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Biomedical subjects

C L Cooper

Publications and source records attributed to C L Cooper.

At least 19 recordsLinked to original sources

A randomized controlled psycho-education intervention trial: Improving psychological readiness for successful HIV medication adherence and reducing depression before initiating HAART.

The purpose of this study was to evaluate a novel psycho-educational intervention intended to increase patients' medication preparedness and treatment adherence skills before initiating highly active antiretroviral therapy (HAART). Sixty-three HIV-positive patients not currently on antiretroviral therapy participated in a randomized controlled trial of a standardized, four-session psycho-educational intervention (Supportive Therapy for Adherence to Antiretroviral Treatment; STAART). Session topics included learning techniques to increase medication adherence and learning effective strategies to cope with stress and depression. Patients completed psychological questionnaires assessing psychological readiness to initiate HAART and depressed mood. They completed both measures at study baseline and at four-weeks post-baseline. After controlling for baseline medication readiness scores, intervention patients (n = 30) reported significantly higher mean medication readiness following the STAART intervention (four-weeks post-baseline) (27.3+/-6.9) compared to controls (n = 33; 24.6+/-9.9; p < 0.05). Among depressed patients (n = 27), those receiving the intervention (n = 15) reported significantly lower mean depression scores at four-weeks post-baseline (22.5+/-12.9) compared to controls (n = 12; 27+/-9.9; p < 0.05). The STAART intervention enhanced HIV treatment readiness by better preparing patients prior to initiating HAART. It was also beneficial for reducing depressive symptoms in depressed, HIV-positive patients.

Adaptation, Psychological↗

Clinical outcomes of first antiretroviral regimen in HIV/hepatitis C virus co-infection.

OBJECTIVES: Despite the benefits of HAART, initiation of antiretroviral therapy in HIV-HCV co-infected patients is often delayed as a consequence of patient and physician concern pertaining to liver toxicity. It is unclear whether this is justified. METHODS: We retrospectively evaluated treatment duration and outcome in 186 patients initiating a first HAART regimen. RESULTS: Despite frequent HIV RNA suppression and CD4 T-cell increase following initiation of HAART, the median duration of therapy was only 8 months. Therapy was discontinued primarily for gastrointestinal intolerance (26%), poor adherence (19%), neurocognitive side effects (13%), and substance abuse (6%). Regimes were changed to reduce pill burden and/or frequency of dosing as well (11%). Only six (4%) subjects interrupted therapy as a result of clinically apparent liver toxicity. None were on low dose ritonavir-containing therapy. In those subjects remaining on HAART for at least 12 months, the median ALT level increased marginally from a baseline of 44 IU/mL to 56 IU/mL. The median AST was 44 IU/mL at baseline and at month 12. CONCLUSIONS: These results support our contention that regimen potency, durability, and extrahepatic side effect profile should remain the paramount considerations related to the selection of HAART regimen in HIV-HCV co-infection.

Adult↗

Evaluation of nevirapine-switch strategies for HIV treatment.

Despite the benefits of protease inhibitor (PI)-based HIV treatment, issues of tolerability, dosing frequency, pill count and long-term metabolic complications necessitate evaluation of alternate treatment strategies. The weight of evidence demonstrates that a switch from a PI-based regimen to one containing nevirapine can be accomplished safely while maintaining virological suppression. There is no immunological cost. There is probably an overall benefit in terms of the metabolic milieu.

Adult↗

Analytical and biological variables influencing quantitative hepatitis C virus (HCV) measurement in HIV-HCV coinfection.

The present review considers issues pertaining to the precision and variability of quantitative hepatitis C virus (HCV) measurement in general, outlines the characteristics of HCV RNA in HIV-HCV coinfection and evaluates those factors which may affect this measure. The clinical relevance of accurate HCV measurement in HIV-HCV coinfection is discussed.

Anti-Retroviral Agents↗

Fluarix, inactivated split-virus influenza vaccine.

Influenza is a potentially fatal respiratory infection resulting from several influenza virus strains. It causes annual epidemics of disease for which vaccination is the cornerstone of public health policy. The inadequacies of vaccine supply in the US during the 2004 influenza season revealed the deficiencies of current vaccine development and delivery. One outcome of this was the accelerated approval of an inactivated split-virus influenza vaccine, Fluarix. This paper reviews the immunogenicity and reactogenicity of this vaccine, and makes recommendations for the incorporation of Fluarix into the public health framework alongside other similar vaccines. Other directions to explore in an effort to secure future vaccine supply are considered.

