Development and preliminary evaluation of the VPS ReplaySuite: a virtual double-headed microscope for pathology

BACKGROUND: Advances in computing and telecommunications have resulted in the availability of a range of online tools for use in pathology training and quality assurance. The majority focus on either enabling pathologists to examine and diagnose cases, or providing image archives that serve as reference material. Limited emphasis has been placed on analysing the diagnostic process used by pathologists to reach a diagnosis and using this as a resource for improving diagnostic performance. METHODS: The ReplaySuite is an online pathology software tool that presents archived virtual slide examinations to pathologists in an accessible video-like format, similar to observing examinations with a double-headed microscope. Delivered through a customised web browser, it utilises PHP (Hypertext PreProcessor) to interact with a remote database and retrieve data describing virtual slide examinations, performed using the Virtual Pathology Slide (VPS). To demonstrate the technology and conduct a preliminary evaluation of pathologists opinions on its potential application in pathology training and quality assurance, 70 pathologists were invited to use the application to review their own and other pathologists examinations of 10 needle-core breast biopsies and complete an electronic survey. 9 pathologists participated, and all subsequently completed an exit survey. RESULTS: Of those who replayed an examination by another pathologist, 83.3% (5/6) agreed that replays provided an insight into the examining pathologists diagnosis and 33.3% (2/6) reconsidered their own diagnosis for at least one case. Of those who reconsidered their original diagnosis, all re-classified either concordant with group consensus or original glass slide diagnosis. 77.7% (7/9) of all participants, and all 3 participants who replayed more than 10 examinations stated the ReplaySuite to be of some or great benefit in pathology training and quality assurance. CONCLUSION: Participants conclude the ReplaySuite to be of some or of great potential benefit to pathology training and quality assurance and consider the ReplaySuite to be beneficial in evaluating the diagnostic trace of an examination. The ReplaySuite removes temporal and spatial issues that surround the use of double-headed microscopes by allowing examinations to be reviewed at different times and in different locations to the original examination. While the evaluation set was limited and potentially subject to bias, the response of participants was favourable. Further work is planned to determine whether use of the ReplaySuite can result in improved diagnostic ability

Are village health sanitation and nutrition committees fulfilling their roles for decentralised health planning and action? A mixed methods study from rural eastern India.

BACKGROUND: In India, Village Health Sanitation and Nutrition Committees (VHSNCs) are participatory community health forums, but there is little information about their composition, functioning and effectiveness. Our study examined VHSNCs as enablers of participatory action for community health in two rural districts in two states of eastern India - West Singhbhum in Jharkhand and Kendujhar, in Odisha. METHODS: We conducted a cross-sectional survey of 169 VHSNCs and ten qualitative focus group discussions with purposively selected better and poorer performing committees, across the two states. We analysed the quantitative data using descriptive statistics and the qualitative data using a Framework approach. RESULTS: We found that VHSNCs comprised equitable representation from vulnerable groups when they were formed. More than 75 % members were women. Almost all members belonged to socially disadvantaged classes. Less than 1 % members had received any training. Supervision of committees by district or block officials was rare. Their work focused largely on strengthening village sanitation, conducting health awareness activities, and supporting medical treatment for ill or malnourished children and pregnant mothers. In reality, 62 % committees monitored community health workers, 6.5 % checked sub-centres and 2.4 % monitored drug availability with community health workers. Virtually none monitored data on malnutrition. Community health and nutrition workers acted as conveners and record keepers. Links with the community involved awareness generation and community monitoring of VHSNC activities. Key challenges included irregular meetings, members' limited understanding of their roles and responsibilities, restrictions on planning and fund utilisation, and weak linkages with the broader health system. CONCLUSIONS: Our study suggests that VHSNCs perform few of their specified functions for decentralized planning and action. If VHSNCs are to be instrumental in improving community health, sanitation and nutrition, they need education, mobilisation and monitoring for formal links with the wider health system

A population-based study of anxiety as a precursor for depression in childhood and adolescence

