Barbara Grimes

Transfusion related acute lung injury: incidence and risk factors

Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related mortality. To determine TRALI incidence by prospective, active surveillance and to identify risk factors by a case-control study, 2 academic medical centers enrolled 89 cases and 164 transfused controls. Recipient risk factors identified by multivariate analysis were higher IL-8 levels, liver surgery, chronic alcohol abuse, shock, higher peak airway pressure while being mechanically ventilated, current smoking, and positive fluid balance. Transfusion risk factors were receipt of plasma or whole blood from female donors (odds ratio = 4.5, 95% confidence interval [CI], 1.85-11.2, P = .001), volume of HLA class II antibody with normalized background ratio more than 27.5 (OR = 1.92/100 mL, 95% CI, 1.08-3.4, P = .03), and volume of anti-human neutrophil antigen positive by granulocyte immunofluoresence test (OR = 1.71/100 mL, 95% CI, 1.18-2.5, P = .004). Little or no risk was associated with older red blood cell units, noncognate or weak cognate class II antibody, or class I antibody. Reduced transfusion of plasma from female donors was concurrent with reduced TRALI incidence: 2.57 (95% CI, 1.72-3.86) in 2006 versus 0.81 (95% CI, 0.44-1.49) in 2009 per 10 000 transfused units (P = .002). The identified risk factors provide potential targets for reducing residual TRALI.

Are the Uninsured Responsible for the Increase in Emergency Department Visits in the United States

STUDY OBJECTIVE The rise in emergency department (ED) use in the United States is frequently attributed to increased visits by the uninsured. We determine whether insurance status is associated with the increase in ED visits. METHODS Using the national Community Tracking Study Household Surveys from 1996 to 1997, 1998 to 1999, 2000 to 2001, and 2003 to 2004, we determined for each period the proportion of reported adult ED visits according to insurance status, family income, usual source of care, health status, and outpatient (non-ED) visits. Trends over time were tested for statistical significance. RESULTS The proportion of adult ED visits by persons without insurance was stable across the decade. Uninsured individuals accounted for 15.5% of ED visits in 1996 to 1997, 16.1% in 1998 to 1999, 15.2% in 2000 to 2001, and 14.5% of visits in 2003 to 2004 (P for trend=.43). The proportion of visits by persons whose family income was greater than 400% of the federal poverty level increased from 21.9% to 29.0% (P=.002). The proportion of visits by those whose usual source of care was a physicians office increased from 52.4% in 1996 to 1997 to 59.0% in 2003 to 2004 (P=.002), whereas the proportion of visits by those without a usual source of care was essentially unchanged (9.7% of visits in 1996 to 1997 and 9.6% in 2003 to 2004; P=.74). CONCLUSION The rise in ED visits between 1996 and 2003 cannot be primarily attributed to the uninsured. Major contributors to increasing ED utilization appear to be disproportionate increases in use by nonpoor persons and by persons whose usual source of care is a physicians office.

Low level of self-reported physical activity in ambulatory patients new to dialysis

Physical inactivity contributes to the frailty and the decline in function that develops over time among patients with end-stage renal disease. We assessed physical activity among 1547 ambulatory patients new to dialysis in the United States Renal Data System Comprehensive Dialysis Study. We used a self-reporting Human Activity Profile that included Maximal and Adjusted Activity Scores and compared results to established norms by age and gender. Physical activity was found to be extremely low with scores for all age and gender categories below the 5th percentile of healthy individuals and 95% of patients had scores consonant with low fitness. Older age, female gender, diabetes, atherosclerotic disease, and a low level of education were associated with lower activity scores assessed by univariate and multivariable linear regression analysis. Higher serum albumin, creatinine, and lower body mass index, but not hemoglobin levels, were associated with greater physical activity. By multivariable analysis, patients on hemodialysis using a catheter reported lower levels of physical activity compared to those on peritoneal dialysis, hemodialysis using an arteriovenous fistula, or with a graft. Lower Maximal and Adjusted Activity Scores were associated with poor physical function and mental health. Hence, physical activity is distressingly low among patients new to dialysis. Thus, strategies to enhance activity in these patients should be explored.

