Predicting Youth Improvement in Community-Based Residential Settings with Practices Derived from the Evidence-Base.

The current investigation conducted descriptive analyses on key variables in community-based residential (CBR) settings and investigated the extent to which disruptive youth between the ages of 13 and 17 years improved based on therapists' reported alignment with using practices derived from the evidence-base (PDEBs). Results from both the descriptive analyses and multilevel modeling suggested that therapists are using practices that both do and do not align with the evidence-base for disruptive youth. In addition, both PDEBs and practices with minimal evidence-support predicted or marginally predicted final average progress rating for these youth. Findings are discussed as they relate to the importance of continued exploration of treatment outcomes for CBR youth.

Computational correction of copy number effect improves specificity of CRISPR-Cas9 essentiality screens in cancer cells.

The CRISPR-Cas9 system has revolutionized gene editing both at single genes and in multiplexed loss-of-function screens, thus enabling precise genome-scale identification of genes essential for proliferation and survival of cancer cells. However, previous studies have reported that a gene-independent antiproliferative effect of Cas9-mediated DNA cleavage confounds such measurement of genetic dependency, thereby leading to false-positive results in copy number-amplified regions. We developed CERES, a computational method to estimate gene-dependency levels from CRISPR-Cas9 essentiality screens while accounting for the copy number-specific effect. In our efforts to define a cancer dependency map, we performed genome-scale CRISPR-Cas9 essentiality screens across 342 cancer cell lines and applied CERES to this data set. We found that CERES decreased false-positive results and estimated sgRNA activity for both this data set and previously published screens performed with different sgRNA libraries. We further demonstrate the utility of this collection of screens, after CERES correction, for identifying cancer-type-specific vulnerabilities.

Periodontitis and bone metabolism in patients with advanced heart failure and after heart transplantation.

AIMS: Heart failure (HF) is a multi-organ, pro-inflammatory syndrome that impairs bone metabolism. Pro-inflammatory cytokines and bone catabolism enhance periodontal disease, a local inflammatory, bacteria-induced disease that causes bone loss and periodontal soft tissue destruction. METHODS AND RESULTS: Medical and dental examinations were performed on patients with HF (n = 39), following heart transplantation (post-HTx, n = 38) and controls (n = 32). Blood, saliva, and gingival crevicular fluid were analysed for bone metabolism and inflammation markers. HF average New York Heart Association classification was III. Average time since HTx was 1414 days. Pro-inflammatory tumour necrosis factor-alpha was higher in HF and HTx as compared with controls (P < 0.05). Both HF and HTx participants had higher levels of bone resorption marker C-terminal telopeptide and parathyroid hormone with subjects in the HF group having the highest serum levels of all groups (P ≤ 0.05). In contrast, 25-hydroxyvitamin D was lowest in HF. HF patients had greater clinical attachment loss, cumulative pockets depth (greater than 3 mm) and probing depth (P < 0.05) as compared with controls. Cumulative pockets depth correlated significantly with measures of the inflammatory burden, ß-glucuronidase in saliva (r = 0.4863, P < 0.01), interleukin-1b in saliva (r = 0.5149, P < 0.01), and gingival crevicular fluid (r = 0.6056, P < 0.001) in HF. However, adjustment of periodontal results for measures of oral hygiene (plaque, bleeding on probing), systemic 25-hydroxyvitamin D, and race attenuated significant differences between groups. CONCLUSIONS: Patients with HF exhibit more severe periodontal disease associated with increased bone turnover markers when compared with control patients. However, local and systemic factors may account for this association and should be evaluated in future studies.

Evidence-Based Practice Implementation Within a Theory of Planned Behavior Framework.

Although significant progress has been made in the identification of youth evidence-based practices, the adoption of these interventions into community-based mental health care remains limited. Dissemination and implementation (DI) research has the potential to bridge this science-practice gap in clinical psychology. The theory of planned behavior (TPB) offers a useful conceptualization of individual behavior change including behavioral intention as defined by attitudes, subjective norms, and perceived behavioral control. To facilitate application of this model to DI efforts, the current study explores perspectives about using evidence-based practice from stakeholders in the field of youth mental health (including clinical supervisors, case managers, administrators at the departments of health and education, and direct service providers in clinic-based, school-based, and intensive in-home settings) within the TPB framework. A set of instrument items was created from this rich qualitative data using a rigorous mixed-method content validation approach. Instrument items are provided for future use in DI research.

Management of an Ailing Anterior Implant Using a Minimally Invasive Flapless Surgical Technique: A Case Report.

