Predictors of obesity in school‐aged Jordanian adolescents

Manal Ibrahim A‐K, Mousa Ali A‐H, Erika Sivarajan F. International Journal of Nursing Practice 2010; 16 : 397–405
Predictors of obesity in school‐aged Jordanian adolescents This cross‐sectional study aimed to estimate the frequency of overweight and obesity in adolescents as defined by the International Obesity Task Force, and to estimate the effect of sociodemographic and health behaviours (eating habits and physical activity) that predict obesity. A stratified (by gender) random sample of 518 adolescents, aged 15 or 16 years was obtained from eight public schools in Amman. In this sample 17.5% were overweight and 9.6% were obese. The predictors of obesity and overweight (excess weight) were: (i) fathers attained primary and secondary education; (ii) total monthly family income ≥ 300 (JD); (iii) working mothers; (iv) family size ≤ 6; and (v) having obese parents. Eating a low quality diet (chips, candy) was a significant dietary predictor of excess weight. The family variables found to be important predictors along with a low quality diet suggest that family interventions would be necessary in the control of adolescent excess weight.     

Antiretroviral therapy adherence among patients living with HIV/AIDS in Thailand

The importance of antiretroviral therapy adherence for patients living with HIV/AIDS has been well documented. Despite this critical need, many do not follow prescribed regimens. To examine the barriers that lead to non‐adherence, we used cross‐sectional survey data from a randomized controlled intervention trial in northern and north‐eastern Thailand. Of the 507 patients that were enrolled in the trial, we analyzed 386 patients on antiretroviral therapy in order to examine the barriers to adherence. In addition to demographic characteristics, depressive symptoms, physical health, access to care, social support, and internalized shame, HIV disclosure and family communication were examined. The correlation analysis revealed that adherence is significantly associated with internalized shame, access to care, depressive symptoms, and family communication. Based on the multiple logistic regression analysis, depressive symptoms, access to care, HIV disclosure, and family communication were significant predictors of adherence. Having depressive symptoms remains a significant barrier to adherence, while access to care, HIV disclosure, and family communication play important positive roles. Our findings underscore the critical importance of addressing these various challenges that can influence adherence to antiretroviral therapy.     

Evaluating Factors Contributing to Dropout in a Large Peritoneal Dialysis Program

BackgroundThe low prevalence of peritoneal dialysis (PD) (9%) vs. hemodialysis (HD) (88.2%) is partly due to patient dropout from therapy.MethodsThis retrospective study identified patients who withdrew from PD between 2016 and 2018 in our program. We evaluated all other factors as controllable losses. Analysis included time on therapy at dropout (very early, early or late) and method of initiation (HD to PD conversion, unplanned PD, or planned start).ResultsEighty-three patients enrolled into our PD program. 27 dropped out; 24 were due to controllable factors, 3 due to death, with a median age at dropout of 52 years old. We determined psychosocial factors (PF) to be the largest controllable factor influencing dropout; contributing a 63% rate among all controllable factors. When considering time until dropout, 100% of very early dropout patients and 50% of late dropout patients did so due to PF. Among early dropout patients 67% dropped out due to other medical reasons. The mean time to dropout for PF, other, and infection (INF) were 13, 26, and 33 months, respectively. When considering type of initiation, we found PF to be the largest attributable factor with 50% of unplanned, 100% of planned, and 50% of conversions stopping therapy.ConclusionsOur study indicates that the primary reason for controllable loss from therapy was secondary to PF regardless of the time on therapy or the method of initiation to therapy.     

Engineering and characterization of the long‐acting glucagon‐like peptide‐1 analogue LY2189265, an Fc fusion protein

Background

Glucagon‐like peptide‐1 (GLP‐1) receptor agonists are novel agents for type 2 diabetes treatment, offering glucose‐dependent insulinotropic effects, reduced glucagonemia and a neutral bodyweight or weight‐reducing profile. However, a short half‐life (minutes), secondary to rapid inactivation by dipeptidyl peptidase‐IV (DPP‐IV) and excretion, limits the therapeutic potential of the native GLP‐1 hormone. Recently, the GLP‐1 receptor agonist exenatide injected subcutaneously twice daily established a novel therapy class. Developing long‐acting and efficacious GLP‐1 analogues represents a pivotal research goal. We developed a GLP‐1 immunoglobulin G (IgG4) Fc fusion protein (LY2189265) with extended pharmacokinetics and activity.

