Intravitreal enzyme replacement for inherited retinal diseases.

PURPOSE OF REVIEW: This paper provides an update on intravitreal (IVT) enzyme replacement therapy (ERT) in metabolic retinal diseases; particularly neuronal ceroid lipofuscinosis type 2 (CLN2) also known as Batten disease. RECENT FINDINGS: ERT is being explored in CLN2 related Batten disease, a fatal neurodegenerative condition associated with retinopathy and blindness that is caused by the deficiency of lysosomal enzyme TPP1. Cerliponase alfa, a recombinant human tripeptidyl-peptidase1 (rhTPP1) administered by intraventricular infusions has been demonstrated to slow the rate of neurodegenerative decline but not retinopathy. A preclinical study of IVT rhTPP1 in a CLN2 canine model demonstrated efficacy in preserving retinal function and retinal morphology shown on histology. More recently, intravitreal (IVT) administration of rhTPP1 was reported in a first-in-human compassionate use study. Patients received 12-18 months of 8-weekly IVT ERT (0.2 mg rhTPP-1 in 0.05 ml) in one eye. No significant ocular adverse reactions were reported. Treatment decreased the rate of retinal thinning but modestly. SUMMARY: The evidence suggests that IVT ERT with rhTPP1 may be a safe and effective treatment for CLN2 retinopathy. However, the optimal dosage and frequency to achieve the best possible outcomes requires further investigation as does patient selection.

Germline heterozygous exons 8-11 pathogenic BARD1 gene deletion reported for the first time in a family with suspicion of a hereditary colorectal cancer syndrome: more than an incidental finding?

BACKGROUND: Colorectal cancer (CRC) is a highly prevalent disease in developed countries. Inherited Mendelian causes account for approximately 5% of CRC cases, with Lynch syndrome and familial adenomatous polyposis being the most prevalent forms. Scientific efforts are focused on the discovery of new candidate genes associated with CRC and new associations of phenotypes with well-established cancer-related genes. BRCA1-associated ring domain (BARD1) gene deleterious germline variants are associated with a moderate increase in the relative risk of breast cancer, but their association with other neoplasms, such as CRC, remains unclear. CASE PRESENTATION: We present the case of a 49-year-old male diagnosed with rectal adenocarcinoma whose maternal family fulfilled Amsterdam clinical criteria for Lynch syndrome. Genetic test confirmed the presence in heterozygosis of a germline pathogenic deletion of exons 8-11 in BARD1 gene. The predictive genetic study of the family revealed the presence of this pathogenic variant in his deceased cancer affected relatives, confirming co-segregation of the deletion with the disease. CONCLUSIONS: To the best of our knowledge, this is the first published work in which this BARD1 deletion is detected in a family with familial colorectal cancer type X (FCCTX) syndrome, in which the clinical criteria for Lynch syndrome without alteration of the DNA mismatch repair (MMR) system are fulfilled. Whether this incidental germline finding is the cause of familial colorectal aggregation remains to be elucidated in scientific forums. Patients should be carefully assessed in specific cancer genetic counseling units to account for hypothetical casual findings in other genes, in principle unrelated to the initial clinical suspicion, but with potential impact on their health.

Foveal Hypoplasia in CRB1-Related Retinopathies.

