Associations between disability-management self-efficacy, participation and life satisfaction in people with long-standing spinal cord injury.

OBJECTIVES: To study disability-management self-efficacy (DMSE) and its correlates in a large sample of Dutch people with long-standing spinal cord injury (SCI). DMSE is the confidence that people with SCI may have in their ability to manage the consequences of their condition with respect to the various domains in their life. Research questions were: (1) What is the level of DMSE in Dutch people with long-standing SCI?; (2) Is DMSE associated with demographic and lesion characteristics?; and (3) Is DMSE associated with participation and life satisfaction if these associations are adjusted for demographic and lesion characteristics and mood? METHODS: Eligible people were identified from all eight rehabilitation centers with a specialty in SCI rehabilitation in the Netherlands (N=261). Data were collected using a self-report questionnaire. DMSE was measured using the University of Washington Self-Efficacy Scale-Short Form (UW-SES-6). Correlation and linear regression analyses were used. RESULTS: Levels of UW-SES-6 scores were largely independent of demographic and lesion characteristics. UW-SES-6 scores were bivariately moderately to strongly associated with mood (0.47), participation (0.39-0.51) and life satisfaction (0.46). In the regression analyses, UW-SES-6 scores still explained a significant amount of variance of participation (standardized ß 0.31-0.33) and life satisfaction (standardized ß 0.21) when controlling for demographic and lesion characteristics and mood, and explained an additional 3.2-8.1% of the variance of participation and life satisfaction. CONCLUSION: DMSE is a psychological resource associated with higher levels of participation and life satisfaction after SCI. The UW-SES-6 is a brief and easy to use measure of this psychological resource.

Summary of recommendations on malaria issues in special hosts.

BACKGROUND: On behalf of the Public Health Agency of Canada, the Committee to Advise on Tropical Medicine and Travel (CATMAT) developed the Canadian Recommendations for the Prevention and Treatment of Malaria Among International Travellers for Canadian health care providers who are preparing patients for travel to malaria-endemic areas and treating travellers who have returned ill. OBJECTIVE: To provide guidelines on malaria issues related to special hosts. METHODS: CATMAT reviewed all major sources of information on malaria prevention, as well as recent research and national and international epidemiological data, to tailor guidelines to the Canadian context. The evidence-based medicine recommendations were developed with associated rating scales for the strength and quality of the evidence. RECOMMENDATIONS: All people visiting malaria endemic regions should use effective personal protective measures (PPM; topical repellants, bed nets, behavioural choices) and the prescribed chemoprophylaxis. Chemoprophylaxis for pregnant and breastfeeding women and for children requires careful consideration in the context of the pregnancy trimester, the age or size of the infant/child as well as their glucose-6-phosphate dehydrogenase (G6PD) status. Recommendations for long-term travellers, expatriates and people visiting friends and relatives (VFRs) do not differ markedly from those for short-term travellers. Some underlying medical conditions may make individuals more vulnerable to malaria. In addition, some conditions or their treatment may preclude the use of one or more antimalarial medications.

Summary of recommendations for the prevention of malaria by the Committee to Advise on Tropical Medicine and Travel (CATMAT).

BACKGROUND: On behalf of the Public Health Agency of Canada, the Committee to Advise on Tropical Medicine and Travel (CATMAT) developed the Canadian Recommendations for the Prevention and Treatment of Malaria Among International Travellers for Canadian health care providers who are preparing patients for travel to malaria-endemic areas and treating travellers who have returned ill. OBJECTIVE: To provide guidelines on risk assessment and prevention of malaria. METHODS: CATMAT reviewed all major sources of information on malaria prevention, as well as recent research and national and international epidemiological data, to tailor guidelines to the Canadian context. The evidence-based medicine recommendations were developed with associated rating scales for the strength and quality of the evidence. RECOMMENDATIONS: Used together and correctly, personal protective measures (PPM) and chemoprophylaxis very effectively protect against malaria infection. PPM include protecting accommodation areas from mosquitoes, wearing appropriate clothing, using bed nets pre-treated with insecticide and applying topical insect repellant (containing 20%-30% DEET or 20% icaridin) to exposed skin. Selecting the most appropriate chemoprophylaxis involves assessment of the traveller's itinerary to establish his/her malaria risk profile as well as potential drug resistance issues. Antimalarials available on prescription in Canada include chloroquine (or hydroxychloroquine), atovaquone-proguanil, doxycycline, mefloquine and primaquine.