INTRODUCTION: Peri-implantitis is an inflammation of the soft and hard tissues surrounding an implant that results in the destruction of alveolar bone. Surgical flaps are usually elevated to allow for thorough debridement and disinfection of the implant surface. This frequently results in gingival recession, crown margin exposure, and a poor esthetic result. This is not desirable in the esthetic zone. In this case report, a minimally invasive flapless technique incorporating the use of curettage and antiseptics is used to successfully disinfect a contaminated dental implant to allow for soft tissue readherence and pocket reduction. Radiographic bone fill is also seen. The results have been maintained for 2 years. CASE PRESENTATION: A 54-year-old female patient presented with peri-implantitis, characterized by episodic pain and suppuration from a buccal fistula on an implant replacing tooth #10. The implant was placed and provisionally restored 10 years previously. It showed radiographic bone loss to the fifth thread, but it was non-mobile. Treatment consisted of removal of the temporary crown and abutment, which provided access for the surgical curettage of the granulomatous tissue and for the mechanical debridement of the implant surface with a titanium curet. Chemical detoxification of the implant surface, as well as the abutment, screw, and screw hole, was achieved with the use of sterile saline and a 0.25% sodium hypochlorite solution. Antibiotics were also prescribed. At a 2-year follow-up, probing depths were reduced to <4 mm, and there was radiographic bone fill. CONCLUSIONS: A minimally invasive flapless technique incorporating surgical curettage debridement of the inflamed soft tissue and chemical detoxification with antiseptics can be a viable alternative for the treatment of anterior implants with peri-implantitis, especially when the patient has a high smile line. Successful and effective debridement and disinfection of a previously contaminated implant surface can be achieved without reflecting a flap.

Randomized trial of a health IT tool to support between-visit-based laboratory monitoring for chronic disease medication prescriptions.

BACKGROUND: Lack of timely medication intensification and inadequate medication safety monitoring are two prevalent and potentially modifiable barriers to effective and safe chronic care. Innovative applications of health information technology tools may help support chronic disease management. OBJECTIVE: To examine the clinical impact of a novel health IT tool designed to facilitate between-visit ordering and tracking of future laboratory testing. DESIGN AND PARTICIPANTS: Clinical trial randomized at the provider level (n = 44 primary care physicians); patient-level outcomes among 3,655 primary care patients prescribed 5,454 oral medicines for hyperlipidemia, diabetes, and/or hypertension management over a 12-month period. MAIN MEASURES: Time from prescription to corresponding follow-up laboratory testing; proportion of follow-up time that patients achieved corresponding risk factor control (A1c, LDL); adverse event laboratory monitoring 4 weeks after medicine prescription. KEY RESULTS: Patients whose physicians were allocated to the intervention (n = 1,143) had earlier LDL laboratory assessment compared to similar patients (n = 703) of control physicians [adjusted hazard ratio (aHR): 1.15 (1.01-1.32), p = 0.04]. Among patients with elevated LDL (486 intervention, 324 control), there was decreased time to LDL goal in the intervention group [aHR 1.26 (0.99-1.62)]. However, overall there were no significant differences between study arms in time spent at LDL or HbA1c goal. Follow-up safety monitoring (e.g., creatinine, potassium, or transaminases) was relatively infrequent (ranging from 7 % to 29 % at 4 weeks) and not statistically different between arms. Intervention physicians indicated that lack of reimbursement for non-visit-based care was a barrier to use of the tool. CONCLUSIONS: A health IT tool to support between-visit laboratory monitoring improved the LDL testing interval but not LDL or HbA1c control, and it did not alter safety monitoring. Adoption of innovative tools to support physicians in non-visit-based chronic disease management may be limited by current visit-based financial and productivity incentives.

Were medicine quality and pharmaceutical management contributing factors in diminishing artemisinin efficacy in Guyana and Suriname?

