Using serial observations to identify predictors of progression to AIDS in the Toronto Sexual Contact Study.

The Toronto Sexual Contact Study comprises a cohort of 249 male sexual contacts of men with HIV disease which has been followed every 3 months for almost 5 years. On enrollment 143 were seropositive and 16 seroconverted during the follow-up period. By 31 December 1989, 41 of the 159 seropositive cohort members had developed AIDS. Using Cox relative risk regression models, we investigated the association of a number of laboratory and clinical variables and progression to AIDS. Fixed covariate models examined laboratory variables from the enrollment visit of cohort members, with time calculated from this date. In models assessing time dependent covariates, time was calculated from the estimated date of HIV infection. In the univariate models of either fixed or time dependent covariates, many variables were significantly associated with risk of progression to AIDS (T4 cell count, T4/T8 ratio, blastogenic responses to phytohemagglutinin, concanavalin A, and pokeweed mitogen, serum IgA, appearance of p24 antigen, and the development of oral hairy leukoplakia, thrush, or herpes zoster). Appearance of persistent generalized lymphadenopathy was not associated with increased risk of progression. In the multivariate model which evaluated fixed laboratory covariates, T4/T8 ratio, IgA level, and PHA response at enrollment were significantly associated with elevated risk.(ABSTRACT TRUNCATED AT 250 WORDS)     

Health-related quality of life of patients with psoriatic arthritis: a comparison with patients with rheumatoid arthritis

OBJECTIVE: To compare health-related quality of life (QOL) between patients with psoriatic arthritis (PsA) and patients with rheumatoid arthritis (RA), using the Medical Outcomes Study Short Form health survey (SF-36) and the Health Assessment Questionnaire (HAQ). METHODS: Both the SF-36 and the HAQ were administered to 107 PsA patients attending the University of Toronto Psoriatic Arthritis Clinic between January 1 and December 31, 1994, and to 43 RA patients attending a University of Toronto-affiliated RA clinic during the same period. Standardized assessments of disease activity and severity were also performed at each clinic visit. Logistic regression analysis was used to compare health-related QOL between PsA and RA. RESULTS: Both patient populations experienced lower physical health compared with that of a general population sample. The RA patients demonstrated more active inflammatory disease at the time of assessment than the PsA patients. The PsA patients were younger, and more were men. Logistic regression analyses showed that patients with PsA reported higher levels of vitality than patients with RA, even after adjusting for the observed differences in clinical and demographic characteristics. PsA patients, however, reported more role limitations due to emotional problems and more bodily pain after adjusting for the difference in vitality and other covariates. CONCLUSIONS: Although both patient populations experienced reduced QOL, there were some meaningful differences in how the 2 conditions affect health-related QOL. Further, it appeared that there may be unique disabilities associated with the psoriasis dimension of PsA.     

Marrow transplantation for severe aplastic anemia. Long-term outcome in fifty "untransfused" patients

Fifty patients with severe aplastic anemia had no transfusions of blood products until just before marrow transplantation from HLA-identical family members. Of the 50, 42 are still alive 1 to 12 years after transplantation (median, 7 years). By actuarial standards, the 10-year probability of survival is 82%. Of the 42 surviving patients, 37 have Karnofsky performance status scores of 100% and 5 with chronic graft-versus-host disease have scores ranging from 50% to 90% (median, 80%). The 8 deaths were caused by early infection in 1, graft rejection in 1, acute graft-versus-host disease in 3, and chronic graft-versus-host disease in 3. All deaths occurred within two years after transplantation. The incidence of graft failure was 10%. Acute graft-versus-host disease developed in 14 of 44 patients at risk and chronic graft-versus-host disease, in 15 of 41. Risk factors for development of chronic graft-versus-host disease included increased age (p = 0.008) and presence of acute graft-versus-host disease (p = 0.001). The only factor associated with increased risk of death was development of acute graft-versus-host disease (p = 0.05). Results of this study extend our previous finding that patients with severe aplastic anemia who have transplants before the onset of transfusion-induced sensitization have an excellent probability of long-term survival and a normal life.     