Switching first-line disease-modifying therapy after failure: impact on the course of relapsing–remitting multiple sclerosis

Background Options for non-responders to relapsing–remitting multiple sclerosis (RRMS) first-line disease-modifying therapies (DMT) are limited. We explored whether switching first-line DMT is effective. Methods Patients with RRMS who first received interferon-beta (IFNB) or glatiramer acetate (GA) were classified in three categories: DMT change because of suboptimal response, DMT change because of other reasons, and no DMT change during follow-up. Outcomes included annualized relapse rate (ARR) and relapse-free proportions. Results We identified 597 patients who initiated first-line DMT. For patients who did not change DMT (n = 240), pre-DMT and on-DMT median ARR were 0.50 and 0 (P < 0.0001). At 24 months, 76% (95%CI = 69–81%) of patients who did not change DMT were relapse-free. Of the 155 who switched because of suboptimal response, 101 switched to another first-line DMT. Median ARR pre-DMT, on first DMT and second DMT were: 0.50, 0.55, and 0.25 for switchers from IFNB to GA (IFNB/GA, n = 12) (pre-DMT versus first DMT: P = 0.92; first versus second DMT: P = 0.31); 0.90, 0.50, and 0 for switchers from GA to IFNB (GA/IFNB, n = 18; P = 0.19; P = 0.01); 0.50, 0.68, and 0 for switchers from an IFNB to another IFNB (IFNB/IFNB’, n = 71; P = 0.34; P = 0.02). Estimated relapse-free proportion after 24 months of treatment was 42% (95%CI=15–66%) during the period on IFNB versus 53% (95%CI = 17–80%) on GA for IFNB/GA (P = 0.21); 12% (95%CI = 0–40%) on GA versus 87% (95%CI = 59–97%) on IFNB for GA/IFNB (P = 0.001); and 41% (95%CI = 29–52%) on initial IFNB versus 67% (95%CI = 53–79%) on subsequent IFNB for IFNB/IFNB’ (P = 0.0001). Conclusions Switching first-line DMT in patients with RRMS failing initial therapy may be effective in many cases.

Infection-Related Hospitalizations in Older Patients With ESRD

BACKGROUND Infection is an important cause of hospitalization and death in patients receiving dialysis. Few studies have examined the full range of infections experienced by dialysis patients. The purpose of this study is to examine types, rates, and risk factors for infection in older persons starting dialysis therapy. STUDY DESIGN Retrospective observational cohort study. SETTING & PARTICIPANTS The cohort was assembled from the US Renal Data System and included patients aged 65-100 years who initiated dialysis therapy between January 1, 2000, and December 31, 2002. Exclusions included prior kidney transplant, unknown dialysis modality, or death, loss to follow-up, or transplant during the first 90 days of dialysis therapy. Patients were followed up until death, transplant, or study end on December 31, 2004. PREDICTORS Baseline demographics, comorbid conditions, and serum albumin and hemoglobin levels. OUTCOMES & MEASUREMENTS Infection-related hospitalizations were ascertained using discharge International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. Hospitalization rates were calculated for each type of infection. The Wei-Lin-Weissfeld model was used to examine risk factors for up to 4 infection-related events. RESULTS 119,858 patients were included, 7,401 of whom were on peritoneal dialysis therapy. During a median follow-up of 1.9 years, infection-related diagnoses were observed in approximately 35% of all hospitalizations. Approximately 50% of patients had at least 1 infection-related hospitalization. Rates (per 100 person-years) of pulmonary, soft-tissue, and genitourinary infections ranged from 8.3-10.3 in patients on peritoneal dialysis therapy and 10.2-15.3 in patients on hemodialysis therapy. Risk factors for infection included older age, female sex, diabetes, heart failure, pulmonary disease, and low serum albumin level. LIMITATIONS Use of ICD-9-CM codes, reliance on Medicare claims to capture hospitalizations, use of the Medical Evidence Form to ascertain comorbid conditions, and absence of data for dialysis access. CONCLUSION Infection-related hospitalization is frequent in older patients on dialysis therapy. A broad range of infections, many unrelated to dialysis access, result in hospitalization in this population.

