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Josep Garre-Olmo,1–3 Anna Ponjoan,1,4–5 José Maria Inoriza,6,7 Jordi Blanch,4 Inma Sánchez-Pérez,6 Rafel Cubí,4 Rosa de Eugenio,7 Oriol Turró-Garriga,1,2 Joan Vilalta-Franch On behalf of the Registry of Dementia of Girona Study Group (ReDeGi Study Group)11Research Group on Ageing, Disability and Health, Girona Biomedical Research Institute (IDIBGI), Catalonia, Spain; 2Registry of Dementia of Girona, Health Assistance Institute, Catalonia, Spain; 3Department of Medical Sciences, School of Medicine, University of Girona, Catalonia, Spain; 4Vascular Health Research Group (ISV-Girona), Foundation University Institute for Primary Health Care Research Jordi Gol I Gurina, Catalonia, Spain; 5Autonomous University of Barcelona, Catalonia, Spain; 6Research Group on Health Services and Health Outcomes (GRESSIRES), Integrated Health Services Baix Empordà (SSIBE), Catalonia, Spain; 7Hospital de Palamós, Integrated Health Services Baix Empordà (SSIBE), Catalonia, SpainBackground: Knowledge on survival after diagnosis is important for all stakeholders. We aimed to estimate the survival and life expectancy after a dementia diagnosis, and to quantify the impact of dementia subtypes on mortality.Methods: Retrospective matched cohort study using a linkage between a dementia-specific registry and two primary care electronic medical records databases. Between 1 January 2007 and 31 December 2015 there were 5,156 subjects aged 60 years and over registered by the Registry of Dementia of Girona and matched to 15,468 age-sex and comorbidity individuals without dementia attended by general practitioners in the province of Girona (Catalonia, Spain).Results: The median survival was 5.2 years (95% CI 5.0 to 5.4), the median life expectancy was 74.7 years (95% CI 71.9 to 76.5), and there were differences by gender. The mortality rate was 127.1 per 1,000 person-years (95% CI 121.6 to 132.7), and the hazard ratio for mortality in persons with dementia ranged between 1.63 (95% CI 1.52 to 1.76) for Alzheimer’s disease and 2.52 (95% CI 1.90 to 3.35) for Parkinson-plus syndromes. There was one death per year attributable to dementia for every 18.6 persons with dementia, and for every 2.4 persons with dementia who die, one death was attributable to dementia.Conclusion: The prognosis after dementia diagnosis is conditioned by demographic and clinical features. Although survival is larger for women, they also experience a higher number of years of life lost. Parkinson-plus syndromes and dementia due to multiple etiologies are among the most malignant subtypes regarding mortality.Keywords: epidemiology, diagnosis, dementia, mortality

Anna Ponjoan,1–3 Josep Garre-Olmo,3 Jordi Blanch,1 Ester Fages,1,4 Lia Alves-Cabratosa,1 Ruth Martí-Lluch,1–3 Marc Comas-Cufí,1 Dídac Parramon,1,4 María García-Gil,1 Rafel Ramos1,51Vascular Health Research Group (ISV-Girona), Jordi Gol Institute for Primary Care Research (IDIAPJGol), Barcelona, Catalonia, Spain; 2Universitat Autònoma de Barcelona, Bellaterra, Catalonia, Spain; 3Girona Biomedical Research Institute (IDIBGI), Girona, Catalonia, Spain; 4Primary Care Services, Catalan Health Institute (ICS), Girona, Catalonia, Spain; 5Department of Medical Sciences, School of Medicine, Campus Salut, University of Girona, Girona, Catalonia, SpainBackground: Electronic health records (EHR) from primary care are emerging in Alzheimer’s disease (AD) research, but their accuracy is a concern. We aimed to validate AD diagnoses from primary care using additional information provided by general practitioners (GPs), and a register of dementias.Patients and methods: This retrospective observational study obtained data from the System for the Development of Research in Primary Care (SIDIAP). Three algorithms combined International Statistical Classification of Diseases (ICD-10) and Anatomical Therapeutic Chemical codes to identify AD cases in SIDIAP. GPs evaluated dementia diagnoses by means of an online survey. We linked data from the Register of Dementias of Girona and from SIDIAP. We estimated the positive predictive value (PPV) and sensitivity and provided results stratified by age, sex and severity.Results: Using survey data from the GPs, PPV of AD diagnosis was 89.8% (95% CI: 84.7–94.9). Using the dataset linkage, PPV was 74.8 (95% CI: 73.1–76.4) for algorithm A1 (AD diagnoses), and 72.3 (95% CI: 70.7–73.9) for algorithm A3 (diagnosed or treated patients without previous conditions); sensitivity was 71.4 (95% CI: 69.6–73.0) and 83.3 (95% CI: 81.8–84.6) for algorithms A1 (AD diagnoses) and A3, respectively. Stratified results did not differ by age, but PPV and sensitivity estimates decreased amongst men and severe patients, respectively.Conclusions: PPV estimates differed depending on the gold standard. The development of algorithms integrating diagnoses and treatment of dementia improved the AD case ascertainment. PPV and sensitivity estimates were high and indicated that AD codes recorded in a large primary care database were sufficiently accurate for research purposes.Keywords: dementia, family physician, survey, algorithm, data accuracy, real-world data, validation, electronic medical records

