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Several scales are commonly used for assessing pain intensity. Among them, the numerical rating scale (NRS), visual analog scale (VAS), and verbal rating scale (VRS) are often used in clinical practice. However, no study has performed psychometric analyses of their reliability and validity in the measurement of osteoarthritic (OA) pain. Therefore, the present study examined the test-retest reliability, validity, and minimum detectable change (MDC) of the VAS, NRS, and VRS for the measurement of OA knee pain. In addition, the correlations of VAS, NRS, and VRS with demographic variables were evaluated. The study included 121 subjects (65 women, 56 men; aged 40-80 years) with OA of the knee. Test-retest reliability of the VAS, NRS, and VRS was assessed during two consecutive visits in a 24 h interval. The validity was tested using Pearson's correlation coefficients between the baseline scores of VAS, NRS, and VRS and the demographic variables (age, body mass index [BMI], sex, and OA grade). The standard error of measurement (SEM) and the MDC were calculated to assess statistically meaningful changes. The intraclass correlation coefficients of the VAS, NRS, and VRS were 0.97, 0.95, and 0.93, respectively. VAS, NRS, and VRS were significantly related to demographic variables (age, BMI, sex, and OA grade). The SEM of VAS, NRS, and VRS was 0.03, 0.48, and 0.21, respectively. The MDC of VAS, NRS, and VRS was 0.08, 1.33, and 0.58, respectively. All the three scales had excellent test-retest reliability. However, the VAS was the most reliable, with the smallest errors in the measurement of OA knee pain.

Leuco-methylthioninium bis(hydromethanesulfonate; LMTM), a stable reduced form of the methylthioninium moiety, acts as a selective inhibitor of tau protein aggregation both in vitro and in transgenic mouse models. Methylthioninium chloride has previously shown potential efficacy as monotherapy in patients with Alzheimer's disease. We aimed to determine whether LMTM was safe and effective in modifying disease progression in patients with mild to moderate Alzheimer's disease. We did a 15-month, randomised, controlled double-blind, parallel-group trial at 115 academic centres and private research clinics in 16 countries in Europe, North America, Asia, and Russia with patients younger than 90 years with mild to moderate Alzheimer's disease. Patients concomitantly using other medicines for Alzheimer's disease were permitted to be included because we considered it infeasible not to allow their inclusion; however, patients using medicines carrying warnings of methaemoglobinaemia were excluded because the oxidised form of methylthioninium in high doses has been shown to induce this condition. We randomly assigned participants (3:3:4) to 75 mg LMTM twice a day, 125 mg LMTM twice a day, or control (4 mg LMTM twice a day to maintain blinding with respect to urine or faecal discolouration) administered as oral tablets. We did the randomisation with an interactive web response system using 600 blocks of length ten, and stratified patients by severity of disease, global region, whether they were concomitantly using Alzheimer's disease-labelled medications, and site PET capability. Participants, their study partners (generally carers), and all assessors were masked to treatment assignment throughout the study. The coprimary outcomes were progression on the Alzheimer's Disease Assessment Scale–Cognitive Subscale (ADAS-Cog) and the Alzheimer's Disease Co-operative Study–Activities of Daily Living Inventory (ADCS-ADL) scales from baseline assessed at week 65 in the modified intention-to-treat population. This trial is registered with Clinicaltrials.gov (NCT01689246) and the European Union Clinical Trials Registry (2012-002866-11). Between Jan 29, 2013, and June 26, 2014, we recruited and randomly assigned 891 participants to treatment (357 to control, 268 to 75 mg LMTM twice a day, and 266 to 125 mg LMTM twice a day). The prespecified primary analyses did not show any treatment benefit at either of the doses tested for the coprimary outcomes (change in ADAS-Cog score compared with control [n=354, 6·32, 95% CI 5·31−7·34]: 75 mg LMTM twice a day [n=257] −0·02, −1·60 to 1·56, p=0·9834, 125 mg LMTM twice a day [n=250] −0·43, −2·06 to 1·20, p=0·9323; change in ADCS-ADL score compared with control [−8·22, 95% CI −9·63 to −6·82]: 75 mg LMTM twice a day −0·93, −3·12 to 1·26, p=0·8659; 125 mg LMTM twice a day −0·34, −2·61 to 1·93, p=0·9479). Gastrointestinal and urinary effects were the most common adverse events with both high doses of LMTM, and the most common causes for discontinuation. Non-clinically significant dose-dependent reductions in haemoglobin concentrations were the most common laboratory abnormality. Amyloid-related imaging abnormalities were noted in less than 1% (8/885) of participants. The primary analysis for this study was negative, and the results do not suggest benefit of LMTM as an add-on treatment for patients with mild to moderate Alzheimer's disease. Findings from a recently completed 18-month trial of patients with mild Alzheimer's disease will be reported soon. TauRx Therapeutics.