Summary of recommendations for the diagnosis and treatment of malaria by the Committee to Advise on Tropical Medicine and Travel (CATMAT).

BACKGROUND: On behalf of the Public Health Agency of Canada, the Committee to Advise on Tropical Medicine and Travel (CATMAT) developed the Canadian Recommendations for the Prevention and Treatment of Malaria Among International Travellers for Canadian health care providers who are preparing patients for travel to malaria-endemic areas and treating travellers who have returned ill. These recommendations aim to achieve appropriate diagnosis and management of malaria, a disease that is still uncommon in Canada. OBJECTIVE: To provide recommendations on the appropriate diagnosis and treatment of malaria. METHODS: CATMAT reviewed all major sources of information on malaria diagnosis and treatment, as well as recent research and national and international epidemiological data, to tailor guidelines to the Canadian context. The evidence-based medicine recommendations were developed with associated rating scales for the strength and quality of the evidence. RECOMMENDATIONS: Malarial management depends on rapid identification of the disease, as well as identification of the malaria species and level of parasitemia. Microscopic identification of blood samples is both rapid and accurate but can be done only by trained laboratory technicians. Rapid diagnostic tests are widely available, are simple to use and do not require specialized laboratory equipment or training; however, they do not provide the level of parasitemia and do require verification. Polymerase chain reaction (PCR), although still limited in availability, is emerging as the gold standard for high sensitivity and specificity in identifying the species.

Volumetric response classification in metastatic solid tumors on MSCT: initial results in a whole-body setting.

PURPOSE: To examine technical parameters of measurement accuracy and differences in tumor response classification using RECIST 1.1 and volumetric assessment in three common metastasis types (lung nodules, liver lesions, lymph node metastasis) simultaneously. MATERIALS AND METHODS: 56 consecutive patients (32 female) aged 41-82 years with a wide range of metastatic solid tumors were examined with MSCT for baseline and follow up. Images were evaluated by three experienced radiologists using manual measurements and semi-automatic lesion segmentation. Institutional ethics review was obtained and all patients gave written informed consent. Data analysis comprised interobserver variability operationalized as coefficient of variation and categorical response classification according to RECIST 1.1 for both manual and volumetric measures. Continuous data were assessed for statistical significance with Wilcoxon signed-rank test and categorical data with Fleiss kappa. RESULTS: Interobserver variability was 6.3% (IQR 4.6%) for manual and 4.1% (IQR 4.4%) for volumetrically obtained sum of relevant diameters (p<0.05, corrected). 4-8 patients' response to therapy was classified differently across observers by using volumetry compared to standard manual measurements. Fleiss kappa revealed no significant difference in categorical agreement of response classification between manual (0.7558) and volumetric (0.7623) measurements. CONCLUSION: Under standard RECIST thresholds there was no advantage of volumetric compared to manual response evaluation. However volumetric assessment yielded significantly lower interobserver variability. This may allow narrower thresholds for volumetric response classification in the future.

Kinase inhibitor recognition by use of a multivariable QSAR model.

We have applied a retrosynthetic program to determine the scaffold and R-group chemical space seen within a library of known kinase inhibitors and non-kinase drug-like molecules. Comparison of the differences quickly revealed that kinase inhibitors are distinct in several chemical fragment and physical properties. We then applied these descriptors in a multivariable quantitative structure-activity relationship (QSAR) model with the goal to distinguish kinase inhibitors from non-kinase drug-like molecules. This model is heuristic in that it was trained over a dataset of 258 known kinase inhibitors and 230 non-kinase drug molecules. The final model recognized 98% of the training set as being kinase inhibitors and had a false positive rate of 15%. This trait for false positives was accepted out of a desire to maintain diversity and not miss possible good kinase inhibitors for screening. The model was validated by reserving a portion of the datasets as test sets, which were not included in the QSAR model building stage. This was done repetitively for different percentiles of the total dataset population. It was seen that model recognition and false positive were only slightly damaged well down to a 70% reserve (30% dataset used for QSAR model training while 70% used for reserve test set). Beyond 70%, the QSAR models were inconsistent, signifying that the training sets were inadequately diverse to represent the greater reserve test sets. We applied this model to evaluate the commercial kinase libraries available from Asinex, BioFocus, ChemDiv and LifeChemicals to facilitate purchase decisions for compounds for HTS for lead compounds. We observed that there are significant differences in populations of recognizable kinase inhibitors across the vendors analyzed, with BioFocus showing the greatest population of kinase like molecules.

