A qualitative study evaluating causality attribution for serious adverse events during early phase oncology clinical trials.

PubMed

Mukherjee, Som D; Coombes, Megan E; Levine, Mitch; Cosby, Jarold; Kowaleski, Brenda; Arnold, Andrew

2011-10-01

In early phase oncology trials, novel targeted therapies are increasingly being tested in combination with traditional agents creating greater potential for enhanced and new toxicities. When a patient experiences a serious adverse event (SAE), investigators must determine whether the event is attributable to the investigational drug or not. This study seeks to understand the clinical reasoning, tools used and challenges faced by the researchers who assign causality to SAE's. Thirty-two semi-structured interviews were conducted with medical oncologists and trial coordinators at six Canadian academic cancer centres. Interviews were recorded and transcribed verbatim. Individual interview content analysis was followed by thematic analysis across the interview set. Our study found that causality assessment tends to be a rather complex process, often without complete clinical and investigational data at hand. Researchers described using a common processing strategy whereby they gather pertinent information, eliminate alternative explanations, and consider whether or not the study drug resulted in the SAE. Many of the interviewed participants voiced concern that causality assessments are often conducted quickly and tend to be highly subjective. Many participants were unable to identify any useful tools to help in assigning causality and welcomed more objectivity in the overall process. Attributing causality to SAE's is a complex process. Clinical trial researchers apply a logical system of reasoning, but feel that the current method of assigning causality could be improved. Based on these findings, future research involving the development of a new causality assessment tool specifically for use in early phase oncology clinical trials may be useful.

2015 Guidance on cancer immunotherapy development in early-phase clinical studies.

PubMed

2015-12-01

The development of cancer immunotherapies is progressing rapidly with a variety of technological approaches. They consist of "cancer vaccines", which are based on the idea of vaccination, "effector cell therapy", classified as passive immunotherapy, and "inhibition of immunosuppression", which intends to break immunological tolerance to autoantigens or immunosuppressive environments characterizing antitumor immune responses. Recent reports showing clinical evidence of efficacy of immune checkpoint inhibitors and adoptive immunotherapies with tumor-infiltrating lymphocytes and tumor-specific receptor gene-modified T cells indicate the beginning of a new era for cancer immunotherapy. This guidance summarizes ideas that will be helpful to those who plan to develop cancer immunotherapy. The aims of this guidance are to discuss and offer important points in early phase clinical studies of innovative cancer immunotherapy, with future progress in this field, and to contribute to the effective development of cancer immunotherapy aligned with the scope of regulatory science. This guidance covers cancer vaccines, effector cell therapy, and inhibition of immunosuppression, including immune checkpoint inhibitors. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Clinical symptoms predict concurrent social and global functioning in an early psychosis sample.

PubMed

Cacciotti-Saija, Cristina; Langdon, Robyn; Ward, Philip B; Hickie, Ian B; Guastella, Adam J

2018-04-01

Although well established in chronic schizophrenia, the key determinants of functioning remain unknown during the early phase of a psychotic disorder. The aim of this study was to comprehensively examine the social cognitive, basic neurocognitive and clinical predictors of concurrent social functioning and global functioning in an early psychosis sample. This study examined the relationship between social cognition, basic neurocognition and clinical symptoms with concurrent functioning in 51 early psychosis individuals. Assessments included a range of self-report, observational and clinician-rated measures of cognitive, symptom severity and functioning domains. Results revealed a significant association between self-reported social function and lower levels of both social interaction anxiety and negative psychotic symptoms. A significant association was also observed between lower levels of negative psychotic symptoms and observed social functioning. Lastly, results demonstrated a significant association between reduced negative psychotic symptoms and clinician-rated global functioning. Clinical domains such as negative symptoms and social interaction anxiety significantly contribute to an optimal model predicting outcome during the early phase of a psychotic disorder. These clinical features may also provide useful markers of an individual's capacity for social participation. Clinical implications include the need for early targeted intervention to address social anxiety and negative psychotic symptoms to facilitate optimum patient outcome. © 2015 Wiley Publishing Asia Pty Ltd.

Challenges and perspective of drug repurposing strategies in early phase clinical trials.

PubMed

Kato, Shumei; Moulder, Stacy L; Ueno, Naoto T; Wheler, Jennifer J; Meric-Bernstam, Funda; Kurzrock, Razelle; Janku, Filip

2015-01-01

Despite significant investments in the development of new agents only 5% of cancer drugs entering Phase I clinical trials are ultimately approved for routine clinical cancer care. Drug repurposing strategies using novel combinations of previously tested anticancer agents could reduce the cost and improve treatment outcomes. At MD Anderson Cancer Center, early phase clinical trials with drug repurposing strategies demonstrated promising outcomes in patients with both rare and common treatment refractory advanced cancers. Despite clinical efficacy advancing drug repurposing strategies in the clinical trial trajectory beyond early phase studies has been challenging mainly due to lack of funding and interest from the pharmaceutical industry. In this review, we delineate our experience and challenges with drug repurposing strategies.

Nursing students' early exposure to clinical practice: an innovation in curriculum development.

PubMed

Hoyles, A; Pollard, C; Lees, S; Glossop, D

2000-08-01

This paper describes a pilot study addressing issues surrounding the balance and status given to both theory and practice in the foundation part of a pre-registration programme. Contemporary thinking seems to suggest that there is a need to reverse recent trends which have placed an emphasis on theory. To facilitate this a framework for clinical learning was adapted to guide students' early exposure to clinical practice. The focus was to develop the students' observational and reflective skills whilst also providing the students with a frame of reference within which they could explore their theoretical studies. The information and experiences gained as a result of this study have led to the integration of an Orientation Framework to support students' early clinical experiences in a pre-registration programme.

The Nun study: clinically silent AD, neuronal hypertrophy, and linguistic skills in early life.

PubMed

Iacono, D; Markesbery, W R; Gross, M; Pletnikova, O; Rudow, G; Zandi, P; Troncoso, J C

2009-09-01

It is common to find substantial Alzheimer disease (AD) lesions, i.e., neuritic beta-amyloid plaques and neurofibrillary tangles, in the autopsied brains of elderly subjects with normal cognition assessed shortly before death. We have termed this status asymptomatic AD (ASYMAD). We assessed the morphologic substrate of ASYMAD compared to mild cognitive impairment (MCI) in subjects from the Nun Study. In addition, possible correlations between linguistic abilities in early life and the presence of AD pathology with and without clinical manifestations in late life were considered. Design-based stereology was used to measure the volumes of neuronal cell bodies, nuclei, and nucleoli in the CA1 region of hippocampus (CA1). Four groups of subjects were compared: ASYMAD (n = 10), MCI (n = 5), AD (n = 10), and age-matched controls (n = 13). Linguistic ability assessed in early life was compared among all groups. A significant hypertrophy of the cell bodies (+44.9%), nuclei (+59.7%), and nucleoli (+80.2%) in the CA1 neurons was found in ASYMAD compared with MCI. Similar differences were observed with controls. Furthermore, significant higher idea density scores in early life were observed in controls and ASYMAD group compared to MCI and AD groups. 1) Neuronal hypertrophy may constitute an early cellular response to Alzheimer disease (AD) pathology or reflect compensatory mechanisms that prevent cognitive impairment despite substantial AD lesions; 2) higher idea density scores in early life are associated with intact cognition in late life despite the presence of AD lesions.

Professional behaviors, sense of belonging, and professional socialization of early career clinical laboratory scientists

NASA Astrophysics Data System (ADS)

Schill, Janna Marie

Professional socialization is a process that individuals experience as members of a profession and consists of the knowledge, attitudes, and experiences that influence and shape their professional identity. The process of professional socialization has not been studied in the clinical laboratory science profession. Clinical laboratory science is an allied health profession that is faced by a workforce shortage that has been caused by a decrease in new graduates, decreased retention of qualified professionals, and increased retirements. Other allied health professions such as nursing, athletic training, and pharmacy have studied professional socialization as a way to identify factors that may influence the retention of early career professionals. This mixed method study, which quantitatively used Hall's Professionalism Scale (1968) in addition to qualitative focus group interviews, sought to identify the professional attitudes and behaviors, sense of belonging, and professional socialization of early career clinical laboratory scientists. Early career clinical laboratory scientists were divided into two groups based upon the amount of work experience they had; new clinical laboratory science graduates have had less than one year of work experience and novice clinical laboratory scientists had between one and three years of work experience. This study found that early career clinical laboratory scientists have established professional identities and view themselves as members of the clinical laboratory science field within four proposed stages of professional socialization consisting of pre-arrival, encounter, adaptation, and commitment. New CLS graduates and novice clinical laboratory scientists were found to be at different stages of the professional stage process. New CLS graduates, who had less than one year of work experience, were found to be in the encounter stage. Novice clinical laboratory scientists, with one to three years of work experience, were found to

Clinical significance of early smoking withdrawal effects and their relationships with nicotine metabolism: preliminary results from a pilot study.

PubMed

Hendricks, Peter S; Delucchi, Kevin L; Benowitz, Neal L; Hall, Sharon M

2014-05-01

Although the early time course of smoking withdrawal effects has been characterized, the clinical significance of early withdrawal symptoms and their predictors are unknown. This study evaluated the relationships of early smoking withdrawal effects with quit attempt outcomes and the rate of nicotine metabolism. Eleven treatment-seeking smokers abstained from smoking for 4 hr in the laboratory before a quit attempt. Withdrawal measures included heart rate, sustained attention, and self-report. Following baseline assessment, withdrawal measures were administered every 30 min. At the conclusion of the 4-hr early withdrawal session, participants received a brief smoking cessation intervention and then returned 1 week and 12 weeks later for outcome assessments that included biochemically confirmed smoking abstinence, cigarettes smoked in the past 24hr, and self-reported withdrawal symptoms. The rate of nicotine metabolism was estimated at intake with the nicotine metabolite ratio (trans-3'-hydroxycotinine/cotinine) measured in saliva. Greater self-reported negative affect and concentration difficulty during early withdrawal, most notably anxiety, were related with poorer quit attempt outcomes. There was some indication that although a faster increase in craving and greater hunger during early withdrawal were associated with more favorable outcomes, a greater decrease in heart rate during this time was associated with poorer outcomes. Faster nicotine metabolism was related to a faster increase in anxiety but a slower increase in craving during early withdrawal. These findings lend support to the clinical significance of early smoking withdrawal effects. The rate of nicotine metabolism may be a useful predictor of early withdrawal symptoms.

Early-Onset Bipolar Disorder: Characteristics and Outcomes in the Clinic.

PubMed

Connor, Daniel F; Ford, Julian D; Pearson, Geraldine S; Scranton, Victoria L; Dusad, Asha

2017-12-01

To assess patient characteristics and clinician-rated outcomes for children diagnosed with early-onset bipolar disorder in comparison to a depressive disorders cohort from a single clinic site. To assess predictors of bipolar treatment response. Medical records from 714 consecutive pediatric patients evaluated and treated at an academic tertiary child and adolescent psychiatry clinic between 2006 and 2012 were reviewed. Charts of bipolar children (n = 49) and children with depressive disorders (n = 58) meeting study inclusion/exclusion criteria were compared on variables assessing clinical characteristics, treatments, and outcomes. Outcomes were assessed by using pre- and post-Clinical Global Impressions (CGI)-Severity and Children's Global Assessment Scale (CGAS) scores, and a CGI-Improvement score ≤2 at final visit determined responder status. Bipolar outcome predictors were assessed by using multiple linear regression. Clinic prevalence rates were 6.9% for early-onset bipolar disorder and 1.5% for very early-onset bipolar disorder. High rates of comorbid diagnoses, symptom severity, parental stress, and child high-risk behaviors were found in both groups. The bipolar cohort had higher rates of aggression and higher lifetime systems of care utilization. The final CGI and CGAS outcomes for unipolar depression patients differed statistically significantly from those for the bipolar cohort, reflecting better clinical status and more improvement at outcome for the depression patients. Both parent-reported Child Behavior Checklist total T-score at clinic admission and the number of lifetime systems-of-care for the child were significantly and inversely associated with improvement for the bipolar cohort. Early-onset bipolar disorder is a complex and heterogeneous psychiatric disorder. Evidence-based treatment should emphasize psychopharmacology with adjunctive family and individual psychotherapy. Strategies to improve engagement in treatment may be especially

Evaluating cardiac risk: exposure response analysis in early clinical drug development.

PubMed

Grenier, Julie; Paglialunga, Sabina; Morimoto, Bruce H; Lester, Robert M

2018-01-01

The assessment of a drug's cardiac liability has undergone considerable metamorphosis by regulators since International Council for Harmonization of Technical Requirement for Pharmaceuticals for Human Use E14 guideline was introduced in 2005. Drug developers now have a choice in how proarrhythmia risk can be evaluated; the options include a dedicated thorough QT (TQT) study or exposure response (ER) modeling of intensive electrocardiogram (ECG) captured in early clinical development. The alternative approach of ER modeling was incorporated into a guidance document in 2015 as a primary analysis tool which could be utilized in early phase dose escalation studies as an option to perform a dedicated TQT trial. This review will describe the current state of ER modeling of intensive ECG data collected during early clinical drug development; the requirements with regard to the use of a positive control; and address the challenges and opportunities of this alternative approach to assessing QT liability.

brief report: Burnout Among Early Career Clinical Investigators

PubMed Central

Primack, Brian A.; Dilmore, Terri C.; Switzer, Galen E.; Bryce, Cindy L.; Seltzer, Deborah L.; Li, Jie; Landsittel, Douglas P.; Kapoor, Wishwa N.; Rubio, Doris M.

2010-01-01

Abstract Burnout is a pervasive problem among clinicians. However, little is known about burnout among early career clinical investigators, who must balance clinical responsibilities with challenges related to research. We aimed to determine the prevalence of and demographic associations with burnout in a cohort of early career clinical investigators. A cross‐sectional questionnaire was administered to 179 trainees at the University of Pittsburgh Institute for Clinical Research Education in 2007–2008. We used chi‐square analyses and Fisher’s exact test to determine whether associations between demographic characteristics and burnout were significant. Of the participants, 29 (16%) reported feeling burned out. Burnout was more prevalent among those over 35 years of age relative to their younger counterparts (29% vs. 13%, p= 0.01) and among females relative to males (22% vs. 10%, p= 0.03). With regard to race and ethnicity, burnout was most common among underrepresented minorities (30%) followed by Caucasians (18%) and Asians (3%); these differences were significant (p= 0.02). Considering the early career status of these research trainees, rates of burnout were concerning. Certain demographic subgroups—including older trainees, females, and underrepresented minorities—had particularly high rates of burnout and may benefit from interventions that provide them with skills needed to sustain successful clinical research careers. Clin Trans Sci 2010; Volume 3: 186–188 PMID:20718821

The Importance of Early Experiences: Clinical, Research, and Policy Perspectives

ERIC Educational Resources Information Center

Zeanah, Charles H.

2009-01-01

The degree to which early adverse experiences exert long term effects on development and how much early adversity may be overcome through subsequent experiences are important mental health questions. The clinical, research and policy perspectives on these questions lead to different answers. From a clinical perspective, change is always possible,…

Predicting Readmission at Early Hospitalization Using Electronic Clinical Data: An Early Readmission Risk Score.

PubMed

Tabak, Ying P; Sun, Xiaowu; Nunez, Carlos M; Gupta, Vikas; Johannes, Richard S

2017-03-01

Identifying patients at high risk for readmission early during hospitalization may aid efforts in reducing readmissions. We sought to develop an early readmission risk predictive model using automated clinical data available at hospital admission. We developed an early readmission risk model using a derivation cohort and validated the model with a validation cohort. We used a published Acute Laboratory Risk of Mortality Score as an aggregated measure of clinical severity at admission and the number of hospital discharges in the previous 90 days as a measure of disease progression. We then evaluated the administrative data-enhanced model by adding principal and secondary diagnoses and other variables. We examined the c-statistic change when additional variables were added to the model. There were 1,195,640 adult discharges from 70 hospitals with 39.8% male and the median age of 63 years (first and third quartile: 43, 78). The 30-day readmission rate was 11.9% (n=142,211). The early readmission model yielded a graded relationship of readmission and the Acute Laboratory Risk of Mortality Score and the number of previous discharges within 90 days. The model c-statistic was 0.697 with good calibration. When administrative variables were added to the model, the c-statistic increased to 0.722. Automated clinical data can generate a readmission risk score early at hospitalization with fair discrimination. It may have applied value to aid early care transition. Adding administrative data increases predictive accuracy. The administrative data-enhanced model may be used for hospital comparison and outcome research.

Role of interleukin-6 as an early marker of fat embolism syndrome: a clinical study.

PubMed

Prakash, Shiva; Sen, Ramesh Kumar; Tripathy, Sujit Kumar; Sen, Indu Mohini; Sharma, R R; Sharma, Sadhna

2013-07-01

A few animal studies have shown that IL-6 can serve as an early marker of fat embolism syndrome. The degree to which this is true in human trauma victims is unknown. In this clinical study, we sought to determine (1) whether elevated serum IL-6 levels at 6, 12, and 24 hours in patients with skeletal trauma were associated with the development of fat embolism syndrome (FES) within 72 hours after injury, and (2) at what time after trauma peak IL-6 levels are observed. Forty-eight patients between 16 and 40 years old who presented to our tertiary trauma center within 6 hours of injury with long bone and/or pelvic fractures were included in this study. Serum IL-6 levels were measured at 6, 12, and 24 hours after injury. The patients were observed clinically and monitored for 72 hours for development of FES symptoms. Gurd's criteria were used to diagnose FES. Elevated serum IL-6 levels 12 hours after trauma correlated with an increased likelihood of having FES develop; no significant relationship was observed between IL-6 levels at 6 or 24 hours and the development of FES. Patients with FES had a mean IL-6 level of 131 pg/mL, whereas those without FES had a mean IL-6 level of 72 pg/mL. Peak IL-6 levels were observed at 12 hours. An elevated serum IL-6 level may be useful as an early marker of FES in patients with isolated skeletal trauma. Level II, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence.

Clinical Placement Before or After Simulated Learning Environments?: A Naturalistic Study of Clinical Skills Acquisition Among Early-Stage Paramedicine Students.

PubMed

Mills, Brennen W; Carter, Owen B J; Rudd, Cobie J; Ross, Nathan P; Claxton, Louise A

2015-10-01

There is conflicting evidence surrounding the merit of clinical placements (CPs) for early-stage health-profession students. Some contend that early-stage CPs facilitate contextualization of a subsequently learned theory. Others argue that training in simulated-learning experiences (SLEs) should occur before CP to ensure that students possess at least basic competency. We sought to investigate both claims. First-year paramedicine students (n = 85) undertook 3 days of CP and SLEs as part of course requirements. Students undertook CP either before or after participation in SLEs creating 2 groups (Clin → Sim/Sim → Clin). Clinical skills acquisition was measured via direct scenario-based clinical assessments with expert observers conducted at 4 intervals during the semester. Perceptions of difficulty of CP and SLE were measured via the National Aeronautics and Space Administration Task Load Index. Students' clinical assessment scores in both groups improved significantly from beginning to end of semester (P < 0.001). However, at semester's end, clinical assessment scores for the Sim → Clin group were statistically significantly greater than those of the Clin → Sim group (P = 0.021). Both groups found SLEs more demanding than CP (P < 0.001). However, compared with the Sim → Clin group, the Clin → Sim group rated SLE as substantially more time-demanding than CP (P = 0.003). Differences in temporal demand suggest that the Clin → Sim students had fewer opportunities to practice clinical skills during CP than the Sim → Clin students due to a more limited scope of practice. The Sim → Clin students contextualized SLE within subsequent CP resulting in greater improvement in clinical competency by semester's end in comparison with the Clin → Sim students who were forced to contextualize skills retrospectively.

Determination of minimal clinically important change in early and advanced Parkinson's disease.

PubMed

Hauser, Robert A; Auinger, Peggy

2011-04-01

Two common primary efficacy outcome measures in Parkinson's disease (PD) are change in Unified Parkinson's Disease Rating Scale (UPDRS) scores in early PD and change in "off" time in patients with motor fluctuations. Defining the minimal clinically important change (MCIC) in these outcome measures is important to interpret the clinical relevance of changes observed in clinical trials and other situations. We analyzed data from 2 multicenter, placebo-controlled, randomized clinical trials of rasagiline; TEMPO studied 404 early PD subjects, and PRESTO studied 472 levodopa-treated subjects with motor fluctuations. An anchor-based approach using clinical global impression of improvement (CGI-I) was used to determine MCIC for UPDRS scores and daily "off" time. MCIC was defined as mean change in actively treated subjects rated minimally improved on CGI-I. Receiver operating characteristic (ROC) curves defined optimal cutoffs discriminating between changed and unchanged subjects. MCIC for improvement in total UPDRS score (parts I-III) in early PD was determined to be -3.5 points based on mean scores and -3.0 points based on ROC curves. In addition, we found an MCIC for reduction in "off" time of 1.0 hours as defined by mean reduction in "off" time in active treated subjects self-rated as minimally improved on CGI-I minus mean reduction in "off" time in placebo-treated subjects self-rated as unchanged (1.9-0.9 hours). We hypothesize that many methodological factors can influence determination of the MCIC, and a range of values is likely to emerge from multiple studies. Copyright © 2011 Movement Disorder Society.

An early oral health care program starting during pregnancy: results of a prospective clinical long-term study.

PubMed

Meyer, Karen; Geurtsen, Werner; Günay, Hüsamettin

2010-06-01

This study covers phase IV of a prospective clinical long-term study. Objective of this clinical investigation was to analyze the effects of a long-term prevention program on dental and oral health of teenagers at the age of 13 to 14 years. The entire study was subdivided into four phases. Phase I comprised an individual preventive care during pregnancy ("primary-primary prevention"); phase II assessed mothers and their young children until the age of 3 years ("primary prevention"); and in phase III, mothers and children at the age of 6 years were investigated. In phase IV of the study, the oral health of 13- to 14-year-old teenagers was examined (13.4 +/- 0.5 years; n = 29). All phases consisted of an examination, education about oral health care, and treatment based on the concept of an early oral health care promotion. The control group consisted of randomly selected adolescents at the same age (n = 30). The following clinical parameters were assessed: decayed/missing/filled teeth (DMF-T)/decayed, missing, and filled surface teeth index, hygiene index, papilla bleeding index, Periodontal Screening Index, and Streptococcus mutans/Lactobacillus concentration in saliva. The teenagers of the "prevention" group of phase IV of our prospective study revealed a share of 89.7% caries-free dentitions (65.5% sound; 24.2% caries-free with fillings). Mean DMF-T was 0.55 +/- 1.0. The control group showed a significantly higher mean DMF-T of 1.5 +/- 1.5 (p < 0.05) and revealed 56.7% of caries-free dentitions (30% sound, 26.7% caries-free with restorations). Our data clearly document that an early oral health care promotion starting during pregnancy may cause a sustained and long-term improvement of the oral health of children.

77 FR 9947 - Guidance for Industry: Early Clinical Trials With Live Biotherapeutic Products: Chemistry...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-21

...] Guidance for Industry: Early Clinical Trials With Live Biotherapeutic Products: Chemistry, Manufacturing... ``Guidance for Industry: Early Clinical Trials With Live Biotherapeutic Products: Chemistry, Manufacturing... for Industry: Early Clinical Trials With Live Biotherapeutic Products: Chemistry, Manufacturing, and...

Clinical outcome of critically ill patients with thrombocytopenia and hypophosphatemia in the early stage of sepsis.

PubMed

Brotfain, Evgeni; Schwartz, Andrei; Boniel, Avi; Koyfman, Leonid; Boyko, Matthew; Kutz, Ruslan; Klein, Moti

2016-01-01

Hypophosphatemia and thrombocytopenia may both be independent risk factors for the development of multiple organ failure and correlate well with the severity of sepsis. In the present study we wanted to analyze the potential clinical role and prognostic significance of both early hypophosphatemia and thrombocytopenia on clinical outcomes of critically ill ICU patients with severe sepsis. We analyzed the clinical data, including the outcome of critically ill ICU patients with severe sepsis who presented during a 5 year period with early hypophosphatemia and thrombocytopenia.This study was retrospective and single centre. All clinical and laboratory data was collected from the patients' ICU and hospital electronic records. All laboratory measurements were done on admission and during the ICU stay. The included patients were distributed into one of three study groups based on the presence of hypophosphatemia and/or thrombocytopenia during the first 24 hours of admission to the ICU: group 1 - early hypophosphatemia; group 2 - early hypophosphatemia and thrombocytopenia and group 3 - early thrombocytopenia. The ICU mortality rate was significantly higher in groups 2 and 3 (25.9% and 22% vs. 9.3%, respectively, P = 0.034). An APACHE II > 27, a TISS > 25 following the first 24 hours of ICU stay , an age higher than 70, male gender and total parenteral nutrition were independent predictors of ICU and hospital mortality in this study population. It may be considered that hypophosphatemia and thrombocytopenia in the early stage of sepsis, even when severe and coexisting, reflect the degree of initial illness severity of sepsis. However, further investigations need to be done for a better understanding of the potential clinical role of these features in the septic critically ill population.

78 FR 39736 - Draft Guidance for Industry: Considerations for the Design of Early-Phase Clinical Trials of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-02

..., choosing a study population, using a control group and blinding, dose selection, treatment plans...] Draft Guidance for Industry: Considerations for the Design of Early-Phase Clinical Trials of Cellular... document entitled ``Guidance for Industry: Considerations for the Design of Early-Phase Clinical Trials of...

Migration characteristics and early clinical results of the NANOS® short-stem hip arthroplasty.

PubMed

Kaipel, Martin; Grabowiecki, Phillip; Sinz, Katrina; Farr, Sebastian; Sinz, Günter

2015-05-01

Femoral short stems promise essential advantages in total hip arthroplasty. Up to now, only short- and midterm clinical studies exist. Data on early stem migration that could predict later aseptic loosening at an early stage are rare. The purpose of this study was to assess migration patterns and clinical outcome 2 years after hip replacement by a metaphyseal anchored cementless short stem. Migration data and clinical results were prospectively assessed in 49 patients. Clinical outcome was measured using the Harris Hip Score (HHS). Migration analyses were performed using the computer-assisted Einzel-Bild-Roentgen-Analyse (EBRA) system. At 2 years after surgery, none of the implants needed revision, and HHS increased from 47.9 up to 98.1. Of 49 patients, 5 (10%) showed increased vertical stem migration (1.5 mm/2a) that might predict late aseptic loosening. Of 49 stems, 44 (90%) showed stable migration patterns indicating a beneficial long-term outcome. Results of this study confirm the excellent clinical data of previous works. Migration patterns strongly suggest that short-stem arthroplasty is not only an innovative but also a reliable strategy in total hip replacement.

A two-stage clinical decision support system for early recognition and stratification of patients with sepsis: an observational cohort study.

PubMed

Amland, Robert C; Lyons, Jason J; Greene, Tracy L; Haley, James M

2015-10-01

To examine the diagnostic accuracy of a two-stage clinical decision support system for early recognition and stratification of patients with sepsis. Observational cohort study employing a two-stage sepsis clinical decision support to recognise and stratify patients with sepsis. The stage one component was comprised of a cloud-based clinical decision support with 24/7 surveillance to detect patients at risk of sepsis. The cloud-based clinical decision support delivered notifications to the patients' designated nurse, who then electronically contacted a provider. The second stage component comprised a sepsis screening and stratification form integrated into the patient electronic health record, essentially an evidence-based decision aid, used by providers to assess patients at bedside. Urban, 284 acute bed community hospital in the USA; 16,000 hospitalisations annually. Data on 2620 adult patients were collected retrospectively in 2014 after the clinical decision support was implemented. 'Suspected infection' was the established gold standard to assess clinical decision support clinimetric performance. A sepsis alert activated on 417 (16%) of 2620 adult patients hospitalised. Applying 'suspected infection' as standard, the patient population characteristics showed 72% sensitivity and 73% positive predictive value. A postalert screening conducted by providers at bedside of 417 patients achieved 81% sensitivity and 94% positive predictive value. Providers documented against 89% patients with an alert activated by clinical decision support and completed 75% of bedside screening and stratification of patients with sepsis within one hour from notification. A clinical decision support binary alarm system with cross-checking functionality improves early recognition and facilitates stratification of patients with sepsis.

Non-clinical studies required for new drug development - Part I: early in silico and in vitro studies, new target discovery and validation, proof of principles and robustness of animal studies.

PubMed

Andrade, E L; Bento, A F; Cavalli, J; Oliveira, S K; Freitas, C S; Marcon, R; Schwanke, R C; Siqueira, J M; Calixto, J B

2016-10-24

This review presents a historical overview of drug discovery and the non-clinical stages of the drug development process, from initial target identification and validation, through in silico assays and high throughput screening (HTS), identification of leader molecules and their optimization, the selection of a candidate substance for clinical development, and the use of animal models during the early studies of proof-of-concept (or principle). This report also discusses the relevance of validated and predictive animal models selection, as well as the correct use of animal tests concerning the experimental design, execution and interpretation, which affect the reproducibility, quality and reliability of non-clinical studies necessary to translate to and support clinical studies. Collectively, improving these aspects will certainly contribute to the robustness of both scientific publications and the translation of new substances to clinical development.

Feasibility of a Clinical Pathway with Early Oral Intake and Discharge for Laparoscopic Gastrectomy.

PubMed

Nakagawa, M; Tomii, C; Inokuchi, M; Otsuki, S; Kojima, K

2017-12-01

Although some studies have reported the safety of early oral intake after gastrectomy, it still remains controversial. This study focused on the feasibility of a clinical pathway with early oral intake and discharge setting for exclusively laparoscopic distal gastrectomy. A clinical pathway was applied to 403 patients until December 2014. In the protocol, patients are allowed to take a sip of water and a soft diet on the first and second days after the operation, respectively, and the discharge day is set as the fifth to seventh day after the operation. Clinicopathological variables were prospectively collected, and risk factors for discharge variances were analyzed. The completion rate of the clinical pathway was 76.9%. There were five re-admissions (1.2%). The overall morbidity rate was 18% ( n = 72), and major complications (Clavien-Dindo IIIa or greater) occurred in 13 patients (3%). Complications were the causes for discharge variances in 68 cases (73%), while the attending surgeons' judgment was the cause in 25 cases (27%). On multivariate analysis, age (odds ratio = 2.23, 95% confidence interval = 1.38-3.60, p = 0.001) and operative time (odds ratio = 2.38, 95% confidence interval = 1.45-3.98, p = 0.001) were independent risk factors for discharge variances. A high completion rate of a clinical pathway with early oral intake and discharge setting for laparoscopic distal gastrectomy was achievable with an acceptably low re-admission rate. Laparoscopic distal gastrectomy is recommended as a first step for a clinical pathway with an early oral intake and discharge protocol.

Assessment of osteopontin in early breast cancer: correlative study in a randomised clinical trial

PubMed Central

2014-01-01

Introduction Osteopontin (OPN) is a malignancy-associated glycoprotein that contributes functionally to tumor aggressiveness. In metastatic breast cancer, we previously demonstrated that elevated OPN in primary tumor and blood was associated with poor prognosis. Methods We measured OPN in plasma by ELISA, and in tumors by immunohistochemistry, in 624 (94%) and 462 (69%), respectively, of 667 postmenopausal women with hormone responsive early breast cancer treated by surgery followed by adjuvant treatment with tamoxifen +/− octreotide in a randomized trial (NCIC CTG MA.14; National Cancer Institute of Canada Clinical Trials Group Mammary.14). Results Plasma OPN was measured in 2,540 samples; 688 at baseline and 1,852 collected during follow-up. Mean baseline plasma OPN was 46 ng/ml (range 22.6 to 290) which did not differ from normal levels. Mean percentage OPN tumor cell positivity was 33.9 (95% CI: 30.2 to 37.9). There was no correlation between plasma and tumor OPN values. In multivariate analysis, neither was associated with event-free survival (EFS), relapse-free survival (RFS), overall survival (OS), bone RFS or non-bone RFS. An exploratory analysis in patients with recurrence showed higher mean OPN plasma levels 60.7 ng/ml (23.9 to 543) in the recurrence period compared with baseline levels. Conclusions The hypothesis that OPN tumor expression would have independent prognostic value in early breast cancer was not supported by multivariate analysis of this study population. Plasma OPN levels in women with hormone responsive early breast cancer in the MA.14 trial were not elevated and there was no evidence for prognostic value of plasma OPN in this defined group of patients. However, our finding of elevated mean OPN plasma level around the time of recurrence warrants further study. Trial registration NCT00002864, http://clinicaltrials.gov/show/NCT00002864 PMID:24451146

A comparison between the clinical significance and growth mixture modelling early change methods at predicting negative outcomes.

PubMed

Flood, Nicola; Page, Andrew; Hooke, Geoff

2018-05-03

Routine outcome monitoring benefits treatment by identifying potential no change and deterioration. The present study compared two methods of identifying early change and their ability to predict negative outcomes on self-report symptom and wellbeing measures. 1467 voluntary day patients participated in a 10-day group Cognitive Behaviour Therapy (CBT) program and completed the symptom and wellbeing measures daily. Early change, as defined by (a) the clinical significance method and (b) longitudinal modelling, was compared on each measure. Early change, as defined by the simpler clinical significance method, was superior at predicting negative outcomes than longitudinal modelling. The longitudinal modelling method failed to detect a group of deteriorated patients, and agreement between the early change methods and the final unchanged outcome was higher for the clinical significance method. Therapists could use the clinical significance early change method during treatment to alert them of patients at risk for negative outcomes, which in turn could allow therapists to prevent those negative outcomes from occurring.

Clinical study of quantitative diagnosis of early cervical cancer based on the classification of acetowhitening kinetics

NASA Astrophysics Data System (ADS)

Wu, Tao; Cheung, Tak-Hong; Yim, So-Fan; Qu, Jianan Y.

2010-03-01

A quantitative colposcopic imaging system for the diagnosis of early cervical cancer is evaluated in a clinical study. This imaging technology based on 3-D active stereo vision and motion tracking extracts diagnostic information from the kinetics of acetowhitening process measured from the cervix of human subjects in vivo. Acetowhitening kinetics measured from 137 cervical sites of 57 subjects are analyzed and classified using multivariate statistical algorithms. Cross-validation methods are used to evaluate the performance of the diagnostic algorithms. The results show that an algorithm for screening precancer produced 95% sensitivity (SE) and 96% specificity (SP) for discriminating normal and human papillomavirus (HPV)-infected tissues from cervical intraepithelial neoplasia (CIN) lesions. For a diagnostic algorithm, 91% SE and 90% SP are achieved for discriminating normal tissue, HPV infected tissue, and low-grade CIN lesions from high-grade CIN lesions. The results demonstrate that the quantitative colposcopic imaging system could provide objective screening and diagnostic information for early detection of cervical cancer.

Early- versus late-onset obsessive-compulsive disorder: investigating genetic and clinical correlates.

PubMed

Hemmings, Sîan M J; Kinnear, Craig J; Lochner, Christine; Niehaus, Dana J H; Knowles, James A; Moolman-Smook, Johanna C; Corfield, Valerie A; Stein, Dan J

2004-09-30

There is increasing evidence that obsessive-compulsive disorder (OCD) is mediated by genetic factors. Although the precise mechanism of inheritance is unclear, recent evidence has pointed towards the involvement of the serotonergic and dopaminergic systems in the disorder's development. Furthermore, early-onset OCD appears to be a subtype that exhibits distinct clinical features and that is associated with greater familial loading. In the present investigation, South African OCD patients (n=252) were stratified according to age of onset and were clinically assessed. Additionally, selected variants in genes encoding serotonergic and dopaminergic components were investigated in a Caucasian OCD subset (n=180). This subgroup was further stratified to evaluate the role that these candidate genes may play in the genetically homogeneous Afrikaner subset (n=80). Analysis of the clinical data revealed an association between early age of onset and an increased frequency of tics, Tourette's disorder, and trichotillomania (TTM). The genetic studies yielded statistically significant results when the allelic distributions of genetic variants in the dopamine receptor type 4 gene (DRD4) were analysed in the Caucasian OCD cohort. These data support a role for the dopaminergic system, which may be relevant to the development of early-onset OCD.

Working in partnership with the voluntary sector: early explorer clinics.

PubMed

Coe, Chris; Barlow, Jane

2010-11-01

The first three years of life have been identified as key to promoting children's later wellbeing, and partnership working across the statutory and voluntary sectors has been proposed as one of the best ways to meet the needs of families. Child health clinics are attended by parents seeking reassurance or help and advice from a health professional regarding child health and development. They have been used in Oxford to develop Early Explorer clinics, in which the statutory health visiting service and voluntary sector Peers Early Education Programme work together with the aim of improving outcomes for children and families. These Early Explorer clinics provide the opportunity to engage parents in supporting their child's development through interaction and non-directed exploratory play. They also offer opportunities to identify vulnerable families, who are provided with additional support. This paper examines a model of partnership working between statutory and voluntary sectors aimed at maximising opportunities to promote the health and wellbeing of infants and their families.

Assessing the Clinical Role of Genetic Markers of Early-Onset Prostate Cancer Among High-Risk Men Enrolled in Prostate Cancer Early Detection

PubMed Central

Hughes, Lucinda; Zhu, Fang; Ross, Eric; Gross, Laura; Uzzo, Robert G.; Chen, David Y. T.; Viterbo, Rosalia; Rebbeck, Timothy R.; Giri, Veda N.

2011-01-01

Background Men with familial prostate cancer (PCA) and African American men are at risk for developing PCA at younger ages. Genetic markers predicting early-onset PCA may provide clinically useful information to guide screening strategies for high-risk men. We evaluated clinical information from six polymorphisms associated with early-onset PCA in a longitudinal cohort of high-risk men enrolled in PCA early detection with significant African American participation. Methods Eligibility criteria include ages 35–69 with a family history of PCA or African American race. Participants undergo screening and biopsy per study criteria. Six markers associated with early-onset PCA (rs2171492 (7q32), rs6983561 (8q24), rs10993994 (10q11), rs4430796 (17q12), rs1799950 (17q21), and rs266849 (19q13)) were genotyped. Cox models were used to evaluate time to PCA diagnosis and PSA prediction for PCA by genotype. Harrell’s concordance index was used to evaluate predictive accuracy for PCA by PSA and genetic markers. Results 460 participants with complete data and ≥1 follow-up visit were included. 56% were African American. Among African American men, rs6983561 genotype was significantly associated with earlier time to PCA diagnosis (p=0.005) and influenced prediction for PCA by the PSA (p<0.001). When combined with PSA, rs6983561 improved predictive accuracy for PCA compared to PSA alone among African American men (PSA= 0.57 vs. PSA+rs6983561=0.75, p=0.03). Conclusions Early-onset marker rs6983561 adds potentially useful clinical information for African American men undergoing PCA risk assessment. Further study is warranted to validate these findings. Impact Genetic markers of early-onset PCA have potential to refine and personalize PCA early detection for high-risk men. PMID:22144497

The variable clinical presentation of tuberculosis otitis media and the importance of early detection.

PubMed

Abes, Generoso T; Abes, Franco Louie L B; Jamir, Joselito C

2011-06-01

Tuberculosis (TB) is a rare cause of otitis media. This study aims to increase awareness on the clinical presentation of TB otitis media and illustrate how early detection affects treatment outcome. Chart review of 12 patients (13 ears) from a tertiary hospital in Manila, Philippines, seen from 2004 to 2009. Clinical predictors of the disease were summarized. Clinical, radiologic, and audiometric outcomes after treatment were compared between treatment groups. The 5 otoscopic presentations were multiple perforations, single perforation with refractory otorrhea and exuberant granulation tissue formation, single perforation with minimal otorrhea and no granulation tissue formation, intact tympanic membrane with middle ear effusion, and intact tympanic membrane with tumorlike tissue in the middle ear. Clinical predictors of the disease were history of pulmonary TB, work-related contamination of the infection, positive purified protein derivative test, positive chest radiographic finding and intraoperative granulation tissue with cheesy material, and temporal bone computed tomographic scan findings. Patients who had no middle ear surgery showed significantly better clinical, radiologic, and audiometric outcomes than those who were diagnosed late and had more complicated surgical procedure. The clinical presentation of TB otitis media is variable. Early detection of the early forms entail less surgical intervention and favors better treatment results.

Salivary pH and Buffering Capacity as Risk Markers for Early Childhood Caries: A Clinical Study.

PubMed

Jayaraj, D; Ganesan, S

2015-01-01

The diagnostic utility of saliva is currently being explored in various branches of dentistry, remarkably in the field of caries research. This study was aimed to determine if assessment of salivary pH and buffering capacity would serve as reliable tools in risk prediction of early childhood caries (ECC). Paraffin-stimulated salivary samples were collected from 50 children with ECC (group I) and 50 caries free children (group II). Salivary pH and buffering capacity (by titration with 0.1 N hydrochloric acid) were assessed using a handheld digital pH meter in both groups. The data obtained were subjected to statistical analysis. Statistically, no significant difference was observed between both the groups for all salivary parameters assessed, except for the buffering capacity level at 150 μl titration of 0.1 N hydrochloric acid (p = 0.73; significant at 1% level). Salivary pH and buffering capacity may not serve as reliable markers for risk prediction of ECC. How to cite this article: Jayaraj D, Ganesan S. Salivary pH and Buffering Capacity as Risk Markers for Early Childhood Caries: A Clinical Study. Int J Clin Pediatr Dent 2015;8(3):167-171.

[Early drop-outs and retentions in substance abuse outpatient clinics: a cross-sectional comparative study of factors that increase or decrease adherence].

PubMed

Calvo, Fran; Carbonell, Xavier; Valero, Ramón; Costa, Jordi; Turró, Oriol; Giralt, Cristina; Ramírez, Marissa

2017-08-23

The aim of this study is to define the risk factors associated with early discharge in out-patients clinics. Cross-sectional and observational study. Substance abuse clinics in Girona (Catalonia, Spain). A total of 264 individuals were included in the sample, and 34.8% of them abandoned the process within two months of starting the therapy (n=92). Clinical and socio-demographic variables of the clinical history were compared between participants with/without adherence. The Student t test was used to measure the comparison, and the chi-squared test was used for the analysis of qualitative variables. A binary logistic regression model was adjusted, with adherence as the dependent variable. The results indicated that attending the appointments unaccompanied (OR=3.13), being female (OR=2.44), having cocaine related issues (OR=1.14), and being younger (OR=0.89) are the factors which increase the risk early abandonment. Contrarily, being referred to specialists from a Primary Health Centre reduces the risk (OR=0.28). It is concluded that special attention must be devoted to the patients' families, women, and young patients. Moreover, the appropriate coordination between specialist services and basic services increases adherence to treatment among drug users. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Early clinical applications for imaging at microscopic detail: microfocus computed tomography (micro-CT).

PubMed

Hutchinson, J Ciaran; Shelmerdine, Susan C; Simcock, Ian C; Sebire, Neil J; Arthurs, Owen J

2017-07-01

Microfocus CT (micro-CT) has traditionally been used in industry and preclinical studies, although it may find new applicability in the routine clinical setting. It can provide high-resolution three-dimensional digital imaging data sets to the same level of detail as microscopic examination without the need for tissue dissection. Micro-CT is already enabling non-invasive detailed internal assessment of various tissue specimens, particularly in breast imaging and early gestational fetal autopsy, not previously possible from more conventional modalities such as MRI or CT. In this review, we discuss the technical aspects behind micro-CT image acquisition, how early work with small animal studies have informed our knowledge of human disease and the imaging performed so far on human tissue specimens. We conclude with potential future clinical applications of this novel and emerging technique.

Effectiveness of a clinical practice intervention in early rheumatoid arthritis.

PubMed

Descalzo, Miguel Ángel; Carbonell, Jordi; González-Álvaro, Isidoro; Sanmartí, Raimon; Balsa, Alejandro; Hernandez-Barrera, Valentín; Román-Ivorra, José Andrés; Ivorra-Cortés, José; Lisbona, Pilar; Alperi, Mercedes; Jiménez-Garcia, Rodrigo; Carmona, Loreto

2012-03-01

To compare the outcome of early rheumatoid arthritis (RA) patients in a country where early clinics were established versus the outcome of patients in nonprotocolized clinics. We compared 2 multicenter cohorts: an RA cohort derived from an early arthritis registry set in 36 reference hospitals in which a specific intervention was established (Evaluation of a Model for Arthritis Care in Spain [SERAP]), and a historical control cohort of patients with early RA attending 34 rheumatology departments (Prognosis in Rheumatoid Arthritis [PROAR] cohort). Effectiveness was tested by comparing the change in the Disease Activity Score in 28 joints (DAS28), the change in the Health Assessment Questionnaire (HAQ), and the change in the Sharp/van der Heijde radiologic score using marginal structural models. A total of 161 early RA patients were recruited in the PROAR cohort and 447 in the SERAP cohort. Being a SERAP patient was inversely correlated with activity, resulting in a decrease of -0.24 (95% confidence interval [95% CI] -0.39, -0.08) units in the population average of the DAS28 after adjustment was made. Moreover, intervention may be seen as a protective factor of radiologic damage, with a decrease of -0.05 (95% CI -0.09, -0.01) units in the logarithm of the total Sharp/van der Heijde score. On the other hand, a decrease in functional impairment was detected, but intervention was not statistically associated with HAQ changes. Preventing major radiographic progression in a 2-year term inside structured and organized special programs for the management of disease, such as early arthritis clinics, are effective compared to nonprotocolized referrals, treatment, and followup. Copyright © 2012 by the American College of Rheumatology.

Early clinical outcomes of primary percutaneous coronary intervention in bharatpur, Nepal.

PubMed

Dubey, Laxman; Bhattacharya, Rabindra; Guruprasad, Sogunuu; Subramanyam, Gangapatnam

2013-06-01

Primary percutaneous coronary intervention represents one of the cornerstone management modalities for patients with acute ST-elevation myocardial infarction and has undergone tremendous growth over the past two decades. This study was aimed to determine the early clinical outcomes of primary percutaneous coronary interventions in a tertiary-level teaching hospital without onsite cardiac surgery backup. This was a prospective descriptive study which included all consecutive patients who were admitted for primary percutaneous coronary interventions between March 2011 and January 2013 at the College of Medical Sciences and Teaching Hospital, Bharatpur, Nepal. Total 68 patients underwent primary percutaneous coronary interventions as a mode of revascularization. The primary end point of the study was to identify in-hospital as well as 30-day clinical outcomes of primary percutaneous coronary interventions. The mean age was 56.31 ± 11.47 years, with age range of 32 years to 91 years. Of the 68 primary percutaneous coronary interventions performed, 15 (22.05%) were carried out in women and 10 (14.70%) in patients over 75 years of age. Primary percutaneous coronary intervention for anterior wall myocardial infarction was more common than for non-anterior wall myocardial infarction (55.88% vs. 44.12%). Proximal artery stenting was performed in 38.50% and the non proximal artery stenting in 61.50%. The outcomes were mortality (5.88%), cardiogenic shock (5.88%), contrast-induced nephropathy requiring dialysis (2.94%), arrhythmias requiring treatment (4.41%), early stent thrombosis (2.94%) and minor complications (14.70%). Primary percutaneous coronary intervention improves the early clinical outcomes in patient with acute ST-elevation myocardial infarction. Despite having no onsite cardiac surgery backup, primary percutaneous coronary intervention was feasible with acceptable complications in a tertiary-care teaching hospital.

Clinical imprinting: the impact of early clinical learning on career long professional development in nursing.

PubMed

Andrew, Nicola

2013-05-01

The literature recognises a relationship between clinical experience and a successful undergraduate experience in nursing; however what constitutes an effective approach remains the subject of debate, particularly in relation to first year of learning. There is evidence from a biological standpoint that early experience impacts on the behavioural development of animals, described by Konrad Lorenz (1903-1989) as 'imprinting'. The concept of imprinting has resonance for nursing. In this article the importance of 'getting it right at the beginning' is explored and what, if anything, Lorenz's theory tells us about the impact of early clinical learning on subsequent professional development. Copyright © 2012 Elsevier Ltd. All rights reserved.

Anything but Shadowing! Early Clinical Reasoning in Emergency Department Improves Clinical Skills

PubMed Central

Royan, Regina; Wu, Christine; Theyyunni, Nik; Montas, Sacha; Cranford, James A.; House, Joseph B.; Lukela, Michael P.; Santen, Sally A.

2018-01-01

Introduction Transitioning from the pre-clinical environment to clerkships poses a challenge to students and educators alike. Students along with faculty developed the Clinical Reasoning Elective (CRE) to provide pre-clinical students exposure to patients in the emergency department and the opportunity to build illness scripts and practice clinical skills with longitudinal mentorship in a low-stakes environment before entering clerkships. It is a voluntary program. Each year, the CRE has received overwhelming positive feedback from students. The objective of this study is to determine if the CRE improved students’ clinical skills and reported comfort in their skills. Methods We examined the relationships between students’ self-reported participation in the CRE and their individual scores on a comprehensive clinical assessment (CCA) at the end of the pre-clerkship period. A total of 178 students took the CCA exam in 2016. Of these, 113 participated in the CRE and 65 did not. Seven students who participated in CRE did not complete the exit survey and were omitted from analysis. We performed regression analysis and dichotomous (participants/nonparticipants) comparisons of means with t-tests. Survey of student reactions was collected. Results Participants completed an average of 10 sessions over the course of the program (range=1–20). Involvement in the CRE was associated with significantly increased scores on Abdominal History; Pulmonary Physical Exam; Overall History-Taking; Overall Communication; and Overall Physical Exam (p<0.05). Nearly all students (97%) reported that the program offered opportunities to enhance clinical skills, increased their comfort with patients, and better prepared them for their clinical years. Conclusion There were measurable improvements in clinical skills performance for students who participated in CRE. As many schools seek to incorporate early clinical exposure to their curricula, this program provides a successful framework to

Psychosis prediction and clinical utility in familial high-risk studies: Selective review, synthesis, and implications for early detection and intervention

PubMed Central

Shah, Jai L.; Tandon, Neeraj; Keshavan, Matcheri S.

2016-01-01

Aim Accurate prediction of which individuals will go on to develop psychosis would assist early intervention and prevention paradigms. We sought to review investigations of prospective psychosis prediction based on markers and variables examined in longitudinal familial high-risk (FHR) studies. Methods We performed literature searches in MedLine, PubMed and PsycINFO for articles assessing performance characteristics of predictive clinical tests in FHR studies of psychosis. Studies were included if they reported one or more predictive variables in subjects at FHR for psychosis. We complemented this search strategy with references drawn from articles, reviews, book chapters and monographs. Results Across generations of familial high-risk projects, predictive studies have investigated behavioral, cognitive, psychometric, clinical, neuroimaging, and other markers. Recent analyses have incorporated multivariate and multi-domain approaches to risk ascertainment, although with still generally modest results. Conclusions While a broad range of risk factors has been identified, no individual marker or combination of markers can at this time enable accurate prospective prediction of emerging psychosis for individuals at FHR. We outline the complex and multi-level nature of psychotic illness, the myriad of factors influencing its development, and methodological hurdles to accurate and reliable prediction. Prospects and challenges for future generations of FHR studies are discussed in the context of early detection and intervention strategies. PMID:23693118

Perinatal complications associated with autism--a case control study in a neurodevelopment and early intervention clinic.

PubMed

Nath, Saswati; Roy, Rita; Mukherjee, Suchandra

2012-08-01

Early and intensive intervention can have a profound impact on the quality of life for children at risk for autism. Hence a high degree of suspicion towards babies exposed to known risk factors is warranted. Previous studies have shown that different perinatal factors like antepartum bleeding, postmaturity, birth asphyxia, meconium aspiration syndrome, anaemia in early infancy and exposure to toxins of various origins makes an infant susceptible to development of autism; attention deficit hyperactivity disorder (ADHD) and other neurodevelopmental disorders in later life.This study aims to find out the association of perinatal risk factors in relation to development of autism spectrum disorders. All babies who are at least three years of age, attending the neurodevelopment and early intervention clinic at SSKM Hospital at Kolkata taken as cases. Age matched controls were taken from general paediatric OPD of the same hospital. After history taking, physical and neurological examination, developmental maturity was assessed by the Denver Developmental Screening Test (DDST) and Vineland Social Maturity Scale (VSMS). A semi-structured parent's questionnaire and the modified checklist for autism in toddlers (M-CHAT) was used to screen for autism. Diagnosis was confirmed by DSM-IV-TR (Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition, Text Revision) criteria. Significant correlation was found between presence of antepartum haemorrhage, pregnancy induced hypertension, preterm delivery and autism in the baby. Perinatal complications are important risk factor for autism. Knowing the risk factors will help clinicians to be aware of the avoidable complications, and to undertake either preventive steps or intense intervention to reduce the degree of disability.

Demographic, tumor and clinical features of clinical trials versus clinical practice patients with HER2-positive early breast cancer: results of a prospective study.

PubMed

Arpino, Grazia; Michelotti, Andrea; Truini, Mauro; Montemurro, Filippo; Russo, Stefania; Palumbo, Raffaella; Zamagni, Claudio; Latorre, Agnese; Bruzzese, Dario; Riccardi, Ferdinando; De Laurentiis, Michelino; Beano, Alessandra; Biganzoli, Laura; Zaniboni, Alberto; Laudadio, Lucio; Malagoli, Maria; Bilancia, Domenico; Schettini, Francesco; Giuliano, Mario; Cazzaniga, Marina Elena; De Placido, Sabino

2016-03-01

Several randomized clinical trials (RCTs) have demonstrated the efficacy of trastuzumab-based adjuvant therapy in HER2-positive breast cancer (BC). However, RCT patients may not invariably be representative of patients routinely seen in clinical practice (CP). To address this issue, we compared the clinical and tumor features of RCT and CP patients with HER2-positive BC. From January to December 2012, 650 consecutive patients with HER2-positive early BC, treated in 36 different types of Italian healthcare facilities, were enrolled in this study. Age, treatment, tumor size (T), nodes (N), grade (G), estrogen receptor (ER) and progesterone receptor (PgR) status were prospectively collected in these CP patients. The same data were extracted from the main adjuvant trastuzumab RCTs and pooled using the random-effects model of DerSimonian and Laird. RCT and CP patients were compared by using the Cochran Q statistics. Versus RCT patients, CP patients were more likely to be older than 50 years (65 vs. 49 %; p < 0.0001) and to have HR (ER and/or PgR)-positive (72 vs. 54 %; p < 0.0001) BC and less likely to have tumor >2 cm (T ≥ 2 cm 39 vs. 59 %; p < 0.0001), positive N (47 vs. 89 %; p < 0.0001) and a high G (61 vs. 67 %; p = 0.0241). CP patients more frequently received adjuvant endocrine therapy (70 vs. 57 %; p < 0.0003) and less frequently adjuvant chemotherapy (97 vs. 99.7 %; p < 0.0001). Most tumor and clinical features differed significantly between CP and RCT patients. These data raise concerns about the applicability of RCT results to CP patients.

