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Enteral nutrition with eicosapentaenoic acid, γ-linolenic acid and antioxidants in the early treatment of sepsis: results from a multicenter, prospective, randomized, double-blinded, controlled study: the INTERSEPT Study
- Alessandro Pontes-Arruda1Email author,
- Laércia Ferreira Martins1,
- Samya Maria de Lima1,
- Alexandre Marini Isola2,
- Diogo Toledo2,
- Ederlon Rezende2,
- Marcelo Maia3,
- Gisele Brocco Magnan3 and
- the Investigating Nutritional Therapy with EPA, GLA and Antioxidants Role in Sepsis Treatment (INTERSEPT) Study Group1, 2, 3
DOI: 10.1186/cc10267
© Pontes-Arruda et al.; licensee BioMed Central Ltd 2011
Received: 21 February 2011
Accepted: 9 June 2011
Published: 9 June 2011
Enteral nutrition (EN) with eicosapentaenoic acid (EPA)/γ-linolenic acid (GLA) is recommended for mechanically ventilated patients with severe lung injury. EPA/GLA has anti-inflammatory benefits, as evidenced by its association with reduction in pulmonary inflammation, improvement in oxygenation and improved clinical outcomes in patients with severe forms of acute lung injury. This study was a prospective, multicenter, randomized, double-blinded, controlled trial designed to investigate whether EPA/GLA could have an effective role in the treatment of patients with early sepsis (systemic inflammatory response syndrome with confirmed or presumed infection and without any organ dysfunction) by reducing the progression of the disease to severe sepsis (sepsis associated with at least one organ failure) or septic shock (sepsis associated with hypotension despite adequate fluid resuscitation). Secondary outcomes included the development of individual organ failure, increased ICU and hospital length of stay, need for mechanical ventilation and 28-day all-cause mortality.
Randomization was concealed, and patients were allocated to receive, for seven days, either an EPA/GLA diet or an isocaloric, isonitrogenous control diet not enhanced with lipids. Patients were continuously tube-fed at a minimum of 75% of basal energy expenditure × 1.3. To evaluate the progression to severe sepsis and/or septic shock, daily screening for individual organ failure was performed. All clinical outcomes were recorded during a 28-day follow-up period.
A total of 115 patients in the early stages of sepsis requiring EN were included, among whom 106 were considered evaluable. Intention-to-treat (ITT) analysis demonstrated that patients fed the EPA/GLA diet developed less severe sepsis and/or septic shock than patients fed the control diet (26.3% versus 50%, respectively; P = 0.0259), with similar results observed for the evaluable patients (26.4% versus 50.9% respectively; P = 0.0217). The ITT analysis demonstrated that patients in the study group developed cardiovascular failure (36.2% versus 21%, respectively; P = 0.0381) and respiratory failure (39.6% versus 24.6%, respectively; P = 0.0362) less often than the control group. Similarly, when considering only the evaluable patients, fewer patientsdeveloped cardiovascular failure (20.7% versus 37.7%, respectively; P = 0.03) and respiratory failure (26.4% versus 39.6%, respectively; P = 0.04). The percentage of patients fed the EPA/GLA diet requiring invasive mechanical ventilation was reduced compared with controls (ITT patients: 18.9% versus 33.9%, respectively; P = 0.394; evaluable patients: 17.5% versus 34.5%, respectively; P = 0.295). Patients nourished with the EPA/GLA diet remained in the ICU fewer days than the control population (ITT patients: 21.1 ICU-free days versus 14.7 ICU-free days, respectively; P < 0.0001; evaluable patients: 20.8 ICU-free days versus 14.3 ICU-free days, respectively; P < 0.0001) and fewer days at the hospital (ITT patients: 19.5 hospital-free days versus 10.3 hospital-free days, respectively; P < 0.0001; evaluable patients: 19.1 hospital-free days versus 10.2 hospital-free days, respectively; P < 0.001) (all numbers expressed as means). No significant differences in 28-day all-cause mortality were observed (ITT patients: 26.2% EPA/GLA diet versus 27.6% control diet, respectively; P = 0.72; evaluable: 26.4 EPA/GLA diet versus 30.18 control diet, respectively; P = 0.79).
These data suggest that EPA/GLA may play a beneficial role in the treatment of enterally fed patients in the early stages of sepsis without associated organ dysfunction by contributing to slowing the progression of sepsis-related organ dysfunction, especially with regard to cardiovascular and respiratory dysfunction.
Trial Registration
ClinicalTrials.gov: NCT00981877
It has been demonstrated that nutritional support by feeding patients specialized diets, as a result of its capacity to interfere with a variety of biological processes, can modulate the chain of inflammatory responses [1–3]. Recent pharmaceutical interventions proposed for sepsis have sought to focus on regulating the chain of pro- and anti-inflammatory mediators [4, 5], which are responsible for causing the systemic characteristics of the disease and consequently leading to multiple organ failure. The inflammatory reaction is capable of activating the synthesis of several lipid mediators which are involved in the complex regulation of the inflammatory process [6].
Lipid mediators are synthesized by three main pathways, cyclooxygenase, 5-lipoxygenase and cytochrome P450, by using fatty acids such as arachidonic acid (AA), eicosapentaenoic acid (EPA) and γ-linolenic acid (GLA) as substrates [7], but the biological anti-inflammatory activities of EPA and GLA are far beyond the simple regulation of eicosanoid production. For instance, EPAs can affect immune cell responses through the regulation of gene expression and subsequent downstream events by acting as ligands for nuclear receptors [8] and as control transcription factors [9]. EPA can also affect the activity of the proinflammatory transcription nuclear factor κB (NF-κB), which regulates the expression of many proinflammatory gene-encoding adhesion molecules, cytokines, chemokines and other effectors of the innate immune response system [10]. Researchers have recently described that the two main active fish oil pharmaconutrients, EPA and docosahexaenoic acid, are substrates of two novel classes of mediators called resolvins and protectins [11, 12], which are involved in the resolution of the inflammatory process [13–15].
In 1999, Gadek and co-workers [16] demonstrated that the use of a diet enriched with EPA, GLA and antioxidants can improve oxygenation status in patients with acute respiratory distress syndrome (ARDS). The same study demonstrated that patients nourished with this diet spend fewer days in the ICU as well as in the hospital. This diet was further evaluated in two additional studies published in 2006 [17, 18]. Singer et al. [17] demonstrated the effectiveness of an EPA/GLA diet in improving oxygenation status and decreasing the ICU and hospital length of stay (LOS) of patients with acute lung injury (ALI). This diet was also associated with lower mortality rates on the basis of 28-day all-cause mortality. Similar results were observed by Pontes-Arruda et al. [18] in which such a diet was fed to patients with ARDS secondary to severe sepsis and/or septic shock.
