• Omega-3s Benefit Children and Teens with ADHD: Meta-Analytic Results
• Ulcerative Colitis Is on the Rise
• Hair-Based Ethyl Glucuronide Accurately Diagnoses Excessive Alcohol Use in Cirrhosis
• Focused Exercise Program for Older Adults Improves Walking Speed and Distance
• Lung Cancer Rates Are Increasing Among Never-Smokers
• Healthy Aging Is Less Likely When Weight Is Gained in Early and Middle Adulthood
• Influenza Vaccine Effectiveness in the United States during the 2015–2016 Season
• Epstein-Barr Virus and Multiple Sclerosis Risk Among Different Races/Ethnicities
• Predicting Individual Responses to Therapy in Multiple Sclerosis
• Cesarean Delivery as a Pathway to Nonmedical Opioid Use
Neuropsychopharmacology 2017 Jul 25
Omega-3s Benefit Children and Teens with ADHD: Meta-Analytic Results
Treatment significantly improved cognition and parents' behavioral ratings. Also, baseline omega-3 red blood cell levels were low.
Studies of omega-3 polyunsaturated fatty acids for attention-deficit/hyperactivity disorder (ADHD) have yielded equivocal results. These researchers conducted a meta-analysis of published, peer-reviewed, randomized, controlled trials or case-control studies (for comparisons of blood levels) involving children aged 4 to 17 years.
Based on seven studies (N=534) using parental ratings of ADHD symptoms, the analysis found a medium effect size for improved behavior with daily docosahexaenoic acid (DHA; dose range, 2.7–640.0 mg) or eicosapentaenoic acid (EPA; range, 80–650 mg). ADHD behaviors improved only with EPA doses of at least 500 mg. In three studies with teachers' ratings (N=334), omega-3s did not alter behavior. In three studies (N=214), omega-3 supplements had positive effects on omission and commission errors, with a high effect size. ADHD groups had significantly lower red blood cell, but not plasma, levels of DHA, EPA, arachidonic acids, and total omega-3 levels than non-ADHD control groups.
COMMENT: Limitations of this meta-analysis include reliance on parental ratings and the wide range of DHA doses. Nevertheless, these data support supplementing diets of ADHD child and adolescent patients with fatty fish high in omega-3s or commercial preparations containing at least 500 mg of EPA. Should all ADHD patients be offered a trial of supplementation before pharmacotherapy?
Other research supports supplementation for multiple other psychiatric conditions, which may be related to the trajectory of changes in dietary polyunsaturated fatty acids over centuries: The 1:1 ratio of omega-3 to omega-6 has now become 1:15 or 1:16 (Biomed Pharmacother 2006; 60:502). Is it possible that the increase in ADHD prevalence reported in some studies is caused by the decrease in dietary omega-3s (J Am Acad Child Adolesc Psychiatry 2014; 53:34)?
Note to readers: At the time we reviewed this paper, its publisher noted that it was not in final form and that subsequent changes might be made.
CITATION(S): Chang J-C et al. Omega-3 polyunsaturated fatty acids in youths with attention deficit hyperactivity disorder (ADHD): A systematic review and meta-analysis of clinical trials and biological studies. Neuropsychopharmacology 2017 Jul 25; [e-pub].
(http://dx.doi.org/10.1038/npp.2017.160)
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Aliment Pharmacol Ther 2017 Aug 17
Ulcerative Colitis Is on the Rise
In Sweden, ulcerative colitis incidence has risen fivefold and prevalence tenfold since the mid-1960s.
Numerous studies document rising incidence rates of inflammatory bowel disease (IBD). A recent population-based study from Sweden illustrates the magnitude of the increase in ulcerative colitis (UC). Data were examined retrospectively but collected prospectively, in a setting with little apparent risk for ascertainment bias, loss of patients to private physicians, or change in the local population with regard to immigration.
During the study period of more than 4 decades (1963–2010), annual incidence rates of UC increased from 4 to 18 per 100,000 and prevalence rates increased from 44 to 474 per 100,000. Disease progression at 10 years after diagnosis was evident in 35% of patients with proctitis at diagnosis compared with 19% of those with left-sided colitis at diagnosis. The risk for colectomy at 10 years postdiagnosis was 39% lower during the latest third of the study period (1991–2005) compared with the earliest third (1963–1975), possibly due to increased use of thiopurines and anti–tumor necrosis factor agents.