Clinically relevant characteristics associated with early treatment drug use versus abstinence.

PubMed

Cochran, Gerald; Stitzer, Maxine; Nunes, Edward V; Hu, Mei-Chen; Campbell, Aimee

2014-04-04

This study describes early treatment drug use status and associated clinical characteristics in a diverse sample of patients entering outpatient substance abuse psychosocial counseling treatment. The goal is to more fully characterize those entering treatment with and without active use of their primary drug in order to better understand associated treatment needs and resilience factors. We examined baseline data from a NIDA Clinical Trials Network (CTN) study (Web-delivery of Treatment for Substance Use) with an all-comers sample of patients (N = 494) entering 10 outpatient treatment centers. Patients were categorized according to self-identified primary drug of abuse (alcohol, cocaine/stimulants, opioids, marijuana) and by baseline drug use status (positive/negative) based on urine testing or self-reports of recent use (alcohol). Characteristics were examined by primary drug and early use status. Classified as drug-negative were 84%, 76%, 62%, and 33% of primary opioid, stimulant, alcohol, and marijuana users; respectively. Drug-positive versus -negative patients did not differ on demographics or rates of substance abuse/dependence diagnoses. However, those negative for active use had better physical and mental health profiles, were less likely to be using a secondary drug, and were more likely to be attending 12-step self-help meetings. Early treatment drug abstinence is common among substance users entering outpatient psychosocial counseling programs, regardless of primary abused drug. Abstinence (by negative UA) is associated with better health and mental health profiles, less secondary drug use, and more days of 12-step attendance. These data highlight differential treatment needs and resiliencies associated with early treatment drug use status. NCT01104805.

Sepsis in Obstetrics: Clinical Features and Early Warning Tools.

PubMed

Parfitt, Sheryl E; Bogat, Mary L; Hering, Sandra L; Ottley, Charlotte; Roth, Cheryl

Morbidity and mortality associated with sepsis has gained widespread attention on a local, state, and national level, yet, it remains a complicated disorder that can be difficult to identify in a timely manner. Sepsis in obstetric patients further complicates the diagnosis as alterations in physiology related to pregnancy can mask sepsis indicators normally seen in the general population. If early signs of sepsis go unrecognized, septic shock can develop, leading to organ dysfunction and potential death. Maternal early warning tools have been designed to assist clinicians in recognizing early indications of illness. Through use of clinical pathway-specific tools, disease processes may be detected early, subsequently benefitting patients with aggressive treatment management and intervention.This article is the second in a series of three that discuss the importance of sepsis and septic shock in pregnancy. Risk factors, causes of sepsis, signs and symptoms, and maternal early warning tools are discussed.

Clinicopathological characteristics of clinical early gastric cancer in the upper-third stomach.

PubMed

Ichikawa, Daisuke; Komatsu, Shuhei; Kosuga, Toshiyuki; Konishi, Hirotaka; Okamoto, Kazuma; Shiozaki, Atsushi; Fujiwara, Hitoshi; Otsuji, Eigo

2015-12-07

To elucidate the clinicopathological characteristics of clinically early gastric cancer in the upper-third stomach and to clarify treatment precautions. A total of 683 patients with clinical early gastric cancer were enrolled in this retrospective study, 128 of whom had gastric cancer in the upper-third stomach (U group). All patients underwent a double contrast barium examination, endoscopy, and computed tomography (CT), and were diagnosed preoperatively based on the findings obtained. The clinicopathological features of these patients were compared with those of patients with gastric cancer in the middle- and lower-third stomach (ML group). We also compared clinicopathological factors between accurate-diagnosis and under-diagnosis groups in order to identify factors affecting the accuracy of a preoperative diagnosis of tumor depth. Patients in the U group were older (P = 0.029), had a higher ratio of males to females (P = 0.015), and had more histologically differentiated tumors (P = 0.007) than patients in the ML group. A clinical under-diagnosis occurred in 57 out of 683 patients (8.3%), and was more frequent in the U group than in the ML group (16.4% vs 6.3%, P < 0.0001). Therefore, the rates of lymph node metastasis and lymphatic invasion were slightly higher in the U group than in the ML group (P = 0.071 and 0.082, respectively). An under-diagnosis was more frequent in histologically undifferentiated tumors (P = 0.094) and in those larger than 4 cm (P = 0.024). The median follow-up period after surgery was 56 mo (range, 1-186 mo). Overall, survival and disease-specific survival rates were significantly lower in the U group than in the ML group (P = 0.016 and 0.020, respectively). However, limited operation-related cancer recurrence was not detected in the U group in the present study. Clinical early gastric cancer in the upper-third stomach has distinguishable characteristics that increase the risk of a clinical under-diagnosis, especially in patients with

Clinical features of early onset, familial Alzheimer`s disease linked to chromosome 14

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mullan, M.; Bennett, C.; Figueredo, C.

1995-02-27

Early onset familial Alzheimer`s disease (AD) has an autosomal dominant mode of inheritance. Two genes are responsible for the majority of cases of this subtype of AD. Mutations in the {beta}-amyloid precursor protein ({beta}APP) gene on chromosome 21 have been shown to completely cosegregate with the disease. We and others have previously described the clinical features of families with {beta}APP mutations at the codon 717 locus in an attempt to define the phenotype associated with a valine to isoleucine (Val {r_arrow} Ile) or a valine to glycine (Val {r_arrow} Gly) change. More recently, a second locus for very early onsetmore » disease has been localized to chromosome 14. The results of linkage studies in some families suggesting linkage to both chromosomes have been explained by the suggestion of a second (centromeric) locus on chromosome 21. Here we report the clinical features and genetic analysis of a British pedigree (F74) with early onset AD in which neither the {beta}APP locus nor any other chromosome 21 locus segregates with the disease, but in which good evidence is seen for linkage on the long arm of chromosome 14. In particular we report marker data suggesting that the chromosome 14 disease locus is close to D14S43 and D14S77. Given the likelihood that F74 represents a chromosome 14 linked family, we describe the clinical features and make a limited clinical comparison with the {beta}APP717 Val {r_arrow} Ile and {beta}APP717 Val {r_arrow} Gly encoded families that have been previously described. We conclude that although several previously reported clinical features occur to excess in early onset familial AD, no single clinical feature demarcates either the chromosome 14 or {beta}APP codon 717 mutated families except mean age of onset. 52 refs., 2 figs., 5 tabs.« less

The early evolution of Jean Piaget's clinical method.

PubMed

Mayer, Susan Jean

2005-11-01

This article analyzes the early evolution of Jean Piaget's renowned "clinical method" in order to investigate the method's strikingly original and generative character. Throughout his 1st decade in the field, Piaget frequently discussed and justified the many different approaches to data collection he used. Analysis of his methodological progression during this period reveals that Piaget's determination to access the genuine convictions of children eventually led him to combine 3 distinct traditions in which he had been trained-naturalistic observation, psychometrics, and the psychiatric clinical examination. It was in this amalgam, first evident in his 4th text, that Piaget discovered the clinical dynamic that would drive the classic experiments for which he is most well known.

[Clinical relevant procedures for early pregnancy diagnosis in the mare].

PubMed

Bostedt, H; Sieme, H; Bartmann, C-P; Handler, J; Sobiraj, A; Wehrend, A

2014-01-01

This review describes stepwise the recto-manual and transrectal ultrasonographic evidence of early pregnancy detection in the horse. The morphological and physiological conditions in the individual phases of early pregnancy are presented in correlation to the potential clinical findings. The importance of embryonic and early foetal losses is presented. Communication and documentation of findings are also addressed. The final section is devoted to the evaluation of the examination effort. In this regard, it is emphasized that the gynaecological examination for the evaluation of the pregnancy status represents a service contract.

Outcomes of laparoscopic fertility-sparing surgery in clinically early-stage epithelial ovarian cancer.

PubMed

Park, Jin-Young; Heo, Eun Jin; Lee, Jeong-Won; Lee, Yoo-Young; Kim, Tae-Joong; Kim, Byoung-Gie; Bae, Duk-Soo

2016-03-01

Fertility-sparing surgery (FSS) is becoming an important technique in the surgical management of young women with early-stage epithelial ovarian cancer (EOC). We retrospectively evaluated the outcome of laparoscopic FSS in presumed clinically early-stage EOC. We retrospectively searched databases of patients who received laparoscopic FSS for EOC between January 1999 and December 2012 at Samsung Medical Center. Women aged ≤40 years were included. The perioperative, oncological, and obstetric outcomes of these patients were evaluated. A total of 18 patients was evaluated. The median age of the patients was 33.5 years (range, 14 to 40 years). The number of patients with clinically stage IA and IC was 6 (33.3%) and 12 (66.7%), respectively. There were 7 (38.9%), 5 (27.8%), 3 (16.7%), and 3 patients (16.7%) with mucinous, endometrioid, clear cell, and serous tumor types, respectively. Complete surgical staging to preserve the uterus and one ovary with adnexa was performed in 4 patients (22.2%). Two out of them were upstaged to The International Federation of Gynecology and Obstetrics stage IIIA1. During the median follow-up of 47.3 months (range, 11.5 to 195.3 months), there were no perioperative or long term surgical complications. Four women (22.2%) conceived after their respective ovarian cancer treatments. Three (16.7%) of them completed full-term delivery and one is expecting a baby. One patient had disease recurrence. No patient died of the disease. FSS in young patients with presumed clinically early-stage EOC is a challenging and cautious procedure. Further studies are urgent to determine the safety and feasibility of laparoscopic FSS in young patients with presumed clinically early-stage EOC.

Outcomes of laparoscopic fertility-sparing surgery in clinically early-stage epithelial ovarian cancer

PubMed Central

Park, Jin-Young; Lee, Yoo-Young; Kim, Tae-Joong; Kim, Byoung-Gie; Bae, Duk-Soo

2016-01-01

Objective Fertility-sparing surgery (FSS) is becoming an important technique in the surgical management of young women with early-stage epithelial ovarian cancer (EOC). We retrospectively evaluated the outcome of laparoscopic FSS in presumed clinically early-stage EOC. Methods We retrospectively searched databases of patients who received laparoscopic FSS for EOC between January 1999 and December 2012 at Samsung Medical Center. Women aged ≤40 years were included. The perioperative, oncological, and obstetric outcomes of these patients were evaluated. Results A total of 18 patients was evaluated. The median age of the patients was 33.5 years (range, 14 to 40 years). The number of patients with clinically stage IA and IC was 6 (33.3%) and 12 (66.7%), respectively. There were 7 (38.9%), 5 (27.8%), 3 (16.7%), and 3 patients (16.7%) with mucinous, endometrioid, clear cell, and serous tumor types, respectively. Complete surgical staging to preserve the uterus and one ovary with adnexa was performed in 4 patients (22.2%). Two out of them were upstaged to The International Federation of Gynecology and Obstetrics stage IIIA1. During the median follow-up of 47.3 months (range, 11.5 to 195.3 months), there were no perioperative or long term surgical complications. Four women (22.2%) conceived after their respective ovarian cancer treatments. Three (16.7%) of them completed full-term delivery and one is expecting a baby. One patient had disease recurrence. No patient died of the disease. Conclusion FSS in young patients with presumed clinically early-stage EOC is a challenging and cautious procedure. Further studies are urgent to determine the safety and feasibility of laparoscopic FSS in young patients with presumed clinically early-stage EOC. PMID:26768783

Clinical assessment of early language development: a simplified short form of the Mandarin communicative development inventory.

PubMed

Soli, Sigfrid D; Zheng, Yun; Meng, Zhaoli; Li, Gang

2012-09-01

The purpose of this study was to develop a practical mean for clinical evaluation of early pediatric language development by establishing developmental trajectories for receptive and expressive vocabulary growth in children between 6 and 32 months of age using a simple, time-efficient assessment tool. Simplified short form versions of the Words and Gestures and Words and Sentences vocabulary inventories in the Mandarin Communicative Development Inventory [1] were developed and used to assess early language development in developmentally normal children from 6 to 32 months of age during routine health checks. Developmental trajectories characterizing the rate of receptive and expressive vocabulary growth between 6 and 32 months of age are reported. These trajectories allow the equivalent age corresponding to a score to be determined after a brief structured interview with the child's parents that can be conducted in a busy clinical setting. The simplified short forms of the Mandarin Communicative Development Inventories can serve as a clinically useful tool to assess early child language development, providing a practical mean of objectively assessing early language development following early interventions to treat young children with hearing impairment as well as speech and language delays. Objective evidence of language development is essential for achievement of effective (re)habilitation outcomes. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

The effect of adult Early Warning Systems education on nurses' knowledge, confidence and clinical performance: A systematic review.

PubMed

Saab, Mohamad M; McCarthy, Bridie; Andrews, Tom; Savage, Eileen; Drummond, Frances J; Walshe, Nuala; Forde, Mary; Breen, Dorothy; Henn, Patrick; Drennan, Jonathan; Hegarty, Josephine

2017-11-01

This review aims to determine the effect of adult Early Warning Systems education on nurses' knowledge, confidence and clinical performance. Early Warning Systems support timely identification of clinical deterioration and prevention of avoidable deaths. Several educational programmes have been designed to help nurses recognize and manage deteriorating patients. Little is known as to the effectiveness of these programmes. Systematic review. Academic Search Complete, CINAHL, MEDLINE, PsycINFO, PsycARTICLES, Psychology and Behavioral Science Collection, SocINDEX and the UK & Ireland Reference Centre, EMBASE, the Turning Research Into Practice database, the Cochrane Central Register of Controlled Trials (CENTRAL) and Grey Literature sources were searched between October and November 2015. This is a quantitative systematic review using Cochrane methods. Studies published between January 2011 - November 2015 in English were sought. The risk of bias, level of evidence and the quality of evidence per outcome were assessed. Eleven articles with 10 studies were included. Nine studies addressed clinical performance, four addressed knowledge and two addressed confidence. Knowledge, vital signs recording and Early Warning Score calculation were improved in the short term. Two interventions had no effect on nurses' response to clinical deterioration and use of communication tools. This review highlights the importance of measuring outcomes using standardized tools and valid and reliable instruments. Using longitudinal designs, researchers are encouraged to investigate the effect of Early Warning Systems educational programmes. These can include interactive e-learning, on-site interdisciplinary Early Warning Scoring systems training sessions and simulated scenarios. © 2017 John Wiley & Sons Ltd.

[Practice and experience in early clinical education of dental students in preventive dentistry].

PubMed

Tao, Dan-ying; Shu, Chen-bin; Pan, Ying; Feng, Xi-ping

2013-02-01

To help dental students acquaint the medical environment, doctor-patient communication and relationship, early clinic education was arranged in our college of stomatology. The interesting topics were chosen to enhance the learning enthusiasm of the students in the teaching practice of preventive dentistry. Students were encouraged to practice the skill of doctor-patient communication. To obtain the satisfactory teaching effect and aim, it was important to pay attention to the aspects in the groups and clinical practice. Early clinic education in preventive dentistry help the students understand the specialty of preventive dentistry.

Incidence of early-onset sepsis in infants born to women with clinical chorioamnionitis.

PubMed

Randis, Tara M; Rice, Madeline Murguia; Myatt, Leslie; Tita, Alan T N; Leveno, Kenneth J; Reddy, Uma M; Varner, Michael W; Thorp, John M; Mercer, Brian M; Dinsmoor, Mara J; Ramin, Susan M; Carpenter, Marshall W; Samuels, Philip; Sciscione, Anthony; Tolosa, Jorge E; Saade, George; Sorokin, Yoram

2018-05-23

To determine the frequency of sepsis and other adverse neonatal outcomes in women with a clinical diagnosis of chorioamnionitis. We performed a secondary analysis of a multi-center placebo-controlled trial of vitamins C/E to prevent preeclampsia in low risk nulliparous women. Clinical chorioamnionitis was defined as either the "clinical diagnosis" of chorioamnionitis or antibiotic administration during labor because of an elevated temperature or uterine tenderness in the absence of another cause. Early-onset neonatal sepsis was categorized as "suspected" or "confirmed" based on a clinical diagnosis with negative or positive blood, urine or cerebral spinal fluid cultures, respectively, within 72 h of birth. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression. Data from 9391 mother-infant pairs were analyzed. The frequency of chorioamnionitis was 10.3%. Overall, 6.6% of the neonates were diagnosed with confirmed (0.2%) or suspected (6.4%) early-onset sepsis. Only 0.7% of infants born in the setting of chorioamnionitis had culture-proven early-onset sepsis versus 0.1% if chorioamnionitis was not present. Clinical chorioamnionitis was associated with both suspected [OR 4.01 (3.16-5.08)] and confirmed [OR 4.93 (1.65-14.74)] early-onset neonatal sepsis, a need for resuscitation within the first 30 min after birth [OR 2.10 (1.70-2.61)], respiratory distress [OR 3.14 (2.16-4.56)], 1 min Apgar score of ≤3 [OR 2.69 (2.01-3.60)] and 4-7 [OR 1.71 (1.43-2.04)] and 5 min Apgar score of 4-7 [OR 1.67 (1.17-2.37)] (vs. 8-10). Clinical chorioamnionitis is common and is associated with neonatal morbidities. However, the vast majority of exposed infants (99.3%) do not have confirmed early-onset sepsis.

Early onset marfan syndrome: Atypical clinical presentation of two cases

PubMed Central

Ozyurt, A; Baykan, A; Argun, M; Pamukcu, O; Halis, H; Korkut, S; Yuksel, Z; Gunes, T; Narin, N

2015-01-01

Early onset Marfan Syndrome (eoMFS) is a rare, severe form of Marfan Syndrome (MFS). The disease has a poor prognosis and most patients present with resistance to heart failure treatment during the newborn period. This report presents two cases of eoMFS with similar clinical features diagnosed in the newborn period and who died at an early age due to the complications related to the involvement of the cardiovascular system. PMID:26929908

Clinical monitoring of early caries lesions using cross polarization optical coherence tomography

NASA Astrophysics Data System (ADS)

Fried, Daniel; Staninec, Michal; Darling, Cynthia L.; Chan, Kenneth H.; Pelzner, Roger B.

New methods are needed for the nondestructive measurement of tooth demineralization and remineralization and to monitor the progression of incipient caries lesions (tooth decay) for effective nonsurgical intervention and to evaluate the performance of anti-caries treatments such as chemical treatments or laser irradiation. Studies have shown that optical coherence tomography (OCT) has great potential to fulfill this role, since it can be used to measure the depth and severity of early lesions with an axial resolution exceeding 10-μm. It is easy to apply in vivo and it can be used to image the convoluted topography of tooth occlusal surfaces. In this paper we present early results from two clinical studies underway to measure the effect of fluoride intervention on early lesions. CP-OCT was used to monitor early lesions on enamel and root surfaces before and after intervention with fluoride varnish. The lesion depth and internal structure were resolved for all the lesions examined and some lesions had well defined surface zones of lower reflectivity that may be indicative of arrested lesions. Changes were also noted in the structure of some of the lesions after fluoride intervention.

The predictive factors for lymph node metastasis in early gastric cancer: A clinical study.

PubMed

Wang, Yinzhong

2015-01-01

To detect the clinicopathological factors associated with lymph node metastases in early gastric cancer. We retrospectively evaluated the distribution of metastatic nodes in 198 patients with early gastric cancer treated in our hospital between May 2008 and January 2015, the clinicopathological factors including age, gender, tumor location, tumor size, macroscopic type, depth of invasion, histological type and venous invasion were studied, and the relationship between various parameters and lymph node metastases was analyzed. In this study, one hundred and ninety-eight patients with early gastric cancer were included, and lymph node metastasis was detected in 28 patients. Univariate analysis revealed a close relationship between tumor size, depth of invasion, histological type, venous invasion, local ulceration and lymph node metastases. Multivariate analysis revealed that the five factors were independent risk factors for lymph node metastases. The clinicopathological parameters including tumor size, depth of invasion, local ulceration, histological type and venous invasion are closely correlated with lymph node metastases, should be paid high attention in early gastric cancer patients.

Local Matrix Metalloproteinase 9 Level Determines Early Clinical Presentation of ST-Segment-Elevation Myocardial Infarction.

PubMed

Nishiguchi, Tsuyoshi; Tanaka, Atsushi; Taruya, Akira; Emori, Hiroki; Ozaki, Yuichi; Orii, Makoto; Shiono, Yasutsugu; Shimamura, Kunihiro; Kameyama, Takeyoshi; Yamano, Takashi; Yamaguchi, Tomoyuki; Matsuo, Yoshiki; Ino, Yasushi; Kubo, Takashi; Hozumi, Takeshi; Hayashi, Yasushi; Akasaka, Takashi

2016-12-01

Early clinical presentation of ST-segment-elevation myocardial infarction (STEMI) and non-ST-segment-elevation myocardial infarction affects patient management. Although local inflammatory activities are involved in the onset of MI, little is known about their impact on early clinical presentation. This study aimed to investigate whether local inflammatory activities affect early clinical presentation. This study comprised 94 and 17 patients with MI (STEMI, 69; non-STEMI, 25) and stable angina pectoris, respectively. We simultaneously investigated the culprit lesion morphologies using optical coherence tomography and inflammatory activities assessed by shedding matrix metalloproteinase 9 (MMP-9) and myeloperoxidase into the coronary circulation before and after stenting. Prevalence of plaque rupture, thin-cap fibroatheroma, and lipid arc or macrophage count was higher in patients with STEMI and non-STEMI than in those with stable angina pectoris. Red thrombus was frequently observed in STEMI compared with others. Local MMP-9 levels were significantly higher than systemic levels (systemic, 42.0 [27.9-73.2] ng/mL versus prestent local, 69.1 [32.2-152.3] ng/mL versus poststent local, 68.0 [35.6-133.3] ng/mL; P<0.01). Poststent local MMP-9 level was significantly elevated in patients with STEMI (STEMI, 109.9 [54.5-197.8] ng/mL versus non-STEMI: 52.9 [33.0-79.5] ng/mL; stable angina pectoris, 28.3 [14.2-40.0] ng/mL; P<0.01), whereas no difference was observed in the myeloperoxidase level. Poststent local MMP-9 and the presence of red thrombus are the independent determinants for STEMI in multivariate analysis. Local MMP-9 level could determine the early clinical presentation in patients with MI. Local inflammatory activity for atherosclerosis needs increased attention. © 2016 American Heart Association, Inc.

Pancreatic cancer early detection: Expanding higher-risk group with clinical and metabolomics parameters

PubMed Central

Urayama, Shiro

2015-01-01

Pancreatic ductal adenocarcinoma (PDAC) is the fourth and fifth leading cause of cancer death for each gender in developed countries. With lack of effective treatment and screening scheme available for the general population, the mortality rate is expected to increase over the next several decades in contrast to the other major malignancies such as lung, breast, prostate and colorectal cancers. Endoscopic ultrasound, with its highest level of detection capacity of smaller pancreatic lesions, is the commonly employed and preferred clinical imaging-based PDAC detection method. Various molecular biomarkers have been investigated for characterization of the disease, but none are shown to be useful or validated for clinical utilization for early detection. As seen from studies of a small subset of familial or genetically high-risk PDAC groups, the higher yield and utility of imaging-based screening methods are demonstrated for these groups. Multiple recent studies on the unique cancer metabolism including PDAC, demonstrate the potential for utility of the metabolites as the discriminant markers for this disease. In order to generate an early PDAC detection screening strategy available for a wider population, we propose to expand the population of higher risk PDAC group with combination clinical and metabolomics parameters. PMID:25684935

Quantifying risk of early relapse in patients with first demyelinating events: Prediction in clinical practice.

PubMed

Spelman, Tim; Meyniel, Claire; Rojas, Juan Ignacio; Lugaresi, Alessandra; Izquierdo, Guillermo; Grand'Maison, Francois; Boz, Cavit; Alroughani, Raed; Havrdova, Eva; Horakova, Dana; Iuliano, Gerardo; Duquette, Pierre; Terzi, Murat; Grammond, Pierre; Hupperts, Raymond; Lechner-Scott, Jeannette; Oreja-Guevara, Celia; Pucci, Eugenio; Verheul, Freek; Fiol, Marcela; Van Pesch, Vincent; Cristiano, Edgardo; Petersen, Thor; Moore, Fraser; Kalincik, Tomas; Jokubaitis, Vilija; Trojano, Maria; Butzkueven, Helmut

2017-09-01

Characteristics at clinically isolated syndrome (CIS) examination assist in identification of patient at highest risk of early second attack and could benefit the most from early disease-modifying drugs (DMDs). To examine determinants of second attack and validate a prognostic nomogram for individualised risk assessment of clinical conversion. Patients with CIS were prospectively followed up in the MSBase Incident Study. Predictors of clinical conversion were analysed using Cox proportional hazards regression. Prognostic nomograms were derived to calculate conversion probability and validated using concordance indices. A total of 3296 patients from 50 clinics in 22 countries were followed up for a median (inter-quartile range (IQR)) of 1.92 years (0.90, 3.71). In all, 1953 (59.3%) patients recorded a second attack. Higher Expanded Disability Status Scale (EDSS) at baseline, first symptom location, oligoclonal bands and various brain and spinal magnetic resonance imaging (MRI) metrics were all predictors of conversion. Conversely, older age and DMD exposure post-CIS were associated with reduced rates. Prognostic nomograms demonstrated high concordance between estimated and observed conversion probabilities. This multinational study shows that age at CIS onset, DMD exposure, EDSS, multiple brain and spinal MRI criteria and oligoclonal bands are associated with shorter time to relapse. Nomogram assessment may be useful in clinical practice for estimating future clinical conversion.

The clinical utility of naturalistic action test in differentiating mild cognitive impairment from early dementia in memory clinic.

PubMed

Bruce, Irene; Ntlholang, Ontefetse; Crosby, Lisa; Cunningham, Conal; Lawlor, Brian

2016-03-01

This study aimed to examine the validity of the Naturalistic Action Test in differentiating Mild Cognitive Impairment from early dementia compared to clinical diagnosis and ascertain Naturalistic Action Test cut-off points. This was a cross-sectional study of 70 consecutive patients diagnosed with Mild Cognitive Impairment attending the memory clinic in St James's Hospital, Dublin, Ireland. Patients with a diagnosis of Mild Cognitive Impairment who attended for routine annual assessment were asked to participate in the study. The Naturalistic Action Test was carried out after the patient had completed their routine assessment in the clinic. The Area under the Curve, AUC ± SE was 0.808 ± 0.058, p < 0.001 with 95% CI (0.695-0.922). There was concordance in 40 and discrepancy in 30 patients between the NAT and the gold standard consensus diagnosis (PPV 38%, NPV 96%, sensitivity 94%, specificity 46% and accuracy 59%) using cut-off point of ≥14 for normal function on Naturalistic Action Test. The difference was not related to age, sex, level of education or informant. Using the Youden index, we determined a Naturalistic Action Test cut-off score of ≥11 for Mild Cognitive Impairment in our study (PPV 50%, NPV 91%, sensitivity 78%, specificity 73% and accuracy of 74%). There was discrepancy in 18 patients using the new cut-off point (≥11 for Mild Cognitive Impairment vs ≤10 for dementia). The Naturalistic Action Test is a useful tool that can increase diagnostic accuracy in differentiating Mild Cognitive Impairment from early dementia. Copyright © 2015 John Wiley & Sons, Ltd.

AWBAT: early clinical experience.

PubMed

Vandenberg, Victoria B

2010-03-15

The purpose of this article is to describe the early clinical experience with AWBAT. Burn patients requiring (1) donor sites or (2) treatment of a superficial burn wound injury were treated. A total of 45 patients with 69 distinct wounds were included. AWBAT-D was evaluated in donor sites and AWBAT-S was evaluated in superficial partial-thickness burns. Days to healing, pain, hematoma/seroma formation, and infection were noted. Ease of application, adherence, transparency, and physical adaptability details were collected. Average period to healing of donor sites treated with AWBAT-D (n=22 patients with n=26 wounds) was 11.2 days, sigma =1.95, with a range of 8-15 days and a median of 11 days. Pain rating at 24 hours was 1.2, sigma =0.43 (n=18) and at 48 hours mean was 1.2, sigma =0.46 (n=15). Average period to healing of superficial burns treated with AWBAT-S (n=15 patients with n=18 wounds) was 8.1 days, sigma =2.48, with a range of 5-13 days and a median of 7 days. Pain rating at 24 hours was 1.5, sigma =0.85 (n=10) and at 48 hours mean was 1.75, sigma =0.89 (n=8). There was zero incidence of hematoma/seroma. No infections were seen. Results indicate that AWBAT was easily applied with good initial adherence. It was noted to be transparent, conformant, and pliable. Early experience demonstrates that AWBAT performs well on donor sites and superficial partial-thickness burns and delivers the desired attributes of a temporary skin substitute including good adherence, infection control, transparency, adapatability, and pain control.

Intestinal microbiota composition after antibiotic treatment in early life: the INCA study.

PubMed

Rutten, N B M M; Rijkers, G T; Meijssen, C B; Crijns, C E; Oudshoorn, J H; van der Ent, C K; Vlieger, A M

2015-12-09

The acquisition and development of infant gut microbiota can be influenced by numerous factors, of which early antibiotic treatment is an important one. However, studies on the effects of antibiotic treatment in early life on clinical outcomes and establishment and development of the gut microbiota of term infants are limited. Disturbed microbiota composition is hypothesized to be an underlying mechanism of an aberrant development of the immune system. This study aims to investigate the potential clinical and microbial consequences of empiric antibiotic use in early life. 450 term born infants, of whom 150 are exposed to antibiotic treatment in early life and 300 are not (control group), are included in this observational cohort study with a one-year follow-up. Clinical outcomes, including coughing, wheezing, fever >38 °C, runny nose, glue ear, rash, diarrhea and >3 crying hours a day, are recorded daily by parents and examined by previously defined doctor's diagnosis. A blood sample is taken at closure to investigate the infant's vaccination response and sensitization for food and inhalant allergens. Fecal samples are obtained at eight time points during the first year of life. Potential differences in microbial profiles of infants treated with antibiotics versus healthy controls will be determined by use of 16S-23S rRNA gene analysis (IS-pro). Microbiota composition will be described by means of abundance, diversity and (dis)similarity. Diversity is calculated using the Shannon index. Dissimilarities between samples are calculated as the cosine distance between each pair of samples and analyzed with principal coordinate analysis. Clinical variables and possible associations are assessed by appropriate statistics. Both clinical quantitative and qualitative microbial effects of antibiotic treatment in early life may be demonstrated. These findings can be important, since there is evidence that manipulation of the infant microbiota by using pre- or probiotics can

The Early Use of Blinding in Therapeutic Clinical Research of Neurological Disorders

PubMed Central

Jensen, Matthew B.; Janik, Erika L.; Waclawik, Andrew J.

2016-01-01

We sought to identify early uses of blinding in therapeutic clinical trials of neurological disorders by multiple search methods. A 1784 report by Benjamin Franklin and others described the evaluation of the use of Mesmerism to treat neurological and other syndromes including headache and epilepsy, using blindfolds and screens. This report demonstrated the usefulness of blinding to reduce bias in clinical research, yet despite this early discovery, blinding was not widely accepted or routinely used until the 20th century. Blinded clinical trials began to be used for various neurological syndromes in the 1950s, sporadically at first and then increasing in frequency in subsequent years. The reason for this delay is unclear, but we propose several hypotheses. PMID:27617324

How can experience in clinical and community settings contribute to early medical education? A BEME systematic review.

PubMed

Dornan, T; Littlewood, S; Margolis, S A; Scherpbier, A; Spencer, J; Ypinazar, V

2006-02-01

Review period January 1992-December 2001. Final analysis July 2004-January 2005. BACKGROUND AND REVIEW CONTEXT: There has been no rigorous systematic review of the outcomes of early exposure to clinical and community settings in medical education. OBJECTIVES OF REVIEW: Identify published empirical evidence of the effects of early experience in medical education, analyse it, and synthesize conclusions from it. Identify the strengths and limitations of the research effort to date, and identify objectives for future research. Ovid search of: BEI, ERIC, Medline, CINAHL and EMBASE Additional electronic searches of: Psychinfo, Timelit, EBM reviews, SIGLE, and the Cochrane databases. Hand-searches of:Medical Education, Medical Teacher, Academic Medicine, Teaching and Learning in Medicine, Advances in Health Sciences Education, Journal of Educational Psychology. Authentic (real as opposed to simulated) human contact in a social or clinical context that enhances learning of health, illness and/or disease, and the role of the health professional. Early: What would traditionally have been regarded as the preclinical phase, usually the first 2 years. Inclusions: All empirical studies (verifiable, observational data) of early experience in the basic education of health professionals, whatever their design or methodology, including papers not in English. Evidence from other health care professions that could be applied to medicine was included. Not empirical; not early; post-basic; simulated rather than 'authentic' experience. Careful validation of selection processes. Coding by two reviewers onto an extensively modified version of the standard BEME coding sheet. Accumulation into an Access database. Secondary coding and synthesis of an interpretation. A total of 73 studies met the selection criteria and yielded 277 educational outcomes; 116 of those outcomes (from 38 studies) were rated strong and important enough to include in a narrative synthesis of results; 76% of those

Using Skype to support remote clinical supervision for health professionals delivering a sustained maternal early childhood programme: a phenomenographical study.

PubMed

Bruce, Tracey; Byrne, Fiona; Kemp, Lynn

2018-02-01

Skype technology was implemented by the Australian Maternal Early Childhood Sustained Home-visiting (MECSH) Support Service as a tool for the remote provision of clinical supervision for clinicians working in the MECSH program in Seoul, South Korea. To gain a better understanding of the processes underpinning sustainable delivery of remote clinical supervision using digital technologies. A phenomenographical study. Recorded notes and reflections on each supervision session, noting exemplars and characteristics of the experience were read and re-read to derive the characterizations of the experience. The experience has provided learnings in three domains: (1) the processes in using Skype; (2) supervisory processes; and (3) language translation, including managing clarity of, and time for translation. Skype has potential for use in remote provision of clinical supervision, including where translation is required. Further research evaluating the benefit of telesupervision from supervisor and supervisee perspectives is necessary to determine if it is a sustainable process.

Clinical and radiological outcomes of 5-year drug-free remission-steered treatment in patients with early arthritis: IMPROVED study.

PubMed

Akdemir, Gülşah; Heimans, Lotte; Bergstra, Sytske Anne; Goekoop, Robbert J; van Oosterhout, Maikel; van Groenendael, Johannes H L M; Peeters, André J; Steup-Beekman, Gerda M; Lard, Leroy R; de Sonnaville, Peter B J; Grillet, Bernard A M; Huizinga, Tom W J; Allaart, Cornelia F

2018-01-01

To determine the 5-year outcomes of early remission induction therapy followed by targeted treatment aimed at drug-free remission (DFR) in patients with early arthritis. In 12 hospitals, 610 patients with early (<2 years) rheumatoid arthritis (RA) or undifferentiated arthritis (UA) started on methotrexate (MTX) 25 mg/week and prednisone (60 mg/day tapered to 7.5 mg/day). Patients not in early remission (Disease Activity Score <1.6 after 4 months) were randomised (single blind) to arm 1, adding hydroxychloroquine 400 mg/day and sulfasalazine 2000 mg/day, or arm 2, switching to MTX plus adalimumab 40 mg/2 weeks. Treatment adjustments over time aimed at DFR. Outcomes were remission percentages, functional ability, toxicity and radiological damage progression after 5 years. After 4 months, 387 patients were in early remission, 83 were randomised to arm 1 and 78 to arm 2. After 5 years, 295/610 (48%) patients were in remission, 26% in sustained DFR (SDFR) (≥1 year) (220/387 (57%) remission and 135/387 (35%) SDFR in the early remission group, 50% remission, 11% SDFR in the randomisation arms without differences between the arms). More patients with UA (37% vs 23% RA, p=0.001) and more anticitrullinated protein antibody (ACPA)-negative patients (37% vs 18% ACPA-positive, p<0.001) achieved SDFR.Overall, mean Health Assessment Questionnaire was 0.6 (0.5), and median (IQR) damage progression was 0.5 (0-2.7) Sharp/van der Heijde points, with only five patients showing progression >25 points in 5 years. Five years of DFR-steered treatment in patients with early RA resulted in almost normal functional ability without clinically relevant joint damage across treatment groups. Patients who achieved early remission had the best clinical outcomes. There were no differences between the randomisation arms. SDFR is a realistic treatment goal. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved

Quality of breast cancer early detection services conducted by well woman clinics in the district of Gampaha, Sri Lanka.

PubMed

Vithana, Palatiyana Vithanage Sajeewanie Chiranthika; Ariyaratne, May; Jayawardana, Pl

2013-01-01

Breast cancer is the most common cancer diagnosed in females in Sri Lanka and early detection can lead to reduction in morbidity and mortality. To evaluate selected aspects of breast cancer early detection services implemented through well woman clinics (WWCs) in the Gampaha District. The study consisted of two components. A retrospective descriptive arm assessed clinical breast examination (CBE) coverage of target age group women (TGW) of 35-59 years in all the WWCs in Gampaha district over 2003- 2007. A cross sectional descriptive study additionally assessed quality of breast cancer early detection services. The Lot Quality Assurance Sampling (LQAS) technique was used to decide on the lot size and threshold values, which were computed as twenty and six clinics. Checklists were employed in assessing coverage, physical facilities and clinic activities. Client satisfaction on WWC services was assessed among 200 TGW attending 20 WWCs using an interviewer-administered questionnaire. CBE coverage in the Gampaha district increased only from 1.1-2.2% over 2003-2007. With regard to physical facilities, the number of clinics that were rated substandard varied between 7-18 (35- 90%). The items that were lacking included dust bins, notice boards, stationary, furniture and linen, and cleanliness of outside premises and toilets. With regard to clinic activities, punctuality of staff, late commencement of clinics, provision of health education, supervision, CBE and breast self-examination (BSE) were substandard in 7- 20 clinics (35-100%). Client satisfaction for WWC services was 45.2% (IQR: 38.7-54.8%) and only 11% had a score of ≥70%, the cut off set for satisfaction. Breast cancer early detection service coverage in the Gampaha district remained low (2.2%) in 2007, 11 years after commencing WWCs. All 20 clinics were substandard for overall CBE and BSE.

Clinical significance of early T-cell precursor acute lymphoblastic leukaemia: results of the Tokyo Children's Cancer Study Group Study L99-15.

PubMed

Inukai, Takeshi; Kiyokawa, Nobutaka; Campana, Dario; Coustan-Smith, Elaine; Kikuchi, Akira; Kobayashi, Miyuki; Takahashi, Hiroyuki; Koh, Katsuyoshi; Manabe, Atsushi; Kumagai, Masaaki; Ikuta, Koichiro; Hayashi, Yasuhide; Tsuchida, Masahiro; Sugita, Kanji; Ohara, Akira

2012-02-01

Early T-cell precursor acute lymphoblastic leukaemia (ETP-ALL) is a recently identified subtype of T-ALL with distinctive gene expression and cell marker profiles, poor response to chemotherapy and a very high risk of relapse. We determined the reliability of restricted panel of cell markers to identify EPT-ALL using a previously classified cohort. Then, we applied the cell marker profile that best discriminated ETP-ALL to a cohort of 91 patients with T-ALL enrolled in the Tokyo Children's Cancer Study Group L99-15 study, which included allogeneic stem cell transplantation (allo-SCT) for patients with poor prednisone response. Five of the 91 patients (5·5%) met the ETP-ALL criteria. There were no significant differences in presenting clinical features between these and the remaining 86 patients. Response to early remission induction therapy was inferior in ETP-ALL as compared with T-ALL. The ETP-ALL subgroup showed a significantly poorer event-free survival (4-year rate; 40%) than the T-ALL subgroup (70%, P=0·014). Of note, three of four relapsed ETP-ALL patients survived after allo-SCT, indicating that allo-SCT can be effective for this drug-resistant subtype of T-ALL. © 2011 Blackwell Publishing Ltd.

78 FR 5816 - Guidance for Industry on Clinical Pharmacogenomics: Premarket Evaluation in Early-Phase Clinical...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-28

.... The guidance provides recommendations on when and how genomic principles should be considered and... recommendations on when and how genomic principles should be considered and applied in early-phase clinical... the larger, later adequate, and well-controlled trials (phase 3) that are needed to support marketing...

AWBATTM: Early Clinical Experience

PubMed Central

Vandenberg, Victoria B.

2010-01-01

Objective: The purpose of this article is to describe the early clinical experience with AWBAT. Methods: Burn patients requiring (1) donor sites or (2) treatment of a superficial burn wound injury were treated. A total of 45 patients with 69 distinct wounds were included. AWBATTM-D was evaluated in donor sites and AWBATTM-S was evaluated in superficial partial-thickness burns. Days to healing, pain, hematoma/seroma formation, and infection were noted. Ease of application, adherence, transparency, and physical adaptability details were collected. Results: Average period to healing of donor sites treated with AWBAT-D (n=22 patients with n=26 wounds) was 11.2 days, σ =1.95, with a range of 8–15 days and a median of 11 days. Pain rating at 24 hours was 1.2, σ =0.43 (n=18) and at 48 hours mean was 1.2, σ =0.46 (n=15). Average period to healing of superficial burns treated with AWBAT-S (n=15 patients with n=18 wounds) was 8.1 days, σ =2.48, with a range of 5–13 days and a median of 7 days. Pain rating at 24 hours was 1.5, σ =0.85 (n=10) and at 48 hours mean was 1.75, σ =0.89 (n=8). There was zero incidence of hematoma/seroma. No infections were seen. Results indicate that AWBAT was easily applied with good initial adherence. It was noted to be transparent, conformant, and pliable. Discussion: Early experience demonstrates that AWBAT performs well on donor sites and superficial partial-thickness burns and delivers the desired attributes of a temporary skin substitute including good adherence, infection control, transparency, adapatability, and pain control. PMID:20361005

Faculty Development for Fostering Clinical Reasoning Skills in Early Medical Students Using a Modified Bayesian Approach.

PubMed

Addy, Tracie Marcella; Hafler, Janet; Galerneau, France

2016-01-01

Clinical reasoning is a necessary skill for medical students to acquire in the course of their education, and there is evidence that they can start this process at the undergraduate level. However, physician educators who are experts in their given fields may have difficulty conveying their complex thought processes to students. Providing faculty development that equips educators with tools to teach clinical reasoning may support skill development in early medical students. We provided faculty development on a modified Bayesian method of teaching clinical reasoning to clinician educators who facilitated small-group, case-based workshops with 2nd-year medical students. We interviewed them before and after the module regarding their perceptions on teaching clinical reasoning. We solicited feedback from the students about the effectiveness of the method in developing their clinical reasoning skills. We carried out this project during an institutional curriculum rebuild where clinical reasoning was a defined goal. At the time of the intervention, there was also increased involvement of the Teaching and Learning Center in elevating the status of teaching and learning. There was high overall satisfaction with the faculty development program. Both the faculty and the students described the modified Bayesian approach as effective in fostering the development of clinical reasoning skills. Through this work, we learned how to form a beneficial partnership between a clinician educator and Teaching and Learning Center to promote faculty development on a clinical reasoning teaching method for early medical students. We uncovered challenges faced by both faculty and early learners in this study. We observed that our faculty chose to utilize the method of teaching clinical reasoning in a variety of manners in the classroom. Despite obstacles and differing approaches utilized, we believe that this model can be emulated at other institutions to foster the development of clinical

The CDKL5 disorder is an independent clinical entity associated with early-onset encephalopathy.

PubMed

Fehr, Stephanie; Wilson, Meredith; Downs, Jenny; Williams, Simon; Murgia, Alessandra; Sartori, Stefano; Vecchi, Marilena; Ho, Gladys; Polli, Roberta; Psoni, Stavroula; Bao, Xinhua; de Klerk, Nick; Leonard, Helen; Christodoulou, John

2013-03-01

The clinical understanding of the CDKL5 disorder remains limited, with most information being derived from small patient groups seen at individual centres. This study uses a large international data collection to describe the clinical profile of the CDKL5 disorder and compare with Rett syndrome (RTT). Information on individuals with cyclin-dependent kinase-like 5 (CDKL5) mutations (n=86) and females with MECP2 mutations (n=920) was sourced from the InterRett database. Available photographs of CDKL5 patients were examined for dysmorphic features. The proportion of CDKL5 patients meeting the recent Neul criteria for atypical RTT was determined. Logistic regression and time-to-event analyses were used to compare the occurrence of Rett-like features in those with MECP2 and CDKL5 mutations. Most individuals with CDKL5 mutations had severe developmental delay from birth, seizure onset before the age of 3 months and similar non-dysmorphic features. Less than one-quarter met the criteria for early-onset seizure variant RTT. Seizures and sleep disturbances were more common than in those with MECP2 mutations whereas features of regression and spinal curvature were less common. The CDKL5 disorder presents with a distinct clinical profile and a subtle facial, limb and hand phenotype that may assist in differentiation from other early-onset encephalopathies. Although mutations in the CDKL5 gene have been described in association with the early-onset variant of RTT, in our study the majority did not meet these criteria. Therefore, the CDKL5 disorder should be considered separate to RTT, rather than another variant.

Early Clinical Features of Dengue Virus Infection in Nicaraguan Children: A Longitudinal Analysis

PubMed Central

Biswas, Hope H.; Ortega, Oscar; Gordon, Aubree; Standish, Katherine; Balmaseda, Angel; Kuan, Guillermina; Harris, Eva

2012-01-01

Background Tens of millions of dengue cases and approximately 500,000 life-threatening complications occur annually. New tools are needed to distinguish dengue from other febrile illnesses. In addition, the natural history of pediatric dengue early in illness in a community-based setting has not been well-defined. Methods Data from the multi-year, ongoing Pediatric Dengue Cohort Study of approximately 3,800 children aged 2–14 years in Managua, Nicaragua, were used to examine the frequency of clinical signs and symptoms by day of illness and to generate models for the association of signs and symptoms during the early phase of illness and over the entire course of illness with testing dengue-positive. Odds ratios (ORs) and 95% confidence intervals were calculated using generalized estimating equations (GEE) for repeated measures, adjusting for age and gender. Results One-fourth of children who tested dengue-positive did not meet the WHO case definition for suspected dengue. The frequency of signs and symptoms varied by day of illness, dengue status, and disease severity. Multivariable GEE models showed increased odds of testing dengue-positive associated with fever, headache, retro-orbital pain, myalgia, arthralgia, rash, petechiae, positive tourniquet test, vomiting, leukopenia, platelets ≤150,000 cells/mL, poor capillary refill, cold extremities and hypotension. Estimated ORs tended to be higher for signs and symptoms over the course of illness compared to the early phase of illness. Conclusions Day-by-day analysis of clinical signs and symptoms together with longitudinal statistical analysis showed significant associations with testing dengue-positive and important differences during the early phase of illness compared to the entire course of illness. These findings stress the importance of considering day of illness when developing prediction algorithms for real-time clinical management. PMID:22413033

Changes in neural circuitry associated with depression at pre-clinical, pre-motor and early motor phases of Parkinson's disease.

PubMed

Borgonovo, Janina; Allende-Castro, Camilo; Laliena, Almudena; Guerrero, Néstor; Silva, Hernán; Concha, Miguel L

2017-02-01

Although Parkinson's Disease (PD) is mostly considered a motor disorder, it can present at early stages as a non-motor pathology. Among the non-motor clinical manifestations, depression shows a high prevalence and can be one of the first clinical signs to appear, even a decade before the onset of motor symptoms. Here, we review the evidence of early dysfunction in neural circuitry associated with depression in the context of PD, focusing on pre-clinical, pre-motor and early motor phases of the disease. In the pre-clinical phase, structural and functional changes in the substantia nigra, basal ganglia and limbic structures are already observed. Some of these changes are linked to motor compensation mechanisms while others correspond to pathological processes common to PD and depression and thus could underlie the appearance of depressive symptoms during the pre-motor phase. Studies of the early motor phase (less than five years post diagnosis) reveal an association between the extent of damage in different monoaminergic systems and the appearance of emotional disorders. We propose that the limbic loop of the basal ganglia and the lateral habenula play key roles in the early genesis of depression in PD. Alterations in the neural circuitry linked with emotional control might be sensitive markers of the ongoing neurodegenerative process and thus may serve to facilitate an early diagnosis of this disease. To take advantage of this, we need to improve the clinical criteria and develop biomarkers to identify depression, which could be used to determine individuals at risk to develop PD. Copyright © 2016 Elsevier Ltd. All rights reserved.

Transient ischaemic attacks clinics provide equivalent and more efficient care than early in-hospital assessment.

PubMed

Martínez-Martínez, M M; Martínez-Sánchez, P; Fuentes, B; Cazorla-García, R; Ruiz-Ares, G; Correas-Callero, E; Lara-Lara, M; Díez-Tejedor, E

2013-02-01

Clinics for early management of transient ischaemic attacks (TIAs) have been developed in some stroke centres, resulting in reduced recurrence rates compared to appointment-based outpatient management, thus saving on hospitalization. We analysed the care process, recurrence rates and economic impact of the first year of work in our early-management TIA clinic and compared these with our previous in-hospital study protocols for low- and moderate-risk TIA patients. This was a prospective evaluation of the management of low- to moderate-risk TIA patients, comparing a new TIA clinic model (2010) with a previous hospitalization model (2009). Demographic data, vascular risk factor profiles, diagnostic test performance, secondary prevention measures, final aetiological diagnoses and cerebrovascular recurrences at 7 and 90 days were compared between in-hospital and TIA clinic assessed patients. We also carried out an economic comparison of the costs of each model's process. Two hundred and eleven low- to moderate-risk TIA patients were included, of whom 40.8% were hospitalized. There were no differences between the TIA clinic assessed and in-hospital assessed patients in terms of risk factor diagnosis and secondary prevention measures. The stroke recurrence rate (2.4% vs. 1.2%; P = 0.65) was low and similar for both groups (CI 95%, 0.214-20.436; P = 0.52). Cost per patient was €393.28 for clinic versus €1931.18 for in-hospital management. Outpatient management resulted in a 77.8% reduction in hospitalizations. Transient ischaemic attacks clinics are efficient for the early management of low- to moderate-risk TIA patients compared to in-hospital assessment, with no higher recurrence rates and at almost one-fifth the cost. © 2012 The Author(s) European Journal of Neurology © 2012 EFNS.

Reaching their potential: Perceived impact of a collaborative academic-clinical partnership programme for early career nurses in New Zealand.

PubMed

McKillop, Ann; Doughty, Lesley; Atherfold, Cheryl; Shaw, Kathy

2016-01-01

The dynamic nature of healthcare ensures that early career nurses enter an uncertain and complex world of practice and consequently require support to develop their practice, build confidence and reach their potential. The New Zealand Nurse Entry to Practice programme for registered nurses in their first year of practice has been operating since 2005 to enable safe and confident practice, improve the quality of care, and positively impact on recruitment and retention. This academic and clinical programme was offered as a partnership between a university and a clinical provider with postgraduate academic credits gained. The aim of this study was to explore the perceived impact of postgraduate university education for early career nurses in one regional health area of New Zealand. Participants were registered nurses who had completed the early career nurse programme and their clinical preceptors. The research was conducted via an online survey of 248 nurses and three focus groups to explore how the programme was experienced and its impact on knowledge and practice. Early career nurses and their preceptors found that the programme enables improved knowledge and skills of patient assessment, application of critical thinking to clinical practice, perceived improvement in patient care delivery and outcomes, enhanced interprofessional communication and knowledge sharing, and had a positive impact on professional awareness and career planning. This clinical-academic partnership positively impacted on the clinical practice and transition experience of early career nurses and was closely aligned to an organization's strategic plan for nursing workforce development. Copyright © 2015 Elsevier Ltd. All rights reserved.

Early-Onset Obsessive-Compulsive Disorder: A Subgroup with a Specific Clinical and Familial Pattern?

ERIC Educational Resources Information Center

Chabane, Nadia; Delorme, Richard; Millet, Bruno; Mouren, Marie-Christine; Leboyer, Marion; Pauls, David

2005-01-01

Background: The familial nature of obsessive-compulsive disorder (OCD) has been previously demonstrated. The identification of candidate symptoms such as age at onset may help to disentangle the clinical and genetic heterogeneity of the disorder. In this study, the specificity of early-onset OCD was investigated, focusing on the effect of gender,…

Incremental Validity in the Clinical Assessment of Early Childhood Development

ERIC Educational Resources Information Center

Liu, Xin; Zhou, Xiaobin; Lackaff, Julie

2013-01-01

The authors demonstrate the increment of clinical validity in early childhood assessment of physical impairment (PI), developmental delay (DD), and autism (AUT) using multiple standardized developmental screening measures such as performance measures and parent and teacher rating scales. Hierarchical regression and sensitivity/specificity analyses…

Predicting distant failure in early stage NSCLC treated with SBRT using clinical parameters.