In a recently published meta-analysis of outcomes, the three above-mentioned studies were combined [19]. For the patients considered evaluable (n = 296), the use of an EPA/GLA diet was associated with a 60% reduction in the risk of 28-day in-hospital all-cause mortality (odds ratio (OR) = 0.40, 95% confidence interval (95% CI) = 0.24 to 0.68; P = 0.001). With regard to the effects of the use of an EPA/GLA diet upon mortality on the basis of intent-to-treat (ITT) analysis (n = 411 patients), a 49% reduction in the risk of 28-day in-hospital all-cause mortality was evident (OR = 0.51, 95% CI 0.33 to 0.79; P = 0.002). Available clinical evidence is also consistent in showing a reduction in time on mechanical ventilation as well as ICU and hospital LOS. In fact, a second meta-analysis including data from unpublished studies [20] demonstrated similar results.
In analyzing the data together, it was clear that feeding patients an EPA/GLA diet was associated with a reduction in the development of new organ dysfunction. Although the Singer et al. study [17] did not assess this variable, both Gadek et al. [16] and Pontes-Arruda et al. [19] demonstrated reductions in this particular outcome. Combined, the feeding patients an EPA/GLA diet was associated with an 83% reduction in the development of new organ failure. If we accept that the development of new organ failure is the pathway that leads patients with sepsis to severe sepsis and septic shock, it appears logical to evaluate the possible benefits of treating patients with this nutritional intervention in the early stages of sepsis (defined as systemic inflammatory response syndrome associated with confirmed or presumed infection and without any organ failure) as a way to prevent the evolution or to slow progression of the disease. Moreover, if we consider that the development of multiple organ failure is associated with increased mortality rates, we can hypothesize that feeding patients a diet including an enteral formulation enriched with EPA/GLA might be a determining factor in reducing the mortality rate.
All previously published trials were performed in critically ill, mechanically ventilated patients with at least one organ failure. Since the effects of the EPA/GLA diet in patients without any organ failure remain uncertain, the aims of this clinical study were to evaluate the role of an enteral formulation enriched with EPA/GLA in patients diagnosed in the very early stages of sepsis, despite respiratory failure, and to compare the results with those obtained with the use of a standard ICU formulation, isocaloric and isonitrogenous to the study diet, and not enhanced with lipids but higher in carbohydrates.
Materials and methods
Study design and ethical aspects
Composition of the study and control diets used
Diet components
Study diet (Oxepa™)a
Control diet (Ensure Plus HN™)a
Percentage of total calories
Concentration, g/L
87% sodium caseinate
13% calcium caseinate
73% sodium caseinate
11% calcium caseinate
16% soy protein isolate
Percentage of total calories
Concentration, g/L
45% maltodextrin
55% sucrose
100% maltodextrin
Percentage of total calories
Concentration, g/L
31.8% canola oil
25% medium chain triglycerides
20% borage oil
20% fish oil
3.2% soy lecithin
50% high oleic safflower oil
30% canola oil
20% medium chain triglycerides
Ω-6:Ω-3 ratio
Ω-3, g/L
Eicosapentaenoic acid (EPA), g/L
γ-Linolenic acid (GLA), g/L
Docosahexaenoic acid (DHA), g/L
C, mg/L
β-carotene, mg/L
Taurine, mg/L
L-carnitine, mg/L
K1, μg/L
Folic acid, μg/L
Thiamine, mg/L
Riboflavin, mg/L
B6, mg/L
B12, mg/L
Niacin, mg/L
Choline, mg/L
Biotin, μg/L
Pantothenic acid, mg/L
Trace minerals
Na, mg/L
K, mg/L
Cl, mg/L
Ca, mg/L
P, mg/L
Mg, mg/L
I, μg/L
Mn, mg/L
Cu, mg/L
Zn, mg/L
Fe, mg/L
Se, μg/L
Cr, μg/L
Mo, μg/L
Caloric density, kcal/mL
Osmolarity, mOsmol/L
This study was approved by the institutional review boards of each participating institution, by the Brazilian Federal Commission of Ethics and Research (CONEP) and by the Brazilian National Agency of Sanitary Vigilance (ANVISA), as required by law, before any patient enrollment. Informed written consent was obtained from all patients or from their legal representatives. This study was performed in accordance with all ethics statements in the Declaration of Helsinki (52nd General Assembly of the World Medical Association, Edinburgh, UK, October 2000) and the Nuremberg Code [21]. All included patients were treated in accordance with the Surviving Sepsis Campaign guidelines for the management of severe sepsis and septic shock [22], which means that adequate initial resuscitation was administered to all patients with sepsis-induced tissue hypoperfusion, in accordance with the protocol described by Rivers et al. [23], and broad spectrum antibiotics were administered within the first hour of ICU admission.
Study patients
The study inclusion criteria were that patients had to be older than 18 years of age, at the ICU with a clinical diagnosis of early sepsis and required enteral nutrition. A 36-hour window was allowed to establish a clinical diagnosis of sepsis, obtain the necessary written informed consent from the patients and randomize the patients. The diagnosis of sepsis was made on the basis of the criteria previously defined by Bone et al. [24] and as modified by Bernard et al. [25]. The following were considered exclusion criteria: severe sepsis (sepsis associated with at least one organ failure) and septic shock (sepsis associated with hypotension despite adequate fluid resuscitation) at baseline, a clinical diagnosis of sepsis for more than 36 hours, pregnancy or breastfeeding, patients younger than 18 years of age, significant limitation of survival prognosis (patients expecting with a life survival expectancy less than 28 days because of a chronic and/or incurable disease such as uncontrolled cancer or other terminal disease), preexisting chronic renal insufficiency and need of hemodialysis or peritoneal dialysis, body mass index (BMI) ≥ 29, acute pancreatitis without established origin, participation in other clinical trials less than 6 months before this trial, head trauma with a Glasgow Coma Scale score ≤ 5, recent stroke or subarachnoid hemorrhage (less than 3 months), severe immunologic suppression (defined as a leukocyte count below 5,000 cells/mm3), HIV infection, no indication for enteral feeding or imminent need for parenteral nutrition, partial parenteral nutrition to achieve caloric goals, presence of uncontrolled diarrhea, recent gastrointestinal bleeding, physician's decision to exclude patients on the basis of the study protocol, or the presence of respiratory failure (defined as evidence of acute pulmonary dysfunction with a ratio of partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2 ratio) < 300 and, if measured, pulmonary capillary wedge pressure not suggestive of central volume overload). Mechanical ventilation at baseline per se was not considered a reason for exclusion as long as the patient maintained a PaO2/FiO2 ratio not indicative of respiratory failure.
