Valoración funcional y niveles de actividad física en personas con discapacidad intelectual; efectos de un programa de actividad física aeróbico, de fuerza y equilibrio

Les persones adultes amb discapacitat intel•lectual (DI) presenten baixos nivells de capacitat cardiovascular i força, al mateix temps que realitzen poca activitat física (AF) i freqüentment presenten problemes funcionals i d’equilibri. Un dels propòsits d’aquesta tesi fou investigar la fiabilitat del salt vertical en adults amb DI sobre una plataforma de contacte comparar-lo amb el test de salt de longitud sense impuls, normalment utilitzat en la bateria EUROFIT Special, per a avaluar la potència de les cames. Un altre objectiu fou avaluar els efectes d’un programa d’AF combinat incloent-hi exercicis aeròbics, de força i d’equilibri sobre la condició física la força, l’equilibri i les mesures funcionals en un estudi controlat. També s’han avaluat les característiques i nivells d’AF en el grup d’adults amb DI que va participar a la intervenció (GI) en comparació a un grup control (GC). Els participants, adults amb DI lleugera i moderada, varen ser assignats a un grup d’intervenció (GI; n = 37) i a un altre grup control (GC; n = 29). El GI va entrenar 3 vegades a la setmana, en sessions d’una hora durant 14 setmanes, mentre que el GC no va participar de cap tipus de programa d’AF. La resistència aeròbica, força, equilibri, flexibilitat i habilitats funcionals varen ser avaluades pre y post entrenament en ambdós grups. Com a resultat, el GI va millorar la seva capacitat aeròbica (26.8 vs. 29.3 ml•Kg-1•min-1), la força de prensió manual (19.2 vs. 21.9 kg), la força de cames i l’equilibri després del període d’entrenament (p < .05). El pes corporal (70.1 vs. 68.1 kg) i l’índex de massa corporal /27.4 vs. 26.6 kg•m-2) també varen disminuir (p < .05) en el GI. El GC no va presentar canvis en aquests paràmetres. Així també, els adults amb DI del GC varen realitzar menors quantitats d’AF moderada i vigorosa (AFMV) que el GI. Però és de senyalar que el comportament sedentari en ambdós grups fou elevat (~79% del temps monitoritzat). El 69.40% y el 32.10% dels participants del GI i GC respectivament varen complir amb les recomanacions de fer ≥150 minuts d’AFMV/setmana. Aquests resultats suggereixen que un programa d’AF aeròbic, de força i equilibri és beneficiós per a adults amb DI. Les intervencions per a disminuir el temps utilitzat en activitats sedentàries i augmentar l’AFMV haurien de formar part de l’horari laboral d’aquestes persones.Las personas adultas con discapacidad intelectual (DI) presentan bajos niveles de capacidad cardiovascular y fuerza, al mismo tiempo que realizan poca actividad física (AF) y frecuentemente presentan problemas funcionales y de equilibrio. Uno de los propósitos de esta tesis fue investigar la fiabilidad del salto vertical en perdonas con DI sobre una plataforma de contacto y compararlo con el test de salto en largo sin impulso, normalmente utilizado en la batería EUROFIT Special, para evaluar la potencia de las piernas. Otro de los objetivos del estudio fue evaluar los efectos de un programa de AF combinado incluyendo ejercicios aeróbicos, de fuerza y de equilibrio sobre la condición física, la fuerza, el equilibrio y medidas funcionales en un estudio controlado. También se evaluaron las características y niveles de AF en el grupo de adultos con DI que participó en la intervención (GI) en comparación con un grupo control (GC). Los participantes, adultos con DI leve a moderada, fueron asignados a un grupo intervención (GI; n = 37) y otro grupo control (GC; n = 29). El GI entrenó 3 veces por semana, 1 hora durante 14 semanas, mientras que el GC no participó en ningún tipo de programa de AF. La resistencia aeróbica, fuerza, equilibrio, flexibilidad y habilidades funcionales fueron evaluadas pre y post entrenamiento en ambos grupos. Como resultado, el GI mejoró su capacidad aeróbica (26.8 vs. 29.3 ml•Kg-1•min-1), la fuerza de prensión manual (19.2 vs. 21.9 kg), la fuerza de piernas y el equilibrio luego del período de entrenamiento (p < .05). El peso corporal (70.1 vs. 68.1 kg) y el índice de masa corporal /27.4 vs. 26.6 kg•m-2) también disminuyeron (p < .05) en el GI. El GC no presentó cambios en estos parámetros. Así también, los adultos con DI del GC realizaron menores cantidades de AF moderada a vigorosa (AFMV) que el GI. Sin embargo, el comportamiento sedentario en ambos grupos fue elevado (~79% del tiempo monitorizado). El 69.40% y el 32.10% de los participantes del GI y GC respectivamente cumplieron con las recomendaciones de realizar ≥150 minutos de AFMV/semana. Estos resultados sugieren que un programa de AF aeróbico, de fuerza y equilibrio es beneficioso para los adultos con DI. Las intervenciones para disminuir el tiempo empleado en actividades sedentarias y aumentar la AFMV deberían formar parte del horario laboral de estas personas.Adults with ID have decreased cardiovascular fitness and strength with lower rates of PA, and often have balance and functional impairments. One of the purposes of this study was to investigate the test-retest reliability of the vertical jump test on a contact platform and compare it with the standing long jump test, normally used in the EUROFIT Special battery, to assess leg power. Other aim of the study was to assess the effects of a combined PA program (CPAP) involving aerobic, strength and balance training on cardiovascular fitness, strength, balance and functional measures in a controlled clinical trial. It was also of interest to know and describe the PA patterns of these groups of adults with ID that participated in the CPAP in comparison to a CG. Adults with mild to moderate ID were randomized into either the intervention group (IG; n = 37) or the control group (CG; n = 29). The IG trained 3 d/wk, 1 h/d over 14 wks, while the CG did not participate in any exercise program. Cardiovascular fitness, strength, balance, flexibility and functional ability were assessed pre-post training. The IG increased cardiovascular fitness, (26.8 vs. 29.3 ml•Kg-1•min-1), handgrip strength (19.2 vs. 21.9 kg), leg strength, and balance following the training period (p < .05). Body weight (70.1 vs. 68.1 kg) and body mass index (27.4 vs. 26.6 kg•m-2) decreased (p < .05) in the IG group. The CG showed no changes in any parameter. Adults with ID in the CG were performing less MVPA than the IG. Nevertheless, important sedentary behaviors were observed in both groups (~79% of their monitoring time). In the IG a 69.4% of participants and a 32.1% in the CG met the PA of recommendations of ≥150 minutes of MVPA/week. These data suggest that a combined aerobic, strength and balance exercise training program is beneficial among individuals with ID. Interventions to decrease sedentary time and increase PA levels should be included into their work days

