Monthly Archives: February 2014

What are the benefits and harms for women considering a mammogram?

Bottom Line:

The paper’s authors suggest that balanced discussions about the benefits and harms of screening mammography should focus on:

  • the possibility of breast cancer deaths avoided but also
  • the possibility of false alarms and overdiagnosis (the detection of abnormalities that will never progress enough to cause symptoms or death during a patient’s lifetime).

Although some women are comfortable with a high rate of false positive results, some women will experience lasting consequences (Ann Fam Med 2013;11:106-15) and should know the risk of harm when making the decision whether to screen.


Welch HG, Passow HJ. Quantifying the benefits and harms of screening mammography. JAMA Intern Med 2014;Dec 30. [Epub ahead of print]


Sometimes we forget there are harms associated with screening for disease. Though the possibility of benefit might be worth the risk of harm, this trade-off should be considered in the decision-making process. The authors of this analysis identified, in the fog of information swirling around cancer screening, 3 outcomes that should be considered:

  1. breast cancer deaths avoided,
  2. false alarms, and
  3. overdiagnosis (the diagnosis of “disease” that will never cause symptoms or death during a patient’s lifetime).

Note that no controlled research has shown decreased overall mortality as a result of screening. The authors used currently available data from trials of annual screening mammography — the most common screening practice in the United States — to give a range of estimates for these 3 outcomes for women at different ages.

  1. breast cancer death avoidance:
    • most optimistic reduction based on randomized trial data, a 36% reduction. Although some randomized studies and epidemiologic data point to no benefit, the authors chose a conservative lower estimate of a 5% reduction.
  2. false-positive rate: a) If you screen 1000 40 year old women for 10 years, 0.1 to 1.6 will avoid dying of breast cancer, 510 to 690 will have at least 1 false alarm, and 60-80 will have a biopsy that confirms a false positive mammogram.  b) Among 1,000 50-year-old women, 0.3 to 3.2 will avoid dying from breast cancer, 490 to 670 will have at least 1 false alarm, with 70 to 100 undergoing a biopsy. c) Among 1,000 60-year-old women: 0.5 to 4.9 will avoid dying from breast cancer 390 to 540 will have at least 1 false alarm, with 50 to 70 undergoing a biopsy
  3. Over-diagnosis: a) Of those 1,000 40-year-old women, up to 11 will be over-diagnosed and treated without the possibility of benefit.  b) Of those 1000 50 year old women, 3 to 14 will be over-diagnosed and treated without the possibility of benefit. c) Among 1,000 60-year-old women, 6 to 20 will be over-diagnosed and treated without the possibility of benefit

This post was modified from the original post by Allen F. Shaughnessy, PharmD, MMedEd, Professor of Family Medicine, Tufts University, Boston, MA

Can your blood pressure pill increase your risk of diabetes?

Article: Shen L, Shah BR, Reyes EM, et al. Role of diuretics, beta blockers, and statins in increasing the risk of diabetes in patients with impaired glucose tolerance: reanalysis of data from the NAVIGATOR study. BMJ. 2013 Dec 9;347:f6745

OBJECTIVE: To examine the degree to which use of beta blockers, statins, and diuretics in patients with impaired glucose tolerance and other cardiovascular risk factors is associated with new onset diabetes.

DESIGN: Reanalysis of data from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial.


PARTICIPANTS: Patients who at baseline (enrollment) were treatment naive to beta blockers (n=5640), diuretics (n=6346), statins (n=6146), and calcium channel blockers (n=6294). Use of calcium channel blocker was used as a metabolically neutral control.

MAIN OUTCOME MEASURES: Development of new onset diabetes diagnosed by standard plasma glucose level in all participants and confirmed with glucose tolerance testing within 12 weeks after the increased glucose value was recorded. The relation between each treatment and new onset diabetes was evaluated using marginal structural models for causal inference, to account for time dependent confounding in treatment assignment.

RESULTS: During the median five years of follow-up, beta blockers were started in 915 (16.2%) patients, diuretics in 1316 (20.7%), statins in 1353 (22.0%), and calcium channel blockers in 1171 (18.6%). After adjusting for baseline characteristics and time varying confounders, diuretics and statins were both associated with an increased risk of new onset diabetes (hazard ratio 1.23, 95% confidence interval 1.06 to 1.44, and 1.32, 1.14 to 1.48, respectively), whereas beta blockers and calcium channel blockers were not associated with new onset diabetes (1.10, 0.92 to 1.31, and 0.95, 0.79 to 1.13, respectively).

CONCLUSIONS: Among people with impaired glucose tolerance and other cardiovascular risk factors and with serial glucose measurements, diuretics and statins were associated with an increased risk of new onset diabetes, whereas the effect of beta blockers was non-significant.



