Phenotypic diversity within a Pseudomonas aeruginosa population infecting an adult with cystic fibrosis.

Chronic airway infections caused by Pseudomonas aeruginosa contribute to the progression of pulmonary disease in individuals with cystic fibrosis (CF). In the setting of CF, within-patient adaptation of a P. aeruginosa strain generates phenotypic diversity that can complicate microbiological analysis of patient samples. We investigated within- and between- sample diversity of 34 phenotypes among 235 P. aeruginosa isolates cultured from sputum samples collected from a single CF patient over the span of one year, and assessed colony morphology as a screening tool for predicting phenotypes, including antimicrobial susceptibilities. We identified 15 distinct colony morphotypes that varied significantly in abundance both within and between sputum samples. Substantial within sample phenotypic heterogeneity was also noted in other phenotypes, with morphotypes being unreliable predictors of antimicrobial susceptibility and other phenotypes. Emergence of isolates with reduced susceptibility to ß-lactams was observed during periods of clinical therapy with aztreonam. Our findings confirm that the P. aeruginosa population in chronic CF lung infections is highly dynamic, and that intra-sample phenotypic diversity is underestimated if only one or few colonies are analyzed per sample.

Heterozygous mutations in the PALB2 hereditary breast cancer predisposition gene impact on the three-dimensional nuclear organization of patient-derived cell lines.

PALB2/FANCN is a BRCA1- and BRCA2-interacting Fanconi Anemia (FA) protein crucial for key BRCA2 genome caretaker functions. Heterozygous germline mutations in PALB2 predispose to breast cancer and biallelic mutations cause FA. FA proteins play a critical role in the telomere maintenance pathway, with telomeric shortening observed in FA cells. Less is known about telomere maintenance in the heterozygous state. Here, we investigate the roles of PALB2 heterozygous mutations in genomic instability, an important carcinogenesis precursor. Patient-derived lymphoblastoid (LCL) and fibroblast (FCL) cell lines with monoallelic truncating PALB2 mutations were investigated using a combination of molecular imaging techniques including centromeric FISH, telomeric Q-FISH and spectral karyotyping (SKY). Mitomycin C and Cisplatin sensitivity was assayed via cellular metabolism of WST-1. The PALB2 c.229delT FCL showed increases in telomere counts associated with increased mean intensity compared with two wild-type FCLs generated from first-degree relatives (P =1.04E-10 and P =9.68E-15) and it showed evidence of chromosomal rearrangements. Significant differences in centromere distribution were observed in one of three PALB2 heterozygous FCLs analyzed when compared with PALB2 wild-type, BRCA1 and BRCA2 heterozygous FCLs. No significant consistently increased sensitivity to Mitomycin C or Cisplatin was observed in LCLs. Our results are suggestive of an altered centromere distribution profile and a telomere instability phenotype. Together, these may indicate critical nuclear organization defects associated with the predisposition to transformation and early stage development of PALB2-related cancers.

Effect of a preventive foot care program on lower extremity complications in diabetic patients with end-stage renal disease.

BACKGROUND: Lower extremity complications are a major cause of morbidity and mortality in patients with end-stage renal disease (ESRD) and diabetes mellitus. Patient education programs may decrease the risk of diabetic foot complications. METHODS: A preventive program was instituted, consisting of regular assessments by a foot care nurse with expertise in foot care and wound management and patient education about foot care practices and footwear selection. Medical records were reviewed and patients were examined. A comparison was made with data about patients from a previous study done from this institution prior to development of the foot care program. RESULTS: Diabetic subjects more frequently had weakness of the left tibialis anterior, left tibialis posterior, and left peroneal muscles than non-diabetic subjects. A smaller percentage of diabetic subjects had sensory neuropathy compared with the previous study from 5years earlier, but a greater percentage of diabetic subjects had absent pedal pulses in the current study. The frequency of inadequate or poor quality footwear was less in the current study compared with the previous study. CONCLUSIONS: The current data suggest that a foot care program consisting of nursing assessments and patient education may be associated with a decrease in frequency of neuropathy and improved footwear adequacy in diabetic patients with ESRD.

