Self-management support interventions for persons with chronic disease: an evidence-based analysis.

BACKGROUND: Self-management support interventions such as the Stanford Chronic Disease Self-Management Program (CDSMP) are becoming more widespread in attempt to help individuals better self-manage chronic disease. OBJECTIVE: To systematically assess the clinical effectiveness of self-management support interventions for persons with chronic diseases. DATA SOURCES: A literature search was performed on January 15, 2012, using OVID MEDLINE, OVID MEDLINE In-Process and Other Non-Indexed Citations, OVID EMBASE, EBSCO Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Wiley Cochrane Library, and the Centre for Reviews and Dissemination database for studies published between January 1, 2000, and January 15, 2012. A January 1, 2000, start date was used because the concept of non-disease-specific/general chronic disease self-management was first published only in 1999. Reference lists were examined for any additional relevant studies not identified through the search. REVIEW METHODS: Randomized controlled trials (RCTs) comparing self-management support interventions for general chronic disease against usual care were included for analysis. Results of RCTs were pooled using a random-effects model with standardized mean difference as the summary statistic. RESULTS: Ten primary RCTs met the inclusion criteria (n = 6,074). Nine of these evaluated the Stanford CDSMP across various populations; results, therefore, focus on the CDSMP. HEALTH STATUS OUTCOMES: There was a small, statistically significant improvement in favour of CDSMP across most health status measures, including pain, disability, fatigue, depression, health distress, and self-rated health (GRADE quality low). There was no significant difference between modalities for dyspnea (GRADE quality very low). There was significant improvement in health-related quality of life according to the EuroQol 5-D in favour of CDSMP, but inconsistent findings across other quality-of-life measures.HEALTHY BEHAVIOUR OUTCOMES: There was a small, statistically significant improvement in favour of CDSMP across all healthy behaviours, including aerobic exercise, cognitive symptom management, and communication with health care professionals (GRADE quality low).Self-efficacy: There was a small, statistically significant improvement in self-efficacy in favour of CDSMP (GRADE quality low).HEALTH CARE UTILIZATION OUTCOMES: There were no statistically significant differences between modalities with respect to visits with general practitioners, visits to the emergency department, days in hospital, or hospitalizations (GRADE quality very low).All results were measured over the short term (median 6 months of follow-up). LIMITATIONS: Trials generally did not appropriately report data according to intention-to-treat principles. Results therefore reflect "available case analyses," including only those participants whose outcome status was recorded. For this reason, there is high uncertainty around point estimates. CONCLUSIONS: The Stanford CDSMP led to statistically significant, albeit clinically minimal, short-term improvements across a number of health status measures (including some measures of health-related quality of life), healthy behaviours, and self-efficacy compared to usual care. However, there was no evidence to suggest that the CDSMP improved health care utilization. More research is needed to explore longer-term outcomes, the impact of self-management on clinical outcomes, and to better identify responders and non-responders. PLAIN LANGUAGE SUMMARY: Self-management support interventions are becoming more common as a structured way of helping patients learn to better manage their chronic disease. To assess the effects of these support interventions, we looked at the results of 10 studies involving a total of 6,074 people with various chronic diseases, such as arthritis and chronic pain, chronic respiratory diseases, depression, diabetes, heart disease, and stroke. Most trials focused on a program called the Stanford Chronic Disease Self-Management Program (CDSMP). When compared to usual care, the CDSMP led to modest, short-term improvements in pain, disability, fatigue, depression, health distress, self-rated health, and health-related quality of life, but it is not possible to say whether these changes were clinically important. The CDSMP also increased how often people undertook aerobic exercise, how often they practiced stress/pain reduction techniques, and how often they communicated with their health care practitioners. The CDSMP did not reduce the number of primary care doctor visits, emergency department visits, the number of days in hospital, or the number of times people were hospitalized. In general, there was high uncertainty around the quality of the evidence, and more research is needed to better understand the effect of self-management support on long-term outcomes and on important clinical outcomes, as well as to better identify who could benefit most from self-management support interventions like the CDSMP.

