• Vitamin D Levels Go Up and Pain Goes Down
• Antihypertensive Therapy plus Nonsteroidal Anti-Inflammatory Drugs Contribute to
Risk for Kidney Injury
• Antibiotics Reduce Mortality in Children with Severe Malnutrition
• Consider Medication as the Culprit in Children with Upper GI Complications
• Trends in Undervaccination: A National Issue
• Extremely Obese Girls at Increased Risk for Pediatric Multiple Sclerosis
• Diagnosing Pneumonia with Ultrasound
• Corticosteroid Injection Associated with Worse 1-Year Outcomes for Tennis Elbow
• 40-Year-Old Data Cast Doubt on Dietary-Fat Guidance
• Mammograms in Older Women Better Done Biennially Than Annually
• Can Imaging Detect Risk for Bipolar Disorder?
• Folate for Treatment-Resistant Depression
• Smarter PSA Screening for Prostate Cancer
• Late Effects of Interventions for Localized Prostate Cancer
• Ascorbic Acid Supplements Linked to Kidney Stones
• No Benefit from Memantine (Namenda(R)) for Frontotemporal Lobar Degeneration
From www.GrassRootsHealth.net
Vitamin D Levels Go Up and Pain Goes Down
As blood levels of Vitamin D - (25(OH)D - increase, it appears that relief from chronic pain diminishes and surprisingly, up to at least 90ng/ml, there does not seem to be an upper limit where benefits cease.
The average pain rating went down from a rating of 5.2 to 4.6 (12% decrease) in those having a serum level of about 80 ng/ml vs a lower level of about 10 ng/ml. Also noted was a 20% reduction in back pain.
Of special interest:
- At this point, we don't see a plateau of effect at 80 ng/ml. Does the benefit extend beyond that? We'll track the participants to see.
- Please note, we are still recommending a serum level range of 40-60 ng/ml (100-150 nmol/L).
- 62% of all participants are reporting pain of some type (the highest level of any health condition).
- We get many individual comments about pain reduction once people start getting their serum levels in the 40-60 ng/ml (100-150 nmol/L) range.
- We'll calculate the effect of individuals changing their serum levels for you next time.
- With all of you reporting your experiences, we can indeed show that there is a broad benefit
Click here to download the chart
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MM: These are 2 conditions that frequently co-exist and I can't even begin to tell you how many times I have seen these classes of drugs ordered together. It demonstrates how important it is that certain medications such as NSAID's are not uniformly placed over the counter. In general, drugs need supervision and it is doing no-one any favors other that he drug manufacturers to enlarge the classes of drugs that are available without a prescription. This is where the knowledge of a pharmacist and a physician becomes even more valuable to the consumer.
BMJ 2013 Jan 8; 346:e8525
Antihypertensive Therapy plus Nonsteroidal Anti-Inflammatory Drugs Contribute to Risk for Kidney Injury
Triple therapy (a diuretic + an angiotensin-converting–enzyme inhibitor or angiotensin-receptor blocker + an NSAID) was associated with excess risk.
Patients with hypertension often have conditions for which nonsteroidal anti-inflammatory drugs (NSAIDs) are indicated. However, both NSAIDs and certain antihypertensive drugs (i.e., diuretics, angiotensin-converting–enzyme [ACE] inhibitors, and angiotensin-receptor blockers [ARBs]) have hemodynamic effects on the kidney. Investigators retrospectively studied a U.K. database to examine whether antihypertensive therapy in combination with regular NSAID use is associated with excess risk for acute kidney injury.
Nearly 490,000 users of antihypertensive drugs were included in the study. During a mean follow-up of 5.9 years, >2200 cases of kidney injury were identified (defined as first hospital admission related to kidney injury). Adjusted for multiple confounders, double therapy (an NSAID, plus either a diuretic, an ACE inhibitor, or an ARB) was not associated with any greater likelihood of kidney injury than was an antihypertensive drug alone. In contrast, triple therapy (an NSAID, plus a diuretic, plus an ACE inhibitor or an ARB) significantly heightened the incidence of kidney injury compared with the same therapy without an NSAID (rate ratio, 1.3). Notably, highest risk was observed during the first 30 days of triple therapy.