Anna Ponjoan,1–3 Josep Garre-Olmo,2 Jordi Blanch,1 Ester Fages,1 Lia Alves-Cabratosa,1 Ruth Martí-Lluch,1–3 Marc Comas-Cufí,1 Dídac Parramon,1,4 María Garcia-Gil,1 Rafel Ramos1,5 1Vascular Health Research Group (ISV-Girona), Jordi Gol Institute for Primary Care Research (IDIAPJGol), Barcelona, Catalonia, Spain; 2Girona Biomedical Research Institute (IDIBGI), Girona, Catalonia, Spain; 3Santa Clara Primary Care Health Center, Catalan Health Institute, Girona, Catalonia, Spain; 4Autonomous University of Barcelona, Bellaterra (Cerdanyola del Vallès), Catalonia, Spain; 5Department of Medical Sciences, School of Medicine, Campus Salut, University of Girona, Girona, Catalonia, Spain Purpose: Updated estimates of incidence and prevalence of dementia are crucial to ensure adequate public health policy. However, most of the epidemiological studies in the population in Spain were conducted before 2010. This study assessed the validity of dementia diagnoses recorded in electronic health records contained in a large primary-care database to determine if they could be used for research purposes. Then, to update the epidemiology of dementia in Catalonia (Spain), we estimated crude and standardized prevalence and incidence rates of dementia in Catalonia in 2016. Methods: The System for the Development of Research in Primary Care (SIDIAP) database contains anonymized information for >80% of the Catalan population. Validity of dementia codes in SIDIAP was assessed in patients at least 40 years old by asking general practitioners for additional evidence to support the diagnosis. Crude and standardized incidence and prevalence (95% CI) in people aged ≥65 years were estimated assuming a Poisson distribution. Results: The positive predictive value of dementia diagnoses recorded in SIDIAP was estimated as 91.0% (95% CI 87.5%–94.5%). Age- and sex-standardized incidence and prevalence of dementia were 8.6/1,000 person-years (95% CI 8.0–9.3) and 5.1% (95% CI 4.5%–5.7%), respectively. Conclusion: SIDIAP contains valid dementia records. We observed incidence and prevalence estimations similar to recent face-to-face studies conducted in Spain and higher than studies using electronic health data from other European populations. Keywords: family physician, accuracy, quality, positive predictive value, electronic medical record, real-world data

