OBJECTIVES:

Currently used metrics for antibiotic utilization are not linked to a diagnosis and may be difficult to interpret. We aimed to describe patterns and variation in antibiotic management of three common infectious disease diagnoses in Veterans Affairs Medical Centers (VAMCs).

METHODS:

This descriptive retrospective cohort study included all veterans discharged between 2007 and 2009 after an acute care admission to a VAMC and a principal ICD-9-CM code for pneumonia (PNEU), skin and soft-tissue infections (SSTI), urinary tract infections (UTI) or non-infectious disease-related diagnoses (NON_INF). Systemic antibiotic use was assessed based on barcode medication administration data. A treatment period was defined as a time of uninterrupted inpatient antibiotic therapy with no gaps of >1 calendar day.

RESULTS:

Over the study period there were 1.44 million discharges with an acute care admission to 128 VAMCs included in the study. Of the discharges, 58 118 had a primary ICD-9-CM diagnosis classifiable as PNEU, 36 797 as SSTI, 30 223 as UTI and 1 243 098 as NON_INF. Empirical antibiotic use during the first 2 hospital days was frequent for all infectious disease diagnoses. Type of empirical coverage varied among facilities for all conditions, as did treatment durations. Roughly half of all empirical courses of therapy where the patient was still hospitalized on day 4 did not exhibit any change to the antibiotic regimen.

CONCLUSIONS:

There is substantial variation in the management of common infectious diseases with regard to choice of empirical agents and duration of therapy. Diagnosis-specific antibiotic use metrics may prove useful for antibiotic stewardship programmes.

INTRODUCTION:

The UK National Institute for Health and Clinical Excellence (NICE) introduced guidelines for the diagnosis, treatment and management of urinary tract infection (UTI) in children and adolescents in August 2007.

AIM:

The primary aim was to determine whether publication of NICE guidelines was associated with a change in the use of diagnostic imaging investigations in patients with a documented first UTI in a tertiary children's hospital. Secondary aims were to describe the epidemiology, microbiology, prescription of prophylactic antibiotics and follow-up for these children, and the incidence of structural renal tract abnormalities, vesicoureteric reflux and renal uptake defects identified.

METHODS:

Retrospective review of the case notes of patients presenting to Princess Margaret Hospital, Perth, Western Australia with a first UTI over a 4-year period (August 2005-2009). Details of demographics, radiological investigations, microbiology and follow-up were obtained. Data for subjects presenting before and after 31 August 2007 were compared.

RESULTS:

Data from 659 subjects, median age 6 (range 0-186) months were analysed. Compared with the pre-NICE period, there was no change in the proportion of patients undergoing renal USS in the 2 years following publication of the guidelines. There was a decrease in the proportion undergoing MCUG (p<0.0001) and receiving antibiotic prophylaxis (p<0.0001) and an increase in the proportion undergoing DMSA (p<0.001).

CONCLUSIONS:

Practice changed following publication of the NICE guidelines. While the reduction in MCUG requests and prescription of antibiotic prophylaxis is in line with NICE guidelines, the increase in DMSA requests is contrary to the recommendations.

BACKGROUND:

The extent to which psychosocial and diet behavior factors affect dietary self-report remains unclear. We examine the contribution of these factors to measurement error of self-report.

METHODS:

In 450 postmenopausal women in the Women's Health Initiative Observational Study doubly labeled water and urinary nitrogen were used as biomarkers of objective measures of total energy expenditure and protein. Self-report was captured from food frequency questionnaire (FFQ), four day food record (4DFR) and 24 hr. dietary recall (24HR). Using regression calibration we estimated bias of self-reported dietary instruments including psychosocial factors from the Stunkard-Sorenson Body Silhouettes for body image perception, the Crowne-Marlowe Social Desirability Scale, and the Three Factor Eating Questionnaire (R-18) for cognitive restraint for eating, uncontrolled eating, and emotional eating. We included a diet behavior factor on number of meals eaten at home using the 4DFR.

RESULTS:

Three categories were defined for each of the six psychosocial and diet behavior variables (low, medium, high). Participants with high social desirability scores were more likely to under-report on the FFQ for energy (beta = -0.174, SE = 0.054, p < 0.05) and protein intake (beta = -0.142, SE = 0.062, p < 0.05) compared to participants with low social desirability scores. Participants consuming a high percentage of meals at home were less likely to under-report on the FFQ for energy (beta = 0.181, SE = 0.053, p < 0.05) and protein (beta = 0.127, SE = 0.06, p < 0.05) compared to participants consuming a low percentage of meals at home. In the calibration equations combining FFQ, 4DFR, 24HR with age, body mass index, race, and the psychosocial and diet behavior variables, the six psychosocial and diet variables explained 1.98%, 2.24%, and 2.15% of biomarker variation for energy, protein, and protein density respectively. The variations explained are significantly different between the calibration equations with or without the six psychosocial and diet variables for protein density (p = 0.02), but not for energy (p = 0.119) or protein intake (p = 0.077).

