Constructing validity evidence from a pilot key-features assessment of clinical decision-making in cerebral palsy diagnosis: application of Kane's validity framework to implementation evaluations.

BACKGROUND: Physician decision-making skills training is a priority to improve adoption of the cerebral palsy (CP) clinical guideline and, through this, lower the age of CP diagnosis. Clinical guideline implementation aims to improve physician practice, but evaluating meaningful change is complex. Limitations in the validity evidence of evaluation instruments impact the evidence base. Validity frameworks, such as Kane's, enable a targeted process to gather evidence for instrument scores, congruent to context and purpose. Yet, application of argument-based methodology to implementation validation is rare. Key-features examination methodology has established validity evidence supporting its use to measure decision-making skills, with potential to predict performance. We aimed to apply Kane's framework to evaluate a pilot key-features examination on physician decision-making in early CP diagnosis. METHODS: Following Kane's framework, we evaluated evidence across inferences of scoring, generalisation, extrapolation and implications in a study design describing the development and pilot of a CP diagnosis key-features examination for practising physicians. If found to be valid, we proposed to use the key-feature scores as an outcome measure of decision-making post education intervention to expedite CP diagnosis and to correlate with real-world performance data to predict physician practice. RESULTS: Supporting evidence for acceptance of scoring inferences was achieved through examination development with an expert group (n = 10) and pilot results (n = 10): (1) high internal consistency (0.82); (2) acceptable mean item-discrimination (0.34); and (3) acceptable reliability of examination scorers (95.2% congruence). Decreased physician acceptance of examination time (70%) was identified as a threat and prioritised in case reduction processes. Partial acceptance of generalisation, extrapolation and implications inferences were defensible with: (1) accumulated development evidence following established key-features methodology; (2) high pilot acceptance for authenticity (90%); and (3) plausibility of assumptions of score correlation with population register data. CONCLUSIONS: Kane's approach is beneficial for prioritising sources of validity evidence alongside the iterative development of a key-features examination in the CP field. The validity argument supports scoring assumptions and use of scores as an outcome measure of physician decision-making for CP guideline education implementation interventions. Scoring evidence provides the foundation to direct future studies exploring association of key-feature scores with real-world performance.

Social incentives are stronger predictors of drinking decisions than alcohol incentives in young adults: The role of alcohol use disorder.

This study investigated the influence of social incentives, alcohol incentives, and responsibility disincentives on decisions to attend and drink at party events in young adult college students (n = 82; 55 women, 27 men) where 36 (20 women; 16 men) had an Alcohol Use Disorder (AUD) and 46 (35 women; 11 men) were control participants without an AUD. In this within-subjects design, participants were presented with a series of hypothetical drinking event scenarios that varied in terms of social incentives (knowing many vs. few people), alcohol incentives (more vs. less alcohol available), and next-day responsibility disincentives (high vs. moderate vs. low). Participants were asked whether they would attend the event and how many drinks they would consume. Social incentives significantly predicted both decisions to attend party events and decisions about how much to drink for all participants. Participants were more likely to decide to attend and drink more at high social incentive party events (where they knew more people). However, while low social incentives generally discouraged attendance decisions, AUD participants were more likely than controls to decide to attend party events in low social incentive contexts. Alcohol incentives did not affect attendance decisions. However, alcohol incentives did increase drinking amount decisions for AUD participants. Finally, while disincentives decreased attendance and drinking amount decisions in general, AUD participants were less deterred by responsibility disincentives than controls. The results highlight the important influence of social rewards on drinking-related decisions and suggest individual differences in how incentives and disincentives affect drinking decisions in persons with an AUD.

Coinjection of IL2 DNA enhances E7-specific antitumor immunity elicited by intravaginal therapeutic HPV DNA vaccination with electroporation.