Objetivos: Alcanzar un consenso sobre los circuitos de atención médica de la paciente con osteoporosis postmenopáusica (OPM), incluyendo los circuitos de derivación y manejo (herramientas de evaluación y pruebas médicas), identificando perfiles de acuerdo con la opinión de expertos en metabolismo óseo pertenecientes al Sistema de Salud Español. Material y métodos: Se empleó la técnica Delphi con dos rondas de consulta sucesivas. Participaron 38 expertos en el manejo de OPM pertenecientes a 14 sociedades científicas. La revisión de la literatura y la opinión del comité científico nutrieron el cuestionario. Los expertos expresaron su “deseo” (1=rechazo total; 9=deseo más fuerte) y “pronóstico” (1=no ocurrirá en absoluto; 9=ocurrirá con máxima probabilidad) acerca de las cuestiones planteadas. Se alcanzó consenso cuando el 75% o más de los participantes puntuaron 1-3 (desacuerdo) o 7-9 (acuerdo). Adicionalmente, los expertos se dividieron en 3 grupos de discusión para complementar la información según los perfiles de pacientes previamente hallados en el método Delphi. Resultados: Se alcanzó consenso en el 75% de las preguntas. Los expertos establecieron tres perfiles de pacientes con OPM: sin fractura, con fractura vertebral y con fractura no vertebral, así como los recursos diagnósticos y terapéuticos que conviene emplear en estas pacientes. La paciente sin fractura debería ser manejada por Atención Primaria o Reumatología y se utilizarán escalas para valorar el riesgo de fractura en fases tempranas de la enfermedad. La paciente con fractura vertebral crónica debería referirse a Reumatología y Rehabilitación, y se derivará a Reumatología; mientras que la paciente con fractura vertebral aguda debería ser tratada por Cirugía Ortopédica, y así es como posiblemente ocurrirá. El diagnóstico de la paciente con fractura vertebral estará basado principalmente en la radiografía. Para la evaluación de la progresión se deberían utilizar cuestionarios sobre la capacidad funcional y escalas del dolor. Sin embargo, no se utilizarán en la práctica habitual debido a la falta de tiempo. La paciente con fractura no vertebral debería ser y será referida a Cirugía Ortopédica, recomendando realizar 3-4 radiografías anuales para asegurar la consolidación de la fractura. Conclusiones: Los resultados del método Delphi muestran los circuitos de derivación de la paciente con OPM, que se concentran en Atención Primaria y Reumatología, cuando no existe fractura, y Cirugía Ortopédica, en caso de fractura.

Inroducción: La adherencia al tratamiento oral del paciente con osteoporosis es baja, con un alto porcentaje de abandonos durante el primer año. La consecuencia más notable es la falta de respuesta terapéutica.Objetivo: Conocer la percepción de los facultativos involucrados en el abordaje del paciente osteoporótico en relación a la adherencia terapéutica de estos pacientes. Material y métodos: Estudio descriptivo transversal realizado mediante una encuesta de opinión dirigida a médicos de Atención Primaria y Atención Especializada involucrados en el tratamiento de la osteoporosis. Los participantes fueron seleccionados mediante muestreo intencionado. Resultados: El cuestionario fue contestado por 235 especialistas de Reumatología (54,5%), Traumatología (10,6%) y Atención Primaria (18,7%). En opinión del 43,8% de los encuentados, más de un 25% de los pacientes olvida alguna vez tomar el tratamiento. Según el 34,9%, más de 75% de los pacientes están concienciados con el tratamiento. Los efectos secundarios y la complejidad de la administración son las razones mayoritarias que propician un cambio de medicación, con una importancia media de 7,94±2,06 y 6±2,01 puntos respectivamente en una escala 0-10. Conclusiones: Los facultativos percibieron baja adherencia terapéutica asociada fundamentalmente a los efectos secundarios, a la polimedicación y a la falta de comunicación entre profesionales. Espaciar la dosificación y el uso de formas galénicas solubles podrían ser opciones para facilitar la adherencia del paciente al tratamiento con bisfosfonatos orales. Mejorar la educación sobre la importancia de la enfermedad o aumentar el seguimiento del paciente serían algunos de los aspectos que podrían favorecer la adherencia terapéutica.