The CRB1 gene plays a role in retinal development and its maintenance. When disrupted, it gives a range of phenotypes such as early-onset severe retinal dystrophy/Leber congenital amaurosis (EOSRD/LCA), retinitis pigmentosa (RP), cone-rod dystrophy (CORD) and macular dystrophy (MD). Studies in CRB1 retinopathies have shown thickening and coarse lamination of retinal layers resembling an immature retina. Its role in foveal development has not yet been described; however, this retrospective study is the first to report foveal hypoplasia (FH) presence in a CRB1-related retinopathy cohort. Patients with pathogenic biallelic CRB1 variants from Moorfields Eye Hospital, London, UK, were collected. Demographic, clinical data and SD-OCT analyses with FH structural grading were performed. A total of 15 (48%) patients had EOSRD/LCA, 11 (35%) MD, 3 (9%) CORD and 2 (6%) RP. FH was observed in 20 (65%; CI: 0.47-0.79) patients, all of whom were grade 1. A significant difference in BCVA between patients with FH and without was found (p = 0.014). BCVA continued to worsen over time in both groups (p < 0.001), irrespective of FH. This study reports FH in a CRB1 cohort, supporting the role of CRB1 in foveal development. FH was associated with poorer BCVA and abnormal retinal morphology. Nonetheless, its presence did not alter the disease progression.

Working Memory Impairment as an Endophenotypic Marker in Patients with Schizophrenia: Failures in Encoding or Maintenance?

INTRODUCTION: Although working memory (WM) dysfunction has been proposed as a schizophrenia (SZ) endophenotype, the specific impaired component (encoding or maintenance) in patients and unaffected relatives remains inconclusive. We compared auditory-verbal and visuospatial WM in patients with SZ, unaffected siblings (USs), and healthy controls under 2 response conditions: immediate (encoding condition) and delayed (maintenance condition). METHODS: We included 22 participants per group, similar in age and gender. Three WM tests (Spatial Span, Backward Digit Span, and Letter-Number Span) were administered under both conditions in a counterbalanced manner to all participants. RESULTS: Poorer performance was found in the SZ group for all tests (p < 0.001). USs showed a better performance than patients, but worse than controls (p < 0.05), except for the Backward Digit Span test, in which their performance was similar to that of the SZ group. The effect of the delayed response in all tasks was not significant in any group. CONCLUSION: Our results indicate that WM impairment, including auditory-verbal and visuospatial modalities, corresponds to a stable feature of the disease as it is present in USs, thus confirming its potential endophenotypic property in SZ patients. No effect of the delayed response was observed, suggesting failures in encoding in both patients and USs.

Double-bellied medial rectus muscle in a patient with Down syndrome and congenital esotropia.

A 13-year-old male with Down syndrome, pseudophakic secondary to congenital cataract presented with esotropia. During bilateral medial rectus recession, a unilateral two-bellied right medial rectus was identified and recessed successfully with complete resolution of the deviation. Clinicians facing a two-bellied medial rectus can consider continuing with their surgical plan.

Cost-effectiveness of strategies to increase screening coverage for cervical cancer in Spain: the CRIVERVA study.

BACKGROUND: The aim of the study is to carry out a cost-effectiveness analysis of three different interventions to promote the uptake of screening for cervical cancer in general practice in the county of Valles Occidental, Barcelona, Spain. METHODS: Women aged from 30 to 70 years (n = 15,965) were asked to attend a general practice to be screened. They were randomly allocated to one of four groups: no intervention group (NIG); one group where women received an invitation letter to participate in the screening (IG1); one group where women received an invitation letter and informative leaflet (IG2); and one group where women received an invitation letter, an informative leaflet and a phone call reminder (IG3). Clinical effectiveness was measured as the percentage increase in screening coverage. A cost-effectiveness analysis was performed from the perspective of the public health system with a time horizon of three to five years - the duration of the randomised controlled clinical trial. In addition, a deterministic sensitivity analysis was performed. Results are presented according to different age groups. RESULTS: The incremental cost-effectiveness ratio (ICER) for the most cost-effective intervention, IG1, compared with opportunistic screening was € 2.78 per 1% increase in the screening coverage. The age interval with the worst results in terms of efficiency was women aged < 40 years. CONCLUSIONS: In a population like Catalonia, with around 2 million women aged 30 to 70 years and assuming that 40% of these women were not attending general practice to be screened for cervical cancer, the implementation of an intervention to increase screening coverage which consists of sending a letter would cost on average less than € 490 for every 1000 women. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01373723 .

