• Hurricane damage in Puerto Rico leads to fears of drug shortages nationwide
• Cigna won't cover oxycodone hydrochloride prescriptions for 2018
• Choosing Wisely: 5 Pediatric Endocrinology Tests to Avoid
• Sex-Specific Risk for Autism Recurrence in Younger Siblings
• Gun Use in Movies Linked to Gun Use by Children
• Triathlon Deaths Caused by Cardiac Arrests
• The Consequences of Stopping Low-Dose Aspirin
• Does Cutting Dietary Fat Affect Breast Cancer Outcomes?
• Periodontal Disease and Cancer Risk: Another Reason to Floss
• Incidence of measles in the United States, 2001–2015
• Treating Apathy in Alzheimer Disease
• Transfusions of Fresh vs. Older Blood in Seriously Ill Patients
• Even Within the Normal Range, Higher Thyroxine Levels Correlate with Earlier Mortality
Hurricane damage in Puerto Rico leads to fears of drug shortages nationwide
New York Times (10/05/17) Thomas, Katie; Kaplan, Sheila
Major pharmaceutical firms and federal officials are scrambling to prevent national shortages of critical drugs for treating cancer, diabetes, and heart disease that are manufactured at 80 plants in hurricane-ravaged Puerto Rico. The U.S. territory has become one of the world's biggest centers for pharmaceutical manufacturing, with its factories making 13 of the world's top-selling brand-name drugs. Drug companies are confronting a range of obstacles on the island, including locating enough diesel fuel for generators to run their factories. "Some of these products are critical to Americans," FDA Commissioner Scott Gottlieb told a congressional panel this week. "A loss of access could have significant public health consequences." Gottlieb, who visited FDA staff in Puerto Rico last week, told the House Energy and Commerce Committee's subcommittee on Health: "We have a list of about 40 drugs that we're very concerned about. It reflects maybe about 10 firms." Thirteen of the drugs, Gottlieb said, are "sole-source." The biggest problem, he said, was not damage to the factories, but the instability of the electric supply. Manufacturers are worried that a long-term lack of connection to a major power grid could jeopardize their products, and they are also wary of relying on the more limited electrical grids that the territory is likely to activate as a first step to restoring power.
https://www.nytimes.com/2017/10/04/health/puerto-rico-hurricane-maria-pharmaceutical-manufacturers.html?emc=edit_th_20171005&nl=todaysheadlines&nlid=73314806
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Cigna won't cover oxycodone hydrochloride prescriptions for 2018
CNBC.com (10/04/17) Mangan, Dan
Cigna announced Wednesday that it will effectively stop covering the cost of use of the opioid oxycodone (OxyContin—Purdue Pharma) by customers of its employer-based health plans beginning in January. Cigna's moves come more than a year after the insurer said it intended to cut opioid use among its customers by 25% by 2019. "Our focus is on helping customers get the most value from their medications—this means obtaining effective pain relief while also guarding against opioid misuse," said Jon Maesner, Cigna's chief pharmacy officer. While Maesner said that Cigna would review individual prescriptions for Purdue Pharma's oxycodone that are deemed "medically necessary" by a physician, the drug essentially is "being removed" from coverage by the insurer. Cigna said that people who have already started using the drug for hospice care or cancer treatments will continue to have that medication covered next year. Cigna in 2016 announced a goal of slashing use of opioids among its customers by 25% over the next 3 years. Cigna said that as part of that initiative it would encourage doctors to prescribe the drugs in lesser quantities and for lesser amounts of time.
https://www.cnbc.com/2017/10/04/cigna-wont-cover-oxycontin-prescriptions-for-2018.html
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Choosing Wisely: 5 Pediatric Endocrinology Tests to Avoid
By Amy Orciari Herman
Edited by David G. Fairchild, MD, MPH, and Lorenzo Di Francesco, MD, FACP, FHM
The endocrinology section of the American Academy of Pediatrics has issued a list of five tests clinicians should avoid as part of the Choosing Wisely campaign.