Introducción: La lactulosa es un oligosacárido ampliamente utilizado como laxante, entre otros usos, que ha demostrado aumentar la absorción intestinal de calcio, por lo que potencialmente podría tener un efecto beneficioso sobre la masa ósea y podría permitir reducir las dosis habituales de calcio, evitando sus efectos secundarios. Objetivos: Se presentan los resultados de un estudio piloto aleatorizado, doble ciego, doble simulación, multicéntrico, cuyo objetivo fue valorar si la adición de lactulosa a 500 mg de calcio y 400 UI de vitamina D durante 12 meses contribuía a mantener la densidad mineral ósea (DMO) en mujeres postmenopáusicas con osteopenia frente a la dosis de 1.000 mg/día de calcio y un mismo suplemento de vitamina D. Material y métodos: Las mujeres del grupo de lactulosa (n=19) tomaron 15 mL/día de lactulosa (equivalente a 10,05 g), 400 UI/día de vitamina D3 y 500 mg/día de carbonato de calcio y 500 mg/día de placebo de calcio, mientras que a las mujeres del grupo placebo (n=22) se les administró lactulosa placebo, 400 UI/día de vitamina D3 y 1.000 mg/día de carbonato de calcio. Los valores iniciales de la ingesta diaria de calcio fueron similares en ambos grupos. Se utilizó un modelo general de regresión lineal para valorar las diferencias finales en comparación con los valores iniciales de la DMO en ambos grupos de estudio. Resultados: Las diferencias de la DMO entre el grupo de la lactulosa y el del placebo no fueron estadísticamente significativas en el conjunto de datos por protocolo (PP) (–0,012; 95% IC, –0,031 a 0,007; p=0,224) ni en el análisis por intención de tratar (ITT) (–0,005; 95% de IC, –0,025 a 0,016; p=0,651). Conclusiones: Los resultados de este estudio piloto permiten concluir que existe un efecto de mantenimiento de la DMO en mujeres postmenopáusicas con baja masa ósea tras 1 año de tratamiento con lactulosa asociada a dosis bajas de calcio y vitamina D.

Introducción: El objetivo de este estudio es analizar la microarquitectura ósea en la artritis reumatoide (AR) en una serie de biopsias de cresta ilíaca ósea previamente realizadas en pacientes sin tratamiento previo con glucocorticoides, utilizando análisis mediante microCT. Material y método: Se obtuvieron 14 especímenes óseos extraídos de la cresta ilíaca de pacientes con AR sin tratamiento previo con glucocorticoides. Ninguno de ellos estaba diagnosticado de enfermedades o tomaba medicaciones que pudieran comprometer al metabolismo mineral óseo. Se les realizó una historia clínica completa y análisis sanguíneo, incluyendo el factor reumatoide. Los especímenes fueron incluidos en metil-metacrilato y estudiados con un scanner microCT eXplorer Locus SP. Los parámetros de adquisición fueron: 80 kVp/80 μA, grosor del filtro de aluminio: 10-3 pulgadas, FOV ≈ 2×2 cm, modo de adquisición de 360°, 720 views, 4 frame averages/view, tiempo de exposición 1.700 ms, voxel resolution: 28 μm. Se seleccionó una Región de Interés (ROI) mediante interpolación, evitando el hueso cortical. Se utilizó un proceso automático de segmentación (thresholding) para diferenciar y segmentar el tejido óseo del hematopoyético. Los parámetros microarquitecturales se generaron automáticamente por ordenador utilizando algoritmos parallel-plate. Los resultados fueron comparados con 14 especímenes procedentes de controles sanos de similar edad y sexo utilizando t de Student para muestras no pareadas. La significancia estadística se fijó en p< 0,05. Resultados: La fracción de volumen óseo (BV/TV) fue significativamente menor en los pacientes con AR que en los controles sanos (p< 0,05). El grosor trabecular (Tb.Th) fue mayor en los controles. La separación trabecular (Tb.Sp) fue mayor en los especímenes con AR (p< 0,05). La conectividad trabecular (Tb.N) fue significativamente mayor en los especímenes control (p< 0,05). Conclusiones: Los pacientes con AR tienen una peor calidad ósea trabecular y una baja conectividad trabecular. El escáner microCT es una herramienta rápida y potente para el estudio de la microestructura trabecular.