Internal Medicine: This study comprise of a re-analyses of the NAVIGATOR RCT in which patients were randomised to valsartan and nateglinide (a 2×2 factorial design), both of which failed to show any convincing effect in delaying the development of NIDDM in a relatively high risk population. The present BMJ paper is thus only an observational cohort study albeit with some confounder adjustment. I have grave concerns that there may be residual confounding, especially in case of statins. To my knowledge, the association between diuretics and risk of NIDDM is not new. Apart from this general skepticism regarding the design, I also in this context regard NIDDM as a proxy outcome. The beneficial effect on death in risk patients treated with statins is well documented, so although there (eventually) could be a slight increase in risk of NIDDM, statins would probably still save lives.

General Practice(GP)/Family Practice(FP): A large study assessing the risk of developing diabetes in patients taking diuretics, statins and beta blockers with results reflecting a number necessary to harm (NNH) of 17 for diuretics and NNH of 12 for statins respectively.

Does pet exposure reduce the risk of atopic dermatitis in children? Yes, if you own a dog.

Bottom Line

Exposure during pregnancy, infancy, or childhood to dogs and other pets (but not cats) is significantly associated with a reduced risk of atopic dermatitis (AD) in childhood. Dogs may drool and cats may rule, but dogs reduce itchy skin disease! Go Sparky!(LOE = 2a)

ReferencePelucchi C, Galeone C, Bach JF, La Vecchia C, Chatenoud L. Pet exposure and risk of atopic dermatitis at the pediatric age: A meta-analysis of birth cohort studies. J Allergy Clin Immunol 2013;132(3):616-622.

Study Design: Meta-analysis (other) Funding: Foundation
Setting: Various (meta-analysis) Allocation: Unknown


The “hygiene hypothesis” proposes that a reduced exposure to infectious agents in early life can affect the developing immune system and increase susceptibility to allergic and autoimmune disorders. These investigators searched MEDLINE and EMBASE and checked the reference lists of pertinent publications for studies reporting data on exposure to pets and AD in infants and children. Eligible studies included either cohort or case-control studies that evaluated exposure to dogs, cats, other pets, or pets overall during pregnancy, infancy, and/or childhood and the subsequent diagnosis of AD during infancy or childhood (12 years or younger). The authors do not report if decisions were performed independently by review team members, but discrepancies on individual study inclusion criteria were resolved by consensus agreement. Multiple analyses were performed to control for covariates, including family history of atopy, parental smoking, geographic area, parental education/income, and period of exposure. A total of 21 publications, all birth cohort studies, were identified, including 15 reporting data for dog exposure, 13 for cat exposure, and 11 to “pets.” Exposure to dogs compared with no exposure was significantly associated with a reduced risk of developing AD (relative risk [RR] = 0.72; 95% CI, 0.61-0.85). There was no significant association between exposure or no exposure to cats and the risk of AD. Exposure to “pets,” including dog or cat or other pet, was also significantly associated with a reduced risk of AD (RR = 0.75; 0.67-0.85). The authors reported minimal, if any, heterogeneity in their results and no evidence of significant publication bias.

David Slawson, MD
Vice Chair, Department of Family Medicine
University of Virginia
Charlottesville, VA

Do statins really impair cognition?

EvidenceUpdates from the BMJ Evidence Centre
Swiger KJ, Manalac RJ, Blumenthal RS, et al. Statins and cognition: a systematic review and meta-analysis of short- and long-term cognitive effects. Mayo Clin Proc. 2013 Nov;88(11):1213-21. doi: 10.1016/j.mayocp.2013.07.013. Epub 2013 Oct 1. (Review) PMID: 24095248
OBJECTIVE: To evaluate the effect of statins on short-term cognitive function and the long-term incidence of dementia.
PATIENTS AND METHODS: A systematic search was performed of MEDLINE, EMBASE, and the Cochrane Central Register from their inception to April 25, 2013. Adults with no history of cognitive dysfunction treated with statins were included from high-quality randomized controlled trials and prospective cohort studies after formal bias assessment.
RESULTS: Sixteen studies were included in qualitative synthesis and 11 in quantitative synthesis. Short-term trials did not show a consistent effect of statin therapy on cognitive end points. Digit Symbol Substitution Testing (a well-validated measure of cognitive function) was the most common short-term end point, with no significant differences in the mean change from baseline to follow-up between the statin and placebo groups (mean change, 1.65; 95% CI, -0.03 to 3.32; 296 total exposures in 3 trials). Long-term cognition studies included 23,443 patients with a mean exposure duration of 3 to 24.9 years. Three studies found no association between statin use and incident dementia, and 5 found a favorable effect. Pooled results revealed a 29% reduction in incident dementia in statin-treated patients (hazard ratio, 0.71; 95% CI, 0.61-0.82).
CONCLUSION: In patients without baseline cognitive dysfunction, short-term data are most compatible with no adverse effect of statins on cognition, and long-term data may support a beneficial role for statins in the prevention of dementia.
  • Cardiology Many patients and physicians seem to believe that statin use can cause or contribute to dementia. This paper suggests that belief is false and that, if anything, long-term statin therapy reduces the risk of dementia
  • General Practice(GP)/Family Practice(FP) This report will surprise some doctors and patients who are familiar with the FDA warnings that statins are associated with forgetfulness, and confusion.
  • Neurology This is a well designed, carefully structured systematic review based on the scrupulous criterion, strictly assessing the risk of bias of selected articles. Though statistically insufficient and clinically restricted, this report should produce an effective counter-evidence against the FDA label revision. This report should provide the most reliable synthesis.

