Missing Potential Opportunities to Reduce Repeat COPD Exacerbations

Introduction

Long-acting beta-agonists (LABA) and/or inhaled corticosteroids (ICS) have been shown to reduce COPD exacerbation risk. Using data from a large integrated health-care system, we sought to examine whether these medication classes were initiated after an exacerbation of COPD.

Methods

We identified patients who experienced an inpatient or outpatient COPD exacerbation within the Veterans Affairs Integrated Service Network (VISN)-20. We assessed the addition of a new inhaled therapy (an ICS, LABA or both) within 180 days after the exacerbation. We assessed independent predictors of adding treatment using logistic regression.

Results

We identified 45,780 patients with COPD, of whom 2,760 patients experienced an exacerbation of COPD. Of these individuals, 2,570 (93.1 %) were on either none or only one long-acting medication studied (LABA or ICS). In the subsequent 180-day period after their exacerbation, only 875 (34.1 %) patients had at least one of these additional therapies dispensed from a VA pharmacy. Among patients who were treated in the outpatient setting, older age [OR 0.98/year, 95 % CI (0.97–0.99)], current tobacco use [OR 0.74, 95 % CI (0.60–0.90)], greater use of ipratropium bromide [OR 0.97/canister, 95 % CI (0.96–0.98)], prior COPD exacerbation [OR 0.55, 95 % CI (0.46–0.67)], depression [OR 0.77, 95 % CI (0.61–0.98)], CHF [OR 0.74, 95 % CI (0.57–0.97)], and diabetes (OR 0.77 (0.60–0.99)] were associated with lower odds of additional therapy. Patients who were treated in the hospital had similar associated predictors.

Conclusion

Among patients treated for an exacerbation of COPD, we found relatively few were subsequently prescribed inhaled therapies known to reduce exacerbations.     

Clinical Outcomes and Cost Analysis of Exacerbations in Chronic Obstructive Pulmonary Disease

Background

Exacerbations are a major cause of disability, hospital admissions, and increased healthcare costs in patients with chronic obstructive pulmonary disease (COPD). This study investigated the clinical outcomes of outpatients with moderate to severe exacerbated COPD and their related costs.

Methods

An observational study on the outcomes of ambulatory exacerbations of COPD was conducted. The course of the exacerbation was evaluated at a follow-up visit at 4 weeks. A cost analysis that encompassed the use of healthcare resources for treatment of the exacerbation was performed.

Results

A total of 260 patients were included, with a mean age of 68.3 years and a mean FEV₁ (% predicted) of 58.9 %. Twenty-two percent of patients had significant cardiovascular comorbidity. The most frequently prescribed antibiotics were moxifloxacin in 137 cases and amoxicillin–clavulanate in 50 cases. The rate of failure at 4 weeks was 12.5 %, with no differences between the two most prescribed antibiotics; however, patients treated with moxifloxacin had symptoms for 1.9 fewer days (P = 0.01). The mean cost of the exacerbation was €344.96 (95 % CI: €48.55–€641.78), with 9.6 % of the costs for drugs and 72.9 % for hospital care of patients for whom treatment had failed.

Conclusions

Antibiotic treatment of our population was in compliance with local guidelines. The rate of failure observed in our study was lower than that reported in previous studies; however, the small percentage of patients that required hospital attention generated almost two-thirds of the total costs of the exacerbations.     

Collateral Damage: Depressive Symptoms in the Partners of COPD Patients

Background

Depression is a frequent comorbidity in COPD patients and is associated with greater physical impairment, increased health-care utilization, and worse outcomes. The presence of depressive symptoms in the partners of COPD patients has not been evaluated.

Methods

We evaluated the partners of 230 consecutive COPD patients included in a prospective study. Depressive symptoms were evaluated using Beck’s Depression Inventory (BDI) on the first day of admission for COPD exacerbation. Patients were followed-up for 1 year.

Results

Significant depressive symptoms were present in 39.6 % of the COPD patients and in 40.9 % of their partners. Beck scores were higher in the partners of patients with severe airflow obstruction and in those with ≥2 exacerbations and ≥1 hospitalizations for COPD exacerbation during the 1-year follow-up. The BDI score of the patients’ partners was significantly correlated with the BDI score of the COPD patients (r _s = 0.422). In multivariate analysis, depressive symptoms in the COPD patients were an independent predictor of depressive symptoms in their partners (OR 4.136, 95 % CI 1.991–8.594; p < 0.001).

