Rafia Bhore

Risk factors in children hospitalized with RSV bronchiolitis versus non-RSV bronchiolitis.

BACKGROUND: The trends in hospitalization rates and risk factors for severe bronchiolitis have not been recently described, especially after the routine implementation of prophylaxis for respiratory syncytial virus (RSV) infections. OBJECTIVES: To define the burden of hospitalizations related to RSV and non-RSV bronchiolitis in a tertiary-care childrens hospital from 2002 to 2007 and to identify the risk factors associated with severe disease. METHODS: Medical records of patients hospitalized for bronchiolitis were reviewed for demographic, clinical, microbiologic, and radiologic characteristics as well as the presence of underlying medical conditions. Differences were evaluated between children with RSV and non-RSV bronchiolitis, and multivariable logistic regression analyses were performed to identify independent risk factors for severe disease. RESULTS: Bronchiolitis hospitalizations in children younger than 2 years old (n = 4800) significantly increased from 536 (3.3%) in 2002 to 1241 (5.5%) in 2007, mainly because of RSV infections. Patients with RSV bronchiolitis (n = 2840 [66%]) were younger at hospitalization and had a lower percentage of underlying medical conditions than children hospitalized with non-RSV bronchiolitis (27 vs 37.5%; P < .001). However, disease severity defined by length of hospitalization and requirement of supplemental oxygen, intensive care, and mechanical ventilation was significantly worse in children with RSV bronchiolitis. RSV infection and prematurity, regardless of the etiology, were identified as independent risk factors for severe bronchiolitis. CONCLUSIONS: There was a significant increase in hospitalizations for RSV bronchiolitis from 2002 to 2007. A majority of the children with RSV bronchiolitis were previously healthy, but their disease severity was worse compared with those hospitalized with non-RSV bronchiolitis.

Reliability assessment and validation of the Melasma Area and Severity Index (MASI) and a new modified MASI scoring method

BACKGROUND The Melasma Area and Severity Index (MASI), the most commonly used outcome measure for melasma, has not been validated. OBJECTIVE We sought to determine the reliability and validity of the MASI. METHODS After standardized training, 6 raters independently rated 21 patients with mild to severe melasma once daily over a period of 2 days to determine intrarater and interrater reliability. Validation was performed by comparing the MASI with the melasma severity scale. The darkness component of the MASI was validated by comparing it with the difference between mexameter scores for affected versus adjacent normal-appearing skin. The area component of the MASI was validated by comparing it with the area of each section of the face determined by computer-based measurement software. RESULTS The MASI score showed good reliability within and between raters and was found to be valid when compared with the melasma severity scale, mexameter scores, and area measurements. Homogeneity assessment by raters showed the least agreement and can be removed from the MASI score without any loss of reliability. LIMITATIONS Patients were limited to Hispanic, African, and Asian backgrounds. CONCLUSION The MASI is a reliable measure of melasma severity. Area of involvement and darkness are sufficient for accurate measurement of the severity of melasma and homogeneity can be eliminated.

Cardiovascular autonomic functions in well-controlled and intractable partial epilepsies.

BACKGROUND Epilepsy is associated with imbalance of sympathetic and parasympathetic activity which may lead to sudden unexplained death in epilepsy (SUDEP). Well-controlled (WcE) and intractable epilepsy (IE) subjects may present different autonomic profiles, which can be helpful in explaining the predisposition of the latter to SUDEP. PURPOSE To compare inter-ictal cardiovascular autonomic function in subjects with partial WcE and IE. METHODS Thirty WcE and 31 IE subjects underwent a battery of autonomic function tests: deep breathing, Valsalva maneuver, isometric exercise, cold pressor and tilt-table. Autonomic tone was assessed by heart rate variability (HRV). Their autonomic severity score and anxiety status was also assessed. RESULTS IE subjects had elevated low frequency component (52.0 vs. 37.6, p=0.047) and decremented high frequency component (114 vs. 397, p=0.013) of HRV and higher diastolic BP (75.62+/-9.77 vs. 68.64+/-0.43, p=0.036). In deep breathing test, they had lesser HR changes (20+/-10.18 vs. 29.68+/-11.23, p=0.007) and lower E:I (1.29+/-0.16 vs. 1.43+/-0.21, p=0.008). IE subjects had higher dysautonomia (chi square 165.0, p<0.0001). CONCLUSIONS We observed a higher vasomotor tone, higher sympathetic tone, lower parasympathetic tone, lower parasympathetic reactivity and more severe dysautonomia in the IE subjects. Refractoriness may lead to an alteration in cardiovascular autonomic regulation, which might be a predisposing factor for SUDEP.

