Clinical Health Updates

Antibiotics and nasal steroids of little/no benefit for acute sinusitis

Clinical Question:
Are antibiotics or nasal steroids truly beneficial in the treatment of acute maxillary sinusitis?

Bottom Line:
Neither an antibiotic nor a topical steroid alone or in combination was effective as a treatment for acute sinusitis in the primary care setting.

Reference:
Williamson IG, Rumsby K, Benge S, et al. Antibiotics and topical nasal steroid for treatment of acute maxillary sinusitis. A randomized controlled trial. JAMA 2007;298(21):2487-2496.

Study Design:
Randomized controlled trial (double-blinded)

Synopsis:
Acute sinusitis is a common clinical problem that usually results in a prescription for antibiotics but the role of antibiotics is debated. Anti-inflammatory drugs such as topical steroids may be beneficial but are underresearched. The authors determine the effectiveness of amoxicillin and topical budesonide in acute maxillary sinusitis. They did a double-blind, randomized, placebo-controlled factorial trial of 240 adults (aged > or =16 years) with acute nonrecurrent sinusitis (had > or =2 diagnostic criteria: purulent rhinorrhea with unilateral predominance, local pain with unilateral predominance, purulent rhinorrhea bilateral, presence of pus in the nasal cavity) at 58 family practices (74 family physicians) between November 2001 and November 2005. Patients were randomized to 1 of 4 treatment groups: antibiotic and nasal steroid; placebo antibiotic and nasal steroid; antibiotic and placebo nasal steroid; placebo antibiotic and placebo nasal steroid. A dose of 500 mg of amoxicillin 3 times per day for 7 days and 200 mug of budesonide in each nostril once per day for 10 days. Proportion clinically cured at day 10 using patient symptom diaries and the duration and severity of symptoms. The proportions of patients with symptoms lasting 10 or more days were 29 of 100 (29%) for amoxicillin vs 36 of 107 (33.6%) for no amoxicillin (adjusted odds ratio, 0.99; 95% confidence interval, 0.57-1.73). The proportions of patients with symptoms lasting 10 or more days were 32 of 102 (31.4%) for topical budesonide vs 33 of 105 (31.4%) for no budesonide (adjusted odds ratio, 0.93; 95% confidence interval, 0.54-1.62). Secondary analysis suggested that nasal steroids were significantly more effective in patients with less severe symptoms at baseline.

Moderate-severe pain unusual following zoster

Clinical Question:
What is the natural history of pain following herpes zoster?

Bottom Line:
In a longitudinal observational study of 94 patients (39 M:55 F, mean age 69) at elevated risk for developing post herpetic neuralgia (PHN), the natural history of pain during the first 6 months after herpes zoster (HZ) rash onset was determined. Pain severity and impact were rated using pain-VAS, SF-MPQ, and MPI. Applying a definition of PHN of average daily pain >0/100 on the pain VAS during the last 48 h, 30 subjects had PHN at 6 months. These 30 subjects reported more pain and a higher SF-MPQ score (p<0.01)> or = 30/100 on the pain VAS). Defining PHN as average daily pain >0/100 at 6 months after rash onset appears to substantially overestimate the number of HZ patients negatively impacted by ongoing pain and disability.

Reference:
Thyregod HG, Rowbotham MC, Peters M, Possehn J, Berro M, Petersen KL. Natural history of pain following herpes zoster. Pain 2007;128:148-156.

Study Design:
Cohort (retrospective)

Synopsis:
The likelihood and severity of PHN has not been well-described in the medical literature, and definitions vary as to what it actually is. To evaluate the natural history of PHN, these investigators enrolled 94 immunocompetent subjects who all completed the 6-month study. All had herpes zoster on the neck or trunk producing pain of at least 20 on a 0 to 100-mm visual analog scale (VAS). The patients were recruited through newspaper advertisements, physician referrals, and community outreach programs in San Francisco. The majority of patients received antiviral treatment. Using a definition of pain as a any score greater than 0 on the VAS, 50% of patients had pain at 3 months and 32% still reported pain at 6 months. The average pain score at 6 months was 11. However, “clinically relevant pain,” defined as a score greater than 30 mm on the VAS, was present in only 3% of patients at 3 months and only 2% of patients at 6 months. Patients with pain were more likely to have zoster in the cervical and lumbar regions.

Hep C infection increases risk of non-Hodgkin lymphoma

Clinical Question:
Does hepatitis C virus infection increase the risk of non-Hodgkin lymphoma?