Inhibiting conjugation as a tool in the fight against antibiotic resistance

Antibiotic resistance, especially in gram-negative bacteria, is spreading globally and rapidly. Development of new antibiotics lags behind; therefore, novel approaches to the problem of antibiotic resistance are sorely needed and this commentary highlights one relatively unexplored target for drug development: conjugation. Conjugation is a common mechanism of horizontal gene transfer in bacteria that is instrumental in the spread of antibiotic resistance among bacteria. Most resistance genes are found on mobile genetic elements and primarily spread by conjugation. Furthermore, conjugative elements can act as a reservoir to maintain antibiotic resistance in the bacterial population even in the absence of antibiotic selection. Thus, conjugation can spread antibiotic resistance quickly between bacteria of the microbiome and pathogens when selective pressure (antibiotics) is introduced. Potential drug targets include the plasmid-encoded conjugation system and the host-encoded proteins important for conjugation. Ideally, a conjugation inhibitor will be used alongside antibiotics to prevent the spread of resistance to or within pathogens while not acting as a growth inhibitor itself. Inhibiting conjugation will be an important addition to our arsenal of strategies to combat the antibiotic resistance crisis, allowing us to extend the usefulness of antibiotics.     

The BILAG2004-Pregnancy index is reliable for assessment of disease activity in pregnant SLE patients

Objective. To assess the inter-rater reliability of the BILAG2004-Pregnancy index for assessment of SLE disease activity in pregnancy. Methods. Pregnant SLE patients were recruited from four centres and assessed separately by two raters/physicians in routine clinical practice. Disease activity was determined using the BILAG2004-Pregnancy index. Reliability was assessed using level of agreement, κ-statistics and analysis of disagreement. Major disagreement was defined as a score difference of A and C/D/E or B and D/E between the two raters, and minor disagreement was a score difference of A and B or B and C between raters. Results. A total of 30 patients (63.3% Caucasian, 13.3% Afro-Caribbean, 16.7% South Asian) were recruited. The majority of patients had low-level disease activity according to the local rater's assessment, and there was no grade A activity, with grade B activity present in the following systems: mucocutaneous (nine patients), musculoskeletal (two patients), cardiorespiratory (one patient) and renal (one patient). The distribution of disease activity was similar to the external rater's assessment. Good levels of agreement (>70%) were achieved in all systems. κ-statistics were not appropriate for use in the gastrointestinal, ophthalmic, constitutional and neuropsychiatric systems, as there was minimal variation between patients but good levels of agreement otherwise. There were three major disagreements (0.1 per patient, all differences between B and D/E) and five minor disagreements (0.17 per patient). Conclusion. The BILAG2004-Pregnancy index is reliable for assessment of disease activity in pregnant SLE patients.     

Platelet adhesion and thrombus formation on subendothelium in platelets deficient in glycoproteins IIb-IIIa, Ib, and storage granules

