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Content 7


The Doctor and the Pharmacist

Radio Show Articles:
April 14, 2012

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New Sexual Adverse Effects Added to Finasteride Labels
Most People Show Some Protection Against Variant Influenza
FDA Rejects BPA Ban
Vitamin D May Not Improve Academic Performance in Children
Total Testosterone or Free Testosterone?
Steep Suicide, Cardiovascular Risks After Cancer Diagnosis
Dietary Fiber and Diverticulosis
Revisiting Variability in Measurement of Vitamin D Levels
Autism More Frequent in Kids Whose Mothers Have Metabolic Conditions
Increased Risk for Retinal Detachment with Fluoroquinolones
Experimental Drug Provides Neuroprotection in Monkeys with Induced Stroke
Few Americans Meet Goals for Cardiovascular Health
Hyposexual Desire Disorder, Depression, and Antidepressant Use
Tools for Preventing Postpartum Psychosis and Mania
What's the Predictive Value of Cholesterol Fractions Other Than LDL?
Do School Bans Lower Sugar-Sweetened Beverage Consumption?
FDA: Birth Control Pills with Drospirenone Might Pose Higher Blood Clot Risk
Study Finds Doubled Cancer Risk with Recent Use of Depo-Provera as a
   Contraceptive for a Year
TMP-SMX–(Bactrim®)-Associated Renal Toxicity
Vitamin D May Cut Death & Disease Risks
PPI Use Associated with Hip-Fracture Risk in Postmenopausal Women
Meta-Analysis: Antibiotics Safe and Effective for Uncomplicated Acute Appendicitis
Heavy Backpacks Are Associated with Back Pain in Teens
How Early Stress Permanently Changes Reactions to Later Stress
Naltrexone Implants for Polydrug Dependence

New Sexual Adverse Effects Added to Finasteride Labels
The labels of the alopecia drug Propecia (finasteride 1 mg) and the benign prostatic hyperplasia drug Proscar (finasteride 5 mg) are being updated with an expanded list of adverse sexual effects, the FDA has announced.
The updates:

The FDA said: "Despite the fact that clear causal links between finasteride ... and sexual adverse events have NOT been established, the cases suggest a broader range of adverse effects than previously reported."
When these drugs were approved in the 1990s, their labels noted sexual side effects that normalized after treatment ended. In 2011, the FDA updated the labels to warn of persistent, posttreatment erectile dysfunction.
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Most People Show Some Protection Against Variant Influenza
A variant influenza virus that has infected a dozen people since August 2011 — almost all under 10 years of age — is less of a threat to adolescents and adults, because they show some cross-reactive antibody to it, according to an MMWR article. All cases recovered fully.
The variant, called influenza A (H3N2)v, carries genes from avian, swine, and human viruses. There is evidence that it is transmissible from person to person.
The CDC reports that roughly a third of people over age 10 have cross-reactive antibodies to this virus "that might provide some protection from infection." The proportion is slightly less in those aged 65 and older.
If the virus starts to show sustained person-to-person transmission, the CDC says a specific vaccine virus has been isolated and could be used to develop a vaccine.
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FDA Rejects BPA Ban
The FDA said on Friday that it does not have enough evidence to ban use of bisphenol A (BPA) in food containers, the Wall Street Journal reports. Previously, the agency expressed "some concern" over BPA's potential effects on fetuses, infants, and young children.
The FDA told the Natural Resources Defense Council, the group that petitioned the ban, that this is "by no means a final" ruling, according to the Journal. The agency plans to reach a more definitive decision later this year.
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MM: This is quite a fascinating article in its entirety. The authors acknowledge that Vitamin D3 levels enhance cognitive function in adults but they make it very clear that higher levels of Vitamin D2 appear to be detrimental to the cognitive function of children. This same correlation does not appear to be the case with Vitamin D3. They also acknowledge that 27% of their sample population was vitamin D deficient (under 27ng/ml).
Vitamin D May Not Improve Academic Performance in Children
Higher levels of vitamin D, associated with better cognitive function in adults, do not show the same association in adolescents, according to prospective cohort study in the Journal of Epidemiology and Community Health.
Researchers examined the serum levels of vitamin D's principal components — 25-hydroxyvitamin D2 and D3 — and later academic performance in over 3000 English children. The participants had their D2 and D3 levels measured at age 10, and their academic performance tested on standard national school tests at age 13 to 14 and again at age 15 to 16.
Contrary to the findings in adults, the children with higher vitamin D levels did not show higher test scores. In fact, there was a trend toward worse test performance in older children with higher D2 levels.
The authors called the D2 results surprising, and comment that protecting children from sun exposure "is unlikely to have any detrimental effect on academic achievement."
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MM: Although the majority of our hormone patients are women, I am frequently asked by practitioners who see men about how to interpret Testosterone lab tests. This article provides a nice guideline as to when free testosterone levels should be taken.
J Urol 2012 Apr; 187:1369
Total Testosterone or Free Testosterone?
A study illustrates the tradeoffs between these two measurements.
In evaluating men with suspected hypogonadism, some clinicians start by ordering total testosterone (T) levels; others order free or bioavailable T levels, which presumably identify biochemical hypogonadism more accurately. Many factors (including obesity, drugs, comorbidities, assay variability, and time of day) affect total T levels.
In this study, Veterans Administration researchers analyzed data from 3700 men (mean age, 60; nearly half obese) in whom evaluation for hypogonadism included measurement of both total T and calculated free T levels. About 15% had low free T levels (<34 pg/mL) and thus were considered to have biochemical hypogonadism. Findings about sensitivity and specificity of total T as an indicator of biochemical hypogonadism were as follows:

Comment: This study provides a rough indication of the limitations of total T measurement for diagnosing hypogonadism. Levels below 150 ng/dL or above 350 ng/dL identify or exclude biochemical hypogonadism reasonably accurately. When levels fall between these thresholds, clinicians should consider measuring free T — particularly when clinical hypogonadism is strongly suspected.
Allan S. Brett, MD Published in Journal Watch General Medicine April 12, 2012
Citation(s): Anawalt BD et al. Performance of total testosterone measurement to predict free testosterone for the biochemical evaluation of male hypogonadism. J Urol 2012 Apr; 187:1369.
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N Engl J Med 2012 Apr 5; 366:1310.
Steep Suicide, Cardiovascular Risks After Cancer Diagnosis
In the first week after receiving a cancer diagnosis, patients show a roughly 10-fold increased risk for suicide and a roughly 5-fold increased risk for cardiovascular death compared with cancer-free people, according to a New England Journal of Medicine study.
Using Swedish national registries of cancer diagnoses and causes of death, researchers assembled a cohort comprising some 6 million people aged 30 and older. In the week immediately following a cancer diagnosis, the relative risk for suicide was 12.6, and for cardiovascular death 5.6, compared with those without a cancer diagnosis. Risks decreased rapidly with time, but remained elevated at the 1-year mark. (Risks were adjusted for several factors, including preexisting conditions.)
Writing in Journal Watch Psychiatry, editor-in-chief Dr. Peter Roy-Byrne points to "the potent effect of emotional distress on cardiovascular health" in addition to the importance of making mental health services easily available to patients with cancer.
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Gastroenterology 2012 Feb; 142:266
Dietary Fiber and Diverticulosis
Study findings challenge the common view that fiber intake protects against diverticulosis.
According to conventional wisdom — but not robust evidence — a high-fiber diet protects against diverticulosis. In a cross-sectional study designed to evaluate this theory, researchers administered detailed food-frequency questionnaires to 2100 adults who underwent colonoscopy (primarily for routine screening). Participants were asked to provide responses that reflected their "usual diet" during the previous year. Those in the highest quartile of fiber intake reported 3-fold higher intakes than those in the lowest quartile.
Colonoscopy revealed diverticulosis in 42% of patients. In adjusted analyses, high fiber intake was not associated with lower prevalence of diverticulosis; in fact, prevalence of diverticulosis was highest in those with the highest fiber intake. No type of fiber — soluble, insoluble, grain-derived, or fruit- or vegetable-derived — was associated with lower prevalence of diverticulosis. Bowel movement frequency was not associated with amount of dietary fiber intake, and patient reports of constipation were not associated with prevalence of diverticulosis.
Comment: These results challenge the belief that high fiber intake protects against diverticulosis. The study's obvious limitation is the distinct possibility that currently reported fiber intake does not accurately reflect long-term dietary patterns. The authors address this concern by citing research suggesting that adult diets don't change dramatically over time. This study is certainly not the final word on the matter, but its results provide a potentially reassuring explanation for patients who adhere to high-fiber diets, then express disbelief when they are discovered to have diverticulosis or diverticulitis.
Allan S. Brett, MD Published in Journal Watch General Medicine April 5, 2012
Citation(s):Peery AF et al. A high-fiber diet does not protect against asymptomatic diverticulosis. Gastroenterology 2012 Feb; 142:266.
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MM: Ironically the data that was used to compare in this study showed low levels across the board. The researchers missed the forest for the trees. The conclusion of whether a person is sufficiently deficient to treat with vitamin D is superfluous. If a person has a 25 hydroxy D level below 60-80ng/ml, then they need vitamin D3 supplementation.
J Clin Endocrinol Metab 2012 Mar; 97:835
Revisiting Variability in Measurement of Vitamin D Levels
On average, serum 25-hydroxyvitamin D levels differed by 5 ng/mL across two assays.
A 2004 study demonstrated that measurements of serum 25-hydroxyvitamin D (25[OH]D) levels are considerably variable across different assays (JW Gen Med Aug 13 2004). Now, researchers at Lebanon's American University of Beirut have revisited this issue. They measured 25(OH)D levels in each of 494 adults using both a radioimmunoassay (Immunodiagnostic Systems RIA; Boldon, U.K.) and an automated chemiluminescent immunoassay (DiaSorin Liaison; Stillwater, Minnesota).
Mean 25(OH)D levels were significantly lower with DiaSorin Liaison than with IDS-RIA (21 vs. 26 ng/mL), and the proportion of people with serum levels measuring <20 ng/mL was significantly higher with DiaSorin Liaison (52% vs. 36%). In 13% of patients, measurements from the two assays differed by more than 10 ng/mL.
Comment: These results should heighten our awareness that vitamin D measurements can differ considerably across assays. In some cases, this variability will be the deciding factor in whether the 25-hydroxyvitamin D level ends up above or below a treatment threshold. When a patient undergoes serial measurements, the same assay should be used for all measurements.
Allan S. Brett, MD Published in Journal Watch General Medicine April 10, 2012
Citation(s): Barake M et al. 25-hydroxyvitamin D assay variations and impact on clinical decision making. J Clin Endocrinol Metab 2012 Mar; 97:835.
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Autism More Frequent in Kids Whose Mothers Have Metabolic Conditions
Autism spectrum disorder is more common among children of mothers with diabetes, hypertension, or obesity during pregnancy, according to a case-control study in Pediatrics.
Researchers studied some 1000 California children ages 2 to 5 years who were enrolled in a population-based study: 500 had autism spectrum disorder, 200 had developmental delay, and 300 with typical development served as controls. Their mothers were questioned about whether they had metabolic conditions (diabetes, hypertension, or obesity) during pregnancy.
Overall, children whose mothers had one of these metabolic conditions were at increased risk for autism spectrum disorder (odds ratio, 1.61) or developmental delay (OR, 2.35). Although when assessed individually, only obesity was significantly associated with these developmental concerns after adjusting for confounders.
The authors conclude: "Our findings raise concerns that these maternal conditions may be associated with neurodevelopmental problems in children and therefore could have serious public health implications."
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JAMA 2012 Apr 4; 307:1414
Increased Risk for Retinal Detachment with Fluoroquinolones
A retrospective pharmacoepidemiologic study suggests that such risk is increased by 4.5-fold in current fluoroquinolone users.
Although generally well tolerated, fluoroquinolones are known to have a destructive effect on connective tissue and have been associated with tendon rupture. Noting several reports of ocular injury linked to these antibiotics, investigators questioned whether such connective-tissue damage in the eye could predispose to retinal detachment. They explored this issue in a retrospective case-control analysis.
The researchers used records in the British Columbia Linked Health Database to identify patients who had visited an ophthalmologist in the province between 2000 and 2007. Patients who had experienced retinal detachment were each matched with 10 controls; all had 1 year of prescription drug data available. A total of 4384 patients and 43,840 controls were included in the analysis.
Risk for retinal detachment was significantly increased with current use of oral fluoroquinolones (adjusted relative risk, 4.5; 95% confidence interval, 3.6–5.7) but not with recent (prescription termination date, 1–7 days before the retinal-detachment index date) or past use. The mean time from fluoroquinolone prescription to retinal detachment was 4.8 days. No risk was seen with current use of oral β-lactam antibiotics or short-acting β-agonists, selected as pharmacologic controls. The absolute increase in risk for retinal detachment was 1 per 2500 person-years.