Comment: In this large retrospective study, triple therapy with a diuretic plus an ACE inhibitor or an ARB plus an NSAID was associated with significant excess risk for kidney injury. These results are biologically plausible: Volume contraction caused by diuretics and renal efferent arteriole dilatation caused by ACE inhibitors and ARBs, together with renal afferent arteriole constriction caused by NSAIDs (due to inhibition of prostacyclin synthesis), likely accounts for the excess risk.
— Paul S. Mueller, MD, MPH, FACP Published in Journal Watch General Medicine February 8, 2013
Citation(s): Lapi F et al. Concurrent use of diuretics, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers with non-steroidal anti-inflammatory drugs and risk of acute kidney injury: Nested case-control study. BMJ 2013 Jan 8; 346:e8525.
(http://dx.doi.org/10.1136/bmj.e8525)
http://www.ncbi.nlm.nih.gov/pubmed/23299844?dopt=Abstract
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MM: The haphazard addition of antibiotics to nutritional regimens is as demonstrative of irresponsibility and as much of an endorsement for malpractice as I can imagine. Where is there any mention of introducing probiotics instead? This would be an inexpensive, effective, safe and appropriate complement to a nutritional program. Has modern medicine learned nothing from its mistakes? If infections are rampant in those with malnutrition, how does introducing or even creating new super-infections and super-microbes sound in the least bit like a sound approach?
N Engl J Med 2013 Jan 31; 368:425.
Antibiotics Reduce Mortality in Children with Severe Malnutrition
Adding antibiotics to sound nutritional therapy improves nutritional outcomes and survival.
Despite aggressive nutritional therapy, severe malnutrition continues to be a major cause of global childhood mortality. In a randomized, double-blind, placebo-controlled trial, researchers examined nutritional outcomes and survival in 2767 severely malnourished Malawian children (age range, 6–59 months) who received aggressive nutritional support plus two daily doses of ampicillin (80–90 mg/kg), cefdinir (14 mg/kg), or placebo for 7 days.
A higher proportion of children who received either antibiotic experienced nutritional recovery than in the placebo group (90% vs. 85%). Nutritional recovery was slowest in children with marasmic kwashiorkor and fastest in children who received cefdinir. Mortality was significantly higher in the placebo group (7.4%) than in the ampicillin (4.8%) or cefdinir group (4.1%). Both nutritional recovery and mortality rates were similar between the two antibiotic groups. Rates of nutritional recovery and survival were lowest in younger children, and in those with HIV infection, marasmic kwashiorkor, stunted growth, and cough at onset. Adverse reactions to the antibiotics were minimal.
Comment: Adding antibiotics to sound nutritional therapy improves nutritional outcomes and survival in children with severe malnutrition. Although widespread use of empiric antibiotics is worrisome, an inexpensive therapy to reduce the terrible toll of malnutrition is welcome. The potential risk for resistant organisms should motivate the continued search for better nutritional therapies.
— F. Bruder Stapleton, MD Published in Journal Watch Pediatrics and Adolescent Medicine February 6, 2013
Citation(s): Trehan I et al. Antibiotics as part of the management of severe acute malnutrition. N Engl J Med 2013 Jan 31; 368:425.
(http://dx.doi.org/10.1056/NEJMoa1202851)
http://www.ncbi.nlm.nih.gov/pubmed/23363496?dopt=Abstract
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MM:Once again we see that medications that have the potential to do good are mismanaged and will tend to create problems as frequently at resolve them.
Arch Dis Child 2012 Dec 21
Consider Medication as the Culprit in Children with Upper GI Complications
Non-steroidal anti-inflammatory drugs, oral corticosteroids, and antibiotics were associated with increased risk.
