• Naltrexone at low doses upregulates a unique gene expression not seen with
normal doses: Implications for its use in cancer therapy
• U.S. Mortality Rate Increases
• Bioengineered Vessels Effectively Provide Access for Chronic Dialysis
• Interrupting Prolonged Sitting with Brief Activity Might Improve Glycemic Control
• Potato Intake Is Associated with Risk for Hypertension
• Larger Bottles Linked to Increased Weight Gain in Formula-Fed Infants
• High-Fat Mediterranean Diet Does Not Promote Weight Gain
• FDA Proposes Rules for Lowering Added Sodium in Food
• High Doses of Imodium Linked to Cardiac Problems and Death
• Women with Atrial Fibrillation at Higher Risk for Cancer
• Predicting the Effects of Modifiable Factors on Breast Cancer Risk
• Long-Term Aspirin Use Reduces Risk for Gastrointestinal Cancer
• Blood Pressure Variability Linked to Cognitive Decline
• Rotating Night Shift Work Can Be Hard on the Heart
• Testing for Cure of Anogenital Gonorrhea
• FDA: Migraine Patch Could Cause Serious Burns and Scars
• The Pharmacogenetic Tool Kit to Guide Depression Treatment Decisions?
• Lithium: Still the One
Naltrexone at low doses upregulates a unique gene expression not seen
with normal doses: Implications for its use in cancer therapy
- Authors: Wai M. Liu, Katherine A. Scott, Jayne L. Dennis, Elwira Kaminska, Alan J. Levett, Angus G. Dalgleish
- Published online on: Tuesday, June 7, 2016
Abstract
It has been reported that lower doses of the opioid antagonist naltrexone are able to reduce tumour growth by interfering with cell signalling as well as by modifying the immune system. We have evaluated the gene expression profile of a cancer cell line after treatment with low-dose naltrexone (LDN), and assessed the effect that adapting treatment schedules with LDN may have on enhancing efficacy. LDN had a selective impact on genes involved with cell cycle regulation and immune modulation. Similarly, the pro-apoptotic genes BAD and BIK1 were increased only after LDN. Continuous treatment with LDN had little effect on growth in different cell lines; however, altering the treatment schedule to include a phase of culture in the absence of drug following an initial round of LDN treatment, resulted in enhanced cell killing. Furthermore, cells pre-treated with LDN were more sensitive to the cytotoxic effects of a number of common chemotherapy agents. For example, priming HCT116 with LDN before treatment with oxaliplatin significantly increased cell killing to 49±7.0 vs. 14±2.4% in cultures where priming was not used. Interestingly, priming with NTX before oxaliplatin resulted in just 32±1.8% cell killing. Our data support further the idea that LDN possesses anticancer activity, which can be improved by modifying the treatment schedule.
https://www.spandidos-publications.com/10.3892/ijo.2016.3567
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U.S. Mortality Rate Increases
By Amy Orciari Herman, Edited by Susan Sadoughi, MD, and Richard Saitz, MD, MPH, FACP, FASAM
The age-adjusted mortality rate in the U.S. rose between 2014 and 2015 — from 723.2 to 729.5 per 100,000 population — according to preliminary data from the CDC's National Center for Health Statistics. It's the first time in a decade that the U.S. has seen a mortality increase.
Among the causes of death that saw significant increases: Alzheimer disease, chronic lower respiratory diseases, drug overdose, homicide, hypertension, liver disease, Parkinson disease, septicemia, stroke, and suicide.
"It's an uptick in mortality and that doesn't usually happen, so it's significant," the chief of mortality statistics at the NCHS told the New York Times. "But the question is, what does it mean? We really need more data to know. If we start looking at 2016 and we see another rise, we'll be a lot more concerned."
http://www.cdc.gov/nchs/products/vsrr.htm
http://www.nytimes.com/2016/06/01/health/american-death-rate-rises-for-first-time-in-a-decade.html?_r=0
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Lancet 2016 May 14; 387:2026
Bioengineered Vessels Effectively Provide Access for Chronic Dialysis
Plastic grafts might become passé.
