Does the use of health technology assessment have an impact on the utilisation of health care resources? Evidence from two European countries.

OBJECTIVES: A centralised approach to health technology assessment (HTA) may facilitate optimal use of HTA resources. A regional approach may increase the chances of local implementation of recommendations. This study aimed to compare assessment procedures in England (centralised HTA approach) with Spain (regional HTA approach) discussing key challenges and opportunities from both approaches. METHODS: We compared technology assessments of anticancer medicines in the two jurisdictions from 2008 to 2015. To assess the implementation of HTA recommendations, we assessed trends in medicine usage using regression methods. We used IQVIA data, from 2011 to 2016, for a sample of 11 medicines. We used CatSalut data from Catalonia to assess the implementation of local recommendations. RESULTS: In England, 66 assessments were undertaken by the National Institute for Health and Care Excellence (NICE), using a standardised methodology. In Spain, there were 79 reports undertaken by a range of bodies using a shared process and coordinated through the GENESIS collaboration; the assessment methods used varied substantially. Overall, the recommendations in the two jurisdictions were similar. Regression analyses indicate that where there is a positive recommendation by HTA bodies, the usage of the medicine responds most strongly (p < 0.001) in Catalonia (4.892), followed by England (3.120) and Spain (1.693). CONCLUSIONS: This study suggests that medicine utilisation does respond to the positive recommendations of HTA bodies. However, if HTA capacity is organised primarily regionally, considerable effort may be required in coordination, to ensure consistent and rigorous assessments and adequate implementation of HTA findings.

First Report of 'Candidatus Liberibacter solanacearum' in Carrot in Mainland Spain.

In the summer of 2008, symptoms of leaf curling with yellow, bronze, and purple discoloration, twisting of petioles, stunting of shoots and tap roots, and proliferation of secondary roots were observed in 18 commercial carrot (Daucus carota L.) fields (~62 ha) severely infested with psyllids (mainly Bactericera sp.) from 52 fields (297 ha) located in Alicante and Albacete provinces of Spain. Incidence of symptomatic plants was variable among fields. Similar symptoms were observed in 2009, 2010, and 2011. Symptoms resembled those associated with phytoplasma, spiroplasma, or the bacterium 'Candidatus Liberibacter solanacearum' infections in carrot (1-4). Aster yellows and stolbur phytoplasmas and Spiroplasma citri have previously been reported from carrot in mainland Spain but liberibacter infection has not been documented in this region (1). Studies were conducted to determine if 'Ca. L. solanacearum' was associated with the symptoms. Petiole samples of symptomatic carrot plants were collected in 2009 (25 from 9 fields in Alicante and Albacete provinces) and early 2010 (21 from 8 fields in Alicante, Albacete, and Valencia provinces) from symptomatic fields where incidence ranged from 50 to 90%. In addition, one sample collected in 2008 in Alicante was included in the assay. Also, samples were collected from five asymptomatic carrot plants. Total DNA was extracted from 0.5 g of petiole tissue of each sample with the CTAB extraction buffer method (3,4). DNA extractions were analyzed by PCR assay using primer pairs OA2/OI2c and CL514F/R to amplify a portion of 16S rDNA and rplJ/rplL ribosomal protein genes, respectively, of 'Ca. L. solanacearum' (3,4). DNA samples were also tested for phytoplasmas and S. citri by nested-PCR assays using primer pairs P1/P7 followed by R16F2n/R16R2n and ScR16F1/ScR16R1 followed by ScR16F1A/ScR16R2, respectively (2). A 1,168-bp fragment of 16S rDNA was detected in DNA extracted from 1, 12, and 12 symptomatic samples collected in 2008, 2009, and 2010, respectively, suggesting the presence of 'Ca. L. solanacearum' in the carrot samples. A 669-bp rplJ/rplL fragment also was amplified from DNA of the same samples. Liberibacter was not detected in asymptomatic plants. Eight and two samples were infected with S. citri and aster yellows phytoplasmas, respectively. Three samples were infected with S. citri and 'Ca. L. solanacearum' and one sample was infected with all three pathogens. Three amplicons obtained from the PCR assays with both primer pairs from carrot samples collected in 2009 and 2010 were sequenced directly. BLAST analysis of the 16S rDNA sequences (GenBank Nos. HQ454302, HQ454303, and HQ454304) showed 99% nucleotide identity to those of 'Ca. L. solanacearum' amplified from carrot in Finland (GU373049). The rplJ/rplL nucleotide sequences (HQ454305, HQ454306, and HQ454307) were 97% identical to sequences of the analogous rplJ/rplL 'Ca. L. solanacearum' ribosomal protein gene from carrot in Finland (GU373051). To our knowledge, this is the first report of 'Ca. L. solanacearum' in carrot in mainland Spain and also the first evidence of mixed infections of S. citri, 'Ca. L. solanacearum', and phytoplasmas in carrot. References: (1) M. C. Cebrián et al. Plant Dis. 94:1264, 2010. (2) I.-M. Lee et al. Plant Dis. 90:989, 2006. (3) J. E. Munyaneza et al. J. Econ. Entomol. 103:1060, 2010. (4) J. E. Munyaneza et al. Plant Dis. 94:639, 2010.

