Study design: Practice guideline
Funding source: Foundation
Setting: Various (guideline)
Synopsis
This guidance from the American College of Physicians focused on how best to avoid premature death due to colorectal cancer (no screening test for colorectal cancer has been shown to reduce all-cause mortality) by screening adults at average risk (i.e., those without a family history or other risks). The guidelines are based on a review of existing guidelines that provide discrepant recommendations. All guidelines except one were from North America, and all were younger than 5 years old. The guidelines were evaluated using the Appraisal of Guidelines for Research & Evaluation (AGREE) II instrument. The guideline committee reported no financial conflicts of interest and, unusual for guideline developers, recused members with intellectual conflicts of interest. The working group included a patient representative. They considered benefits, risks, and costs in their recommendations (some groups, such as the United States Preventive Services Task Force, do not consider cost). The guideline continues to suggest beginning screening at 50 years of age and stopping at 75 years of age, or earlier if patients have a life expectancy of 10 years or less. They suggest not screening asymptomatic average-risk adults between the ages of 45 to 49 years; at the very least, benefits and harms of screening should be discussed before setting up screening. They continue to suggest presenting benefits, harms, costs, and frequency data to patients and letting them decide whether they want to be screened via (1) fecal immunochemical test (FIT) or high sensitivity guaiac-based fecal occult blood testing every 2 years; (2) colonoscopy every 10 years; or (3) flexible sigmoidoscopy every 10 years with FIT every 2 years. The guideline recommends against screening using stool DNA, computed tomography colonography, capsule endoscopy, urine, or serum screening tests for colorectal cancer.
Allen F. Shaughnessy, PharmD, MMedEd
Professor of Family Medicine
Tufts University
Boston, Mass.
Clinical question
What medications are problematic for older patients according to the AGS?
Bottom line
The 2023 AGS Beers list provides many resources to assist in the rational prescribing of medications for patients 65 years and older. The AGS panel properly encourages the use of these resources judiciously and their use in shared decision-making.
Reference
The 2023 American Geriatrics Society Beers Criteria Update Expert Panel. American Geriatrics Society 2023 updated AGS Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2023;71(7):2052-2081.
Study design: Practice guideline
Funding source: Self-funded or unfunded
Setting: Various (guideline)
Synopsis
The American Geriatric Society (AGS) convened a 12-person panel to evaluate systematic reviews and other evidence to update the 2019 AGS Beers Criteria® (I dislike the word "criteria" here; it sounds like a mandate). The panel used an iterative voting process to develop their final recommendations. One decision, taken to simplify the list, was to eliminate medications from the previous list that are rarely prescribed in the United States or are no longer on the market (such as flurazepam or reserpine). The list is fairly exhaustive, but the panel calls out a few noteworthy changes. For example, in their recommendations on using anticoagulants—always a challenge in balancing benefits and harms—the authors recommend not using warfarin as initial therapy for adults with nonvalvular atrial fibrillation or for treating venous thromboembolic phenomena. Additionally, the panel recommends avoiding anticholinergic drugs, oral and transdermal estrogen, sulfonylureas, and aspirin for the primary prevention of cardiovascular disease. The panel also expanded the sections on drug–disease and drug–drug interactions. Scattered throughout are recommendations for deprescribing medications on the list that patients already take. The panel attempted to address many limitations to their list. In my mind, the most significant limitation is the inability to distinguish between the very real potential harms in the frail patient and the potential harms, as well as benefits, in the healthy older patient. This means that clinicians should use this list as a guide to therapeutic decisions, but not as an absolute mandate. Now if only our e-prescribing systems could stop nagging us when we make reasonable decisions.
Henry C. Barry, MD, MS
Professor
Michigan State University
East Lansing, MI
Clinical question
What are the latest evidence-based guidelines for the management of functional dyspepsia?
Bottom line
These thoughtful, evidence-based guidelines provide a helpful framework for evaluating and treating dyspepsia. The guidance regarding imaging and the use of upper endoscopy is probably on the conservative side for U.S. physicians. The authors acknowledge that approximately half of the recommendations are based on low- or very low-quality evidence.
Reference
Black CJ, Paine PA, Agrawal A, et al. British Society of Gastroenterology guidelines on the management of functional dyspepsia. Gut. 2022;71(9):1697-1723.
Study design: Practice guideline
Funding source: Foundation
Setting: Outpatient (any)
Synopsis
This 2022 guideline, last updated in 1996, was based on a series of systematic reviews and network meta-analyses. The authors recommend urgent evaluation of patients with upper gastrointestinal alarm symptoms, such as anyone with dysphagia, or persons 55 years or older with weight loss and either dyspepsia, upper abdominal pain, or reflux. They also recommend urgent evaluation for patients 40 years or older who are either from a region where gastric cancer is common or who have a family history of gastroesophageal cancer. Other alarm symptoms warranting a less urgent evaluation include hematemesis; and in persons 55 years or older, treatment-resistant dyspepsia, dyspepsia, or upper abdominal pain with elevated platelet count, low hemoglobin, nausea or vomiting, or nausea or vomiting with any weight loss, reflux, dyspepsia, or upper abdominal pain. Patients without alarm symptoms who present with at least 2 months of epigastric burning or pain, early satiety, and/or postprandial fullness should be given a diagnosis of functional dyspepsia and be told that it is a disorder of gut-brain interaction. As part of the initial evaluation, all patients 55 years or older should have a complete blood count with platelets, those with overlapping irritable bowel symptoms should have celiac serology, and those 60 or older with abdominal pain and weight loss should have an abdominal CT to evaluate for pancreatic cancer.
All patients with dyspepsia should be evaluated for the presence of helicobacter pylori (HP) using a stool or breath test, and if the results are abnormal the patient should be treated to eradicate HP (another recent study confirms that eradication not only reduces the risk of ulcer but is also effective for functional dyspepsia). Confirmation of HP eradication is recommended only for patients at increased risk of gastric cancer, although it should also be considered in patients whose symptoms persist. The guidelines recommend against the routine use of gastric emptying tests or 24-hour pH monitoring. For patients who are HP negative, first-line therapy includes acid-suppressive therapy with a histamine antagonist or proton pump inhibitor and regular aerobic exercise; the guidelines do not recommend specific diets such as a FODMAPS diet. Prokinetics may be an effective treatment, with the strongest evidence supporting tegaserod. Second-line therapies include low-to-moderate dose tricyclic antidepressants (e.g., amitriptyline 10 mg once daily, titrating to 30 mg to 50 mg). The authors recommend against selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and buspirone. Finally, cognitive behavioral therapy, psychodynamic interpersonal psychotherapy, stress management, and hypnotherapy may be effective. Patients with refractory or persistent symptoms should be referred to a gastroenterologist. It is important to note that approximately half of the 35 recommendations in the guidelines are based on low- or very low-certainty evidence.
Mark H. Ebell, MD, MS
Professor
University of Georgia
Athens, GA
Levels of Evidence definitions from Essential Evidence Plus
POEMs are provided by Essential Evidence Plus, a point-of-care clinical decision support system published by Wiley-Blackwell. For more information, please see http://www.essentialevidenceplus.com.