BLISS index for analyzing knee osteoarthritis trials data

OBJECTIVES: Different pain thresholds were investigated, using the WOMAC Pain Scale (WOMAC-P) to determine if they could differentiate between treatment groups (hylan G-F 20 vs. appropriate care) at low and very low levels of state attainment in patients with knee osteoarthritis (OA). A method, termed the BLISS (Bellamy et al. Low Intensity Symptom State-attainment) Index, for analyzing OA knee clinical trials data, was proposed. STUDY DESIGN AND SETTING: Five analyses were performed: time to first BLISS day, BLISS days over 12 months, patients with a BLISS response at month 12, patients with a BLISS response at any time, and number of BLISS periods over 12 months. For each analysis, five levels of WOMAC-P were examined: 相似文献   

Stroke surveillance: population-based estimates and projections for New Zealand

OBJECTIVE: To estimate the incidence, prevalence and mortality of stroke in New Zealand (NZ) in 2001, projected to 2011. METHODS: Multistate lifetable models were constructed using smoothed rates of first-ever stroke incidence and relative risks of mortality estimated from the most recent Auckland Regional Community Stroke (ARCOS) Study. Estimates of the burden of stroke in NZ were calculated by applying rates output by the model to the 2001 population. Stroke incidence, prevalence and mortality were then projected to 2011, assuming similar trends in stroke incidence and case fatality to those estimated between the 1991/92 and 2002/03 studies. RESULTS: A total of 5,200 first-ever strokes were estimated to have occurred in NZ in 2001. Rates of stroke rose exponentially with increasing age and were 20% higher among males than females at most ages. Nevertheless, the lifetable risk of stroke was lower for males (16%) than females (18%). On average, males survived a year longer than females after a first-ever stroke (9.0 vs. 8.2 years). The incidence rates of first-ever stroke declined by approximately 1% per year between 1991 and 2003. The lifetable risk of stroke remained stable for females but increased for males (from 14% to 16%) over this period. Stroke prevalence also increased by approximately 1% per year, whereas stroke-related mortality fell by 4% per year. If these trends continue, approximately 6,000 first-ever strokes (2% annual increase), 45,000 stroke survivors (2% annual increase) and 2,000 stroke-related deaths (1% annual decline) are expected in 2011. CONCLUSION: Stroke mortality is falling faster than stroke incidence. This, together with population growth and ageing, will lead to a rising burden of stroke-related disability over the next decade.     

Does bisphenol A induce superfeminization in Marisa cornuarietis? Part II: toxicity test results and requirements for statistical power analyses

This study presents results of the effects of bisphenol A (BPA) on adult egg production, egg hatchability, egg development rates and juvenile growth rates in the freshwater gastropod, Marisa cornuarietis. We observed no adult mortality, substantial inter-snail variability in reproductive output, and no effects of BPA on reproduction during 12 weeks of exposure to 0, 0.1, 1.0, 16, 160 or 640 μg/L BPA. We observed no effects of BPA on egg hatchability or timing of egg hatching. Juveniles showed good growth in the control and all treatments, and there were no significant effects of BPA on this endpoint. Our results do not support previous claims of enhanced reproduction in Marisa cornuarietis in response to exposure to BPA. Statistical power analysis indicated high levels of inter-snail variability in the measured endpoints and highlighted the need for sufficient replication when testing treatment effects on reproduction in M. cornuarietis with adequate power.     

Mutation D30N is not preferentially selected by human immunodeficiency virus type 1 subtype C in the development of resistance to nelfinavir

Differences in baseline polymorphisms between subtypes may result in development of diverse mutational pathways during antiretroviral treatment. We compared drug resistance in patients with human immunodeficiency virus subtype C (referred to herein as "subtype-C-infected patients") versus subtype-B-infected patients following protease inhibitor (PI) therapy. Genotype, phenotype, and replication capacity (Phenosense; Virologic) were determined. We evaluated 159 subtype-C- and 65 subtype-B-infected patients failing first PI treatment. Following nelfinavir treatment, the unique nelfinavir mutation D30N was substantially less frequent in C (7%) than in B (23%; P = 0.03) while L90M was similar (P < 0.5). Significant differences were found in the rates of M36I (98 and 36%), L63P (35 and 59%), A71V (3 and 32%), V77I (0 and 36%), and I93L (91 and 32%) (0.0001 < P < 0.05) in C and B, respectively. Other mutations were L10I/V, K20R, M46I, V82A/I, I84V, N88D, and N88S. Subtype C samples with mutation D30N showed a 50% inhibitory concentration (IC(50)) change in susceptibility to nelfinavir only. Other mutations increased IC(50) correlates to all PIs. Following accumulation of mutations, replication capacity of the C virus was reduced from 43% +/- 22% to 22% +/- 15% (P = 0.04). We confirmed the selective nature of the D30N mutation in C, and the broader cross-resistance of other common protease inhibitor mutations. The rates at which these mutational pathways develop differ in C and subtype-B-infected patients failing therapy, possibly due to the differential impact of baseline polymorphisms. Because mutation D30N is not preferentially selected in nelfinavir-treated subtype-C-infected patients, as it is in those infected with subtype B, the consideration of using this drug initially to preserve future protease inhibitor options is less relevant for subtype-C-infected patients.     

