Cerebrovascular reactivity after cessation of menopausal hormone treatment.

OBJECTIVE: Women who are currently using menopausal hormone therapy (MHT) have higher cerebrovascular reactivity when compared with postmenopausal women who are not taking MHT; however, the effect of cessation of MHT on cerebrovascular reactivity is not known. Given that MHT can have structural and activational effects on vascular function, this study was performed to characterize cerebrovascular reactivity following cessation of MHT in women at low risk for cerebrovascular disease. METHODS: Cerebrovascular reactivity was measured in a subset of women from the Kronos Early Estrogen Prevention Study (KEEPS) 3 years after cessation of the study drug (oral conjugated equine estrogen, transdermal 17ß-estradiol, or placebo [PLA]). RESULTS: Age, body mass index, and blood pressure were comparable among groups. At rest, the middle cerebral artery velocity (MCAv), cerebrovascular conductance index, mean arterial pressure, and cerebral pulsatility index did not differ among groups. Slope-based summary measures of cerebrovascular reactivity did not differ significantly among groups. However, utilizing repeated-measures modeling, there was a significant upward shift in MCAv responses (p = 0.029) in the combined MHT group compared with the PLA group. CONCLUSION: MHT has a marginal sustained effect on cerebrovascular reactivity when measured 3 years after cessation of hormone treatment.

Pregnancy history, coronary artery calcification and bone mineral density in menopausal women.

OBJECTIVE: This study examined relationships, by pregnancy histories, between bone mineral density (BMD) and coronary artery calcification (CAC) in postmenopausal women. METHODS: Forty women identified from their medical record as having pre-eclampsia (PE) were age/parity-matched with 40 women having a normotensive pregnancy (NP). Vertebral (T4-9) BMD and CAC were assessed by quantitative computed tomography in 73 (37 with PE and 36 with NP) of the 80 women. Analyses included linear regression using generalized estimating equations. RESULTS: Women averaged 59 years of age and 35 years from the index pregnancy. There were no significant differences in cortical, trabecular or central BMD between groups. CAC was significantly greater in the PE group (p = 0.026). In multivariable analysis, CAC was positively associated with cortical BMD (p = 0.001) and negatively associated with central BMD (p = 0.036). There was a borderline difference in the association between CAC and central BMD by pregnancy history (interaction, p = 0.057). CONCLUSIONS: Although CAC was greater in women with a history of PE, vertebral BMD did not differ between groups. However, both cortical and central BMD were associated with CAC. The central BMD association was marginally different by pregnancy history, suggesting perhaps differences in underlying mechanisms of soft tissue calcification.

Creation of a model to predict survival in patients with refractory coeliac disease using a multinational registry.

BACKGROUND: Refractory coeliac disease is a severe complication of coeliac disease with heterogeneous outcome. AIM: To create a prognostic model to estimate survival of patients with refractory coeliac disease. METHODS: We evaluated predictors of 5-year mortality using Cox proportional hazards regression on subjects from a multinational registry. Bootstrap resampling was used to internally validate the individual factors and overall model performance. The mean of the estimated regression coefficients from 400 bootstrap models was used to derive a risk score for 5-year mortality. RESULTS: The multinational cohort was composed of 232 patients diagnosed with refractory coeliac disease across seven centres (range of 11-63 cases per centre). The median age was 53 years and 150 (64%) were women. A total of 51 subjects died during a 5-year follow-up (cumulative 5-year all-cause mortality = 30%). From a multiple variable Cox proportional hazards model, the following variables were significantly associated with 5-year mortality: age at refractory coeliac disease diagnosis (per 20 year increase, hazard ratio = 2.21; 95% confidence interval, CI: 1.38-3.55), abnormal intraepithelial lymphocytes (hazard ratio = 2.85; 95% CI: 1.22-6.62), and albumin (per 0.5 unit increase, hazard ratio = 0.72; 95% CI: 0.61-0.85). A simple weighted three-factor risk score was created to estimate 5-year survival. CONCLUSIONS: Using data from a multinational registry and previously reported risk factors, we create a prognostic model to predict 5-year mortality among patients with refractory coeliac disease. This new model may help clinicians to guide treatment and follow-up.

Predictive scoring model of mortality in Gram-negative bloodstream infection.