PubMed

Zhou, Zhiguo; Folkert, Michael; Cannon, Nathan; Iyengar, Puneeth; Westover, Kenneth; Zhang, Yuanyuan; Choy, Hak; Timmerman, Robert; Yan, Jingsheng; Xie, Xian-J; Jiang, Steve; Wang, Jing

2016-06-01

The aim of this study is to predict early distant failure in early stage non-small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT) using clinical parameters by machine learning algorithms. The dataset used in this work includes 81 early stage NSCLC patients with at least 6months of follow-up who underwent SBRT between 2006 and 2012 at a single institution. The clinical parameters (n=18) for each patient include demographic parameters, tumor characteristics, treatment fraction schemes, and pretreatment medications. Three predictive models were constructed based on different machine learning algorithms: (1) artificial neural network (ANN), (2) logistic regression (LR) and (3) support vector machine (SVM). Furthermore, to select an optimal clinical parameter set for the model construction, three strategies were adopted: (1) clonal selection algorithm (CSA) based selection strategy; (2) sequential forward selection (SFS) method; and (3) statistical analysis (SA) based strategy. 5-cross-validation is used to validate the performance of each predictive model. The accuracy was assessed by area under the receiver operating characteristic (ROC) curve (AUC), sensitivity and specificity of the system was also evaluated. The AUCs for ANN, LR and SVM were 0.75, 0.73, and 0.80, respectively. The sensitivity values for ANN, LR and SVM were 71.2%, 72.9% and 83.1%, while the specificity values for ANN, LR and SVM were 59.1%, 63.6% and 63.6%, respectively. Meanwhile, the CSA based strategy outperformed SFS and SA in terms of AUC, sensitivity and specificity. Based on clinical parameters, the SVM with the CSA optimal parameter set selection strategy achieves better performance than other strategies for predicting distant failure in lung SBRT patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Early treatment of posterior crossbite - a randomised clinical trial

PubMed Central

2013-01-01

Background The aim of this randomised clinical trial was to assess the effect of early orthodontic treatment in contrast to normal growth effects for functional unilateral posterior crossbite in the late deciduous and early mixed dentition by means of three-dimensional digital model analysis. Methods This randomised clinical trial was assessed to analyse the orthodontic treatment effects for patients with functional unilateral posterior crossbite in the late deciduous and early mixed dentition using a two-step procedure: initial maxillary expansion followed by a U-bow activator therapy. In the treatment group 31 patients and in the control group 35 patients with a mean age of 7.3 years (SD 2.1) were monitored. The time between the initial assessment (T1) and the follow-up (T2) was one year. The orthodontic analysis was done by a three-dimensional digital model analysis. Using the ‘Digimodel’ software, the orthodontic measurements in the maxilla and mandible and for the midline deviation, the overjet and overbite were recorded. Results Significant differences between the control and the therapy group at T2 were detected for the anterior, median and posterior transversal dimensions of the maxilla, the palatal depth, the palatal base arch length, the maxillary arch length and inclination, the midline deviation, the overjet and the overbite. Conclusions Orthodontic treatment of a functional unilateral posterior crossbite with a bonded maxillary expansion device followed by U-bow activator therapy in the late deciduous and early mixed dentition is an effective therapeutic method, as evidenced by the results of this RCT. It leads to three-dimensional therapeutically induced maxillary growth effects. Dental occlusion is significantly improved, and the prognosis for normal craniofacial growth is enhanced. Trial registration Registration trial DRKS00003497 on DRKS PMID:23339736

Recent early clinical drug development for acute kidney injury.

PubMed

Gallagher, Kevin M; O'neill, Stephen; Harrison, Ewen M; Ross, James A; Wigmore, Stephen J; Hughes, Jeremy

2017-02-01

Despite significant need and historical trials, there are no effective drugs in use for the prevention or treatment of acute kidney injury (AKI). There are several promising agents in early clinical development for AKI and two trials have recently been terminated. There are also exciting new findings in pre-clinical AKI research. There is a need to take stock of current progress in the field to guide future drug development for AKI. Areas covered: The main clinical trial registries, PubMed and pharmaceutical company website searches were used to extract the most recent clinical trials for sterile, transplant and sepsis-associated AKI. We summarise the development of the agents recently in clinical trial, update on their trial progress, consider reasons for failed efficacy of two agents, and discuss new paradigms in pre-clinical targets for AKI. Agents covered include- QPI-1002, THR-184, BB-3, heme arginate, human recombinant alkaline phosphatase (recAP), ciclosporin A, AB103, levosimendan, AC607 and ABT-719. Expert opinion: Due to the heterogenous nature of AKI, agents with the widest pleiotropic effects on multiple pathophysiological pathways are likely to be most effective. Linking preclinical models to clinical indication and improving AKI definition and diagnosis are key areas for improvement in future clinical trials.

Early indicators and risk factors for ethical issues in clinical practice.

PubMed

Pavlish, Carol; Brown-Saltzman, Katherine; Hersh, Mary; Shirk, Marilyn; Nudelman, Olga

2011-03-01

Nurses in all clinical settings encounter ethical issues that frequently lead to moral distress. This critical incident study explored nurses' descriptions of ethically difficult situations to identify risk factors and early indicators of ethical conflicts. Employing the critical incident technique, researchers developed a questionnaire that collected information on ethically difficult situations, their risk factors and early indicators, nurse actions, and situational outcomes. Two nurse researchers independently analyzed and categorized data using a constant comparison technique. Most of the ethically difficult situations pertained to end-of-life care for children and adults. Conflicts in interpersonal relationships were prevalent. Nurses were especially moved by patient and family suffering and concerned about patient vulnerability, harm-benefit ratio, and patient autonomy. Researchers discovered risk factor categories for patients, families, healthcare providers, and health systems. Additionally, researchers found subcategories in six major categories of early indicators: signs of conflict, patient suffering, nurse distress, ethics violation, unrealistic expectations, and poor communication. Nurses are keenly aware of pertinent risk factors and early indicators of unfolding ethical conflicts. Many nurses reported feeling powerless in the face of ethical conflict. Research that develops interventions to strengthen nurses' voices in ethically difficult situation is warranted. Nurses are in a key position to identify patient situations with a high risk for ethical conflict. Initiating early ethics consultation and interventions can alter the course of pending conflicts and diminish the potential for patient and family suffering and nurses' moral distress. © 2011 Sigma Theta Tau International.

The clinical and histopathological characteristics of early-onset basal cell carcinoma in Asians.

PubMed

Yang, M Y; Kim, J M; Kim, G W; Mun, J H; Song, M; Ko, H C; Kim, B S; Kim, H S; Kim, M B

2017-01-01

Basal cell carcinoma (BCC) is by far the most common cancer in white populations. In addition, recent reports have demonstrated an increasing incidence of BCC in Korea. We have observed a significant number of early-onset BCC cases in which the disease occurred in patients younger than 50 years. To investigate the clinicopathological characteristics of early-onset BCC in an Asian population, specifically in Koreans. One hundred and five patients with early-onset BCC were enrolled from a total of 1047 BCC patients who underwent surgery between January 1997 and December 2014 (942 patients over the age of 50 years were designated as the control group). Early-onset BCC accounted for 10.03% of all 1047 cases and the incidence over time displayed an incremental trend. The early-onset group displayed similar results as the control group, with a predominance of female BCC patients and the majority of tumours displaying the following characteristics: small in size, occurring in sun-exposed areas and belonging to the noduloulcerative clinical subtype and nodular histopathological subtype. In comparison with a previous study in a Western population, the incidence of the disease in non-exposed areas of the body, as well as the proportion of tumours of the superficial histological subtype, were lower in Asian patients. Although the clinicopathological characteristics of BCC are well-known, these characteristics have not been determined for early-onset BCC in an Asian population. Therefore, this study is the first report on early-onset BCC in Asians, specifically in a Korean patient group. © 2016 European Academy of Dermatology and Venereology.

[Personalized cell therapy for early postoperative bullous keratopathy (experimental proof and clinical results)].

PubMed

Kasparov, A A; Kasparova, Evg A; Fadeeva, L L; Subbot, A M; Borodina, N V; Kasparova, E A; Kobzova, M V; Musaeva, G M; Pavliuk, A S

2013-01-01

The article presents the results of a long-term research on development and clinical application of personalized cell therapy (PCT) for treatment of early postoperative (manifesting within the first 3 months after surgery) bullous keratopathy (BK). The method of intracameral PCT implies in vitro incubation of the patient's blood sample with poly(A:U) stimulator, separation of the serum with activated leukocytes, and injection of the final cell preparation into the anterior chamber. The fundamental part of the research was aimed at a detailed description of the cell preparation and investigation of its possible mechanisms of action. Cytokine and growth factor level in the cell preparation suggested that its high clinical efficacy might be due to its ability to improve regeneration of damaged corneal endothelium. The clinical study was conducted on a group of 52 patients with early BK. A significant effect (smoothing of the Descement's membrane folds, complete resorption of corneal edema, improvement of corneal transparency, reduction of corneal thickness and increase of visual acuity by 0.49 +/- 0.27) was achieved in 44.2% of patients, while partial effect was seen in 21.1% of patients. There was no clinical effect in 34.6% of patients. In those patients who developed significant or partial clinical effect after the PCT, many endotheliocytes appeared to have multiple nuclei (2 and more). In some patients polyploid nuclei persisted for 3-5 years after the treatment. Polyploidy results from incomplete mitosis which might be due to regenerative processes in the endothelium stimulated by the PCT. Obviously, high efficacy and relative simplicity of the method should promote its further clinical introduction.

The CDKL5 disorder is an independent clinical entity associated with early-onset encephalopathy

PubMed Central

Fehr, Stephanie; Wilson, Meredith; Downs, Jenny; Williams, Simon; Murgia, Alessandra; Sartori, Stefano; Vecchi, Marilena; Ho, Gladys; Polli, Roberta; Psoni, Stavroula; Bao, Xinhua; de Klerk, Nick; Leonard, Helen; Christodoulou, John

2013-01-01

The clinical understanding of the CDKL5 disorder remains limited, with most information being derived from small patient groups seen at individual centres. This study uses a large international data collection to describe the clinical profile of the CDKL5 disorder and compare with Rett syndrome (RTT). Information on individuals with cyclin-dependent kinase-like 5 (CDKL5) mutations (n=86) and females with MECP2 mutations (n=920) was sourced from the InterRett database. Available photographs of CDKL5 patients were examined for dysmorphic features. The proportion of CDKL5 patients meeting the recent Neul criteria for atypical RTT was determined. Logistic regression and time-to-event analyses were used to compare the occurrence of Rett-like features in those with MECP2 and CDKL5 mutations. Most individuals with CDKL5 mutations had severe developmental delay from birth, seizure onset before the age of 3 months and similar non-dysmorphic features. Less than one-quarter met the criteria for early-onset seizure variant RTT. Seizures and sleep disturbances were more common than in those with MECP2 mutations whereas features of regression and spinal curvature were less common. The CDKL5 disorder presents with a distinct clinical profile and a subtle facial, limb and hand phenotype that may assist in differentiation from other early-onset encephalopathies. Although mutations in the CDKL5 gene have been described in association with the early-onset variant of RTT, in our study the majority did not meet these criteria. Therefore, the CDKL5 disorder should be considered separate to RTT, rather than another variant. PMID:22872100

Early repolarization in Wolff-Parkinson-White syndrome: prevalence and clinical significance.

PubMed

Mizumaki, Koichi; Nishida, Kunihiro; Iwamoto, Jotaro; Nakatani, Yosuke; Yamaguchi, Yoshiaki; Sakamoto, Tamotsu; Tsuneda, Takayuki; Inoue, Hiroshi; Sakabe, Masao; Fujiki, Akira

2011-08-01

Idiopathic ventricular fibrillation (IVF) with early repolarization (ER) has recently been reported; however, ER is a common finding in healthy subjects and is also found sporadically in patients with Wolff-Parkinson-White (WPW) syndrome. The present study was designed to evaluate the prevalence and clinical significance of ER in patients with WPW syndrome. One hundred and eleven patients with WPW syndrome were studied retrospectively. Early repolarization was defined as QRS slurring or notching with J-point elevation ≥ 1 mm. The prevalence of ER was determined before and after successful catheter ablation. Before ablation, ER was found in 35 of 75 patients with a left free wall, 6 of 23 with a right free wall, and 7 of 13 with a septal accessory pathway (48 of 111, 43% as a whole). Early repolarization was always observed in leads with positive deflection of the initial part of the delta wave. After successful ablation of accessory pathways, ER was preserved in 28 (25%), disappeared in 20 (18%), and newly developed in 8 (7%) patients. In the remaining 55 (50%) patients, ER was not observed either before or after ablation. In patients with persistent ER, the amplitude and width of ER were significantly decreased 3-7 days after the ablation (1.7 ± 0.7 vs. 1.4 ± 0.6 mm, P < 0.005 and 42 ± 11 vs. 34 ± 9 ms, P < 0.001, respectively). In patients with WPW syndrome, ER could be partly related to early depolarization through the accessory pathway. However, persistent ER and new ER appearing after the ablation were frequently found. Therefore, in these patients, mechanisms other than early depolarization may be involved in the genesis of ER.

Patient-specific instrumentation improved mechanical alignment, while early clinical outcome was comparable to conventional instrumentation in TKA.

PubMed

Anderl, Werner; Pauzenberger, Leo; Kölblinger, Roman; Kiesselbach, Gabriele; Brandl, Georg; Laky, Brenda; Kriegleder, Bernhard; Heuberer, Philipp; Schwameis, Eva

2016-01-01

The aim of this prospective study was to compare early clinical outcome, radiological limb alignment, and three-dimensional (3D)-component positioning between conventional and computed tomography (CT)-based patient-specific instrumentation (PSI) in primary mobile-bearing total knee arthroplasty (TKA). Two hundred ninety consecutive patients (300 knees) with severe, debilitating osteoarthritis scheduled for TKA were included in this study using either conventional instrumentation (CVI, n = 150) or PSI (n = 150). Patients were clinically assessed before and 2 years after surgery according to the Knee-Society-Score (KSS) and the visual-analog-scale for pain (VAS). Additionally, the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) and the Oxford-Knee-Score (OKS) were collected at follow-up. To evaluate accuracy of CVI and PSI, hip-knee-ankle angle (HKA) and 3D-component positioning were assessed on postoperative radiographs and CT. Data of 222 knees (CVI: n = 108, PSI: n = 114) were available for analysis after a mean follow-up of 28.6 ± 5.2 months. At the early follow-up, clinical outcome (KSS, VAS, WOMAC, OKS) was comparable between the two groups. Mean HKA-deviation from the targeted neutral mechanical axis (CVI: 2.2° ± 1.7°; PSI: 1.5° ± 1.4°; p < 0.001), rates of outliers (CVI: 22.2%; PSI: 9.6%; p = 0.016), and 3D-component positioning outliers were significantly lower in the PSI group. Non-outliers (HKA: 180° ± 3°) showed better clinical results than outliers at the 2-year follow-up. CT-based PSI compared with CVI improves accuracy of mechanical alignment restoration and 3D-component positioning in primary TKA. While clinical outcome was comparable between the two instrumentation groups at early follow-up, significantly inferior outcome was detected in the subgroup of HKA-outliers. Prospective comparative study, Level II.

Radiofrequency ablation versus resection for Barcelona clinic liver cancer very early/early stage hepatocellular carcinoma: a systematic review.

PubMed

He, Zhen-Xin; Xiang, Pu; Gong, Jian-Ping; Cheng, Nan-Sheng; Zhang, Wei

2016-01-01

To compare the long-term survival outcomes of radiofrequency ablation and liver resection for single very early/early stage hepatocellular carcinoma (HCC). The Cochrane Library (Issue 3, 2015), Embase (1974 to March 15, 2015), PubMed (1950 to March 15, 2015), Web of Science (1900 to March 15, 2015), and Chinese Biomedical Literature Database (1978 to March 15, 2015) were searched to identify relevant trials. Only trials that compared radiofrequency ablation and liver resection for single very early stage (≤2 cm) or early stage (≤3 cm) HCC according to the Barcelona clinic liver cancer (BCLC) staging system were considered for inclusion in this review. The primary outcomes that we analyzed were the 3-year and 5-year overall survival (OS) rates, and the secondary outcomes that we analyzed were the 3-year and 5-year disease-free survival (DFS) rates. Review Manager 5.3 was used to perform a cumulative meta-analysis. Possible publication bias was examined using a funnel plot. A random-effects model was applied to summarize the various outcomes. Six studies involving 947 patients were identified that compared radiofrequency ablation (n=528) to liver resection (n=419) for single BCLC very early HCC. In these six studies, the rates of 3-year OS, 5-year OS, 3-year DFS, and 5-year DFS were significantly lower in the radiofrequency ablation group than in the liver resection group (risk ratio [RR] =0.90, 95% confidence interval [CI]: 0.83-0.98, P=0.01; RR =0.84, 95% CI: 0.75-0.95, P=0.004; RR =0.77, 95% CI: 0.60-0.98, P=0.04; and RR =0.70, 95% CI: 0.52-0.94, P=0.02, respectively). Ten studies involving 2,501 patients were identified that compared radiofrequency ablation (n=1,476) to liver resection (n=1,025) for single BCLC early HCC. In these ten studies, the rates of 3-year OS, 5-year OS, 3-year DFS, and 5-year DFS were also significantly lower in the radiofrequency ablation group than in the liver resection group (RR =0.93, 95% CI: 0.88-0.98, P=0.003; RR =0.84, 95% CI

Radiofrequency ablation versus resection for Barcelona clinic liver cancer very early/early stage hepatocellular carcinoma: a systematic review

PubMed Central

He, Zhen-Xin; Xiang, Pu; Gong, Jian-Ping; Cheng, Nan-Sheng; Zhang, Wei

2016-01-01

Aim To compare the long-term survival outcomes of radiofrequency ablation and liver resection for single very early/early stage hepatocellular carcinoma (HCC). Methods The Cochrane Library (Issue 3, 2015), Embase (1974 to March 15, 2015), PubMed (1950 to March 15, 2015), Web of Science (1900 to March 15, 2015), and Chinese Biomedical Literature Database (1978 to March 15, 2015) were searched to identify relevant trials. Only trials that compared radiofrequency ablation and liver resection for single very early stage (≤2 cm) or early stage (≤3 cm) HCC according to the Barcelona clinic liver cancer (BCLC) staging system were considered for inclusion in this review. The primary outcomes that we analyzed were the 3-year and 5-year overall survival (OS) rates, and the secondary outcomes that we analyzed were the 3-year and 5-year disease-free survival (DFS) rates. Review Manager 5.3 was used to perform a cumulative meta-analysis. Possible publication bias was examined using a funnel plot. A random-effects model was applied to summarize the various outcomes. Results Six studies involving 947 patients were identified that compared radiofrequency ablation (n=528) to liver resection (n=419) for single BCLC very early HCC. In these six studies, the rates of 3-year OS, 5-year OS, 3-year DFS, and 5-year DFS were significantly lower in the radiofrequency ablation group than in the liver resection group (risk ratio [RR] =0.90, 95% confidence interval [CI]: 0.83–0.98, P=0.01; RR =0.84, 95% CI: 0.75–0.95, P=0.004; RR =0.77, 95% CI: 0.60–0.98, P=0.04; and RR =0.70, 95% CI: 0.52–0.94, P=0.02, respectively). Ten studies involving 2,501 patients were identified that compared radiofrequency ablation (n=1,476) to liver resection (n=1,025) for single BCLC early HCC. In these ten studies, the rates of 3-year OS, 5-year OS, 3-year DFS, and 5-year DFS were also significantly lower in the radiofrequency ablation group than in the liver resection group (RR =0.93, 95% CI: 0.88–0

Effectiveness of the Lidcombe Program for early stuttering in Australian community clinics.

PubMed

O'Brian, Sue; Iverach, Lisa; Jones, Mark; Onslow, Mark; Packman, Ann; Menzies, Ross

2013-12-01

This study explored the effectiveness of the Lidcombe Program for early stuttering in community clinics. Participants were 31 speech-language pathologists (SLPs) using the Lidcombe Program in clinics across Australia, and 57 of their young stuttering clients. Percentage of syllables stuttered (%SS) was collected 9 months after beginning treatment along with information about variables likely to influence outcomes. The mean %SS for the 57 children 9 months after starting treatment was 1.7. The most significant predictor of outcome was Lidcombe Program Trainers Consortium (LPTC) training. The children of trained SLPs (n = 19), compared to the children of untrained SLPs, took 76% more sessions to complete stage 1, but achieved 54% lower %SS scores, 9 months after starting treatment. Results suggest that outcomes for the Lidcombe Program in the general community may be comparable to those obtained in clinical trials when SLPs receive formal training and support.

Inside information: Financial conflicts of interest for research subjects in early phase clinical trials.

PubMed

Helft, Paul R; Ratain, Mark J; Epstein, Richard A; Siegler, Mark

2004-05-05

In recent years, several research subjects have told us that they had bought or intended to buy stock in the companies sponsoring the clinical trials in which they were enrolled. This situation has led us to ask what, if any, are physician-investigators' scientific, ethical, and legal responsibilities concerning research subjects who choose to buy stock in the companies sponsoring the clinical trials in which they are participating. Although the scope of this problem is unknown and is likely to be small, this commentary examines the scientific, ethical, and legal concerns raised by such activities on the part of research subjects enrolled in early phase clinical trials. In addition, this commentary also outlines the basis for our opinion that research subjects involved in an early phase clinical trial should avoid the financial conflicts of interest created by trading stock in the company sponsoring the clinical trial.

Renal Blood Flow, Glomerular Filtration Rate, and Renal Oxygenation in Early Clinical Septic Shock.

PubMed

Skytte Larsson, Jenny; Krumbholz, Vitus; Enskog, Anders; Bragadottir, Gudrun; Redfors, Bengt; Ricksten, Sven-Erik

2018-06-01

Data on renal hemodynamics, function, and oxygenation in early clinical septic shock are lacking. We therefore measured renal blood flow, glomerular filtration rate, renal oxygen consumption, and oxygenation in patients with early septic shock. Prospective comparative study. General and cardiothoracic ICUs. Patients with norepinephrine-dependent early septic shock (n = 8) were studied within 24 hours after arrival in the ICU and compared with postcardiac surgery patients without acute kidney injury (comparator group, n = 58). None. Data on systemic hemodynamics and renal variables were obtained during two 30-minute periods. Renal blood flow was measured by the infusion clearance of para-aminohippuric acid, corrected for renal extraction of para-aminohippuric acid. Renal filtration fraction was measured by renal extraction of chromium-51 labeled EDTA. Renal oxygenation was estimated from renal oxygen extraction. Renal oxygen delivery (-24%; p = 0.037) and the renal blood flow-to-cardiac index ratio (-21%; p = 0.018) were lower, renal vascular resistance was higher (26%; p = 0.027), whereas renal blood flow tended to be lower (-19%; p = 0.068) in the septic group. Glomerular filtration rate (-32%; p = 0.006) and renal sodium reabsorption (-29%; p = 0.014) were both lower in the septic group. Neither renal filtration fraction nor renal oxygen consumption differed significantly between groups. Renal oxygen extraction was significantly higher in the septic group (28%; p = 0.022). In the septic group, markers of tubular injury were elevated. In early clinical septic shock, renal function was lower, which was accompanied by renal vasoconstriction, a lower renal oxygen delivery, impaired renal oxygenation, and tubular sodium reabsorption at a high oxygen cost compared with controls.

Ultra-wide-field scanning laser ophthalmoscopy assists in the clinical detection and evaluation of asymptomatic early-stage familial exudative vitreoretinopathy.

PubMed

Lyu, Jiao; Zhang, Qi; Wang, Shi-Yuan; Chen, Yi-Ye; Xu, Yu; Zhao, Pei-Quan

2017-01-01

This study aims to investigate the ability of the ultra-wide-field scanning laser ophthalmoscope (UWF SLO) in clinically detecting and evaluating asymptomatic early-stage familial exudative vitreoretinopathy (FEVR). We retrospectively reviewed 163 eyes of 83 asymptomatic family members of 48 patients with FEVR. UWF SLO imaging (Optos® PLC, Scotland, UK) was performed on asymptomatic family members as a preliminary screening test for fundus anomalies, and the findings were compared with subsequent examinations using indirect fundus ophthalmoscopy in full mydriasis, fluorescein angiography (FA), fundus autoflourescence, and genetic sequencing. A total of 86 eyes of 43 asymptomatic family members were clinically diagnosed with early-stage FEVR, and 17 of the affected 43 family members were also genetically diagnosed. Compared with FA as a standard, the UWF SLO was highly effective in diagnosing FEVR with a sensitivity and specificity of 93.0 % and 97.5 %, respectively. The UWF SLO was able to diagnose early-stage FEVR in 93.0 % of eyes, and guided the selection of therapies in 46.5 % of the eyes studied. UWF SLO is a valuable imaging tool for detecting fundus anomalies related to early-stage FEVR, and this tool can assist in the clinical diagnosis and evaluation of early-stage FEVR in asymptomatic family members of patients with FEVR.

Clinical Implications of a Dimensional Approach: The Normal:Abnormal Spectrum of Early Irritability.

PubMed

Wakschlag, Lauren S; Estabrook, Ryne; Petitclerc, Amelie; Henry, David; Burns, James L; Perlman, Susan B; Voss, Joel L; Pine, Daniel S; Leibenluft, Ellen; Briggs-Gowan, Margaret L

2015-08-01

The importance of dimensional approaches is widely recognized, but an empirical base for clinical application is lacking. This is particularly true for irritability, a dimensional phenotype that cuts across many areas of psychopathology and manifests early in life. We examine longitudinal, dimensional patterns of irritability and their clinical import in early childhood. Irritability was assessed longitudinally over an average of 16 months in a clinically enriched, diverse community sample of preschoolers (N = 497; mean = 4.2 years; SD = 0.8). Using the Temper Loss scale of the Multidimensional Assessment Profile of Disruptive Behavior (MAP-DB) as a developmentally sensitive indicator of early childhood irritability, we examined its convergent/divergent, clinical, and incremental predictive validity, and modeled its linear and nonlinear associations with clinical risk. The Temper Loss scale demonstrated convergent and divergent validity to child and maternal factors. In multivariate analyses, Temper Loss predicted mood (separation anxiety disorder [SAD], generalized anxiety disorder [GAD], and depression/dysthymia), disruptive (oppositional defiant disorder [ODD], attention-deficit/hyperactivity disorder [ADHD], and conduct disorder [CD]) symptoms. Preschoolers with even mildly elevated Temper Loss scale scores showed substantially increased risk of symptoms and disorders. For ODD, GAD, SAD, and depression, increases in Temper Loss scale scores at the higher end of the dimension had a greater impact on symptoms relative to increases at the lower end. Temper Loss scale scores also showed incremental validity over DSM-IV disorders in predicting subsequent impairment. Finally, accounting for the substantial heterogeneity in longitudinal patterns of Temper Loss significantly improved prediction of mood and disruptive symptoms. Dimensional, longitudinal characterization of irritability informs clinical prediction. A vital next step will be empirically generating

Identifying autism early: The Toddlers at Risk of Autism Clinic model.

PubMed

Davis, Tessa; Clifton, Deirdre; Papadopoulos, Con

2015-07-01

This paper describes the Toddlers at Risk of Autism Clinic (TRAC), which utilises the Social Attention and Communication Study (SACS) and/or Autism Detection in Early Childhood (ADEC) play-based assessments to facilitate the early diagnosis of autism. A retrospective audit was conducted of all 42 children assessed over a 3-year period in the TRAC. A semi-structured interview and play-based assessment (SACS and ADEC) were used to aid experienced clinicians in diagnosing autism. Intervention was recommended, and families were routinely followed up. Analysis was conducted on the tools used, the outcomes of assessment, diagnosis and stability of diagnosis on follow-up. During this period, 35 boys and 7 girls were assessed, with a mean age of 25 months. The average waiting time for clinic was 11.6 weeks. Twenty-five patients were diagnosed with autism; 90.5% of toddlers given an initial diagnosis retained that diagnosis at follow-up. Out of the 17 children who were not diagnosed with autism in the TRAC, one child was later diagnosed with autism. Experienced clinicians can use the SACS and/or ADEC to assist with a Diagnostic and Statistical Manual diagnosis of autism in toddlers. © 2015 The Authors. Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

[The clinical characteristics of the early manifestations of radiation exposure in children].

PubMed

Evdokimov, I K

1993-11-01

The article substantiates the necessity to conduct the thorough study not only of the remote consequences of the Chernobyl APS disaster, but also of the early clinical manifestations of radiation influence in children, as a most vulnerable group in respect to radiation. Age factor is considered to be one of the dominant features which influence upon the absorptive capacity of thyroid gland in respect to radioiodine, and thus provoking a high vulnerability of children in crisis situations. The authors study hematological peculiarities of radioreactions in children and adults. There are recommendations for preventing the reception of radionuclides by babies during lactation.

The H2 robotic exoskeleton for gait rehabilitation after stroke: early findings from a clinical study.

PubMed

Bortole, Magdo; Venkatakrishnan, Anusha; Zhu, Fangshi; Moreno, Juan C; Francisco, Gerard E; Pons, Jose L; Contreras-Vidal, Jose L

2015-06-17

Stroke significantly affects thousands of individuals annually, leading to considerable physical impairment and functional disability. Gait is one of the most important activities of daily living affected in stroke survivors. Recent technological developments in powered robotics exoskeletons can create powerful adjunctive tools for rehabilitation and potentially accelerate functional recovery. Here, we present the development and evaluation of a novel lower limb robotic exoskeleton, namely H2 (Technaid S.L., Spain), for gait rehabilitation in stroke survivors. H2 has six actuated joints and is designed to allow intensive overground gait training. An assistive gait control algorithm was developed to create a force field along a desired trajectory, only applying torque when patients deviate from the prescribed movement pattern. The device was evaluated in 3 hemiparetic stroke patients across 4 weeks of training per individual (approximately 12 sessions). The study was approved by the Institutional Review Board at the University of Houston. The main objective of this initial pre-clinical study was to evaluate the safety and usability of the exoskeleton. A Likert scale was used to measure patient's perception about the easy of use of the device. Three stroke patients completed the study. The training was well tolerated and no adverse events occurred. Early findings demonstrate that H2 appears to be safe and easy to use in the participants of this study. The overground training environment employed as a means to enhance active patient engagement proved to be challenging and exciting for patients. These results are promising and encourage future rehabilitation training with a larger cohort of patients. The developed exoskeleton enables longitudinal overground training of walking in hemiparetic patients after stroke. The system is robust and safe when applied to assist a stroke patient performing an overground walking task. Such device opens the opportunity to study means

Critical illness polyneuropathy (CIP) in neurological early rehabilitation: clinical and neurophysiological features.

PubMed

Schmidt, Simone B; Rollnik, Jens D

2016-12-15

Critical illness polyneuropathy (CIP) is a complex disease affecting 30-70% of critically ill patients. Clinical (Barthel index, length of stay (LOS), morbidity, duration of mechanical ventilation, routine lab results) and neurophysiological (neurography) data of 191 patients admitted to neurological early rehabilitation and diagnosed with CIP have been analyzed retrospectively. CIP diagnosis was correct in 159 cases (83%). In this study, systemic inflammation, sepsis, systemic inflammatory response syndrome (SIRS), multiple organic failure (MOF), chronic renal failure, liver dysfunction, mechanical ventilation, diabetes, dyslipidemia and impaired ion homeostasis (hypocalcaemia, hypokalemia) were associated with CIP. Neurography, in particular of the peroneal, sural, tibial and median nerves, helped to identify CIP patients. Compound muscle action potential amplitude (r = -0.324, p < 0.05), as well as sensory (r = -0.389, p < 0.05) and motor conduction velocity (r = -0.347, p < 0.05) of the median nerve correlated with LOS in neurological early rehabilitation but not with outcome measures. In most cases, diagnosis of CIP among neurological early rehabilitation patients seems to be correct. Neurography may help to verify the diagnosis and to learn more about CIP pathophysiology, but it does not allow outcome prediction. Further studies on CIP are strongly encouraged.

Clinical and molecular characterization of KCNT1-related severe early-onset epilepsy

PubMed Central

Nair, Umesh; Malhotra, Sony; Meyer, Esther; Trump, Natalie; Gazina, Elena V.; Papandreou, Apostolos; Ngoh, Adeline; Ackermann, Sally; Ambegaonkar, Gautam; Appleton, Richard; Desurkar, Archana; Eltze, Christin; Kneen, Rachel; Kumar, Ajith V.; Lascelles, Karine; Montgomery, Tara; Ramesh, Venkateswaran; Samanta, Rajib; Scott, Richard H.; Tan, Jeen; Whitehouse, William; Poduri, Annapurna; Scheffer, Ingrid E.; Chong, W.K. “Kling”; Cross, J. Helen; Topf, Maya; Petrou, Steven

2018-01-01

Objective To characterize the phenotypic spectrum, molecular genetic findings, and functional consequences of pathogenic variants in early-onset KCNT1 epilepsy. Methods We identified a cohort of 31 patients with epilepsy of infancy with migrating focal seizures (EIMFS) and screened for variants in KCNT1 using direct Sanger sequencing, a multiple-gene next-generation sequencing panel, and whole-exome sequencing. Additional patients with non-EIMFS early-onset epilepsy in whom we identified KCNT1 variants on local diagnostic multiple gene panel testing were also included. When possible, we performed homology modeling to predict the putative effects of variants on protein structure and function. We undertook electrophysiologic assessment of mutant KCNT1 channels in a xenopus oocyte model system. Results We identified pathogenic variants in KCNT1 in 12 patients, 4 of which are novel. Most variants occurred de novo. Ten patients had a clinical diagnosis of EIMFS, and the other 2 presented with early-onset severe nocturnal frontal lobe seizures. Three patients had a trial of quinidine with good clinical response in 1 patient. Computational modeling analysis implicates abnormal pore function (F346L) and impaired tetramer formation (F502V) as putative disease mechanisms. All evaluated KCNT1 variants resulted in marked gain of function with significantly increased channel amplitude and variable blockade by quinidine. Conclusions Gain-of-function KCNT1 pathogenic variants cause a spectrum of severe focal epilepsies with onset in early infancy. Currently, genotype-phenotype correlations are unclear, although clinical outcome is poor for the majority of cases. Further elucidation of disease mechanisms may facilitate the development of targeted treatments, much needed for this pharmacoresistant genetic epilepsy. PMID:29196579

Nerve Growth Factor: Early Studies And Recent Clinical Trials.

PubMed

Rocco, Maria Luisa; Soligo, Marzia; Manni, Luigi; Aloe, Luigi

2018-04-11

Since its discovery, nerve growth factor (NGF) has long occupied a critical role in developmental and adult neurobiology for its many important regulatory functions on the survival, growth and differentiation of nerve cells in the peripheral and central nervous system. NGF is the first discovered member of a family of neurotrophic factors, collectively indicated as neurotrophins, (which include brain-derived neurotrophic factor, neurotrophin-3 and neurotrophin 4/5). NGF was discovered for its action on the survival and differentiation of selected populations of peripheral neurons. Since then, an enormous number of basic and human studies were undertaken to explore the role of purified NGF to prevent the death of NGF-receptive cells. These studies revealed that NGF possesses important therapeutic properties, after topical administration, on human cutaneous pressure ulcer, corneal ulcers, glaucoma, retinal maculopathy, Retinitis Pigmentosa and in pediatric optic gliomas and brain traumas. The aim of this review is to present our previous, recent and ongoing clinical studies on the therapeutic properties of NGF. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Concentration-Response Modeling of ECG Data From Early-Phase Clinical Studies as an Alternative Clinical and Regulatory Approach to Assessing QT Risk - Experience From the Development Program of Lemborexant.

PubMed

Murphy, Patricia J; Yasuda, Sanae; Nakai, Kenya; Yoshinaga, Takashi; Hall, Nancy; Zhou, Meijian; Aluri, Jagadeesh; Rege, Bhaskar; Moline, Margaret; Ferry, Jim; Darpo, Borje

2017-01-01

Lemborexant is a novel dual orexin receptor antagonist being developed to treat insomnia. Its potential to cause QT prolongation was evaluated using plasma concentration-response (CR) modeling applied to data from 2 multiple ascending-dose (MAD) studies. In the primary MAD study, placebo or lemborexant (2.5 to 75 mg) was administered for 14 consecutive nights. In another MAD study designed to "bridge" pharmacokinetic and safety data between Japanese and non-Japanese subjects (J-MAD), placebo or lemborexant (2.5, 10, or 25 mg) was administered for 14 consecutive nights. QT intervals were estimated using a high-precision measurement technique and evaluated using a linear mixed-effects CR model, for each study separately and for the pooled data set. When each study was analyzed separately, the slopes of the CR relationship were shallow and not statistically significant. In the pooled analysis, the slope of the CR relationship was -0.00002 milliseconds per ng/mL (90%CI, -0.01019 to 0.01014 milliseconds). The highest observed C max was 400 ng/mL, representing a margin 8-fold above exposures expected for the highest planned clinical dose. The model-predicted QTc effect at 400 ng/mL was 1.1 milliseconds (90%CI, -3.49 to 5.78 milliseconds). In neither the J-MAD study nor the pooled analysis was an effect of race identified. CR modeling of data from early-phase clinical studies, including plasma levels far exceeding those anticipated clinically, indicated that a QT effect >10 milliseconds could be excluded. Regulatory agreement with this methodology demonstrates the effectiveness of a CR modeling approach as an alternative to thorough QT studies. © 2016, The American College of Clinical Pharmacology.

Early- and Late-Onset Depression in Late Life: A Prospective Study on Clinical and Structural Brain Characteristics and Response to Electroconvulsive Therapy.

PubMed

Dols, Annemiek; Bouckaert, Filip; Sienaert, Pascal; Rhebergen, Didi; Vansteelandt, Kristof; Ten Kate, Mara; de Winter, Francois-Laurent; Comijs, Hannie C; Emsell, Louise; Oudega, Mardien L; van Exel, Eric; Schouws, Sigfried; Obbels, Jasmien; Wattjes, Mike; Barkhof, Frederik; Eikelenboom, Piet; Vandenbulcke, Mathieu; Stek, Max L

2017-02-01

The clinical profile of late-life depression (LLD) is frequently associated with cognitive impairment, aging-related brain changes, and somatic comorbidity. This two-site naturalistic longitudinal study aimed to explore differences in clinical and brain characteristics and response to electroconvulsive therapy (ECT) in early- (EOD) versus late-onset (LOD) late-life depression (respectively onset <55 and ≥55 years). Between January 2011 and December 2013, 110 patients aged 55 years and older with ECT-treated unipolar depression were included in The Mood Disorders in Elderly treated with ECT study. Clinical profile and somatic health were assessed. Magnetic resonance imaging (MRI) scans were performed before the first ECT and visually rated. Response rate was 78.2% and similar between the two sites but significantly higher in LOD compared with EOD (86.9 versus 67.3%). Clinical, somatic, and brain characteristics were not different between EOD and LOD. Response to ECT was associated with late age at onset and presence of psychotic symptoms and not with structural MRI characteristics. In EOD only, the odds for a higher response were associated with a shorter index episode. The clinical profile, somatic comorbidities, and brain characteristics in LLD were similar in EOD and LOD. Nevertheless, patients with LOD showed a superior response to ECT compared with patients with EOD. Our results indicate that ECT is very effective in LLD, even in vascular burdened patients. Copyright © 2017 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

76 FR 70152 - Pilot Program for Early Feasibility Study Investigational Device Exemption Applications

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-10

...] Pilot Program for Early Feasibility Study Investigational Device Exemption Applications AGENCY: Food and... feasibility study investigational device exemption (IDE) applications. The pilot program will conform to the... Feasibility Medical Device Clinical Studies, Including Certain First in Human (FIH) Studies.'' Under the pilot...

[Early clinical trials in paediatric oncology in Spain: a nationwide perspective].

PubMed

Bautista, Francisco; Gallego, Soledad; Cañete, Adela; Mora, Jaume; Díaz de Heredia, Cristina; Cruz, Ofelia; Fernández, José María; Rives, Susana; Berlanga, Pablo; Hladun, Raquel; Juan Ribelles, Antonio; Madero, Luis; Ramírez, Manuel; Fernández Delgado, Rafael; Pérez-Martínez, Antonio; Mata, Cristina; Llort, Anna; Martín Broto, Javier; Cela, María Elena; Ramírez, Gema; Sábado, Constantino; Acha, Tomás; Astigarraga, Itziar; Sastre, Ana; Muñoz, Ascensión; Guibelalde, Mercedes; Moreno, Lucas

2017-09-01

Cancer is the leading cause of death between the first year of life and adolescence, and some types of diseases are still a major challenge in terms of cure. There is, therefore, a major need for new drugs. Recent findings in cancer biology open the door to the development of targeted therapies against individual molecular changes, as well as immunotherapy. Promising results in adult anti-cancer drug development have not yet been translated into paediatric clinical practice. A report is presented on the activity in early paediatric oncology trials (phase I-II) in Spain. All members of the Spanish Society of Paediatric Haematology Oncology (SEHOP) were contacted in order to identify early clinical trials in paediatric cancer opened between 2005 and 2015. A total of 30 trials had been opened in this period: 21 (70%) in solid tumours, and 9 (30%) in malignant haemopathies. A total of 212 patients have been enrolled. The majority was industry sponsored (53%). Since 2010, four centres have joined the international consortium of Innovative Therapies for Children with Cancer (ITCC), which has as its aim to develop novel therapies for paediatric tumours. A significant number of new studies have opened since 2010, improving the treatment opportunities for our children. Results of recently closed trials show the contribution of Spanish investigators, the introduction of molecularly targeted agents, and their benefits. The activity in clinical trials has increased in the years analysed. The SEHOP is committed to develop and participate in collaborative academic trials, in order to help in the advancement and optimisation of existing therapies in paediatric cancer. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Early and intermediate age-related macular degeneration: update and clinical review.

PubMed

García-Layana, Alfredo; Cabrera-López, Francisco; García-Arumí, José; Arias-Barquet, Lluís; Ruiz-Moreno, José M

2017-01-01

Age-related macular degeneration (AMD) is the leading cause of irreversible central vision loss in developed countries. With the aging of population, AMD will become globally an increasingly important and prevalent disease worldwide. It is a complex disease whose etiology is associated with both genetic and environmental risk factors. An extensive decline in the quality of life and progressive need of daily living assistance resulting from AMD among those most severely affected highlights the essential role of preventive strategies, particularly advising patients to quit smoking. In addition, maintaining a healthy diet, controlling other risk factors (such as hypertension, obesity, and atherosclerosis), and the use of nutritional supplements (antioxidants) are recommendable. Genetic testing may be especially important in patients with a family history of AMD. Recently, unifying criteria for the clinical classification of AMD, defining no apparent aging changes; normal aging changes; and early, intermediate, and late AMD stages, are of value in predicting AMD risk of progression and in establishing recommendations for the diagnosis, therapeutic approach, and follow-up of patients. The present review is focused on early and intermediate AMD and presents a description of the clinical characteristics and ophthalmological findings for these stages, together with algorithms for the diagnosis and management of patients, which are easily applicable in daily clinical practice.

Early and intermediate age-related macular degeneration: update and clinical review

PubMed Central

García-Layana, Alfredo; Cabrera-López, Francisco; García-Arumí, José; Arias-Barquet, Lluís; Ruiz-Moreno, José M

2017-01-01

Age-related macular degeneration (AMD) is the leading cause of irreversible central vision loss in developed countries. With the aging of population, AMD will become globally an increasingly important and prevalent disease worldwide. It is a complex disease whose etiology is associated with both genetic and environmental risk factors. An extensive decline in the quality of life and progressive need of daily living assistance resulting from AMD among those most severely affected highlights the essential role of preventive strategies, particularly advising patients to quit smoking. In addition, maintaining a healthy diet, controlling other risk factors (such as hypertension, obesity, and atherosclerosis), and the use of nutritional supplements (antioxidants) are recommendable. Genetic testing may be especially important in patients with a family history of AMD. Recently, unifying criteria for the clinical classification of AMD, defining no apparent aging changes; normal aging changes; and early, intermediate, and late AMD stages, are of value in predicting AMD risk of progression and in establishing recommendations for the diagnosis, therapeutic approach, and follow-up of patients. The present review is focused on early and intermediate AMD and presents a description of the clinical characteristics and ophthalmological findings for these stages, together with algorithms for the diagnosis and management of patients, which are easily applicable in daily clinical practice. PMID:29042759

Clinical and economic consequences of early discharge of patients following supratentorial stereotactic brain biopsy.

PubMed

Kaakaji, W; Barnett, G H; Bernhard, D; Warbel, A; Valaitis, K; Stamp, S

2001-06-01

The goal of this study was to determine the clinical and economic consequences of early discharge (< 8 hours) of patients following stereotactic brain biopsy (SBB). The records of all patients who underwent percutaneous SBB at The Cleveland Clinic Foundation, a tertiary care teaching hospital, during 1994 and 1995 (Group A) were retrospectively reviewed to collect data on the nature and timing of perioperative (< 48 hours) clinical and radiological complications. Biopsies were performed using image-guided stereotaxy either with or without a frame. Based on the results, guidelines for early discharge of patients following SBB were implemented. Information on the nature and timing of perioperative complications was also collected prospectively in all patients who underwent percutaneous SBB from January 1996 through July 1998 (Group B). Hospital financial records for patients who underwent SBB in 1997 and 1998 were also reviewed and assessed for net revenue stratified by discharge status: early discharge (< 8 hours), extended outpatient observation (> or = 8 and < 24 hours). and inpatient hospitalization (> or = 24 hours). In Group A, 130 biopsies were performed. There were five serious complications (3.8%), of which four were transient, and there was one death (0.8%). The death and any sustained deficit occurred in patients in whom a clot had been demonstrated on postoperative CT scans. All complications were detected within 6 hours after surgery. Intraoperative bleeding occurred in 12 patients (9.2%), but was associated with only 40% of cases in which hemorrhage appeared on postoperative CT scans. Guidelines for early discharge (< 8 hours) following SBB were developed and stipulated the absence of the following: 1) intraoperative hemorrhage; 2) new postoperative deficit; and 3) clot on a postoperative CT scan. In Group B, 139 biopsies were performed. There were three serious complications (2.2%), one of which was sustained due to a clot that had been demonstrated on

Diagnosis and prognosis of early-onset intrahepatic cholestasis of pregnancy: a prospective study.

PubMed

Lin, Jing; Gu, Wei; Hou, Yanyan

2017-11-07

To explore the gestational age of early-onset intrahepatic cholestasis (ICP) of pregnancy, and to analyze the relationship between the clinical biochemical indices and pregnancy outcomes in order to arrive at a reasonable diagnosis and administer appropriate treatment. This is a retrospective clinical study. We selected 47,260 pregnant women who received prenatal care and underwent childbirth at the International Peace Maternity and Child Health Hospital affiliated to Shanghai Jiao Tong University from January 2014 to December 2016 for participating in this study. Of these 47,260 women, 407 developed ICP. To calculate the gestational week cutoff between early- and late-onset ICP by the receiver-operating characteristic (ROC) curve and Youden's index. Two independent samples t tests and chi square test were used to compare the differences in biochemical indices and pregnancy outcomes between the two groups. We found that 34 weeks is the most appropriate cutoff gestational age for the diagnosis of early-onset ICP. Early-onset ICP is characterized by early onset, long disease duration and a higher incidence of preterm labor, fetal distress, and fetal low birth weight compared to late-onset ICP. Thirty-four weeks is the most appropriate cutoff gestational age for the diagnosis of early-onset ICP. And to reduce the adverse pregnancy outcomes in cases of early-onset ICP, we suggest prolonging gestation up to 37 weeks as far as possible before selecting iatrogenic birth.

Is Early-onset in Major Depression a Predictor of Specific Clinical Features with More Impaired Social Function?

PubMed Central

Liu, Yan-Hong; Chen, Lin; Su, Yun-Ai; Fang, Yi-Ru; Srisurapanont, Manit; Hong, Jin Pyo; Hatim, Ahmad; Chua, Hong Choon; Bautista, Dianne; Si, Tian-Mei

2015-01-01

Background: Early-onset major depressive disorder (MDD) (EOD) is often particularly malignant due to its special clinical features, accompanying impaired social function, protracted recovery time, and frequent recurrence. This study aimed to observe the effects of age onset on clinical characteristics and social function in MDD patients in Asia. Methods: In total, 547 out-patients aged 18–65 years who were from 13 study sites in five Asian countries were included. These patients had MDD diagnose according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria. Clinical features and social function were assessed using Symptom Checklist-90-revised (SCL-90-R) and Sheehan Disability Scale (SDS). Quality of life was assessed by a 36-item Short-form Health Survey (SF-36). Analyses were performed using a continuous or dichotomous (cut-off: 30 years) age-of-onset indicator. Results: Early-onset MDD (EOD, <30 years) was associated with longer illness (P = 0.003), unmarried status (P < 0.001), higher neuroticism (P ≤ 0.002) based on the SCL-90-R, and more limited social function and mental health (P = 0.006, P = 0.007) based on the SF-36 and SDS. The impairment of social function and clinical severity were more prominent at in-patients with younger onset ages. Special clinical features and more impaired social function and quality of life were associated with EOD, as in western studies. Conclusions: EOD often follows higher levels of neuroticism. Age of onset of MDD may be a predictor of clinical features and impaired social function, allowing earlier diagnosis and treatment. PMID:25758278

Clinical and dosimetric implications of intensity-modulated radiotherapy for early-stage glottic carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ward, Matthew Christopher, E-mail: wardm3@ccf.org; Pham, Yvonne D.; Kotecha, Rupesh

2016-04-01

Conventional parallel-opposed radiotherapy (PORT) is the established standard technique for early-stage glottic carcinoma. However, case reports have reported the utility of intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) with or without image guidance (image-guided radiotherapy, IGRT) in select patients. The proposed advantages of IMRT/VMAT include sparing of the carotid artery, thyroid gland, and the remaining functional larynx, although these benefits remain unclear. The following case study presents a patient with multiple vascular comorbidities treated with VMAT for early-stage glottic carcinoma. A detailed explanation of the corresponding treatment details, dose-volume histogram (DVH) analysis, and a review of the relevant literaturemore » are provided. Conventional PORT remains the standard of care for early-stage glottic carcinoma. IMRT or VMAT may be beneficial for select patients, although great care is necessary to avoid a geographical miss. Clinical data supporting the benefit of CRT are lacking. Therefore, these techniques should be used with caution and only in selected patients.« less

[Clinical characteristics and renal uric acid excretion in early-onset gout patients].

PubMed

Li, Q H; Liang, J J; Chen, L X; Mo, Y Q; Wei, X N; Zheng, D H; Dai, L

2018-03-01

Objective: To investigate clinical characteristics and renal uric acid excretion in early-onset gout patients. Methods: Consecutive inpatients with primary gout were recruited between 2013 and 2017. The patients with gout onset younger than 30 were defined as early-onset group while the others were enrolled as control group. Clinical characteristics and uric acid (UA) indicators were compared between two groups. Results: Among 202 recruited patients, the early-onset group included 36 patients (17.8%). Compared with control group, the early-onset group presented more patients with obesity [13 patients (36.1%) vs. 22 patients (13.3%), P< 0.05], significantly higher serum UA level [(634±124)μmol/L vs.(527±169)μmol/L] and glomerular load of UA[(7.2±2.8)mg·min(-1)·1.73m(-2) vs. (4.4±2.2)mg·min(-1)·1.73m(-2)] and estimated glomerular filtration rate (GFR) [(83±21)ml·min(-1)·1.73m(-2) vs. (67±21)ml·min(-1)·1.73m(-2)] (all P< 0.05), lower fractional excretion of UA [4.4% (3.4%,6.1%) vs. 7.2% (5.2%,9.6%), P< 0.05], whereas 24h urinary UA excretion was comparable [(2 788±882)μmol/1.73m(2) vs. (2 645±1 140)μmol/1.73m(2), P= 0.274]. Subgroup analysis of patients without chronic kidney disease showed significantly lower fractional excretion of UA in the early-onset group [4.5%(3.3%,6.1%) vs. 6.7% (5.1%,8.7%), P< 0.05]. Logistic regression analysis showed that obesity ( OR= 3.25) and fractional excretion of UA less than 7% ( OR= 9.01, all P< 0.05) were risk factors of gout early onset. Conclusion: The gout patients with early-onset younger than 30 present high serum and glomerular load of uric acid which might be due to obesity and relative under-excretion of renal uric acid.

A Mobile Health Platform for Clinical Monitoring in Early Psychosis: Implementation in Community-Based Outpatient Early Psychosis Care

PubMed Central

Iosif, Ana-Maria; Zakskorn, Lauren N; Nye, Kathleen E; Zia, Aqsa; Niendam, Tara Ann

2018-01-01

Background A growing body of literature indicates that smartphone technology is a feasible add-on tool in the treatment of individuals with early psychosis (EP) . However, most studies to date have been conducted independent of outpatient care or in a research clinic setting, often with financial incentives to maintain user adherence to the technology. Feasibility of dissemination and implementation of smartphone technology into community mental health centers (CMHCs) has yet to be tested, and whether young adults with EP will use this technology for long periods of time without incentive is unknown. Furthermore, although EP individuals willingly adopt smartphone technology as part of their treatment, it remains unclear whether providers are amenable to integrating smartphone technology into treatment protocols. Objective This study aimed to establish the feasibility of implementing a smartphone app and affiliated Web-based dashboard in 4 community outpatient EP clinics in Northern California. Methods EP individuals in 4 clinics downloaded an app on their smartphone and responded to daily surveys regarding mood and symptoms for up to 5 months. Treatment providers at the affiliated clinics viewed survey responses on a secure Web-based dashboard in sessions with their clients and between appointments. EP clients and treatment providers filled out satisfaction surveys at study end regarding usability of the app. Results Sixty-one EP clients and 20 treatment providers enrolled in the study for up to 5 months. Forty-one EP clients completed the study, and all treatment providers remained in the study for their duration in the clinic. Survey completion for all 61 EP clients was moderate: 40% and 39% for daily and weekly surveys, respectively. Completion rates were slightly higher in the participants who completed the study: 44% and 41% for daily and weekly surveys, respectively. Twenty-seven of 41 (66%) EP clients who completed the study and 11 of 13 (85%) treatment

Early Rebleeding after Brain Arteriovenous Malformation Rupture, Clinical Impact and Predictive Factors: A Monocentric Retrospective Cohort Study.

PubMed

Shotar, Eimad; Pistocchi, Silvia; Haffaf, Idriss; Bartolini, Bruno; Jacquens, Alice; Nouet, Aurélien; Chiras, Jacques; Degos, Vincent; Sourour, Nader-Antoine; Clarençon, Frédéric

2017-01-01

Brain arteriovenous malformations (BAVMs) are a leading cause of intracranial hemorrhage in young adults. This study aimed to identify individual predictive factors of early rebleeding after BAVM rupture and determine its impact on prognosis. Early rebleeding was defined as a spontaneous intracranial hemorrhage within 30 days of BAVM rupture in patients with nonobliterated BAVMs. One hundred fifty one patients with 158 BAVM hemorrhagic events admitted to a tertiary care center during 14 years were included. Univariate followed by multivariate logistic regression was performed to assess the impact of early rebleeding on in-hospital mortality and modified Rankin Scale (mRS) score beyond 3 months and to identify independent predictors of early rebleeding. Eight early rebleeding events were observed, 6 of which occurred during the first 7 days. Early rebleeding was independently and significantly associated with poor outcome (mRS ≥3 beyond 3 months, p = 0.004) but not with in-hospital mortality (p = 0.9). Distal flow-related aneurysms (p = 0.009) and altered consciousness with a Glasgow coma scale score of 3 (p = 0.01) were independently associated with early rebleeding. Early rebleeding is a severe complication that can occur after BAVM-related hemorrhage. Distal flow-related aneurysms and initial altered consciousness are associated with early rebleeding. © 2017 S. Karger AG, Basel.

