Empiric Strategy Research Articles

Persistencia de la segregación residencial y composición del capital humano por barrios en la ciudad de Cali

This paper analyzes the link between residential segregation and human capital composition in neighborhoods of Cali (Colombia). The empiric strategy starts with the calculation of local and global indexes using census data for neighborhoods by 1993 and 2005. The evidence suggest the existence of spatial clusters: highly skilled persons locate in longitudinal central zone, while the black community with low educational level locates in the suburbs of the city. The paper shows a number of interesting results: identify hot and cold spots or very homogeneous areas of the city, describes the changes in residential segregation in Cali over time and, finally, the paper contrasts the hypothesis of persistence in the segregation through spatial econometrics models. Results show that there is a great deal of spatial persistence in segregation.

PIN38 Real Life Study of Antifungal Treatment in Greek ICUs: Therapeutic Strategy and Hospital Resource Utilization – Estimator Study

The ESTIMATOR study aims to provide information on clinical and economic outcomes associated with the management of fungal infections across intensive care units (ICUs) in Greece. ESTIMATOR was a non-interventional prospective cohort study conducted in 14 ICUs in Greece. Adult patients initiating therapy with a systemic antifungal agent between July 2011 and February 2012 were included. Information on predisposing factors, management and therapeutic strategies, clinical outcomes and length of ICU stay (LOICUS) were recorded until end of therapy or death. A total of 155 eligible patients were recruited. 68% of patients presented at least 5 predisposing factors for fungal infection at antifungal treatment (AT) onset, while the mean APACHE score was 22.4 (s.d. 5.9). Median time until AT initiation was 6 days after ICU admission, while the median LOICUS was 31 days. 49.7% of patients received treatment with an empiric strategy while prophylaxis, pre-emptive and definitive strategies where used at 6.4%, 20.0% and 23.9% of the study population respectively. Echinocandins (57.3%), Fluconazole (20.0%) and Itraconazole (12.9%) were the most utilized therapies in the study. The overall treatment success and mortality rates were 43.9% and 49.7% respectively. Variations in death and response rates were observed when adjusted to the treatment strategy and the class of drug used. The mean total cost per patient treated was estimated at 22,012 Euros. Average LOICUS accounts for the 80.8% of total direct costs, while antifungal treatment, tests and investigations account for the remaining 19.2%. Limited efficacy of first line antifungal agent is associated with an increase in economic costs of 74%. Treating patients for fungal infections imposes a high economic burden to hospitals. Significant cost drivers are prolonged LOICUS and treatment failure. Treatment options that result in LOICUS reduction and increased first line efficacy have the potential to reduce hospital cost.

The Use of Intravenous Antibiotics at the Onset of Neutropenia in Patients Receiving Outpatient-Based Hematopoietic Stem Cell Transplants

Empirical antibiotics at the onset of febrile neutropenia are one of several strategies for management of bacterial infections in patients undergoing Hematopoietic Stem Cell Transplant (HSCT) (empiric strategy). Our HSCT program aims to perform HSCT in an outpatient setting, where an empiric antibiotic strategy was employed. HSCT recipients began receiving intravenous antibiotics at the onset of neutropenia in the absence of fever as part of our institutional policy from 01 Jan 2009; intravenous Prophylactic strategy. A prospective study was conducted to compare two consecutive cohorts [Year 2008 (Empiric strategy) vs. Year 2009 (Prophylactic strategy)] of patients receiving HSCT. There were 238 HSCTs performed between 01 Jan 2008 and 31 Dec 2009 with 127 and 111 in the earlier and later cohorts respectively. Infection-related mortality pre- engraftment was similar with a prophylactic compared to an empiric strategy (3.6% vs. 7.1%; p = 0.24), but reduced among recipients of autologous HSCT (0% vs. 6.8%; p = 0.03). Microbiologically documented, blood stream infections and clinically documented infections pre-engraftment were reduced in those receiving a prophylactic compared to an empiric strategy, (11.7% vs. 28.3%; p = 0.001), (9.9% vs. 24.4%; p = 0.003) and (18.2% vs. 33.9% p = 0.007) respectively. The prophylactic use of intravenous once-daily ceftriaxone in patients receiving outpatient based HSCT is safe and may be particularly effective in patients receiving autologous HSCT. Further studies are warranted to study the impact of this Prophylactic strategy in an outpatient based HSCT program.