Bottom Line:
Hepatitis C virus infection confers a 20% to 30% increased risk of non-Hodgkin lymphoma overall, and a 3-fold higher risk of Waldenström macroglobulinemia, a low-grade lymphoma. Risks were also increased for cryoglobulinemia. These results support an etiological role for HCV in causing lymphoproliferation and causing non-Hodgkin lymphoma.

Reference:
Giordano TP, Henderson L, Landgren O, et al. Risk of non-Hodgkin lymphoma and lymphoprolierative precursor disease in UA veterans with hepatitis C virus. JAMA 2007;297:2010-2017.

Study Design:
Cohort (retrospective)

Synopsis:
These investigators conducted a large population-based retrospective cohort study including 146,394 US veterans infected with hepatitis C virus (HCV). Cases were compared with 572,303 noninfected control patients matched to sex and age. Individuals blinded to HCV status reviewed inpatient and outpatient records and death registries from more than 150 veterans’ hospitals in the United States. Nearly all patients (97%) were male, with a mean age of 52 years. Data from 1989 through 2004 were included. HCV-infected patients were significantly more likely to develop non-Hodgkin lymphoma. In addition, a significantly increased risk of Waldenstrom macroglobulinemia and cryoglobulinemia occurred in HCV-infected individuals. Both of these diseases are considered related lymphoproliferative precursors to lymphoma. No increased risk of other hematologic malignancies or thyroid cancer was detected.

Drotrecogin ineffective in septic children (RESOLVE)

Clinical Question:
Is drotrecogin effective in treating septic children?

Bottom Line:
Drotrecogin (Xigris) is no more effective than placebo in improving outcomes in septic children.

Reference:
Nadel S, Goldstein B, Williams MD, et al for the REsearching severe Sepsis and Organ dysfunction in children: a gLobal perspective (RESOLVE) study group. Drotrecogin alfa (activated) in children with severe sepsis: a multicentre phase III randomised controlled trial. Lancet 2007;369:836-843.

Study Design:
Randomized controlled trial (double-blinded)

Synopsis:
Drotrecogin alfa (activated) (DrotAA) is used for the treatment of adults with severe sepsis who have a high risk of dying. A phase 1b open-label study has indicated that the pharmacokinetics and pharmacodynamics of DrotAA are similar in children and adults. The authors initiated the RESOLVE (REsearching severe Sepsis and Organ dysfunction in children: a gLobal perspectiVE) trial to investigate the efficacy and safety of the drug in children. They recruited children aged between 38 weeks’ corrected gestational age and 17 years with sepsis-induced cardiovascular and respiratory failure were randomly assigned to receive placebo or DrotAA (24 microg/kg/h) for 96 h. We used a prospectively defined, novel primary endpoint of Composite Time to Complete Organ Failure Resolution (CTCOFR) score. Secondary endpoints were 28-day mortality, major amputations, and safety. Analysis was by intention-to-treat. This trial is registered with clinicaltrials.gov, number NCT00049764. As to their finfings, 477 patients were enrolled; 237 received placebo, and 240 DrotAA. Results showed no significant difference between groups in CTCOFR score (p=0.72) or in 28-day mortality (placebo 17.5%; DrotAA, 17.2%; p=0.93). Although there was no difference in overall serious bleeding events during the 28-day study period (placebo 6.8%; DrotAA 6.7%; p=0.97), there were numerically more instances of CNS bleeding in the DrotAA group (11 [4.6%], vs 5 [2.1%] in placebo, p=0.13), particularly in children younger than 60 days. For CTCOFR score days 1-14, correlation coefficient was -0.016 (95% CI -0.106 to 0.74); relative risk for 28-day mortality was 1.06 (95% CI 0.66 to 1.46) for DrotAA compared with placebo.

Yogurt prevents antibiotic-associated diarrhea

Clinical Question:
Is yogurt effective in the prevention of antibiotic-associated diarrhea?

Bottom Line:
Dietary supplementation with Vanilla-flavored yogurt is a simple, effective, and safe treatment that decreases the incidence and duration of antibiotic-associated diarrhea (AAD) . Tell your patients to look for yogurt that contains active cultures. If they can’t find it, consider probiotic agents.

Reference:
Beniwal RS, Arena VC, Thomas L, et al. A randomized trial of yogurt for prevention of antibiotic-associated diarrhea. Dig Dis Science 2003; 48:2077-82.