Impact of patient smoking behavior on empathic helping by family caregivers in lung cancer.

PURPOSE/OBJECTIVES: To test the impact of patient smoking behavior on family caregiver judgments of responsibility, emotions, empathic responses, and helping behavior. DESIGN: Structural equation modeling. SETTING: Five oncology outpatient settings in Canada. SAMPLE: 304 dyads consisting of patients with lung cancer and their primary caregivers. METHODS: Self-report questionnaires, abstracted medical record data, confirmatory factor analysis, and structural equation modeling. MAIN RESEARCH VARIABLES: Smoking history, judgments of responsibility for controlling the disease, anger, pride, empathic responses, and helping behaviors. FINDINGS: The impact of patient smoking behavior on caregiver help was mediated by caregiver judgments of responsibility, affective reactions of anger and pride, and empathic responses by caregivers. CONCLUSIONS: When patients continued to engage in smoking behavior, despite a diagnosis of lung cancer, caregivers tended to ascribe more responsibility and feel more anger and less pride in the patients' efforts to manage the disease, therefore placing caregivers at risk for less empathy and helping behavior. IMPLICATIONS FOR NURSING: Caregiver blame and anger must be assessed, particularly when the patient with lung cancer continues to smoke. If caregiver judgments of blame and anger are evident, then an attribution approach is indicated involving a dialogue between the caregiver and the patient, with the aim of enhancing the caregiver's understanding of how negative attributions and linked emotions impact his or her ability to engage in empathic helping behaviors.

Characterizing the HIV epidemic in the prairie provinces.

BACKGROUND: The numbers and demographics of HIV-positive patients in care between 2003 and 2007 in the prairie provinces were examined. METHODS: Estimates of HIV-positive patients presenting to care between 2003 and 2007 were obtained from four clinic registries in Manitoba, Saskatchewan and southern Alberta. Detailed data were collected from clinical records of new patients in 2007. RESULTS: By the end of December 2007, 2263 HIV-positive persons were in care in Manitoba, Saskatchewan and southern Alberta. Males and females accounted for 1674 (74.0%) and 589 of the cases, respectively. Overall, there was a 12% increase per year in new HIV cases to care between 2003 and 2007 (P=0.026), with the rate of increase for males being 60% higher than for females over this time period (P=0.002). In 2007, there were 222 new HIV cases to care (37.4% female). Heterosexual contact was the most common HIV risk, but diversity was seen across sites with frequent injection drug use and men who have sex with men risk in Saskatchewan and southern Alberta, respectively. The Aboriginal population remains heavily over-represented, with approximately 36.0% of new cases being Aboriginal. Late presentation was common across all care sites, with 35.1% of cases presenting with CD4 counts of less than 200 cells/mm(3). DISCUSSION: Heterosexual risk is the most common risk reported for HIV acquisition, but injection drug use risk remains significant in Saskatchewan. Aboriginals are over-represented at all sites, and in Saskatchewan accounted for the majority of new cases seen. In contrast to national trends, numbers of new and late diagnoses are increasing in the praire provinces, and this has significant treatment implications and potential public health consequences. Further efforts need to be made to facilitate earlier testing and linkage to care. BACKGROUND: The numbers and demographics of HIV-positive patients in care between 2003 and 2007 in the prairie provinces were examined. METHODS: Estimates of HIV-positive patients presenting to care between 2003 and 2007 were obtained from four clinic registries in Manitoba, Saskatchewan and southern Alberta. Detailed data were collected from clinical records of new patients in 2007. RESULTS: By the end of December 2007, 2263 HIV-positive persons were in care in Manitoba, Saskatchewan and southern Alberta. Males and females accounted for 1674 (74.0%) and 589 of the cases, respectively. Overall, there was a 12% increase per year in new HIV cases to care between 2003 and 2007 (P=0.026), with the rate of increase for males being 60% higher than for females over this time period (P=0.002). In 2007, there were 222 new HIV cases to care (37.4% female). Heterosexual contact was the most common HIV risk, but diversity was seen across sites with frequent injection drug use and men who have sex with men risk in Saskatchewan and southern Alberta, respectively. The Aboriginal population remains heavily over-represented, with approximately 36.0% of new cases being Aboriginal. Late presentation was common across all care sites, with 35.1% of cases presenting with CD4 counts of less than 200 cells/mm3. DISCUSSION: Heterosexual risk is the most common risk reported for HIV acquisition, but injection drug use risk remains significant in Saskatchewan. Aboriginals are over-represented at all sites, and in Saskatchewan accounted for the majority of new cases seen. In contrast to national trends, numbers of new and late diagnoses are increasing in the praire provinces, and this has significant treatment implications and potential public health consequences. Further efforts need to be made to facilitate earlier testing and linkage to care.