Comment: This study is limited in relying on administrative data both to define cases of retinal detachment and to determine prescription of fluoroquinolones. The small population of patients with recent fluoroquinolone use (12) makes it difficult to interpret the difference in risk between recent and current use. Finally, although the relative risk increase is notable, the absolute risk for retinal detachment with fluoroquinolones remains low.
Richard T. Ellison III, MD Published in Journal Watch Infectious Diseases April 11, 2012
Citation(s):Etminan M et al. Oral fluoroquinolones and the risk of retinal detachment. JAMA 2012 Apr 4; 307:1414
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MM: Although a name of the drug discussed and whether the research was sponsored by a particular big drug company is not made, the author is the owner of a small biotech company in Canada called NoNo Biotech. This is a company that may be worth watching in the future.
Nature 2012 Mar 8; 483:213
Experimental Drug Provides Neuroprotection in Monkeys with Induced Stroke
Neurological function — not just infarct size — was substantially improved by an agent that may lessen the neurotoxicity caused by ischemia.
Neuroscientists and neurologists have long tried to develop strategies to protect brain cells from the destructive effects of ischemia. Despite some successes in animals (mostly rodents), nothing has worked in humans. Undaunted, a Canadian team has used a stroke model in monkeys to test a drug that may alleviate the neurotoxicity caused by ischemia.
Twenty monkeys were randomly assigned to receive intravenous infusion of the drug or placebo 1 hour after an experimentally induced stroke. At 30 days, the treated animals had a mean 70% reduction in infarct volume and performed much better on cognitive testing than did animals that received placebo. In a separate study, the drug remained effective even when administered 3 hours after the stroke. In a third study, the drug improved the response to thrombolytic therapy with tissue plasminogen activator — even when thrombolysis was delayed by 4.5 hours. Pathology studies revealed preservation of the capacity for gene expression in the infarcted tissue of drug-treated monkeys.
Comment: Despite the long and unhappy history of neuroprotective agents that have worked in animal models but failed in humans, this report is generating some excitement. First, monkey brains clearly surpass rodent brains as models for conditions in humans. Also, these results showed that neurological function (not just infarct size) was greatly improved. Lastly, treatment was beneficial even when delayed 3 hours after stroke onset, a window of time that is compatible with successful treatment of stroke victims.
Anthony L. Komaroff, MD Published in Journal Watch General Medicine April 12, 2012
Citation(s):Cook DJ et al. Treatment of stroke with a PSD-95 inhibitor in the gyrencephalic primate brain. Nature 2012 Mar 8; 483:213.
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JAMA 2012 Mar 28; 307:1273
Few Americans Meet Goals for Cardiovascular Health
Healthy behaviors are significantly associated with decreased mortality, but recent decades have seen little progress toward improving those behaviors.
Cardiovascular disease remains the number-one killer in the U.S. Therefore, the American Heart Association has challenged the American public to improve cardiovascular health by (1) not smoking; (2) being physically active; achieving normal (3) blood pressure, (4) blood glucose and (5) total cholesterol levels, and (6) weight; and (7) eating a healthy diet. To examine trends in cardiovascular health, as related to all-cause and cardiovascular mortality risk, investigators studied National Health and Nutrition Examination Survey (NHANES) data from 1988–1994, 1999–2004, and 2005–2010, and from the NHANES III Linked Mortality File (through 2006).
Of nearly 45,000 participants, very few met all seven cardiovascular health goals (1988–1994, 2.0%; 2005–2010, 1.2%). Absolute mortality risks were significantly lower in participants meeting six or more goals than in those meeting one or fewer goals (see table). Compared with participants who met one or fewer goals, adjusted hazard ratios in those who met six or more goals were 0.49 for all-cause mortality and 0.24 for cardiovascular mortality.
Comment: Not unexpectedly, according to this large study, the more cardiovascular health goals we meet, the lower our risks for all-cause and cardiovascular mortality. Unfortunately — but also unsurprisingly — few Americans meet these goals. Importantly, the investigators did not study how changes in individuals' cardiovascular health profiles affect risk. Nonetheless, these findings should renew efforts to create and intensify primary prevention programs designed specifically to improve these metrics.
JoAnne M. Foody, MD Published in Journal Watch Cardiology April 4, 2012
Citation(s):Yang Q et al. Trends in cardiovascular health metrics and associations with all-cause and CVD mortality among US adults. JAMA 2012 Mar 28; 307:1273.
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Psychosom Med 2012 Apr; 74:305
Hyposexual Desire Disorder, Depression, and Antidepressant Use
Depression is common in women with HSDD, but many are not — and have never been — depressed.
Hyposexual desire disorder (HSDD) affects approximately 27% of premenopausal women (Arch Intern Med 2008168:1441). It is diagnosed by deficient desire for sexual activity plus sexually related personal distress, which are not better accounted for by a nonsexual Axis I disorder or by direct physiological effects of a substance or medical condition. Using HSDD Registry for Women data on 1088 premenopausal women enrolled primarily from sexual medicine and obstetrics-gynecology clinics, investigators in this industry-supported study examined relationships among depression, antidepressant use, alcohol and substance abuse, and general health and well-being.
Overall, 714 women (66%) were classified as not currently depressed on the Patient Health Questionnaire–9. Of the 374 women (34%) classified as having depression, 32% had not been diagnosed with depression before study entry. Depressed patients were more likely than nondepressed patients to screen positive for alcohol or substance abuse (12% vs. 5%) and to report binge drinking (27% vs. 19%), relationship difficulties, lower frequency of sex, lower general well-being (ratings lower than "good," 11% vs. 4%), and difficulties in forming and maintaining relationships. Depressed and nondepressed women showed no meaningful differences in sexual desire or self-assessed HSDD severity. Among women using antidepressants, those with continuing depressive symptoms had significantly lower sexual desire than those without current depressive symptoms. Ratings of desire or sexual functioning were not significantly different between nondepressed, unmedicated women and antidepressant users without continued depressive symptoms.
Comment: These findings underscore the complex, multidirectional associations among low sexual desire, depression, and antidepressant medications. Ongoing depression may be more important than antidepressants in contributing to ongoing low sexual desire, and many women with low sexual desire are not and have never been depressed. Screening for depression is essential when assessing women with hyposexual desire.
Joel Yager, MD Published in Journal Watch Psychiatry April 9, 2012
Citation(s): Clayton AH et al. Depression in premenopausal women with HSDD: Baseline findings from the HSDD Registry for Women. Psychosom Med 2012 Apr; 74:305
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MM: These are all viable approaches to treating post partum depression or psychosis (PPD) but where is bio-identical progesterone addressed? The very nature of the condition is assiociated with the physical, chemical and psychological stress that the post partum patient experiences. Progesterone capsules, lozenges, suppositories, injections and creams have been successfully used for more than 20 years for these patients. It does not have to be a choice of one treatment or another. For those practitioners who are on the fence, progesterone may be used in combination with these other therapies. That is what a truly integrative approach is; using multiple modalities to achieve the most optimal outcome in the safest and most effective manner.