These include:
- Hormone tests (luteinizing hormone, follicle-stimulating hormone, and estradiol or testosterone) in children with pubic hair or body odor but without other signs of puberty
- Screening tests for chronic illness or endocrine conditions in healthy children growing at or above the third percentile for height (at a normal growth rate) and with appropriate weight gain
- Routine measurement of serum vitamin D in healthy children, including those who are overweight or obese
- Measurement of thyroid function or insulin levels in obese children
- Routine ultrasound of the thyroid in children with simple goiters or autoimmune thyroiditis
LINK(S):
AAP Choosing Wisely list (Free)
Background: Physician's First Watch coverage of AAP's list of newborn tests and treatments to avoid.
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JAMA Pediatr 2017 Sep 25
Sex-Specific Risk for Autism Recurrence in Younger Siblings
Recurrence risk was highest among male siblings of affected girls and lowest among female siblings of affected boys.
Autism recurrence risk — the probability of an autism spectrum disorder (ASD) diagnosis in a younger sibling of an affected child — has been documented at 6% to 19% in prior studies (NEJM JW Pediatr and Adolesc Med Oct 2011 and Pediatrics 2011; 128:e488 and NEJM JW Pediatr and Adolesc Med Nov 2013 and JAMA Pediatr 2013; 167:947). ASD is known to occur four times as often in males, yet sex-specific recurrence risk among younger siblings is unclear.
To address this issue, researchers reviewed an Aetna administrative database containing diagnostic billing codes between 2008 and 2016 to identify two-child families with an older child diagnosed with ASD who had a younger sibling.
Of more than 3 million children in such families (mean age, 4–18 years), 1.25% had ASD (mean age at diagnosis, 5–6 years); prevalence was 1.96% in males and 0.5% in females. Of the 21,000 families in which the older child had ASD, recurrence risk was highest in younger male siblings of girls with ASD (16.7%), followed by younger male siblings of boys with ASD (12.9%) and younger female siblings of girls with ASD (7.6%); the lowest risk was in female siblings of boys with ASD (4.2%).
COMMENT: Parents are eager to know autism recurrence risk for the purposes of family planning and monitoring younger children, and scientists seek more evidence of the gene–environment interactions influencing autism risk. This study offers valuable information about the chances that additional offspring will develop autism. Despite the lower recurrence risk among younger female siblings of boys, the risk for these girls is still more than eight times higher than for females in the general population. Therefore, primary care providers should have a low threshold for referring all younger siblings for autism evaluations when developmental concerns arise. These results also support etiologic theories that girls require a heavier genetic burden of ASD-related mutations than boys in order to develop autism symptoms.
CITATION(S): Palmer N et al. Association of sex with recurrence of autism spectrum disorder among siblings. JAMA Pediatr 2017 Sep 25; [e-pub].
(http://dx.doi.org/10.1001/jamapediatrics.2017.2832)
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JAMA Pediatr 2017 Sep 25
Gun Use in Movies Linked to Gun Use by Children
Watching gun use was associated with significantly more gun holding and trigger pulls.
Exposure to gun use in movies, television, and other forms of media may influence how children interact with guns when they find them. To determine the extent to which this may be true, researchers randomized 52 pairs of children 8 to 12 years of age to watch a 20-minute PG-rated movie clip, either with or without scenes involving gun use. The pairs were then allowed to play for 20 minutes in a secretly recorded room containing toys and games. Hidden in a drawer was a disabled real handgun with a trigger sensor. Primary outcomes were time spent holding the gun and the number of trigger pulls. Covariates included sex, age, race, guns in the home, and attitudes toward guns.
Of the 43 pairs of children who found the handgun, 22 (51%) handled it, and 14 (33%) alerted researchers to its presence. Children who watched gun scenes versus those who didn't held the handgun longer (adjusted median number of seconds, 53.1 vs. 11.1) and pulled the trigger more times (adjusted median pulls, 2.80 vs. 0.01). Character of play also differed, as children watching gun scenes were observed to play more aggressively and shoot at their play partners and people passing by outdoors.