HISTORIQUE: Les chercheurs ont examiné le nombre et la démographie des patients positifs au VIH soignés entre 2003 et 2007 dans les provinces des Prairies. MÉTHODOLOGIE: Les chercheurs ont pu évaluer le nombre de patients positifs au VIH qui ont consulté pour la première fois entre 2003 et 2007 d'après quatre registres cliniques du Manitoba, de la Saskatchewan et du sud de l'Alberta. Ils ont également recueilli les données détaillées des dossiers cliniques de nouveaux patients en 2007. RÉSULTATS: À la fin de décembre 2007, 2 263 personnes positives au VIH étaient soignées au Manitoba, en Saskatchewan et dans le sud de l'Alberta. Les hommes et les femmes représentaient 1 674 (74,0 %) et 589 cas, respectivement. Dans l'ensemble, on a constaté une augmentation annuelle de 12 % des nouveaux cas de VIH soignés entre 2003 et 2007 (P=0,026), le taux d'augmentation pour les hommes étant 60 % plus élevé que pour les femmes (P=0,002). En 2007, on a recensé 222 nouveaux cas de VIH soignés (37,4 % de femmes). Le contact hétérosexuel représentait le principal risque de VIH, mais on remarquait une diversité selon les lieux, le risque posé par la consommation fréquente de drogues par injection et par les relations sexuelles entre hommes étant observé en Saskatchewan et au sud de l'Alberta, respectivement. La population autochtone demeure lourdement surreprésentée, puisqu'environ 36,0 % des nouveaux cas étaient d'origine autochtone. Une présentation tardive était fréquente partout, la numération de CD4 étant inférieure à 200 cellules/mm3 à la présentation dans 35,1 % des cas. EXPOSÉ: Les contacts hétérosexuels constituent le principal risque déclaré d'acquisition du VIH, mais la consommation de drogues par injection demeure importante en Saskatchewan. Les Autochtones sont surreprésentés partout, et en Saskatchewan, ils représentent la majorité des nouveaux cas observés. Contrairement aux tendances nationales, le nombre de nouveaux diagnostics et de diagnostics tardifs augmente dans les provinces des Prairies, ce qui a des répercussions thérapeutiques importantes et des conséquences potentielles en matière de santé publique. Il faut faire davantage d'efforts pour favoriser la tenue de tests et des mises en relation plus rapides vers les soins.

A comparison of patient and family caregiver prospective control over lung cancer.

AIM: This paper is a report of our secondary analysis of patient and family caregiver prospective control in lung cancer. BACKGROUND: Control beliefs underlie self-care in sickness and health. Self-care often involves 'shared' activities between the afflicted individual and caregiving family and friends. However, depending on how control is perceived, conflicts can occur in decision-making thus jeopardizing optimal self-care. We need to comprehend how control beliefs compare between patients and caregivers and how their control beliefs are linked with dealing with serious illness. METHODS: Based on questionnaire data collected in our larger study between September 2005 and February 2009, we conducted exploratory comparative analyses of 304 patients' and caregivers' control beliefs in managing lung cancer. Eight 5-point response items captured prospective control. Exploratory factor analysis with promax rotation was conducted to compare dyadic perceptions on the dimensionality of prospective control. We also conducted exploratory correlations between control beliefs and smoking cessation, attributional reactions, caregiver helping and symptom reports. RESULTS: Principal component analysis identified the same factors for patients and caregivers: factor 1, Fate control and factor 2, Team control. Patient and caregiver 'Fate' and 'Team' control sub-scales were respectively associated with hope, caregiver helping and patient smoking cessation. CONCLUSION: Clinicians need to support, adapt or develop a philosophy of cancer care that is inclusive of partnerships, drawing on beliefs of patients and caregivers that controlling lung cancer is a team effort which in turn is tentatively linked to patient smoking cessation, positive emotions and caregiver helping.

