Evaluation of Gamma Interferon Immune Response Elicited by the Newly Constructed PstS-1(285-374):CFP10 Fusion Protein To Detect Mycobacterium tuberculosis Infection

The PstS1 antigen is highly immunogenic, principally when combined with CFP10 during both latent and active TB infection. In the present study, a selected pstS1 gene fragment was cloned, fused with CFP10, and expressed in Escherichia coli. The product [PstS-1(285-374):CFP10] was compared to the recombinant fused RD1 (region of deletion 1) protein (ESAT-6:CFP10) in detecting Mycobacterium tuberculosis infection in 108 recent contacts of pulmonary tuberculosis (TB) cases, considering a positive tuberculin skin test (TST) to be the baseline. The release of gamma interferon (IFN-γ) in 22-h whole-blood and 5-day lymphocyte stimulation assays primed with each antigen was determined. All contacts were clinically followed for up to 1 year, and 87% of the tuberculin skin test-positive (TST^positive) patients accepted preventative treatment. Concerning the IFN-γ response to PstS-1(285-374):CFP10 in the 22-h and 5-day assays, a slight increase in contact-TST^positive detection was observed (23/54 and 26/54) compared to the level seen with the RD1 protein (18/54 and 24/54) whereas in the TST^negative group, similarly lower numbers (≤5/48) of responders were achieved for both antigens, except for RD1 in the 5-day assay (8/48). By combining the IFN-γ responders to both antigens in the 5-day assays, slightly higher increases in positivity were found in the TST^positive (32/54) and TST^negative (10/48) groups. Two of 12 untreated TST^positive contacts progressed to active TB and were concordantly positive in all assays, except for one contact who lacked positivity in the RD1 5-day assay. We demonstrated for the first time that PstS-1(285-374):CFP10 slightly increased contact positivity and detection of active disease progression, suggesting its potential application as a TB infection marker.     

Deriving estimates of contralateral footedness from prevalence rates in samples of Brazilian and non-Brazilian right- and left-handers

Although footedness is closely associated with handedness, accurate prevalence rates of contralateral footedness in right- and left-handed populations were previously unavailable to researchers studying the relationship between phenotypic and hemispheric asymmetries. We collected preference data from 2081 Brazilian children and adolescents, and relate the prevalence of crossed hand/foot preferences to values reported elsewhere in the literature. In our samples, about 4% of the dextrals and 33% of the sinistrals exhibited a contralateral kicking preference. This is in close agreement with the weighted means from our analysis of 19 papers in the literature, which yields 4.0% left-footed kicking in dextrals and 33.5% right-footed kicking in sinistrals. These values are in marked contrast to the 50% figure for right-footed kicking in sinistrals as given by MacNeilage and colleagues (1988, 1991). Among Brazilians with mixed handedness, there was a substantial increase in incongruent footedness. Male consistent right- and left-handers showed a higher prevalence of cross-footed preferences in their kicking preference than females. The sex difference in dextrals was attributed to a training effect in soccer-related activities, and to a sampling bias in sinistrals.     

Influence of severity of the cutaneous manifestations and age on the prevalence of several cardiovascular risk factors in patients with psoriasis

Introduction Psoriasis is a disease with proinflammatory state that has been associated with an increased risk of cardiovascular disease. Method This is a cross‐sectional, observational study, with analysis of 98 patients being treated for psoriasis. Several variables were analysed: gender, age, weight, height, Psoriasis Area and Severity Index (PASI), blood pressure, blood glucose, blood lipids, obesity, metabolic syndrome (MS) and Framingham score. Results Ninety‐eight patients were analysed (51 men; 52.0%). Age ranged from 12 years to 98 years. About 67% of the patients had dyslipidaemia, 14.3% had type 2 diabetes mellitus and 59.2% had systemic arterial hypertension. Forty‐four percentage of patients had the MS and 27.6% had a body mass index >30 kg/m². The Psoriasis Area and Severiy Index were equal or over 10 in 27 patients, 18 of whom had dyslipidaemia (P = 0.929) and 14 of whom had the MS (P = 0.327). Seventy‐four patients were over the age of 40 years and, of these, 56 had dyslipidaemia (P = 0.002) and 41 had the MS (P < 0.001). For 89 patients, whose cardiovascular risk was calculated according to the Framingham criteria, 71.4% at high or moderate risk had a PASI below 10 (P = 0.945) and 100% at high or moderate risk were over the age of 40 years (P = 0.001). Conclusion There was strong evidence that psoriasis patients have an increased cardiovascular risk, chiefly those over the age of 40 years, probably because of the chronic inflammatory state. It seems that the severity of the cutaneous manifestations was not associated with a higher risk in these patients.     

Articular Ultrasound in Asymptomatic Volunteers: Identification of the Worst Measures of Synovial Hypertrophy,Synovial Blood Flow and Joint Damage Among Small-, Medium- and Large-Sized Joints

Articular ultrasound of 6500 joint recesses was performed for the purpose of identifying which joint had the highest measurements among small-sized (SSJ), medium-sized (MSJ) and large-sized (LSJ) joints. Quantitative measurements of synovial hypertrophy (QSR) and semiquantitative measurements of synovial hypertrophy (SSH), power Doppler (SPD) and bone erosion (SBE) (score: 0–3) were made. Higher measurements (p < 0.01) of QSR were obtained in the second metatarsophalangeal joint (MTP), talonavicular joint, and hip. The highest SSH scores (2/3) were obtained in the second MTP, talonavicular joint, hip and knee; the highest SPD scores (1/2/3) in the first MTP, second MTP, dorsal second metacarpophalangeal (MCP) and radiocarpal recesses; and the highest SBE scores (2/3) in the radiocarpal, ulnocarpal and posterior recesses of the glenohumeral joint. In conclusion, higher measurements of synovial hypertrophy were found in the first and second MTPs (SSJ), talonavicular recess (MSJ) and hip (LSJ). Synovial blood flow was frequent in the first MTP and radiocarpal recess. Bone erosion stood out only in the glenohumeral joint.     

Cost‐utility analysis of idelalisib in combination with rituximab in relapsed or refractory chronic lymphocytic leukaemia

Objective

To evaluate the incremental cost‐utility ratio (ICUR) of idelalisib in combination with rituximab (IR) versus rituximab monotherapy (R) in the treatment of patients with relapsed or refractory (R/R) chronic lymphocytic leukaemia (CLL), from the Spanish National Health System (NHS) perspective.

Methods

A partitioned survival Markov model for a lifetime horizon (30 years) was developed to estimate costs (€, 2016) and quality‐adjusted life years (QALY) with IR and R. Initial cohort included patients with CLL receiving a second or subsequent line (2L) of treatment with IR or R. Survival data were based on CLL clinical trial. Drug, administration, monitoring, adverse events and clinical management of CLL costs were included in the model. Costs and outcomes were discounted using a 3% annually. Deterministic and probabilistic sensitivity analyses (PSA) were performed.

Results

Compared to R, 2L IR treatment resulted in QALY gain of 3.147 (4.965 versus 1.818). Total costs were €118 254 for IR versus €23 874 for R. ICUR was €29 990/QALY gained with IR versus R. In the PSA, IR was cost‐effective in 78% of iterations using a threshold of €45 000/QALY.

Conclusion

IR can be considered a cost‐effective treatment compared to R, in the treatment of R/R CLL patients for the Spanish NHS.