Sunitinib malate for gastrointestinal stromal tumour in imatinib mesylate-resistant patients: recommendations and evidence.

QUESTION: Is sunitinib malate-marketed as Sutent (Pfizer Canada, Kirkland, QC)-superior to placebo or other interventions for primary outcomes of interest in adult patients with gastrointestinal stromal tumour (GIST) who have developed resistance or who exhibit intolerance to imatinib mesylate (IM)? BACKGROUND: In patients with resectable disease, surgery is the mainstay of treatment for GIST; in patients with unresectable or metastatic disease, the tyrosine kinase inhibitor IM is the therapy of choice. However, some patients have primary resistance or intolerance to IM, or they progress after optimal exposure (including an escalated dose). Here, we review the evidence for treating IM-resistant GIST with sunitinib malate. METHODS: Studies of sunitinib malate were identified through MEDLINE, EMBASE, the Cochrane Library databases, and Web sites of guideline organizations. Outcomes of interest included time to progression, progression-free survival, overall survival, and toxicity. RESULTS: One phase III randomized controlled trial, and one abstract and presentation describing that trial, served as the evidentiary base for this clinical practice guideline. Trial data confidently show that both time to progression and progression-free survival are highly statistically significant (p < 0.0001) in favour of sunitinib malate over placebo. Overall survival was improved with sunitinib malate (hazard ratio: 0.49; 95% confidence interval: 0.29 to 0.83; p = 0.007; absolute difference in weeks not reported). The most frequent of all adverse effects (experienced in greater proportion by patients on sunitinib malate) were grades 1 and 2 leucopenia (52% vs. 5% with placebo), neutropenia (43% vs. 4%), and thrombocytopenia (36% vs. 4%). Grade 3 hematologic adverse events were also reported more frequently in the sunitinib malate group, including leucopenia (4% vs. 0%), neutropenia (8% vs. 4%), lymphopenia (9% vs. 2%), and thrombocytopenia (4% vs. 0%). Toxicity comparisons did not include p values. The incidence of grades 1-3 fatigue was greater for the sunitinib malate group (34% vs. 22% with placebo). Other grade 3 nonhematologic treatment-related adverse events that occurred more frequently on sunitinib malate included hand-foot syndrome (4% vs. 0%), diarrhea (3% vs. 0%), and hypertension (3% vs. 0%). No grade 4 adverse events were observed. CONCLUSIONS: In the target population, sunitinib malate is the recommended option for second-line therapy of metastatic GIST.

The role of oxytocin, protein kinase A, and ERK-related MAP-kinase in the control of porcine ovarian follicle functions.

The aim of our in vitro experiments was to study the role of oxytocin (OT), cAMP/protein kinase A (PKA), and mitogen-activated protein kinase (ERKs MAP-kinase) in the control of ovarian cell functions as well as the role of PKA and MAPK in mediating OT effects on these processes. The whole porcine ovarian follicles were cultured in the presence or absence of OT (1, 10, 100 ng/ml), PKA inhibitor Rp-cAMPS (10 nM), MAP-kinase inhibitor PD98059 (1 microg/ml), or their combination. The release of prostaglandins F (PGF) and E (PGE) were determined by RIA, PKA (alpha-cat subunit), the proliferation-associated peptide PCNA and ERK-1, -2 expression in cell lyzates were analysed by Western-blotting. OT stimulated the release of PGF and PGE, and accumulation of PKA, ERK-1/-2, and PCNA in cell lysate. PD98059 decreased the basal PGF and PGE output, as well as reduced both ERK-1 and ERK-2 accumulation in cell lysates. Rp-cAMPS decreased PKA accumulation in cell lysates. Rp-cAMPS prevented the OT-induced stimulation of PKA, ERK-1, ERK-2, PGF, and PGE, PD98059 did so for PKA, PGF, and PGE. However, PD98059 reduced either basal or OT-induced p-ERK level. OT-stimulated PCNA accumulation was only slightly modified by these blockers. These observations suggest that OT, PKA, and ERKs MAPK can be involved in the control of PGs release and proliferation of ovarian cells. The influence of OT on both PKA and MAPK, and the ability of PKA and MAPK blockers to prevent completely or partially OT effects suggest, that effects of OT on PGF and PGE can be mediated by both PKA and MAPK. The role of MAPK and PKA in mediating the proliferative effects of OT seems to be minor assuming the involvement of other intracellular messengers.

