PP231 Safety, Effectiveness And Economic Analysis Of Exercise Intervention For Prevention Of Cognitive And Functional Deterioration In Hospitalized Patients

IntroductionCognitive and functional deterioration is common in hospital setting and occurs in 40 percent of admitted older patients. One of its main causes is physical inactivity. The objective of our health technology assessment was to assess the safety and clinical effectiveness of a structured multicomponent intervention of physical exercise (Vivifrail) for the prevention of the cognitive and functional deterioration in hospitalized patients aged 70 years or older and to estimate costs and the budgetary impact for the Spanish National Health Service.MethodsA systematic review of available scientific literature (including experimental and observational designs) on the safety and effectiveness of Vivifrail was performed. A costing study and budgetary impact analysis of the incorporation of Vivifrail as a therapeutic alternative to standard care with a time horizon of 5 years was performed.ResultsOne randomized controlled trial (RCT) (n = 370) showed positive effects of Vivifrail compared to usual care in functional capacity (mean difference (MD) = 2.20, 95% confidence interval (CI) 1.78 to 2.62), cognitive state (MD = 1.80, 95% CI 1.24 to 2.36), and quality of life (MD = 13.20, 95% CI 12.70 to 13.70). Regarding other variables, the Vivifrail increased the grip strength of the dominant hand (MD = 2.30; 95% CI = 1.79 to 2.81), verbal fluency (MD = 2.15; 95% CI = 1.56 to 2.74), performance of double tasks (MD = 0.10; 95% CI = 0.07 to 0.13), executive function (MD = −31.07; 95% CI = −49.23 to −12.91) and emotional state (MD = −2.00; 95% CI = −2.50 to −1.50).The total cost of implementing Vivifrail in a 1,000-bed general hospital would be EUR18,000 per year (adjusted to 2020 currency), with approximately 150 patients older than 75 years benefited. This represents a cost of EUR120 per patient.ConclusionsThe Vivifrail could improve functional and cognitive capacity, although available evidence on the Vivifrail is very scarce. More well designed and executed RCT and cost-effectiveness study confirming or refuting the promising findings are needed for a new assessment.

Pharmacogenetics studies in stroke patients treated with rtPA: a review of the most interesting findings

Recombinant tissue-plasminogen activator (rtPA) is the only drug used during the acute phase of stroke. Despite its important benefits, a percentage of patients suffer symptomatic hemorrhagic transformations or a lack of early recanalization rates. These undesirable effects are associated with acute neurological and long-term functional deterioration. For the past 20 years, pharmacogenetic studies have tried to find the genetic risk factors associated with rtPA response. Most of these studies have used a gene-candidate strategy; however, recent genome-wide association studies have emerged indicating that genetic predisposition could modulate rtPA response. This review summarizes the most interesting findings in this field, including which genes and genetic variations are associated with hemorrhagic transformations and recanalization rates after thrombolytic therapy.

RASAYANA AND DEGENERATIVE EYE DISORDERS

As eyes are in continuous exposure to the light and face both anatomical as well as functional deterioration with increasing age, there is a high incidence of issues in visual functioning of the eye that affects day to day activities of the individual and has a great impact on the physical, social and mental state of a person. As with today's world, the intake of unhealthy food and improper lifestyle is the main cause of to produce Ama, which is the ma- jor cause of development of all the diseases including ocular disorders. Rasayana Chikitsa is well known for its effective and potential role in degenerative disorders.

The α2-isoform of the Na+/K+-ATPase protects against pathological remodeling and β-adrenergic desensitization after myocardial infarction

Reduced systolic and diastolic calcium levels in cardiomyocytes from NKA-α2 transgenic mice minimize the desensitization of the β-adrenergic signaling system. These effects result in an improved β-adrenergic reserve and prevent functional deterioration and cardiac remodeling.

Macular Microvascular Modifications in Progressive Lamellar Macular Holes

Lamellar macular holes (LMHs) may show morphological and functional deterioration over time, yet no definite prognostic factor for progression has been identified. Since neurovascular retinal unit impairment may take part in neurodegeneration, we compare progressive LMHs to stable ones in optical coherence tomography (OCT) angiography parameters. Methods: OCT B scans of eyes with LMH were analyzed to detect the presence of tissue loss (TL) over time, allowing us to identify a TL group and a stable (ST) group (14 patients each). The best corrected visual acuity (BCVA) at each considered imaging time point was collected. Lastly, patients underwent macular OCT angiography. Results: BCVA at last follow up was significantly reduced in the TL group compared to both the ST group and TL group baseline assessment. SCP foveal vessel density (VD), SCP and deep capillary plexus (DCP) perfusion density (PD) and parafoveal PD were lower in the TL group. Linear correlations between quantitative TL over time and parafoveal PD in SCP and between the speed of TL and BCVA variation during follow up were also detected. Conclusions: TL in LMHs is associated with both OCT angiography modifications and BCVA deterioration over time. We suggest these findings to be a manifestation of foveal Muller cell impairment in progressive LMHs.

