Azithromycin (Zpack) and levofloxacin (Levaquin) carry higher arrhythmia and mortality 
risks than amoxicillin, according to an observational study in the 
Annals of Family Medicine. The FDA issued a cardiac warning on 
azithromycin in March 2013.

Researchers studied nearly 1.8 million U.S. veterans (mean age, 57) 
who received outpatient prescriptions for one of the three antibiotics 
from 1999 to 2012. On weighted analysis, the numbers of deaths by day 
5 of treatment per million antibiotics dispensed were 154 for 
amoxicillin, 228 for azithromycin, and 384 for levofloxacin. Patients 
receiving azithromycin had roughly a 50% increased risk for death and 
an 80% increased risk for serious arrhythmia, compared with those on 
amoxicillin. Risk increases were even greater for levofloxacin.

The researchers conclude: “There are usually multiple antibiotic 
choices available for older patients, especially those with cardiac 
comorbidities; physicians may consider prescribing medications other 
than azithromycin and levofloxacin.”

Annals of Family Medicine article

The effect size is similar to that of antidepressant treatment.

Many smokers cite relief of psychological symptoms as a reason for 
continued smoking. However, the relation between smoking and mental 
health is unclear. In this meta-analysis of 26 prospective, 
observational studies conducted in various countries worldwide, 
investigators compared changes in mental health (anxiety, depression, 
mixed anxiety and depression, quality of life, positive affect, and 
stress) at ≥6 weeks’ post–smoking cessation with changes after the 
same amount of time among people who continued to smoke.

After a median follow-up of 6 to 12 months, smoking cessation, 
compared with continued smoking, was associated with significant 
decreases in anxiety, depression, mixed anxiety and depression, and 
stress and significant increases in psychological quality of life and 
positive affect (all measured via questionnaires). The effect size was 
similar between participants from general populations and those with 
physical or psychiatric illnesses.

COMMENT

In this study, smoking cessation was associated with improved mental 
health outcomes. Although these observational associations do not 
prove causality, they do challenge widely held beliefs that smoking 
relieves psychological symptoms and that trying to quit smoking 
aggravates such symptoms. As the authors note, if the associations are 
causal, the effect size of smoking cessation is similar to that of 
drug treatment for depression or generalized anxiety disorder. At 
least, these results should inspire us to be more proactive in 
encouraging smoking cessation among patients with anxiety and 
depression.

Taylor G et al. Change in mental health after smoking cessation: 
Systematic review and meta-analysis. BMJ 2014 Feb 13; 348:g1151. (http://dx.doi.org/10.1136/bmj.g1151
)Abstract/FREE Full Text

Higher urinary levels of bisphenol A (BPA) are linked to early-onset 
prostate cancer, according to a PLoS ONE study.

Researchers measured urinary BPA concentrations in 60 urology 
patients, about half of whom had prostate cancer. Concentrations were 
significantly higher in patients with than without cancer, 
particularly among those younger than 65.

In addition, when prostate cancer cells were treated in vitro with low 
doses of BPA, there was a significant increase in the proportion of 
cells with three or more centrosomes (untreated cells showed no such 
increase). This “centrosome amplification,” the researchers say, 
commonly occurs in human tumors and “may contribute to neoplastic 
transformation of the prostate.”

BPA, found in many plastics and food and beverage containers, is 
detectable in the urine of over 90% of Americans, the researchers note.

PLoS ONE article

Vitamins C and E adversely affect muscle mitochondria response to 
exercise, and can cause post workout pain, and muscle fatigue.

Several studies have shown that vitamins C and E impair glucose 
regulation (NEJM JW Psychiatry Jun 8 2009) and raise risk for 
Alzheimer disease (NEJM JW Psychiatry Apr 23 2012). Here is another 
study to relate to our patients who believe that these antioxidant 
vitamins “can’t hurt.”

In a double-blind study partially funded by supplement manufacturers, 
54 individuals (28 women; mean age, 24) were randomized to receive 
placebo or vitamin C (1000 mg/day) plus vitamin E (DL-alpha-tocopherol 
acetate, 235 mg/day) while they participated in an 11-week endurance 
training program. The two groups did not differ in change in 
performance over time (VO2max, submaximal running, and a shuttle run 
test). However, only the placebo group showed improvement at 11 weeks 
in mitochondrial markers (obtained via muscle biopsy). Only the 
placebo group had significantly improved fat oxidation and reduced 
heart rates at submaximal workloads.

Paulsen G et al. J Physiol 2014 Feb 3.

Drugs such as exenatide (Byetta) and sitagliptin (Januvia), cause no 
apparent increase in pancreatic side effects, according to a joint 
statement from the U.S. Food and Drug Administration and the European 
Medicines Agency.

The drugs were the subject of a JAMA Internal Medicine study in 2013 
that linked their use to a doubled risk for hospitalization for acute 
pancreatitis.

In the New England Journal of Medicine, the agencies say that they 
have separately “explored multiple streams of data” and that 
assertions of a link between the drugs and pancreatic side effects 
“are inconsistent with the current data.” However, they also write 
that “the FDA and the EMA have not reached a final conclusion at this 
time regarding such a causal relationship.”

Among men with nonmetastatic prostate cancer, prostatectomy appears to 
reduce disease-specific mortality better than radiotherapy, an 
observational study in BMJ finds.

Using the Swedish national prostate cancer registry, researchers 
examined outcomes among nearly 35,000 men who underwent radical 
prostatectomy or radiotherapy as their primary treatment between 1996 
and 2010. Median follow-up was 5 years.

