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Rabu, 11 April 2012

Diagnosing and Treating Rhinosinusitis: New Guidelines

The Infectious Diseases Society of America has published its first-ever recommendations for the diagnosis and management of acute bacterial rhinosinusitis (ABRS) infections.[1] The guidelines used the new GRADE system (Grading of Recommendations Assessment, Development and Evaluation), which is designed to more clearly assess the quality of evidence and report the strength of recommendations. The ABRS guidelines were posted online March 21, 2012, and will appear in the April 15, 2012, issue of Clinical Infectious Diseases.
Because the infection causes inflammation of both the sinuses and the nasal cavity, the ABRS guidelines use the term "rhinosinusitis" instead of the more common "sinusitis." The purpose of the guidelines is to provide clarity and guidance to physicians and other primary care providers in diagnosing and treating the infection. The guidelines specifically address the following:
  • The inability of existing clinical criteria to accurately differentiate bacterial from viral acute rhinosinusitis, leading to excessive and inappropriate antimicrobial therapy;
  • Gaps in knowledge and quality evidence about empiric antimicrobial therapy for ABRS as a result of imprecise patient selection criteria;
  • Changing prevalence and antimicrobial susceptibility profiles of bacterial isolates associated with ABRS; and
  • The effect of conjugated vaccines for Streptococcus pneumoniae on the emergence of nonvaccine serotypes associated with ABRS.
Although rhinosinusitis is quite common -- affecting nearly 1 in 7 adults each year -- the prevalence of bacterial infection during acute rhinosinusitis is estimated to be only 2%-10% of all patients with symptoms of sinusitis.[2,3] Antibiotics are significantly overprescribed for rhinosinusitis, which is the fifth leading indication for antimicrobial prescriptions by physicians in office practice.[4]One national survey conducted during 1998-2003 revealed that 81% of adults presenting with symptoms of sinusitis in an outpatient setting received an antibiotic prescription.[5] Overprescription of antibiotics is a serious concern because it is costly, exposes patients to unnecessary side effects, and fosters drug resistance.
Due to the lack of precision and practicality of current diagnostic methods, clinicians must rely on clinical presentations to distinguish bacterial from viral rhinosinusitis. The guidelines suggest that the infection is probably bacterial if any of the following are true:
  • Onset with persistent symptoms or signs compatible with acute rhinosinusitis lasting for ≥ 10 days without any evidence of clinical improvement;
  • Onset with severe symptoms or signs of high fever (≥ 39°C or 102°F) and purulent nasal discharge or facial pain lasting for at least 3-4 consecutive days at the beginning of an illness; or
  • Onset with worsening symptoms or signs characterized by new onset of fever, headache, or increase in nasal discharge following a typical viral upper respiratory infection that lasted 5-6 days and initially improved ("double-sickening").

Antibiotic Treatment for Rhinosinusitis

First-line therapy:
Once a bacterial cause is established based on these clinical presentations, empiric antimicrobial therapy should be initiated immediately with amoxicillin-clavulanate, which has better coverage than amoxicillin. This recommendation is a result of the following:
  • Increasing prevalence of Haemophilus influenzae among other respiratory tract infections in children since the introduction of the pneumococcal vaccines; and
  • High prevalence of beta-lactamase-producing respiratory pathogens in ABRS among recent respiratory tract isolates, particularly H influenzae.
Second-line therapy:
  • Doxycycline may be used as an alternate regimen in adults;
  • The following are not recommended because of resistance issues: macrolides, such as clarithromycin and azithromycin; trimethoprim-sulfamethoxazole; and second- and third-generation oral cephalosporins;
  • Combination therapy with a third-generation oral cephalosporin plus clindamycin may be used in children with non-type-1 penicillin allergy or who are from geographic regions with high endemic rates of penicillin-nonsusceptible S pneumoniae. Levofloxacin is recommended for children with type-1 penicillin allergy; and
  • Respiratory fluoroquinolones may be used in patients in whom first-line therapy failed or who have risk factors for antibiotic resistance.
Length of therapy:
  • Adults: 5-7 days for uncomplicated ABRS
  • Children: 10-14 days
Adjunct therapy:
  • Intranasal saline irrigations with physiologic or hypertonic saline may be helpful in adults but are less likely to be tolerated in children;
  • Intranasal corticosteroids are recommended in persons with a history of allergic rhinitis; and
  • Topical and oral decongestants and antihistamines are not recommended.