The effect of an ergonomic computer device on muscle activity of the upper trapezius muscle during typing.

OBJECTIVE: Investigate whether an ergonomic computer device, characterised by an inclined working area and keyboard localisation close to the screen (the Up-Line), decreases the muscle activity of the upper trapezius muscle. METHODS: In a crossover design 19 healthy subjects and 19 patients with Whiplash Associated Disorder (WAD) typed during 10 min at the Up-Line and at a standard workstation with 15 min of rest in between. During typing surface EMG was measured of the trapezius muscle. The subjects were asked to rate sitting comfort and complaints. RESULTS: Although most subjects subjectively preferred the Up-Line, on average no significant differences were found in muscle activity between the two workstations for both patients and healthy subjects. Individually in 5 healthy subjects (25%) and in 6 patients (31%) muscle activity was lower when working at the Up-Line. CONCLUSION: Although some subjects subjectively prefer the Up-Line in sitting comfort, on average the Up-Line did not decrease the muscle activity, both in healthy subjects as in patients with WAD.

Women with complete spinal cord injury: a phenomenological study of sexual experiences.

This study examines psychosocial, emotional, and relationship aspects of sexuality in the lives of 15 women who sustained complete spinal cord injury (SCI) between the levels of T6 and L2. Phenomenological interviews were organized to chronologically sequence events with the intention of describing the trajectory of sexuality in women with complete SCI. A set of themes emerged from postinjury data that were labeled cognitive-genital dissociation, sexual disenfranchisement, and sexual rediscovery. Broadening the scope of the research beyond the physiological offers insight as to the interplay between the mind and sexual response and guidance for educational and therapeutic interventions.

Clinical and biological relevance of hepatocyte apoptosis in alcoholic hepatitis.

BACKGROUND/AIMS: Although human and experimental studies have shown that apoptosis plays a role in hepatocyte death in alcoholic liver disease, its clinical and biological significance has not been investigated in alcoholic hepatitis (AH). The aim of this study was to quantify hepatocyte apoptosis in AH and to attempt to relate it to the clinical and biological severity of the disease. METHODS: The hepatocyte apoptotic index was determined using a double in situ transferase-mediated dUTP nick end (TUNEL) and CD15 (neutrophils) labelling on 35 liver biopsies from patients with AH lesions of different severities. The specificity of TUNEL labelling for apoptosis was monitored both by morphology and fractin (a caspase actin cleavage site) immunostaining. RESULTS: The hepatocyte apoptotic index ranged from 0.3 to 28% and was related to the severity of alcoholic hepatitis as measured by the Maddrey score (P < 0.05; Mann-Whitney test) while ballooning (which reflects hepatocytes potentially undergoing necrosis) and neutrophil indexes were not. CONCLUSIONS: This suggests that hepatocyte apoptosis could be a therapeutic target to treat or to prevent alcoholic hepatitis in cirrhotic patients. Co-localization of apoptotic hepatocytes with neutrophils and the strong quantitative correlation would suggest an apoptosis dependent transmigration of neutrophils.

Enhanced surveillance of acute hepatitis B and C in four health regions in Canada, 1998 to 1999.

OBJECTIVE: To assess the incidence and risk factors for acute hepatitis B and acute hepatitis C in a defined Canadian population. PATIENTS AND METHODS: An enhanced surveillance system was established in October 1998 to identify cases of acute hepatitis B and C infections in four regions in Canada, with a total population of approximately 3.2 million people. Information on demographic and clinical characteristics, laboratory results and potential risk factors was collected using predefined questionnaires. RESULTS: A total of 79 cases of acute hepatitis B and 102 cases of acute hepatitis C were identified from October 1998 to December 1999, resulting in an incidence rate of 2.3 and 2.9/100,000 person-years, respectively. Males had higher incidence rates than females. The incidence of acute hepatitis B peaked at age 30 to 39 years for both males and females, whereas acute hepatitis C peaked at 30 to 39 years for males and 15 to 29 years for females. At least 34% of acute hepatitis B and 63% of acute hepatitis C were associated with injection drug use. Persons who were 15 to 39 years of age were more likely to report injection drug use as a risk factor. Heterosexual contact was reported to be a risk factor for 36.6% of acute hepatitis B cases and 3.5% of acute hepatitis C cases. CONCLUSIONS: The surveillance provides national incidence estimates of clinically recognized acute hepatitis B and C. Both hepatitis B and C are important public health threats to Canadians. Prevention efforts for both diseases should focus on injection drug use, especially for people aged 15 to 39 years. Risky sexual behaviour is also a major concern in prevention of hepatitis B in Canada.