Conclusions

A large proportion of the partners of COPD patients present significant depressive symptoms. The identification of those patients and their partners represents a possible target for intervention.     

Antibiotic use in acute pancreatitis: An Indian multicenter observational study

Introduction

Prophylactic antibiotics are used frequently for acute pancreatitis (AP). Consensus guidelines do not recommend this currently, based on moderate quality evidence. In this study, we aimed to evaluate the antibiotic use pattern in AP in India and propose a risk-directed approach to antibiotic use in AP.

Material and Methods

This multicenter study was conducted from 1 May 2013 to 31 July 2013. Eleven participants from eight tertiary centers completed a questionnaire that captured patient demographics, etiology, admission status, presence of (peri)pancreatic necrosis, severity of pancreatitis, details of antibiotic use, and clinical outcomes (total hospital stay, persistent organ failure, need for ICU, total days in ICU, development of infections, in-hospital mortality).

Results

A total of 200 proformas were analyzed. Seventy-three (36.5 %) had acute necrotizing pancreatitis (ANP). Eighty-nine (44.5 %), 52 (26 %), and 55 (27.5 %) patients had mild AP (MAP), moderately severe AP (MSAP), and severe AP (SAP), respectively. Forty-five (22.5 %) patients developed infections (unifocal 29; multifocal 16). One hundred thirty-four (67 %) patients received antibiotics, of which 89 (66.4 %) received prophylactic, while 45 (33.6 %) received therapeutic antibiotics. The distribution of antibiotic use according to the severity of AP was 43 (48.3 %) in patients with MAP (prophylactic in 41; therapeutic in 2), 36 (69.2 %) in patients with MSAP (prophylactic in 29; therapeutic in 7), and 55 (100 %) in patients with SAP (prophylactic in 19; therapeutic in 36). Therapeutic antibiotics were prescribed based on culture and sensitivity in 21 (46.7 %) patients.

Conclusions

Despite nonrecommendation, prophylactic antibiotics are used frequently in AP. We emphasize on the need for multicenter randomized controlled trials on prophylactic antibiotics for AP based on a risk-directed approach, rather than a “blanket approach.”     

Inflammatory Biomarkers in Sputum Predict COPD Exacerbations

Introduction

Exacerbations in chronic obstructive pulmonary disease (COPD) reduce quality of life and are associated with a more rapid deterioration of the disease. It is desirable to predict an oncoming exacerbation before it occurs. The aim of the present study was to identify biomarkers that may predict a forthcoming exacerbation.

Materials and Methods

Forty-three patients with COPD in their stable state were included and followed up monthly until exacerbation, or for a maximum of 6 months. The patients come for an extra visit (prior to a scheduled visit) when exacerbated. The patients completed the questionnaires CCQ and MRC. Exhaled breath condensate (EBC) was collected followed by spirometry, impulse oscillometry, and sputum induction.

Results

Twenty-five patients had an exacerbation within the 6-month period. Leukotriene B₄ in sputum was the only biomarker that was increased at the visit prior to exacerbation compared to at the stable phase (p = 0.05). There also was a tendency for a similar but not significant increase in the sputum levels of 8-isoprostane, myeloperoxidase activity, and interleukin-8, as well as additional increases during exacerbation. Sputum purulence was not increased until exacerbation (p = 0.02). In contrast, none of the inflammatory biomarkers in EBC, the quality-of-life questionnaire score, CRP, spirometric parameters, or impulse oscillometry parameters were increased at the visit prior to exacerbation compared to the values at the stable phase.

Conclusion

Sputum biomarkers, especially leukotriene B₄, could be used as predictors of a forthcoming exacerbation and worsening of COPD. This would be of great value for the patient, who may be a subject for early treatment and thereby avoid a progression of the disease.     

Microbiological Diagnosis and Antibiotic Therapy in Patients with Community-Acquired Pneumonia and Acute COPD Exacerbation in Daily Clinical Practice: Comparison to Current Guidelines

Background

The aim of this secondary analysis was to evaluate current microbiological approaches, microbiology, and antibiotic therapy in patients with community-acquired pneumonia (CAP) and acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in clinical practice and to compare them with current international guidelines.

Methods

A total of 362 patients with suspected CAP were enrolled in 14 European centers in a prospective multicenter study.

