Citations

ABSTRACT Invasive fungal infections are a significant cause of morbidity and mortality in patients who receive immunosuppressive therapy, such as solid organ and hematopoietic stem cell transplant (HSCT) recipients. Many of the fungi associated with these infections are angioinvasive and are best diagnosed by visualizing the organism in or culturing the organism from deep tissue. However, obtaining such tissue often requires an invasive procedure. Many HSCT recipients are thrombocytopenic, making such procedure too risky because of potential bleeding complications. Additionally, positive blood cultures are rare for patients with angioinvasive fungal infections, making this diagnostic strategy of little value. Undiagnosed fungal infections in these patient populations are a significant cause of mortality. Prophylactic use of antifungal agents, such as the echinocandins, during periods of neutropenia or graft-versus-host disease may prevent some fungal infections but increase the risk for others. Detection of fungal antigens in body fluids, including cryptococcus capsular polysaccharide, histoplasma antigen, galactomannan, and β- d -glucan, is viewed as being clinically useful for at least the presumptive diagnosis of invasive fungal infections. β- d -Glucan is an attractive antigen in that it is found in a broad range of fungal agents, including the commonly encountered agents Candida spp., Aspergillus spp., and Pneumocystis jirovecii. Cross-reactions with certain hemodialysis filters, beta-lactam antimicrobials, and immunoglobulins, which raise concerns about false-positive tests, have also been described. As a result, the use of this testing must be closely monitored. In this point-counterpoint, we have asked Elitza Theel, who directs the Infectious Disease Serology Laboratory at the Mayo Clinic, to address why she believes that this test has value in the diagnosis of invasive fungal infections. We have asked Christopher Doern, Director of Clinical Microbiology at Children's Medical Center of Dallas, why he questions the clinical value of β- d -glucan testing.

A 23-year-old woman presented to the emergency department with severe occipital headache, nausea and fever. She was treated with intravenous antibiotics for suspected meningitis. After a brief period of response, her symptoms relapsed and remained refractory despite continuing intravenous antibiotics for 10 days leading to referral to our centre. Physical examination was significant for tender right cervical lymph node. Initial tests included pancytopenia, elevated C reactive protein, lactate dehydrogenase and unremarkable cerebrospinal fluid. Extensive infectious and rheumatology work-up was negative. Massive posterior cervical, axillary and inguinal lymphadenopathy was revealed on imaging. Excisional biopsy of the deep cervical lymph node showed histiocytic necrotising lymphadenitis suggesting a diagnosis of Kikuchi disease. Her course was complicated by acute renal failure. Her symptoms resolved in about a week with supportive treatment along with improvement in pancytopenia and renal function. She had two additional self-limited recurrences in the next 3 months and remains symptom free thereafter.

Purpose: To determine the factors that affect mean absorbed dose and fluoroscopic times during renal artery stent placement. Materials and Methods: After institutional review board approval, the HI-IQ database was queried for patients undergoing renal artery stent placement only from January 2007 to June 2010. Procedures that were performed as part of other procedures such as iliac artery stents were excluded. The HI-IQ data included fluoroscopy time ( f) and radiation dose (mGy). Demographic, medical history, procedural details, and advanced preprocedural renal artery stent imaging were obtained. Variables (number of stents, average body mass index , number of stents placed per year and number of years’ service of an interventional physician, pre-procedural imaging, and use of embolic protection device) were analyzed using a t test after log transformation and testing for variance with an F test. Results: A total of 134 patients (75 males, 70.6 ± 10.5 years old) underwent the placement of 177 renal artery stents (unilateral [n = 95], average stent per patient = 1.3). Mean fluoroscopy time was 15.6 minutes and mean absorbed dose to the patient was 1729 mGy. The average fluoroscopic time and absorbed dose was significantly higher with bilateral stent placement compared to unilateral placement (13.8 vs 19.7 minutes, P = .002; 1803 vs 2380 mGy, P = .03). The average fluoroscopic time was significantly higher in patients undergoing abdominal aortogram prior to renal artery selection and stent placement. Conclusion: The placement of more than 1 stent with an abdominal angiogram prior to renal artery stent placement results in increased fluoroscopic time and mean absorbed dose.

Significant progress in molecular genetics has advanced our understanding of the genetic basis of migraine. The fundamentals of molecular genetics, and the recent advances in the field, are important for clinicians to understand, as they provide a foundation for critical appraisal of the literature, unprecedented insights into the pathogenesis of the disorder, and reveal promising treatment targets for future drug development. This paper provides a primer of molecular genetics and will be followed by a companion paper on the genetic advances in migraine, the methodology of genome wide association studies, and the potential clinical implications.

Outcomes of external beam radiotherapy (EBRT) in advanced medullary thyroid carcinoma (MTC) are largely unknown. Retrospective review of data from patients with MTC, diagnosed from June 1, 1970, through December 31, 2007. Overall survival and locoregional tumor control rates were calculated. Seventeen patients had adjuvant or palliative EBRT delivered to 41 sites. Six patients initially had adjuvant EBRT (median, 60.80 Gy); none had relapse in the treated area. Five patients with locoregional recurrence after surgery were treated (median, 59.40 Gy), and durable disease control was achieved in 3. Twelve patients received palliative EBRT to 29 sites of metastatic disease (median, 30.00 Gy), which provided sustained symptom relief at 45% of sites. Five- and ten-year overall survival rates were 44% and 19%, respectively. Adjuvant EBRT may be most effective for prevention of locoregional recurrence. EBRT may provide sustained control of advanced, metastatic disease in select patients.