Oral medications are associated with upper gastrointestinal (UGI) complications in adults. To examine this association in children, researchers in Italy compared medication use in 486 children (median age, 41 months) hospitalized for UGI complications (cases) and 1930 controls admitted for neurological conditions in 2010. UGI complications were defined as clinically defined hematemesis (67%), melena (6%), or both (6%), or endoscopically confirmed gastroduodenal lesions (21%). Half the cases underwent endoscopy.
Frequency of chronic GI and other chronic diseases was low and similar in the two groups (about 15%). On the basis of parent report, cases were significantly more likely than controls to have received at least one drug during the 3 weeks before hospitalization (73% vs. 54%). Risk for UGI complications was increased in cases compared with controls for use of steroids (adjusted odds ratio, 2.9), non-steroidal anti-inflammatory drugs (NSAIDs; 2.9), and antibiotics (2.3). Risk was higher for ibuprofen (3.7) than for paracetamol (2.0). Median duration of medication use was short and similar in the two groups (2–4 days for NSAIDS and steroids).
Comment: A number of conditions can result in upper gastrointestinal complications, but if the patient is being treated with non-steroidal anti-inflammatory drugs, ibuprofen, oral corticosteroids, or antibiotics, medication should be considered as a possible culprit. The authors estimate that drug-related UGI complications accounted for 2.4 admissions per 10,000 pediatric emergency room visits in 2010. The results serve as another reminder to use all medications judiciously.
— F. Bruder Stapleton, MD Published in Journal Watch Pediatrics and Adolescent Medicine February 6, 2013
Citation(s): Bianciotto M et al. Drug use and upper gastrointestinal complications in children: A case–control study. Arch Dis Child 2012 Dec 21; [e-pub ahead of print].
(http://dx.doi.org/10.1136/archdischild-2012-302100)
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JAMA Pediatr 2013 Jan 21
Trends in Undervaccination: A National Issue
Prevalence is increasing, and undervaccinated children have fewer outpatient visits but more hospitalizations.
Researchers retrospectively examined the ongoing issue of undervaccination and associated healthcare utilization patterns in 323,247 children born between 2004 and 2008 in eight managed care organizations in the U.S. Vaccination and utilization data were captured from electronic health records.
From 2004 to 2008, the prevalence of delayed (
1 day) vaccination according to the Centers for Disease Control and Prevention schedule for the first 2 years increased significantly from 41.8% to 54.4%, and the mean delay increased significantly from 28 to 44 days. Parental choice was the reason for undervaccination in approximately 13% of children. Compared with a matched cohort of children with on-time vaccinations, undervaccinated children had significantly lower rates of outpatient visits (incidence rate ratio, 0.89), but significantly higher rates of inpatient admissions (IRR, 1.21). Inpatient admission rates were not increased in the small group of children who were undervaccinated because of parental refusal for nonmedical reasons.
Comment: The results of this large study represent a wide geographic spread and clearly indicate that undervaccination is a national issue. The reasons for disparities in healthcare utilization were not explored, but the increased risk for hospitalization in undervaccinated children is clear; the risk might not have been increased in the parental-refusal group because 60% of children did not have a documented reason for undervaccination. Although more information is needed to better understand the utilization rates, the correlation between undervaccination and subsequent hospitalization should be discussed with parents who refuse vaccines for their children.
— Peggy Sue Weintrub, MD Published in Journal Watch Pediatrics and Adolescent Medicine February 6, 2013
Citation(s): Glanz JM et al. A population-based cohort study of undervaccination in 8 managed care organizations across the United States. JAMA Pediatr 2013 Jan 21; [e-pub ahead of print].
(http://dx.doi.org/10.1001/jamapediatrics.2013.502)
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MM: We do not know what the cause or etiology of MS truly is but as clinicians we must constantly look for trends. If MS is truly an auto-immune disease - which we propose it is - then inflammation and obesity may be reasonable possibilities as to what is disrupting these systems. Unfortunately MS is not limited to the obese so as a uniform explanation this simply does not hold water. Since this data was positive in obese girls but not boys, I would maintain that the female obesity established a dysfunction of the hormonal balance (excess estrogen and insufficient progesterone) of these children that may have led to MS like symptoms appearing.