Results

A total of 279 inpatients (CAP, n = 222; AECOPD, n = 57) were evaluated. A total of 83 (37 %) CAP patients and 25 (44 %) AECOPD patients did not undergo any microbiological tests. In patients with CAP/AECOPD, blood culture was performed in 109 (49 %)/16 (28.1 %), urinary antigen tests for Legionella pneumophila in 67 (30 %)/9 (16 %), and sputum investigation in 55 (25 %)/17 (30 %), respectively. The most frequent pathogens in CAP were Streptococcus pneumoniae, Mycoplasma pneumoniae, Chlamydia pneumoniae, L. pneumophila, Staphylococcus aureus, and Enterobacter cloacae; in AECOPD they were Escherichia coli, Haemophilus haemolyticus, Haemophilus influenzae, and Moraxella catarrhalis. All CAP patients (mean = 11.1 days) and 35 (61.4 %) of AECOPD patients (mean = 8.9 days) received antibiotics. CAP patients were given mostly aminopenicillin with β-lactamase inhibitors and AECOPD patients were given mostly cephalosporins.

Conclusions

Pathogens isolated in CAP and AECOPD and the antibiotic therapy used are in good accordance with the guidelines. Blood culture, recommended for all CAP patients, was performed in only 50 % of the cases and antibiotic therapy lasted longer than the suggested 5–7 days. Therefore, international guidelines regarding performance of blood culture and duration of antibiotic therapy should be adopted more often. This duration was independent of the number of isolated pathogens and number of symptoms on admission. Therefore, the question arises as to whether microbiological data are necessary only for patients who are resistant to initial therapy.     

Use of an Electronic Health Record Clinical Decision Support Tool to Improve Antibiotic Prescribing for Acute Respiratory Infections: The ABX-TRIP Study

BACKGROUND

Antibiotics are often inappropriately prescribed for acute respiratory infections (ARIs).

OBJECTIVE

To assess the impact of a clinical decision support system (CDSS) on antibiotic prescribing for ARIs.

DESIGN

A two-phase, 27-month demonstration project.

SETTING

Nine primary care practices in PPRNet, a practice-based research network whose members use a common electronic health record (EHR).

PARTICIPANTS

Thirty-nine providers were included in the project.

INTERVENTION

A CDSS was designed as an EHR progress note template. To facilitate CDSS implementation, each practice participated in two to three site visits, sent representatives to two project meetings, and received quarterly performance reports on antibiotic prescribing for ARIs.

MAIN OUTCOME MEASURES

1) Use of antibiotics for inappropriate indications. 2) Use of broad spectrum antibiotics when inappropriate. 3) Use of antibiotics for sinusitis and bronchitis.

KEY RESULTS

The CDSS was used 38,592 times during the 27-month intervention; its use was sustained for the study duration. Use of antibiotics for encounters at which diagnoses for which antibiotics are rarely appropriate did not significantly change through the course of the study (estimated 27-month change, 1.57 % [95 % CI, ?5.35 %, 8.49 %] in adults and ?1.89 % [95 % CI, ?9.03 %, 5.26 %] in children). However, use of broad spectrum antibiotics for ARI encounters improved significantly (estimated 27 month change, ?16.30 %, [95 % CI, ?24.81 %, ?7.79 %] in adults and ?16.30 [95%CI, ?23.29 %, ?9.31 %] in children). Prescribing for bronchitis did not change significantly, but use of broad spectrum antibiotics for sinusitis declined.

CONCLUSIONS

This multi-method intervention appears to have had a sustained impact on reducing the use of broad spectrum antibiotics for ARIs. This intervention shows promise for promoting judicious antibiotic use in primary care.     

Effect of empiric antibiotic treatment on plasma endotoxin activity in septic patients

Objectives

Efficient empiric antibiotic therapy remains the cornerstone of sepsis treatment. However, antibiotics could be responsible for the transient clinical deterioration provoked by the release of bacterial cell-wall constituents, such as endotoxin, into the blood stream. The aim of this study was to evaluate if a transient elevation of endotoxin level occurred in septic patients following antibiotic administration.

Methods

Thirty-three septic intensive care unit (ICU) patients were enrolled in this prospective trial. Four blood samples were collected from each of these patients during a 24-h period, and endotoxin activity was measured in these samples by the chemiluminescence technique. Fifteen ICU non-septic patients and 15 healthy volunteers were also observed for possible daily fluctuations in endotoxin activity.