Autologous arteriovenous fistulas for chronic dialysis cannot always be created, particularly in older patients or those with major comorbidities. Plastic grafts are the alternative, but they incur relatively high rates of thrombosis and infection.
To provide an alternative, an international team created artery-sized tubes, composed of biodegradable polymers, and then washed banked vascular smooth muscle cells onto this “scaffolding.” The smooth muscle cells proceeded to make collagen and other structural proteins, which supported the vessel wall as the biodegradable scaffolding disappeared. A blood vessel was formed de novo, but one with cells that would not be bioidentical to those of a potential graft recipient. So, the researchers destroyed the living cells in these new vessels, leaving just tubes of structural proteins, which were implanted in the arms of 60 patients in whom fistulas could not be created or had failed. Circulating stem cells homed to the structural proteins and transformed into new, bioidentical endothelial and vascular smooth muscle cells.
Patients were followed for a mean 16 months. Chronic dialysis was successful in all. Ultrasound revealed no degradation of the vessel walls over time. Rates of thrombosis and infection were superior to those seen historically in plastic grafts, and no evidence of immune rejection was noted.
COMMENT: This remarkable accomplishment in “regenerative medicine” might mean we can dispense with plastic grafts for chronic dialysis access someday. Larger and longer controlled studies will be required to establish the value of this approach.
CITATION(S):Lawson JH et al. Bioengineered human acellular vessels for dialysis access in patients with end-stage renal disease: Two phase 2 single-arm trials. Lancet 2016 May 14; 387:2026.
(http://dx.doi.org/10.1016/S0140-6736(16)00557-2)
http://www.ncbi.nlm.nih.gov/pubmed/27203778?access_num=27203778&link_
type=MED&dopt=Abstract
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Diabetes Care 2016 Jun; 39:964
Interrupting Prolonged Sitting with Brief Activity might improve Glycemic Control
In type 2 diabetic adults, frequent 3-minute exercise breaks lowered glucose and insulin levels.
Australian researchers have shown that brief interruptions of prolonged sitting improve glucose metabolism in overweight sedentary nondiabetic adults (NEJM JW Gen Med Jul 1 2012 and Diabetes Care 2012; 35:976). Now, the same team has conducted a similar randomized crossover study in 24 overweight sedentary diabetic adults (mean glycosylated hemoglobin [HbA1c], 7.2%) who were taking either no antidiabetic medication or metformin only.
On three different days, separated by 1- to 2-week washout periods, participants sat for 7 hours and ate standardized breakfasts and lunches. On one day, participants remained seated the entire time, except to void; on a second day, they interrupted sitting with 3 minutes of light-intensity (3.2 km/hour) walking on a treadmill every 30 minutes; and, on a third day, they interrupted sitting with 3 minutes of simple resistance activities (half-squats, calf raises, gluteal contractions, knee raises) every 30 minutes. Blood glucose and insulin levels were measured every half hour.
The primary outcome was change in the incremental area under the curve (iAUC) for glucose and insulin — an integrated measure of glucose and insulin above fasting levels during the 7-hour sessions. The iAUCs for both glucose and insulin were significantly lower (by ≈35%–40%) during both the walking and simple resistance sessions than during uninterrupted sitting.
COMMENT: Interrupting prolonged sitting with brief periods of walking or resistance activities might improve glycemic control in sedentary diet-controlled or metformin-controlled diabetic patients. The challenge for employers is to find nondisruptive ways for employees to integrate intermittent physical activity into otherwise sedentary workdays.
CITATION(S): Dempsey PC et al. Benefits for type 2 diabetes of interrupting prolonged sitting with brief bouts of light walking or simple resistance activities. Diabetes Care 2016 Jun; 39:964.
(http://dx.doi.org/10.2337/dc15-2336)
http://care.diabetesjournals.org/content/39/6/964?ijkey=e0db68773e1c8c0baed597
119d6f5b6d792f0d57&keytype2=tf_ipsecsha
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BMJ 2016 May 17; 353:i2351
Potato Intake Is Associated with Risk for Hypertension
Potatoes' high glycemic index could be the culprit.