Randomization and study diet administration
Study and control diets were similar in consistency and color. To maintain adequate blinding, the diets were poured into similar and sealed containers before being delivered to the ICU. The containers were connected to an infusion pump (Patrol Enteral Feeding Pump; Abbott Nutrition, Chicago, IL, USA) using a closed system to prevent any detection of the diet smell by the blinded subjects. Enteral feeding was delivered at a constant rate to achieve a minimum of 50% basal energy expenditure (BEE) × 1.3 within the first 24 hours. If well tolerated, enteral nutrition was advanced to achieve a minimum of 75% of BEE × 1.3 within 72 hours. Diets were delivered continuously without night pause and using the same protocol in all participating institutions. The enteral diets were delivered for a total of seven days or until they were interrupted at the physician's discretion or because of the development of any adverse event that could be related to the enteral feeding. The diet could also be interrupted if there was an indication to start oral feeding or parenteral nutrition. After the diet was interrupted, and if the patient was still in need of enteral nutrition, each individual institution was allowed to freely select the most appropriate diet to continue the enteral nutrition therapy. The day on which patients started receiving the diet was considered study day 1.
Laboratory data, outcome measures and statistical analysis
Blood samples were obtained for routine laboratory testing on a daily basis. Severity scores, including the Acute Physiology and Chronic Health Evaluation II (APACHE II) score and the Sequential Organ Failure Assessment score (SOFA), were automatically calculated by the web-based system, taking into consideration the individual values inserted for each patient to avoid possible human errors in the calculations of the severity scores.
Criteria used to define individual organ dysfunctiona
Type of dysfunction
Systolic arterial pressure ≤ 90 mmHg after adequate fluid resuscitation
PaO2/FiO2 ratio ≤ 300 and, if measured, pulmonary capillary wedge pressure not suggestive of central volume overload
Platelet count ≤ 100,000/mm3 or 50% drop in the past 72 hours or relevant changes in coagulation profile (INR > 1.5 or aPTT > 60 seconds)
Urine output < 0.5 mL/kg/hour for at least 2 hours, even after fluid resuscitation or creatinine > 2.0 mg/dL
pH < 7.30 or base excess less than -5 mEq/L with plasma lactate > 1.5 × normal value
Total bilirubin > 2.0 mg/dL or 35 mmol/L
At the conclusion of the study, the whole database and the source documentation were independently audited to ensure the quality of the information collected, and the database was analyzed by an independent statistical company (Bioestatística, Montreal, QC, Canada). Categorical variables were compared between the two groups using the χ2 test or Fisher's exact test as appropriate [26]. Quantitative normally distributed variables between the groups were compared using an unpaired two-sample t-test. For quantitative non-normally distributed data, the nonparametric Wilcoxon rank-sum test was used [26]. Normality was assessed by using the Shapiro-Wilk test [26, 27]. Normally distributed data are reported as means with standard deviations (SDs), and non-normally distributed data are expressed as medians and interquartile ranges (IQRs, 25th to 75th percentiles). Categorical variables are expressed as numbers and percentages.
Estimates of survival curves during a 28-day follow-up period were calculated according to the Kaplan-Meier product limit method [28] and compared by using the log-rank test [29]. All statistical analyses were performed using SAS version 9.2 software (SAS Institute, Inc., Cary, NC, USA). All P values are two-tailed. P < 0.05 was considered statistically significant.
Patients and demographic characteristics
Baseline demographic characteristics of the patientsa
Study (n= 53)
Control (n= 53)
P value
Age, yearsb
70 (64 to 78)
72 (65 to 82)
Males, n (%)
32 (60.4)
29 (54.7)
Females, n (%)
21 (39.6)
24 (45.3)
Weight, kg
59.3 ± 12.5
61.2 ± 11.7
Height, cm
166.2 ± 11.4
167.7 ± 10.4
APACHE II scoreb
19.5 (17 to 25)
20 (16 to 23)
SOFA scoreb
5.5 (4 to 9)
6 (4 to 8)
MODS scoreb
4 (3 to 6)
4 (3 to 5)
Lactate, mmol/Lb
3.75 (2.9 to 4.65)
3.7 (2.8 to 4.3)
Blood glucose, mg/dLb
103 (89 to 149)
102 (87 to 125)
Temperature, °Cb
39.4 (38.2 to 39.8)
38.9 (37.2 to 39.5)
GCS score
10.1 ± 2.2
10.8 ± 2.1
White blood cells, 1 × 109 cells/L
19.3 ± 0.9
20.7 ± 0.7
Platelets, 1 × 109 cells/Lb
198 (144 to 259)
211 (178 to 256)
Serum creatinine, mg/dLb
1.15 (0.9 to 1.6)
0.9 (0.8 to 1.3)
Total bilirubin, mg/dLb
0.9 (0.7 to 1.3)
0.8 (0.7 to 1.5)
Serum Na, mEq/Lb
139 (133 to 145)
135 (137 to 144)
Serum K, mEq/L
3.9 ± 0.7
4.0 ± 0.8
Patients supported with MV, n (%)c
1 (1.9)
2 (3.8)
Patients treated with sedatives, n (%)
3 (5.7)
5 (9.4)
Baseline comorbidities, n (%)
Recent surgery (< 3 months)
6 (11.3)
9 (16.9)
History of alcoholism
10 (18.9)
8 (15.1)
12 (22.6)
17 (32.1)
10 (18.9)
9 (16.9)
11 (20.75)
12 (22.6)
4 (7.5)
4 (7.5)
1 (1.9)
1 (1.9)
History of illicit drug use
4 (7.5)
2 (3.8)
Primary source of infection, n (%)
38 (71.7)
33 (62.3)
6 (11.3)
8 (15.1)
Urinary tract
4 (7.6)
2 (3.7)
5 (9.4)
10 (18.9)
Dietary intake
Nutritional parameters of the included patientsa
Study (n= 53)
Control (n= 53)
P value
SGA nutritional status, n (%)
20 (37.7)
25 (47.2)
Moderately undernourished
22 (41.5)
21 (39.6)
Severely undernourished
11 (20.8)
7 (13.2)
Type of enteral feeding, n (%)
25 (47.2)
23 (43.4)
19 (35.8)
21 (39.6)
6 (11.3)
5 (9.4)
3 (5.7)
4 (7.6)
Daily nutritional values
Days receiving diet, n
6.09 ± 0.4
6.17 ± 0.8
Calculated caloric goal, kcal/dayb
1,557 (1,367 to 1,812)
1,560 (1,422 to 1,820)
Calculated caloric volume, mL/dayb
1,038 (911 to 1,208)
1,040 (948 to 1,213)
Calories, kcal/dayb
1,538 (1,295 to 1,890)
1,523 (1,370 to 1,950)
Volume, mL/dayb
1,025 (863 to 1,260)
1,015 (913 to 1,300)
Lipids, g/day
96.04 ± 37.2
49.8 ± 19.0
< 0.0001
Carbohydrates, g/day
104.2 ± 38.9
205.6 ± 77.4
< 0.0001
Proteins, g/day
63.4 ± 22.8
62.6 ± 24.3
EPA, g/day
4.6 ± 1.8
< 0.0001
GLA, g/day
4.4 ± 1.7
< 0.0001
DHA, g/day
2.05 ± 0.7
< 0.0001
Time to start enteral feeding, hours
8.4 ± 2.6
7.6 ± 3.1
Time to reach 75% of caloric goal, hours
35.2 ± 8.7
32.0 ± 6.4
The incidence of diarrhea and vomiting was also evaluated. A total of two patients in the study group (3.8%) and three patients in the control group (5.7%) experienced vomiting. In addition, four patients in the study group (7.5%) and seven patients in the control group (13.2%) had uncontrolled diarrhea. The differences between the two groups were not considered statistically significant in terms of either vomiting (P = 0.74) or diarrhea (P = 0.43). During this study, no serious adverse events were recorded.