COMMENT: Adding a randomized controlled trial to the literature on how gun violence affects children's behavior may not change the political tide on gun control or reduce gun ownership in the U.S., but it should rally and inform pediatricians in the effort to help parents safely store firearms in their homes. It also reminds us to directly address with parents how they can manage children's exposure to violence in various media by actively mediating what children view and helping them think critically about media content, rather than passively consuming it.
CITATION(S): Dillon KP and Bushman BJ.Effects of exposure to gun violence in movies on children's interest in real guns. JAMA Pediatr 2017 Sep 25; [e-pub].
(http://jamanetwork.com/journals/jamapediatrics/fullarticle/2654597)
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Ann Intern Med 2017 Sep 19
Triathlon Deaths Caused by Cardiac Arrests
Male, first-time participants had the highest mortality risk, and most arrests occurred during the swimming portion of events.
Approximately 500,000 participants compete annually in USA Triathlon (USAT) events, which include cycling, swimming, and running. Some deaths occur during events, which raises concern about safety, but little is known about death rates during triathlons. Investigators identified 135 triathlon-related deaths and cardiac arrests during USAT events among >9 million participants during 30 years.
Eighty-five percent of arrests occurred in men, and most (67%) occurred during the swim portion of the triathlon. Older competitors expectedly had higher risk, but race length did not affect arrest rate. When only athletes in whom competition history was known were considered, nearly 40% of arrests occurred among first-time triathlon participants. When autopsy records were available, cardiac disease — most commonly substantial coronary artery disease — was noted in 44% of decedents. Cardiac-arrest survival was only 11% during triathlons, much lower than the 29% survival after arrests reported in marathon runners (N Engl J Med 2012; 366:130).
COMMENT: How should we use these case-series data — currently the best evidence available for outcomes in this narrow population? Athlete education and prerace evaluations (especially for older and first-time participants) perhaps could identify and mitigate individual risk prior to events. Additionally, knowing about elevated risk for arrest during the swim portion of triathlons might help race organizers design strategies to lower risk and to identify and rescue victims sooner.
CITATION(S): Harris KM et al. Death and cardiac arrest in U.S. triathlon participants, 1985 to 2016: A case series. Ann Intern Med 2017 Sep 19; [e-pub].
(http://dx.doi.org/10.7326/M17-0847)
Ho RT and Glanz K.Sudden death during triathlons: The heart of the swim. Ann Intern Med 2017 Sep19; [e-pub].
(http://dx.doi.org/10.7326/M17-2031)
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Circulation 2017 Sep 26; 136:1183
The Consequences of Stopping Low-Dose Aspirin
The risk for cardiovascular events rises soon after discontinuation, according to this large-scale, observational study.
Aspirin is a mainstay in the treatment of patients with coronary artery disease and has been used for primary prevention. To learn about the effect of discontinuing aspirin, investigators examined Swedish national databases to conduct a partially industry-funded, cohort study of approximately 600,000 users of low-dose aspirin for primary or secondary prevention between 2005 and 2009.
Included were people aged >40, without cancer histories, and with an 80% adherence during the first year of aspirin use (mean age, 73; 52% women; diabetes, 16%); 54% used aspirin for secondary prevention, whereas the others likely used aspirin as primary prevention. Almost 63,000 cardiovascular events occurred during a median follow-up of 3 years (incidence rate, 42/1000 person-years at risk).
In adjusted analyses, persistent aspirin treatment was associated with the lowest cumulative incidence of cardiovascular events. Patients who discontinued aspirin had a 37% higher rate of cardiovascular events (13.5 events/1000 person-years at risk). In subgroup analyses, older individuals and those with prior cardiovascular disease faced even higher risks for events off aspirin. Treatment with oral anticoagulants or other antiplatelet drugs, however, was not associated with risk for cardiovascular events off aspirin.
COMMENT: One of every 74 Swedes who discontinued aspirin experienced an additional cardiovascular event within 1 year. The risk for cardiovascular events increased soon after the discontinuation of aspirin therapy and did not wane over time. This study provides strong evidence for the continuation of aspirin indefinitely in patients with known cardiovascular disease.
