Morbidity and aging in HIV-infected persons: the Swiss HIV cohort study.

BACKGROUND: Patterns of morbidity and mortality among human immunodeficiency virus (HIV)-infected individuals taking antiretroviral therapy are changing as a result of immune reconstitution and improved survival. We studied the influence of aging on the epidemiology of non-AIDS diseases in the Swiss HIV Cohort Study. METHODS: The Swiss HIV Cohort Study is a prospective observational cohort established in 1988 with continuous enrollment. We determined the incidence of clinical events (per 1000 person-years) from January 2008 (when a new questionnaire on non-AIDS-related morbidity was introduced) through December 2010. Differences across age groups were analyzed using Cox regression, adjusted for CD4 cell count, viral load, sex, injection drug use, smoking, and years of HIV infection. RESULTS: Overall, 8444 (96%) of 8848 participants contributed data from 40,720 semiannual visits; 2233 individuals (26.4%) were aged 50-64 years, and 450 (5.3%) were aged ≥65 years. The median duration of HIV infection was 15.4 years (95% confidence interval [CI], 9.59-22.0 years); 23.2% had prior clinical AIDS. We observed 994 incident non-AIDS events in the reference period: 201 cases of bacterial pneumonia, 55 myocardial infarctions, 39 strokes, 70 cases of diabetes mellitus, 123 trauma-associated fractures, 37 fractures without adequate trauma, and 115 non-AIDS malignancies. Multivariable hazard ratios for stroke (17.7; CI, 7.06-44.5), myocardial infarction (5.89; 95% CI, 2.17-16.0), diabetes mellitus (3.75; 95% CI, 1.80-7.85), bone fractures without adequate trauma (10.5; 95% CI, 3.58-30.5), osteoporosis (9.13; 95% CI, 4.10-20.3), and non-AIDS-defining malignancies (6.88; 95% CI, 3.89-12.2) were elevated for persons aged ≥65 years. CONCLUSIONS: Comorbidity and multimorbidity because of non-AIDS diseases, particularly diabetes mellitus, cardiovascular disease, non-AIDS-defining malignancies, and osteoporosis, become more important in care of HIV-infected persons and increase with older age.

Y-90-Ibritumomab Tiuxetan (Zevalin (R)) Consolidation of First Remission In Advanced-Stage Follicular Non-Hodgkin's Lymphoma: Updated Results After a Median Follow-up of 66.2 Months From the International, Randomized, Phase III First-Line Indolent Trial (FIT) In 414 Patients

The FIT trial was conducted to evaluate the safety and efficacy of 90Y-ibritumomab tiuxetan (0.4 mCi/kg; maximum dose 32 mCi) when used as consolidation of first complete or partial remission in patients with previously untreated, advanced-stage follicular lymphoma (FL). Patients were randomly assigned to either 90Y-ibritumomab treatment (n = 207) or observation (n = 202) within 3 months (mo) of completing initial induction therapy (chemotherapy only: 86%; rituximab in combination with chemotherapy: 14%). Response status prior to randomization did not differ between the groups: 52% complete response (CR)/CR unconfirmed (CRu) to induction therapy and 48% partial response (PR) in the 90Y-ibritumomab arm vs 53% CR/CRu and 44% PR in the control arm. The primary endpoint was progression-free survival (PFS) of the intent-to-treat (ITT) population. Results from the first extended follow-up after a median of 3.5 years revealed a significant improvement in PFS from the time of randomization with 90Y-ibritumomab consolidation compared with control (36.5 vs 13.3 mo, respectively; P < 0.0001; Morschhauser et al. JCO. 2008; 26:5156-5164). Here we report a median follow-up of 66.2 mo (5.5 years). Five-year PFS was 47% in the 90Y-ibritumomab group and 29% in the control group (hazard ratio (HR) = 0.51, 95% CI 0.39-0.65; P < 0.0001). Median PFS in the 90Y-ibritumomab group was 49 mo vs 14 mo in the control group. In patients achieving a CR/CRu after induction, 5-year PFS was 57% in the 90Y-ibritumomab group, and the median had not yet been reached at 92 months, compared with a 43% 5-year PFS in the control group and a median of 31 mo (HR = 0.61, 95% CI 0.42-0.89). For patients in PR after induction, the 5-year PFS was 38% in the 90Y-ibritumomab group with a median PFS of 30 mo vs 14% in the control group with a median PFS of 6 mo (HR = 0.38, 95% CI 0.27-0.53). Patients who had received rituximab as part of induction treatment had a 5-year PFS of 64% in the 90Y-ibritumomab group and 48% in the control group (HR = 0.66, 95% CI 0.30-1.47). For all patients, time to next treatment (as calculated from the date of randomization) differed significantly between both groups; median not reached at 99 mo in the 90Y-ibritumomab group vs 35 mo in the control group (P < 0.0001). The majority of patients received rituximab-containing regimens when treated after progression (63/82 [77%] in the 90Y-ibritumomab group and 102/122 [84%] in the control group). Overall response rate to second-line treatment was 79% in the 90Y-ibritumomab group (57% CR/CRu and 22% PR) vs 78% in the control arm (59% CR/CRu, 19% PR). Five-year overall survival was not significantly different between the groups; 93% and 89% in the 90Y-ibritumomab and control groups, respectively (P = 0.561). To date, 40 patients have died; 18 in the 90Y-ibritumomab group and 22 in the control group. Secondary malignancies were diagnosed in 16 patients in the 90Y-ibritumomab arm vs 9 patients in the control arm (P = 0.19). There were 6 (3%) cases of myelodysplastic syndrome (MDS)/acute myelogenous leukemia (AML) in the 90Y-ibritumomab arm vs 1 MDS in the control arm (P = 0.063). In conclusion, this extended follow-up of the FIT trial confirms the benefit of 90Y-ibritumomab consolidation with a nearly 3 year advantage in median PFS. A significant 5-year PFS improvement was confirmed for patients with a CR/CRu or a PR after induction. Effective rescue treatment with rituximab-containing regimens may explain the observed no difference in overall survival between both patient groups who were - for the greater part - rituximab-naïve.

