The effect of parathyroid hormone (1-84) treatment on serum bone morphogenetic protein 4 and vascular endothelial growth factor in postmenopausal women with established osteoporosis.

PURPOSE: To investigate the effect of 18 months' parathyroid hormone 1-84 (PTH 1-84) treatment on serum levels of bone morphogenetic protein 4 (BMP4) and vascular endothelial growth factor (VEGF), in postmenopausal women with established osteoporosis. METHODS: Thirty-seven postmenopausal women with osteoporosis (mean age 72.9 ± 8.1 years old) and 23 healthy controls (mean age 68.9 ± 9.9 years old) were enrolled. Patients were treated with daily subcutaneous injections of PTH (1-84) 100 mcg for 18 months, plus calcium 1 gr and vitamin D 800 IU per os daily. Blood samples were taken every 6 months during the study. RESULTS: At baseline, there were no differences considering anthropometric parameters, co-morbidities, current medications used between patients and controls. Mean serum VEGF levels were significantly higher in osteoporotic patients compared to controls (436.7 ± 259.7 vs. 260.3 ± 184.3 pg/ml, p = 0.006), while there were no differences in mean serum values of BMP4 (5.3 ± 1.7 vs. 5.7 ± 1.6 pg/ml, p = 0.40). Serum VEGF levels increased by approximately 20% after 12 months of PTH (1-84) treatment compared to baseline (p = 0.03) and by 22% after 18 months (p = 0.01). A significant increase of 10% in mean serum BMP4 levels was observed after 18 months of PTH (1-84) treatment compared to baseline (p = 0.02). In the control group we found no differences after 18 months compared to baseline in BMP4 (5.7 ± 1.6 vs. 6.0 ± 1.5 pg/ml, p = 0.53) and VEGF (260.3 ± 184.3 vs. 257.4 ± 107.1 pg/ml, p = 0.94). CONCLUSIONS: PTH (1-84) treatment increased serum levels of VEGF and BMP4 in postmenopausal women with severe osteoporosis.

Results of a national multicentric study on compliance to treatment with various disphosphonate formulations in patients with postmenopausal osteoporosis.

AIM: Compliance to pharmacological treatment for osteoporosis is crucial if the risk of fracture is to be reduced. Case series show that treatment with traditional bisphosphonates in the form of tablets has a compliance of between approximately 30% and 70%. The aims of this paper were to assess compliance to treatment with various formulations of bisphonates and to identify those at highest risk of discontinuation. METHODS: In this multicentre retrospective observational study, a population of 387 women diagnosed with postmenopausal osteoporosis under treatment with bisphosphonates (risedronate, ibandronate, alendronate in tablet form, alendronate in a fluid solution per os) was observed for at least a year. Demographic data and information pertaining to the type of drug taken, compliance to treatment, side effects, reasons for discontinuation, the basal examination and follow-up at 18 months and later were recorded. RESULTS AND CONCLUSION: Analysis of patient compliance to a prescribed treatment plan showed a significantly higher persistence (P<0.001) in the group taking alendronate in soluble solution form (83.3%) compared to the group taking any bisphosphonate in tablet form (66.7%). At the same time, patientspresenting comorbidity, receiving more than one therapy, not taking vitamin D, and in surgical menopause, risked discontinuation.

Approach in glucocorticoid-induced osteoporosis prevention: results from the Italian multicenter observational EGEO study.