First Report of Spiroplasma citri in Carrot in Europe.

In 2008 and 2009, symptoms of curling, yellow and purple discoloration of leaves, stunting of shoots and tap roots, and formation of bunchy, fibrous secondary roots were observed in commercial carrot (Daucus carota L.) fields located in several production areas of Spain (Alicante, Albacete, Segovia, and Valladolid). Incidence of this disease was almost 100% in individual affected fields. Similar symptoms were reported from 1997 to 1998 in various carrot production areas of Spain (the Canary Islands, Segovia, and Madrid) and were associated with infection of stolbur and aster yellows phytoplasmas (2). Moreover, the observed symptoms resembled those caused by Spiroplasma citri in carrots affected by the carrot purple leaf disease recently reported in the United States (4). Studies were conducted to investigate whether S. citri and phytoplasmas were associated with the observed carrot symptoms. Total DNA was extracted from 0.5 g of phloem tissue of 13 symptomatic and 3 asymptomatic plants with DNeasy Plant Mini Kit (Qiagen, Valencia, CA). DNA samples were analyzed by nested-PCR assays using primers pair P1/P7 (1) and R16F2n/R16R2n (3) for phytoplasmas and ScR16F1/ScR16R1 followed by ScR16F1A/ScR16R2 (4) for S. citri detection. DNA of a known strain of S. citri (Sediag, Longvic, France) was used as a positive control of the assay. Analyses revealed that 8 of the 13 symptomatic plants tested positive for S. citri; the plants were collected from three different provinces of Spain, namely, Alicante, Valladolid, and Segovia. Two symptomatic plants were double infected by S. citri and a phytoplasma strain belonging to the Aster yellows group (16SrI), subgroup 16SrI-A. However, none of the symptomatic plants presented single infection with phytoplasmas. S. citri identity was determined by sequencing two nested PCR products (1.1 kb) that yielded identical sequences deposited in the GenBank database (Accession Nos. HM124555 and HM124556). BLAST analysis showed 100% nt identity with a sequence of S. citri from carrot (Accession No. DQ112019) associated with the new carrot disease referred to as 'carrot purple leaf reported in Washington State (4). To our knowledge, this is the first report of S. citri associated with carrot in Europe. References: (1) S. Deng and C. Hiruki. J. Microbiol. Methods 14:53, 1991. (2) M. I. Font et al. Bol. San. Veg. Plagas 25:415, 1999. (3) I. M. Lee et al. Int. J. Syst. Bacteriol. 48:1153, 1998. (4) I. M. Lee et al. Plant Dis. 90:989, 2006.

Toxoplasma gondii: comparison of human CD34+ and monocyte-derived dendritic cells after parasite infection.

