Effect of Cranberry Capsules on Bacteriuria Plus Pyuria Among Older Women in Nursing Homes: A Randomized Clinical Trial.

Importance: Bacteriuria plus pyuria is highly prevalent among older women living in nursing homes. Cranberry capsules are an understudied, nonantimicrobial prevention strategy used in this population. Objective: To test the effect of 2 oral cranberry capsules once a day on presence of bacteriuria plus pyuria among women residing in nursing homes. Design, Setting, and Participants: Double-blind, randomized, placebo-controlled efficacy trial with stratification by nursing home and involving 185 English-speaking women aged 65 years or older, with or without bacteriuria plus pyuria at baseline, residing in 21 nursing homes located within 50 miles (80 km) of New Haven, Connecticut (August 24, 2012-October 26, 2015). Interventions: Two oral cranberry capsules, each capsule containing 36 mg of the active ingredient proanthocyanidin (ie, 72 mg total, equivalent to 20 ounces of cranberry juice) vs placebo administered once a day in 92 treatment and 93 control group participants. Main Outcomes and Measures: Presence of bacteriuria (ie, at least 105 colony-forming units [CFUs] per milliliter of 1 or 2 microorganisms in urine culture) plus pyuria (ie, any number of white blood cells on urinalysis) assessed every 2 months over the 1-year study surveillance; any positive finding was considered to meet the primary outcome. Secondary outcomes were symptomatic urinary tract infection (UTI), all-cause death, all-cause hospitalization, all multidrug antibiotic-resistant organisms, antibiotics administered for suspected UTI, and total antimicrobial administration. Results: Of the 185 randomized study participants (mean age, 86.4 years [SD, 8.2], 90.3% white, 31.4% with bacteriuria plus pyuria at baseline), 147 completed the study. Overall adherence was 80.1%. Unadjusted results showed the presence of bacteriuria plus pyuria in 25.5% (95% CI, 18.6%-33.9%) of the treatment group and in 29.5% (95% CI, 22.2%-37.9%) of the control group. The adjusted generalized estimating equations model that accounted for missing data and covariates showed no significant difference in the presence of bacteriuria plus pyuria between the treatment group vs the control group (29.1% vs 29.0%; OR, 1.01; 95% CI, 0.61-1.66; P = .98). There were no significant differences in number of symptomatic UTIs (10 episodes in the treatment group vs 12 in the control group), rates of death (17 vs 16 deaths; 20.4 vs 19.1 deaths/100 person-years; rate ratio [RR], 1.07; 95% CI, 0.54-2.12), hospitalization (33 vs 50 admissions; 39.7 vs 59.6 hospitalizations/100 person-years; RR, 0.67; 95% CI, 0.32-1.40), bacteriuria associated with multidrug-resistant gram-negative bacilli (9 vs 24 episodes; 10.8 vs 28.6 episodes/100 person-years; RR, 0.38; 95% CI, 0.10-1.46), antibiotics administered for suspected UTIs (692 vs 909 antibiotic days; 8.3 vs 10.8 antibiotic days/person-year; RR, 0.77; 95% CI, 0.44-1.33), or total antimicrobial utilization (1415 vs 1883 antimicrobial days; 17.0 vs 22.4 antimicrobial days/person-year; RR, 0.76; 95% CI, 0.46-1.25). Conclusions and Relevance: Among older women residing in nursing homes, administration of cranberry capsules vs placebo resulted in no significant difference in presence of bacteriuria plus pyuria over 1 year. Trial Registration: clinicaltrials.gov Identifier: NCT01691430.

Pilot testing of intervention protocols to prevent pneumonia in nursing home residents.