The generation and use of therapeutic human papillomavirus (HPV) DNA vaccines represent an appealing treatment method against HPV-associated cervical cancer owing to their safety and durability. Previously, we created a therapeutic HPV DNA vaccine candidate by linking the HPV16-E7 DNA sequence to calreticulin (CRT/E7), which we showed could generate significant E7-specific cytotoxic T lymphocyte (CTL)-mediated antitumor immune responses against HPV16 oncogenes expressing murine tumor model TC-1. Here we assess the therapeutic efficacy of intravaginal immunization with pcDNA3-CRT/E7 followed by electroporation. In addition, we examined whether coadministration of DNA-encoding interleukin 2 (IL2) with the pcDNA3-CRT/E7 could improve the T-cell responses elicited by pcDNA3-CRT/E7. TC-1 tumor-bearing mice vaccinated intravaginally with both pcDNA3-CRT/E7 and IL2 DNA followed by electroporation induced stronger local antitumor CTL response in comparison to mice that received other treatment regimens. Additionally, we found that coadministration of IL2 DNA with pcDNA3-CRT/E7 modified the tumor microenvironment by decreasing the population of regulatory T cells and myeloid-derived suppressor cells relative to that of CTLs. Our data demonstrate the translational potential of local administration of IL2 and pcDNA3-CRT/E7 followed by electroporation in treating cervicovaginal tumors.

Optimising molecular diagnostic capacity for effective control of tuberculosis in high-burden settings.

The World Health Organization's 2035 vision is to reduce tuberculosis (TB) associated mortality by 95%. While low-burden, well-equipped industrialised economies can expect to see this goal achieved, it is challenging in the low- and middle-income countries that bear the highest burden of TB. Inadequate diagnosis leads to inappropriate treatment and poor clinical outcomes. The roll-out of the Xpert(®) MTB/RIF assay has demonstrated that molecular diagnostics can produce rapid diagnosis and treatment initiation. Strong molecular services are still limited to regional or national centres. The delay in implementation is due partly to resources, and partly to the suggestion that such techniques are too challenging for widespread implementation. We have successfully implemented a molecular tool for rapid monitoring of patient treatment response to anti-tuberculosis treatment in three high TB burden countries in Africa. We discuss here the challenges facing TB diagnosis and treatment monitoring, and draw from our experience in establishing molecular treatment monitoring platforms to provide practical insights into successful optimisation of molecular diagnostic capacity in resource-constrained, high TB burden settings. We recommend a holistic health system-wide approach for molecular diagnostic capacity development, addressing human resource training, institutional capacity development, streamlined procurement systems, and engagement with the public, policy makers and implementers of TB control programmes.

Effect of reducing dietary forage in lower starch diets on performance, ruminal characteristics, and nutrient digestibility in lactating Holstein cows.

This experiment evaluated the effect of feeding a lower starch diet (21% of dry matter) with different amounts of forage (52, 47, 43, and 39% of dry matter) on lactational performance, chewing activity, ruminal fermentation and turnover, microbial N yield, and total-tract nutrient digestibility. Dietary forage consisted of a mixture of corn and haycrop silages, and as dietary forage content was reduced, chopped wheat straw (0-10% of dry matter) was added in an effort to maintain chewing activity. Dietary concentrate was adjusted (corn meal, nonforage fiber sources, and protein sources) to maintain similar amounts of starch and other carbohydrate and protein fractions among the diets. Sixteen lactating Holstein cows were used in replicated 4×4 Latin squares with 21-d periods. Dry matter intake increased while physically effective neutral detergent fiber (peNDF1.18) intake was reduced as forage content decreased from 52 to 39%. However, reducing dietary forage did not influence milk yield or composition, although we observed changes in dry matter intake. Time spent chewing, eating, and ruminating (expressed as minutes per day or as minutes per kilogram of NDF intake) were not affected by reducing dietary forage. However, addition of chopped wheat straw to the diets resulted in greater time spent chewing and eating per kilogram of peNDF1.18 consumed. Reducing dietary forage from 52 to 39% did not affect ruminal pH, ruminal digesta volume and mass, ruminal pool size of NDF or starch, ruminal digesta mat consistency, or microbial N yield. Ruminal acetate-to-propionate ratio was reduced, ruminal turnover rates of NDF and starch were greater, and total-tract digestibility of fiber diminished as dietary forage content decreased. Reducing the dietary forage content from 52 to 39% of dry matter, while increasing wheat straw inclusion to maintain chewing and rumen function, resulted in similar milk yield and composition although feed intake increased. With the lower starch diets in this short-term study, the minimal forage content to maintain lactational performance was between 39 and 43%.