A prospective population-based study of triggers of symptomatic flares in IBD.

OBJECTIVES: We aimed to determine whether any of the nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics, infections, and stress trigger symptomatic flares of inflammatory bowel diseases (IBDs). METHODS: Participants drawn from a population-based IBD research registry were surveyed every 3 months for 1 year. They simultaneously tracked the use of NSAIDs, antibiotics, infections, major life events, mood, and perceived stress. Social networks, childhood socioeconomic status, and smoking were assessed at baseline. Disease flare was identified using the Manitoba Inflammatory Bowel Disease Index, a validated disease activity index. Across any two consecutive survey periods, participants were categorized as having a flare (inactive/active), having no flare (inactive/inactive), or remaining active (active/active). Potential triggers were evaluated for the first 3-month period to determine predictive rather than concurrent relationships. Data from only one pair of 3-month periods from an individual were analyzed. RESULTS: A total of 704 participants completed the baseline survey; 552 (78.3%) returned all 5 surveys. In all, 174 participants who had a flare were compared with 209 who had no flare. Perceived stress, negative affect (mood), and major life events were the only trigger variables significantly associated with flares. There were no differences between those who flared and those who did not, in the use of NSAIDs, antibiotics, or in the presence of infections. Multivariate logistic regression analyses indicated that only high-perceived stress (adjusted odds ratio=2.40 (1.35, 4.26)) was associated with an increased risk of flare. CONCLUSIONS: This study adds to the growing evidence that psychological factors contribute to IBD symptom flares. There was no support for differential rates of use of NSAIDS, antibiotics, or for the occurrence of (non-enteric) infections related to IBD flares.

Obstetrical and neonatal outcomes in obese parturients.

OBJECTIVE: Obstetrical risk is increased with maternal obesity. This prospective study was designed to simultaneously evaluate the outcomes in obese parturients and their newborns. METHODS: Patients with a body mass index (BMI) > or =35 were prospectively identified and compared to an equal number of normal weight parturients. Maternal and neonatal outcome measures were compared for the peripartum and neonatal period. RESULTS: We identified 580 obese parturients over a 6 month period and compared them to an equal number of normal weight parturients. The incidence of obesity in this population was 23%. Obesity was associated with increased rates of hypertension, diabetes, and cesarean section. Obese patients were more likely to develop postpartum complications. Neonatal outcomes were compared for infants > or =37 weeks gestation excluding multiple births (496 neonates in the obese group and 520 in the control group). The neonates of obese parturients were more likely to be macrosomic, have 1-minute Apgar scores of < or =7.0 and require admission to a special care unit. Sub-group analysis showed that negative outcomes for parturients and their neonates correlated with increasing BMI. Neonates born to obese diabetic parturients had the highest risk of poor outcomes. CONCLUSIONS: Maternal obesity confers increased risks for both the parturient and their newborn.

Etiology and determinants of sexually transmitted infections in Karnataka state, south India.

