Jharna N Shah

University of Texas MD Anderson Cancer Center, Houston, Texas, United States

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Publications (14)46.56 Total impact

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    ABSTRACT: We developed an Immunodeficiency Scoring Index for Respiratory Syncytial Virus (ISI-RSV) infection, based on a cohort of 237 allogeneic hematopoietic cell transplant (allo-HCT) recipients, that can predict the risk of progression to lower respiratory tract infection (LRTI) and RSV-associated mortality. A weighted index was calculated using adjusted hazard ratios for immunodeficiency markers including age> 40, absolute neutrophils and lymphocytes counts. Based on the ISI-RSV (range: 0-12), patients were stratified into low (0-2), moderate (3-6), and high (7-12) risk groups. A significant trend of increasing incidence of progression to LRTI and RSV-associated mortality was observed as the risk increased from low to moderate to high (p < .001). Patients in the high-risk group had the greatest benefit of ribavirin-based therapy at the upper respiratory tract infection stage and the highest risk for progression to LRTI and death when antiviral therapy was not given [6.5 (95% CI, 1.8-23.6) and 8.1 (95% CI, 1.1-57.6), respectively]. The ISI-RSV is designed to stratify allo-HCT recipients with RSV infection into groups according to their risk for progression to LRTI and RSV-associated mortality. Identification of high-risk groups using this index would distinguish patients who would benefit the most from antiviral therapy, mainly with aerosolized ribavirin. The ISI-RSV should be validated in a multi-institutional study.
    Blood 04/2014; · 9.78 Impact Factor
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    ABSTRACT: Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections (LRTIs) in children, especially those with cancer. Data on RSV infections in this vulnerable population is limited. We conducted a retrospective study of all RSV infections in children with cancer from 1998 to 2009 to determine characteristics and outcomes of these infections, identify risk factors for LRTI and mortality, and the effect of antiviral therapy on these outcomes. We identified 59 patients with a median age of 5 years; 53% had hematologic malignancy, 32% were hematopoietic stem cell transplant recipients, 39% had received corticosteroids, and 76% cytotoxic chemotherapy within 1 month before RSV infection. LRTI developed in 22 (37%) patients with a trend of higher rate in males (odds ratio=2.57 [0.86-7.62], P=0.09) and children with lymphocytopenia (odds ratio=2.95 [0.86-10.12], P=0.085). No significant differences were observed in the rates of progression to LRTI (3/10 [30%] vs. 19/49 [39%], P=0.729) and RSV-associated mortality (0/10 [0%] vs. 3/49 [6%], P=0.422) for patients receiving antiviral therapy at upper respiratory tract infection stage compared with those who did not. However, patients with LRTI had significantly better outcomes when treated with aerosolized ribavirin plus immunomodulators (mainly palivizumab) when compared with aerosolized ribavirin alone (mortality rates: 0/6 [0%] vs. 3/4 [75%], P=0.03). Ribavirin did not show any benefit in reducing LRTI or mortality; however, addition of palivizumab to the treatment regimen may be potentially beneficial, especially for children with LRTI.
    Journal of Pediatric Hematology/Oncology 12/2013; · 0.97 Impact Factor
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    ABSTRACT: OBJECTIVES: Respiratory syncytial virus (RSV) infections are well recognized as a significant cause of morbidity and mortality in allogeneic haematopoietic stem cell transplant (allo-HSCT) recipients. We evaluated the spectrum of clinical manifestations, management (including ribavirin-based antiviral therapy) and outcomes of RSV infections and determined the risk factors associated with RSV lower respiratory tract infection (LRTI) and all-cause mortality. METHODS: In this retrospective study, we analysed clinical data from all laboratory-confirmed RSV infections in allo-HSCT recipients (n = 280) who presented at our institution from January 1996 to May 2009. RESULTS: Of the 280 patients, 80 (29%) developed LRTI within 20 days (median 1 day, range 0-19 days) and 44 (16%) died within 90 days (median 26 days, range 1-82 days) from RSV diagnosis. Multivariable logistic regression analyses identified several significant risk factors associated with RSV LRTI and all-cause mortality, including age, male sex, neutropenia, lymphocytopenia and lack of ribavirin-based antiviral therapy at the upper respiratory tract infection (URTI) stage. Aerosolized ribavirin-based therapy at the URTI stage was the single most significant factor in reducing the risk of RSV LRTI (83%), all-cause mortality (57%) and RSV-associated mortality (87%) in these patients (P < 0.05), irrespective of the year of RSV diagnosis. CONCLUSIONS: Our results demonstrate that RSV infections are a significant cause of morbidity and mortality in high-risk allo-HSCT recipients and ribavirin-based antiviral therapy at the URTI stage had a positive impact on both outcomes in this vulnerable population with multiple risk factors.