Neurology 2013 Jan 30
Extremely Obese Girls at Increased Risk for Pediatric Multiple Sclerosis
A population-based study reveals a potentially modifiable environmental trigger.
To examine whether childhood obesity is associated with risk for pediatric multiple sclerosis (MS) or clinically isolated syndrome (CIS), researchers reviewed data from more than 900,000 children (aged 18 years or younger) from one private Southern California healthcare system. The authors categorized body-mass index (BMI) as underweight (<5th percentile), normal (5th to <85th percentile), overweight (
85th percentile or BMI 
25 kg/m2), moderately obese (
95th percentile or BMI 
30 kg/m2), or extremely obese (95th percentile or BMI 
35 kg/m2). Logistic regression adjusted for sex, age, and race/ethnicity.
Of the children, 75 had a new diagnosis of CIS or MS. Many of the children with MS or CIS were Hispanic (52%), and children with MS or CIS were more likely than the other children to be categorized as overweight or obese (51%). The three features associated with MS or CIS were age 12 to 18 years, African-American ethnicity, and weight class; sex and education were no different compared with controls. In a subset analysis stratified by sex, extremely obese girls were 3.76 times more likely to have CIS or MS than girls who were underweight or normal weight; no such association was found among boys. Girls in the overweight and moderately obese categories did not have significant risks for MS, but an increasing trend confirmed the elevated risk with increasing weight in girls.
Comment: The findings of this population-based study suggest that teenage girls with BMI 
35 kg/m2 are almost four times more likely to develop MS or CIS during childhood than those who are underweight or normal weight. These findings need to be replicated in other populations, as the demographics of this Southern California population are different from many other countries or other parts of the U.S. Similarly, evaluating whether other pediatric autoimmune disorders interact with obesity could prove insightful. Weight may contribute to disease initiation by elevating sex hormones and inflammatory mediators associated with adipocytes and obesity. Future studies might seek to determine whether weight loss can be a beneficial modifier of MS once it is diagnosed.
— Robert T. Naismith, MD Published in Journal Watch Neurology January 30, 2013
Citation(s): Langer-Gould A et al. Childhood obesity and risk of pediatric multiple sclerosis and clinically isolated syndrome. Neurology 2013 Jan 30; [e-pub ahead of print].
(http://dx.doi.org/10.1212/WNL.0b013e31828154f3)
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MM: Any time that we can utilize a less invasive or safer approach as a diagnostic tool, I applaud that activity. An added advantage is that ultrasound may be ultimately less expensive than traditional x-rays.
Arch Pediatr Adolesc Med 2012 Dec 10
Diagnosing Pneumonia with Ultrasound
Compared with chest radiography, ultrasonography identified pneumonia with 86% sensitivity and 89% specificity.
Because clinical findings are not always reliable in determining whether a child has pneumonia, clinicians often obtain a chest radiograph (CXR) to help make the diagnosis. Ultrasonography (US) has shown promise for diagnosis of pneumonia, and smaller devices make point-of-care use more feasible. Researchers prospectively examined the accuracy of US in 200 patients (age, <21 years; median age, 3 years) who presented to a New York City emergency department with clinical suspicion of community-acquired pneumonia requiring CXR.
Patients were determined to have pneumonia if the radiologist read the CXR as "consolidation," "infiltrate," or "pneumonia." Emergency physicians with 1 hour of chest US training conducted point-of-care US. US was considered positive for pneumonia if it showed lung consolidation with sonographic air bronchograms. Interobserver agreement was high when US findings were reviewed by experienced chest sonographers.
In all, 36 patients (18%) had positive CXRs and 31 also had US findings suggesting pneumonia (sensitivity, 86%). Of the 164 patients with negative CXR findings, 146 had negative US findings (specificity, 89%; positive likelihood ratio [LR], 7.8). In comparison, overall clinical impression had a sensitivity of 84% compared with CXR, but was less specific than US (positive LR, 1.4). When researchers excluded 13 patients with negative CXRs and positive US findings showing consolidations smaller than 1 cm, specificity of US improved to 97% with a positive LR of 28.2. The authors justified excluding these "false positives" because they might have been true pneumonias too small to detect by CXR.