Geographical analysis of the sporadic Creutzfeldt-Jakob disease distribution in the autonomous community of the Basque Country for the period 1995-2008.

BACKGROUND: The Basque Country, in Spain, shows one of the highest sporadic Creutzfeldt-Jakob disease (sCJD) incidence rates in Europe. The purpose is to analyse a possible focus of unidentified external or environmental factors which could trigger the high incidence rates of sCJD in the Basque Country. METHODS: We estimated the relative risk and the posterior relative risk distribution of sCJD cases for each town of the Basque Country and for the period 1995-2008. RESULTS: 58 sCJD cases (44 definite and 14 probable) were selected for the geographic cluster analysis. In a first approach, referring to the relative risk, several municipalities in the Autonomous Community of the Basque Country showed more sCJD cases than expected. However, the posterior relative risk distribution showed no excess risk areas. CONCLUSIONS: RESULTS from this survey indicate that a possible common source of development of the disease does not seem to be the reason of the high sCJD incidence.

Enhanced Learning and Memory in Patients with CRB1 Retinopathy.

Mutations in the CRB1 gene are associated with a diverse spectrum of retinopathies with phenotypic variability causing severe visual impairment. The CRB1 gene has a role in retinal development and is expressed in the cerebral cortex and hippocampus, but its role in cognition has not been described before. This study compares cognitive function in CRB1 retinopathy individuals with subjects with other retinopathies and the normal population. METHODS: Neuropsychological tests of cognitive function were used to test individuals with CRB1 and non-CRB1 retinopathies and compare results with a standardised normative dataset. RESULTS: CRB1 retinopathy subjects significantly outperformed those with non-CRB1 retinopathy in list learning tasks of immediate (p = 0.001) and delayed memory (p = 0.007), tests of semantic verbal fluency (p = 0.017), verbal IQ digit span subtest (p = 0.037), and estimation test of higher execution function (p = 0.020) but not in the remaining tests of cognitive function (p > 0.05). CRB1 retinopathy subjects scored significantly higher than the normal population in all areas of memory testing (p < 0.05) and overall verbal IQ tests (p = 0.0012). Non-CRB1 retinopathy subjects scored significantly higher than the normal population in story recall, verbal fluency, and overall verbal IQ tests (p = 0.0016). CONCLUSIONS: Subjects with CRB1 retinopathy may have enhanced cognitive function in areas of memory and learning. Further work is required to understand the role of CRB1 in cognition.

Longitudinal Changes of Retinal Structure in Molecularly Confirmed C1QTNF5 Patients With Late-Onset Retinal Degeneration.

Purpose: The purpose of this study was to present our findings on the natural history of late-onset retinal degeneration (LORD) in patients with molecularly confirmed C1QTNF5 heterozygous pathogenic variants and assess suitability of retinal structure parameters for disease monitoring. Methods: Sixteen patients with C1QTNF5-LORD were retrospectively identified from Moorfields Eye Hospital, UK. Fundus autofluorescence (FAF), optical coherence tomography (OCT) scans, and best-corrected visual acuity (BCVA) were collected. Area of atrophy (AA) was manually drawn in FAF images. Ellipsoid zone (EZ) width and foveal retinal thickness of the whole retina and outer retina were extracted from OCT scans. Age-related changes were tested with linear-mixed models. Results: Patients had median age of 62.3 years (interquartile range [IQR] = 58.8-65.4 years) at baseline, and median follow-up of 5.1 years (IQR = 2.6-7.6 years). AA, EZ width, and retinal thickness parameters remained unchanged until age 50 years, but showed significant change with age thereafter (all P < 0.0001). AA and EZ width progressed rapidly (dynamic range normalized rates = 4.3-4.5%/year) from age 53.9 and 50.8 years (estimated inflection points), respectively. Retinal thickness parameters showed slower progression rates (range = 1.6-2.5%/year) from age 60 to 62.3. BCVA (median = 0.3 LogMAR, IQR = 0.0-1.0 at baseline) showed a rapid decline (3.3%) from age 70 years. Findings from patients with earlier disease showed FAF atrophy manifests in the temporal retina initially, and then progresses nasally. Conclusions: Patients with LORD remained asymptomatic until age 50 years, before suffering rapid outer retinal degeneration. EZ width and AA showed rapid progression and high interocular correlation, representing promising outcome metrics. Clinical measures also capturing the temporal retina may be preferable, enabling earlier detection and better disease monitoring. Translational Relevance: Area of atrophy in FAF images and OCT-measured EZ width represent promising outcome metrics for disease monitoring in patients with C1QTNF5-LORD.