CITATION(S): Sundström J et al. Low-dose aspirin discontinuation and risk of cardiovascular events. Circulation 2017Sep 26; 136:1183. (http://dx.doi.org/10.1161/CIRCULATIONAHA.117.028321)
http://circ.ahajournals.org/content/136/13/1183?ijkey=
7cab0301849f1d44d99f5bb67fe2b625b9f71949&keytype2=tf_ipsecsha
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J Clin Oncol 2017 Sep 1; 35:2919
Does Cutting Dietary Fat Affect Breast Cancer Outcomes?
Women's Health Initiative randomized trial findings suggest lowering dietary fat also lowers mortality after breast cancer.
In the Women's Health Initiative dietary modification trial, investigators randomized women beginning in 1993 (age range, 50–70) to usual diet or a diet characterized by reduced fat and increased fruit, vegetables, and grains. Results at a median of 8 years indicated that fewer deaths from breast cancer occurred in women assigned to this dietary modification. The current report extends follow-up to a median of 16 years, focusing on the impact of dietary modification on deaths from breast cancer as well as overall mortality in participants with breast cancer diagnoses.
Although most breast cancer characteristics were similar between groups, a significantly smaller proportion of cancers in the dietary modification participants were of the poor-prognosis, estrogen-receptor–positive, progesterone-receptor–negative type. During the extended follow-up, among 3030 participants with incident breast cancer, deaths attributed to breast cancer were modestly (but not significantly) less common in the dietary modification group. However, overall mortality after breast cancer was significantly lower among women in the dietary modification group (234 vs. 443 deaths; hazard ratio, 0.82; P=0.01). Adjustment for weight change during the dietary intervention did not alter these findings.
COMMENT; The authors note that a favorable effect of this dietary intervention on cardiovascular mortality could have contributed to their findings. Furthermore, they point out that chemotherapy and radiation therapy can contribute to cardiovascular mortality in breast cancer patients. Whether the reduced overall mortality among women with incident breast cancer was caused by a direct positive effect of the dietary modification on breast cancer characteristics, or whether the benefits were not oncologic, these findings provide additional evidence for the benefits of a plant-based, low-fat diet.
CITATION(S): Chlebowski RT et al. Low-fat dietary pattern and breast cancer mortality in the Women's Health Initiative randomized controlled trial. J Clin Oncol 2017 Sep 1; 35:2919.
(http://dx.doi.org/10.1200/JCO.2016.72.0326)
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Cancer Epidemiol Biomarkers Prev 2017 Aug; 26:1255
Periodontal Disease and Cancer Risk: Another Reason to Floss
Postmenopausal women with periodontal disease had excess risk for cancer of the breast, lung, esophagus, and gallbladder and for melanoma.
Periodontal disease has been linked to adverse reproductive outcomes in women, and some studies also suggest an increased risk for cancer. Investigators for the Women's Health Initiative Observational Study examined rates of incident cancer in >65,000 women (mean age, 68; 85% white) who were asked about periodontal disease at baseline and followed for a mean of 8 years.
Risk for developing any cancer was 14% higher among women with periodontal disease than among those without gum disease. Statistically significant excess risks were also noted for cancer of the breast (13%), lung (31%), esophagus (>200%), and gallbladder (73%) and for melanoma (23%). Results were similar regardless of smoking status.
COMMENT: It's unclear whether the association between periodontal disease and oncogenesis is causal. However, some studies have shown bacteria associated with periodontitis in tumors or distal tissues such as lymph nodes, and the strikingly high excess risk for esophageal cancer is consistent with tracking of periodontal pathogens to the gut. Periodontal disease is also indicative of a systemic proinflammatory state that may contribute to risk for preterm birth, although treatment of periodontal disease during pregnancy does not abrogate this increased risk (NEJM JW Womens Health Apr 2010) and Am J Obstet Gynecol 2010; 202:147.e1). Whether treating periodontal disease will lower the increased risk for malignancy is unknown. I find a careful examination of the mouth helpful, as it tells me about the general health of the patient — and it may precipitate referral for dental care. Now, I will also think about the patient's risk for cancer.