BACKGROUND: Syndromic case management remains the cornerstone for STI (sexually transmitted infection) treatment in many countries. We undertook this study to better understand the etiology of STIs in adults in south India and to inform STI management guidelines. METHODS: Adult males and females presenting with genital complaints were recruited from clinics in Karnataka state, south India. A questionnaire was administered, physical examination performed, and blood collected for herpes simplex virus-type 2 (HSV-2) and syphilis serology. Men with urethral discharge (UD) and women with vaginal discharge were tested for Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT) and Trichomonas vaginalis (TV). Vaginal swabs were also tested for bacterial vaginosis and yeast infection. Participants with genital ulcers were tested for Treponema pallidum (TP), Haemophilus ducreyi (HD), and HSV-2. human immunodeficiency virus (HIV) testing was offered to all individuals. RESULTS: There were 401 male and 412 female participants, and rates of HIV infection were high (men, 17%; women, 15%). HSV-2 was significantly associated with HIV in men and women. Among men with the complaint of UD, NG was identified in 35%, CT in 10.5%, and TV in 8.5%. Very little NG or CT was detected among women with vaginal discharge. However, bacterial vaginosis was identified in approximately 40% of women, with significant amounts of TV and Candida also detected. HSV-2 was the most commonly identified pathogen among participants with genital ulcer disease, and the clinical distinction of herpetic versus nonherpetic lesions was not helpful. CONCLUSIONS: Current STI management guidelines should be reevaluated in south India. Consideration should be given to treating all persons with GUD for both HSV-2 and syphilis, and to adding initial treatment for TV for men with UD in areas of high background prevalence of HSV-2 and TV, respectively. This population is at high risk for HIV, and should be counseled and tested appropriately.

Predictors of early inactive disease in a juvenile idiopathic arthritis cohort: results of a Canadian multicenter, prospective inception cohort study.

OBJECTIVE: To determine early predictors of 6-month outcomes in a prospective cohort of patients with juvenile idiopathic arthritis (JIA). METHODS: Patients selected were those enrolled in an inception cohort study of JIA, the Research in Arthritis in Canadian Children Emphasizing Outcomes Study, within 6 months after diagnosis. The juvenile rheumatoid arthritis core criteria set and quality of life measures were collected at enrollment and 6 months later. Outcomes evaluated included inactive disease, Juvenile Arthritis Quality of Life Questionnaire (JAQQ) scores, and Childhood Health Assessment Questionnaire (C-HAQ) scores at 6 months. RESULTS: Thirty-three percent of patients had inactive disease at 6 months. Onset subtype and most baseline core criteria set measures correlated with all 3 outcomes. Relative to oligoarticular JIA, the risks of inactive disease were lower for enthesitis-related arthritis, polyarthritis rheumatoid factor (RF)-negative JIA, and polyarthritis RF-positive JIA, and were similar for psoriatic arthritis. In multiple regression analyses, the baseline JAQQ score was an independent predictor of all 3 outcomes. Other independent baseline predictors included polyarthritis RF-negative and systemic JIA for inactive disease; C-HAQ score and polyarthritis RF-positive JIA for the 6-month C-HAQ score; and active joint count, pain, and time to diagnosis for the 6-month JAQQ score. CONCLUSION: Clinical measures soon after diagnosis predict short-term outcomes for patients with JIA. The JAQQ is a predictor of multiple outcomes. Time to diagnosis affects quality of life in the short term.

Immunogenetic risks of anti-cyclical citrullinated peptide antibodies in a North American Native population with rheumatoid arthritis and their first-degree relatives.

OBJECTIVE: To determine the prevalence of anti-cyclic citrullinated peptide (anti-CCP) antibodies in unaffected relatives of North American Native probands with rheumatoid arthritis (RA); and the associations of the shared epitope (SE) and HLA-DRB1*0901 with RA and anti-CCP antibodies. METHODS: The subjects were RA probands, affected relatives, unaffected first-degree (FDR) and more distant relatives, and unaffected controls from the same population. HLA-DRB1 typing was determined by DNA sequencing and anti-CCP antibodies were determined by ELISA. RESULTS: DRB1*0901, SE, and SE/DRB1*0901 genotypes were all associated with RA. SE/DRB1*0901, but not other SE genotypes, was associated with disease onset at age<16 years. The frequency of anti-CCP antibodies was 82% in RA probands, 17% in FDR, 11% in more distant relatives, and 3% in controls. Among unaffected relatives, a significant increased risk of anti-CCP was associated with SE/DRB1*0901 genotype, but not with SE. CONCLUSION: An independent association of the non-SE allele DRB1*0901 with RA was confirmed in this population, and this allele in combination with a SE allele was associated with younger age at disease onset. FDR of RA probands have a higher prevalence of anti-CCP antibodies than more distant relatives and unrelated controls, suggesting a gradient of risk for disease development. Immunogenetic risks may act early in disease pathogenesis at the level of initiation of RA autoantibody formation; however, it is not clear what additional genetic and environmental risks are involved in progression to clinical disease.

