Antibiotic prophylaxis after extraction of urinary catheter prevents urinary tract infections: A systematic review and meta-analysis

ObjectiveTo investigate the effect of antibiotic prophylaxis for consequent urinary tract infections (UTIs) after extraction of urinary catheter and further explore the association between the outcome and clinical characteristics of patients.MethodsWe systematically searched PubMed, Cochrane Library, EMBASE, and ClinicalTrials.gov databases through March 2020. Studies were included if they inquired into antibiotic prophylaxis for UTIs after extraction of a temporary (≤14 days) urinary catheter. We used fixed-effect models to obtain pooled risk ratio (RR) estimates. Heterogeneity was evaluated with I² value. Sensitivity analysis and subgroup analysis were also conducted to assess heterogeneity.ResultsWe finally included 8 randomized controlled trials in our study. Only 2 studies showed that antibiotic prophylaxis can reduce the consequent UTIs after extraction of urinary catheters while 6 did not. Overall, antibiotic prophylaxis was associated with reduced UTIs (RR, 0.47, 95% confidence interval [CI] 0.28-0.72, P< .01, I² = 31%). Subgroup analysis indicated that patients who are older than 60 (RR = 0.50, 95% CI: 0.33-0.76, P< .05, I² = 29%) or received Trimethoprim/sulfamethoxazole (TMP/SMX; RR = 0.21, 95% CI: 0.09-0.48, P< .01, I² = 0%) or indwelling catheters for more than 5 days (RR = 0.34, 95% CI: 0.19-0.63, P< .01, I² = 0%) could get more benefit from antibiotic prophylaxis after extraction of catheters.ConclusionsPatients with catheters removed might get benefit from antibiotic prophylaxis as a result of fewer consequent UTIs, and those who have advanced age (over 60 years old) or long-term catheterization (over 5 days) could get more benefit from prophylaxis. And TMP/SMX could be a good choice of prophylaxis for UTIs after extraction of urinary catheters. This approach should apply to high-risk patients (advanced age or long-term catheterization) due to the potential harm of widespread antibacterial agents such as side effects and bacterial resistance.     

A prospective randomized trial comparing the toxicity and safety of atovaquone with trimethoprim/sulfamethoxazole as Pneumocystis carinii pneumonia prophylaxis following autologous peripheral blood stem cell transplantation.

Pneumonia due to Pneumocystis carinii is an infrequent complication following autologous stem cell transplantation (ASCT) which is associated with a high mortality. Although administration of trimethoprim/sulfa- methoxazole (TMP/SMX) is an effective prophylactic strategy for Pneumocystis carinii pneumonia (PCP), treatment-associated toxicity frequently results in discontinuation of therapy. We have conducted a prospective randomized trial comparing atovaquone, a new anti-Pneumocystis agent, with TMP/SMX for PCP prophylaxis following autologous peripheral blood stem cell (PBSC) transplantation. Thirty-nine patients were studied. Twenty patients received atovaquone suspension and 19 patients received TMP/SMX. The median ages were 44 (range 20-68) and 47 (range 32-63) years, respectively. A similar number of patients with solid tumors (14 vs 15) and hematologic malignancies (five vs five) were treated in each group. Either TMP/SMX (160/800 mg) or atovaquone (1500 mg) was administered daily from transplant day -5 until day -1, discontinued from day 0 to engraftment, then resumed 3 days per week until day +100 post-transplant. The median time to engraftment (ANC >0.5 x 109/l) was similar in both groups. Eighty percent of the patients randomized to atovaquone prophylaxis completed the study. Four atovaquone-treated patients were removed from study; two patients (10%) did not receive a transplant and two patients (10%) were removed due to a protocol violation. None of the 16 patients treated with atovaquone experienced treatment-associated adverse effects. Of the 19 patients randomized to receive TMP/SMX, 55% completed the study. Nine TMP/SMX-treated patients were removed from the study; one patient (5%) did not receive a transplant and eight patients (40%) were removed due to drug intolerance (P < 0.003). The rate of intolerance to TMP/SMX led to the early discontinuation of this randomized trial. Intolerance of TMP/SMX included elevated transaminase levels (n = 1), nausea or vomiting (n = 3), thrombocytopenia (n = 2) and neutropenia (n = 2). All episodes of TMP/SMP intolerance occurred following transplantation after a median duration of 17.5 (range 2-48) days and a median of 7 (range 1-20) doses. Resolution of adverse side-effects occurred in all eight patients within a median of 7 (range 2-20) days following discontinuation of therapy. Neither PCP nor bacterial infections were identified in any of the patients treated. This prospective randomized study demonstrated that atovaquone is well-tolerated for anti-Pneumocystis prophylaxis in autologous PBSC transplant patients intolerant of TMP/SMX.     