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Calidad de Vida en Pacientes con Diabetes Mellitus Tipo 2 Atendidos en el Instituto Nacional del Diabético, Tegucigalpa, Honduras

Objetivo. Evaluar la calidad de vida de pacientes con diabetes mellitus tipo 2 atendidos en el Instituto Nacional del Diabético, Tegucigalpa, Honduras y determinar la confiabilidad de la versión modificada en español del cuestionario de medida de calidad de vida específica para Diabetes (EsDQOL).  Materiales y Métodos. Se realizó un estudio transversal cuantitativo con una muestra de 350 pacientes. El instrumento utilizado fue la versión modificada del EsDQOL. El procesamiento estadístico se desarrolló con IBM SPSS statistics versión 23,0. Resultados. Los coeficientes de consistencia interna del instrumento mostraron una confiabilidad aceptable (rangos entre 0,63 a 0,85). Todas las preguntas se correlacionaron positivamente (p <0,01) con su dominio y con la puntuación total del cuestionario. En una escala tipo Likert que califica de 1 a 5, de acuerdo con el sistema original de calificación, una menor puntuación implica una mejor calidad de vida observando en la presente investigación una puntuación promedio total de 1,81± 0,39 (IC 95%, 1,07 – 3,30); en la subescala «satisfacción» fue de 1,75 ± 0,56 (IC 95%, 1,0 – 4,93), «impacto» 1,94 ± 0,49 (IC 95%, 1,0 – 3,76), «preocupación social o vocacional» 1,29 ± 0,44 (IC 95%, 1,0 – 3,57) y «preocupación relacionado con la diabetes» 2,44 ± 0,84 (IC 95%, 1,0 – 5,0). Conclusión. Los valores obtenidos en este estudio afirman la fiabilidad y buena consistencia interna de la versión modificada del EsDQOL para medir calidad de vida en pacientes de Honduras así, como puntuaciones que reflejan de forma general una buena percepción de calidad de vida.