Trends of hepatitis B and hepatitis C mortality in Canada, 1979-1997.

Mortality data from Statistics Canada were analyzed to measure the temporal trends and burden of illness attributed to viral hepatitis in Canada. Analysis of age-standardized mortality rates from 1979 to 1997 showed an increasing trend in mortality for both hepatitis B and non-A, non-B hepatitis (NANBH), most of which are attributed to hepatitis C infections. Hepatitis B and NANBH age-standardized mortality rates increased respectively, from 0.03 and 0.12 deaths per 100,000 population in 1979 to 0.26 and 0.41 deaths per 100,000 in 1997. Male mortality rates were consistently higher than female for both diseases. Among deaths from chronic liver disease, over 1,000 deaths were estimated to have been caused by hepatitis B and hepatitis C annually. Although the hepatitis B or NANBH recorded deaths largely underestimate the true burden of HBV and HCV in Canada, the temporal trends are useful as they reflect changes in the impact of both diseases.

The neutralization of type I IFN biologic actions by anti-IFNAR-2 monoclonal antibodies is not entirely due to inhibition of Jak-Stat tyrosine phosphorylation.

A panel of monoclonal antibodies (mAb) derived against human interferon-alpha/beta receptor-2 (IFNAR-2) was evaluated for their ability to antagonize the biologic effects of type 1 interferons (IFN-alpha1, IFN-alpha2a, and IFN-beta). Anti-IFNAR-2 mAb 117.7, 35.9, 53.2, and 51.44 neutralized type I IFN-mediated antiviral, antiproliferative, and major histocompatibility complex (MHC) class I upregulation functions. However, only mAb 51.44 neutralized IFN-alpha2a and IFN-beta-mediated natural killer (NK) cell cytotoxicity. In BIAcore and cell binding studies, only mAb 51.44 and 234.28 inhibited IFN-alpha2a and IFN-beta binding to its receptor. The receptor blockade by mAb 51.44 and 234.28 resulted in the inhibition of IFN-alpha2a and IFN-beta-induced tyrosine phosphorylation of Jak1, Tyk2, Stat1/2/3, and IFNAR-1/2 and inhibition of IFN-stimulated gene factor 3 (ISGF3) formation. mAb 117.7, 35.9, and 53.2, although antagonists of IFN's biologic activities, did not block the binding of IFN-alpha/beta to its receptor. The 117.7 mAb, representative of this class of receptor nonblocking mAb, induced hyper-tyrosine phosphorylation of IFNAR-2 in the presence of IFN-alpha/beta but did not inhibit IFN-alpha/beta-induced Jak-Stat tyrosine phosphorylation and ISGF3 complex formation. These results show that the neutralization of type I IFN biologic actions by anti-IFNAR-2 mAb cannot be entirely explained by inhibition of Jak-Stat tyrosine phosphorylation.

Prediction of hepatitis C burden in Canada.

To assess the risk of hepatitis C in Canada and to predict the burden that this disease may pose to the Canadian society in the near future, expected numbers of persons at different stages of the disease currently and in the next decade were estimated by simulation using a published hepatitis C natural history model with no treatment effect being applied. Based on the estimate of 240,000 persons who are currently infected with the hepatitis C virus in Canada, the simulation analysis demonstrated that the number of hepatitis C cirrhosis cases would likely increase by 92% from 1998 to the year 2008. It was also projected that the number of liver failures and hepatocellular carcinomas related to hepatitis C would increase by 126% and 102%, respectively, in the next decade. The number of liver-related deaths associated with hepatitis C is expected to increase by 126% in 10 years. The medical and social care systems in Canada may not be ready to support these large increases. These results highlight the importance of both the control of disease progression of hepatitis C virus-infected persons and the primary prevention of hepatitis C infections in Canada.

Psychiatric advance directives: an alternative to coercive treatment?

Psychiatric Advance Directives (PADs) are a legal means by which persons with mental illness, while competent to make healthcare decisions, may specify their preferences for treatment and may designate a surrogate decision-maker to act on their behalf in the event of an incapacitating mental health crisis. PADs have been advocated as a strategy to increase autonomy and decrease coercion in the treatment of severe psychiatric illness, but there has been little research on the actual use and effects of PADs. This article develops a conceptual model for how PADs might work, both directly and indirectly. According to the model proposed here, PADs might provide an effective tool for managing psychiatric crises but might also help to improve participation in regular outpatient treatment. This article further examines arguments for and against PADs and looks optimistically toward their use as an alternative to more coercive approaches to mental health treatment such as outpatient commitment (OPC).