Am J Psychiatry 2012 Mar 8;
Tools for Preventing Postpartum Psychosis and Mania
Intrapartum lithium helps to minimize bipolar episodes, and postpartum lithium and sleep hygiene help to avoid postpartum psychosis.
Women with bipolar disorder or histories of postpartum psychosis are at high risk for repeat episodes during subsequent pregnancies. Investigators in the Netherlands studied rates of exacerbation among 41 pregnant bipolar patients with or without ongoing treatment and rates of repeat episodes among 29 pregnant women with no bipolar illness but with prior postpartum psychosis, who initiated or declined prophylaxis immediately postpartum (mean postpartum follow-up, 12.6 weeks).
The recommended treatment was lithium, but alternative mood stabilizers or antipsychotics were allowed. Postpartum patients were encouraged to not breast-feed. To ensure sufficient sleep, they were encouraged to stay on the hospital inpatient service for the first week, assisted by nurses providing overnight feedings, and to take lorazepam.
Ten bipolar patients relapsed during pregnancy (24%; with treatment, 6; without treatment, 4), and nine relapsed postpartum (22%; 6 had also relapsed during pregnancy). Of the eight patients with bipolar diagnoses and previous postpartum episodes, four (50%) relapsed.
Among women with only prior postpartum psychosis, rates were significantly different based on treatment. Postpartum psychosis occurred in none of the 20 who initiated postpartum prophylaxis within 24 hours of delivery but occurred in 4 of 9 (44%) opting against medication (mostly because they wanted to breast-feed).
Comment: These findings highlight the considerable risk for relapse among bipolar patients during pregnancy and the peripartum period, even with ongoing medication. The results also point out the considerable value of immediate initiation of postpartum medication and of careful attention to adequate sleep in the peripartum period among women who had previously experienced postpartum psychosis. Although few U.S. hospitals are likely to permit a week's postpartum stay to aid sleep quality, preventive interventions that combine medication and careful attention to sleep appear to be quite effective.
Joel Yager, MD Published in Journal Watch Psychiatry April 9, 2012
Citation(s):Bergink V et al. Prevention of postpartum psychosis and mania in women at high risk. Am J Psychiatry 2012 Mar 8; [e-pub ahead of print].
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JAMA 2012 Mar 28; 307:1302
What's the Predictive Value of Cholesterol Fractions Other Than LDL?
In patients treated with statins, non–HDL cholesterol was the best predictor of CVD risk.
A patient's low-density lipoprotein cholesterol (LDL-C) level is the primary metric by which statin treatment is titrated. Given that other cholesterol fractions — specifically apolipoprotein B (apoB) and non–high-density lipoprotein cholesterol (non–HDL-C) — are thought to predict risk for cardiovascular disease (CVD) even better than LDL-C, researchers conducted a meta-analysis to evaluate the various possibilities in statin-treated patients. A comprehensive search yielded eight randomized, controlled trials of statins in which relevant cholesterol fractions were measured and follow-up lasted ≥2 years. Among 38,000 statin recipients, roughly 6300 major cardiovascular events (e.g., myocardial infarction, stroke, unstable angina) occurred.
For all cholesterol fractions analyzed, patients in the highest quartile had significantly greater CVD risk than those in the lowest quartile. However, hazard ratios were higher for non–HDL-C (1.42) and apoB (1.33) than for LDL-C (1.26). In addition, more of the benefit of statin therapy was explained by changes in non–HDL-C (64%) than apoB (54%) or LDL-C (50%).
Comment: This analysis of statin-treated participants in randomized trials extends our understanding of the predictive value of non–high-density lipoprotein cholesterol and apolipoprotein B relative to low-density lipoprotein cholesterol. The biological plausibility of apoB as a predictor is particularly clear, but its incremental benefit over more-commonly measured parameters is not. The authors note that HDL testing methods in clinical laboratories are not identical to methods used in these clinical trials. This limitation applies to non–HDL-C (which is calculated from total and HDL-C), and may apply to LDL-C for those laboratories that calculate LDL-C from total cholesterol, HDL-C, and triglycerides. An advantage of using non–HDL-C is that, unlike LDL-C, a fasting blood specimen is not required for its calculation.
Thomas L. Schwenk, MD Published in Journal Watch General Medicine April 3, 2012
Citation(s):Boekholdt SM et al. Association of LDL cholesterol, non–HDL cholesterol and apolipoprotein B levels with risk of cardiovascular events among patients treated with statins: A meta-analysis. JAMA 2012 Mar 28; 307:1302.
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Arch Pediatr Adolesc Med 2012 Mar; 166:256
Do School Bans Lower Sugar-Sweetened Beverage Consumption?
Bans lowered only in-school consumption but not overall consumption.
Sugar-sweetened beverages — including soda, sports drinks, and fruit drinks — are significant contributors to childhood obesity. Many states have instituted policies banning access to sugar-sweetened beverages in public schools in an attempt to reduce children's intake. To find our if these policies work, investigators compared longitudinal survey data from 6900 children in 5th grade and again in 8th grade in 11 states that banned soda only, 7 states that banned all sugar-sweetened beverages, and 22 states without bans.
Eighth graders in states that banned soda only reported similar rates of in-school access to and weekly purchase of sugar-sweetened beverages (67% and 29% respectively) as students in states without bans. The rates were somewhat lower in states that banned all sugar-sweetened beverages (53% and 20%, respectively). Rates had increased between 5th grade and 8th grade in states with soda-only or no bans but remained stable in states that banned all sugar-sweetened beverages. After adjustment for race and ethnicity, poverty status, school locale, and state obesity prevalence, banning all sugar-sweetened beverages reduced in-school access and weekly purchasing by 15% and 7%, respectively. However, in all states, reported overall weekly and daily consumption of sugar-sweetened beverages remained around 85% and 30%, respectively, regardless of state policy.
Comment: This study confirms two apparent facts about children's sugar-sweetened beverage consumption. When only soda is banned, kids substitute other available sugar-sweetened beverages (such as fruit drinks and sports drinks) and continue consuming the same amount of sugar-sweetened beverages in school. And, even when schools limit access to all sugar-sweetened beverages, kids compensate by drinking sugar-sweetened beverages outside school, resulting in no difference in overall consumption. Policies paired with broad education in various settings (school, home, etc.) might have more potential to reduce the large amount of sugar-sweetened beverages that kids drink.
Cornelius W. Van Niel, MD Published in Journal Watch Pediatrics and Adolescent Medicine April 11, 2012
Citation(s): Taber DR et al. Banning all sugar-sweetened beverages in middle schools: Reduction of in-school access and purchasing but not overall consumption.
Arch Pediatr Adolesc Med 2012 Mar; 166:256.
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FDA: Birth Control Pills with Drospirenone Might Pose Higher Blood Clot Risk
The FDA has concluded that drospirenone-containing oral contraceptives (e.g., Yaz) may carry higher risk for venous thromboembolism than other progestin-containing formulations, the agency announced on Tuesday. The product labels will be changed to reflect this update.
The revised labels will note that while some observational studies found as high as a threefold increase in blood clot risk with drospirenone-containing products (vs. other progestin-containing pills), other studies found no increase in risk.
To put the relative risk into perspective, the FDA reminds clinicians: "The risk of blood clots is higher when using any birth control pills than not using them, but still remains lower than the risk of developing blood clots in pregnancy and in the postpartum period."

