Mass SARS-CoV-2 serological screening, a population-based study in the Principality of Andorra.

BACKGROUND: Andorra is a small country located in the Pyrenees attracting millions of visitors for tourism, mostly associated with skiing, and nature-related activities. As its neighbouring countries, Spain and France, it has been heavily affected by the COVID-19 pandemic. We estimated SARS-CoV-2 seroprevalence in the entire country by universal serological testing under a lockdown environment. METHODS: A total of 77,543 inhabitants of Andorra were invited to participate in the study. From 4-28 May, 2020, two cross sectional serological surveys were conducted using a rapid serological test (nCOV IgG/IgM) on a finger prick blood sample in 59 drive-through or walk-through checkpoints, all over Andorra. We calculated seroprevalence of antibodies against SARS-CoV-2 and analysed the main sociodemographic factors associated with being seropositive. FINDINGS: 70,494 inhabitants (90.9% of the population) participated in at least one survey. Overall seroprevalence was 11.0%. The most affected age groups were those over 90 years old (15.2%) and 80-89 (13.8%), followed by adults 50-59 (13.6%) and adolescents 10-19 (13.7%). Most seropositive participants, 6,061 (95.1%), were asymptomatic before the surveys. The multivariable analysis showed that the odds of being seropositive was higher among seasonal workers (OR 2.41; 95% CI 1.07-5.45) or in the population living in La Massana region, a popular ski-related area (OR 2.66; 95% CI 2.44-2.89). A higher seroprevalence was observed in those familiar nuclei with greater numbers of cohabitants: 18% in families with 6 household members or more; 13% in medium size families (3/4/5 people) and 12% in small size (1 to 2 people) nuclei. INTERPRETATION: The prevalence of antibodies against SARS-CoV-2 in the population of Andorra was high during the first wave of the pandemic. Seasonal workers and inhabitants based in La Massana presented a higher seroprevalence. Mass antibody screening allows to identify infection hotspots and should contribute to the design of tailored interventions to prevent SARS-CoV-2 transmission in Andorra. FUNDING: Andorran Ministry of Health, Andorran Health Services.

COVID-19 mortality risk factors in older people in a long-term care center.

PURPOSE: Despite high rates of COVID-19 infection and increased related mortality have been reported among older adults admitted in long-term care facilities, a limited amount of information is available about the natural course of this pandemic and prognostic factors in such population. In the current study, we aimed to investigate the epidemiologic, demographics, clinical, or therapeutic factors that may predict the prognosis in a cohort of COVID-19 infected institutionalized older in a nursing home. METHODS: We conducted a retrospective analysis of all COVID-19 confirmed institutionalized older in a nursing home from March 15 to June 5, 2020. Epidemiological, demographic, and frailty status before infection, and clinical, laboratory, treatment, and outcome data during infection were collected. We used bivariate analysis and multivariate logistic regression to identify risk factors for mortality. RESULTS: The analysis comprised all 100 COVID-19 confirmed cases during the study period. The median age was 85 years; 62% were female. The case fatality rate was 20%. In the bivariate analysis, male gender, fever, respiratory symptoms, severe cognitive decline, a low Barthel index, and lymphocytopenia were significantly associated with mortality. Patients treated with hydroxychloroquine plus azithromycin were related to a higher chance of survival than those without pharmacological treatment. Multivariate logistic regression analysis identified male gender, low Barthel index, no pharmacological treatment, and lymphocytopenia as independent risk factors associated with mortality. CONCLUSIONS: Male gender, low Barthel index, and lymphocytopenia are independent risk factors for COVID-19 mortality in institutionalized older patients in long-term care nursing homes. Treatment with hydroxychloroquine and azithromycin was associated with lower mortality in these patients.

Whole-exome sequencing identifies rare pathogenic variants in new predisposition genes for familial colorectal cancer.