Pneumocystis jiroveci pneumonia prophylaxis during maintenance therapy influences methotrexate/6-mercaptopurine dosing but not event-free survival for childhood acute lymphoblastic leukemia

Trimethoprim-sulfamethoxazole (TMP/SMX) is used in children with acute lymphoblastic leukemia (ALL) to prevent Pneumocystis pneumonia (PCP). We explored to which extent TMP/SMX influenced methotrexate (MTX)/6-mercaptopurine (6MP) dosage, myelosuppression, and event-free survival (EFS) during maintenance therapy. Of 447 study patients treated by the NOPHO ALL92 protocol, 120 patients received TMP/SMX continuously for 2-7 d/wk (TMP/SMX(2-7) ) and 287 patients never received TMP/SMX (TMP/SMX(never) ). Ten patients (all TMP/SMX(never) ) developed PCP, eight of which occurred within 7 months from the start of maintenance therapy. The TMP/SMX(2-7) group received lower oral 6MP doses than TMP/SMX(never) patients (50.6 vs. 63.9 mg/m(2) /d; P<0.001) but had lower absolute neutrophil counts (ANC) (median 1.7 vs. 2.0 × 10(9) /L; P<0.001). In Cox multivariate analysis, higher ANC levels (P=0.04) and male gender (P=0.06) were related to reduced EFS. ANC had no effect on EFS among TMP/SMX(2-7) patients (P=0.40) but did for TMP/SMX(never) patients (P=0.02). The difference in the effect on EFS between TMP/SMX(2-7) and TMP/SMX(never) patients was not significant (P=0.46). EFS did not differ between TMP/SMX(2-7) and TMP/SMX(never) patients (0.83 vs. 0.83; P=0.82). These results suggest that TMP/SMX is effective in preventing PCP and may have an antileukemic effect. TMP/SMX should be given the entire duration of maintenance therapy.     

Effects of trimethoprim-sulfamethoxazole and insecticide-treated bednets on malaria among HIV-infected Ugandan children

BACKGROUND: Trimethoprim-sulfamethoxazole (TMP/SMX) prophylaxis and insecticide-treated bednets reduce malaria risk among HIV-infected adults. The efficacy of TMP/SMX may be diminished where antifolate resistance to malaria is high. We evaluated the efficacy of these interventions for malaria prevention among Ugandan children. METHODS: We concurrently followed 300 HIV-infected children aged 1-10 years and a community-based cohort of 561 healthy children aged 1-11 years over 11 months in Kampala, Uganda. The HIV-infected children received TMP/SMX prophylaxis and insecticide treated bednets. In the community cohort, insecticide-treated bednets were introduced during the observation period. Children from both cohorts were followed using a standardized protocol to measure the incidence of malaria. RESULTS: Only nine episodes of malaria were diagnosed among HIV-infected children (incidence = 0.07/person-year) in comparison with 440 episodes among children from the community (incidence = 0.90/person-year; P < 0.0001). The use of insecticide-treated bednets was associated with a 43% reduction in malaria incidence (P < 0.001), and a combination of TMP/SMX and use of insecticide-treated bednets with a 97% reduction in malaria incidence (P < 0.001). The prevalence of five mutations associated with antifolate resistance was high among malaria cases detected in both the HIV (100%) and community cohorts (75%). Malaria accounted for only 4% of febrile episodes in the HIV cohort in comparison with 33% in the community-based cohort (P < 0.0001). CONCLUSION: In a malaria endemic area with a high level of molecular markers of antifolate resistance, the combined use of TMP/SMX prophylaxis and insecticide-treated bednets was associated with a dramatic reduction in malaria incidence among HIV-infected children.     

