A Systematic Evaluation for Oropharyngeal Dysphagia in Non-institutionalized Elderly Patients with Home Care-based in the Community.

Oropharyngeal Dysphagia (OD) increases the risk of hospitalization and the use of health services; however, it is often detected and studied in institutionalized patients with limited attention given to the community. The aim of this study was to determine the prevalence of OD and its associated factors after conducting a program consisting of a systematic assessment of OD for in patients living independently in their dwellings and requiring home-based care. We conducted a cross-sectional study involving a systematic assessment of disabled and elderly patients enrolled in a home-based primary care program at three urban centers (Barcelona, Spain). OD was assessed using the Volume-Viscosity Swallow Test. Data on morbidity, incontinence, functional independence, pressure sore risk, brain deficit, social risk, nutritional status, and healthcare utilization were collected. Prevalence was determined, and differences between OD and non-OD patients were analysed using independent tests. Associations between OD and hospital admissions, emergency department visits, emergency home ambulance use, and consultations with family physicians or primary care nurses were examined using logistic regression models adjusted for covariates. We included 1,002 patients with a mean age of 88.75 years old (SD = 8.19), 73.05% of whom were female. The prevalence of OD was 25.95% (95% CI 23.26%-28.78%). OD was associated with past pneumonia episodes (adjusted OR: 5.09, 95% CI: 2.2-11.79), increased frequency of cough and common cold (adjusted OR: 1.11, 95% CI: 1.05-1.18), and more family physician consultations (adjusted OR: 1.07, 95% CI: 1.03-1.10). These findings highlight that OD remains an underdiagnosed geriatric syndrome in the community setting. Implementing systematic OD diagnoses assessments, especially among home care-based patients could reduce the incidence of secondary pneumonia, decrease cough episodes, and lower the frequency of clinician consultations.

Hoarding behaviour: special features and complications in real-world clinical practice.

OBJECTIVE: Hoarding behaviour is a common but poorly characterised problem in real-world clinical practice. Although hoarding behaviour is the key component of Hoarding Disorder (HD), there are people who exhibit hoarding behaviour but do not suffer from HD. The aim of the present study was to characterise a clinical sample of patients with clinically relevant hoarding behaviour and evaluate the differential characteristics between patients with and without HD. METHODS: This study included patients who received treatment at the home visitation program in Barcelona (Spain) from January 2013 through December 2020, and scored ≥ 4 on the Clutter Image Rating scale. Sociodemographic, DSM-5 diagnosis, clinical data and differences between patients with and without an HD diagnosis were assessed. RESULTS: A total of 243 subjects were included. Hoarding behaviour had been unnoticed in its early stages and the median length in the sample was 10 years (IQR 15). 100% of the cases had hoarding-related complications. HD was the most common diagnosis in 117 patients (48.1%). CONCLUSIONS: The study found several differential characteristics between patients with and without HD diagnosis. Alcohol use disorder could play an important role among those without HD diagnosis. Home visitation programs could improve earlier detection, preventing hoarding-related complications.

Real-world analysis of main clinical outcomes in patients with polycythemia vera treated with ruxolitinib or best available therapy after developing resistance/intolerance to hydroxyurea.