PURPOSE: Colorectal cancer is an important cause of mortality in the developed world. Hereditary forms are due to germ-line mutations in APC, MUTYH, and the mismatch repair genes, but many cases present familial aggregation but an unknown inherited cause. The hypothesis of rare high-penetrance mutations in new genes is a likely explanation for the underlying predisposition in some of these familial cases. METHODS: Exome sequencing was performed in 43 patients with colorectal cancer from 29 families with strong disease aggregation without mutations in known hereditary colorectal cancer genes. Data analysis selected only very rare variants (0-0.1%), producing a putative loss of function and located in genes with a role compatible with cancer. Variants in genes previously involved in hereditary colorectal cancer or nearby previous colorectal cancer genome-wide association study hits were also chosen. RESULTS: Twenty-eight final candidate variants were selected and validated by Sanger sequencing. Correct family segregation and somatic studies were used to categorize the most interesting variants in CDKN1B, XRCC4, EPHX1, NFKBIZ, SMARCA4, and BARD1. CONCLUSION: We identified new potential colorectal cancer predisposition variants in genes that have a role in cancer predisposition and are involved in DNA repair and the cell cycle, which supports their putative involvement in germ-line predisposition to this neoplasm.

The MLH1 c.1852_1853delinsGC (p.K618A) variant in colorectal cancer: genetic association study in 18,723 individuals.

Colorectal cancer is one of the most frequent neoplasms and an important cause of mortality in the developed world. Mendelian syndromes account for about 5% of the total burden of CRC, being Lynch syndrome and familial adenomatous polyposis the most common forms. Lynch syndrome tumors develop mainly as a consequence of defective DNA mismatch repair associated with germline mutations in MLH1, MSH2, MSH6 and PMS2. A significant proportion of variants identified by screening these genes correspond to missense or noncoding changes without a clear pathogenic consequence, and they are designated as "variants of uncertain significance", being the c.1852_1853delinsGC (p.K618A) variant in the MLH1 gene a clear example. The implication of this variant as a low-penetrance risk variant for CRC was assessed in the present study by performing a case-control study within a large cohort from the COGENT consortium-COST Action BM1206 including 18,723 individuals (8,055 colorectal cancer cases and 10,668 controls) and a case-only genotype-phenotype correlation with several clinical and pathological characteristics restricted to the Epicolon cohort. Our results showed no involvement of this variant as a low-penetrance variant for colorectal cancer genetic susceptibility and no association with any clinical and pathological characteristics including family history for this neoplasm or Lynch syndrome.

New genes emerging for colorectal cancer predisposition.

Colorectal cancer (CRC) is one of the most frequent neoplasms and an important cause of mortality in the developed world. This cancer is caused by both genetic and environmental factors although 35% of the variation in CRC susceptibility involves inherited genetic differences. Mendelian syndromes account for about 5% of the total burden of CRC, with Lynch syndrome and familial adenomatous polyposis the most common forms. Excluding hereditary forms, there is an important fraction of CRC cases that present familial aggregation for the disease with an unknown germline genetic cause. CRC can be also considered as a complex disease taking into account the common disease-commom variant hypothesis with a polygenic model of inheritance where the genetic components of common complex diseases correspond mostly to variants of low/moderate effect. So far, 30 common, low-penetrance susceptibility variants have been identified for CRC. Recently, new sequencing technologies including exome- and whole-genome sequencing have permitted to add a new approach to facilitate the identification of new genes responsible for human disease predisposition. By using whole-genome sequencing, germline mutations in the POLE and POLD1 genes have been found to be responsible for a new form of CRC genetic predisposition called polymerase proofreading-associated polyposis.

¿Dónde está y hacia dónde va nuestro sistema sanitario? / Health care system: where is now and where it goes?

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Genetic susceptibility variants associated with colorectal cancer prognosis.