Prevalence of anemia in the nursing home: contribution of chronic kidney disease

OBJECTIVES: To assess the independent contribution of chronic kidney disease (CKD) and age to anemia in older nursing home residents. DESIGN: Retrospective. SETTING: Skilled nursing facility. PARTICIPANTS: Nursing home residents with records in the Beverly Healthcare Data Warehouse who were admitted to a nursing home between January 1, 2002, and December 31, 2003; were alive as of January 31, 2004; and had hemoglobin and serum creatinine (SCr) values available for analysis. MEASUREMENTS: Prevalence of anemia (hemoglobin <13 g/dL for men and <12 g/dL for women) and CKD (estimated glomerular filtration rate <60 mL/min per 1.73 m(2), according to Modification of Diet in Renal Disease criteria) and the contribution of CKD and age to the prevalence of anemia. RESULTS: Six thousand two hundred resident records were analyzed (70% female, 85% Caucasian). Overall, 59.6% of residents were anemic, and 43.1% had CKD, and residents with CKD were more likely to have anemia (64.9% with vs 55.7% without CKD; odds ratio (OR)=1.47, 95% confidence interval (CI)=1.33-1.63). Although older age was associated with lower hemoglobin values primarily in residents without CKD (Spearman rank correlation coefficient (r)=-0.10, P<.001), age had no association with hemoglobin in CKD (Spearman r=0.01, P=.60). The greater risk of anemia in the presence of CKD persisted in each age category (OR=2.07, 95% CI=1.53-2.80, aged 65-74; OR=1.44, 95% CI=1.21-1.70, aged 75-84; and OR=1.35, 95% CI=1.15-1.57, aged > or =85). CONCLUSION: Overall, these results suggest that CKD contributes more strongly than older age to the high prevalence of anemia in older nursing home residents.     

Does ingestion of cranberry juice reduce symptomatic urinary tract infections in older people in hospital? A double-blind, placebo-controlled trial

BACKGROUND: cranberry juice is often given to older people in hospital to prevent urinary tract infection (UTI), although there is little evidence to support its use. OBJECTIVE: to assess whether cranberry juice ingestion is effective in reducing UTIs in older people in hospital. DESIGN: randomised, placebo-controlled, double-blind trial. SETTING: Medicine for the Elderly assessment and rehabilitation hospital wards. SUBJECTS: 376 older patients in hospital. METHODS: participants were randomised to daily ingestion of 300 ml of cranberry juice or matching placebo beverage. The primary outcome was time to onset of first UTI. Secondary outcomes were adherence to beverage drinking, courses of antibiotics prescribed, and organisms responsible for UTIs. RESULTS: a total of 21/376 (5.6%) participants developed a symptomatic UTI: 14/189 in the placebo group and 7/187 in the cranberry juice group. These between-group differences were not significant, relative risk (RR) 0.51 [95% CI 0.21-1.22, P = 0.122). Although there were significantly fewer infections with Escherichia coli in the cranberry group (13 versus 4) RR 0.31 [95% CI 0.10-0.94, P = 0.027], this should be interpreted with caution as it was a secondary outcome. CONCLUSION: despite having the largest sample size of any clinical trial yet to have examined the effect of cranberry juice ingestion, the actual infection rate observed was lower than anticipated, making the study underpowered. This study has confirmed the acceptability of cranberry juice to older people. Larger trials are now required to determine whether it is effective in reducing UTIs in older hospital patients.     

Clindamycin–primaquine for pneumocystis jiroveci pneumonia in renal transplant patients

Background

Trimethoprim/sulfamethoxazole (TMP/SMX) is considered first-line therapy for pneumocystis jiroveci pneumonia (PCP) in renal transplant patients. Alternatives have not been formally studied. Clindamycin–primaquine (C–P) is effective in HIV-associated PCP, but data in renal transplant patients are lacking.

Patients and methods

Retrospective cohort study of 57 consecutive renal transplant patients who developed PCP and were treated with C–P (n = 23) or TMP/SMX (n = 34).