Animals↗

The relationship between job satisfaction and health: a meta-analysis.

BACKGROUND: A vast number of published studies have suggested a link between job satisfaction levels and health. The sizes of the relationships reported vary widely. Narrative overviews of this relationship have been published, but no systematic meta-analysis review has been conducted. METHODS: A systematic review and meta-analysis of 485 studies with a combined sample size of 267 995 individuals was conducted, evaluating the research evidence linking self-report measures of job satisfaction to measures of physical and mental wellbeing. RESULTS: The overall correlation combined across all health measures was r = 0.312 (0.370 after Schmidt-Hunter adjustment). Job satisfaction was most strongly associated with mental/psychological problems; strongest relationships were found for burnout (corrected r = 0.478), self-esteem(r = 0.429), depression (r = 0.428), and anxiety(r = 0.420). The correlation with subjective physical illness was more modest (r = 0.287). CONCLUSIONS: Correlations in excess of 0.3 are rare in this context. The relationships found suggest that job satisfaction level is an important factor influencing the health of workers. Organisations should include the development of stress management policies to identify and eradicate work practices that cause most job dissatisfaction as part of any exercise aimed at improving employee health. Occupational health clinicians should consider counselling employees diagnosed as having psychological problems to critically evaluate their work-and help them to explore ways of gaining greater satisfaction from this important aspect of their life.

Burnout, Professional↗

Safety and immunogenicity of CPG 7909 injection as an adjuvant to Fluarix influenza vaccine.

CPG 7909, a 24-mer B-Class CpG oligodeoxynucleotide (ODN), was tested for safety, tolerability and its ability to augment the immunogenicity of a commercial trivalent killed split influenza vaccine (Fluarix containing A/Beijing/262/95, A/Sydney/5/97 and B/Harbin/7/94; SmithKline Beecham) in a phase Ib blinded, randomized, controlled clinical trial. Sixty healthy volunteers were recruited in two consecutive cohorts of 30 subjects, who were randomly assigned to receive Fluarix plus 1mg CPG 7909 or Fluarix plus saline control (15 subjects each). Vaccines were administered by intramuscular injection on a single occasion with subjects in the first cohort receiving a 1/10th dose of Fluarix and those in the second cohort receiving the full-dose. All safety measures including physical evaluation, laboratory blood assays, and assays for DNA autoimmunity were within normal values except for transient and clinically inconsequential decreases in total white blood cell counts in groups receiving CPG 7909. All vaccines were found to be generally well tolerated with similar frequency and intensity for most adverse reactions for groups receiving CPG 7909 as controls. Exceptions were injection site pain and headache, which were reduced in frequency in subjects receiving the 1/10th Fluarix dose without CpG, compared to the frequency in all other groups. There was a lack of pre-existing immunity, defined as hemagglutinin inhibition (HI) activity < or =20, for all subjects to the influenza strains A/Beijing/262/95 and B/Harbin/7/94 and for some subjects to A/Sydney/5/97. Post-vaccination humoral immune responses, as determined 2 and 4 weeks later by assay of HI activity and ELISA to detect antibodies against hemagglutinin (anti-HA) were similar for both full and reduced Fluarix doses but the cellular immune responses (measured as PBMC antigen-specific IFN-gamma secretion) were reduced in the 1/10th Fluarix dose group. Humoral responses were not significantly enhanced by the addition of CPG 7909, except in individuals with pre-existing immunity to A/Sydney/5/97 strain (baseline HI activity titre >20), where there was a trend to higher HI activity with CPG 7909 (P = 0.06). The addition of CPG 7909 to the 1/10th dose of Fluarix did however result in significantly higher levels of IFN-gamma secretion from peripheral blood mononuclear cells recovered at 4 weeks and restimulated ex vivo with A/Beijing/262/95 (P = 0.048) and B/Harbin/7/94 (P = 0.0057), restoring these to the level seen with full-dose vaccine. These results suggest that addition of CPG 7909 to Fluarix may allow the use of reduced vaccine doses without reduced immunogenicity.

Adjuvants, Immunologic↗

CPG 7909, an immunostimulatory TLR9 agonist oligodeoxynucleotide, as adjuvant to Engerix-B HBV vaccine in healthy adults: a double-blind phase I/II study.