Colorectal cancer (CRC) is the second leading cause of cancer-related death among men and women in Western countries. Once a tumour develops, a differentiated prognosis could be determined by lifestyle habits or inherited and somatic genetic factors. Finding such prognostic factors will be helpful in order to identify cases with a shorter survival or at a higher risk of recurrence that may benefit from more intensive treatment and follow-up surveillance. Sixteen CRC genetic susceptibility variants were directly genotyped in a cohort of 1235 CRC patients recruited by the EPICOLON Spanish consortium. Univariate Cox and multivariate regression analyses were performed taking as primary outcomes overall survival (OS), disease-free survival and recurrence-free interval. Genetic variants rs9929218 at 16q22.1 and rs10795668 at 10p14 may have an effect on OS. The G allele of rs9929218 was linked with a better OS [GG genotype, genotypic model: hazard ratio (HR) = 0.65, 95% confidence interval (CI) 0.45-0.93, P = 0.0179; GG/GA genotypes, dominant model: HR = 0.66, 95% CI 0.47-0.94, P = 0.0202]. Likewise, the G allele of rs10795668 was associated with better clinical outcome (GG genotype, genotypic model: HR = 0.73, 95% CI 0.53-1.01, P = 0.0570; GA genotype, genotypic model: HR = 0.66, 95% CI 0.47-0.92, P = 0.0137; GG/GA genotypes, dominant model: HR = 0.68, 95% CI 0.50-0.94, P = 0.0194). In conclusion, CRC susceptibility variants rs9929218 and rs10795668 may exert some influence in modulating patient's survival and they deserve to be further tested in additional CRC cohorts in order to confirm their potential as prognosis or predictive biomarkers.

Assessment of anti-prothrombin antibodies in thrombosis complicating inflammatory bowel diseases.

PURPOSE: In inflammatory bowel diseases (IBD), risk of thrombosis and production of antibodies are increased. In autoimmune and inflammatory disorders, a role of anti-prothrombin (aPT) antibodies in developing thrombosis has been hypothesised. The aim of the study is to evaluate the prevalence of aPT antibodies in IBD patients, with and without thrombosis. METHODS: Thirty-three IBD patients with thrombosis, 33 IBD patients without thrombosis matched for sex, age, diagnosis and disease activity and 66 sex- and age-matched healthy controls were enrolled. Thrombosis was considered recent when blood sample was obtained within 3 months from the event. RESULTS: Prevalence of aPT antibodies in thrombotic IBD patients (3/33, 9.1 %), non-thrombotic IBD patients (4/33, 12.1 %) and in healthy subjects (3/66, 4.5 %) did not result significantly different (p = 0.377). The prevalence of aPT antibodies was more frequent in ulcerative colitis (6/32, 18.7 %) than in Crohn's disease (1/34, 2.9 %) and healthy controls (p = 0.022). Among thrombotic IBD patients, the prevalence of aPT antibodies was higher in those with recent (2/9, 22.2 %) than in those with previous thrombosis (1/24, 4.2 %) (p = 0.103). All thrombotic IBD patients with aPT antibodies were affected by ulcerative colitis with previous history of deep venous thrombosis. CONCLUSIONS: aPT antibodies do not appear to play a relevant role in thrombosis complicating IBD course. A possible association in ulcerative colitis patients with DVT could not be excluded.

Transcriptional analysis of the intestinal mucosa of patients with ulcerative colitis in remission reveals lasting epithelial cell alterations.

OBJECTIVE: Ulcerative colitis (UC) is a chronic condition characterised by the relapsing inflammation despite previous endoscopic and histological healing. Our objective was to identify the molecular signature associated with UC remission. DESIGN: We performed whole-genome transcriptional analysis of colonic biopsies from patients with histologically active and inactive UC, and non-inflammatory bowel disease (non-IBD) controls. Real-time reverse transcriptase-PCR and immunostaining were used for validating selected genes in independent cohorts of patients. RESULTS: Microarray analysis (n=43) demonstrates that UC patients in remission present an intestinal transcriptional signature that significantly differs from that of non-IBD controls and active patients. Fifty-four selected genes were validated in an independent cohort of patients (n=30). Twenty-nine of these genes were significantly regulated in UC-in-remission subjects compared with non-IBD controls, including a large number of epithelial cell-expressed genes such as REG4, S100P, SERPINB5, SLC16A1, DEFB1, AQP3 and AQP8, which modulate epithelial cell growth, sensitivity to apoptosis and immune function. Expression of inflammation-related genes such as REG1A and IL8 returned to control levels during remission. REG4, S100P, SERPINB5 and REG1A protein expression was confirmed by immunohistochemistry (n=23). CONCLUSIONS: Analysis of the gene signature associated with remission allowed us to unravel pathways permanently deregulated in UC despite histological recovery. Given the strong link between the regulation of some of these genes and the growth and dissemination of gastrointestinal cancers, we believe their aberrant expression in UC may provide a mechanism for epithelial hyper-proliferation and, in the context of malignant transformation, for tumour growth.