Methods

In vitro and in vivo activity of LY2189265 was characterized in rodent and primate cell systems and animal models.

Results

LY2189265 retained full receptor activity in vitro and elicited insulinotropic activity in islets similar to native peptide. Half‐life in rats and cynomolgus monkeys was 1.5–2 days, and serum immunoreactivity representing active compound persisted > 6 days. In rats, LY2189265 enhanced insulin responses during graded glucose infusion 24 h after one dose. LY2189265 increased glucose tolerance in diabetic mice after one dose and lowered weight and delayed hyperglycaemia when administered twice weekly for 4 weeks. In monkeys, LY2189265 significantly increased glucose‐dependent insulin secretion for up to a week after one dose, retained efficacy when administered subchronically (once weekly for 4 weeks) and was well tolerated.

Conclusions

LY2189265 retains the effects of GLP‐1 with increased half‐life and efficacy, supporting further evaluation as a once‐weekly treatment of type 2 diabetes. Copyright © 2010 John Wiley & Sons, Ltd.     

Blockade of the MEK/ERK signalling cascade by AS703026, a novel selective MEK1/2 inhibitor,induces pleiotropic anti‐myeloma activity in vitro and in vivo

This study investigated the cytotoxicity and mechanism of action of AS703026, a novel, selective, orally bioavailable MEK1/2 inhibitor, in human multiple myeloma (MM). AS703026 inhibited growth and survival of MM cells and cytokine‐induced osteoclast differentiation more potently (9‐ to 10‐fold) than AZD6244. Inhibition of proliferation induced by AS703026 was mediated by G₀‐G₁ cell cycle arrest and was accompanied by reduction of MAF oncogene expression. AS703026 further induced apoptosis via caspase 3 and Poly ADP ribose polymerase (PARP) cleavage in MM cells, both in the presence or absence of bone marrow stromal cells (BMSCs). Importantly, AS703026 sensitized MM cells to a broad spectrum of conventional (dexamethasone, melphalan), novel or emerging (lenalidomide, perifosine, bortezomib, rapamycin) anti‐MM therapies. Significant tumour growth reduction in AS703026‐ vs. vehicle‐treated mice bearing H929 MM xenograft tumours correlated with downregulated pERK1/2, induced PARP cleavage, and decreased microvessels in vivo. Moreover, AS703026 (<200 nmol/l) was cytotoxic against the majority of tumour cells tested from patients with relapsed and refractory MM (84%), regardless of mutational status of RAS and BRAF genes. Importantly, BMSC‐induced viability of MM patient cells was similarly blocked within the same dose range. Our results therefore support clinical evaluation of AS703026, alone or in combination with other anti‐MM agents, to improve patient outcome.     

Prediction of significant liver fibrosis in kidney transplant patients with chronic hepatitis C virus infection: the TX‐3 index

Summary. HCV infection is highly prevalent among kidney transplant (KT) recipients. The natural history and management of these patients are controversial. We sought to assess the diagnostic value of noninvasive markers of liver fibrosis in KT HCV‐infected patients. This cross‐sectional study included 102 KT individuals with positive HCV‐RNA. Bivariate and multivariate analyses were used to identify variables associated with significant fibrosis (METAVIR ≥ F2). Significant fibrosis was observed in 20 patients (20%). Time after transplantation, AST level, and platelet count were identified as independent predictors of significant fibrosis. Based on the regression model, a simplified index was devised. The AUROC for the TX‐3 model was 0.867 ± 0.081 (0.909, when adjusted by DANA). Values ≤4.0 of TX‐3 showed a NPV of 97% and scores >9.6 exhibited a PPV of 71%. If biopsy indication was restricted to scores in the intermediate range of TX‐3, this could have been correctly avoided in 68% of cases. The APRI score provided a correct diagnosis in only 47 individuals (46%) and exhibited lower diagnostic indices for both cutoffs, as compared to the TX‐3 index. Comparison of AUROCs showed a trend towards superior diagnostic accuracy for TX‐3 over APRI, although the difference between AUROCs did not reach statistical significance (0.867 ± 0.053 vs 0.762 ± 0.066, respectively, P = 0.064). In conclusion, significant liver fibrosis can be reliably predicted in KT HCV‐infected subjects by simple and widely available parameters. If additional studies confirm our results, this model might obviate the requirement for a liver biopsy in a significant proportion of those patients.     

