Effectiveness and costs of phototest in dementia and cognitive impairment screening

BACKGROUND To assess and compare the effectiveness and costs of Phototest, Mini Mental State Examination (MMSE), and Memory Impairment Screen (MIS) to screen for dementia (DEM) and cognitive impairment (CI). METHODS A phase III study was conducted over one year in consecutive patients with suspicion of CI or DEM at four Primary Care (PC) centers. After undergoing all screening tests at the PC center, participants were extensively evaluated by researchers blinded to screening test results in a Cognitive-Behavioral Neurology Unit (CBNU). The gold standard diagnosis was established by consensus of expert neurologists. Effectiveness was assessed by the proportion of correct diagnoses (diagnostic accuracy [DA]) and by the kappa index of concordance between test results and gold standard diagnoses. Costs were based on public prices and hospital accounts. RESULTS The study included 140 subjects (48 with DEM, 37 with CI without DEM, and 55 without CI). The MIS could not be applied to 23 illiterate subjects (16.4%). For DEM, the maximum effectiveness of the MMSE was obtained with different cutoff points as a function of educational level [k = 0.31 (95% Confidence interval [95%CI], 0.19-0.43), DA = 0.60 (95%CI, 0.52-0.68)], and that of the MIS with a cutoff of 3/4 [k = 0.63 (95%CI, 0.48-0.78), DA = 0.83 (95%CI, 0.80-0.92)]. Effectiveness of the Phototest [k = 0.71 (95%CI, 0.59-0.83), DA = 0.87 (95%CI, 0.80-0.92)] was similar to that of the MIS and higher than that of the MMSE. Costs were higher with MMSE (275.9 ± 193.3€ [mean ± sd euros]) than with Phototest (208.2 ± 196.8€) or MIS (201.3 ± 193.4€), whose costs did not significantly differ. For CI, the effectiveness did not significantly differ between MIS [k = 0.59 (95%CI, 0.45-0.74), DA = 0.79 (95%CI, 0.64-0.97)] and Phototest [k = 0.58 (95%CI, 0.45-0.74), DA = 0.78 (95%CI, 0.64-0.95)] and was lowest for the MMSE [k = 0.27 (95%CI, 0.09-0.45), DA = 0.69 (95%CI, 0.56-0.84)]. Costs were higher for MMSE (393.4 ± 121.8€) than for Phototest (287.0 ± 197.4€) or MIS (300.1 ± 165.6€), whose costs did not significantly differ. CONCLUSION MMSE is not an effective instrument in our setting. For both DEM and CI, the Phototest and MIS are more effective and less costly, with no difference between them. However, MIS could not be applied to the appreciable percentage of our population who were illiterate.

Diagnostic accuracy, effectiveness and cost for cognitive impairment and dementia screening of three short cognitive tests applicable to illiterates

BACKGROUND Illiteracy, a universal problem, limits the utilization of the most widely used short cognitive tests. Our objective was to assess and compare the effectiveness and cost for cognitive impairment (CI) and dementia (DEM) screening of three short cognitive tests applicable to illiterates. METHODS Phase III diagnostic test evaluation study was performed during one year in four Primary Care centers, prospectively including individuals with suspicion of CI or DEM. All underwent the Eurotest, Memory Alteration Test (M@T), and Phototest, applied in a balanced manner. Clinical, functional, and cognitive studies were independently performed in a blinded fashion in a Cognitive Behavioral Neurology Unit, and the gold standard diagnosis was established by consensus of expert neurologists on the basis of these results. Effectiveness of tests was assessed as the proportion of correct diagnoses (diagnostic accuracy [DA]) and the kappa index of concordance (k) with respect to gold standard diagnoses. Costs were based on public prices at the time and hospital accounts. RESULTS The study included 139 individuals: 47 with DEM, 36 with CI, and 56 without CI. No significant differences in effectiveness were found among the tests. For DEM screening: Eurotest (k = 0.71 [0.59-0.83], DA = 0.87 [0.80-0.92]), M@T (k = 0.72 [0.60-0.84], DA = 0.87 [0.80-0.92]), Phototest (k = 0.70 [0.57-0.82], DA = 0.86 [0.79-0.91]). For CI screening: Eurotest (k = 0.67 [0.55-0.79]; DA = 0.83 [0.76-0.89]), M@T (k = 0.52 [0.37-0.67]; DA = 0.80 [0.72-0.86]), Phototest (k = 0.59 [0.46-0.72]; DA = 0.79 [0.71-0.86]). There were no differences in the cost of DEM screening, but the cost of CI screening was significantly higher with M@T (330.7 ± 177.1 €, mean ± sd) than with Eurotest (294.1 ± 195.0 €) or Phototest (296.0 ± 196. 5 €). Application time was shorter with Phototest (2.8 ± 0.8 min) than with Eurotest (7.1 ± 1.8 min) or M@T (6.8 ± 2.2 min). CONCLUSIONS Eurotest, M@T, and Phototest are equally effective. Eurotest and Phototest are both less expensive options but Phototest is the most efficient, requiring the shortest application time.