Seeking genetic susceptibility variants for colorectal cancer: the EPICOLON consortium experience.

The EPICOLON consortium was initiated in 1999 by the Gastrointestinal Oncology Group of the Spanish Gastroenterology Association. It recruited consecutive, unselected, population-based colorectal cancer (CRC) cases and control subjects matched by age and gender without personal or familial history of cancer all over Spain with the main goal of gaining knowledge in Lynch syndrome and familial CRC. This epidemiological, prospective and multicentre study collected extensive clinical data and biological samples from ∼2000 CRC cases and 2000 controls in Phases 1 and 2 involving 25 and 14 participating hospitals, respectively. Genetic susceptibility projects in EPICOLON have included candidate-gene approaches evaluating single-nucleotide polymorphisms/genes from the historical category (linked to CRC risk by previous studies), from human syntenic CRC susceptibility regions identified in mouse, from the CRC carcinogenesis-related pathways Wnt and BMP, from regions 9q22 and 3q22 with positive linkage in CRC families, and from the mucin gene family. This consortium has also participated actively in the identification 5 of the 16 common, low-penetrance CRC genetic variants identified so far by genome-wide association studies. Finishing their own pangenomic study and performing whole-exome sequencing in selected CRC samples are among EPICOLON future research prospects.

Susceptibility genetic variants associated with early-onset colorectal cancer.

Colorectal cancer (CRC) is the second most common cancer in Western countries. Hereditary forms only correspond to 5% of CRC burden. Recently, genome-wide association studies have identified common low-penetrant CRC genetic susceptibility loci. Early-onset CRC (CRC<50 years old) is especially suggestive of hereditary predisposition although 85-90% of heritability still remains unidentified. CRC<50 patients (n = 191) were compared with a late-onset CRC group (CRC>65 years old) (n = 1264). CRC susceptibility variants at 8q23.3 (rs16892766), 8q24.21 (rs6983267), 10p14 (rs10795668), 11q23.1 (rs3802842), 15q13.3 (rs4779584), 18q21 (rs4939827), 14q22.2 (rs4444235), 16q22.1 (rs9929218), 19q13.1 (rs10411210) and 20p12.3 (rs961253) were genotyped in all DNA samples. A genotype-phenotype correlation with clinical and pathological characteristics in both groups was performed. Risk allele carriers for rs3802842 [Odds ratio (OR) = 1.5, 95% confidence interval (CI) 1.1-2.05, P = 0.0096, dominant model) and rs4779584 (OR = 1.39, 95% CI 1.02-1.9, P = 0.0396, dominant model) were more frequent in the CRC<50 group, whereas homozygotes for rs10795668 risk allele were also more frequent in the early-onset CRC (P = 0.02, codominant model). Regarding early-onset cases, 14q22 (rs4444235), 11q23 (rs3802842) and 20p12 (rs961253) variants were more associated with family history of CRC or tumors of the Lynch syndrome spectrum excluding CRC. In our entire cohort, sum of risk alleles was significantly higher in patients with a CRC family history (OR = 1.40, 95% CI 1.06-1.85, P = 0.01). In conclusion, variants at 10p14 (rs10795668), 11q23.1 (rs3802842) and 15q13.3 (rs4779584) may have a predominant role in predisposition to early-onset CRC. Association of CRC susceptibility variants with some patient's familiar and personal features could be relevant for screening and surveillance strategies in this high-risk group and it should be explored in further studies.

