• Association between Proton-Pump Inhibitors and Dementia?
• Healthy Living could mean a lot Fewer Cancers
• FDA Calls for more Restrictions on Fluoroquinolone Use
• Managing Chronic Insomnia
• Can Vitamin D Supplementation Prevent Type 2 Diabetes?
• Metabolic Studies Might Explain why Keeping Weight Off is so Hard
• Fertility in Obese Women: Benefits of Weight Loss
• Weight Loss before Fertility Treatment didn't Boost Odds of
Delivering Healthy Baby Vaginally
• Obesity has Long-Term Cardiovascular Effects
• Replacing Saturated Fats with Linoleic Acid–Rich Vegetable Oils lowers
Total Cholesterol but not Mortality
• Mitoxantrone in Multiple Sclerosis: Malignancy Risk Higher than previously Appreciated
• Tai Chi as Effective as Physical Therapy for Knee Osteoarthritis
• Women Who attend Religious Services might live Longer
• Radiotherapy does not Improve Outcome in Locally Advanced Pancreatic Cancer
• First U.S. Penile Transplant Performed
• Variability in Laboratory Reference Ranges for Testosterone
• Could ADHD Beginning in Adulthood be a Unique Syndrome?
JAMA Neurol 2016 Apr; 73:410
Association between Proton-Pump Inhibitors and Dementia?
An observational study that suggested this association has considerable limitations.
In February 2016, a study that linked proton-pump inhibitors (PPIs) to dementia was published online and attracted considerable media attention. Because patients who use PPIs continue to ask their physicians about this presumed dementia risk, we thought it worthwhile to revisit the study (the original article now has been published in print).
Drawing from an insurance claims database, researchers compared older (age, ≥75) regular PPI users (≈3000) with older PPI nonusers (≈71,000); patients had no history of dementia at baseline. During about 6 years of follow-up, risk for a new diagnosis of dementia was significantly higher among PPI users than among nonusers (hazard ratio, 1.44).
COMMENT
Media coverage of this study did not adequately emphasize that most observational studies — including this one — do not establish cause and effect. One problem is that the researchers controlled for only a few potentially confounding variables; they did not control for alcohol use or cigarette smoking, which could be associated with both PPI use and propensity for dementia. Additionally, type of dementia was not specified for most patients. Patients who take PPIs for valid reasons (e.g., those with peptic ulcer or severe reflux symptoms, and those who take PPIs for guideline-recommended ulcer prophylaxis) should not stop taking the drugs because of this study. However, this study — and others that raise concerns about various potential adverse effects — might motivate patients who take PPIs for no good reason to discontinue them.
CITATION(S): Gomm W et al. Association of proton pump inhibitors with risk of dementia: A pharmacoepidemiological claims data analysis. JAMA Neurol 2016 Apr; 73:410. (http://dx.doi.org/10.1001/jamaneurol.2015.4791)
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Healthy Living could mean a lot Fewer Cancers
By Kelly Young, Edited by André Sofair, MD, MPH, and William E. Chavey, MD, MS
Adopting a healthy lifestyle could avert at least a quarter of cancers and half of cancer-related deaths, suggests a JAMA Oncology study.
Researchers studied 28,000 healthcare professionals who met four healthy lifestyle criteria: never or past smoking, moderate or no alcohol consumption, BMI of 18.5–27.4, and regular physical activity. These participants were compared with over 100,000 participants who didn't meet all four criteria.
The researchers calculated that 25% of cancers in women and 33% in men might not have occurred if everyone adopted the healthy lifestyle. Similarly, 48% of cancer deaths in women and 44% in men might have been averted. When comparing the healthy group to the U.S. white population in general, the reductions were even greater. Lung and esophageal cancers saw the greatest reductions.
Editorialists write: "As a society, we need to avoid procrastination induced by thoughts that chance drives all cancer risk or that new medical discoveries are needed to make major gains against cancer, and instead we must embrace the opportunity to reduce our collective cancer toll by implementing effective prevention strategies and changing the way we live."
http://oncology.jamanetwork.com/article.aspx?articleid=2522371
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FDA Calls for more Restrictions on Fluoroquinolone Use
By Kristin J. Kelley, Edited by Susan Sadoughi, MD, and André Sofair, MD, MPH
The risks for "disabling and potentially permanent" side effects associated with systemic fluoroquinolone antibacterials (e.g., ciprofloxacin, moxifloxacin) generally outweigh the benefits in patients with sinusitis, bronchitis, and uncomplicated urinary tract infections, the FDA warned late last week. Fluoroquinolones should only be used for these indications when patients don't have other treatment options, the agency said.
