Rationale and methods of the multicenter randomised trial of a heart failure management programme among geriatric patients (HF-Geriatrics)

<p>Abstract</p> <p>Background</p> <p>Disease management programmes (DMPs) have been shown to reduce hospital readmissions and mortality in adults with heart failure (HF), but their effectiveness in elderly patients or in those with major comorbidity is unknown. The Multicenter Randomised Trial of a Heart Failure Management Programme among Geriatric Patients (HF-Geriatrics) assesses the effectiveness of a DMP in elderly patients with HF and major comorbidity.</p> <p>Methods/Design</p> <p>Clinical trial in 700 patients aged ≥ 75 years admitted with a primary diagnosis of HF in the acute care unit of eight geriatric services in Spain. Each patient should meet at least one of the following comorbidty criteria: Charlson index ≥ 3, dependence in ≥ 2 activities of daily living, treatment with ≥ 5 drugs, active treatment for ≥ 3 diseases, recent emergency hospitalization, severe visual or hearing loss, cognitive impairment, Parkinson's disease, diabetes mellitus, chronic obstructive pulmonary disease (COPD), anaemia, or constitutional syndrome. Half of the patients will be randomly assigned to a 1-year DMP led by a case manager and the other half to usual care. The DMP consists of an educational programme for patients and caregivers on the management of HF, COPD (knowledge of the disease, smoking cessation, immunizations, use of inhaled medication, recognition of exacerbations), diabetes (knowledge of the disease, symptoms of hyperglycaemia and hypoglycaemia, self-adjustment of insulin, foot care) and depression (knowledge of the disease, diagnosis and treatment). It also includes close monitoring of the symptoms of decompensation and optimisation of treatment compliance. The main outcome variables are quality of life, hospital readmissions, and overall mortality during a 12-month follow-up.</p> <p>Discussion</p> <p>The physiological changes, lower life expectancy, comorbidity and low health literacy associated with aging may influence the effectiveness of DMPs in HF. The HF-Geriatrics study will provide direct evidence on the effect of a DMP in elderly patients with HF and high comorbidty, and will reduce the need to extrapolate the results of clinical trials in adults to elderly patients.</p> <p>Trial registration</p> <p>(ClinicalTrials.gov number, <a href="http://www.clinicaltrials.gov/ct2/show/NCT01076465">NCT01076465</a>).</p

Scleredema Diabeticorum in a Patient with Type 2 Diabetes Mellitus

Background. Scleredema adultorum, a connective tissue disorder of unknown aetiology, is characterized by a thickening of the reticular dermis in the upper back of the body that may decrease the mobility of the affected tissues. It has been reported in diabetic patients with poor metabolic control. Therapeutic options are limited with generally poor results. Case Report. 53-year-old white male with type 2 diabetes mellitus was referred to our department for evaluation of incipient nephropathy and retinopathy. On examination, he presented erythematous, indurated, painless and ill-defined plaque on the skin of the upper back with limited movement of shoulders. A biopsy was done revealing scleredema. PUVA treatment and physiotherapy were started with the amelioration of mobility and acquiring some elasticity of the upper back. Discussion. The development of scleredema in diabetic patients has been related to prolonged exposure to chronic hyperglycaemia. Our patient has had diabetes for 20 years with an acceptable glucose control, however he developed the scleredema 10 years ago. Conclusions. Scleredema is a rare connective disorder that seems to appear most frequently in diabetic subjects. Good metabolic control seems not to preclude its development. PUVA treatment and physiotherapy are therapeutic options that seem to be of some help

Receptor activator of nuclear factor-kB ligand -RANKL- as a novel prognostic marker in prostate carcinoma

Combined immunodetection of parathyroid hormone-related protein (PTHrP) and receptor activator of NF-kB ligand (RANKL) has shown to successfully distinguish poorly- and well-differentiated prostate carcinoma (PCa). In the present study, we aimed to assess whether immunohistochemical evaluation of these factors, and also osteoprotegerin (OPG) and Ki67, in radical prostatectomy specimens can predict biochemical recurrence. Fifty nine PCa cases undergoing radical prostatectomy between 1995 and 1998, without history of neoadjuvant hormonal therapy, were studied. Preoperative serum prostate-specific antigen (PSA), Gleason-sum score, pathologic stage, perineural invasion, seminal vesicle involvement, and positive surgical margins were assessed in these patients. Biochemical recurrence, defined by PSA > 0.4 ng/mL at 90 days or later after prostatectomy, occurred in 32/59 patients. In these patients, positivity for OPG and RANKL in the tumoral epithelium was higher than in those patients with no biochemical recurrence. Using univariate analysis, Gleason-sum score, surgical margins, and seminal vesicle involvement, as well as OPG and RANKL immunostaining (using a score value corresponding to moderate staining as cut-off) were significant predictors of biochemical recurrence (p<0.05). Using the multivariate Cox model, among the evaluated factors only RANKL expression (hazard ratio 11.6; p <0.001) was an independent prognostic indicator. Our findings suggest that immunohistochemical evaluation of RANKL in the primary tumor is a potential risk factor in PCa patients

Immunohistochemical analysis of low‐grade and high‐grade prostate carcinoma: relative changes of parathyroid hormone‐related protein and its parathyroid hormone 1 receptor, osteoprotegerin and receptor activator of nuclear factor‐kB ligand

AIM: To investigate multiple bone cytokines produced by prostate carcinoma (PCa) as a novel strategy to differentiate potential aggressiveness in localised PCa using immunohistochemical analysis. METHODS: A total of 47 cases of PCa undergoing radical prostatectomy or transurethral prostatic resection at our institution (Fundación Jiménez Díaz (Grupo Capio), Madrid, Spain) between January 1991 and June 1998 were identified as low‐grade (⩽4; n = 22) or high‐grade (⩾7, excluding 7 (3+4) cases; n = 25) PCa according to Gleason grade. PCa specimens were immunostained for: parathyroid hormone (PTH)‐related protein (PTHrP), the PTH1 receptor, osteoprotegerin and receptor activator of nuclear factor‐κ B ligand (RANKL), as well as Ki67 (a proliferation marker) and CD34 (an angiogenesis marker). RESULTS: PCa samples showed an increased immunostaining for both osteoprotegerin and RANKL, associated with tumour grade and PTHrP positivity, in the tumoral epithelium. Using a score value of 4—corresponding to moderate staining—as cut‐off, the best sensitivity value was for PTHrP (with C‐terminal antiserum C6; 100 %); wheras the best specificity value was for RANKL (95 %). CONCLUSIONS: All the evaluated factors are overexpressed mainly in the high‐grade tumours. Our findings indicate that, in most patients with PCa (with Ki67 values between 1% and 9%), sequential determination of C‐terminal PTHrP and RANKL immunoreactivities is a useful approach to discriminate low‐grade and high‐grade tumours