Results

A non-significantly higher failure rate was observed in patients on C–P due to lack of efficacy (30.4 versus 20.6 %, p = 0.545). The difference was more pronounced in severe PCP (60 versus 37.5 %, p = 0.611) and a significantly lower efficacy of C–P was seen when used as salvage therapy. The two patients who had received C–P after not responding to TMP/SMX failed this regimen, but all seven patients who had failed initial treatment with C–P and had been switched to TMP/SMX were cured (p = 0.028). No treatment-limiting adverse reactions were reported for patients on C–P while six patients (17.6 %) on TMP/SMX developed possibly related treatment-limiting toxicity (p = 0.071). However, in only two patients adverse events were definitely related to TMP/SMX (5.9 %).

Conclusions

Clindamycin–primaquine appears to be safe and well tolerated for treating PCP in renal transplant patients but is probably less effective than TMP/SMX, the standard regimen. However, our data indicates that C–P represents an acceptable alternative for patients with contraindications or treatment emergent toxicities during TMP/SMX use. Notably, TMP/SMX was also acceptably tolerated in most patients. TMP/SMX remains an effective salvage regimen in case of C–P failure.     

Prevalence and 10‐Year Outcomes of Frailty in Older Adults in Relation to Deficit Accumulation

OBJECTIVES: To evaluate the prevalence and 10‐year outcomes of frailty in older adults in relation to deficit accumulation. DESIGN: Prospective cohort study. SETTING: The National Population Health Survey of Canada, with frailty estimated at baseline (1994/95) and mortality follow‐up to 2004/05. PARTICIPANTS: Community‐dwelling older adults (N=2,740, 60.8% women) aged 65 to 102 from 10 Canadian provinces. During the 10‐year follow‐up, 1,208 died. MEASUREMENTS: Self‐reported health information was used to construct a frailty index (Frailty Index) as a proportion of deficits accumulated in individuals. The main outcome measure was mortality. RESULTS: The prevalence of frailty increased with age in men and women (correlation coefficient=0.955–0.994, P<.001). The Frailty Index estimated that 622 (22.7%, 95% confidence interval (CI)=21.0–24.4%) of the sample was frail. Frailty was more common in women (25.3%, 95% CI=23.2–27.5%) than in men (18.6%, 95% CI=15.9–21.3%). For those aged 85 and older, the Frailty Index identified 39.1% (95% CI=31.3–46.9%) of men as frail, compared with 45.1% (95% CI=39.7–50.5%) of women. Frailty significantly increased the risk of death, with an age‐ and sex‐adjusted hazard ratio for the Frailty Index of 1.57 (95% CI=1.41–1.74). CONCLUSION: The prevalence of frailty increases with age and at any age lessens survival. The Frailty Index approach readily identifies frail people at risk of death, presumably because of its use of multiple health deficits in multidimensional domains.     

Functional-task exercise versus resistance strength exercise to improve daily function in older women: a randomized, controlled trial

OBJECTIVES: To determine whether a functional-task exercise program and a resistance exercise program have different effects on the ability of community-living older people to perform daily tasks. DESIGN: A randomized, controlled, single-blind trial. SETTING: Community leisure center in Utrecht, the Netherlands. PARTICIPANTS: Ninety-eight healthy women aged 70 and older were randomly assigned to the functional-task exercise program (function group, n=33), a resistance exercise program (resistance group, n=34), or a control group (n=31). Participants attended exercise classes three times a week for 12 weeks. MEASUREMENTS: Functional task performance (Assessment of Daily Activity Performance (ADAP)), isometric knee extensor strength (IKES), handgrip strength, isometric elbow flexor strength (IEFS), and leg extension power were measured at baseline, at the end of training (at 3 months), and 6 months after the end of training (at 9 months). RESULTS: The ADAP total score of the function group (mean change 6.8, 95% confidence interval (CI)=5.2-8.4) increased significantly more than that of the resistance group (3.2, 95% CI=1.3-5.0; P=.007) or the control group (0.3, 95% CI=-1.3-1.9; P<.001). Moreover, the ADAP total score of the resistance group did not change significantly compared with that of the control group. In contrast, IKES and IEFS increased significantly in the resistance group (12.5%, 95% CI=3.8-21.3 and 8.6%, 95% CI=3.1-14.1, respectively) compared with the function group (-2.1%, 95% CI=-5.4-1.3; P=.003 and 0.3%, 95% CI=-3.6-4.2; P=.03, respectively) and the control group (-2.7%, 95% CI=-8.6-3.2, P=.003 and 0.6%, 95% CI=-3.4-4.6; P=.04, respectively). Six months after the end of training, the increase in ADAP scores was sustained in the function group (P=.002). CONCLUSION: Functional-task exercises are more effective than resistance exercises at improving functional task performance in healthy elderly women and may have an important role in helping them maintain an independent lifestyle.     