A novel form of human disease with a protease-sensitive prion protein and heterozygosity methionine/valine at codon 129: Case report.

BACKGROUND: Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare neurodegenerative disorder in humans included in the group of Transmissible Spongiform Encephalopathies or prion diseases. The vast majority of sCJD cases are molecularly classified according to the abnormal prion protein (PrPSc) conformations along with polymorphism of codon 129 of the PRNP gene. Recently, a novel human disease, termed "protease-sensitive prionopathy", has been described. This disease shows a distinct clinical and neuropathological phenotype and it is associated to an abnormal prion protein more sensitive to protease digestion. CASE PRESENTATION: We report the case of a 75-year-old-man who developed a clinical course and presented pathologic lesions compatible with sporadic Creutzfeldt-Jakob disease, and biochemical findings reminiscent of "protease-sensitive prionopathy". Neuropathological examinations revealed spongiform change mainly affecting the cerebral cortex, putamen/globus pallidus and thalamus, accompanied by mild astrocytosis and microgliosis, with slight involvement of the cerebellum. Confluent vacuoles were absent. Diffuse synaptic PrP deposits in these regions were largely removed following proteinase treatment. PrP deposition, as revealed with 3F4 and 1E4 antibodies, was markedly sensitive to pre-treatment with proteinase K. Molecular analysis of PrPSc showed an abnormal prion protein more sensitive to proteinase K digestion, with a five-band pattern of 28, 24, 21, 19, and 16 kDa, and three aglycosylated isoforms of 19, 16 and 6 kDa. This PrPSc was estimated to be 80% susceptible to digestion while the pathogenic prion protein associated with classical forms of sporadic Creutzfeldt-Jakob disease were only 2% (type VV2) and 23% (type MM1) susceptible. No mutations in the PRNP gene were found and genotype for codon 129 was heterozygous methionine/valine. CONCLUSIONS: A novel form of human disease with abnormal prion protein sensitive to protease and MV at codon 129 was described. Although clinical signs were compatible with sporadic Creutzfeldt-Jakob disease, the molecular subtype with the abnormal prion protein isoforms showing enhanced protease sensitivity was reminiscent of the "protease-sensitive prionopathy". It remains to be established whether the differences found between the latter and this case are due to the polymorphism at codon 129. Different degrees of proteinase K susceptibility were easily determined with the chemical polymer detection system which could help to detect proteinase-susceptible pathologic prion protein in diseases other than the classical ones.

Atypical/Nor98 scrapie in the Basque Country: a case report of eight outbreaks.

BACKGROUND: Since 2002, an active surveillance program for transmissible spongiform encephalopathy in small ruminants in European Union countries allowed identification of a considerable number of atypical cases with similarities to the previously identified atypical scrapie cases termed Nor98. CASE PRESENTATION: Here we report molecular and neuropathological features of eight atypical/Nor98 scrapie cases detected between 2002 and 2009. Significant features of the affected sheep included: their relatively high ages (mean age 7.9 years, range between 4.3 and 12.8), their breed (all Latxa) and their PRNP genotypes (AFRQ/ALRQ, ALRR/ALRQ, AFRQ/AFRQ, AFRQ/AHQ, ALRQ/ALRH, ALRQ/ALRQ). All the sheep were confirmed as atypical scrapie by immunohistochemistry and immunoblotting. Two cases presented more PrP immunolabelling in cerebral cortex than in cerebellum. CONCLUSIONS: This work indicates that atypical scrapie constitutes the most common small ruminant transmissible spongiform encephalopathy form in Latxa sheep in the Spanish Basque Country. Moreover, a new genotype (ALRQ/ALRH) was found associated to atypical scrapie.