Meta-Analysis of Gender Differences in Efficacy Outcomes for HIV-Positive Subjects in Randomized Controlled Clinical Trials of Antiretroviral Therapy (2000–2008)

Women are often underrepresented in randomized clinical trials (RCT) of HIV-1 drugs. As a result, determining whether women have different virologic outcomes compared to men is not always possible because the gender-related analyses usually lack statistical power. To address this important public health concern, the Food and Drug Administrations (FDA) Division of Antiviral Products (DAVP) created a database including 20,328 HIV-positive subjects from 40 RCTs in 18 New Drug Applications (NDAs) submitted to the FDA between 2000 and 2008. These RCTs were conducted for at least 48 weeks in duration and were used to support approval of new molecular entity, new formulation, or major label change. To delineate potential gender differences in antiretroviral treatment (ART), we evaluated the percentage of subjects with HIV RNA less than 50 copies per milliliter at 48 weeks. Analyses of the database represent the most systematic review of gender-related ART efficacy data to date. Overall, the meta-analyses did not demonstrate statistically or clinically significant gender differences in virologic outcome at week 48. However, the corresponding subgroup analyses appear to show several statistically significant gender differences favoring males.

Addressing multiplicity issues of a composite endpoint and its components in clinical trials.

Randomized controlled clinical trials often use a composite endpoint as a primary endpoint especially when treatment effects or frequency of individual components of the composite are likely to be small and combining them makes clinical sense for the disease under study. An advantage of the composite endpoint is that, as it combines multiple endpoints to a single endpoint, it reduces or eliminates the multiplicity problem of testing multiple endpoints. In addition, accumulating evidence from individual endpoints into the composite endpoint can lead to better study power and reduce the study size and the duration of the trial. However, composite endpoints can also lead to ambiguous findings and consequently cause difficulty in interpreting study results, for example, when individual component endpoints of a composite show treatment effects in different directions. Also, multiplicity issues will arise if a study sponsor seeks efficacy claims for specific components of the composite or for a targeted subgroup of patients. This paper visits some of these issues and presents some solutions through applications of multiple testing strategies.

Acute Kidney Injury and Chronic Kidney Disease in Hospitalized Patients With Cirrhosis

Background Renal dysfunction is a common and potentially life-threatening complication in hospitalized patients with cirrhosis. Aims To determine the prevalence, cause, and outcome of patients with cirrhosis and acute kidney injury (AKI) and/or chronic kidney disease (CKD). Methods This retrospective analysis examined hospital records of 152 consecutive patients with cirrhosis and creatinine levels of 1.5 mg/dL or greater. Multiple clinical and laboratory variables were abstracted for each subject. Precise definitions were used to define cirrhosis and etiologies of renal dysfunction. Univariate and multivariable logistic regression analyses were performed to identify features with prognostic value for hospital mortality. Results The most common type of renal dysfunction was AKI, present in 107 patients (70%). Acute kidney injury plus CKD was found in 26 patients (17%), and CKD alone was present in 19 patients (13%). Prerenal azotemia was the most common cause of AKI (69%), often occurring secondary to gastrointestinal hemorrhage. The overall mortality for the cohort was 31%, with the highest mortality occurring in patients with type 1 hepatorenal syndrome (HRS) (11/14, 79%). We were unable to identify any patient meeting diagnostic criteria for type 2 HRS. The development of AKI on preexisting CKD did not infer worse prognosis than AKI alone. The presence of upper gastrointestinal bleeding, bacteremia, and HRS-1 predicted mortality. Conclusions Both AKI and CKD are common in hospitalized patients with cirrhosis, often occurring simultaneously. Type 2 HRS was not identified, suggesting that its diagnostic criteria may need reevaluation or that this syndrome may not represent a unique functional kidney disorder.

Indexing Severity of Diabetic Foot Infection With 99mTc-WBC SPECT/CT Hybrid Imaging

OBJECTIVE Management of diabetic foot infection (DFI) has been hampered by limited means of accurately classifying disease severity. New hybrid nuclear/computed tomography (CT) imaging techniques elucidate a combination of wound infection parameters not previously evaluated as outcome prognosticators. Our aim is to determine if a novel standardized hybrid image–based scoring system, Composite Severity Index (CSI), has prognostic value in DFI. RESEARCH DESIGN AND METHODS Masked retrospective 99mTc-white blood cell (WBC) single photon emission CT (SPECT)/CT image interpretation and independent chart review of 77 patients (101 feet) suspected of DFI-associated osteomyelitis at a large municipal hospital between January 2007 and July 2009. CSI scores were correlated with probability of favorable outcome (no subsequent amputation/readmission after therapeutic intervention) during median 342-day follow-up. RESULTS CSI ranged from 0–13. Receiver operating characteristic accuracy for predicting favorable outcome was 0.79 (optimal cutoff CSI, ≤2; odds ratio of therapeutic failure for CSI >2, 15.1 [95% CI 4.4–51.5]). CSI of 0 had a 92% chance of favorable outcome, which fell progressively to 25% as indices rose to ≥7. Image-based osteomyelitis versus no osteomyelitis assessment was less accurate than CSI at predicting outcome (P = 0.016). In patients with intermediate severity (CSI 3–6), treatment failure decreased from 68 to 36% when antibiotic duration was extended to ≥42 days (P = 0.026). CONCLUSIONS 99mTc-WBC SPECT/CT hybrid image–derived wound infection parameters incorporated into a standardized scoring system, CSI, has prognostic value in DFI.