Anticoagulation in women with non-valvular atrial fibrillation in the stroke prevention using an oral thrombin inhibitor (SPORTIF) trials.

AIMS: The risk of stroke is greater among women with atrial fibrillation (AF) than men. Warfarin protects against stroke, but treatment-related bleeding occurs more often in women than in men. METHODS AND RESULTS: SPORTIF III (open label, n=3410) and V (double-blind, n=3922) included 2257 women with AF and one or more stroke risk factors randomized to warfarin [target international normalized ratio (INR) 2.0-3.0] or ximelagatran (36 mg twice daily). Primary outcomes were all stroke (ischaemic/haemorrhagic) and systemic embolic event. Women were older, on average, than men, 73.4+/-8.0 vs. 69.8+/-9.0 years (P<0.0001). More women were >75-years old and women had more risk factors than men had (P<0.0001). The INR on warfarin (mean 2.5+/-0.7) was within target range for 67% of follow-up regardless of gender. Women more often developed primary events [2.08%/year, 95% confidence interval (CI) 1.60-2.56%/year vs. 1.44%/year, 95% CI 1.18-1.71%/year in men; P=0.016). Major bleeding rates were similar (P=0.766) but women experienced more overall (major/minor) bleeding (P<0.001). Warfarin was associated with more overall bleeding in both genders and more major bleeding in women than in men (P=0.001). CONCLUSION: When compared with men with AF, women in these studies were older and had more stroke risk factors. Women were more prone to anticoagulant-related bleeding; the higher rate of thrombo-embolism among women was related to more frequent interruption of anticoagulant therapy.     

Ethnic differences in the frequency and circumstances of falling in older community-dwelling women

OBJECTIVES: To examine ethnic differences in fall rates and fall circumstances in older community-dwelling Caucasian and African-American women. DESIGN: Prospective analysis of incident falls and a nested retrospective analysis of fall circumstances over 5.7 years. SETTING: Monongahela Valley, Pennsylvania. PARTICIPANTS: A total of 1,821 Caucasian and African-American women (mean age+/-standard deviation 76+/-5) enrolled in the Study of Osteoporotic Fractures and participating in 1993/94. Circumstances of 338 falls were collected on a subsample of 197 women who fell. MEASUREMENTS: Fall rates and fall circumstances. RESULTS: Women reported 4,547 falls in 9,508 person-years, averaging 0.48 falls per woman annually (95% confidence interval (CI)=0.43-0.53). Age-adjusted fall rates were nonsignificantly higher in Caucasians than African Americans (relative risk (RR)=1.30, 95% CI=0.93-1.83%). In women younger than 75, fall rates were similar in Caucasians and African Americans (RR=1.17, P=.46). In women aged 75 and older, fall rates were 50% higher in Caucasians than in African Americans (RR=1.50, 95% CI=0.90-2.49), although this difference was not significant (P=.12). Fall circumstances differed by ethnicity. Caucasian women were significantly more likely than African Americans to fall outdoors versus indoors (odds ratio (OR)=1.6, 95% CI =1.0-2.7) and laterally versus forward (OR=2.0, 95% CI =1.1-3.4) but less likely to fall on the hand/wrist (OR=0.6, 95% CI =0.3-1.0). Ninety-eight percent of individuals falling on their hand/wrist reported that they extended their hand to attempt to break their fall. CONCLUSION: Although the circumstances of falling differed for older Caucasian and African-American women, there were no differences in the frequencies of falling. These findings suggest that ethnic differences in fracture risk in older women may be due in part to the different ways in which older Caucasian and African-American women fall, rather than how often they fall. More information will be needed on fall circumstances to determine whether interventions need to be tailored by ethnic group.     

Prevalence of combined fecal and urinary incontinence: a community-based study.