Potatoes are rich in potassium, and appropriate potassium intake is associated with diminished risk for hypertension. To assess the relation between potato intake and hypertension, researchers pooled data from three prospective cohort studies (the Nurses' Health Studies and the Health Professionals Follow-Up Study) and adjusted for many potential confounding variables (e.g., age, ethnicity, body-mass index, smoking status, physical activity, medications).
Of >187,000 participants without hypertension at baseline, 78,000 participants reported receiving diagnoses of hypertension during follow-up. Participants who consumed ≥1 serving daily of baked, boiled, or mashed potatoes or French fries had excess risk for hypertension compared with those who consumed ≤1 serving monthly (multivariate hazard ratio, 1.12). Similar results were obtained for consumption of baked, boiled, or mashed potatoes alone and consumption of French fries alone (≥4 servings weekly vs. ≤1 serving monthly). However, potato chip consumption alone was not associated with excess risk.
COMMENT: In this study, consuming baked, boiled, or mashed potatoes or French fries was associated with excess risk for hypertension. The authors speculate that potatoes' high glycemic load, which is associated with oxidative stress, inflammation, and endothelial dysfunction, might account for their findings. However, these results should be interpreted with caution: For example, potatoes often are consumed with salt (although the authors claim that adjusting for sodium intake did not affect their results), and intake of potatoes, salt, and other nutrients, as well as diagnoses of hypertension were all self-reported. As noted by editorialists, dietary behaviors are complex; rather than focusing on individual foods and nutrients (and labeling some of them as “bad”), focusing on patients' overall dietary patterns probably would be more useful.
CITATION(S): Borgi L et al. Potato intake and incidence of hypertension: Results from three prospective US cohort studies. BMJ 2016 May 17; 353:i2351.
(http://dx.doi.org/10.1136/bmj.i2351)
http://www.bmj.com/content/353/bmj.i2351?ijkey=bccb39839a8df4a27a9c589c
94612db7863dc791&keytype2=tf_ipsecsha
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Pediatrics 2016 Jul; 138:e20154538
Larger Bottles linked to increased Weight Gain in Formula-Fed Infants
Feeding formula in bottles holding ≥6 ounces may be a modifiable risk factor for obesity.
Weight gain in infancy has been tied to weight status later in life, with overweight infants more likely to become overweight children. Bottle size may play a role in the weight gain observed in formula-fed infants, but its role is less well understood than other modifiable risk factors, such as nutritional content and timing of feedings.
To examine the association between bottle size and three outcomes — weight gain at the 6-month visit, increases in weight-for-age (WAZ), and weight-for-length Z scores (WLZ) — researchers analyzed data from 386 infant-parent dyads already enrolled in a cluster-randomized, longitudinal obesity prevention trial. Bottle size was determined at the 2-month visit by direct verification or through parents identifying the bottle “most like the one they usually used to feed” from a set of 4-, 6-, and 8-ounce bottles. Weight and recumbent length were measured at the 2-month and 6-month visits. A majority of dyads were black (41%) or Hispanic (35%), lived in low-income households (62% earned <$20,000 a year), and involved parents with an educational level of ≤ high school diploma (63%).
All three measures increased significantly more (an additional 0.21 kg in weight, 0.24 U in WAZ, and 0.31 U in WLZ) in infants fed using larger bottles (≥6 ounces), when adjusted for birth weight, time between visits, study site, and socioeconomic characteristics.
COMMENT: Although we continue to strongly promote exclusive breast-feeding, finding ways to minimize the risks associated with formula feeding should be a top priority. This study offers a possible addition to our counseling on safe bottle feeding, which already includes advice on bottle propping, formula mixing, milk warming safety, and cleaning methods. Guiding parents toward smaller bottles (<6 ounces) in early infancy is a simple step that could benefit babies.
CITATION(S):Wood CT et al. Bottle size and weight gain in formula-fed infants. Pediatrics 2016 Jul; 138:e20154538.
