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1.
Nat Commun ; 12(1): 4211, 2021 Jul 09.
Article in English | MEDLINE | ID: mdl-34244511

ABSTRACT

The margins of the Caribbean and associated hazards and resources have been shaped by a poorly understood history of subduction. Using new data, we improve teleseismic P-wave imaging of the eastern Caribbean upper mantle and compare identified subducted-plate fragments with trench locations predicted from plate reconstruction. This shows that material at 700-1200 km depth below South America derives from 90-115 Myr old westward subduction, initiated prior to Caribbean Large-Igneous-Province volcanism. At shallower depths, an accumulation of subducted material is attributed to Great Arc of the Caribbean subduction as it evolved over the past 70 Ma. We interpret gaps in these subducted-plate anomalies as: a plate window and tear along the subducted Proto-Caribbean ridge; tearing along subducted fracture zones, and subduction of a volatile-rich boundary between Proto-Caribbean and Atlantic domains. Phases of back-arc spreading and arc jumps correlate with changes in age, and hence buoyancy, of the subducting plate.

2.
Clin Pharmacol Drug Dev ; 6(3): 224-233, 2017 May.
Article in English | MEDLINE | ID: mdl-27139158

ABSTRACT

Two multicenter, randomized, placebo-controlled, adaptive-design trials of desvenlafaxine for fibromyalgia syndrome (FMS) were conducted. In study 1, male and female patients were randomized to a 27-week treatment with placebo or desvenlafaxine 50, 100, 200, or 400 mg/d. In study 2, female patients were randomized to an 8-week treatment with placebo, desvenlafaxine 200 mg/d, or pregabalin 450 mg/d after a placebo run-in. The primary efficacy end point was change from baseline in numeric rating scale (NRS) pain score. Protocol-specified interim analyses were planned after 12 (study 1) and 8 (study 2) weeks of treatment. Safety data were collected. In all, 697 patients were randomly assigned to treatment in study 1. At the interim analysis (n = 346), none of the desvenlafaxine doses met the efficacy criteria (mean [SE] advantage over placebo, -0.21 [0.36] to 0.04 [0.35]), and the study was terminated. Study 2 was stopped for business reasons before the planned interim analysis. NRS scores in week 8 were -1.98 (0.37), -1.60 (0.37), and -1.70 (0.38) for placebo (n = 26), desvenlafaxine 250 mg/d (n = 24), and pregabalin 450 mg/d (n = 21), respectively; neither active treatment differed significantly from placebo. Desvenlafaxine was generally safe and well tolerated. Efficacy of desvenlafaxine for pain associated with FMS was not demonstrated.


Subject(s)
Desvenlafaxine Succinate/administration & dosage , Fibromyalgia/drug therapy , Pregabalin/administration & dosage , Adult , Desvenlafaxine Succinate/therapeutic use , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Humans , Male , Middle Aged , Pregabalin/therapeutic use , Treatment Failure
3.
J Public Health Policy ; 37(Suppl 2): 201-212, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27899795

ABSTRACT

MomConnect is an mHealth initiative giving pregnant women information via SMS. We report on an analysis of the compliments and especially complaints component of the feedback. We scrutinised the electronic databases containing information on the first seventeen months of operation of MomConnect. During this time, 583,929 pregnant women were registered on MomConnect, representing approximately 46 per cent of pregnant women booking their pregnancy in the public sector in South Africa. These women gave feedback on services received: 4173 compliments and 690 complaints. Nearly three quarters (74 per cent) of all complaints were resolved. The complaints were classified into those related to health services (29 per cent), staff (22 per cent), health systems (42 per cent) and other (6 per cent). These complaints were fed back to managers in the health facilities. This has resulted in improvements in the quality of services, e.g. decreased drug stock-outs and change of behaviour of some health workers.


Subject(s)
Maternal-Child Health Services/supply & distribution , Telemedicine/methods , Cell Phone , Female , Humans , Infant , Infant, Newborn , Maternal-Child Health Services/organization & administration , Pregnancy , South Africa
4.
J Pain Res ; 7: 339-51, 2014.
Article in English | MEDLINE | ID: mdl-25018648

ABSTRACT

PURPOSE: To assess the safety and efficacy of the serotonin-norepinephrine reuptake inhibitor desvenlafaxine in adults with painful diabetic peripheral neuropathy (DPN). CLINICALTRIALSGOV IDENTIFIERS: NCT00283842, NCT01050218. PATIENTS AND METHODS: This was a 13-week, randomized, double-blind, placebo-controlled, fixed-dose study of desvenlafaxine in adults with painful DPN. The primary efficacy endpoint was change from baseline in numeric rating scale (NRS) score. Patients who completed the 13-week trial could continue in a 9-month open-label, flexible-dose extension study. RESULTS: A total of 412 patients were randomized to treatment with placebo or desvenlafaxine 50, 100, 200, or 400 mg/day. Of those, 240 patients continued in the extension study. After a planned interim analysis, conducted when the first 225 patients had completed 6 weeks of treatment in the short-term study, randomization to the 50 mg or 400 mg doses was stopped. At week 13, the mean change from baseline in NRS score was significantly greater compared with placebo in the desvenlafaxine 200 mg (difference [95% confidence interval {CI}]: 1.10 [0.50 to 1.70]; P<0.001) and 400 mg groups (0.91 [95% CI: 0.23 to 1.59]; P=0.027); differences from placebo were not statistically significant for the 50 mg (0.58 [95% CI: -0.08 to 1.25]) and 100 mg (0.59 [95% CI: -0.03 to 1.21]) groups. Nausea and dizziness were the most common treatment-emergent adverse events reported in the short-term study, and the most common adverse events leading to discontinuation in the short-term study and the extension. Adverse events rates were dose-dependent in the short-term studies. CONCLUSION: Desvenlafaxine was effective in relieving pain associated with DPN at doses of 200 and 400 mg/day, and improved activity impairment at all doses assessed. Desvenlafaxine was generally well-tolerated in the short-term and long-term studies.

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