Therapeutic Drug Monitoring of Tumor Necrosis Factor Antagonists in Inflammatory Bowel Disease

Although tumor necrosis factor (TNF) antagonists have shown clear benefits over conventional treatments for inducing and maintaining clinical remission in both Crohn's disease and ulcerative colitis, a high proportion of patients lose response over time. Given the scarce alternative of treatments when treatment failure occurs, it is highly desirable to optimize both initial response and long-term continuation of TNF antagonists. One of the most well-characterized factors associated with loss of response to these agents is the development of immunogenicity, whereby the production of neutralizing antidrug antibodies accelerates drug clearance, leading to subtherapeutic drug concentrations and, ultimately, to treatment failure. However, other patient-related factors, such as sex and/or body size, and disease severity, including TNF burden and serum albumin concentration among others, also may influence the pharmacokinetics of these agents. Nevertheless, the evidence generated to date about these complex interactions is scarce, and further prospective studies evaluating their influence on the pharmacokinetics of TNF antagonists are needed. Drug adjustment empirically based on clinical symptoms often is inaccurate and may lead to suboptimal outcomes. Recent evidence shows that maintenance of an optimal therapeutic drug concentration is associated with improved clinical outcomes. Therefore, incorporation of therapeutic drug monitoring into clinical practice may allow clinicians to optimize treatment by maintaining effective drug concentrations over time.

Guide Regarding Choice of Second‐line Therapy to Obtain a High Cumulative Cure Rate

Manfredi et al. [1] report in this issue of Helicobacter that, in their experience, in a large population, more than 95% of Helicobacter pylori infections were eradicated by the empiric strategy of administrating sequential therapy as the first-line therapy followed by a 10-day fluoroquinolone-containing triple therapy. The eradication rate was 92.6% with sequential therapy but only 75% with the second-line fluoroquinolone triple therapy yielding the cumulative result of 97.8% per-protocol eradication. Theirs is one of a few studies looking at overall community results rather than separately focusing on the results of first and second-line therapy [2,3]. They go on to suggest that fluoroquinolone triple therapy might be an excellent recue to eradicate H. pylori infection in only two rounds [1].

Cyclic di‐nucleotides: new era for small molecules as adjuvants

SummaryThe implementation of vaccination as an empiric strategy to protect against infectious diseases was introduced even before the advent of hygiene and antimicrobials in the medical practice. Nevertheless, it was not until a few decades ago that we really started understanding the underlying mechanisms of protection triggered by vaccination. Vaccines were initially based on attenuated or inactivated organisms. Subunit vaccines were then introduced as more refined formulations, exhibiting improved safety profiles. However, purified antigens tend to be poorly immunogenic and often require the use of adjuvants to achieve adequate stimulation of the immune system. Vaccination strategies, such as mucosal administration, also require potent adjuvants to improve performance. In the 1990s, immunologists found that pathogens could be sensed as ‘danger signals’ by receptors recognizing conserved motifs. Although our knowledge is still limited, tremendous advances were made in the understanding of host defence mechanisms regulated by these evolutionary conserved receptors, and the molecular structures which are recognized by them. This opened a new era in adjuvant development. Some of the latest players arrived to this field are the cyclic di‐nucleotides, which are ubiquitous prokaryotic intracellular signalling molecules. This review is focused on their potential for the development of vaccines and immunotherapies.

Value investor anomaly: return enhancement by portfolio replication—an empiric portfolio strategy analysis

Empirical analyses have consistently confirmed problems with the efficient market hypothesis. In this article light is shed on another market anomaly examining the use of publicly available information from value style investors proven to be using long-term successful value investment strategies. It can be shown that utilizing this information to form portfolios based on different investment strategies results in returns above the market return, violating the efficient market hypothesis. Additionally it can be shown that these strategies can be implemented without capturing higher risks applying traditional risk measures.