Oligodeoxynucleotides containing immunostimulatory CpG motifs (CpG ODN) act as potent Th1-like immune enhancers with many antigens in animal models. We have extended these observations to the first clinical evaluation of the safety, tolerability and immunogenicity of CPG 7909 when added to a commercial HBV vaccine. In a randomized, double-blind phase I dose escalation study, healthy volunteers aged 18-35 years were vaccinated at 0, 4 and 24 weeks by intramuscular injection with Engerix-B (GlaxoSmithKline). The regular adult dose of 20 microg recombinant hepatitis B surface antigen (HBsAg) adsorbed to alum was administered mixed with saline (control) or with CPG 7909 at one of three doses (0.125, 0.5 or 1.0 mg). HBsAg-specific antibody responses (anti-HBs) appeared significantly sooner and were significantly higher at all timepoints up to and including 24 weeks in CPG 7909 recipients compared to control subjects (p< or = 0.001). Strikingly, most CpG 7909-vaccinated subjects developed protective levels of anti-HBs IgG within just two weeks of the priming vaccine dose. A trend towards higher rates of positive cytotoxic T cell lymphocyte responses was noted in the two higher dose groups of CPG 7909 compared to controls. The most frequently reported adverse events were injection site reactions, flu-like symptoms and headache. While these were more frequent in CPG 7909 groups than in the control group (p<0.0001), most were reported to be of mild to moderate intensity regardless of group. In summary, CPG 7909 as an adjuvant to Engerix-B was well-tolerated and enhanced vaccine immunogenicity. CPG 7909 may allow the development of a two-dose prophylactic HBV vaccine.

Adjuvants, Immunologic↗

A review of low-dose ritonavir in protease inhibitor combination therapy.

The pharmacokinetics of protease inhibitors center around the microsomal enzyme cytochrome P-450 3A4. As a potent inhibitor of this enzyme, ritonavir can increase the bioavailability and half-life of coadministered protease inhibitors. Evidence suggests that increased exposure to protease inhibitors is clinically relevant. Antiretroviral treatment with low-dose ritonavir-boosted lopinavir, indinavir, and saquinavir has durable virological activity and shows impressive immune reconstitution. Although tolerable in most cases, gastrointestinal side effects, hepatotoxicity, and blood lipid abnormalities remain relevant issues. Additional study will elucidate the advantages and disadvantages of twice-daily, low-dose ritonavir-boosted regimens and determine whether once-daily regimens based on this principle will have a lasting role in clinical practice.

Antiretroviral Therapy, Highly Active↗

Gö6976 inhibits LPS-induced microglial TNFalpha release by suppressing p38 MAP kinase activation.

Microglial responses to endotoxin, including the synthesis of inflammatory factors, contribute to gliosis and neuron degeneration in cultured brain tissue. We have previously shown that Gö6976, a protein kinase C (PKC) inhibitor, suppressed the lipopolysaccharide (LPS)-induced production of inflammatory factors in microglia and afforded marked protection of neurons from glia-mediated cytotoxicity. The purpose of this study was to identify the signal transduction pathway underlying the neuroprotective effect of Gö6976. Gö6976 suppressed the LPS-induced release of tumor necrosis factor alpha (TNFalpha) in the microglial cell line, BV2. We show in this study the inhibitory effect of Gö6976 on TNFalpha release occurring through suppression of p38 mitogen-activated protein kinase (MAPK) phosphorylation and not through a PKC mechanism. While Gö6976 did not inhibit the activity of p38 MAPK directly, it did suppress its activation by phosphorylation, indicating the target of action of Gö6976 is a signaling event upstream of p38 MAPK. Although Gö6976 is considered a selective inhibitor of certain PKC isozymes, suppression of TNFalpha production was not mediated through inhibition of PKC activity. Gö6976 appears to play a novel role in neuroprotection by suppressing the release of pro-inflammatory factors by inhibiting the activation of p38 MAPK in microglia, rather than a PKC isoform.

Animals↗

Age differences in coping and locus of control: a study of managerial stress in Hong Kong.

The present study involved data collection from 3 samples of Hong Kong managers to examine mechanisms by which age would relate to work well-being. A total of 634 managers was drawn by random sampling and purposive sampling methods. The results showed that age was positively related to well-being (job satisfaction and mental well-being). Furthermore, older managers reported fewer sources of stress, better coping, and a more internal locus of control. Multiple regression analyses suggested that the relations of age with 2 well-being indicators can be attributed to various combinations of coping, work locus of control, sources of stress, managerial level, and organizational tenure.

Adaptation, Psychological↗

Contingent employment, health and sickness absence.