Molecular evidence of founder effects of fatal familial insomnia through SNP haplotypes around the D178N mutation.

This work presents a detailed investigation of the genomic region surrounding the PRNP gene in a sample of patients diagnosed with fatal familial insomnia (FFI) from several European countries, notably Spain. The main focus of the study was to explore the origins of the chromosomes carrying the D178N mutation by designing a single-nucleotide polymorphism (SNP) haplotype around the PRNP gene. Haplotypes were constructed by genotyping six SNPs (rs2756271, rs13040327, rs6037932, rs13045348, rs6116474, and rs6116475) in 25 FFI patients from all over Spain. To augment the geographical scope of our study, 13 further FFI cases from Germany (9) and Italy (4) were also examined. Genotyping of SNPs in conjunction with the analysis of genealogical data for a group of FFI patients revealed the existence of two distinct haplotypes potentially associated with the D178N mutation. Of them, GCATTA-M proved to be the common haplotype of Spanish patients, whereas ACATTA-M was typical of the German cases. It is interesting to note that both haplotypes were identified in the Italian samples: GCATTA-M in a family from the Tuscany region and ACATTA-M in a family from the Veneto region. Our findings suggest the occurrence of two independent D178N-129M mutational events in Europe, preserved and transmitted from one generation to the next until nowadays. Likewise, results based on the analysis of SNP data indicate that previous hypotheses postulating that the D178N mutation had independent origins for each family and that its global distribution was determined by recurrent mutational events must be regarded with caution.

5-Hydroxytryptamine 6 receptor (5-HT(6)) receptor and apolipoprotein E (ApoE) polymorphisms in patients with Alzheimer's disease in the Basque Country.

Although there is considerable evidence implicating apolipoprotein E (ApoE) epsilon4 in the development of the Alzheimer's disease (AD), additional factors are also known to be involved. Thus, an association has been described between C267T polymorphism of the 5-hydroxytryptamine 6 receptor (5-HT(6)) receptor gene and AD. This case-control study analyzes the ApoE and 5-HT(6) receptor polymorphisms in 173 cases and 102 age and sex matched controls from Araba and Bizkaia (The Basque Country, Spain). The analysis of ApoE showed the frequencies of epsilon4 allele to be significantly higher in AD patients (0.292) than in the controls (0.083). When 5-HT(6) receptor polymorphism was analyzed, a greater frequency of 267C allele was observed in AD patients than in controls, though the difference was not statistically significant. Likewise regarding ApoE epsilon4 status, no statistically significant difference was observed. In conclusion, the association of ApoE epsilon4 to AD in a sample of patients from the Basque Country is confirmed, though the association to C267T polymorphism of the 5-HT(6) receptor has not been observed.

Coexistence of protease sensitive and resistant prion protein in 129VV homozygous sporadic Creutzfeldt-Jakob disease: a case report.

