Update on treatment of worsening pharyngitis

The Buzz: There's a new possibility to consider when evaluating patients with worsening pharyngitis
Citation: Avoiding sore throat morbidity and mortality: when is it not "just a sore throat?" American Family Physician January 1, 2011 Vol 83:1 p26-7 
Summary: Fusobacterium necrophorum (Fn) is a newly recognized bacterial cause of sore throat and can result a potentially very serious complication called Lemierre syndrome, or septic thrombophlebitis of the internal jugular vein resulting in metastatic pulmonary infections. Patients typically complain of a sore throat which initially improves after 4-5 days but then worsens with symptoms including rigors, fever, night sweats. Mortality is up to 5% of those affected. Lemierre syndrome occurs most often in those aged 15-30 years. Unfortunately there is no laboratory method for diagnosing Fn infections.

So what's a doc to do? First of all, the article reminds us of the differential diagnosis of worsening sore throat including non-group A strep, untreated group A strep (often due to a false negative rapid strep test which can miss up to 10% of cases), infectious mononucleosis, acute HIV infection, peritonsillar abscess, and Lemierre syndrome. Second, we should remember to consider antibiotic treatment in patients with 3 or more of the following: fever, absence of cough, tender anterior cervical lymph nodes and tonsillar exudate. Penicillin remains the drug of choice for presumed strep infections. It also has activity against Fn. If we suspect Lemiere syndrome (recurrence of sore throat with new rigors or fever), clindamycin can be used in well-appearing patients though ER referral/hospital admission for IV antibiotics should be considered for ill-appearing patients with high fevers, rigors, or unilateral neck swelling.
Commentary: While the data are still being gathered, it's a good idea to keep this info in mind when treating patients with persistent or worsening symptoms. 
By: Spencer Blackman MD

Updated guidelines on management of CA-MRSA infections

The Buzz: Updated guidelines clarify approach to this growing problem
Citation: Clinical Infectious Diseases 2011:52  http://cid.oxfordjournals.org/content/early/2011/01/04/cid.ciq146.full.pdf
Summary: Community acquired methicillin-resistant S. Aures (CA-MRSA) infections continue to be on the rise and knowing the appropriate treatment and prevention guidelines is crucial. The Infections Disease Society of America released updated guidelines for the management of skin and soft tissue infections due to CA-MRSA which include the following key points:
- The primary treatment for cutaneous abscess is immediate incision and drainage.
- Antibiotic treatment should be also used for any of the following: multiple sites of infection, signs of systemic infection (fever, etc), rapidly growing infection, concomitant cellulitis, extremes of age, immunocompromise, significant comorbidities, difficult area to drain (e.g. face, hand, genitalia), lack of response to I&D alone.
- For cellulitis with purulence, antibiotic coverage should include empiric CA-MRSA coverage (Bactrim DS 1-2 po bid, Doxy 100 bid, Clinda 300-450 tid, linezolid). Duration of treament is 5-10 days and should be individualized.
- For cellulitis without purulence, empiric beta-hemolytitc streptococcus coverage should be used (Bactrim, Keflex 500 qid, Clinda) but CA-MRSA coverage is likely not needed.
-The use of rifampin as a single agent or as adjunct therapy is not indicated 


The management of recurrent infections with CA-MRSA was also addressed and included:
- Education around frequent hand washing and good hygiene practices
- Avoid reusing personal grooming items (disposable razors, e.g.) and wash all towels/clothes/linens that come in contact with open wounds.
- Focus cleaning efforts on high-touch surfaces like doorknobs and counter tops.
- Decolonization protocols may also be employed and include twice daily intranasal mupirocin 2% for 5-14 days, bathing with antibacterial soaps (chlorhexadine) for 5-10 days, and dilute bleach baths (1/4 cup bleach to 1/4 tub or 13 gallons water) for 15 min twice weekly for up to 3 months.
- Decolonization of household contacts can be considered.

By: Spencer Blackman MD

Comparing approaches to diabetes screening

The Buzz: ADA guidelines outperform the updated USPSTF approach to screening for diabetes

Citation: A Sheehy et. al. Analysis of Guidelines for Screening Diabetes Mellitus un an Ambulatory Population.  Mayo Clinic Proc. January 2010; 85(1):27-35

Summary: Of the estimated 25 million Americans currently with diabetes, approximately 40% continue to be undiagnosed, and determining the most effective screening method may prevent significant morbidity and mortality. Currently, the American Diabetes Association (ADA) and the US Preventative Services Task Force (USPSTF) have issued vastly different guidelines for screening for diabetes. This retrospective study included 28,842 patients from a large, Midwestern primary care practice, comparing the performance of both approaches to screening. The study found that adhering to USPSTF guidelines would have identified 33% fewer new cases of diabetes, and the authors recommended using the ADA guidelines due to their superior performance. One caveat is the population of patients under 45 who are non-obese with hypertension, for whom the USPSTF recommends screening and the ADA guidelines do not. Study authors point out this is an important group to screen as well.  The study also found that a history of pre-diabetes or polycystic ovarian syndrome conferred the highest risks for developing diabetes.