CITATION(S): Nwizu NN et al. Periodontal disease and incident cancer risk among postmenopausal women: Results from the Women's Health Initiative observational cohort. Cancer Epidemiol Biomarkers Prev 2017 Aug; 26:1255.
(http://dx.doi.org/10.1158/1055-9965.EPI-17-0212)
http://cebp.aacrjournals.org/content/26/8/1255?ijkey=
11d60fbf2eeac116ed36ebfefa3b82a075bcf3e4&keytype2=tf_ipsecsha
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Incidence of measles in the United States, 2001–2015
Journal of the American Medical Association (10/03/17) Vol. 318, No. 13, P. 1279 Clemmons, Nakia S.; Wallace, Gregory S.; Patel, Manisha; et al.
Although endemic measles was wiped out in the United States in 2000, outbreaks have continued to sprout as a result of the virus being brought in from other countries. CDC researchers analyzed data on all cases occurring from January 2001–December 2015, in an effort to characterize the post-elimination trend. Of particular interest were patients' age, whether or not they had been vaccinated, and importation status. In the 15 years after endemic elimination, 1,789 measles cases were reported among U.S. residents—which reflects an extremely low annual rate compared with the global population. Nearly 70% of affected Americans were not immunized, almost 13% were, and vaccination status was unconfirmed for the remaining 17.7%. When foreign visitors and patients with unknown residency were included, the total number of cases climbed to 2,012. Nearly three-quarters were acquired within the United States, with the remaining one-fourth or so imported internationally. Additionally, the rate of measles infection was lower in older populations, with declines starting at age 16 months. The data suggest that low vaccination uptake—rather than poor vaccine performance—is responsible for measles transmission.
https://jamanetwork.com/journals/jama/article-abstract/2656158
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Am J Psychiatry 2017 Sep 15
Treating Apathy in Alzheimer Disease
Methylphenidate improved motivation, cognition, mood, functioning, and caregiver burden in community-dwelling men with mild disease.
Apathy, a prominent feature of Alzheimer disease, impairs motivation, reduces spontaneous behavior, and has been associated with a heavier caregiver burden. In a 12-week trial, investigators randomized 60 community-dwelling male veterans with mild Alzheimer disease and apathy to methylphenidate (target dose, 10 mg twice daily) or placebo (mean age, 77; mean Mini-Mental State Exam [MMSE] score, 24; >90% white).
Participants did not have active psychosis, frontotemporal dementia, or current major depression, although 58% had depressive symptoms. About 85% had hypertension, and 47% had coronary artery disease. Polypharmacy was common (cholinesterase inhibitors, 63%; antidepressants, 55%; memantine, 30%).
Significant improvements for methylphenidate vs. placebo were first seen at 4 weeks for overall apathy scores; at 8 weeks for the behavior, cognition, and motivation domains of apathy; and at 12 weeks for depression and emotion scores, MMSE scores, activities of daily living, and caregiver burden. Adverse events and serious adverse events were similar in the groups, with only one serious event possibly attributable to medication.
COMMENT: These results bear replication in larger samples and both sexes. Still, the study suggests several clinically important points. First, treating apathy might help to reduce depressive symptoms, but apathy and depression should be distinguished from each other and warrant separate attention. Second, in these elderly patients with hypertension and cardiovascular disease, adverse effects were no more frequent for modestly dosed methylphenidate than for placebo. Third, improvements occurred within 4 weeks for apathy but more gradually in other psychological and functional areas. Fourth, cognitive improvements at 12 weeks were comparable to those reported for cholinesterase inhibitors. Overall, treating apathy with methylphenidate may benefit both patients with mild Alzheimer disease and their caregivers.
CITATION(S): Padala PR et al. Methylphenidate for apathy in community-dwelling older veterans with mild Alzheimer's disease: A double-blind, randomized, placebo-controlled trial. Am J Psychiatry 2017 Sep 15; [e-pub].