(http://dx.doi.org/10.1542/peds.2015-4538)
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High-Fat Mediterranean Diet Does Not Promote Weight Gain
By Amy Orciari Herman, Edited by David G. Fairchild, MD, MPH, and Jaye Elizabeth Hefner, MD
A high-fat Mediterranean diet doesn't lead to weight gain — rather, it might help with weight loss — according to a subanalysis from the PREDIMED study published in the Lancet Diabetes and Endocrinology.
Roughly 7500 older men and women in Spain were randomized to follow a high-fat Mediterranean diet supplemented with either nuts or extra-virgin olive oil, or a lower-fat control diet. The Mediterranean diets aimed to increase fat intake to more than 40% of daily calories, while the control diet aimed to reduce fat intake to less than 30% of calories.
During 5 years' follow-up, participants following the olive oil-rich Mediterranean diet lost significantly more weight than the control group (about half a kilogram more). In addition, waist circumference was lower with the two Mediterranean diets than with the control diet.
A commentator writes: "Dietary guidelines should be revised to lay to rest the outdated, arbitrary limits on total fat consumption. ... We must abandon the myth that lower-fat, lower-calorie products lead to less weight gain."
http://www.thelancet.com/journals/landia/article/PIIS2213-8587(16)30085-7/abstract
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FDA Proposes Rules for Lowering Added Sodium in Food
By Kelly Young, Edited by Susan Sadoughi, MD, and Richard Saitz, MD, MPH, FACP, FASAM
The FDA has announced draft guidance for industry for voluntarily reducing sodium in processed and restaurant food.
The average American consumes about 3400 mg of sodium daily. The short-term (2-year) target aims to reduce sodium intake to roughly 3000 mg per day. The long-term (10-year) target aims for intake below 2300 mg per day, following the Dietary Guidelines for Americans'recommendation.
The FDA notes that 75% of sodium consumption in the U.S. is from salt added to food before it is sold.
In response to some studies showing increased cardiovascular risk withlow sodium intake, CDC Director Thomas Frieden and others make a case for why the association is not causal in a New England Journal of Medicine sounding board article. They conclude: "Reducing population sodium intake, through reducing excess sodium in manufactured and restaurant food in the United States, represents an important opportunity to prevent heart disease and stroke and reduce health care costs."
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm503874.htm
https://s3.amazonaws.com/public-inspection.federalregister.gov/2016-12950.pdf
http://www.nejm.org/doi/full/10.1056/NEJMsb1607161?query=pfw&jwd=
000101421649&jspc=
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High Doses of Imodium Linked to Cardiac Problems and Death
By Kelly Young, Edited by David G. Fairchild, MD, MPH, and Lorenzo Di Francesco, MD, FACP, FHM
The FDA is cautioning that higher-than-recommended doses of the antidiarrheal drug loperamide (Imodium) are associated with potentially fatal cardiac problems. The drug is increasingly being misused for its opioid effects by patients either seeking euphoria or self-treating for opioid withdrawal.
Since 1976, some 48 cases of serious cardiac events associated with loperamide have been reported to the FDA, but more than half of these occurred after 2010.
The agency recommends that clinicians consider loperamide toxicity in patients presenting with unexplained cardiac problems, including syncope, cardiac arrest, QT interval prolongation, and torsades de pointes or other ventricular arrhythmias. Opioid drug screens don't test for loperamide, so a specific loperamide test should be requested to measure blood levels.
Risk for adverse cardiac effects may be elevated when high doses are taken with medications that interact with loperamide (e.g., clarithromycin, erythromycin, gemfibrozil, itraconazole, ketoconazole, quinine, quinidine, ritonavir).
http://www.fda.gov/Safety/MedWatch/SafetyInformation/
SafetyAlertsforHumanMedicalProducts/ucm505303.htm
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Women with Atrial Fibrillation at Higher Risk for Cancer
By Kelly Young, Edited by Susan Sadoughi, MD
Newly diagnosed atrial fibrillation (AF) in women is associated with increased cancer risk and vice versa, suggests a JAMA Cardiology study.