Side effects can compromise the nerves, central nervous system, tendons, muscles, and joints. Symptoms may include confusion; hallucinations; joint, muscle, and tendon pain; or a tingling sensation (i.e., "pins and needles").
The action follows advisory panel recommendations made in late 2015 for stronger label warnings. The labels were previously updated in 2013 to warn of increased risk for peripheral neuropathy. Additionally, in 2008, a boxed warning was added to note risks for tendinitis and tendon rupture.
See the linked FDA drug safety communication for a full list of fluoroquinolones currently approved for systemic use.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/
SafetyAlertsforHumanMedicalProducts/ucm500665.htm
http://www.fda.gov/Drugs/DrugSafety/ucm500143.htm
http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/Anti-InfectiveDrugsAdvisoryCommittee/UCM467383.pdf
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Managing Chronic Insomnia
Jamaluddin Moloo, MD, MPH reviewing Qaseem A et al. Ann Intern Med 2016 May 3. Kathol RG and Arnedt JT. Ann Intern Med 2016 May 3. Wilt TJ et al. Ann Intern Med 2016 May 3. Brasure M et al. Ann Intern Med 2016 May 3.
The American College of Physicians recommends first-line cognitive-behavioral therapy and add-on pharmacological therapy if needed.
Sponsoring Organization: American College of Physicians (ACP)
Target Audience: All clinicians
Background
Chronic insomnia is defined as insomnia that occurs for at least 3 nights weekly for ≥3 months, it must cause clinically significant functional distress or impairment and must not be linked to another medical or mental disorder. A new guideline from the ACP is based on a systematic review of randomized trials and provides recommendations on managing chronic insomnia.
Key Points:
- Options to manage insomnia include psychological, pharmacological, or combination therapy.
- Psychological therapy includes sleep hygiene, stimulus control, sleep restriction, relaxation training, and cognitive-behavioral therapy (CBT). Moderate-quality evidence demonstrated that CBT improved multiple components of sleep and could be delivered by different methodologies including one-on-one therapy, group therapy, self-help books, and Web-based modules.
- Pharmacological options approved by the FDA include benzodiazepines, nonbenzodiazepine hypnotics (i.e., zolpidem, eszopiclone, and zaleplon), an orexin-receptor antagonist (i.e., suvorexant [Belsomra]), a melatonin-receptor agonist (i.e., ramelteon), and doxepin. Various drug classes such as antihistamines, antipsychotics, and melatonin are used off-label. Low-to-moderate quality evidence demonstrated that doxepin, suvorexant, eszopiclone, zolpidem, and extended-release zolpidem each improved total sleep time (by approximately 15–45 minutes). Zaleplon failed to extend total sleep time, and data were insufficient to evaluate efficacy of benzodiazepines, melatonin, or trazodone.
- ACP recommendations:
- All adults with chronic insomnia should receive CBT as first-line treatment (strong recommendation; moderate-quality evidence).
- Clinicians should use shared decision making to determine whether short-term pharmacologic treatment should be added if CBT alone is unsuccessful (weak recommendation; low-quality evidence).
COMMENT: This guideline highlights the high prevalence of chronic insomnia and the relatively poor quality of evidence available to guide management. Although the guideline recommends CBT as first-line treatment, this recommendation might frustrate some clinicians: Most primary care practices are not equipped to deliver CBT, and affordable CBT is not readily available in many communities.
CITATION(S):
Qaseem A et al. Management of chronic insomnia disorder in adults: A clinical practice guideline from the American College of Physicians. Ann Intern Med 2016 May 3; [e-pub]. (http://dx.doi.org/10.7326/M15-2175);
Kathol RG and Arnedt JT.Cognitive behavioral therapy for chronic insomnia: Confronting the challenges to implementation. Ann Intern Med 2016 May 3; [e-pub]. (http://dx.doi.org/10.7326/M16-0359)
Wilt TJ et al. Pharmacologic treatment of insomnia disorder: An evidence report for a clinical practice guideline by the American College of Physicians. Ann Intern Med 2016 May 3; [e-pub]. (http://dx.doi.org/10.7326/M15-1781).