INTRODUCTION: The coexistence of different molecular types of classical protease-resistant prion protein in the same individual have been described, however, the simultaneous finding of these with the recently described protease-sensitive variant or variably protease-sensitive prionopathy has, to the best of our knowledge, not yet been reported. CASE PRESENTATION: A 74-year-old Caucasian woman showed a sporadic Creutzfeldt-Jakob disease clinical phenotype with reactive depression, followed by cognitive impairment, akinetic-rigid Parkinsonism with pseudobulbar syndrome and gait impairment with motor apraxia, visuospatial disorientation, and evident frontal dysfunction features such as grasping, palmomental reflex and brisk perioral reflexes. She died at age 77.Neuropathological findings showed: spongiform change in the patient's cerebral cortex, striatum, thalamus and molecular layer of the cerebellum with proteinase K-sensitive synaptic-like, dot-like or target-like prion protein deposition in the cortex, thalamus and striatum; proteinase K-resistant prion protein in the same regions; and elongated plaque-like proteinase K-resistant prion protein in the molecular layer of the cerebellum. Molecular analysis of prion protein after proteinase K digestion revealed decreased signal intensity in immunoblot, a ladder-like protein pattern, and a 71% reduction of PrPSc signal relative to non-digested material. Her cerebellum showed a 2A prion protein type largely resistant to proteinase K. Genotype of polymorphism at codon 129 was valine homozygous. CONCLUSION: Molecular typing of prion protein along with clinical and neuropathological data revealed, to the best of our knowledge, the first case of the coexistence of different protease-sensitive prion proteins in the same patient in a rare case that did not fulfill the current clinical diagnostic criteria for either probable or possible sporadic Creutzfeldt-Jakob disease. This highlights the importance of molecular analyses of several brain regions in order to correctly diagnose rare and atypical prionopathies.

Validation of the Minnesota living with heart failure questionnaire in primary care.

INTRODUCTION AND OBJECTIVES: To evaluate the applicability, internal consistency and validity of the Minnesota Living with Heart Failure Questionnaire (MLHFQ) when used in primary care, compared with the Short Form-36 (SF-36) health survey. METHODS: The two questionnaires were administered to 589 patients with chronic heart failure who were registered with 97 primary care physicians. The applicability, internal consistency and validity of the MLHFQ were evaluated and comparisons were made with the SF-36. RESULTS: More than 90% of patients completed the questionnaires. The percentage of uncompleted items was low. Cronbach's alpha ranged from 0.79 to 0.94 for the various MLHFQ dimensions. Exploratory factorial analysis identified two factors that explained 65.8% of the variance. Moderate to good correlations were observed between similar dimensions of the MLHFQ and SF-36 (correlation coefficient -0.43 to -0.73). There were significant associations between scores on the MLHFQ and clinical measures of disease severity. CONCLUSIONS: When used in primary care, the MLHFQ had a high level of acceptability and good psychometric properties compared with the SF-36. Consequently, it would be useful for assessing health-related quality of life in patients with chronic heart failure.

A novel PRNP Y218N mutation in Gerstmann-Sträussler-Scheinker disease with neurofibrillary degeneration.

Gerstmann-Sträussler-Scheinker (GSS) disease is a prion disease associated with prion protein gene (PRNP) mutations. We report a novel PRNP mutation (Y218N) associated with GSS disease in a pathologically confirmed case and in two other affected family members. The clinical features of these cases met criteria for possible Alzheimer disease and possible frontotemporal dementia. Neuropathologic analysis revealed deposition of proteinase K-resistant prion protein (PrP(res)), widespread hyperphosphorylated tau pathology, abnormal accumulation of mitochondria in the vicinity of PrP deposits, and expression of mutant ubiquitin (UBB(+1)) in neurofibrillary tangles and dystrophic neurites. Prion protein immunoblotting using 3F4 and 1E4 antibodies disclosed multiple bands ranging from approximately 20 kd to 80 kd and lower bands of 15 kd and approximately 10 kd, the latter only seen after a long incubation. These bands were partially resistant to proteinase K pretreatment. This pattern differs from those seen in Creutzfeldt-Jakob disease andresembles those reported in other GSS cases. The approximately 10kd band was recognized with anti-PrP C-terminus antibodies but not with anti-N terminus antibodies, suggesting PrP truncation at the N terminal. This new mutation extends the list of known mutations responsible for GSS disease and reinforces its clinical heterogeneity. Genetic examination of the PRNP gene should be included in the workup of patients with poorly classifiable dementia.