    Journal of Antimicrobial Chemotherapy 04/2013; · 5.34 Impact Factor
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    ABSTRACT: Clinical trial outcomes often involve an ordinal scale of subjective functional assessments but the optimal way to quantify results is not clear. In stroke, the most commonly used scale, the modified Rankin Score (mRS), a range of scores ("Shift") is proposed as superior to dichotomization because of greater information transfer. The influence of known uncertainties in mRS assessment has not been quantified. We hypothesized that errors caused by uncertainties could be quantified by applying information theory. Using Shannon's model, we quantified errors of the "Shift" compared to dichotomized outcomes using published distributions of mRS uncertainties and applied this model to clinical trials. We identified 35 randomized stroke trials that met inclusion criteria. Each trial's mRS distribution was multiplied with the noise distribution from published mRS inter-rater variability to generate an error percentage for "shift" and dichotomized cut-points. For the SAINT I neuroprotectant trial, considered positive by "shift" mRS while the larger follow-up SAINT II trial was negative, we recalculated sample size required if classification uncertainty was taken into account. Considering the full mRS range, error rate was 26.1%±5.31 (Mean±SD). Error rates were lower for all dichotomizations tested using cut-points (e.g. mRS 1; 6.8%±2.89; overall p<0.001). Taking errors into account, SAINT I would have required 24% more subjects than were randomized. We show when uncertainty in assessments is considered, the lowest error rates are with dichotomization. While using the full range of mRS is conceptually appealing, a gain of information is counter-balanced by a decrease in reliability. The resultant errors need to be considered since sample size may otherwise be underestimated. In principle, we have outlined an approach to error estimation for any condition in which there are uncertainties in outcome assessment. We provide the user with programs to calculate and incorporate errors into sample size estimation.
    PLoS ONE 01/2013; 8(7):e67754. · 3.53 Impact Factor
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    ABSTRACT: Background. Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSIs) can cause significant morbidity and mortality in patients with cancer. However, data on outcomes of patients treated with vancomycin are lacking.Methods. We identified 223 patients with cancer who developed MRSA BSIs between January 2001 and June 2009 and were treated with vancomycin. Treatment failure was defined as death within 60 days of infection, persistent bacteremia ≥5 days, fever ≥4 days, recurrence or relapse, and secondary MRSA infection.Results. The treatment failure rate was 52% (116 of 223 patients). These patients were more likely to have been hospitalized, been treated with steroids within the previous 3 months, developed acute respiratory distress syndrome, required mechanical ventilation, required intensive care unit care, and community-onset infections (all p < .05). Risk factors for MRSA-associated mortality (27 of 223 patients; 12%) included hematologic malignancy and hematopoietic stem cell transplantation, community-onset infection, secondary BSI, MRSA with minimum inhibitory concentration (MIC) ≥2.0 μg/mL, mechanical ventilation, and a late switch to an alternative therapy (≥4 days after treatment failure; all p < .05). On multivariate analysis, mechanical ventilation and recent hospitalization were identified as independent predictors of vancomycin failure, and community-onset infection, secondary BSIs, and MIC ≥2 μg/mL were identified as significant predictors of MRSA-associated mortality.Conclusions. We found a high treatment failure rate for vancomycin in patients with cancer and MRSA BSIs, as well as a higher mortality. A vancomycin MIC ≥2 μg/mL was an independent predictor of MRSA-associated mortality. An early switch to an alternative therapy at the earliest sign of failure may improve outcome.
