• Combined Aerobic and Resistance Exercise Is Best for Dieting Obese Elders
• Predicting Short-Term Mortality in Older Patients with End-Stage Renal Disease
• Minocycline for Early Multiple Sclerosis
• Pravastatin Shows No Benefit for Primary Prevention in Older Adults
• Statins Are Associated with Improved Survival After Colon Cancer Diagnosis
• Daily Texting and Media Use Linked to Worse Mental Health Symptoms in at-Risk Teens
• A New Policy on Fruit Juices
• How Common Are Cotton-Tip Applicator Ear Injuries in Children?
• ADHD Is More Common in Kids with Adverse Childhood Experiences
• Which Doctors Are More Likely to Overuse Antibiotics?
• The Beginning of the End for Bioresorbable Coronary Scaffolds?
• NSAIDs, Selective COX-2 Inhibitors, and PPIs: What's the Best Combination to Reduce PUB?
• Proton-Pump Inhibitor Use and Ischemic Stroke
N Engl J Med 2017 May 18; 376:1943
Combined Aerobic and Resistance Exercise Is Best for Dieting Obese Elders
Thrice weekly combined exercise resulted in better conditioning than either exercise type alone.
Obesity causes frailty in older adults, but weight loss might promote loss of muscle and bone mass, and the relative merits of aerobic and resistance exercise are unclear. Investigators conducted a trial in 141 obese sedentary older adults (age, ≥65) with mild-to-moderate frailty on a formal Physical Performance Test, which included assessments of walking, stair-climbing, fine motor skills, strength, and balance. Participants were assigned to one of three exercise groups (aerobic, resistance, or combined) or a nonexercise control group. All exercise participants received instruction on a balanced weight-loss diet. The aerobic and resistance groups each exercised 40 minutes thrice weekly. The combined aerobic-and-resistance group performed aerobic and resistance exercises, each for 30 to 40 minutes, thrice weekly.
After 6 months, mean improvements on the Physical Performance Test (the primary outcome) were significantly better in the combined group than in the aerobic or resistance groups. Strength increased more in the resistance and combined groups than in the aerobic group. Peak oxygen consumption increased more in the aerobic and combined groups than in the resistance group. Lean mass and bone-mineral density decreased less in the resistance and combined groups than in the aerobic group. Weight loss was identical (9%) in the three exercise groups. Each of these outcomes was substantially better in the exercise groups than in controls.
COMMENT: In this study, weight loss and a combination of both aerobic and resistance exercise was better than either aerobic or resistance exercise alone in older adults with mild-to-moderate frailty. Presumably, these findings also would apply to physically similar younger adults.
CITATION(S): Villareal DT et al. Aerobic or resistance exercise, or both, in dieting obese older adults. N Engl J Med2017 May 18; 376:1943.
(http://dx.doi.org/10.1056/NEJMoa1616338)
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Am J Kidney Dis 2017 May; 69:568
Predicting Short-Term Mortality in Older Patients with End-Stage Renal Disease
Overall 6-month mortality was 17% after dialysis initiation.
Older patients with end-stage renal disease are more likely than younger patients to develop complications during hemodialysis. In this study of the 2200 older adults (age, ≥65; mean age, 75) living in Alberta, Canada, who began maintenance hemodialysis during a recent 9-year period, researchers derived and validated a 6-month mortality prediction tool.
Overall, 17% of patients died within 6 months after starting dialysis. Seven variables independently predicted 6-month mortality: age ≥80, estimated glomerular filtration rate ≥10 mL/minute/1.732 when dialysis was initiated, atrial fibrillation, congestive heart failure, metastatic cancer, lymphoma, and hospitalization within the past 6 months. Points were assigned to each predictor, weighted for their effect on mortality (maximal score, 19 points). For example, 6-month mortality was less than 10% in patients with 0 to 2 points, and about 40% in patients with 9 to 10 points.
