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Context: The impact of clinical decision support systems (CDSS) on antimicrobial prescribing in ambulatory settings has not previously been evaluated., Objective: To measure the added value of CDSS when coupled with a community intervention to reduce inappropriate prescribing of antimicrobial drugs for acute respiratory tract infections., Design, Participants and Setting: Cluster randomized trial that included 407,460 inhabitants and 334 primary care clinicians in 12 rural communities in Utah and Idaho (6 with 1 shared characteristic and 6 with another), and a third group of 6 communities that served as nonstudy controls. The preintervention period was January to December 2001 and the postintervention period was January 2002 to September 2003. Acute respiratory tract infection diagnoses were classified into groups based on indication for antimicrobial use. Multilevel regression methods were applied to account for the clustered design., Intervention: Six communities received a community intervention alone and 6 communities received community intervention plus CDSS that were targeted toward primary care clinicians. The CDSS comprised decision support tools on paper and a handheld computer to guide diagnosis and management of acute respiratory tract infection., Main Outcome Measure: Community-wide antimicrobial usage was assessed using retail pharmacy data. Diagnosis-specific antimicrobial use was compared by chart review., Results: Within CDSS communities, 71% of primary care clinicians participated in the use of CDSS. The prescribing rate decreased from 84.1 to 75.3 per 100 person-years in the CDSS arm vs 84.3 to 85.2 in community intervention alone, and remained stable in the other communities (P = .03). A total of 13,081 acute respiratory tract infection visits were abstracted. The relative decrease in antimicrobial prescribing for visits in the antibiotics "never-indicated" category during the post-intervention period was 32% in CDSS communities and 5% in community intervention-alone communities (P = .03). Use of macrolides decreased significantly in CDSS communities but not in community intervention-alone communities., Conclusion: CDSS implemented in rural primary care settings reduced overall antimicrobial use and improved appropriateness of antimicrobial selection for acute respiratory tract infections., Trial Registration: ClinicalTrials.gov Identifier: NCT00235703.

Background: Use of the heptavalent pneumococcal conjugate vaccine (PCV-7 [Prevnar]) has been associated with decreased a incidence of invasive pneumococcal disease (IPD) among children in the United States., Methods: Cases of IPD in children < 18 years of age insured by or receiving health care from Intermountain Health Care during 1996-2003 were identified. Isolates of S. pneumoniae from children with IPD treated at Primary Children's Medical Center (PCMC; Salt Lake City, UT) during 1997-2003 were serogrouped. Temporal trends of IPD, serogroup distribution of pneumococci, and antibiotic resistance among pneumococci were analyzed., Results: A total of 1535 cases of IPD were identified. The rate of IPD decreased 27% after the introduction of PCV7. Among children with IPD who were cared for at PCMC, disease in 73% was caused by PCV7 serogroups in 1997-2000, compared with 50% in 2001-2003 (P < .001), and the percentage of isolates resistant to penicillin decreased from 34% in 1997-2000 to 22% in 2001-2003 (P = .04). The percentage of IPD cases that were empyema increased from 16% to 30% (P = .015), and the percentage of severe cases of IPD increased from 57% to 71% (P = .026). Children with IPD due to non-PCV7 serogroups were older, were more likely to have parapneumonic empyema, and had longer hospital stays., Conclusions: The incidence of IPD in the IMW decreased by 27% after the introduction of the PCV7 vaccine. During the postvaccine period (2001-2003), there were significant decreases in the proportion of cases of IPD caused by PCV7 and antibiotic-resistant serogroups. These benefits were accompanied by a significant increase in the proportion of IPD cases due to non-PCV7 serogroups, with increases in the incidence of empyema and severe IPD.

The impact and prevalence of antimicrobial drug resistance in rural community healthcare settings is uncertain. Prospective surveillance in 51 rural hospitals in Idaho and Utah examined the epidemiologic features of clinical cases of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Thirty-two cases of VRE were reported; for 6, the patient had no prior healthcare exposure or coexisting condition. Among the 724 MRSA cases available for evaluation, 405 (56%) were healthcare-associated (HA-MRSA), and 319 (44%) were community-associated (CA-MRSA). The characteristics of HA-MRSA and CA-MRSA patients with coexisting factors were similar, which suggests community transmission of healthcare strains. CA-MRSA cases without coexisting factors, however, demonstrated features previously reported for community strains. MRSA infections were substantially more frequent than VRE in rural communities in the western United States. Based on epidemiologic criteria, a large proportion of MRSA cases were community-associated. CA-MRSA rates were predictive of institutional MRSA rates.