Clinical characteristics and outcomes in patients with pulmonary blastomycosis.

BACKGROUND: Blastomycosis is an uncommon granulomatous infection caused by the thermally dimorphic fungus Blastomyces dermatitidis. The most frequent clinical infections involve the lung, skin, and bone. Pulmonary manifestations range from asymptomatic self-limited infection to severe diffuse pneumonia causing respiratory failure. OBJECTIVES: To establish the clinical characteristics and outcomes of patients with pulmonary blastomycosis diagnosed at hospitals in Manitoba and northwestern Ontario, Canada. METHODS: A retrospective review of medical records was done for 318 patients with blastomycosis in these regions. RESULTS: The majority of patients were Caucasian (198 (62.5%) patients), male (193 (61%) patients), and residents of Ontario (209 (65.7%) patients). Most patients were treated in an inpatient hospital ward (266 (84%) patients) and survived (294 (92%) patients). Pulmonary involvement, either alone or associated with other sites, was present in 296 (93%) of the 318 patients; 22 (7%) patients had no evidence of pulmonary blastomycosis. The majority of patients had localized lung disease (1-3 quadrants on chest radiograph involved; 225 (82%) patients). Of 294 (92%) patients requiring hospitalization, 266 (90%) patients received all inpatient care on a general medical ward; 28 (10%) patients received some care in the intensive care unit (ICU). Factors associated with ICU admission included diffuse pulmonary disease (four quadrants involved on chest radiograph), diabetes, and prior use of antimicrobial therapy. Twenty-four (8%) patients died, and multivariate analysis showed that older age and Aboriginal ethnicity were the significant risk factors for death from blastomycosis. CONCLUSION: Blastomycosis is a cause of serious, potentially life-threatening pulmonary infection in this geographic region.

Computed tomographic scan evaluation of pulmonary blastomycosis.

BACKGROUND: Blastomycosis is an uncommon granulomatous pulmonary and extrapulmonary infectious disease caused by the thermally dimorphic fungus Blastomyces dermatitidis. Diagnosis may be delayed or difficult because of varied presentation. The characteristics of blastomycosis on computed tomographic (CT) scan of the chest are not well characterized. METHODS: The images from 34 chest CT scans from patients with confirmed pulmonary blastomycosis were retrospectively reviewed. RESULTS: The most common CT findings were air bronchograms in 22 patients (65%), consolidation in 21 patients (62%), nodules (smaller than 3 cm) in 21 patients (62%) and lymph node enlargement (mediastinal and hilar nodes combined) in 12 patients (35%). Only four patients (12%) had a miliary pattern. CONCLUSIONS: A specific abnormality characteristic of pulmonary blastomycosis was not identified on CT scanning. The diagnosis can only be made in the context of a high index of clinical suspicion with histological or culture confirmation.

Risk factors for acquisition of endemic blastomycosis.

BACKGROUND: Blastomycosis is potentially fatal, but environmental risk factors for acquiring blastomycosis are not well established. METHOD: Matched cross-sectional questionnaire of 112 patients with history of blastomycosis and 118 control subjects in Manitoba and northwestern Ontario. RESULTS: The most common tissues involved with blastomycosis were pulmonary, skin and soft tissues, and bone. A significantly greater proportion of patients with blastomycosis than control subjects were involved in outdoor occupations. A significantly greater percentage of patients with blastomycosis were immunosuppressed either from collagen vascular disease or immunosuppressive therapy, or had hypothyroidism. A significant association between canine and human blastomycosis was not observed. CONCLUSIONS: Independent risk factors for development of blastomycosis included immunosuppression for any reason (including drugs or disease), collagen vascular disease, being an outdoor worker, and having a coworker with blastomycosis. Canine blastomycosis was not a risk factor for human disease in dog owners.