Factors affecting the perception of recovery quality in horses after anaesthesia.

REASONS FOR PERFORMING STUDY: A significant effect of gender, experience and background, i.e. an evaluator's relationship with horses as equine anaesthetists, orthopaedic surgeons, practitioners or owners, on perceptions of recovery quality after anaesthesia would reduce the validity of recovery quality scoring systems. OBJECTIVES: To determine the effects of evaluator background, experience and gender on their perceptions of recovery quality; and questionnaire response rate as a function of background. STUDY DESIGN: Cross-sectional survey. METHODS: A total of 440 potential evaluators were invited to evaluate the video-recorded recoveries of 24 horses using a visual analogue scale (VAS) in which 0 = worst, 100 = best possible recovery. A mean score was generated for each of the 1-24 recoveries within each background group. These were compared using Spearman's rank correlation. The effect of gender and experience on VAS scores were analysed using an ordinal logistic regression after scores were categorised into 'intermediate, 'worst' and 'best' recovery categories based on median, 25th and 75th percentile VAS scores, respectively. RESULTS: The overall response rate was 35%. The greatest was from the anaesthetists (78%) followed by surgeons (43%). The response rate among owners and practitioners was 26%. Correlation among VAS scores across all background groups was high (Spearman rank > 0.90; P < 0.001). Among the combined veterinarians, there was no significant gender (P = 0.551) or experience (P = 0.103) effect. Among horse owners, the effect of experience was not significant (P = 0.116) although gender was (P = 0.027). Male horse owners awarded significantly greater scores than females. CONCLUSIONS: When VAS are used to grade recovery quality, neither the background nor the gender of veterinary evaluators affects quality perception. Male owners awarded greater scores than female owners, implying that they are less critical of recovery quality and a gender effect among horse owners must be considered when VAS are used to score recovery quality.

ABLE - assessment based learning.

Over the past decade the Australian health care system has moved rapidly toward a greater emphasis on medical care being provided within the community. This trend can only continue as our population ages and levels of chronic and complex illness continue to rise. Primary care now includes: a higher proportion of general practitioners working in group practices supported by practice nurses and allied health professionals- both on site and in the community, increased patient presentations for chronic and complex disease - often compounded by mental health and social issues, and, more hospital in the home, early discharge and similar programmes enabling shared management of sicker patients in the community.

Pain flashbacks following the July 7th 2005 London bombings.

Flashbacks in posttraumatic stress disorder (PTSD) are commonly experienced as visual, auditory, olfactory or tactile re-livings of a previously experienced traumatic event. We present the case report of one survivor of the July 7th 2005 London underground bombings who was diagnosed with PTSD and who experienced painful flashbacks. We present retrospective multidimensional measures of his pain using standardised instruments. The case provides further evidence that somatosensory re-experiencing of pain memories is possible. Findings are discussed with regards to memory for pain.

Standards and performance--attainment and maintenance of professional capabilities.

The nature of The Royal Australian College of General Practitioners (RACGP) examination came under scrutiny in a recent debate among RACGP members, some of who suggested exploring an alternative pathway for assessment linked to continuing medical education. This article outlines key issues underpinning the examination that is part of the requirements for attaining Fellowship of the RACGP (FRACGP). It provides an overview of the theory and practice of assessment for general practice. The RACGP examination has an international reputation for quality, validity and reliability, a reason why the RACGP has been asked to assist many others in establishing and/or reviewing their own examination processes.