Background: Antibiotic prescribing for upper respiratory tract infections (URTIs) is widespread, is often inappropriate, and may contribute to antibiotic resistance among community-acquired pathogens, such as Streptococcus pneumoniae., Methods: A multifaceted intervention involving health care professionals and patients was introduced to a small rural Utah community and included the repetitive use of printed diagnostic and treatment algorithms by professionals. Data on the quantity and class of antibiotic prescribing, which were collected from multiple sources, were measured for the intervention period (from January through June) in 2001 and compared with data for the baseline period during the same months in 2000., Results: Medicaid claims data revealed that the percentage of patients in the community who received antibiotics for URTIs during the intervention period was 15.6% less than that for the baseline period, whereas the percentage in the rest of rural Utah was relatively stable, with a 1.5% decrease (P=.006). The greatest impact of the intervention was on prescribing for acute bronchitis (decreases of 56.1% and 1.7% in the community and rural Utah, respectively; P=.024) and on prescribing of macrolides (decreases of 13.4% and 0.2% in the community and rural Utah, respectively; P<.001). Community pharmacy data likewise revealed a 17.5% decrease in the rate of antibiotic prescribing during the intervention period (P<.001), with the largest decrease observed for macrolide prescribing (50.9%; P<.001). Chart review data, in contrast, revealed no significant decrease in the percentage of patients with URTI who were prescribed an antibiotic (3.8%; P=.49), although there was a significant decrease of 11.2% in macrolide use (P=.045)., Conclusions: A multifaceted intervention involving the repetitive use of printed algorithms resulted in modest improvements in antibiotic prescribing for outpatient URTIs, although one data source did not corroborate this. However, macrolide prescribing decreased sharply, irrespective of the source of data.

The ALS Functional Rating Scale-Revised (ALSFRS-R) is used in the clinic to chart progression and as a primary endpoint measure in clinical trials. In the original description of the scale, evaluations were to be performed by the patient or caregiver, but ratings are commonly performed by health care providers. We determined whether there are differences in scoring based on whether the provider, patient or caregiver performed the evaluation. Overall, all evaluators assessed similar changes in function over time, but significant visit-specific differences were found with higher scores when the patient and provider were the evaluators. We modeled how a change in evaluators at the end of a 9-month trial would influence statistical analysis, if the patient was unable to travel to the study site and the final assessment was performed by telephone. If 25% of the final visit assessments were performed by the patient, in place of the provider, the change in score is less than one point on the ALSFRS-R (-0.7: 95% Confidence Interval -2.1 to 0.3). We conclude that the ALSFRS-R can be successfully used even if evaluators change.

Objectives: To document the trend of ampicillin-resistant infections in newborns weighing at least 1500 g and to determine factors associated with ampicillin-resistant neonatal early-onset infection in the era of routine group B streptococcal prophylaxis., Design: Case-control study., Setting: Referral hospital with level I through level III nurseries.Patients Newborns aged 0 to 7 days with cultures positive for bacterial infection, born from January 1994 to August 2002 (n = 53). Random controls were matched to admission year and nursery level (n = 159)., Main Outcome Measures: Trends of and factors associated with ampicillin-resistant infections., Results: Trends in our institution were the same as those found in some recent reports, a decrease in group B streptococcal early-onset infections without a concomitant increase in gram-negative early-onset infections. Specifically, when stratified by birth weight, newborns weighing at least 1500 g had no increase in gram-negative pathogens in the eras both before and after group B streptococcal prophylaxis (0.8 per 1000 live births to 0.3 per 1000 live births; incidence ratio, 2.3 [95% confidence interval, 0.5-10.9]). No increase in ampicillin resistance was seen during the same 3 periods (50%, 60%, and 50%, respectively; P =.97). Independent risk factors associated with ampicillin-resistant early-onset infection were intrapartum antibiotics for a 24-hour duration or longer (odds ratio, 4.8 [95% confidence interval, 1.0-23.3]) and clinical chorioamnionitis (odds ratio, 9.2 [95% confidence interval, 2.6-32.9])., Conclusions: No increase in early-onset infections with gram-negative or ampicillin-resistant pathogens was detected. Ampicillin-resistant early-onset infection was associated with intrapartum antibiotics given for 24 hours or longer prior to delivery and with clinical chorioamnionitis. Ampicillin sodium and gentamicin sulfate remain appropriate initial antibiotic therapies for early-onset infection in newborns weighing at least 1500 g and without these risk factors.