Primary outcome: development of severe sepsis and septic shock
Secondary outcomes
Use of hospital resourcesa
Study (n= 53)
Control (n= 53)
P value
Mechanical ventilation support, n (%)
10 (18.9%)
18 (34%)
5 (9.4%)
6 (11.3%)
Duration, days
Mechanical ventilation supportb
7 (4 to 12)
15 (9 to 21)
ICU stayb
7 (4 to 12)
13 (9 to 18)
< 0.0001
Hospital stayb
9 (6 to 14)
19 (13 to 24)
< 0.0001
No patients requiring vasopressors or inotropic drugs were included at baseline. During the 28-day follow-up period, dobutamine was required for 9 patients (17%) in the study group and 13 patients (24.5%) in the control group (P = 0.34), with similar daily doses used for both groups (9.96 μg/kg/minute for the study group and 9.57 μg/kg/minute for the control group; P = 0.77). Dopamine was used to treat 12 patients (22.6%) in the study group and 17 patients (32.1%) in the control group (P = 0.28), with mean daily doses of 23.4 μg/kg/minute in the study group and 21.5 μg/kg/minute in the control group (P = 0.87). Norepinephrine was used to treat 9 patients (17%) in the study group and 11 patients (20.7%) in the control group (P = 0.61), with mean daily doses of 2.2 μg/kg/minute in the study group and 1.8 μg/kg/minute in the control group (P = 0.81).
Currently available strategies for the treatment of patients with sepsis focus on the management of the more severe forms of the disease (severe sepsis and/or septic shock), when the patients already have multiple-system organ dysfunctions, which is always associated with elevated death risk [30, 31]. The contradiction is that there is also a consensus that, when treating patients with sepsis, most, if not all, available strategies are time-dependent [32].
Unfortunately, information about possible strategies to be applied in the early stages of sepsis is extremely limited, as is the number of trials evaluating possible therapies this early in the disease time line. The main purpose, and probably the most interesting characteristic of the present trial, was to apply a nutritional strategy that has proven to be of great value in the management of patients with late sepsis-associated respiratory failure [1], and is associated with an important reduction in the development of new organ failures [20], early in the evolutionary stage of sepsis when no organ dysfunction has been identified and to test whether this nutritional strategy can be used to help slow the progression of the disease.
In this study, we found an association of the use of an EPA/GLA diet with reduced incidence of severe sepsis and/or septic shock. Although the mechanisms underlying the results of the present trial are unclear, there are several possible roles associated with EPA, GLA and antioxidants which, acting alone or together, may help us to understand how this diet can lead to the observed effects, among them being the regulation of AA levels in the inflammatory cell membranes, downregulation of NF-κB, lower production of inflammatory eicosanoids, antioxidant-mediated reduction in overall reactive oxygen species levels and a quicker recovery from inflammation due to production of resolvins and protectins, among several others.
In this trial, we used a control diet different from those used in previously published works [16–18]. Our control diet was not enhanced with lipids but was higher in carbohydrates and was considered a standard ICU diet. The reason for our use of that control diet was that one major focus of criticism of previous work is precisely the control diet that was used (Pulmocare; Abbott Nutrition). Maybe the main reason for such criticism is that a high-lipid enteral diet is not considered by many to be a standard diet for critically ill patients. It is a common misunderstanding that enteral formulas enriched with Ω-6 lipids such as linoleic acid (LA, or 18:2n6; for example, from corn oil) can produce upregulation of the inflammatory response and, for that reason, such formulas may not be used to feed patients with hyperinflammatory diseases. Production of AA from LA involves three key enzymatic steps: Δ-6-desaturation to form 18:3n6 (GLA), followed by elongation to 20:3n6 (dihomo-GLA (DGLA)) and a Δ-5-desaturation step to produce 20:4n6. Thus, LA-enriched formulas cannot worsen inflammation simply because the activity of the enzymes Δ-5-desaturase and Δ-6-desaturase are severely compromised during critical illness by the release of stress and catabolic hormones (for example, glucocorticoids and catecholamines) [33, 34] limiting the ability to form AA despite the provision of LA [35]. GLA is a metabolite of LA that can bypass the decreased expression of Δ-6-desaturase. Its elongation product, DGLA, is incorporated into the inflammatory cell membranes, and the formation of DGLA suppresses leukotriene biosynthesis and can be metabolized to form prostaglandin E1, a potent pulmonary vasodilator [36, 37]. DGLA is also metabolized by 5-lipoxygenase to form 15-hydroxyeicosatrienoic acid, which inhibits the formation of leukotriene B4. In fact, an enteral diet enriched with GLA cannot increase AA levels in immune cell membranes [38] and, on the other hand, can increase anti-inflammatory activity by incorporating DGLA into the immune cell membranes. Despite all of the above-mentioned evidence, the previous criticism of other studies highlights the importance of this trial as the first one to demonstrate a positive result in terms of primary and secondary outcomes comparing the EPA/GLA diet with a standard ICU formula.