Factors associated with isolated anti‐hepatitis B core antibody in HIV‐positive patients: impact of compromised immunity

Summary. In regions that are hyperendemic for chronic hepatitis B virus (HBV) infection, prevalence of and risk factors associated with isolated anti‐hepatitis B core antibody (anti‐HBc) in HIV‐positive patients are less well described. HIV‐positive patients who were tested for hepatitis B surface antigen (HBsAg), anti‐hepatitis B surface antibody (anti‐HBs) and anti‐HBc at designated hospitals for HIV care in Taiwan were included for analysis. HBV DNA was detected by real‐time polymerase chain reaction in patients with and without isolated anti‐HBc. Of 2351 HIV‐positive patients, 450 (19.1%) were HBsAg positive, 411 (17.5%) were anti‐HBc positive alone and 963 (41.0%) for both anti‐HBs and anti‐HBc. Compared with patients who were positive for both anti‐HBs and anti‐HBc, patients with isolated anti‐HBc were older, less likely to have anti‐hepatitis C virus antibody (anti‐HCV), had lower CD4 lymphocyte counts and higher plasma HIV RNA loads. Older age (adjusted odds ratio, 1.029; 95% confidence interval, 1.015–1.043) and CD4 <100 cells/μL (adjusted odds ratio, 1.524; 95% confidence interval, 1.025–2.265) were independently associated with isolated anti‐HBc by logistic regression, while presence of anti‐HCV and injecting drug use were not. HBV DNA was detectable in 8.3% of 277 patients with isolated anti‐HBc and 14.3% of 56 patients with both anti‐HBs and anti‐HBc (P = 0.160). In a country hyperendemic for HBV infection, HIV‐positive patients at older age and with CD4 <100 cells/μL were more likely to have isolated anti‐HBc, suggesting that compromised immunity plays a role in the presence of this marker.     

The effect of food consumption on lumefantrine bioavailability in African children receiving artemether–lumefantrine crushed or dispersible tablets (Coartem®) for acute uncomplicated Plasmodium falciparum malaria

Objectives Artemether–lumefantrine (AL) is first‐line treatment for uncomplicated malaria in many African countries. Concomitant food consumption may affect absorption of lumefantrine but data in the most important target population, i.e. children, are lacking. Therefore, we evaluated the effect of food intake on oral lumefantrine bioavailability in African children with malaria. Methods In a randomised, investigator‐blinded, multicentre phase III efficacy trial, 899 infants and children with acute uncomplicated Plasmodium falciparum malaria received six doses of AL according to body weight over 3 days either as crushed tablets (Coartem^®) or as dispersible tablets. Single blood samples were obtained for lumefantrine plasma concentration determination in a subset of 621 patients, and a two‐compartment pharmacokinetic model was constructed. Results The mean observed lumefantrine plasma concentration for crushed tablet and dispersible tablet, respectively, was 100% and 55% higher with a concomitant meal at the time of dose intake than when taken alone. Similarly, consumption of milk (the most common meal) increased model‐estimated lumefantrine bioavailability by 57% (90% CI: 29–96%) with crushed tablets and 65% (90% CI: 28–109%) with dispersible tablets compared to no food. The 28‐day PCR‐corrected cure rate (primary study endpoint) in the evaluable population was 582/587 [99.1% (95% CI: 98.0–99.7%)] and was not related to food intake. Conclusions AL was highly efficacious. Concomitant food intake increased lumefantrine absorption in children with malaria.