COMMENT: Although this study was population-based (within a Canadian province), its prediction tool should be validated in other populations. Perhaps the most important observation is that one in six older patients who initiated dialysis died within 6 months; in a U.S. study of Medicare patients (mean age, 77), 6-month mortality findings were similar (Am J Kidney Dis 2015; 66:1024). Although discussions about prognosis can be difficult or uncomfortable in older patients who are considering chronic dialysis, it's important to share this information with patients and their families.
CITATION(S): Wick JP et al. A clinical risk prediction tool for 6-month mortality after dialysis initiation among older adults. Am J Kidney Dis 2017 May; 69:568.
(http://dx.doi.org/10.1053/j.ajkd.2016.08.035)
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N Engl J Med 2017 Jun 1; 376:2122
Minocycline for Early Multiple Sclerosis
In a placebo-controlled trial, clinical benefits were apparent at 6 months, but other endpoints were inconsistent.
Minocycline showed early promise as a disease-modifying therapy for multiple sclerosis (MS) with favorable pricing. In this multicenter study, conducted from 2009 through 2013, investigators recruited 142 participants with clinically isolated syndrome (by 2005 McDonald criteria) or early MS (by 2010 criteria), and randomized them 1:1 to 100 mg minocycline twice daily or placebo.
A significant reduction in confirmed diagnosis by 2005 McDonald criteria was observed at 6 months (the primary endpoint); after adjustment for baseline magnetic resonance imaging (MRI) enhancing lesion number, rates of conversion were 43% with minocycline versus 62% with placebo. However, conversion and MRI outcomes were not significant at 24 months. Side effects included rash, teeth discoloration, and dizziness.
COMMENT: Minocycline has inconsistent effects on MS disease activity and requires further investigation before being recommended to patients. This trial was underpowered and did not require patients to continue through 24 months. An imbalance in randomization resulted in more placebo patients having features concerning for early conversion: presence of gadolinium enhancing lesions at onset, spinal cord presentation, and multifocal presentation. Indeed, more placebo recipients would have been classified at study entry as having clinically definite MS by the McDonald 2010 criteria, based on the presence of an asymptomatic gadolinium enhancing lesion at baseline. Although adjusted analyses continued to show an unsustained 6-month benefit, one cannot recommend minocycline based on this placebo-controlled trial as a viable substitute for an approved disease-modifying therapy. Whether minocycline can be added to another therapy was not studied and remains unknown.
CITATION(S): Metz LM et al. Trial of minocycline in a clinically isolated syndrome of multiple sclerosis. N Engl J Med2017 Jun 1; 376:2122.
(http://dx.doi.org/10.1056/NEJMoa1608889)
Xia Z and Friedlander RM.Minocycline in multiple sclerosis — compelling results but too early to tell. N Engl J Med 2017 Jun 1; 376:2191.
(http://dx.doi.org/10.1056/NEJMe1703230)
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JAMA Intern Med 2017 May 22
Pravastatin Shows No Benefit for Primary Prevention in Older Adults
In a secondary analysis from a randomized trial, pravastatin did not lower 6-year cardiovascular-related mortality.
One quarter to one third of older adults (age, ≥75) in the U.S. take statins for primary prevention of coronary heart disease (CHD). Researchers undertook a secondary analysis of data from the lipid-lowering component of the ALLHAT trial (NEJM JW Gen Med Feb 1 2003 and JAMA 2002; 288:2998), from which they identified 2867 adults (age, ≥65; mean age, 71) who were randomized to pravastatin (40 mg daily) or usual care. Participants had stage 1 or 2 hypertension and at least one additional CHD risk factor (≈25% were smokers; 50% had type 2 diabetes) but no known CHD. About one third of usual-care patients had crossed over to statin treatment by year 6. Data were analyzed according to original randomization.
Six-year all-cause mortality in patients who were 65 to 74 was 15.5 per 100 pravastatin participants and 14.2 per 100 usual-care participants — a nonsignificant difference. All-cause mortality among the oldest participants (age, ≥75) was 31.0 per 100 pravastatin participants and 22.7 per 100 usual-care participants (P=0.07). No differences in cardiovascular-specific mortality were found between groups.