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Study Finds Doubled Cancer Risk with Recent Use of Depo-Provera as a Contraceptive for a Year
There appears to be a link between Depo-Provera, a progestin-only birth control, and an increased risk of breast cancer in young women. The increased risk appeared to diminish within months after women stopped using the contraceptive, and women who used the contraceptive for less than a year or who had stopped using it more than a year earlier did not have any increased risk of breast cancer; the findings will be published in the journal Cancer Research.
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MM: This is a drug that is routinely given for acne, UTI’s and MRSA. It appears that we need to be a bit more cautious when receiving or prescribing this antibiotic.
J Antimicrob Chemother 2012 Feb 20
TMP-SMX–(Bactrim®)-Associated Renal Toxicity
Acute kidney injury occurred in 11% of TMP-SMX recipients but nearly always resolved after drug discontinuation.
Trimethoprim-sulfamethoxazole (TMP-SMX) is widely used to treat urinary tract and soft-tissue infections. Despite anecdotal reports indicating the possibility of TMP-SMX–associated renal toxicity, systematic investigation has been lacking.
To remedy this situation, researchers in Texas reviewed the records of consecutive male inpatients at a Veterans Affairs Medical Center who, during a 3-year period, had received TMP-SMX for ≥6 days to treat urinary tract or soft-tissue infections. All had blood urea nitrogen (BUN) and serum creatinine levels measured both ≤7 days before starting and ≤3 days after completing therapy.
Among 573 patients, 64 (11%) had increases in both BUN and serum creatinine levels that met predetermined criteria for acute kidney injury. The kidney injury was classified as probably caused by TMP-SMX in 33 patients (6%), possibly caused by TMP-SMX in 28 (5%), and probably unrelated to the drug in 3.
No relation was found between the dose of TMP-SMX — or the duration of treatment — and the likelihood of acute kidney injury. On multivariate analysis, hypertension and diabetes were the only independent risk factors for such injury. Fifty-four of the 64 patients with kidney injury had follow-up testing ≤1 month after TMP-SMX discontinuation; in 52 (93%), renal function had returned to baseline. One patient required dialysis.
Comment: TMP-SMX–associated renal toxicity seems to occur more often than previously thought. Although this effect appears to be transient, regular monitoring of renal function is warranted during and immediately after TMP-SMX therapy.
Thomas Glück, MD Published in Journal Watch Infectious Diseases April 4, 2012
Citation(s): Fraser TN et al. Acute kidney injury associated with trimethoprim/sulfamethoxazole. J Antimicrob Chemother 2012 Feb 20; [e-pub ahead of print].
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Vitamin D May Cut Death & Disease Risks
Higher levels linked to lower risk of heart disease and diabetes; Vitamin D pills linked to lower death risk; authors urge intakes above the RDA
by Craig Weatherby