Introduction: Adherence to oral treatment of patients with osteoporosis is low, with a high dropout rate in the first year. The most noteworthy result is the lack of therapeutic response. Objective: To ascertain the perception of physicians working with osteoporotic patients regarding adherence of these patients. Methods: Cross-sectional study conducted by opinion survey aimed at primary care physicians and specialists involved in osteoporosis treatment. Participants were selected by purposive sampling. Results: The questionnaire was answered by 235 specialists encompassing rheumatology (54.5%), orthopedics (10.6%) and primary care (18.7%). In 43.8% of participants, more than 25% of patients sometimes forget to take their treatment. According to 34.9%, more than 75% of patients are aware of treatment. Side effects and management complexity are the majority reasons that lead to a change in medication, mean value of 7.94±2.06 6±2.01 points respectively on a 0-10 scale. Conclusions: Overall, medical specialists attributed low adherence to side effects, polypharmacy and lack of communication between professionals. Dosage and space use of soluble dosage forms may be options to facilitate patient adherence to treatment with oral bisphosphonates. Improved education concerning the importance of the disease or increased patient monitoring could foster adherence. [ABSTRACT FROM AUTHOR]

Background:Granulation tissue after transoral laser microsurgery can make it difficult to distinguish between normal healing and tumour recurrence.Materials and methods:We carried out a retrospective analysis of 316 consecutive glottic carcinomas (Tis–T3). Presence of granulation tissue at one and six months was correlated with demographic and clinical data, tumour and surgical characteristics, and tumour relapse.Results:Granulation tissue appeared in 53.8 per cent of patients at month 1, resolving spontaneously in 41.8 per cent. Revision surgery was performed in 60.1 per cent and was effective in 41.1 per cent. At month 6, 14.9 per cent of patients presented with granulation tissue. In 74.5 per cent the tissue was surgically removed and was positive for malignancy in 62.9 per cent. Tumour relapse presented in 29.4 per cent with granulation tissue at month 1 and in 61.7 per cent at month 6 (p = 0.000). Granulation tissue at month 1 correlated with thyroid cartilage exposure and continued smoking. At month 6, granulation tissue correlated with thyroid cartilage exposure, the affected surgical margins and diabetes.Conclusion:Granulation tissue after transoral laser microsurgery is frequent. When it persists at six months, revision surgery is formally recommended. [ABSTRACT FROM PUBLISHER]

We report the results of a randomized, double-blind, double-dummy, multicenter, parallel group pilot study, the objective of which was to assess whether the addition of lactulose to vitamin D and calcium supplementation for 12 months contributed to bone mineral density (BMD) maintenance in postmenopausal women with osteopenia (T-score -1 to -2.5 SD). Women in the lactulose group (n=19) received lactulose 15 mL/day (equivalent to 10.05 g), vitamin D3 400 IU/day and calcium carbonate 500 mg/day, and women (n=22) in the placebo group were administered lactulose placebo, vitamin D3 400 IU/day and calcium carbonate 1,000 mg/day. The baseline daily calcium intake was similar in both study groups. The primary endpoint was the BMD in the lumbar spine at the final visit. A generalized liner model was used to assess final versus baseline differences in BMD in both study groups. Differences in least-square means of BMD between lactulose and placebo were not statistically significant both in the per-protocol data set (-0.012, 95% CI -0.031 to 0.007, P=0.224) and in the intention-to-treat population (-0.005, 95% CI -0.025 to 0.016, P=651). As we have not found differences within the two study groups, the addition of lactulose to 500 mg of calcium carbonate associated with vitamin D supplementation could have similar effects on lumbar BMD as 1.000 mg of calcium carbonate. These findings may indicate that lactulose may improve calcium absorption in postmenopausal women. A long follow-up study with a greater number of subjects would be necessary to confirm these preliminary observations. [ABSTRACT FROM AUTHOR]