Comment: In this emergency department study of pneumonia diagnosis, ultrasound was quite sensitive and specific when compared with chest radiography. An actual head-to-head comparison of US and CXR would require a true gold standard, such as chest computed tomography, for the diagnosis of pneumonia. Regardless, point-of-care US has a potentially useful application in this setting; it is more convenient (especially in developing countries) and does not expose patients to ionizing radiation. Two editorialists think routine ultrasound for diagnosis of childhood pneumonia is ready for prime time.
— Cornelius W. Van Niel, MD Published in Journal Watch Pediatrics and Adolescent Medicine January 30, 2013
Citation(s):Shah VP et al. Prospective evaluation of point-of-care ultrasonography for the diagnosis of pneumonia in children and young adults. Arch Pediatr Adolesc Med 2012 Dec 10; [e-pub ahead of print].
(http://dx.doi.org/10.1001/2013.jamapediatrics.107)
Darge K and Chen A. Ultrasonography of the lungs and pleurae for the diagnosis of pneumonia in children: Prime time for routine use. Arch Pediatr Adolesc Med 2012 Dec 10; [e-pub ahead of print].
(http://dx.doi.org/10.1001/2013.jamapediatrics.409)
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MM: I don't know if these statistics would mimic results in other intra-articular injections such as the spine but I imagine they might. Unfortunately, when we are in pain we will reach for whatever solution we can irrespective of whether or not it is ultimately effective. It is also unfortunate when these actions lead to only short term relief but ultimately increase the longitudinal pain and discomfort as these steroidal injections appear to do.
Corticosteroid Injection Associated with Worse 1-Year Outcomes for Tennis Elbow
By Kelly Young
Patients with chronic unilateral lateral epicondylalgia experienced worse clinical outcomes 1 year after receiving a corticosteroid injection, relative to placebo, according to a JAMA study. In addition, physiotherapy did not provide any benefits at 1 year.
Researchers randomized 165 patients with unilateral lateral epicondylalgia lasting longer than 6 weeks to receive one of four treatments:
- A single corticosteroid injection
- Placebo injection
- Corticosteroid injection plus physiotherapy (8 weeks of elbow mobilization with movement and exercise)
- Placebo plus physiotherapy
Corticosteroid treatment was associated with complete recovery or "much improvement" at 4 weeks, but by 1 year, patients given corticosteroids were less likely to recover than those given placebo (83% vs. 96%). Moreover, corticosteroid patients were more likely to have a recurrence at 1 year, compared with patients who received placebo (54% vs. 12%).
Physiotherapy also provided early relief in the placebo group, but in all patients, the benefit had disappeared by 1 year.
The authors write: "This evidence does not support the clinical practice of using corticosteroid injection to facilitate active rehabilitation."
http://jama.jamanetwork.com/article.aspx?articleid=1568252
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40-Year-Old Data Cast Doubt on Dietary-Fat Guidance
By Joe Elia
Data recovered from an old trial confirm the increased risks of substituting dietary omega-6 linoleic acid (
-6 LA) for saturated fats, calling American Heart Association advice into question. The data appear in BMJ.
Cardiovascular outcome data from the 1966–1973 Sydney Diet Heart Study were analyzed for the first time. The trial, conducted among some 450 men with recent coronary events, tested the effect of replacing dietary saturated fats with 
-6 LA. Reports after the end of the trial showed increased all-cause mortality among those receiving 
-6 LA. The recovered data, which had been stored on tape, also show increased risks for mortality from cardiovascular disease (hazard ratio, 1.70) and coronary disease (1.74).
An editorialist writes: "These findings argue against the 'saturated fat bad, omega-6 [polyunsaturated fatty acid] good' dogma."
http://www.bmj.com/content/346/bmj.e8707
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Mammograms in Older Women Better Done Biennially Than Annually
By Joe Elia
Older women undergoing mammography every 2 years versus annually are at lower risk for false-positive screens and at equal risk for advanced-stage disease, according to a study in the Journal of the National Cancer Institute.