Herpes Simplex Virus Infection in Young Infants During 2 Decades of Empiric Acyclovir Therapy

To describe the clinical presentation of HSV-infected young infants and to seek distinctive features that could permit a targeted approach to empiric use of acyclovir. Case study of neonatal HSV during a 22-year period of an institutional strategy of consistent use of acyclovir empirically in all infants with onset of an illness at ≤ 21 days of age for which antibiotics were given empirically. Multiple sources were used to optimize HSV case data, and to estimate the rate of HSV infection in empirically treated infants. A total of 32 infants with perinatally acquired HSV infection were identified. All received acyclovir empirically at admission. At presentation, 50% of infants had only nonspecific complaints, which was fever in 75%. After testing, 75% of infants with HSV had central nervous system (CNS) infection, including 40% who presented with mucocutaneous lesions, 83% with seizures, and 94% with nonspecific complaints. Cerebrospinal fluid (CSF) polymerase chain reaction confirmed CNS infection in 16 of 22 (73%) patients tested. Cultures of mucocutaneous lesion yielded HSV in 8 of 10 cases, but culture of CSF was negative in all 26 cases tested, and screening cultures of unaffected mucosal sites were the only HSV-confirmatory test in a single patient. Laboratory and CSF findings were not distinctive in patients with HSV. Age of ≤ 21 days at onset of symptoms captured 90% of all infants with HSV and 94% of those with nonspecific complaints. An estimated 1.3% of empirically treated patients had HSV infection. Early manifestations of perinatally acquired HSV are frequently nonspecific, yet CNS infection is common. Empiric acyclovir strategy narrowly restricted to infants with onset of illness at ≤ 21 days of age, who would receive antibiotics empirically, captured 90% of HSV cases and anticipated a rate of HSV CNS infection similar to that of bacterial meningitis.

Use of empiric antimicrobial therapy in neutropenic fever

AbstractAdministration of empiric antimicrobial therapy is standard practice in the management of neutropenic fever, but there remains considerable debate about the selection of an optimal regimen. In view of emerging evidence regarding efficacy and toxicity differences between empiric treatment regimens, and strong evidence of heterogeneity in clinical practice, the current guidelines were developed to provide Australian clinicians with comprehensive guidance for selecting an appropriate empiric strategy in the setting of neutropenic fever. Beta‐lactam monotherapy is presented as the treatment of choice for all clinically stable patients while early treatment with combination antibiotic therapy is considered for patients at higher risk. Due consideration is given to the appropriate use of glycopeptides in this setting. Several clinical caveats, accounting for institution‐ and patient‐specific risk factors, are provided to help guide the judicious use of the agents described. Detailed recommendations are also provided regarding time to first dose, timing of blood cultures, selection of a first‐line antibiotic regimen, subsequent modification of antibiotic choice and cessation of therapy.

The Use of Intravenous Antibiotics at the Onset of Neutropenia In Patients Receiving Hematopoietic Stem Cell Transplants: A Pre-Emptive Strategy.

AbstractAbstract 4516 Background:Hematopoietic Stem Cell Transplant (HSCT) recipients are at risk for fatal bacterial infections during the engraftment period. Empirical antibiotic(s) at the onset of febrile neutropenia remain the standard of care. HSCT recipients began receiving intravenous once daily ceftriaxone at the onset of neutropenia (neutrophils< 1.0) regardless of fever as part of The Ottawa Hospital Blood and Marrow Outpatient Programme policy from Jan 2009; “pre-emptive” approach. We examined the impact of this policy on HSCT recipient outcomes. Methods:A retrospective “before-after” study was conducted to compare 2 cohorts [Jan 2008 - Dec 2008 (Empiric strategy) vs. Jan 09 - Dec 2009 (Pre-emptive strategy)] of patients receiving HSCT. Baseline characteristics between the groups were compared with 2 sample tests. Categorical variables and continuous variables were compared using Chi-squared and Wilcoxan rank-sum tests respectively. Results:There were 238 HSCTs performed between Jan 2008 and Dec 2009 with 127 and 111 in the earlier and later cohorts respectively. Baseline characteristics between the cohorts were similar. Infection related mortality at 100 days after HSCT and during the engraftment period was similar with a pre-emptive strategy compared to an empiric strategy (7.2% vs 10.2%; p=0.41 and 3.6% vs 7.1%; p=0.24) respectively. Further, there were no differences in ICU admissions or length of hospital stay. Both microbiologically (MDI) and clinically documented infections (CDI) were reduced (11.7% vs 29.1%; p=0.001 and 18.2% vs33.9%; p=0.007) with the pre-emptive strategy compared with an empiric strategy. Importantly, recipients of autologous HSCT appear to have a lower infection related mortality and reduced infection related ICU admissions during the engraftment period with the pre-emptive strategy compared to an empiric strategy (0% vs 6.8%; p=0.03 and 2.9% vs 12.2% p= 0.04). The need for escalation of antimicrobial treatments, resistance pattern of MDIs and cost of antimicrobial treatment were not different between the two groups. Conclusion:The use of once daily intravenous ceftriaxone at the onset of neutropenia in patients receiving HSCT is safe and effective particularly in patients receiving autologous HSCT. Further studies are warranted to study the impact of this “pre-emptive” strategy. Disclosures:No relevant conflicts of interest to declare.