Brasure M et al. Psychological and behavioral interventions for managing insomnia disorder: An evidence report for a clinical practice guideline by the American College of Physicians. Ann Intern Med 2016 May 3; [e-pub].
(http://dx.doi.org/10.7326/M15-1782)
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J Clin Endocrinol Metab 2016 Apr; 101:1647
Can Vitamin D Supplementation Prevent Type 2 Diabetes?
In prediabetic adults, supplementation did not stop progression to overt diabetes.
Animal experiments and observational studies in humans suggest that vitamin D deficiency might play a role in development of diabetes. To examine whether supplementation affects progression to diabetes, investigators in Norway randomized 511 adults with prediabetes (impaired fasting glucose or impaired glucose tolerance) to receive either vitamin D3 (20,000 IU weekly) or placebo for 5 years. At baseline, mean serum 25-hydroxyvitamin D (25(OH)D) level was 24 ng/mL; during the study, levels doubled in the treatment group and remained unchanged in the placebo group.
At 5 years, the proportions of patients who developed type 2 diabetes were similar in the vitamin D and placebo groups (40% vs. 44%; P=0.45); annual rates of progression to diabetes also were similar in the two groups. In addition, vitamin D supplementation did not prevent diabetes in a subgroup of 112 patients who were vitamin D–deficient at baseline (i.e., 25(OH)D level <20 ng/mL).
COMMENT: Vitamin D supplementation did not prevent progression from prediabetes to type 2 diabetes in this 5-year trial (the largest such trial to date); vitamin D should not be given for this purpose. Whether supplementation might alter the natural history of prediabetes or diabetes in patients with severe vitamin D deficiency remains unclear.
CITATION(S): Jorde R et al. Vitamin D 20 000 IU per week for five years does not prevent progression from prediabetes to diabetes. J Clin Endocrinol Metab 2016 Apr; 101:1647. (http://dx.doi.org/10.1210/jc.2015-4013)
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Obesity (Silver Spring) 2016 May 2
Metabolic Studies Might Explain why Keeping Weight Off is so Hard
Surprising results were obtained when researchers evaluated participants in “The Biggest Loser.”
Unfortunately for us well-fed individuals in developed nations, tens of thousands of years ago our ancestors often were hungry. Evolution selected for a trait that helped protect our hungry ancestors: In the face of substantial weight loss, our resting metabolic rate (RMR) falls. We burn fewer calories, thereby discouraging further weight loss.
A team at the NIH studied 14 contestants in “The Biggest Loser” — a televised weight-loss competition. The participants' average weight at baseline was 328 pounds; during 30 weeks of supervised diet and exercise, they had lost an average of 128 pounds. As expected, average RMR also fell greatly, along with weight. At 6 years after their weight loss, they all had regained considerable weight (average weight, 290 pounds). As they regained weight, mean RMR actually declined further, rather than rising along with the weight gain as the researchers had expected.
COMMENT: This long-term study of massively obese subjects with substantial weight loss achieved through diet and exercise has identified an apparent failure of readaptation — failure of the resting metabolic rate to rise along with body weight, after weight loss. This failure makes regaining weight easier and losing weight harder. Interestingly, patients who lose large amounts of weight after bariatric surgery do not appear to suffer this failure. Better understanding of the forces that control RMR might make it easier to attain a healthy weight.
CITATION(S): Fothergill E et al. Persistent metabolic adaptation 6 years after “The Biggest Loser” competition. Obesity (Silver Spring) 2016 May 2; [e-pub]. (http://dx.doi.org/10.1002/oby.21538)
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N Engl J Med 2016 May 19; 374:1942.
Fertility in Obese Women: Benefits of Weight Loss
In a randomized trial, reduced calorie intake and increased physical activity raised the odds of natural conception in obese infertile women.
High body-mass index (BMI) and sedentary lifestyles decrease fertility potential. To test the efficacy of weight loss and increased activity on augmenting fertility, Dutch investigators randomized 574 infertile women (BMI ≥29 kg/m2; median, 36 kg/m2) to a 6-month lifestyle intervention followed by infertility treatment or to immediate treatment (control). The intervention consisted of reduced caloric intake (to lower BMI by ≥5%) and increased activity (10,000 steps daily plus 30 minutes of moderate exercise 2–3 times weekly).