Human dendritic cells (DC) obtained in vitro from CD34(+) progenitors (CD34-DC) or blood monocytes (mo-DC) are different DC which may be used in a model of T. gondii infection. We compared the survival, infection rate and cell surface receptor expression of both DC types after living T. gondii tachyzoite infection. CD34-DC appeared less resistant to the parasite than mo-DC. At 48h post-infection, chemokine receptors responsible for DC homing and migration were absent in mo-DC, while down regulation of CCR6 and up regulation of CCR7 was observed in CD34-DC. This result, suggesting migration ability of CD34-DC, was confirmed by in vitro migration experiments against different chemokines. Tachyzoite supernatant, used as chemokine, attracted immature CD34-DC as observed by MIP3alpha, while MIP3beta, as expected, attracted mature CD34-DC. Under similar conditions, no significant difference was noticed between mature or immature mo-DC. These data indicated that CD34-DC represent an alternative model that allows migration assay of infected DC by T. gondii.

[Female incontinence: urodynamic evaluation]. / Incontinencia femenina: evaluación urodinámica.

OBJECTIVE: To evaluate the functional studies in women with stress urinary incontinence. METHODS: Emphasis is placed on comprehensive understanding of stress urinary incontinence in women as well as Urodynamic techniques and findings which apply to women with this condition. RESULTS: Although prospective randomized controlled trials to evaluate the clinical efficacy, cost-effectiveness and effect on quality of life of a pre-operative Urodynamic assessment are necessary, to date only Urodynamic Investigation (Non-invasive uroflowmetry, filling cystometrogram, valsalva leak point pressure, pressure-flow studies and urethral profile) provide enough information for treatment decisions and prognosis in cases of female urinary incontinence.

[Urinary incontinence surgery: TVT procedure]. / Tratamiento quirúrgico de la incontinencia: TVT.

The T.V.T. procedure has become a technique for Urinary incontinence and its different presentations. Many trials have reported the efficacy of this technique for different situations, as well as its results and complications. We review the literature and analyze the results and complications, comparing this technique with other such procedures.

Papel del laboratorio en el control metabólico del paciente diabético / Role of laboratory in the metabolic control of the diabetic patient

Los objetivos planteados en el presente estudio son, evaluar el grado de control glucémico a largo plazo de pacientes diabéticos de nuestra área sanitaria en función de la glicohemoglobina (HbA1c), según los criterios definidos por el European NIDDM Policy Group, así como evaluar una de las complicaciones crónicas más frecuentes de los diabéticos, la afectación renal, mediante la cuantificación de microalbuminuria (MA) como marcador precoz para predecir el desarrollo de nefropatía diabética en dichos pacientes, y de esta forma permitir que se inicien tratamientos destinados a revertir o enlentecer su progresión hacia la enfermedad renal. Los resultados que se presentan se obtuvieron del análisis de HbA1c de sangre procedentes de 6374 pacientes diabéticos, y del análisis de las muestras de orina procedentes de 2961 pacientes diabéticos. De los pacientes a los que se les midió la HbA1c, 1803 (28,2 por ciento) presentaban resultados óptimos (8 por ciento). De los pacientes a los que se les midió la microalbuminuria, 1997 (67,4 por ciento) presentaban valores de microalbuminuria negativas (01,9 mg/dl), 520 (17,5 por ciento) presentaban valores altos (2,0-5,7 mg/dl) y 444 (14,9 por ciento) presentaban valores muy altos de microalbuminuria (>5,7 mg/dl). La frecuencia de microalbuminuria (32,4 por ciento) encontrada en nuestro estudio es similar a la hallada en otros estudios, por lo que habrá que incidir en este grupo de población, con una atención integral e individual de dichos pacientes en los que la determinación de microalbuminuria tiene interés pronóstico en los diabéticos tipo 1 en los que anuncia una nefropatía diabética. También permite evaluar un riesgo de naturaleza cardiovascular. En los diabéticos tipo 2, la microalbuminuria predice una mortalidad prematura, estando asociada a factores de riesgo cardiovasculares clásicos, no específicos de la diabetes, aunque frecuentemente, más precoces y más graves como hipertensión arterial y dislipemias (AU)

[What is and who created chiropractic massage?]. / Qué es y quién creó el quiromasaje.