Mortality is a well-recognized complication of Gram-negative bloodstream infection (BSI). The aim of this study was to develop a model to predict mortality in patients with Gram-negative BSI by using the Pitt bacteraemia score (PBS) and other clinical and laboratory variables. A cohort of 683 unique adult patients who were followed for at least 28 days after admission to Mayo Clinic Hospitals with Gram-negative BSI from 1 January 2001 to 31 October 2006 and who received clinically predefined appropriate empirical antimicrobial therapy was retrospectively identified. Multivariable logistic regression was used to identify independent risk factors for 28-day all-cause mortality. Regression coefficients from a multivariable model were used to develop a risk score to predict mortality following Gram-negative BSI. Malignancy (OR 3.48, 95% CI 1.94-6.22), liver cirrhosis (OR 5.42, 95% CI 2.52-11.65), source of BSI other than urinary tract or central venous catheter infection (OR 5.54, 95% CI 2.42-12.69), and PBS (OR 1.98, 95% CI 0.92-4.25 for PBS of 2-3 and OR 6.42, 95% CI 3.11-13.24 for PBS ≥4) were identified as independent risk factors for 28-day mortality in patients with Gram-negative BSI. A risk-score model was created by adding points for each independent risk factor, and had a c-statistic of 0.84. Patients with risk scores of 0, 4, 8, 12 and 16 had estimated 28-day mortality rates of approximately 0%, 3%, 14%, 45%, and 81%, respectively. The Gram-negative BSI risk score described herein estimated mortality risk with high discrimination in patients with Gram-negative BSI who received clinically adequate empirical antimicrobial therapy.

Epidemiology and outcome of Gram-negative bloodstream infection in children: a population-based study.

Population-based studies of Gram-negative bloodstream infection (BSI) in children are lacking. Therefore, we performed this population-based investigation in Olmsted County, Minnesota, to determine the incidence rate, site of acquisition, and outcome of Gram-negative BSI in children aged ⩽18 years. We used Kaplan-Meier method and Cox proportional hazard regression for mortality analysis. We identified 56 unique children with Gram-negative BSI during the past decade. The gender-adjusted incidence rate of Gram-negative BSI per 100 000 person-years was 129·7 [95% confidence interval (CI) 77·8-181·6]) in infants, with a sharp decline to 14·6 (95% CI 6·0-23·2) and 7·6 (95% CI 4·3-10·9) in children aged 1-4 and 5-18 years, respectively. The urinary tract was the most commonly identified source of infection (34%) and Escherichia coli was the most common pathogen isolated (38%). Over two-thirds (68%) of children had underlying medical conditions that predisposed to Gram-negative BSI. The overall 28-day and 1-year all-cause mortality rates were 11% (95% CI 3-18) and 18% (95% CI 8-28), respectively. Younger age and number of underlying medical conditions were associated with 28-day and 1-year mortality, respectively. Nosocomial or healthcare-associated acquisition was associated with both 28-day and 1-year mortality.

Temporal trends in Enterobacter species bloodstream infection: a population-based study from 1998-2007.

Enterobacter species are the fourth most common cause of Gram-negative bloodstream infection (BSI). We examined temporal changes and seasonal variation in the incidence rate of Enterobacter spp. BSI, estimated 28-day and 1-year mortality, and determined in vitro antimicrobial resistance rates of Enterobacter spp. bloodstream isolates in Olmsted County, Minnesota, from 1 January 1998 to 31 December 2007. Multivariable Poisson regression was used to examine temporal changes and seasonal variation in incidence rate and Kaplan-Meier method was used to estimate 28-day and 1-year mortality. The median age of patients with Enterobacter spp. BSI was 58 years and 53% were female. The overall age- and gender-adjusted incidence rate of Enterobacter spp. BSI was 3.3 per 100,000 person-years (95% CI 2.3-4.4). There was a linear trend of increasing incidence rate from 0.8 (95% CI 0-1.9) to 6.2 (95% CI 3.0-9.3) per 100,000 person-years between 1998 and 2007 (p 0.002). There was no significant difference in the incidence rate of Enterobacter spp. BSI during the warmest 4 months compared to the remainder of the year (incidence rate ratio 1.06; 95% CI 0.47-2.01). The overall 28-day and 1-year mortality rates of Enterobacter spp. BSI were 21% (95% CI 8-34%) and 38% (95% CI 22-53%), respectively. Up to 13% of Enterobacter spp. bloodstream isolates were resistant to third-generation cephalosporins. To our knowledge, this is the first population-based study to describe the epidemiology and outcome of Enterobacter spp. BSI. The increase in incidence rate of Enterobacter spp. BSI over the past decade, coupled with its associated antimicrobial resistance, dictate the need for further investigation of this syndrome.

Efficacy and safety of rifampin containing regimen for staphylococcal prosthetic joint infections treated with debridement and retention.