COMMENT: The lack of benefit with pravastatin for either all-cause or cardiovascular-specific mortality in older adults with CHD risk factors but without actual CHD should influence decision making about our use of statins for primary CHD prevention in older adults.
CITATION(S): Han BH et al. Effect of statin treatment vs usual care on primary cardiovascular prevention among older adults: The ALLHAT-LLT randomized clinical trial. JAMA Intern Med 2017 May 22; [e-pub].
(http://dx.doi.org/10.1001/jamainternmed.2017.1442)
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Gastroenterology 2017 May 13
Statins Are Associated with Improved Survival After Colon Cancer Diagnosis
The mechanism is likely activation of bone morphogenetic protein pathway signaling in colon cancer cells.
Aspirin and nonsteroidal anti-inflammatory drugs, and also statins, have been shown to reduce the risk for incident colorectal cancer. Regular aspirin use has also been shown to improve survival after colorectal cancer diagnosis.
In the current retrospective study, researchers evaluated the effect of statins on colon cancer survival among 1000 patients treated in 10 hospitals in the Netherlands. Colon but not rectal cancers were considered. Twenty-one percent were statin users, defined as patients receiving a prescription for statins for 14 days or more after colon cancer diagnosis. The mean number of statin prescriptions per patient was 23.
Five-year survival in statin nonusers was 55%, compared with 66% for users. After adjustment for confounders, statin use was associated with a 33% reduction in death from any cause and a 34% reduction in cancer death. Risk reductions were observed for stages II and IV cancers but not for stages I and III.
The statin effect was independent of whether tumors had KRAS mutations, but was strongly associated with intact bone morphogenetic protein (BMP) signaling. Patients with tumors with intact BMP signaling had a 61% reduction in cancer mortality, whereas tumors without intact BMP signaling had a 21% risk reduction that was not statistically significant.
COMMENT: The BMP signaling pathway is activated in bone by statins, and these data indicate that statins act by a similar mechanism in colon cancer. BMP signaling in colon cancer is impaired by inactivation of the SMAD4 gene in cancer cells.
These data suggest that statins, like aspirin, are a simple, safe, and effective adjuvant treatment for patients with established colon cancer.
Note to readers: At the time NEJM Journal Watch reviewed this paper, its publisher noted that it was not in final form and that subsequent changes might be made.
CITATION(S): Voorneveld PW et al. Statin use after diagnosis of colon cancer and patient survival. Gastroenterology2017 May 13; [e-pub].
(http://dx.doi.org/10.1053/j.gastro.2017.05.011)
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Child Dev 2017 May 3
Daily Texting and Media Use Linked to Worse Mental Health Symptoms in
at-Risk Teens
An in-depth examination of teens' daily texting and technology use demonstrates that mental health symptoms and media use may influence each other over time.
Adolescents with mental health problems are known to use more media, but directionality of associations has been unclear, and many prior studies were conducted before most teens owned mobile devices.
Researchers conducted an intensive assessment of daily technology use in 151 at-risk teens (i.e., from low-income households with parent report of behavioral difficulties, inattention or hyperactivity, substance use) ages 11 to 15 years. After completing baseline mental health surveys, teens were provided with smartphones that beeped 3 times per day for 30 days with brief surveys about that day's mental health symptoms and technology use. Self-regulation and conduct problems were assessed at 18 months.
Participants reported being online an average of 2.3 hours each day and sent an average of 41 text messages. Technology use was positively associated with same-day symptoms of attention-deficit hyperactivity disorder (ADHD) and conduct disorder. ADHD symptoms were predictive of next-day increases in texting and social media use, but not the converse. Teens reporting more overall technology use and more texting had higher levels of conduct problems and self-regulation deficits at the follow-up assessment after controlling for baseline symptoms.
COMMENT: Providers often encounter higher-risk teens in clinic (who are often on their devices) and wonder about whether and how to intervene. This study used more-reliable daily self-report methods to show that daily mental health symptoms and technology use are closely linked, with implications for longer-term outcomes. Providers should help build self-awareness in teens by discussing their emotional antecedents and consequences of texting and technology use. However, studies are needed to assess whether changing technology use habits can alter mental health symptom trajectories.