Women in the intervention and control groups lost a mean of 4.4 kg (9.7 lb) and 1.1 kg (2.4 lb), respectively (P<0.001). Natural conception was achieved by 26% of women in the intervention group and 16% of those in the control group (rate ratio, 1.6). However, 22% of women in the intervention group discontinued participation within 3 months — and, overall, only 38% of those in the intervention group achieved weight loss of ≥5%. Within the 2 years after randomization, ongoing pregnancy was achieved with fertility treatments in 28% and 43% of women in the intervention and control groups, respectively. Treatments included ovulation induction, intrauterine insemination, and in vitro fertilization. Ovulation induction resulted in the greatest number of pregnancies in either group.
COMMENT: The chances of natural conception can be augmented by achieving an optimal BMI; thus, for young infertile women with high BMI, modest weight loss and increased exercise should be considered and encouraged before initiating resource-intensive fertility treatments. This study shows that such lifestyle intervention makes natural conception more likely, thereby helping to obviate the need for fertility interventions. However, achieving the target goal of ≥5% weight reduction was difficult for most participants (despite guidance and coaching). In the real world, more-effective intervention strategies are clearly needed.
CITATION(S): Mutsaerts MAQ et al. Randomized trial of a lifestyle program in obese infertile women. N Engl J Med 2016 May 19; 374:1942.
(http://dx.doi.org/10.1056/NEJMoa1505297)
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Weight Loss Before Fertility Treatment didn't Boost Odds of Delivering Healthy Baby Vaginally
By Amy Orciari Herman, Edited by Susan Sadoughi, MD
For obese infertile women, a lifestyle intervention to lose weight before fertility treatment might not increase the chances of delivering a healthy baby vaginally, a New England Journal of Medicine study finds.
Nearly 580 infertile Dutch women with BMIs of 29 or higher were randomized either to a 6-month lifestyle intervention followed by 18 months of infertility treatment, or to immediate infertility treatment for 24 months. The lifestyle intervention aimed to reduce body weight by 5%–10% through fewer calories and increased activity.
At 6 months, the intervention group had, on average, lost more weight than the control group (4.4 vs. 1.1 kg). However, the primary outcome — vaginal birth of a healthy singleton at term within 24 months — occurred less often in the intervention group (27% vs. 35%).
In NEJM Journal Watch Women's Health, Dr. Robert Barbieri points out that more women in the intervention than control group had ongoing pregnancies resulting from natural conception (26% vs. 16%). He writes: "The chances of natural conception can be augmented by achieving an optimal BMI; thus, for young infertile women with high BMI, modest weight loss and increased exercise should be considered and encouraged before initiating resource-intensive fertility treatments. This study shows that such lifestyle intervention makes natural conception more likely, thereby helping to obviate the need for fertility interventions."
http://www.nejm.org/doi/full/10.1056/NEJMoa1505297?query=pfw&jwd=
000101421649&jspc=
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N Engl J Med 2016 Apr 13
Obesity has Long-Term Cardiovascular Effects
High BMI in late adolescence is associated with increases in cardiovascular deaths in adulthood.
Investigators from Israel used military induction and hospital records to evaluate the effect of body-mass index (BMI) in adolescence on later death from cardiovascular causes. BMI data were collected from 2.3 million Israeli adolescents (mean age, 17) from 1967 to 2010, and were categorized according to age- and sex-specific percentiles from U.S. CDC schedules. Follow-up continued through mid-2011.