Glucocorticoid-induced osteoporosis (GIO) is the most frequent cause of secondary osteoporosis. GIO is linked to glucocorticoids (GC) daily assumption with maximum effect within first months of treatment and decreasing to basal levels as the therapy is discontinued. In Italy, primary prevention of GIO is suggested when GC therapy (prednisone >5 mg/day or equivalent) is taken for longer than 3 months. Lazio GISMO (Italian Group for Study and Diagnosis of Bone Metabolism Diseases) group organized the GC and Osteoporosis Epidemiology study (EGEO) to evaluate physician's approach in preventing GIO. The study involved 19 osteoporosis centers. Patients taking long-term GC therapy were recruited and information collected: medical history and anthropometric data, GC therapy, primary disease, physician's specialty, osteopororosis screening, and pharmacological intervention. The study included 1334 patients. Mean age was 63 ± 13 yr; 243 (18%) patients had a history of falls from standing position in the previous 12 months, 78 (35%) vertebral fractures, 91 (41%) fractures other than vertebral, 27 (12%) femoral fractures, and 27 (12%) multiple sites fractures. The molecules of GC more often prescribed were prednisone and 6-metil prednisolone. One thousand and forty patients (78%) were taking GC for more than 6 months. GC therapy was prescribed more frequently by rheumatologists (62%). Antiosteoporotic drugs for GIO prevention were prescribed in 431 patients (32%). Among the patients, only 27% (360) received calcium and vitamin D supplements, and 39% (319) treated by rheumatologists received anti-resorptive drugs. In conclusion, our data show that in Italy, as already described elsewhere, only a small subpopulation of GC-treated patients was supported by an anti-osteoporotic therapy, indicating the need to further stimulate awareness of both patients and specialists, prescribing GC therapy, to an appropriate and prompt GIO prevention.

The impact of prophylactic treatment on post-traumatic epilepsy after severe traumatic brain injury.

AIM: To assess the incidence of late post-traumatic epilepsy (PTE) in patients with very severe traumatic brain injury (TBI) who either received or did not receive anti-epileptic prophylactic treatment. METHODS: Two populations were studied: 55 patients retrospectively and 82 subjects prospectively. RESULTS: Ten patients (18%) in the first population showed late PTE. Although the incidence was lower in patients who did not receive prophylactic treatment, the difference between the treated and the non-treated group was not statistically significant. Sixty-nine patients in the second group (84%) had prophylactic treatment. Twenty-seven patients (39%) suffered from late PTE during the 2-year follow-up period and 17 of them (63%) showed EEG epileptic abnormalities. No patient who did not receive preventive therapy suffered from late PTE during the observation period. CONCLUSIONS: Due to the negative cognitive effects of anti-epileptic drugs, the preliminary results are of considerable interest for the rehabilitation of patients with very severe TBI.

Early clinical predictive factors during coma recovery.

In severe brain injury patients few studies have examined the role of early clinical factors emerging before recovery of consciousness. Patients suffering from vegetative state and minimally conscious state in fact may need variable periods of time for recovery of the ability to follow commands. In a previous study we retrospectively examined a population of very severe traumatic brain injury patients with coma duration of at least 15 days (prolonged coma), and we found, as significant predictive factors for the final outcome, the time interval from brain injury to the recovery of the following clinical variables: optical fixation, spontaneous motor activity and first safe oral feeding. Psychomotor agitation and bulimia during coma recovery were also favourable prognostic factors for the final outcome. In a further study, also as for the neuropsychological recovery, the clinical variable with the best significant predictive value was the interval from head trauma to the recovery of safe oral feeding. In the present study the presence of psychomotor agitation diagnosed by means of LCF (score 4 = confused-agitated) at the admission time in rehabilitation predicted a statistically significant better outcome at the discharge time in comparison with patients without agitation.

Clinical predictors and neuropsychological outcome in severe traumatic brain injury patients.