Oral PUVA and topical steroids for treatment of oral manifestations of chronic graft-vs.-host disease.

BACKGROUND: Oral manifestations of chronic graft-vs.-host disease (cGVHD) can significantly affect the quality of life and severity often does not correlate with systemic manifestations. We evaluated the use of topical corticosteroids and the intraoral application of psoralen-UVA (PUVA) for treatment of oral manifestations of cGVHD. METHODS: Overall, 18 patients with oral manifestations of cGVHD were treated with either intraoral PUVA (n=7) or with topical corticosteroids (n=16). Four patients received intraoral PUVA after failure of topical steroids and one patient was treated with topical corticosteroids after failing treatment with intraoral PUVA. A glass fiber extension of an UVA source was used for manual intraoral application. Treatment with topical corticosteroids consisted of 0.1 mg/ml dexamethasone mouth wash four times a day in combination with antifungal prophylaxis. RESULTS: Four patients showed complete local response (CR) due to intraoral PUVA, two improved and one did not respond. Topical corticosteroids resulted in nine patients in CR, two improved and five did not respond. CONCLUSION: Intraoral PUVA as well as topical corticosteroids are effective in treatment of oral manifestations of oral GVHD with few side-effects and improve quality of life in patients with cGVHD.

Selecting performance assessment methods for experienced physicians.

BACKGROUND: While much is now known about how to assess the competence of medical practitioners in a controlled environment, less is known about how to measure the performance in practice of experienced doctors working in their own environments. The performance of doctors depends increasingly on how well they function in teams and how well the health care system around them functions. METHODS: This paper reflects the combined experiences of a group of experienced education researchers and the results of literature searches on performance assessment methods. CONCLUSION: Measurement of competence is different to measurement of performance. Components of performance could be re-conceptualised within a different domain structure. Assessment methods may be of a different utility to that in competence assessment and, indeed, of different utility according to the purpose of the assessment. An exploration of the utility of potential performance assessment methods suggests significant gaps that indicate priority areas for research and development.

Epithelial plugs in radial keratotomy: the origin of incisional keratitis?

PURPOSE: Incisions in radial keratotomy (RK) patients were examined histopathologically to explore the cause of delayed infections occurring following this procedure. METHODS: Four corneas from two successful RK patients were obtained postmortem and 1 cornea from an unsuccessful RK was collected following lamellar keratoplasty. The tissue was prepared for light and transmission electron microscopy. RESULTS: All incisions examined contained an epithelial plug. The average depth of the plugs for left and right corneas in the 2 successful cases were 142.58 microm (range: 36.46-183.04 microm) and 58.44 microm (range: 29.27-115.66 microm), whereas the unsuccessful case these measurements were 121.06 microm (range: 70.03-172.01 microm). In the successful cases, the plugs were on average 4.2 cells deep (range: 2-5) in one case and for the other the plugs were 8.78 cells deep (range: 1.5-11.5) and 2.72 cells wide (range: 2-4). In the unsuccessful case the plugs were on average 6.89 cells deep (range: 5-11) and 8.56 cells wide (range: 4-13). The average epithelial thickness, measured 200 microm on either side away from the plug, was 47.11 microm and 55.09 microm for the successful cases, and 27.52 microm for the unsuccessful case. Degenerate cells were often observed within the plug and along the overlying surface. Lamellae cut during surgery remained severed in all corneas observed. The stroma adjacent to the incision contained an elevated number of stromal cells (8%-78%). CONCLUSIONS: Healing did not include repair of anterior limiting lamina or stromal lamellae, which all remained severed in all incisions observed. Epithelial plugs were invariably present in all incisions regardless of clinical outcome, thus, increasing the distance a basal cell travels to reach the epithelial surface by 2 to 4 times. Since the epithelial cell has a limited life, it is hypothesized that cells originating in the plug may die before reaching the surface, thus, leading to intermittent loss of surface integrity. The loss of the epithelial barrier allows invasion of microorganisms and the delayed onset of keratitis. The larger the plug the greater the possibility of surface defects and resultant infection.