OBJECTIVE: To assess the prevalence of combined fecal and urinary incontinence. DESIGN: A cross-sectional, community-based study. SETTING: Olmsted County, Minnesota. PARTICIPANTS: Men (n = 778) and women (n = 762), aged 50 years or older, selected randomly from the population. MEASUREMENTS: Participants completed a previously validated self-administered questionnaire that assessed the occurrence of fecal and urinary incontinence in the previous year. RESULTS: The age-adjusted prevalence of incontinence was 11.1% (95% Confidence Interval (CI), 8.8-13.5) in men and 15.2% (95% CI, 12.5-17.9) in women for fecal incontinence; 25.6% (95% CI, 22.5-28.8) in men and 48.4% (95% CI, 44.7-52.2) in women for urinary incontinence; and 5.9% (95% CI, 4.1-7.6) in men and 9.4% (95% CI, 7.1-11.6) in women for combined urinary and fecal incontinence. The prevalence of fecal incontinence increased with age in men but not in women, from 8.4% among men in their fifties to 18.2% among men in their eighties (P for trend = .001). For women, the prevalence increased from 13.1% among 50-year-old women to 20.7% among women 80 years or older (P for trend = .5). Among persons with fecal incontinence, the prevalence of concurrent urinary incontinence was 51.1% among men and 59.6% among women (P = .001 and P = .003, respectively). Cross-sectionally, the age-adjusted, relative odds of fecal incontinence among persons with urinary incontinence was greater in men than in women (Odds Ratio (OR) = 3.0; 95% CI, 1.9-4.8 in men and OR = 1.8; 95% CI, 1.2-2.7 in women, P = .04). CONCLUSIONS: These findings suggest that persons with one form of incontinence are likely to have the other form as well. Despite the higher prevalence of urinary and fecal incontinence among women, the association between fecal incontinence and urinary incontinence was stronger among men than women. This finding, and the significant association between fecal incontinence and age observed in men but not in women, suggest that the etiologies may be more closely linked in men than in women.     

Effect of hormone therapy on risk of hip and knee joint replacement in the Women's Health Initiative

OBJECTIVE: To determine the effect of hormone therapy on arthroplasty rates. METHODS: We examined data from the Women's Health Initiative placebo-controlled, double-blind, randomized trials. Community-dwelling women ages 50-79 years were enrolled at 40 US clinics. Women with prior arthroplasty were excluded, yielding a sample size of 26,321 subjects. Women who had had hysterectomies (n = 10,272) were randomly assigned to receive 0.625 mg/day conjugated equine estrogens (n = 5,076), or placebo (n = 5,196), with a mean followup of 7.1 years. Those who had not had hysterectomies (n = 16,049) were randomly assigned to receive estrogen plus progestin (n = 8,240), given as 0.625 mg/day conjugated equine estrogens plus 2.5 mg/day medroxyprogesterone acetate, or placebo (n = 7,809), with a mean followup of 5.6 years. Participants reported hospitalizations, and arthroplasties were identified by procedure codes. Arthroplasties due to hip fracture were censored. Cox proportional hazards regression was used to assess hazard ratios (HRs) and 95% confidence intervals (95% CIs) using intent-to-treat methods and outcome of time to first procedure. RESULTS: In the estrogen-alone trial, women receiving hormone therapy had significantly lower rates of any arthroplasty (HR 0.84 [95% CI 0.70-1.00], P = 0.05). However, this effect was borderline statistically significant for hip arthroplasty (HR 0.73 [95% CI 0.52-1.03], P = 0.07), and not significant for knee arthroplasty (HR 0.87 [95% CI 0.71-1.07], P = 0.19). In the estrogen-plus-progestin trial, there was no association for total arthroplasty (HR 0.99 [95% CI 0.82-1.20], P = 0.92) or for individual hip (HR 1.14 [95% CI 0.83-1.57], P = 0.41) or knee (HR 0.91 [95% CI 0.72-1.15], P = 0.41) arthroplasties. CONCLUSION: These data suggest that hormone therapy may influence joint health, but this observed decrease in risk may be limited to unopposed estrogen and may possibly be more important in hip than in knee osteoarthritis.     

Long-term use of oral anticoagulants and the risk of fracture.