BACKGROUND: Anxiety and depression co-occur in children and adolescents with anxiety commonly preceding depression. Although there is some evidence to suggest that the association between early anxiety and later depression is explained by a shared genetic aetiology, the contribution of environmental factors is less well examined and it is unknown whether anxiety itself is a phenotypic risk factor for later depression. These explanations of the association between early anxiety and later depression were evaluated. METHODS: Anxiety and depressive symptoms were assessed longitudinally in a U.K. population-based sample of 676 twins aged 5–17 at baseline. At baseline, anxiety and depression were assessed by parental questionnaire. Depression was assessed three years later by parental and adolescent questionnaire. RESULTS: Shared genetic effects between early anxiety and later depression were found. A model of a phenotypic risk effect from early anxiety on later depression provided a poor fit to the data. However, there were significant genetic effects specific to later depression, showing that early anxiety and later depression do not index entirely the same genetic risk. CONCLUSIONS: Anxiety and depression are associated over time because they share a partly common genetic aetiology rather than because the anxiety phenotype leads to later depression

Predictors of Change Following Cognitive-Behavioral Treatment of Children with Anxiety Problems: A Preliminary Investigation on Negative Automatic Thoughts and Anxiety Control

The purpose of the present study was to evaluate negative automatic thoughts and anxiety control as predictors of change produced by cognitive-behavioral treatment of youths with anxiety disorders. Forty-five high-anxious children aged between 9 and 12 years who were selected from the primary school population, received a standardized CBT intervention that was provided in a group format. Before and after the intervention, children completed scales of negative automatic thoughts and perceived control over anxiety-related events as well as a questionnaire for measuring DSM-defined anxiety disorders symptoms, which was the outcome measure. Results indicated that CBT was effective in reducing children’s anxiety symptoms. Most importantly, the reduction of anxiety disorders symptoms was significantly associated with a decrease in negative automatic thoughts and an increase of anxiety control, which provides support for the notion that these variables are candidate mediators of CBT in anxious youths

Study design of 'FRIENDS for Life': process and effect evaluation of an indicated school-based prevention programme for childhood anxiety and depression

Background: Anxiety disorders and depression are highly prevalent in children and affect their current and future functioning. 'FRIENDS for Life' is a cognitive-behavioural programme teaching children skills to cope more effectively with feelings of anxiety and depression. Although 'FRIENDS for Life' is increasingly being implemented at Dutch schools, its effectiveness as a preventive intervention in Dutch schools has never been investigated. The aim of the study is to evaluate the effectiveness of 'FRIENDS for Life' as an indicated school-based prevention programme for children with early or mild signs of anxiety or depression. Methods/Design. This study is a controlled trial with one pre-intervention and three post-intervention measurements (directly after, and 6 and 12 months after the end of the programme). The study sample consists of children aged 10-12 years (grades 6, 7 and 8 of Dutch primary schools), who show symptoms of anxiety or depressive disorder. Data are collected through self-report, teacher report and peer nomination. A process evaluation is conducted to investigate programme integrity (whether the programme has been executed according to protocol) and to evaluate children's and parents' opinions about 'FRIENDS for Life' using online focus groups and interviews. Discussion. The present study will provide insight into the effectiveness of 'FRIENDS for Life' as an indicated school-based prevention programme for children with early or mild signs of anxiety or depression

Epigenetics as a mechanism driving polygenic clinical drug resistance

Aberrant methylation of CpG islands located at or near gene promoters is associated with inactivation of gene expression during tumour development. It is increasingly recognised that such epimutations may occur at a much higher frequency than gene mutation and therefore have a greater impact on selection of subpopulations of cells during tumour progression or acquisition of resistance to anticancer drugs. Although laboratory-based models of acquired resistance to anticancer agents tend to focus on specific genes or biochemical pathways, such 'one gene : one outcome' models may be an oversimplification of acquired resistance to treatment of cancer patients. Instead, clinical drug resistance may be due to changes in expression of a large number of genes that have a cumulative impact on chemosensitivity. Aberrant CpG island methylation of multiple genes occurring in a nonrandom manner during tumour development and during the acquisition of drug resistance provides a mechanism whereby expression of multiple genes could be affected simultaneously resulting in polygenic clinical drug resistance. If simultaneous epigenetic regulation of multiple genes is indeed a major driving force behind acquired resistance of patients' tumour to anticancer agents, this has important implications for biomarker studies of clinical outcome following chemotherapy and for clinical approaches designed to circumvent or modulate drug resistance

Earlier Physical Therapy Input is Associated with a Reduced Length of Hospital Stay and Reduced Care Needs on Discharge in Frail Older Inpatients: An Observational Study