    The Oncologist 06/2012; · 4.10 Impact Factor
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    ABSTRACT: Novel 2009/H1N1 influenza has significant impact on immunocompromised children with cancer; however, it is uncertain how it compares with seasonal influenza (SFlu) in this vulnerable population. We compared clinical characteristics and outcomes for these 2 infections in children with cancer and identified risk factors for progression to lower respiratory infection (LRI) and/or death. Influenza infections confirmed by positive viral culture and/or fluorescence antigen test between January 1998 and February 2010 were identified from microbiology databases at a comprehensive cancer center. Characteristics and outcomes were compared for the 2 groups. Kaplan-Meier survival curves and Cox proportional hazards model were generated to identify risk factors for LRI and/or death. When compared with SFlu, 2009/H1N1 cases had significantly lower acute physiology and chronic health evaluation II score (median: 9 versus 14), fewer comorbidities (15% versus 46%), fewer hematopoietic stem-cell transplantation (5% versus 16%), more solid tumors (45% versus 16%), higher LRI at presentation (20% versus 4%), higher rates of antiviral therapy (90% versus 48%) and higher mortality (10% versus 0%). Male gender (hazard ratio [HR]: 8.4, 95% confidence interval [CI]: 1.08-65.2, P = 0.042), acute physiology and chronic health evaluation II score > 15 (HR: 3.29, 95% CI: 1.04-10.39, P = 0.027) and a 24-hour delay in initiation of antiviral treatment (HR: 1.12, 95% CI: 1.02-1.23, P = 0.015) were the most significant predictors of progression to LRI and mortality, regardless of virus strain. Significant differences between 2009/H1N1 and SFlu with respect to clinical presentation, management and associated outcomes were identified. Early diagnosis and prompt initiation of antiviral therapy may prevent serious complications of influenza in children with cancer.
    The Pediatric Infectious Disease Journal 01/2012; 31(4):373-8. · 3.57 Impact Factor
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    ABSTRACT: Schizophrenia (SZP) has been historically referred to as "dementia praecox" because of the recognition that its onset is associated with deficits in memory, attention and visuospatial orientation. We wondered whether there is evidence for additional cognitive decline late in the course of chronic SZP. This review examined the evidence (1) for cognitive decline late in the course of chronic SZP, (2) for how often the late cognitive decline occurs, and (3) whether the cognitive decline in late-life SZP is related to pathophysiology of SZP versus the superimposition of another type of dementia. A PUBMED search was performed combining the MESH terms schizophrenia and dementia, cognitive decline, cognitive impairment and cognitive deficits. A manual search of article bibliographies was also performed. We included longitudinal clinical studies employing standard tests of cognition. Cross-sectional studies and those that did not test cognition through standard cognitive tests were excluded. The initial search produced 3898 studies. Employing selection criteria yielded twenty-three studies. Our data extraction tool included the number of patients in the study, whether a control group was present, the age of patients at baseline and follow-up, the study setting (inpatients versus outpatients), the cognitive tests employed, study duration, and results. Only three longitudinal studies tested for dementia using Diagnostic and statistical manual of mental disorder (DSM) or International classification of disease (ICD) criteria and compared them to controls: two studies demonstrated an increase in the prevalence of dementia and one did not. Twenty longitudinal studies tested for one or more cognitive domains without employing standard criteria for dementia: twelve studies demonstrated a heterogeneous pattern of cognitive decline and eight did not. Studies generally did not control for known risk factors for cognitive impairment such as education, vascular risk factors, apolipoprotein (ApoE) genotype and family history. The evidence for late cognitive decline in SZP is mixed, but, slightly more studies suggest that it occurs. If it occurs, it is unclear whether it is related to SZP or other risks for cognitive impairment. Hence, prospective, longitudinal, controlled studies are needed to confirm that there is progressive cognitive decline in chronic SZP which occurs independent of other risk factors for cognitive impairment.
