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

Key Points

Question  Do cranberry capsules with sufficient proanthocyanidin content affect the presence of bacteriuria plus pyuria in older women living in nursing homes?

Findings  In this randomized clinical trial of 185 women nursing home residents, after adjusting for missing data and covariates, there was no statistically significant difference in presence of bacteriuria plus pyuria between the treatment (29.1%) and control (29.0%) groups over 1 year.

Meaning  Among older women living in nursing homes, cranberry capsules, compared with placebo, did not have a significant effect on the presence of bacteriuria plus pyuria over 1 year.


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

OnabotulinumtoxinA vs Sacral Neuromodulation on Refractory Urgency Urinary Incontinence in Women A Randomized Clinical Trial

Importance  Women with refractory urgency urinary incontinence are treated with sacral neuromodulation and onabotulinumtoxinA with limited comparative information.

Objective  To assess whether onabotulinumtoxinA is superior to sacral neuromodulation in controlling refractory episodes of urgency urinary incontinence.

Design, Setting, and Participants  Multicenter open-label randomized trial (February 2012-January 2015) at 9 US medical centers involving 381 women with refractory urgency urinary incontinence.

Interventions  Cystoscopic intradetrusor injection of 200 U of onabotulinumtoxinA (n = 192) or sacral neuromodulation (n = 189).

Main Outcomes and Measures  Primary outcome, change from baseline mean number of daily urgency urinary incontinence episodes over 6 months, was measured with monthly 3-day diaries. Secondary outcomes included change from baseline in urinary symptom scores in the Overactive Bladder Questionnaire Short Form (SF); range, 0-100, higher scores indicating worse symptoms; Overactive Bladder Satisfaction questionnaire; range, 0-100; includes 5 subscales, higher scores indicating better satisfaction; and adverse events.

Results  Of the 364 women (mean [SD] age, 63.0 [11.6] years) in the intention-to-treat population, 190 women in the onabotulinumtoxinA group had a greater reduction in 6-month mean number of episodes of urgency incontinence per day than did the 174 in the sacral neuromodulation group (−3.9 vs −3.3 episodes per day; mean difference, 0.63; 95% CI, 0.13 to 1.14; P = .01). Participants treated with onabotulinumtoxinA showed greater improvement in the Overactive Bladder Questionnaire SF for symptom bother (−46.7 vs −38.6; mean difference, 8.1; 95% CI, 3.0 to 13.3; P = .002); treatment satisfaction (67.7 vs 59.8; mean difference, 7.8; 95% CI, 1.6 to 14.1;P = .01) and treatment endorsement (78.1 vs 67.6; mean difference; 10.4, 95% CI, 4.3 to 16.5; P < .001) than treatment with sacral neuromodulation. There were no differences in convenience (67.6 vs 70.2; mean difference, −2.5; 95% CI, −8.1 to 3.0; P = .36), adverse effects (88.4 vs 85.1; mean difference, 3.3; 95% CI, −1.9 to 8.5; P = .22), and treatment preference (92.% vs 89%; risk difference, −3%; 95% CI, −16% to 10%; P = .49). Urinary tract infections were more frequent in the onabotulinumtoxinA group (35% vs 11%; risk difference, −23%; 95% CI, −33% to −13%; P < .001). The need for self-catheterization was 8% and 2% at 1 and 6 months in the onabotulinumtoxinA group. Neuromodulation device revisions and removals occurred in 3%.

Conclusions and Relevance  Among women with refractory urgency urinary incontinence, treatment with onabotulinumtoxinA compared with sacral neuromodulation resulted in a small daily improvement in episodes that although statistically significant is of uncertain clinical importance. In addition, it resulted in a higher risk of urinary tract infections and need for transient self-catheterizations.

Migraine and risk of cardiovascular disease in women: prospective cohort study

Objective To evaluate the association between migraine and incident cardiovascular disease and cardiovascular mortality in women.

Design Prospective cohort study among Nurses’ Health Study II participants, with follow-up from 1989 and through June 2011.

Setting Cohort of female nurses in United States.

Participants 115 541 women aged 25-42 years at baseline and free of angina and cardiovascular disease. Cumulative follow-up rates were more than 90%.

Main outcome measures The primary outcome of the study was major cardiovascular disease, a combined endpoint of myocardial infarction, stroke, or fatal cardiovascular disease. Secondary outcome measures included individual endpoints of myocardial infarction, stroke, angina/coronary revascularization procedures, and cardiovascular mortality.

