• Best Surgery Days? During Joint Commission Surveys
• Commercial Weight Management Program Is Effective in Adolescents
• Possible Breakthrough in Restoring Hearing Loss, in Mice
• Long-Term Trends in Pediatric Opioid Use and Misuse in the U.S.
• Interleukin-1 Blocker Doesn't Diminish Symptoms of Chronic Fatigue Syndrome
• Nodding Syndrome: Autoimmune Epilepsy Triggered by a Parasite?
• Acid Reflux Control Aids Success in Barrett Esophagus Ablation
• Consider the Evidence Before Prescribing Antidepressants Off-Label
Best Surgery Days? During Joint Commission Surveys
Overall, patients treated during a Joint Commission survey week had a 1.5% lower risk of dying, on average, within 30 days of admissions compared to the patients treated in the three weeks before or after an inspection. A proposed reason may be due to the fact that clinicians are aware they are under scrutiny and are, therefore, more vigilant, according to a new study published in JAMA Internal Medicine.
Researchers analyzed Medicare admissions at 1,984 surveyed hospitals from 2008 through 2012 in the three-week period before the survey, during the survey, and three weeks after the survey and included approximately 245,000 patients admitted during Joint Commission surveys, and more than 1,462,000 in the three weeks before and after the surveys.
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J Pediatr 2017 Mar 9
Commercial Weight Management Program Is Effective in Adolescents
Compared with standard weight loss recommendations, a 12-week commercial program was associated with greater reduction in BMI z scores and better self-esteem and quality of life.
Weight loss in overweight and obese adolescents is challenging. In an Australian study conducted in and funded by commercial weight loss centers (Jenny Craig), researchers compared the effectiveness of a 12-week structured dietary/behavioral program versus standard healthy eating and lifestyle recommendations. Teens with BMI z scores ≥90th percentile who were seeking weight loss management at the centers were randomized to the intervention group (42 teens) or control group (32).
Intervention group participants met weekly with a counselor and initially had food delivered to them, with gradual transition to planning and preparing their own menus. Controls met once with a consultant and were given a booklet on healthy eating and “advised to maintain their current lifestyle habits” (they could participate in the intervention at the end of the study).
After 12 weeks, the intervention group had a significantly greater mean decrease in BMI z score (−0.22 vs. −0.01) and body weight (−5.0 vs. +1.6 kg). The intervention group also had significantly greater reductions in caloric intake and greater increases in physical activity, body esteem, and quality of life. The 15 intervention group participants available for follow-up at 36 weeks had, on average, not only sustained their weight loss but continued to lose weight and reduce their BMI.
COMMENT; This study shows that a commercial structured lifestyle intervention is effective for managing weight in adolescents in the first 9 months of follow-up. Longer-term follow-up will be important to determine whether the improvements are sustained. The study did not compare different commercial programs or assess costs. It is unclear whether the U.S. health system would provide the resources for adolescents to participate in these programs.
CITATION(S): Bonham MP et al. Evaluation of a commercially delivered weight management program for adolescents.J Pediatr 2017 Mar 9; [e-pub].
(http://dx.doi.org/10.1016/j.jpeds.2017.01.042)
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Cell Reports 2017 Feb 21; 18:1917
Possible Breakthrough in Restoring Hearing Loss, in Mice
Researchers have discovered a way to regenerate hair cells in the cochlea.
During one's lifetime, a series of insults (e.g., loud noises, toxic drugs, viral infections) gradually depletes the number cochlear hair cells, leading to hearing loss. Cochlear stem cells do not replace this loss.
A team from Harvard and MIT identified a “cocktail” of small molecules that produced substantial expansion of cochlear stem cells and induced those stem cells to become hair cells. The induced cells all had the elements necessary for hearing (i.e., hair cells that transduce signals to nerves). When the technique was applied to healthy human ear tissue (an explant from cancer surgery), it led to the generation of human hair cells, in vitro. Finally, explants of entire cochleas from mice were treated with the small molecules, and treatment induced both more stem cells and differentiation of the stem cells into hair cells. Hair-cell restoration was achieved even in cochleas in which hair cells had been badly damaged by gentamicin.
COMMENT: These experiments, largely in mice, offer hope that human hair cells might be restored, in vivo, by a similar cocktail of small molecules. Perhaps the biggest question to be answered is whether small-molecule growth factors, if given systemically, cause adverse effects outside the ear, because other epithelial stem cells also respond to these agents.