  1. Chow AW, Benninger MS, Brook I, et al. IDSA clinical practice guideline for acute bacterial rhinosinusitis in children and adults. Clin Infect Dis. 2012;54:1041-1045. Accessed March 21, 2012.
  2. Pleis JR, Lucas JW, Ward BW. Summary health statistics for U.S. adults: National Health Interview Survey, 2008. Vital Health Stat. 10;2009:1-157.
  3. Gwaltney JM Jr, Wiesinger BA, Patrie JT. Acute community-acquired bacterial sinusitis: the value of antimicrobial treatment and the natural history. Clin Infect Dis. 2004;38:227-233. Abstract
  4. Anand VK. Epidemiology and economic impact of rhinosinusitis. Ann Otol Rhinol Laryngol Suppl. 2004;193:3-5.Abstract
  5. Gill JM, Fleischut P, Haas S, Pellini B, Crawford A, Nash DB. Use of antibiotics for adult upper respiratory infections in outpatient settings: a national ambulatory network study. Fam Med. 2006;38:349-354. Abstract

Minggu, 01 April 2012

Diabetes Prevention With Metformin Is Safe, Well-Tolerated

 Long-term treatment with metformin is safe for preventing or delaying the development of type 2 diabetes, according to an article published in the April issue of Diabetes Care.
New data from the open-label Diabetes Prevention Program Outcomes Study (DPPOS) demonstrate that metformin is linked to "modest but durable weight loss" of 2% body weight over the course of 10 years, and appears to be safe and well tolerated.
The findings support the conclusions of the original 3-year DPP double-blind study showing that use of metformin (850 mg twice daily) encouraged stable weight loss. In both the metformin and placebo groups, weight loss was a strong predictor of diabetes prevention.
According to the Diabetes Prevention Program Research Group, the pattern of metformin-associated weight loss appears to differ from that observed with caloric restriction, in that adipose tissue is affected more than lean tissue mass. Metformin may also mimic the effects of exercise.
As previously reported by Medscape Medical News, metformin therapy may represent a more cost-effective alternative to lifestyle changes for preventing diabetes.
"We now know how to prevent type 2 diabetes and have the data to show that doing so is not only safe, it is cost-effective," said Vivian Fonseca, MD, president, medicine and science, American Diabetes Association, in a news release. "We should be taking much greater steps on a broad scale to reduce this serious health epidemic in our country.... I would encourage every American to estimate their own risk using simple tools (for example see and then, if at risk, take simple measures to prevent the disease."
Metformin Linked to Modest but Durable Weight Loss Over the Course of 10 Years
In the DPP, overweight and obese participants with impaired glucose tolerance were randomly assigned to lifestyle intervention, metformin, or placebo. Results reported in 2002 indicated that metformin therapy resulted in a 31% reduction in the development of diabetes during an average 2.8 years of follow-up.
During the study, participants randomly assigned to receive metformin experienced a decrease in body weight and waist circumference relative to placebo (mean, 2.06% ± 5.65% vs 0.02% ± 5.52%, and 2.13 cm ± 7.06 cm vs 0.79 cm ± 6.54 cm, respectively; P < .001 for both).
Throughout the unblinded follow-up study that covered 10 years from the start, weight loss remained significantly greater in the metformin group relative to placebo (2.0% vs 0.2%; P < .001), and was directly associated with the degree of therapeutic compliance (P < .001).
Participants highly adherent to metformin therapy achieved a weight loss of 3.5% (3.1 kg, 6.8 pounds), whereas those in the low-adherence group experienced an initial weight loss followed by weight changes similar to placebo until 5 years, at which point weight increased.
The authors note that waist circumference increased after 2 years, with the exception of highly adherent participants for whom the increase occurred after the 5-year point. Because body weight did not increase, the authors deduced that central adiposity was increased by a redistribution of body fat.
"[M]etformin-induced weight loss is almost exclusively confined to reductions in adipose mass with little change in lean tissue," the authors write, emphasizing that the pattern is different than that observed with caloric restriction, which tends to induce loss of lean, as well as adipose, tissue.
The authors also note that metformin also has several effects on energy metabolism that parallel physical exercise, such as phosphorylation of AMP-activated protein kinase, which is an important regulator of mitochondrial biogenesis, hepatic and muscle fatty acid oxidation, glucose transport, insulin secretion, and lipogenesis.
"Collectively, the clinical data suggesting 'durable weight loss' combined with the proposed cellular effects on energy metabolism continue to support metformin as a viable strategy for widespread translational efforts in prevention," comments William T. Cefalu, MD, from the Pennington Biomedical Research Center at Louisiana State University in Baton Rouge, in an accompanying editorial.
Long-Term Use of Metformin Is Generally Safe and Well-Tolerated
During the DPP through year 4, metformin-treated participants reported study drug–related gastrointestinal symptoms more frequently than those receiving placebo (9.5% vs 1.1%; P < .001). Reports declined over time, and rates were similar between groups during years 6 through 9 (P > .10).
Nonserious hypoglycemia and anemia were uncommon, and occurred at similar rates in metformin and placebo participants during nearly 18,000 patient-years of follow-up (n = 7 vs 8 and 50 vs 38, respectively). Serious adverse events were rare: there were only 3 reports of anemia (metformin, 2; placebo, 1), and no reports of lactic acidosis or hypoglycemia.
During the DPP, average hemoglobin and hematocrit declined slightly during the first year among metformin-treated participants, but remained stable thereafter (13.6 mg/dL vs 13.8 mg/dL and 40.6% vs 41.1%; P < .001 for both).
Although the proportion of participants with low hemoglobin was similar between groups (11.2% vs 7.6%; P = .17), low hematocrit was more common among metformin-treated participants (12.6% vs 8.4%; P = .035).
The authors note that 12% of DPP participants chose not to continue into the follow-up study, potentially because of adverse events that may have influenced the safety and tolerability profile observed.
The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. Bristol-Myers Squibb and Parke-Davis provided additional funding and material support during the DPP. Lipha (Merck-Sante) provided medication, and LifeScan Inc donated materials, during the DPP and DPPOS. One coauthor reports receiving grants from Novo Nordisk, the Swedish Heart-Lung Foundation, the Swedish Diabetes Association, and the Swedish Research Council. The other authors and Dr. Cefalu have disclosed no relevant financial relationships.
Diabetes Care. 2012;35:663-665, 731-737.