    Psychiatric Quarterly 08/2011; 83(2):127-44. · 1.26 Impact Factor
  • Jharna N. Shah, Roy F. Chemaly
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    ABSTRACT: Herpes simplex virus (HSV) pneumonia is rare and is usually seen in immunocompromised patients. Patients with hematologic malignancies and hematopoietic stem cell transplant (HSCT) are at risk. Most of the cases of HSV pneumonia are caused by HSV-1; however, cases caused by HSV-2 have also been reported. Mucocutaneous disease often precedes the development of pneumonia, with nonspecific symptoms that include fever, cough, and dyspnea. Worsening oxygenation and failure to wean off mechanical ventilation despite broad-spectrum antimicrobial coverage is also a common presentation. Diagnosis requires a high degree of suspicion and is based on isolation of the virus from respiratory secretions and demonstration of cytopathic effects on histopathology. Acyclovir is the most widely used drug for treatment and prophylaxis. With increasing evidence of resistance to acyclovir and its analogs, newer agents such as foscarnet and cidofovir are being recommended as treatment options. Prophylaxis in patients with seropositive HSV undergoing chemotherapy or in the immediate post-HSCT period has been shown to reduce HSV disease rates and mortality rates. This chapter will focus on incidence and transmission, pathogenesis, risk factors, clinical features, diagnosis, and management of HSV pneumonia in patients with hematologic malignancies and HSCT, as well as outcome and prognosis.
    01/2011;
  • Jharna N Shah, Roy F Chemaly
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    ABSTRACT: Respiratory syncytial virus (RSV) is a common cause of seasonal respiratory viral infection in patients who have undergone hematopoietic stem cell transplantation. RSV usually presents as an upper respiratory tract infection in this patient population but may progress rapidly to lower respiratory tract infection. Available therapies that have been used for the treatment of RSV infections are limited to ribavirin, intravenous immunoglobulin, and palivizumab. The use of aerosolized ribavirin, alone or in combination with either palivizumab or intravenous immunoglobulin, remains controversial. In this comprehensive review, we present and discuss the available literature on management of RSV infections in adult hematopoietic stem cell transplantation recipients with a focus on therapeutic modalities and outcomes.
    Blood 12/2010; 117(10):2755-63. · 9.78 Impact Factor
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    ABSTRACT: Methicillin-resistant Staphylococcus aureus (MRSA) infections remain a significant cause of morbidity and mortality. We experienced an increased incidence of MRSA surgical-site infections (MRSA SSIs) at our institution. However, to our knowledge, no studies have evaluated the risk factors and outcomes of MRSA SSIs in cancer patients. We conducted a case-control study and identified all patients who had developed MRSA SSIs at our institution from July 1, 2002 to July 30, 2003, and all patients who had undergone surgery by the same surgical team during the same time period but who had not developed MRSA SSIs. Cases and controls were age-matched at 1:2 ratio. The study included 29 cases and 58 controls. Mean interval between surgery and MRSA SSI onset was 17.8 days (range 3-75 days). Cases were more likely than controls to have progressive cancer (72 versus 38%), have received antibiotics (mainly quinolones) within 24 h of surgery (17 versus 2%), have had ongoing infection (10 versus 0%), and have had longer hospital and intensive care unit stays (11.0 versus 7.8 days and 3.4 versus 1.5 days) (all P < 0.05). In a multivariate logistic regression analysis, significant predictors of MRSA SSI in cancer patients were antibiotics use <24 h of surgery and progressive cancer. No surgical factors (i.e., procedure time or timing of perioperative antibiotics) were associated with increased risk of MRSA SSI. Several clinical and postoperative factors were associated with increased risk of MRSA SSI in cancer patients, but antibiotic use before surgery (especially quinolones) and progressive cancer were the only independent predictors.