OBJECTIVES: To test intervention protocols for feasibility, staff adherence, and effectiveness in reducing pneumonia risk factors (impaired oral hygiene, swallowing difficulty) in nursing home residents. DESIGN: Prospective study. SETTING: Two nursing homes. PARTICIPANTS: Fifty-two nursing home residents. INTERVENTION: Thirty residents with impaired oral hygiene were randomly assigned to manual oral brushing plus 0.12% chlorhexidine oral rinse at different frequencies daily. Twenty-two residents with swallowing difficulty were randomly assigned to upright feeding positioning, teaching swallowing techniques, or manual oral brushing. All protocols were administered over 3 months. MEASUREMENTS: Feasibility was assessed monthly and defined as high if the protocol took less than 10 minutes to administer. Adherence was assessed weekly and defined as high if full staff adherence was demonstrated in more than 75% of assessments. Effectiveness for improved oral hygiene (reduction in oral plaque score) and swallowing (reduction in cough during swallowing) was compared at baseline and 3 months. RESULTS: Daily manual oral brushing plus 0.12% chlorhexidine rinse demonstrated high feasibility, high staff adherence, and effectiveness in improving oral hygiene (P<.001 vs baseline); this combination administered twice per day showed the highest plaque score reduction. Daily manual oral brushing and upright feeding positioning demonstrated high feasibility, high staff adherence, and effectiveness in improving swallowing. CONCLUSION: Manual oral brushing, 0.12% chlorhexidine oral rinse, and upright feeding positioning demonstrated high feasibility, high staff adherence, and effectiveness in pneumonia risk factor reduction. A protocol combining these components warrants testing for its ability to reduce pneumonia in nursing home residents.

Health outcome priorities among competing cardiovascular, fall injury, and medication-related symptom outcomes.

OBJECTIVES: To determine the priority that older adults with coexisting hypertension and fall risk give to optimizing cardiovascular outcomes versus fall- and medication symptom-related outcomes. DESIGN: Interview. SETTING: Community. PARTICIPANTS: One hundred twenty-three cognitively intact persons aged 70 and older with hypertension and fall risk. MEASUREMENTS: Discrete choice task was used to elicit the relative importance placed on reducing the risk of three outcomes: cardiovascular events, serious fall injuries, and medication symptoms. Risk estimates with and without antihypertensive medications were obtained from the literature. Participants chose between 11 pairs of options that displayed lower risks for one or two outcomes and a higher risk for the other outcome(s), versus the reverse. Results were used to calculate relative importance scores for the three outcomes. These scores, which sum to 100, reflect the relative priority participants placed on the difference between the risk estimates of each outcome. RESULTS: Sixty-two participants (50.4%) placed greater importance on reducing risk of cardiovascular events than reducing risk of the combination of fall injuries and medication symptoms; 61 participants did the converse. A lower percentage of participants with chronic obstructive pulmonary disease (P=.02), unsteadiness (P=.02), functional dependency (P=.04), lower cognition (P=.02) and depressive symptoms (P=.03) prioritized cardiovascular outcomes over fall injuries and medication symptoms than did participants without these characteristics. CONCLUSION: Interindividual variability in the face of competing outcomes supports individualizing decision-making to individual priorities. In the current example, this may mean forgoing antihypertensive medications or compromising on blood pressure reduction for some individuals.

Development of a tool for eliciting patient priority from among competing cardiovascular disease, medication-symptoms, and fall injury outcomes.

OBJECTIVES: To develop a choice task for eliciting priorities in the face of competing cardiovascular disease (CVD) outcomes, medication-related symptoms, and fall injuries. DESIGN: Conjoint analysis. SETTING: Senior housing site. PARTICIPANTS: Convenience sample of 15 senior housing residents for the pretest, 13 residents for the pilot test. MEASUREMENTS: The final task included 11 sets of choices. In each, one option optimized the risk of one or two of the three outcomes at the expense of the other(s); the second option did the reverse. Relative importance scores for CVD, fall injury, and medication-symptom outcomes were calculated. Reliability was assessed for two administrations using intraclass correlations (ICCs). Wilcoxon rank sum tests were used to evaluate order effects. RESULTS: The ICCs between choice task administrations were 0.70 for fall injuries, 0.73 for medication symptoms, and 0.56 for CVD outcomes. The ICCs with removal of two outliers were 0.84, 0.72, and 0.84, respectively. Whether CVD or fall injuries appeared first had no effect on scores. CONCLUSION: Preliminary evidence of comprehensibility and reliability supports using the choice task to determine whether individuals' priorities differ in the face of competing outcomes.

Prevaccine determination of the expression of costimulatory B7 molecules in activated monocytes predicts influenza vaccine responses in young and older adults.