CONCLUSIONS:

The addition of psychosocial and diet behavior factors to calibration equations significantly increases the amount of total variance explained for protein density and their inclusion would be expected to strengthen the precision of calibration equations correcting self-report for measurement error.Trial Registration: ClinicalTrials.gov identifier: NCT00000611.

Nonfunctional paragangliomas are slow-growing, typically benign tumors that arise from the extra-adrenal paraganglion of the autonomic nervous system. They are identified and characterized with the use of computed tomography and other imaging methods; for definitive diagnosis, histopathologic evaluation is crucial. Surgical resection is the treatment of choice, and results of postoperative biochemical testing can reveal recurrence. Because of this lesion's familial association, genetic testing is suggested. We report the case of an 81-year-old woman who presented with neck pain, intermittent palpitations, hypertension, and dyspnea. Contrast-enhanced computed tomography of the chest revealed a multilobular, high-density lesion between the aorta and the pulmonary artery in the superior mediastinum. The patient's 24-hour urinary vanillylmandelic acid levels were not elevated, which suggested a nonfunctional tumor. Mediastinal exploration revealed a large, vascular, irregular, consistently firm mass that adhered to the aortic arch. Upon histopathologic analysis after complete resection, the mass was determined to be a paraganglioma with a low index of mitosis. The patient had postoperative respiratory insufficiency that necessitated tracheostomy, but she recovered well after rehabilitation. In addition to reporting our patient's case, we discuss the nature, diagnosis, and treatment of paragangliomas.

BACKGROUND:

The treatment of complicated urinary tract infection in children is still a matter of debate. In our hospital, antimicrobial treatment is initiated intravenously, and the duration of this treatment is adapted according to the results of a Tc-99m dimercaptosuccinic acid (DMSA) scintigraphy.

AIM:

This study was conducted to evaluate retrospectively the frequency and the importance of late renal sequelae when treating intravenously for 7 days those patients with an abnormal acute DMSA.

METHODS:

A review was conducted of the medical charts of all patients consecutively admitted between 2005 and 2008 with positive urine culture and clinical and biological evidence of complicated urinary tract infection (UTI).

RESULTS:

There were 144 patients (59 %) with abnormal early DMSA scintigraphy and 98 (41 %) with normal scintigraphy. The median duration of intravenous treatment was 7.0 days in the children with DMSA lesions and 5.0 days in those without lesions. Obvious renal sequelae were observed on late DMSA scintigraphy in 4 (6 %) out of the 65 patients with an abnormal early DMSA who came back for control scintigraphy.

CONCLUSION:

Sequelae of acute DMSA lesions observed during complicated UTI treated 7 days intravenously were infrequent. Whether the mode and duration of antimicrobial treatment might explain the low rate of sequelae remains to be demonstrated.

Background:

Febrile neutropenia (FN) is a significant adverse effect post-chemotherapy due to its high morbidity and mortality. There are few studies in our country with these kind of patients.

Objective:

To describe the characteristics and mortality in patients with hematologic neoplasms who developed FN post-chemotherapy. Methodology: A descriptive case series in patients with hematologic neoplasms who developed FN post-chemotherapy in Hospital Pablo Tobón Uribe.

Results:

101 episodes of FN in 43 patients. The median age was 44 years. 63.5% of patients had no apparent clinical focus of infection at admission, 11.8% had soft tissue compromise and 8.9% urinary tract infection. Bacteremia was documented in 41.5% and catheter-associated bacteremia in 3.9%. The most common organisms were Escherichia coli 43.4%, Klebsiella pneumoniae 17.3% and Staphylococcus aureus 8.6%. Of those isolated in blood 84.7% were Gram negative rods and 15.2% were Gram positive bacteria. Piperacillin/tazobactam was the most common empirically prescribed antibiotic (81.1%). Mortality of FN episodes occurred in 8 (7.92%) patients, 5 (62.5%) attributable to infection and 3 (37.5%) due to progression of hematologic malignancy with a resolution of FN.

Conclusions:

In our case series of FN the microbiological characteristics differed significantly from developed countries, but a similar mortality rate per episode was observed.

BACKGROUND:

Matrix Metalloproteinases (MMPs) are key molecules for tumor growth, invasion and metastasis. Over-expression of different MMPs in tumor tissues can disturb the homeostasis and increase the level of various body fluids. Many MMPs including high molecular weights (HMWs) were detected in the urine of prostate and bladder cancer patients. Our aim here is to assess the usefulness of HMW MMPs as non invasive biomarkers in bilharzial bladder cancer in Egyptian patients.

METHODS:

The activity of different MMPs including HMW species was determined using zymographic analysis technique in the urine samples procured from sixty six bladder cancer patients (bilharzial and non-bilharzial) as well as hundred healthy control subjects. Also, the correlation between these HMW MMPs activities and different clinico-pathological parameters was investigated.