Researchers examined data from 35,000 healthy women from the Women's Health Study. During a median 19 years' follow-up, 4% developed AF and 15% developed cancer. Women who developed AF had significantly higher rates of incident cancer than women without AF (1.4 vs. 0.8 events per 100 person-years). The effect persisted beyond 1 year after AF diagnosis.
The reverse was also true — women diagnosed with cancer had higher subsequent AF rates than women without cancer (0.38 vs. 0.24 events per 100 person-years). The difference was only significant in the first 3 months.
Editorialists write: "The mechanisms underlying the interrelations are probably multifactorial and include shared risk factors, increased detection due to bleeding with anticoagulation (suggested by the prominence of colon cancer), or other systemic processes… Based on available data, cancer screening beyond standard routine health care is currently not merited with a new diagnosis of AF."
http://cardiology.jamanetwork.com/article.aspx?articleid=2525428
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JAMA Oncol 2016 May 26
Predicting the Effects of Modifiable Factors on Breast Cancer Risk
According to a new model, almost one third of breast cancers among U.S. white women could be prevented by adopting healthy lifestyles.
Modifiable risk factors for breast cancer include postmenopausal obesity, menopausal estrogen-progestin therapy (EPT), and alcohol consumption. Non-modifiable risk factors evaluated in this study include family history of breast cancer, age at menarche and menopause, parity, breast density, atypical hyperplasia, and single nucleotide polymorphisms (SNPs; genetic markers associated with risk). To predict absolute risk for invasive breast cancer in U.S. white women, investigators developed a model that incorporated 92 SNPs plus epidemiologic elements (family history, anthropometric features, and menstrual, reproductive, and lifestyle factors).
When all risk factors were included, average absolute risk ranged from 4.4% to 23.5%. Overall, average cumulative risk for breast cancer by age 80 was 11.3% for a 30-year-old woman. For women at highest risk due to non-modifiable factors, those who had low body-mass index, did not drink alcohol or smoke, and did not use menopausal hormone therapy had risks comparable to the average in the general population. The authors estimate that, among all white women in the U.S., almost one in three breast cancer cases could be prevented if modifiable risk factors were kept at the lowest possible levels.
COMMENT: Study limitations include incomplete data on 68 of the 92 SNPs, necessitating use of simulations from previously published risk estimates. Furthermore, the investigators did not capture differing risks associated with estrogen-only versus estrogen-progestin menopausal hormone therapy; they also lacked data on atypical hyperplasia and breast-feeding. Nonetheless, it's encouraging to see how much risk can be lowered by maintaining a lean body mass and limiting alcohol intake. The reduction in breast cancer risk from avoiding exposure to estrogen-progestin therapy can be individualized based on quality-of-life concerns as well as baseline risks for breast cancer and osteoporosis. Further validation is required before models such as this can be used to guide clinical practice or screening recommendations.
Dr. Samiian is Assistant Professor of Surgery and Chief, Section of Breast Surgery at University of Florida College of Medicine–Jacksonville.
CITATION(S): Maas P et al. Breast cancer risk from modifiable and nonmodifiable risk factors among white women in the United States. JAMA Oncol 2016 May 26; [e-pub].
(http://dx.doi.org/10.1001/jamaoncol.2016.1025)
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JAMA Oncol 2016 Mar 3
Long-Term Aspirin Use Reduces Risk for Gastrointestinal Cancer
Risks were reduced for colorectal cancers in particular and were seen only after 5 years.
Retrospective and prospective studies have suggested that aspirin use reduces the risk for colorectal cancer. However, whether aspirin reduces risks for other cancers and whether it supplements the benefit of colorectal cancer screening have not been clearly established.
Investigators now report long-term follow-up from a cohort analysis of more than 135,000 healthcare professionals (88,000 women and 47,000 men) assessed in the Nurses' Health Study and the Health Professionals Follow-up Study. The researchers assessed effect of aspirin dose, frequency of use, and duration of use on the development of cancer in the pooled cohort, as well as the impact of aspirin on colorectal cancer in the context of colonoscopy screening in participants aged 50 or older.