Of 32,127 deaths at follow-up, 2918 (9.1%) had cardiovascular causes (coronary heart disease, 1497; sudden death, 893; stroke, 528). In multivariate analysis controlling for age, birth year, sex, sociodemographics, and height, both cardiovascular mortality and all-cause mortality were associated with increasing BMI. Mortality began to increase with BMIs in the 50th to 74th percentiles for age and sex. Compared with a reference group of individuals with BMIs in the 5th to 24th percentiles, the obese group (BMI, ≥95th percentile) had significantly higher risk for:
- Total cardiovascular mortality: hazard ratio, 3.5
- Coronary heart disease death: HR, 4.9
- Death from stroke: HR, 2.6
- Sudden death: HR, 2.1
COMMENT: In this analysis, risks for total mortality and death from cardiovascular causes increased along with increasing BMI as measured during late adolescence. The heightened risk began in 50th percentile of adolescent BMI values and was noted in both men and women. Most of the participants were middle-aged and not yet in the demographic where cardiovascular deaths are greatest. These trends can be expected to continue and become magnified as the cohort ages. The data highlight the importance of managing cardiovascular risk factors even in adolescence and portend a potential explosion in cardiovascular morbidity and mortality as the childhood and adolescence overweight and obesity epidemic continues.`
CITATION(S): Twig G et al. Body-mass index in 2.3 million adolescents and cardiovascular death in adulthood. N Engl J Med 2016 Apr 13; [e-pub]. (http://dx.doi.org/10.1056/NEJMoa1503840)
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BMJ 2016 Apr 12; 353:i1246
Replacing Saturated Fats with Linoleic Acid–Rich Vegetable Oils lowers Total Cholesterol but not Mortality
A meta-analysis and an analysis of older study data show flaws in the traditional diet–heart hypothesis.
Randomized trials have shown that replacing dietary saturated fats with linoleic acid (an ω-6 polyunsaturated fat) lowers total cholesterol and LDL cholesterol levels, but none have shown that doing so prevents coronary heart disease (CHD) or lengthens survival. In this study, researchers recovered and analyzed unpublished data from the 1968–1973 Minnesota Coronary Experiment (MCE), a double-blind, randomized trial designed to test whether serum cholesterol-lowering with a diet that replaces saturated fats with vegetable oil rich in linoleic acid protects against CHD and all-cause death. The researchers also conducted a meta-analysis of pooled data from the MCE and four similar trials.
About 9400 residents of state hospitals and a nursing home received the intervention diet (13.2% of calories from linoleic acid; 9.2% of calories from saturated fat) or the control diet (4.7% of calories from linoleic acid; 18.5% of calories from saturated fat). Among participants who followed the study diet for at least 1 year and for whom cholesterol data were available, the intervention group had a significantly greater mean decrease in total cholesterol (14% v. 1%); however, the intervention group did not have lower risk for all-cause death, less coronary atherosclerosis, or fewer myocardial infarctions at autopsy. The meta-analysis showed similar results.
COMMENT: Results of this study and meta-analysis refute the notion that lowering blood cholesterol levels by replacing saturated fats in the diet with vegetable oils rich in linoleic acid will prevent CHD and lengthen survival. An important limitation of the MCE study is that results might not be generalizable, given that the study population consisted of institutionalized mental health patients and nursing home residents. Also, in the MCE and some other trials included in the meta-analysis, concentrated vegetable oils were used as the source of linoleic acid; hence, results should not be generalized to unprocessed foods containing linoleic acid (e.g., nuts).
CITATION(S): Ramsden CE et al. Re-evaluation of the traditional diet-heart hypothesis: Analysis of recovered data from Minnesota Coronary Experiment (1968-73).
BMJ 2016 Apr 12; 353:i1246.
(http://dx.doi.org/10.1136/bmj.i1246)
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Neurology 2016 May 11
Mitoxantrone in Multiple Sclerosis: Malignancy Risk Higher than
Previously Appreciated
Rates of acute myeloid leukemia and colorectal cancer after mitoxantrone use were higher than background risk in a retrospective analysis.
Several studies have found the incidence of acute myeloid leukemia (AML) after mitoxantrone (Novantrone) use is about 0.8%. Mitoxantrone continues to be used as induction therapy and for progressive multiple sclerosis (MS). Therefore, researchers at an MS center in Germany examined malignancy outcomes in 676 patients treated with mitoxantrone with a minimal follow-up of 3 years.
The authors identified 37 patients (5.5%) with confirmed malignancy diagnosed during follow-up, including breast cancer (n=9); colorectal cancer (n=7); AML (n=4); 2 each of glioblastoma multiforme, lung cancer, pancreatic cancer, and prostate cancer; and 1 each of nine other malignancy types. Median time to AML diagnosis from mitoxantrone initiation was 35 months. There were 12 deaths attributed to malignancy. The AML incidence rate was tenfold increased compared with the general population, and the colorectal cancer rate was threefold increased.