Device-specific weighted T-score for two quantitative ultrasounds: operational propositions for the management of osteoporosis for 65 years and older women in Switzerland.

The World Health Organization (WHO) criteria for the diagnosis of osteoporosis are mainly applicable for dual X-ray absorptiometry (DXA) measurements at the spine and hip levels. There is a growing demand for cheaper devices, free of ionizing radiation such as promising quantitative ultrasound (QUS). In common with many other countries, QUS measurements are increasingly used in Switzerland without adequate clinical guidelines. The T-score approach developed for DXA cannot be applied to QUS, although well-conducted prospective studies have shown that ultrasound could be a valuable predictor of fracture risk. As a consequence, an expert committee named the Swiss Quality Assurance Project (SQAP, for which the main mission is the establishment of quality assurance procedures for DXA and QUS in Switzerland) was mandated by the Swiss Association Against Osteoporosis (ASCO) in 2000 to propose operational clinical recommendations for the use of QUS in the management of osteoporosis for two QUS devices sold in Switzerland. Device-specific weighted "T-score" based on the risk of osteoporotic hip fractures as well as on the prediction of DXA osteoporosis at the hip, according to the WHO definition of osteoporosis, were calculated for the Achilles (Lunar, General Electric, Madison, Wis.) and Sahara (Hologic, Waltham, Mass.) ultrasound devices. Several studies (totaling a few thousand subjects) were used to calculate age-adjusted odd ratios (OR) and area under the receiver operating curve (AUC) for the prediction of osteoporotic fracture (taking into account a weighting score depending on the design of the study involved in the calculation). The ORs were 2.4 (1.9-3.2) and AUC 0.72 (0.66-0.77), respectively, for the Achilles, and 2.3 (1.7-3.1) and 0.75 (0.68-0.82), respectively, for the Sahara device. To translate risk estimates into thresholds for clinical application, 90% sensitivity was used to define low fracture and low osteoporosis risk, and a specificity of 80% was used to define subjects as being at high risk of fracture or having osteoporosis at the hip. From the combination of the fracture model with the hip DXA osteoporotic model, we found a T-score threshold of -1.2 and -2.5 for the stiffness (Achilles) determining, respectively, the low- and high-risk subjects. Similarly, we found a T-score at -1.0 and -2.2 for the QUI index (Sahara). Then a screening strategy combining QUS, DXA, and clinical factors for the identification of women needing treatment was proposed. The application of this approach will help to minimize the inappropriate use of QUS from which the whole field currently suffers.

Biomedical risk assessment as an aid for smoking cessation.