An Early CT-Diagnosis Based Treatment Strategy for Invasive Fungal Infection in Allogeneic Transplant Recipients Using Caspofungin First Line: An Effective Strategy with Low Mortality.

Empirical antifungal therapy is the standard treatment in allogeneic transplant patients who have persistent febrile neutropenia. This approach can be associated with increased cost, toxicity and breakthrough infections. There are limited reports to date of strategies for the early diagnosis of invasive fungal infection (IFI). These include either invasive investigations or serum testing. (Oshima K et al, J Antimicrobial Chemother 2007 Aug; 60(2): 350–5, Maertens J et al, Clin Infect Dis 2005; 41:1242–50). To our knowledge, there are no reports to date of treatment strategies based only on high resolution computerised tomography (HRCT) scans.We used a CT-diagnosis based treatment strategy for early invasive aspergillosis in 99 consecutive patients undergoing allogeneic transplantation over a two year time period. A retrospective review of the electronic patient record, notes and drug charts was undertaken in all patients receiving an allogeneic transplant in our unit from 1st January 2006 to 31st December 2007. The study protocol was approved by the Royal Marsden Hospital audit committee. Patients received primary antifungal prophylaxis with itraconazole or secondary prophylaxis with voriconazole from day + 1. Patients had a HRCT scan performed if they had antibiotic resistant fever for > 72 hours. Parenteral antifungal treatment with caspofungin was commenced in patients with a positive HRCT result. Cavitation, air crescent sign and halo sign were classified as major changes. Nodules and new infiltrates including consolidation and effusions were classified as minor changes. Serum testing was not used due to the possibility of false positive results with tazobactampiperacillin antimicrobials and low sensitivity in patients receiving mould active azoles as prophylaxis.Neutropenic fever developed in 89/99 patients (90%). Fifty-four percent (53/99) of patients developed antibiotic resistant fever for > 72 hours and would have received parenteral antifungal treatment if an empiric strategy had been used. The HRCT-based strategy reduced the use of parenteral antifungal treatment to 17% of patients (17/99). Four of these patients had engrafted (absolute neutrophil count >0.5x109 cells/L for 3 days) at time of commencing caspofungin following a period of persistent neutropenic fever. Fifteen patients had a positive HRCT scan and 2 were treated empirically until a HRCT could be performed. The remaining 36/53 patients (68%) did not receive antifungal treatment although they would have met criteria for standard empirical therapy. Our nonempiric strategy reduced the use of parenteral antifungal treatment from 54% to 17% of allogeneic transplant patients. These findings represent a 68% reduction in use of parenteral antifungal agentsCaspofungin (70mg once daily IV on day 1 and 50mg once daily IV thereafter) was given for a median of 13 days (3–34 days) and 11 patients responded to treatment. Six patients required second line antifungal therapy. Only one patient died from IFI after 100 days of follow-up. No patients had to stop caspofungin due to toxicity. Three of the 36 patients who did not receive initial antifungal treatment went on to receive empiric caspofungin within 100 days. One of these 3 patients died of enterococcal septicaemia. The other 2 patients recovered. None of this group had probable or proven IFI. During the extended follow-up period of 3–27 months (median 13 months) only 3/99 patients (3%) died of IFI.These results suggest that this non-empiric strategy of parenteral antifungal treatment based on HRCT scanning is feasible and may help to reduce toxicity, cost and breakthrough infections associated with the use of antifungal agents. Caspofungin may be a useful first line agent in this setting. A randomised controlled trial is warranted to further evaluate these results.

