Case management for child protection services:A multi-level evaluation study

This article presents an evaluation study of a case management method for child protection services, the Delta Method for Family Supervision, in terms of supervision order duration and occurrence and duration of out-of-home placements. Additionally, case and case manager characteristics were examined. Data was collected about 224 cases, 58 case managers and 30 team managers of all 15 offices of the Child and Youth Protection Services in the Netherlands. In all cases the Delta Method was applied. Data were obtained by interviews, questionnaires and case files. Multi-level analysis was performed to study the influence of independent variables on supervision order duration, and the occurrence and duration of out-of-home placements. Case characteristics related to 87% of the differences in the duration of supervision order, case manager characteristics to 13% of the differences. Some case manager characteristics about applying the Delta Method were significantly related to shorter duration of the supervision order and the occurrence and duration of out-of-home placement. Case characteristics also showed strong relations. Together with the more general aspects of case management supported by this study, such as a one family and one worker approach, this contributes to a more effective practice of case management for child protection services

Evaluation of the efficacy and safety of artemether-lumefantrine in the treatment of acute uncomplicated Plasmodium falciparum malaria in Nigerian infants and children

<p>Abstract</p> <p>Background</p> <p>The six-dose regimen of artemether-lumefantrine (AL) is now considered the gold standard for the treatment of uncomplicated <it>Plasmodium falciparum </it>malaria. There are few reports evaluating co-artemether in very young Nigerian infants and children. Results of the evaluation of the six-dose regimen in very young infants and children in Nigeria are presented in this report.</p> <p>Methods</p> <p>As part of a larger African study, this open label, non-comparative trial, assessed the efficacy and safety of six-dose regimen of AL tablets in 103 Nigerian infants and children weighing between five and 25 kg suffering from acute uncomplicated malaria. Treatment was administered under supervision over three days with children as in-patients. 12-lead ECG tracings were taken pre-treatment and at day 3.</p> <p>Results</p> <p>Ninety-three infants and children completed the study as stipulated by the protocol. Mean fever and parasite clearance times for the intent to treat population (ITT) were 24.9 h ± (1.28) and 26 h ± (4.14) and the corresponding figures for the per-protocol population (PP) were 19.24 h ± 13.9 and 25.62 h ± 11.25 respectively. Day 14 cure rates for the ITT and PP were 95.1% and 100% respectively while day 28 cure rates were 91.3% and 95.7% respectively. The overall PCR corrected day 28 cure rate was 95.1% for the ITT. The six-dose regimen of AL was well tolerated with no drug-related serious adverse events. Although six patients recorded a QTc prolongation of > 60 ms on D3 over D0 recording, no patient recorded a QTc interval > 500 ms.</p> <p>Conclusion</p> <p>The six-dose regimen of AL tablets is safe and effective for the treatment of acute uncomplicated malaria in Nigerian infants and children weighing between five and 25 kg.</p> <p>Trial registration</p> <p>NCT00709969</p

Intravenous pharmacokinetics, oral bioavailability, dose proportionality and in situ permeability of anti-malarial lumefantrine in rats

<p>Abstract</p> <p>Background</p> <p>Despite the wide spread use of lumefantrine, there is no study reporting the detailed preclinical pharmacokinetics of lumefantrine. For the development of newer anti-malarial combination(s) and selection of better partner drugs, it is long felt need to understand the detailed preclinical pharmacokinetics of lumefantrine in preclinical experimental animal species. The focus of present study is to report bioavailability, pharmacokinetics, dose linearity and permeability of lumefantrine in rats.</p> <p>Methods</p> <p>A single dose of 10, 20 or 40 mg/kg of lumefantrine was given orally to male rats (N = 5 per dose level) to evaluate dose proportionality. In another study, a single intravenous bolus dose of lumefantrine was given to rats (N = 4) at 0.5 mg/kg dose following administration through the lateral tail vein in order to obtain the absolute oral bioavailability and clearance parameters. Blood samples were drawn at predetermined intervals and the concentration of lumefantrine and its metabolite desbutyl-lumefantrine in plasma were determined by partially validated LC-MS/MS method. <it>In-situ </it>permeability study was carried in anaesthetized rats. The concentration of lumefantrine in permeability samples was determined using RP-HPLC.</p> <p>Results</p> <p>For nominal doses increasing in a 1:2:4 proportion, the C_maxand AUC_0-∞values increased in the proportions of 1:0.6:1.5 and 1:0.8:1.8, respectively. For lumefantrine nominal doses increasing in a 1:2:4 proportion, the C_maxand the AUC_0-tvalues for desbutyl-lumefantrine increased in the proportions of 1:1.45:2.57 and 1:1.08:1.87, respectively. After intravenous administration the clearance (Cl) and volume of distribution (Vd) of lumefantrine in rats were 0.03 (± 0.02) L/h/kg and 2.40 (± 0.67) L/kg, respectively. Absolute oral bioavailability of lumefantrine across the tested doses ranged between 4.97% and 11.98%. Lumefantrine showed high permeability (4.37 × 10^-5cm/s) in permeability study.</p> <p>Conclusions</p> <p>The pharmacokinetic parameters of lumefantrine and its metabolite desbutyl-lumefantrine were successfully determined in rats for the first time. Lumefantrine displayed similar pharmacokinetics in the rat as in humans, with multiphasic disposition, low clearance, and a large volume of distribution resulting in a long terminal elimination half-life. The absolute oral bioavailability of lumefantrine was found to be dose dependent. Lumefantrine displayed high permeability in the <it>in-situ </it>permeability study.</p