Using data from the Breast Cancer Surveillance Consortium, researchers examined outcomes in some 140,000 older women who underwent mammography from 1999 to 2006. Roughly 3000 were diagnosed with breast cancer. The benefits of screening intervals were examined, along with adjustment for comorbidities.
The cumulative probability of a false-positive mammogram between ages 66 and 74 was 48% among those screened annually, versus 29% among the biennials. Tumor characteristics did not differ between the groups by comorbidity or screening interval.
http://jnci.oxfordjournals.org/content/early/2013/02/01/jnci.djs645.abstract
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Biol Psychiatry 2013 Jan 15; 73:144
Can Imaging Detect Risk for Bipolar Disorder?
Enlarged gray-matter volumes in the right inferior frontal gyrus were consistently found in two separate analyses.
Bipolar mood disorder is diagnosed an average of 10 years after symptom onset, often because depression is the most common presenting symptom. To identify brain structural alterations that might reflect vulnerability factors, illness sequelae, and treatment effects, researchers used voxel-based morphometry in two analyses.
In one analysis, 50 unaffected and 36 affected children (age range, 15–30 years; from two countries) of patients with bipolar disorder and 49 unaffected controls underwent brain imaging. Both offspring groups had larger gray-matter volumes in the right inferior frontal gyrus (rIFG) than the control group; rIFG volumes in affected participants correlated negatively with illness duration.
The other analysis involved 12 bipolar-disorder patients with minimal exposure to lithium (mean illness duration, 26 years), 17 bipolar-disorder patients with extensive lithium exposure (mean, 11 years; mean illness duration, 27 years), and 11 controls. Only the minimal-lithium group had smaller rIFG volumes than the control group and an inverse correlation between rIFG volume and illness duration.
Comment: Enlarged rIFG cortical volume seems to be a true risk factor for bipolar disorder: It was present in both affected and unaffected relatives of people with bipolar disorder from two different populations and in another sample of bipolar-disorder patients. As the investigators and an editorialist note, the IFG, an essential region for emotional regulation and social and emotional learning, may increase in size early in the illness to compensate for other malfunctioning regions involved in affect control (e.g., the amygdala). Later on, the illness's neurotoxic elements may overcome this compensatory effect, which the neurotrophic properties of lithium may preserve or even stimulate. Imaging the rIFG may help to distinguish between bipolar and unipolar mood disorders in unclear cases, perhaps combined with assessment for other abnormalities such as low white-matter connectivity, deep white-matter hyperintensities, and low habenula volume (Biol Psychiatry 2013; 73:111).
— Steven Dubovsky, MD Published in Journal Watch Psychiatry January 28, 2013
Citation(s): Hajek T et al. Brain structural signature of familial predisposition for bipolar disorder: Replicable evidence for involvement of the right inferior frontal gyrus. Biol Psychiatry 2013 Jan 15; 73:144.
(http://dx.doi.org/10.1016/j.biopsych.2012.06.015)
http://www.ncbi.nlm.nih.gov/pubmed/22818781?dopt=Abstract
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Am J Psychiatry 2012 Dec 1; 169:1267
Folate for Treatment-Resistant Depression
Supplementing SSRIs with the biologically available form of folate increases response but not remission rates.
Folic-acid and related deficiencies have been associated with depression. A promising strategy for treatment-resistant depression is to target the one-carbon cycle involving homocysteine's conversion to methionine, where L-methylfolate, facilitated by vitamin B12, acts as a methyl donor; methionine next combines with ATP to form S-adenosylmethionine, a methyl donor facilitating dopamine, norepinephrine, and serotonin synthesis. Researchers recently reported results from two manufacturer-funded, randomized, controlled, double-blind, L-methylfolate studies using a complex, two-phase "sequenced parallel comparison design."