Association between Body Composition and Frailty among Prevalent Hemodialysis Patients: A US Renal Data System Special Study

Studies of frailty among patients on hemodialysis have relied on definitions that substitute self-reported functioning for measures of physical performance and omit weight loss or substitute alternate criteria. We examined the association between body composition and a definition of frailty that includes measured physical performance and weight loss in a cross-sectional analysis of 638 adult patients receiving maintenance hemodialysis at 14 centers. Frailty was defined as having three of following characteristics: weight loss, weakness, exhaustion, low physical activity, and slow gait speed. We performed logistic regression with body mass index (BMI) and bioelectrical impedance spectroscopy (BIS)-derived estimates of intracellular water (ICW), fat mass, and extracellular water (ECW) as the main predictors, and age, sex, race, and comorbidity as covariates. Overall, 30% of participants were frail. Older age (odds ratio [OR], 1.31 per 10 years; 95% confidence interval [95% CI], 1.14 to 1.50), diabetes (OR, 1.65; 95% CI, 1.13 to 2.40), higher fat mass (OR, 1.18; 95% CI, 1.02 to 1.37), and higher ECW (OR, 1.33; 95% CI, 1.20 to 1.47) associated with higher odds of frailty. Higher ICW associated with lower odds of frailty (OR, 0.80 per kg; 95% CI, 0.73 to 0.87). The addition of BMI data did not change the area under the receiver operating characteristics curve (AUC; AUC=0.66 versus 0.66; P=0.71), but the addition of BIS data did change the AUC (AUC=0.72; P<0.001). Thus, individual components of body composition but not BMI associate strongly with frailty in this cohort of patients receiving hemodialysis.

Citalopram Provides Little or No Benefit in Nondepressed Patients With Irritable Bowel Syndrome

BACKGROUND & AIMS Data on the benefit of selective serotonin reuptake inhibitors (SSRIs) in irritable bowel syndrome (IBS) are conflicting. The longitudinal relationship between clinical symptoms and sensitivity to barostat-mediated rectal distension in IBS remains unclear. We assessed the benefit of citalopram and explored the relationships between symptoms, quality of life (QOL), and rectal sensitivity to barostat distension in non-depressed IBS patients. METHODS Patients from primary, secondary, and tertiary care settings were randomly assigned to receive citalopram (20 mg/day for 4 weeks, then 40 mg/day for 4 weeks) or placebo in a study with double-masking and concealed allocation. Symptoms were assessed weekly, and IBS-QOL and rectal sensation by barostat were assessed at the beginning and end of the study. RESULTS Patients receiving citalopram did not achieve a higher rate of adequate relief of IBS symptoms than patients receiving placebo (12/27 [44%] vs 15/27 [56%]; P = .59), regardless of IBS subtype. The odds ratio for weekly response with citalopram vs placebo was 0.80 (95% confidence interval, 0.61-1.04). Improvements in specific symptom and IBS-QOL scores were not superior for citalopram. Changes in IBS-QOL score and pressure eliciting pain showed a modest correlation (r = 0.33; 95% confidence interval, 0.03-0.57), but changes in symptoms and IBS-QOL scores or rectal sensitivity were not correlated substantially. CONCLUSIONS Citalopram was not superior to placebo in treating non-depressed IBS patients. Changes in symptoms were not substantially correlated with changes in rectal sensation assessed by barostat. Any benefit of citalopram in non-depressed IBS patients is likely to be modest at best.