Late Allograft Failure After Heart Transplantation: 2 Unusual Cases

Cardiac allograft failure is most commonly caused by acute rejection and cardiac allograft vasculopathy. Consequently, heart transplant recipients who present with heart failure are empirically treated at many transplant centers with augmented immunosuppression despite negative endomyocardial biopsies. We report 2 unusual cases of acute allograft dysfunction that highlight the importance of caution in adopting an empiric strategy of profound immunosuppression in the absence of objective data to support graft rejection.

Management of the Dyspeptic Patient: Anything Goes?

Guidelines on the initial management of dyspeptic patients are remarkably conflicting or ambiguous and recommend a variety of initial approaches and no single strategy has been successfully implemented in primary care. In this issue of the American Journal of Gastroenterology, Jarbol and colleagues report the results of a large Danish trial comparing a test-and-treat strategy, an empiric PPI strategy, and a combined strategy with Helicobacter testing if symptoms improved after the PPI. Patient-related outcomes at 1 yr did not differ, but the use of endoscopy was highest in the PPI strategy. From the patient's perspective it seems that anything goes as long as the clinician sticks to a well-defined and proven strategy. Helicobacter pylori testing is still recommendable owing to the long-term benefits, but the rapidly decreasing Helicobacter prevalence will soon make the test-and-treat strategy cost-ineffective as the initial step.

Endoscopic screening for esophageal varices in cirrhosis: Is it ever cost effective?

Current guidelines for the management of patients with compensated cirrhosis recommend universal screening endoscopy followed by prophylactic β-blocker therapy to prevent initial hemorrhage in those found to have esophageal varices. However, the cost-effectiveness of this recommendation has not been established. Our objective was to determine whether screening endoscopy is cost-effective compared with empiric medical management in patients with compensated cirrhosis. Decision analysis with Markov modeling was used to calculate the cost-effectiveness of 6 competing strategies: (1) universal screening endoscopy (EGD) followed by β-blocker (BB) therapy (EGD→BB) if varices are present, (2) EGD followed by endoscopic band ligation (EBL) (EGD→EBL) if varices are present, (3) selective screening endoscopy (sEGD) in high risk patients followed by BB therapy if varices are present (sEGD→BB), (4) selective screening endoscopy followed by EBL (sEGD→EBL) if varices are present, (5) empiric β-blocker therapy in all patients, and (6) no prophylactic therapy (“Do Nothing”). Cost estimates were from a third-party payer perspective. The main outcome measure was the cost per initial variceal hemorrhage prevented. The “Do Nothing” strategy was the least expensive yet least effective approach. Compared with the “Do Nothing” strategy, the empiric β-blocker strategy cost an incremental $12,408 per additional variceal bleed prevented. Compared with the empiric β-blocker strategy, in turn, both the EGD→BB and the EGD→EBL strategies cost over $175,000 more per additional bleed prevented. The sEGD→BB and sEGD→EBL strategies were more expensive and less effective than the empiric β-blocker strategy. In conclusion, empiric β-blocker therapy for the primary prophylaxis of variceal hemorrhage is a cost-effective measure, as the use of screening endoscopy to guide therapy adds significant cost with only marginal increase in effectiveness. (H EPATOLOGY 2003;37:366-377.)

Bacteremia and Fungemia in Pediatric Versus Adult Cancer Patients after Chemotherapy: Comparison of Etiology, Risk Factors and Outcome

One hundred and eighteen (118) episodes of bacteremia and fungemia in children with cancer were compared to 401 episodes of bacteremia and fungemia in adults with cancer to assess differences in etiology, risk factors and outcome. A retrospective univariate analysis was performed of all episodes of bacteremia in national pediatric and adult cancer institutions appearing in 1990- 1996. A total of 519 episodes of bacteremia were assessed and compared. Both cancer centers differed in prophylactic antibiotic policies. About 50% of adults but less than 5% of children received quinolone prophylaxis during neutropenia, even though the empiric antibiotic therapeutic strategy was similar.There were differences in etiology between the groups: staphylococci and Stenotrophomonas maltophilia were more frequently observed in children (P<0.01), Pseudomonas aeruginosa and Acinetobacter spp. in adults (P<0.05). Gram-positive bacteremia was surprisingly more commonly observed in adults (65.7% vs 33.3%, P<0.01). Mixed polymicrobial bacteremia occurred more commonly in adults (31.8% vs 7.6%, P<0.001) than in children. Analysis of risk factors did not observe differences in risk factors except for underlying disease (acute leukemia was more frequently observed in children - 48.3% vs adults 33.7%, P<0.05 and prophylaxis: (prior prophylaxis with quinolones was more common in adults (47.5%) than in children (2.5%) P<0.0001). Overall and attributable mortality in pediatric bacteremia was significantly lower than in adults (P<0.03).