Commentary: This study suggests we combine USPSTF and ADA guidelines in an effort to identify more cases of diabetes.

By: Maxwell Jen, MSIII & Spencer Blackman, MD

Time 2 take ur pill

The Buzz: Text message-based reminder system for OCP use does not seem to improve adherence.
Citation: Hou MY et al. Using daily text-message reminders to improve adherence with oral contraceptives: A randomized controlled trial. Obstet Gynecol 2010 Sep; 116:633.
Summary: Study authors randomized 82 predominantly white, all high-school graduate new or resuming OCP users to to receive daily text-message reminders or no reminders for three cycles. The number of missed pills per cycle was the same in both groups (around 4.5/month). There were no pregnancies in either group.
Commentary: The high rate of missed pills reported in this study suggests that even with advanced reminder systems, many women on OCPs are at higher risk for pregnancy then we might think. OCPs are still a valid option, but this study may aid in shared decision-making around optimal methods.  
By: Spencer Blackman MD

Rosiglitazone (Avandia) and increased risk of CV events

The Buzz: FDA advisory committees recommend removing rosiglitazone
Citation: AAFP News Now, 7/20/2010
Summary: Members of two FDA advisory committees have expressed concerns over the safety of rosiglitazone (Avandia) and have recommended removing the medication from the list of approved drugs. While investigation into the safety of rosiglitazone has been ongoing since 2007, two recent studies from JAMA and the Archives of Internal Medicine
reported significant elevation in CV risk associated with its use. Of note, GlaxoSmithKline, the maker of Avandia, has said that it will record a $2.36 billion legal charge in the second quarter of fiscal year 2010 for settlements related to rosiglitazone.
Commentary: While FDA has yet to make a decision, we should consider getting our patients off rosiglitazone, and certainly not write new prescriptions for it. Pioglitazone (Actos) is considered safer than rosiglitazone, though it should be considered only in patients refractory to or intolerant of first- and second-line therapies.
By: Spencer Blackman MD

UPDATE (9/25/2010): Rosiglitazone has been pulled from the European market, and will only be offered to US patients in whom "every other" diabetes medication has been tried.

Controversy Alert: Statins for Primary Prevention of CVD

The Buzz: Should statins be used to prevent CVD in patients without known disease? 
Citation: Arch Intern Med 170:12 June 20, 2010 
Summary: Three quarters of the patients who are taking statins are using them for primary prevention, i.e. to delay or prevent the onset of atherosclerosis and to reduce the incidence of heart attacks, strokes and other sequelae. The debate over the evidence for this use has been simmering for some time, and a recent issue of Archives of Internal Medicine presents two new papers which add significant fuel to the fire.

The first, by Ray et al, is a meta-analysis of 11 RCTs involving 65,229 patients (including the recent JUPITER trial) which found no significant reduction in risk associated with the use of statins. The strengths of this study include its large size, exclusion of patients with known CVD, and apparent lack of authors' conflict of interest. However, the average period of follow-up among the studies included in the report was just 3.7 years, and it is possible that longer term use may confer additional benefit no found in this report, though evidence for this is lacking.

The second, by de Lorgeril et al, is an analysis of the 2008 JUPITER study, a controversial trial which was ended early after just two years and reported a significant reduction in CVD-related events with the use of rosuvastatin (Crestor). In this current reappraisal of JUPITER, the authors point out a number of serious flaws with the methodology and results, including:

• The premature termination of the JUPITER trial due to the "clear benefit" in the treatment arm was based on unclear criteria, and truncated trials have been shown to be associated with greater effect sizes than those which are not stopped early.
• Significant conflicts of interest existed in the JUPITER trial. It was sponsored by the makers of Crestor, 9 of 14 authors have financial ties to the sponsor, and the principle investigator is a co-holder of the patent for the CRP test, which would be used much more frequently if the results of the trial are to be believed.
• The all-cause mortality curves were converging when the trial was stopped, suggesting the difference between the two groups may have disappeared with more time
• The authors found a number of inconsistencies that suggested major limitations to the data set. For example, the number of participants who had an MI who died (the case-fatality rate) was extremely low in the study (5-18%) as compared to the expected rate of 40-50%. Moreover, treatment with rosuvastatin appeared to triple the case-fatality rate, an effect which does not seem credible.