Bacterial infection modulated by glucan: a search for the host defense potentiation mechanisms.

Interactions between bacteria and the host were studied from day 0 up to day 10 post-challenge in mice pretreated with soluble glucan (20 mg/kg i.p.) and challenged supralaryngeally with a virulent strain of Klebsiella pneumoniae. In the initial phase of infection, clearance of bacteria in the airways of glucan-treated mice was improved to an extent comparable with the vaccinated group but, in contrast to the immunized animals, subsequent regrowth of the bacterial inoculum was not prevented. The efficacy of defense, based during the entire course of infection mainly upon phagocytosis by neutrophils, markedly increased at intervals corresponding to the onset of humoral immune response. No evidence was obtained to indicate an enhanced involvement of alveolar macrophages in the phagocytosis of bacteria in glucan-stimulated mice. The results further support the notion that improvement of specific immune responsiveness rather than activation of nonspecific effector functions might be the most important expression of the host-defense-potentiating capacity of glucan and related stimulants of microbial origin.

Informative value of a mouse model of Klebsiella pneumoniae infection used as a host-resistance assay.

To obtain a host-resistance assay (HRA) for quantitative evaluation of immunostimulatory effects of various substances, an experimental model of K. pneumoniae inhalatory infection was elaborated. The highly virulent bacterial strain (inhalation LD50 = 400 CFU), applied via the natural route into the respiratory tract elicits an acute infectious process possessing characteristic dynamics. Although the intensity of clearance in the bronchoalveolar lavage after challenge or the mean survival time can be used in individual cases for quantitative resistance determination, the inhalation LD50 values yielded the most standard results. Systemic immunization with the corpuscular K. pneumoniae vaccine provided a high protection expressed by increasing the inhalation LD50 by two orders of magnitude. The antibodies formed, detectable by the ELISA test, are specific for capsular polysaccharide. The type-specific immunity was also found in the protection test. The nonspecific stimulatory effect of the peptidopolysaccharide complex isolated from Listeria monocytogenes (EiF) was manifested at the level of one LD50 only while with higher infectious doses it was absent. However, the adjuvant activity of EiF was significant. The HRA can distinguish and quantitatively determine both nonspecific and specific stimulatory effects of immunomodulatory substances.

Group B streptococci in the milk of lactating mothers.

A total of 1132 samples of maternal milk expressed from the disinfected breast on the first days after parturition were subjected to microbiological examination. Contamination by group B streptococci (Streptococcus agalactiae) was demonstrated in 40 samples (3.53%). Strains carrying the antigens Ia, Ia/c, Ib/c, II, III and R were represented among the isolates. Type Ia/c was the commonest; antigens II and III were always combined with the R antigen. The milk was either very strongly contaminated with almost pure culture demonstrable by direct cultivation of the milk sediment, or only isolated colonies were obtained in primary culture, often not until after enrichment. If the first samples gave dense growths, second-sample cultures were also positive. The strains isolated from samples of the individual mothers milk differed by their antigenic type structure; this gave evidence that the infection was not of nosocomial origin. Immunoglobulin levels in the whey of positive samples were not different from the whey of mothers not shedding group B streptococci. The health of both mothers and infants did not deviate from the general average for normal mothers and infants. No signs common to all the mothers shedding group B streptococci in their milk and no marked effect on the infants' health up to the age of 1-2 years were established.