Study Design:
Randomized controlled trial (nonblinded)

Synopsis:
The authors determined the effectiveness of a dietary supplement of yogurt for prevention of AAD. Two hundred two hospitalized patients receiving oral or intravenous antibiotics were randomized to receive or not receive a dietary yogurt supplement, consisting of 227 grams of commercial yogurt, and followed for 8 days. Mean age of the study group was 70 years and 43% were male. Compliance and 8-day follow-up were 85% and 91%, respectively. Patients receiving yogurt reported less frequent diarrhea (12% vs 24%; P = 0.04), and significantly less total diarrhea] days (23 vs 60). The cumulative proportions of patients without diarrhea were significantly different (P = 0.02) between patients receiving and not receiving yogurt.

Dapsone gel effective for acne vulgaris treatment

Clinical Question:
Is dapsone gel 5% effective in the treatment of acne vulgaris?

Bottom Line:
Dapsone gel 5% (Aczone) is marginally more effective than placebo (NNT = 13, 9-23) in the treatment of acne vulgaris. At 12 weeks of treatment, less than half the patients in the treatment group received acne assessment scores of “none” or “minimal”. No serious adverse events were reported, but data from follow-up longer than 3 months is forthcoming.

Reference:
Draelos ZD, Carter E, Maloney M, et al. Two randomized studies demonstrate the efficacy and safety of dapsone gel, 5% for the treatment of acne vulgaris. J Am Acad Dermatol 2007;published online 1/4/07.

Study Design:
Randomized controlled trial (double-blinded)

Synopsis:
A new aqueous gel formulation of dapsone has been developed that allows clinically-effective doses of dapsone to be administered topically with minimal systemic absorption. The authors evaluated the efficacy and safety of dapsone gel, 5% in the treatment of acne. Patients 12 years of age and older with acne vulgaris (N = 3010) participated in two identically-designed 12-week, randomized, double-blind studies of twice-daily monotherapy with dapsone gel, 5%, versus a vehicle gel. Dapsone gel-treated patients achieved superior results in terms of the investigator’s global acne assessment (P < .001) and the mean percentage reduction in inflammatory, noninflammatory, and total lesion counts (all, P < .001) at week 12. Reductions in inflammatory lesion counts favoring dapsone gel over vehicle were apparent as early as 2 weeks and reached statistical significance by 4 weeks. No clinically significant changes in laboratory parameters, including hemoglobin, even among glucose-6-phosphate dehydrogenase-deficient patients, were observed. Adverse events were comparable between the treatment groups and rarely led to discontinuation.
LIMITATIONS:
Adjunctive topical treatments and their impact on acne were not studied in this trial.

Best way to perform lumbar puncture and analyze results

Clinical Question:
What is the optimal method for performing a lumbar puncture and for analyzing the results to accurately diagnose bacterial meningitis?

Bottom Line:
Data suggest that small-gauge, atraumatic needles may decrease the risk of headache after diagnostic LP. Reinsertion of the stylet before needle removal should occur and patients do not require bed rest after the procedure. Future research should focus on evaluating interventions to optimize the success of a diagnostic LP and to enhance training in procedural skills.

Reference:
Straus SE, Thorpe KE, Holroyd-Leduc J. How do I perform a lumbar puncture and analyze the results to diagnose bacterial meningitis? JAMA 2006;296:2012-2022.

Study Design:
Systematic review

Synopsis:
Diagnostic lumbar punctures (LPs), commonly used to rule out meningitis, are associated with adverse events. The authors systematically review the evidence about diagnostic LP techniques that may decrease the risk of adverse events and the evidence about test accuracy of cerebrospinal fluid (CSF) analysis in adult patients with suspected bacterial meningitis. They searched the Cochrane Library, MEDLINE (using Ovid and PubMed) from 1966 to January 2006 and EMBASE from 1980 to January 2006 without language restrictions to identify relevant studies and identified others from the bibliographies of retrieved articles. They included randomized trials of patients aged 18 years or older undergoing interventions to facilitate a successful diagnostic LP or to potentially reduce adverse events. Studies assessing the accuracy of biochemical analysis of the CSF for possible bacterial meningitis were also identified. Two investigators independently appraised study quality and extracted relevant data. For studies of the LP technique, data on the intervention and the outcome were extracted. For studies of the laboratory diagnosis of bacterial meningitis, data on the reference standard and test accuracy were extracted. They found 15 randomized trials. A random-effects model was used for quantitative synthesis. Five studies of 587 patients compared atraumatic needles with standard needles and found a nonsignificant decrease in the odds of headache with an atraumatic needle (absolute risk reduction [ARR], 12.3%; 95% confidence interval [CI], -1.72% to 26.2%). Reinsertion of the stylet before needle removal decreased the risk of headache (ARR, 11.3%; 95% CI, 6.50%-16.2%). The combined results from 4 studies of 717 patients showed a nonsignificant decrease in headache in patients who were mobilized after LP (ARR, 2.9%; 95% CI, -3.4 to 9.3%). Four studies on the accuracy of biochemical analysis of CSF in patients with suspected meningitis met inclusion criteria. A CSF-blood glucose ratio of 0.4 or less (likelihood ratio [LR], 18; 95% CI, 12-27]), CSF white blood cell count of 500/muL or higher (LR, 15; 95% CI, 10-22), and CSF lactate level of 31.53 mg/dL or more (> or =3.5 mmol/L; LR, 21; 95% CI, 14-32) accurately diagnosed bacterial meningitis.