Informatics tools to improve clinical research study implementation.

PubMed

Brandt, Cynthia A; Argraves, Stephanie; Money, Roy; Ananth, Gowri; Trocky, Nina M; Nadkarni, Prakash M

2006-04-01

There are numerous potential sources of problems when performing complex clinical research trials. These issues are compounded when studies are multi-site and multiple personnel from different sites are responsible for varying actions from case report form design to primary data collection and data entry. We describe an approach that emphasizes the use of a variety of informatics tools that can facilitate study coordination, training, data checks and early identification and correction of faulty procedures and data problems. The paper focuses on informatics tools that can help in case report form design, procedures and training and data management. Informatics tools can be used to facilitate study coordination and implementation of clinical research trials.

Early palliative care in advanced lung cancer: a qualitative study.

PubMed

Yoong, Jaclyn; Park, Elyse R; Greer, Joseph A; Jackson, Vicki A; Gallagher, Emily R; Pirl, William F; Back, Anthony L; Temel, Jennifer S

2013-02-25

BACKGROUND Early ambulatory palliative care (PC) is an emerging practice, and its key elements have not been defined. We conducted a qualitative analysis of data from a randomized controlled trial that demonstrated improved quality of life, mood, and survival in patients with newly diagnosed metastatic non-small cell lung cancer who received early PC integrated with standard oncologic care vs standard oncologic care alone. Our objectives were to (1) identify key elements of early PC clinic visits, (2) explore the timing of key elements, and (3) compare the content of PC and oncologic visit notes at the critical time points of clinical deterioration and radiographic disease progression. METHODS We randomly selected 20 patients who received early PC and survived within 4 periods: less than 3 months (n = 5), 3 to 6 months (n = 5), 6 to 12 months (n = 5), and 12 to 24 months (n = 5). We performed content analysis on PC and oncologic visit notes from the electronic health records of these patients. RESULTS Addressing symptoms and coping were the most prevalent components of the PC clinic visits. Initial visits focused on building relationships and rapport with patients and their families and on illness understanding, including prognostic awareness. Discussions about resuscitation preferences and hospice predominantly occurred during later visits. Comparing PC and oncologic care visits around critical time points, both included discussions about symptoms and illness status; however, PC visits emphasized psychosocial elements, such as coping, whereas oncologic care visits focused on cancer treatment and management of medical complications. CONCLUSIONS Early PC clinic visits emphasize managing symptoms, strengthening coping, and cultivating illness understanding and prognostic awareness in a responsive and time-sensitive model. During critical clinical time points, PC and oncologic care visits have distinct features that suggest a key role for PC involvement and enable

Inhaled corticosteroids do not influence the early inflammatory response and clinical presentation of hospitalized subjects with COPD exacerbation.

PubMed

Crisafulli, Ernesto; Guerrero, Mónica; Menéndez, Rosario; Huerta, Arturo; Martinez, Raquel; Gimeno, Alexandra; Soler, Néstor; Torres, Antoni

2014-10-01

Inhaled corticosteroids are anti-inflammatory medications that can down-regulate the immunologic response in patients with COPD; however, their role at onset of COPD exacerbation is still not understood. The aim of this study was to assess the early inflammatory response and clinical presentation of patients with COPD exacerbation mediated by inhaled corticosteroids. Prospective data were collected on 123 hospitalized subjects with COPD exacerbation over a 30-month period at 2 Spanish university hospitals. Based on domiciliary use, comparative analyses were performed between subjects who did not use inhaled corticosteroids (n = 58) and subjects who did (n = 65). Measurements of serum biomarkers were recorded on admission to the hospital (day 1) and on day 3; clinical, physiological, microbiological, and severity data and mortality/readmission rates were also recorded. At days 1 and 3, both groups showed a similar inflammatory response; fluticasone produced lower levels of interleukin-8 compared with budesonide (P < .01). All clinical features considered were similar in the 2 groups; multivariate analysis predicting clinical complications on hospitalization showed air-flow obstruction severity as the only predictive factor (odds ratio 3.13, 95% CI 1.13-8.63, P = .02). Our study demonstrates a lack of inhaled corticosteroid influence in the early systemic inflammatory response to and clinical presentation of COPD exacerbation. Copyright © 2014 by Daedalus Enterprises.

Early termination of cardiovascular trials as a consequence of poor accrual: analysis of ClinicalTrials.gov 2006-2015.

PubMed

Baldi, Ileana; Lanera, Corrado; Berchialla, Paola; Gregori, Dario

2017-06-15

To present a snapshot of experimental cardiovascular research with a focus on geographical and temporal patterns of early termination due to poor accrual. The Aggregate Analysis of ClinicalTrials.gov (AACT) database, reflecting ClinicalTrials.gov as of 27 March 2016. The AACT database was searched for all cardiovascular clinical trials that started from January 2006 up to December 2015. Thirteen thousand and seven hundred twenty-nine cardiovascular trials were identified. Of these, 8900 (65%) were classified as closed studies. Globally, 11% of closed trials were terminated. This proportion varied from 9.6% to 14% for trials recruiting from Europe and Americas, respectively, with a slightly decreasing trend (p=0.02) over the study period. The most common reason for trials failing to complete was poor accrual (41%). Intercontinental trials exhibited lower figures of poor accrual as the reason for their early stopping, as compared with trials recruiting in a single continent (28% vs 44%, p=0.002). Poor accrual significantly challenges the successful completion of cardiovascular clinical trials. Findings are suggestive of a positive effect of globalisation of cardiovascular clinical research on the achievement of enrolment goals within a reasonable time frame. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The Interplay between Inflammation, Coagulation and Endothelial Injury in the Early Phase of Acute Pancreatitis: Clinical Implications

PubMed Central

Dumnicka, Paulina; Maduzia, Dawid; Ceranowicz, Piotr; Olszanecki, Rafał; Drożdż, Ryszard; Kuśnierz-Cabala, Beata

2017-01-01

Acute pancreatitis (AP) is an inflammatory disease with varied severity, ranging from mild local inflammation to severe systemic involvement resulting in substantial mortality. Early pathologic events in AP, both local and systemic, are associated with vascular derangements, including endothelial activation and injury, dysregulation of vasomotor tone, increased vascular permeability, increased leukocyte migration to tissues, and activation of coagulation. The purpose of the review was to summarize current evidence regarding the interplay between inflammation, coagulation and endothelial dysfunction in the early phase of AP. Practical aspects were emphasized: (1) we summarized available data on diagnostic usefulness of the markers of endothelial dysfunction and activated coagulation in early prediction of severe AP; (2) we reviewed in detail the results of experimental studies and clinical trials targeting coagulation-inflammation interactions in severe AP. Among laboratory tests, d-dimer and angiopoietin-2 measurements seem the most useful in early prediction of severe AP. Although most clinical trials evaluating anticoagulants in treatment of severe AP did not show benefits, they also did not show significantly increased bleeding risk. Promising results of human trials were published for low molecular weight heparin treatment. Several anticoagulants that proved beneficial in animal experiments are thus worth testing in patients. PMID:28208708

Audit of the autoantibody test, EarlyCDT®-lung, in 1600 patients: an evaluation of its performance in routine clinical practice.

PubMed

Jett, James R; Peek, Laura J; Fredericks, Lynn; Jewell, William; Pingleton, William W; Robertson, John F R

2014-01-01

EarlyCDT(®)-Lung may enhance detection of early stage lung cancer by aiding physicians in assessing high-risk patients through measurement of biological markers (i.e., autoantibodies). The test's performance characteristics in routine clinical practice were evaluated by auditing clinical outcomes of 1613 US patients deemed at high risk for lung cancer by their physician, who ordered the EarlyCDT-Lung test for their patient. Clinical outcomes for all 1613 patients who provided HIPAA authorization are reported. Clinical data were collected from each patient's treating physician. Pathology reports when available were reviewed for diagnostic classification. Staging was assessed on histology, otherwise on imaging. Six month follow-up for the positives/negatives was 99%/93%. Sixty-one patients (4%) were identified with lung cancer, 25 of whom tested positive by EarlyCDT-Lung (sensitivity=41%). A positive EarlyCDT-Lung test on the current panel was associated with a 5.4-fold increase in lung cancer incidence versus a negative. Importantly, 57% (8/14) of non-small cell lung cancers detected as positive (where stage was known) were stage I or II. EarlyCDT-Lung has been extensively tested and validated in case-control settings and has now been shown in this audit to perform in routine clinical practice as predicted. EarlyCDT-Lung may be a complementary tool to CT for detection of early lung cancer. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Interventional Treatment of Severe Tricuspid Regurgitation: Early Clinical Experience in a Multicenter, Observational, First-in-Man Study.

PubMed

Lauten, Alexander; Figulla, Hans R; Unbehaun, Axel; Fam, Neil; Schofer, Joachim; Doenst, Torsten; Hausleiter, Joerg; Franz, Marcus; Jung, Christian; Dreger, Henryk; Leistner, David; Alushi, Brunilda; Stundl, Anja; Landmesser, Ulf; Falk, Volkmar; Stangl, Karl; Laule, Michael

2018-02-01

Transcatheter caval valve implantation is under evaluation as a treatment option for inoperable patients with severe tricuspid regurgitation (TR). The procedure involves the catheter-based implantation of bioprosthetic valves in the inferior vena cava and superior vena cava to treat symptoms associated with TR. This study is the first to evaluate the feasibility, safety, and efficacy of this interventional concept. Twenty-five patients (mean age, 73.9±7.6 years; women, 52.0%) with severe symptomatic TR despite optimal medical treatment deemed unsuitable for surgery were treated with caval valve implantation under a compassionate clinical use program. Technical feasibility defined as procedural success, hemodynamic effect defined as venous pressure reduction, and safety defined as periprocedural adverse events were evaluated, with clinical follow-up at discharge and up to 12 months. The functional impact was evaluated by assessment of New York Heart Association class at the time of hospital discharge. The total number of valves implanted in the caval position was 31. Patients were treated with single (inferior vena cava-only; n=19; 76.0%) or bicaval valve implantation (inferior vena cava+superior vena cava; n=6; 24.0%). Either balloon-expandable valves (Sapien XT/3: n=18; 72.0%) or self-expandable valves (TricValve: n=6; 24.0%; Directflow: n=1; 4.0%) were used. Procedural success was achieved in 96% (n=24). Early and late valve migration requiring surgical intervention occurred in 1 patient each. Thirty-day and in-hospital mortality were 8% (2 of 25) and 16% (4 of 25). Causes of in-hospital mortality included respiratory (n=1) or multiple organ failure (n=3) and were not linked to the procedure. Mean overall survival in the study cohort was 316±453 days (14-1540 days). Caval valve implantation for the treatment of severe TR and advanced right ventricular failure is associated with a high procedural success rate and seems safe and feasible in an excessive

Early termination of cardiovascular trials as a consequence of poor accrual: analysis of ClinicalTrials.gov 2006–2015

PubMed Central

Baldi, Ileana; Lanera, Corrado; Berchialla, Paola; Gregori, Dario

2017-01-01

Objectives To present a snapshot of experimental cardiovascular research with a focus on geographical and temporal patterns of early termination due to poor accrual. Setting The Aggregate Analysis of ClinicalTrials.gov (AACT) database, reflecting ClinicalTrials.gov as of 27 March 2016. Design The AACT database was searched for all cardiovascular clinical trials that started from January 2006 up to December 2015. Results Thirteen thousand and seven hundred twenty-nine cardiovascular trials were identified. Of these, 8900 (65%) were classified as closed studies. Globally, 11% of closed trials were terminated. This proportion varied from 9.6% to 14% for trials recruiting from Europe and Americas, respectively, with a slightly decreasing trend (p=0.02) over the study period. The most common reason for trials failing to complete was poor accrual (41%). Intercontinental trials exhibited lower figures of poor accrual as the reason for their early stopping, as compared with trials recruiting in a single continent (28% vs 44%, p=0.002). Conclusions Poor accrual significantly challenges the successful completion of cardiovascular clinical trials. Findings are suggestive of a positive effect of globalisation of cardiovascular clinical research on the achievement of enrolment goals within a reasonable time frame. PMID:28619765

Dopamine Transporter Neuroimaging as an Enrichment Biomarker in Early Parkinson's Disease Clinical Trials: A Disease Progression Modeling Analysis.

PubMed

Conrado, Daniela J; Nicholas, Timothy; Tsai, Kuenhi; Macha, Sreeraj; Sinha, Vikram; Stone, Julie; Corrigan, Brian; Bani, Massimo; Muglia, Pierandrea; Watson, Ian A; Kern, Volker D; Sheveleva, Elena; Marek, Kenneth; Stephenson, Diane T; Romero, Klaus

2018-01-01

Given the recognition that disease-modifying therapies should focus on earlier Parkinson's disease stages, trial enrollment based purely on clinical criteria poses significant challenges. The goal herein was to determine the utility of dopamine transporter neuroimaging as an enrichment biomarker in early motor Parkinson's disease clinical trials. Patient-level longitudinal data of 672 subjects with early-stage Parkinson's disease in the Parkinson's Progression Markers Initiative (PPMI) observational study and the Parkinson Research Examination of CEP-1347 Trial (PRECEPT) clinical trial were utilized in a linear mixed-effects model analysis. The rate of worsening in the motor scores between subjects with or without a scan without evidence of dopamine transporter deficit was different both statistically and clinically. The average difference in the change from baseline of motor scores at 24 months between biomarker statuses was -3.16 (90% confidence interval [CI] = -0.96 to -5.42) points. Dopamine transporter imaging could identify subjects with a steeper worsening of the motor scores, allowing trial enrichment and 24% reduction of sample size. Published 2017. This article is a U.S. Government work and is in the public domain in the USA. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Teachers' Perceptions of Their Mentoring Role in Three Different Clinical Settings: Student Teaching, Early Field Experiences, and Entry Year Teaching

ERIC Educational Resources Information Center

Gut, Dianne M.; Beam, Pamela C.; Henning, John E.; Cochran, Deborah C.; Knight, Rhonda Talford

2014-01-01

The purpose of this study was to determine the differences in mentoring across three different clinical settings: student teaching, early field experiences, and entry year teachers. Eighteen teachers with mentoring experience in all three clinical settings were selected and interviewed. The teachers' expectations for teacher development,…

Three steps to writing adaptive study protocols in the early phase clinical development of new medicines

PubMed Central

2014-01-01

This article attempts to define terminology and to describe a process for writing adaptive, early phase study protocols which are transparent, self-intuitive and uniform. It provides a step by step guide, giving templates from projects which received regulatory authorisation and were successfully performed in the UK. During adaptive studies evolving data is used to modify the trial design and conduct within the protocol-defined remit. Adaptations within that remit are documented using non-substantial protocol amendments which do not require regulatory or ethical review. This concept is efficient in gathering relevant data in exploratory early phase studies, ethical and time- and cost-effective. PMID:24980283

Microcephaly and Zika virus: Neuroradiological aspects, clinical findings and a proposed framework for early evaluation of child development.

PubMed

Cicuto Ferreira Rocha, Nelci Adriana; de Campos, Ana Carolina; Cicuto Ferreira Rocha, Fellipe; Pereira Dos Santos Silva, Fernanda

2017-11-01

As the recent outbreak of microcephaly cases caused by Zika virus has been declared a global health emergency, providing assessment guidelines for multidisciplinary teams providing early developmental screening and stimulation to infants with microcephaly is much needed. Thus, the aim of this manuscript is to provide an overview on what is known about neuroradiological aspects and clinical findings in infants with microcephaly caused by Zika virus and to propose a framework for early evaluation of child development. The keywords "Zika virus" and "microcephaly" were searched in PubMed database for articles published from incept to May 2017. These texts were reviewed, and the ones addressing neuroradiological and clinical findings in infants were selected. Recommendations for early assessment were made based on the International Classification of Functionality Disability and Health (ICF) model. The database search yielded 599 publications and 36 were selected. The studies detected microcephaly with diffuse brain malformations and calcifications, ventriculomegaly, optic nerve hypoplasia, macular atrophy, cataracts, impaired visual and hearing function, arthrogryposis, spasticity, hyperreflexia, irritability, tremors, and seizures, but very little is known about early development. Early assessments were described based on the ICF domains (Body Function and Structures, Activities and Participation and Contextual factors). Studies published showed abnormal brain, optic, neurologic and orthopedic findings, but very little is known about other aspects of functioning in infants with microcephaly caused by Zika virus. The biopsychosocial model based on the ICF paradigm provides an adequate framework to describe the condition of the infant with microcephaly receiving rehabilitative efforts to minimize disability. Efforts towards early identification of developmental delays should be taken within the first six months of life. Copyright © 2017 Elsevier Inc. All rights reserved.

An estimate of the cost of burnout on early retirement and reduction in clinical hours of practicing physicians in Canada

PubMed Central

2014-01-01

Background Interest in the impact of burnout on physicians has been growing because of the possible burden this may have on health care systems. The objective of this study is to estimate the cost of burnout on early retirement and reduction in clinical hours of practicing physicians in Canada. Methods Using an economic model, the costs related to early retirement and reduction in clinical hours of physicians were compared for those who were experiencing burnout against a scenario in which they did not experience burnout. The January 2012 Canadian Medical Association Masterfile was used to determine the number of practicing physicians. Transition probabilities were estimated using 2007–2008 Canadian Physician Health Survey and 2007 National Physician Survey data. Adjustments were also applied to outcome estimates based on ratio of actual to planned retirement and reduction in clinical hours. Results The total cost of burnout for all physicians practicing in Canada is estimated to be $213.1 million ($185.2 million due to early retirement and $27.9 million due to reduced clinical hours). Family physicians accounted for 58.8% of the burnout costs, followed by surgeons for 24.6% and other specialists for 16.6%. Conclusion The cost of burnout associated with early retirement and reduction in clinical hours is substantial and a significant proportion of practicing physicians experience symptoms of burnout. As health systems struggle with human resource shortages and expanding waiting times, this estimate sheds light on the extent to which the burden could be potentially decreased through prevention and promotion activities to address burnout among physicians. PMID:24927847

Early diagnosis of amyotrophic lateral sclerosis mimic syndromes: pros and cons of current clinical diagnostic criteria.

PubMed

Cortés-Vicente, Elena; Pradas, Jesús; Marín-Lahoz, Juan; De Luna, Noemi; Clarimón, Jordi; Turon-Sans, Janina; Gelpí, Ellen; Díaz-Manera, Jordi; Illa, Isabel; Rojas-Garcia, Ricard

2017-08-01

To describe the frequency and clinical characteristics of patients referred to a tertiary neuromuscular clinic as having amyotrophic lateral sclerosis (ALS) but who were re-diagnosed as having an ALS mimic syndrome, and to identify the reasons that led to the revision of the diagnosis. We reviewed the final diagnosis of all patients prospectively registered in the Sant Pau-MND register from 1 January 2004 to 31 December 2015. A detailed clinical evaluation and a clinically-guided electrophysiological study were performed at first evaluation. Twenty of 314 (6.4%) patients included were re-diagnosed as having a condition other than ALS, in 18 cases already at first evaluation. An alternative specific diagnosis was identified in 17 of those 20, consisting of a wide range of conditions. The main finding leading to an alternative diagnosis was the result of the electrophysiological study. Fifty per cent did not fulfil the El Escorial revised criteria (EECr) for ALS. The most common clinical phenotype at onset in patients with ALS mimic syndromes was progressive muscular atrophy (PMA). Misdiagnosing ALS is still a common problem. Early identification of ALS mimic syndromes is possible based on atypical clinical features and a clinically-guided electrophysiological study. Patients should be attended in specialised centres. The application of EECr helps to identify ALS misdiagnoses.

Parkinson's Disease Diagnostic Observations (PADDO): study rationale and design of a prospective cohort study for early differentiation of parkinsonism.

PubMed

van Rumund, Anouke; Aerts, Marjolein B; Esselink, Rianne A J; Meijer, Frederick J A; Verbeek, Marcel M; Bloem, Bastiaan R

2018-05-16

Differentiation of Parkinson's disease (PD) from the various types of atypical parkinsonism (AP) such as multiple system atrophy (MSA), progressive supranuclear palsy (PSP), dementia with Lewy bodies (DLB), corticobasal syndrome (CBS) and vascular parkinsonism (VP), can be challenging, especially early in the disease course when symptoms overlap. A major unmet need in the diagnostic workup of these disorders is a diagnostic tool that differentiates the various disorders, preferably in the earliest disease stages when the clinical presentation is similar. Many diagnostic tests have been evaluated, but their added value was studied mostly in retrospective case-control studies that included patients with a straightforward clinical diagnosis. Here, we describe the design of a prospective cohort study in patients with parkinsonism in an early disease stage who have an uncertain clinical diagnosis. Our aim is to evaluate the diagnostic accuracy of (1) detailed clinical examination by a movement disorder specialist, (2) magnetic resonance imaging (MRI) techniques and (3) cerebrospinal fluid (CSF) biomarkers. Patients with parkinsonism with an uncertain clinical diagnosis and a disease course less than three years will be recruited. Patients will undergo extensive neurological examination, brain MRI including conventional and advanced sequences, and a lumbar puncture. The diagnosis (including level of certainty) will be defined by a movement disorders expert, neuroradiologist and neurochemist based on clinical data, MRI results and CSF results, respectively. The clinical diagnosis after three years' follow-up will serve as the "gold standard" reference diagnosis, based on consensus criteria and as established by two movement disorder specialists (blinded to the test results). Diagnostic accuracy of individual instruments and added value of brain MRI and CSF analysis after evaluation by a movement disorder expert will be calculated, expressed as the change in percentage of

Barriers to implementing evidence-based clinical guidelines: A survey of early adopters

PubMed Central

Spallek, Heiko; Song, Mei; Polk, Deborah E; Bekhuis, Tanja; Frantsve-Hawley, Julie; Aravamudhan, Krishna

2010-01-01

Objective The purpose of this study is to identify barriers that early-adopting dentists perceive as common and challenging when implementing recommendations from evidence-based (EB) clinical guidelines. Method This is a cross-sectional study. Dentists who attended the 2008 Evidence-based Dentistry Champion Conference were eligible for inclusion. Forty-three dentists (34%) responded to a 22-item questionnaire administered online. Two investigators independently coded and categorized responses to open-ended items. Descriptive statistics were computed to assess the frequency of barriers and perceived challenges. Results The most common barriers to implementation are difficulty in changing current practice model, resistance and criticism from colleagues, and lack of trust in evidence or research. Barriers perceived as serious problems have to do with lack of up-to-date evidence, lack of clear answers to clinical questions, and contradictory information in the scientific literature. Conclusions Knowledge of barriers will help improve translation of biomedical research for dentists. Information in guidelines needs to be current, clear, and simplified for use at chairside; dentists’ fears need to be addressed. PMID:21093800

Clinical and MRI responses to etanercept in early non-radiographic axial spondyloarthritis: 48-week results from the EMBARK study

PubMed Central

Maksymowych, Walter P; Dougados, Maxime; Sieper, Joachim; Braun, Jürgen; Citera, Gustavo; Van den Bosch, Filip; Logeart, Isabelle; Wajdula, Joseph; Jones, Heather; Marshall, Lisa; Bonin, Randi; Pedersen, Ron; Vlahos, Bonnie; Kotak, Sameer; Bukowski, Jack F

2016-01-01

Objective To evaluate the efficacy and safety of etanercept (ETN) after 48 weeks in patients with early active non-radiographic axial spondyloarthritis (nr-axSpA). Methods Patients meeting Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axSpA, but not modified New York radiographic criteria, received double-blind ETN 50 mg/week or placebo (PBO) for 12 weeks, then open-label ETN (ETN/ETN or PBO/ETN). Clinical, health, productivity, MRI and safety outcomes were assessed and the 48-week data are presented here. Results 208/225 patients (92%) entered the open-label phase at week 12 (ETN, n=102; PBO, n=106). The percentage of patients achieving ASAS40 increased from 33% to 52% between weeks 12 and 48 for ETN/ETN and from 15% to 53% for PBO/ETN (within-group p value <0.001 for both). For ETN/ETN and PBO/ETN, the EuroQol 5 Dimensions utility score improved by 0.14 and 0.08, respectively, between baseline and week 12 and by 0.23 and 0.22 between baseline and week 48. Between weeks 12 and 48, MRI Spondyloarthritis Research Consortium of Canada sacroiliac joint (SIJ) scores decreased by −1.1 for ETN/ETN and by −3.0 for PBO/ETN, p<0.001 for both. Decreases in MRI SIJ inflammation and C-reactive protein correlated with several clinical outcomes at weeks 12 and 48. Conclusions Patients with early active nr-axSpA demonstrated improvement from week 12 in clinical, health, productivity and MRI outcomes that was sustained to 48 weeks. Trial registration number NCT01258738. PMID:26269397

Birdshot Retinochoroidopathy: Differences in Clinical Characteristics between Patients with Early and Late Age of Onset.

PubMed

Silpa-Archa, Sukhum; Cao, Jennifer H; Boonsopon, Sutasinee; Lee, Joan; Preble, Janine M; Foster, C Stephen

2017-10-01

To describe differences in the clinical characteristics of birdshot retinochoroidopathy (BSRC) patients diagnosed early and later in life. This is a retrospective cohort study. Age was primarily analyzed and 50 years of age at diagnosis was selected as a cut-off point. A total of 144 patients (288 eyes) were included; 68 with early-onset and 76 with late-onset BSRC. The younger group had a statistically significant higher rate of more severe iritis (p = 0.04); an average number of non-steroidal immunosuppressants and biologic agents (NSIB) (p = 0.04); and a prolonged time to initiation of NSIB (p = 0.01). There were only four patients (3%) who had >0.5+ cells in the anterior chamber. Patients with early-onset BSRC carried a higher risk for anterior segment inflammation, had a more prolonged delay to initiation of treatment with NSIB, and required a greater number of NSIBs to achieve remission.

Early Diagnosis of Gestational Diabetes Mellitus (EDoGDM) study: a protocol for a prospective, longitudinal cohort study

PubMed Central

Liu, Bin; Xu, Yun; Zhang, Ying; Cai, Jian; Deng, Langhui; Yang, Jianbo; Zhou, Yi; Long, Yuhang; Zhang, Jinxin; Wang, Zilian

2016-01-01

Introduction A diagnosis of gestational diabetes mellitus (GDM) in low-risk pregnant women is based on an oral glucose tolerance test (OGTT) between 24 and 28 gestational weeks. However, there is insufficient evidence for why the test is performed in this time period. Moreover, the fetus may be exposed to hyperglycaemia prior to the current testing time frame, making earlier administration potentially advantageous. The main purpose of the present study is to investigate the GDM diagnostic value of an OGTT performed at 18–20 gestational weeks. The results of the study may provide scientific insight into the most beneficial time of OGTT for pregnant women. Methods and analysis As a prospective, longitudinal cohort study, the Early Diagnosis of Gestational Diabetes Mellitus (EDoGDM) study will recruit 570 pregnant women who meet the inclusion and exclusion criteria outlined below. OGTTs will be performed between 18 and 20 gestational weeks (early OGTT) and 24–28 gestational weeks (regular OGTT). Clinical and laboratory information of the mother and their offspring will be collected for analysis. The prevalence of GDM at 18–20 gestational weeks will be described, and the sensitivity, specificity, positive predictive value and negative predictive value of early OGTT on diagnosis of GDM will be studied. Clinical outcomes associated with hyperglycaemia will be compared between groups diagnosed by early or regular OGTT. Ethics and dissemination The study was approved by The Ethical Committees of The First Affiliated Hospital of Sun Yat-sen University (number 2016-042). Signed informed consent will be obtained from all participants. The results of this study will be disseminated in peer-reviewed journals. Trial registration number NCT02740283. PMID:27872115

Clinical characteristics of early-stage osteonecrosis of the ankle and treatment outcomes.

PubMed

Issa, Kimona; Naziri, Qais; Kapadia, Bhaveen H; Lamm, Bradley M; Jones, Lynne C; Mont, Michael A

2014-05-07

The purposes of this study were to describe the clinical manifestations of osteonecrosis involving the distal tibia and talus, to identify risk factors associated with the disease, and to evaluate the efficacy of percutaneous drilling for the treatment of ankles with early-stage symptomatic osteonecrosis. One hundred and one ankles in seventy-three patients with symptomatic osteonecrosis of the talus and/or distal tibia treated with percutaneous drilling were identified. There were eighty-one ankles in fifty-nine patients treated only at our institution and twenty ankles in fourteen patients with a failed prior core decompression at outside institutions. The parameters evaluated included demographics, disease characteristics, clinical outcomes including the American Orthopaedic Foot & Ankle Society score, Short-Form-36 scores, University of California Los Angeles activity scores, and visual analog scale pain scores, and radiographic outcomes at a mean follow-up duration of five years (range, two to nine years). Eighty-five ankles had isolated talus osteonecrosis, eleven ankles had involvement of the distal tibia and talus, and five ankles had isolated distal tibial disease. Twenty-nine patients (40%) had initially presented with symptomatic osteonecrosis of another joint, most commonly the knee (37%), the hip (29%), and the shoulder (25%). The most common identifiable risk factors included chronic corticosteroid use (49.3%), alcohol abuse (35.6%), tobacco use (29%), and hypertension (20.5%). Overall, 83% of ankles did not demonstrate further disease progression after the procedure. There were significant improvements (p < 0.05) in clinical and patient-reported outcomes after surgical treatment. The presence of human immunodeficiency virus and sickle cell disease was associated with a higher odds ratio of disease progression to joint collapse. Osteonecrosis of the distal tibia and talus was usually part of multifocal disease, and concurrent knee osteonecrosis was

Leber congenital amaurosis/early-onset severe retinal dystrophy: clinical features, molecular genetics and therapeutic interventions.

PubMed

Kumaran, Neruban; Moore, Anthony T; Weleber, Richard G; Michaelides, Michel

2017-09-01

Leber congenital amaurosis (LCA) and early-onset severe retinal dystrophy (EOSRD) are both genetically and phenotypically heterogeneous, and characterised clinically by severe congenital/early infancy visual loss, nystagmus, amaurotic pupils and markedly reduced/absent full-field electroretinograms. The vast genetic heterogeneity of inherited retinal disease has been established over the last 10 - 20 years, with disease-causing variants identified in 25 genes to date associated with LCA/EOSRD, accounting for 70-80% of cases, with thereby more genes yet to be identified. There is now far greater understanding of the structural and functional associations seen in the various LCA/EOSRD genotypes. Subsequent development/characterisation of LCA/EOSRD animal models has shed light on the underlying pathogenesis and allowed the demonstration of successful rescue with gene replacement therapy and pharmacological intervention in multiple models. These advancements have culminated in more than 12 completed, ongoing and anticipated phase I/II and phase III gene therapy and pharmacological human clinical trials. This review describes the clinical and genetic characteristics of LCA/EOSRD and the differential diagnoses to be considered. We discuss in further detail the diagnostic clinical features, pathophysiology, animal models and human treatment studies and trials, in the more common genetic subtypes and/or those closest to intervention. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Clinical abnormalities, early intervention program of Down syndrome children: Queen Sirikit National Institute of Child Health experience.

PubMed

Fuengfoo, Adidsuda; Sakulnoom, Kim

2014-06-01

Queen Sirikit National Institute of Child Health is a tertiary institute of children in Thailand, where early intervention programs have been provided since 1990 by multidisciplinary approach especially in Down syndrome children. This aim of the present study is to follow the impact of early intervention on the outcome of Down syndrome children. The school attendance number of Down syndrome children was compared between regular early intervention and non-regular early intervention. The present study group consists of 210 Down syndrome children who attended early intervention programs at Queen Sirikit National Institute of Child Health between June 2008 and January 2012. Data include clinical features, school attendance developmental quotient (DQ) at 3 years of age using Capute Scales Cognitive Adaptive Test/Scale (CAT/CLAMS). Developmental milestones have been recorded as to the time of appearance of gross motor, fine motor, language, personal-social development compared to those non-regular intervention patients. Of 210 Down syndrome children, 117 were boys and 93 were girls. About 87% received regular intervention, 68% attended speech training. Mean DQ at 3 years of age was 65. Of the 184 children who still did follow-up at developmental department, 124 children (59%) attended school: mainstream school children 78 (63%) and special school children 46 (37%). The mean age at entrance to school was 5.8 ± 1.4 years. The school attendance was correlated with maternal education and regular early intervention attendance. Regular early intervention starts have proven to have a positive effect on development. The school attendance number of Down syndrome children receiving regular early intervention was statistically and significantly higher than the number of Down syndrome children receiving non-regular early intervention was. School attendance correlated with maternal education and attended regularly early intervention. Regular early intervention together with maternal

Migration characteristics and early clinical results of a novel-finned press-fit acetabular cup.

PubMed

Kaipel, Martin; Prenner, Anton; Bachl, Sebastian; Farr, Sebastian; Sinz, Günter

2014-04-01

Ana Nova® is a novel-finned press-fit acetabular cup which showed superior biomechanical characteristics in an experimental set-up. Using Einzel Bild Röntgen Analyse (EBRA) measurements should offer the opportunity to predict implant survival at an early stage. The purpose of this study was to assess migration and clinical outcome 2 years after total hip replacement by a novel-finned press-fit acetabular cup. In this study, migration and clinical results of the implant were prospectively assessed in 67 patients. Clinical outcome was assessed using the Harris hip score (HHS). Migration analyses were performed using the computer assisted EBRA system. Data were analyzed for normal distribution using the Kolmogorov-Smirnov test. Group comparisons were performed using the analysis of variance (ANOVA) test. P-values less than 0.05 were considered statistically significant. At 2 years after surgery, none of the implants needed revision and HHS increased from 39.7 up to 92.2. In contrast to the beneficial clinical outcome, 17 of 44 patients showed increased total migration ( 1 mm/2a). Adverse migration data in this study might predict aseptic loosening and decreased survival of the implant. According to previous studies, it is possible that this effect occurred because of limited accuracy of the EBRA system. In our opinion, migration analyses may not be recommended as a screening tool in a 2 year follow-up.

[Genetic, epidemiologic and clinical study of familial prostate cancer].

PubMed

Valéri, Antoine

2002-01-01

Prostate cancer (CaP) is the most frequent cancer among men over 50 and its frequency increases with age. It has become a significant public health problem due to the ageing population. Epidemiologists report familial aggregation in 15 to 25% of cases and inherited susceptibility with autosomal dominant or X-linked model in 5 to 10% of cases. Clinical and biological features of familial CaP remain controversial. To perform: (1) Genetic study of familial Cap (mapping of susceptibility genes), (2) epidemiologic study (prevalence, associated cancers in the genealogy, model of transmission), and clinical study of familial CaP. (I) conducting a nationwide family collection (ProGène study) with 2+ CaP we have performed a genomewide linkage analysis and identified a predisposing locus on 1q42.2-43 named PCaP (Predisposing to Cancer of the Prostate); (II) conducting a systematic genealogic analysis of 691 CaP followed up in 3 University departments of urology (Hospitals of Brest, Paris St Louis and Nancy) we have observed: (1) 14.2% of familial and 3.6% of hereditary CaP, (2) a higher risk of breast cancer in first degree relatives of probands (CaP+) in familial CaP than in sporadic CaP and in early onset CaP (< 55 years) when compared with late onset CaP ([dG]75 years), (3) an autosomal dominant model with brother-brother dependance), (4) the lack of specific clinical or biological feature (except for early onset) in hereditary CaP when compared with sporadic CaP. (1) The mapping of a susceptibility locus will permit the cloning of a predisposing gene on 1q42.2-43, offer the possibility of genetic screening in families at risk and permit genotype/phenotype correlation studies; (2) the transmission model will improve parameteric linkage studies; (3) the lack of distinct specific clinical patterns suggest diagnostic and follow up modalities for familial and hereditary CaP similar to sporadic cancer while encouraging early screening of families at risk, given the earlier

Early detection of psychosis: finding those at clinical high risk.

PubMed

Addington, Jean; Epstein, Irvin; Reynolds, Andrea; Furimsky, Ivana; Rudy, Laura; Mancini, Barbara; McMillan, Simone; Kirsopp, Diane; Zipursky, Robert B

2008-08-01

In early detection work, recruiting individuals who meet the prodromal criteria is difficult. The aim of this paper was to describe the development of a research clinic for individuals who appear to be at risk of developing a psychosis and the process for educating the community and obtaining referrals. The outcome of all referrals to the clinic over a 4-year period was examined. Following an ongoing education campaign that was over inclusive in order to aid recruitment, approximately 27% of all referrals met the criteria for being at clinical high risk of psychosis. We are seeing only a small proportion of those in the community who eventually go on to develop a psychotic illness. This raises two important issues, namely how to remedy the situation, and second, the impact of this on current research in terms of sampling bias and generalizability of research findings. © 2008 The Authors. Journal compilation © 2008 Blackwell Publishing Asia Pty Ltd.

Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS): Demographic and Clinical Characteristics

ERIC Educational Resources Information Center

Frazier, Jean A.; McClellan, Jon; Findling, Robert L.; Vitiello, Benedetto; Anderson, Robert; Zablotsky, Benjamin; Williams, Emily; McNamara, Nora K.; Jackson, Joseph A.; Ritz, Louise; Hlastala, Stefanie A.; Pierson, Leslie; Varley, Jennifer A.; Puglia, Madeline; Maloney, Ann E.; Ambler, Denisse; Hunt-Harrison, Tyehimba; Hamer, Robert M.; Noyes, Nancy; Lieberman, Jeffrey A.; Sikich, Linmarie

2007-01-01

Objective: We examined baseline demographic and clinical profiles of youths enrolled from 2001 to 2006 in the publicly funded multicenter, randomized controlled trial Treatment of Early-Onset Schizophrenia Spectrum Disorders. Method: Youths (8-19 years) with schizophrenia (SZ) and schizoaffective disorder were recruited at four academic sites.…

Clinical, psychological and maternal characteristics in early functional constipation.

PubMed

Kilincaslan, Huseyin; Abali, Osman; Demirkaya, Sevcan Karakoc; Bilici, Mustafa

2014-08-01

This cross-sectional study investigated the clinical features of functional constipation (FC) at preschool age, as well as emotional and behavioral characteristics of the children, psychological symptom level and parental attitudes of the mothers, and compared these with that of non-referred typically developing controls with normal intestinal habits. Participants included 65 children with FC (mean age, 43.6 ± 15.4 months; range, 25-72 months), 59 healthy controls (mean age, 46.9 ± 14.5 months; range, 25-72 months) and the mothers of the children. The Childhood Behavior Checklist, Symptom Checklist 90 and Parental Attitude Research Instrument were filled in by the mothers. Participants with FC had higher problem scores than the comparison children in a variety of emotional and behavioral parameters. Approximately half exhibited internalizing and one-third had externalizing problems in the clinical range. The mothers of the patient group had higher levels of psychological distress, overprotective parenting and strict discipline. On multiple logistic regression analysis child psychopathology, maternal education level and maternal distress were independently associated with FC. Behavior problems are common in children with FC from an early age. Low level of education and high psychological distress of the mothers seem to be important risk factors for constipation and should be assessed carefully in the management of these cases. © 2013 Japan Pediatric Society.

Factor Structure of the Devereux Early Childhood Assessment Clinical Form in Low-Income Hispanic American Bilingual Preschool Children

ERIC Educational Resources Information Center

Oades-Sese, Geraldine V.; Kaliski, Pamela K.; Weiss, Karen

2010-01-01

The Devereux Early Childhood Assessment Clinical Form (DECA-C) is the first instrument to measure the social-emotional resilience of young children from ages 2 to 5 years. This study is an important step toward gathering validity evidence for the teacher-rated DECA-C. This is the first study to investigate the DECA-C factor structure and the first…

On-treatment decrease of NKG2D correlates to early emergence of clinically evident hepatocellular carcinoma after interferon-free therapy for chronic hepatitis C.

PubMed

Chu, Po-Sung; Nakamoto, Nobuhiro; Taniki, Nobuhito; Ojiro, Keisuke; Amiya, Takeru; Makita, Yuko; Murata, Hiroko; Yamaguchi, Akihiro; Shiba, Shunsuke; Miyake, Rei; Katayama, Tadashi; Ugamura, Aya; Ikura, Akihiko; Takeda, Karin; Ebinuma, Hirotoshi; Saito, Hidetsugu; Kanai, Takanori

2017-01-01

Interferon (IFN)- free direct antiviral agents (DAAs) with rapid HCV eradication might evoke immunological reconstitutions, and some early recurrences of HCC after IFN-free DAAs have been reported. This study aimed to investigate whether natural killer group 2, member D (NKG2D) predicts early emergence of HCC after IFN-free DAAs. We conducted a clinical practice-based observational study of 101 patients infected with genotype 1 HCV who received IFN-free (DAAs), and stratified them into those who did or did not develop early (i.e., during the 6-month surveillance period following treatment.) recurrence or occurrence of clinically evident HCC. We also analyzed the peripheral blood mononuclear cells, both before treatment and at end of treatment (EOT), of 24 of the patients who received IFN-free DAAs, and 16 who received IFN-combined protease inhibitor. We found early emergence of clinically evident HCC after IFN-free DAAs in 12 (12%) patients. Higher pre-treatment NKG2D expression, higher FIB-4 score, previous HCC history and failure to achieve sustained viral response were significant factors correlating to early HCC emergence. After IFN-free DAAs, a rapid decrease of NKG2D at EOT correlated with early HCC emergence in the IFN-free DAA-treated patients, but not in patients treated with the IFN-combined regimen. The decrease of NKG2D until EOT was predictive of early HCC emergence at a cut-off of -52% (AUC = 0.92). On-treatment decrease of NKG2D may be a useful predictor of early emerging HCC in patients treated with IFN-free DAAs.

Current status of amorphous formulation and other special dosage forms as formulations for early clinical phases.

PubMed

Kawakami, Kohsaku

2009-09-01

Although most chemists in the pharmaceutical industry have a good understanding on favorable physicochemical properties for drug candidates, formulators must still deal with many challenging candidates. On the other hand, formulators are not allowed to spend much time on formulation development for early phases of the clinical studies. Thus, it is basically difficult to apply special dosage form technologies to the candidates for the first-in-human formulations. Despite the availability of numerous reviews on oral special dosage forms, information on their applicability as the early phase formulation has been limited. This article describes quick review on the oral special dosage forms that may be applied to the early clinical formulations, followed by discussion focused on the amorphous formulations, which still has relatively many issues to be proved for the general use. The major problems that inhibit the use of the amorphous formulation are difficulty in the manufacturing and the poor chemical/physical stability. Notably, the poor physical stability can be critical, because of not the poor stability itself but the difficulty in the timely evaluation in the preclinical developmental timeframes. Research directions of the amorphous formulations are suggested to utilize this promising technology without disturbing the preclinical developmental timelines.

Cognitive function in early clinical phase huntington disease after rivastigmine treatment.

PubMed

Sešok, Sanja; Bolle, Nika; Kobal, Jan; Bucik, Valentin; Vodušek, David B

2014-09-01

In Huntington disease (HD) patients receiving rivastigmine treatment improvement of behavioral symptoms and of cognitive function (assessed with screening diagnostic instruments) has been reported. The aim of the present study was to verify such improvement in cognitive function by cognitive function assessment with a detailed neuropsychological battery covering all relevant cognitive systems expected to be impaired in early phase HD. Eighteen (18) HD patients entered the study and were randomly allocated to the rivastigmine and placebo group. All subjects underwent neuropsychological assessment at baseline. Follow-up neuropsychological assessment was applied after 6 months of rivastigmine or placebo treatment. Eighteen (18) healthy controls entered the study to control for practice effect and underwent neuropsychological assessment at baseline and after 6 months, without treatment. The neuropsychological battery consisted of assessment tools that are sensitive to cognitive impairment seen in early phase HD: CTMT, SDMT, Stroop (attention and information control), RFFT, TOL, Verbal fluency (executive functioning), CVLT-II, RCFT (learning and memory). Effect of rivastigmine and possible effect of practice was assessed using the mixed ANOVA model. No statistically significant effect of rivastigmine treatment on cognitive function in HD patients was detected. There was no evidence for practice or placebo effect. Detailed neuropsychological assessment did not confirm previously reported effect of rivastigmine treatment on cognitive function in HD patients. The limitations of our study are, in particular, small sample size and the lack of a single measure of relevant cognitive functioning in HD patients. Instead of focusing solely on statistical significance, a clinical relevance study is proposed to clarify the issue of rivastigmine effects in HD.

Early phase clinical trials with human immunodeficiency virus-1 and malaria vectored vaccines in The Gambia: frontline challenges in study design and implementation.

PubMed

Afolabi, Muhammed O; Adetifa, Jane U; Imoukhuede, Egeruan B; Viebig, Nicola K; Kampmann, Beate; Bojang, Kalifa

2014-05-01

Human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) and malaria are among the most important infectious diseases in developing countries. Existing control strategies are unlikely to curtail these diseases in the absence of efficacious vaccines. Testing of HIV and malaria vaccines candidates start with early phase trials that are increasingly being conducted in developing countries where the burden of the diseases is high. Unique challenges, which affect planning and implementation of vaccine trials according to internationally accepted standards have thus been identified. In this review, we highlight specific challenges encountered during two early phase trials of novel HIV-1 and malaria vectored vaccine candidates conducted in The Gambia and how some of these issues were pragmatically addressed. We hope our experience will be useful for key study personnel involved in day-to-day running of similar clinical trials. It may also guide future design and implementation of vaccine trials in resource-constrained settings.

The clinical presentation and early outcomes of necrotizing fasciitis in a Ugandan Tertiary Hospital--a prospective study.

PubMed

Magala, John; Makobore, Patson; Makumbi, Timothy; Kaggwa, Sam; Kalanzi, Edris; Galukande, Moses

2014-07-28

Necrotizing fasciitis is an infectious process characterized by rapidly progressing necrosis of superficial fascia and subcutaneous tissue with subsequent necrosis of overlying skin.Necrotizing fasciitis is a rare but fatal infection. The worldwide incidence is at 0.4 per 100,000. Mortality is up to 80% with no intervention, and 30-50% with intervention. Delay in intervention is associated with poor outcome. The risk factors for necrotizing fasciitis are diabetes mellitus, HIV, malignancy, illicit drug use, malnutrition among others.The aim of this study was to describe the clinical presentation and early outcomes of necrotizing fasciitis amongst Ugandan patients. A prospective descriptive case series study conducted at Mulago National Referral and Teaching hospital from 5th January to 30th April 2011. Patients with necrotizing fasciitis were consecutively recruited after clinical evaluation, laboratory and microbiological tests were performed. Aggressive debridement was done and broad-spectrum antibiotics administered. Patients were followed up on surgical wards. Ethical approval was obtained. Thirty five patients were recruited over a 4 months period. More males were affected with, M: F 3:1. The 20-40 years age group was most affected. Attainment of healthy granulation tissue took 19 days on average. Mortality rate was 14% (5/35). Limbs were the most affected body parts 20/35 (57%), the scrotum and perineum (23%). Among infants the scalp was the most affected. Co-morbidities included HIV 8/35 (17%), and DM (5%) among others. The commonest organisms were gram negative. Split skin grafting was necessary in 74% (26/35) of patients. There were a high number of patients with necrotizing fasciitis; it was associated with low mortality but high morbidity (long hospital stay). There was a high preponderance to males and limbs were the more affected body parts.

The clinical presentation and early outcomes of necrotizing fasciitis in a Ugandan Tertiary Hospital- a prospective study

PubMed Central

2014-01-01

Background Necrotizing fasciitis is an infectious process characterized by rapidly progressing necrosis of superficial fascia and subcutaneous tissue with subsequent necrosis of overlying skin. Necrotizing fasciitis is a rare but fatal infection. The worldwide incidence is at 0.4 per 100,000. Mortality is up to 80% with no intervention, and 30-50% with intervention. Delay in intervention is associated with poor outcome. The risk factors for necrotizing fasciitis are diabetes mellitus, HIV, malignancy, illicit drug use, malnutrition among others. The aim of this study was to describe the clinical presentation and early outcomes of necrotizing fasciitis amongst Ugandan patients. Methods A prospective descriptive case series study conducted at Mulago National Referral and Teaching hospital from 5th January to 30th April 2011. Patients with necrotizing fasciitis were consecutively recruited after clinical evaluation, laboratory and microbiological tests were performed. Aggressive debridement was done and broad-spectrum antibiotics administered. Patients were followed up on surgical wards. Ethical approval was obtained. Results Thirty five patients were recruited over a 4 months period. More males were affected with, M: F 3:1. The 20-40 years age group was most affected. Attainment of healthy granulation tissue took 19 days on average. Mortality rate was 14% (5/35). Limbs were the most affected body parts 20/35 (57%), the scrotum and perineum (23%). Among infants the scalp was the most affected. Co-morbidities included HIV 8/35 (17%), and DM (5%) among others. The commonest organisms were gram negative. Split skin grafting was necessary in 74% (26/35) of patients. Conclusion There were a high number of patients with necrotizing fasciitis; it was associated with low mortality but high morbidity (long hospital stay). There was a high preponderance to males and limbs were the more affected body parts. PMID:25069415

Development and Evaluation of a New Technological Way of Engaging Patients and Enhancing Understanding of Drug Tolerability in Early Clinical Development: PROACT.

PubMed

Hughes, Andrew; Landers, Donal; Arkenau, Hendrik-Tobias; Shah, Saj; Stephens, Richard; Mahal, Amrik; Simmons, Matthew; Lemech, Charlotte; Royle, Jennifer

2016-06-01

During early clinical testing of a new medication, it is critical to understand and characterise patient tolerability. However, in early clinical studies, it is difficult for patients to contribute directly to the sponsors' understanding of a new compound. Patient reported opinions about clinical tolerability (PROACT) provides a new, simple and innovative way in which patients can collaborate using an application downloaded to a mobile computer or smartphone. PROACT was designed with special consideration given to patient confidentiality, patient engagement and data security. A pilot study was conducted to investigate patient uptake of PROACT and to characterize clinical trial information it captured. Patients recruited to Phase I oncology trials at a UK center were eligible to participate but were required to have a tablet computer or smartphone. Patients used PROACT to upload audio/video messages that became available instantly to their clinical team, who were able to reply to the patient within PROACT. The patient's message was also analyzed, personally-identifiable information removed and anonymized information then made available to the sponsor in an analytics module for decision-making. In parallel, a patient focus group was engaged to provide feedback on communication needs during early clinical trials and the PROACT concept. Of the 16 patients informed of PROACT, 8 had a smart device and consented to take part. Use of PROACT varied and all messages volunteered were relevant and informative for drug development. Topics disclosed included tolerability impacts, study design, and drug formulation. Alignment with the clinical study data provided a richer understanding of tolerability and treatment consequences. This information was available to be shared among the clinical team and the sponsor, to improve patient support and experience. Patient forum feedback endorsed the concept and provided further information to enhance the application. Overall, PROACT

Colorado Early Childhood Study.

ERIC Educational Resources Information Center

Colorado State Dept. of Education, Denver. Planning and Evaluation Unit.

The Colorado State Board of Education allocated Title IV-V funds in 1975 for a study of the status of early childhood education in Colorado. The purposes of the study were to: (1) gather data relevant to early childhood education on the status of all children from birth through age 5; (2) identify needs of children of this age within the state;…

Webcam delivery of the Lidcombe program for early stuttering: a phase I clinical trial.

PubMed

O'Brian, Sue; Smith, Kylie; Onslow, Mark

2014-06-01

The Lidcombe Program is an operant treatment for early stuttering shown with meta-analysis to have a favorable odds ratio. However, many clients are unable to access the treatment because of distance and lifestyle factors. In this Phase I trial, we explored the potential efficacy, practicality, and viability of an Internet webcam Lidcombe Program service delivery model. Participants were 3 preschool children who stuttered and their parents, all of whom received assessment and treatment using webcam in their homes with no clinic attendance. At 6 months post-Stage 1 completion, all children were stuttering below 1.0% syllables stuttered. The webcam intervention was acceptable to the parents and appeared to be practical and viable, with only occasional audiovisual problems. At present, there is no reason to doubt that a webcam-delivered Lidcombe Program will be shown with clinical trials to have comparable efficacy with the clinic version. Webcam-delivered Lidcombe Program intervention is potentially efficacious, is practical and viable, and requires further exploration with comparative clinical trials and a qualitative study of parent and caregiver experiences.

A Systematic Review of Early Warning Systems' Effects on Nurses' Clinical Performance and Adverse Events Among Deteriorating Ward Patients.

PubMed

Lee, Ju-Ry; Kim, Eun-Mi; Kim, Sun-Aee; Oh, Eui Geum

2018-04-25

Early warning systems (EWSs) are an integral part of processes that aim to improve the early identification and management of deteriorating patients in general wards. However, the widespread implementation of these systems has not generated robust data regarding nurses' clinical performance and patients' adverse events. This review aimed to determine the ability of EWSs to improve nurses' clinical performance and prevent adverse events among deteriorating ward patients. The PubMed, CINAHL, EMBASE, and Cochrane Library databases were searched for relevant publications (January 1, 1997, to April 12, 2017). In addition, a grey literature search evaluated several guideline Web sites. The main outcome measures were nurses' clinical performance (vital sign monitoring and rapid response team notification) and patients' adverse events (in-hospital mortality, cardiac arrest, and unplanned intensive care unit [ICU] admission). The search identified 888 reports, although only five studies fulfilled the inclusion criteria. The findings of these studies revealed that EWSs implementation had a positive effect on nurses' clinical performance, based on their frequency of documenting vital signs that were related to the patient's clinical deterioration. In addition, postimplementation reductions were identified for cardiac arrest, unplanned ICU admission, and unexpected death. It seems that EWSs can improve nurses' clinical performance and prevent adverse events (e.g., in-hospital mortality, unplanned ICU admission, and cardiac arrest) among deteriorating ward patients. However, additional high-quality evidence is needed to more comprehensively evaluate the effects of EWSs on these outcomes.

Clinical and MRI responses to etanercept in early non-radiographic axial spondyloarthritis: 48-week results from the EMBARK study.