After 32 years of follow-up, 20,414 cancers were observed in women and 7571 cancers were observed in men. Regular aspirin use versus no aspirin use resulted in a slight but significant reduction in overall cancer risk (relative risk, 0.97), primarily due to a reduction in gastrointestinal cancer (RR, 0.85) and in colorectal cancer, in particular (RR, 0.81). Aspirin use was also associated with a trend toward reduced risk for gastroesophageal cancer (RR, 0.85). Reduced gastrointestinal cancer risk was observed only after 5 years of aspirin use, was independent of sex, and was dose-dependent at 0.5 to 1.5 standard tablets or more weekly. No association was observed between aspirin use and risk for breast, prostate, or lung cancer. Risks were unaffected by the presence or absence of screening.
COMMENT: This update of the Nurses' Health Study and the Health Professionals Follow-up Study continues to support a benefit of regular aspirin use to reduce risk for colorectal cancer and, potentially, esophagogastric cancer, but not for other cancers. The benefit was independent of utilization of colorectal cancer screening. A preventive benefit for regular aspirin use is supported by the risk reduction achieved with aspirin use after curative treatment for established colorectal cancer and the significant reduction in colorectal cancer risk reported in patients taking aspirin who carry the gene for Lynch syndrome.
CITATION(S): Cao Y et al. Population-wide impact of long-term use of aspirin and the risk for cancer. JAMA Oncol 2016 Mar 3; [e-pub].
(http://dx.doi.org/10.1001/jamaoncol.2015.6396)
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Blood Pressure Variability Linked to Cognitive Decline
By Kelly Young, Edited by David G. Fairchild, MD, MPH, and Jaye Elizabeth Hefner, MD
Blood pressure readings that vary significantly over time are associated with faster cognitive decline among older adults, according to aHypertension study.
Nearly 1000 Chinese adults aged 55 years and older who had BP readings taken during three or four visits subsequently underwent repeated cognitive screening tests over 5 years.
After multivariable adjustment, participants who were in the highest third of systolic BP variability had significantly faster declines in cognitive function and verbal memory, compared with participants in the lowest third. Among adults aged 55 to 64 — but not older adults — highly variable diastolic BP was associated with faster cognitive decline, compared with the lowest third. Mean BP readings were not associated with cognitive decline.
The authors note that magnetic resonance imaging studies have found that BP variability was tied to white matter hyperintensities or lesions, reduced hippocampal volume, cerebral microbleeds, and cortical infarcts.
http://hyper.ahajournals.org/content/early/2016/05/23/
HYPERTENSIONAHA.116.07494.full.pdf+html
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JAMA 2016 Apr 26; 315:1726
Rotating Night Shift Work Can Be Hard on the Heart
Nurses' Health Study data point to night shift rotation for 5 or more years as a CHD risk factor.
Short-term studies have suggested links between night shift rotation and risk for coronary heart disease (CHD). Now, extended findings from the prospective Nurses' Health Studies (NHS, baseline age range, 30–55; and NHS2, baseline age range, 25–42; all participants female, primarily white), confirm this association. History of working ≥3 night shifts monthly (in addition to day and evening shifts) was assessed at baseline and subsequent intervals.
During 24 years of follow-up, 73,623 NHS participants and 115,535 NHS2 participants without baseline CHD experienced a total of 10,822 events (myocardial infarction, coronary artery bypass graft, angioplasty, coronary artery stent, and angina pectoris). Compared with women who never performed night shift rotation, those who did so for >5 years had modestly but significantly higher CHD incidence (5–9-year shift rotation history, 525.7 events/100,000 person-years [hazard ratio, 1.21] in the NHS cohort and 152.6 [HR, 1.22] in the NHS2). For nurses with ≥10 years of night shift rotation, rates were 596.9 (HR, 1.36) in the NHS and 178.0 (HR, 1.34) in the NHS2. Adjustment for CHD risk factors attenuated but did not eliminate significantly higher risk; longer time since last shift rotation decreased risk somewhat. Additional adjustments for sleep disturbance and social isolation did not substantially affect results.