BACKGROUND: The aim of the study was to evaluate the possible significant role of some clinical factors in predicting cognitive outcome in a group of severe traumatic brain injury (TBI) patients, with Glasgow Coma Scale (GCS) lower than 8 and duration of unconsciousness for at least 15 days (prolonged coma). METHOD: A consecutive sample of 25 survivors of severe TBI attending the Physical and Cognitive Rehabilitation program participated in this study. The neuropsychological test battery included: Word-list Learning, Prose recall, Rey Figure Delayed recall, Word fluency, Raven's Progressive Matrices' 47. The clinical variables evaluated in correlation with the neuropsychological outcome were the following: age, duration of unconsciousness, duration of post-traumatic amnesia, interval from head trauma to neuropsychological evaluation, interval from head trauma to recovery of oral feeding, and finally interval from head trauma to first verbal communication. FINDINGS: The clinical variable with a significant predictive value on most neuropsychological scores was the interval from head trauma to the recovery of oral feeding. CONCLUSIONS: If this result is confirmed in larger samples, time interval of oral feeding recovery from head trauma should be considered as a possible predictor of neuropsychological outcome in TBI patients with prolonged coma.

Time interval of oral feeding recovery as a prognostic factor in severe traumatic brain injury.

PRIMARY OBJECTIVES: To assess the outcome of severe traumatic brain injury at least 1 year after trauma, in relation to some early clinical prognostic factors occurring during coma recovery. RESEARCH DESIGN: Retrospective study conducted at the post-coma unit of a rehabilitation hospital. METHODS AND PROCEDURES: A total of 43 patients were included. All of the patients sustained severe traumatic brain injury and prolonged coma, i.e. coma lasting at least 15 days. Outcome was assessed by means of Glasgow Coma Scale, Barthel Index and Mini Mental State 1 year after trauma, in relation to some early clinical prognostic factors occurring during coma recovery. MAIN OUTCOMES AND RESULTS: At the 1 year follow-up, a statistically significant correlation was found with both the Glasgow Outcome Scale and the Barthel Index for the time interval from brain injury to recovery of the following clinical variables: optical fixation, ability to obey commands, spontaneous motor activity and first safe oral feeding. Psychomotor agitation and bulimia were also favourable prognostic factors for the final outcome. CONCLUSIONS: In the present study, first safe oral feeding during coma recovery represents the clinical feature that better predicts the final outcome of patients with severe traumatic brain injury and prolonged coma.

Active music therapy in the rehabilitation of severe brain injured patients during coma recovery.

Active improvised music therapy may offer an adjuvant from of treatment in the early rehabilitation of severe brain-injured patients. Active music therapy consists of musical improvisation between patient and therapist by singing or by playing different musical instruments, according to the vital functions, the neurological conditions and the motor abilities of the patients. We studied 34 severe brain-injured patients with a mean coma duration of 52 days +/- 37.21 and a mean interval from coma onset to the beginning of rehabilitation of 154 days on average. Our preliminary results show a significant improvement of the collaboration of the severe brain-injured patients and a reduction of undesired behaviours such as inertia (reduced psychomotor initiative) or psychomotor agitation.

Immunological and endocrinological disturbances in patients after prolonged coma following head injury.

It has been previously reported that following severe brain damage, a deficit of cellular immunity could be detected in the early phase after the occurence of the lesion. We report here the results of a cross-sectional study on long term effects of severe brain damage on immunological and neuro-endocrine changes in patients who recovered from prolonged coma caused by head injury. Results obtained from post-comatose (PC) patients were compared with those obtained from two control groups made up of spinal-cord injury (SCI) patients and healthy subjects, respectively. The following parameters were studied: lymphomonocyte subsets; interleukin 2 (IL-2) production; natural killer (NK) activity and serum levels of adrenocorticotrophic hormone (ACTH), cortisol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, tri-iodothyronine (T3) and thyroxine (T4). With respect to healthy controls the PC1 subgroup, i.e. patients examined 3-6 months after injury, showed a statistically significant decrease in IL-2 production, NK activity and CD25+ lymphocytes. Similar immunological disturbances were observed in SCI but not in the PC2 subgroup, i.e. patients examined later than 6 months after injury. The same sub-group of PC1 patients showed high serum levels of cortisol and PRL. These results could be related to the immunological status and may be interpreted as a transient but prolonged condition of chronic stress or "chronic alarm reaction". Copyright Rapid Science Ltd