COMMENT; With a fivefold rise in incidence and a tenfold increase in prevalence of UC, as well as a dramatic expansion in the armamentarium and toxicity of therapeutic agents, it's easy to see why IBD management is trending toward its own subspecialty, particularly in academic centers. The causes of increasing UC rates remain uncertain, though the declining rate of cigarette smoking is one clear factor.
CITATION(S): Eriksson C et al. Changes in medical management and colectomy rates: A population-based cohort study on the epidemiology and natural history of ulcerative colitis in Örebro, Sweden, 1963-2010.Aliment Pharmacol Ther 2017 Aug 17; [e-pub].
(http://dx.doi.org/10.1111/apt.14268)
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Clin Gastroenterol Hepatol 2017 Aug 19
Hair-Based Ethyl Glucuronide Accurately Diagnoses Excessive Alcohol Use
in Cirrhosis
This biomarker should replace other tools used to assess alcohol abuse.
As a part of liver transplantation candidacy evaluation, assessment of alcohol abuse is essential, as risk for ongoing alcohol use posttransplantation is common among those with alcohol addiction. Checking levels of urine ethyl glucuronide, a byproduct of ethanol, assesses alcohol use during the previous few days only, whereas measuring ethyl glucuronide in scalp hair (hEtG) provides a diagnostic time window of several months.
To validate its use in patients with cirrhosis, researchers assessed the accuracy of hEtG in diagnosing chronic excessive alcohol use (>60 g/day) during the previous 3 months in approximately 100 patients with alcoholic cirrhosis and 40 healthy volunteers. Each patient completed a detailed alcohol use questionnaire and contributed a 3-cm strand of hair for hEtG testing.
A hair EtG level ≥30 pg/mg had a high diagnostic accuracy for chronic excessive alcohol use in the previous 3 months (sensitivity, 100%; specificity, 97%; positive-predictive value, 95%; negative-predictive value, 100%). Using a cutoff of ≥50 pg/mg achieved perfect diagnostic accuracy. Liver function based on the model for end-stage liver disease score did not affect hEtG level. Among approximately 40 patients with alcoholic cirrhosis who underwent liver biopsy, those with an hEtG level <50 pg/mg had no histologic signs of alcohol-related injury.
COMMENT: These findings validate the use of hEtG levels in patients with cirrhosis and show that a cutoff of ≥30 pg/mg can accurately diagnose chronic excessive alcohol use during a 3-month period. This biomarker should replace other tools used to assess alcohol abuse in clinical practices where patients with liver disease are seen.
Note to readers: At the time we reviewed this paper, its publisher noted that it was not in final form and that subsequent changes might be made.
CITATION(S): Verbeek J et al. Hair ethyl glucuronide is a highly accurate biomarker of chronic excessive alcohol use in patients with alcoholic cirrhosis. Clin Gastroenterol Hepatol 2017 Aug 19; [e-pub].
(http://dx.doi.org/10.1016/j.cgh.2017.08.019)
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JAMA Intern Med 2017 Aug 14
Focused Exercise Program for Older Adults Improves Walking Speed
and Distance
An approach that incorporates walking biomechanics and coordination was more effective than general exercise.
Preserving mobility in older adults is critical to maintaining independence and limiting morbidity. Group exercise programs to improve mobility typically focus on muscle strengthening and general conditioning. In this multisite randomized trial, researchers compared an exercise program called “On the Move” (OTM) with a general strengthening and aerobic exercise program (usual care) in 298 older adults (mean age, 80) who resided in independent living centers or senior housing. OTM teaches biomechanical skills, timing, and coordination through a series of stepping sequences, walking patterns, and weight-shifting exercises. In both groups, exercise was delivered twice weekly in 50-minute sessions led by physical therapy staff members.
At 12 weeks, OTM participants showed modest but significant gains in walking distance and speed. Mean 6-minute walk distance increased from 273 m to 294 m in the OTM group, compared with a mean 4-m gain in the usual-care group; corresponding gain in walking speed with OTM was 0.05 m/second (from a baseline speed of 0.9 m/second), compared with no change in usual-care participants.
COMMENT: The improvements here are modest, and the investment of time and effort is considerable. However, the outcomes demonstrate, once again, that older, fairly frail adults can benefit from focused and selectively designed exercise training.