Among men with nonmetastatic disease, prostate cancer mortality was 
significantly lower with surgery than with radiotherapy (1.4% vs. 
4.9%). Men who were younger, had fewer comorbidities, and had higher-
risk cancer appeared to benefit most from surgery.

Among men with metastatic cancer, on the other hand, disease-specific 
mortality did not differ according to treatment.

The authors, while acknowledging limitations to their research, 
conclude: “Our study suggests that surgery might result in improved 
outcomes compared with radiotherapy in terms of survival for men with 
non-metastatic prostate cancer.”

BMJ article

Postmenopausal women who gain elevated serum 25-hydroxyvitamin D3 
through supplementation see reductions in LDL cholesterol, according 
to a study in Menopause.

Researchers measured lipids among some 600 Women’s Health Initiative 
participants who’d been randomized to receive either daily vitamin D 
(400 IU) plus calcium (1000 mg), or placebo. At 2 years, the mean 
serum vitamin D level was significantly higher in the supplement 
versus placebo group (24.3 vs. 18.2 ng/mL). Further, supplement 
recipients had a 4.5-mg/dL decrease in LDL cholesterol relative to 
placebo recipients — an effect mediated by serum vitamin D levels.

The researchers conclude: “Although further studies are needed to 
determine whether these findings translate into clinically meaningful 
results, this should be viewed as a reminder that women at higher risk 
for 25OHD3 deficiency should consider supplementation” with calcium 
and vitamin D.

Menopause

Delayed antibiotic prescription is not associated with increased 
symptom severity in patients with respiratory tract infections, 
according to a BMJ study.

Clinicians in the U.K. assessed nearly 900 patients aged 3 years and 
older presenting with respiratory tract infections. A third were 
deemed to require immediate antibiotics. The remainder were randomized 
to one of five strategies: They were asked to recontact the clinic for 
an antibiotic prescription if needed; received a post-dated 
prescription; were instructed to wait but allowed to collect the 
prescription from the front desk; received a prescription but were 
asked to wait to use it; or did not receive a prescription.

The primary outcome — patient-reported symptom severity on days 2 to 
4 — did not differ significantly among the groups, including the 
group prescribed antibiotics immediately. Antibiotic use was also not 
significantly different across the randomized groups (26%-39%).

BMJ article

An experimental blood test has used 10 phospholipid biomarkers to 
accurately predict preclinical Alzheimer disease in cognitively normal 
adults, according to a research letter published in Nature Medicine.

Researchers tested blood samples from community-dwelling adults aged 
70 and older. Three years later, 53 had amnestic mild cognitive 
impairment or mild Alzheimer’s, 18 of whom had developed their 
impairment over the course of the study. Blood test results for these 
adults were matched with those of 53 cognitively normal participants.

The researchers identified 10 different metabolites that were depleted 
in patients who later became impaired. In a validation phase, the test 
was over 90% accurate in predicting which people would develop mild 
cognitive impairment or Alzheimer’s within 2 to 3 years.

The authors emphasize that their panel requires external validation 
before it is ready for clinical use.

Nature Medicine research letter

Do vitamin and mineral supplements really prevent disease? In two 
clinical trials and a meta-analysis, researchers evaluated the 
efficacy of dietary supplements.

In a double-blind trial, investigators evaluated whether oral 
multivitamins prevent adverse cardiovascular events in people with 
histories of myocardial infarction. More than 1700 patients (mean age, 
65) were randomized to a 28-component, high-dose multivitamin and 
mineral supplement or to placebo. Only half of participants adhered to 
study preparations for at least 3 years. After a median follow-up of 
4.6 years, incidences of recurrent adverse cardiovascular events were 
similar in the two groups (about 30%). In subgroup analysis of people 
who didn’t take statins at baseline, event rates were lower in the 
supplement group than in the placebo group (hazard ratio, 0.62). No 
evidence of harm with vitamin use was reported.

In a second randomized study, researchers from the Physicians’ Health 
Study II (NEJM JW Gen Med Nov 15 2012) examined the effects of 
multivitamin supplementation on cognitive function later in life. Male 
physicians (age, ≥65) received daily multivitamin or placebo 
supplements for a mean of 8.5 years; no difference was noted in change 
in cognitive function, as measured by five different cognition tests.

Finally, in an analysis for the U.S. Preventive Services Task Force, 
authors conducted a systematic review of studies that involved vitamin 
and mineral supplements for primary prevention of cardiovascular 
disease, cancer, or all-cause mortality among healthy individuals. No 
consistent evidence suggested a benefit from supplements. However, 
findings were limited by the small number of fair- and good-quality 
studies available for analysis of supplements other than β-carotene or 
vitamin E. For vitamin E, the researchers found good evidence of a 
null effect, whereas β-carotene was associated strongly with excess 
lung cancers and death among individuals whose risk for lung cancer 
was high.

COMMENT

In a strongly worded editorial, writers summarize the findings of 
these three studies by stating, “Most supplements do not prevent 
chronic disease or death, their use is not justified, and they should 
be avoided.” They do leave open the potential for a small benefit or 
harm in certain population subgroups.

Lamas GA et al. Ann Intern Med 
2013 Dec 17. Grodstein F et al. Ann Intern Med 2013 Dec 17. Fortmann 
SP et al. Ann Intern Med 2013 Dec 17. Guallar E et al. Ann Intern Med 
2013 Dec 17.