CITATION(S): George MJ et al. Concurrent and subsequent associations between daily digital technology use and high-risk adolescents' mental health symptoms.
Child Dev 2017 May 3; [e-pub].
(http://dx.doi.org/10.1111/cdev.12819)
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Pediatrics 2017 Jun; 139:e20170967
A New Policy on Fruit Juices
An AAP policy statement recommends that consumption be avoided in infants and limited in older children and adolescents.
Fruit juices are often offered as a source of vitamins, water, and sometimes calcium for infants and children. They are high in carbohydrates, varying between 11 and 16 grams-percent. By comparison, human milk and infant formulas have 7 grams-percent of carbohydrates plus beneficial nutrients, including magnesium and protein.
Because of concerns about the association of fruit juices with dental caries and obesity in infants, children, and adolescents, the American Academy of Pediatrics (AAP) has recently updated its policy on the consumption of fruit juices. The recommendations include the following:
- Avoid giving fruit juice to infants before 1 year of age. It offers no nutritional benefit. If fruit juice is consumed, it should be offered only after 6 months of age and then in a cup, as bottle feeding of juices is associated with dental caries. However, mashed or pureed whole fruits are encouraged for infants.
- Overconsumption of fruit juices in children older than 1 year should be avoided or closely monitored. Some studies suggest that the risk for dental caries and obesity is increased if fruit juices are part of the diet.
COMMENT: This recent AAP policy clearly states that fruit juices should be avoided in infants and young children until 6 years of age. After that, consumption should be closely monitored. On the other hand, consumption of whole fruit is encouraged in all age groups.
CITATION(S): Heyman MB et al. Fruit juice in infants, children, and adolescents: Current recommendations. Pediatrics2017 Jun; 139:e20170967.
(http://dx.doi.org/10.1542/peds.2017-0967)
http://pediatrics.aappublications.org/content/139/6/e20170967?ijkey=
180baa508c3dc2db6e75dc4d9a66ca33fc96996e&keytype2=tf_ipsecsha
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J Pediatr 2017 May
How Common Are Cotton-Tip Applicator Ear Injuries in Children?
More than 260,000 children presented to emergency departments with ear injuries from cotton-tip applicators from 1990 to 2010.
Investigators used the National Electronic Injury Surveillance System database to characterize cotton-tip applicator (CTA)–related injuries among patients younger than 18 years of age who were treated in U.S. hospital emergency departments between 1990 and 2010.
Results were as follows:
- An estimated 263,338 children (mean age, 6 years) were treated for CTA injuries, 99% of which occurred at home.
- Of the 31% of CTA injuries with documented mechanism of injury, 73% were associated with cleaning, 10% with playing, and 9% with a slip or fall.
- The person handling the CTA was the parent in 79% of children <4 years of age and 10% of children 8 to 17 years of age.
- The most common reasons patients with CTA injuries sought care were foreign-body sensation (39%), bleeding (35%), and ear pain (17%).
- 99% of all patients with CTA injuries were treated and released, but the authors note that this does not imply that the injuries were not serious; potential complications include need for surgical repair of the tympanic membrane, ossicular dislocation, perilymphatic fistulas, facial nerve paralysis, hearing loss, and intracranial infections.
COMMENT: The ear canal does not require cleaning, because it has self-cleaning mechanisms. The authors suggest using gentle irrigation, cerumenolytics, or instrument removal by an otolaryngologist. However, I confess to using CTAs to clean my own ears. I like getting the water and maybe a little wax out after bathing, even though I know use of the CTA may lead to cerumen impaction. So maybe we need CTAs with a large cotton head that can't be placed deeply in the ear canal. But, despite my own hypocrisy, we really should be telling our patients to avoid cleaning their ears with CTAs.