PubMed

Maksymowych, Walter P; Dougados, Maxime; van der Heijde, Désirée; Sieper, Joachim; Braun, Jürgen; Citera, Gustavo; Van den Bosch, Filip; Logeart, Isabelle; Wajdula, Joseph; Jones, Heather; Marshall, Lisa; Bonin, Randi; Pedersen, Ron; Vlahos, Bonnie; Kotak, Sameer; Bukowski, Jack F

2016-07-01

To evaluate the efficacy and safety of etanercept (ETN) after 48 weeks in patients with early active non-radiographic axial spondyloarthritis (nr-axSpA). Patients meeting Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axSpA, but not modified New York radiographic criteria, received double-blind ETN 50 mg/week or placebo (PBO) for 12 weeks, then open-label ETN (ETN/ETN or PBO/ETN). Clinical, health, productivity, MRI and safety outcomes were assessed and the 48-week data are presented here. 208/225 patients (92%) entered the open-label phase at week 12 (ETN, n=102; PBO, n=106). The percentage of patients achieving ASAS40 increased from 33% to 52% between weeks 12 and 48 for ETN/ETN and from 15% to 53% for PBO/ETN (within-group p value <0.001 for both). For ETN/ETN and PBO/ETN, the EuroQol 5 Dimensions utility score improved by 0.14 and 0.08, respectively, between baseline and week 12 and by 0.23 and 0.22 between baseline and week 48. Between weeks 12 and 48, MRI Spondyloarthritis Research Consortium of Canada sacroiliac joint (SIJ) scores decreased by -1.1 for ETN/ETN and by -3.0 for PBO/ETN, p<0.001 for both. Decreases in MRI SIJ inflammation and C-reactive protein correlated with several clinical outcomes at weeks 12 and 48. Patients with early active nr-axSpA demonstrated improvement from week 12 in clinical, health, productivity and MRI outcomes that was sustained to 48 weeks. NCT01258738. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Phantom-to-clinic development of hypofractionated stereotactic body radiotherapy for early-stage glottic laryngeal cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ding, Chuxiong; Chun, Stephen G.; Sumer, Baran D.

The purpose of this study was to commission and clinically test a robotic stereotactic delivery system (CyberKnife, Sunnyvale, CA) to treat early-stage glottic laryngeal cancer. We enrolled 15 patients with cTis-T2N0M0 carcinoma of the glottic larynx onto an institutional review board (IRB)-approved clinical trial. Stereotactic body radiotherapy (SBRT) plans prescribed 45 Gy/10 fractions to the involved hemilarynx. SBRT dosimetry was compared with (1) standard carotid-sparing laryngeal intensity-modulated radiation therapy (IMRT) and (2) selective hemilaryngeal IMRT. Our results demonstrate that SBRT plans improved sparing of the contralateral arytenoid (mean 20.0 Gy reduction, p <0.001), ipsilateral carotid D{sub max} (mean 20.6 Gy reduction, p <0.001), contralateral carotidmore » D{sub max} (mean 28.1 Gy reduction, p <0.001), and thyroid D{sub mean} (mean 15.0 Gy reduction, p <0.001) relative to carotid-sparing IMRT. SBRT also modestly improved dose sparing to the contralateral arytenoid (mean 4.8 Gy reduction, p = 0.13) and spinal cord D{sub max} (mean 4.9 Gy reduction, p = 0.015) relative to selective hemilaryngeal IMRT plans. This “phantom-to-clinic” feasibility study confirmed that hypofractionated SBRT treatment for early-stage laryngeal cancer can potentially spare dose to adjacent normal tissues relative to current IMRT standards. Clinical efficacy and toxicity correlates continue to be collected through an ongoing prospective trial.« less

Pilot study assessing the feasibility of applying bilateral subthalamic nucleus deep brain stimulation in very early stage Parkinson's disease: study design and rationale.

PubMed

Charles, David; Tolleson, Christopher; Davis, Thomas L; Gill, Chandler E; Molinari, Anna L; Bliton, Mark J; Tramontana, Michael G; Salomon, Ronald M; Kao, Chris; Wang, Lily; Hedera, Peter; Phibbs, Fenna T; Neimat, Joseph S; Konrad, Peter E

2012-01-01

Deep brain stimulation provides significant symptomatic benefit for people with advanced Parkinson's disease whose symptoms are no longer adequately controlled with medication. Preliminary evidence suggests that subthalamic nucleus stimulation may also be efficacious in early Parkinson's disease, and results of animal studies suggest that it may spare dopaminergic neurons in the substantia nigra. We report the methodology and design of a novel Phase I clinical trial testing the safety and tolerability of deep brain stimulation in early Parkinson's disease and discuss previous failed attempts at neuroprotection. We recently conducted a prospective, randomized, parallel-group, single-blind pilot clinical trial of deep brain stimulation in early Parkinson's disease. Subjects were randomized to receive either optimal drug therapy or deep brain stimulation plus optimal drug therapy. Follow-up visits occurred every six months for a period of two years and included week-long therapy washouts. Thirty subjects with Hoehn & Yahr Stage II idiopathic Parkinson's disease were enrolled over a period of 32 months. Twenty-nine subjects completed all follow-up visits; one patient in the optimal drug therapy group withdrew from the study after baseline. Baseline characteristics for all thirty patients were not significantly different. This study demonstrates that it is possible to recruit and retain subjects in a clinical trial testing deep brain stimulation in early Parkinson's disease. The results of this trial will be used to support the design of a Phase III, multicenter trial investigating the efficacy of deep brain stimulation in early Parkinson's disease.

The early economic evaluation of novel biomarkers to accelerate their translation into clinical applications.

PubMed

de Graaf, Gimon; Postmus, Douwe; Westerink, Jan; Buskens, Erik

2018-01-01

Translating prognostic and diagnostic biomarker candidates into clinical applications takes time, is very costly, and many candidates fail. It is therefore crucial to be able to select those biomarker candidates that have the highest chance of successfully being adopted in the clinic. This requires an early estimate of the potential clinical impact and commercial value. In this paper, we aim to demonstratively evaluate a set of novel biomarkers in terms of clinical impact and commercial value, using occurrence of cardiovascular disease (CVD) in type-2 diabetes (DM2) patients as a case study. We defined a clinical application for the novel biomarkers, and subsequently used data from a large cohort study in The Netherlands in a modeling exercise to assess the potential clinical impact and headroom for the biomarkers. The most likely application of the biomarkers would be to identify DM2 patients with a low CVD risk and subsequently withhold statin treatment. As a result, one additional CVD event in every 75 patients may be expected. The expected downstream savings resulted in a headroom for a point-of-care device ranging from €119.09 at a willingness to accept of €0 for one additional CVD event, to €0 at a willingness to accept of €15,614 or more. It is feasible to evaluate novel biomarkers on outcomes directly relevant to technological development and clinical adoption. Importantly, this may be attained at the same point in time and using the same data as used for the evaluation of association with disease and predictive power.

Disorganization at the stage of schizophrenia clinical outcome: Clinical-biological study.

PubMed

Nestsiarovich, A; Obyedkov, V; Kandratsenka, H; Siniauskaya, M; Goloenko, I; Waszkiewicz, N

2017-05-01

According to the multidimensional model of schizophrenia, three basic psychopathological dimensions constitute its clinical structure: positive symptoms, negative symptoms and disorganization. The latter one is the newest and the least studied. Our aim was to discriminate disorganization in schizophrenia clinical picture and to identify its distinctive biological and socio-psychological particularities and associated genetic and environmental factors. We used SAPS/SANS psychometrical scales, scales for the assessment of patient's compliance, insight, social functioning, life quality. Neuropsychological tests included Wisconsin Card Sorting Test (WCST), Stroop Color-Word test. Neurophysiological examination included registration of P300 wave of the evoked cognitive auditory potentials. Environmental factors related to patient's education, family, surrounding and nicotine use, as well as subjectively significant traumatic events in childhood and adolescence were assessed. Using PCR we detected SNP of genes related to the systems of neurotransmission (COMT, SLC6A4 and DRD2), inflammatory response (IL6, TNF), cellular detoxification (GSTM1, GSTT1), DNA methylation (MTHFR, DNMT3b, DNMT1). Disorganization is associated with early schizophrenia onset and history of psychosis in family, low level of insight and compliance, high risk of committing delicts, distraction errors in WCST, lengthened P300 latency of evoked cognitive auditory potentials, low-functional alleles of genes MTHFR (rs1801133) and DNMT3b (rs2424913), high level of urbanicity and psychotraumatic events at early age. Severe disorganization at the stage of schizophrenia clinical outcome is associated with the set of specific biological and social-psychological characteristics that indicate its epigenetic nature and maladaptive social significance. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Linear Combinations of Multiple Outcome Measures to Improve the Power of Efficacy Analysis ---Application to Clinical Trials on Early Stage Alzheimer Disease

PubMed Central

Xiong, Chengjie; Luo, Jingqin; Morris, John C; Bateman, Randall

2018-01-01

Modern clinical trials on Alzheimer disease (AD) focus on the early symptomatic stage or even the preclinical stage. Subtle disease progression at the early stages, however, poses a major challenge in designing such clinical trials. We propose a multivariate mixed model on repeated measures to model the disease progression over time on multiple efficacy outcomes, and derive the optimum weights to combine multiple outcome measures by minimizing the sample sizes to adequately power the clinical trials. A cross-validation simulation study is conducted to assess the accuracy for the estimated weights as well as the improvement in reducing the sample sizes for such trials. The proposed methodology is applied to the multiple cognitive tests from the ongoing observational study of the Dominantly Inherited Alzheimer Network (DIAN) to power future clinical trials in the DIAN with a cognitive endpoint. Our results show that the optimum weights to combine multiple outcome measures can be accurately estimated, and that compared to the individual outcomes, the combined efficacy outcome with these weights significantly reduces the sample size required to adequately power clinical trials. When applied to the clinical trial in the DIAN, the estimated linear combination of six cognitive tests can adequately power the clinical trial. PMID:29546251

Factors associated with early detection of choroidal neovascularization in age-related macular degeneration in the clinic setting.

PubMed

Lichtinger, Alejandro; Caraza, Mauricio; Galbinur, Tural; Chowers, Itay

2012-06-01

Delayed diagnosis of choroidal neovas cularization (CNV) in age-related macular degeneration (AMD) adversely affects visual outcome. To identify factors associated with early detection of CNV in the clinic setting. Demographic and clinical data and lesion characteristics were retrospectively collected from 76 consecutive AMD patients who had a history of CNV in one eye and presented with CNV in the second eye. These data were evaluated for association with visual acuity (VA) at the time of presentation. Better VA was associated with a history of CNV in the fellow eye (P < 0.0001), adherence to follow-up every 4 months (P = 0.015), younger age (P = 0.03), smaller lesion (P < 0.0001), and non-subfoveal location (P = 0.048). VA of the fellow eye did not correlate with VA at presentation with CNV. These data suggest that patients' experience of CNV, regardless of VA, facilitates early diagnosis in the fellow eye. Adherence to follow-up in the routine clinic setting also facilitates early detection of CNV.

Neonatal Early Warning Tools for recognising and responding to clinical deterioration in neonates cared for in the maternity setting: A retrospective case-control study.

PubMed

Paliwoda, Michelle; New, Karen; Bogossian, Fiona

2016-09-01

All newborns are at risk of deterioration as a result of failing to make the transition to extra uterine life. Signs of deterioration can be subtle and easily missed. It has been postulated that the use of an Early Warning Tool may assist clinicians in recognising and responding to signs of deterioration earlier in neonates, thereby preventing a serious adverse event. To examine whether observations from a Standard Observation Tool, applied to three neonatal Early Warning Tools, would hypothetically trigger an escalation of care more frequently than actual escalation of care using the Standard Observation Tool. A retrospective case-control study. A maternity unit in a tertiary public hospital in Australia. Neonates born in 2013 of greater than or equal to 34(+0) weeks gestation, admitted directly to the maternity ward from their birthing location and whose subsequent deterioration required admission to the neonatal unit, were identified as cases from databases of the study hospital. Each case was matched with three controls, inborn during the same period and who did not experience deterioration and neonatal unit admission. Clinical and physiological data recorded on a Standard Observation Tool, from time of admission to the maternity ward, for cases and controls were charted onto each of three Early Warning Tools. The primary outcome was whether the tool 'triggered an escalation of care'. Descriptive statistics (n, %, Mean and SD) were employed. Cases (n=26) comprised late preterm, early term and post-term neonates and matched by gestational age group with 3 controls (n=78). Overall, the Standard Observation Tool triggered an escalation of care for 92.3% of cases compared to the Early Warning Tools; New South Wales Health 80.8%, United Kingdom Newborn Early Warning Chart 57.7% and The Australian Capital Territory Neonatal Early Warning Score 11.5%. Subgroup analysis by gestational age found differences between the tools in hypothetically triggering an escalation of

Landscape of early clinical trials for childhood and adolescence cancer in Spain.

PubMed

Bautista, F; Gallego, S; Cañete, A; Mora, J; Diaz de Heredia, C; Cruz, O; Fernández, J M; Rives, S; Madero, L; Castel, V; Cela, M E; Ramírez, G; Sábado, C; Acha, T; Astigarraga, I; Sastre, A; Muñoz, A; Guibelalde, M; Moreno, L

2016-07-01

Despite numerous advances, survival remains dismal for children and adolescents with poor prognosis cancers or those who relapse or are refractory to first line treatment. There is, therefore, a major unmet need for new drugs. Recent advances in the knowledge of molecular tumor biology open the door to more adapted therapies according to individual alterations. Promising results in the adult anticancer drug development have not yet been translated into clinical practice. We report the activity in early pediatric oncology trials in Spain. All members of the Spanish Society of Pediatric Hematology Oncology (SEHOP) were contacted to obtain information about early trials open in each center. 22 phase I and II trials were open as of May 2015: 15 for solid tumors (68 %) and 7 for hematological malignancies (32 %). Fourteen (64 %) were industry sponsored. Since 2010, four centers have joined the Innovative Therapies For Children With Cancer, an international consortium whose aim is developing novel therapies for pediatric cancers. A substantial number of studies have opened in these 5 years, improving the portfolio of trials for children. Results of recently closed trials show the contribution of Spanish investigators, the introduction of molecularly targeted agents and their benefits. Clinical trials are the way to evaluate new drugs, avoiding the use of off-label drugs that carry significant risks. The Spanish pediatric oncology community through the SEHOP is committed to develop and participate in collaborative academic trials, to favor the advancement and optimization of existing therapies in pediatric cancer.

[Clinical significance of early percutaneous coronary intervention in patients with Braunwald III-B type unstable angina pectoris].

PubMed

Nozaki, Katsuhiro; Nakao, Koichi; Horiuchi, Kenji; Kasanuki, Hiroshi; Honda, Takashi

2003-06-01

To assess the efficacy of early invasive strategy for the treatment of Braunwald III-B type unstable angina pectoris. This study included 573 consecutive patients of whom 267 underwent percutaneous coronary intervention (PCI) (312 lesions). The patients were divided into two groups, 95 treated with the early invasive strategy of coronary angiography within 24 hr of admission (Group PCI-I) and the remaining 172 treated with the early conservative strategy of coronary angiography 24 hr after admission (Group PCI-C). No significant differences were noted in the baseline characteristics of the two groups except for ST segment elevation on electrocardiography at presentation, which occurred significantly less frequently in Group PCI-C (36.8% vs 8.1%, p < 0.0001). The initial success rate of percutaneous coronary intervention was sufficiently high in both groups (Group PCI-I: 96.9% vs Group PCI-C: 97.7%, NS). Acute myocardial infarction occurred in six patients of Group PCI-C (3.5%) because of the side branch occlusion. There was no in-hospital death or emergent coronary artery bypass grafting. During the 6-month follow-up, there were no significant differences in the death rates (2.1% vs 1.7%), the death or myocardial infarction rates (5.3% vs 5.8%) and the target lesion revascularization ratio (26.0% vs 25.7%) between Group PCI-I and Group PCI-C. The clinical outcomes of the early invasive strategy for unstable angina pectoris were almost equivalent to those of the early conservative strategy, despite more frequent ST segmental elevation at admission in Group PCI-I. These findings suggest that the early invasive strategy for unstable angina pectoris may be acceptable even in the current Japanese clinical setting without the use of GP IIb/IIIa receptor antagonist, low molecular weight heparin or clopidogrel.

Early versus later response to treatment in patients with community-acquired pneumonia: analysis of the REACH study.

PubMed

Blasi, Francesco; Ostermann, Helmut; Racketa, Jill; Medina, Jesús; McBride, Kyle; Garau, Javier

2014-01-22

Key goals in the treatment of CAP include early response to treatment and achievement of clinical stability. The US FDA recommends early response endpoints (72 hours after initiation of treatment) in clinical trials for the treatment of community-acquired bacterial pneumonia. REACH (REtrospective Study to Assess the Clinical Management of Patients With Moderate-to-Severe Complicated Skin and Soft Tissue Infections [cSSTI] or CAP in the Hospital Setting) was a retrospective observational study, providing current data on the clinical management and resource burden of CAP in real-life settings in European hospitals. This analysis reviews the characteristics and outcomes of patients showing early positive response to treatment (time to clinical stability [TCS] ≤4 days, as assessed by Halm's criteria) compared with patients with later positive response (TCS >4 days). Patients were adults, hospitalized with CAP (2010-2011) and requiring in-hospital treatment with intravenous antibiotics. Of the 2039 patients included in REACH, 585 (28.7%) had TCS assessed by Halm's criteria: 332 (56.8%) showed early response (median 3.0 days), and 253 (43.2%) showed later response to treatment (median 7.0 days). Use of Halm's criteria varied across participating countries, ranging from 0% (Belgium) to 49.1% (UK). Patient characteristics and relevant medical history were similar between the two groups. There were no notable differences in initial antibiotic therapy between groups, except that more early responders had been treated with amoxicillin-clavulanate and amoxicillin monotherapy (22.6%; 7.5%, respectively) than later responders (5.9%; 1.2%, respectively). Initial treatment modification and re-infection or recurrences were less frequent in early responders compared with later responders (14.2% and 3.3% vs. 34.8% and 5.9%, respectively). Early responders had a shorter duration of hospitalization (mean 9.4 ± SD 7.0; median 8.0 days vs. mean 15.6 ± SD 10.5; median 12

Adjuvant bisphosphonates in early breast cancer: consensus guidance for clinical practice from a European Panel.

PubMed

Hadji, P; Coleman, R E; Wilson, C; Powles, T J; Clézardin, P; Aapro, M; Costa, L; Body, J-J; Markopoulos, C; Santini, D; Diel, I; Di Leo, A; Cameron, D; Dodwell, D; Smith, I; Gnant, M; Gray, R; Harbeck, N; Thurlimann, B; Untch, M; Cortes, J; Martin, M; Albert, U-S; Conte, P-F; Ejlertsen, B; Bergh, J; Kaufmann, M; Holen, I

2016-03-01

Bisphosphonates have been studied in randomised trials in early breast cancer to investigate their ability to prevent cancer treatment-induced bone loss (CTIBL) and reduce the risk of disease recurrence and metastasis. Treatment benefits have been reported but bisphosphonates do not currently have regulatory approval for either of these potential indications. This consensus paper provides a review of the evidence and offers guidance to breast cancer clinicians on the use of bisphosphonates in early breast cancer. Using the nominal group methodology for consensus, a systematic review of the literature was augmented by a workshop held in October 2014 for breast cancer and bone specialists to present and debate the available pre-clinical and clinical evidence for the use of adjuvant bisphosphonates. This was followed by a questionnaire to all members of the writing committee to identify areas of consensus. The panel recommended that bisphosphonates should be considered as part of routine clinical practice for the prevention of CTIBL in all patients with a T score of <-2.0 or ≥2 clinical risk factors for fracture. Compelling evidence from a meta-analysis of trial data of >18,000 patients supports clinically significant benefits of bisphosphonates on the development of bone metastases and breast cancer mortality in post-menopausal women or those receiving ovarian suppression therapy. Therefore, the panel recommends that bisphosphonates (either intravenous zoledronic acid or oral clodronate) are considered as part of the adjuvant breast cancer treatment in this population and the potential benefits and risks discussed with relevant patients. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Risk for Speech Disorder Associated with Early Recurrent Otitis Media with Effusion: Two Retrospective Studies.

ERIC Educational Resources Information Center

Shriberg, Lawrence D.; Flipsen, Peter, Jr.; Thielke, Helen; Kwiatkowski, Joan; Kertoy, Marilyn K.; Katcher, Murray L.; Nellis, Robert A.; Block, Michael G.

2000-01-01

A study of 35 3-year-olds followed since infancy in a university-affiliated pediatrics clinic and 50 Native American children followed since infancy in a tribal health clinic found early recurrent otitis media with effusion was only associated with increased risk for speech disorder in the Native American children. (Contains extensive references.)…

The Educational Impact of Exposure to Clinical Psychiatry Early in an Undergraduate Medical Curriculum.

PubMed

Brown, Menna; Barnes, Jacob; Silver, Katie; Williams, Nicholas; Newton, Philip M

2016-04-01

The medical school at Swansea University provides compulsory early exposure to clinical education through short learning opportunities in the clinical setting (LOCS). These are 3-4-h sessions chosen by students from a list of over 900. Students are required to complete ten LOCS in each of their first 2 years of medical school, with at least one per year being in psychiatry. The objective of this study was to evaluate the educational experience of students undertaking LOCS in psychiatry, in part to understand whether this experience affects student understanding of psychiatry and the likelihood that they will pursue it as a career. A mixed methods approach was used. Qualitative focus group discussions were conducted with medical students to explore perceptions of psychiatry and experiences of psychiatry LOCS. Findings informed the development of a structured quantitative survey aimed at a larger sample of students. Six qualitative themes emerged: (1) limited exposure to psychiatry, (2) organizational issues, (3) positive LOCS experiences, (4) stigma, (5) anticipated emotional burden, (6) psychiatry at odds with current understanding of medicine. Questionnaire data showed that psychiatry is not a popular future career choice when compared to other specialties. Psychiatry LOCS are extremely popular with students and have a positive effect on their understanding of the specialty but did little to influence their stated likelihood of pursuing psychiatry as a career. Early exposure to clinical psychiatry through LOCS gives students positive experiences, which improve understanding and awareness of psychiatry. They do not, however, affect stated career intentions for psychiatry as a profession.

Non-clinical studies in the process of new drug development - Part II: Good laboratory practice, metabolism, pharmacokinetics, safety and dose translation to clinical studies.

PubMed

Andrade, E L; Bento, A F; Cavalli, J; Oliveira, S K; Schwanke, R C; Siqueira, J M; Freitas, C S; Marcon, R; Calixto, J B

2016-12-12

The process of drug development involves non-clinical and clinical studies. Non-clinical studies are conducted using different protocols including animal studies, which mostly follow the Good Laboratory Practice (GLP) regulations. During the early pre-clinical development process, also known as Go/No-Go decision, a drug candidate needs to pass through several steps, such as determination of drug availability (studies on pharmacokinetics), absorption, distribution, metabolism and elimination (ADME) and preliminary studies that aim to investigate the candidate safety including genotoxicity, mutagenicity, safety pharmacology and general toxicology. These preliminary studies generally do not need to comply with GLP regulations. These studies aim at investigating the drug safety to obtain the first information about its tolerability in different systems that are relevant for further decisions. There are, however, other studies that should be performed according to GLP standards and are mandatory for the safe exposure to humans, such as repeated dose toxicity, genotoxicity and safety pharmacology. These studies must be conducted before the Investigational New Drug (IND) application. The package of non-clinical studies should cover all information needed for the safe transposition of drugs from animals to humans, generally based on the non-observed adverse effect level (NOAEL) obtained from general toxicity studies. After IND approval, other GLP experiments for the evaluation of chronic toxicity, reproductive and developmental toxicity, carcinogenicity and genotoxicity, are carried out during the clinical phase of development. However, the necessity of performing such studies depends on the new drug clinical application purpose.

A Clinical Update on Delirium: From Early Recognition to Effective Management

PubMed Central

Cerejeira, Joaquim; Mukaetova-Ladinska, Elizabeta B.

2011-01-01

Delirium is a neuropsychiatric syndrome characterized by altered consciousness and attention with cognitive, emotional and behavioural symptoms. It is particularly frequent in elderly people with medical or surgical conditions and is associated with adverse outcomes. Predisposing factors render the subject more vulnerable to a congregation of precipitating factors which potentially affect brain function and induce an imbalance in all the major neurotransmitter systems. Early diagnosis of delirium is crucial to improve the prognosis of patients requiring the identification of subtle and fluctuating signs. Increased awareness of clinical staff, particularly nurses, and routine screening of cognitive function with standardized instruments, can be decisive to increase detection rates of delirium. General measures to prevent delirium include the implementation of protocols to systematically identify and minimize all risk factors present in a particular clinical setting. As soon as delirium is recognized, prompt removal of precipitating factors is warranted together with environmental changes and early mobilization of patients. Low doses of haloperidol or olanzapine can be used for brief periods, for the behavioural control of delirium. All of these measures are a part of the multicomponent strategy for prevention and treatment of delirium, in which the nursing care plays a vital role. PMID:21994844

Early Generalized Overgrowth in Autism Spectrum Disorder: Prevalence Rates, Gender Effects, and Clinical Outcomes

PubMed Central

Campbell, Daniel J.; Chang, Joseph; Chawarska, Katarzyna

2014-01-01

Objective Although early head and body overgrowth have been well-documented in autism spectrum disorder (ASD), their prevalence and significance remain unclear. It is also unclear whether overgrowth affects males and females differentially, and whether it is associated with clinical outcomes later in life. Method To evaluate prevalence of somatic overgrowth, gender effects, and associations with clinical outcomes, head circumference, height, and weight measurements were collected retrospectively between birth and 2 years of age in toddlers with ASD (n=200) and typically developing (TD; n=147) community controls. Symptom severity, verbal, and nonverbal functioning were assessed at 4 years. Results Abnormalities in somatic growth in infants with ASD were consistent with early generalized overgrowth (EGO). Boys but not girls with ASD were larger and exhibited an increased rate of extreme EGO compared to community controls (18.0% versus 3.4%). Presence of a larger body at birth and postnatal overgrowth were associated independently with poorer social, verbal, and nonverbal skills at 4 years. Conclusion Although early growth abnormalities in ASD are less common than previously thought, their presence is predictive of lower social, verbal, and nonverbal skills at 4 years, suggesting that they may constitute a biomarker for identifying toddlers with ASD at risk for less-optimal outcomes. The results highlight that the search for mechanisms underlying atypical brain development in ASD should consider factors responsible for both neural and non-neural tissue development during prenatal and early postnatal periods, and can be informed by the finding that early overgrowth may be more readily observed in males than females with ASD. PMID:25245350

Prospective Clinical Utility Study of the Use of the 21-Gene Assay in Adjuvant Clinical Decision Making in Women With Estrogen Receptor-Positive Early Invasive Breast Cancer: Results From the SWITCH Study

PubMed Central

Pivot, Xavier B.; Jacot, William; Naman, Hervé L.; Spaeth, Dominique; Misset, Jean-Louis; Largillier, Rémy; Sautiere, Jean-Loup; de Roquancourt, Anne; Pomel, Christophe; Rouanet, Philippe; Rouzier, Roman; Penault-Llorca, Frederique M.

2015-01-01

Background. The 21-gene Oncotype DX Recurrence Score assay is a validated assay to help decide the appropriate treatment for estrogen receptor-positive (ER+), early-stage breast cancer (EBC) in the adjuvant setting. The choice of adjuvant treatments might vary considerably in different countries according to various treatment guidelines. This prospective multicenter study is the first to assess the impact of the Oncotype DX assay in the French clinical setting. Methods. A total of 100 patients with ER+, human epidermal growth factor receptor 2-negative EBC, and node-negative (pN0) disease or micrometastases in up to 3 lymph nodes (pN1mi) were enrolled. Treatment recommendations, physicians’ confidence before and after knowing the Recurrence Score value, and physicians’ perception of the assay were recorded. Results. Of the 100 patients, 95 were evaluable (83 pN0, 12 pN1mi). Treatment recommendations changed in 37% of patients, predominantly from chemoendocrine to endocrine treatment alone. The proportion of patients recommended chemotherapy decreased from 52% pretest to 25% post-test. Of patients originally recommended chemotherapy, 61% were recommended endocrine treatment alone after receiving the Recurrence Score result. For both pN0 and pN1mi patients, post-test recommendations appeared to follow the Recurrence Score result for low and high values. Physicians’ confidence improved significantly. Conclusion. These are the first prospective data on the impact of the Oncotype DX assay on adjuvant treatment decisions in France. Using the assay was associated with a significant change in treatment decisions and an overall reduction in chemotherapy use. These data are consistent with those presented from European and non-European studies. Implications for Practice: This study shows that in estrogen receptor-positive, human epidermal growth factor receptor 2-negative early breast cancer (either node-negative or with micrometastases in up to 3 lymph nodes

An evaluation of learning clinical decision-making for early rehabilitation in the ICU via interactive education with audience response system.

PubMed

Toonstra, Amy L; Nelliot, Archana; Aronson Friedman, Lisa; Zanni, Jennifer M; Hodgson, Carol; Needham, Dale M

2017-06-01

Knowledge-related barriers to safely implement early rehabilitation programs in intensive care units (ICUs) may be overcome via targeted education. The purpose of this study was to evaluate the effectiveness of an interactive educational session on short-term knowledge of clinical decision-making for safe rehabilitation of patients in ICUs. A case-based teaching approach, drawing from published safety recommendations for initiation of rehabilitation in ICUs, was used with a multidisciplinary audience. An audience response system was incorporated to promote interaction and evaluate knowledge before vs. after the educational session. Up to 175 audience members, of 271 in attendance (129 (48%) physical therapists, 51 (19%) occupational therapists, 31 (11%) nursing, 14 (5%) physician, 46 (17%) other), completed both the pre- and post-test questions for each of the six unique patient cases. In four of six patient cases, there was a significant (p< 0.001) increase in identifying the correct answer regarding initiation of rehabilitation activities. This learning effect was similar irrespective of participants' years of experience and clinical discipline. An interactive, case-based, educational session may be effective for increasing short-term knowledge, and identifying knowledge gaps, regarding clinical decision-making for safe rehabilitation of patients in ICUs. Implications for Rehabilitation Lack of knowledge regarding the safety considerations for early rehabilitation of ICU patients is a barrier to implementing early rehabilitation. Interactive educational formats, such as the use of audience response systems, offer a new method of teaching and instantly assessing learning of clinically important information. In a small study, we have shown that an interactive, case-based educational format may be used to effectively teach clinical decision-making for the safe rehabilitation of ICU patients to a diverse audience of clinicians.

Early exposure to probiotics in a canine model of atopic dermatitis has long-term clinical and immunological effects.

PubMed

Marsella, Rosanna; Santoro, Domenico; Ahrens, Kim

2012-04-15

Probiotics modulate the immune response and may have protective effects against atopic dermatitis (AD). Clinical trials using dogs with spontaneous disease are limited by confounding factors such as different diets, environments and sensitizations while a more controlled evaluation is possible using experimental models. A validated model of canine AD showed that early exposure to Lactobacillus rhamnosus GG (LGG) significantly decreases allergen-specific IgE and partially prevents AD in the first 6 months of life. This study is a follow-up three years after discontinuation of LGG. Clinical signs were evaluated after allergen challenge with ragweed, timothy, Dermatophagoides farinae. Allergen-specific IgE, IL-10 and TGF-β were measured on the 1st day of challenge, before allergen exposure. Normal dogs were included as controls. Analyses included seven dogs in the non-probiotic and nine in the probiotic litter. For clinical scores, a 2-Group × 9-Time Analysis of Variance showed significant effects of group (p=0.0003, probioticEarly exposure to probiotics has long-term clinical and immunological effects in this model and larger studies using dogs with spontaneous disease are needed. Copyright © 2012 Elsevier B.V. All rights reserved.

EVERREST prospective study: a 6-year prospective study to define the clinical and biological characteristics of pregnancies affected by severe early onset fetal growth restriction.

PubMed

Spencer, Rebecca; Ambler, Gareth; Brodszki, Jana; Diemert, Anke; Figueras, Francesc; Gratacós, Eduard; Hansson, Stefan R; Hecher, Kurt; Huertas-Ceballos, Angela; Marlow, Neil; Marsál, Karel; Morsing, Eva; Peebles, Donald; Rossi, Carlo; Sebire, Neil J; Timms, John F; David, Anna L

2017-01-23

Fetal growth restriction (FGR) is a serious obstetric condition for which there is currently no treatment. The EVERREST Prospective Study has been designed to characterise the natural history of pregnancies affected by severe early onset FGR and establish a well phenotyped bio-bank. The findings will provide up-to-date information for clinicians and patients and inform the design and conduct of the EVERREST Clinical Trial: a phase I/IIa trial to assess the safety and efficacy of maternal vascular endothelial growth factor (VEGF) gene therapy in severe early onset FGR. Data and samples from the EVERREST Prospective Study will be used to identify ultrasound and/or biochemical markers of prognosis in pregnancies with an estimated fetal weight (EFW) <3rd centile between 20+0 and 26+6 weeks of gestation. This is a 6 year European multicentre prospective cohort study, recruiting women with a singleton pregnancy where the EFW is <3rd centile for gestational age and <600 g at 20+0 to 26+6 weeks of gestation. Detailed data are collected on: maternal history; antenatal, peripartum, and postnatal maternal complications; health economic impact; psychological impact; neonatal condition, progress and complications; and infant growth and neurodevelopment to 2 years of corrected age in surviving infants. Standardised longitudinal ultrasound measurements are performed, including: fetal biometry; uterine artery, umbilical artery, middle cerebral artery, and ductus venosus Doppler velocimetry; and uterine artery and umbilical vein volume blood flow. Samples of maternal blood and urine, amniotic fluid (if amniocentesis performed), placenta, umbilical cord blood, and placental bed (if caesarean delivery performed) are collected for bio-banking. An initial analysis of maternal blood samples at enrolment is planned to identify biochemical markers that are predictors for fetal or neonatal death. The findings of the EVERREST Prospective Study will support the development of a novel

Pilot Study Assessing the Feasibility of Applying Bilateral Subthalamic Nucleus Deep Brain Stimulation in Very Early Stage Parkinson's Disease: Study design and rationale

PubMed Central

Charles, David; Tolleson, Christopher; Davis, Thomas L.; Gill, Chandler E.; Molinari, Anna L.; Bliton, Mark J.; Tramontana, Michael G.; Salomon, Ronald M.; Kao, Chris; Wang, Lily; Hedera, Peter; Phibbs, Fenna T.; Neimat, Joseph S.; Konrad, Peter E.

2014-01-01

Background Deep brain stimulation provides significant symptomatic benefit for people with advanced Parkinson's disease whose symptoms are no longer adequately controlled with medication. Preliminary evidence suggests that subthalamic nucleus stimulation may also be efficacious in early Parkinson's disease, and results of animal studies suggest that it may spare dopaminergic neurons in the substantia nigra. Objective We report the methodology and design of a novel Phase I clinical trial testing the safety and tolerability of deep brain stimulation in early Parkinson's disease and discuss previous failed attempts at neuroprotection. Methods We recently conducted a prospective, randomized, parallel-group, single-blind pilot clinical trial of deep brain stimulation in early Parkinson's disease. Subjects were randomized to receive either optimal drug therapy or deep brain stimulation plus optimal drug therapy. Follow-up visits occurred every six months for a period of two years and included week-long therapy washouts. Results Thirty subjects with Hoehn & Yahr Stage II idiopathic Parkinson's disease were enrolled over a period of 32 months. Twenty-nine subjects completed all follow-up visits; one patient in the optimal drug therapy group withdrew from the study after baseline. Baseline characteristics for all thirty patients were not significantly different. Conclusions This study demonstrates that it is possible to recruit and retain subjects in a clinical trial testing deep brain stimulation in early Parkinson's disease. The results of this trial will be used to support the design of a Phase III, multicenter trial investigating the efficacy of deep brain stimulation in early Parkinson's disease. PMID:23938229

The Etiology and Clinical Course of Chronic Pancreatitis in Children With Early Onset of the Disease.

PubMed

Wejnarska, Karolina; Kolodziejczyk, Elwira; Wertheim-Tysarowska, Katarzyna; Dadalski, Maciej; Sobczynska-Tomaszewska, Agnieszka; Kierkus, Jarosław; Bal, Jerzy; Rygiel, Agnieszka Magdalena; Oracz, Grzegorz

2016-12-01

The etiological factors of chronic pancreatitis (CP) in children differ from those in adults. To date, no study has assessed the clinical course of CP in young children. The aim of our study was to evaluate the etiology and the clinical presentation of the disease in children with disease onset before 5 years of age in comparison to later-onset of CP. A total of 276 children with CP, hospitalized from 1988 to 2015, were enrolled in the study. Data on presentation, diagnostic findings, and treatment were reviewed. Two hundred sixty patients were screened for the most frequent mutations in major pancreatitis-associated genes, such as cationic trypsinogen/serine protease gene (PRSS1), serine protease inhibitor, Kazal type 1 gene (SPINK1), and cystic fibrosis transmembrane conductance regulator gene (CFTR). The disease onset before the age of 5 years occurred in 51 patients (group 1), the later onset in 225 patients (group 2). We found no significant discrepancies in distribution of the etiological factors between groups. The youngest patients (group 1) had more pancreatitis episodes (median 5.0 vs 3.00; P < 0.05) and underwent surgeries more frequently (25.5% vs 8.9%; P < 0.05). It could be associated with significantly longer follow-up in early onset group (median 6 vs 4 years; P < 0.05). There were no differences in nutritional status or exocrine and endocrine pancreatic function. Early- and later-onset pancreatitis have similar etiological factors with predominance of gene mutations. The most frequent mutation found was p.Asn34Ser (N34S) in SPINK1 gene. The clinical presentation differed in number of pancreatitis episodes and frequency of surgeries.

[Clinical study of induced abortion of early-early pregnancy: an analysis of 10, 404 cases].

PubMed

Kang, Jian; Wang, Xue-fen; Zhang, Li; Liu, Jian-hua

2012-01-03

To evaluate the advantages and disadvantages of early-early pregnancy induced abortion (EPIA). A total of 10 404 cases of EPIA performed at our hospital from January 1993 to December 2003 were retrospectively analyzed and compared with 9434 cases of common induced abortion (CIA). The amount of hemorrhage and operative duration, degree of pain, rate of induced-abortion syndrome, rate of incomplete abortion, menstrual changes and post-operative onset of Asherman's syndrome were observed and compared between 2 groups. The average age, ratio of parous cases, ratio of the cases of first-pregnancy induced abortion were not different between 2 groups (P > 0.05). The amount of hemorrhage bleeding ((4.9 ± 3.2) ml), operative duration ((90.3 ± 12.4) s), degree of pain, rate of induced-abortion syndrome, menstrual changes and the rate of Asherman's syndrome in the EPIA group were all significantly less than those in the CIA group (P < 0.05). However, the rate of incomplete abortion (0.44%) in the EPIA group was significantly higher than that (0.21%) in the CIA group (P < 0.05). EPIA has the advantages of lesser hemorrhage, less pain, shorter operative duration and fewer complications over CIA. Therefore the recovery of EPIA cases is earlier than that of CIA cases. While the risk of incomplete abortion stays high.

Early functional MRI activation predicts motor outcome after ischemic stroke: a longitudinal, multimodal study.

PubMed

Du, Juan; Yang, Fang; Zhang, Zhiqiang; Hu, Jingze; Xu, Qiang; Hu, Jianping; Zeng, Fanyong; Lu, Guangming; Liu, Xinfeng

2018-05-15

An accurate prediction of long term outcome after stroke is urgently required to provide early individualized neurorehabilitation. This study aimed to examine the added value of early neuroimaging measures and identify the best approaches for predicting motor outcome after stroke. This prospective study involved 34 first-ever ischemic stroke patients (time since stroke: 1-14 days) with upper limb impairment. All patients underwent baseline multimodal assessments that included clinical (age, motor impairment), neurophysiological (motor-evoked potentials, MEP) and neuroimaging (diffusion tensor imaging and motor task-based fMRI) measures, and also underwent reassessment 3 months after stroke. Bivariate analysis and multivariate linear regression models were used to predict the motor scores (Fugl-Meyer assessment, FMA) at 3 months post-stroke. With bivariate analysis, better motor outcome significantly correlated with (1) less initial motor impairment and disability, (2) less corticospinal tract injury, (3) the initial presence of MEPs, (4) stronger baseline motor fMRI activations. In multivariate analysis, incorporating neuroimaging data improved the predictive accuracy relative to only clinical and neurophysiological assessments. Baseline fMRI activation in SMA was an independent predictor of motor outcome after stroke. A multimodal model incorporating fMRI and clinical measures best predicted the motor outcome following stroke. fMRI measures obtained early after stroke provided independent prediction of long-term motor outcome.

The Clinical Utility and Diagnostic Performance of MRI for Identification of Early and Advanced Knee Osteoarthritis: A Systematic Review

PubMed Central

Quatman, Carmen E.; Hettrich, Carolyn M.; Schmitt, Laura C.; Spindler, Kurt P.

2013-01-01

Background Current diagnostic strategies for detection of structural articular cartilage abnormalities, the earliest structural signs of osteoarthritis, often do not capture the condition until it is too far advanced for the most potential benefit of non-invasive interventions. Purpose Systematically review the literature relative to the following questions: (1) Is MRI a valid, sensitive, specific, accurate and reliable instrument to identify knee articular cartilage abnormalities compared to arthroscopy? (2) Is MRI a sensitive tool that can be utilized to identify early cartilage degeneration? Study Design Systematic Review Methods A systematic search was performed in November 2010 using PubMed MEDLINE (from 1966), CINAHL (from 1982), SPORTDiscus (from 1985), and SCOPUS (from 1996) databases. Results Fourteen level I and 13 level II studies were identified that met inclusion criteria and provided information related to diagnostic performance of MRI compared to arthroscopic evaluation. The diagnostic performance of MRI demonstrated a large range of sensitivities, specificities, and accuracies. The sensitivity for identifying articular cartilage abnormalities in the knee joint was reported between 26–96%. Specificity and accuracy was reported between 50–100% and 49–94%, respectively. The sensitivity, specificity, and accuracy for identifying early osteoarthritis were reported between 0–86%, 48–95%, and 5–94%, respectively. As a result of inconsistencies between imaging techniques and methodological shortcomings of many of the studies, a meta-analysis was not performed and it was difficult to fully synthesize the information to state firm conclusions about the diagnostic performance of MRI. Conclusions There is evidence in some MRI protocols that MRI is a relatively valid, sensitive, specific, accurate, and reliable clinical tool for identifying articular cartilage degeneration. Due to heterogeneity of MRI sequences it is not possible to make definitive

MRI evidence of persistent joint inflammation and progressive joint damage despite clinical remission during treatment of early rheumatoid arthritis.

PubMed

Forslind, K; Svensson, B

2016-01-01

To determine the value of magnetic resonance imaging (MRI) of bones and joints in patients with recent-onset rheumatoid arthritis (RA) treated for 2 years from diagnosis with disease-modifying anti-rheumatic drugs (DMARDs) and glucocorticoids. Thirteen patients with early RA were treated according to clinical practice and followed with MRI, radiographs, and Disease Activity Score calculated on 28 joints (DAS28) at inclusion (baseline) and after 1, 4, 7, 13, and 25 months. MRI of the dominant wrist and metacarpophalangeal (MCP) joints were assessed for synovitis, bone oedema, and erosions using the RA MRI Score (RAMRIS) and for tenosynovitis by an MRI tenosynovitis scoring method. Radiographs were assessed by the van der Heijde modified Sharp score (SHS). Clinical remission was defined by a DAS28 < 2.6. MRI at baseline detected inflammation in joints and tendons in all patients as well as erosions in 10 out of 13 patients. Over time, the erosion score increased while the synovitis and tenosynovitis scores remained almost unchanged. Bone oedema strongly correlated with synovitis. Synovitis and tenosynovitis correlated well with the erosion score at baseline but not thereafter. The MRI changes showed that joint damage started early and continued in the presence of persistent synovial and tenosynovial inflammation. The observations made in this small study suggest that the treatment goal of 'clinical remission' should be supplemented by a 'joint remission' goal. To this end, MRI is an appropriate tool. Further studies are needed to evaluate the optimal use of MRI in early RA.

Accuracy of a pediatric early warning score in the recognition of clinical deterioration.

PubMed

Miranda, Juliana de Oliveira Freitas; Camargo, Climene Laura de; Nascimento, Carlito Lopes; Portela, Daniel Sales; Monaghan, Alan

2017-07-10

to evaluate the accuracy of the version of the Brighton Pediatric Early Warning Score translated and adapted for the Brazilian context, in the recognition of clinical deterioration. a diagnostic test study to measure the accuracy of the Brighton Pediatric Early Warning Score for the Brazilian context, in relation to a reference standard. The sample consisted of 271 children, aged 0 to 10 years, blindly evaluated by a nurse and a physician, specialists in pediatrics, with interval of 5 to 10 minutes between the evaluations, for the application of the Brighton Pediatric Early Warning Score for the Brazilian context and of the reference standard. The data were processed and analyzed using the Statistical Package for the Social Sciences and VassarStats.net programs. The performance of the Brighton Pediatric Early Warning Score for the Brazilian context was evaluated through the indicators of sensitivity, specificity, predictive values, area under the ROC curve, likelihood ratios and post-test probability. the Brighton Pediatric Early Warning Score for the Brazilian context showed sensitivity of 73.9%, specificity of 95.5%, positive predictive value of 73.3%, negative predictive value of 94.7%, area under Receiver Operating Characteristic Curve of 91.9% and the positive post-test probability was 80%. the Brighton Pediatric Early Warning Score for the Brazilian context, presented good performance, considered valid for the recognition of clinical deterioration warning signs of the children studied. avaliar a acurácia da versão traduzida e adaptada do Brighton Paediatric Early Warning Score para o contexto brasileiro, no reconhecimento da deterioração clínica. estudo de teste diagnóstico para medir a acurácia do Brighton Paediatric Early Warning Score, para o contexto brasileiro, em relação a um padrão de referência. A amostra foi composta por 271 crianças de 0 a 10 anos, avaliadas de forma cega por uma enfermeira e um médico, especialistas em pediatria, com

HLA-B*5701 clinical testing: early experience in the United States.

PubMed

Faruki, Hawazin; Heine, Uwe; Brown, Trisha; Koester, Ruth; Lai-Goldman, Myla

2007-10-01

HLA-B*5701 testing to provide risk stratification for abacavir hypersensitivity has the potential to reduce incidence of hypersensitivity reactions in susceptible individuals. Early experience with clinical HLA-B*5701 testing of the first 100 specimens, from a large clinical reference laboratory in the United States, is presented. Patient samples were tested using a two-step approach. The first step allowed rapid identification of most HLA-B*5701-negative samples in a high throughput mode. The second step involved resolution of putative positives by DNA sequencing to identify B*5701 specifically as well as other B57 subtypes. Test reporting included a phone call from a genetic counselor to obtain the ethnic background and indication for testing and to provide a patient-specific interpretation. The patients population was comprised of Caucasians, 84%; Hispanics, 13%; and African Americans, 3%. Among the 100 samples tested, 92% were HLA-B*5701-negative and 8% were positive for the HLA-B*5701 allele. All HLA-B*5701 allele positives were identified in Caucasian patients. Where the indication for testing was obtainable (57 patients), pre-abacavir therapy screening was the indication 67% of the time. Clarification of previous suspected history of hypersensitivity was the indication 33% of the time. Among samples tested to help clarify a previous history of hypersensitivity, 16/19 or 84% did not carry the HLA-B*5701 allele whereas 3/19 (16%) were carriers of the HLA-B*5701 allele. Early utilization of HLA-B*5701 testing in community practice was not always consistent with the clinical indications for testing. Post-test communication assisted in providing physician education and interpretation of patient-specific results.

Clinical outcomes of an early intervention program for preschool children with Autism Spectrum Disorder in a community group setting.

PubMed

Eapen, Valsamma; Crnčec, Rudi; Walter, Amelia

2013-01-07

Available evidence indicates that early intervention programs, such as the Early Start Denver Model (ESDM), can positively affect key outcomes for children with Autism Spectrum Disorder (ASD). However, programs involving resource intensive one-to-one clinical intervention are not readily available or deliverable in the community, resulting in many children with ASD missing out on evidence-based intervention during their early and most critical preschool years. This study evaluated the effectiveness of the ESDM for preschool-aged children with ASD using a predominantly group-based intervention in a community child care setting. Participants were 26 children (21 male) with ASD with a mean age of 49.6 months. The ESDM, a comprehensive early intervention program that integrates applied behaviour analysis with developmental and relationship-based approaches, was delivered by trained therapists during the child's attendance at a child care centre for preschool-aged children with ASD. Children received 15-20 hours of group-based, and one hour of one-to-one, ESDM intervention per week. The average intervention period was ten months. Outcome measures were administered pre- and post-intervention, and comprised a developmental assessment - the Mullen Scales of Early Learning (MSEL); and two parent-report questionnaires - the Social Communication Questionnaire (SCQ) and Vineland Adaptive Behaviours Scales-Second Edition (VABS-II). Statistically significant post-intervention improvements were found in children's performance on the visual reception, receptive language and expressive language domains of the MSEL in addition to their overall intellectual functioning, as assessed by standardised developmental quotients. Parents reported significant increases in their child's receptive communication and motor skills on the VABS-II, and a significant decrease in autism-specific features on the SCQ. These effects were of around medium size, and appeared to be in excess of what may

Using tablet-based technology in patient education about systemic therapy options for early-stage breast cancer: a pilot study.

PubMed

Morgan, E R; Laing, K; McCarthy, J; McCrate, F; Seal, M D

2015-10-01

Patient education in early-stage breast cancer has been shown to improve patient well-being and quality of life, but it poses a challenge given the increasingly complex regimens and time constraints in clinical practice. Technology-aided teaching in the clinic could help to improve the understanding of adjuvant systemic therapy for patients. In this prospective pilot study, we used a clinician-administered, tablet-based teaching aid to teach patients with early-stage breast cancer about adjuvant systemic therapy. Participation was offered to newly diagnosed patients with early-stage breast cancer presenting for their first medical oncology visit at a provincial cancer centre. Participants were shown a tablet-based presentation describing procedures, rationales, risks, and benefits of adjuvant systemic therapy as an adjunct to a discussion with the medical oncologist. After the clinic visit, participants completed a questionnaire measuring satisfaction with the visit and knowledge of the treatment plan discussed. The 25 patients recruited for the study had a mean age of 57 years. An offer of upfront chemotherapy alone was made to 12 participants (48%), chemotherapy with trastuzumab to 4 (16%), and hormonal therapy to 9 (36%). Correct answers to all questions related to treatment knowledge were given by 22 patients (88%). Satisfaction with the clinic visit was high (mean satisfaction score: 4.53 ± 0.1 of a possible 5). We found that a tablet-based presentation about adjuvant systemic therapy was satisfactory to patients with early-stage breast cancer and that knowledge retention after the clinic visit was high. Tablet-based teaching could be a feasible and effective way of educating patients in the breast oncology clinic and warrants further investigation in randomized studies.

Evaluation of a clinical tool for early etiology identification in status epilepticus

PubMed Central

Alvarez, Vincent; Westover, M. Brandon; Drislane, Frank W.; Dworetzky, Barbara A.; Curley, David

2016-01-01

Summary Objectives Because early etiologic identification is critical to select appropriate specific status epilepticus (SE) management, we aim to validate a clinical tool we developed that uses history and readily available investigations to guide prompt etiologic assessment. Methods This prospective multicenter study included all adult patients treated for SE of all but anoxic causes from four academic centers. The proposed tool is designed as a checklist covering frequent precipitating factors for SE. The study team completed the checklist at the time the patient was identified by electroencephalography (EEG) request. Only information available in the emergency department or at the time of in-hospital SE identification was used. Concordance between the etiology indicated by the tool and the determined etiology at hospital discharge was analyzed, together with interrater agreement. Results Two hundred twelve patients were included. Concordance between the etiology hypothesis generated using the tool and the finally determined etiology was 88.7% (95% confidence interval (CI) 86.4–89.8) (κ = 0.88). Interrater agreement was 83.3% (95% CI 80.4–96) (κ = 0.81). Significance This tool is valid and reliable for identification early the etiology of an SE. Physicians managing patients in SE may benefit from using it to identify promptly the underlying etiology, thus facilitating selection of the appropriate treatment. PMID:25385281

New Round of Studies Begin in Phase 0/I/II Cancer Prevention Clinical Trials Program | Division of Cancer Prevention

Cancer.gov

The NCI Division of Cancer Prevention’s Phase 0/I/II Cancer Prevention Clinical Trials Program, also known as the Consortia for Early Phase Prevention Trials, is beginning a new round of studies in the effort toward systematic early clinical development of promising preventive agents for people at increased risk of developing cancer. |

Early recognition of Cushing's disease: a case study.

PubMed

Iuliano, Sherry L; Laws, Edward R

2013-08-01

To present a case study of a 34-year-old woman with Cushing's disease and provide nurse practitioners (NPs) with the understanding of the clinical presentation needed for early recognition and treatment of the disease. A comprehensive review of published literature on Cushing's disease. Findings from history, physical examination, and diagnostic studies of a woman presenting to primary care NPs, physicians and other healthcare providers with multiple symptoms of Cushing's disease. Cushing's disease is the result of the pituitary gland producing excess amounts of adrenocorticotropic hormone (ACTH) causing the overproduction of cortisol. The disease is fairly rare and is seen mostly in women. Common chief complaints include increased facial hair, weight gain, amenorrhea, changes in the face, neck, and abdomen, with muscle wasting of the lower extremities. Untreated, diabetes mellitus and hypertension can occur and increase the patient's morbidity and mortality. Early recognition and appropriate referral can reverse the signs and symptoms over time and lead to a significantly improved quality of life. This case presented the challenges faced by NPs and physicians in diagnosing patients with Cushing's disease. ©2013 The Author(s) ©2013 American Association of Nurse Practitioners.

[Anthology of the first clinical studies with hypothalamic hormones: a story of successful international cooperation].

PubMed

Schally, Andrew V; Gual, Carlos

2002-01-01

Our early pioneering clinical trials in Mexico with natural and synthetic thyrotropin-releasing hormone (TRH) and luteinizing hormone releasing hormone (LH-RH) also known as gonadotropin releasing hormone (Gn-RH), were reviewed. Highly purified TRH of porcine origin was shown to stimulate Thyrotropin (TSH) release in hypothyroid cretins. Subsequent tests with synthetic TRH also demonstrated significant increases in plasma TSH in normal men and women as well as in patients with primary hypothyroidism and other endocrine disorders. Even more extensive clinical studies were carried out with highly purified natural porcine LH-RH. Subjects with normal basal serum levels of gonadotropins, low levels (men and women pretreated with steroids) and high levels (e.g. post menopausal women) all responded to LH-RH with a release of LH and FSH. The results of these early studies with the natural LH-RH were confirmed by the use of synthetic LH-RH. These investigations made in Mexico with TRH and LH-RH preceded all other clinical studies by a wide margin. Subsequently various clinical investigations with LH-RH agonists and antagonists were also carried out. All these studies played a major role in introducing hypothalamic-releasing hormones into clinical medicine.