The aim of this study was to evaluate the efficacy and safety of rifampin for Staphylococcus aureus (SA) or coagulase negative staphylococci (CNS) prosthetic joint infection (PJI) treated with debridement and retention (D/R). We calculated the treatment failure cumulative incidence (TF) of a cohort of 101 patients with SA or CNS PJI treated with D/R and antimicrobial therapy. The effect of the use of a rifampin-based regimen was evaluated. Cox proportional hazards regression evaluated the association between treatment and time-to-TF controlling for the propensity to treat with rifampin and temporal confounders. Seven percent (1/14) of the prospective rifampin-treated patients, 32% (10/31) of the historical rifampin-treated patients and 38% (21/56) of the historical non-rifampin treated patients developed TF. After controlling for the propensity to treat with rifampin and American Society of Anesthesia scores, patients in the prospective cohort had a lower risk of TF compared to patients in the historical cohort not treated with rifampin (HR 0.11; 95%CI 0.01-0.84). None (0/14) of the patients in the prospective study developed hepatotoxicity. The outcome of staphylococcal PJI treated with D/R and rifampin-based regimens was better when compared with a historical cohort treated without rifampin.

The economics of coeliac disease: a population-based study.

BACKGROUND: Despite increasing prevalence, the economic implications of coeliac disease are just emerging. AIMS: To assess the impact of coeliac disease diagnosis on healthcare costs and the incremental costs associated with coeliac disease. METHODS: Administrative data for a population-based cohort of coeliac disease cases and matched controls from Olmsted County, Minnesota were used to compare (i) direct medical costs 1 year pre- and post-coeliac disease diagnosis for 133 index cases and (ii) 4-year cumulative direct medical costs incurred by 153 index cases vs. 153 controls. Analyses exclude diagnostic-related and out-patient pharmaceutical costs. RESULTS: Average total costs were reduced by $1764 in the year following diagnosis (pre-diagnosis cost of $5023 vs. $3259; 95% CI of difference: $688 to $2993). Over a 4-year period, coeliac disease cases experienced higher out-patient costs (mean difference of $1457; P = 0.016) and higher total costs than controls (mean difference of $3964; P = 0.053). Excess average total costs were concentrated among males with coeliac disease ($14,191 vs. $4019 for male controls; 95% CI of difference: $2334 to $20,309). CONCLUSIONS: Coeliac disease-associated costs indicate a significant economic burden of disease, particularly for diseased males. Diagnosis and treatment of coeliac disease reduce medical costs of care suggesting an economic advantage to earlier detection and treatment.

Tuberculosis attributed to household contacts in the Philippines.

Data on the burden of disease from tuberculosis (TB) in Filipino households are limited. To determine the magnitude of undiagnosed TB in TB households, and the demographic and socio-economic factors associated with TB in the Philippines, household contacts of adult smear-positive TB patients seen from July 2001 to June 2003 were assessed based on interview, chest X-ray, tuberculin skin test and sputum examination. History of TB and older age were independently associated with TB disease, and age and duration of cohabitation with TB infection. TB and TB infection are highly prevalent in TB households in the Philippines.

Seasonal variation in Escherichia coli bloodstream infection: a population-based study.

Seasonal variation in the rates of infection with certain Gram-negative organisms has been previously examined in tertiary-care centres. We performed a population-based investigation to evaluate the seasonal variation in Escherichia coli bloodstream infection (BSI). We identified 461 unique patients in Olmsted County, Minnesota, from 1 January 1998 to 31 December 2007, with E. coli BSI. Incidence rates (IR) and IR ratios were calculated using Rochester Epidemiology Project tools. Multivariable Poisson regression was used to examine the association between the IR of E. coli BSI and average temperature. The age- and gender-adjusted IR of E. coli BSI per 100 000 person-years was 50.2 (95% CI 42.9-57.5) during the warmest 4 months (June through September) compared with 37.1 (95% CI 32.7-41.5) during the remainder of the year, resulting in a 35% (95% CI 12-66%) increase in IR during the warmest 4 months. The average temperature was predictive of increasing IR of E. coli BSI (p 0.004); there was a 7% (95% CI 2-12%) increase in the IR for each 10-degree Fahrenheit (c. 5.5 degrees C) increase in average temperature. To our knowledge, this is the first study to demonstrate seasonal variation in E. coli BSI, with a higher IR during the warmest 4 months than during the remainder of the year.