$\textbf{Background and Purpose}$: Pressures on hospital bed occupancy in the English National Health Service (NHS) have focused attention on enhanced service delivery models and methods by which physical therapists might contribute to effective cost savings, while retaining a patient-centered approach. Earlier access to physical therapy may lead to better outcomes in frail older inpatients, but this has not been well studied in acute NHS hospitals. Our aim was to retrospectively study the associations between early physical therapy input and length of hospital stay (LOS), functional outcomes and care needs on discharge. $\textbf{Methods}$: This was a retrospective observational study in a large tertiary university NHS hospital in the United Kingdom. We analyzed all admission episodes of people admitted to the Department of Medicine for the Elderly wards over 3 months in 2016. Patients were categorized into 2 groups: those examined by a physical therapist within 24 hours of admission and those examined after 24 hours of admission. The outcome variables were: LOS (days), functional measures on discharge (Elderly Mobility Scale and walking speed over 6 meters), and the requirement of formal care on discharge. Characterization variables on admission were: age, gender, existence of a formal care package, pre-admission abode, the Clinical Frailty Scale, Charlson Comorbidity Index, the Emergency Department Modified Early Warning Score, C-reactive protein level on admission, and the 4-item version of the Abbreviated Mental Test. The association between the delay to physical therapy input and LOS before discharge home was evaluated using a Cox proportional hazards regression model. $\textbf{Results and Discussion}$: There were 1022 hospital episodes over the study period. We excluded 19 who were discharged without being examined by a physical therapist. Of the remaining 1003, 584 (58.2%) were examined within 24 hours of admission (early assessment), and 419 (41.8%) after 24 hours of admission (late assessment). The median (interquartile range: IQR) LOS of the early assessment group was 6.7 (3.1–13.7) versus 10.0 (4.2-20.1) days in the late assessment group, P < 0.001. The early assessment group was less likely to require formal care on discharge: n=110 (20.3%) versus n=105 (27.0%), P = 0.016. No other statistically significant differences were seen between the 2 groups. In the unadjusted Cox proportional hazards model, the hazard ratio for early assessment compared to late assessment was 1.29 (95% confidence interval: 1.12-1.48, P < 0.001). Early assessment was associated with a 29% higher probability of discharge to usual residence within the first 21 days after admission, compared to late assessment. Adjustment for possible confounding variables increased the hazard ratio: 1.34 (1.16 – 1.55) P < 0.001. $\textbf{Conclusions}$: Early physical therapy input was associated with a shorter LOS and lower odds of needing care on discharge. This may be due to the beneficial effect of early physical therapy in preventing hospital-related deconditioning in frail older adults. However, causality cannot be inferred and further research is needed to investigate causal mechanisms

Earlier Physical Therapy Input is Associated with a Reduced Length of Hospital Stay and Reduced Care Needs on Discharge in Frail Older Inpatients: An Observational Study

$\textbf{Background and Purpose}$: Pressures on hospital bed occupancy in the English National Health Service (NHS) have focused attention on enhanced service delivery models and methods by which physical therapists might contribute to effective cost savings, while retaining a patient-centered approach. Earlier access to physical therapy may lead to better outcomes in frail older inpatients, but this has not been well studied in acute NHS hospitals. Our aim was to retrospectively study the associations between early physical therapy input and length of hospital stay (LOS), functional outcomes and care needs on discharge. $\textbf{Methods}$: This was a retrospective observational study in a large tertiary university NHS hospital in the United Kingdom. We analyzed all admission episodes of people admitted to the Department of Medicine for the Elderly wards over 3 months in 2016. Patients were categorized into 2 groups: those examined by a physical therapist within 24 hours of admission and those examined after 24 hours of admission. The outcome variables were: LOS (days), functional measures on discharge (Elderly Mobility Scale and walking speed over 6 meters), and the requirement of formal care on discharge. Characterization variables on admission were: age, gender, existence of a formal care package, pre-admission abode, the Clinical Frailty Scale, Charlson Comorbidity Index, the Emergency Department Modified Early Warning Score, C-reactive protein level on admission, and the 4-item version of the Abbreviated Mental Test. The association between the delay to physical therapy input and LOS before discharge home was evaluated using a Cox proportional hazards regression model. $\textbf{Results and Discussion}$: There were 1022 hospital episodes over the study period. We excluded 19 who were discharged without being examined by a physical therapist. Of the remaining 1003, 584 (58.2%) were examined within 24 hours of admission (early assessment), and 419 (41.8%) after 24 hours of admission (late assessment). The median (interquartile range: IQR) LOS of the early assessment group was 6.7 (3.1–13.7) versus 10.0 (4.2-20.1) days in the late assessment group, P < 0.001. The early assessment group was less likely to require formal care on discharge: n=110 (20.3%) versus n=105 (27.0%), P = 0.016. No other statistically significant differences were seen between the 2 groups. In the unadjusted Cox proportional hazards model, the hazard ratio for early assessment compared to late assessment was 1.29 (95% confidence interval: 1.12-1.48, P < 0.001). Early assessment was associated with a 29% higher probability of discharge to usual residence within the first 21 days after admission, compared to late assessment. Adjustment for possible confounding variables increased the hazard ratio: 1.34 (1.16 – 1.55) P < 0.001. $\textbf{Conclusions}$: Early physical therapy input was associated with a shorter LOS and lower odds of needing care on discharge. This may be due to the beneficial effect of early physical therapy in preventing hospital-related deconditioning in frail older adults. However, causality cannot be inferred and further research is needed to investigate causal mechanisms