Antibacterial immunity of lower airways: local or localized?

Clearance of bacteria in the bronchoalveolar lavage, the level and functional activity of IgA and changes in the cellular composition of BAL were examined in mice after supralaryngeal immunization and subsequent challenge with Klebsiella pneumoniae. More than 60% of the bacterial inoculum was removed by nonspecific mechanisms within 90 min after inoculation; within the time interval 1.5-3.5 h, clearance was significantly accelerated in locally immunized mice. The enhancement of clearance effectiveness is specific and increases proportionally with the length of immunization (1 less than 2 less than 4 weeks); it is of short duration and towards the end of the 3rd week after immunization, in 73% of immunized animals, the clearance values did not differ from values found in controls. The local immunization did not influence the total level of IgA in BAL, the formation of specific IgA antibody was minimal, in vivo binding of IgA to klebsiella could not be demonstrated. In immunized mice, a significant increase in the numbers of PMN and lymphocytes, as well as an increased activity of phagocytic cell (PMN, MP) was found in BAL. The time interval of 1.5-3.5 h after challenge bounds the space for mechanisms, activated by local immunization in lower airways. The actual participation of individual factors in the accelerated elimination of bacteria from the lumen of airways, remains unclear so far.

[Frequency of excretion of group B streptococci (Streptococcus agalactiae) in the milk during subclinical forms of mammary gland diseases in cows]. / Frekvence vylucování streptokoku skupiny B (Streptococcus agalactiae) mlékem v prubehu subklinické formy onemocnení mlécné zlázy skotu.

The milk excretion of group B streptococci (Streptococcus agalactiae) from the udder quarters was examined in thirty cows of a heavily infected herd. Six samplings were performed in ten- to fourteen-day intervals. With respect to excretion rate, the set of cows could be divided into three groups: 1. group of cows excreting S. agalactiae from all udder quarters permanently and absolutely regularly; 2. cows excreting S. agalactiae regularly only from some quarters, certain quarter being negative at all samplings; 3. cows excreting streptococci from all quarters absolutely irregularly, without any conclusive order or dependence. The cytological picture of all samples exhibited no signs of inflammation. The discussion deals with some factors that may influence the excretion of streptococci with milk.

Mechanisms of antibacterial immunity of mucous membranes.

A survey based on both literary data and the authors own results, concerning the mechanisms of sIgA-mediated antibacterial immunity, is presented. Secretory IgA is characterized as a specific component of the immune system of mucous membranes, which can recognize harmful bacterial and distinguish them from indigenous microflora physiologically colonizing the mucous membranes, to fix them to the mucous membrane surface and to direct further factors, such as mucin, lysozyme, etc. (which form the effector component of the mucous membrane immunity system) for their final inactivation and neutralization.

Modification of Oudin's method of single immunodiffusion in agar gel for detection of IgA in bronchoalveolar lavage of white mice.

Oudin's principle of single immunodiffusion in agar gel was modified for quantitative determination of IgA in bronchoalveolar lavage (BAL) of normal 20-25 g mice. The reaction took place at 25 degrees C in 0.3% agarose with 16.7% pig serum against mouse IgA, and was evaluated on the basis of a relationship between the progress of the precipitin zone and the square root of time. The linear dependence of the derived constant k on the logarithmic concentration of antibody in the sample permitted to express the results as titre, corresponding to a dilution where k = 0. Examination of seven samples of pooled blood serum of normal mice showed that (1) the IgA level was practically constant, (2) serum IgA possessed under given conditions similar properties as IgA from the bronchoalveolar secretion; it is therefore possible to employ pooled sera as a reliable control of the immunodiffusion system in case of lack of reference standards with defined IgA content. Examination of 82 individual BAL samples of normal mice revealed that the mean IgA concentration in 2.5 mL samples was almost 1000 times lower than in blood serum.