In this study, we report a reduction in both ICU and hospital LOS for patients fed a diet with EPA/GLA compared to the control population. The differences represent a mean of 6.5 additional ICU-free days and 8.9 additional hospital-free days associated with the use of the study diet. These results are in accord with previously published studies [16–18] in which EPA/GLA diets were used to treat critically ill patients requiring mechanical ventilation, all of which reported reductions in ICU and hospital LOS. In fact, a recent meta-analysis [19] associated the use of EPA/GLA with a mean of 4.3 more ICU-free days compared to patients fed a control diet. Sepsis represents an important financial burden on the healthcare system [39, 40], and any reduction in terms of LOS must be considered to have a potential economic impact regarding reductions in the overall cost of care.
It is important to note that the reported number of patients requiring mechanical ventilation (invasive or noninvasive) was slightly different in the study groups with regard to the number of patients considered to have developed respiratory failures since the end of the study. The reason for that finding was that, during the 28-day follow-up period, one patient in the study group and three patients in the control group required noninvasive mechanical ventilation but did not fulfill the PaO2/FiO2 ratio criterion for respiratory failure.
Previously published works [17, 18] and the present study have many relevant characteristics in common. They all used a study diet containing carbohydrates and proteins together with high levels of EPA/GLA. They all started enteral nutrition as early as possible and delivered the diet continuously using an enteral feeding pump. In a recent study (the EDEN-Omega Study) conducted by the EDEN-Omega NHLBI ARDS Network, investigators reported different findings when treating critically ill patients [41]. They found no benefit in using a module containing EPA/GLA to treat patients requiring mechanical ventilation, and the study was stopped because of futility. Comparison of the EDEN-Omega Study with the previously published works can lead to dangerous misinterpretation of the current evidence. First and foremost, the patients enrolled in the EDEN-Omega study received a bolus of EPA/GLA twice daily, not an enteral formula containing EPA/GLA as part of it. It is uncertain whether these pharmaconutrients act differently if not provided using continuous feeding and as part of an enteral nutrition formula. Absorption of individual macronutrients (such as lipids) at the intestinal level can be drastically affected by the presence or absence of other nutrients. Additionally, it has been demonstrated [42] that the delivery of an EPA/GLA diet by continuous feeding can produce important changes in the production of inflammatory mediators associated with modulation of plasma phospholipid levels. It is not clear whether a bolus of EPA/GLA given twice daily can provide similar changes in plasma phospholipids. Unfortunately, to date, the EDEN-Omega NHLBI ARDS Network investigators have not made publicly available the plasma phospholipid measurements of the patients included in the EDEN-Omega study, data that are of pivotal importance to allow a fair trial comparison between their trial and those previously published. Moreover, the EDEN-Omega study did not control for several other variables, including the different levels of other macronutrients (such as proteins) in the underlying diets fed to their patients, producing a huge source of bias in their data. Finally, the EDEN-Omega study was not designed as an early intervention trial, but was in fact an early versus late intervention study, whereas early enteral feeding was described as a key factor in all previous trials. The currently available nutrition guidelines continue to unanimously recommend the use of an EPA/GLA diet in critically ill and mechanically ventilated patients with ALI/ARDS [1, 20]; therefore, not to use this strategy in the indicated population of patients merely on the basis of the results of an unpublished single trial in which so many important questions remain to be answered does not appear to be justifiable.
Interaction between fish oil and sepsis is very complex and variable, depending on the dose administered and probably the route of administration as well. Most of the available evidence associated with the benefits of fish oil was produced when this active pharmaconutrient was used as part of enteral nutrition formulations. However, the number of trials testing parenterally administered fish oil in a variety of clinical situations, including sepsis, is growing [43, 44]. For instance, in a recently published study using a fish oil-based lipid emulsion in patients with sepsis, Barbosa and co-workers [45] demonstrated significant improvements in the PaO2/FiO2 ratio that were similar to the effects reported with the use of enteral nutrition.
Although in the present study we have demonstrated a reduction in the development of cardiovascular and respiratory failure in the patient population nourished with EPA/GLA as compared to the control population, this was not associated with a significant reduction in mortality. The probable reason for this finding is that this study included patients with early sepsis and no organ dysfunction, a clinical situation usually associated with lower mortality rates than are found in patients with severe sepsis and/or septic shock [46]. The sample size of this trial was not calculated to demonstrate mortality differences, and this particular variable should be evaluated in future studies.
Some important limitations need to be considered when evaluating the results of the present study. One of the most important is that this study included only those patients in need of enteral nutrition. During the enrollment of the patients, the investigators considered this to be very relevant and to represent a limitation in terms of the number of potential patients who could be included in this trial, since most patients whom we found to be in the early stages of sepsis did not require enteral nutrition, being able to receive oral feeding. In addition, the study included only patients at the ICU, which reduced even more the number of potential patients to be included, since the majority of the patients with early sepsis are usually not at the ICU but in the general wards. As a result of these important limitations, we believe that the population of patients included in this study was somehow selected, being constituted by elderly patients, most of whom were already receiving treatment and enteral feeding at their homes because of previous limitations such as stroke and eventually developing diseases such as community-acquired pneumonia, therefore requiring hospital treatment. In addition, this study excluded patients with a BMI ≥ 29, and for this reason generalization of the results to the obese population of patients is not possible. Finally, it was not possible to report changes in the Δ or component SOFA scores, since this trial was not designed to collect daily SOFA scores. Therefore, it is uncertain whether the observed reduction in the development of severe sepsis and/or septic shock is associated with reductions in the SOFA score over time. This association represents an important variable to be evaluated in future trials in which an EPA/GLA diet is fed to septic patients.
It will be important to produce further evidence and reproduce the present work in a more broad population of patients in the early stages of sepsis using an EPA/GLA diet, maybe as an oral supplement, and not delivering these pharmaconutrients only when an enteral feeding tube is in place.
The present study presents evidence that enteral nutrition with EPA/GLA and elevated antioxidants, when used in the early stages of sepsis in patients without any organ failure and in need of enteral nutrition, can play a beneficial role by slowing the progression of the disease to severe sepsis and septic shock. The possible benefit of EPA/GLA supplementation in patients receiving oral feeding needs further evaluation.
Key messages
Although EPA/GLA is currently recommended for critically ill, mechanically ventilated patients with ALI/ARDS in accordance with international guidelines, there is no evidence that this diet has any benefit when used in the early stages of sepsis.
This report describes a prospective, multicenter, double-blinded, controlled study designed to evaluate the effects of enteral nutrition with EPA/GLA in critically ill patients with early sepsis without organ failure.
When used in the above-mentioned patient population, enteral nutrition enriched with EPA/GLA was associated with less development of severe sepsis and/or septic shock, primarily because of the reduced number of cardiovascular and respiratory failures in the study population.