CITATION(S): McLean WJ et al. Clonal expansion of Lgr5-positive cells from mammalian cochlea and high-purity generation of sensory hair cells. Cell Reports 2017 Feb 21; 18:1917.
(http://dx.doi.org/10.1016/j.celrep.2017.01.066)
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Pediatrics 2017 Mar 20
Long-Term Trends in Pediatric Opioid Use and Misuse in the U.S.
Christine M. Judge, MS, Louis M. Bell, MD reviewing Allen JD et al. Pediatrics 2017 Mar 20. McCabe SE et al. Pediatrics 2017 Mar 20. Rosen DA and Murray PJ. Pediatrics 2017 Mar 20.
Despite recent downward trends in reported use by high school seniors and poisonings in children and teens, the public health impact of heavy opioid prescribing remains high.
Two new studies provide long-term U.S. data trends on prescription opioid use and misuse among U.S. children and teenagers.
In an annual cross-sectional survey administered to U.S. high school seniors between 1976 and 2015, students were asked whether they had ever taken prescription opioids because a doctor told them to do so (medical use) or without a doctor's advice (nonmedical). Rates ranged from a low of 13% in 1997 to a high of 20% in 1989 and 2002 for medical use and were lower for nonmedical use (approximate range, 6%–13%); the two were consistently and strongly correlated over time (especially among male adolescents). Both uses declined between 2013 and 2015. Among respondents who reported both uses, medical use followed by nonmedical use was the most common pattern.
Data from U.S. poison control centers from 2000 to 2015 showed 188,468 exposures to opioids among children and adolescents (14 per 100,000). Most exposures occurred among children aged <5 years (60%) and were unintentional (56%), although among teens, 72% of exposures were intentional (including suspected suicide, abuse, and misuse). In all age groups, opioid exposures increased from 2000 to 2009 and declined from 2009 to 2015. Teens were more likely than other age groups to be admitted to a healthcare facility or have a serious outcome. Although exposure from buprenorphine was low overall (3%), it accounted for 88% of exposures and the highest rates of admissions and serious outcomes in children under 5. Also, exposures to buprenorphine rose during 2014 and 2015.
COMMENT: Louis M. Bell, MD
The people of the U.S. consume more of the world's prescription opioid supply than all other countries combined. The large data sets analyzed in these two studies confirm that the nonmedical use of opioids rises and falls with medical prescriptions and that teenagers are frequent intentional users of nonmedical opioids. As a result, opioids are now a major cause of mortality and morbidity in this age group. I think it is safe to say that we, the medical community, could be better stewards of prescription opioids. While important in helping our patients with the aftermath of painful injuries or postsurgical pain, opioids don't address chronic suffering. A better approach would include both patient and physician education, as well as changes in how we support patients with chronic pain.
CITATION(S):
- Allen JD et al. Prescription opioid exposures among children and adolescents in the United States: 2000–2015. Pediatrics 2017 Mar 20; [e-pub].
(http://dx.doi.org/10.1542/peds.2016-3382)
- McCabe SE et al. Trends in medical and nonmedical use of prescription opioids among US adolescents: 1976–2015. Pediatrics 2017 Mar 20; [e-pub].
(http://dx.doi.org/10.1542/peds.2016-2387)
- Rosen DA and Murray PJ.Clues to the opioid crisis in monitoring the future but still looking for solutions.Pediatrics 2017 Mar 20; [e-pub].
(http://dx.doi.org/10.1542/peds.2017-0209)
Ann Intern Med 2017 Mar 7
Interleukin-1 Blocker Doesn't Diminish Symptoms of Chronic Fatigue Syndrome
Anakinra does not benefit CFS patients.
One theory holds that symptoms of chronic fatigue syndrome (CFS) are caused by excessive levels of various cytokines (primarily proinflammatory cytokines) that are produced in, or that reach, the brain. A team from the Netherlands conducted a small randomized trial of one particular cytokine blocker, anakinra (Kineret), that targets proinflammatory interleukin (IL) –1α and IL-1β.
Fifty participants received daily subcutaneous injections of either anakinra or placebo for 4 weeks and then were followed for 20 additional weeks. Researchers noted no significant differences in severity of fatigue, pain, physical or social functioning, or psychological distress at 4 or at 20 weeks.
COMMENT: Although small, this study indicates that anakinra therapy is unlikely to improve symptoms or functioning in patients with CFS: No trend favored active therapy, so we have no reason to believe that any benefit would have reached statistical significance in a larger study. Whether anakinra penetrates the blood-brain barrier is unknown and was not assessed in this study; failure of this drug to reach the brain parenchyma might explain the negative results. The negative result does not preclude the possibility that other IL-1–family blockers, or blockers of other cytokines, would be effective; however, for patients who suffer from this illness, these results will be disappointing.