Kinetics of interferon-gamma producing cytomegalovirus (CMV)-specific CD4+ and CD8+ T lymphocytes and the risk of subsequent CMV viremia after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Deficiencies in cytomegalovirus (CMV)-specific T lymphocytes impair the immunologic response against CMV reactivation after allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: A time-dependent analysis was conducted to determine the association between the percentages and kinetics of interferon-gamma-producing CMV-specific CD4+ and CD8+ T lymphocytes and CMV viremia among 30 allogeneic HSCT recipients. RESULTS: Higher percentages of CD4+ T lymphocytes activated with CMVpp65 (hazard ratio [HR]: 2.06; 95% confidence interval [95% CI]: 1.18-3.6; P=0.011) and CMV lysate (HR: 1.18; 95% CI: 0.99-1.42; P=0.072), and higher percentages of CD8+ T lymphocytes activated by CMV immediate early-1 (HR: 1.2; 95% CI: 1.01-1.43; P=0.038) and CMVpp65 (HR: 1.12; 95% CI: 1.0-1.27; P=0.060) were associated with time-to-CMV viremia. Furthermore, a higher degree in the decline of CMV lysate-activated CD4+ T lymphocytes (HR: 1.14; 95% CI: 0.96-1.36; P=0.125) and CMVpp65-activated CD8+ T lymphocytes (HR: 1.36; 95% CI: 1.03-1.78; P=0.031) was suggestive of or significantly associated with time-to-CMV viremia. CONCLUSIONS: Higher levels of CMV-specific CD4+ and CD8+ T lymphocytes were associated with subsequent CMV viremia after HSCT. The association between CMV viremia and the degree of decline in CMV-specific T lymphocytes suggests that severe disruption in homeostatic CMV-specific immune environment contributes to the immunopathogenesis of CMV after allogeneic HSCT.

Predictors of the placebo response in functional dyspepsia.

BACKGROUND: Trials in functional dyspepsia report placebo response rates of 30% to 40%. AIM: We aimed to identify predictors of the placebo response. METHODS: Patients from primary, secondary and tertiary practices with functional dyspepsia defined by Rome II criteria were enrolled into one of four clinical trials; 220 patients were randomized to receive placebo. Scintigraphic assessment of gastric emptying at baseline was repeated at the end of the treatment in those with delayed emptying. After a 2 week run-in period, patients were followed for 8 weeks on placebo. Response was assessed on a weekly basis and a responder was defined as satisfactory relief of meal-related symptoms on at least 50% of weeks. RESULTS: The mean age was 44 years (range 18-82) and 74% were female; 76 (35%) were placebo responders. The predominant symptom was an unstable measure over the trial. Independent predictors of a lower placebo response were lower body mass index and a more consistent predominant symptom pattern (both P < 0.05). No association was seen with age, gender, centre type, baseline symptom score, baseline or change in gastric emptying, or baseline quality of life. CONCLUSION: In functional dyspepsia, a consistent predominant symptom pattern and lower body mass index may be associated with a lower placebo response rate.

Functional dyspepsia, delayed gastric emptying, and impaired quality of life.

BACKGROUND: It remains controversial as to whether delayed gastric emptying in functional dyspepsia is associated with a specific symptom pattern, and it is unknown if gastric emptying in functional dyspepsia is a driver of impaired health related quality of life (HRQOL). We aimed to evaluate the relationship between functional dyspepsia symptoms, gastric emptying, and HRQOL. METHODS: US patients (n=864; mean age 44 years (range 18-82); 74% female) with functional dyspepsia, as defined by Rome II criteria, were enrolled into one of four clinical trials. All patients had a baseline scintigraphic assessment of gastric emptying of an egg substitute meal, and the trials were stratified on this assessment. Delayed gastric emptying was defined as having at least 6.3% residual volume at four hours. A total of 290 (34%) patients had delayed gastric emptying. HRQOL was assessed by the SF 36 and Nepean dyspepsia index (NDI). RESULTS: Postprandial fullness was independently associated with delayed gastric emptying but the association was weak (odds ratio (OR) 1.98 (95% confidence interval (CI) 1.02, 3.86); p=0.04). No independent association was seen with epigastric pain, early satiety, nausea, or bloating. Mean SF 36 physical composite score (PCS) was 42.3 (95% CI 41.6, 43.0) and the mean SF 36 mental composite score (MCS) was 46.8 (95% CI 46.0, 47.5); both mean scores were significantly lower than age and sex adjusted national norms of 50 (p<.0001). Female sex, increasing age, and higher symptom scores for fullness, epigastric pain, and nausea were each independently associated with decreased PCS scores (all p<0.05). Higher baseline nausea symptom score, lower gastric emptying rates at one hour, and lower body mass index were associated with decreased MCS (all p<0.05). Female sex, epigastric pain, and nausea, but not gastric emptying, were associated with an impaired score on the NDI. However, the magnitude of the significant associations were all small. CONCLUSIONS: In patients with functional dyspepsia selected for a clinical trial programme, gastric emptying did not usefully stratify them symptomatically. Quality of life of patients with functional dyspepsia enrolled in this clinical trial programme was significantly impaired but this was not explained by delayed gastric emptying.