Plant defense in the absence of jasmonic acid: the role of cyclopentenones.

The Arabidopsis opr3 mutant is defective in the isoform of 12-oxo-phytodienoate (OPDA) reductase required for jasmonic acid (JA) biosynthesis. Oxylipin signatures of wounded opr3 leaves revealed the absence of detectable 3R,7S-JA as well as altered levels of its cyclopentenone precursors OPDA and dinor OPDA. In contrast to JA-insensitive coi1 plants and to the fad3 fad7 fad8 mutant lacking the fatty acid precursors of JA synthesis, opr3 plants exhibited strong resistance to the dipteran Bradysia impatiens and the fungus Alternaria brassicicola. Analysis of transcript profiles in opr3 showed the wound induction of genes previously known to be JA-dependent, suggesting that cyclopentenones could fulfill some JA roles in vivo. Treating opr3 plants with exogenous OPDA powerfully up-regulated several genes and disclosed two distinct downstream signal pathways, one through COI1, the other via an electrophile effect of the cyclopentenones. We conclude that the jasmonate family cyclopentenone OPDA (most likely together with dinor OPDA) regulates gene expression in concert with JA to fine-tune the expression of defense genes. More generally, resistance to insect and fungal attack can be observed in the absence of JA.

Surface-to-air signals.

Powerful volatile regulators of gene expression, pheromones and other airborne signals are of great interest in biology. Plants are masters of volatile production and release, not just from flowers and fruits, but also from vegetative tissues. The controlled release of bouquets of volatiles from leaves during attack by herbivores helps plants to deter herbivores or attract their predators, but volatiles have other roles in development and in the control of defence gene expression. Some of these roles may include long-distance signalling within and perhaps between plants.

Use of the Dermatology Life Quality Index (DLQI) in a midwestern US urban clinic.

BACKGROUND: The Dermatology Life Quality Index (DLQI), a self-administered general dermatology quality of life instrument, was originally developed and published in a dermatology clinic at University Hospital of Wales. OBJECTIVE: Our goal was to test the feasibility of having patients answer the DLQI in a busy dermatology clinic and to find out to what extent results vary from those published in Wales. We also wanted to examine the validity of the index in terms of the correlation between DLQI scores and stage of illness (disease severity). METHODS: We administered the DLQI to 200 consecutive patients who were seen in a dermatology clinic at Indiana University Medical Center. Results were examined in light of results found by those who originated the DLQI. A pilot group of patients were given the DLQI and rated for severity of disease by means of the Dermatology Index of Disease Severity (DIDS). RESULTS: Overall, the DLQI is easy to administer and can be completed within 3 minutes. The scores in our study were compatible with those previously reported by the DLQI originators. There was a "ceiling" effect in that 11% of the patients indicated no quality of life impairment on the DLQI rating. This index shows stratification with severity of disease. CONCLUSION: The DLQI is an easy and efficient instrument for assessing quality of life in dermatology patients. Patients needed minimal assistance with the form. Our results were similar to those of the DLQI originators, and this further shows reliability and validity of the DLQI. In addition, this study further supports the use of DLQI as a quality of life instrument suitable for use in international studies.

Developmental science, systems of care, and prevention of emotional and behavioral problems in youth.

Developmental science, a metatheoretical framework for investigating individual development across the lifecourse, is discussed in terms of its application to prevention and treatment of emotional and behavioral problems. The multifaceted, dynamic, and bidirectional contribution of factors, both internal and external to the individual, is thus emphasized. Key aspects of developmental science, systems of care, and prevention are described, and the implications for delivery of mental health services to children and youth are discussed.