COMMENT: Mitoxantrone has numerous disadvantages for use in MS, including dose limitation due to cardiotoxicity, and high incidence of malignancy. Mitoxantrone continues to be used predominantly in Europe. Several more-favorable alternatives exist for patients with aggressive inflammatory MS.
CITATION(S): Buttmann M et al. Malignancies after mitoxantrone for multiple sclerosis: A retrospective cohort study. Neurology 2016 May 11; [e-pub]. (http://dx.doi.org/10.1212/WNL.0000000000002745)
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Tai Chi as Effective as Physical Therapy for Knee Osteoarthritis
By Amy Orciari Herman, Edited by David G. Fairchild, MD, MPH
Tai Chi is at least as effective as physical therapy for treating knee osteoarthritis, according to a randomized trial in the Annals of Internal Medicine.
Some 200 adults aged 40 or older with knee osteoarthritis were randomized to Tai Chi or physical therapy. Tai Chi included two group sessions weekly for 12 weeks, while physical therapy involved two outpatient sessions weekly for 6 weeks followed by continued home exercises for 6 weeks.
At 12 weeks, both groups saw significant reductions in a 500-point osteoarthritis index measuring pain (mean decreases of 167 points with Tai Chi and 143 with physical therapy); the difference between groups was not significant. The Tai Chi group had significantly greater improvements in depression and quality-of-life scores. In both groups, treatment effects persisted to 52 weeks.
The authors conclude that "standardized Tai Chi should be considered as an effective therapeutic option for knee osteoarthritis.
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Women Who attend Religious Services might live Longer
By Amy Orciari Herman, Edited by David G. Fairchild, MD, MPH
Women who regularly attend religious services appear to have a lower mortality risk than those who never attend, suggests an observational study in JAMA Internal Medicine.
Some 75,000 Nurses' Health Study participants (average age, ~60) reported on their attendance at religious services in 1996 and then were followed until 2012. All were free of cancer and cardiovascular disease at baseline. Most were Protestant or Catholic.
During follow-up, nearly 14,000 women died. After multivariable adjustment, those who reported attending religious services more than once weekly had a 33% lower mortality risk than those who never went. Risk reductions were significant for both cancer and cardiovascular mortality. Analyses identified depressive symptoms, smoking, social support, and optimism as "potentially important" mediators of the protective effect.
A commentator cautions that readers should "not attempt to generalize beyond the evidence," noting that the study did not examine specific religious experiences and also was limited to educated women.
http://archinte.jamanetwork.com/article.aspx?articleid=2521827
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JAMA 2016 May 3; 315:1844
Radiotherapy does not Improve Outcome in Locally Advanced Pancreatic Cancer
Survival was similar with chemoradiotherapy or chemotherapy alone in patients without progression after induction chemotherapy.
The role of radiation therapy for patients with pancreatic cancer remains controversial. Recent studies have indicated no survival benefit in locally unresectable disease from the use of radiation followed by chemotherapy versus chemotherapy alone. Also controversial is the contribution of the approved agent erlotinib for patients with metastatic disease.
Investigators now report the results of an international, randomized, open-label phase III trial involving 442 patients with locally advanced pancreatic cancer that addressed two questions: the contribution of erlotinib to chemotherapy and the role of radiotherapy in patients maintaining local disease after a period of induction chemotherapy.
Patients were treated with up-front chemotherapy and randomized to weekly gemcitabine with or without oral erlotinib. The median age of patients was 63–64 years, 90%–91% had performance status 0–1, and 66%–71% had tumors of the pancreatic head. After 4 months, the 269 patients (61%) with progression-free disease were randomized to an additional 2 months of chemotherapy or chemoradiotherapy (54 Gy plus capecitabine).
At a median follow-up of 36.7 months, overall survival was similar with chemotherapy or chemoradiotherapy (16.5 and 15.2 months, respectively), as was progression-free survival (8.4 and 9.9 months). For all patients, overall survival was similar with gemcitabine alone or with erlotinib (13.6 and 11.9 months, respectively).
COMMENT: This landmark trial evaluated the role of delayed radiation therapy after induction chemotherapy in locally advanced pancreatic cancer. These data further question the role of adding radiotherapy to locally unresectable disease in patients treated with gemcitabine monotherapy. The addition of erlotinib to gemcitabine also failed to improve outcome. Whether more active systemic regimens such as FOLFIRINOX or gemcitabine plus nab-paclitaxel will enhance radiotherapy in locally advanced disease remains to be established.