Results

There was no significant increase in endotoxin levels following the initiation of empiric antibiotic therapy in septic patients. A clinical deterioration in the 4 h following antibiotic administration was observed in 14 septic patients (42 %). These patients had significantly higher endotoxin levels than stable septic patients.

Conclusions

Although endotoxin levels failed to increase after the administration of antibiotic(s) to critically ill patients, they were higher in the septic patients presenting a transient deterioration than in the other patients. This observation suggests that a possible release of endotoxin due to bacteria lysis by antibiotics could be responsible for the observed clinical deterioration.     

Effect of prior chemotherapy regimens on the efficacy of endocrine therapy within a German cohort of the TEAM trial

Purpose

Prior chemotherapy may affect the efficacy of endocrine therapy.

Methods

The tamoxifen exemestane adjuvant multinational (TEAM) trial compared 5 years of adjuvant exemestane with the sequence of tamoxifen followed by exemestane in postmenopausal women with hormone-receptor-positive breast cancer. A total of 1,502 patients were enrolled in Germany (739 received tamoxifen followed by exemestan and 610 exemestan alone). A retrospective analysis of the German cohort of TEAM was conducted to determine whether prior chemotherapy affected clinical outcome of endocrine therapy.

Results

Overall survival, disease-free survival and distant recurrence were similar between patients who received sequential therapy and those who received exemestane monotherapy, irrespective of prior chemotherapy. Overall survival was not significantly different between patients who had received prior chemotherapy and those who had not (P = 0.2836). Disease-free survival and distant recurrence were significantly better in patients who had not received prior chemotherapy versus those who had (P = 0.0308 and P = 0.0001). In patients receiving sequential therapy, there were no significant differences in overall survival according to prior chemotherapy use (P = 0.1812). However, disease-free survival and distant recurrence were significantly different dependent on prior chemotherapy (P = 0.0143 and P = 0.0053).

Conclusion

In conclusion, there was no difference in overall survival between breast cancer patients who did receive prior chemotherapy before endocrine therapy and those who had not. Patients who had not received prior chemotherapy had significantly improved disease-free survival and less distant recurrence versus those who had received chemotherapy.     

Hospital Readmissions with Exacerbation of Obstructive Pulmonary Disease in Illicit Drug Smokers

Purpose

Patients with obstructive pulmonary disease (asthma or chronic obstructive pulmonary disease—COPD) who smoke illicit drugs are at an increased risk of hospital admissions. We compared hospital readmission rates due to exacerbations of obstructive pulmonary disease amongst patients who were current/ex-illicit drug smokers versus current/ex-tobacco smokers.

Methods

We reviewed all the admissions between January 2009 and September 2011 with a presumptive diagnosis of an ‘exacerbation of COPD’ retrospectively from our COPD admission database.

Results

There were 950 sequential hospital admissions in 709 patients over a 33-month period; 250 ex-tobacco smokers, 370 current tobacco smokers and 89 current/ex-illicit drug smokers. Recurrent hospital admission rates with exacerbation of obstructive pulmonary disease were higher in the illicit drug smokers compared with current/ex-tobacco smokers (1.00 versus 0.22/0.26, p < 0.001). Illicit drug smokers were younger [50 versus 72.9/69.9 (mean 71.2) years, p < 0.001] and had shorter length of hospital stay [7.44 versus 9.28/10.69 (mean 9.87) days, p = 0.038]. Illicit drug smokers with FEV₁ < 1 litre (L) had higher readmissions than ex/current tobacco smokers with FEV₁ < 1 L (p < 0.001). Admissions requiring non-invasive ventilation for type 2 respiratory failure were more common in illicit drug smokers (8.4 versus 3 %, p < 0.002).

Conclusion

We have shown that readmission rates in illicit drug smokers with FEV₁ < 1 L are higher than in tobacco smokers. Studies are needed to determine whether targeting these illicit drug users with an intensive community intervention package (to include early therapy, pulmonary rehabilitation) will reduce readmission rates in this often neglected population.     

Ciprofloxacin reduces the risk of hemolytic uremic syndrome in patients with Escherichia coli O104:H4-associated diarrhea

Background

Whether antibiotic treatment in patients with enterohemorrhagic Escherichia coli (EHEC)-associated diarrhea influences the risk of hemolytic uremic syndrome (HUS) has still to be elucidated.