BACKGROUND: Ruxolitinib is approved for patients with polycythemia vera (PV) who are resistant/intolerant to hydroxyurea, but its impact on preventing thrombosis or disease-progression is unknown. METHODS: A retrospective, real-world analysis was performed on the outcomes of 377 patients with resistance/intolerance to hydroxyurea from the Spanish Registry of Polycythemia Vera according to subsequent treatment with ruxolitinib (n = 105) or the best available therapy (BAT; n = 272). Survival probabilities and rates of thrombosis, hemorrhage, acute myeloid leukemia, myelofibrosis, and second primary cancers were calculated according to treatment. To minimize biases in treatment allocation, all results were adjusted by a propensity score for receiving ruxolitinib or BAT. RESULTS: Patients receiving ruxolitinib had a significantly lower rate of arterial thrombosis than those on BAT (0.4% vs 2.3% per year; P = .03), and this persisted as a trend after adjustment for the propensity to have received the drug (incidence rate ratio, 0.18; 95% confidence interval, 0.02-1.3; P = .09). There were no significant differences in the rates of venous thrombosis (0.8% and 1.1% for ruxolitinib and BAT, respectively; P = .7) and major bleeding (0.8% and 0.9%, respectively; P = .9). Ruxolitinib exposure was not associated with a higher rate of second primary cancers, including all types of neoplasia, noncutaneous cancers, and nonmelanoma skin cancers. After a median follow-up of 3.5 years, there were no differences in survival or progression to acute leukemia or myelofibrosis between the 2 groups. CONCLUSIONS: The results suggest that ruxolitinib treatment for PV patients with resistance/intolerance to hydroxyurea may reduce the incidence of arterial thrombosis. LAY SUMMARY: Ruxolitinib is better than other available therapies in achieving hematocrit control and symptom relief in patients with polycythemia vera who are resistant/intolerant to hydroxyurea, but we still do not know whether ruxolitinib provides an additional benefit in preventing thrombosis or disease progression. We retrospectively studied the outcomes of 377 patients with resistance/intolerance to hydroxyurea from the Spanish Registry of Polycythemia Vera according to whether they subsequently received ruxolitinib (n = 105) or the best available therapy (n = 272). Our findings suggest that ruxolitinib could reduce the incidence of arterial thrombosis, but a disease-modifying effect could not be demonstrated for ruxolitinib in this patient population.

Low-risk polycythemia vera treated with phlebotomies: clinical characteristics, hematologic control and complications in 453 patients from the Spanish Registry of Polycythemia Vera.

Hematological control, incidence of complications, and need for cytoreduction were studied in 453 patients with low-risk polycythemia vera (PV) treated with phlebotomies alone. Median hematocrit value decreased from 54% at diagnosis to 45% at 12 months, and adequate hematocrit control over time (< 45%) was observed in 36%, 44%, and 32% of the patients at 6, 12, and 24 months, respectively. More than 5 phlebotomies per year in the maintenance phase were required in 19% of patients. Worsening thrombocytosis, age > 60 years, and microvascular symptoms constituted the main indications for starting cytoreduction. Median duration without initiating cytoreduction was significantly longer in patients younger than 50 years (< 0.0001). The incidence rate of thrombosis under phlebotomies alone was 0.8% per year and the estimated probability of thrombosis at 10 years was 8.5%. The probability of arterial thrombosis was significantly higher in patients with arterial hypertension whereas there was a trend to higher risk of venous thrombosis in cases with high JAK2V617F allele burden. Rates of major bleeding and second primary neoplasm were low. With a median follow-up of 9 years, survival probability at 10 years was 97%, whereas the probability of myelofibrosis at 10 and 20 years was 7% and 20%, respectively. Progression to acute myeloid leukemia was documented in 3 cases (1%). Current management of low-risk PV patients is associated with low rate of thrombosis and long survival. New treatment strategies are needed for improving hematological control and, in the long term, reducing progression to myelofibrosis.

Cytoreductive treatment in patients with CALR-mutated essential thrombocythaemia: a study comparing indications and efficacy among genotypes from the Spanish Registry of Essential Thrombocythaemia.

The present study assessed the criteria for initiating cytoreduction and response to conventional therapies in 1446 patients with essential thrombocythemia (ET), 267 (17%) of which were CALR-mutated. In low risk patients, time from diagnosis to cytoreduction was shorter in CALR-positive than in the other genotypes (2·8, 3·2, 7·4 and 12·5 years for CALR, MPL, JAK2V617F and TN, respectively, P < 0·0001). A total of 1104 (76%) patients received cytoreductive treatment with hydroxycarbamide (HC) (n = 977), anagrelide (n = 113), or others (n = 14). The estimated cumulative rates of complete haematological response (CR) at 12 months were 40 % and 67% in CALR and JAK2V617F genotypes, respectively. Median time to CR was 192 days for JAK2V617F, 343 for TN, 433 for MPL, and 705 for CALR genotypes (P < 0·0001). Duration of CR was shorter in CALR-mutated ET than in the remaining patients (P = 0·003). In CALR-positive patients, HC and anagrelide had similar efficacy in terms of response rates and duration. CALR-mutated patients developed resistance/intolerance to HC more frequently (5%, 23%, 27% and 15% for JAK2V617F, CALR, MPL and TN, respectively; P < 0·0001). In conclusion, conventional cytoreductive agents are less effective in CALR-mutated ET, highlighting the need for new treatment modalities and redefinition of haematologic targets for patients with this genotype.