COMMENT: Women might work night shift rotation because of economic advantages, family schedules, or job requirements. Perhaps we should start considering night shift rotation for ≥5 years to be a modifiable CHD risk factor.
CITATION(S): Vetter C et al. Association between rotating night shift work and risk of coronary heart disease among women. JAMA 2016 Apr 26; 315:1726. (http://dx.doi.org/10.1001/jama.2016.4454)
http://www.ncbi.nlm.nih.gov/pubmed/27115377?access_num=27115377&link_
type=MED&dopt=Abstract
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Clin Infect Dis 2016 Jun 1; 62:1348
Testing for Cure of Anogenital Gonorrhea
In a prospective study, both RNA- and DNA-based nucleic acid amplification tests were negative in 95% of participants by 6 and 9 days, respectively.
Diagnosis of gonorrhea is recommended to be based not on culture, but on nucleic acid amplification tests (NAATs). Concerns about antimicrobial resistance and asymptomatic infection have led to a call for a test of cure (TOC) to monitor treatment outcome. Because data using NAATs to ascertain TOC are limited, Dutch investigators conducted a prospective cohort study to assess the appropriate timing of TOC using NAATs after treatment of anogenital gonorrhea. In 2014, 62 adults with anogenital gonorrhea self-collected pretreatment anal, vaginal, or urine samples for RNA- and DNA-based NAATs. After treatment with a single intramuscular dose of 500-mg ceftriaxone, participants collected samples from the same anatomical site for the next 28 days. Cultures for Neisseria gonorrhoeae were obtained before treatment and at the end-of-study visit.
Of the 61 evaluable participants, none had a treatment failure or resistance to ceftriaxone found on culture. The median time to RNA clearance was 2 days, and 95% of participants were negative by 6 days. Clearance was significantly slower for endocervical compared with urethral (P=0.01) and rectal infections (P=0.03), and clearance was significantly slower for women compared with men (P=0.03). Results were similar for DNA NAAT, with 95% of participants negative by 9 days.
COMMENT: As editorialists point out, although there has been controversy about the need to perform TOC, this study demonstrates that the vast majority of patients with anogenital gonorrhea will have negative NAATs by 10 days after appropriate therapy. The effect of therapy on pharyngeal gonorrhea, a potential reservoir of infection, remains unexamined.
CITATION(S): Wind CM et al. Test of cure for anogenital gonorrhoea using modern RNA-based and DNA-based nucleic acid amplification tests: A prospective cohort study. Clin Infect Dis 2016 Jun 1; 62:1348.
(http://dx.doi.org/10.1093/cid/ciw141)
http://cid.oxfordjournals.org/content/62/11/1348?ijkey=32e184be8a5b0dc2a80fc
873554ca7021df6dcf5&keytype2=tf_ipsecsha
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FDA: Migraine Patch Could Cause Serious Burns and Scars
By Kristin J. Kelley, Edited by Susan Sadoughi, MD, and André Sofair, MD, MPH
Patients using the sumatriptan iontophoretic transdermal patch (Zecuity) to treat migraines could be burned or permanently scarred, warns the FDA. The agency says it has received a "large number" of reports of skin reactions associated with the patch since it went on the market in September 2015.
The patch — battery-powered and wrapped around the thigh or upper-arm — is meant to be used only once, for up to 4 hours. Reactions have included blistering, cracked skin, pain, redness, and skin discoloration.
Common side effects listed by the manufacturer include discomfort, itching, pain, redness where the patch is applied, and tingling. The manufacturer also warns of potential serious adverse events, including heart attack. (High-risk patients must get a heart exam prior to beginning treatment.)
The FDA will review the risk for serious skin reactions and may take further regulatory action. In the meantime, patients who experience pain at the application site should remove the patch and consult a healthcare provider.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/
SafetyAlertsforHumanMedicalProducts/ucm504736.htm
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Lancet Psychiatry 2016 Jun; 3:585
The Pharmacogenetic Tool Kit to Guide Depression Treatment Decisions?