Synaptic loss and deficits in functional connectivity are hypothesized to contribute to symptoms associated with major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). The synaptic vesicle glycoprotein 2A (SV2A) can be used to index the number of nerve terminals, an indirect estimate of synaptic density. Here, we used positron emission tomography (PET) with the SV2A radioligand [ 11 C]UCB-J to examine synaptic density in n  = 26 unmedicated individuals with MDD, PTSD, or comorbid MDD/PTSD. The severity of depressive symptoms was inversely correlated with SV2A density, and individuals with high levels of depression showing lower SV2A density compared to healthy controls ( n  = 21). SV2A density was also associated with aberrant network function, as measured by magnetic resonance imaging (MRI) functional connectivity. This is the first in vivo evidence linking lower synaptic density to network alterations and symptoms of depression. Our findings provide further incentive to evaluate interventions that restore synaptic connections to treat depression. Lowered synaptic density is believed to occur in major depressive disorder and PTSD, possibly as an effect of stress. Here, the authors use positron emission tomography (PET) to measure levels of the synaptic marker SV2A and show that SV2A density is lower in those with more severe symptoms of depression.

Background While the gold standard for the diagnosis of mental disorders remains the structured clinical interview, self-report measures continue to play an important role in screening and measuring progress, as well as being frequently employed in research studies. Two widely-used self-report measures in the area of depression and anxiety are Zung’s Self-Rating Depression Scale (SDS) and Self Rating Anxiety Scale (SAS). However, considerable confusion exists in their application, with clinical cut-offs often applied incorrectly. This study re-examines the credentials of the Zung scales by comparing them with the Depression Anxiety Stress Scale (DASS) in terms of their ability to predict clinical diagnoses of anxiety and depression made using the Patient Health Questionnaire (PHQ). Method A total sample of 376 adults, of whom 87 reported being in receipt of psychological treatment, completed the two-page version of the PHQ relating to depression and anxiety, together with the SDS, the SAS and the DASS. Results Overall, although the respective DASS scales emerged as marginally stronger predictors of PHQ diagnoses of anxiety and depression, the Zung indices performed more than acceptably in comparison. The DASS also had an advantage in discriminative ability. Using the current recommended cut-offs for all scales, the DASS has the edge on specificity, while the Zung scales are superior in terms of sensitivity. There are grounds to consider making the Zung cut-offs more conservative, and doing this would produce comparable numbers of ‘Misses’ and ‘False Positives’ to those obtained with the DASS. Conclusions Given these promising results, further research is justified to assess the Zung scales ability against full clinical diagnoses and to further explore optimum cut-off levels.

Poor-quality early childhood education and care (ECEC) can be detrimental to the development of children, as it may lead to poor social, emotional, educational, health, economic, and behavioral outcomes. A lack of consensus, however, regarding the strength of the relationship between teacher qualification and the quality of the ECEC environment makes it difficult to identify strategies that could enhance developmental and educational outcomes. This meta-analytic review examines evidence on the correlation between teacher qualifications and the quality of ECEC environments. Results show that higher teacher qualifications are significantly correlated with higher quality ECEC environments. Specifically, the education level of teachers or caregivers is positively correlated to overall ECEC qualities, as well as subscale ratings including program structure, language, and reasoning.

Smith and colleagues developed the Brief Resilience Scale (BRS) to assess the individual ability to recover from stress despite significant adversity. This study aimed to validate the German version of the BRS. We used data from a population-based (sample 1: n = 1.481) and a representative (sample 2: n = 1.128) sample of participants from the German general population (age ≥ 18) to assess reliability and validity. Confirmatory factor analyses (CFA) were conducted to compare one- and two-factorial models from previous studies with a method-factor model which especially accounts for the wording of the items. Reliability was analyzed. Convergent validity was measured by correlating BRS scores with mental health measures, coping, social support, and optimism. Reliability was good (α = .85, ω = .85 for both samples). The method-factor model showed excellent model fit (sample 1: χ2/df = 7.544; RMSEA = .07; CFI = .99; SRMR = .02; sample 2: χ2/df = 1.166; RMSEA = .01; CFI = 1.00; SRMR = .01) which was significantly better than the one-factor model (Δχ2(4) = 172.71, p < .001) or the two-factor model (Δχ2(3) = 31.16, p < .001). The BRS was positively correlated with well-being, social support, optimism, and the coping strategies active coping, positive reframing, acceptance, and humor. It was negatively correlated with somatic symptoms, anxiety and insomnia, social dysfunction, depression, and the coping strategies religion, denial, venting, substance use, and self-blame. To conclude, our results provide evidence for the reliability and validity of the German adaptation of the BRS as well as the unidimensional structure of the scale once method effects are accounted for.

