METHODS: One hundred thirteen patients who met International Headache Society criteria for migraine and who did not experience satisfactory response to nonsteroidal anti-inflammatory drugs, received open-label treatment with a 40-mg dose of eletriptan for one migraine attack. Efficacy assessments were made at 1, 2, 4, and 24 hours postdose and consisted of headache and pain-free response rates, absence of associated symptoms, and functional response. Global ratings of treatment effectiveness and preference were obtained at 24 hours.
RESULTS: The pain-free response rate at 2 hours postdose was 25% and at 4 hours postdose, 55%; the headache response rate at 2 hours was 66% and at 4 hours, 87%. At 2 hours postdose, relief of baseline associated symptoms was achieved by 41% of patients with nausea compared to 82% of patients at 4 hours; for patients with phonophobia, 67% were relieved at 2 hours and 93% at 4 hours, and for patients with photophobia, 70% were relieved at 2 hours and 91% at 4 hours. Functional response was achieved by 70% of patients by 2 hours postdose. The high level of acute response was maintained over 24 hours, with only 24% of patients experiencing a headache recurrence and only 10% using rescue medication. At 24 hours postdose, 74% of patients rated eletriptan as preferable to any previous treatment for migraine. The most frequent reasons cited for this treatment preference were faster headache improvement (83%) and functional response (78%). Overall, eletriptan was well tolerated; most adverse events were transient and mild to moderate in severity. No serious adverse events were reported.
CONCLUSION: Results of this open-label trial found the 40-mg dose of eletriptan to have a high degree of efficacy and tolerability among patients who responded poorly to nonsteroidal anti-inflammatory drugs.
METHODS: In this open-label, multicentre phase 2 trial, we recruited patients aged 21 years or older with relapsed or refractory peripheral T-cell lymphoma who had received at least one previous line of systemic therapy from five tertiary hospitals in Singapore, Malaysia, and South Korea. Patients received 20 mg oral panobinostat three times a week and 1·3 mg/m(2) intravenous bortezomib two times a week, both for 2 of 3 weeks for up to eight cycles. The primary endpoint was the proportion of patients who achieved an objective response in accordance with the International Working Group revised response criteria; analyses were by intention to treat. The study is completed and is registered with ClinicalTrials.gov, number NCT00901147.
FINDINGS: Between Nov 9, 2009, and Nov 26, 2013, we enrolled 25 patients with various histological subtypes of peripheral T-cell lymphoma. Of 23 patients assessable for responses, ten (43%, 95% CI 23-63) patients had an objective response, of which five were complete responses. Serious adverse events were reported in ten (40%) of 25 patients. Common treatment-related grade 3-4 adverse events included thrombocytopenia (17 [68%]), neutropenia (ten [40%]), diarrhoea (five [20%]), and asthenia or fatigue (two [8%]). We recorded peripheral neuropathy of any grade in ten (40%) patients.
INTERPRETATION: Combined proteasome and histone deacetylase inhibition is safe and feasible and shows encouraging activity for patients with peripheral T-cell lymphoma. Our findings validate those of preclinical studies showing synergism in the combination and represent a rational way forward in harnessing the full potential of novel agents in peripheral T-cell lymphoma.
FUNDING: Novartis Pharmaceuticals, Janssen Pharmaceuticals, and Singhealth Foundation.
METHODS AND RESULTS: This was a retrospective longitudinal study of HF patients aged ≥18 years hospitalized at a tertiary healthcare center between January 1, 2009 and December 31, 2013 in Ghana. Patients were eligible if they were discharged from first admission for HF (index admission) and followed up to time of all-cause, cardiovascular, and HF mortality or end of study. Multivariable time-dependent Cox model and inverse-probability-of-treatment weighting of marginal structural model were used to estimate associations between statin treatment and outcomes. Adjusted hazard ratios were also estimated for lipophilic and hydrophilic statin compared with no statin use. The study included 1488 patients (mean age 60.3±14.2 years) with 9306 person-years of observation. Using the time-dependent Cox model, the 5-year adjusted hazard ratios with 95% CI for statin treatment on all-cause, cardiovascular, and HF mortality were 0.68 (0.55-0.83), 0.67 (0.54-0.82), and 0.63 (0.51-0.79), respectively. Use of inverse-probability-of-treatment weighting resulted in estimates of 0.79 (0.65-0.96), 0.77 (0.63-0.96), and 0.77 (0.61-0.95) for statin treatment on all-cause, cardiovascular, and HF mortality, respectively, compared with no statin use.
CONCLUSIONS: Among Africans with HF, statin treatment was associated with significant reduction in mortality.