Patients and methods

During the EHEC epidemic which occurred in northern Germany in spring 2011, 24 patients with E. coli O104:H4 infection were treated at our hospitals, 19 of whom developed HUS. The use of antibiotics before and after the onset of HUS was documented, and the outcome in patients with and without antibiotic treatment was evaluated.

Results

Of the 24 patients with EHEC-associated diarrhea, seven received antibiotics before any signs of HUS were present (ciprofloxacin, cefotaxime, amoxicillin and/or metronidazole). Four of these seven patients (57 %) and 15 of the 17 patients (88 %) who were treated without antibiotics developed HUS (p = 0.12). Microbiological testing showed all E. coli O104:H4 to be extended-spectrum beta lactamase producers and thus susceptible only to fluoroquinolones, aminoglycosides and carbapenems. Two of the five patients (40 %) treated with ciprofloxacin and 17 of the 19 patients (89 %) treated without ciprofloxacin developed HUS (p = 0.043).

Conclusion

In our E. coli O104:H4-infected patients, treatment of diarrhea with antibiotics did not increase the risk of HUS. Significantly fewer patients treated with ciprofloxacin developed HUS than patients who did not receive ciprofloxacin.     

Early Oral Antibiotic Switch Compared with Conventional Intravenous Antibiotic Therapy for Acute Cholangitis with Bacteremia

Background

Biliary decompression with antibiotic therapy is the mainstay treatment for acute cholangitis with bacteremia. A few studies have been conducted to investigate the optimal duration and route of antibiotic therapy in biliary tract infection with bacteremia.

Methods

Patients with acute cholangitis with bacteremia who achieved successful biliary drainage were randomly assigned to an early oral antibiotic switch group (group A, n = 29) and a conventional intravenous antibiotics group (group B, n = 30). Patients were discharged when they were afebrile over 2 days after oral antibiotic switch and showed consecutive improvement in the laboratory index. They were followed up and assessed at 30 days after diagnosis to evaluate the eradication of bacteria, recurrence of acute cholangitis, and 30-day mortality rate.

Results

There were no statistically significant differences between the two groups in baseline characteristics, clinical and laboratory index, severity of acute cholangitis, bacteria isolated from blood cultures, and clinical outcomes. The rate of eradication of bacteria was 93.1 % in group A and 93.3 % in group B, respectively (p = 0.97). Using non-inferiority tests, the rate of eradication of bacteria in group A was not inferior to that in group B (95 % CI ?0.13 to 0.14, p = 0.97). There was no statistically significant difference in the recurrence of acute cholangitis and a 30-day mortality rate between the two groups.

Conclusions

Early switch to oral antibiotic therapy following adequate biliary drainage for treatment of acute cholangitis with bacteremia was not inferior to conventional 10-day intravenous antibiotic therapy.     

Prospective randomized trial comparing short-term antibiotic therapy versus standard therapy for acute uncomplicated sigmoid diverticulitis

Purpose

To date, the standard therapy used for acute episodes of uncomplicated sigmoid diverticulitis has been a 7–10-day antibiotic treatment regimen. Thanks to the development of highly potent, broad-spectrum antibiotics such as ertapenem, the question arises as to whether the duration of treatment of acute uncomplicated sigmoid diverticulitis can be reduced by using highly effective antibiotics.

Methods

To compare the efficacy of short-term therapy (4 days) versus standard therapy (7 days) for uncomplicated sigmoid diverticulitis, a prospective randomized multicenter trial was conducted. Patients were randomized to treatment groups after 4 days. Both patient groups were monitored until discharge and were followed up after 4–6 weeks and 52 months. The results were standardized and statistically evaluated.

Results

Between 16 December 2004 and 15 November 2007, 123 patients from 11 hospitals were enrolled in the study. Seventeen patients dropped out. In the remaining 106 cases, no significant differences were discerned between the two groups in terms of the basic data, apart from the mean number of diverticulitis episodes (short term 1.28?±?0.64 versus standard 1.64?±?1.07, p?=?0.037). The mean hospital stay was 8.8 days, with significant differences seen between short-term and standard therapy (7.8?±?2.8 versus 9.7?±?3.2 days; p?=?0.002). After 4 days, treatment was classified as having proved successful in 98.0% of cases and after 7 days in 98.2% of cases. An overall success rate of 95.1% (94.0% versus 96.2%, n.s.) was recorded after 1 month.

Conclusion

The results obtained with short-term ertapenem therapy (4 days) showed that this was as effective as standard therapy (7 days) for treatment of uncomplicated sigmoid diverticulitis.     