The papers were accompanied by an editorial which concluded that "we do not know" if there is any benefit of statins in primary prevention of CVD.
Commentary: These papers call into serious question whether we should be prescribing statins to patients without known CVD, especially if it decreases the importance we place on improvements in lifestyle, including smoking cessation, exercise, and diet. 
By: Spencer Blackman, MD

Genetic test predicts lifespan? Not ready for prime time.

The Buzz: Researchers report a study identifying genetic markers for longevity
Citation: New York Times; July 2, 2010
Summary: A study published in this week's issue of Science reports the identification of genetic markers associated with living to 100, and claims a 77% acuracy rate. Researchers analyzed the DNA of 1,055 centenarians and identified a pattern of 150 genetic markers which seemed to confer longevity. They then looked at another group of centenarians and found 77% of them had the same pattern. While the study authors admit the biology behind these findings has yet to be explained, they feel this may be an importnat step towards understanding the genetics of longevity. Of special interest, the centenarians had equal numbers of disease-related genetic markers, suggesting these 150 may be protective factors that delay the onset of diseases of old age.
Commentary: The bottom line - this is simply a statistical analysis that correlates a certain genetic make-up with longevity. The test is not available to the general public and is likely not to be any time soon. But given the amount of press it is getting, understanding the implications, and lack thereof, may be helpful in talking to our patients.
By: Spencer Blackman MD

Homocysteine-lowering fails to prevent CV events

The Buzz: A new study published in JAMA provides further evidence against the use of folic acid & B12 to prevent cardiovascular events
Citation: JAMA. 2010;303(24):2486-2494.
Summary: Elevated homocysteine has been found to be associated with increased risk for cardiovascular events (MI, stroke, revascularization, death) but lowering homocysteine levels has not been shown to improve outcomes. This double-blind, placebo-controlled study followed 12,064 British survivors of MI over an average of 6.7 years and found no reduction in CVD events for those on the vitamins. This is consistent with a 2009 Cochrane meta-analysis which included people with and without known CVD.
Commentary: While the more recent study was funded my Merck, who makes cholesterol-lowering drugs, the results are consistent with previous data and suggest we should not be recommending these vitamins for CVD prevention.
By: Spencer Blackman MD

Vitamin D levels and viral illness

The Buzz: Raising serum 25(OH)D3 levels above 38 ng/ml may significantly reduce susceptibility to viral respiratory illness
Citation: Sabetta JR et al. "Serum 25-hydroxyvitamin D and the incidnece of acute viral respiratory tract infections in healthy adults." PLoS ONE 5(6):e11088 June 2010
Summary: This past winter, researchers at Yale University prospectively measured serum 25(OH)D3 concentrations in 198 healthy adults and tracked the incidence of acute respiratory tract infections, reporting a two-fold reduction in risk of developing infection for those with concentrations > 38 ng/ml.
Commentary: A high quality (blinded, prospective) trial which suggests a new way to reduce the burden of viral respiratory illness. A better study design would be placebo-controlled, but these findings are suggestive of a benefit.
By: Spencer Blackman MD

PPIs - time to rethink our use?

The Buzz: Benefits of PPIs may not outweigh the risks for many patients
Citation: Arch Int Med 170(9) May 10, 2010
Summary: The May 10, 2010 issue of Archives of Internal Medicine is centered around the theme "Less is more", and a number of articles focus on PPI use. "A staggering 113.4 million prescriptions for PPIs are filled each year, making this classs of drugs, at $13.9 billion in sales, the third highest seller in the United States," one editor points out. He goes on to suggest that "between 53% and 69% of PPI prescriptions are for inappropriate indications." Other highlights from this issue include:

• Evidence-based indications for PPIs include errosive and ulcerative esophagitis, Barrett esophagus, Zollinger-Ellison syndrome, severe GERD, short-term treatment of ulcers, eradication of H. Plyori, and ulcer prevention with NSAID use.
• A study of 130,487 postmenopausal women with 7.8 years of follow-up found PPIs were associated with and increased rate of spine, lower arm, and total fractures. (HR = 1.25)
• A study of more than 1,000,000 hospital discharges found daily PPI use contributed to a 73% increased risk of C difficile infection
• PPIs also significantly increase the risk of hospital and community-acquired pneumonia

While this seems very convincing, those of us on the front-lines deal with the reality that 25% of adults report dyspepsia and PPIs do help. Moreover, PPI use fits our current medical model of naming symptoms and treating them with a pill. The authors suggest we should instead offer other treatments than PPIs for functional dyspepsia, prescribe short courses of PPIs (after disclosure of possible risks and benefits), and consider a trial of discontinuing PPIs in asymptomatic patients.