Secondary cytoreductive surgery for recurrent platinum‐sensitive ovarian cancer

To determine the risks and benefits of secondary cytoreductive surgery for recurrent platinum‐sensitive ovarian cancer.

Change in Fibrosis Score as a Predictor of Mortality Among HIV-Infected Patients with Viral Hepatitis

Noninvasive markers of liver fibrosis, measured at baseline, have been shown to predict liver-related mortality. It remains unknown if a change in the value of the scores over time predicts mortality in patients with HIV and viral hepatitis. In this retrospective study, survival in HIV/hepatitis B virus (HBV; n = 67), HIV/hepatitis C virus (HCV; n = 43), and HIV/HBV/HCV (n = 41) patients was examined using Kaplan-Meier life table analysis. Aspartate aminotransferase (AST)-to-platelet ratio index (APRI) and FIB-4 scores, two noninvasive markers of liver fibrosis, were calculated at baseline and at last available clinical follow-up to determine the change in fibrosis score. Factors associated with mortality were assessed by Cox proportional hazards, including the change in the noninvasive marker score between the two time points. All-cause mortality was determined by Social Security Death Index and chart review. Sixty-seven were coinfected with HIV/HBV, 43 with HIV/HCV, and 41 were triply infected (HIV/HBV/HCV). Kaplan-Meier analysis showed similar survival for the three groups at 7 years of follow-up (p = 0.10). However, median length of follow-up was lower in HIV/HCV (60.5; range 0-102) compared to HIV/HBV (75.7; 12.3-126.5) and HIV/HBV/HCV (80.0; 2.7-123) months, respectively, p = 0.02. Baseline fibrosis score (p = 0.002), an increase in the value for noninvasive measurements for fibrosis (p < 0.001), and the presence of HIV/HCV coinfection (p = 0.041) were each associated with higher risk for mortality. Baseline fibrosis score (p = 0.03) and an increase in FIB-4 score (p = 0.05) were independent predictors of all-cause mortality, but liver-related mortality was not evaluated. In this study, baseline fibrosis score was predictive of 7-year all-cause mortality. Further studies are needed in a prospective cohort to evaluate the predictive value of monitoring changes in fibrosis scores over time to predict mortality in patients with viral hepatitis.

The hematocrit level in upper gastrointestinal hemorrhage: safety of endoscopy and outcomes.

OBJECTIVE In patients with acute upper gastrointestinal hemorrhage, standard practice is to transfuse packed red blood cells, often to an arbitrary level of hemoglobin or hematocrit (typically 10 g/dL and 30%, respectively) before endoscopy. Therefore, we aimed to determine first whether performing endoscopy in patients with upper gastrointestinal hemorrhage and a low hematocrit is safe and whether it predicts outcomes. METHODS This cohort study included patients with carefully defined upper gastrointestinal hemorrhage captured in our gastrointestinal Healthcare Registry who underwent esophagogastroduodenoscopy. Patients were placed into 2 groups: low hematocrit (<30%) or high hematocrit (>30%). Clinical variables and outcomes, including cardiovascular events, intensive care unit transfer, and death, were measured. RESULTS A total of 920 patients meeting entry criteria were identified. Baseline features among those with a low and high hematocrit were identical. Eight cardiovascular events occurred during or after esophagogastroduodenoscopy, including 5 of 587 (1%) in the less than 30% hematocrit group and 3 of 333 (1%) in the greater than 30% hematocrit group (P=.29). Blood transfusions were more common in the low hematocrit group (74% vs 24%, P<.001). However, correlation between the amount of blood transfused and hematocrit level was poor, and the number units of blood transfused was highly variable. There was no significant mortality difference in the 2 hematocrit groups. CONCLUSION Most patients with upper gastrointestinal hemorrhage presented with a hematocrit less than 30%. Performing endoscopy in patients with a low hematocrit was clearly safe; these data strongly imply that waiting for the hematocrit to reach a certain level before endoscopy is not necessary.