Demyelinating events in early multiple sclerosis have inherent severity and recovery

Background: It is unclear whether the severity of and recovery from the initial demyelinating event (IDE) are recapitulated in subsequent multiple sclerosis (MS) relapses. We sought to identify the factors associated with relapse severity and recovery and to evaluate whether events have inherent severity or recovery. Methods: Patients seen at the UCSF MS Clinic within 1 year of disease onset were identified from a prospective database. Ordinal logistic regression was used to analyze predictors of three-level categorizations of event severity and recovery. Results: We identified 330 patients with MS or clinically isolated syndrome; 152 had a second event and 63 had a third event. Nonwhite and younger patients were at an increased risk of more severe demyelinating events. A severe prior event predicted a substantial increase in the odds of being above any given severity cutoff for a severe subsequent event (for second event severity, odds ratio [OR] = 5.62, 95% confidence interval [CI] [2.39, 13.26], p < 0.0001; for third event severity, OR = 6.74, 95% CI [1.67, 27.18], p = 0.007). Similarly, poor recovery of the IDE predicted poor second event recovery (OR = 5.28, 95% CI [1.95, 14.25], p = 0.001), while fair or poor second event recovery predicted about a 5- or 13-fold increase in the odds of poor third event recovery. A more severe event also predicted a substantial increase in the odds of poor recovery. Conclusions: Patients with severe presentation and poor recovery at disease onset continue on a similar trajectory with subsequent demyelinating events. Whether genetic or other biologic factors are responsible for this pattern remains to be determined.

The association between cervical human papillomavirus infection and HIV acquisition among women in Zimbabwe

Background:The prevalence of human papillomavirus (HPV) is higher among HIV-positive women, but the prevalence of HPV prior to HIV acquisition has not been carefully evaluated. Objective:This study evaluated whether HPV infection is independently associated with heterosexual HIV acquisition in a cohort of Zimbabwean women. Design:Case–control study nested within a large multicenter cohort study (HC-HIV). Methods:Cases consisted of Zimbabwean women with incident HIV infection observed during follow-up (n = 145). HIV-uninfected controls were selected and matched to cases (n = 446). The prevalence of cervical HPV infections was compared at the visit prior to HIV infection in the cases and at the same follow-up visit in the matched controls. Results:The odds of acquiring HIV were 2.4 times higher in women with prior cervical HPV infection after adjustment for behavioral and biologic risk factors. There was no statistically significant difference in the risk of HIV acquisition between women infected with high-risk vs. low-risk HPV types. Loss of detection of at least one HPV DNA type was significantly associated with HIV acquisition [odd ratio = 5.4 (95% confidence interval 2.9–9.9)] (P < .0001). Conclusion:Cervical HPV infection is associated with HIV acquisition among women residing in a region with a high prevalence of both infections. Further studies are required to evaluate whether the observed association is causal.

Vitamin D deficiency, self-reported physical activity and health-related quality of life: the Comprehensive Dialysis Study

BACKGROUND As research has identified a wide array of biological functions of vitamin D, the consequences of vitamin D deficiency in persons with chronic kidney disease has attracted increased attention. The objective of this study was to determine the extent of 25-hydroxyvitamin D (25-OH vitamin D) deficiency and its associations with self-reported physical activity and health-related quality of life (HRQoL) among participants of the Comprehensive Dialysis Study (CDS). METHODS The nutrition substudy of the CDS enrolled patients new to dialysis from 68 dialysis units throughout the USA. Baseline 25-OH vitamin D concentration was measured using the Direct Enzyme Immunoassay (Immunodiagnostic Systems Inc.). Physical activity was measured with the Human Activity Profile (HAP); the Medical Outcomes Study Short Form-12 (SF-12) was employed to measure HRQoL. RESULTS Mean age of the participants (n = 192) was 62 years. There were 124 participants (65%) with 25-OH vitamin D concentrations < 15 ng/mL, indicating deficiency, and 64 (33%) with 25-OH vitamin D ≥ 15 to <30 ng/mL, indicating insufficiency. After adjusting for age, sex, race/ethnicity, diabetes, season and center, lower 25-OH vitamin D concentrations were independently associated with lower scores on the HAP and on the Mental Component Summary of the SF-12 (P < 0.05 for both), but not with the Physical Component Summary of the SF-12. CONCLUSION In a well-characterized cohort of incident dialysis patients, lower 25-OH vitamin D concentrations were associated with lower self-reported physical activity and poorer self-reported mental health.