Predictive variables for the occurrence of early clinical mastitis in primiparous Holstein cows under field conditions in France.

PubMed Central

Barnouin, J; Chassagne, M

2001-01-01

Holstein heifers from 47 dairy herds in France were enrolled in a field study to determine predictors for clinical mastitis within the first month of lactation. Precalving and calving variables (biochemical, hematological, hygienic, and disease indicators) were collected. Early clinical mastitis (ECM) predictive variables were analyzed by using a multiple logistic regression model (99 cows with ECM vs. 571 without clinical mastitis throughout the first lactation). Two variables were associated with a higher risk of ECM: a) difficult calving and b) medium and high white blood cell (WBC) counts in late gestation. Two prepartum indicators were associated with a lower ECM risk: a) medium and high serum concentrations of immunoglobulin G1 (IgG1) and b) high percentage of eosinophils among white blood cells. Calving difficulty and certain biological blood parameters (IgG1, eosinophils) could represent predictors that would merit further experimental studies, with the aim of designing programs for reducing the risk of clinical mastitis in the first lactation. PMID:11195522

Early-Onset Multiple Sclerosis in Isfahan, Iran: Report of the Demographic and Clinical Features of 221 Patients.

PubMed

Etemadifar, Masoud; Nourian, Sayed-Mohammadamin; Nourian, Niloofaralsadat; Abtahi, Seyed-Hossein; Sayahi, Farnaz; Saraf, Zahra; Fereidan-Esfahani, Mahboobeh

2016-06-01

It is estimated that early-onset multiple sclerosis multiple sclerosis (early-onset multiple sclerosis) approximately incorporates 3-5% of the multiple sclerosis population. In this report on early-onset multiple sclerosis, the authors aimed to define demographic, clinical and imaging features in a case-series of true-childhood multiple sclerosis and to compare its characteristics with juvenile multiple sclerosis. The authors inspected the records of multiple sclerosis patients who were registered by Isfahan MS Society. Clinical and demographic data of children with less than 16 years of age were reviewed retrospectively. Out of 4536 multiple sclerosis patients referred to the authors' center, 221 patients (4.8%) had multiple sclerosis starting at the age of 16 or less (11 true-childhood multiple sclerosis vs 210 juvenile-onset multiple sclerosis); the female to male ratio was 4.81:1. In the mean follow-up period of 6.2 years, 22 patients (10.5%) had positive family history of multiple sclerosis, 196 (88.6%) patients were classified as relapsing-remitting multiple sclerosis, the mean (± SD Expanded Disability Status Scale) was 1.5 ± 1.1 at the last evaluation. The most common initial presentation was optic nerve involvement (36.1%) and cerebellar sign and symptoms (14.6%). In all, 13 patients (5.8%) had experienced seizure in the course of multiple sclerosis. This study indicated that early-onset multiple sclerosis is not rare condition and overwhelmingly affects girls even at prepubertal onset. Physicians should consider multiple sclerosis in suspicious pediatric cases. © The Author(s) 2016.

Pelvic girdle pain--associations between risk factors in early pregnancy and disability or pain intensity in late pregnancy: a prospective cohort study.

PubMed

Robinson, Hilde Stendal; Veierød, Marit B; Mengshoel, Anne Marit; Vøllestad, Nina K

2010-05-13

Recent studies have shown high prevalence rates for pelvic girdle pain (PGP) in pregnancy. Some risk factors for developing PGP have been suggested, but the evidence is weak. Furthermore there is almost no data on how findings from clinical examinations are related to subsequent PGP. The main purpose for this study was to study the associations between socio-demographical, psychological and clinical factors measured at inclusion in early pregnancy and disability or pain intensity in gestation week 30. This is a prospective cohort study following women from early to late pregnancy. Eligible women were recruited at their first attendance at the maternity care unit. 268 pregnant women answered questionnaires and underwent clinical examinations in early pregnancy and in gestation week 30. We used scores on disability and pain intensity in gestation week 30 as outcome measures to capture the affliction level of PGP. Multiple linear regression analysis was used to study the associations between potential risk factors measured in early pregnancy and disability or pain intensity in gestation week 30. Self-reported pain locations in the pelvis, positive posterior pelvic pain provocation (P4) test and a sum of pain provocation tests in early pregnancy were significantly associated with disability and pain intensity in gestation week 30 in a multivariable statistic model. In addition, distress was significantly associated with disability. The functional active straight leg raise (ASLR) test, fear avoidance beliefs and the number of pain sites were not significantly associated with either disability or pain intensity. The results suggest that a clinical examination, including a few tests, performed in early pregnancy may identify women at risk of a more severe PGP late in pregnancy. The identification of clinical risk factors may provide a foundation for development of targeted prevention strategies.

Pilot evaluation of parent-child interaction therapy delivered in an Australian community early childhood clinic setting.

PubMed

Phillips, Jane; Morgan, Susan; Cawthorne, Karen; Barnett, Bryanne

2008-08-01

Parent-child interaction therapy (PCIT) is a short-term, evidence-based parent training intervention used widely in the treatment of behaviourally disordered preschool-aged children. Outcome studies have shown PCIT to be associated with lasting improvements in child and sibling behaviours and in the interactional styles, stress levels, confidence, and psychological functioning of parents. To date, however, all outcome studies have been conducted in university research clinic settings, and therefore understanding about the effectiveness of PCIT applied in a real-world setting has been limited. The present study evaluated the effectiveness of PCIT delivered to families in an Australian community-based early childhood clinic. Participants included 43 families with children aged 19-52 months who were referred for treatment of disruptive child behaviours and who completed PCIT treatment at the Karitane Toddler Clinic, in Sydney, Australia. Parents provided pre- and post-treatment ratings of child behaviours, parental stress, parental psychopathology and parental attitudes to therapy. At the end of the programme, clinically and statistically significant improvements were seen in child behaviours and parental well-being, and parents reported high levels of satisfaction with treatment. Implications for the implementation of PCIT programmes in community-based settings are discussed and areas of further research are identified.

Teacher Candidates and Latina/o English Learners at Fenton Elementary School: The Role of Early Clinical Experiences in Urban Teacher Education

ERIC Educational Resources Information Center

Nasir, Ambareen; Heineke, Amy J.

2014-01-01

This study investigates how early clinical experiences impact teacher candidates' learning and experiences with Latina/o English learners in a field-based program housed in a multilingual, urban elementary school. We draw on multiple-case study design and use discourse analysis to explore cases of three candidates. Findings reveal exploration of…

Learning curve and early clinical outcomes for a robotic surgery novice performing robotic single site cholecystectomy.

PubMed

Angus, Andrew A; Sahi, Saad L; McIntosh, Bruce B

2014-06-01

A rapid training protocol has been developed for robotic surgery novices to learn robotic single-incision techniques. This study assesses the learning curve and early clinical results for a robotic surgery novice starting single-site cholecystectomy. A chart review was performed on the surgeon's first 55 patients to undergo this procedure. Average patient age was 46.01 ± 4.25 (range 21-86) years and BMI was 26.57 ± 4.25 (range 19.4-36.6) kg/m(2) . The mean port placement with docking time was 11.34 ± 3.74 (range 7-23) min. Mean console time was 28.74 ± 11.04 (range 15-66) min. Average total OR time was 61.84 ± 14.66 (range 40-105) min. All procedures were successfully completed without conversion or added ports. Complications included several minor procedural gall bladder perforations and miscellaneous postoperative symptomatic complaints. Robotic single site cholecystectomy can be safely performed by a robotic novice within a minimal learning curve and have early clinical results that are comparable to the published data of robotic experts. Copyright © 2013 John Wiley & Sons, Ltd.

Neuromuscular findings in thyroid dysfunction: a prospective clinical and electrodiagnostic study

PubMed Central

Duyff, R.; Van den Bosch, J.; Laman, D; van Loon, B.-J. P.; Linssen, W.

2000-01-01

OBJECTIVES—To evaluate neuromuscular signs and symptoms in patients with newly diagnosed hypothyroidism and hyperthyroidism.
METHODS—A prospective cohort study was performed in adult patients with newly diagnosed thyroid dysfunction. Patients were evaluated clinically with hand held dynamometry and with electrodiagnosis. The clinical features of weakness and sensory signs and the biochemical data were evaluated during treatment.
RESULTS—In hypothyroid patients 79% had neuromuscular complaints, 38% had clinical weakness (manual muscle strength testing) in one or more muscle groups, 42% had signs of sensorimotor axonal neuropathy, and 29% had carpal tunnel syndrome. Serum creatine kinase did not correlate with weakness. After 1 year of treatment 13% of the patients still had weakness. In hyperthyroid patients 67% had neuromuscular symptoms, 62% had clinical weakness in at least one muscle group that correlated with FT4 concentrations, but not with serum CK. Nineteen per cent of the patients had sensory-motor axonal neuropathy and 0% had carpal tunnel syndrome. The neuromuscular signs developed rapidly, early in the course of the disorder and were severe, but resolved rapidly and completely during treatment (average time 3.6months).
CONCLUSIONS—Neuromuscular symptoms and signs were present in most patients. About 40% of the hypothyroid patients and 20% of the hyperthyroid patients had predominantly sensory signs of a sensorimotor axonal neuropathy early in the course of thyroid disease. Weakness in hyperthyroidism evolved rapidly at an early stage of the disorder and resolved completely during treatment, suggesting a functional muscle disorder. Hand held dynamometry is sensitive for the detection of weakness and for the clinical evaluation of treatment effects. Weakness in hypothyroidism is more difficult to treat, suggesting myopathy.

 PMID:10811699

Neuromuscular findings in thyroid dysfunction: a prospective clinical and electrodiagnostic study.

PubMed

Duyff, R F; Van den Bosch, J; Laman, D M; van Loon, B J; Linssen, W H

2000-06-01

To evaluate neuromuscular signs and symptoms in patients with newly diagnosed hypothyroidism and hyperthyroidism. A prospective cohort study was performed in adult patients with newly diagnosed thyroid dysfunction. Patients were evaluated clinically with hand held dynamometry and with electrodiagnosis. The clinical features of weakness and sensory signs and the biochemical data were evaluated during treatment. In hypothyroid patients 79% had neuromuscular complaints, 38% had clinical weakness (manual muscle strength testing) in one or more muscle groups, 42% had signs of sensorimotor axonal neuropathy, and 29% had carpal tunnel syndrome. Serum creatine kinase did not correlate with weakness. After 1 year of treatment 13% of the patients still had weakness. In hyperthyroid patients 67% had neuromuscular symptoms, 62% had clinical weakness in at least one muscle group that correlated with FT4 concentrations, but not with serum CK. Nineteen per cent of the patients had sensory-motor axonal neuropathy and 0% had carpal tunnel syndrome. The neuromuscular signs developed rapidly, early in the course of the disorder and were severe, but resolved rapidly and completely during treatment (average time 3.6 months). Neuromuscular symptoms and signs were present in most patients. About 40% of the hypothyroid patients and 20% of the hyperthyroid patients had predominantly sensory signs of a sensorimotor axonal neuropathy early in the course of thyroid disease. Weakness in hyperthyroidism evolved rapidly at an early stage of the disorder and resolved completely during treatment, suggesting a functional muscle disorder. Hand held dynamometry is sensitive for the detection of weakness and for the clinical evaluation of treatment effects. Weakness in hypothyroidism is more difficult to treat, suggesting myopathy.

Key components of a service model providing early childhood support for women attending opioid treatment clinics: an Australian state health service review.

PubMed

Harvey, Susan R; Schmied, Virginia; Nicholls, Daniel; Dahlen, Hannah

2012-09-01

To report the findings of a service review--specifically the strategy to provide early childhood services 'on site' at opioid treatment clinics to address access difficulties. Child and family health nurses are skilled in the assessment and support of families during early childhood. However, women with a history of substance abuse are often cautious when engaging with universal and other health services, with the result that the infant may miss recommended developmental screening and early referral to improve health outcomes. In 2006, an internal review was undertaken of the integration of early childhood and parenting services at opioid treatment clinics in a large Area Health Service of New South Wales, Australia. A qualitative study design, using semi-structured interview questions was used. Data were collected via six focus groups (4-15 participants in each group) and individual interview of child and family health nurses, nurse unit managers and clinical staff (n=58). Three key components of a model for providing early childhood support in collaboration with opioid treatment services were identified. First, the importance of building a trusting relationship between the woman and the child and family health nurses, second, maintaining continuity of care and a multidisciplinary/multiagency approach, and finally the importance of staff education, support and professional development. The provision of early childhood and parenting services on site, as part of a multidisciplinary 'one stop shop' approach to service delivery was a clear recommendation of the review. Reduction of access difficulties to specialised early childhood support is of benefit to clients, community health services attempting to provide a service to this difficult to reach population and to drug and alcohol services seeking to provide a high level of holistic care for clients. © 2012 Blackwell Publishing Ltd.

The role of the dorsolateral prefrontal cortex in early threat processing: a TMS study.

PubMed

Sagliano, Laura; D'Olimpio, Francesca; Panico, Francesco; Gagliardi, Serena; Trojano, Luigi

2016-12-01

Previous studies demonstrated that excitatory (high frequency) offline transcranial magnetic stimulation (TMS) over the left and right dorsolateral prefrontal cortex (DLPFC) modulates attention allocation on threatening stimuli in non-clinical samples. These studies only employed offline TMS protocol that did not allow investigating the effect of the stimulation on the early stage of threat processing. In this study, the role of the right and left dorsolateral prefrontal cortex in early threat processing was investigated in high and low anxious individuals by means of an inhibitory single-pulse online TMS protocol. Our results demonstrated the role of the left DLPFC in an early stage of threat processing and that this effect is modulated by individuals' anxiety level. The inhibitory stimulation of the left DLPFC determined a disengagement bias in high anxious individuals, while the same stimulation determined an attentional avoidance in low anxious individuals. The findings of the present study suggest that right and left DLPFC are differently involved in early threat processing of healthy individuals. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

75 FR 63188 - Draft Guidance for Industry: Early Clinical Trials With Live Biotherapeutic Products: Chemistry...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-14

...] Draft Guidance for Industry: Early Clinical Trials With Live Biotherapeutic Products: Chemistry...: Chemistry, Manufacturing, and Control Information'' dated September 2010. The draft guidance provides... Products: Chemistry, Manufacturing, and Control Information'' dated September 2010. The draft guidance...

Early experiences in establishing a regional quantitative imaging network for PET/CT clinical trials.

PubMed

Doot, Robert K; Thompson, Tove; Greer, Benjamin E; Allberg, Keith C; Linden, Hannah M; Mankoff, David A; Kinahan, Paul E

2012-11-01

The Seattle Cancer Care Alliance (SCCA) is a Pacific Northwest regional network that enables patients from community cancer centers to participate in multicenter oncology clinical trials where patients can receive some trial-related procedures at their local center. Results of positron emission tomography (PET) scans performed at community cancer centers are not currently used in SCCA Network trials since clinical trials customarily accept results from only trial-accredited PET imaging centers located at academic and large hospitals. Oncologists would prefer the option of using standard clinical PET scans from Network sites in multicenter clinical trials to increase accrual of patients for whom additional travel requirements for imaging are a barrier to recruitment. In an effort to increase accrual of rural and other underserved populations to Network trials, researchers and clinicians at the University of Washington, SCCA and its Network are assessing the feasibility of using PET scans from all Network sites in their oncology clinical trials. A feasibility study is required because the reproducibility of multicenter PET measurements ranges from approximately 3% to 40% at national academic centers. Early experiences from both national and local PET phantom imaging trials are discussed, and next steps are proposed for including patient PET scans from the emerging regional quantitative imaging network in clinical trials. There are feasible methods to determine and characterize PET quantitation errors and improve data quality by either prospective scanner calibration or retrospective post hoc corrections. These methods should be developed and implemented in multicenter clinical trials employing quantitative PET imaging of patients. Copyright © 2012 Elsevier Inc. All rights reserved.

Factors affecting clinical outcome following treatment of early childhood caries under general anaesthesia: a two-year follow-up.

PubMed

El Batawi, H Y

2014-06-01

To investigate factors that might affect the clinical outcome of early childhood caries treatment under dental general anaesthesia (DGA). Retrospective longitudinal study. The medical records of paediatric patients with early childhood caries who underwent full dental rehabilitation under DGA during 2011 in a private medical facility in Jeddah, Saudi Arabia, were investigated. Study parameters were the patient's financial arrangements and compliance with suggested recall plan. Statistical analysis of caries recurrence and the need to repeat the rehabilitation process was also performed. Eighteen percent failed to attend any post-operative visit. Twenty-six percent did not comply with the post-operative preventive plan. The overall relapse rate was high (58.5%), with the highest percentage (68%) among the non-compliant group. The highest frequency of repeat DGA (10%) was in the non-compliant group. Despite the high rate of post-operative caries recurrence, DGA is still an acceptable treatment option as it minimises the need for future dental treatment. Compliance by caregivers with post-operative care plans is as important as the procedure itself. In Saudi Arabia, targeting the actual caregivers with post-operative dental health education presents challenges that might affect the clinical outcome of DGA.

Assessing risk factors for early hip osteoarthritis in activity-related hip pain: a Delphi study

PubMed Central

Jackson, K A; Glyn-Jones, S; Batt, M E; Arden, N K; Newton, J L

2015-01-01

Objective Hip pain and injury as a result of activity can lead to the development of early hip osteoarthritis (OA) in susceptible individuals. Our understanding of the factors that increase susceptibility continues to evolve. The ability to clearly identify individuals (and cohorts) with activity-related hip pain who are at risk of early hip OA is currently lacking. The purpose of this study was to gain expert consensus on which key clinical measures might help predict the risk of early hip OA in individuals presenting with activity-related hip pain. The agreed measures would constitute a standardised approach to initial clinical assessment to help identify these individuals. Methods This Dephi study used online surveys to gain concordance of expert opinion in a structured process of ‘rounds’. In this study, we asked ‘What outcome measures are useful in predicting hip OA in activity-related hip pain?’ The Delphi panel consisted of experts from sport and exercise medicine, orthopaedics, rheumatology, physiotherapy and OA research. Results The study identified key clinical measures in the history, examination and investigations (plain anteroposterior radiograph and femoroacetabular impingement views) that the panel agreed would be useful in predicting future risk of hip OA when assessing activity-related hip pain. The panel also agreed that certain investigations and tests (eg, MR angiography) did not currently have a role in routine assessment. There was a lack of consensus regarding the role of MRI, patient-reported outcome measures (PROMs) and certain biomechanical and functional assessments. Conclusions We provide a standardised approach to the clinical assessment of patients with activity-related hip pain. Assessment measures rejected by the Delphi panel were newer, more expensive investigations that currently lack evidence. Assessment measures that did not reach consensus include MRI and PROMs. Their role remains ambiguous and would benefit from further

Toward a clinically useful method of predicting early breast-feeding attrition.

PubMed

Lewallen, Lynne Porter; Dick, Margaret J; Wall, Yolanda; Zickefoose, Kimberly Taylor; Hannah, Susan Hensley; Flowers, Janet; Powell, Wanda

2006-08-01

The overall purpose of this study was to revise and test an instrument to identify, during the early postpartum period, women at risk for early breast-feeding attrition. This study was completed in two phases: the first phase tested a revision of the Breast-Feeding Attrition Prediction Tool (BAPT); the second, a new instrument, the Breast-Feeding Attitude Scale (BrAS), which was adapted from the BAPT. The two phases of this study involved 415 pregnant and postpartum women. Women answered questions either by phone (pregnant women) or in their hospital rooms after delivery (postpartum women). Data were analyzed using t tests and reliability analysis. The BAPT did not predict early breast-feeding attrition; however, the BrAS did differentiate between the attitudes of breast-feeding women and those of formula-feeding women and had adequate reliability. Women at risk for early breast-feeding attrition should be identified early so nursing interventions can be directed toward preventing early unintended weaning. Although the BrAS did not reliably identify women at risk in this sample, it did highlight important differences between breast-feeding and formula-feeding women that can be used in designing preconceptional or prenatal educational assessments and interventions.

Early clinical experience: do students learn what we expect?

PubMed

Helmich, Esther; Bolhuis, Sanneke; Laan, Roland; Koopmans, Raymond

2011-07-01

Early clinical experience is thought to contribute to the professional development of medical students, but little is known about the kind of learning processes that actually take place. Learning in practice is highly informal and may be difficult to direct by predefined learning outcomes. Learning in medical practice includes a socialisation process in which some learning outcomes may be valued, but others neglected or discouraged. This study describes students' learning goals (prior to a Year 1 nursing attachment) and learning outcomes (after the attachment) in relation to institutional educational goals, and evaluates associations between learning outcomes, student characteristics and place of attachment. A questionnaire containing open-ended questions about learning goals and learning outcomes was administered to all Year 1 medical students (n = 347) before and directly after a 4-week nursing attachment in either a hospital or a nursing home. Two confirmatory focus group interviews were conducted and data were analysed using qualitative and quantitative content analyses. Students' learning goals corresponded with educational goals with a main emphasis on communication and empathy. Other learning goals included gaining insight into the organisation of health care and learning to deal with emotions. Self-reported learning outcomes were the same, but students additionally mentioned reflection on professional behaviour and their own future development. Women and younger students mentioned communication and empathy more often than men and older students. Individual learning goals, with the exception of communicating and empathising with patients, did not predict learning outcomes. Students' learning goals closely match educational goals, which are adequately met in early nursing attachments in both hospitals and nursing homes. Learning to deal with emotions was under-represented as a learning goal and learning outcome, which may indicate that emotional aspects

Effect of early amniotomy on dystocia risk and cesarean delivery in nulliparous women: a randomized clinical trial.

PubMed

Ghafarzadeh, Masoomeh; Moeininasab, Samira; Namdari, Mehrdad

2015-08-01

Artificial rupture of amniotic membranes (amniotomy) which induces or accelerates labor is the most common obstetrical procedure. There is controversy about the effect of early amniotomy on dystocia and cesarean delivery. The study aim was to determine the effect of early amniotomy on the risk of dystocia and cesarean delivery in nulliparous women. This randomized controlled clinical trial was conducted on 300 nulliparous women. They were randomly assigned into the experimental (early amniotomy; artificial amniotomy at cervical dilation ≤ 4 cm) and control (routine management) groups (each 150 women). Length of labor, dystocia, cesarean delivery, placental abruption, and umbilical cord prolapse were compared between the groups. Early amniotomy shortened labor duration significantly in experimental group (7.5 ± 0.7 h) compared to control group (9.9 ± 1.0 h) (P < 0.001). Dystocia (6.7 vs. 25.3 %, P < 0.0001), cesarean delivery (11.3 vs. 39.3 %, P < 0.001), and placental abruption (4.7 vs. 13.3 %, P = 0.009) were significantly lower in experimental group compared to the control group. Multiple logistic regression showed that early amniotomy decreased the odds of dystocia 80.6 % (95 % CI 58.6-90.1 %) and the odds of cesarean section 81.7 % (95 % CI 66.2-90.1 %). Early amniotomy was associated with lower rate of dystocia and cesarean delivery as well as shorter duration of labor.

Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline.

PubMed

Harris, Lyndsay N; Ismaila, Nofisat; McShane, Lisa M; Andre, Fabrice; Collyar, Deborah E; Gonzalez-Angulo, Ana M; Hammond, Elizabeth H; Kuderer, Nicole M; Liu, Minetta C; Mennel, Robert G; Van Poznak, Catherine; Bast, Robert C; Hayes, Daniel F

2016-04-01

To provide recommendations on appropriate use of breast tumor biomarker assay results to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer. A literature search and prospectively defined study selection sought systematic reviews, meta-analyses, randomized controlled trials, prospective-retrospective studies, and prospective comparative observational studies published from 2006 through 2014. Outcomes of interest included overall survival and disease-free or recurrence-free survival. Expert panel members used informal consensus to develop evidence-based guideline recommendations. The literature search identified 50 relevant studies. One randomized clinical trial and 18 prospective-retrospective studies were found to have evaluated the clinical utility, as defined by the guideline, of specific biomarkers for guiding decisions on the need for adjuvant systemic therapy. No studies that met guideline criteria for clinical utility were found to guide choice of specific treatments or regimens. In addition to estrogen and progesterone receptors and human epidermal growth factor receptor 2, the panel found sufficient evidence of clinical utility for the biomarker assays Oncotype DX, EndoPredict, PAM50, Breast Cancer Index, and urokinase plasminogen activator and plasminogen activator inhibitor type 1 in specific subgroups of breast cancer. No biomarker except for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 was found to guide choices of specific treatment regimens. Treatment decisions should also consider disease stage, comorbidities, and patient preferences. © 2016 by American Society of Clinical Oncology.

Differences between WHO AND CDC early growth measurements in the assessment of Cystic Fibrosis clinical outcomes.

PubMed

Usatin, Danielle; Yen, Elizabeth H; McDonald, Catherine; Asfour, Fadi; Pohl, John; Robson, Jacob

2017-07-01

Early childhood growth status has been used to predict long-term clinical outcomes in Cystic Fibrosis (CF) patients. Adulthood CF outcomes based on early weight-for-length (WFL) measurements, using either World Health Organization (WHO) or Centers for Disease Control (CDC) scales, have not been compared. Cystic Fibrosis Foundation registry patients were studied (n=3014). Participants were categorized at age two years as WFL <50th percentile on both WHO and CDC scales, ≥50th percentile on WHO but not CDC, or ≥50th percentile on both. Pulmonary function and overall survival were assessed at age 18years. Stepwise gains in pulmonary function and lung transplant-free survival were noted across the three increasing WFL categories. Children with CF who achieve higher WFL at age two years have improved pulmonary and survival outcomes into adulthood. CF providers should continue to utilize current early growth recommendations, with goal WFL ≥50th percentile on CDC growth charts before age two. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Understanding Treatment Burden and Quality of Life Impact of Participating in an Early-Phase Pediatric Oncology Clinical Trial: A Pilot Study.

PubMed

Crane, Stacey; Backus, Lori; Stockman, Beth; Carpenter, Janet S; Lin, Li; Haase, Joan

Early-phase clinical trials (EPTs) have led to new, more effective treatment options for children with cancer. Despite the extensive use of EPTs in pediatric oncology, little is known about parent and child experiences during EPT participation. The purposes of this pilot study were to assess the feasibility and preliminary results of having children with cancer and their parents complete measures of treatment burden and quality of life (QOL) concurrent with EPT participation. In this descriptive, longitudinal, pilot study, parents and children were followed for the first 60 days of an EPT. Feasibility was assessed by participant enrollment and retention and completion of measures. Measures completed included the following: demographic form (completed at baseline); Diary of Trial Experiences to capture treatment burden (completed ongoing); and PedsQL™ Quality of Life Inventories, Cancer Modules, and Family Impact Module (completed at baseline, post-first disease evaluation, and off-study). Data were analyzed using descriptive statistics. Feasibility goals of enrollment, retention, and measure completion were partially met. Preliminary treatment burden and QOL results are provided. While QOL assessments may provide insight into EPT experiences, future studies need to be conducted at multiple sites and enrollment goals must account for participant attrition.

Clinical features of pathologic childhood aerophagia: early recognition and essential diagnostic criteria.

PubMed

Hwang, Jin-Bok; Choi, Won Joung; Kim, Jun Sik; Lee, Sang Yun; Jung, Chul-Ho; Lee, Young Hwan; Kam, Sin

2005-11-01

This study investigated the early recognition and diagnosis of pathologic childhood aerophagia to avoid unnecessary diagnostic approaches and serious complications. Between 1995 and 2003, data from 42 consecutive patients with pathologic childhood aerophagia, aged 2 to 16 years, were reviewed. An esophageal air sign was defined as an abnormal air shadow on the proximal esophagus adjacent to the trachea on a full-inflated chest radiograph. Of the 42 patients, the chief complaints were abdominal distention (52.4%), recurrent abdominal pain syndrome (21.4%), chronic diarrhea (11.9%), acute abdominal pain (7.1%) and others (7.2%). Mean symptom duration before diagnosis was 10.6 months (range, 1 to 60 months), and it exceeded 12 months for 16 (38.1%) patients. The clinical features common to all patients were abdominal distention that increased progressively during the day, increased flatus on sleep, increased bowel sound on auscultation and an air-distended stomach with increased gas in the small and large bowel by radiography. Visible or audible air swallowing (26.2%) and repetitive belching (9.5%) were also noted. Esophageal air sign was observed in 76.2% of the patients and in 9.7% of the controls (P=0.0001). The subgroups of pathologic childhood aerophagia divided by underlying associations were pathologic childhood aerophagia without severe mental retardation (76.2%), which consisted of psychological stresses and uncertain condition, and pathologic childhood aerophagia with severe mental retardation (23.8%). The common manifestations of pathologic childhood aerophagia may be its essential diagnostic criteria, and esophageal air sign may be useful for the early recognition of pathologic childhood aerophagia. Our observations show that the diagnostic clinical profiles suggested by Rome II criteria should be detailed and made clearer if they are to serve as diagnostic criteria for pathologic childhood aerophagia.

A controlled trial of rasagiline in early Parkinson disease: the TEMPO Study.

PubMed

2002-12-01

Monotherapy with rasagiline mesylate may be useful in early Parkinson disease (PD). To evaluate the safety and efficacy of the selective monoamine oxidase type B inhibitor rasagiline. Multicenter, 26-week, parallel-group, randomized, double-blind, placebo-controlled clinical trial. Academically based movement disorders clinics. Patients with early PD not requiring dopaminergic therapy (n = 404). Research participants were randomized to rasagiline mesylate at dosages of 1 mg or 2 mg per day or matching placebo. A 1-week escalation period was followed by a 25-week maintenance period. The primary prespecified measure of efficacy was the change in the total Unified Parkinson's Disease Rating Scal score between baseline and 26 weeks of treatment, comparing each active treatment group with the placebo group. Monotherapy with rasagiline was effective in this 26-week study. The adjusted effect size for the total Unified Parkinson's Disease Rating Scale was -4.20 units comparing 1 mg of rasagiline and placebo (95% confidence interval, -5.66 to -2.73 units; P<.001) and -3.56 units comparing a 2-mg dosage and placebo (95% confidence interval, -5.04 to -2.08 units; P<.001). There were no meaningful differences in the frequency of adverse events or premature withdrawals among the treatment groups. Rasagiline is effective as monotherapy for patients with early PD. The 2 dosages in this trial were both effective relative to placebo. Further study is warranted to evaluate the longer-term effects of rasagiline in PD.

A WHO study of treatment schedules for early syphilis in use throughout the world

PubMed Central

Willcox, R. R.

1954-01-01

Ten years have elapsed since penicillin was introduced in the treatment of syphilis. In order to appraise recent trends in syphilotherapy in the world, WHO carried out a detailed study of treatment practices in early syphilis. A questionnaire was circulated to leading venereologists and clinics in the world, and 277 replies were received from 55 countries giving particulars of 294 schedules. A total of 65.3% of the participants used penicillin alone and 28.9% used it in combination with other drugs. In North America all clinics relied solely on penicillin as against 52.2% in Europe; and procaine penicillin G in oil with aluminium monostearate (PAM) was used in 91% of clinics in the Americas and Asia and in 60.6% of European clinics. The most common dosage of penicillin in all stages of early syphilis was 4.8-6.0 million units; but appreciably larger doses were used in Europe than elsewhere, some 39.4% of schedules using 10.8 million units or more. There were single instances of 36 million units being given. Consolidation treatment was given in none of the North American clinics; seldom in Asia; by about one-third of the participants in Central and South America; and, for secondary syphilis, in 59% of European schedules. This study shows that with intensive treatment with PAM the saving in drug cost to clinics over the classical courses of arsenic and bismuth may be as much as £4 per case, but the overhead expenses are, of course, not reduced. PMID:13182588

Depression and anxiety in women with early breast cancer: five year observational cohort study

PubMed Central

Burgess, Caroline; Cornelius, Victoria; Love, Sharon; Graham, Jill; Richards, Michael; Ramirez, Amanda

2005-01-01

Objective To examine the prevalence of, and risk factors for, depression and anxiety in women with early breast cancer in the five years after diagnosis. Design Observational cohort study. Setting NHS breast clinic, London. Participants 222 women with early breast cancer: 170 (77%) provided complete interview data up to either five years after diagnosis or recurrence. Main outcome measures Prevalence of clinically important depression and anxiety (structured psychiatric interview with standardised diagnostic criteria) and clinical and patient risk factors, including stressful life experiences (Bedford College life events and difficulties schedule). Results Nearly 50% of the women with early breast cancer had depression, anxiety, or both in the year after diagnosis, 25% in the second, third, and fourth years, and 15% in the fifth year. Point prevalence was 33% at diagnosis, falling to 15% after one year. 45% of those with recurrence experienced depression, anxiety, or both within three months of the diagnosis. Previous psychological treatment predicted depression, anxiety, or both in the period around diagnosis (one month before diagnosis to four months after diagnosis). Longer term depression and anxiety, were associated with previous psychological treatment, lack of an intimate confiding relationship, younger age, and severely stressful non-cancer life experiences. Clinical factors were not associated with depression and anxiety, at any time. Lack of intimate confiding support also predicted more protracted episodes of depression and anxiety. Conclusion Increased levels of depression, anxiety, or both in the first year after a diagnosis of early breast cancer highlight the need for dedicated service provision during this time. Psychological interventions for women with breast cancer who remain disease free should take account of the broader social context in which the cancer occurs, with a focus on improving social support. PMID:15695497

Clinical guideline for nurse-led early extubation after coronary artery bypass: an evaluation.

PubMed

Hawkes, Claire; Foxcroft, David R; Yerrell, Paul

2010-09-01

This paper is a report of an investigation of the development, implementation and outcomes of a clinical guideline for nurse-led early extubation of adult coronary artery bypass graft patients. Healthcare knowledge translation and utilization is an emerging but under-developed research area. The complex context for guideline development and use is methodologically challenging for robust and rigorous evaluation. This study contributes one such evaluation. This was a mixed methods evaluation, with a dominant quantitative study with a secondary qualitative study in a single UK cardiac surgery centre. An interrupted time series study (N = 567 elective coronary artery bypass graft patients) with concurrent within person controls was used to measure the impact of the guideline on the primary outcome: time to extubation. Semi-structured interviews with 11 clinical staff, informed by applied practitioner ethnography, explored the process of guideline development and implementation. The data were collected between January 2001 and January 2003. There was no change in the interrupted time series study primary outcome as a consequence of the guideline implementation. The qualitative study identified three themes: context, process and tensions highlighting that the guideline did not require clinicians to change their practice, although it may have helped maintain practice through its educative role. Further investigation and development of appropriate methods to capture the dynamism in healthcare contexts and its impact on guideline implementation seems warranted. Multi-site mixed methods investigations and programmes of research exploring knowledge translation and utilization initiatives, such as guideline implementation, are needed.

[The importance of early exercise therapy in the treatment of Colles' fracture. A clinically controlled study].

PubMed

Grønlund, B; Harreby, M S; Kofoed, R; Rasmussen, L

1990-08-27

Forty patients participated in a study of the importance of early occupational therapy for the prognosis in stable Colles' fractures. Seventeen patients were treated by an occupational therapist 1-3 days after the injury, and the need for appliances and home-care was estimated. Twenty-three patients completed the usual treatment. Five weeks after the injury, we found significantly (p less than 0.05) better function of the hand in the 17 patients with early occupational therapy. This difference in function could not be found after 13 weeks. The rate of complications was the same in the two groups. The results indicate that contact with the occupational therapist shortly after the injury is valuable in patients with stable Colles' fractures.

Clinical Practice of Adjuvant Chemotherapy in Patients with Early-Stage Epithelial Ovarian Cancer.

PubMed

Frielink, Lindy M J; Pijlman, Brenda M; Ezendam, Nicole P M; Pijnenborg, Johanna M A

2016-01-01

Adjuvant platinum-based chemotherapy improves survival in women with early-stage epithelial ovarian cancer (EOC). Yet, there is a wide variety in clinical practice. All patients diagnosed with FIGO I and IIa EOC (2006-2010) in the south of the Netherlands were analyzed. The percentage of patients that received adjuvant chemotherapy was determined as well as the comprehensiveness of staging and outcome. Forty percent (54/135) of the patients with early-stage EOC received adjuvant chemotherapy. Treatment with adjuvant chemotherapy was associated with FIGO stage, clear-cell histology and nonoptimal staging. Optimal staging was achieved in 50%, and nonoptimal staging was associated with advanced age, comorbidity and treatment in a non-referral hospital. Overall, there was no difference in outcome between patients with and without adjuvant chemotherapy. Yet, in grade 3 tumors, adjuvant chemotherapy seems beneficial. Selective treatment of patients with early-stage EOC might reduce adjuvant chemotherapy without compromising outcome. © 2016 S. Karger AG, Basel.

Relationship of Basal laminar deposit and membranous debris to the clinical presentation of early age-related macular degeneration.

PubMed

Sarks, Shirley; Cherepanoff, Svetlana; Killingsworth, Murray; Sarks, John

2007-03-01

To correlate basal laminar deposit (BLamD) and membranous debris, including basal linear deposit (BLinD), with the evolution of early age-related macular degeneration (AMD). A clinicopathologic collection of 132 eyes with a continuous layer of BLamD was reviewed. The thickness and type of BLamD and the sites of membranous debris deposition were correlated with the clinical progression of the disease. Two types of BLamD, termed early and late, were identified based on light microscopic appearance by using the picro-Mallory stain. The progressive accumulation of late type BLamD correlated well with increasing BLamD thickness, advancing RPE degeneration, poorer vision, increasing age, and clinically evident pigment changes. Membranous debris initially accumulated diffusely as BLinD, most eyes with BLinD and early BLamD remaining funduscopically normal. However, membranous debris also formed focal collections as basal mounds internal to the RPE basement membrane and as soft drusen external to the basement membrane. Eyes in which membranous debris remained confined to basal mounds belonged to older patients with poorer vision, whereas patients with soft drusen were younger and had better vision. The presence of BLinD and early BLamD define threshold AMD, which manifests clinically as a normal fundus. Although late BLamD correlates most closely with clinical pigment abnormalities, it is the quantity and sites of membranous debris accumulation that appear to determine whether the disease develops pigment changes only or follows the alternative pathway of soft drusen formation with its attendant greater risk of choroidal neovascularization (CNV).

Clinical multifactorial analysis of early postoperative seizures in elderly patients following meningioma resection

PubMed Central

ZHANG, BO; WANG, DAN; GUO, YUNBAO; YU, JINLU

2015-01-01

The aim of the present study was to identify the major factors correlated with early postoperative seizures in elderly patients who had undergone a meningioma resection, and subsequently, to develop a logistic regression equation for assessing the seizures risk. Fourteen factors possibly correlated with early postoperative seizures in a cohort of 209 elderly patients who had undergone meningioma resection, as analyzed by multifactorial stepwise logistic regression. Phenobarbital sodium (0.1 g, intramuscularly) was administered to all 209 patients 30 min prior to undergoing surgery. All the patients had no previous history of seizures. The correlation of the 14 clinical factors (gender, tumor site, dyskinesia, peritumoral brain edema (PTBE), tumor diameter, pre- and postoperative prophylaxes, surgery time, tumor adhesion, circumscription, blood supply, intraoperative transfusion, original site of the tumor and dysphasia) was assessed in association with the risk for post-operative seizures. Tumor diameter, postoperative prophylactic antiepileptic drug (PPAD) administration, PTBE and tumor site were entered as risk factors into a mathematical regression model. The odds ratio (OR) of the tumor diameter was >1, and PPAD administration showed an OR >1, relative to a non-prophylactic group. A logistic regression equation was obtained and the sensitivity, specificity and misdiagnosis rates were 91.4, 74.3 and 25.7%, respectively. Tumor diameter, PPAD administration, PTBE and tumor site were closely correlated with early postoperative seizures; PTBE and PPAD administration were risk and protective factors, respectively. PMID:26137257

A study to derive a clinical decision rule for triage of emergency department patients with chest pain: design and methodology

PubMed Central

Hess, Erik P; Wells, George A; Jaffe, Allan; Stiell, Ian G

2008-01-01

Background Chest pain is the second most common chief complaint in North American emergency departments. Data from the U.S. suggest that 2.1% of patients with acute myocardial infarction and 2.3% of patients with unstable angina are misdiagnosed, with slightly higher rates reported in a recent Canadian study (4.6% and 6.4%, respectively). Information obtained from the history, 12-lead ECG, and a single set of cardiac enzymes is unable to identify patients who are safe for early discharge with sufficient sensitivity. The 2007 ACC/AHA guidelines for UA/NSTEMI do not identify patients at low risk for adverse cardiac events who can be safely discharged without provocative testing. As a result large numbers of low risk patients are triaged to chest pain observation units and undergo provocative testing, at significant cost to the healthcare system. Clinical decision rules use clinical findings (history, physical exam, test results) to suggest a diagnostic or therapeutic course of action. Currently no methodologically robust clinical decision rule identifies patients safe for early discharge. Methods/design The goal of this study is to derive a clinical decision rule which will allow emergency physicians to accurately identify patients with chest pain who are safe for early discharge. The study will utilize a prospective cohort design. Standardized clinical variables will be collected on all patients at least 25 years of age complaining of chest pain prior to provocative testing. Variables strongly associated with the composite outcome acute myocardial infarction, revascularization, or death will be further analyzed with multivariable analysis to derive the clinical rule. Specific aims are to: i) apply standardized clinical assessments to patients with chest pain, incorporating results of early cardiac testing; ii) determine the inter-observer reliability of the clinical information; iii) determine the statistical association between the clinical findings and the

High-Definition transcranial direct current stimulation in early onset epileptic encephalopathy: a case study.

PubMed

Meiron, Oded; Gale, Rena; Namestnic, Julia; Bennet-Back, Odeya; David, Jonathan; Gebodh, Nigel; Adair, Devin; Esmaeilpour, Zeinab; Bikson, Marom

2018-01-01

Early onset epileptic encephalopathy is characterized by high daily seizure-frequency, multifocal epileptic discharges, severe psychomotor retardation, and death at infancy. Currently, there are no effective treatments to alleviate seizure frequency and high-voltage epileptic discharges in these catastrophic epilepsy cases. The current study examined the safety and feasibility of High-Definition transcranial direct current stimulation (HD-tDCS) in reducing epileptiform activity in a 30-month-old child suffering from early onset epileptic encephalopathy. HD-tDCS was administered over 10 intervention days spanning two weeks including pre- and post-intervention video-EEG monitoring. There were no serious adverse events or side effects related to the HD-tDCS intervention. Frequency of clinical seizures was not significantly reduced. However, interictal sharp wave amplitudes were significantly lower during the post-intervention period versus baseline. Vital signs and blood biochemistry remained stable throughout the entire study. These exploratory findings support the safety and feasibility of 4 × 1 HD-tDCS in early onset epileptic encephalopathy and provide the first evidence of HD-tDCS effects on paroxysmal EEG features in electroclinical cases under the age of 36 months. Extending HD-tDCS treatment may enhance electrographic findings and clinical effects.

Early Antibody Response Contributes to the Virus Eradication and Clinical Recovery of H7N9 Influenza Infection.

PubMed

Liu, Xi; Yang, Zheng; Yuan, Jing; Liao, Jian; Duan, Lian; Wang, Wenfei; Zhang, Fuping; Chen, Xinchun; Zhou, Boping

2017-09-01

A new type of highly pathogenic avian influenza virus, H7N9, has been a great threat to public health since its 2013 outbreak. The humoral immune response plays a critical role in protection from the influenza virus, but its role and kinetics in H7N9-infected patients remain to be determined. In this study, we performed a retrospective investigation of the antibody response in plasma samples from 37 cases of hospitalized patients and analysed the relationship between the antibody response and the clinical outcomes. Our results showed that the HA7-binding antibody was generated earlier than the neutralizing antibody. Higher titer of HA7-binding antibody during the first 14 days after disease onset were associated with a shorter virus-positive continuation period, which is an important risk predictor ( P <0.05). Additionally, the titers of HA7-binding antibody were consistently and significantly lower in patients who died than those who recovered from the severe disease. Unexpectedly, no correlation between the titer of neutralizing antibody and the resulting clinical outcomes was found, suggesting that a neutralizing antibody-independent mechanism also contributed to virus control. In summary, our data suggests that an early antibody response against H7N9 influenza virus contributes to the eradication of the virus. A higher, early HA7-binding antibody response is associated with better clinical outcomes in H7N9 patients. © 2017 by the Association of Clinical Scientists, Inc.

A Light at the End of the Tunnel: The Impact of Early Clinical Experiences on Medical Students.

ERIC Educational Resources Information Center

Mann, Mary Pat

This paper describes the impact of early clinical contact (ECC) on medical students. The concepts emerged from a grounded theory analysis of interviews with students and faculty in the ECC program at Ohio University College of Osteopathic Medicine, which places first-year and second-year students in a variety of clinical settings in ambulatory…

Custom-fit minimally invasive total knee arthroplasty: effect on blood loss and early clinical outcomes.

PubMed

Pietsch, M; Djahani, O; Zweiger, Ch; Plattner, F; Radl, R; Tschauner, Ch; Hofmann, S

2013-10-01

Recently, new custom-fit pin guides in total knee arthroplasty (TKA) have been introduced. Use of these guides may reduce operating time. Use of the guides combined with the absence of intramedullary alignment jigs may lead to reduced blood loss and improved early outcomes. Our aim was to evaluate blood loss and early clinical outcomes in patients undergoing minimally invasive TKA using custom-fit magnetic resonance imaging (MRI)-based pin guides. A prospective study in 80 patients was carried out. Patients were divided randomly into 2 equal groups. In one group, intramedullary alignment jigs were used. In the second group, custom-fit MRI-based pin guides were used. All patients received the same cemented posterior-stabilized implant through a mini-midvastus approach. The volume in the drain bottles was recorded after 48 h. Hb loss was estimated by subtracting the postoperative from the preoperative Hb level. Transfusion requirements and surgical time were recorded. Outcome measures were Knee Society Scores (KSS), knee flexion, knee swelling and pain. There was lower mean drainage of blood in the custom-fit group (391 ml vs. 603 ml; p < 0.0001). There was no difference in estimated loss of Hb (3.6 g/dl vs. 4.1 g/dl; n.s.) and in transfusion requirements (7.5 % vs. 10 %; n.s.). Surgical time was reduced in the custom-fit group (12 min less; p = 0.001). KSS measured at week 2, 6 and 12 showed no significant difference between groups. Knee flexion measured on days 7, 10 and at week 6, 12 and knee swelling and pain measured on days 1, 3, 10 and at week 6, 12 showed no significant difference between groups. Using custom-fit pin guides reduces blood drainage, but not the estimated Hb loss in minimally invasive TKA and does not affect transfusion rate. Surgical time is reduced. There is no effect on the early clinical outcomes. Therapeutic study, Level I.

Primary care-led commissioning: applying lessons from the past to the early development of clinical commissioning groups in England.

PubMed

Checkland, Kath; Coleman, Anna; McDermott, Imelda; Segar, Julia; Miller, Rosalind; Petsoulas, Christina; Wallace, Andrew; Harrison, Stephen; Peckham, Stephen

2013-09-01

The current reorganisation of the English NHS is one of the most comprehensive ever seen. This study reports early evidence from the development of clinical commissioning groups (CCGs), a key element in the new structures. To explore the development of CCGs in the context of what is known from previous studies of GP involvement in commissioning. Case study analysis from sites chosen to provide maximum variety across a number of dimensions, from September 2011 to June 2012. A case study analysis was conducted using eight detailed qualitative case studies supplemented by descriptive information from web surveys at two points in time. Data collection involved observation of a variety of meetings, and interviews with key participants. Previous research shows that clinical involvement in commissioning is most effective when GPs feel able to act autonomously. Complicated internal structures, alongside developing external accountability relationships mean that CCGs' freedom to act may be subject to considerable constraint. Effective GP engagement is also important in determining outcomes of clinical commissioning, and there are a number of outstanding issues for CCGs, including: who feels 'ownership' of the CCG; how internal communication is conceptualised and realised; and the role and remit of locality groups. Previous incarnations of GP-led commissioning have tended to focus on local and primary care services. CCGs are keen to act to improve quality in their constituent practices, using approaches that many developed under practice-based commissioning. Constrained managerial support and the need to maintain GP engagement may have an impact. CCGs are new organisations, faced with significant new responsibilities. This study provides early evidence of issues that CCGs and those responsible for CCG development may wish to address.

Immediate versus early non-occlusal loading of dental implants placed flapless in partially edentulous patients: a 3-year randomized clinical trial.

PubMed

Merli, Mauro; Moscatelli, Marco; Mariotti, Giorgia; Piemontese, Matteo; Nieri, Michele

2012-02-01

To compare immediate versus early non-occlusal loading of dental implants placed flapless in a 3-year, parallel group, randomized clinical trial. The study was conducted in a private dental clinic between July 2005 and July 2010. Patients 18 years or older were randomized to receive implants for fixed partial dentures in cases of partial edentulism. The test group was represented by immediate non-occlusal implant loading, whereas the control group was represented by early non-occlusal implant loading. The outcome variables were implant failure, complications and radiographic bone level at implant sites 3 years after loading, measured from the implant-abutment junction to the most coronal point of bone-to-implant contact. Randomization was computer-generated with allocation concealment by opaque sequentially numbered sealed envelopes, and the measurer was blinded to group assignment. Sixty patients were randomized: 30 to the immediately loaded group and 30 to the early loaded group. Four patients dropped out; however, the data of all patients were included in the analysis. No implant failure occurred. Two complications occurred in the control group and one in the test group. The mean bone level at 3 years was 1.91 mm for test group and 1.59 mm for control group. The adjusted difference in bone level was 0.26 mm (CI 95% -0.08 to 0.59, p = 0.1232). The null hypothesis of no difference in failure rates, complications and bone level between implants that were loaded immediately or early at 3 years cannot be rejected in this randomized clinical trial. © 2011 John Wiley & Sons A/S.

Early dialogue between the developers of new technologies and pricing and reimbursement agencies: a pilot study.

PubMed

Backhouse, Martin E; Wonder, Michael; Hornby, Edward; Kilburg, Anne; Drummond, Michael; Mayer, Friedrich Karl

2011-06-01

It is common practice for developers of new health care technologies to engage in early dialogue with the major regulatory agencies; such discussions frequently center around the proposed clinical trial designs to support the registration of new interventions and suggestions on their improvement. Pricing and reimbursement agencies are increasingly using the results from health technology assessments to inform their decision making for new technologies. Such assessments are invariably underpinned by the phase 3 clinical trial evidence which may not provide answers to the key questions. Technology developers are beginning to realize that direct, early dialogue on the evidence requirements of the major pricing and reimbursement agencies, before phase 3 clinical trial designs for their key development compounds have been finalized, may be beneficial. This article reports on the pioneering efforts of one technology developer in seeking early dialogue with seven pricing and reimbursement agencies in five countries globally in 2007-2008 on their likely evidence requirements for a new oral treatment for patients with chronic plaque psoriasis. The pilot project demonstrated that a feasible process of early dialogue could be established, through a face-to-face meeting with prior circulation of a briefing book. Although there was some variation in the advice the similarities far outweighed the differences. More experience of early dialogue needs to be accumulated, involving a wider range of pricing and reimbursement agencies and compounds. The conclusion of this study, however, was that early dialogue can be a worthwhile process for all parties and can lead to a common understanding about evidence development for market access. Copyright © 2011 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Determining the prevalence and risk factors for early childhood caries in a community dental health clinic.

PubMed

Schroth, Robert J; Cheba, Vivek

2007-01-01

The purposes of this study were to: (1) determine the prevalence of early childhood caries (ECC) among young children accessing dental services at a community dental clinic; (2) identify factors associated with the presence of ECC; and (3) determine the percentage of children who received treatment for ECC in this setting and the number who required referral to specialists. The study population comprised children younger than 72 months attending the clinic between 1991 and 2004. A chart review was conducted. Eight hundred thirty-four charts met inclusion criteria; 71% had ECC, while the mean deft was 3.7+/-3.9 (SD). The average age at the first visit was 50.0+/-12.7 (SD) months. Those with ECC were significantly older at the first visit (P<.001), and the prevalence increased with family size (P=.011) and number of siblings (P=.019). ECC children were significantly more likely to come from households with lower monthly incomes (P=.033). The prevalence of ECC did not vary according to specific areas in Winnipeg where children resided (P=.20). Key risk factors for ECC included: (1) the child's sex; (2) low monthly income; (3) whether the child resided with both parents; and (4) a history of foiled dental visits. These data may assist in identifying children at greatest risk for ECC and may help public health agencies develop appropriate prevention strategies, including promoting early dental visits for infants.

Is there subclinical enthesitis in early psoriatic arthritis? A clinical comparison with power doppler ultrasound.

PubMed

Freeston, J E; Coates, L C; Helliwell, P S; Hensor, E M A; Wakefield, R J; Emery, P; Conaghan, P G

2012-10-01

Enthesitis is a recognized feature of spondylarthritides (SpA), including psoriatic arthritis (PsA). Previously, ultrasound imaging has highlighted the presence of subclinical enthesitis in established SpA, but there are little data on ultrasound findings in early PsA. The aim of our study was to compare ultrasound and clinical examination (CE) for the detection of entheseal abnormalities in an early PsA cohort. Forty-two patients with new-onset PsA and 10 control subjects underwent CE of entheses for tenderness and swelling, as well as gray-scale (GS) and power Doppler (PD) ultrasound of a standard set of entheses. Bilateral elbow lateral epicondyles, Achilles tendons, and plantar fascia were assessed by both CE and ultrasound, the latter scored using a semiquantitative (SQ) scale. Inferior patellar tendons were assessed by ultrasound alone. A GS SQ score of >1 and/or a PD score of >0 was used to describe significant ultrasound entheseal abnormality. A total of 24 (57.1%) of 42 patients in the PsA group and 0 (0%) of 10 controls had clinical evidence of at least 1 tender enthesis. In the PsA group, for sites assessed by both CE and ultrasound, 4% (7 of 177) of nontender entheses had a GS score >1 and/or a PD score >0 compared to 24% (9 of 37) of tender entheses. CE overestimated activity in 28 (13%) of 214 of entheses. All the nontender ultrasound-abnormal entheses were in the lower extremity. The prevalence of subclinical enthesitis in this early PsA cohort was low. CE may overestimate active enthesitis. The few subclinically inflamed entheses were in the lower extremity, where mechanical stress is likely to be more significant. Copyright © 2012 by the American College of Rheumatology.