Commercially available tool kits are not yet ready for widespread adoption.
With the suboptimal response to many psychiatric treatments given by trial and error, clinicians and patients await the “personalizing” of treatment. Commercially available support tools for pharmacogenetic decision making are now being marketed to psychiatrists and, in the U.S., are reimbursed by some insurers. In an excellent review, these authors focus on tools offered by 22 companies.
The tools usually include multigene panels, based on single nucleotide polymorphisms, and are heavily focused on pharmacokinetic genes, less so on pharmacodynamic genes. For three support tools, published studies suggest improved clinical outcomes in depressed patients when prescribers follow the gene-based proprietary recommendations to prioritize the selection of specific medications. However, most studies were uncontrolled, and the combinatorial algorithms behind these recommendations were unpublished. Only a small number of included genes have been shown to singly have pharmacological implications. None of the tools included environmental factors potentially affecting therapeutic response or accounted for well-known ancestry effects.
COMMENT: This excellent review should be read by any psychiatrists wanting to use this kind of testing in their patients. In my own inspection of some of the published papers, the mean differences between groups had significant overlap, and no sensitivity or specificity analyses were provided.
Although some clinicians may argue that such testing “can't hurt and might help,” current psychopharmacological practice is complex, usually including combinations of multiple medications, and patients can have multiple comorbidities, both psychiatric and medical. Hence the meager available evidence, although promising, does not support routine use of these kits (although testing in some treatment-resistant patients might be reasonable). Even in medical specialties (e.g., oncology) that are much farther along in the understanding of genetic factors in illness pathophysiology, genetic testing to guide treatment is still in its infancy.
CITATION(S):Bousman CA and Hopwood M.Commercial pharmacogenetic-based decision-support tools in psychiatry.Lancet Psychiatry 2016 Jun; 3:585.
(http://dx.doi.org/10.1016/S2215-0366(16)00017-1)
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JAMA Psychiatry 2016 May11
Lithium: Still the One
A retrospective cohort study found lower rates of self-harm and unintentional injury with lithium in patients with bipolar disorder.
To test the hypothesis that lithium is associated with reduced rates of self-harm, unintentional injury, and suicide in patients with bipolar disorder, researchers studied electronic health records collected from a representative sample of 6671 British patients from 1995 through 2013. The patients had a diagnosis of bipolar disorder and received maintenance medication in primary care practices (the standard in the U.K. after diagnosis by a psychiatrist) with lithium, valproate, olanzapine, or quetiapine.
Analyses were performed with and without adjustment for various features thought to influence the propensity to prescribe one or another medication (e.g., demographic factors, medical comorbidity, previous treatment, anxiety, depression, insomnia). In most comparisons, there were significantly higher rates of self-harm and unintentional injury with the three other drugs than with lithium; the number of suicides was too small to calculate differential risks. These differences held for comparisons with individual alternatives to lithium, except for olanzapine and unintentional injury. There was no difference between valproate, olanzapine, and quetiapine for any of the outcome measures.
COMMENT: The authors speculate that lithium's similar superiority for intentional and unintentional self-injury indicates benefit specifically for impulsivity rather than mood stabilization, but this is not supported by data on mood, functioning, or even medication doses. It seems equally likely that patients taking lithium had better symptomatic and functional recovery, of which fewer injuries was one marker. In either case, the results support long-standing observations that lithium reduces injury as well as suicidality
(NEJM JW Psychiatry Aug 2013 and BMJ 2013; 346:f3646) and contradicts earlier reports that anticonvulsants increase suicidality. The low incidence of suicide in this study probably reflects patients treated entirely in primary care being less severely ill than those in specialty practice.
CITATION(S):Hayes JF et al. Self-harm, unintentional injury, and suicide in bipolar disorder during maintenance mood stabilizer treatment: A UK population-based electronic health records study. JAMA Psychiatry 2016 May11; [e-pub]. (http://dx.doi.org/10.1001/jamapsychiatry.2016.0432)
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