Greater continuity of care associated with fewer preventable hospitalizations

Clinical Question

In the elderly Medicare population, does greater continuity of care lower the risk of preventable hospitalizations?

Bottom Line

Elderly patients who are treated by a smaller set of providers or by a single provider (ie, have greater continuity of care) may be less likely to have preventable hospitalizations. (LOE = 2b)


Nyweide DJ, Anthony DL, Bynum JP, et al. Continuity of care and the risk of preventable hospitalization in older adults. JAMA Intern Med 2013;173(20):1879-1885.

Study Design:  Cohort (retrospective)  Setting:  Outpatient

Funding: Government  Allocation: Concealed


Using Medicare data, these investigators identified preventable hospitalizations for Medicare fee-for-service beneficiaries older than 65 years using definitions previously provided by the Agency for Healthcare Research and Quality.Preventable hospitalizations were conditions that can potentially be treated with good outpatient care, such as asthma, chronic obstructive pulmonary disease, congestive heart failure, and bacterial pneumonia. Continuity of care was defined by 2 metrics: the continuity of care score and the usual provider continuity score. The continuity of care score measures physicians’ shares of a patient’s visits, with higher scores indicating a greater number of visits with fewer providers, whereas the usual provider continuity score measures the percentage of a patient’s total visits to a single provider. Both are scored on a scale from 0 to 1, with higher scores indicating greater continuity of care. Only data from patients with 4 or more visits during a course of a year were analyzed.Of approximately 3.2 million patients, 13% of this cohort had a preventable hospitalization over a 24-month observation period. These patients were more likely to have a higher illness burden at baseline and were more likely to have Medicaid dual eligibility. The top 2 reasons for preventable hospitalizations were congestive heart failure and bacterial pneumonia. As compared with those without preventable hospitalizations, patients with preventable hospitalizations had lower scores on both continuity metrics. After adjusting for patient characteristics, illness burden, and regional market-related and practice-related characteristics, a 0.1-unit increase in either continuity metric was associated with a 2% decrease in preventable hospitalizations.

Nita Shrikant Kulkarni, MD
Assistant Professor in Hospital Medicine
Northwestern University
Chicago, IL

Steroids Reduce Time to Discharge from Observation Unit in Infants with Acute Bronchiolitis and Suspected Asthma

Reference: (Pediatrics 2013 Oct;132(4):e810) (level 1 [likely reliable] evidence)

Bronchiolitis commonly affects young children, and is the most frequent cause of hospitalization among infants during winter months. A recent Cochrane review (Cochrane Database Syst Rev 2013 Jun 4;(6):CD004878) found that systemic and inhaled corticosteroids do not reduce rates of hospital admission or readmission in children with acute bronchiolitis, and current guidelines do not recommend routine use of steroids in this patient population (Pediatrics 2006 Oct;118(4):1774-93). However, some infants initially presenting with bronchiolitis are subsequently diagnosed with asthma, where corticosteroids are used for long-term symptom control. Data evaluating efficacy of steroids in infants with bronchiolitis who are at high risk for asthma have been limited thus far. Now, a recent randomized trial has compared oral dexamethasone vs. placebo in 200 such infants.

Infants (median age 3.5 months) presenting for emergency care with acute bronchiolitis were randomized to dexamethasone (1 mg/kg orally on day 1 followed by 0.6 mg/kg orally once daily for 4 more days) vs. placebo. All infants were at high risk for asthma based on either the presence of eczema or history of asthma in a first-degree relative. All infants received nebulized salbutamol 2.5 mg 4 times over first 2 hours and every 2 hours until discharge, and infants could receive nebulized epinephrine or other treatments at the discretion of the treating physician. Infants were evaluated for readiness for discharge from an observation unit at least every 6 hours, and were followed for 1 week after discharge.

A modified intention-to-treat analysis was used to assess the efficacy of dexamethasone after excluding 10 infants for admission to intensive care unit, failure to meet inclusion criteria, or withdrawal after randomization. The mean time to readiness for discharge was 18.6 hours with dexamethasone vs. 27.1 hours with placebo (p = 0.015), and the dexamethasone group had a lower rate of nebulized epinephrine use (19% vs. 34.4%, p = 0.03, NNT 7). However, the frequency of return visit within 1 week of discharge was 22% for dexamethasone vs. 21% for placebo (not significant). No hospitalizations or adverse events occurred in either group.

Collectively, these results suggest that oral dexamethasone may be useful for treatment of bronchiolitis in the emergency department in this subpopulation by substantially decreasing the amount of time infants spend under observation. The increased turnaround associated with short-term dexamethasone treatment may be particularly beneficial during winter months, when cases of bronchiolitis in the emergency department are at their maximum frequency. However, these data do not support continued treatment for 5 days, since there was no reduction in return visits in the week following discharge.

For more information, see the Bronchiolitis topic in DynaMed.