CITATION(S): Brach JS et al. Effectiveness of a timing and coordination group exercise program to improve mobility in community-dwelling older adults: A randomized clinical trial. JAMA Intern Med 2017 Aug 14; [e-pub].
(http://dx.doi.org/10.1001/jamainternmed.2017.3609)
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J Natl Cancer Inst 2017 Jul; 109:djw295
Lung Cancer Rates Are Increasing Among Never-Smokers
From 1990 through 2013, the percentage of patients with non–small-cell lung cancer who never smoked rose from 8.0% to 14.9%.
In a 2004 Surgeon General report, the percentage of lung cancer patients who never smoked was estimated to be 10% to 15% of the total lung cancer population.
To reassess that figure, investigators performed a retrospective analysis of lung cancer registry data for the years 1990 to 2013 from three diverse sources: the University of Texas Southwestern Medical Center private patient facilities in Dallas, Parkland charitable county hospital in Dallas, and Vanderbilt University in Nashville. A total of 10,593 patients with non–small-cell lung cancer (NSCLC) and 1510 patients with small-cell lung cancer (SCLC) were evaluated.
Results were as follows:
- The percentage of NSCLC patients who never smoked increased from 8.0% to 14.9% from the years 1990–1995 to 2011–2013 (P<0.001); the increase was consistent across all three hospitals.
- The percentage of women with NSCLC who never smoked increased from 10.2% to 22.1% from 1990 through 2013 (P<0.001), and the percentage of men with NSCLC who never smoked increased from 6.6% to 8.9% during the same period (P=0.006).
- The percentage of patients with SCLC or squamous NSCLC who never smoked did not change significantly from 1990–1995 to 2011–2013.
The authors contend that referral bias to academic centers was not a factor in these findings, as the charitable county hospital saw a similar rise in never-smoking NSCLC patients.
COMMENT
This study suggests that the rate of never-smoking NSCLC adenocarcinoma is rising in U.S. men and women and indicates the need for additional research to validate these results and to determine the epidemiologic and possibly molecular etiology. If these findings are subsequently confirmed, the largest concern is that there is an environmental carcinogen inducing NSCLC in never-smokers.
CITATION(S): Pelosof L et al. Proportion of never-smoker non–small cell lung cancer patients at three diverse institutions. J Natl Cancer Inst 2017 Jul; 109:djw295.
(http://dx.doi.org/10.1093/jnci/djw295)
https://www.ncbi.nlm.nih.gov/pubmed/28132018?access_num=
28132018&link_type=MED&dopt=Abstract
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JAMA 2017 Jul 18; 318:255
Healthy Aging Is Less Likely When Weight Is Gained in Early and Middle Adulthood
Several chronic diseases occurred more commonly in those who gained as little as 2.5 to 10.0 kg.
Mean weight gain in U.S. adults is about 1 to 2 pounds annually during early and middle adulthood. In this study, investigators followed about 118,000 young and middle-aged adults enrolled in two large national studies of healthcare professionals (mean age at enrollment, ≈45) to assess the consequences of weight gain. Participants recalled their weight at age 18 (for women) or 21 (for men) and were weighed at age 55. Every 2 years after age 55, participants were evaluated for onset of major chronic diseases.
At age 55, women had gained a mean 12.6 kg, and men had gained a mean 9.7 kg. Significant associations were noted between weight gain and incidence of most major chronic diseases. For example, gain of ≥20 kg (vs. maintaining stable weight) was associated with 8-fold and 11-fold higher risks for developing type 2 diabetes in men and women, respectively; weight gain of 2.5 to 10 kg doubled risk for diabetes. After weight gain of 10 to 20 kg, likelihood of healthy aging (defined as absence of major chronic disease, cognitive difficulties, and physical limitations) declined by 44% for women and by 34% for men.
COMMENT: These results are not surprising but do provide some details on risks associated with even moderate weight gain that could be used to counsel patients.
CITATION(S): Zheng Y et al. Associations of weight gain from early to middle adulthood with major health outcomes later in life. JAMA 2017 Jul 18; 318:255.
(http://dx.doi.org/10.1001/jama.2017.7092)
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Influenza Vaccine Effectiveness in the United States during
the 2015–2016 Season
N Engl J Med 2017; 377:534-543 August 10, 2017 DOI: 10.1056/NEJMoa1700153
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BACKGROUND; The A(H1N1)pdm09 virus strain used in the live attenuated influenza vaccine was changed for the 2015–2016 influenza season because of its lack of effectiveness in young children in 2013–2014. The Influenza Vaccine Effectiveness Network evaluated the effect of this change as part of its estimates of influenza vaccine effectiveness in 2015–2016.