We studied the effects of phosphorus fertilisation on foliar terpene concentrations and foliar volatile terpene emission rates in six half-sib families of Pinus pinaster Ait. seedlings. Half of the seedlings were resistant to attack of the pine weevil Hylobius abietis L., a generalist phloem feeder, and the remaining seedlings were susceptible to this insect. We hypothesised that P stress could modify the terpene concentration in the needles and thus lead to altered terpene emission patterns relevant to plant-insect signalling. The total concentration and emission rate ranged between 5732 and 13,995 μg·g−1 DW and between 2 and 22 μg·g−1 DW·h−1, respectively. Storage and emission were dominated by the isomers α- and β-pinene (77.2% and 84.2% of the total terpene amount amassed and released, respectively). In both resistant and susceptible families, P stress caused an increase of 31% in foliar terpene concentration with an associated 5-fold decrease in terpene emission rates. A higher terpene content in the leaves implies that the 'excess carbon', available under limiting growth conditions (P scarcity), is allocated to terpene production. Sensitive families showed a greater increase in terpene emission rates with increasing P concentrations, which could explain their susceptibility to H. abietis. [ABSTRACT FROM AUTHOR]

Current antiretroviral therapy has lead to longer survival in patients infected with HIV, but it is also associated with new and important problems. Body fat redistribution and metabolic abnormalities, the so-called lipodystrophy syndrome, are among the most prevalent and worrisome ones. While an increasing number of patients infected with HIV are becoming affected by this syndrome, the pathogenesis of this syndrome and how to prevent and treat the problem all remain largely unknown. Body fat changes stigmatise the bodies of patients infected with HIV giving them a similar look to that seen in patients some years ago when the wasting syndrome was more prevalent and HIV infection was ultimately fatal. The psychological impact of body fat changes may be severe enough to affect a patients' desire to continue with antiretroviral therapy. Metabolic abnormalities, probably with the exception of symptomatic diabetes mellitus and hypertriglyceridaemia-induced pancreatitis, do not have an immediate impact on the quality of the lives of patients with HIV. However, their potential long term cardiovascular and bone consequences may increase the morbidity and the mortality of patients infected with HIV through noninfectious diseases. The impact of lipodystrophy on patients infected with HIV is not readily captured with the classic instruments used to measure quality of life and hence it is necessary to modify them urgently. Though treating lipodystrophy seems fully justified, there is no proven treatment for this problem, although a number of treatments have been used with varying success. Despite the recognition that lipodystrophy may have important psychological repercussions, the best psychological approach for this problem is not known at present. Although lipodystrophy has its own peculiarities, existing knowledge about how to psychologically help other patients with deforming body changes might be of help for patients infected with HIV, or at least may act as a starting point. [ABSTRACT FROM AUTHOR]

Pregnancy-associated osteoporosis is a rare and poorly characterized clinical entity. We describe two women, aged 28 and 31 yr, who developed vertebral osteopaenia with non-traumatic compression fractures within a few months after delivery. In both women secondary causes of osteoporosis were excluded and routine laboratory data including indices of calcium metabolism were normal. In one patient (Patient 1) spontaneous secretion of IL-1 by cultured blood monocytes was elevated 6 months after delivery and a bone biopsy revealed histomorphometric indices consistent with accelerated bone remodelling. BMD was measured by quantitative computed tomography (QCT) and/or dual energy X-ray absorptiometry (DXA). In Patient 1, BMD, measured with QCT, 6 months after delivery was 3.32 Z-score units below the predicted value for age and sex-matched subjects. At that time treatment (phosphate followed by sodium etidronate) was instituted, and QCT measurements obtained 24 and 30 months after delivery revealed a BMD of −2.98 and −2.67 Z-score units, respectively. The treatment was discontinued just before she became pregnant again, and 3 months after the second delivery QCT showed a BMD of −3.06 Z-score units. Further BMD assessments were obtained with DXA at 15 and 18 months after the second delivery, and the BMD values were −1.41 and −1.08, respectively. In Patient 2, spine BMD, measured with QCT, 4 and 10 months after delivery were −1.68 and −1.59 Z-score units, respectively. At 10, 16 and 22 months after delivery, BMD was assessed with DXA. The initial measurement with this technique disclosed a BMD of 0.52 Z-score units. Subsequent assessments showed no further significant changes in spine BMD. Although coherent treatment in Patient 1 might have affected BMD, the present long-term study suggests that post-partum osteoporosis is not progressive and possibly, partially, reversible. Further pregnancies need not be contraindicated; however, BMD monitoring is required to assess future fracture risk. [ABSTRACT FROM PUBLISHER]