La mutación R92Q del gen TNFRSF1A se asocia con manifestaciones extra-intestinales en la enfermedad de Crohn / The TNFRSF1A gene R92Q mutation is associated with extra-intestinal manifestations of Crohn’s disease

It has been suggested that the R92Q mutation of the tumour necrosis factor receptor superfamily 1A (TNFRS1A) gene may be implicated in different inflammatory disorders. The aim of this study was to establish the role of this mutation as a determinant of Crohn`s disease (CD) susceptibility and/or clinical phenotype. One hundred and sixty-five CD patients and 203 healthy controls were prospectively included. The frequency of individuals carrying the R92Q mutation was similar between CD patients (4.24 percent) and controls (4.43 percent) (OR: 0.95; 95 percent CI = 0.34-2.62). In the genotype-phenotype evaluation, the univariate analysis showed that extra-intestinal manifestations were positively associated with the presence of R92Q mutation (p = 0.025; OR: 5.56; 95 percent CI = 1.04-29.6). In the multivariate analysis, presence of R92Q mutation was independently associated to extra-intestinal manifestations of CD, specially cutaneous manifestations (p = 0.02; OR: 5.17, 95 percent CI = 1.07-24.8). The R92Q mutation of TNFRSF1A gene is not a determinant of CD susceptibility, but contributes to the appearance of extra-intestinal manifestations of the disease.

Se ha sugerido que la mutación R92Q del gen de la super-familia del receptor del factor de necrosis tumoral 1A (TNFRS1A) podría estar relacionada con diversos trastornos inflamatorios. El objetivo de este estudio fue determinar el papel de esta mutación como factor determinante de la susceptibilidad y/o fenotipo clínico de la enfermedad de Crohn (EC). Ciento sesenta y cinco pacientes con EC y 203 controles sanos fueron incluidos de manera prospectiva. La frecuencia de individuos portadores de la mutación R92Q fue similar entre los pacientes con EC (4,24 por ciento) y los controles (4,43 por ciento) (OR: 0,95; 95 por ciento IC = 0,34-2,62). En la evaluación genotipo-fenotipo, el análisis univariado indicó que las manifestaciones extra-intestinales estaban relacionadas con la presencia de la mutación R92Q (p = 0,025; OR: 5,56; 95 por ciento IC = 1,04-29,6). En el análisis multivariado, la presencia de la mutación R92Q estuvo relacionada de manera independiente con las manifestaciones extra-intestinales de la EC, especialmente manifestaciones cutáneas (p = 0,02; OR: 5,17, 95 por ciento IC = 1,07-24,8). La mutación R92Q del gen TNFRSF1A no es un factor determinante de susceptibilidad a EC, pero contribuye a la aparición de manifestaciones extra-intestinales de la enfermedad.

Case-control study for colorectal cancer genetic susceptibility in EPICOLON: previously identified variants and mucins.

BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer death in developed countries. Familial aggregation in CRC is also important outside syndromic forms and, in this case, a polygenic model with several common low-penetrance alleles contributing to CRC genetic predisposition could be hypothesized. Mucins and GALNTs (N-acetylgalactosaminyltransferase) are interesting candidates for CRC genetic susceptibility and have not been previously evaluated. We present results for ten genetic variants linked to CRC risk in previous studies (previously identified category) and 18 selected variants from the mucin gene family in a case-control association study from the Spanish EPICOLON consortium. METHODS: CRC cases and matched controls were from EPICOLON, a prospective, multicenter, nationwide Spanish initiative, comprised of two independent stages. Stage 1 corresponded to 515 CRC cases and 515 controls, whereas stage 2 consisted of 901 CRC cases and 909 controls. Also, an independent cohort of 549 CRC cases and 599 controls outside EPICOLON was available for additional replication. Genotyping was performed for ten previously identified SNPs in ADH1C, APC, CCDN1, IL6, IL8, IRS1, MTHFR, PPARG, VDR and ARL11, and 18 selected variants in the mucin gene family. RESULTS: None of the 28 SNPs analyzed in our study was found to be associated with CRC risk. Although four SNPs were significant with a P-value < 0.05 in EPICOLON stage 1 [rs698 in ADH1C (OR = 1.63, 95% CI = 1.06-2.50, P-value = 0.02, recessive), rs1800795 in IL6 (OR = 1.62, 95% CI = 1.10-2.37, P-value = 0.01, recessive), rs3803185 in ARL11 (OR = 1.58, 95% CI = 1.17-2.15, P-value = 0.007, codominant), and rs2102302 in GALNTL2 (OR = 1.20, 95% CI = 1.00-1.44, P-value = 0.04, log-additive 0, 1, 2 alleles], only rs3803185 achieved statistical significance in EPICOLON stage 2 (OR = 1.34, 95% CI = 1.06-1.69, P-value = 0.01, recessive). In the joint analysis for both stages, results were only significant for rs3803185 (OR = 1.12, 95% CI = 1.00-1.25, P-value = 0.04, log-additive 0, 1, 2 alleles) and borderline significant for rs698 and rs2102302. The rs3803185 variant was not significantly associated with CRC risk in an external cohort (MCC-Spain), but it still showed some borderline significance in the pooled analysis of both cohorts (OR = 1.08, 95% CI = 0.98-1.18, P-value = 0.09, log-additive 0, 1, 2 alleles). CONCLUSIONS: ARL11, ADH1C, GALNTL2 and IL6 genetic variants may have an effect on CRC risk. Further validation and meta-analyses should be undertaken in larger CRC studies.