Increased Sympathetic Nerve Activity in COPD is Associated with Morbidity and Mortality

Background

Chronic obstructive lung disease (COPD) is a major cause of comorbidity and mortality. Systemic effects, such as sympathetic activation, might contribute to progression and severity of the disease.

Objectives

This study investigated whether increased sympathetic activity is associated with increased long-term morbidity and mortality with COPD.

Methods

Following a baseline registration of muscle sympathetic nerve activity (MSNA), 21 COPD patients and 21 matched healthy control subjects were contacted after a mean follow-up period of 7 years. Information about the number of hospitalizations during follow-up was obtained from patients who were still alive. Information about the time of death was collected from relatives of the deceased and local registration offices. The primary endpoint was the comparison of MSNA in living patients without hospitalizations versus MSNA in the patients who died or had at least one hospitalization due to exacerbation of COPD.

Results

At baseline, MSNA was significantly increased, whereas forced expiratory volume in 1 s and arterial oxygen tension (PaO₂) were significantly decreased in patients compared with controls. MSNA was significantly higher in COPD patients who had reached the combined endpoint of hospitalization or death during follow-up (n = 12) compared with patients who were still alive at follow-up and had not been hospitalized (n = 8): 60.3 ± 15.8 (SD) bursts/min versus 40.5 ± 17.5 bursts/min; p = 0.022.

Conclusions

Our data suggest that sympathetic activation is related to adverse outcome in COPD. Although this finding has to be replicated in larger studies, it implies that neurohumoral activation could be a potential therapeutic target in COPD.     

Septic arthritis: patients with or without isolated infectious agents have similar characteristics

Purpose

Septic arthritis can be disabling and life-threatening, requiring prompt diagnosis and treatment. The infectious agent is not always identified in these patients. We revaluate septic arthritis cases discharged from our department, describing the affected population, causative microorganisms and antibiotic therapy used, and characterised differences between patients with and without isolated pathogenic agents.

Methods

Sixty-eight septic arthritis patients were included in this study. Diagnosis was based on clinical findings, and/or the presence of joint purulent material, and/or bacterial pathogen isolation from joint fluid/synovial membrane/blood cultures and response to antibiotics. Data analysis was performed using SPSS 20.

Results

Patients had a mean age of 61.1 ± 18.8 years, without sex predominance. 26.5 % had an infection ≤15 days before septic arthritis diagnosis. Besides previous infection, 57.4 % had ≥1 risk factors for septic arthritis, most commonly pharmacological immunosuppression (20.6 %), diabetes mellitus type 2 (19.1 %) and rheumatoid arthritis (17.6 %). The knee was the most often affected (54.3 %). Only 39.7 % presented fever from clinical onset until hospital admission (mean 13.4 ± 18.9 days). Leucocytosis was present in 45.6 % of patients, elevated erythrocyte sedimentation rate (ESR) in 75 % and elevated C-reactive protein (CRP) in 97.1 %. 5.9 % had articular damage attributable to septic arthritis. An infectious agent was isolated in 41.2 % of patients, with Staphylococcus aureus being the most frequent. 38.7 % of synovial fluid and 23.5 % of synovial membrane cultures were positive. Patients with an identified infectious agent have no significant differences other than more days of hospitalisation (p = 0.003) and in-hospital antibiotic treatment (p = 0.017).

Conclusion

Synovial fluid and synovial membrane cultures more often identified pathogens compared to blood or urine cultures. Patients with and without an identified infectious agent have similar demographic, clinical, laboratory and radiographic characteristics.     

Listeria monocytogenes meningoencephalitis in adults: analysis of factors related to unfavourable outcome

Purpose

To analyse the short-term outcome in patients with Listeria monocytogenes meningoencephalitis (LMME) to improve management and outcome.

Methods

Observational study with adult patients with LMME between 1977 and 2009 at a tertiary hospital in Barcelona, Spain. Parameters that predicted outcome were assessed with univariate and logistic regression analysis.