In vivo cell tracking of mouse embryonic myoblasts and fast fibers during development.

Fast and slow TnI are co-expressed in E11.5 embryos, and fast TnI is present from the very beginning of myogenesis. A novel green fluorescent protein (GFP) reporter mouse lines (FastTnI/GFP lines) that carry the primary and secondary enhancer elements of the mouse fast troponin I (fast TnI), in which reporter expression correlates precisely with distribution of the endogenous fTnI protein was generated. Using the FastTnI/GFP mouse model, we characterized the early myogenic events in mice, analyzing the migration of GFP+ myoblasts, and the formation of primary and secondary myotubes in transgenic embryos. Interestingly, we found that the two contractile fast and slow isoforms of TnI are expressed during the migration of myoblasts from the somites to the limbs and body wall, suggesting that both participate in these events. Since no sarcomeres are present in myoblasts, we speculate that the function of fast TnI in early myogenesis is, like Myosin and Tropomyosin, to participate in cell movement during the initial myogenic stages. genesis

Identification of the Transcriptional Regulatory Role of RUNX2 by Network Analysis in Lung Cancer Cells.

The use of a new bioinformatics pipeline allowed the identification of deregulated transcription factors (TFs) coexpressed in lung cancer that could become biomarkers of tumor establishment and progression. A gene regulatory network (GRN) of lung cancer was created with the normalized gene expression levels of differentially expressed genes (DEGs) from the microarray dataset GSE19804. Moreover, coregulatory and transcriptional regulatory network (TRN) analyses were performed for the main regulators identified in the GRN analysis. The gene targets and binding motifs of all potentially implicated regulators were identified in the TRN and with multiple alignments of the TFs' target gene sequences. Six transcription factors (E2F3, FHL2, ETS1, KAT6B, TWIST1, and RUNX2) were identified in the GRN as essential regulators of gene expression in non-small-cell lung cancer (NSCLC) and related to the lung tumoral process. Our findings indicate that RUNX2 could be an important regulator of the lung cancer GRN through the formation of coregulatory complexes with other TFs related to the establishment and progression of lung cancer. Therefore, RUNX2 could become an essential biomarker for developing diagnostic tools and specific treatments against tumoral diseases in the lung after the experimental validation of its regulatory function.

Secondary enhancers synergise with primary enhancers to guarantee fine-tuned muscle gene expression.

Although tight quantitative control of gene expression is required to ensure that organs and tissues function correctly, the transcriptional mechanisms underlying this process still remain poorly understood. Here, we describe novel and evolutionary conserved secondary enhancers that are needed for the regulation of the expression of Troponin I genes. Secondary enhancers are silent when tested individually in electroporated muscles but interact with the primary enhancers and are required to precisely control the appropriate timing, the tissue and fibre specificity, and the quantitative expression of these genes during muscle differentiation. Synergism is completely dependent of the fully conserved MEF2 site present on the primary enhancers core of skeletal muscle Troponin I genes. Thus, while each of these paired enhancers has a different function, the concerted action of both is crucial to recapitulate endogenous gene expression. Through comparative genomics, we predict that this mechanism has also arisen in other mammalian muscle genes. Our results reveal the existence of a novel mechanism, conserved from flies to mammals, to fine-tune gene expression in each muscle and probably other tissues.

Hb Palencia: a novel δßδ-type two-way fusion variant with ß-globin-like expression levels.