Evaluación de la preferencia de los pacientes con enfermedad por reflujo gastroesofágico y disfagia por el tratamiento con comprimidos bucodispersables de lansoprazol / Evaluation of preferences in patients with gastroesophageal reflux disease and dysphagia concerning treatment with lansoprazole orally disintegrating tablets

Introducción y objetivoRecientemente se dispone de una nueva formulación de lansoprazol en forma de comprimidos bucodispersables (CBD) que puede contribuir a mejorar la aceptabilidad y el cumplimiento con este tipo de medicación. El objetivo del presente estudio fue evaluar la preferencia del paciente con enfermedad por reflujo gastroesofágico (ERGE) y disfagia por los CBD en comparación con las cápsulas de lansoprazol.Material y métodosSe diseñó un estudio clínico fase IV, multicéntrico, cruzado, abierto y aleatorizado en pacientes con síntomas de ERGE y disfagia asociada. Los pacientes se trataron durante 3 días con cápsulas de lansoprazol (30mg) y otros 3 días con CBD de lansoprazol (30mg). El orden del tratamiento (primero cápsulas y después CBD o al revés) fue determinado mediante aleatorización en bloques de forma centralizada. La variable principal del estudio fue la puntuación en una escala visual analógica (EVA), en la que se solicitaba al paciente que valorara su grado de preferencia por los CBD o las cápsulas.ResultadosSe incluyó a 145 pacientes y se evaluó finalmente a 126 por protocolo. Un 47% (59 de 126) de los pacientes prefirió los CBD, un 33% (42 de 126) prefirió las cápsulas y al resto (25 de 126) le fue indiferente. El valor medio de preferencia en la EVA fue de 5,31 (4,72±5,90), favorable a los CBD aunque sin significación estadística. En general, las diferencias a favor de los CBD se acentuaron en los pacientes de mayor edad. El porcentaje de pacientes libres de pirosis al final de ambas secuencias de tratamiento estuvo alrededor del 75% y no fue distinto entre los que habían empezado con cápsulas o los que habían empezado con CBD. Finalmente, la valoración de preferencia mediante las técnicas de disponibilidad para pagar obtuvo resultados similares, que de nuevo fueron más favorables a los CBD (4,18±6,86 euros frente a 3,47±5,78 euros)(AU)

ConclusiónLas formulaciones farmacéuticas en cápsulas y CBD de lansoprazol tienen una aceptación comparable entre los pacientes con ERGE que presentan disfagia. Sin embargo, y aunque sin potencia suficiente para demostrar significación estadística, se ha observado una clara tendencia hacia la preferencia por los CBD entre los pacientes de mayor edad(AU)