First, 148 nonpsychotic, unipolar depressed patients who failed to respond to selective serotonin reuptake inhibitors (SSRIs) continued their medications, augmented with 7.5 mg/day of L-methylfolate or placebo for 1 month, followed by placebo or 7.5 mg/day or 15/mg/day of L-methylfolate for another month. The second study, involving 75 patients, used a similar design but only the higher L-methylfolate dose. No differences were seen in remission rates. However, the 15-mg dose had a higher response rate than placebo (32% vs. 15%), with a respectable "number needed to treat" of 6. Adverse effect rates were similar for drug and placebo.
Comment: Other studies in treatment-resistant depressed patients have similarly signaled the potential value of augmenting SSRIs with methyl donors that enhance the pathway from homocysteine to S-adenosylmethionine. Editorialists note that individuals homozygous for the T allele on a gene converting folate to L-methylfolate (8%–20% of white Americans) have only 30% of the converting capacity of C carriers and modestly but significantly higher depression rates; such patients may prove to particularly benefit from folate supplementation. Folate deficiency can also result from the use of some anticonvulsants and other medications, malabsorption and dietary deficiencies, alcoholism, various chronic diseases, and gastric cancer. Because folate administration can mask B12 deficiency, clinicians should order B12 laboratory studies before patients start L-methylfolate.
— Joel Yager, MD Published in Journal Watch Psychiatry January 7, 2013
Citation(s): Papakostas GI et al. L-methylfolate as adjunctive therapy for SSRI-resistant major depression: Results of two randomized, double-blind, parallel-sequential trials. Am J Psychiatry 2012 Dec 1; 169:1267.
(http://dx.doi.org/10.1176/appi.ajp.2012.11071114)
http://www.ncbi.nlm.nih.gov/pubmed/23212058?dopt=Abstract
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Smarter PSA Screening for Prostate Cancer
By Cara Adler
Raising the prostate-specific antigen threshold for biopsy referral in older men and screening less often in men with low PSA levels might improve the harm-benefit tradeoff of PSA screening for prostate cancer, according to an Annals of Internal Medicine study.
Researchers used a computer model to compare 35 screening strategies that varied in age to start and stop screening, screening interval, and PSA threshold for biopsy referral. Compared with standard screening, using a higher PSA threshold for biopsy referral in older men and longer screening intervals in men with low PSA levels would reduce the harms of screening (for example, overdiagnosis, unnecessary biopsy, and treatment) without lowering the number of lives saved.
A commentator writes that the results, "involving calculations that often differ by only a fraction of a percentage point, are not likely to change clinical practice."
http://annals.org/article.aspx?articleid=1567368
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N Engl J Med 2013 Jan 31; 368:436
Late Effects of Interventions for Localized Prostate Cancer
At 15 years, men undergoing surgery or radiotherapy experienced similar declines in urinary, bowel, and sexual function.
When patients with prostate cancer are presented with management options — including surgery (laparoscopic, robotic, or open) or radiotherapy (external beam, brachytherapy, or a combination of the two) — the next question is what is the best treatment. Unfortunately, rigorous prospective trials comparing these approaches have not been performed and likely never will be. However, for many patients with favorable risk factors, recent studies suggest excellent clinical outcomes for all current therapeutic approaches, leaving clinicians and patients to focus on differences in treatment morbidities.
To help provide guidance in this setting, investigators have analyzed survey data from 1655 men in the Prostate Cancer Outcomes Study with clinically localized prostate cancer (aged 55–74) who underwent prostatectomy or radiotherapy within 1 year of diagnosis and completed either a 2-year or 5-year follow-up survey. Of these, 70.3% had undergone prostatectomy, and 29.7% had received radiotherapy. Status was assessed at baseline and 2, 5, and 15 years. At 15 years, 27.7% in the prostatectomy group and 50.3% in the radiotherapy group had died. The researchers assessed urinary, bowel, and sexual function and compared the extent to which patients were bothered by functional declines 15 years after prostatectomy or radiotherapy. Results were as follows:
- Men in the prostatectomy group were more likely to report urinary leakage at 2 and 5 years; at 15 years, occurrence rates were similar in each group, although men in the prostatectomy group were more likely to wear incontinence pads at all study time points.