The value of vitamin D gained more verification from an observational study in more than 10,000 men and women. University of Kansas researchers found lower rates of heart disease and diabetes among those with higher vitamin D blood levels. And people who reported taking vitamin D supplements were less likely to have died during the study, which lasted almost six years.

The scientists noted that their findings fit with prior evidence:
“Recent evidence supports an association between vitamin D deficiency and hypertension, vascular disease, diabetes, metabolic syndrome, coronary artery disease, and heart failure.” (Vacek JL et al. 2012)
The greatest risk reductions from vitamin D supplements were seen in people considered deficient in vitamin D.

This led the researchers to suggest that the Institute of Medicine didn’t go far enough when it raised the recommended daily allowance (RDA) from 200 IU to 600 IU at the close of 2010. The few clinical studies conducted to date have been small, short, and have produced inconsistent results … and crucially, they tested relatively low doses.

As the Kansas team noted, daily intakes well above the current RDA are more likely to reliably raise vitamin blood levels into the optimal range:
“Many previous studies … have used doses of 400 to 800 IU, which might not be adequate to ensure optimal serum [blood] levels, with more appropriate daily supplement doses suggested as 1,000 to 2,000 IU.” (Vacek JL et al. 2012)

Findings affirm D’s general value and make the case for supplements
University of Kansas researchers led by James Vacek, M.D., set out to see how people’s vitamin D levels and use of vitamin D supplements might affect the risks for cardiovascular disease, diabetes, and death. The study involved 10,899 men (29 percent) and women (71 percent). Their average age at the outset was 58 plus or minus 15 years, and they were followed for five years and eight months. Participants were classified as vitamin D deficient if their blood levels fell below 30 ng/ml (nanograms per milliliter). Blood tests showed that the volunteers’ average vitamin D level was 24 ng/ml, and that 70 percent were deficient in the nutrient.

At the end of the study period, the people classified vitamin D deficient had significantly higher rates of cardiovascular and metabolic diseases … including hypertension, coronary artery disease, and diabetes. And the risk of death from any cause was 164 percent higher in people classified as vitamin D deficient.

Conversely, people who used vitamin D supplements were 61 percent more likely to have avoided death over the course of the study. The Kansas group offered a clear conclusion: “Our study suggests a significant association of vitamin D supplement use and improved survival in deficient subjects, supporting the potential benefit of this intervention.” (Vacek JL et al. 2012) They also noted that vitamin D deficiency and insufficiency remains widespread, and called for campaigns designed to boost supplementation … which could make a hefty impact on public health.