CITATION(S): Hammel P et al. Effect of chemoradiotherapy vs chemotherapy on survival in patients with locally advanced pancreatic cancer controlled after 4 months of gemcitabine with or without erlotinib: The LAP07 randomized clinical trial. JAMA 2016 May 3; 315:1844. (http://dx.doi.org/10.1001/jama.2016.4324)
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First U.S. Penile Transplant Performed
By the Editors of Journal Watch
The nation's first successful penis transplant was performed earlier this month, Massachusetts General Hospital announced on Monday.
The 64-year-old recipient had a partial penectomy in 2012 after being diagnosed with penile cancer.
The primary goals of the genitourinary vascularized composite allograft are to restore the external genitalia's natural appearance, re-establish normal urinary function, and achieve sexual function, if possible.
http://www.massgeneral.org/about/pressrelease.aspx?id=1937
http://www.jwatch.org/fw109983/2015/03/16/worlds-first-successful-penis-transplant-reported?query=pfw&jwd=000101421649&jspc=
http://www.sun.ac.za/english/Lists/news/DispForm.aspx?ID=2328
https://www.washingtonpost.com/news/speaking-of-science/wp/2015/03/13/surgeons-announce-worlds-first-successful-penis-transplant/
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J Urol 2016 May; 195:1556
Variability in Laboratory Reference Ranges for Testosterone
Lower limits of “normal” ranged from 160 to 300 ng/dL.
Defining a clinically relevant lower limit of “normal” blood testosterone level is challenging, in part because levels decline gradually as men age. An additional complication is that laboratories post varying reference ranges for testosterone levels, which is the issue examined in this survey of 120 hospital-associated laboratories in 47 U.S. states.
Mean lower and upper limits for total testosterone reference ranges at surveyed laboratories were 231 ng/dL and 850 ng/dL, respectively. However, lower limits ranged from 160 to 300 ng/dL, and upper limits ranged from 726 to 1130 ng/dL. About one third of hospitals sent specimens to large outside reference laboratories (e.g., Quest, Mayo, ARUP). About one third of hospitals used age-stratified reference ranges. Reference ranges often were adapted from the product insert for the analyzer used by the laboratory. Most labs did not validate these reference ranges independently in local population samples. The researchers reviewed the procedural guides from four analyzer manufacturers and found little specific information on the sample populations from which their “normal” ranges were derived. Specimens for free testosterone measurement usually were sent to outside laboratories, and normal ranges also varied for this test.
COMMENT: Testosterone levels are influenced by various factors including age, obesity, comorbidities, and assay technique. This study highlights yet another factor — variation in laboratory reference ranges — that makes interpreting testosterone levels difficult, particularly when they are on the lower side in middle-aged or older men.
CITATION(S): Le M et al. Current practices of measuring and reference range reporting of free and total testosterone in the United States. J Urol 2016 May; 195:1556. (http://dx.doi.org/10.1016/j.juro.2015.12.070)
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Could ADHD Beginning in Adulthood be a Unique Syndrome?
By Kelly Young, Edited by Susan Sadoughi, MD
Childhood and adult attention-deficit/hyperactivity disorder (ADHD) may represent two "distinct syndromes," suggest two studies in JAMA Psychiatry.
In one study, researchers followed 2000 twins from ages 5 to 18. Roughly 12% had childhood-onset ADHD, while 8% had an early-adult onset. Only 3% had a childhood onset that persisted into early adulthood. Later-onset ADHD was associated with higher IQ and fewer externalizing problems in childhood, relative to persistent ADHD, but both groups had similar rates of symptoms, impairments, and mental health disorders.
In the second study, researchers followed 5200 children up to age 19. At age 11, 9% of the cohort had ADHD. By age 19, the proportion had increased to 12%. Of the 500 with ADHD in young adulthood, only 12% had been diagnosed as children.
Instead of "distinct syndromes," editorialists hypothesize that the studies could point to "the existence of subthreshold childhood ADHD" before it emerges in young adulthood.
http://archpsyc.jamanetwork.com/article.aspx?articleid=2522750
http://archpsyc.jamanetwork.com/article.aspx?articleid=2522749
http://archpsyc.jamanetwork.com/article.aspx?articleid=2522743
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