The effect of length of incubation on adherence of group B streptococci to epithelial cells.

Adhesion of group B streptococci to human epithelial vaginal and buccal cells proceeded in three phases which differed qualitatively. Maximum adhesion took place within 10 min of interaction, during the second phase (10-15 min), the percentage of adherent cells decreased significantly (P less than 0.05) whereas during the last phase the decrease became stabilized at a value which differed significantly from the maximum (P less than 0.01). The cause of variability in the number of positively reacting cells in relation to the exposure time is discussed.

Experimental model of Klebsiella infection in mice for studies on mechanisms of local immunity of the respiratory tract.

An experimental model in white mice, infected with a mildly virulent strain of Klebsiella pneumoniae, was elaborated for studies on local immunity of the respiratory tract. Instillation of klebsiella into the supralaryngeal space of anaesthetised animals proved to be more suitable than the commonly used method of intranasal infection. The strain administered by the supralaryngeal route, persisted in the lungs of most mice at approximately equal level 1 d after infection, in some animals it could be demonstrated even after 2-3 d. Using this model (based on various rates of lung clearance), one can demonstrate faster elimination of klebsiella after a local (supralaryngeal) than systemic (intraperitoneal) immunization with a heat-inactivated vaccine, prepared from a homologous strain of K. pneumoniae.

Adherence of group B streptococci isolated from man and cattle to human and bovine epithelial cells.

Proof of adherence of group B streptococci (GBS) to human and bovine vaginal epithelial cells and to bovine cells of milk cisternae of the mammary gland was employed as a criterion determining the possibility of colonization of these organs with GBS, or as another method of testing the transfer of GBS between man and cattle. GBS of both human and animal origin adhered to human epithelial cells in a similar way. On the other hand, a significantly stronger adherence of bovine GBS to vaginal epithelial cells and cells of milk cisternae of cattle was found than of human GBS. Thus the direction of colonization - animal is more probable than the opposite way. Neither in animal nor in human strains a correlation between the equipment of strains with type antigens and intensity of adherence could be found.

The effect of pH on the adherence of group B streptococci to epithelial cells.

Hydrogen ion concentration in a medium in which the adherence of group B streptococci to vaginal and buccal cells takes place, significantly influences the reaction intensity. At physiological pH, group B streptococci adhere significantly more weakly than at pH 5.5 to buccal epithelia, and at pH 7.2 to vaginal epithelia. Thus at nonphysiological pH values the percentage of adherent cells is markedly higher.

Isolation and chemical characterization of compounds isolated from Aspergillus flavus conidia.

Three types of heterogeneous preparations and four types of preparations of polysaccharide nature were obtained in studies aimed at the isolation of active compounds from Aspergillus flavus conidia bearing their biological stimulatory activity. Extraction with trichloroacetic acid at 0 degrees C yielded a preparation in which the protein component predominated over the polysaccharide moiety at a ratio of 3 : 1. In the preparation isolated from the phenolic phase of the phenol-water mixture at 68 degrees C the protein polysaccharide ratio was 1 : 1. In the material extracted in the aqueous phase and in that obtained by extraction with acetic acid at 100 degrees C the polysaccharide portion highly predominated (8 : 1 and 7 : 1 respectively).

A lipopolysaccharide from Aspergillus flavus conidia.

A lipopolysaccharide was isolated by extraction of Aspergillus flavus conidia with 45% phenol at 68-70 degrees C. Quantitative analysis revealed 7% nucleic acids, 5.5% proteins, 46% polysaccharides and 49% liquids, of which 12% were covalently bound. Glucose, mannose, galactose and fucose were detected as monosaccharide components of the polysaccharide moiety by gas chromatography; palmitic acid, stearic acid, oleic acid, linoleic acid and myristic acid were mainly present in the lipidic fraction. This material differs from the bacterial lipopolysaccharides, both in composition of the polysaccharide moiety and representation of fatty acids in the lipidic fraction.