(http://dx.doi.org/10.1176/appi.ajp.2017.17030316)
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N Engl J Med 2017 Sep 27
Transfusions of Fresh vs. Older Blood in Seriously Ill Patients
Use of fresh blood does not improve survival for intensive-care patients.
Standard blood bank practice is to release older units of red cells first (“first-in, first out”). Would acutely ill patients fare better if they were transfused with fresh rather than older blood?
To address this question, investigators conducted an international, multicenter, randomized, double-blind trial involving 4919 intensive-care patients who received a median of two red cell units of either fresh blood (stored for a mean of 11.8 days) or older, standard-issue blood (stored for a mean 22.4 days).
At 90-day follow-up, risk for death was similar with fresh versus older blood (24.8% and 24.1%, respectively), and was even higher with fresh blood for patients with APACHE III predicted risk for death ≥21.5% (37.7% vs. 34.0%; P=0.05). Other outcome measures, such as death at 28 days, persistent organ dysfunction, and duration of hospitalization, were similar with fresh versus older blood.
COMMENT: In 2008, investigators reported that 1-year survival rates were higher for coronary artery bypass patients who received blood that was ≤2 versus >2 weeks old (NEJM JW Oncol Hematol May 2008 and N Engl J Med 2008; 358:1229). However, a survival benefit could not be confirmed by a smaller cardiac surgery study using blood that was a mean 7.8 versus 28.3 days old (NEJM JW Oncol Hematol May 2015 and N Engl J Med 2015; 372:1419). Also, a multicenter, randomized, blinded trial comparing the use of blood that was a mean 6.1 versus 22.0 days old in critically ill adults observed no difference in 90-day mortality (NEJM JW Oncol Hematol May 2015 and N Engl J Med 2015; 372:1410). Most recently, mortality did not differ in a large study of general hospital patients following transfusion of blood that was a mean 13.0 versus 23.6 days old (N Engl J Med 2016; 375:1937). These findings along with the results of the current study show that transfusions of fresh blood are not more advantageous than standard issue blood.
CITATION(S): Cooper DJ et al. Age of red cells for transfusion and outcomes in critically ill adults. N Engl J Med 2017 Sep 27; [e-pub].
(http://dx.doi.org/10.1056/NEJMoa1707572)
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JAMA Intern Med 2017 Sep 18
Even Within the Normal Range, Higher Thyroxine Levels Correlate with
Earlier Mortality
Higher levels also correlated with higher cardiovascular risk.
Some studies suggest that patients with high-normal thyroid function have excess risk for cardiovascular disease (CVD) and early death. In this population-based Dutch cohort study, 7785 adults (mean age, 65) without known thyroid disease (thyrotropin and free thyroxine [FT4] within normal reference ranges) were identified. Patients were divided into tertiles according to both thyrotropin and FT4 levels.
During median follow-up of 8.1 years, fatal or nonfatal adverse CVD events occurred in 10% of patients, and 17% died overall. Outcomes were as follows:
- People in the highest FT4 tertile had 32% higher risk for incident CVD.
- People in the highest FT4 tertile were ≈50% more likely to die than people in the lowest tertile.
- People in the lowest FT4 tertile lived about 3 years longer than people in highest tertile.
- No association was found between thyrotropin levels and incident adverse CVD events; however, people in the highest thyrotropin tertile were about 20% less likely to die than people in other tertiles.
COMMENT: These results, and similar results of prior studies, might make us question how to manage patients who are receiving thyroid replacement therapy and who believe they feel better at higher replacement doses with suppressed thyrotropin. I am less likely to push replacement doses beyond a middle range of thyrotropin suppression based on symptoms alone.
CITATION(S): Bano A et al. Association of thyroid function with life expectancy with and without cardiovascular disease: The Rotterdam study. JAMA Intern Med 2017 Sep 18; [e-pub].
(http://dx.doi.org/10.1001/jamainternmed.2017.4836)
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