CITATION(S): Ameen ZS et al. Pediatric cotton-tip applicator-related ear injury treated in United States emergency departments, 1990-2010. J Pediatr 2017 May 1; [e-pub].
(http://dx.doi.org/10.1016/j.jpeds.2017.03.049)
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Acad Pediatr 2017 May/Jun; 17:349
ADHD Is More Common in Kids with Adverse Childhood Experiences
Population-based studies show links between ACEs and attention-deficit/hyperactivity disorder risk, both cross-sectionally and over time.
Children with adverse childhood experiences (ACEs) such as poverty, maltreatment, or parent mental illness/substance abuse have more negative mental and physical health outcomes. Mechanisms include effects of elevated stress hormones on brain areas that control executive function, emotion regulation, and memory — deficits all found in attention-deficit/hyperactivity disorder (ADHD). Researchers address the link between ACEs and ADHD in two recent U.S. population-based studies.
In a cross-sectional study, researchers analyzed data provided by caregivers of approximately 76,000 children aged 4 to 17 years in a national telephone survey. ACEs were associated with parent-reported ADHD diagnosis in a graded fashion; adjusted odds ratios were 1.6, 2.2, 3.1, and 4.0 for 1, 2, 3, and 4+ ACE exposures, respectively. Poverty and parent mental illness were each associated with higher severity of ADHD.
The second study was an analysis of mother-reported data from a longitudinal birth cohort study of some 1600 children living in large U.S. cities. Among children in middle childhood (ages 5–9 years), 42% experienced at least one ACE. Having 1, 2, or 3+ ACE exposures in middle childhood was associated with an approximately doubled risk for parent-reported ADHD at 9 years, even after adjustment for prior ACE exposure and ADHD diagnosis at age 5.
COMMENT: Although these studies were limited by use of parent-reported ADHD diagnosis, their illustration of links between ACEs and ADHD risk and severity on a population scale implies that screening for ACEs should be a part of any ADHD workup. While we often think of early childhood as the crucial time to identify toxic stress, these results show that middle and later childhood ACE exposure predict behavioral health as well.
Dr. Radesky is Assistant Professor of Developmental Behavioral Pediatrics, University of Michigan, Ann Arbor, MI.
CITATION(S): Brown NM et al. Associations between adverse childhood experiences and ADHD diagnosis and severity.Acad Pediatr 2017 May/Jun; 17:349.
(https://doi.org/10.1016/j.acap.2016.08.013)
Jimenez ME et al. Adverse childhood experiences and ADHD diagnosis at age 9 years in a national urban sample. Acad Pediatr 2017 May/Jun; 17:356.
(https://doi.org/10.1016/j.acap.2016.12.009)
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Ann Intern Med 2017 May 9
Which Doctors Are More Likely to Overuse Antibiotics?
A study identifies older, busier practitioners and those trained abroad.
Antibiotic misuse occurs everywhere in medical practice, but it is most difficult to control in the outpatient setting. Studies show that some physicians write far more antibiotic prescriptions for common colds and other viral illnesses than do other physicians (NEJM JW Gen Med Mar 15 2016 and Lancet 2016; 387:1743), but reasons behind these practice differences are largely speculative. In this retrospective analysis, researchers in Ontario reviewed billing and claims data for older adults (age, >65) who sought care during 2012 for acute respiratory illnesses. Immunocompromised patients and those deemed likely to have bacterial infections were excluded.
Of 185,000 patients, 85,500 (46%) were prescribed antibiotics, including 32% of those with nasopharyngitis, 67% of those with bronchitis, 58% of those with sinusitis, and 35% of those with laryngitis. Patients given antibiotic prescriptions were more likely to have received antibiotics during the previous year than those who did not but were otherwise similar in age and comorbidities. Among 9000 treating physicians, those who prescribed antibiotics were more likely to be in practice for more than 10 years, to see more than 25 patients daily, and to be international medical graduates (rather than U.S. or Canadian graduates).