Multidisciplinary treatment of diabetic foot ulcers in Canadian Aboriginal and non-Aboriginal people.

BACKGROUND: Diabetic foot ulcers are a major cause of morbidity and mortality. This study evaluated the clinical outcomes in Canadian non-Aboriginal and Aboriginal diabetic patients with foot ulcers managed at a multidisciplinary, tertiary care diabetic foot clinic. METHODS: A retrospective review of medical records was done for 325 patients receiving care during a 2-year period. All patients were followed at least 1 year after the initial visit. RESULTS: There were 224 (69%) non-Aboriginal and 101 (31%) Aboriginal patients with 697 foot ulcers. At the initial office visit, 204 (63%) patients had lesions in Wagner grades 2-4. At the most recent evaluation (average, 79+/-73 weeks after initial clinic visit), 190 (58%) patients were rated as having a good outcome (either healed or healing), but a poor outcome (static, progression, amputation, or death) was noted in 135 (42%) patients. At the most recent evaluation, the majority of the 697 ulcers that were noted at the initial or subsequent clinic visits were healed. Aboriginal patients had a shorter average time from initial clinic visit to major lower extremity amputation (Aboriginal, 50+/-64 weeks; non-Aboriginal, 62+/-56 weeks; P<0.01). Residence in a rural or reserve community also correlated with shorter average time from initial clinic visit to major lower extremity amputation (rural or reserve, 45+/-56 weeks; urban, 66+/-61 weeks; P<0.002). When controlled for non-urban residence, Aboriginal ethnicity was not associated with poorer clinical outcome. Earlier major lower extremity amputation was significantly associated with non-urban residence, Aboriginal ethnicity, and arterial insufficiency. Poor clinical outcome was significantly associated with being referred with a lesion present, age greater than 60 years, prior lower extremity amputation or revascularization, arterial insufficiency, more than one lesion on initial presentation, longer duration of type 2 diabetes, and a higher initial Wagner grade for the most advanced lesion. CONCLUSIONS: A multidisciplinary diabetic foot clinic may be successful in treating diabetic foot ulcers in Aboriginal and non-Aboriginal people. However, the frequency of poor outcome is high, consistent with the high prevalence of associated significant risk factors in this population.

Impact of diabetes on maternal-fetal outcomes in Manitoba: Relationship with ethnic and environmental factors.

PURPOSE: To examine the impact of gestational diabetes mellitus (GDM) on maternal-fetal outcomes in Manitoba. METHODS: The rates of macrosomia, stillbirth, cesarean section (C/S) and shoulder dystocia (S/D) in 324,605 births in Manitoba during 1985-2004, and their relationships with diabetes and demographical factors were analyzed. RESULTS: The incidence of macrosomia, stillbirth, C/S and S/D were 15.3%, 0.57%, 16.0%, and 1.2%, respectively. The rates of macrosomia were elevated in mothers with GDM, type 2 DM (T2DM), rural living, First Nations (FN) status, or >or=35 years of age. Increased rates of stillbirth were associated with women with T2DM, FN status or >or=35 years, but not those with GDM. C/S and S/D were increased in women with GDM or T2DM. FN status in combination with GDM increased the risk of S/D. CONCLUSIONS: GDM, T2DM, advanced maternal age, FN status or rural living affected pregnancy outcomes in Manitoba.

Systematic analysis of host immunological pressure on the envelope gene of human immunodeficiency virus type 1 by an immunobioinformatics approach.

