Health-Related Quality of Life in Amyotrophic Lateral Sclerosis: Determining a Meaningful Deterioration

This paper uses the standard error of measurement (SEM) and the standard error of the difference (S(diff)) in relation to data on individuals with amyotrophic lateral sclerosis (ALS) to calculate the minimum change scores required by statistical criteria for each dimension of the Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40). Data collected from a longitudinal study was used to evaluate the usefulness of SEM and S(diff) criteria and to compare these criteria with an anchor-based approach in determining meaningful change. Questionnaires were completed on two occasions, 3 months apart. 764 questionnaires were returned. Questionnaires included the ALSAQ-40 and dimension specific transition items. The ALSAQ-40 is a disease specific health-related quality of life instrument for use in studies of patients with ALS or other motor neuron diseases. For all dimensions of the ALSAQ-40 the patterns of SEMs were similar over time. The results suggest that, for example, six points change on a 0-100 transformed scoring of the physical mobility dimension may be considered on distributional grounds a minimum meaningful change. The demonstrated consistency of SEMs for the dimensions of the ALSAQ-40 is empirical evidence of the theoretically claimed advantage of this measure of sample independence, and supports use of this distributional approach to calculate meaningful change.     

应用改进的眼震图检查先天性眼球震颤

目的评价改进后的眼震图对先天性眼球震颤波形的分析,为其手术治疗提供较为精确的量化标准.方法改进电生理仪的视网膜电图(EOG)程序,分别记录68例患者33cm原在位、右5°、10°、15°、20°,左5°、10°、15°、20°,3m原在位及闭眼的波形,并对其中28例手术患者术前和术后的眼震图进行比较.结果68例患者中,跳动型48例,其中水平跳动46例,垂直跳动2例;水平钟摆型20例.跳动型中,有代偿头位的40例,钟摆型无明显代偿头位.28例手术患者中,水平跳动型26例,水平钟摆型2例.26例跳动型患者均有中间位和代偿头位.术后20例代偿头位消失,6例代偿头位在左5°～10°.按震频、振幅、震强的分组中,处于中等震频、振幅、震强范围内的多见.结论改进的眼震图可以对眼震的振幅、震频、震强、中间位进行量化的检测,从而指导其治疗.     

A comparison of Rasch with Likert scoring to discriminate between patients' evaluations of total hip replacement surgery

The purpose of this study was to examine whether there are advantages in terms of outcome assessment of using Rasch methods of scoring the 12-item Oxford Hip Score (OHS) questionnaire over conventionally Likert scores. As part of a prospective cohort study of total hip replacements in five former regions of England the OHS was sent to patients pre-operatively, at 3 months and 1 year post-operatively. Post-operative data was collected on over 5000 cases. Based on the level of satisfaction with surgery, patients were divided into satisfied and dissatisfied. Analyses were performed to test the relative precision (RP) of Rasch scoring vs. conventionally Likert scores in discriminating the groups experiencing different level of satisfaction. Considerable gains in precision were achieved with Rasch scoring methods when groups were compared 3 and 12 months post-operatively. The results from the current study suggest that in some situations there may be substantial gains in measuring health related outcomes using Rasch-based scoring methods.     

The ALS Health Profile Study: quality of life of amyotrophic lateral sclerosis patients and carers in Europe

The measurement of functioning and well-being from the perspective of the patient has in recent years become central to the assessment of health and the evaluation of treatment regimes. The past decade has seen an enormous growth in the application of measures designed to assess quality of life in a vast array of medical specialities. However, the use of such measures in neurology has been relatively limited, and this has certainly been the case in amyotrophic lateral sclerosis (ALS). The European ALS Health Profile Study is a longitudinal survey of patients diagnosed with ALS or other motor neurone diseases in which patients are aksed to complete questionnaires concerning their subjective health status. Data from clinical assessments are also collected. It is intended that the information collected will provide more systematic and detailed evidence of the impact of the disease from the perspective of the patient. This contribution documents results from baseline assessment obtained from data supplied by clinicians, carers and patients themselves. Three outcome measured are assessed in this paper: the SF-36, a generic measure of well being and functioning, the ALS Functinal Rating Scale and the Carer Strain Index. The evidence presented here suggests that these measures provide a meaningful and valid picture of the impact of the disease. The data indicate that ALS has substantial adverse effects both upon the functioning and well being of patients and carers, as well as an association between the emotional health status of patients and carers, and between the physical health status of patients and carers. Received: 4 January 2000 / Received in revised form: 15 March 2000 / Accepted: 3 May 2000     

In vitro and in vivo antifungal activities of the eight steroid saponins from Tribulus terrestris L. with potent activity against fluconazole-resistant fungal pathogens