BACKGROUND: Vitamin K participates in bone metabolism and, since oral anticoagulants antagonize vitamin K, their use may increase the risk of osteoporosis. OBJECTIVE: To evaluate fracture risk at all skeletal sites following exposure to oral anticoagulants. METHODS: In a population-based retrospective cohort study, 572 Olmsted County, Minnesota, women 35 years or older at their first lifetime venous thromboembolism event between 1966 and 1990 were followed up for fractures. Risk was assessed by comparing new fractures with the number expected from sex- and age-specific fracture incidence rates for the general population (standardized incidence ratio [SIR]). RESULTS: Altogether, 480 fractures occurred during 6314 person-years of follow-up. Increasing exposure to oral anticoagulation was associated with an increased SIR for vertebral fractures: at less than 3 months of exposure, 2.4 (95% confidence interval [CI], 1.6-3.4); 3 to less than 12 months, 3.6 (95% CI, 2.5-4.9); and 12 months or more, 5.3 (95% CI, 3.4-8.0); and for rib fractures: at less than 3 months, 1.6 (95% CI, 0.9-2.7); 3 to less than 12 months, 1.6 (95% CI, 0.9-2.6); and 12 months or more, 3.4 (95% CI, 1.8-5.7). The data revealed no increased risk for other types of fractures. Oral anticoagulation for 12 months or more was an independent predictor of vertebral fractures (P = .009) and rib fractures (P = .02), but not other fractures. CONCLUSIONS: Long-term exposure to oral anticoagulation is associated with an increased risk of vertebral and rib fractures. The mechanism by which this occurs is still unclear and needs further investigation.     

Relationship Between Higher Estradiol Levels and 9-Year Mortality in Older Women: The Invecchiare in Chianti Study

OBJECTIVES: To investigate the relationship between total estradiol (E2) levels and 9-year mortality in older postmenopausal women not taking hormone replacement therapy (HRT).
DESIGN: Population-based study of persons living in the Chianti geographic area (Tuscany, Italy).
SETTING: Community.
PARTICIPANTS: A representative sample of 509 women aged 65 and older with measures of total E2.
MEASUREMENTS: Serum total E2 was measured at the University of Parma using ultrasensitive radioimmunoassay (RIA).
RESULTS: Women who died (n=135) during 9 years of follow up were older; had higher total E2 levels; and were more likely to have evidence of stroke, hypertension, diabetes mellitus, and congestive heart failure at baseline than survivors. Higher E2 levels were associated with a greater likelihood of death (hazard ratio (HR)=1.03, 95% confidence interval (CI)=1.01–1.06), and the relationship was independent of age, waist:hip ratio, C-reactive protein, education, cognitive function, physical activity, caloric intake, smoking, and chronic disease (HR=1.08 pg/mL, 95% CI=1.03–1.13, P =.003). The excessive risk of death associated with higher total E2 was not attenuated after adjustment for total testosterone (HR=1.12, 95% CI=1.02–1.18, P <.001) and after further adjustment for insulin resistance evaluated using the homeostasis model assessment (HR=1.07, 95% CI=1.03–1.17, P <.001).
Total E2 was highly predictive of death after more than 5 years (HR=1.42: CI 1.01–1.91, P =.04) and not predictive of death for less than 5 years ( P =.78).
CONCLUSION: Higher total E2 concentration predicts mortality in older women not taking HRT.     

A dose-escalation regimen of trimethoprim–sulfamethoxazole is tolerable for prophylaxis against Pneumocystis jiroveci pneumonia in rheumatic diseases

Abstract

Objective To investigate the safety and efficacy of a dose-escalation regimen of trimethoprim–sulfamethoxazole (TMP/SMX) for prophylaxis against Pneumocystis jiroveci pneumonia (PCP) in rheumatic diseases.

Methods Data from 41 patients, who received glucocorticoids with or without immunosuppressive agents and prophylactic use of TMP/SMX, were retrospectively analyzed. Thirteen patients were started on a daily dose of 10 % of single-strength (SS) TMP/SMX, which was increased gradually (dose-escalation group), while 28 patients were started on 1 SS tablet daily (routine group).