CITATION(S): Roerink ME et al. Cytokine inhibition in patients with chronic fatigue syndrome: A randomized trial. Ann Intern Med 2017 Mar 7; [e-pub].
(http://dx.doi.org/10.7326/M16-2391)
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Onchocerca volvulus. Sci Transl Med 2017 Feb 15; 9:eaaf6953
Nodding Syndrome: Autoimmune Epilepsy Triggered by a Parasite?
New evidence suggests a role for leiomodin-1 antibody in a parainfectious autoimmune reaction to Onchocerca volvulus.
Nodding syndrome is a seizure disorder characterized by atonic seizures, among other central nervous system symptoms, affecting children in Sub-Saharan Africa (primarily Uganda and South Sudan). This disease may have an epidemiologic link to Onchocerca volvulus parasitic infection. To investigate an autoimmune cause for nodding syndrome, researchers used a proteome microarray (with > 9000 targets) to screen sera from patients with nodding syndrome and healthy controls. A distinct signal for leiomodin-1 was detected. Subsequently, serum samples from cases and controls were screened (by ELISA) for leiomodin-1 antibody. The authors also tested: (1) leiomodin-1 antigen specificity (with a transfected cell line), (2) leiomodin-1 antibody-mediated neurotoxicity (measuring live neuron viability), and (3) leiomodin-1antibody and O. volvulus antigen cross-reactivity (Western blot of O. volvulus lysates probed with affinity-purified leiomodin-1 antibody).
The authors detected serum immunoglobulin M and G antibodies reactive with leiomodin-1 more commonly in affected children (52.7%) than in unaffected controls from the same village (30.1%) or in U.S. healthy controls (none). Among 54 villagers without nodding syndrome, 12 had both O. volvulus infection and leiomodin-1 antibodies. The authors also reported findings supportive of leiomodin-1 antibody having neurotoxic effects and cross-reactivity with O. volvulus antigens. The authors conclude that their findings support nodding syndrome having a parainfectious autoimmune neurological cause triggered by O. volvulus.
COMMENT: This evidence supports autoimmunity in patients with nodding syndrome and in those at risk for the disorder. Limitations include the principal antibody detection method, ELISA, which is prone to false positives. Unknowns include the neuropathogenic significance of leiomodin-1 antibody, which may be generated as a response to neurologic injury rather than causing it, particularly because the antigen is intracellular (and thus unlikely to be accessible to antibody) and is not nervous system exclusive. Future immunologic and neuropathologic studies may demonstrate a cytotoxic T cell-mediated pathogenesis for which leiomodin-1 antibody (or another neural antibody) would serve as a diagnostic biomarker.
Dr. McKeon is Professor of Neurology, Mayo Clinic, Rochester, MN.
CITATION(S): Johnson TP et al. Nodding syndrome may be an autoimmune reaction to the parasitic worm Onchocerca volvulus. Sci Transl Med 2017 Feb 15; 9:eaaf6953.
(http://dx.doi.org/10.1126/scitranslmed.aaf6953)
http://stm.sciencemag.org/content/9/377/eaaf6953?ijkey=
c6596b02f927821784acb577e8cba4b9a4190166&keytype2=tf_ipsecsha
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Am J Gastroenterol 2017 Feb 14
Acid Reflux Control Aids Success in Barrett Esophagus Ablation
Using a standardized reflux management protocol, recurrence of intestinal metaplasia and dysplasia after complete eradication was low.
Poorly controlled gastroesophageal reflux is implicated as a risk factor for recurrence of Barrett esophagus (BE) after endoscopic eradication therapy (EET), recently estimated at an annual rate of 9.6% (NEJM JW Gastroenterol Nov 9 2016; [e-pub] and Am J Gastroenterol 2017; 112:87). However, the magnitude of the effect is unclear.
In a single-center observational study, researchers assessed complete eradication of intestinal metaplasia and its recurrence in 221 consecutive patients with BE who were managed with a standardized reflux therapy protocol. Participants were administered omeprazole (40 mg twice daily) prior and subsequent to EET with radiofrequency ablation (RFA); monitored for compliance; evaluated for symptom control; given reflux testing for nonresponse; and provided with necessary regimen adjustments, adherence counseling, or surgery referral.
