Introduction: Efforts on malaria drug discovery are expected to increase in the coming years to achieve malaria eradication. Owing to the increasing number of new potential candidates together with the actual limitations of the primate models, humanized mouse models infected with human Plasmodium spp. (HmHP) now appear as an alternative to the primate model.
Areas covered: The authors review the progress obtained in the HmHP in the last two decades, with a special emphasis of their input on the drug discovery pathway. The authors discuss the methodologies and strategies used in these models to obtain an accurate assessment of the compound activity and a reliable prediction of the human efficacious regimen.
Expert opinion: Research efforts have led us to an era in which HmHP can successfully be infected with P. falciparum, P vivax and P. ovale. Furthermore, it is now a reality that the complete human cycle of P. falciparum can be obtained in HmHP. The HmHP has shown a real input mainly in the preclinical evaluation of new compounds against the erythrocytic stages of P. falciparum. However, further technical improvements are needed before HmHP may replace the primate model. 相似文献
Objectives: Previous studies have shown that serum levels of vitamin D were lower in attention deficit hyperactivity disorder (ADHD) children compared to healthy controls. The aim of the study was to determine the effect of vitamin D supplementation as adjunctive therapy to methylphenidate on symptoms of children with ADHD.Methods: Sixty-two children aged 5–12 years with a diagnosis of ADHD based on DSM-IV criteria were randomly assigned into two groups to receive either 2000IU vitamin D or placebo in addition to methylphenidate for 8 weeks. Symptoms severity was assessed by Conner's Parent Rating Scale-Revised[S] (CPRS), ADHD rating scale-IV (ADHD-RS), and Weekly Parent Ratings of Evening and Morning Behavior (WPREMB) at weeks 0, 4, and 8. Serum levels of 25(OH)D were measured at baseline and after 8 weeks. Anthropometric variables, dietary intake, physical activity, sun exposure, and side effects were assessed.Results: Fifty-four participants completed the trial. After 8 weeks of supplementation, serum levels of 25(OH)D significantly increased in the vitamin D group. ADHD symptoms decreased significantly in both groups (P?0.05). Evening symptoms and total score of WPREMB scale were significantly different at weeks 4 and 8 between the two groups (P?=?0.013, 0.016, respectively), but no differences were found in symptoms by CPRS and ADHD-RS scales.Discussion: Vitamin D supplementation as adjunctive therapy to methylphenidate improved ADHD evening symptoms. Future research is needed to clarify vitamin D effects as monotherapy in ADHD and its mechanism.The trial was registered in www.irct.ir is (IRCT201404222394N10). 相似文献
Established by the Affordable Care Act, the National Quality Strategy (NQS) is the national policy goals aimed at improving the quality of health care for all Americans. The NQS established six priorities to provide better, more affordable care for individuals and communities. This is the first analysis of data on the NQS and access measures that focus on sex differences, health conditions, trends, and disparities.
Methods
Measures from the 2015 National Healthcare Quality and Disparities Report (QDR) for the four National Quality Strategy priorities (Patient Safety, Person Centered Care, Effective Treatment, and Healthy Living), access to care, and health conditions for women were compared to measures for men. Trends were analyzed for women by health condition and the four NQS priorities and access to care. Baseline year (2000-2002) and most current year (2012-2013) were compared to assess disparity trends. All non-institutionalized women and men in the U.S. over the age of 18 were included in the sample.
Results
Disparities between males and females for the four NQS priority and access measures did not change for 83 percent of measures (n=81); disparities remained constant. The greatest improvement over time for females from the baseline year was in the patient safety measures (3.66 percent increase per year). Access of care measures showed the least amount of improvement with a median change of -1.20 percent per year. The greatest improvement in quality of care by health condition was amongst chronic kidney disease (11.95 median percent change) and HIV/AIDS (6.63 median percent change) measures. Behavioral health measures showed the least amount of improvement with a median change of -0.33 percent per year.
Conclusions
This analysis highlights cardiovascular disease, behavioral health, and access to care as problem areas for women that require immediate attention. It is of concern that 83% of the measures showed a persistent disparity over time between men and women. These results indicate that there is room for improving the quality of healthcare received by women and reducing sex-based disparities experienced by women in the healthcare delivery system. 相似文献
To examine the concordance of labor induction measures derived from birth certificate and hospital discharge data with each other and with maternal report.
Methods
Birth certificate data were linked with hospital discharge data and structured interviews of 2,851 mothers conducted 1 month after first childbirth. Those who reported that a doctor or nurse tried to cause their labor to begin, and were not in labor before that event, were classified as undergoing labor induction. The mothers were aged 18 to 35 years at study entry and delivered at 78 hospitals (76 in Pennsylvania and 2 out of state) from 2009 to 2011.
Results
The labor induction rate was 34.3% measured by maternal report, 29.4% by birth certificate data, and 26.2% by hospital discharge data. More than one-third of the women who reported labor induction were not reported as having been induced in the birth certificate data (33.6%), with similar results for the hospital discharge data (36.5%). The rate of underreporting of labor induction in the birth certificate data was higher for inductions occurring before 39 weeks of gestation (43.9%) than for inductions at 39 weeks or later (29.9%; p < .0001). Agreement between birth certificate and hospital discharge data was relatively low (kappa = 0.56), as was agreement between maternal report and birth certificate data (kappa = 0.58), and maternal report and hospital discharge data (kappa = 0.60).