Investigation of porcine parvovirus among persons with hemophilia receiving Hyate:C porcine factor VIII concentrate.

BACKGROUND: Porcine clotting factor has been used for more than 15 years to treat severe bleeding episodes in persons with hemophilia who have antibodies to human clotting factor. In 1996, QC procedures revealed for the first time the presence of porcine parvovirus (PPV) in the product. This report describes an investigation to determine the extent of product contamination and to evaluate past recipients of porcine clotting factor (Hyate:C, Speywood Biopharm) for evidence of PPV infection. STUDY DESIGN AND METHODS: Stored specimens from 22 lots of previously released Hyate:C were tested for the presence of PPV DNA by PCR and nested PCR assays. Serum specimens from 98 recipients of Hyate:C and 24 controls who did not receive Hyate:C were tested for PPV antibodies by an immunofluorescence assay. RESULTS: PPV DNA was detected in product from 21 of the 22 lots of Hyate:C, primarily by nested PCR testing. In contrast, none of the serum specimens from the 98 Hyate:C recipients tested positive for PPV IgG antibodies. CONCLUSION: The risk of human disease from percutaneous exposure to low levels of PPV seems to be low. Nevertheless, the theoretical risk of human infection with PPV has led to manufacturing changes, including PCR screening of all porcine plasma, which are designed to eliminate this risk.

Incidence and onset of critical illness polyneuropathy in patients with septic shock.

BACKGROUND: To estimate the incidence and onset of critical illness polyneuropathy (CIP) in patients in septic shock. METHODS: Prospective, observational study, no interventions, in a general 9-bed ICU of a large teaching hospital. Twenty-five patients consecutively admitted to the ICU for treatment of septic shock were studied. Within 72 h of admission to the ICU a complete neurological examination and electromyografic studies were done. Studies were repeated weekly until discharge of ICU or death or CIP confirmed. RESULTS: Nineteen patients developed CIP (76%), with a majority (80%) within 72 h after onset of septic shock. All twenty-two patients with multi organ dysfunction syndrome (MODS) had CIP. The three patients without MODS did not have CIP (P<0.01). CONCLUSIONS: In a group of patients suffering from septic shock the incidence of CIP is high (76%). The onset is early, within 72 h after onset of septic shock. CIP is an early feature of MODS, developing after septic shock.

Epstein-Barr virus and gastric carcinoma in Western patients: comparison of pathological parameters and p53 expression in EBV-positive and negative tumours.

AIMS: The presence of Epstein-Barr virus (EBV) was studied in 56 gastric carcinomas from Western patients by in-situ hybridization for EBV-encoded RNAs (EBER). EBV-positive and negative carcinomas were compared for various pathological parameters including p53 overexpression. METHODS AND RESULTS: EBERs transcripts were detected in seven cases overall: four cases of 52 conventional carcinomas (7. 7%) and three cases of four gastric carcinomas with lymphoid stroma (75%). EBER positivity was diffuse in five cases and restricted to a localized area of the tumour in two cases of conventional carcinoma. A monoclonal EBV genomic pattern was demonstrated in the case tested by Southern blot analysis. By immunohistochemical analysis, neither EBV latent or lytic cycle proteins nor C3d/EBV receptor were expressed by neoplastic cells. EBER positivity was significantly correlated with prominent lymphoid reaction (P = 0.0002) which was associated with numerous PS100-positive dendritic cells and with HLA-DR expression by tumour cells (P = 0.03). p53 immunoreactivity in more than 30% of tumour cells was detected in 25 out 49 EBV-negative cases and was absent in EBV-positive cases except in one case with focal EBER-positivity. CONCLUSIONS: Focal staining for EBER is an unusual finding in the setting of gastric carcinoma and these results suggest that there might be two types of EBV-associated gastric carcinoma in which the viral infection will play a different role. The presence of a stromal lymphoid reaction which is strongly correlated with EBV positivity, is associated with antigen-presenting ability by HLA-DR-positive tumour cells or abundant dendritic cells. The function of p53 appears preserved in all EBV-associated carcinomas except in one case with focal EBER expression whereas the immunohistochemical pattern of p53 is suggestive of a mutational phenomenon in 51% of EBV-negative cases.