BACKGROUND: Recent studies in Guyana and Suriname unveiled diminished efficacy of artemisinin derivatives based on day-3 parasitaemia. The migrant characteristics of the population at risk and the potential development of resistance pose a serious health threat in the region. Assessment of factors that may have contributed to this situation is warranted, and analysis of the data generated in those countries on quality and pharmaceutical managements of anti-malarials may contribute to a better understanding of this occurrence. METHODS: Data on malaria medicine quality and pharmaceutical management, generated in the context of the Amazon Malaria Initiative (AMI), was reviewed and discussed. RESULTS: Numerous substandard artemisinin-containing malaria medicines were identified in both countries, particularly in Guyana, where a larger number and variety of anti-malarials were sampled. Poor quality was more frequent in the private and informal sector than in the public sector, posing a greater threat to the populations at risk, which are mostly located in hard to reach areas with scarce public facilities. Stock-outs identified in the public sector in Guyana could enhance the need to access those alternative sectors, exacerbating the risk of utilizing poor quality medicines. The availability of monotherapies and other non-recommended therapies for Plasmodium falciparum malaria, could also have contributed to the diminished efficacy. The type of quality deficiencies identified -reduced content of active pharmaceutical ingredient (API) and/or poor dissolution- and the irrational use of non-recommended treatments could result in non-sustained or lower levels of API in blood, favouring survival of more resistant mutants by exposing parasites to sub-lethal doses of the active ingredient. CONCLUSIONS: The quality of malaria medicines and the availability and use of non-recommended treatments could have played a role in the diminished efficacy of artemisinin derivatives described in Guyana and Suriname. However, also other factors need to be considered and a more comprehensive and extensive assessment on quality and pharmaceutical management is necessary to establish a tighter cause-effect correlation. Nevertheless, relevant authorities in these and neighbouring countries should take into consideration the reviewed data to properly address the problem when implementing corrective actions.

Engineering youth service system infrastructure: Hawaii's continued efforts at large-scale implementation through knowledge management strategies.

Hawaii's Child and Adolescent Mental Health Division provides a unique illustration of a youth public mental health system with a long and successful history of large-scale quality improvement initiatives. Many advances are linked to flexibly organizing and applying knowledge gained from the scientific literature and move beyond installing a limited number of brand-named treatment approaches that might be directly relevant only to a small handful of system youth. This article takes a knowledge-to-action perspective and outlines five knowledge management strategies currently under way in Hawaii. Each strategy represents one component of a larger coordinated effort at engineering a service system focused on delivering both brand-named treatment approaches and complimentary strategies informed by the evidence base. The five knowledge management examples are (a) a set of modular-based professional training activities for currently practicing therapists, (b) an outreach initiative for supporting youth evidence-based practices training at Hawaii's mental health-related professional programs, (c) an effort to increase consumer knowledge of and demand for youth evidence-based practices, (d) a practice and progress agency performance feedback system, and (e) a sampling of system-level research studies focused on understanding treatment as usual. We end by outlining a small set of lessons learned and a longer term vision for embedding these efforts into the system's infrastructure.

Developing a systematic evaluation approach for training programs within a train-the-trainer model for youth cognitive behavior therapy.

The purpose of this small pilot study was three-fold: (a) to begin development of a coding scheme for supervisor and therapist skill acquisition, (b) to preliminarily investigate a pilot train-the-trainer paradigm for skill development, and (c) to evaluate self-reported versus observed indicators of skill mastery in that pilot program. Participants included four supervisor-therapist dyads (N = 8) working with public mental health sector youth. Master trainers taught cognitive-behavioral therapy techniques to supervisors, who in turn trained therapists on these techniques. Supervisor and therapist skill acquisition and supervisor use of teaching strategies were repeatedly assessed through coding of scripted role-plays with a multiple-baseline across participants and behaviors design. The coding system, the Practice Element Train the Trainer - Supervisor/Therapist Versions of the Therapy Process Observational Coding System for Child Psychotherapy, was developed and evaluated though the course of the investigation. The coding scheme demonstrated excellent reliability (ICCs [1,2] = 0.81-0.91) across 168 video recordings. As calculated through within-subject effect sizes, supervisor and therapist participants, respectively, evidenced skill improvements related to teaching and performing therapy techniques. Self-reported indicators of skill mastery were inflated in comparison to observed skill mastery. Findings lend initial support for further developing an evaluative approach for a train-the-trainer effort focused on disseminating evidence-based practices.

Otolaryngology clinic of North America: evidence-based practice: management of hoarseness/dysphonia.

This article reviews the evidence for the evaluation and management for patients with dysphonia. The evidence behind laryngoscopy, laryngostroboscopy, laryngeal imaging, laryngeal electromyography, and disease-specific questionnaires are reviewed. The evidence for management of some of the common conditions leading to dysphonia is also reviewed. This article reviews the evidence for voice therapy for various voice pathologies; medical management of dysphonia, including antibiotics, steroids, and antireflux therapy; and surgical management of glottic insufficiency and some benign laryngeal masses.

Rapid assessment of the performance of malaria control strategies implemented by countries in the Amazon subregion using adequacy criteria: case study.