An additional benefit was found in terms of reduced hospital and ICU LOS, which represents an important reduction in the overall cost of care for the treatment of this patient population.
No effect was observed with regard to 28-day all-cause mortality.
acute lung injury
Acute Physiology and Chronic Health Evaluation II
acute respiratory distress syndrome
basal energy expenditure
body mass index
confidence interval
docosahexaenoic acid
eicosapentaenoic acid
γ-linolenic acid
interquartile range, 25th to 75th percentiles
intention to treat
length of stay
Multiple Organ Dysfunction Score
- NF-κB:
nuclear factor κB
odds ratio
Subjective Global Assessment
Sequential Organ Failure Assessment.
This study was partially supported by funding from Abbott Nutrition/Abbott Laboratories (Chicago, IL, USA). The INTERSEPT study was sponsored by the Centro de Estudos João Pompeu Lopes Randal (Fortaleza, Ceará, Brazil) with the coordination of the Latin American Sepsis Institute (São Paulo, Brazil). We thank Frederico Rafael Moreira (Bioestatística, Montreal, QC, Canada) for statistical analysis. We thank all participating institutions and investigators of the INTERSEPT Study Group for their perspective and guidance, especially the following institutions for having included patients in the study: Hospital Fernandes Távora (Fortaleza, CE, Brazil), Hospital do Servidor Público Estadual de São Paulo (São Paulo, SP, Brazil), Hospital Santa Luzia (Brasília, DF, Brazil), Hospital Pró-Cardíaco (Rio de Janeiro, RJ, Brazil) and Hospital Português (Salvador, BA, Brazil). The following hospitals approved the study and were registered as participating centers with the regulatory authorities but did not include any patients during their participation: Centro Hospitalar UNIMED (Joinville, SC, Brazil), Hospital Dona Helena (Joinville, SC, Brazil), Hospital de Base de São José do Rio Preto (São José do Rio Preto, SP, Brazil), Hospital São Paulo/UNIFESP (São Paulo, SP, Brazil), Clínica São Vicente (Rio de Janeiro, RJ, Brazil), Hospital Salvador (Salvador, BA, Brazil) and Hospital Universitário da Universidade Federal da Paraíba (João Pessoa, PB, Brazil). The results of this study have been published previously only in abstract form [47, 48].
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Stephen Whited
The Same Seaby Amos Oz
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The Same Sea is Amos Oz's most adventurous and inventive novel, the book by which he would like to be remembered. The cast of characters ranges from a prodigal son to a widowed father who has taken in his son's enticing young girlfriend, who in turn sleeps with her boyfriend's close friend. The author himself receives phone calls from his characters, criticizing the way he portrays them in his novel. In this human profusion there is chaos and order, love and eroticism, loyalty and betrayal, and ultimately an extraordinary energy.
"I wrote this book with everything I have. Language, music, structure--everything that I have. . . . This is the closest book I've written. Close to me, close to what I always wanted. . . . I went as far as I could."--Amos Oz
Editorial Reviews
Stephen Whited
"In a world full of hype, noise, and confusion, the simple lucidity of The Same Sea is totally unexpected."--The New York Times Book Review
"This lovely, lyrical territory, irrigated by numerous streams of consciousness, reminded me of some of the great things a novel can do."--Chicago Tribune
Product Details
- 9780547710587
- Publisher:
- Houghton Mifflin Harcourt
- Publication date:
- 10/01/2002
- Sold by:
- Houghton Mifflin Harcourt
- Format:
- NOOK Book
- Pages:
- 208
- Sales rank:
- 689,849
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Read an Excerpt
Chapter One
A cat
Not far from the sea, Mr. Albert Danon lives in Amirim Street, alone. He is fond of olives and feta; a mild accountant, he lost his wife not long ago. Nadia Danon died one morning of ovarian cancer, leaving some clothes, a dressing table, some finely embroidered place mats. Their only son, Enrico David, has gone off mountaineering in Tibet.
Here in Bat Yam the summer morning is hot and clammy but on those mountains night is falling. Mist is swirling low in the ravines. A needle-sharp wind howls as though alive, and the fading light looks more and more like a nasty dream.
At this point the path forks: one way is steep, the other gently sloping. Not a trace on the map of the fork in the path. And as the evening darkens and the wind lashes him with sharp hailstones, Rico has to guess whether to take the shorter or the easier way down.
Either way, Mr. Danon will get up now and switch off his computer. He will go and stand by the window. Outside in the yard on the wall is a cat. It has spotted a lizard. It will not let go.
A bird
Nadia Danon. Not long before she died a bird on a branch woke her. At four in the morning, before it was light, narimi narimi said the bird.
What will I be when I'm dead? A sound or a scent or neither. I've started a mat. I may still finish it. Dr. Pinto is optimistic: the situation is stable. The left one is a little less good. The right one is fine. The X-rays are clear. See for yourself: no secondaries here.
At four in the morning, before it is light, Nadia Danon begins to remember. Ewes' milk cheese. A glass of wine. A bunch of grapes. A scent of slow evening on the Cretan hills, the taste of cold water, the whispering of pines, the shadow of the mountains spreading over the plain, narimi narimi the bird sang there. I'll sit here and sew. I'll be finished by morning.
Rico David was always reading. He thought the world was in a bad way. The shelves are covered with piles of his books, pamphlets, papers, publications, on all sorts of wrongs: black studies, women's studies, lesbians and gays, child abuse, drugs, race, rain forests, the hole in the ozone layer, not to mention injustice in the Middle East. Always reading. He read everything. He went to a left-wing rally with his girlfriend Dita Inbar. Left without saying a word. Forgot to call. Came home late. Played his guitar.
Your mother begs you, his father pleaded. She's not feeling too and you're making it worse. Rico said, OK, give me a break. But how can anyone be so insensitive? Forgetting to switch off. Forgetting to close. Forgetting to get back before three in the morning.
Dita said: Mr. Danon, try to see it his way. It's painful for him too. Now you're making him feel guilty; after all, it's not his fault she's dead. He has a right to a life of his own. What did you expect him to do? Sit holding her hand? Life goes on. One way or another everyone gets left alone. I'm not much for this trip to Tibet either, but still, he's entitled to try to find himself. Especially after losing his mother. He'll be back, Mr. Danon, but don't hang around waiting for him. Do some work, get some exercise, whatever. I'll drop by sometime.
And since then he goes out to the garden at times. Prunes the roses. Ties up the sweet peas. Inhales the smell of the sea from afar, salt, seaweed, the warm dampness. He might call her tomorrow. But Rico forgot to leave her number and there are dozens of Inbars in the phone book.