Conclusions
Both the birth certificate and hospital discharge data exhibit relatively poor agreement with maternal report of labor induction and seem to miss a substantial portion of labor inductions. 相似文献
Value sets for the EQ‐5D‐5L are required to facilitate its use in estimating quality‐adjusted life years. An international protocol has been developed to guide the collection of stated preference data for this purpose and has been used to generate EQ‐5D‐5L valuation data for England. The aim of this paper is report the innovative methods used for modelling those data to obtain a value set. Nine hundred and ninety‐six members of the English general public completed time trade‐off (TTO) and discrete choice experiment (DCE) tasks. We estimate models, with and without interactions, using DCE data only, TTO data only, and TTO/DCE data combined. TTO data are interpreted as both left and right censored. Heteroskedasticity and preference heterogeneity between individuals are accounted for. We use Bayesian methods in the econometric analysis. The final model is chosen based on the deviance information criterion (DIC). Censoring and taking account of heteroskedasticity have important effects on parameter estimation. For DCE data only, TTO data only, and DCE/TTO data combined, models with parameters for all dimensions and levels perform best, as judged by the DIC. Taking account of heterogeneity improves fit, and the multinomial model reports the lowest DIC. This paper presents approaches that suit observed characteristics of EQ‐5D‐5L valuation data and recognise respondents' preference heterogeneity. The methods described are potentially relevant to other value set studies. 相似文献
Body-altering surgery may affect perceptions of one’s self. For those with abdominal stoma surgeries, altered perceptions amplified by peristomal skin condition can increase health burdens.
Objectives
To assess health utility and health-related quality of life in an adult US ostomy sample in the presence of three levels of peristomal skin condition: intact, moderately compromised, and severely compromised.
Methods
The short form 36 health survey version 2, a generic health survey incorporating the six-dimensional health state short form preference-based utility index, was chosen to assess the sample. Analysis of covariance adjusted for age and time from surgery was used.
Results
The six-dimensional health state short form utilities for those with intact skin and physical component summary (PCS) levels indicating no physical limitations varied significantly from those with severely compromised skin and indicating the greatest degree of physical limitation (0.833 vs. 0.527). Peristomal skin condition decreases were associated with health utility decreases across all levels of the PCS. Because peristomal skin conditions are intermittent, the analysis presents quality-adjusted life-days (QALDs) per month. Ostomates with intact skin and PCS levels indicating no physical limitations demonstrated significant differences from those with severe skin condition and indicating the greatest degree of physical limitations (26.5 d/mo vs. 15.8 d/mo). As peristomal skin condition worsened, QALDs decreased across all levels of the PCS. A minimally important expected value of health was estimated to be an increase of 2.18 QALDs/mo.
Conclusions
Successful treatment from a clinical perspective is more than the elimination of conditions—it is also a return of quality time to an individual. 相似文献
To model the relationship between the three-level (3L) and the five-level (5L) EuroQol five-dimensional questionnaire and examine how differences have an impact on cost effectiveness in case studies.
Methods
We used two data sets that included the 3L and 5L versions from the same respondents. The EuroQol Group data set (n = 3551) included patients with different diseases and a healthy cohort. The National Data Bank data set included patients with rheumatoid disease (n = 5205). We estimated a system of ordinal regressions in each data set using copula models to link responses of the 3L instrument to those of the 5L instrument and its UK tariff, and vice versa. Results were applied to nine cost-effectiveness studies.
Results
Best-fitting models differed between the EuroQol Group and the National Data Bank data sets in terms of the explanatory variables, copulas, and coefficients. In both cases, the coefficients of the covariates and latent factors between the 3L and the 5L instruments were significantly different, indicating that moving between instruments is not simply a uniform re-alignment of the response levels for most dimensions. In the case studies, moving from the 3L to the 5L caused a decrease of up to 87% in incremental quality-adjusted life-years gained from effective technologies in almost all cases. Incremental cost-effectiveness ratios increased, often substantially. Conversely, one technology with a significant mortality gain saw increased incremental quality-adjusted life-years.
Conclusions
The 5L shifts mean utility scores up the utility scale toward full health and compresses them into a smaller range, compared with the 3L. Improvements in quality of life are valued less using the 5L than using the 3L. The 3L and the 5L can produce substantially different estimates of cost effectiveness. There is no simple proportional adjustment that can be made to reconcile these differences. 相似文献
Venous thromboembolism (VTE) is common in cancer patients and its treatment is associated with a high risk of recurrent VTE (rVTE) and bleeding.
Objectives
To analyze data from the Comparison of Acute Treatments in Cancer Hemostasis (CATCH) trial to describe the impact of rVTE and bleeding events on health-related quality of life.
Methods
The three-level EuroQol five-dimensional questionnaire (EQ-5D) data were collected monthly for up to 7 months in patients starting anticoagulation for newly diagnosed VTE. Analyses were designed to describe the impact of rVTE and bleeding on EQ-5D scores while controlling for effects of covariates such as background and clinical variables and longitudinal changes. A repeated-measures model with specification of the variance-covariance matrix to characterize the intrapatient correlation was used to estimate the utility values. The impact of an rVTE or a bleeding event was assumed to be reflected in the utility value when it occurred within 2 weeks from a planned data collection point.
Results
Data were available from 883 patients. A total of 76 rVTE and 159 bleeding events occurred during follow-up. rVTE had a significant impact on EQ-5D scores, with a decrement of ?0.075 on the basis of our reference case (male, no metastasis, Eastern Cooperative Oncology Group score = 1, Western European), but different patients might have different decrements. Bleeding events had a smaller (nonstatistically significant) impact on EQ-5D scores.
Conclusions
This data set study has quantified the decline in EQ-5D scores associated with experiencing rVTE or bleeding events in cancer patients. These results indicate the net gain in quality of life and impact on cost-effectiveness of secondary VTE prevention. 相似文献