BACKGROUND: The objective of this study was to implement a rapid assessment of the performance of four malaria control strategies (indoor spraying, insecticide-treated bed nets, timely diagnosis, and artemisinin-based combination therapy) using adequacy criteria. The assessment was carried out in five countries of the Amazon subregion (Bolivia, Colombia, Ecuador, Guyana, and Peru). METHODS: A list of criteria in three areas was created for each of the four strategies: preliminary research that supports the design and adaptation of the control strategies, coverage of the control strategies and quality of the implementation of the strategies. The criteria were selected by the research team and based on the technical guidelines established by the World Health Organization. Each criterion included in the four lists was graded relative to whether evidence exists that the criterion is satisfied (value 1), not satisfied (value 0) or partially satisfied (value 0.5). The values obtained were added and reported according to a scale of three implementation categories: adequate, intermediate and deficient. RESULTS: Implementation of residual indoor spraying and timely diagnosis was adequate in one country and intermediate or deficient in the rest. Insecticide-treated bed nets ranged between deficient and intermediate in all the countries, while implementation of artemisinin-based combination therapy (ACT) was adequate in three countries and intermediate in the other two countries evaluated. CONCLUSIONS: Although ACT is the strategy with the better implementation in all countries, major gaps exist in implementation of the other three malaria control strategies in terms of technical criteria, coverage and quality desired. The countries must implement action plans to close the gaps in the various criteria and thereby improve the performance of the interventions. The assessment tools developed, based on adequacy criteria, are considered useful for a rapid assessment by malaria control authorities in the different countries.

Mejora en el diagnóstico y tratamiento oportuno de malaria con el uso de pruebas rápidas por promotores de salud en la Amazonía Peruana / Improvements in timely malaria diagnosis and appropriate therapy with the use of rapid tests by health promoters in Peruvian Amazon jungle

Objetivos. Comparar la oportunidad en el diagnóstico y tratamiento apropiado de la malaria antes y después de la incorporación del uso de pruebas rápidas por promotores de salud en comunidades periféricas de Iquitos. Material y métodos. Estudio longitudinal con evaluación pre y postintervención. En ambas evaluaciones se recolectó un número mínimo de 200 pacientes febriles (casos sospechosos de malaria) que habían sido atendidos por el promotor en las seis semanas previas, datos relacionados a la oportunidad en el diagnóstico y tratamiento, y los diagnósticos confirmatorios por gota gruesa. Resultados. Con la intervención hubo una disminución significativadel tiempo transcurrido entre el inicio de síntomas y el inicio del tratamiento de 110 horas (4,6 días) a 46,3 horas (1,9 días) (p menor que0,001). Dicha variación fue debida mayormente a la reducción del tiempo transcurrido desde la consulta al promotor hasta la obtención del diagnóstico del paciente, de 69 horas (2,9 días) a sólo 20 minutos (p menor que 0,001). Además, hubo un incremento significativo de la proporción de pacientes con malaria que recibieron tratamiento antimalárico oportuno de 15,5 a 54,9 por ciento (p menor que 0,001), la proporción de pacientes con malaria que recibieron tratamiento apropiado a la especie del parásito de 26,7 por ciento a 83,5 por ciento (p menor que 0,001) y la proporción de pacientes conmalaria falciparum que recibieron tratamiento apropiado de 5,3 a 73,1 por ciento (p mneor que 0,001). Conclusiones. A través de la incorporación del uso de pruebas rápidas por promotores de salud en las comunidades seleccionadas, se ha mejorado la oportunidad en el diagnóstico y tratamiento apropiado de la malaria.

Objectives. To compare the achievement of a timely diagnosis and appropriate therapy for malaria before and after the incorporation of rapid tests for diagnosing this disease used by health promoters in peripheral communities in Iquitos. Material and methods. Alongitudinal study with pre- and post- intervention assessments was performed. Two hundred febrile patients (suspected malaria cases) seen by health promoters during the last 6 weeks were selected, and data related to a timely malaria diagnosis and therapy, as well as confirmatory diagnoses using thick smears was collected. Results. There was a significant decrease in the time elapsed from symptom onset to therapy initiation with the intervention, from 110 hours (4.6 days) to 46,3 hours (1.9 days) (p minor that 0.001). This variation was mainly due to a reduction of the time since the patient was first seen by a health promoter until the time when a diagnosis was achieved, from 69 hours (2.9 days) to only 20 minutes (p minor that 0.001). There was also a significant increase in the frequency of malaria patients who received timely antimalarial therapy, from 1,5 per cent to 54,9 per cent (p minor that0.001); the proportion of malaria patients receiving appropriate therapy according to the parasite species increased from 26.7 per cent to 83.5 per cent (p minor that 0.001), and the proportion of P. falciparum malaria patients who received appropriate therapy rose from 5.3 per cent to 73.1 per cent (p minor that 0.001). Conclusions. Now it is possible to achieve a timely diagnosis and appropriate therapy formalaria with the use of rapid tests by health promoters in these selected communities.