Safety profile of Coartem®: the evidence base

This article reviews the comprehensive data on the safety and tolerability from over 6,300 patients who have taken artemether/lumefantrine (Coartem®) as part of Novartis-sponsored or independently-sponsored clinical trials. The majority of the reported adverse events seen in these studies are mild or moderate in severity and tend to affect the gastrointestinal or nervous systems. These adverse events, which are common in both adults and children, are also typical of symptoms of malaria or concomitant infections present in these patients. The wealth of safety data on artemether/lumefantrine has not identified any neurological, cardiac or haematological safety concerns. In addition, repeated administration is not associated with an increased risk of adverse drug reactions including neurological adverse events. This finding is especially relevant for children from regions with high malaria transmission rates who often receive many courses of anti-malarial medications during their lifetime. Data are also available to show that there were no clinically relevant differences in pregnancy outcomes in women exposed to artemether/lumefantrine compared with sulphadoxine-pyrimethamine during pregnancy. The six-dose regimen of artemether/lumefantrine is therefore well tolerated in a wide range of patient populations. In addition, post-marketing experience, based on the delivery of 250 million treatments as of July 2009, has not identified any new safety concerns for artemether/lumefantrine apart from hypersensitivity and allergies, known class effects of artemisinin derivatives

Low Socioeconomic Status Is Associated with Worse Outcomes After Curative Surgery for Colorectal Cancer: Results from a Large, Multicenter Study

Background: Socioeconomic status (SES) has been associated with early mortality in cancer patients. However, the association between SES and outcome in colorectal cancer patients is largely unknown. The aim of this study was to investigate whether SES is associated with short- and long-term outcome in patients undergoing curative surgery for colorectal cancer. Methods: Patients who underwent curative surgery in the region of Rotterdam for stage I–III colorectal cancer between January 2007 and July 2014 were included. Gross household income and survival status were obtained from a national registry provided by Statistics Netherlands Centraal Bureau voor de Statistiek. Patients were assigned percentiles according to the national income distribution. Logistic regression and Cox proportional hazard regression were performed to assess the association of SES with 30-day postoperative complications, overall survival and cancer-specific survival, adjusted for known prognosticators. Results: For 965 of the 975 eligible patients (99%), gross household income could be retrieved. Patients with a lower SES more often had diabetes, more often underwent an open surgical procedure, and had more comorbidities. In addition, patients with a lower SES were less likely to receive (neo) adjuvant treatment. Lower SES was independently associated with an increased risk of postoperative complications (Odds rati

social laughter is correlated with an elevated pain threshold

Although laughter forms an important part of human non-verbal communication, it has received rather less attention than it deserves in both the experimental and the observational literatures. Relaxed social (Duchenne) laughter is associated with feelings of wellbeing and heightened affect, a proximate explanation for which might be the release of endorphins. We tested this hypothesis in a series of six experimental studies in both the laboratory (watching videos) and naturalistic contexts (watching stage performances), using change in pain threshold as an assay for endorphin release. The results show that pain thresholds are significantly higher after laughter than in the control condition. This pain-tolerance effect is due to laughter itself and not simply due to a change in positive affect. We suggest that laughter, through an endorphin-mediated opiate effect, may play a crucial role in social bonding