METHODS; We enrolled patients 6 months of age or older who presented with acute respiratory illness at ambulatory care clinics in geographically diverse U.S. sites. Using a test-negative design, we estimated vaccine effectiveness as (1−OR)×100, in which OR is the odds ratio for testing positive for influenza virus among vaccinated versus unvaccinated participants. Separate estimates were calculated for the inactivated vaccines and the live attenuated vaccine.
RESULTS: Among 6879 eligible participants, 1309 (19%) tested positive for influenza virus, predominantly for A(H1N1)pdm09 (11%) and influenza B (7%). The effectiveness of the influenza vaccine against any influenza illness was 48% (95% confidence interval [CI], 41 to 55; P<0.001). Among children 2 to 17 years of age, the inactivated influenza vaccine was 60% effective (95% CI, 47 to 70; P<0.001), and the live attenuated vaccine was not observed to be effective (vaccine effectiveness, 5%; 95% CI, −47 to 39; P=0.80). Vaccine effectiveness against A(H1N1)pdm09 among children was 63% (95% CI, 45 to 75; P<0.001) for the inactivated vaccine, as compared with −19% (95% CI, −113 to 33; P=0.55) for the live attenuated vaccine.
CONCLUSIONS: Influenza vaccines reduced the risk of influenza illness in 2015–2016. However, the live attenuated vaccine was found to be ineffective among children in a year with substantial inactivated vaccine effectiveness. Because the 2016–2017 A(H1N1)pdm09 strain used in the live attenuated vaccine was unchanged from 2015–2016, the Advisory Committee on Immunization Practices made an interim recommendation not to use the live attenuated influenza vaccine for the 2016–2017 influenza season. (Funded by the Centers for Disease Control and Prevention and the National Institutes of Health.)
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Neurology 2017 Aug 30
Epstein-Barr Virus and Multiple Sclerosis Risk Among Different Races/Ethnicities
This U.S. study found EBV exposure to be associated with increased MS risk.
Epstein-Barr virus (EBV) exposure appears to be a necessary permissive step in the development of multiple sclerosis (MS). Investigators studied the association between EBV and MS among different races/ethnicities in patients enrolled in Kaiser Permanente Southern California. Each case was matched with at least one control. Serum IgG antibodies were measured against the EBV viral capsid antigen, EB nuclear antigen-1 (EBNA-1), EBV early antigen, and cytomegalovirus (CMV). DNA samples were obtained for HLA genotyping.
Cases included 235 non-Hispanic white, 111 black, and 173 Hispanic patients. CMV positivity was significantly higher among Hispanic controls than cases, but did not differ between cases and controls among blacks or whites. White and Hispanic MS patients were more likely to carry HLA-DRB1*15:01 than controls, whereas black MS patients were more likely to carry HLA-DRB1*15:03 than controls. EBNA-1 titers were elevated in all three MS groups, compared with their controls. CMV appeared protective against MS in Hispanics after adjusting for EBNA-1 positivity and other variables.
COMMENT: Investigators confirmed higher rates of EBV exposure prior to MS, and this remains a common association among different races/ethnicities. MS is a complex genetic disorder with environmental influences. While EBV does not “cause” MS in the strictest sense, exposure appears to be a necessary part of a multistep process. The possibility that CMV is protective against MS is intriguing, as roughly 60% of the U.S. population has evidence of prior exposure. However, CMV seropositivity varies based on socioeconomic status and may be a surrogate for several other types of protective exposures. These types of epidemiologic studies help determine the causes of MS by considering important environmental exposures in the context of different genetic backgrounds.
CITATION(S): Langer-Gould A et al. Epstein-Barr virus, cytomegalovirus, and multiple sclerosis susceptibility: A multiethnic study. Neurology 2017 Aug 30; [e-pub].
(http://dx.doi.org/10.1212/WNL.0000000000004412)
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Brain 2017 Aug 3
Predicting Individual Responses to Therapy in Multiple Sclerosis
This initiative used empirical data to “treat the right patient with the right drug at the right time.”