    Annals of Surgical Oncology 06/2010; 17(6):1499-506. · 4.12 Impact Factor
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    ABSTRACT: Background Methicillin-resistant Staphylococcus aureus (MRSA) infections remain a significant cause of morbidity and mortality. We experienced an increased incidence of MRSA surgical-site infections (MRSA SSIs) at our institution. However, to our knowledge, no studies have evaluated the risk factors and outcomes of MRSA SSIs in cancer patients. Methods We conducted a case–control study and identified all patients who had developed MRSA SSIs at our institution from July 1, 2002 to July 30, 2003, and all patients who had undergone surgery by the same surgical team during the same time period but who had not developed MRSA SSIs. Cases and controls were age-matched at 1:2 ratio. Results The study included 29 cases and 58 controls. Mean interval between surgery and MRSA SSI onset was 17.8 days (range 3–75 days). Cases were more likely than controls to have progressive cancer (72 versus 38%), have received antibiotics (mainly quinolones) within 24 h of surgery (17 versus 2%), have had ongoing infection (10 versus 0%), and have had longer hospital and intensive care unit stays (11.0 versus 7.8 days and 3.4 versus 1.5 days) (all P
    Annals of Surgical Oncology 03/2010; · 4.12 Impact Factor
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    ABSTRACT: Background: Parainfluenza viral (PIV) infections are common cause of respiratory illness in children. Lack of treatment for PIV may be contributing to high morbidity and mortality in children. Studies focusing on PIV in children with cancer are limited. Methods: We identified 32 PIV infections in pediatric cancer patients (pts) from 1/1998- 12/2008. Data on demographics, underlying cancer type, risk factors for progression from upper (URI) to lower respiratory tract infection (LRI) & treatment were collected. Outcomes were determined within 60 days from the first positive viral culture/ direct fluorescent antigen test. Pts were classified with severe immunodeficiency (SID) if they have at least 2 of the following- HSCT within 6 mth, chemotherapy/steroids, neutropenia (ANC<500/μl), and lymphopenia (ALC<200/μl) < 2 wks. Results: Median age was 6 y (Range: 0.6 -18y); 69% were males. Most pts were HSCT recipients [44%] or had hematologic malignancies [44%-mainly ALL [79%]. SID was found in 66% pts. LRI developed in 41% pts & these pts were more likely to be males [77% vs. 63%], HSCT recipients [69% vs. 26%], AML [15% vs. 0%], SID [90% vs. 63%], have higher APACHE II score at onset [19±2 vs. 16±3], have higher rate of coinfections [92% vs. 47%)], longer symptom duration (d) [27±19 vs. 12±7], longer length of stay (d) [12±11 vs. 6±3] and higher 60-d mortality [15% vs. 0%], (all p≤0.05) as compared to URI pts. Aerosolized Ribavirin was used in 4 SID pts after progression to LRI with 1 death at 60-d. SID pts had higher 60-d mortality [9% vs. 0%, p=0.003] as compared to mild-moderate immunodeficient pts. Cancer treatment was delayed in 28% pts. HSCT pts had more LRI [64% vs.29%], longer symptom duration (d) [25±20 vs. 12±6], more ICU stays [29% vs. 27%], more comorbidities [57% vs. 36%], more coinfections [79% vs. 57%] & more 60-d mortality [14% vs. 0%], (all p<0.05)] as compared to hematologic cancer pts. Conclusion: PIV is associated with significant morbidity & mortality in pediatric cancer pts, especially in pts with SID & HSCT recipients. This highlights the need for an effective PIV-specific antiviral medication to improve 60-d outcomes in this population.
