Alfacalcidol is a safe and effective treatment strategy to decrease fatigue and improve QoL in patients with MS.

Objectives: Because impaired renal function is detrimental for the conversion of calcidiol to calcitriol (D-hormone) and since D-hormone analogues have been shown to decrease the risk of falls, we investigated whether creatinine clearance (CrCl) is associated with the number of fallers and falls in elderly men and women. Methods: Within a randomized controlled study, we observed for 36 weeks 186 placebo-treated community-dwelling elderly men and women over 70, in an attempt to determine the influence of baseline CrCl on calcitropic hormone serum levels, as well as the influence of baseline CrCl on the number of fallers and falls over time. With the help of questionnaires, we regularly assessed fall incidence and frequency. The risk of falls and the risk of becoming a faller were assessed in multivariate-controlled logistic regression models according to a cutoff value of the CrCl set at 65 ml/min. Results: At baseline, serum levels of 1.25(OH) 2 D 3 and iPTH were, in multivariate-controlled analyses, significantly associated with CrCl (p<0.0001, p=0.001, respectively), whereas serum levels of 25(OH)D 3 were not associated with CrCl. Below a CrCl of 65 ml/min, 1.25(OH) 2 D 3 serum levels steadily declined. We therefore chose a CrCl of 65 ml/min as cutoff for further analyses. During the 36 weeks of observation, elderly people with a CrCl of <65 ml/min had, in multivariate controlled analyses, compared with elderly with a CrCl of ‡65 ml/min, a significantly higher incidence of number of fallers (25/70 vs 21/116; OR=4.01; 95% CI, 1.48-10.98; p=0.006), and a significantly higher incidence of falls (28/70 vs 23/ 116; OR=3.68; 95% CI, 1.38-9.82; p=0.009). Conclusions: For the first time we showed that in a communitydwelling population of elderly men and women, a CrCl of less than 65 ml/min is a significant and independent risk factor for fallers and falls.

We previously observed that a creatinine clearance (CrCl) of <65 ml/min is a significant and independent risk factor for the number of fallers and falls in a community-dwelling elderly population and postulated that this increased risk is due to the associated significant lower D-hormone serum levels. To test our hypothesis, we investigated in a post hoc analysis of a double-blind randomized study whether treatment with alfacalcidol, a synthetic prodrug of the D-hormone, can reduce the high incidence of fallers and the high risk of falls associated with low CrCl. Of 378 Swiss community-dwelling women (n=191) and men (n=187), aged 70 years and older, 191 received randomly 1 lg capsules of alfacalcidol (AlphaD3: Teva), and 187 received one capsule of placebo daily. With the help of questionnaires we regularly assessed the incidence and frequency of falls. The risk of becoming a faller and the risk of falling were assessed in multivariate-controlled logistic regression models according to treatment groups and according to a CrCl cut-off of 65 ml/min. The presented results are from ITT analyses. In participants with a CrCl of <65 ml/min, the 36 weeks of treatment with alfacalcidol was, compared with placebo, associated with a significant reduction in the number of fallers (14/72 versus 25/70; OR 0.26, 95% CI 0.08-0.80, P=0.019), and a significant reduction of the number of falls (16/72 versus 28/70; OR 0.29, 95% CI 0.09-0.88, P=0.028). No such association was observed in participants with a CrCl of ‡65 ml/min (for fallers 26/120 versus 21/116; OR 0.92 95% CI 0.34-2.52, P=0.875; for falls 32/120 versus 23/116; OR 0.93 95% CI 0.34-2.54, P=0.885). In the placebo group frequency of falls was dependent on CrCl (P=0.006), whereas in the alfacalcidol treatment group frequency of falls was independent of CrCl (P=0.494). No cases of clinically relevant hypercalcemia were observed. In a community-dwelling population of elderly men and women with a CrCl of <65 ml/min, treatment with alfacalcidol can significantly and safely reduce the low CrCl associated increased number of fallers and the high risk of falls.

No abstract

One of the major problems in the treatment of glaucoma is the limited therapeutic effect (6 to 8 hours) of pilocarpine eye drops. Consequently many attempts have been made to prolong the hypotensive effect of pilocarpine. Increase in concentration of pilocarpine above 4 % has failed to show a significant increase or prolongation of therapeutic effect (Harris