Investigators used MSBase (a data repository from a global cohort spanning 34 countries) to develop models to predict individual treatment responses for each of seven commonly used disease-modifying therapies. Models were based on demographic, clinical, and paraclinical features. For each treatment, 27 clinical predictors were evaluated in a subset of some 8500 patients, followed by validation in a separate cohort of 1200, and then an independent external validation in a cohort of 3000. Response was analyzed regarding disability progression, disability regression, relapse frequency, conversion to secondary progressive disease, change in disease burden, and treatment discontinuation.
Median follow-up was 8 years, with Expanded Disability Status Score of 2.5 (mild disability), and 7 years' disease duration. The strongest predictors were age, disease duration, disease course, relapse activity, disability, relapse phenotype, and prior therapy. Associations varied with therapy. The results largely support current treatment recommendations for treatment escalation. For example, for a patient aged 43 years with moderate current disability, 10-year disease duration, 10 relapses since disease onset, and disease activity in the prior year, a switch to high-efficacy medication was associated with a lower rate of progression and conversion to secondary progressive MS.
COMMENT: These results could lead to a clinical model providing probabilities of disability worsening and secondary progressive MS. For example, such a model may predict within an individual patient a 25% risk of disability worsening in 10 years on standard-efficacy therapy versus a 10% risk on high-efficacy therapy. Such models will provide a more rational basis to select treatments and counsel patients, delivering more-personalized medicine.
CITATION(S): Kalincik T et al. Towards personalized therapy for multiple sclerosis: prediction of individual treatment response. Brain 2017 Aug 3; [e-pub].
(http://dx.doi.org/10.1093/brain/awx185)
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Obstet Gynecol 2017 Jul; 130:36
Cesarean Delivery as a Pathway to Nonmedical Opioid Use
Are clinicians providing too many pills after cesareans?
Opioid-related death rates are rising among child-bearing women, whose drug use often originates with prescribed medication. In particular, pain management after cesarean delivery (the most common major surgery in the U.S.) presents an opportunity for excessive use or abuse. Investigators at one U.S. academic center queried 179 women 2 weeks after cesarean delivery regarding their use of the opioids they had received (most commonly, 30 pills of 5-mg oxycodone). After discharge, 22% took all prescribed opioids, 61% took some, and 17% took none. About 75% had leftover opioids (median, 10 pills). Women who took more opioids while in the hospital (as well as smokers) were more likely to take more pills after discharge.
In a survey of 720 women interviewed 2 weeks after cesarean delivery at 6 U.S. academic centers, a median of 40 pills (mostly oxycodone) were prescribed versus 20 consumed. Fewer than 5% of women with leftover pills had disposed of them. Satisfaction with pain control did not vary with number of pills prescribed, although the number of pills taken correlated with the number prescribed. More women considered the amount of opioids dispensed to be excessive (36%) than insufficient (15%).
In a third study, researchers evaluated a 10-minute shared decision-making intervention about postcesarean opioid use. A physician explained the expected course of postsurgical pain; then, with the assistance of a computer-based decision aid, 51 participants selected the desired number of 5-mg oxycodone pills (standard prescription, 40 pills; offered range, 0–40). A median of 20 pills was selected, and 15 were consumed during the 2 weeks after discharge. Additional prescriptions were necessary for four women, three of whom had complications likely to increase pain.
COMMENT: These studies show that the quantity of opioids prescribed after cesarean delivery is often excessive. The amount of medication for adequate pain control differs for each woman, so shared decision making seems appropriate. The reasons for this wide spectrum of need for pain control are partly physiologic, but also probably reflect differential social support, understanding of normal postpartum events, and awareness of nonopioid analgesics such as nonsteroidal anti-inflammatory drugs and acetaminophen. Concern about reaching a clinician during off hours and receiving an appropriate evaluation may also contribute, and facilitating follow-up may mitigate these anxieties.
CITATION(S): Osmundson SS et al. Postdischarge opioid use after cesarean delivery. Obstet Gynecol 2017 Jul; 130:36.
(http://dx.doi.org/10.1097/AOG.0000000000002095)
Bateman BT et al. Patterns of opioid prescription and use after cesarean delivery. Obstet Gynecol 2017Jul; 130:29.
(http://dx.doi.org/10.1097/AOG.0000000000002093)
Prabhu M et al. A shared decision-making intervention to guide opioid prescribing after cesarean delivery. Obstet Gynecol 2017 Jul; 130:42.
(http://dx.doi.org/10.1097/AOG.0000000000002094)
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