Later, in Tibet
One summer morning, when he was young, he and his mother took the bus from Bat Yam to Jaffa, to see his Aunt Clara. The night before he refused to sleep: he was afraid the alarm clock would stop in the night, and he wouldn't wake. And what if it rains, or if we are late.
Between Bat Yam and Jaffa a donkey cart had overturned. Smashed watermelons on the asphalt, a blood bath. Then the fat driver took offense and shouted at another fat man, with greased hair. An old lady yawned at his mother. Her mouth was a grave, empty and deep. On a bench at a stop sat a man in a tie and white shirt, wearing his jacket over his knees. He wouldn't board the bus. Waved it on. Maybe he was waiting for another bus. Then they saw a squashed cat. His mother pressed his head to her tummy: don't look, you'll cry out again in your sleep. Then a girl with her head shaved: lice? Her crossed leg almost revealed a glimpse. And an unfinished building and dunes of sand. An Arab coffee house. Wicker stools. Smoke, acrid and thick. Two men bending forward, heads almost touching.
A ruin. A church. A fig tree. A bell. A tower. A tiled roof. Wrought-iron grilles. A lemon tree. The smell of fried fish. And between two walls a sail and a sea rocking.
Then an orchard, a convent, palm trees, date palms perhaps, and shattered buildings; if you continue along this road you eventually reach south Tel Aviv. Then the Yarkon. Then citrus groves. Villages. And beyond the mountains. And after that it is already night. The uplands of Galilee. Syria. Russia. Or Lapland. The tundra. Snowy steppes.
Later, in Tibet, more asleep than awake, he remembers his mother. If we don't wake up we've had it. We'll be late. In the snow in the tent in the sleeping-bag he stretches to press his head to her tummy.
In Amirim Street Mr. Danon is still awake. It's two in the morning. On the screen before him the figures don't add up. Some company or other. A mistake or a fraud? He checks. Can't spot anything. On an embroidered mat the tin clock ticks. He puts on his coat and goes out. It's six now in Tibet. A smell of rain but no rain in the street in Bat Yam. Which is empty. Silent. Blocks of flats. A mistake or a fraud. Tomorrow we'll see.
A mosquito
Dita slept with a good friend of Rico's, Giggy Ben-Gal. He got on her nerves when he called screwing intercourse. He disgusted her by asking her afterwards how good it had been for her on a scale of nought to a hundred. He had an opinion about everything. He started yammering on about the female orgasm being less physical, more emotional. Then he discovered a fat mosquito on her shoulder. He squashed it, brushed it off, rustled the local paper and fell asleep on his back. Arms spread out in a cross. Leaving no room for her. His cock shrivelled too and went to sleep with a mosquito on it: blood vengeance.
She took a shower. Combed her hair. Put on a black T-shirt that Rico had left in one of her drawers. Less. Or more. Emotional. Physical. Sexy. Bullshit. Sensual. Sexual. Opinions night and day. That's wrong. That's right. What's squashed can't be unsquashed. I ought to go and see how the old man's doing.
Excerpted from The Same Sea by AMOS OZ. Copyright © 1999 by Amos Oz and Keter Publishing House Ltd.. Excerpted by permission. All rights reserved. No part of this excerpt may be reproduced or reprinted without permission in writing from the publisher.
Meet the Author
AMOS OZ was born in Jerusalem in 1939. He is the author of fourteen novels and collections of short fiction, and numerous works of nonfiction. His acclaimed memoir A Tale of Love and Darkness was an international bestseller and recipient of the prestigious Goethe Prize, as well as the National Jewish Book Award. Scenes from Village Life, a New York Times Notable Book, was awarded the Prix Méditerranée Étranger in 2010. He lives in Tel Aviv, Israel.
NICHOLAS DE LANGE is a professor at the University of Cambridge and a renowned translator. He has translated Amos Oz's work since the 1960s.
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The Same Sea by Amos Oz. Five Stars. What a beautiful book! But, not at all for readers who must have things simply clear cut and well dried. This is a book for the unashamedly naive and unashamedly mature. The Same Sea is not a page turner; it is a thought provoker. This is a book for those who seek insight and can recognize their own hungry questions and create their own nourishing answers. This is a book of for introspection, self awareness, and honesty. The Same Sea is evidence, if evidence is needed, that Amos Oz has spent his lifetime living and learning and perfecting his art. Surely he has equalled if not surpassed all of his teachers. There is nothing engagingly superficial about The Same Sea and readers of the superficial need not apply. Do not come to this book knowing nothing about the book or the author. That Amos Oz lives in the same sea as do we is a gift to us.

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Not to be Outdone by FedExCup Champion Vijay Singh, FedExCup Runner-Up Camilo Villegas Increases Commitment to Children of St. Jude
For Villegas and Singh, exceeding expectations extends beyond thetournaments. In December, this pair of PGA pros, along with Pressel, gatheredat St. Jude in Memphis to help present a record-breaking $2.57 milliondonation to the hospital raised through the 2008 Eagles for St. Jude programand the 2008 Stanford St. Jude Championship. Villegas donated $30,000, morethan double his commitment of $3,000 per eagle, and Singh donated $300,000 toSt. Jude, well above his commitment of $5,000 per eagle he carded. The $2.57million donation also included Stanford Financial Group's donation of $1,000for each of the 1,118 eagles recorded on the PGA TOUR and the 469 eaglescarded on the LPGA Tour. It also comprised donations from FedEx and from thegeneral public who supported the Eagles program throughout the year via theEagles for St. Jude Web site and online auction.
"When I joined Vijay in supporting the Eagles for St. Jude program lastyear, I had no idea how much it would change my life," said Villegas. "Themore time I spend with these incredible kids who are battling deadly diseases,the more I want to help them. While we were at St. Jude in December, Vijayand I talked about ways to get more golfers to support Eagles, so I'm puttingmy money where my mouth is. I also can't be outdone by Vijay," added Villegaswith a laugh.
Singh, who serves as Global Ambassador for the Eagles for St. Judeprogram, said, "This is great news for the kids of St. Jude! I know Camilohas been moved by these kids the past year, and I am not at all surprised hehas increased his support to the program. Camilo is a great golfer, so I'msure his donation for the 2009 TOUR will be significant! We only hope thatother golfers join us in helping the kids of St. Jude by supporting the Eaglesfor St. Jude program," added Singh.
The Eagles for St. Jude program, created during Stanford Financial Group'sinaugural sponsorship year of the Stanford St. Jude Championship out of thedesire to provide a season-long fundraising component to the Memphis PGA TOURevent, began with Stanford's commitment to donate $1,000 to St. Jude for everyeagle made on the PGA TOUR in the name of the player that makes the eagle.The program has grown exponentially in just two short years and continues togather momentum with Villegas, Singh and Pressel promoting it along with theGolf Channel.