 Sources: Forman JP, Giovannucci E, Holmes MD, Bischoff-Ferrari HA, Tworoger SS, Willett WC, Curhan GC. Plasma 25-hydroxyvitamin D levels and risk of incident hypertension. Hypertension. 2007 May;49(5):1063-9. Epub 2007 Mar 19. Jorde R, Bonaa KH. Calcium from dairy products, vitamin D intake, and blood pressure: the Tromso Study. Am.J.Clin.Nutr. 000;71:1530-5. Krause R, Buhring M, Hopfenmuller W, Holick MF, Sharma AM. Ultraviolet B and blood pressure [letter]. Lancet 1998;352:709-10. MacPherson A, Balint J, Bacso J. Beard calcium concentration as a marker for coronary heart disease as affected by supplementation with micronutrients including selenium. Analyst 1995;120:871-5. Martins D, Wolf M, Pan D, Zadshir A, Tareen N, Thadhani R, Felsenfeld A, Levine B, Mehrotra R, Norris K. Prevalence of cardiovascular risk factors and the serum levels of 25-hydroxyvitamin D in the United States: data from the Third National Health and Nutrition Examination Survey. Arch Intern Med. 2007 Jun 11;167(11):1159-65. Michos ED, Melamed ML. Vitamin D and cardiovascular disease risk. Curr Opin Clin Nutr Metab Care. 2008 Jan;11(1):7-12. Review. Rostand SG. Ultraviolet light may contribute to geographic and racial blood pressure differences [see comments]. Hypertension 1997;30:150-6. Sardar S, Chakraborty A, Chatterjee M. Comparative effectiveness of vitamin D3 and dietary vitamin E on peroxidation of lipids and enzymes of the hepatic antioxidant system in Sprague—Dawley rats. Int.J.Vitam.Nutr.Res. 1996;66:39-45. Schilli MB, Paus R, Czarnetzki BM, Reichrath J. [Vitamin D3 and its analogs as multifunctional steroid hormones. Molecular and clinical aspects from the dermatologic viewpoint]. Hautarzt 1994;45:445-52. Segall JJ. Latitude and ischaemic heart disease [letter]. Lancet 1989;1:1146. Sugihara N, Matsuzaki M, Kato Y. [Assessment of the relation between bone mineral metabolism and mitral annular calcification or aortic valve sclerosis—the relation between mitral annular calcification and post menopausal osteoporosis in elderly patients]. Nippon Ronen Igakkai Zasshi 1990;27:605-15. Vacek JL, Vanga SR, Good M, Lai SM, Lakkireddy D, Howard PA. Vitamin D deficiency and supplementation and relation to cardiovascular health. Am J Cardiol. 2012 Feb 1;109(3):359-63. Epub 2011 Nov 8. Wang TJ, Pencina MJ, Booth SL, Jacques PF, Ingelsson E, Lanier K, Benjamin EJ, D'Agostino RB, Wolf M, Vasan RS. Vitamin D deficiency and risk of cardiovascular disease. Circulation. 2008 Jan 29;117(4):503-11. Epub 2008 Jan 7. Wang TJ, Pencina MJ, Booth SL, Jacques PF, Ingelsson E, Lanier K, Benjamin EJ, D'Agostino RB, Wolf M, Vasan RS. Vitamin D deficiency and risk of cardiovascular disease. Circulation. 2008 Jan 29;117(4):503-11. Epub 2008 Jan 7. Watson KE, Abrolat ML, Malone LL et al. Active serum vitamin D levels are inversely correlated with coronary calcification. Circulation 1997;96:1755-60. Williams FL, Lloyd OL. Latitude and heart disease [letter]. Lancet 1989;1:1072-3. Wiseman H. Vitamin D is a membrane antioxidant. Ability to inhibit iron-dependent lipid peroxidation in liposomes compared to cholesterol, ergosterol and tamoxifen and relevance to anticancer action. FEBS Lett. 1993 Jul 12;326(1-3):285-8. Wiseman H. Vitamin D is a membrane antioxidant. Ability to inhibit iron-dependent lipid peroxidation in liposomes compared to cholesterol, ergosterol and tamoxifen and relevance to anticancer action. FEBS Lett. 1993;326:285-8.
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BMJ 2012 Jan 31; 344:e372.
PPI Use Associated with Hip-Fracture Risk in Postmenopausal Women
Data from a large, prospective cohort study showed risk to be highest in smokers and in women with lengthy PPI use.
Several studies have suggested an association between proton-pump inhibitor (PPI) use and hip fracture. To explore this issue, investigators used data on PPI use from 79,899 postmenopausal women enrolled in the Nurses' Health Study — a large, prospective cohort study.
During 565,786 person-years of follow-up, 893 hip fractures occurred. The incidence of hip fracture per 1000 person-years was 2.0 in regular PPI users versus 1.5 in nonusers (age-adjusted hazard ratio, 1.35; 95% confidence interval, 1.13–1.62). The risk remained similarly elevated after adjustment for known risk factors and rose with duration of PPI use; it did not vary by indication for PPI prescription. Discontinuation of PPIs for >2 years returned the risk to that of nonusers. Regular use of histamine-2–receptor antagonists showed a more modest association with hip fracture (adjusted hazard ratio, 1.23; 95% CI, 1.02–1.50). Using stratified analysis, the investigators showed that the increased risk for fracture with PPI use was seen in current and previous smokers, but not in never-smokers.
The authors also performed a meta-analysis of 10 previous studies exploring the relationship between PPI use and hip fracture. The pooled odds ratio of hip fracture with chronic PPI use was 1.28 (95% CI, 1.19–1.37), with moderate across-study heterogeneity.
Comment: Although previous studies have demonstrated an association between PPI use and hip fracture, data from the Nurses' Health Study suggest that this effect might occur predominantly in smokers. This information might shed light on a potential mechanism for the association.
David J. Bjorkman, MD, MSPH (HSA), SM (Epid.) Published in Journal Watch Gastroenterology March 23, 2012
Citation(s):Khalili H et al. Use of proton pump inhibitors and risk of hip fracture in relation to dietary and lifestyle factors: A prospective cohort study. BMJ 2012 Jan 31; 344:e372.
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MM: If the transient use of antibiotics in this group of patients resulted in a 31% decrease in complications associated with acute appendicitis, I have to wonder if similar results might be achieved with aggressive high doses of probiotics. Probiotics are known for reducing GI inflammation from mouth to south and the appendix is considered a “storehouse” for the body’s probiotics.
Meta-Analysis: Antibiotics Safe and Effective for Uncomplicated
Acute Appendicitis