Development and Preliminary Evaluation of a Rapid Oligochromatographic Assay for Specific Detection of New Human Influenza A H1N1 Virus

A new oligochromatographic assay, Speed-Oligo Novel Influenza A H1N1, was designed and optimized for the specific detection of the 2009 influenza A H1N1 virus. The assay is based on a PCR method coupled to detection of PCR products by means of a dipstick device. The target sequence is a 103-bp fragment within the hemagglutinin gene. The analytical sensitivity of the new assay was measured with serial dilutions of a plasmid that contained the target sequence, and we determined that down to one copy per reaction of the plasmid was reliably detected. Diagnostic performance was assessed with 103 RNAs from suspected cases (40 positive and 63 negative results) previously analyzed with a reference real-time PCR technique. All positive cases were confirmed, and no false-positive results were detected with the new assay. No cross-reactions were observed when other viral strains or clinical samples with other respiratory viruses were tested. According to these results, this new assay has 100% sensitivity and specificity. The turnaround time for the whole procedure was 140 min. The assay may be especially useful for the specific detection of 2009 H1N1 virus in laboratories not equipped with real-time PCR instruments

Alterations of specific biomarkers of metabolic pathways in vascular tree from patients with Type 2 diabetes.

The aims of this study were to check whether different biomarkers of inflammatory, apoptotic, immunological or lipid pathways had altered their expression in the occluded popliteal artery (OPA) compared with the internal mammary artery (IMA) and femoral vein (FV) and to examine whether glycemic control influenced the expression of these genes. The study included 20 patients with advanced atherosclerosis and type 2 diabetes mellitus, 15 of whom had peripheral arterial occlusive disease (PAOD), from whom samples of OPA and FV were collected. PAOD patients were classified based on their HbA1c as well (HbA1c ≤ 6.5) or poorly (HbA1c > 6.5) controlled patients. Controls for arteries without atherosclerosis comprised 5 IMA from patients with ischemic cardiomyopathy (ICM). mRNA, protein expression and histological studies were analyzed in IMA, OPA and FV. After analyzing 46 genes, OPA showed higher expression levels than IMA or FV for genes involved in thrombosis (F3), apoptosis (MMP2, MMP9, TIMP1 and TIM3), lipid metabolism (LRP1 and NDUFA), immune response (TLR2) and monocytes adhesion (CD83). Remarkably, MMP-9 expression was lower in OPA from well-controlled patients. In FV from diabetic patients with HbA1c ≤6.5, gene expression levels of BCL2, CDKN1A, COX2, NDUFA and SREBP2 were higher than in FV from those with HbA1c >6.5. The atherosclerotic process in OPA from diabetic patients was associated with high expression levels of inflammatory, lipid metabolism and apoptotic biomarkers. The degree of glycemic control was associated with gene expression markers of apoptosis, lipid metabolism and antioxidants in FV. However, the effect of glycemic control on pro-atherosclerotic gene expression was very low in arteries with established atherosclerosis.