Background: Apathy is usually defined as reduced interest and participation in various activities. It is a frequent consequence of neurological and psychiatric disorders. Although various scoring methods have been proposed, there is a lack of validated, standardised instruments for detecting apathy and assessing its severity. Objective: To develop an apathy rating scale using a structured standardised interview capable of distinguishing between the condition’s various features. Methods: The Lille Apathy Rating Scale (LARS) is based on a structured interview. It includes 33 items, divided into nine domains. Responses are scored on a dichotomous scale. The participants used to validate the scale consisted of 159 patients with probable Parkinson’s disease and 58 healthy control subjects. The Marin Apathy Scale, the Montgomery and Asberg Depression Rating Scale, and the Mattis Dementia Rating Scale were also administered. Results: Principal component analysis showed that the LARS probed a single construct which forms the root of an oblique factor structure reflecting four dimensions: intellectual curiosity, self awareness, emotion, and action initiation. The main psychometric properties of the LARS (internal consistency, inter-rater and test-retest reliability) were satisfactory. Concurrent validity was evaluated by reference to the Marin scale and to judgements provided by expert clinicians. Conclusions: Standard validity indices showed that the LARS is sensitive and capable of distinguishing between apathy and depression. As a screening tool, the scale is able to support dichotomous judgements accurately and, when greater measurement sensitivity is required, also determine the severity of apathy within a four category classification.

The format of the original Hamilton Rating Scale for Depression (HAM-D) was unstructured: only general instructions were provided for rating individual items. Over the years, a number of modified versions of the HAM-D have been proposed. They differ not only in the number of items, but also in modalities of administration. Structured versions, including item definitions, anchor points and semi-structured or structured interview questions, were developed. This comprehensive review was conducted to examine the clinimetric properties of the different versions of the HAM-D. The aim was to identify the HAM-D versions that best display the clinimetric properties of reliability, validity, and sensitivity to change. The search was conducted on MEDLINE, Scopus, Web of Science, and PubMed, and yielded a total of 35,473 citations, but only the most representative studies were included. The structured versions of the HAM-D were found to display the highest inter-rater and test-retest reliability. The Clinical Interview for Depression and the 6-item HAM-D showed the highest sensitivity in differentiating active treatment from placebo. The findings indicate that the HAM-D is a valid and sensitive clinimetric index, which should not be discarded in view of obsolete and not clinically relevant psychometric criteria. The HAM-D, however, requires an informed use: unstructured forms should be avoided and the type of HAM-D version that is selected should be specified in the registration of the study protocol and in the methods of the trial.

The majority of previous research that has examined the validity of pain intensity rating scales has been conducted in western and developed countries. Research to evaluate the generalizability of previous findings in non-developed countries is necessary for identifying the scales that are most appropriate for use in international research. The aims of the current study were to (1) evaluate the validity and utility of four commonly used measures of pain intensity in a sample of patients with chronic pain from Thailand and (2) compare findings in the current sample with published findings from research conducted in other countries, in order to identify the measure or measures which might be most appropriate for cross-country research. Three hundred and sixty patients with chronic pain seen in a hospital in Bangkok, Thailand, were asked to rate their current pain and average, worst, and least pain intensity in the past week using the Visual Analogue Scale (VAS), 6-point Verbal Rating Scale (VRS-6), 0-10 Numerical Rating Scale (NRS-11), and Faces Pain Scale-Revised (FPS-R). We evaluated the utility and validity of each measure by examining the (1) rates of correct responding and (2) association of each measure with a factor score representing the variance shared across measures, respectively. We also evaluated the associations between incorrect response rates and both age and education level, and then compared the findings from this sample with the findings from research conducted in other countries. The results indicated support for the validity of all measures among participants who were able to use these measures. However, there was variability in the incorrect response rates, with the VAS having the highest (45%) and the NRS-11 having the lowest (15%) incorrect response rates. The VAS was also the least preferred (9%) and the NRS-11 the most preferred (52%) scale. Education and age were significantly associated with incorrect response rates, and education level with scale preference. The findings indicate that the NRS-11 has the most utility in our sample of Thai individuals with chronic pain. However, when considered in light of the findings from other countries, the results of this study suggest that the FPS-R may have the most utility for use in cross-cultural and international research. Research in additional samples in developing countries is needed to evaluate the generalizability of the current findings.