Risk factors for functional deterioration in a cohort with late effects of poliomyelitis: A ten-year follow-up study

BACKGROUND: More than 7000 patients developed poliomyelitis during the main epidemic in the fifties in Israel. In recent years, there is a further deterioration in their condition due to accelerated aging process and post-polio syndrome. OBJECTIVE: To evaluate the risk factors for the progression of functional status in a cohort of patients with late effect of poliomyelitis over a period of ten years. METHODS: A cross-sectional cohort study including 82 individuals with late effect of poliomyelitis evaluated over ten years. Mean age was 67±8.5 years, 52.4%were men and 79.3%were Jewish. Functional status was evaluated by activities of daily living (ADL) questionnaire. Risk factors, including general comorbidities, history of poliomyelitis infection, use of assistive devices, employment, and physical activity statuses were evaluated using specific questionnaires. RESULTS: Independence in ADL functions deteriorated significantly over ten years. Older age, ethnicity, use of a wheelchair, and use of orthotic devices in childhood were risk factors for deterioration in ADL function. No correlation was found between the presence of other comorbidities or poliomyelitis parameters and worsening of ADL functions. CONCLUSIONS: Late effect of poliomyelitis was associated with deterioration in ADL functions probably due to the combined effect of the initial severity of the paralytic poliomyelitis symptoms and accelerated aging.

S-Methyl-L-Ergothioneine to L-Ergothioneine Ratio in Urine Is a Marker of Cystine Lithiasis in a Cystinuria Mouse Model

Cystinuria, a rare inherited aminoaciduria condition, is characterized by the hyperexcretion of cystine, ornithine, lysine, and arginine. Its main clinical manifestation is cystine stone formation in the urinary tract, being responsible for 1–2% total and 6–8% pediatric lithiasis. Cystinuria patients suffer from recurrent lithiasic episodes that might end in surgical interventions, progressive renal functional deterioration, and kidney loss. Cystinuria is monitored for the presence of urinary cystine stones by crystalluria, imaging techniques or urinary cystine capacity; all with limited predicting capabilities. We analyzed blood and urine levels of the natural antioxidant L-ergothioneine in a Type B cystinuria mouse model, and urine levels of its metabolic product S-methyl-L-ergothioneine, in both male and female mice at two different ages and with different lithiasic phenotype. Urinary levels of S-methyl-L-ergothioneine showed differences related to age, gender and lithiasic phenotype. Once normalized by L-ergothioneine to account for interindividual differences, the S-methyl-L-ergothioneine to L-ergothioneine urinary ratio discriminated between cystine lithiasic phenotypes. Urine S-methyl-L-ergothioneine to L-ergothioneine ratio could be easily determined in urine and, as being capable of discriminating between cystine lithiasis phenotypes, it could be used as a lithiasis biomarker in cystinuria patient management.

The intersection of Mineralocorticoid Receptor (MR) activation and the FGF23 – Klotho cascade. A Duopoly that promotes renal and cardiovascular injury

The nexus of CKD and cardiovascular disease (CVD) amplifies the morbidity and mortality of CKD, emphasizing the need for defining and establishing therapeutic initiatives to modify and abrogate the progression of CKD and concomitant CV risks. In addition to the traditional CV risk factors, disturbances of mineral metabolism are specific risk factors that contribute to the excessive CV mortality in patients with CKD. These risk factors include dysregulations of circulating factors that modulate phosphate metabolism including fibroblast growth factor 23 (FGF23) and soluble Klotho. Reduced circulating levels and suppressed renal klotho expression may be associated with adverse outcomes in CKD patients. While elevated circulating concentrations or locally produced FGF23 in the strained heart exert pro-hypertrophic mechanisms on the myocardium, Klotho attenuates tissue fibrosis, progression of CKD, cardiomyopathy, endothelial dysfunction, vascular stiffness, and vascular calcification. Mineralocorticoid receptor (MR) activation in non-classical targets, mediated by aldosterone and other ligands, amplifies CVD in CKD. In concert, we detail how the interplay of elevated FGF23, activation of the MR, and concomitant reductions of circulating Klotho in CKD, may potentiate each other’s deleterious effects on kidney and the heart, thereby contributing to the initiation and progression of kidney and cardiac functional deterioration, acting through multipronged albeit complementary mechanistic pathways.