A Multitrait–Multimethod Analysis of the Construct Validity of Child Anxiety Disorders in a Clinical Sample

The present study examines the construct validity of separation anxiety disorder (SAD), social phobia (SoP), panic disorder (PD), and generalized anxiety disorder (GAD) in a clinical sample of children. Participants were 174 children, 6 to 17 years old (94 boys) who had undergone a diagnostic evaluation at a university hospital based clinic. Parent and child ratings of symptom severity were assessed using the Multidimensional Anxiety Scale for Children (MASC). Diagnostician ratings were obtained from the Anxiety Disorders Interview Schedule for Children and Parents (ADIS: C/P). Discriminant and convergent validity were assessed using confirmatory factor analytic techniques to test a multitrait–multimethod model. Confirmatory factor analyses supported the current classification of these child anxiety disorders. The disorders demonstrated statistical independence from each other (discriminant validity of traits), the model fit better when the anxiety syndromes were specified than when no specific syndromes were specified (convergent validity), and the methods of assessment yielded distinguishable, unique types of information about child anxiety (discriminant validity of methods). Using a multi-informant approach, these findings support the distinctions between childhood anxiety disorders as delineated in the current classification system, suggesting that disagreement between informants in psychometric studies of child anxiety measures is not due to poor construct validity of these anxiety syndromes

Predictors of mortality of patients with acute respiratory failure secondary to chronic obstructive pulmonary disease admitted to an intensive care unit: A one year study

BACKGROUND: Patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) commonly require hospitalization and admission to intensive care unit (ICU). It is useful to identify patients at the time of admission who are likely to have poor outcome. This study was carried out to define the predictors of mortality in patients with acute exacerbation of COPD and to device a scoring system using the baseline physiological variables for prognosticating these patients. METHODS: Eighty-two patients with acute respiratory failure secondary to COPD admitted to medical ICU over a one-year period were included. Clinical and demographic profile at the time of admission to ICU including APACHE II score and Glasgow coma scale were recorded at the time of admission to ICU. In addition, acid base disorders, renal functions, liver functions and serum albumin, were recorded at the time of presentation. Primary outcome measure was hospital mortality. RESULTS: Invasive ventilation was required in 69 patients (84.1%). Fifty-two patients survived to hospital discharge (63.4%). APACHE II score at the time of admission to ICU {odds ratio (95 % CI): 1.32 (1.138–1.532); p < 0.001} and serum albumin (done within 24 hours of admission) {odds ratio (95 % CI): 0.114 (0.03-0.432); p = 0.001}. An equation, constructed using the adjusted odds ratio for the two parameters, had an area under the ROC curve of 91.3%. For the choice of cut-off, sensitivity, specificity, positive and negative predictive value for predicting outcome was 90%, 86.5%, 79.4% and 93.7%. CONCLUSION: APACHE II score at admission and SA levels with in 24 hrs after admission are independent predictors of mortality for patients with COPD admitted to ICU. The equation derived from these two parameters is useful for predicting outcome of these patients