COMMENT: These data enable some rough profiling of physicians who overuse antibiotics, but the numbers do not capture the reasons behind their actions. Are doctors who misuse antibiotics too rushed, too worried, too eager to please their patients? As editorialists point out, behavior change is likely to come only when doctors understand on a gut emotional level that antibiotic misuse harms patients.
CITATION(S): Silverman M et al. Antibiotic prescribing for nonbacterial acute upper respiratory infections in elderly persons. Ann Intern Med 2017 May 9; [e-pub].
(http://dx.doi.org/10.7326/M16-1131)
Jones BE and Samore MH.Antibiotic overuse: Clinicians are the solution. Ann Intern Med 2017 May 9; [e-pub].
(http://dx.doi.org/10.7326/M17-1061)
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N Engl J Med 2017 Mar 29
The Beginning of the End for Bioresorbable Coronary Scaffolds?
A worrying increase is seen in thrombosis risk with bioresorbable coronary scaffolds compared to standard metallic stents in a large randomized controlled trial.
Coronary angioplasty was performed for years by simple balloon angioplasty, which brought problems of recoil and high restenosis rates. The invention of stents dramatically reduced the restenosis risk but at the price of stent thrombosis. Therefore, the concept of bioresorbable vascular scaffolds was intriguing, and the first one (ABSORB) was widely used, despite scarce data. Now, researchers have reported results from one of the largest randomized, controlled trials evaluating bioresorbable scaffolds.
The industry-funded trial randomized 1845 patients to percutaneous coronary intervention with an everolimus-eluting bioresorbable scaffold or an everolimus-eluting metallic stent (stable coronary artery disease, 40% of patients; ST-segment elevation myocardial infarction, 25%; non–ST-segment elevation acute coronary syndrome, 35%).
At 2 years, no significant group differences were seen on the primary endpoint (a composite of cardiac death, target-vessel myocardial infarction, or target-vessel revascularization; scaffold group, 11.7%; stent group, 10.7%) or on most secondary endpoints. However, the scaffold group experienced an about 3.5-fold higher rate of definite or probable device thrombosis (3.5% vs. 0.9%). The safety monitoring board recommended early data reporting because of safety concerns.
COMMENT — CARDIOLOGY
Although disappointing for most cardiologists and patients, these results fall in line with previous data indicating higher thrombosis rates with scaffolds (NEJM JW Cardiol Jan 2017 and Lancet 2016; 388:2479). The present study, showing a clearly significant elevation in thrombosis rates, will definitely change clinical practice. Scaffolds have further disadvantages such as longer procedure times involving additional radiation and costs; there is currently no rationale for using scaffolds. The manufacturer has decided to restrict use of the scaffold in Europe to clinical studies exclusively, starting May 31, 2017. The concept itself remains interesting and should not be abandoned. Future-generation scaffolds with thinner struts might improve outcomes.
COMMENT — GENERAL MEDICINE
Allan S. Brett, MD
Some cardiology groups and hospitals still are promoting bioresorbable scaffolds, even after publication of these results. For example, the website of a hospital in my geographic area boasts that it is the first local hospital to offer the device, and it calls the device “the most significant advancement in cardiology since stenting began decades ago.” Primary care clinicians and hospitalists should be aware of this trial, so that patients can be directed to interventional cardiologists who acknowledge these findings. The FDA is currently investigating the safety of the Absorb scaffold, which was used in this study.
CITATION(S): Wykrzykowska JJ et al. Bioresorbable scaffolds versus metallic stents in routine PCI. N Engl J Med 2017Mar 29; [e-pub].
(http://dx.doi.org/10.1056/NEJMoa1614954)
Mukherjee D.Device thrombosis with bioresorbable scaffolds. N Engl J Med 2017 Mar 29; [e-pub].
(http://dx.doi.org/10.1056/NEJMe1703202)
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Pharmacoepidemiol Drug Saf 2017 Mar 31
NSAIDs, Selective COX-2 Inhibitors, and PPIs: What's the Best Combination to Reduce PUB?