Antibiotics are safe and effective for the primary treatment of uncomplicated acute appendicitis, according to a BMJ meta-analysis.
The analysis included four studies that randomized 900 patients to either appendectomy or to antibiotic therapy with surgery if needed.
Overall, the antibiotic group showed a 31% reduction in the risk for complications, such as perforated appendicitis and peritonitis. In addition, there were no differences between the groups in length of stay, treatment efficacy, or risk for complicated appendicitis. Of 470 patients in the antibiotic group, 40% ultimately underwent appendectomy.
The authors conclude that "initial antibiotic treatment merits consideration as a primary treatment option for early uncomplicated appendicitis." Asked to comment, Journal Watch Emergency Medicine editor-in-chief Ron Walls said: "Until we know which patients might best be treated with antibiotics, the specter of perforation with long-term complications and the significant number of patients ultimately needing appendectomy within a year argue strongly in favor of continuing our practice of primary appendectomy."
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Arch Dis Child 2012 Mar 10;
Heavy Backpacks Are Associated with Back Pain in Teens
Risk for back pain was 50% higher among those with the heaviest versus lightest backpacks.
Although experts recommend schoolchildren carry backpacks that weigh less than 10% of their body weight, many carry loads that are heavier. In a cross-sectional study of 1403 children (age range, 12–17 years) at 11 schools in Spain, researchers examined the relation between the weight of children's backpacks and the presence of back pain lasting longer than 15 days during the prior year and previously diagnosed back pathology (e.g., scoliosis or kyphosis). Students were grouped into quartiles by backpack weight.
Mean backpack weight was 7 kg. More than half the children (61%) carried backpacks that weighed more than 10% of their body weight, and 18% carried backpacks that exceeded 15% of their body weight. One quarter of the cohort reported >15 days of back pain in the previous year. In analysis adjusted for body-mass index and sports activity, students carrying the heaviest backpacks had a 50% higher risk for back pain than those who carried the lightest backpacks. Girls had higher risk for back pain than boys, and risk increased with age. Back pathology was not significantly associated with backpack weight.
Comment: The weight of these children's backpacks is astonishing — no wonder 25% of them have back pain. Students, girls especially, should be encouraged to limit the weight of their cargo. With increasing use of electronic textbooks, perhaps the need for hauling books will decrease. But I'm not sure it's only books that weigh down those backpacks.
F. Bruder Stapleton, MD Published in Journal Watch Pediatrics and Adolescent Medicine April 4, 2012
Citation(s):Rodríquez-Oviedo P et al. School children's backpacks, back pain and back pathologies. Arch Dis Child 2012 Mar 10; [e-pub ahead of print].
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Biol Psychiatry 2012 Feb 1; 71:224.
How Early Stress Permanently Changes Reactions to Later Stress
Overexpression of the glucocorticoid receptor in early life may have effects throughout the lifespan.
Two research groups recently examined mechanisms of the well-known association between adversity early in life and psychiatric disorders affected by patient stress.
Wei and colleagues created transgenic mice that could be induced to overexpress forebrain glucocorticoid receptor (GR) only in early life (before weaning), throughout the animal's lifetime, or in adulthood (after weaning). Early-life and lifetime but not adult groups had anxiety-like behavior and cocaine sensitization (i.e., increased locomotor activity). Early-life and lifetime GR overexpression altered the expression of 4500 genes in the dentate gyrus of the hippocampus; the two groups shared 62% of these changes. Conversely, 71% and 85% of genes with altered expression in the nucleus accumbens were specific to the early-life or the lifetime group, respectively; genes in the GR signaling pathway were altered in the lifetime group only.
In van Zuiden and colleagues' prospective study of 448 Dutch soldiers deployed to combat zones in Afghanistan, the 35 participants with significant self-reported post-traumatic stress disorder (PTSD) symptoms on return had higher anxiety and depressive symptoms, baseline PTSD symptoms, and more childhood trauma than the other soldiers. In peripheral blood cells, more predeployment GRs, higher expression of the GR target gene GILZ, and lower expression of the GR target gene FKBP5 increased the likelihood of elevated postdeployment PTSD symptoms (as did childhood trauma).
Comment: One inference from these findings (and others summarized by an editorialist): Exposure to stress in a critical early-life period can result in longstanding hippocampal glucocorticoid-receptor overexpression, which permanently intensifies and prolongs the stress response through multiple effects on downstream genes and predisposes the individual to stress-related syndromes. Early stress seems sufficient for GR induction in the nucleus accumbens to influence dopaminergic circuits in the striatum. However, adult stress also may affect genes influencing the stress response. Researchers need to study whether cocaine sensitization in GR-overexpressing animals is a mechanism of vulnerability to substance abuse — which is often comorbid with other disorders — or indicates excessive activation by dopaminergic signals.
Steven Dubovsky, MD Published in Journal Watch Psychiatry March 5, 2012
Citation(s):Wei Q et al. Early-life forebrain glucocorticoid receptor overexpression increases anxiety behavior and cocaine sensitization. Biol Psychiatry 2012 Feb 1; 71:224.
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Am J Psychiatry 2012 Feb 17
Naltrexone Implants for Polydrug Dependence
In a randomized, controlled trial, naltrexone implants decreased both heroin and amphetamine use.
Patients with polydrug dependence are notoriously difficult to treat in real-world settings. Studies have shown that implants of naltrexone, an opioid receptor antagonist, successfully reduced drug use in heroin-dependent patients with no other coexisting drug dependence. In this government-funded study, investigators in Russia extended this work by randomizing 100 outpatients with concurrent amphetamine and heroin dependence to naltrexone or placebo implants. The naltrexone implants, which contain 1000 mg of naltrexone, block opioid effects for 8 to 10 weeks. Patients with significant comorbid psychiatric or medical conditions were excluded.
In an intent-to-treat analysis, at trial's end (10 weeks), naltrexone compared with placebo was associated with higher rates of study retention (52% vs. 28%), clinical global improvement (56% vs. 14%), drug-free urines (38% vs. 16%), and heroin-free urines (52% vs. 20%; naltrexone marginally improved amphetamine-free urines). Patients on naltrexone reported greater reductions in the euphoriant effects of amphetamine. Both groups reported statistically similar, reduced cravings for opioids or amphetamine. No significant adverse events were reported, and no significant changes were seen in alanine aminotransferase or aspartate aminotransferase levels.
Comment: Elsewhere, oral naltrexone treatment has proved ineffective for opioid dependence due to poor treatment adherence and has been associated with accidental overdose and death. Thus, these findings for naltrexone implants are encouraging, and this approach merits further testing for safety and effectiveness and for longer-term impact and effectiveness. Other areas for future study are the effect of naltrexone implants on the concurrent use of other substances commonly seen in polydrug dependence (e.g., alcohol, cannabis, and benzodiazepines). Testing of intramuscular depot naltrexone, recently approved by the FDA, would also be of interest for polydrug dependence.
Joel Yager, MD Published in Journal Watch Psychiatry April 2, 2012
Citation(s):Tiihonen J et al. Naltrexone implant for the treatment of polydrug dependence: A randomized controlled trial. Am J Psychiatry 2012 Feb 17; [e-pub ahead of print]. (http://dx.doi.org/10.1176/appi.ajp.2011.11071121

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