Antifungal activity of natural products is being studied widely. Saponins are known to be antifungal and antibacterial. We have isolated eight steroid saponins from Tribulus terrestris L. , namely TTS-8, TTS-9, TTS-10, TTS-11, TTS-12, TTS-13, TTS-14 and TTS-15. TTS-12 and TTS-15 were identified as tigogenin-3-O-β-D-xylopyranosyl（1→ 2）-[-β-D-xylopyranosyl（ 1 → 3 ） 3-β- D-glucopyranosyl （ 1 → 4 ）- 1- α-L-rhamnopyranosyl （ 1 → 2 ） 3-β-D-galactopyranoside and tigogenin-3-O-β-D-glucopyranpyranosyl（1→2）-[-β-D-xylopyranosyl（1→ 3）3-β-D-glucopyranosyl（1→4）-β-D-galactopyranoside, respectively. The in vitro antifungal activities of the eight saponins against six fluconazole-resistant yeasts, Candida albicans, Candida glabrata, Candida para psilosis , Candida tropicalis , Candida krusei , and Cryptococcus neo f ormans were studied using microbroth dilution assay. The results showed that TTS-12 and TTS-15 were very effective against several pathogenic candidal species and C. neoformans in vitro. It is noteworthy that TTS-12 and TTS-15 were very active against fluconazole-resistant C. albicans （MIC80 = 4.4, 9.4 mg/ml）, C. neoformans （MIC80 =10.7, 18.7 mg/ml） and inherently resistant C. krusei （MIC80 =8.8, 18.4 mg/ml）. So in vivo activity of TTS-12 in a vaginal infection model with fluconazole-resistant C. albicans was studied in particular. Our studies revealed TTS-12 also showed in vivo activities against fluconazole-resistant yeasts. In conclusion, steroid saponins TTS-12 and TTS-15 from Tribulus terrestris L. have significant in vitro antifungal activity against fluconazole-resistant fungi, especially TTS-12 also showed in vivo activity against fluconazole-resistant C. albicans.     

Analysis of Chlamydomonas thiamin metabolism in vivo reveals riboswitch plasticity

Thiamin (vitamin B₁) is an essential micronutrient needed as a cofactor for many central metabolic enzymes. Animals must have thiamin in their diet, whereas bacteria, fungi, and plants can biosynthesize it de novo from the condensation of a thiazole and a pyrimidine moiety. Although the routes to biosynthesize these two heterocycles are not conserved in different organisms, in all cases exogenous thiamin represses expression of one or more of the biosynthetic pathway genes. One important mechanism for this control is via thiamin-pyrophosphate (TPP) riboswitches, regions of the mRNA to which TPP can bind directly, thus facilitating fine-tuning to maintain homeostasis. However, there is little information on how modulation of riboswitches affects thiamin metabolism in vivo. Here we use the green alga, Chlamydomonas reinhardtii, which regulates both thiazole and pyrimidine biosynthesis with riboswitches in the THI4 (Thiamin 4) and THIC (Thiamin C) genes, respectively, to investigate this question. Our study reveals that regulation of thiamin metabolism is not the simple dogma of negative feedback control. Specifically, balancing the provision of both of the heterocycles of TPP appears to be an important requirement. Furthermore, we show that the Chlamydomonas THIC riboswitch is controlled by hydroxymethylpyrimidine pyrophosphate, as well as TPP, but with an identical alternative splicing mechanism. Similarly, the THI4 gene is responsive to thiazole. The study not only provides insight into the plasticity of the TPP riboswitches but also shows that their maintenance is likely to be a consequence of evolutionary need as a function of the organisms’ environment and the particular pathway used.     

Associations of Pre- and Postnatal Air Pollution Exposures with Child Blood Pressure and Modification by Maternal Nutrition: A Prospective Study in the CANDLE Cohort

Background: Limited data suggest air pollution exposures may contribute to pediatric high blood pressure (HBP), a known predictor of adult cardiovascular diseases.Methods: We investigated this association in the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) study, a sociodemographically diverse pregnancy cohort in the southern United States with participants enrolled from 2006 to 2011. We included 822 mother–child dyads with available address histories and a valid child blood pressure measurement at 4–6 y. Systolic (SBP) and diastolic blood pressures (DBP) were converted to age-, sex-, and height-specific percentiles for normal-weight U.S. children. HBP was classified based on SBP or DBP ≥90th percentile. Nitrogen dioxide (NO2) and particulate matter ≤2.5μm in aerodynamic diameter (PM2.5) estimates in both pre- and postnatal windows were obtained from annual national models and spatiotemporal models, respectively. We fit multivariate Linear and Poisson regressions and explored multiplicative joint effects with maternal nutrition, child sex, and maternal race using interaction terms.Results: Mean PM2.5 and NO2 in the prenatal period were 10.8 [standard deviation (SD): 0.9] μg/m3 and 10.0 (SD: 2.4) ppb, respectively, and 9.9 (SD: 0.6) μg/m3 and 8.8 (SD: 1.9) ppb from birth to the 4-y-old birthday. On average, SBP percentile increased by 14.6 (95% CI: 4.6, 24.6), and DBP percentile increased by 8.7 (95% CI: 1.4, 15.9) with each 2-μg/m3 increase in second-trimester PM2.5. PM2.5 averaged over the prenatal period was only significantly associated with higher DBP percentiles [β= 11.6 (95% CI: 2.9, 20.2)]. Positive associations of second-trimester PM2.5 with SBP and DBP percentiles were stronger in children with maternal folate concentrations in the lowest quartile (pinteraction= 0.05 and 0.07, respectively) and associations with DBP percentiles were stronger in female children (pinteraction= 0.05). We did not detect significant association of NO2, road proximity, and postnatal PM2.5 with any outcomes.Conclusions: The findings suggest that higher prenatal PM2.5 exposure, particularly in the second trimester, is associated with elevated early childhood blood pressure. This adverse association could be modified by pregnancy folate concentrations. https://doi.org/10.1289/EHP7486