OBJECTIVES: This study explored the health and sickness absences of contingent employees. METHODS: Analyses of self-reported health and recorded spells of sickness absence were based on a cohort of 5650 employees (674 men, 4976 women) in 10 Finnish hospitals. RESULTS: After adjustment for demographic and work-related characteristics, contingent employees had a better self-rated health status [odds ratio 0.76, 95% confidence interval (95% CI) 0.62-0.94 of poor or average health status]. There were no differences in the prevalence of diagnosed chronic diseases and minor psychiatric morbidity between the groups. After adjustment for self-rated health and confounding, female, but not male, contingent employees had a lower rate of self-certified (1-3 days) sickness absences than permanent employees (rate ratio 0.90, 95% CI 0.85-0.95). Contingent employees, irrespective of gender, had a 0.77 (95% CI 0.71-0.84) times lower rate of medically certified (>3 days) sickness absence than permanent employees. Poor self-rated health status, reported diagnosed chronic diseases, and minor psychiatric morbidity were associated with medically certified absences to a less extent among contingent employees than among permanent employees. CONCLUSIONS: These findings suggest better self-rated health and a lower sickness absence rate for contingent employees than for permanent employees. The difference in sickness absence between the groups seems not only to be associated with actual differences in health, but also with different thresholds of taking sick leave or working while ill.

Adult↗

Infectious complications related to the use of the angio-seal hemostatic puncture closure device.

One hundred and eight coronary angiography procedures in which the Angio-Seal device was utilized were complicated by eight (7.4%) hematomas, of which two (1.9%) subsequently developed infection (Staphylococcus aureus endarteritis and S. aureus septic hematoma). The Angio-Seal device may be a risk factor for infection for two reasons: excessive hematoma formation (a known risk factor for endarteritis), and foreign material remaining within the arterial lumen and wall, thereby creating a nidus for infection.

Adult↗

Adhesion receptor expression by hematopoietic cell lines and murine progenitors: modulation by cytokines and cell cycle status.

Hematopoietic progenitor cells are incubated with cytokine combinations for in vitro expansion of stem cells and to enhance retrovirus-mediated gene transfer. Optimization of the engraftment of these treated cells would be critical to the success of stem cell transplantation or gene therapy. Previous studies demonstrated that a 48-hour incubation of donor BALB/c bone marrow with a mixture of four cytokines (IL-3, IL-6, IL-11, and SCF), resulted in expansion of primitive progenitor/stem cells but a loss of long-term engraftment in nonmyeloablated or myeloablated recipients. We have established the expression pattern for a number of adhesion receptors by normal hematopoietic progenitors and cell lines and the modulation in expression induced by cytokines or cell cycle progression to ascertain the molecular basis for such defective engraftment. Northern blot analysis demonstrated that the cytokine combination of IL-3, IL-6, IL-11, and SCF dramatically down-regulated alpha 4 integrin receptor expression in HL-60 cells. Synchronized FDC-P1 cells exhibited modulation of alpha 4 expression through cell cycle progression, both by quantitative RT-PCR and flow cytometry. Normal murine bone marrow lineage-depleted, Sca+ cells expressed a number of adhesion receptors, including alpha L, alpha 1, alpha 3, alpha 4, alpha 5, alpha 6, beta 1, L-selectin, CD44, and PECAM as assessed by flow cytometry, immunofluorescence, and RT-PCR. There was modulation of the expression of several of these receptors after incubation in the four cytokines for 24 and/or 48 hours: the proportion of cells expressing alpha L, alpha 5, alpha 6, and PECAM increased, whereas the proportion of cells expressing alpha 4 and beta 1 decreased, after cytokine incubation. There was a demonstrable concomitant decline in adhesion of these cells to fibronectin after the cytokine incubation, a finding that correlates with the decrease in expression of alpha 4. These changes in adhesion receptor expression and function with cytokines and during cell cycle transit may be critical to stem cell homing and engraftment after transplantation, as multiple receptors could be involved in the process of rolling, attachment to endothelium, endothelial transmigration, and migration within the marrow space.

Animals↗

The work-family research agenda in changing contexts.

This article argues that research on the work-family interface has evolved against a backdrop of dramatic and ongoing social and workplace change and must continue to reflect current and future context. The article overviews current trends that have implications for work and family and considers some possible future scenarios. It identifies a number of research areas and questions that build on previous theoretical and practical developments in the work-family field and reflect current trends. It is argued that questions about the well-being and sustainability of workplace human resources, of families in their diverse forms, and of communities are of overriding significance for the work-family research agenda, particularly if current trends continue unabated.

Family Relations↗