The involvement of thaumatin-like proteins in plant food cross-reactivity: a multicenter study using a specific protein microarray

Cross-reactivity of plant foods is an important phenomenon in allergy, with geographical variations with respect to the number and prevalence of the allergens involved in this process, whose complexity requires detailed studies. We have addressed the role of thaumatin-like proteins (TLPs) in cross-reactivity between fruit and pollen allergies. A representative panel of 16 purified TLPs was printed onto an allergen microarray. The proteins selected belonged to the sources most frequently associated with peach allergy in representative regions of Spain. Sera from two groups of well characterized patients, one with allergy to Rosaceae fruit (FAG) and another against pollens but tolerant to food-plant allergens (PAG), were obtained from seven geographical areas with different environmental pollen profiles. Cross-reactivity between members of this family was demonstrated by inhibition assays. Only 6 out of 16 purified TLPs showed noticeable allergenic activity in the studied populations. Pru p 2.0201, the peach TLP (41%), chestnut TLP (24%) and plane pollen TLP (22%) proved to be allergens of probable relevance to fruit allergy, being mainly associated with pollen sensitization, and strongly linked to specific geographical areas such as Barcelona, Bilbao, the Canary Islands and Madrid. The patients exhibited >50% positive response to Pru p 2.0201 and to chestnut TLP in these specific areas. Therefore, their recognition patterns were associated with the geographical area, suggesting a role for pollen in the sensitization of these allergens. Finally, the co-sensitizations of patients considering pairs of TLP allergens were analyzed by using the co-sensitization graph associated with an allergen microarray immunoassay. Our data indicate that TLPs are significant allergens in plant food allergy and should be considered when diagnosing and treating pollen-food allergy.

Graph based study of allergen cross-reactivity of plant lipid transfer proteins (LTPs) using microarray in a multicenter study.

The study of cross-reactivity in allergy is key to both understanding. the allergic response of many patients and providing them with a rational treatment In the present study, protein microarrays and a co-sensitization graph approach were used in conjunction with an allergen microarray immunoassay. This enabled us to include a wide number of proteins and a large number of patients, and to study sensitization profiles among members of the LTP family. Fourteen LTPs from the most frequent plant food-induced allergies in the geographical area studied were printed into a microarray specifically designed for this research. 212 patients with fruit allergy and 117 food-tolerant pollen allergic subjects were recruited from seven regions of Spain with different pollen profiles, and their sera were tested with allergen microarray. This approach has proven itself to be a good tool to study cross-reactivity between members of LTP family, and could become a useful strategy to analyze other families of allergens.

Selective use of postoperative neck radiotherapy in oral cavity and oropharynx cancer: a prospective clinical study.

BACKGROUND In cervical postoperative radiotherapy, the target volume is usually the same as the extension of the previous dissection. We evaluated a protocol of selective irradiation according to the risk estimated for each dissected lymph node level. METHODS Eighty patients with oral/oropharyngeal cancer were included in this prospective clinical study between 2005 and 2008. Patients underwent surgery of the primary tumor and cervical dissection, with identification of positive nodal levels, followed by selective postoperative radiotherapy. Three types of selective nodal clinical target volume (CTV) were defined: CTV0, CTV1, and CTV2, with a subclinical disease risk of <10%, 10-25%, and 25% and a prescribed radiation dose of <35 Gy, 50 Gy, and 66-70 Gy, respectively. The localization of node failure was categorized as field, marginal, or outside the irradiated field. RESULTS A consistent pattern of cervical infiltration was observed in 97% of positive dissections. Lymph node failure occurred within a high-risk irradiated area (CTV1-CTV2) in 12 patients, marginal area (CTV1/CTVO) in 1 patient, and non-irradiated low-risk area (CTV0) in 2 patients. The volume of selective lymph node irradiation was below the standard radiation volume in 33 patients (mean of 118.6 cc per patient). This decrease in irradiated volume was associated with greater treatment compliance and reduced secondary toxicity. The three-year actuarial nodal control rate was 80%. CONCLUSION This selective postoperative neck irradiation protocol was associated with a similar failure pattern to that observed after standard neck irradiation and achieved a significant reduction in target volume and secondary toxicity.

Prospective registry of symptomatic severe aortic stenosis in octogenarians: a need for intervention.