AIMS: Fusion proteins of unequal recombination events at the ß-globin locus have pathological effect. The haemoglobin (Hb) variants of type Lepore are fusion proteins characterised by ß-like globin chains with a δ-globin (HBD) N-terminus and a ß-globin (HBB) C-terminus, whereas reciprocal products of underlying crossover events hold a HBB N-terminus and HBD C-terminus instead. Finally, Hb Parchman contains a ß-like globin chain with a central HBB fragment and HBD-derived N-termini and C-termini, whereas reciprocal hybrid proteins are as yet unknown. METHODS: The propositus was an 80-year-old Caucasian man, whose HbA1c quantification by HPLC (Variant II turbo) for exclusion of type-2 diabetes revealed an abnormal peak. Haemoglobins were analysed by ion-exchange HPLC (Variant II) and capillary electrophoresis (Sebia Capillarys Flex) and DNA by automatic Sanger sequencing of δ-globin and ß-globin genes. RESULTS: Sequencing showed an HBB-HBD-HBB hybrid gene, with HBD-derived central codons 9-31, and HBB-derived UTRs and complementary coding regions. The corresponding new hybrid haemoglobin (Hb Palencia) is represented at ≈40%, similar to HbA. CONCLUSION: Hb Palencia contains the first globin variant with internal HBD sequences and HBB-derived N-terminal and C-terminal and regulatory sequences. Relative quantity of the new ßδß-type variant suggests transcriptional control by HBB elements and a half-life similar to normal HBB.

[New therapies for hepatitis C]. / Nuevos tratamientos para la hepatitis C.

Hepatitis C virus is an important public health threat, not only because of the high prevalence of this infection in western and third world countries, but also because of the high rate of resistance to the available antiviral therapy that consists on the use of pegylated interferon plus ribavirin. Currently, new forms of therapy are being developed based on a more precise knowledge of the structure and function of the viral proteins and of the strategies used by the virus to escape the immune and interferon systems. The new therapeutic approaches aim at different objectives: a) the inhibition of viral replication by blocking the viral protease and/or replicase; b) the use of other types of interferon with more potent antiviral effect, c) the induction of a specific anti-viral immune response by means of immunomodulatory compounds or therapeutic vaccination, d) the blockade of "de novo" infection of other cells with neutralizing antibodies, e) the induction of a antiviral state in the liver by transferring to this organ the gene of interferon and/or immunostimulating cytokines.

[Chronotherapy in hypertension]. / Cronoterapia en hipertensión.

Arterial blood pressure values measured in a doctor's office are often used as a reference at the moment to take decisions regarding a hypertensive patient and frequently these values are above the real pressure measurements a patient has since these can endure modifications due to multiple factors. Therefore, it is necessary to know what can exercise an influence on the control of arterial blood pressure measurements and to take advantage of those measurements available to professionals in order to obtain the maximum information possible regarding the degree of control over those who suffer hypertension.

Adherence to the "Mediterranean Diet" in Spain and Its Relationship with Cardiovascular Risk (DIMERICA Study).

BACKGROUND: Nutritional studies focus on traditional cultural models and lifestyles in different countries. The aim of this study was to examine the adherence to the Mediterranean diet, life habits, and risk factors associated with cardiovascular diseases among people living in different geographical regions in Spain. METHODS: A descriptive cross-sectional study was conducted in each region. The sampling scheme consisted of a random three-stage stratified sampling program according to geographic region, age, and gender. A total of 1732 subjects were asked to complete a questionnaire designed to assess their nutrient intake, dietary habits, and exercise. A diet score that assesses the adherence of participants to the Mediterranean diet (range 0-10) was also applied. RESULTS: Southeastern Spain had the lowest score for adherence to the Mediterranean diet because of the low consumption of fish and plant products. A lower adherence score to the Mediterranean diet was strongly associated with the prevalence of hypertension (p = 0.018). CONCLUSIONS: A low level of adherence to the Mediterranean diet is accompanied by a high prevalence of hypertension and, therefore, a raised cardiovascular risk in the country. The adherence score could help identify individuals at greater cardiovascular risk.

Effectiveness of nutritional supplementation on muscle mass in treatment of sarcopenia in old age: a systematic review.

BACKGROUND: Much interest has been focused on nutritional treatment of sarcopenia, loss of muscle mass and performance associated to aging; however, its benefits are unclear. OBJECTIVE: To analyze the relevance of nutritional treatment of sarcopenia and assess the effects of supplementation on muscle mass and function within the aged population. METHODS: We searched Medline and the Cochrane Library for controlled trials published between 1991 and 2012. We have assessed the quality, type of intervention, the cohort used, the way muscle mass was measured, and the outcomes of the various studies. RESULTS: We have included 17 studies, with a total of 1287 patients, aged between 65 and 85 on average. An improvement in muscle mass was proven, whether measured with bioelectrical impedance analysis or dual energy x-ray absorptiometry, and an improvement in strength was also proven. CONCLUSION: Nutritional supplementation is effective in the treatment of sarcopenia in old age, and its positive effects increase when associated with physical exercise. The main limitation of this treatment is lack of long-term adherence. A healthy diet associated with a physically active lifestyle and possibly with aerobic exercise are the basis of healthy aging, which is the aim of all doctors treating aged people must seek.