Even though many massage techniques are called chiromassage, this term must be used to describe a technique created by its inventor, Dr. Ferrándiz, who based on knowledge from German, Swiss and Oriental techniques, developed his own technique and in order to differentiate it from other techniques, gave it the name chiro-meaning hand-massage; which is to say massage using hands, without the use of any apparatus. Once this clarification has been made, the author analyzes the parts which compose a good chiromassage: 1) preparatory exercises: exploration, initial contact, magnetic sedative passes, etc. 2) kneading: in order to distort and elongate muscle fibers, 3) specific exercises: distinct one for each individual case, and 4) finalizing exercises: vibrations, drumming with one's fingers, venal drainage and magnetic sedative passes.

[Point processes as a tool for analyzing possible sources of contamination]. / Procesos puntuales como herramienta para el análisis de posibles fuentes de contaminación.

Point pattern analysis pattern comprises a series of techniques that enables the distribution of a series of events occurring in the vicinity of a particular region of a map to be studied. In epidemiology, this problem arises when a potential source of environmental contamination, possibly leading to cases of a specific disease, is investigated.The present study provides a brief description of point pattern analysis. The approach is illustrated through determination of the environmental source and study of the areas of greatest risk of incidence of an outbreak of legionella pneumonia that occurred between the middle of September and beginning of October in the city of Alcoi in Alicante (Spain).Point pattern analysis was able to confirm the environmental source of the outbreak and identify the areas of the city at greatest risk. This provided the justification for an exhaustive inspection of the installations generating aerosols after which, to date, the epidemics ceased.

Procesos puntuales como herramienta para el análisis de posibles fuentes de contaminación / Point processes as a tool for analyzing possible sources of contamination

El análisis de un patrón puntual engloba una serie de técnicas que permiten estudiar la distribución de un conjunto de eventos ocurridos sobre una región del plano. Este problema surge en epidemiología cuando se investiga una potencial fuente de contaminación ambiental alrededor de la cual se sospecha que surgen casos de una determinada enfermedad. En el presente trabajo, se explica brevemente en qué consiste el análisis de un patrón puntual y se ilustra con una aplicación a la determinación del origen medioambiental y al estudio de las zonas de mayor riesgo de incidencia en un brote de neumonía por Legionella ocurrido entre mediados de septiembre y principios de octubre en la ciudad de Alcoi (Alicante). El estudio permitió confirmar el origen medioambiental del brote y señalar las zonas de la ciudad con mayor riesgo, convirtiéndose en el argumento básico para llevar a cabo una exhaustiva inspección de las instalaciones generadoras de aerosoles, tras la cual, hasta la fecha, cesaron los brotes epidémicos (AU)

Point pattern analysis pattern comprises a series of techniques that enables the distribution of a series of events occurring in the vicinity of a particular region of a map to be studied. In epidemiology, this problem arises when a potential source of environmental contamination, possibly leading to cases of a specific disease, is investigated. The present study provides a brief description of point pattern analysis. The approach is illustrated through determination of the environmental source and study of the areas of greatest risk of incidence of an outbreak of legionella pneumonia that occurred between the middle of September and beginning of October in the city of Alcoi in Alicante (Spain). Point pattern analysis was able to confirm the environmental source of the outbreak and identify the areas of the city at greatest risk. This provided the justification for an exhaustive inspection of the installations generating aerosols after which, to date, the epidemics ceased (AU)

Guías de práctica clínica. Un paso hacia delante / Clinical practice guidelines. A step foward

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Cellular immune responses to recombinant antigens in pregnant women chronically infected with Toxoplasma gondii.

The parasite Toxoplasma gondii can infect most mammals and birds, sometimes causing severe pathology. Primary infection during pregnancy can result in abortion or fetal defects. Host immunity, particularly cellular immunity towards antigenic peptides, can control infection, but an efficient vaccine is not yet available. We have evaluated T-cell responses to a crude soluble toxoplasma antigen (ST-Ag) and to five recombinant peptide antigens of cells in whole-blood cultures from 22 pregnant women with preexisting infections and from 7 pregnant negative controls. Cells from all infected patients but from none of the controls responded specifically to ST-Ag by expressing surface CD25 on culture. Responses to the recombinant antigens showed considerable variation between individuals. rGRA1 elicited a response in 16 of the 22 samples (73%), rSAG1 in 13, rGRA7 in 9, rGRA6-CT in 4, and rGRA6-NT in only 1. Most responding cells were CD4(+). Cells from infected subjects cultured with ST-Ag all released high levels of gamma interferon (IFN-gamma) into the culture supernatant (4,343 +/- 2,536 pg/ml). Cells from 12 patients released IFN-gamma after culture with rGRA1 (130 +/- 98 pg/ml), those from 10 patients released it after culture with rSAG1 (183 +/- 128 pg/ml), and those from 4 patients released it after culture with rGRA7 (324 +/- 374 pg/ml). Intensity of IFN-gamma production in response to the latter two recombinant antigens correlated with responses to ST-Ag (r = 0.61 and 0.53, respectively; P < 0.01). Interleukin-4 was always absent from supernatants of cells stimulated with toxoplasma antigens. The heterogeneity of human responses to individual recombinant toxoplasma antigens should be considered in the design of potential vaccines.