Fusogenic vesicular stomatitis virus for the treatment of head and neck squamous carcinomas.

OBJECTIVES: This study investigates the efficacy of recombinant fusogenic VSV [rVSV-NDV/F(L289A) or rVSV-F] in the treatment of head and neck squamous cell carcinoma (HNSCC). STUDY DESIGN AND SETTING: The in vitro replication and cytotoxicity of rVSV-F were studied in two human SCC cell lines, in one murine SCC cell line, and in human keratinocytes. The effects on tumor size and animal survival were investigated following in vivo rVSV-F treatment of floor-of-mouth tumor model C3H/HeJ mice. RESULTS: Recombinant VSV-F preferentially induced rapid syncytia formation, and replicated in (P < 0.04) and killed (P < 1 x 10(-13)) all three SCC lines tested. The virus had no observable effect on human keratinocytes. Tumor size was smaller (P < 0.03) and overall survival was better (P < 0.001) for treated animals than for control animals. CONCLUSION/SIGNIFICANCE: Recombinant VSV-F confers a modest survival benefit for HNSCC in this orthotopic murine model. This oncolytic virus holds promise as a novel cancer treatment for recurrent HNSCC.

Prediction in annotation based guideline encoding.

The encoding of clinical practice guidelines into machine operable representations poses numerous challenges and will require considerable human intervention for the foreseeable future. To assist and potentially speed up this process, we have developed an incremental approach to guideline encoding which begins with the annotation of the original guideline text using markup techniques. A modular and flexible sequence of subtasks results in increasingly inter-operable representations while maintaining the connections to all prior source representations and supporting knowledge. To reduce the encoding bottleneck we also employ a number of machine-assisted learning and prediction techniques within a knowledge-based software environment. Promising results with a straightforward incremental learning algorithm illustrate the feasibility of such an approach.

Improving pulmonary artery catheter waveform interpretation.

The pulmonary artery catheter (PAC) guides diagnosis and treatment in the intensive care unit (ICU), but studies have shown that physicians and nurses collectively have inadequate skill in interpreting PAC waveforms. We have developed a Web-based application that provides physicians and nurses with rapid access to relevant PAC-related content for use in patient care situations in real time. The application begins with a visual index that assists in the recognition of both normal and abnormal waveforms and provides waveform-specific links to concise advice on making accurate pressure measurements, troubleshooting system problems, and avoiding complications of catheter use. Evaluation of the application's efficacy will consist of a before-and-after trial to determine whether the application improves test performance in the areas of waveform recognition, accuracy of measurement, and appropriateness of action. We have completed the pre-intervention testing of nurses in the medical intensive care unit and found performance ranging from a mean of 68% for those with less than two years of experience to a mean of 76% for those with more than 6 years of experience.

Fiebre amarilla en el Perú / Yellow fever in Peru

La fiebre amarilla en el Per

Seroepidemiología de hepatitis B en cuatro comunidades de la selva central del Perú / Seroepidemiology for hepatitis B in four communities in the peruvian central jungle

Se investigó la prevalencia de infección con el virus de la hepatitis B en personas sanas de 4 localidades de la Selva Central del Perú. Mediante la prueba de ELISA, se determinó la presencia en suero de Antígeno de superficie de hepatitis B (HBsAg), de Anticuerpos contra HBsAg (anti-HBs), y de anticuerpos contra el antígeno de Hepatitis Delta (anti-HD). Se encontró prevalencias de 6,8 a 53 para el caso de anti-HBs y de 1,2 a 4,4 en el caso de HBsAg. Se identificó factores de riesgo probables en cada población, pero no hubo uno que fuera común a las cuatro. El contacto cercano con eprsonas infectadas pareció tener un rol importante, mientras no se encontró evidencia de que la transmisión parenteral fuera importante

Programa de entrenamiento para administradores de salud (PEAS) / Training program fror health administrators (PHA)

El objetivo central del programa fue mejorar la capacidad de gestión de los profesionales a cargo de la administración de servicios del Ministerio de SAlud, fundamentalmente a nivel local, proporcionándoles capacitación en administración y epidemiología