Patients whose platelets are deficient in glycoprotein (GP) Ib, IIb- IIIa (thrombasthenia), or granule substances (storage pool deficiency, SPD) were studied to define further the properties of platelets that mediate platelet adhesion and thrombus formation on subendothelium. Both nonanticoagulated and citrated blood were exposed to everted, de- endothelialized rabbit vessel segments under controlled flow conditions and shear rates varying from 650 to 3,300 sec-1. Morphometry was used to measure platelet thrombus dimensions and the percentage of the subendothelial surface covered with contact (C) or spread (S) platelets. Adhesion was defined as C + S. The results in SPD demonstrated (1) reduced thrombus dimensions in delta-SPD (pure dense granule deficiency) in proportion to the magnitude of the dense granule defect; (2) an even greater reduction in thrombus dimensions in patients with combined deficiencies of alpha and dense granules (alpha delta-SPD); and (3) impaired platelet adhesion at several conditions in alpha delta-SPD and, in delta-SPD, a hematocrit-dependent impairment of adhesion in citrated blood at 2,600 sec-1. In thrombasthenia, platelets were present as a monolayer on the subendothelial surface in both nonanticoagulated and citrated blood, indicating an absolute requirement for GPIIb-IIIa in promoting platelet-platelet interaction at all shear rates and perfusion times. Two types of abnormalities in platelet-vessel wall interactions were observed. In nonanticoagulated blood, the percentage of platelets in the C phase was consistently increased at all shear rates, but C + S values were normal. These observations indicate that platelets deficient in GPIIb-IIIa do not spread normally on the subendothelial surface exposed to nonanticoagulated blood. With citrated blood, the C + S value in thrombasthenia was reduced at both 800 and 2,600 sec-1, as in von Willebrand's disease, and a similar degree of reduction (about 50%) was observed in normal blood treated with a monoclonal antibody to GPIIb- IIIa. The findings, together with theoretical considerations, are consistent with an hypothesis that GPIIb-IIIa mediates the spreading of platelets on subendothelium following the initial attachment through GPIb and that GPIIb-IIIa may be considered an adhesion site on the platelet membrane. Abnormalities of GPIIb-IIIa may, depending on the conditions of study, result in either increased values of C platelets or decreased values of C + S. The results of the study further suggest that a complex interaction of platelet granule factors and membrane GP mediate platelet adhesion and thrombus formation.     

The role of hla antigens as indicators of disease progression in psoriatic arthritis

Objective. To identify HLA markers for the development of severe disease in psoriatic arthritis (PsA). Methods. Patients with PsA who were followed up prospectively over a 14-year period were included. Clinical and laboratory assessments of both active inflammation and clinical damage were performed at 6-month intervals according to a standard protocol, which also included serologic HLA typing for class I and II antigens. Progression of damage was defined as transition into higher damage states, defined by the number of damaged joints. Both univariate and multivariate models were developed to identify predictors for progression of damage. Results. Univariate analysis revealed that the HLA antigens B27, B39, and DQw3 were associated with disease progression, while HLA-DR7 was “protective.” The best multivariate model identified the HLA antigens B27, when DR7 was present, and DQw3, when DR7 was not present, as predicting disease progression across all transitions, while HLA-B39 was associated with progression in early disease. The addition of these HLA indicators to a model containing clinical variables resulted in a significant improvement in fit. Conclusion. The HLA antigens associated with PsA, B27 and B39, are risk factors for disease progression, as is the HLA class II antigen DQw3. In combination with clinical measures of disease, these HLA variables are the dominant predictors of progression.     

Enduring impact of communication skills training: results of a 12-month follow-up

The efficacy of a communication skills training programme was shown through a randomised trial. Oncologists (N=160) from 34 cancer centres were allocated to written feedback plus course; course alone; written feedback alone or control. Each clinician had 6 - 10 interviews with patients videotaped at baseline and 3 months postintervention. Analysis of videotapes revealed improvements in the communication skills of clinicians randomised to training (n=80) compared with others (n=80). A 12-month follow-up assessment is reported here. Robust Poisson conditional analyses of counts of changes in communication behaviours revealed no demonstrable attrition in those who had shown improvement previously, including fewer leading questions, appropriate use of focused and open-ended questions and responses to patient cues. Additional skills, not apparent at 3 months, were now evident; the estimated effect sizes corresponded to 81% fewer interruptions (P=0.001) and increased summarising of information to 38% (P=0.038). However, expressions of empathy (54%, P=0.001) declined. The overall results show that 12 - 15 months postintervention, clinicians had integrated key communication skills into clinical practice and were applying others. This is the first RCT to show an enduring effect of communication skills training with transfer into the clinic.