BACKGROUND: A possible strategy for increasing smoking cessation rates could be to provide smokers who have contact with healthcare systems with feedback on the biomedical or potential future effects of smoking, e.g. measurement of exhaled carbon monoxide (CO), lung function, or genetic susceptibility to lung cancer. We reviewed systematically data on smoking cessation rates from controlled trials that used biomedical risk assessment and feedback. OBJECTIVES: To determine the efficacy of biomedical risk assessment provided in addition to various levels of counselling, as a contributing aid to smoking cessation. SEARCH STRATEGY: We systematically searched he Cochrane Collaboration Tobacco Addiction Group Specialized Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1966 to 2004), and EMBASE (1980 to 2004). We combined methodological terms with terms related to smoking cessation counselling and biomedical measurements. SELECTION CRITERIA: Inclusion criteria were: a randomized controlled trial design; subjects participating in smoking cessation interventions; interventions based on a biomedical test to increase motivation to quit; control groups receiving all other components of intervention; an outcome of smoking cessation rate at least six months after the start of the intervention. DATA COLLECTION AND ANALYSIS: Two assessors independently conducted data extraction on each paper, with disagreements resolved by consensus. MAIN RESULTS: From 4049 retrieved references, we selected 170 for full text assessment. We retained eight trials for data extraction and analysis. One of the eight used CO alone and CO + Genetic Susceptibility as two different intervention groups, giving rise to three possible comparisons. Three of the trials isolated the effect of exhaled CO on smoking cessation rates resulting in the following odds ratios (ORs) and 95% confidence intervals (95% CI): 0.73 (0.38 to 1.39), 0.93 (0.62 to 1.41), and 1.18 (0.84 to 1.64). Combining CO measurement with genetic susceptibility gave an OR of 0.58 (0.29 to 1.19). Exhaled CO measurement and spirometry were used together in three trials, resulting in the following ORs (95% CI): 0.6 (0.25 to 1.46), 2.45 (0.73 to 8.25), and 3.50 (0.88 to 13.92). Spirometry results alone were used in one other trial with an OR of 1.21 (0.60 to 2.42).Two trials used other motivational feedback measures, with an OR of 0.80 (0.39 to 1.65) for genetic susceptibility to lung cancer alone, and 3.15 (1.06 to 9.31) for ultrasonography of carotid and femoral arteries performed in light smokers (average 10 to 12 cigarettes a day). AUTHORS' CONCLUSIONS: Due to the scarcity of evidence of sufficient quality, we can make no definitive statements about the effectiveness of biomedical risk assessment as an aid for smoking cessation. Current evidence of lower quality does not however support the hypothesis that biomedical risk assessment increases smoking cessation in comparison with standard treatment. Only two studies were similar enough in term of recruitment, setting, and intervention to allow pooling of data and meta-analysis.

Prospective comparison of clinical prognostic scores in elderly patients with pulmonary embolism.

Background: The Geneva Prognostic Score (GPS), the Pulmonary Embolism Severity Index (PESI), and its simplified version (sPESI) are well known clinical prognostic scores for pulmonary embolism (PE).Objectives: To compare the prognostic performance of these scores in elderly patients with PE. Patients/Methods: In a multicenter Swiss cohort of elderly patients with venous thromboembolism, we prospectively studied 449 patients aged ≥65 years with symptomatic PE. The outcome was 30-day overall mortality. We dichotomized patients as low- vs. higher-risk in all three scores using the following thresholds: GPS scores ≤2 vs. >2, PESI risk classes I-II vs. III-V, and sPESI scores 0 vs. ≥1. We compared 30-day mortality in low- vs. higher-risk patients and the areas under the receiver operating characteristic curve (ROC). Results: Overall, 3.8% of patients (17/449) died within 30 days. The GPS classified a greater proportion of patients as low risk (92% [413/449]) than the PESI (36.3% [163/449]) and the sPESI (39.6% [178/449]) (P<0.001 for each comparison). Low-risk patients based on the sPESI had a mortality of 0% (95% confidence interval [CI] 0-2.1%) compared to 0.6% (95% CI 0-3.4%) for low-risk patients based on the PESI and 3.4% (95% CI 1.9-5.6%) for low-risk patients based on the GPS. The areas under the ROC curves were 0.77 (95%CI 0.72-0.81), 0.76 (95% CI 0.72-0.80), and 0.71 (95% CI 0.66-0.75), respectively (P=0.47). Conclusions: In this cohort of elderly patients with PE, the GPS identified a higher proportion of patients as low-risk but the PESI and sPESI were more accurate in predicting mortality.

Predicting recurrence after unprovoked venous thromboembolism: prospective validation of the updated Vienna Prediction Model.

The updated Vienna Prediction Model for estimating recurrence risk after an unprovoked venous thromboembolism (VTE) has been developed to identify individuals at low risk for VTE recurrence in whom anticoagulation (AC) therapy may be stopped after 3 months. We externally validated the accuracy of the model to predict recurrent VTE in a prospective multicenter cohort of 156 patients aged ≥65 years with acute symptomatic unprovoked VTE who had received 3 to 12 months of AC. Patients with a predicted 12-month risk within the lowest quartile based on the updated Vienna Prediction Model were classified as low risk. The risk of recurrent VTE did not differ between low- vs higher-risk patients at 12 months (13% vs 10%; P = .77) and 24 months (15% vs 17%; P = 1.0). The area under the receiver operating characteristic curve for predicting VTE recurrence was 0.39 (95% confidence interval [CI], 0.25-0.52) at 12 months and 0.43 (95% CI, 0.31-0.54) at 24 months. In conclusion, in elderly patients with unprovoked VTE who have stopped AC, the updated Vienna Prediction Model does not discriminate between patients who develop recurrent VTE and those who do not. This study was registered at www.clinicaltrials.gov as #NCT00973596.