OBJECTIVE To study the factors associated with choice of therapy and prognosis in octogenarians with severe symptomatic aortic stenosis (AS). STUDY DESIGN Prospective, observational, multicenter registry. Centralized follow-up included survival status and, if possible, mode of death and Katz index. SETTING Transnational registry in Spain. SUBJECTS We included 928 patients aged ≥80 years with severe symptomatic AS. INTERVENTIONS Aortic-valve replacement (AVR), transcatheter aortic-valve implantation (TAVI) or conservative therapy. MAIN OUTCOME MEASURES All-cause death. RESULTS Mean age was 84.2 ± 3.5 years, and only 49.0% were independent (Katz index A). The most frequent planned management was conservative therapy in 423 (46%) patients, followed by TAVI in 261 (28%) and AVR in 244 (26%). The main reason against recommending AVR in 684 patients was high surgical risk [322 (47.1%)], other medical motives [193 (28.2%)], patient refusal [134 (19.6%)] and family refusal in the case of incompetent patients [35 (5.1%)]. The mean time from treatment decision to AVR was 4.8 ± 4.6 months and to TAVI 2.1 ± 3.2 months, P < 0.001. During follow-up (11.2-38.9 months), 357 patients (38.5%) died. Survival rates at 6, 12, 18 and 24 months were 81.8%, 72.6%, 64.1% and 57.3%, respectively. Planned intervention, adjusted for multiple propensity score, was associated with lower mortality when compared with planned conservative treatment: TAVI Hazard ratio (HR) 0.68 (95% confidence interval [CI] 0.49-0.93; P = 0.016) and AVR HR 0.56 (95% CI 0.39-0.8; P = 0.002). CONCLUSION Octogenarians with symptomatic severe AS are frequently managed conservatively. Planned conservative management is associated with a poor prognosis.

Salvage radiosurgery for selected patients with recurrent malignant gliomas.

Purpose. To analyse the survival after salvage radiosurgery and to identify prognostic factors. Methods. We retrospectively reviewed 87 consecutive patients, with recurrent high-grade glioma, that underwent stereotactic radiosurgery between 1997 and 2010. We evaluated the survival after initial diagnosis and after reirradiation. The prognostic factors were analysed by bivariate and multivariate Cox regression model. Results. The median age was 48 years old. The primary histology included anaplastic astrocytoma (47%) and glioblastoma (53%). A margin dose of 18 Gy was administered in the majority of cases (74%). The median survival after initial diagnosis was 21 months (39 months for anaplastic astrocytoma and 18.5 months for glioblastoma) and after reirradiation it was 10 months (17 months for anaplastic astrocytoma and 7.5 months for glioblastoma). In the bivariate analyses, the prognostic factors significantly associated with survival after reirradiation were age, tumour and treatment volume at recurrence, recursive partitioning analyses classification, Karnofsky performance score, histology, and margin to the planning target volume. Only the last four showed significant association in the multivariate analyses. Conclusion. stereotactic radiosurgery is a safe and may be an effective treatment option for selected patients diagnosed with recurrent high-grade glioma. The identified prognostic factors could help individualise the treatment.

Prospective registry of symptomatic severe aortic stenosis in octogenarians: a need for intervention.

OBJECTIVE To study the factors associated with choice of therapy and prognosis in octogenarians with severe symptomatic aortic stenosis (AS). STUDY DESIGN Prospective, observational, multicenter registry. Centralized follow-up included survival status and, if possible, mode of death and Katz index. SETTING Transnational registry in Spain. SUBJECTS We included 928 patients aged ≥80 years with severe symptomatic AS. INTERVENTIONS Aortic-valve replacement (AVR), transcatheter aortic-valve implantation (TAVI) or conservative therapy. MAIN OUTCOME MEASURES All-cause death. RESULTS Mean age was 84.2 ± 3.5 years, and only 49.0% were independent (Katz index A). The most frequent planned management was conservative therapy in 423 (46%) patients, followed by TAVI in 261 (28%) and AVR in 244 (26%). The main reason against recommending AVR in 684 patients was high surgical risk [322 (47.1%)], other medical motives [193 (28.2%)], patient refusal [134 (19.6%)] and family refusal in the case of incompetent patients [35 (5.1%)]. The mean time from treatment decision to AVR was 4.8 ± 4.6 months and to TAVI 2.1 ± 3.2 months, P < 0.001. During follow-up (11.2-38.9 months), 357 patients (38.5%) died. Survival rates at 6, 12, 18 and 24 months were 81.8%, 72.6%, 64.1% and 57.3%, respectively. Planned intervention, adjusted for multiple propensity score, was associated with lower mortality when compared with planned conservative treatment: TAVI Hazard ratio (HR) 0.68 (95% confidence interval [CI] 0.49-0.93; P = 0.016) and AVR HR 0.56 (95% CI 0.39-0.8; P = 0.002). CONCLUSION Octogenarians with symptomatic severe AS are frequently managed conservatively. Planned conservative management is associated with a poor prognosis.