Results In the dose-escalation group, the retention rate was 100 % at 6 months. In the routine group, 5 patients discontinued TMP/SMX; the retention rate was 82.1 %. Moreover, the retention rate when taking a daily dose of 50 % or more of SS TMP/SMX, or 1 SS tablet thrice-weekly, was significantly higher in the dose-escalation group (100 versus 71.4 %, P = 0.032). No PCP was observed in the dose-escalation group; however, 1 patient in the routine group, who had discontinued TMP/SMX, developed PCP. The rate of adverse effects was less, although nonsignificant, in the dose-escalation group (30.8 versus 46.4 %, P = 0.344).

Conclusions In rheumatic diseases, a dose-escalation regimen of TMP/SMX resulted in a higher retention rate and was safer than the routine regimen.     

Cost-effectiveness of prophylaxis against Pneumocystis carinii pneumonia in patients with Wegner's granulomatosis undergoing immunosuppressive therapy

OBJECTIVE: To assess the incremental cost-effectiveness of 3 Pneumocystis carinii pneumonia (PCP) prophylaxis strategies in patients with Wegener's granulomatosis (WG) receiving immunosuppressive therapies: 1) no prophylaxis; 2) trimethoprim/sulfamethoxazole (TMP/SMX) 160 mg/800 mg 3 times a week, which is discontinued if patients experience an adverse drug reaction (ADR); and 3) TMP/SMX 160 mg/800 mg 3 times a week, which is replaced by monthly aerosolized pentamidine (300 mg) if patients experience an ADR. METHODS: A Markov state-transition model was developed to follow a hypothetical cohort of WG patients over their lifetimes starting from the time of initial exposure to the immunosuppressive therapy. The effect of PCP prophylaxis on life expectancy, quality-adjusted life expectancy, average discounted lifetime cost (ADLC), and incremental cost-effectiveness was estimated based on data obtained from a literature review. Direct medical costs were examined from a societal perspective, and costs and benefits were discounted at 3% annually. RESULTS: No prophylaxis resulted in a life expectancy of 13.36 quality-adjusted life years (QALY) at an ADLC of $4,538. In comparison, prophylaxis with TMP/ SMX alone increased the QALY to 13.54 and was cost saving, with an ADLC of $3,304. The addition of pentamidine in patients who had an ADR to TMP/SMX resulted in 13.61 QALY, with an ADLC of $7,428. Compared with TMP/SMX alone, TMP/SMX followed by pentamidine increased the QALY by 0.07 at an incremental cost of $58,037 per QALY. Both TMP/SMX alone and TMP/SMX followed by pentamidine prophylaxis strategies dominated the no prophylaxis strategy until the incidence of PCP fell below 0.2% and 2.25%, respectively. Institution of pentamidine therapy for patients with a TMP/SMX ADR increased quality-adjusted life expectancy compared with that with TMP/ SMX alone until the incidence of PCP rose above 7.5%. CONCLUSION: Prophylaxis using TMP/SMX alone increased life expectancy and reduced cost for patients with WG receiving immunosuppressive therapy. Replacing TMP/SMX with monthly aerosolized pentamidine in cases of ADR further increased life expectancy, although at an increased cost.     

Norfloxacin versus cotrimoxazole for infection prophylaxis in granulocytopenic patients with acute leukemia. A prospective randomized study

Norfloxacin (NOR) or cotrimoxazole (TMP/SMX) were randomly administered to 59 granulocytopenic patients with acute leukemia for prevention of bacterial infections. Nineteen NOR patients (65%) and 22 TMP/SMX patients (73%) complained of febrile or infectious episodes during the study. The mean incidence of febrile complications per patient was higher in the TMP/SMX group: 1.05 vs 0.68 (p less than 0.05). Eleven of 16 microbiologically documented infections in the TMP/SMX group and 7 of 11 in the NOR group were caused by gram negative bacilli (GNB). NOR recipients had fewer days of fever, fewer days on parenteral antibiotics and a lower proportion of time spent febrile. Fecal surveillance cultures showed intestinal GNB colonization in 42/80 specimens in the TMP/SMX group (resistant strains: 93%) and in 8/75 specimens in the NOR group (1 resistant strain). Overall, NOR seems to be effective in eradicating GNB from the digestive tract without selection of resistant strains and in preventing febrile episodes in neutropenic patients.