Ancestral origins of the prion protein gene D178N mutation in the Basque Country.

Fatal familial insomnia (FFI) and familial Creutzfeldt-Jakob disease (fCJD) are familial prion diseases with autosomal dominant inheritance of the D178N mutation. FFI has been reported in at least 27 pedigrees around the world. Twelve apparently unrelated FFI and fCJD pedigrees with the characteristic D178N mutation have been reported in the Prion Diseases Registry of the Basque Country since 1993. The high incidence of familial prion diseases in this region may reflect a unique ancestral origin of the chromosome carrying this mutation. In order to investigate this putative founder effect, we developed "happy typing", a new approach to the happy mapping method, which consists of the physical isolation of large haploid genomic DNA fragments and their analysis by the Polymerase Chain Reaction in order to perform haplotypic analysis instead of pedigree analysis. Six novel microsatellite markers, located in a 150-kb genomic segment flanking the PRNP gene were characterized for typing haploid DNA fragments of 285 kb in size. A common haplotype was found in patients from the Basque region, strongly suggesting a founder effect. We propose that "happy typing" constitutes an efficient method for determining disease-associated haplotypes, since the analysis of a single affected individual per pedigree should provide sufficient evidence.

Validación del Minnesota Living With Heart Failure Questionnaire en atención primaria / Validation of the Minnesota Living With Heart Failure Questionnaire in primary care

Introducción y objetivos. Evaluar la aplicabilidad, la consistencia interna y la validez del Minnesota Living with Heart Failure Questionnaire (MLHFQ) en atención primaria, comparándolo con el Short-Form Health Survey (SF-36). Métodos. Se aplicaron ambos cuestionarios a 589 pacientes con insuficiencia cardiaca crónica documentada atendidos por médicos de atención primaria. Analizamos la factibilidad, la consistencia interna y la validez del MLHFQ comparado con el SF-36. Resultados. Respondió los cuestionarios más del 90% de la muestra. El porcentaje de ítems no respondido es bajo. El coeficiente alfa de Cronbach oscila entre 0,79 y 0,94 para las dimensiones del MLHFQ. Del análisis factorial exploratorio, se extraen dos factores que explican una varianza total del 65,8%. Los coeficientes de correlación entre dimensiones similares del MLHFQ y el SF-36 fueron de moderados a altos (–0,43 a –0,73). Las puntuaciones del MLHFQ se asocian significativamente con variables clínicas de gravedad. Conclusiones. En atención primaria el MLHFQ, comparado con el SF-36, muestra buena aceptabilidad y buenas propiedades psicométricas que lo hacen útil para medir la calidad de vida relacionada con la salud en pacientes con insuficiencia cardiaca crónica (AU)

Introduction and objectives. To evaluate the applicability, internal consistency and validity of the Minnesota Living with Heart Failure Questionnaire (MLHFQ) when used in primary care, compared with the Short Form-36 (SF-36) health survey. Methods. The two questionnaires were administered to 589 patients with chronic heart failure who were registered with 97 primary care physicians. The applicability, internal consistency and validity of the MLHFQ were evaluated and comparisons were made with the SF-36. Results. More than 90% of patients completed the questionnaires. The percentage of uncompleted items was low. Cronbach’s alpha ranged from 0.79 to 0.94 for the various MLHFQ dimensions. Exploratory factorial analysis identified two factors that explained 65.8% of the variance. Moderate to good correlations were observed between similar dimensions of the MLHFQ and SF- 36 (correlation coefficient –0.43 to –0.73). There were significant associations between scores on the MLHFQ and clinical measures of disease severity. Conclusions. When used in primary care, the MLHFQ had a high level of acceptability and good psychometric properties compared with the SF-36. Consequently, it would be useful for assessing health-related quality of life in patients with chronic heart failure (AU)