Malnutrition risk and its association with appetite, functional and psychosocial status among elderly Malays in an agricultural settlement.

INTRODUCTION: Malnutrition is a common phenomenon among the elderly and quite often related to psychosocial problems. The objective of this study was to determine malnutrition risk and its association with appetite, functional and psychosocial status among elderly Malays in an agricultural settlement, i.e. FELDA Sungai Tengi, Selangor. METHODS: A cross-sectional study was conducted among 160 subjects (men = 36.2%), with a mean age of 65.0 +/- 3.9 years, who were interviewed to obtain information on malnutrition risk and appetite using Mini Nutritional Assessment Short Form and Simplified Nutritional Appetite Questionnaire, respectively. Functional status was determined using Instrumental Activities of Daily Living (IADL), Elderly Mobility Scale (EMS) and handgrip strength. Mini Mental Status Examination (MMSE), Geriatric Depression Scale and De Jong Gierveld Loneliness Scale were used to identify cognitive impairment, depressive symptoms and loneliness status of subjects respectively. A total of 42.5% of subjects were at risk of malnutrition and 61.2% had poor appetite. The mean scores of IADL and EMS were lower in subjects at risk of malnutrition, compared to those who were not at high risk (p < 0.05 for both parameters). Multiple linear regression showed that 19.8% of malnutrition risk was predicted by poor appetite, decreased functional status (IADL) and depression. CONCLUSION: Malnutrition risk was prevalent and associated with poor appetite, functional status and psychosocial problems among the elderly subjects. The psychosocial aspect should also be incorporated in nutrition intervention programmes in order to improve mental well-being and functional independancy.

Dose selection of corifollitropin alfa by modeling and simulation in controlled ovarian stimulation.

In controlled ovarian stimulation (COS), a single subcutaneous dose of corifollitropin alfa is used to initiate and sustain multifollicular growth for 7 days. The objective of this study was to determine the optimal dose of corifollitropin alfa. A pharmacokinetic model was developed to describe the time profile of corifollitropin alfa concentrations. Multiple parameters reflecting ovarian response were included in a pharmacokinetic-pharmacodynamic (PK-PD) model framework. An early decline in serum inhibin B was shown to be a sensitive marker for COS failure. Simulations were performed to select the lowest corifollitropin alfa dose that would result in a minimal cancellation rate: 100 microg for a group of women weighing 60 kg. With these doses, the predicted mean number of oocytes per started COS cycle was similar in the two groups, i.e., 12.1 and 13.2, respectively. The selected doses were tested in prospective clinical trials and were proven to be adequate.

A double-blind, non-inferiority RCT comparing corifollitropin alfa and recombinant FSH during the first seven days of ovarian stimulation using a GnRH antagonist protocol.

BACKGROUND: Corifollitropin alfa, a fusion protein lacking LH activity, has a longer elimination half-life and extended time to peak levels than recombinant FSH (rFSH). A single injection of corifollitropin alfa may replace seven daily gonadotrophin injections during the first week of ovarian stimulation. METHODS: In this large, double-blind, randomized, non-inferiority trial the ongoing pregnancy rates were assessed after one injection of 150 microg corifollitropin alfa during the first week of stimulation and compared with daily injections of 200 IU rFSH using a standard GnRH antagonist protocol. RESULTS: The study population comprised 1506 treated patients with mean age of 31.5 years and body weight of 68.6 kg. Ongoing pregnancy rates of 38.9% for the corifollitropin alfa group and 38.1% for rFSH were achieved, with an estimated non-significant difference of 0.9% [95% confidence interval (CI): -3.9; 5.7] in favor of corifollitropin alfa. Stratified analyses of pregnancy rates confirmed robustness of this primary outcome by showing similar results regardless of IVF or ICSI, or number of embryos transferred. A slightly higher follicular response with corifollitropin alfa resulted in a higher number of cumulus-oocyte-complexes compared with rFSH [estimated difference 1.2 (95% CI: 0.5; 1.9)], whereas median duration of stimulation was equal (9 days) and incidence of (moderate/severe) ovarian hyperstimulation syndrome was the same (4.1 and 2.7%, respectively P = 0.15). CONCLUSION: Corifollitropin alfa is a novel and effective treatment option for potential normal responder patients undergoing ovarian stimulation with GnRH antagonist co-treatment for IVF resulting in a high ongoing pregnancy rate, equal to that achieved with daily rFSH. The trial was registered under ClinicalTrials.gov identifier NTC00696800.

Design and analysis issues for crossover designs in phase I clinical studies.

To assess the efficacy of potential new drugs in the initial phase of clinical research, one must use an efficient design that satisfies conditions to guarantee the safety of the subjects. For a parallel design, a two-period crossover design, two three-period crossover designs, and a Latin square design with three periods, we compared variances of estimators based on a mixed analysis of variance model. The proposed three-period crossover designs turned out to be only slightly less efficient than the Latin square design, which is not capable of satisfying the necessary safety conditions. The analysis of data from the crossover design poses several problems, including nonconstant variances for all observations and the possibility of carryover effects. To resolve these issues, we generalized the Box-Cox transformations to the mixed model at hand and, using simulation, investigated the sensitivity of the analysis to the presence of (first-order) carryover effects. This showed that results from the model without carryover are reliable for only very small carryover effects.