Rationale, design, and baseline characteristics in Evaluation of LIXisenatide in Acute Coronary Syndrome, a long-term cardiovascular end point trial of lixisenatide versus placebo

BACKGROUND: Cardiovascular (CV) disease is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Furthermore, patients with T2DM and acute coronary syndrome (ACS) have a particularly high risk of CV events. The glucagon-like peptide 1 receptor agonist, lixisenatide, improves glycemia, but its effects on CV events have not been thoroughly evaluated. METHODS: ELIXA (www.clinicaltrials.gov no. NCT01147250) is a randomized, double-blind, placebo-controlled, parallel-group, multicenter study of lixisenatide in patients with T2DM and a recent ACS event. The primary aim is to evaluate the effects of lixisenatide on CV morbidity and mortality in a population at high CV risk. The primary efficacy end point is a composite of time to CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. Data are systematically collected for safety outcomes, including hypoglycemia, pancreatitis, and malignancy. RESULTS: Enrollment began in July 2010 and ended in August 2013; 6,068 patients from 49 countries were randomized. Of these, 69% are men and 75% are white; at baseline, the mean ± SD age was 60.3 ± 9.7 years, body mass index was 30.2 ± 5.7 kg/m(2), and duration of T2DM was 9.3 ± 8.2 years. The qualifying ACS was a myocardial infarction in 83% and unstable angina in 17%. The study will continue until the positive adjudication of the protocol-specified number of primary CV events. CONCLUSION: ELIXA will be the first trial to report the safety and efficacy of a glucagon-like peptide 1 receptor agonist in people with T2DM and high CV event risk

Effect of SGLT2 Inhibitors on Stroke and Atrial Fibrillation in Diabetic Kidney Disease: Results From the CREDENCE Trial and Meta-Analysis

BACKGROUND AND PURPOSE: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus.METHODS: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-analysis.RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (&lt;45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]).CONCLUSIONS: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02065791

Kidney and Cardiovascular Effects of Canagliflozin According to Age and Sex: A Post Hoc Analysis of the CREDENCE Randomized Clinical Trial

Rationale &amp; Objective: It is unclear whether the effect of canagliflozin on adverse kidney and cardiovascular events in those with diabetic kid-ney disease varies by age and sex. We assessed the effects of canagliflozin among age group categories and between sexes in the Canagli-flozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study.Study Design: Secondary analysis of a random-ized controlled trial. Setting &amp; Participants: Participants in the CREDENCE trial. Intervention: Participants were randomly assigned to receive canagliflozin 100 mg/d or placebo.Outcomes: Primary composite outcome of kid-ney failure, doubling of serum creatinine con-centration, or death due to kidney or cardiovascular disease. Prespecified secondary and safety outcomes were also analyzed. Out-comes were evaluated by age at baseline (&lt;60, 60-69, and &gt;_70 years) and sex in the intention-to-treat population using Cox regression models.Results: The mean age of the cohort was 63.0 &amp; PLUSMN; 9.2 years, and 34% were female. Older age and female sex were independently associ-ated with a lower risk of the composite of adverse kidney outcomes. There was no evidence that the effect of canagliflozin on the primary outcome (acomposite of kidney failure, a doubling of serum creatinine concentration, or death from kidney or cardiovascular causes) differed between age groups (HRs, 0.67 [95% CI, 0.52-0.87], 0.63 [0.4 8-0.82], and 0.89 [0.61-1.29] for ages &lt;60, 60-69, and &gt;_70 years, respectively; P = 0.3 for interaction) or sexes (HRs, 0.71 [95% CI, 0.5 4-0.95] and 0.69 [0.56-0.8 4] in women and men, respectively; P = 0.8 for interaction). No differences in safety outcomes by age group or sex were observed.Limitations: This was a post hoc analysis with multiple comparisons.Conclusions: Canagliflozin consistently reduced the relative risk of kidney events in people with diabetic kidney disease in both sexes and across age subgroups. As a result of greater background risk, the absolute reduction in adverse kidney outcomes was greater in younger participants.Funding: This post hoc analysis of the CREDENCE trial was not funded. The CREDENCE study was sponsored by Janssen Research and Development and was conducted collaboratively by the sponsor, an academic-led steering committee, and an academic research organization, George Clinical.Trial Registration: The original CREDENCE trial was registered at ClinicalTrials.gov with study number NCT02065791