Efficacy and Long-term Safety of Dexibuprofen [S(+)-Ibuprofen]: A Short-term Efficacy Study in Patients with Osteoarthritis of the Hip and a 1-Year Tolerability Study in Patients with Rheumatic Disorders

ObjectiveDeep brain stimulation (DBS) of the ventral intermediate thalamic nucleus (Vim) is established for medically refractory severe essential tremor (ET), but long-term efficacy is controversial.MethodsTwenty patients with ET with DBS had standardized video-documented examinations at baseline, in the stimulation-on condition at short term (13.1 ± 1.9 months since surgery, mean ± SEM), and in the stimulator switched on and off (stim-ON/OFF) at long term; all assessments were done between 32 and 120 months (71.9 ± 6.9 months) after implantation. The primary outcome was the Tremor Rating Scale (TRS) blindly assessed by 2 trained movement disorder neurologists. Secondary outcomes were TRS subscores A, B, and C; Archimedes spiral score; and activities of daily living score. At long-term follow-up, tremor was additionally recorded with accelerometry. The rebound effect after switching the stimulator off was assessed for 1 hour in a subgroup.ResultsTremor severity worsened considerably over time in both in the nonstimulated and stimulated conditions. Vim-DBS improved the TRS in the short term and long term significantly. The spiral score and functional measures showed similar improvements. All changes were highly significant. However, the stimulation effect was negatively correlated with time since surgery (ρ = −0.78, p < 0.001). This was also true for the secondary outcomes. Only one-third of the patients had a rebound effect terminated 60 minutes after the stimulator was switched off. Long-term worsening of the TRS was more profound during stim-ON than in the stim-OFF condition, indicating habituation to stimulation.ConclusionVim-DBS loses efficacy over the long term. Efforts are needed to improve the long-term efficacy of Vim-DBS.Classification of evidenceThis study provides Class IV evidence that for patients with medically refractory severe ET, the efficacy of Vim-DBS severely decreases over 10 years.

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Short- and Long-Term Efficacy of Hexadecylphosphocholine against Established Leishmania infantum Infection in BALB/c Mice

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.42.3.654 ◽

1998 ◽

Vol 42 (3) ◽

pp. 654-658 ◽

Cited By ~ 46

Author(s):

Yves Le Fichoux ◽

Déborah Rousseau ◽

Bernard Ferrua ◽

Sandrine Ruette ◽

Alain Lelièvre ◽

...

Keyword(s):

Leishmania Infantum ◽

Immunocompetent Host ◽

Short Term ◽

Fatal Disease ◽

Promising Candidate ◽

Term Efficacy ◽

End Of Treatment ◽

Immunosuppressed Patients ◽

Short And Long Term

ABSTRACT In the immunocompetent host, visceral leishmaniasis (VL) is a fatal disease if untreated. In immunosuppressed patients, VL is an opportunistic infection for which there is no effective treatment for relapses. Here we report on the long-term activity of orally administered hexadecylphosphocholine (HDPC) against establishedLeishmania infantum infection in BALB/c mice. HDPC is a synthetic phospholipid with antiproliferative properties that has been extensively studied for its cancerostatic activity. Its short-term leishmanicidal effects in mice recently infected with viscerotropicLeishmania species have been previously reported. First, we show that 5 days of oral therapy with HDPC (20 mg/kg of body weight/day) led to amastigote suppression in the liver and the spleen of 94 and 78%, respectively (versus 85 and 55% suppression by meglumine antimonate in the liver and spleen, respectively), in mice infected 6 weeks before treatment and examined 3 days after the end of treatment. These results demonstrate the short-term efficacy of HDPC against an established Leishmania infection. Next, the long-term efficacy of HDPC was examined. In HDPC-treated mice both the hepatic and splenic amastigote loads were significantly reduced (at least 89%) 10, 31, and 52 days after the end of the treatment. In the treated mice, the increase of the splenic load was significantly slower than that in the untreated mice, demonstrating that the HDPC-exerted inhibition of Leishmania growth persisted for at least 7 to 8 weeks. Orally administered HDPC—the safe doses and side effects of which are at least partially known—appears to be a promising candidate for the treatment of VL.

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