Effective methods for preventing pressure ulcers

Clinical Question:
Which interventions are effective for the prevention of pressure ulcers?

Bottom Line:
Given current evidence, using support surfaces, repositioning the patient, optimizing nutritional status, and moisturizing sacral skin are appropriate strategies to prevent pressure ulcers. Although a number of RCTs have evaluated preventive strategies for pressure ulcers, many of them had important methodological limitations. There is a need for well-designed RCTs that follow standard criteria for reporting nonpharmacological interventions and that provide data on cost-effectiveness for these interventions.

Reference:
Reddy M, Gill SS. Rochon PA. Preventing pressure ulcers: a systematic review. JAMA 2006;296:974-984.

Study Design:
Systematic review

Synopsis:
Multiple preventive approaches are used in the management of pressure ulcers. These authors systematically searched multiple evidence-based databases including the Cochrane Registry, bibliographies of identified articles, and scientific meeting abstracts for randomized controlled trials (RCTs) evaluating preventive measures for pressure ulcers. No language restrictions were applied. They used standard methods to critically appraise individual RCTs. The search strategy identified 763 citations, from which 59 trials meeting eligibility criteria were selected. The methodologic quality of the RCTs was generally suboptimal. Interventions were grouped into 3 categories: those addressing impairments in (1) mobility, (2) nutrition, and (3) skin health. Effective strategies for those with impaired mobility included the use of support surfaces (mattresses, beds, and cushions), mattress overlays on operating tables, and specialized foam and sheepskin overlays. Frequent repositioning is effective, but the optimal schedule for turning (every 2 vs every 4 hours) is uncertain. Nutritional supplements are beneficial in patients with impaired nutrition. Simple skin moisturizers, specifically to the sacral area, were helpful, but the incremental benefit of other specific topical agents is minimal.

Effect of Lactobacillus casei on the incidence of infectious conditions in children

Clinical Question:
Does Lactobacillus casei reduced duration and incidence of infectious disorders in children?

Bottom Line:
The study shows a tendency to the reduction of duration and incidence of some infectious disorders in those children receiving two daily Actimel during 20 weeks.

Reference:
Effect of Lactobacillus casei on the incidence of infectious conditions in children, Cobo Sanz JM, Mateos JA, Munoz Conejo A.Nutr Hosp. 2006 Jul-Aug;21(4):547-51

Study Design:
Randomized Controlled Trial (double blind)

Synopsis:
To analyse the effect of continuous consumption of Lactobacillus casei (DN-114001) fermented milk on the incidence of the infectious disorders frequent in children. The authors studied children from 3 to 12 years from two schools in Barcelona. A total of 251 children from both sexes participated in the study. A nutritional intervention study was carried out during 20 weeks with a parallel, prospective, double-blind and randomised by pragmatic clusters design. Participants were children from 3 to 12 years from two schools in Barcelona. One of the centres was assigned to receive two daily units of Actimel” and the other to two units of Placebo. From the 251 participants, 109 receiving placebo and 142 receiving Actimel”. Basal demographic characteristics and clinical history data were recorded, and the symptoms related to infectious disorders or other illnesses were monitored at weeks 12, 16 and 20. The analysis of the data was carried out on the intention-to-treat (ITT) population, being the principal endpoint the duration of respiratory and gastrointestinal symptoms. A one day difference, but non-significant, was seen in the median of total duration of days with illness through the study (Actimel group: 1 day vs Placebo group: 2 days). The same nonsignificant difference was also seen in the duration of days with respiratory (high and low respiratory tract infections) and with gastrointestinal (diarrhoea, vomiting, stomach pain and constipation) disorders. There was a statistical significantly difference found in favour of Actimel in the duration of the low respiratory tract infections, bronchitis or pneumonia, and in the duration of fatigue. There was also detected a lower incidence of children with low respiratory tract infections (32% vs. 49%) and with fatigue (3% vs. 13%) in the Actimel group compared to placebo. The satisfaction levels with the nutritional intervention were very high, over 80%.