Functional indexes of reactive cognitive control: ERPs in cued go/no‐go tasks

We aimed to determine the functional meaning of latent (hidden) components decomposed from ERPs, in the context of a go/no‐go paradigm. To accomplish this, we used a new group blind source separation method, based on joint diagonalization of covariance matrices of ERPs. Four variants of a frequently used go/no‐go paradigm were designed, in which operations of reactive cognitive control, such as conflict detection and action inhibition, were independently manipulated. The results showed that a latent component, generated in the anterior cingulate cortex, induced N2/P3 fluctuation only in conditions in which the prepotent model was violated, and thus can be associated with conflict detection operations. In contrast, the two latent components generated in the vicinity of the central sulcus induced P3‐like fluctuations in conditions in which the prepared action was suppressed, and thus can be associated with action inhibition operations. The advantages and limitations of the new blind source separation method in relation to ERP research are also discussed.     

Plasmodium falciparum rhoptry protein RSP2 triggers destruction of the erythroid lineage

The destruction of erythrocytes and defects in erythropoiesis are among the most frequently observed causes of morbidity in severe Plasmodium falciparum malaria. The molecular mechanisms involved remain unclear, despite extensive investigation. We show here, for the first time, that tagging with the parasite rhoptry protein ring surface protein 2 (RSP2) is not restricted to the surfaces of normal erythrocytes, as previously reported, but that it extends to erythroid precursor cells in the bone marrow of anemic malaria patients. Monoclonal mouse antibodies and human sera from patients with severe anemia, reacting with RSP2-tagged erythrocytes, induced cell destruction by phagocytosis and complement activation in vitro. Our observations reveal a new parasite mechanism implicated in the destruction of normal erythrocytes and probably dyserythropoiesis in malaria patients. These data suggest that the tagging of host cells with RSP2 may trigger anemia in falciparum malaria.     

Colorectal signet‐ring cell carcinoma: benefit from adjuvant chemotherapy but a poor prognostic factor

Colorectal signet‐ring cell carcinoma (SRCC) has been associated with poor survival compared with mucinous adenocarcinoma (MC) and the more common adenocarcinoma (AC). Efficacy of adjuvant chemotherapy in SRCC has never been assessed. This study analyzes the prognostic impact of SRCC and determines whether colonic SRCC patients benefit from adjuvant chemotherapy equally compared with MC and AC patients. Data on 196,757 colorectal cancer (CRC) patients in the period 1989–2010 was included in this Dutch nationwide population‐based study. Five‐year relative survival estimates were calculated and multivariate relative survival analyses using a multiple regression model of relative excess risk (RER) were performed. SRCC was found in 1,972 (1.0%) patients. SRCC patients presented more frequently with stage III or IV disease than AC patients (75.2% vs. 43.6%, p < 0.0001) and SRCC was more frequently found in the proximal colon (57.7 vs. 32.0%, p < 0.0001). SRCC patients had a poor 5‐year relative survival of 30.8% (95% CI 28.1–33.6%) in the colon and 19.5% (95% CI 14.7–24.8%) in the rectum compared with 56.8% (95% CI 56.4–57.1%) and 58.5% (95% CI 57.9–59.1%) for AC. This survival difference was found in stage II, but was most prominent in stage III. Compared with AC, there was no significant interaction between SRCC and adjuvant chemotherapy (RER 1.10, 95% CI 0.81–1.51), suggesting a comparable benefit from adjuvant chemotherapy in AC and SRCC. In conclusion, the prognostic impact of SRCC is dismal in both colon and rectal cancer patients, but adjuvant chemotherapy is associated with improved survival in AC, MC, and SRCC patients.