Community-acquired pneumonia in the elderly. Clinical and nutritional aspects.

Community-acquired pneumonia (CAP) in the elderly has a different clinical presentation than CAP in other age groups. Confusion, alteration of functional physical capacity, and decompensation of underlying illnesses may appear as unique manifestations. Malnutrition is also an associated feature of CAP in this population. We undertook a study to assess the clinical and nutritional aspects of CAP requiring hospitalization in elderly patients (over 65 yr of age). One hundred and one patients with pneumonia, consecutively admitted to a 1,000-bed teaching hospital over an 8-mo period, were studied (age: 78 +/- 8 yr, mean +/- SD). Nutritional aspects and the mental status of patients with pneumonia were compared with those of a control population (n = 101) matched for gender, age, and date of hospitalization. The main symptoms were dyspnea (n = 71), cough (n = 67), and fever (n = 64). The association of these symptoms with CAP was observed in only 32 patients. The most common associated conditions were cardiac disease (n = 38) and chronic obstructive pulmonary disease (COPD) (n = 30). Seventy-seven (76%) episodes of pneumonia were clinically classified as typical and 24 as atypical. There was no association between the type of isolated microorganism and the clinical presentation of CAP, except for pleuritic chest pain, which was more common in pneumonia episodes caused by classical microorganisms (p = 0.02). This was confirmed by a multivariate analysis (relative risk [RR] = 11; 95% confidence interval [CI]: 1.7 to 65; p = 0.0099). The prevalence of chronic dementia was similar in the pneumonia cohort (n = 25) and control group (n = 18) (p = 0.22). However, delirium or acute confusion were significantly more frequent in the pneumonia cohort than in controls (45 versus 29 episodes; p = 0.019). Only 16 patients with pneumonia were considered to be well nourished, as compared with 47 control patients (p = 0.001). Kwashiorkor-like malnutrition was the predominant type of malnutrition (n = 65; 70%) in the pneumonia patients as compared with the control patients (n = 31; 31%) (p = 0.001). The observed mortality was 26% (n = 26). Pleuritic chest pain is the only clinical symptom that can guide an empiric therapeutic strategy in CAP (typical versus atypical pneumonia). Both delirium and malnutrition were very common clinical manifestations of CAP in our study population.

Cucurbitacin E-induced disruption of the actin and vimentin cytoskeleton in prostate carcinoma cells

Cucurbitacin E has been identified by an empiric screening strategy as a sterol with potent growth inhibitory activity in vitro directed against prostate carcinoma explants ( ic 50 of 7–50 nM in 2- to 6-day exposures). The mechanism of cucurbitacin cytoxicity has not been elucidated previously. In the present study, we observed that cucurbitacin E caused marked disruption of the actin cytoskeleton, and in a series of cucurbitacin analogues, anti-proliferative activity correlated directly with the disruption of the F-actin cytoskeleton. The distribution of vimentin was also altered in cells exposed to cucurbitacin E, as vimentin associated with drug-induced membrane blebs. The appearance of microtubules was unaffected. Western blot analysis of intracellular actin in cells exposed to cucurbitacins and quantitation of rhodamine-phalloidin binding support the hypothesis that cucurbitacin treatment leads to an inappropriate increase in the filamentous or polymerized actin fraction in prostate carcinoma cells. We conclude that cucurbitacins are potent disruptors of cytoskeletal integrity. Prostate carcinoma cells appear notably sensitive to growth inhibition by cucurbitacin E.

Nonulcer Dyspepsia: A Look Into the Future

Nonulcer Dyspepsia: A Look Into the Future