Introduction and objectiveRecently, a new lansoprazole formulation consisting of orally disintegrating tablets has become available, which could improve acceptability and compliance with this type of medication. The aim of the present study was to evaluate preferences in patients with gastroesophageal reflux disease concerning lansoprazole orally disintegrating tablets compared with lansoprazole capsules.Material and methodsA phase IV, multicenter, crossed, open and randomized clinical trial was performed in patients with symptoms of gastroesophageal reflux disease and associated dysphagia. The patients were treated with 30mg lansoprazole capsules for 3 days and with 30mg lansoprazole orally disintegrating tablets for another 3 days. The order of treatment (first capsules followed by orally disintegrating tablets or vice versa) was determined by centralized block randomization. The main measure was the visual analog scale (VAS) score in which patients was asked to rate their degree of preference for the orally disintegrating tablets or the capsules.ResultsOf the 145 patients included, 126 could be evaluated by the protocol. A total of 47% (59/126) of the patients preferred the orally disintegrating tablets, 33% (42/126) preferred the capsules and the remainder (25/126) had no preference. The mean preference value in the VAS was 5.31 (4.72 ± 5.90) in favor of the orally disintegrating tablets, although this difference was not statistically significant. In general, differences in favor of the orally disintegrating tables were more marked in older patients. The percentage of patients free of pyrosis at the end of both treatment sequences was approximately 75% with no differences according to which treatment was administered first. Finally, preference evaluation through willingness to pay techniques showed similar results, again in favor of the orally disintegrating tablets (4.18 € ± 6.86 € vs 3.47 € ± 5.78 €)(AU)

ConclusionThe acceptability of pharmaceutical formulations of lansoprazole in capsules and orally disintegrating tables is similar among patients with gastroesophageal reflux disease and associated dysphagia. However, a clear, but nonsignificant, trend was observed in favor of orally disintegrating tablets among older patients(AU)

[Evaluation of preferences in patients with gastroesophageal reflux disease and dysphagia concerning treatment with lansoprazole orally disintegrating tablets]. / Evaluación de la preferencia de los pacientes con enfermedad por reflujo gastroesofágico y disfagia por el tratamiento con comprimidos bucodispersables de lansoprazol.

INTRODUCTION AND OBJECTIVE: Recently, a new lansoprazole formulation consisting of orally disintegrating tablets has become available, which could improve acceptability and compliance with this type of medication. The aim of the present study was to evaluate preferences in patients with gastroesophageal reflux disease concerning lansoprazole orally disintegrating tablets compared with lansoprazole capsules. MATERIAL AND METHODS: A phase IV, multicenter, crossed, open and randomized clinical trial was performed in patients with symptoms of gastroesophageal reflux disease and associated dysphagia. The patients were treated with 30mg lansoprazole capsules for 3 days and with 30mg lansoprazole orally disintegrating tablets for another 3 days. The order of treatment (first capsules followed by orally disintegrating tablets or vice versa) was determined by centralized block randomization. The main measure was the visual analog scale (VAS) score in which patients was asked to rate their degree of preference for the orally disintegrating tablets or the capsules. RESULTS: Of the 145 patients included, 126 could be evaluated by the protocol. A total of 47% (59/126) of the patients preferred the orally disintegrating tablets, 33% (42/126) preferred the capsules and the remainder (25/126) had no preference. The mean preference value in the VAS was 5.31 (4.72 +/- 5.90) in favor of the orally disintegrating tablets, although this difference was not statistically significant. In general, differences in favor of the orally disintegrating tables were more marked in older patients. The percentage of patients free of pyrosis at the end of both treatment sequences was approximately 75% with no differences according to which treatment was administered first. Finally, preference evaluation through willingness to pay techniques showed similar results, again in favor of the orally disintegrating tablets (4.18 euro +/- 6.86 euro vs 3.47 euro +/- 5.78 euro). CONCLUSION: The acceptability of pharmaceutical formulations of lansoprazole in capsules and orally disintegrating tables is similar among patients with gastroesophageal reflux disease and associated dysphagia. However, a clear, but nonsignificant, trend was observed in favor of orally disintegrating tablets among older patients.