The anorexia of ageing: physiopathology, prevalence, associated comorbidity and mortality. A systematic review.

The physiological processes of ageing and factors prevalent in the elderly such as comorbidities and polypharmacy often cause loss of appetite in the elderly, which we call anorexia of ageing. Social factors, together with changes in the sensory organs, can be important causes of a reduction in both appetite and ingestion. This review assesses the regulation of appetite in the elderly and the development of anorexia of ageing. It also examines the prevalence of this type of anorexia, its associated comorbidities and mortality rates. We have reviewed 27 studies, with a total of 6208 patients. These reported changes in the secretion and response of both central and peripheral hormones that regulate appetite. Anorexia, very prevalent among hospitalized and institutionalized elderly people, is associated with comorbidity and represents a predictive factor for mortality. No treatment for it has been proved to be effective. The mechanism regulating ingestion in elderly people is complex and difficult to resolve. Comorbidity as a cause or a consequence of anorexia of ageing has become a research field of great interest in geriatrics. A correct nutritional evaluation is a fundamental part of an integrated geriatric assessment.

Study protocol: High-protein nutritional intervention based on ß-hydroxy-ß-methylbutirate, vitamin D3 and calcium on obese and lean aged patients with hip fractures and sarcopenia. The HIPERPROT-GER study.

INTRODUCTION: Loss of muscle strength is associated with falls, which, in turn, are the main cause of hip fractures in elderly people. The factors that most influence loss of strength in elderly people are a decrease in muscle mass, i.e. sarcopenia, and an increase in fat, i.e. obesity. METHODS: A prospective randomized clinical trial among patients who have undergone an operation for a traumatic hip fracture and who are aged 65 or above will be implemented. We shall compare a control diet against a high-protein diet enriched with ß-hydroxy-ßmethylbutirate, calcium and vitamin D. The diet will be administered during 30 days of hospitalization in the orthopaedic geriatric rehabilitation unit. There will be 50 patients in each arm of the study. The main objective is to assess whether the experimental diet, together with rehabilitation, improves functional recovery, measured on the Barthel index. Secondary objectives are to assess changes in body composition and the prevalence of sarcopenia, obesity and mortality one year after the hip fracture. We shall also assess whether there is a relationship between specific inflammatory markers, sarcopenia and functional recovery. CONCLUSIONS: Ageing is accompanied by changes in body composition that increase the risk of falls and progressive functional loss. These factors are a public health problem because they are highly associated with disability in older people. The present study seeks to gain knowledge of those factors that are most often associated with the onset of disability and those that can be modified through diet.

Sarcopenia in the elderly: diagnosis, physiopathology and treatment.

Sarcopenia, defined as a syndrome rather than as a pathology, is the loss of muscle mass and function associated with age. Sarcopenia is an enigma for medicine, and despite the numerous publications available in the literature and the number of papers currently being published, there is no agreement about its definition, and even less about its root causes. One salient aspect that proves the lack of consensus is the fact that different working groups are still debating about the right name for this syndrome (which is associated with the loss of muscle mass and strength in the elderly). In hospitalized patients, sarcopenia has been shown to raise the risk of complications such as infections, pressure ulcers, loss of autonomy, institutionalization and poor quality of life, as well as to increase mortality. The factors that contribute to the development of sarcopenia in the elderly are: the state of chronic inflammation, atrophy of motoneurons, reduced protein intake (secondary among others to the condition defined as geriatric anorexia), and immobility. There is ongoing debate about the causes of sarcopenia, but the aspect that generates most interest today is the quest to achieve repeatable and clinically useful diagnostic criteria for its diagnosis, prevention and treatment. The aim of this narrative review is to summarise the abundant information available in the literature and to draw useful conclusions.