- Men in the prostatectomy group were less likely to have bowel urgency at 2 and 5 years; at 15 years, odds of urgency were similar in each group.
- Men in the prostatectomy group were more likely to report insufficient erections for intercourse at 2 and 5 years; at 15 years, dysfunction rates were similarly high in the prostatectomy and radiotherapy groups (87.0% and 93.9%, respectively).
Comment: This report adds to the body of patient-reported outcomes following local therapy for prostate cancer. For patients with disease requiring treatment, this data provides some insight into these issues during the 2- to 5-year time frame. However, the functional declines reported in all domains at 15 years regardless of therapy remind us that there are important quality-of-life implications for any intervention.
— Robert Dreicer, MD, MS, FACP Published in Journal Watch Oncology and Hematology January 30, 2013
Citation(s): Resnick MJ et al. Long-term functional outcomes after treatment for localized prostate cancer. N Engl J Med 2013 Jan 31; 368:436
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Ascorbic Acid Supplements Linked to Kidney Stones
By Kelly Young
Use of vitamin C (ascorbic acid) supplements is associated with development of kidney stones in men, according to a study in JAMA Internal Medicine.
Nearly 50,000 men in Sweden completed questionnaires about their use of ascorbic acid. Over 11 years' follow-up, 0.9% developed kidney stones. Men who reported using ascorbic acid had nearly double the risk for incident kidney stones (adjusted relative risk, 1.92). Doses and brands were not available, but ascorbic acid supplements in Sweden typically contain 1000 mg per tablet.
The authors conclude: "Currently there are no well-documented benefits of high-dose ascorbic acid supplement use, and, therefore, it seems prudent to advise that high-dose preparations be avoided, particularly by those with a history of kidney stones."
http://archinte.jamanetwork.com/article.aspx?articleid=1568519
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Lancet Neurol 2013 Feb; 12:149
No Benefit from Memantine (Namenda(R)) for Frontotemporal Lobar Degeneration
Memantine fared no better than placebo in a double-blind, randomized trial.
Frontotemporal lobar degeneration (FTLD) is a pathologically and clinically heterogeneous dementing disorder characterized by progressive decline in behavioral and language function. No FDA-approved disease-specific medications or disease-modifying therapies for FTLD are currently available. Acetylcholinesterase inhibitors, approved to treat symptomatic Alzheimer disease, are not recommended for FTLD. In clinical practice, the N-methyl-D-aspartate receptor antagonist memantine is often prescribed for FTLD on the basis of anecdotal evidence and open-label trial findings of a modest benefit in mitigating behavioral symptoms (e.g., Alzheimer Dis Assoc Disord 2009; 23:211).
In a new, manufacturer-funded, double-blind trial, researchers randomized 81 patients (age range, 40–80) who met criteria for behavioral-variant FTLD or semantic dementia to receive memantine (20 mg daily) or placebo for 26 weeks.
Among the 76 patients who completed the trial, improvements in the total Neuropsychiatric Inventory score and Clinical Global Impression of Change score did not differ significantly between the memantine and placebo groups. The drug was well tolerated, although significantly more memantine recipients than placebo recipients experienced adverse cognitive events.
Comment: The authors note that recruitment challenges may have affected their study. Families of patients with FTLD are often desperate to find relief for these typically young-onset dementias. Many prefer that clinicians prescribe memantine or an acetylcholinesterase inhibitor off-label, without clear evidence of benefit, rather than participate in a clinical trial. Nevertheless, the current findings do not justify the expense of memantine treatment for FTLD.
— Brandy R. Matthews, MD Published in Journal Watch Neurology February 5, 2013
Citation(s): Boxer AL et al. Memantine in patients with frontotemporal lobar degeneration: A multicentre, randomised, double-blind, placebo-controlled trial. Lancet Neurol 2013 Feb; 12:149.
(http://dx.doi.org/10.1016/S1474-4422(12)70320-4)
http://www.ncbi.nlm.nih.gov/pubmed/23290598?dopt=Abstract
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