"Thanks to Eagles for St. Jude and Stanford, excellence on the golf courseis translated into research and care at St. Jude," said David L. McKee, ChiefOperating Officer and interim CEO of ALSAC, the fundraising organization ofSt. Jude. "We are so grateful for this remarkable program and for the amazingcommitment Camilo, Vijay and Morgan have made to the kids of St. Jude."
For more information on the Eagles for St. Jude program, please visitwww.eaglesforstjude.com.
About St. Jude Children's Research Hospital
St. Jude Children's Research Hospital is internationally recognized forits pioneering work in finding cures and saving children with cancer and othercatastrophic diseases. St. Jude is the first and only pediatric cancer centerto be designated as a Comprehensive Cancer Center by the National CancerInstitute. Founded by the late entertainer Danny Thomas and based in Memphis,Tenn., St. Jude freely shares its discoveries with scientific and medicalcommunities around the world. St. Jude is the only pediatric cancer researchcenter where families never pay for treatments not covered by insurance. Nochild is ever denied treatment because of the family's inability to pay. St.Jude is financially supported by ALSAC, its fundraising organization. For moreinformation, please visit www.stjude.org.
About Stanford Financial Group
Stanford Financial Group is a privately held global network ofindependent, affiliated financial services companies led by Chairman of theBoard Sir Allen Stanford. The first Stanford company was founded by hisgrandfather, Lodis B. Stanford in 1932. Stanford's core businesses are privatewealth management, institutional consulting and investment banking forinstitutions and emerging growth companies.
The Stanford Financial Group of companies provides private andinstitutional investors with global expertise in asset allocation strategies,investment advisory services, award-winning policy and equity research,international private banking and trust administration, commercial banking,investment banking, merchant banking, institutional sales and trading, realestate investment and insurance. Stanford has more than $50 billion in assetsunder management or advisement.
Stanford Financial has made it a priority to invest in the communities inwhich it operates across the globe through signature corporate philanthropyinitiatives with nonprofit organizations such as St. Jude Children's ResearchHospital and countless local and national charities that strengthencommunities.
Securities products and services are offered in the United States throughStanford Group Company, member FINRA/SIPC. Stanford Financial Group is not alegal entity, but a registered trademark that encompasses the global networkof independent, but affiliated, privately held and wholly owned entities.More information can be found at www.stanfordfinancial.com.
SOURCE Stanford Financial Group
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Originally Posted by Gyp Rosetti
Interesting. I honestly wouldn't mind going fun and young, losing Jefferson and Millsap, getting someone new who doesn't demand much PT, and having Tomic as our 4th big next year.
Originally Posted by Hotttnickkk
Yep agree with this. Lose both Jefferson & Millsap. If Tomic is decent, I'd actually have him as our 3rd big with Evans as our 4th.
Originally Posted by Hack
So now its better to have Tomic on your team rather than Jefferson and Millsap.
I know we are down on them, but is Tomic really better than both of them?
No, but he is an offensively talented 7'2 player coming off the bench who could probably create mismatches against backup big men.
I'm down!!
I wish he wasn't so soft on defense. He's pretty skilled on offense though.
Would be a good back post Big Al/Sap era
"les grandes défaites forgent les grands hommes" - Rudy Gobert
Do we even still have his rights
Long Live JYD
Originally Posted by Sneakers
Do we even still have his rights
If we do we should either bring him over next season or trade the rights. This Tomic thing is getting out of hand.
Cy is a Baker, he doesn't work fast food. Don't make that mistake, he doesn't like it.
I thought we traded his rights to Minnesota or Atlanta...
Originally Posted by NAOS
Wouldn't we have to over pay to get him here? Isn't this a dead issue?
I believe there's a limit on how much can be paid to a foreign team for a buyout. The remaining amount must be paid by the player. Raul Lopez basically pocketed nothing his first season. Tomic will never play in the NBA. But his rights may be traded to even out a deal at some point, just like Fehse.
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Mod_perl 2 User's Guide
By (author) Stas Bekman Jim Brandt
Format: Paperback
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Mod_perl 2 User's Guide by Stas Bekman
Book Descriptionmod_perl 2, the next generation of the Apache Perl module, gives you full access to the Apache 2 internals via the Perl programming language, just as mod_perl 1 gave you access to Apache 1. New features in Apache and Perl make mod_perl 2 even more powerful and useful than before, allowing you to quickly write and deploy fast, robust web applications. As with any major upgrade, there are new features and key changes to mod_perl from the 1.x generation. The mod_perl 2 User's Guide explains these key changes and demonstrates the tools you can use to port modules and migrate your existing code. Improvements in Apache 2 and mod_perl 2 include: * Multi-Processing Model modules (MPMs) allow for process-based and thread-based processing models. The addition of thread support makes mod_perl viable on Win32 and introduces the potential for improved performance on other platforms. * Protocol Modules give Apache and mod_perl the potential to serve any protocol, not just HTTP. * A mod_perl 2 interface to the Apache filtering API gives full access to input and output filters from Perl.* Support for creating custom Apache configuration directives in pure Perl, improved options for passing values to Perl modules from Apache, and greater access to the Apache configuration values. * The Apache::Test framework, useful for Perl and non-Perl Apache modules, allows you to develop fully-tested web applications to verify features and guard against regression. * The ability to easily subclass ModPerl::Registry and override methods as needed. This guide provides installation and configuration guidelines, as well as details on all the ways you can plug into the Apache request cycle. You'll also learn how to write mod_perl handlers to deliver content with rapid response times and to leverage your existing CGI scripts with ModPerl::Registry. Whether you're new to mod_perl or migrating from mod_perl 1, the mod_perl 2 User's Guide will give you the information you need to get up and running on Apache 2 and mod_perl 2. Half of all proceeds from the sale of this book will be donated to The Perl Foundation.
Buy Mod_perl 2 User's Guide book by Stas Bekman from Australia's Online Bookstore, Boomerang Books.
Book DetailsISBN: 9780977920112
(229mm x 152mm x 22mm)
Pages: 432
Imprint: Onyx Neon Press
Publisher: Onyx Neon Press
Publish Date: 21-Jul-2007
Country of Publication: United States
Books By Author Stas Bekman
Practical Mod-Perl, Paperback (June 2003)» View all books by Stas Bekman
This volume offers detailed instructions on how to use, optimize, and troubleshoot modperl. The authors provide tips and advice from their experience, as well as those from the modperl community at large.
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