Previous studies showed that sicker patients were initiated on dialysis at higher GFR as estimated by the Modification of Diet in Renal Disease (MDRD) formula. It was previously shown that patients with low creatinine production were malnourished and had low serum creatinine levels and creatinine clearances (CrCl) but high MDRD GFR at initiation of dialysis. Therefore, a propensity score approach was used to examine the associations of MDRD GFR and measured CrCl at the initiation of dialysis with subsequent mortality. Baseline data and outcomes were obtained from the Dialysis Morbidity Mortality Study Wave II. Propensity scores for early initiation derived by logistic regression were used in Cox models to examine mortality. Each 5-ml/min increase in MDRD GFR at initiation of dialysis in the entire cohort was associated with increased hazard of death in multivariable Cox model (hazard ratio [HR] 1.14; P = 0.002). In the subgroup of patients with reported CrCl, higher MDRD GFR was associated with increased risk of death (for each 5-ml/min increase, HR 1.27; P < 0.001) but not CrCl (for each 5-ml/min increase, HR 0.98; P = 0.81). These divergent results might reflect erroneous GFR estimation by the MDRD formula. Furthermore, these data do not support earlier initiation of dialysis. Therefore, for patients without clinical indications for initiation of dialysis, the appropriate GFR level for initiation of dialysis is unknown.

This study examined the validity and clinical implications of the assumption of the Modification of Diet in Renal Disease Study (MDRD) formula that age, gender, race, and BUN account for creatinine production (CP). The relationships of MDRD GFR, CP, and nutrition were examined in 1074 Dialysis Morbidity and Mortality Study Wave II patients with reported measured creatinine clearances at initiation of dialysis. Age, gender, race, BUN, and serum creatinine (Scr) were used to calculate MDRD GFR. The measured 24-h urinary creatinine was used to estimate CP. In linear regression, Scr positively correlated with CP independent of age, gender, race, and BUN. Compared with the highest CP quartile, the lowest CP quartile had lower creatinine clearance (5.8 +/- 2.9 versus 11.3 +/- 3.4 ml/min, P <.01) despite lower Scr (5.8 +/- 2.6 versus 8.6 +/- 3.1 mg%, P <.01). There was an excellent correlation between the reciprocal of Scr and the MDRD GFR (r = 0.90). As a result, the MDRD GFR was higher in the lowest CP quartile (10.9 +/- 4.6 versus 7.6 +/- 2.4 ml/min, P <.01). Malnutrition (48% versus 26%, P <.01) was more common in the lowest CP quartile. Each 5-ml/min increase in MDRD GFR was associated with 21% higher odds of malnutrition (P = 0.046) in a multivariable logistic regression, which was abolished by controlling for CP. The fundamental assumption of the MDRD formula is invalid in patients with advanced renal failure, and the use of this formula in these patients might introduce biases.

Nitric oxide (NO) production and mononuclear cell NO synthase 2 (NOS2) expression are high in healthy Tanzanian children but low in those with cerebral malaria. Factors that downregulate NOS2 also diminish factors involved in cellular uptake and biosynthesis of L-arginine, the substrate for NO synthesis. We therefore postulated that L-arginine concentrations would be low in individuals with cerebral malaria. We measured concentrations of L-arginine in cryopreserved plasma samples from Tanzanian children with and without malaria. L-arginine concentrations were low in individuals with cerebral malaria (mean 46 micromol/L, SD 14), intermediate in those with uncomplicated malaria (70 micromol/L, 20), and within the normal range in healthy controls (122 micromol/L, 22; p<0.0001). Analysis by logistic regression showed that hypoargininaemia was significantly associated with cerebral malaria case-fatality. Hypoargininaemia may contribute to limited NO production in children with cerebral malaria and to severe disease.

Purpose: Dialysis patients frequently have comorbid conditions. We examined the effects of age and comorbid conditions on technique failure (i.e., transfer to hemodialysis), death, hospital costs, and kidney transplantation in patients treated with peritoneal dialysis., Methods: We studied 97 patients who began peritoneal dialysis from January 1, 1993, to December 31, 1998, at the University of Pittsburgh outpatient dialysis unit. Demographic characteristics, comorbid conditions, and outcomes were determined by reviewing the Medical Archival Retrieval System database and outpatient records. Because the comorbidity (Charlson) score was colinear with age, we used a modified version of the score without an age component. Low, moderate, and high comorbidity groups were defined based on the 33rd and 66th percentiles of the comorbidity score., Results: In multivariate-adjusted models, each decade increase in age was associated with an increased risk of death (hazard ratio [HR] = 1.7; 95% confidence interval [CI]: 1.1 to 2.5) and technique failure (HR = 1.5; 95% CI: 1.0 to 2.3). High (versus low) comorbidity was associated with an increased risk of death or technique failure (HR = 3.5; 95% CI: 1.0 to 12) and significantly higher average inpatient costs. There were no differences in age or comorbidity score between patients who transferred to hemodialysis and those who died., Conclusion: Patients who are older and more ill have a greater risk of death and of transfer to hemodialysis from peritoneal dialysis.