Use of a COX-2 inhibitor with a proton-pump inhibitor was the most effective alternative to nonselective nonsteroidal anti-inflammatory drug use alone in reducing bleeding risk.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with peptic ulcer bleeding (PUB). This risk may be decreased but not eliminated by using selective COX-2 inhibitors. Concomitant proton-pump inhibitor (PPI) therapy reduces the risk in both situations.
In a population-based case-control study, Dutch researchers compared PUB risks among subgroups of patients currently using nonselective NSAIDs (nsNSAIDs) or COX-2 inhibitors (but not both) with or without PPIs. Cases were 2634 patients hospitalized for PUB and were matched by birth year and sex with 5074 control patients without PUB.
Compared with users of nsNSAIDs alone, patients using both a COX-2 inhibitor and a PPI had the lowest relative risk for PUB (adjusted odds ratio, 0.51). The next lowest risk was for COX-2 inhibitor use alone (aOR, 0.66), followed by use of nsNSAIDs with a PPI (aOR, 0.79). The risk reduction benefit of using nsNSAIDs with a PPI compared with nsNSAIDs alone was greater among patients aged ≥75 years versus <75, whereas the risk reduction associated with using COX-2 inhibitors alone versus nsNSAIDs alone was lower in the older group versus the younger one. The risks were similar in men and women.
COMMENT: These results may be limited by failure to capture individual risk, history of PUB, and over-the-counter PPI use. Nonetheless, the data support other studies demonstrating that the risk for nsNSAID-related PUB can be reduced by substituting a COX-2 inhibitor or adding a PPI. The lowest risk was seen with use of both a COX-2 inhibitor and a PPI, which should be the standard of care in patients at high risk for PUB who have an indication for NSAID therapy.
CITATION(S): Bakhriansyah M et al. Gastrointestinal toxicity among patients taking selective COX-2 inhibitors or conventional NSAIDs, alone or combined with proton pump inhibitors: A case-control study.Pharmacoepidemiol Drug Saf 2017 Mar 31; [e-pub].
(http://dx.doi.org/10.1002/pds.4183)
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Am J Gastroenterol 2017 Apr 11
Proton-Pump Inhibitor Use and Ischemic Stroke
Risks for first-time stroke were greater with PPI use versus nonuse, but the clinical significance of these findings is doubtful.
Multiple population-based studies have suggested an association between the use of proton-pump inhibitors (PPIs) and a host of medical conditions.
To determine whether PPI use is associated with ischemic stroke, investigators used the Taiwan National Insurance Database to propensity match current PPI users with nonuser controls and measured occurrence of first-time ischemic stroke during a 120-day period. Analysis of 198,000 PPI treatment courses and nonuse control periods showed that risk for stroke was higher for PPI users than controls (hazard ratio, 1.36) and that the association was more prominent in patients younger than 60 years of age.
The researchers also performed a nested case-control analysis of more than 15,378 patients hospitalized with first-time ischemic stroke and the same number of matched controls. Compared with nonuse of PPIs, risks for stroke were higher with PPI use within 30 days (adjusted odds ratio, 1.77), between 31 and 90 days (AOR, 1.65), and between 91 and 180 days (AOR, 1.28). PPI use was not associated with increased risk for stroke beyond 180 days.
COMMENT: These results suggest that PPI use is associated with a modest increased risk for first-time ischemic stroke. But, like many other population-based studies linking PPI use to various disorders, this study is limited by the potential for residual confounding from a host of factors, including PPI users having a higher underlying risk for stroke. In fact, the finding that the association was less prominent in older patients, in whom the risk for stroke should be greater, suggests that residual confounding exists. Moreover, the short duration of the study raises the question of a physiologic explanation for the effect, and the absence of data on the duration of therapy or a dose-response relationship casts doubt on a causal effect. As such, the clinical significance of these findings is doubtful.
CITATION(S): Wang YF et al. Proton-pump inhibitor use and the risk of first-time ischemic stroke in the general population: A nationwide population-based study. Am J Gastroenterol 2017 Apr 11; [e-pub].
(http://dx.doi.org/10.1038/ajg.2017.101)
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