RESULTS:

High frequency of urine MMPs (uMMPs) activity was determined in 63.6% of examined tumor cases, however, none of the control cases showed any uMMPs activity. MMP-9 had the highest activity (62%) followed by MMP9/NGAL (60%), MMP-2 (54.5%), MMP-9 dimer (53%), ADAMTS (25.6%), and the lowest one was MMP-9/TIMP-1 (12%) only. There was no correlation between uMMPs and any of clinico-pathological parameters including age, gender, tumor size and type, bilharziasis, grade, lymph node involvement, and invasion to the prostate. A significant correlation was established only between MMP-9/TIMP-1 activities with the tumor size.

CONCLUSIONS:

This study revealed that the detection of urinary MMPs including HMWs activity might be sensitive biomarkers for prediction of bladder cancer. It is also demonstrate that the detection of these urinary HMW gelatinases could not differentiate between bilharzial and non bilharzial bladder cancer subtypes.

The purpose of this study was to monitor patient pain score with transperineal prostatic gold seed implantation in the absence of conscious sedation.All patients who were scheduled for image-guided external beam radiation (IGRT) and referred for gold seed fiducials were eligible to participate. Gold seed implants were performed by two radiation oncologists between December 2007 and April 2008. Patients received only local and deep anesthetic. No patients had prophylactic IV cannulation for the procedure. Three gold seeds were inserted transperineally into the prostate. A visual analogue scale from 0 to 10 was used to assess the pain at baseline, local and deep anesthetic infiltration, with each seed drop, and after the completion of the procedure.A total of 30 patients were accrued to this study. The highest recorded increase in pain score was at the time point of deep local anesthesia, at which the mean pain score was 3.8. The mean pain scores at each seed drop were 0.8 (standard deviation [SD]=1.24), 1 (SD=1.26), and 0.5 (SD=0.90), respectively. All gold seed insertion procedures were well-tolerated, with no patients having significant pain post-procedure, and no significant procedural complications. There were only slight increases in dysuria, urinary frequency, constipation, urinary retention and flatulence in 7 patients - none of which required intervention.Transperineal ultrasound-guided gold seed implantation without conscious sedation is well-tolerated and associated with a low complication rate. It is a convenient outpatient procedure obviating the need for resource intensive postoperative monitoring.

Ezogabine (also known by the international nonproprietary name of retigabine) is an antiepileptic drug codeveloped and comarketed by Valeant Pharmaceuticals North America and GlaxoSmithKline, which reduces neuronal excitability by enhancing the activity of potassium channels and has the potential to have effects on the urinary system through a pharmacologic action on bladder smooth muscle. In a single post-herpetic neuralgia trial, but not in an extensive epilepsy development program, proteinuria was unexpectedly reported in patients receiving ezogabine. Consequently, investigations were conducted to determine whether the reported proteinuria represented a true or false-positive finding.Patients receiving ezogabine 900-1200 mg/day in an open-label extension (Study 303) of a Phase III epilepsy trial voluntarily provided urine samples. Fresh samples were analyzed immediately at the study site, and stabilized aliquots were analyzed 1-3 days after collection at two central laboratories. In an open-label study in healthy volunteers receiving ezogabine 600-900 mg/day (Study RTG114137), urine samples were analyzed fresh (<2 hours after collection) and, using two different stabilizers and storage at room temperature, after 24 and 72 hours. Fluid intake was restricted prior to one sample point. Albumin:creatinine ratios were assessed in both studies.In Study 303, there was notable variation in clarity, color, and proteinuria between fresh and stored urine samples, and between samples analyzed at different laboratories. In RTG114137, reporting rates of proteinuria were elevated following storage using one stabilizer, and the frequency of color change from fresh to stored samples differed between the stabilizers and between 24 and 72 hours with one stabilizer. Following fluid restriction, proteinuria rates were elevated with both stabilizers. Poor tolerability of ezogabine 750-900 mg/day resulted in limited titration beyond 750 mg/day and early termination of RTG114137.Hydration status, interval between urine collection and analysis, and the type of stabilizer used are all factors that may lead to false-positive proteinuria findings in patients receiving ezogabine and should be borne in mind if abnormalities are reported.

Nitric oxide and the cyclic nucleotide monophosphates cAMP and cGMP have a role in control of the micturition process and hence, are suggested to be involved in the pathophysiology of storage and voiding disorders. Phosphodiesterase enzymes (PDEs) hydrolyse cAMP and cGMP. Inhibition of PDEs increases cAMP and cGMP levels and relaxes urinary bladder smooth musculature. Although many preclinical studies have been conducted, to date, only PDE1 and PDE5 inhibitors have been tested clinically for the management of storage and voiding disorders. Treatment with PDE1 inhibitors might improve micturition frequency in patients with overactive bladder, whereas inhibition of PDE5 improves lower urinary tract symptoms in men, either with or without BPH and erectile dysfunction (ED). Furthermore, the combination of a PDE5 inhibitor and an α-adrenoceptor antagonist has superior efficacy to monotherapy with either agent. However, the role of PDE5 inhibitors in the treatment of women with detrusor overactivity remains unclear. The clinical application of agents that inhibit other PDEs, including PDE4, also certainly merits scientific attention. PDE inhibitors seem likely to become a valuable alternative treatment for patients with storage and voiding disorders in the future.