Results

Of 59 cases of LMME, 28 occurred in the last decade. Since 1987, a new protocol has been used and 29/45 patients (64 %) treated since then received adjuvant dexamethasone. In patients who received this treatment there was a trend towards fewer neurological sequelae (5 vs 33 %; p = 0.052). Antiseizure prophylaxis with phenytoin was administered in 13/45 (28 %) patients. Seizures occurred in 7/45 (16 %) patients, all in the group who did not receive phenytoin. Hydrocephalus presented in 8/59 (14 %). It was never present at admission and five patients needed neurosurgical procedures. Sequelae after 3 months were present in 8/45 (18 %), mostly cranial nerve palsy. Rhombencephalitis (RE) was related to the presence of neurologic sequelae (OR: 20.4, 95 % CI: 1.76–236). Overall mortality was 14/59 (24 %), 9/59 (15 %) due to neurological causes related to hydrocephalus or seizures. Mortality was defined as early in 36 % and late in 64 %. In the multivariate analysis, independent risk factors for mortality were presence of hydrocephalus (OR: 17.8, 95 % CI: 2.753–114) and inappropriate empirical antibiotic therapy (OR: 6.5, 95 % CI: 1.201–35).

Conclusions

Outcome of LMME may be improved by appropriate empirical antibiotic therapy, suspicion and careful management of hydrocephalus. Use of adjuvant dexamethasone or phenytoin in a subgroup of these patients might have a benefit.     

The requirement for a sufficient period of corticosteroid treatment in combination with nucleoside analogue for severe acute exacerbation of chronic hepatitis B

Background

The prognosis of severe acute exacerbation of chronic hepatitis B is very poor if signs of liver failure appear. We have reported the efficacy of the early introduction of sufficient doses of corticosteroids (CSs) and nucleoside analogues (NAs), but the optimal period of immunosuppressive therapy has not been well demonstrated. In this study, we analyzed patients with severe acute exacerbation of chronic hepatitis B treated with CSs and NAs, prospectively, in order to clarify the factors affecting their outcome.

Methods

Ten patients, admitted to our liver unit between 2000 and 2009, were defined as having severe exacerbation of chronic hepatitis B based on our uniform criteria, and were enrolled in this study. NAs and sufficient doses of CS were introduced as soon as possible after making the diagnosis of severe disease prospectively.

Results

Seven of the 10 patients recovered. The absence of fulminant hepatitis on admission, the improvement of prothrombin time (PT) activity and the decline of hepatitis B virus (HBV) DNA during the first 2 and 4 weeks, respectively, were significant in the recovered patients, while the worsening of total bilirubin level during 4 weeks, especially between week 2 and week 4, was significant in those who died.

Conclusions

In severe acute exacerbation of chronic hepatitis B, more than a few weeks of CS treatment in combination with an NA is required in the early stage, whereas a short period of conventional pulse therapy would be insufficient for treating this condition.     

Risk factors for the exacerbation of esophageal varices or portosystemic encephalopathy after sustained virological response with IFN therapy for HCV-related compensated cirrhosis

Background

We aimed to identify risk factors contributing to the exacerbation of esophageal varices (EV) or portosystemic encephalopathy after hepatitis C virus (HCV) eradication with interferon (IFN) therapy in patients with compensated cirrhosis. Also, the prognosis after HCV eradication was analyzed.

Methods

Fifty-two patients with sustained virological response to IFN treatment for HCV-related compensated cirrhosis were enrolled in this retrospective cohort study.

Results

At the achievement of HCV eradication, in 31 of the 52 patients (60 %), feeding vessels for EVs (left gastric vein, posterior gastric vein, short gastric vein) were shown, and in 18 patients (35 %) there were extrahepatic portosystemic shunts (paraesophageal vein, paraumbilical vein, and splenorenal shunt). Although the HCV eradication was successful, significant improvements were not observed in portosystemic collateral vessels 1 year after HCV eradication, and EVs were exacerbated in 19 (36 %) patients. The cumulative 1- and 3-year rates of EV exacerbation were 13 % and 49 %, respectively. By multivariate analysis, the existence of feeding vessels for EVs at HCV eradication was an independent predictive factor for the exacerbation of EVs (P = 0.009). Seven patients who had an extrahepatic portosystemic shunt at HCV eradication developed portosystemic encephalopathy during follow up. The 1-, 3-, and 5-year incidences of portosystemic encephalopathy were 6, 21, and 34 %, respectively. The cumulative 5-year survival rate of the cohort was 81 %. Two patients died of hepatocellular carcinoma (HCC).

Conclusions

Our findings suggest that the existence of radical portosystemic collateral vessels at successful HCV eradication increases the risk of the exacerbation of EVs and the incidence of portosystemic encephalopathy in patients with HCV-related cirrhosis.