As the number of HIV-1 sequences has increased in the public database and new tools of immunological bioinformatics have become available, making it possible to better understand at a population level how host immune response drives the evolution of HIV-1 envelope (Env). We analyzed 1100 unique full-length envelope sequences and systematically determined positive selection (PS) sites by QUASI analysis and found that PS sites were widely dispersed across Env. The frequency of Env PS sites appears to be relatively stable over time. Moreover, between 25% and 61% of PS sites are shared between subtypes A, B, C, and D, suggesting that host immune responses target the same regions of Env gene across different clades at the population level. Significant correlations were observed between PS sites and Neutralizing antibody (NAb) response, as well as PS sites and Th epitopes. Furthermore, NAb sites in combination with cytotoxic-T lymphocyte (CTL) epitopes and proteasome cleavage sites were also significantly associated with PS sites, suggesting NAb may be the major force driving the evolution of HIV-1 Env. We also identified regions that are free from PS, but heavily targeted by CTL or NAb, implying that functional constraints may be responsible for the lack of positive selection in these regions. These findings should help researchers to identify epitopes or regions of HIV-1 that may aid in designing vaccines.

Does blaming the patient with lung cancer affect the helping behavior of primary caregivers?

PURPOSE/OBJECTIVES: To examine whether primary caregivers' helping behaviors are predicted by their illness attribution reactions as proposed in Weiner's model. DESIGN: Latent-variable structural equation modeling. SETTING: Five oncology outpatient settings in central Canada. SAMPLE: 100 dyads consisting of patients with lung cancer and their primary caregivers. METHODS: Self-report questionnaires, abstracted medical record data, confirmatory factor analysis, and structural equation modeling. MAIN RESEARCH VARIABLES: Smoking history, judgments of responsibility for controlling the disease, anger, pride, and helping behaviors. FINDINGS: An interrelation was seen between judgments of responsibility toward patients to control aspects of the disease, affective reactions of anger and pride, and helping behavior. Anger and pride had a stronger influence on helping behavior than smoking history did. CONCLUSIONS: Judgments of responsibility for controlling lung cancer and anger toward patients put caregivers at risk for dysfunctional helping behavior, particularly if patients had a history of tobacco use. IMPLICATIONS FOR NURSING: Primary caregivers' affective states directly affect their helping behavior toward patients with lung cancer. Clinicians should be aware that caregivers who perceive the patient to be largely responsible for managing the disease also may be angry toward that patient. Angry caregivers are at risk of providing suboptimal helping behavior.

Gestational diabetes in Manitoba during a twenty-year period.

PURPOSE: This retrospective cohort study was designed to examine the prevalence and risk factors of gestational diabetes mellitus (GDM) in Manitoba. METHODS: A total of 324,605 deliveries by 165,969 women were reported to Manitoba Health in the years 1985-2004. Data on maternal ages, delivery dates, GDM, self-declared First Nation (FN) status, rural or urban residence and previous GDM were collected for the study. Data were analyzed using multivariate logistic regression models. RESULTS: The prevalence of GDM during the 20-year period was 2.9%, which was 2.3% in 1985-1989 and 3.7% in 1999-2004 (P < 0.01). The trend of increase in the prevalence of GDM continued after major modifications on the screening and diagnostic criteria for GDM in 1998. The prevalence of GDM in FN women was 3-times greater than that in non-FN women. Higher prevalence of GDM was detected in FN pregnant women living in rural areas compared to those in urban areas (P < 0.01), which was opposite for non-FN pregnant women living in rural and urban areas. The prevalence of GDM in pregnant women > or =35 yr was 2.3-fold higher than that in those < 35 yr (P < 0.01). The recurrent rate of GDM was 44.4%. Adjusted odds ratios of GDM for FN status, advanced age, a history of GDM and rural living were 2.2, 2.4, 25.1 and 0.8, respectively. CONCLUSIONS: The prevalence of GDM is increased in Manitoba. FN status, advanced age and a history of GDM, but not rural living, are independent predictors for GDM.

Risk factors for infectious spondylodiscitis in patients receiving hemodialysis.

A retrospective case-control and cohort analysis of hemodialysis patients was done to identify risk factors for spondylodiscitis. These risk factors included bacteremia, receipt of blood products, invasive procedures, and establishment of vascular access. The death rate was greater for case subjects than for control subjects (odds ratio, 2.7).