SUMMARY Induced accommodation and changes in vision (distance and near) were measured monocularly and binocularly in 9 young healthy volunteers in a double blind study after administering to them pilocarpine hydrochloride 4%, Piloplex 3 4, and saline eye drop instillations. Piloplex 3.4, a new long-acting pilocarpine polymer salt, and pilocarpine hydrochloride 4 % (both contain equal amounts of pilocarpine-3-4 %) induced changes in vision and accommodation. These changes were greater with pilocarpine hydrochloride than with Piloplex. The maximum changes occurred half an hour after instillation and the effect vanished after an additional period up to 3 hours. The changes were greater when measured monocularly than binocularly. Piloplex initiates a prolonged hypotensive effect which lasts for 12 hours. Patients with glaucoma are thus able to use Piloplex on a twice-daily schedule. Consequently, visual disturbances occur only once a day in contrast to pilocarpine hydrochloride given 4 times a day, which induces 3 visual disturbances during the day.The advantage of Piloplex-a new pilocarpine polymer salt-over pilocarpine hydrochloride (PHCI) has been previously presented (Ticho et al., 1978;Blumenthal et al., 1979). Piloplex eye drops were found to have a prolonged and increased hypotensive effect, allowing them to be given on a twice-daily schedule in contrast to a 4-times daily schedule necessary for PHCI. The hypotensive effect of miotic drugs, however, is accompanied by miosis and accommodative spasm, inducing blurred vision. These side effects are predominant in young patients (Place et al., 1975;Brown et al., 1976). Adverse side effects of this nature have not been encountered with Piloplex treatment so far.This communication reports on a study in which the induced visual effects of pilocarpine hydrochloride and Piloplex were compared in young normal persons. Patients and methodsNine medical students who had no record of ophthalmic disturbances were selected for the study.

This is a preplanned subgroup analysis on 318 patients with glucocorticoid-induced osteoporosis (GIOP) from an open, prospective, multi-centered, uncontrolled study on a large cohort of elderly patients with a high risk of falls and fractures. The entire group of 2579 patients was recruited by 818 practicing physicians and treated for three months with a new combination package containing 4 or 12 self-explanatory one-week blisters, each with one tablet of 70 mg alendronate (CAS 260055-05-8) and 7 capsules of 1 pg alfacalcidol (CAS 41294-56-8) (Tevabone"). The average age of the GIOP patients was 71 years and the mean body mass index 26.7 kg/m2. 58% had a diagnosis of increased risk of falls, prevalent vertebral and non-vertebral fractures were documented in 70% and 65% of the patients, respectively, and a creatinine clearance (CrCl) below 65 ml/min was documented in 55 %. Main outcome parameters were the Chair Rising Test (CRT), Timed Up and Go Test (TUG), back pain and safety at onset and after 3 months. In addition, an evaluation of the package design was done at the end of the study. The percentage of patients able to perform the CRT within 10 sec increased from 21.1% to 39.4% after 3 months (increase 87%, p < 0.0001), while successful performance of TUG within 10 sec increased by 84% (p < 0.0001) from 23.1% at onset to 42.4% after 3 months. The mean time required to perform the CRT decreased after 3 months from an average of 15.92 to 14.02 sec (p = 0.0025) (difference of 1.9 sec) and for the TUG the mean time decreased from 16.86 sec to 14.64 sec (p = 0.0056) (difference of 2.2 sec). Mean back pain measured by a 0-10 visual analogue scale decreased significantly by 43% from 6.0 to 3.4 (p < 0.0001). Throughout the study 23 adverse events (AE) were reported in 11 of the 318 GIOP patients (incidence: 3.5 %). There were no patients who experienced serious AE. Patients using the new combined regimen of alfacalcidol plus alendronate for treating GIOP achieved significant improvements in CRT, TUG and back pain already after 3 months, with a high safety profile and good compliance. This may contribute to the previously shown significant effect on reducing falls and fractures with the same regimen during a controlled long-term trial in primary osteoporosis.

One hundred and seventeen Israeli-Friesian cows from herds with a milk fever incidence of more than 15 per cent were injected intramuscularly with either 350 micrograms 1 alpha hydroxyvitamin D3 (1 alpha OHD3) in propylene glycol or with the vehicle alone, close to calving. If parturition had not occurred within 72 hours a second injection was administered; parturition was induced two days after the second injection if necessary. There were 10 cases of milk fever among 57 control cows as opposed to two cases among the 60 animals treated with 1 alpha OHD3. In an attempt to prolong the effect of the drug, Israeli-Friesian cows were injected intramuscularly with 350 micrograms 1 alpha OHD3 in either 10 ml propylene glycol or arachis oil. 1 alpha OHD3 in arachis oil did not prolong the effect of the drug. 1 alpha OHD3 in propylene glycol increased plasma calcium concentrations more rapidly than when the drug was administered in oil. Additional cows of the same breed and age were injected intramuscularly with 350 micrograms 1 alpha OHD3 in propylene glycol. Five of the animals received a second dose four days, and five received a second dose five days after the first injection. Five animals served as uninjected controls. The plasma calcium levels of the injected cows were significantly higher (P less than 0.01) than those of the controls from the second until the 14th day after the first injection. Based on these results 451 Israeli-Friesian cows from herds with a milk fever incidence of more than 15 per cent were injected intramuscularly with 1 alpha OHD3 close to calving.(ABSTRACT TRUNCATED AT 250 WORDS)