Results 17 531 (15.2%) women reported a physician’s diagnosis of migraine. Over 20 years of follow-up, 1329 major cardiovascular disease events occurred and 223 women died from cardiovascular disease. After adjustment for potential confounding factors, migraine was associated with an increased risk for major cardiovascular disease (hazard ratio 1.50, 95% confidence interval 1.33 to 1.69), myocardial infarction (1.39, 1.18 to 1.64), stroke (1.62, 1.37 to 1.92), and angina/coronary revascularization procedures (1.73, 1.29 to 2.32), compared with women without migraine. Furthermore, migraine was associated with a significantly increased risk for cardiovascular disease mortality (hazard ratio 1.37, 1.02 to 1.83). Associations were similar across subgroups of women, including by age (<50/≥50), smoking status (current/past/never), hypertension (yes/no), postmenopausal hormone therapy (current/not current), and oral contraceptive use (current/not current).

Conclusions Results of this large, prospective cohort study in women with more than 20 years of follow-up indicate a consistent link between migraine and cardiovascular disease events, including cardiovascular mortality. Women with migraine should be evaluated for their vascular risk. Future targeted research is warranted to identify preventive strategies to reduce the risk of future cardiovascular disease among patients with migraine.

BMJ 2016;353:i2610

Association Between Rotating Night Shift Work and Risk of Coronary Heart Disease Among Women

Importance  Prospective studies linking shift work to coronary heart disease (CHD) have been inconsistent and limited by short follow-up.

Objective  To determine whether rotating night shift work is associated with CHD risk.

Design, Setting, and Participants  Prospective cohort study of 189 158 initially healthy women followed up over 24 years in the Nurses’ Health Studies (NHS [1988-2012]: N = 73 623 and NHS2 [1989-2013]: N = 115 535).

Exposures  Lifetime history of rotating night shift work (≥3 night shifts per month in addition to day and evening shifts) at baseline (updated every 2 to 4 years in the NHS2).

Main Outcomes and Measures  Incident CHD; ie, nonfatal myocardial infarction, CHD death, angiogram-confirmed angina pectoris, coronary artery bypass graft surgery, stents, and angioplasty.

Results  During follow-up, 7303 incident CHD cases occurred in the NHS (mean age at baseline, 54.5 years) and 3519 cases in the NHS2 (mean age, 34.8 years). In multivariable-adjusted Cox proportional hazards models, increasing years of baseline rotating night shift work were associated with a significantly higher CHD risk in both cohorts. In the NHS, the age-standardized incidence rate (IR) for less than 5 years of rotating night shift work per 100 000 person-years was 435.1 (hazard ratio [HR], 1.02; 95% CI, 0.97-1.08); the IR for 5 to 9 years of rotating night shift work was 525.7 (HR, 1.12; 95% CI, 1.02-1.22); and the IR for 10 years or more of rotating night shift work was 596.9 (HR, 1.18; 95% CI, 1.10-1.26; P<.001 for trend) vs an IR of 425.5 in women who never worked rotating night shifts. In the NHS2, the IR for less than 5 years was 130.6 (HR, 1.05; 95% CI, 0.97-1.13); the IR for 5 to 9 years was 151.6 (HR,1.12; 95% CI, 0.99-1.26); and the IR for 10 years or more was 178.0 (HR, 1.15; 95% CI, 1.01-1.32; P = .01 for trend) vs an IR of 122.6 in women who never worked rotating night shifts. In the NHS, the association between duration of rotating night shift work and CHD was stronger in the first half of follow-up (IR for <5 years, 382.4; HR, 1.10 [95% CI, 1.01-1.21]; IR for 5-9 years, 483.1; HR, 1.19 [95% CI, 1.03-1.39]; and IR for ≥10 years, 494.4; HR, 1.27 [95% CI, 1.13-1.42]; P<.001 for trend) than in the second half (IR for <5 years, 424.8; HR, 0.98 [95% CI, 0.92-1.05]; IR for 5-9 years, 520.7; HR, 1.08 [95% CI, 0.96-1.21]; IR for ≥10 years, 556.2; HR, 1.13 [95% CI, 1.04-1.24]; P = .004 for trend; P = .02 for interaction), suggestive of waning risk after cessation of shift work. Longer time since quitting shift work was associated with decreased CHD risk among ever shift workers in the NHS2 (P<.001 for trend).

Conclusions and Relevance  Among women who worked as registered nurses, longer duration of rotating night shift work was associated with a statistically significant but small absolute increase in CHD risk. Further research is needed to explore whether the association is related to specific work hours and individual characteristics.

JAMA. 2016;315(16):1726-1734. doi:10.1001/jama.2016.4454.