BACKGROUND: Innate immunity, including Toll-like receptor (TLR)-mediated expression of the B7 costimulatory molecules CD80 and CD86, is critical for vaccine immunity. We examined whether CD80 and CD86 expression vary with aging and predict response to the trivalent inactivated influenza vaccine. METHODS: One hundred sixty-two subjects between 21 and 30 years of age (the young group) or > or =65 years of age (the older group) enrolled before vaccination. We determined TLR-induced monocyte CD80/CD86 expression by flow cytometry and vaccine antibody responses by hemagglutination inhibition. RESULTS: The mean increase in TLR-induced CD80(+) monocytes was reduced in older, compared with young, adults by 68% (P=.0002), and each decile increase of CD80(+) cells was associated with an 8.5% increase in mean number of vaccine strains with a > or =4-fold titer increase (P=.01) and a 3.8% increase in mean number of strains with a postvaccine titer > or =1 : 64 (P=.037). Each decile decrease of CD86(+) cells was associated with an 11% increase in the mean number of strains with a 4-fold increase (P=.002) and a 3.9% increase in the mean number of strains with a postvaccine titer > or =1 : 64 (P=.07). CONCLUSIONS: CD80 and CD86 expression on activated monocytes is highly associated with influenza vaccine response. This approach prospectively identifies adults unlikely to respond to immunization who may benefit from alternative vaccines or antiviral prophylaxis during influenza outbreaks.

Age-associated defect in human TLR-1/2 function.

The effects of aging on human TLR function remain incompletely understood. We assessed TLR function and expression in peripheral blood monocytes from 159 subjects in 2 age categories, 21-30 and >65 years of age, using a multivariable mixed effect model. Using flow cytometry to assess TLR-induced cytokine production, we observed a substantial, highly significant defect in TLR1/2-induced TNF-alpha (p = 0.0003) and IL-6 (p < 0.0001) production, in older adults compared with young controls. In contrast to findings in aged mice, other TLR (including TLR2/6)-induced cytokine production appeared largely intact. These differences were highly significant even after correcting for covariates including gender, race, medications, and comorbidities. This defect in TLR1/2 signaling may result from alterations in baseline TLR1 surface expression, which was decreased by 36% in older adults (p < 0.0001), whereas TLR2 surface expression was unaffected by aging. Production of IL-6 (p < 0.0001) and TNF-alpha (p = 0.003) after stimulation by N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2R,S)-propyl]-Cys-[S]-Ser1-[S]-Lys(4) trihydrochloride was strongly associated with TLR1 surface expression. Diminished TLR1/2 signaling may contribute to the increased infection-related morbidity and mortality and the impaired vaccine responses observed in aging humans.

Modifiable risk factors for nursing home-acquired pneumonia.

BACKGROUND: This study sought to identify modifiable risk factors for pneumonia in elderly nursing home residents. METHODS: A cohort of 613 elderly residents (age, >65 years) of 5 nursing homes in the New Haven, Connecticut, area was followed-up prospectively from February 2001 through March 2003. The primary outcome was radiographically documented pneumonia within a 12-month surveillance period. Baseline modifiable risk factors were evaluated for their independent association with pneumonia. RESULTS: Of 613 elderly nursing home residents, 131 (21%) died, and an additional 112 (18%) developed a radiographically documented case of pneumonia during the 12-month surveillance period. Among the 9 candidate modifiable risk factors that were evaluated individually in Cox proportional hazards models adjusting for covariates (i.e., nursing home facility, age, race, coexisting conditions, and immobility), inadequate oral care (hazard ratio [HR], 1.60; 95% confidence interval [CI], 1.06-2.35; P=.024) and swallowing difficulty (HR, 1.65; 95% CI, 1.04-2.62; P=.033) were associated with pneumonia. When modifiable risk factors were evaluated simultaneously in the same Cox proportional hazards model, inadequate oral care (HR, 1.55; 95% CI, 1.04-2.30; P=.030) and swallowing difficulty (HR, 1.61; 95% CI, 1.02-2.55; P=.043) remained independently associated with pneumonia, adjusting for the same covariates. Calculation of population-based attributable fractions showed that 21% of all cases of pneumonia in our cohort could have been avoided if inadequate oral care and swallowing difficulty were not present. CONCLUSIONS: Two biologically plausible and modifiable risk factors increased the risk of pneumonia in elderly nursing home residents. These results provide a framework for the development and testing of a targeted pneumonia prevention strategy.