[Autism and Early Neurodevelopmental Milestones].

PubMed

Ferreira, Xavier; Oliveira, Guiomar

2016-03-01

Autism spectrum disorder, also referred to in this study as autism, is a neurodevelopmental chronic disease that manifests early in childhood by impairment in social interaction, communication and repetitive behavior. Since there are no specific biomarkers available, the diagnosis is based exclusively on clinical criteria. The purpose of the present study is to determine which are the early psychomotor development or neurodevelopmental milestones that present a significant correlation with the severity of the main symptoms of autism, development quotients, and adaptive function. We performed a retrospective study on a sample of 1572 individuals with a diagnosis of autism that were monitored at Hospital Pediátrico do Centro Hospitalar e Universitário de Coimbra, in the Neurodevelopment and Autism Unit. We analyzed six early psychomotor developmental milestones: age of acquisition of 'walking', 'first words', 'first phrases', 'daytime control of bladder sphincter', 'night-time control of bladder sphincter', and age of first complaints. Afterwards, we divided the sample in three subgroups regarding clinical severity, according to the Childhood Autism Rating Scale, and we analyzed significant differences among each other concerning the six milestones established beforehand. The milestone 'age of first phrases' was, from the six milestones, the one with a stronger correlation with the variables of clinical manifestations of autism, development/intelligence quotients, and adaptive function. In division of the sample into subgroups of clinical severity, it was the most severe that showed later ages of acquisition of the neurodevelopmental milestones and earlier ages of first complaints. This study proves the clinical utility to know the age of achievement of early psychomotor developmental skills, since they act as predictors of clinical severity of autism, cognition, and adaptive function of a wide population with autism. Therefore, this data contribute for prognostic

Early antihypertensive treatment and clinical outcomes in acute ischemic stroke: subgroup analysis by baseline blood pressure.

PubMed

He, William J; Zhong, Chongke; Xu, Tan; Wang, Dali; Sun, Yingxian; Bu, Xiaoqing; Chen, Chung-Shiuan; Wang, Jinchao; Ju, Zhong; Li, Qunwei; Zhang, Jintao; Geng, Deqin; Zhang, Jianhui; Li, Dong; Li, Yongqiu; Yuan, Xiaodong; Zhang, Yonghong; Kelly, Tanika N

2018-06-01

We studied the effect of early antihypertensive treatment on death, major disability, and vascular events among patients with acute ischemic stroke according to their baseline SBP. We randomly assigned 4071 acute ischemic stroke patients with SBP between 140 and less than 220 mmHg to receive antihypertensive treatment or to discontinue all antihypertensive medications during hospitalization. A composite primary outcome of death and major disability and secondary outcomes were compared between treatment and control stratified by baseline SBP levels of less than 160, 160-179, and at least 180 mmHg. At 24 h after randomization, differences in SBP reductions were 8.8, 8.6 and 7.8 mmHg between the antihypertensive treatment and control groups among patients with baseline SBP less than 160, 160-179, and at least 180 mmHg, respectively (P < 0.001 among subgroups). At day 14 or hospital discharge, the primary and secondary outcomes were not significantly different between the treatment and control groups among subgroups. However, there was a significant interaction between antihypertensive treatment and baseline SBP subgroups on death (P = 0.02): odds ratio (95% CI) of 2.42 (0.74-7.89) in patients with baseline SBP less than 60 mmHg and 0.34 (0.11-1.09) in those with baseline SBP at least 180 mmHg. At the 3-month follow-up, the primary and secondary clinical outcomes were not significantly different between the treatment and control groups by baseline SBP levels. Early antihypertensive treatment had a neutral effect on clinical outcomes among acute ischemic stroke patients with various baseline SBP levels. Future clinical trials are warranted to test BP-lowering effects in acute ischemic stroke patients by baseline SBP levels. ClinicalTrials.gov Identifier: NCT01840072.

Utilizing Existing Clinical and Population Biospecimen Resources for Discovery or Validation of Markers for Early Cancer Detection

Cancer.gov

Utilizing Existing Clinical and Population Biospecimen Resources for Discovery or Validation of Markers for Early Cancer Detection, a 2013 workshop sponsored by the Epidemiology and Genomics Research Program.

Do early career indicators of clinical skill predict subsequent career outcomes and practice characteristics for general internists?

PubMed

Gray, Bradley; Reschovsky, James; Holmboe, Eric; Lipner, Rebecca

2013-06-01

To study relationships between clinical skill measures assessed at the beginning of general internists' careers and their career outcomes and practice characteristics. General Internist Community Tracking Study Physician Survey respondents (2000-2001, 2004-2005) linked with residency program evaluations and American Board of Internal Medicine board certification examination score records; n = 2,331. Cross-sectional regressions of career outcome and practice characteristic measures on board examination scores/success, residency evaluations interacted with residency type, and potential confounding variables. Failure to achieve board certification was associated with $27,206 (18 percent, p < .05) less income and 14.9 percent more minority patients relative to physicians scoring in the bottom quartile on their initial examination who eventually became certified (p < .01). Other skill measures were not associated with income. Scoring in the top rather than bottom quartile on the board certification examination was associated with 9 percent increased likelihood of reporting high career satisfaction (p < .05). Among physicians trained in community hospital residency programs, lower evaluations were associated with 14.5 percent higher share of minority patients (p < .05). Both skill measures were associated with practice type. There are associations between early career skill measures and career outcomes. In addition, minority patients are more likely to be treated by physicians with lower early career clinical skills measures than nonminority patients. © Health Research and Educational Trust.

Early clinical observations on the use of imatinib mesylate in FOP: A report of seven cases.

PubMed

Kaplan, Frederick S; Andolina, Jeffrey R; Adamson, Peter C; Teachey, David T; Finklestein, Jerry Z; Ebb, David H; Whitehead, Benjamin; Jacobs, Benjamin; Siegel, David M; Keen, Richard; Hsiao, Edward; Pignolo, Robert J

2018-04-01

Fibrodysplasia ossificans progressiva (FOP) is an ultrarare genetic disorder of progressive, disabling heterotopic ossification (HO) for which there is presently no definitive treatment. Research studies have identified multiple potential targets for therapy in FOP, and novel drug candidates are being developed for testing in clinical trials. A complementary approach seeks to identify approved drugs that could be re-purposed for off-label use against defined targets in FOP. One such drug is imatinib mesylate, a tyrosine kinase inhibitor originally developed for use in patients with chronic myeloid leukemia (CML). Imatinib has the desirable effect of attacking multiple targets involved in the early hypoxic and inflammatory stages of FOP flare-ups, including HIF1-α, PDGFRα, c-KIT, and multiple MAP kinases. Based on compelling biologic rationale, strong preclinical data, and a favorable safety profile, imatinib has been prescribed on an off-label basis in a non-trial setting in seven children with continuous FOP flare-ups, predominantly in the axial regions, and which were not responsive to standard-of-care regimens. Anecdotal reports in these seven isolated cases document that the medication was well-tolerated with a ubiquitous reported decrease in the intensity of flare-ups in the six children who took the medication. These early clinical observations support the implementation of clinical trials in children with uncontrolled FOP flare-ups to determine if imatinib may ameliorate symptoms or alter the natural history of this debilitating and life-threatening disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluating markers for the early detection of cancer: overview of study designs and methods.

PubMed

Baker, Stuart G; Kramer, Barnett S; McIntosh, Martin; Patterson, Blossom H; Shyr, Yu; Skates, Steven

2006-01-01

The field of cancer biomarker development has been evolving rapidly. New developments both in the biologic and statistical realms are providing increasing opportunities for evaluation of markers for both early detection and diagnosis of cancer. To review the major conceptual and methodological issues in cancer biomarker evaluation, with an emphasis on recent developments in statistical methods together with practical recommendations. We organized this review by type of study: preliminary performance, retrospective performance, prospective performance and cancer screening evaluation. For each type of study, we discuss methodologic issues, provide examples and discuss strengths and limitations. Preliminary performance studies are useful for quickly winnowing down the number of candidate markers; however their results may not apply to the ultimate target population, asymptomatic subjects. If stored specimens from cohort studies with clinical cancer endpoints are available, retrospective studies provide a quick and valid way to evaluate performance of the markers or changes in the markers prior to the onset of clinical symptoms. Prospective studies have a restricted role because they require large sample sizes, and, if the endpoint is cancer on biopsy, there may be bias due to overdiagnosis. Cancer screening studies require very large sample sizes and long follow-up, but are necessary for evaluating the marker as a trigger of early intervention.

Early childhood predictors of early onset of smoking: a birth prospective study.

PubMed

Hayatbakhsh, Reza; Mamun, Abdullah A; Williams, Gail M; O'Callaghan, Michael J; Najman, Jake M

2013-10-01

Early onset of smoking is associated with subsequent abuse of other substances and development of negative health outcomes. This study aimed to examine early life predictors of onset of smoking in an Australian young cohort. Data were from the Mater Hospital and University of Queensland Study of Pregnancy (MUSP), a population-based prospective birth cohort study (1981-2012). The present study is based on a cohort of 3714 young adults who self-reported smoking status and age of onset of smoking at the 21-year follow-up. Of these, data were available for 3039 on early childhood factors collected between the baseline and 14-year follow-up of the study. Of 3714 young adults, 49.6% (49.9% males and 49.3% females) reported having ever smoked cigarettes. For those who had ever smoked, mean and median ages at first smoke were 15.5 and 16.0years, respectively. In multivariate Cox proportional hazard analysis mother's education, change in maternal marital status, maternal cigarette smoking and alcohol consumption, maternal depression and child externalizing when the child was 5years statistically significantly predicted early onset of smoking. The data suggest that individuals exposed to personal and environmental risk factors during the early stage of childhood are at increased risk of initiation to cigarette smoking at an earlier age. Identification of the pathways of association between these early life factors and initiation to cigarette smoking may help reduce risk of tobacco smoking in adolescents and its adverse consequences. Copyright © 2013 Elsevier Ltd. All rights reserved.

QIN. Early experiences in establishing a regional quantitative imaging network for PET/CT clinical trials

PubMed Central

Doot, Robert K.; Thompson, Tove; Greer, Benjamin E.; Allberg, Keith C.; Linden, Hannah M.; Mankoff, David A.; Kinahan, Paul E.

2012-01-01

The Seattle Cancer Care Alliance (SCCA) is a Pacific Northwest regional network that enables patients from community cancer centers to participate in multicenter oncology clinical trials where patients can receive some trial-related procedures at their local center. Results of positron emission tomography (PET) scans performed at community cancer centers are not currently used in SCCA Network trials since clinical trials customarily accept results from only trial-accredited PET imaging centers located at academic and large hospitals. Oncologists would prefer the option of using standard clinical PET scans from Network sites in multicenter clinical trials to increase accrual of patients for whom additional travel requirements for imaging is a barrier to recruitment. In an effort to increase accrual of rural and other underserved populations to Network trials, researchers and clinicians at the University of Washington, SCCA and its Network are assessing feasibility of using PET scans from all Network sites in their oncology clinical trials. A feasibility study is required because the reproducibility of multicenter PET measurements ranges from approximately 3% to 40% at national academic centers. Early experiences from both national and local PET phantom imaging trials are discussed and next steps are proposed for including patient PET scans from the emerging regional quantitative imaging network in clinical trials. There are feasible methods to determine and characterize PET quantitation errors and improve data quality by either prospective scanner calibration or retrospective post hoc corrections. These methods should be developed and implemented in multicenter clinical trials employing quantitative PET imaging of patients. PMID:22795929

Development and validation of simulated virtual patients to impart early clinical exposure in endocrine physiology.

PubMed

Gupta, Akriti; Singh, Satendra; Khaliq, Farah; Dhaliwal, Upreet; Madhu, S V

2018-03-01

In the country presently, preclinical medical students are not routinely exposed to real patients. Thus, when they start clinical postings, they are found to have poor clinical reasoning skills. Simulated virtual patients (SVPs) can improve clinical skills without endangering real patients. This pilot study describes the development of two SVPs in endocrine physiology and their validation in terms of acquisition of clinical knowledge and student engagement. Two SVPs, Nandini Sharma (unintentional weight gain) and Sunil Yadav (polyuria), were created and published on the i-Human Patients platform through an iterative, interdisciplinary, and transdisciplinary collaborative process using the conceptual framework of Kim et al. (Kim S, Phillips WR, Pinsky L, Brock D, Phillips K, Keary J. Med Educ 40: 867-876, 2006). After internal and external peer validation, the SVPs were piloted on 40 students (20 students per virtual patient) over 2 wk. A cognitive pretest was conducted before exposure, and a posttest soon after. Faculty and student feedback were collected. Faculty found SVPs authentic, helpful as teaching-learning tools, and useful for giving feedback and for assessment. Students found SVPs more engaging than paper cases and helpful in developing clinical reasoning and in imparting clinical exposure. Pretest and posttest scores indicated knowledge gain ( P < 0.01). Although challenging to create, SVPs created on the i-Human Patients platform improved learning in endocrine physiology and were well accepted by students and faculty as a means to provide early clinical exposure. More SVPs can be developed through collaboration between stakeholder departments and integrated into the curriculum for greater benefit.

How good is "evidence" from clinical studies of drug effects and why might such evidence fail in the prediction of the clinical utility of drugs?

PubMed

Naci, Huseyin; Ioannidis, John P A

2015-01-01

Promising evidence from clinical studies of drug effects does not always translate to improvements in patient outcomes. In this review, we discuss why early evidence is often ill suited to the task of predicting the clinical utility of drugs. The current gap between initially described drug effects and their subsequent clinical utility results from deficits in the design, conduct, analysis, reporting, and synthesis of clinical studies-often creating conditions that generate favorable, but ultimately incorrect, conclusions regarding drug effects. There are potential solutions that could improve the relevance of clinical evidence in predicting the real-world effectiveness of drugs. What is needed is a new emphasis on clinical utility, with nonconflicted entities playing a greater role in the generation, synthesis, and interpretation of clinical evidence. Clinical studies should adopt strong design features, reflect clinical practice, and evaluate outcomes and comparisons that are meaningful to patients. Transformative changes to the research agenda may generate more meaningful and accurate evidence on drug effects to guide clinical decision making.

Cognitive behavioral therapy for early adolescents with autism spectrum disorders and clinical anxiety: a randomized, controlled trial.

PubMed

Wood, Jeffrey J; Ehrenreich-May, Jill; Alessandri, Michael; Fujii, Cori; Renno, Patricia; Laugeson, Elizabeth; Piacentini, John C; De Nadai, Alessandro S; Arnold, Elysse; Lewin, Adam B; Murphy, Tanya K; Storch, Eric A

2015-01-01

Clinically elevated anxiety is a common, impairing feature of autism spectrum disorders (ASD). A modular CBT program designed for preteens with ASD, Behavioral Interventions for Anxiety in Children with Autism (BIACA; Wood et al., 2009) was enhanced and modified to address the developmental needs of early adolescents with ASD and clinical anxiety. Thirty-three adolescents (11-15 years old) were randomly assigned to 16 sessions of CBT or an equivalent waitlist period. The CBT model emphasized exposure, challenging irrational beliefs, and behavioral supports provided by caregivers, as well as numerous ASD-specific treatment elements. Independent evaluators, parents, and adolescents rated symptom severity at baseline and posttreatment/postwaitlist. In intent-to-treat analyses, the CBT group outperformed the waitlist group on independent evaluators' ratings of anxiety severity on the Pediatric Anxiety Rating Scale (PARS) and 79% of the CBT group met Clinical Global Impressions-Improvement scale criteria for positive treatment response at posttreatment, as compared to only 28.6% of the waitlist group. Group differences were not found for diagnostic remission or questionnaire measures of anxiety. However, parent-report data indicated that there was a positive treatment effect of CBT on autism symptom severity. The CBT manual under investigation, enhanced for early adolescents with ASD, yielded meaningful treatment effects on the primary outcome measure (PARS), although additional developmental modifications to the manual are likely warranted. Future studies examining this protocol relative to an active control are needed. Copyright © 2014. Published by Elsevier Ltd.

Early miscarriage rate in lean polycystic ovary syndrome women after euploid embryo transfer - a matched-pair study.

PubMed

Luo, Lu; Gu, Fang; Jie, Huying; Ding, Chenhui; Zhao, Qiang; Wang, Qiong; Zhou, Canquan

2017-11-01

The early miscarriage rate is reported to be higher in patients with polycystic ovary syndrome (PCOS) compared with non-PCOS patients. However, whether PCOS is an independent risk factor for early miscarriage is still controversial; to what extent embryonic aneuploidy accounts for miscarriages of PCOS is still unknown. In this 1:3 matched-pair study, 67 lean PCOS patients and 201 controls matched for age, body mass index (BMI) and embryo scores undergoing a single euploid blastocyst transfer in vitrified-warmed cycles were analysed. Clinical pregnancy, early miscarriage and live birth rates were compared. Logistic regression analysis was performed to further evaluate the factors associated with early miscarriage and live birth. Clinical pregnancy rates were 50.7% in PCOS and 55.2% in control groups. Early miscarriage rate was significantly (P = 0.029) increased in the PCOS group compared with controls; non-PCOS patients had a significantly higher live birth rate than PCOS patients, P < 0.001. Further regression analyses showed that PCOS was significantly associated with a higher risk of early miscarriage and decreased chance of live birth. In conclusion, PCOS in women undergoing pre-implantation genetic diagnosis may, independently from BMI and karyotype, increase the risk of miscarriage. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Early changes in emotional processing as a marker of clinical response to SSRI treatment in depression.

PubMed

Godlewska, B R; Browning, M; Norbury, R; Cowen, P J; Harmer, C J

2016-11-22

Antidepressant treatment reduces behavioural and neural markers of negative emotional bias early in treatment and has been proposed as a mechanism of antidepressant drug action. Here, we provide a critical test of this hypothesis by assessing whether neural markers of early emotional processing changes predict later clinical response in depression. Thirty-five unmedicated patients with major depression took the selective serotonin re-uptake inhibitor (SSRI), escitalopram (10 mg), over 6 weeks, and were classified as responders (22 patients) versus non-responders (13 patients), based on at least a 50% reduction in symptoms by the end of treatment. The neural response to fearful and happy emotional facial expressions was assessed before and after 7 days of treatment using functional magnetic resonance imaging. Changes in the neural response to these facial cues after 7 days of escitalopram were compared in patients as a function of later clinical response. A sample of healthy controls was also assessed. At baseline, depressed patients showed greater activation to fear versus happy faces than controls in the insula and dorsal anterior cingulate. Depressed patients who went on to respond to the SSRI had a greater reduction in neural activity to fearful versus happy facial expressions after just 7 days of escitalopram across a network of regions including the anterior cingulate, insula, amygdala and thalamus. Mediation analysis confirmed that the direct effect of neural change on symptom response was not mediated by initial changes in depressive symptoms. These results support the hypothesis that early changes in emotional processing with antidepressant treatment are the basis of later clinical improvement. As such, early correction of negative bias may be a key mechanism of antidepressant drug action and a potentially useful predictor of therapeutic response.

Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline

PubMed Central

Harris, Lyndsay N.; McShane, Lisa M.; Andre, Fabrice; Collyar, Deborah E.; Gonzalez-Angulo, Ana M.; Hammond, Elizabeth H.; Kuderer, Nicole M.; Liu, Minetta C.; Mennel, Robert G.; Van Poznak, Catherine; Bast, Robert C.; Hayes, Daniel F.

2016-01-01

Purpose To provide recommendations on appropriate use of breast tumor biomarker assay results to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer. Methods A literature search and prospectively defined study selection sought systematic reviews, meta-analyses, randomized controlled trials, prospective-retrospective studies, and prospective comparative observational studies published from 2006 through 2014. Outcomes of interest included overall survival and disease-free or recurrence-free survival. Expert panel members used informal consensus to develop evidence-based guideline recommendations. Results The literature search identified 50 relevant studies. One randomized clinical trial and 18 prospective-retrospective studies were found to have evaluated the clinical utility, as defined by the guideline, of specific biomarkers for guiding decisions on the need for adjuvant systemic therapy. No studies that met guideline criteria for clinical utility were found to guide choice of specific treatments or regimens. Recommendations In addition to estrogen and progesterone receptors and human epidermal growth factor receptor 2, the panel found sufficient evidence of clinical utility for the biomarker assays Oncotype DX, EndoPredict, PAM50, Breast Cancer Index, and urokinase plasminogen activator and plasminogen activator inhibitor type 1 in specific subgroups of breast cancer. No biomarker except for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 was found to guide choices of specific treatment regimens. Treatment decisions should also consider disease stage, comorbidities, and patient preferences. PMID:26858339

Effects of Long-Term Etanercept Treatment on Clinical Outcomes and Objective Signs of Inflammation in Early Nonradiographic Axial Spondyloarthritis: 104-Week Results From a Randomized, Placebo-Controlled Study.

PubMed

Dougados, Maxime; van der Heijde, Désirée; Sieper, Joachim; Braun, Jürgen; Citera, Gustavo; Lenaerts, Jan; van den Bosch, Filip; Wei, James Cheng-Chung; Pedersen, Ron; Bonin, Randi; Jones, Heather; Marshall, Lisa; Logeart, Isabelle; Vlahos, Bonnie; Bukowski, Jack F; Maksymowych, Walter P

2017-10-01

To evaluate the long-term clinical and imaging efficacy of etanercept in patients with early, active nonradiographic axial spondyloarthritis (SpA). Adult patients who satisfied the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axial SpA (but not the modified New York radiographic criteria), with symptom duration >3 months to <5 years, and who were unresponsive to ≥2 nonsteroidal antirheumatic drugs (NSAIDs) received double-blind etanercept 50 mg/week or placebo for 12 weeks, followed by open-label etanercept 50 mg/week to week 104. Clinical, magnetic resonance imaging (MRI; Spondyloarthritis Research Consortium of Canada [SPARCC] scores), and safety outcomes at 104 weeks were analyzed. Of 215 randomized patients (etanercept: n = 106; placebo: n = 109), 205 entered the study (etanercept/etanercept: n = 100; placebo/etanercept: n = 105) and 169 completed the open-label period (etanercept/etanercept: n = 83; placebo/etanercept: n = 86). At week 104, 61 of 81 (75%), 49 of 81 (61%), 48 of 80 (60%), and 57 of 81 (70%) patients who received etanercept throughout the trial achieved ASAS20, ASAS40, Ankylosing Spondylitis Disease Activity Score (ASDAS) inactive disease, and Bath Ankylosing Spondylitis Disease Activity Index criteria for 50% improvement (BASDAI 50) scores, respectively (observed). From baseline to week 104, continued improvements in clinical outcomes (ASDAS-C-reactive protein: -1.5 and -1.7; BASDAI: -3.3 and -3.8 [last observation carried forward]), and SPARCC MRI scores (sacroiliac joint: -6.0 and -3.4; spinal: -2.1 and -0.8 [observed]) were seen in patients receiving etanercept/etanercept and placebo/etanercept. During the study, 8% in the etanercept/etanercept group and 7% in the placebo/etanercept group had serious adverse events; no new safety signals were seen. Patients with early, active nonradiographic axial SpA and an inadequate response to at least 2 NSAIDs demonstrated improvement

Early-Life Trauma in Hospitalized Patients With Mood Disorders and Its Association With Clinical Outcomes.

PubMed

Parsaik, Ajay K; Abdelgawad, Noha; Chotalia, Jigar K; Lane, Scott D; Pigott, Teresa A

2017-01-01

The prevalence of childhood trauma and its impact on clinical outcomes in hospitalized patients with mood disorders is unknown. We studied the frequency of childhood trauma among inpatient adults with mood disorders and its association with clinical outcomes. Patients admitted to our hospital with a primary diagnosis of mood disorders completed the short form of the Early Trauma Inventory-Self-Report (ETISR-SF), the Sheehan Disability Scale, and the Clinician-Rated Dimensions of Psychosis Symptom Severity scale. A regression model adjusted for multiple comparisons was used to examine the association between scores on the ETISR-SF and clinical outcomes. Subjects were 167 patients, all of whom reported ≥1 types of childhood trauma: 90% general trauma, 75% physical abuse, 71% emotional abuse, 50% sexual abuse, and 35% all 4 types of abuse. The subtypes of abuse did not differ by sex or race. Diagnoses in the sample were bipolar disorder 56%, major depressive disorder 24%, schizoaffective disorder 14%, and substance-induced mood disorder 5%. The mean age in the sample was 35±11.5 years, 53% were male, and 64% also had substance abuse disorders. Higher scores on the ETISR-SF were associated with longer hospital stays [odds ratio (OR)=1.13; 95% confidence interval (CI), 1.05-1.22], and greater disruption of work/school life (OR=1.12; 95% CI, 1.04-1.21). There was also a trend for higher ETISR-SF scores to be associated with more severe psychotic symptoms (OR=1.13; 95% CI, 1.01-1.27) and more disruption in social (OR=1.14; 95% CI, 1.06-1.22) and family life (OR=1.09; 95% CI, 1.02-1.17). Childhood trauma was reported by all of the 167 patients, with general trauma the most common and approximately half reporting sexual abuse. Childhood trauma was associated with poor clinical outcomes. Early recognition of trauma and trauma-related therapeutic interventions may improve outcomes.

Understanding Treatment Burden and Quality of Life Impact of Participating in an Early Phase Pediatric Oncology Clinical Trial: A Pilot Study

PubMed Central

BACKUS, LORI; STOCKMAN, BETH; CARPENTER, JANET S.; LIN, LI; HAASE, JOAN

2017-01-01

Purpose Early phase clinical trials (EPTs) have led to new, more effective treatment options for children with cancer. Despite the extensive use of EPTs in pediatric oncology, little is known about parent and child experiences during EPT participation. The purposes of this pilot study were to assess the feasibility and preliminary results of having children with cancer and their parents complete measures of treatment burden and quality of life (QOL) concurrent with EPT participation. Methods In this descriptive, longitudinal, pilot study, parents and children were followed for the first 60 days of an EPT. Feasibility was assessed by participant enrollment and retention, and completion of measures. Measures completed included: Demographic form (completed at baseline); Diary of Trial Experiences to capture treatment burden (completed ongoing); and PedsQL™ Quality of Life Inventories, Cancer Modules, and Family Impact Module (completed at baseline, post-first disease evaluation, and off-study). Data were analyzed using descriptive statistics. Results Feasibility goals of enrollment, retention, and measure completion were partially met. Preliminary treatment burden and QOL results are provided. Conclusions While QOL assessments may provide insight into EPT experiences, future studies need to be conducted at multiple sites and enrollment goals must account for participant attrition. PMID:28849701

Evaluation with mTHPC of early squamous cell carcinomas of the cheek pouch mucosa of Golden Syrian hamsters as a model for clinical PDT of early cancers in the upper aerodigestive tract, the esophag

NASA Astrophysics Data System (ADS)

Glanzmann, Thomas M.; Theumann, Jean-Francois; Forrer, Martin; Braichotte, Daniel; Wagnieres, Georges A.; van den Bergh, Hubert; Andrejevic-Blant, Snezana; Savary, Jean-Francois; Monnier, Philippe

1995-03-01

Golden Syrian hamsters are evaluated as an animal model for light induced fluorescence (LIF) photodetection and phototherapy of early squamous cell carcinomas of the upper aerodigestive tract, the esophagus, and the traecheo-bronchial tree. Carcinomas of this type are induced on the hamster cheek pouch mucosa by the application of the carcinogen 7,12-DMBA. For phototherapeutic experiments on the animals we utilized meso-(tetrahydoxyphenyl) chlorin (mTHPC). This drug is currently in phase I and II clinical trials for ENT patients presenting superficial `early' squamous cell carcinomas. By means of LIF we measured in vivo the kinetics of the uptake and removal of mTHPC in the normal and tumoral cheek mucosa and in the skin. The photodynamic therapy (PDT) reaction of the tissue after excitation of the photosensitizer with laser light at 652 nm was studied. Both pharmacokinetics and PDT efficacy are compared between animal model and clinical results with special emphasis on selectivity between normal and tumoral mucosa. These first experiments show that this tumor model in the hamster cheek pouch seems to be suitable for testing new photosensitizers preceding their clinical application as well as for optimization of the multiple parameters of clinical PDT.

Spiritual Diversity and Living with Early-Stage Dementia.

PubMed

McGee, Jocelyn Shealy; Zhao, Holly Carlson; Myers, Dennis R; Seela Eaton, Hannah

2018-01-01

Attention to spiritual diversity is necessary for the provision of culturally informed clinical care for people with early-stage dementia and their family members. In this article, an evidence-based theoretical framework for conceptualizing spiritual diversity is described in detail (Pargament, 2011). The framework is then applied to two clinical case studies of people living with early-stage dementia to elucidate the multilayered components of spiritual diversity in this population. The case studies were selected from a larger mixed-methods study on spirituality, positive psychological factors, health, and well-being in people living with early-stage dementia and their family members. To our knowledge this is the first systematic attempt to apply a theoretical framework for understanding spiritual diversity in this population. Implications for clinical practice are provided.

LC-MS/MS-based approach for obtaining exposure estimates of metabolites in early clinical trials using radioactive metabolites as reference standards.

PubMed

Zhang, Donglu; Raghavan, Nirmala; Chando, Theodore; Gambardella, Janice; Fu, Yunlin; Zhang, Duxi; Unger, Steve E; Humphreys, W Griffith

2007-12-01

An LC-MS/MS-based approach that employs authentic radioactive metabolites as reference standards was developed to estimate metabolite exposures in early drug development studies. This method is useful to estimate metabolite levels in studies done with non-radiolabeled compounds where metabolite standards are not available to allow standard LC-MS/MS assay development. A metabolite mixture obtained from an in vivo source treated with a radiolabeled compound was partially purified, quantified, and spiked into human plasma to provide metabolite standard curves. Metabolites were analyzed by LC-MS/MS using the specific mass transitions and an internal standard. The metabolite concentrations determined by this approach were found to be comparable to those determined by valid LC-MS/MS assays. This approach does not requires synthesis of authentic metabolites or the knowledge of exact structures of metabolites, and therefore should provide a useful method to obtain early estimates of circulating metabolites in early clinical or toxicological studies.

Clinical characteristics of an Afrikaner founder population recruited for a schizophrenia genetic study.

PubMed

Roos, Johannes Lodewikus; Pretorius, Herman Walter; Karayiorgou, Maria

2009-01-01

The clinical characteristics of an Afrikaner founder population sample recruited for a schizophrenia genetic study are described. Comparisons on several clinical characteristics between this sample and a U.S. sample of schizophrenia patients show that generalization of findings in a founder population to the population at large is applicable. The assessment of the frequency of the 22q11 deletion in Afrikaner schizophrenia patients is approximately 2%, similar to findings in a U.S. sample. Results of analysis of early non-psychotic deviant behavior in subjects under the age of 10 years in the Afrikaner population broadly replicated findings in a U.S. sample. Approximately half of male schizophrenia patients and a quarter of female patients in the Afrikaner schizophrenia database used or abused cannabis. Male users of cannabis with severe early deviant behavior had the lowest mean age of criteria onset, namely 18.4 years. These findings confirm previous findings, indicating that early deviance is linked to later outcome of disease. The clinical characteristics and premorbid variables in 12 childhood-onset Afrikaner schizophrenia patients thus far recruited in this study compare favorably with what is known about childhood-onset schizophrenia in a U.S. sample. The prevalence of co-morbid OCD/OCS in this Afrikaner schizophrenia founder sample was 13.2% which is in keeping with that of co-morbid OCD in schizophrenia, estimated at 12.2% by the U.S. National Institute of Mental Health. These findings confirm that the clinical characteristics of a schizophrenia sample drawn from the Afrikaner founder population can be generalized to the schizophrenia population at large when compared to findings reported in the literature.

A systematic review of the reporting of Data Monitoring Committees' roles, interim analysis and early termination in pediatric clinical trials

PubMed Central

2009-01-01

Background Decisions about interim analysis and early stopping of clinical trials, as based on recommendations of Data Monitoring Committees (DMCs), have far reaching consequences for the scientific validity and clinical impact of a trial. Our aim was to evaluate the frequency and quality of the reporting on DMC composition and roles, interim analysis and early termination in pediatric trials. Methods We conducted a systematic review of randomized controlled clinical trials published from 2005 to 2007 in a sample of four general and four pediatric journals. We used full-text databases to identify trials which reported on DMCs, interim analysis or early termination, and included children or adolescents. Information was extracted on general trial characteristics, risk of bias, and a set of parameters regarding DMC composition and roles, interim analysis and early termination. Results 110 of the 648 pediatric trials in this sample (17%) reported on DMC or interim analysis or early stopping, and were included; 68 from general and 42 from pediatric journals. The presence of DMCs was reported in 89 of the 110 included trials (81%); 62 papers, including 46 of the 89 that reported on DMCs (52%), also presented information about interim analysis. No paper adequately reported all DMC parameters, and nine (15%) reported all interim analysis details. Of 32 trials which terminated early, 22 (69%) did not report predefined stopping guidelines and 15 (47%) did not provide information on statistical monitoring methods. Conclusions Reporting on DMC composition and roles, on interim analysis results and on early termination of pediatric trials is incomplete and heterogeneous. We propose a minimal set of reporting parameters that will allow the reader to assess the validity of trial results. PMID:20003383

Early descriptions of acromegaly and gigantism and their historical evolution as clinical entities.

PubMed

Mammis, Antonios; Eloy, Jean Anderson; Liu, James K

2010-10-01

Giants have been a subject of fascination throughout history. Whereas descriptions of giants have existed in the lay literature for millennia, the first attempt at a medical description was published by Johannes Wier in 1567. However, it was Pierre Marie, in 1886, who established the term "acromegaly" for the first time and established a distinct clinical diagnosis with clear clinical descriptions in 2 patients with the characteristic presentation. Multiple autopsy findings revealed a consistent correlation between acromegaly and pituitary enlargement. In 1909, Harvey Cushing postulated a “hormone of growth" as the underlying pathophysiological trigger involved in pituitary hypersecretion in patients with acromegaly. This theory was supported by his observations of clinical remission in patients with acromegaly in whom he had performed hypophysectomy. In this paper, the authors present some of the early accounts of acromegaly and gigantism, and describe its historical evolution as a medical and surgical entity.

Primary care-led commissioning: applying lessons from the past to the early development of clinical commissioning groups in England

PubMed Central

Checkland, Kath; Coleman, Anna; McDermott, Imelda; Segar, Julia; Miller, Rosalind; Petsoulas, Christina; Wallace, Andrew; Harrison, Stephen; Peckham, Stephen

2013-01-01

Background The current reorganisation of the English NHS is one of the most comprehensive ever seen. This study reports early evidence from the development of clinical commissioning groups (CCGs), a key element in the new structures. Aim To explore the development of CCGs in the context of what is known from previous studies of GP involvement in commissioning. Design and setting Case study analysis from sites chosen to provide maximum variety across a number of dimensions, from September 2011 to June 2012. Method A case study analysis was conducted using eight detailed qualitative case studies supplemented by descriptive information from web surveys at two points in time. Data collection involved observation of a variety of meetings, and interviews with key participants. Results Previous research shows that clinical involvement in commissioning is most effective when GPs feel able to act autonomously. Complicated internal structures, alongside developing external accountability relationships mean that CCGs’ freedom to act may be subject to considerable constraint. Effective GP engagement is also important in determining outcomes of clinical commissioning, and there are a number of outstanding issues for CCGs, including: who feels ‘ownership’ of the CCG; how internal communication is conceptualised and realised; and the role and remit of locality groups. Previous incarnations of GP-led commissioning have tended to focus on local and primary care services. CCGs are keen to act to improve quality in their constituent practices, using approaches that many developed under practice-based commissioning. Constrained managerial support and the need to maintain GP engagement may have an impact. Conclusion CCGs are new organisations, faced with significant new responsibilities. This study provides early evidence of issues that CCGs and those responsible for CCG development may wish to address. PMID:23998841

The Illinois Articulation Initiative Major Fields Panels' Recommendations for Business, Clinical Laboratory Science, Education--Early Childhood, Education--Elementary, Education--Secondary, Music, Nursing, Psychology.

ERIC Educational Resources Information Center

Illinois Community Coll. Board, Springfield.

Developed by the Illinois Articulation Initiative (IAI), this report provides recommendations for improving articulation through state high schools, community colleges, and institutions of higher education. The recommendations are presented by field of study for business, clinical laboratory science, early childhood education, elementary…

Grating visual acuity results in the early treatment for retinopathy of prematurity study.

PubMed

Dobson, Velma; Quinn, Graham E; Summers, C Gail; Hardy, Robert J; Tung, Betty; Good, William V

2011-07-01

To compare grating (resolution) visual acuity at 6 years of age in eyes that received early treatment (ET) for high-risk prethreshold retinopathy of prematurity (ROP) with that in eyes that underwent conventional management (CM). In a randomized clinical trial, infants with bilateral, high-risk prethreshold ROP (n = 317) had one eye undergo ET and the other eye undergo CM, with treatment only if ROP progressed to threshold severity. For asymmetric cases (n = 84), the high-risk prethreshold eye was randomized to ET or CM. Grating visual acuity measured at 6 years of age by masked testers using Teller acuity cards. Monocular grating acuity results were obtained from 317 of 370 surviving children (85.6%). Analysis of grating acuity results for all study participants with high-risk prethreshold ROP showed no statistically significant overall benefit of ET (18.1% vs 22.8% unfavorable outcomes; P = .08). When the 6-year grating acuity results were analyzed according to a clinical algorithm (high-risk types 1 and 2 prethreshold ROP), a benefit was seen in type 1 eyes (16.4% vs 25.2%; P = .004) undergoing ET, but not in type 2 eyes (21.3% vs 15.9%; P = .29). Early treatment of eyes with type 1 ROP improves grating acuity outcomes, but ET for eyes with type 2 ROP does not. APPLICATION TO CLINICAL MEDICINE: Type 1 eyes should be treated early; however, based on acuity results at 6 years of age, type 2 eyes should be cautiously monitored for progression to type 1 ROP. Trial Registration clinicaltrials.gov Identifier: NCT00027222.

Early Language Development in Blind and Severely Visually Impaired Children. Interim Report on Pilot Study.

ERIC Educational Resources Information Center

Moore, Vanessa; McConachie, Helen

This study investigated variables that might be associated with outcome differences in language development of 10 children (ages 10-20 months) with blindness or severe visual impairments, attending a developmental vision clinic in southern England. Subjects' early patterns of expressive language development were examined and related to observed…

Comparative study of clinical and neuropsychological characteristics between early-, late and very-late-onset schizophrenia-spectrum disorders.

PubMed

Hanssen, Manon; van der Werf, Margriet; Verkaaik, Mike; Arts, Baer; Myin-Germeys, Inez; van Os, Jim; Verhey, Frans; Köhler, Sebastian

2015-08-01

To compare the clinical and neurocognitive profile of early-onset (EOP, <40 years), late-onset (LOP, 40-59 years) and very-late-onset (VLOP, ≥60 years) psychosis. Cross-sectional observational study. Secondary, tertiary, and community mental health care. Patients with a DSM-IV diagnosis of non-affective psychotic disorder were included from two complementary studies (GROUP and PSITE) on genetic and environmental risk factors of psychosis in the Netherlands and Belgium. Main outcome measures were the severity of positive and negative symptoms, quality of life, and age-corrected scores on measures of general intelligence, verbal memory, attention, and executive function. One-year follow-up data were used to validate diagnoses and exclude participants with possible or probable dementia. 286 EOP (85%), 24 LOP (7%) and 28 VLOP (8%) participated. VLOP patients reported significantly more positive symptoms than EOP patients. Age-at-onset groups had similar age-corrected scores on IQ, verbal memory, attention and executive functions. A significantly better performance was found in VLOP compared with LOP on the CAMCOG total score, though scores were still within the normal range. After controlling for possible confounding, however, VLOP differed significantly on an attention accuracy task compared with LOP patients. Re-entering data for probable dementia patients (N = 4) did change the results regarding cognition outcomes. VLOP patients show more positive symptoms but do not appear to differ on neuropsychological tests from EOP and LOP when age is controlled for. This questions the idea that VLOP is the expression of underlying neurodegeneration. Copyright © 2015 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Clinical efficacy and safety of bevacizumab monotherapy in patients with metastatic melanoma: predictive importance of induced early hypertension.

PubMed

Schuster, Cornelia; Eikesdal, Hans P; Puntervoll, Hanne; Geisler, Jürgen; Geisler, Stephanie; Heinrich, Daniel; Molven, Anders; Lønning, Per E; Akslen, Lars A; Straume, Oddbjørn

2012-01-01

VEGF driven angiogenesis plays a key role in cancer progression. We determined the clinical efficacy of bevacizumab monotherapy in patients with metastatic melanoma. Thirty-five patients with metastatic melanoma in progression were enrolled in this phase II, single arm clinical trial. Each patient received bevacizumab monotherapy 10 mg/kg q14 d until intolerable toxicity or disease progression occurred. Clinical efficacy was evaluated as objective response, disease control (DC), and survival. We observed one complete (3%) and 5 partial (14%) responses. In addition, 5 patients experienced stable disease >6 months (14%) while 24 patients had progressive disease (PD, 69%), corresponding to a total DC at 6 months in 11 out of 35 patients (31%). Median progression free survival (PFS) was 2.14 months and median overall survival (OS) was 9 months (1.12-49). Seven of the 11 patients experiencing DC developed early hypertension (<2 months) compared to 3/24 of patients with PD (P = 0.001), and hypertension was associated with PFS (P = 0.005) and OS (P = 0.013). Bevacizumab monotherapy demonstrated promising clinical efficacy in patients with metastatic melanoma with disease control in 31% of the patients. Induced early hypertension was a marker for clinical efficacy of bevacizumab. ClinicalTrials.gov NCT00139360.

POSTSURGICAL RECURRENT CUSHING DISEASE: CLINICAL BENEFIT OF EARLY INTERVENTION IN PATIENTS WITH NORMAL URINARY FREE CORTISOL.

PubMed

Carroll, Ty B; Javorsky, Bradley R; Findling, James W

2016-10-01

To assess the performance of biochemical markers in the detection of recurrent Cushing disease (CD), as well as the potential benefit of early intervention in recurrent CD patients with elevated late-night salivary cortisol (LNSC) and normal urinary free cortisol (UFC). The design was a single-center, retrospective chart review. Patients treated by the authors from 2008-2013 were included. Recurrence was defined by postsurgical remission of CD with subsequent abnormal LNSC, UFC, or dexamethasone suppression test (DST). We identified 15 patients with postsurgical recurrent CD after initial remission; all but one underwent testing with LNSC, DST, and UFC. Although 12 of 15 patients had normal UFC at time of recurrence, DST was abnormal in 11 of 15, and all 14 patients with LNSC results had ≥1 elevated measurement. Nine patients (7 with normal UFC) showed radiologic evidence of a pituitary tumor at time of recurrence. Among the 14 patients with available follow-up data, 12 have demonstrated significant improvement since receiving treatment. Five patients underwent repeat pituitary surgery and 4 achieved clinical and biochemical remission. Eight patients received mifepristone or cabergoline, and 6 showed clinical and/or biochemical improvement. Three patients (2 with prior mifepristone) underwent bilateral adrenalectomy and 2 demonstrated significant clinical improvements. LNSC is more sensitive than UFC or DST for detection of CD recurrence. Prompt intervention when LNSC is elevated, despite normal UFC, may yield significant clinical benefit for many patients with CD. Early treatment for patients with recurrent CD should be prospectively evaluated, utilizing LNSC elevation as an early biochemical marker. ACTH = adrenocorticotropic hormone CD = Cushing disease CS = Cushing syndrome CV = coefficient of variation DST = dexamethasone suppression test IPSS = inferior petrosal sinus sampling LNSC = late-night salivary cortisol QoL = quality of life TSS = transsphenoidal

Optical elastic scattering for early label-free identification of clinical pathogens

NASA Astrophysics Data System (ADS)

Genuer, Valentin; Gal, Olivier; Méteau, Jérémy; Marcoux, Pierre; Schultz, Emmanuelle; Lacot, Éric; Maurin, Max; Dinten, Jean-Marc

2016-03-01

We report here on the ability of elastic light scattering in discriminating Gram+, Gram- and yeasts at an early stage of growth (6h). Our technique is non-invasive, low cost and does require neither skilled operators nor reagents. Therefore it is compatible with automation. It is based on the analysis of the scattering pattern (scatterogram) generated by a bacterial microcolony growing on agar, when placed in the path of a laser beam. Measurements are directly performed on closed Petri dishes. The characteristic features of a given scatterogram are first computed by projecting the pattern onto the Zernike orthogonal basis. Then the obtained data are compared to a database so that machine learning can yield identification result. A 10-fold cross-validation was performed on a database over 8 species (15 strains, 1906 scatterograms), at 6h of incubation. It yielded a 94% correct classification rate between Gram+, Gram- and yeasts. Results can be improved by using a more relevant function basis for projections, such as Fourier-Bessel functions. A fully integrated instrument has been installed at the Grenoble hospital's laboratory of bacteriology and a validation campaign has been started for the early screening of MSSA and MRSA (Staphylococcus aureus, methicillin-resistant S. aureus) carriers. Up to now, all the published studies about elastic scattering were performed in a forward mode, which is restricted to transparent media. However, in clinical diagnostics, most of media are opaque, such as blood-supplemented agar. That is why we propose a novel scheme capable of collecting back-scattered light which provides comparable results.

Early experiences in evolving an enterprise-wide information model for laboratory and clinical observations.

PubMed

Chen, Elizabeth S; Zhou, Li; Kashyap, Vipul; Schaeffer, Molly; Dykes, Patricia C; Goldberg, Howard S

2008-11-06

As Electronic Healthcare Records become more prevalent, there is an increasing need to ensure unambiguous data capture, interpretation, and exchange within and across heterogeneous applications. To address this need, a common, uniform, and comprehensive approach for representing clinical information is essential. At Partners HealthCare System, we are investigating the development and implementation of enterprise-wide information models to specify the representation of clinical information to support semantic interoperability. This paper summarizes our early experiences in: (1) defining a process for information model development, (2) reviewing and comparing existing healthcare information models, (3) identifying requirements for representation of laboratory and clinical observations, and (4) exploring linkages to existing terminology and data standards. These initial findings provide insight to the various challenges ahead and guidance on next steps for adoption of information models at our organization.

Riociguat in patients with chronic thromboembolic pulmonary hypertension: results from an early access study.

PubMed

McLaughlin, Vallerie V; Jansa, Pavel; Nielsen-Kudsk, Jens E; Halank, Michael; Simonneau, Gérald; Grünig, Ekkehard; Ulrich, Silvia; Rosenkranz, Stephan; Gómez Sánchez, Miguel A; Pulido, Tomás; Pepke-Zaba, Joanna; Barberá, Joan Albert; Hoeper, Marius M; Vachiéry, Jean-Luc; Lang, Irene; Carvalho, Francine; Meier, Christian; Mueller, Katharina; Nikkho, Sylvia; D'Armini, Andrea M

2017-12-28

Following positive results from the Phase III CHEST-1 study in patients with inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH), the Phase IIIb CTEPH early access study (EAS) was designed to assess the safety and tolerability of riociguat in real-world clinical practice, as well as to provide patients with early access to riociguat before launch. Riociguat is approved for the treatment of inoperable and persistent/recurrent CTEPH. We performed an open-label, uncontrolled, single-arm, early access study in which 300 adult patients with inoperable or persistent/recurrent CTEPH received riociguat adjusted from 1 mg three times daily (tid) to a maximum of 2.5 mg tid. Patients switching from unsatisfactory prior pulmonary arterial hypertension (PAH)-targeted therapy (n = 84) underwent a washout period of at least 3 days before initiating riociguat. The primary aim was to assess the safety and tolerability of riociguat, with World Health Organization functional class and 6-min walking distance (6MWD) as exploratory efficacy endpoints. In total, 262 patients (87%) completed study treatment and entered the safety follow-up (median treatment duration 47 weeks). Adverse events were reported in 273 patients (91%). The most frequently reported serious adverse events were syncope (6%), right ventricular failure (3%), and pneumonia (2%). There were five deaths, none of which was considered related to study medication. The safety and tolerability of riociguat was similar in patients switched from other PAH-targeted therapies and those who were treatment naïve. In patients with data available, mean ± standard deviation 6MWD had increased by 33 ± 42 m at Week 12 with no clinically relevant differences between the switched and treatment-naïve subgroups. Riociguat was well tolerated in patients with CTEPH who were treatment naïve, and in those who were switched from other PAH-targeted therapies. No new safety signals were

Renal excretion of ingested gastrografin: clinical relevance in early postoperative treatment of patients who have undergone gastric surgery.

PubMed

Sohn, Kyung-Myung; Lee, Sung-Yong; Kwon, Oh-Han

2002-05-01

We performed this study to evaluate the clinical relevance of renal excretion of ingested Gastrografin (methylglucamine diatrizoate) revealed on CT in the early treatment of patients who have undergone gastric surgery. Unenhanced abdominal CT was performed before and then 1 hr to 1 hr 30 min after Gastrografin ingestion in 30 patients 7 days after gastric surgery and in 19 healthy adults who served as the control group. CT scans were reviewed for the opacification of the renal collecting system or urinary bladder after Gastrografin ingestion, a finding that represents renal excretion of the ingested contrast medium. In the control group, four (21 %) of the 19 healthy adults showed renal excretion of ingested Gastrografin visualized as opacification of the urinary tract on CT scans obtained 1 hr to 1 hr 30 min after ingestion of the substance. Renal excretion of the ingested Gastrografin was seen in 19 (63%) of the 30 patients, a significantly larger percentage than in the control group (z score, p < 0.01). No patient showed either radiologic or clinical evidence of leakage from the anastomotic site. Renal excretion of ingested Gastrografin is frequently visualized on CT in patients without anastomotic leakage during the early postoperative period after gastric surgery, and this phenomenon is not rare, even in healthy adults. Therefore, renal excretion seen on CT should not be regarded as a sign of anastomotic leakage in early postoperative patients.

Clinical progression, acute urinary retention, prostate-related surgeries, and costs in patients with benign prostatic hyperplasia taking early versus delayed combination 5α-reductase inhibitor therapy and α-blocker therapy: a retrospective analysis.

PubMed

Morlock, Robert; Goodwin, Bridgett; Gomez Rey, Gabriel; Eaddy, Michael

2013-05-01

Two previous retrospective database analyses compared early combination therapy with an α-blocker (AB) and 5-α reductase inhibitor (5-ARI) to delayed combination therapy and found that patients receiving the delayed combination therapy were more likely to have clinical progression, acute urinary retention (AUR), and surgery. Although these studies indicate the clinical benefits of early treatment, both studies failed to take into account important baseline clinical measures, such as prostate-specific antigen (PSA) values. This study was designed to compare clinical and cost differences in men with benign prostatic hyperplasia (BPH) who initiated early versus delayed combination therapy with a 5-ARI + an AB, factoring in baseline PSA values. This retrospective claims data analysis assessed data from >14 million US men with linked medical data, pharmacy data, laboratory results, and enrollment information from January 1, 2000, to December 31, 2009. Men aged 50 or older and treated for BPH with a 5-ARI + an AB were identified. Patients were required to be eligible for services at least 6 months before and 12 months after the index medication date. Patients were assigned to 1 of 2 treatment groups based on therapy (early or delayed) and 3 cohorts based on availability of PSA laboratory values (patients with a PSA value, patients with a PSA value >1.5 and <10, and all patients). Using a logistic model, the likelihood of clinical progression (defined as the occurrence of AUR or prostate surgery) during the 12 months after the date of first prescription fill was compared between BPH patients receiving early versus delayed combination therapy. BPH-related medical costs (excluding pharmacy costs) were assessed using generalized linear models. Among the 13,551 patients identified for study inclusion, the highest risks for clinical progression, AUR, and prostate-related surgery were consistently demonstrated in patients with a PSA >1.5 and <10. Across all 3 cohorts, the

Juxtapapillary duodenal diverticula early and late clinical and therapeutical implications.

PubMed

Straja, D; Marincaş, M; Alecu, M; Boroghina, G; Simion, L; Stanescu, A; Drilea, E; Brătucu, E

2009-01-01

The aim of this paper is to identify the early and late implications of JPDD for biliary pathology, as well as for endoscopic therapy and classical surgery dealing mainly with lithiasis. This paper is based on a retrospective study comprising a number of 675 ERCP performed on 601 patients between 1997-2007, out of which 399 cases were followed by therapeutic measures. A total of 79 procedures were performed on 65 cases with JPDD. The main criteria were: gender, age, indications regarding the performance of ERCP+/-ES, complications that occurred while carrying out these procedures. In all the cases examined (601) the percentage of JPDD reported was of 10.81%. The rate of complications in the sphincterotomized patients without JPDD was 5.75% and the rate in the sphincterotomized patients with JPDD was 14.89%. In conclusion, the paper discusses the clinical and therapeutic implications of JPDD in biliary pathology. It has been found that JPDD is an important etiological cause for the late diseases occurring after cholelithiasis surgery. JPDD also leads to immediate therapeutic implications such as: difficult cannulation and high incidence of ERCP+/-ES complications.

A Study of the Relationship between Early Childhood Program Attributes and Early Childhood Reading Achievement

ERIC Educational Resources Information Center

Washington, Novella M.

2012-01-01

This quantitative correlational study focuses on the relationship between early childhood program attributes and early childhood reading success. Data will be gathered from early childhood sites with grades prekindergarten through second grade in which early childhood program attributes exist and early childhood reading is measured by the…

Phrenic Nerve Conduction Study in the Early Stage of Guillain-Barre Syndrome as a Predictor of Respiratory Failure.