Diabetes Risk Increased by 3 Independent Factors

Insulin resistance (IR), overweight/obesity, and fatty liver commonly occur together but are independently associated with an increased risk of developing type 2 diabetes mellitus, according to results from a Korean study published onlineFebruary 14 and in the April print issue of Diabetes Care.
Investigators led by Ki-Chul Sung, MD, PhD, from the Sungkyunkwan University School of Medicine in Seoul, Republic of Korea, found that IR was linked to an almost quadrupled risk for diabetes (odds ratio [OR], 3.92; 95% confidence interval [CI], 2.86 - 5.37; P < .0001) during a 5-year period, whereas fatty liver and overweight/obesity increased the risk by factors of 2.42 (95% CI, 1.74 - 3.36; P < .0001) and 1.62 (95% CI, 1.17 - 2.24; P < .004), respectively.
Among those with 2 risk factors, the combination of overweight/obesity and fatty liver was associated with the lowest risk for diabetes (OR, 3.23; 95% CI, 1.78 - 5.89; P < .001), and IR/fatty liver with the highest risk (OR, 6.73; 95% CI, 3.49 - 12.73; P < .001).
A cluster of all 3 factors was linked to more than a 14-fold increased risk for diabetes during the 5-year period (OR, 14.13; 95% CI, 8.99 - 22.21; P < .001).
When evaluating the association of each of these risk factors with type 2 diabetes, adjustments were made for age, sex, educational status, smoking status, alcohol consumption, and exercise frequency as well as triglycerides and alanine aminotransferase levels.
Although IR, overweight/obesity, and fatty liver are strongly correlated, the dissociation between these risk factors suggests that different pathogenetic mechanisms may be in play.
"The clustering of IR, overweight/obesity, and fatty liver is common and markedly increases the odds of developing type 2 diabetes, but these factors also have effects independently of each other and confounding factors," the authors write, adding that treatment for each factor may be warranted.
For the study, investigators recruited 12,853 nondiabetic individuals from a South Korean occupational cohort in 2003.
At a 5-year follow-up in 2008, 223 cases of incident cases of diabetes were identified: 26 of those diagnosed (12%) had none of the 3 risk factors, 37 (17%) had 1 risk factor, 56 (25%) had 2 risk factors, and 104 (47%) had all 3 risk factors.
"Fatty liver is emerging as an independent risk factor for diabetes, and our data suggest that its association with incident diabetes may be stronger than that of overweight/obesity and weaker than that of IR," the authors write.
Because of the striking and marked increase in odds of diabetes with the occurrence of all 3 risk factors, the authors suggest that targeted specific approaches to ameliorating the effects of each factor may have great effect on reducing the risk of developing diabetes.
Study limitations include a preponderance of men in an occupational cohort derived from 1 ethnic group, and use of ultrasound to identify fatty liver, which picks up moderate fatty liver disease (ie, >30% liver fat infiltration) but not minor amounts of fatty liver infiltration. In addition, no data were available on family history of diabetes, use of drugs, and other key information that may increase one’s risk of diabetes.
"Further research is needed to understand the separate pathogenetic mechanisms by which IR, overweight/obesity, and fatty liver contribute individually to the development of type 2 diabetes," the authors write, noting that the efficacy of lifestyle and pharmaceutical interventions may vary for different combinations of risk factors.
The study was partially supported by a grant from Samsung Biomedical Research, as well as in part by the Southampton National Institute for Health Research Biomedical Research Unit in Nutrition, Lifestyle and Obesity. The authors have disclosed no relevant conflicts of interest.
Diabetes Care. Published online February 14, 2012. Abstract