Seventy-one percent of patients achieved complete eradication in ≤3 RFA sessions. Of 48 who did not and received subsequent pH impedance testing, after modification of reflux treatment (medication timing and compliance with twice-daily dosing) in 9 and fundoplication in 39, 45 (94%) had complete eradication after a mean of 1.1 more RFA treatments. The final complete eradication rate was 93%. Recurrence was 4.8% for intestinal metaplasia and 1.5% for dysplasia during a mean follow-up of 44±18 months and did not occur after the first 3 years.
COMMENT: Effective acid control is needed not only to facilitate BE eradication but also to ensure its long-term durability. It is unclear why these researchers chose a target of >5% for abnormal pH on twice-daily proton-pump inhibitors (PPIs), as the normal value used in practice is <1.6% of total time pH<4. Also, the recent American College of Gastroenterology guideline indicates that patients with BE should receive PPIs once daily, not twice daily, unless symptoms or erosive esophagitis are noted. Guidelines may need modification for treatment of patients undergoing EET, which is perhaps best guided by posttreatment esophageal impedance pH monitoring and, for those found to have reflux symptoms or endoscopic esophagitis, specific counseling on the importance of medication timing (30–60 minutes before meals) and compliance.
CITATION(S): Komanduri S et al. Recurrence of Barrett's esophagus is rare following endoscopic eradication therapy coupled with effective reflux control. Am J Gastroenterol 2017 Feb 14; [e-pub].
(http://dx.doi.org/10.1038/ajg.2017.13)
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BMJ 2017 Feb 21; 356:j603
Consider the Evidence Before Prescribing Antidepressants Off-Label
For only a few depression medications does strong evidence support use for nondepression indications.
A recent study showed that about half of antidepressants prescribed by Quebec primary care clinicians were for off-label, nondepression indications, such as anxiety, pain, and insomnia (NEJM JW Gen Med Jul 1 2016 and JAMA 2016; 315:2230). Now, the same researchers analyzed this data set again to investigate the frequency of, and scientific evidence supporting, off-label antidepressant prescriptions.
Their findings were as follows:
- Of 107,000 antidepressant prescriptions, written for 21,000 adults, 29% were for off-label indications.
- By class, tricyclic antidepressants (TCAs) showed the highest prevalence of off-label prescribing (81% of all TCA prescriptions) followed by “other” antidepressants (trazodone, bupropion, and mirtazapine; 42%), and selective serotonin reuptake inhibitors (SSRIs; 22%).
- Off-label prescriptions for TCAs largely were for amitriptyline, which was prescribed almost entirely for pain, insomnia, and migraine. Off-label prescriptions for “other” antidepressants largely were for trazodone, mostly for insomnia.
- The most common drug–off-label indication pairs were trazodone–insomnia (26% of all off-label prescriptions), citalopram–anxiety (18%), amitriptyline–pain (14%), and amitriptyline–insomnia (6%).
- Strong evidence supported only three pairs (amitriptyline–pain, escitalopram–panic disorder, and venlafaxine–obsessive compulsive disorder), which accounted for only 16% of all off-label prescriptions. For 40% of prescriptions, strong evidence supported another drug in the same class (but not the prescribed drug). For 45% of prescriptions, neither the prescribed drug nor any other drug in the same class had strong evidence for the indication.
COMMENT: In this study, only one in six off-label antidepressant drug prescriptions written by primary care physicians was supported by strong evidence and, for nearly half of these prescriptions, strong evidence the prescribed drug or any drug in the same class did not exist. Nonetheless, these findings raise complex issues. On the one hand, some approved indications (e.g., amitriptyline for depression) have become somewhat outdated with the advent of newer, better-tolerated options. On the other hand, off-label prescribing often is recommended by specialists and supported by guidelines. For example, trazodone, which is almost never used for depression, is prescribed commonly for insomnia despite lack of strong evidence. Yet its use for insomnia is suggested by an American Academy of Sleep Medicine guideline (J Clin Sleep Med 2017; 13:307) and a recent review article (N Engl J Med 2015; 373:1437). Clinicians should consider the evidence supporting off-label prescriptions before writing them.
CITATION(S): Wong J et al. Off-label indications for antidepressants in primary care: Descriptive study of prescriptions from an indication based electronic prescribing system. BMJ 2017 Feb 21; 356:j603.
(http://dx.doi.org/10.1136/bmj.j603)
http://www.bmj.com/content/356/bmj.j603?ijkey=
631d315a3295463c5bc40ea61eb86e8e50e88b27&keytype2=tf_ipsecsha
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