Commentary: Improving health care often means doing less, and this is one example where we may be helping our patients by steering them away from PPIs when not indicated.
By: Spencer Blackman MD

What is the best way to diagnose GERD?

The Buzz: A simple point-of-care tool can help with the diagnosis of GERD
Citation: "Diagnosis of Gastroesophageal Reflux Disease" AFP  2010 May 15;81(10):1278-1280.
Summary: Upper abdominal symptoms are common in primary care, and this article presents two clinically-validated point-of-care tools for the diagnosis of GERD. The first, called "GerdQ", is a 5-item survey which predicts the likelihood of the diagnosis of GERD. This can be given to the patient at registration and was shown to be comparable to diagnosis by a specialist. The second is a clinical scoring guide which uses BMI and a few other data points to predict response to omeprazole. While calculating the score is slightly more time-consuming, the authors point out that in patients of average or increased weight, nighttime pain or recent antacid use predicts a good response to omeprazole*, a rule which provides an even more efficient way to decide if its use is worth recommending.
Commentary: Any shortcuts to the diagnosis and management of this common condition are welcome. *See recent post on PPIs.
By: Spencer Blackman MD

Cochrane: Opioids for OA?

The Buzz: In OA of the hip and knee, opioids provide modest benefits that do not outweigh the risks
Citation: "Cochrane for Clinicians: Opioids for Osteoarthritis of the Knee or Hip" AFP May 1, 2010 81:9 1094-95 
Summary: The study authors reviewed ten outpatient trials involving 2,268 patients, reporting a response rate of 35% of patients in the treatment group, vs 31% in the control group (number needed to treat [NNT] = 25), as defined by a reduction of at least half of their pain. This was offset by adverse effects, though major adverse events were rare. No one opioid was found to be superior. The article authors recommend clinicians consider other interventions as outlined  by the Osteoarthritis Research Society International. They also recommended tramadol, as well as codeine, in patients with refractory pain.
Commentary: This seemingly focused review brings up a number of larger issues, including the overuse of narcotic medications (hydrocodone is the most prescribed medication in the US), and the approach to chronic pain. In addition, it points out a very useful resource available to California clinicians, the California Prescription Drug Monitoring Program (register here), which allows real-time controlled prescription reports on individual patients.
By: Spencer Blackman MD

Hgba1c as an independent risk factor for diabetes, CVD and death?

The Buzz: Glycated hemoglobin may be a useful marker for predicting development of diabetes, cardiovascular risk and death
Citation:  "Glycated Hemoglobin, Diabetes and Cardiovascular Risk in Nondiabetic Adults." NEJM 362;9 March 4, 2010 800-11

Summary: This multi-center study followed 11,092 middle-aged adults without diabetes over a 15 year period in order to study the use of glycated hemoglobin to predict risk of diabetes, coronary heart disease and death. Using thawed blood samples taken during subjects' earlier visits, researchers calculated adjusted hazard ratios for those with HgbA1c values below 7.0%, ie nondiabetics. HgbA1c values were as good as fasting glucose values for predicting risk of developing diabetes, and appeared to be better than fasting glucose as a predictor of long-term macrovascular event risk. For A1c values of <5.0%, 5.0%-<5.5%, 5.5%-<6.0%, 6.0%-<6.5% and >6.5%, the multivariable-adjusted hazard ratios were 0.52, 1.00, 1.86, 4.48 and 16.47, respectively for developing diabetes, and 0.96, 1.00, 1.23, 1.78, and 1.95, respectively for coronary heart disease (all values significant). Similar findings were reported for stroke and death from any cause.The authors concluded that not only does this study further support the use of glycated hemoglobin values to predict diabetes risk, but that values over 6.0% may be an independent risk factor for cardiovascular disease and death.
Commentary: This study, while observational, suggests we have another tool to help establish risk for developing diabetes, heart disease and death. However, the authors do not suggest which patients this would be useful for, nor do these findings change the approach to patients at elevated risk. Modifying lifestyle factors is still key in this battle.
By: Spencer Blackman MD