    Infectious Diseases Society of America 2009 Annual Meeting; 10/2009
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    ABSTRACT: Background: An increase in CDI cases is seen over the past decade and multiple outbreaks due to a virulent strain of CDI (BI/NAP1/027) have been reported in many hospitals as well as in our institution in May’07. There is a lack of data on risk factors and outcome of CDI amongst cancer patients (pts) Methods: There was an increase in CDI at our institution from May’07 to Sept’07 (0.38 in Feb’07 to 1.92/1000 pts-days in May’07, p<0.05). We evaluated 100 pts (Cases) during the outbreak and collected data on demographics, risk factors & outcome of CDI and compared it to 2 control groups of 100 pts each matched for age and cancer [positive control group (PCG): pts with CDI 2 y prior to the outbreak and the negative control group (NCG): pts who had diarrhea during the outbreak period but no CDI] Results: Demographics and average length of the stay were similar between the 3 groups. When compared to NCG, cases had a higher APACHE score (14.1 vs. 11.9, p=0.04), were more likely to have a co-infection (54 vs. 39, p=0.04) with a trend of more likely to be on quinolones (65 vs. 52, p=0.08) and antacids (74 vs. 62, p=0.09) within 30 days of CDI. Thirty five cases had severe CDI as compared to 23 pts in PCG (p=0.08). Amongst the cases, pts with Leukemia were more likely to develop severe CDI (37% vs. 21% p=0.01), had a higher co-infection rate (70% vs. 21% p<0.01), relapse rate (14% vs. 5%, p=0.04) and APACHE score (14.2 vs. 9.6, p=0.03) as compared to pts with HSCT, with no difference in mortality. Amongst cases, pts with severe CDI were more likely to be transferred to the ICU (25% vs. 8% p=0.03) and die from CDI (22% vs. 6% p=0.02). When treated with metronidazole, cases with severe CDI had higher mortality (30% vs. 13%, p<0.01) and relapse rate (11% vs. 2.8%, p=0.04) as compared to pts on oral vancomycin. Conclusion: During the outbreak, more cancer pts developed severe CDI which probably was due to the circulating BI/NAP1/027 strain at our institution. Patients with severe CDI had higher mortality and relapse rates especially if they were treated with metronidazole instead of vancomycin. We recommend the usage of Oral Vancomycin in cancer pts with severe CDI
    Infectious Diseases Society of America 2009 Annual Meeting; 10/2009
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    ABSTRACT: Background: RSV is a major cause of respiratory tract infections in pediatric patients (pts). Immunodeficiency can be a major risk factor for severe infection & mortality. Data on RSV infection in children with cancer is limited. Methods: We identified 56 RSV infections in pediatric cancer pts between 1/1998 and 1/2009. Data on demographics, underlying cancer type, risk factors for progression from upper (URI) to lower respiratory tract infection (LRI) & treatment were collected. Outcomes were determined within 60 days from the first positive viral culture &/or direct fluorescent antigen test. Pts were classified with severe immunodeficiency (SID) if they have at least 2 of the following, including HSCT within 6 mth, chemotherapy/steroids, neutropenia (ANC<500/μl), and lymphopenia (ALC<200/μl) < 2 wks. Some pts were treated with aerosolized ribavirin ± palivizumab or IV Ig. Results: Median age was 6.5 y (range: 1-18 y) and 29 (52%) were males. Majority (36, 64%) had hematologic malignancies - mainly ALL (29/36, 80%); 13 (23%) were HSCT recipients. Median APACHE II score was 17 (Range: 11-22). SID was found in 26/56 (46%) pts. LRI developed in 22 (39%) pts. When compared to pts treated at URI stage, pts who were not treated had higher rate of progression to LRI [3/11 (27%) vs. 19/45 (42%), p=0.03] & higher 60-d mortality [0/11 (0%) vs. 3/45 (7%), p=0.01]. More pts with SID had progression to LRI [14/23 (61%) vs. 1/3 (33%), p<0.001] and died at 60 d [2/23 (9%) vs. 0/3 (0%), p=0.003] when not treated at URI stage. Out of 14 pts who were treated after progression to LRI, 3 (21%) died within 60d. Multivariate analysis identified SID (p=0.01) to be a significant predictor of progression to LRI. Conclusion: Treatment at URI stage may reduce progression to LRI & lower 60-d mortality, especially in pts with SID.
    Infectious Diseases Society of America 2009 Annual Meeting; 10/2009