AbstractAimsThe number of elderly persons with end‐stage renal disease is increasing with many requiring hospitalizations. This study examines the causes and predictors of hospitalization in older haemodialysis patients.MethodsWe reviewed hospitalizations of older (≥65 years) incident chronic haemodialysis patients initiating therapy between 1 January 2007 and 31 December 2009 under the care of a single Midwestern United States dialysis provider.ResultsOf 125 patients, the mean age was 76 ± 7 years and 72% were male. At first dialysis, 68% used a central venous catheter (CVC) and 51% were in the hospital. Mean follow‐up was 1.8 ± 1.0 years. At least one hospitalization occurred in 89 (71%) patients and half of all patients were hospitalized once within the first 223 days. Total hospital admission rate was 1.48 per patient year with hospital days totalling 8.54 days per patient year. The three most common reasons for first admission were cardiac (33%), infection (18%) and gastrointestinal (12%). Predictors of future hospitalization included the first dialysis occurring in hospital (hazard ratios (HR) 2.1, 95% CI 1.4–3.3, P = 0.0005) and the use of a CVC at first haemodialysis (HR 2.6, CI 1.6–4.4, P < 0.0001).ConclusionHospitalizations are common in older incident haemodialysis patients. Access preparation and overall burden of illness leading to the initial hospitalization appear to play a role. Identification of additional factors associated with hospitalization will allow for focused interventions to reduce hospitalization rates and increase the value of care.

Collaborative care management (CCM) for depression has been demonstrated to improve clinical outcomes. The impetus for this study was to determine if outpatient utilization patterns would be associated with depression outcomes. The hypothesis was that depression remission would be independently correlated with outpatient utilization at 6 and 12 months after enrollment into CCM. The study was a retrospective chart review analysis of 773 patients enrolled into CCM with 6- and 12-month follow-up data. The data set comprised baseline demographic data, patient intake self-assessment scores (Patient Health Questionnaire [PHQ-9], Generalized Anxiety Disorder-7, Mood Disorder Questionnaire, and Alcohol Use Disorders Identification Test), the number of outpatient visits, and follow-up PHQ-9 scores. To control for individual patient complexity and pattern of usage, the number of outpatient visits for 6 months prior to enrollment also was measured. With a logistic regression model for outpatient visit outlier status as the dependent variable, remission at 6 months (odds ratio [OR] 0.519, CI [confidence interval] 0.349–0.770, P =0.001) and remission at 12 months (OR 0.573, CI 0.354–0.927, P =0.023) were predictive. With this inverse relationship between remission and outlier status, those patients who were not in remission had an OR of 1.928 for outpatient visit outlier status at 6 months after enrollment and an OR of 1.745 at 12 months. Patients who improved clinically to remission while in CCM had decreased odds of outlier status for outpatient utilization at 6 and 12 months when controlling for all other study variables. Improvement in health care outcomes by CCM could translate into decreased outpatient utilization for depressed patients. ( Population Health Management 2014;17:48–53)

Summary Purpose To review the efficacy and tolerability of stiripentol in the treatment of U . S . children with D ravet syndrome. Methods U . S . clinicians who had prescribed stiripentol for two or more children with D ravet syndrome between March 2005 and 2012 were contacted to request participation in this retrospective study. Data collected included overall seizure frequency, frequency of prolonged seizures, and use of rescue medications and emergency room ( ER )/hospital visits in the year preceding stiripentol initiation, and with stiripentol therapy. We separately assessed efficacy in the following treatment groups: g roup A , stiripentol without clobazam or valproate; g roup B , stiripentol with clobazam but without valproate; g roup C , stiripentol with valproate but without clobazam; and g roup D , stiripentol with clobazam and valproate. In addition, adverse effects were recorded. Key Findings Thirteen of 16 clinicians contacted for study participated and provided data on 82 children. Stiripentol was initiated a median of 6.0 years after seizure onset and 1.2 years after diagnosis of D ravet syndrome. Compared to baseline, overall seizure frequency was reduced in 2/6 in g roup A , 28/35 in g roup B , 8/14 in g roup C , and 30/48 in g roup D . All children with prolonged seizure frequency greater than quarterly during the baseline period experienced a reduction in this frequency on the various treatment arms with stiripentol. Similarly, 2/4 patients in g roup A , 25/25 in g roup B , 5/10 in g roup C , and 26/33 in g roup D experienced reduction in frequency of rescue medication use and 1/1 in g roup A , 12/12 in g roup B , 3/5 in g roup C , and 18/19 in group D had reduction in frequency of ER /hospital visits. Adverse effects were reported in 38, most commonly sedation and reduced appetite. Four patients (5%) discontinued stiripentol for adverse effects and two (2%) for lack of efficacy. Significance Stiripentol is an effective and well‐tolerated therapy that markedly reduced frequency of prolonged seizures in D ravet syndrome.