[Predicted duration of protective anti-HBs antigens in Peruvian health care workers after six years of vaccination]. / Pronóstico de duración de títulos protectores anti-HBs ag en trabajadores de la salud del perú luego de 6 años de vacunados.

Given the importance attributed to the protection of health care workers against viral Hepatitis B (VHB) by the World Health Organization (WHO) and the Center for Disease Control (CDC), in 1993, the Instituto Peruano del Seguro Social (Social Security Peruvian Institute), today known as ESSALUD, ruled the vaccination of personnel in risk working in the 4 national hospitals, using Cuban vaccine Heberbiovac HB (20mg, schedule 0, 1, 2 months). Our purpose was to evaluate the antibody persistence in the vaccinated individuals after six years from immunization, and the possible presence of HB virus infection markers. Sera from 144 health care workers were studied, for a 70.24% coverage, in relation to the initially seroprotected in the 1993 study. For markers detection, commercial immunoenzymatic methods were used. HBsAg and anti-HBc were negative in all the serology samples studied, thus we conclude that no evidence of infection by this virus was found in any of the vaccinated subjects. AntiHBs was positive, being all of them seroconverted, with seroprotection and hyperresponse as of 91.6% and 43.7% respectively. The mean life time of antiHBs (t 1/2) is three years,predicting that the antibodies level will be over 10 IU/l until after 15 years from the end of the schedule. The subjects under 40 had significantly higher levels of seroprotection and hyperresponse, being the females those that stayed in the upper categories of response. Evaluation of the post-reinforcement memory in the seroconverted, not protected cases, is recommended, as well as extend the work with ESSALUD to other hospitals in the country.

[Radical prostatectomy in stage pT3C stage prostatic adenocarcinoma]. / Prostatectomía radical en adenocarcinoma de próstata estadio pT3C.

OBJECTIVES: To assess the efficacy of surgery in pT3c patients; to discern whether this is an independent influential factor for survival and clinical factor for diagnostic prediction. MATERIAL AND METHODS: Forty-five pT3c (TNM 1982) patients from a cohort of 220 subjects with T1-T2 prostate cancer who underwent radical prostatectomy. Mean and median follow-up: 42 and 36 months, respectively. RESULTS: pT3 stage accounts for 20% (45/220) patients. They display a significantly higher mean PSA (25 +/- 2 ng/ml) (0.001), worse Gleason (0.0002) and clinical stage (0.0003), greater margins involvement (0.0007), and biochemical (0.02), local (0.05) and metastatic (0.001) progression. Independent influential factors are: PSA > 20 ng/ml; T2bc and Gleason 7-10. From these values patients can be divided into 3 risk groups: a) Group I (0-1 unfavourable variables): risk of seminal vesicle involvement 7%; Group II (2 unfavourable variables): risk 47%; Group III (3 unfavourable variables): risk 61%. Progression-free survival: significantly lower than patients with pT2 (58 +/- 8% vs 66 +/- 6% at 5 years) (0.002), but similar to those with pT3ab (0.91). Seminal vesicle involvement is not an independent influential factor (Cox's multivariate study). Influential factors are PSA, Gleason and clinical stage. CONCLUSIONS: pT3c tumours are not an independently influential group in progression-free survival. Progression-free survival is lower than pT2 but similar to pT3ab. Their poor prognosis is dependent on association to negatively influential clinico-pathological factors.