PubMed

Sen, Barun Kumar; Pandit, Alak

2018-01-01

Guillain-Barré syndrome (GBS) has unpredictable clinical course with severe complication of respiratory failure. To identify clinical profiles and electrophysiological study particularly non-invasive Phrenic nerve conduction study in patients of early GBS to predict respiratory failure. 64 adult (age≥18yrs) patients of early GBS (onset ≤ 14 days) during the study period from January 2014 to October 2015 were evaluated by clinical profiles of age, gender, antecedent infection, time to peak disability, single breath counts, cranial nerve involvement, autonomic dysfunction and non-invasive Phrenic nerve conduction study. Patients with predisposition factors of polyneuropathy like diabetes mellitus, hypothyroidism, vitamin deficiency, renal failure were excluded. Among 64 patients abnormal phrenic nerve conduction study was seen in 65.62% cases (42/64) and 45.23% (19/42) of them developed respiratory failure. Phrenic nerve sum latency, amplitude, duration and area were abnormal in those who developed respiratory failure and they had sum of phrenic nerve latency >28 msec, sum of CMAP amplitude <300 μV, sum of CMAP duration >50 msec and sum of area < 4 mVmS. None with normal phrenic nerve study developed respiratory failure. It was found that age, gender, preceding infection, autonomic involvement and types of GB syndrome had no influence on development of respiratory failure (p>0.05). Rapid disease progression to peak disability, more severe disease, shorter single breath counts and cranial nerve involvement were seen more often in patients with respiratory failure. Abnormal Phrenic nerve conduction study in the early Guillain-Barré syndrome might be of great value independently in predicting impending respiratory failure.

EARLY: a pilot study on early diagnosis of atrial fibrillation in a primary healthcare centre.

PubMed

Benito, Luisa; Coll-Vinent, Blanca; Gómez, Eva; Martí, David; Mitjavila, Joan; Torres, Ferran; Miró, Òscar; Sisó, Antoni; Mont, Lluís

2015-11-01

Atrial fibrillation (AF) is associated with high morbidity and mortality. Early diagnosis is likely to improve therapy and prognosis. The study objective was to evaluate the usefulness of a programme for early diagnosis of AF in patients from an urban primary care centre. Participants were recruited from a randomized sample of patients not diagnosed with AF but having relevant risk factors: age ≥ 65 years, ischaemic and/or valvular heart disease, congestive heart failure, hypertension, and/or diabetes. Patients were randomly assigned to the intervention group (IG) or control group (CG). The intervention included (i) initial visit with clinical history, electrocardiogram, and instruction about pulse palpation and warning signs and (ii) electrocardiogram every 6 months during a 2-year follow-up. The main endpoint of the study was the proportion of new cases diagnosed at 6 months. Secondary endpoints were number of new AF diagnoses and complications associated with the arrhythmia in both groups. A total of 928 patients were included (463 IG and 465 CG). At 6 months, AF was diagnosed in 8 IG patients and 1 CG patient (1.7 vs. 0.2%, respectively, P = 0.018). After 2 years of follow-up, 11 IG patients and 6 CG patients had newly diagnosed AF (2.5 vs. 1.3%, respectively, P = 0.132). Time to first diagnosis of AF was shorter in IG patients [median (inter-quartile range): 7 (192) days vs. 227 (188.5) days in CG, P = 0.029]. The simple screening proposed could be useful for the early detection of AF in primary care. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Early Recognition of High Risk of Bipolar Disorder and Psychosis: An Overview of the ZInEP "Early Recognition" Study.

PubMed

Theodoridou, Anastasia; Heekeren, Karsten; Dvorsky, Diane; Metzler, Sibylle; Franscini, Maurizia; Haker, Helene; Kawohl, Wolfram; Rüsch, Nicolas; Walitza, Susanne; Rössler, Wulf

2014-01-01

Early detection of persons with first signs of emerging psychosis is regarded as a promising strategy to reduce the burden of the disease. In recent years, there has been increasing interest in early detection of psychosis and bipolar disorders, with a clear need for sufficient sample sizes in prospective research. The underlying brain network disturbances in individuals at risk or with a prodrome are complex and yet not well known. This paper provides the rationale and design of a prospective longitudinal study focused on at-risk states of psychosis and bipolar disorder. The study is carried out within the context of the Zurich Program for Sustainable Development of Mental Health services (Zürcher Impulsprogramm zur Nachhaltigen Entwicklung der Psychiatrie). Persons at risk for psychosis or bipolar disorder between 13 and 35 years of age are examined by using a multi-level-approach (psychopathology, neuropsychology, genetics, electrophysiology, sociophysiology, magnetic resonance imaging, near-infrared spectroscopy). The included adolescents and young adults have four follow-ups at 6, 12, 24, and 36 months. This approach provides data for a better understanding of the relevant mechanisms involved in the onset of psychosis and bipolar disorder, which can serve as targets for future interventions. But for daily clinical practice a practicable "early recognition" approach is required. The results of this study will be useful to identify the strongest predictors and to delineate a prediction model.

RNA-seq Analysis of Clinical-Grade Osteochondral Allografts Reveals Activation of Early Response Genes

PubMed Central

Lin, Yang; Lewallen, Eric A.; Camilleri, Emily T.; Bonin, Carolina A.; Jones, Dakota L.; Dudakovic, Amel; Galeano-Garces, Catalina; Wang, Wei; Karperien, Marcel J.; Larson, Annalise N.; Dahm, Diane L.; Stuart, Michael J.; Levy, Bruce A.; Smith, Jay; Ryssman, Daniel B.; Westendorf, Jennifer J.; Im, Hee-Jeong; van Wijnen, Andre J.; Riester, Scott M.; Krych, Aaron J.

2016-01-01

Preservation of osteochondral allografts used for transplantation is critical to ensure favorable outcomes for patients after surgical treatment of cartilage defects. To study the biological effects of protocols currently used for cartilage storage, we investigated differences in gene expression between stored allograft cartilage and fresh cartilage from living donors using high throughput molecular screening strategies. We applied next generation RNA sequencing (RNA-seq) and real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR) to assess genome-wide differences in mRNA expression between stored allograft cartilage and fresh cartilage tissue from living donors. Gene ontology analysis was used to characterize biological pathways associated with differentially expressed genes. Our studies establish reduced levels of mRNAs encoding cartilage related extracellular matrix (ECM) proteins (i.e., COL1A1, COL2A1, COL10A1, ACAN, DCN, HAPLN1, TNC, and COMP) in stored cartilage. These changes occur concomitantly with increased expression of “early response genes” that encode transcription factors mediating stress/cytoprotective responses (i.e., EGR1, EGR2, EGR3, MYC, FOS, FOSB, FOSL1, FOSL2, JUN, JUNB, and JUND). The elevated expression of “early response genes” and reduced levels of ECM-related mRNAs in stored cartilage allografts suggests that tissue viability may be maintained by a cytoprotective program that reduces cell metabolic activity. These findings have potential implications for future studies focused on quality assessment and clinical optimization of osteochondral allografts used for cartilage transplantation. PMID:26909883

Early phase drugs and biologicals clinical trials on worldwide leading causes of death: a descriptive analysis.

PubMed

Dal-Ré, Rafael

2011-06-01

To describe the global effort targeting the major causes of mortality in terms of "open" early phase clinical trials with drugs and biologicals. Sixteen of the 20 leading causes of death were chosen; 9 of these were also amongst the top 10 causes of death in low-income countries. Studies were identified from the ClinicalTrials.gov database and included phase 1 and/or 2 "interventional" "open" trials, i.e. those recruiting or about to start recruitment. Trials were considered in terms of sponsorship [industry, universities and other organisations (UNO), and US federal agencies (NIH included)], genders and age groups included, and whether they were conducted with drugs and/or biologicals. The search was performed in March 2010. A total of 2,298 (824 phase 1; 1,474 phase 2) trials were retrieved. Of these, 67% were on trachea, bronchus, and lung cancers (25%); diabetes mellitus (15%); colon and rectum cancers (14%); and HIV/AIDS (12%). In contrast, only 4% were trials on diarrhoeal disease, nephrosis and nephritis, liver cirrhosis, and prematurity and low birth weight. UNO were the first source of funding. Fifty-two percent of phase 1 non-cancer trials were on healthy volunteers. Twenty-nine percent of all trials were co-funded. There were 4.6 times as many drug trials as those with biologicals. Only 7% were conducted with a combination of drugs and biologicals, the majority (78%) on cancers. Discrimination in terms of gender or age group was not observed. Four of the 16 diseases considered represented 2/3 of early phase trials. Cancers were a top priority for all sponsors. Increasing attention should be given to conditions with current and projected global high mortality rates that had few "open" early phase trials.

The definition of severe and early-onset preeclampsia. Statements from the International Society for the Study of Hypertension in Pregnancy (ISSHP).

PubMed

Tranquilli, Andrea L; Brown, Mark A; Zeeman, Gerda G; Dekker, Gustaaf; Sibai, Baha M

2013-01-01

There is discrepancy in the literature on the definitions of severe and early-onset pre-eclampsia. We aimed to determine those definitions for clinical purposes and to introduce them in the classification of the hypertensive disorders of pregnancy for publication purposes. We circulated a questionnaire to the International Committee of the International Society for the Study of Hypertension in Pregnancy focusing on the thresholds for defining severe preeclampsia and the gestation at which to define early-onset preeclampsia, and on the definition and inclusion of the HELLP syndrome or other clinical features in severe preeclampsia. The questions were closed, but all answers had space for more open detailed comments. There was a general agreement to define preeclampsia as severe if blood pressure was >160mmHg systolic or 110mmHg diastolic. There was scarce agreement on the amount of proteinuria to define severity. The HELLP syndrome was considered a feature to include in the severe classification. Most investigators considered early-onset preeclampsia as that occurring before 34weeks. A definition of pre-eclampsia is paramount for driving good clinical practice. Classifications on the other hand are useful to enable international comparisons of clinical data and outcomes. We used the results of this survey to update our previous classification for the purposes of providing clinical research definitions of severe and early onset pre-eclampsia that will hopefully be accepted in the international literature. Copyright © 2012 International Society for the Study of Hypertension in Pregnancy. All rights reserved.

WWC Review of the Report "Early College, Early Success: Early College High School Initiative Impact Study." What Works Clearinghouse Single Study Review

ERIC Educational Resources Information Center

What Works Clearinghouse, 2014

2014-01-01

Early College High Schools partner with colleges and universities to provide students with an opportunity to earn an Associate's degree or college credits toward a Bachelor's degree at no or low cost to students. In a recent study, researchers found that attending Early College High Schools improved some high school and postsecondary outcomes for…

Recognizing Business Issues in Professional Psychology for Clinical PsyD Trainees and Early Career Psychologists

ERIC Educational Resources Information Center

Maciel, Michelle

2012-01-01

The largest number of licensed psychologists are centralized in California. More PsyD than PhD degrees in clinical psychology are now awarded, and California houses 16 of the 59 APA-accredited programs. Post-millennia Early Career Psychologists (ECPs) typically accumulate over $120,000 in education debt, and may be concerned with the cost-benefit…

Nurse leaders' perceptions of the ethical recruitment of study subjects in clinical research.

PubMed

Nurmi, Sanna-Maria; Pietilä, Anna-Maija; Kangasniemi, Mari; Halkoaho, Arja

2015-11-01

The aim of this study was to describe nurse leaders' perceptions of ethical recruitment in clinical research. Nurse leaders are expected to get involved in clinical research, but there are few studies that focus on their role, particularly the ethical issues. Qualitative data were collected from ten nurse leaders using thematic one-to-one interviews and analysed with content analysis. Nurse leaders considered clinical research at their workplace in relation to the key issues that enabled ethical recruitment of study subjects in clinical research. These were: early information and collaboration for incorporating clinical research in everyday work, an opportune and peaceful recruitment moment and positive research culture. Getting involved in clinical research is part of the nurse leader's professional responsibility in current health care. They have an essential role to play in ensuring that recruitment is ethical and that the dignity of study subjects is maintained. The duty of nurse leaders is to maintain good contact with other collaborators and to ensure good conditions for implementing clinical research at their site. This requires a comprehensive understanding of the overall situation on their wards. Implementing clinical research requires careful planning, together with educating, supporting and motivating nursing staff. © 2014 John Wiley & Sons Ltd.

The economic and clinical burden of early versus late initiation of celecoxib among patients with osteoarthritis

PubMed Central

Shelbaya, Ahmed; Solem, Caitlyn T; Walker, Chris; Wan, Yin; Johnson, Courtney; Cappelleri, Joseph C

2018-01-01

Objective This study aimed to evaluate the characteristics associated with early versus late initiation of celecoxib treatment after osteoarthritis (OA) diagnosis and whether economic and safety outcomes differ between patients with early versus late initiation of celecoxib. Methods Adults (≥18 years) with a confirmed OA diagnosis (International Classification of Diseases, 9th Edition, Clinical Modifications code: 715.XX), ≥12 months of continuous pre- and post-index enrollment, and ≥1 post-index claim for celecoxib were included from the MarketScan® Commercial Claims and Encounter Database (2009–2013). Index date was defined as initial OA diagnosis. Patients were categorized as initiating celecoxib early (within 6 months of index date) or late (≥6 months after index date). Logistic regressions were used to assess characteristics associated with early versus late celecoxib initiation. Key outcomes included health care resource utilization (HCRU) and costs post-index, and adverse event incidence post-celecoxib initiation. Unadjusted and adjusted comparisons (using generalized linear models with a gamma distribution for costs and Poisson distribution for event and resource utilization) were made between early and late celecoxib initiators. Results Of the 62,434 OA patients identified, 27,402 were early and 35,032 were late initiators. Post-index hospital admissions and length of stay did not differ statistically between early versus late initiators after controlling for pre-index event rates and covariates, but early patients had significantly fewer outpatient (incidence rate ratio [IRR]: 0.96; 95% confidence interval [CI]: 0.95, 0.97) and emergency room visits (IRR: 0.89; 95% CI: 0.84, 0.95). After adjustment for key covariates, early initiators (versus late initiators) had lower all-cause (US$12,909 versus US$13,781, P<0.001) and OA-related (US$4,988 versus US$5,178, P=0.015) costs per person-year. Early initiators had no statistically significant

SheppHeartCABG trial—comprehensive early rehabilitation after coronary artery bypass grafting: a protocol for a randomised clinical trial

PubMed Central

Moons, Philip; Hansen, Niels Viggo; La Cour, Søren; Olsen, Peter Skov; Gluud, Christian; Winkel, Per; Lindschou, Jane; Thygesen, Lau Caspar; Egerod, Ingrid; Berg, Selina Kikkenborg

2017-01-01

Introduction Patients undergoing coronary artery bypass graft surgery often experience a range of symptoms. Studies indicate that non-pharmacological interventions such as exercise training and psychoeducation have a positive physiological and psychological effect in early outpatient rehabilitation. The SheppHeartCABG trial will investigate the effect of early comprehensive rehabilitation in early phase rehabilitation versus usual care. The aim of this paper is to present the protocol for the SheppHeartCABG trial. Methods/analysis SheppHeartCABG is an investigator-initiated randomised clinical superiority trial with blinded outcome assessment, employing 1:1 central randomisation to rehabilitation plus usual care versus usual care alone. On the basis of a sample size calculation, 326 patients undergoing coronary artery bypass grafting will be included from two clinical sites. All patients receive usual care and patients allocated to the experimental intervention follow 4 weeks rehabilitation consisting of an exercise programme, psycho-educative consultations and a compact mindfulness programme. The primary outcome is physical function measured by the 6-min walk test. The secondary outcomes are mental health and physical activity measured by the Medical Outcome Study Short Form (SF-12), anxiety and depression measured by the Hospital Anxiety and Depression Scale questionnaire, physical, emotional and global scores by the HeartQoL questionnaire, sleep measured by the Pittsburgh Sleep Quality Index, pain measured by the Örebro Musculoskeletal Screening Questionnaire and muscle endurance measured by the sit-to-stand test. A number of explorative analyses will also be conducted. Ethics and dissemination SheppHeartCABG is approved by the regional ethics committee (no. H-4-2014-109) and the Danish Data Protection Agency (no. 30-1309) and is performed in accordance with good clinical practice and the Declaration of Helsinki in its latest form. Positive, neutral and

Clinical Efficacy and Safety of Bevacizumab Monotherapy in Patients with Metastatic Melanoma: Predictive Importance of Induced Early Hypertension

PubMed Central

Schuster, Cornelia; Eikesdal, Hans P.; Puntervoll, Hanne; Geisler, Jürgen; Geisler, Stephanie; Heinrich, Daniel; Molven, Anders; Lønning, Per E.; Akslen, Lars A.; Straume, Oddbjørn

2012-01-01

Background VEGF driven angiogenesis plays a key role in cancer progression. We determined the clinical efficacy of bevacizumab monotherapy in patients with metastatic melanoma. Methods and Findings Thirty-five patients with metastatic melanoma in progression were enrolled in this phase II, single arm clinical trial. Each patient received bevacizumab monotherapy 10 mg/kg q14 d until intolerable toxicity or disease progression occurred. Clinical efficacy was evaluated as objective response, disease control (DC), and survival. We observed one complete (3%) and 5 partial (14%) responses. In addition, 5 patients experienced stable disease >6 months (14%) while 24 patients had progressive disease (PD, 69%), corresponding to a total DC at 6 months in 11 out of 35 patients (31%). Median progression free survival (PFS) was 2.14 months and median overall survival (OS) was 9 months (1.12–49). Seven of the 11 patients experiencing DC developed early hypertension (<2 months) compared to 3/24 of patients with PD (P = 0.001), and hypertension was associated with PFS (P = 0.005) and OS (P = 0.013). Conclusion Bevacizumab monotherapy demonstrated promising clinical efficacy in patients with metastatic melanoma with disease control in 31% of the patients. Induced early hypertension was a marker for clinical efficacy of bevacizumab. Trial Registration ClinicalTrials.gov NCT00139360. PMID:22719881

Dopamine Transporter Neuroimaging as an Enrichment Biomarker in Early Parkinson's Disease Clinical Trials: A Disease Progression Modeling Analysis

PubMed Central

Nicholas, Timothy; Tsai, Kuenhi; Macha, Sreeraj; Sinha, Vikram; Stone, Julie; Corrigan, Brian; Bani, Massimo; Muglia, Pierandrea; Watson, Ian A.; Kern, Volker D.; Sheveleva, Elena; Marek, Kenneth; Stephenson, Diane T.; Romero, Klaus

2017-01-01

Abstract Given the recognition that disease‐modifying therapies should focus on earlier Parkinson's disease stages, trial enrollment based purely on clinical criteria poses significant challenges. The goal herein was to determine the utility of dopamine transporter neuroimaging as an enrichment biomarker in early motor Parkinson's disease clinical trials. Patient‐level longitudinal data of 672 subjects with early‐stage Parkinson's disease in the Parkinson's Progression Markers Initiative (PPMI) observational study and the Parkinson Research Examination of CEP‐1347 Trial (PRECEPT) clinical trial were utilized in a linear mixed‐effects model analysis. The rate of worsening in the motor scores between subjects with or without a scan without evidence of dopamine transporter deficit was different both statistically and clinically. The average difference in the change from baseline of motor scores at 24 months between biomarker statuses was –3.16 (90% confidence interval [CI] = –0.96 to –5.42) points. Dopamine transporter imaging could identify subjects with a steeper worsening of the motor scores, allowing trial enrichment and 24% reduction of sample size. PMID:28749580

Confocal microendoscopy: Characterization of imaging bundles, fluorescent contrast agents, and early clinical results

NASA Astrophysics Data System (ADS)

Udovich, Joshua Anthony

Ovarian cancer is the fifth leading cause of cancer related deaths among women. Early detection improves the chances of survival following diagnosis, and new imaging modalities have the potential to reduce deaths due to this disease. The confocal microendoscope (CME) is a non-destructive in-vivo imaging device for visualization of the ovaries that operates in real-time. Two components of the CME system are evaluated in this paper, and initial results from an ongoing clinical trial are presented. Fiber-optic imaging bundles are used in the CME imaging catheter to relay images over distances of up to 20 feet. When detecting fluorescent signals from investigated tissue, any fluorescence in the system can potentially reduce contrast in images. The emission and transmission properties of three commercially available fiber optic imaging bundles were evaluated. Emission maps of fluorescence from bundles were generated at multiple excitation wavelengths to determine the profile and amount of fluorescence present in bundles manufactured by Sumitomo, Fujikura, and Schott. Results are also presented that show the variation of transmittance as a function of illumination angle in these bundles. Users of high-resolution fiber-optic imaging bundles should be aware of these properties and take them into account during system design. Contrast is improved in images obtained with the CME through the application of topical dyes. Acridine orange (AO) and SYTO 16 are two fluorescent stains that are used to show the size, shape, and distribution of cell nuclei. Unfortunately, little is known about the effects of these dyes on living tissues. This study was undertaken to evaluate the effects of dye treatment on peritoneal tissues in mice. Seventy-five Balb/c mice were split into five groups of fifteen and given peritoneal injections of dye or saline. The proportions of negative outcomes for the control and test groups were compared using confidence intervals and the Fisher's exact test

Early weaning from incubator and early discharge of preterm infants: randomized clinical trial.

PubMed

Zecca, Enrico; Corsello, Mirta; Priolo, Francesca; Tiberi, Eloisa; Barone, Giovanni; Romagnoli, Costantino

2010-09-01

The goal was to assess the feasibility of earlier weaning from the incubator for preterm infants. This was a prospective, randomized study with preterm infants with birth weights of <1600 g who were admitted to a neonatal subintensive ward. Findings for 47 infants who were transferred from an incubator to an open crib at >1600 g (early transition group) were compared with those for 47 infants who were transferred from an incubator to an open crib at >1800 g (standard transition [ST] group). The primary outcome of the study was length of stay. Secondary outcomes were the number of infants returned to an incubator, the growth velocity in an open crib and during the first week at home, the proportions of breastfeeding at discharge and during the first week at home, and the hospital readmission rate. The length of stay was significantly shorter in the early transition group than in the standard transition group (23.5 vs 33 days; P=.0002). No infants required transfer back to the incubator. Only 1 infant in the standard transition group was readmitted to the hospital during the first week after discharge. Growth velocities and individual amounts of breastfeeding were similar between the 2 groups. In this study, weaning of moderately preterm infants from incubators to open cribs at 1600 g was safe and resulted in earlier discharge.

Early Onset Recurrent Subtype of Adolescent Depression: Clinical and Psychosocial Correlates

ERIC Educational Resources Information Center

Hammen, Constance; Brennan, Patricia A.; Keenan-Miller, Danielle; Herr, Nathaniel R.

2008-01-01

Background: Evaluated trajectories of adolescent depression and their correlates in a longitudinal study of a community sample: early onset (by age 15) with major depression (MDE) recurrence between 15 and 20; early onset with no recurrence; later onset of major depression after age 15 with and without recurrence by 20; and never-depressed.…

Preclinical students’ experiences in early clerkships after skills training partly offered in primary health care centers: a qualitative study from Indonesia

PubMed Central

2012-01-01

Background Students may encounter difficulties when they have to apply clinical skills trained in their pre-clinical studies in clerkships. Early clinical exposure in the pre-clinical phase has been recommended to reduce these transition problems. The aim of this study is to explore differences in students' experiences during the first clerkships between students exclusively trained in a skills laboratory and peers for whom part of their skills training was substituted by early clinical experiences (ECE). Methods Thirty pre-clinical students trained clinical skills exclusively in a skills laboratory; 30 peers received part of their skills training in PHC centers. Within half a year after commencing their clerkships all 60 students shared their experiences in focus group discussions (FGDs). Verbatim transcripts of FGDs were analyzed using Atlas-Ti software. Results Clerkship students who had participated in ECE in PHC centers felt better prepared to perform their clinical skills during the first clerkships than peers who had only practiced in a skills laboratory. ECE in PHC centers impacted positively in particular on students’ confidence, clinical reasoning, and interpersonal communication. Conclusion In the Indonesian setting ECE in PHC centers reduce difficulties commonly encountered by medical students in the first clerkships. PMID:22640419

[Studies of termination of early pregnancy with Bromo-Geraminum].

PubMed

Hou, Z K; Liu, D G; Kao, F S; Chen, S L

1984-08-01

The authors introduced 3 ml of 2-3% Bromo-Geraminum (BG) solution into the uterine cavities to induce abortion in 356 early pregnant women from March 1979 through June 1980. The success rate in the termination of early pregnancy was 80.1% and even 96.5% in those who had been pregnant for less than 5 weeks. The mean abortion time was 40.9 porn 19.7 hours. It was noticed that the blood HCG level dropped dramatically after introducing into the uterine cavity. It has been demonstrated experimentally and clinically that this method is effective, safe, simple, and inexpensive and that the normal menstrual cycle recovers very soon without side effects.

The Critical Role of Early Dengue Surveillance and Limitations of Clinical Reporting – Implications for Non-Endemic Countries

PubMed Central

Kao, Jui-Hung; Chen, Chaur-Dong; Chu, Yin-Hsia; Cheng, Hau-Yuan; Liu, Jien-Wei; Shih, Fuh-Yuan; Shu, Pei-Yun; Lin, Chien-Chou; Tsai, Wu-Hsiung; Ku, Chia-Chi; Ho, Chi-Kung; King, Chwan-Chuen

2016-01-01

The increasing dengue burden and epidemic severity worldwide have highlighted the need to improve surveillance. In non-endemic areas such as Taiwan, where outbreaks start mostly with imported cases from Southeast Asia, a closer examination of surveillance dynamics to detect cases early is necessary. To evaluate problems with dengue surveillance and investigate the involvement of different factors at various epidemic stages, we investigated 632 laboratory-confirmed indigenous dengue cases in Kaohsiung City, Taiwan during 2009–2010. The estimated sensitivity of clinical surveillance was 82.4% (521/632). Initially, the modified serological surveillance (targeting only the contacts of laboratory-confirmed dengue cases) identified clinically unrecognized afebrile cases in younger patients who visited private clinics and accounted for 30.4% (35/115) of the early-stage cases. Multivariate regression indicated that hospital/medical center visits [Adjusted Odds Ratio (aOR): 11.6, 95% confidence interval (CI): 6.3–21.4], middle epidemic stage [aOR: 2.4 (1.2–4.7)], fever [aOR: 2.3 (2.3–12.9)], and musculo-articular pain [aOR: 1.9 (1.05–3.3)] were significantly associated with clinical reporting. However, cases with pruritus/rash [aOR: 0.47 (0.26–0.83)] and diarrhea [aOR: 0.47 (0.26–0.85)] were underreported. In conclusion, multiple factors contributed to dengue surveillance problems. To prevent a large-scale epidemic and minimize severe dengue cases, there is a need for integrated surveillance incorporating entomological, clinical, serological, and virological surveillance systems to detect early cases, followed by immediate prevention and control measures and continuous evaluation to ensure effectiveness. This effort will be particularly important for an arbovirus, such as Zika virus, with a high asymptomatic infection ratio. For dengue- non-endemic countries, we recommend serological surveillance be implemented in areas with high Aedes mosquito indices or many

Value analysis of postoperative staging imaging for asymptomatic, early-stage breast cancer: implications of clinical variation on utility and cost.

PubMed

Pellet, Andrew C; Erten, Mujde Z; James, Ted A

2016-06-01

Routine staging imaging for early-stage breast cancer is not recommended. Despite this, there is clinical practice variation with imaging studies obtained for asymptomatic patients with a positive sentinel node (SN+). We characterize the utility, cost, and clinical implications of imaging studies obtained in asymptomatic SN+ patients. A retrospective review was performed of asymptomatic, clinically node-negative patients who were found to have a positive sentinel node after surgery. The type of imaging, subsequent tests/interventions, frequency of additional malignancy detected, and costs were recorded. From April 2009 to April 2013, a total of 50 of 113 (44%) asymptomatic patients underwent staging imaging for a positive sentinel node; 11 (22%) patients had at least 1 subsequent imaging study or diagnostic intervention. No instance of metastatic breast cancer was identified, with a total cost of imaging calculated at $116,905. Staging imaging for asymptomatic SN+ breast cancer demonstrates clinical variation. These tests were associated with low utility, increased costs, and frequent false positives leading to subsequent testing/intervention. Evidence-based standardization may help increase quality by decreasing unnecessary variation and cost. Copyright © 2015 Elsevier Inc. All rights reserved.

Phrenic Nerve Conduction Study in the Early Stage of Guillain–Barre Syndrome as a Predictor of Respiratory Failure

PubMed Central

Sen, Barun Kumar; Pandit, Alak

2018-01-01

Background: Guillain-Barré syndrome (GBS) has unpredictable clinical course with severe complication of respiratory failure. Objective: To identify clinical profiles and electrophysiological study particularly non-invasive Phrenic nerve conduction study in patients of early GBS to predict respiratory failure. Methods: 64 adult (age≥18yrs) patients of early GBS (onset ≤ 14 days) during the study period from January 2014 to October 2015 were evaluated by clinical profiles of age, gender, antecedent infection, time to peak disability, single breath counts, cranial nerve involvement, autonomic dysfunction and non-invasive Phrenic nerve conduction study. Patients with predisposition factors of polyneuropathy like diabetes mellitus, hypothyroidism, vitamin deficiency, renal failure were excluded. Results: Among 64 patients abnormal phrenic nerve conduction study was seen in 65.62% cases (42/64) and 45.23% (19/42) of them developed respiratory failure. Phrenic nerve sum latency, amplitude, duration and area were abnormal in those who developed respiratory failure and they had sum of phrenic nerve latency >28 msec, sum of CMAP amplitude <300 μV, sum of CMAP duration >50 msec and sum of area < 4 mVmS. None with normal phrenic nerve study developed respiratory failure. It was found that age, gender, preceding infection, autonomic involvement and types of GB syndrome had no influence on development of respiratory failure (p>0.05). Rapid disease progression to peak disability, more severe disease, shorter single breath counts and cranial nerve involvement were seen more often in patients with respiratory failure. Conclusion: Abnormal Phrenic nerve conduction study in the early Guillain-Barré syndrome might be of great value independently in predicting impending respiratory failure. PMID:29720799

Comparing early signs and basic symptoms as methods for predicting psychotic relapse in clinical practice.

PubMed

Eisner, Emily; Drake, Richard; Lobban, Fiona; Bucci, Sandra; Emsley, Richard; Barrowclough, Christine

2018-02-01

Early signs interventions show promise but could be further developed. A recent review suggested that 'basic symptoms' should be added to conventional early signs to improve relapse prediction. This study builds on preliminary evidence that basic symptoms predict relapse and aimed to: 1. examine which phenomena participants report prior to relapse and how they describe them; 2. determine the best way of identifying pre-relapse basic symptoms; 3. assess current practice by comparing self- and casenote-reported pre-relapse experiences. Participants with non-affective psychosis were recruited from UK mental health services. In-depth interviews (n=23), verbal checklists of basic symptoms (n=23) and casenote extracts (n=208) were analysed using directed content analysis and non-parametric statistical tests. Three-quarters of interviewees reported basic symptoms and all reported conventional early signs and 'other' pre-relapse experiences. Interviewees provided rich descriptions of basic symptoms. Verbal checklist interviews asking specifically about basic symptoms identified these experiences more readily than open questions during in-depth interviews. Only 5% of casenotes recorded basic symptoms; interviewees were 16 times more likely to report basic symptoms than their casenotes did. The majority of interviewees self-reported pre-relapse basic symptoms when asked specifically about these experiences but very few casenotes reported these symptoms. Basic symptoms may be potent predictors of relapse that clinicians miss. A self-report measure would aid monitoring of basic symptoms in routine clinical practice and would facilitate a prospective investigation comparing basic symptoms and conventional early signs as predictors of relapse. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Clinical utility of cerebrospinal fluid biomarkers in the diagnosis of early Alzheimer’s disease

PubMed Central

Blennow, Kaj; Dubois, Bruno; Fagan, Anne M.; Lewczuk, Piotr; de Leon, Mony J.; Hampel, Harald

2015-01-01

Several potential disease-modifying drugs for Alzheimer’s disease (AD) have failed to show any effect on disease progression in clinical trials, conceivably because the AD subjects are already too advanced to derive clinical benefit from treatment and because diagnosis based on clinical criteria alone introduces a high misdiagnosis rate. Thus, well-validated biomarkers for early detection and accurate diagnosis are crucial. Low cerebrospinal fluid (CSF) concentrations of the amyloid-β (Aβ1-42) peptide, in combination with high total tau and phosphorylated tau, are sensitive and specific biomarkers highly predictive of progression to AD dementia in patients with mild cognitive impairment. However, interlaboratory variations in the results seen with currently available immunoassays are of concern. Recent worldwide standardization efforts and quality control programs include standard operating procedures for both preanalytical (e.g., lumbar puncture and sample handling) and analytical (e.g., preparation of calibration curve) procedures. Efforts are also ongoing to develop highly reproducible assays on fully automated instruments. These global standardization and harmonization measures will provide the basis for the generalized international application of CSF bio-markers for both clinical trials and routine clinical diagnosis of AD. PMID:24795085

Early rehabilitation for severe acquired brain injury in intensive care unit: multicenter observational study.

PubMed

Bartolo, Michelangelo; Bargellesi, Stefano; Castioni, Carlo A; Bonaiuti, Donatella; Antenucci, Roberto; Benedetti, Angelo; Capuzzo, Valeria; Gamna, Federica; Radeschi, Giulio; Citerio, Giuseppe; Colombo, Carolina; Del Casale, Laura; Recubini, Elena; Toska, Saimir; Zanello, Marco; D'Aurizio, Carlo; Spina, Tullio; Del Gaudio, Alredo; Di Rienzo, Filomena; Intiso, Domenico; Dallocchio, Giulia; Felisatti, Giovanna; Lavezzi, Susanna; Zoppellari, Roberto; Gariboldi, Valentina; Lorini, Luca; Melizza, Giovanni; Molinero, Guido; Mandalà, Giorgio; Pignataro, Amedeo; Montis, Andrea; Napoleone, Alessandro; Pilia, Felicita; Pisu, Marina; Semerjian, Monica; Pagliaro, Giuseppina; Nardin, Lorella; Scarponi, Federico; Zampolini, Mauro; Zava, Raffaele; Massetti, Maria A; Piccolini, Carlo; Aloj, Fulvio; Antonelli, Sergio; Zucchella, Chiara

2016-02-01

The increased survival after a severe acquired brain injury (sABI) raise the problem of making most effective the treatments in Intensive Care Unit (ICU)/Neurointensive Care Unit (NICU), also integrating rehabilitation care. Despite previous studies reported that early mobilization in ICU was effective in preventing complications and reducing hospital stay, few studies addressed the rehabilitative management of sABI patients in ICU/NICU. To collect clinical and functional data about the early rehabilitative management of sABI patients during ICU/NICU stay. Prospective, observational, multicenter study. Fourteen facilities supplied by intensive neurorehabilitation units and ICU/NICUs. Consecutive sABI patients admitted to ICU/NICU. Patients were evaluated at admission and then every 3-5 days. Clinical, functional and rehabilitative data, including Glasgow Coma Scale (GCS), Disability Rating Scale (DRS), The Rancho Los Amigos Levels of Cognitive Functioning Scale (LCF), Early Rehabilitation Barthel Index (ERBI), Glasgow Outcome scale (GOS) and Functional Independence Measure (FIM) were collected. One hundred and two patients (F/M 44/58) were enrolled. The mean duration of ICU stay was 24.7±13.9 days and the first rehabilitative evaluation occurred after 8.7±8.8 days. Regular postural changes and multijoint mobilization were prescribed in 63.7% and 64.7% cases, respectively. The mean session duration was 38±11.5 minutes. Swallowing evaluation was performed in 14.7% patients, psychological support was provided to 12.7% of patients' caregivers, while 17.6% received a psycho-educational intervention, and 28.4% were involved in interdisciplinary team meetings. The main discharge destinations were Severe Acquired Brain Injury rehabilitation units for 43.7%, intensive neurorehabilitation units for 20.7%. Data showed that early rehabilitation was not diffusely performed in sABI subjects in ICU/NICU and rehabilitative interventions were variable; one-third of subjects were

Early Otitis Media Among Minnesota American Indians: The Little Ears Study

PubMed Central

Daly, Kathleen A.; Pirie, Phyllis L.; Rhodes, Kristine L.; Hunter, Lisa L.; Davey, Cynthia S.

2007-01-01

Objectives. We examined relationships between otitis media risk factors, sociodemographic characteristics, and maternal knowledge and attitudes and early onset of otitis media. Methods. Pregnant women from Minnesota American Indian reservations and an urban clinic were enrolled in our study between 1998 and 2001. Follow-up was performed on enrollees’ infants until the children were 2 years old. Research nurses collected data by ear examination, from interviews and questionnaires given to enrolled mothers, and otitis media episodes that were abstracted from medical records. Results. Sixty-three percent of infants had experienced an otitis media episode by 6 months of age. Logistic regression analyses showed that maternal otitis media history, infant history of upper respiratory infection, and compliance with study visits were significantly related to early otitis media onset. Although high percentages of infants were exposed to cigarette smoke and other children and were formula fed, these factors were not related to otitis media. Mothers’ prenatal awareness of otitis media risks associated with environmental tobacco smoke exposure and formula feeding did not predict their postpartum behaviors. Conclusions. We found that infant history of upper respiratory infection and maternal otitis media history are risk factors for early otitis media in American Indian infants. Mothers’ prepartum knowledge and attitudes regarding otitis media did not predict their postpartum avoidance of risk behaviors. PMID:17194873

[Early diagnosis of Hansen disease: study of the health services in Recife (Pernambuco), Brazil].

PubMed

Feliciano, K V; Kovacs, M H; Alzate, A

1998-07-01

This paper presents the results of a descriptive study carried out in the city of Recife, state of Pernambuco, Brazil, between March and September 1994. The study aimed at health services available for performing early diagnosis of Hansen's disease with emphasis on accessibility and quality of the services provided. The sample consisted of 32 health clinics visited for diagnostic purposes by 183 patients with Hansen's disease. Information on organizational infrastructures was collected by means of interviews with health clinic managers. Information regarding routine procedures in the 32 clinics was collected by observation, with special attention given to archival and inspection activities. A total of 1,998 patients were interviewed to determine accessibility of services. Time spent in consultation with the physician was determined for 1,000 patients who were seen by 123 physicians at the clinics during the interviews. To explore physicians' attitude and knowledge regarding Hansen's disease, 133 were randomly selected from a list of names. The following factors were identified as hindering early diagnosis of Hansen's disease: the large number of people seeking service who could not be seen by a physician on the same day; the long time elapsed between appointment scheduling and the actual visit (for those not seen on the same day); the long wait for the consultation; the brevity of the consultation; the low availability of trained personnel; the low proportion of physicians who examined all body surfaces; difficulties in the clinical recognition of the disease; and physicians not prepared to make a differential diagnosis. These obstacles can precipitate the physical deterioration of Hansen's disease patients and stimulate the persistence of transmissibility; therefore, they need to be overcome if Hansen's disease is to be eliminated.

Multisite Semiautomated Clinical Data Repository for Duplication 15q Syndrome: Study Protocol and Early Uses.

PubMed

Ajayi, Oluwaseun Jessica; Smith, Ebony Jeannae; Viangteeravat, Teeradache; Huang, Eunice Y; Nagisetty, Naga Satya V Rao; Urraca, Nora; Lusk, Laina; Finucane, Brenda; Arkilo, Dimitrios; Young, Jennifer; Jeste, Shafali; Thibert, Ronald; Reiter, Lawrence T

2017-10-18

Chromosome 15q11.2-q13.1 duplication syndrome (Dup15q syndrome) is a rare disorder caused by duplications of chromosome 15q11.2-q13.1, resulting in a wide range of developmental disabilities in affected individuals. The Dup15q Alliance is an organization that provides family support and promotes research to improve the quality of life of patients living with Dup15q syndrome. Because of the low prevalence of this condition, the establishment of a single research repository would have been difficult and more time consuming without collaboration across multiple institutions. The goal of this project is to establish a national deidentified database with clinical and survey information on individuals diagnosed with Dup15q syndrome. The development of a multiclinic site repository for clinical and survey data on individuals with Dup15q syndrome was initiated and supported by the Dup15q Alliance. Using collaborative workflows, communication protocols, and stakeholder engagement tools, a comprehensive database of patient-centered information was built. We successfully established a self-report populating, centralized repository for Dup15q syndrome research. This repository also resulted in the development of standardized instruments that can be used for other studies relating to developmental disorders. By standardizing the data collection instruments, it allows us integrate our data with other national databases, such as the National Database for Autism Research. A substantial portion of the data collected from the questionnaires was facilitated through direct engagement of participants and their families. This allowed for a more complete set of information to be collected with a minimal turnaround time. We developed a repository that can efficiently be mined for shared clinical phenotypes observed at multiple clinic sites and used as a springboard for future clinical and basic research studies. ©Oluwaseun Jessica Ajayi, Ebony Jeannae Smith, Teeradache Viangteeravat

Deep brain stimulation may reduce the relative risk of clinically important worsening in early stage Parkinson's disease.

PubMed

Hacker, Mallory L; Tonascia, James; Turchan, Maxim; Currie, Amanda; Heusinkveld, Lauren; Konrad, Peter E; Davis, Thomas L; Neimat, Joseph S; Phibbs, Fenna T; Hedera, Peter; Wang, Lily; Shi, Yaping; Shade, David M; Sternberg, Alice L; Drye, Lea T; Charles, David

2015-10-01

The Vanderbilt pilot trial of deep brain stimulation (DBS) in early Parkinson's disease (PD) enrolled patients on medications six months to four years without motor fluctuations or dyskinesias. We conducted a patient-centered analysis based on clinically important worsening of motor symptoms and complications of medical therapy for all subjects and a subset of subjects with a more focused medication duration. Continuous outcomes were also analyzed for this focused cohort. A post hoc analysis was conducted on all subjects from the pilot and a subset of subjects taking PD medications 1-4 years at enrollment. Clinically important worsening is defined as both a ≥ 3 point increase in UPDRS Part III and a ≥ 1 point increase in Part IV. DBS plus optimal drug therapy (DBS + ODT) subjects experienced a 50-80% reduction in the relative risk of worsening after two years. The DBS + ODT group was improved compared to optimal drug therapy (ODT) at each time point on Total UPDRS and Part III (p = 0.04, p = 0.02, respectively, at 24 months). Total UPDRS, Part IV, and PDQ-39 scores significantly worsened in the ODT group after two years (p < 0.003), with no significant change in the DBS + ODT group. DBS + ODT in early PD may reduce the risk of clinically important worsening. These findings further confirm the need to determine if DBS + ODT is superior to medical therapy for managing symptoms, reducing the complications of medications, and improving quality of life. The FDA has approved the conduct of a large-scale, pivotal clinical trial of DBS in early stage PD. Copyright © 2015 Elsevier Ltd. All rights reserved.

Early aging in Chernobyl clean-up workers: long-term study.

PubMed

Krasnov, V; Kryukov, V; Samedova, E; Emelianova, I; Ryzhova, I

2015-01-01

This paper represents data of long-term open prospective study. 312 male clean-up workers, who participated in elimination of the Chernobyl disaster consequences in 1986-87, were observed and examined in Moscow Research Institute of Psychiatry. The average age of patients was 57,0 ± 6,8 years. All patients were diagnosed with psychoorganic syndrome, caused by combination of different factors, which led to early cerebrovascular pathology, which was confirmed by clinical, neuropsychological, and instrumental examination. Anamnesis and the level of social adaptation were also assayed. Clinical estimation was done with the use of specially developed Clinical Psychopathological Chart. All the symptoms were divided into 4 groups (asthenic, psychovegetative, dysthymic, and cognitive symptom-complexes). No pronounced signs of dementia were observed. The control group included 44 clean-up workers without mental disorders. Predomination of various exogenous factors before and after accident was noted. Therapy included different vasotropic remedies, as well as family therapy, art therapy, and cognitive training. The possibilities of the reverse development of symptoms were statistically proved. The results allow making a conclusion that these disorders could not be explained either by radiation effects or by PTSD but connected with cerebrovascular pathology.

Compilation and Clinical Applicability of an Early Auditory Processing Assessment Battery for Young Children.

ERIC Educational Resources Information Center

Fair, Lisl; Louw, Brenda; Hugo, Rene

2001-01-01

This study compiled a comprehensive early auditory processing skills assessment battery and evaluated the battery to toddlers with (n=8) and without (n=9) early recurrent otitis media. The assessment battery successfully distinguished between normal and deficient early auditory processing development in the subjects. The study also found parents…

Early Recognition of High Risk of Bipolar Disorder and Psychosis: An Overview of the ZInEP “Early Recognition” Study

PubMed Central

Theodoridou, Anastasia; Heekeren, Karsten; Dvorsky, Diane; Metzler, Sibylle; Franscini, Maurizia; Haker, Helene; Kawohl, Wolfram; Rüsch, Nicolas; Walitza, Susanne; Rössler, Wulf

2014-01-01

Early detection of persons with first signs of emerging psychosis is regarded as a promising strategy to reduce the burden of the disease. In recent years, there has been increasing interest in early detection of psychosis and bipolar disorders, with a clear need for sufficient sample sizes in prospective research. The underlying brain network disturbances in individuals at risk or with a prodrome are complex and yet not well known. This paper provides the rationale and design of a prospective longitudinal study focused on at-risk states of psychosis and bipolar disorder. The study is carried out within the context of the Zurich Program for Sustainable Development of Mental Health services (Zürcher Impulsprogramm zur Nachhaltigen Entwicklung der Psychiatrie). Persons at risk for psychosis or bipolar disorder between 13 and 35 years of age are examined by using a multi-level-approach (psychopathology, neuropsychology, genetics, electrophysiology, sociophysiology, magnetic resonance imaging, near-infrared spectroscopy). The included adolescents and young adults have four follow-ups at 6, 12, 24, and 36 months. This approach provides data for a better understanding of the relevant mechanisms involved in the onset of psychosis and bipolar disorder, which can serve as targets for future interventions. But for daily clinical practice a practicable “early recognition” approach is required. The results of this study will be useful to identify the strongest predictors and to delineate a prediction model. PMID:25325050

Comparing three forms of early intervention for youth with borderline personality disorder (the MOBY study): study protocol for a randomised controlled trial.

PubMed

Chanen, Andrew; Jackson, Henry; Cotton, Sue M; Gleeson, John; Davey, Christopher G; Betts, Jennifer; Reid, Sophie; Thompson, Katherine; McCutcheon, Louise

2015-10-21

Borderline personality disorder is a severe mental disorder that usually has its onset in youth, but its diagnosis and treatment are often delayed. Psychosocial 'early intervention' is effective in improving symptoms and behaviours, but no trial has studied adaptive functioning as a primary outcome, even though this remains the major persistent impairment in this patient group. Also, the degree of complexity of treatment and requirements for implementation in mainstream health services are unclear. The primary aim of this trial is to evaluate the effectiveness of three forms of early intervention for borderline personality disorder in terms of adaptive functioning. Each treatment is defined by combining either a specialised or a general service delivery model with either an individual psychotherapy or a control psychotherapy condition. The study is a parallel-group, single-blind, randomised controlled trial, which has randomised permuted blocking, stratified by depression score, sex and age. The treatments are: (1) the specialised Helping Young People Early service model plus up to 16 sessions of individual cognitive analytic therapy; (2) the Helping Young People Early service plus up to 16 sessions of a control psychotherapy condition known as 'befriending'; (3) a general youth mental health care model plus up to 16 sessions of befriending. Participants will comprise 135 help-seeking youth aged 15-25 years with borderline personality disorder. After baseline assessment, staff blind to the study design and treatment group allocation will conduct assessments at 3, 6, 12 and 18 months. At the 12-month primary endpoint, the primary outcome is adaptive functioning (measures of social adjustment and interpersonal problems); secondary outcomes include measures of client satisfaction, borderline personality disorder features, depression and substance use. The results of this trial will help to clarify the comparative effectiveness of a specialised early intervention

Impact of early postoperative enteral nutrition on clinical outcomes in patients with gastric cancer.

PubMed

Li, B; Liu, H Y; Guo, S H; Sun, P; Gong, F M; Jia, B Q

2015-06-29

The impact of early enteral nutrition (EEN) on clinical outcomes of gastric cancer patients was investigated. Three hundred pa-tients undergoing gastric cancer surgery from July 2010 to May 2014 were randomly divided into experimental and control groups (n = 150/group). Experimental group patients received enteral nutrition in water during the early postoperative period. Control group patients received conventional perioperative treatment. Patients' clinical outcomes, post-operative immune function, and nutritional statuses were compared, which revealed that the postoperative fever duration (80.2 ± 6.0 vs 88.1 ± 8.1 h, P < 0.05), anal exhaust time (78.8 ± 9.3 vs 85.3 ± 8.4 h, P < 0.05), and length of hospitalization (7.73 ± 2.13 vs 9.77 ± 1.76 days, P < 0.01) differed significantly. Treatment costs in thousands of dol-lars were 31.24 ± 3.21 for the experimental group and 35.61 ± 2.32 for the control group; this difference was statistically significant (P < 0.01). The incidence of postoperative complications did not significantly differ between the experimental and control groups [14.0% (21/150) vs 17.3% (26/150), P > 0.05]. At postoperative days 3 and 7, the CD3(+), CD4(+), natural killer cell, albumin, and prealbumin levels and CD4(+)/CD8(+) ra-tio were significantly higher in the experimental group than the control group (all P < 0.05). CD8(+) cell counts were significantly lower in the experimental group than the control group (P < 0.05). Postsurgical oral EEN can improve nutritional status and immune function and promote early recovery of intestinal function in patients with gastric cancer.

Final visual acuity results in the early treatment for retinopathy of prematurity study.

PubMed

Good, William V; Hardy, Robert J; Dobson, Velma; Palmer, Earl A; Phelps, Dale L; Tung, Betty; Redford, Maryann

2010-06-01

To compare visual acuity at 6 years of age in eyes that received early treatment for high-risk prethreshold retinopathy of prematurity (ROP) with conventionally managed eyes. Infants with symmetrical, high-risk prethreshold ROP (n = 317) had one eye randomized to earlier treatment at high-risk prethreshold disease and the other eye managed conventionally, treated if ROP progressed to threshold severity. For asymmetric cases (n = 84), the high-risk prethreshold eye was randomized to either early treatment or conventional management. The main outcome measure was ETDRS visual acuity measured at 6 years of age by masked testers. Retinal structure was assessed as a secondary outcome. Analysis of all subjects with high-risk prethreshold ROP showed no statistically significant benefit for early treatment (24.3% vs 28.6% [corrected] unfavorable outcome; P = .15). Analysis of 6-year visual acuity results according to the Type 1 and 2 clinical algorithm showed a benefit for Type 1 eyes (25.1% vs 32.8%; P = .02) treated early but not Type 2 eyes (23.6% vs 19.4%; P = .37). Early-treated eyes showed a significantly better structural outcome compared with conventionally managed eyes (8.9% vs 15.2% unfavorable outcome; P < .001), with no greater risk of ocular complications. Early treatment for Type 1 high-risk prethreshold eyes improved visual acuity outcomes at 6 years of age. Early treatment for Type 2 high-risk prethreshold eyes did not. Application to Clinical Practice Type 1 eyes, not Type 2 eyes, should be treated early. These results are particularly important considering that 52% of Type 2 high-risk prethreshold eyes underwent regression of ROP without requiring treatment. Trial Registration clinicaltrials.gov Identifier: NCT00027222.

Clinical Phenotype Predicts Early Staged Bilateral Deep Brain Stimulation in Parkinson’s Disease

PubMed Central

Sung, Victor W.; Watts, Ray L.; Schrandt, Christian J.; Guthrie, Stephanie; Wang, Deli; Amara, Amy W.; Guthrie, Barton L.; Walker, Harrison C.

2014-01-01

Object While many centers place bilateral DBS systems simultaneously, unilateral STN DBS followed by a staged contralateral procedure has emerged as a treatment option for many patients. However little is known about whether the preoperative phenotype predicts when staged placement of a DBS electrode in the opposite subthalamic nucleus will be required. We aimed to determine whether preoperative clinical phenotype predicts early staged placement of a second subthalamic deep brain stimulation (DBS) electrode in patients who undergo unilateral subthalamic DBS for Parkinson's disease (PD). Methods Eighty-two consecutive patients with advanced PD underwent unilateral subthalamic DBS contralateral to the most affected hemibody and had at least 2 years of follow-up. Multivariate logistic regression determined preoperative characteristics that predicted staged placement of a second electrode in the opposite subthalamic nucleus. Preoperative measurements included aspects of the Unified Parkinson Disease Rating Scale (UPDRS), motor asymmetry index, and body weight. Results At 2 years follow-up, 28 of the 82 patients (34%) had undergone staged placement of a contralateral electrode while the remainder chose to continue with unilateral stimulation. Statistically significant improvements in UPDRS total and part 3 scores were retained at the end of the 2 year follow-up period in both subsets of patients. Multivariate logistic regression showed that the most important predictors for early staged placement of a second subthalamic stimulator were low asymmetry index (odds ratio 13.4; 95% confidence interval 2.8, 64.9), high tremor subscore (OR 7.2; CI 1.5, 35.0), and low body weight (OR 5.5; CI 1.4, 22.3). Conclusions This single center study provides evidence that elements of the preoperative PD phenotype predict whether patients will require early staged bilateral subthalamic DBS. These data may aid in the management of patients with advanced PD who undergo subthalamic DBS. PMID

Fulminant liver failure: clinical and experimental study.

PubMed Central

Slapak, M.

1975-01-01

Clinical experience of some newer methods of hepatic support is described. The results are unpredictable and far from satisfactory. The need for an animal model in which potential therapeutic methods can be studied is emphasized. Such a model based on carefully imposed ischaemic insult to the liver in the absence of portacaval shunting is described. It is suggested that bacterial presence in the bowel together with a depression of the liver reticuloendothelial function plays an important part in the early and rapid mortality of acute liver failure. Temporary auxiliary liver transplantation using an allograft or a closely related primate heterograft seem to be the 2 best available methods of hepatic support for potentially reversible acute liver failure. Images Fig. 8 PMID:812415

Integrating partner professionals. The Early Explorers project: Peers Early Education Partnership and the health visiting service.

PubMed

Barlow, J; Coe, C

2013-01-01

  A range of voluntary sector organizations are involved in the delivery of services to children, particularly within the Early Year's sector and children's centres. Peers Early Education Partnership (PEEP) Early Explorers project is one example of the way in which explicit partnerships are being forged across statutory and voluntary sectors with the aim of improving outcomes for children and families. This paper reports an exploration of stakeholder views and experiences of two Early Explorer clinics located in areas of high deprivation.   Semi-structured interviews were conducted with a purposive sample of stakeholders (n= 25) from children's centres, PEEP, the health visiting service and service users. Data were fully transcribed and analysed using a thematic approach.   The data suggest that the two key groups of stakeholders providing Early Explorer clinics (i.e. health visitors and PEEP practitioners) had quite different objectives in terms of their early goals for the clinic, but that despite these differences good progress was achieved in terms of working together effectively. All stakeholders including service users referred to the presence of PEEP as having improved the quality of the clinic environment, and participating mothers identified a wide range of benefits from the enhanced service. However, somewhat restricted views about the role of practitioners within the clinics were identified by users, and the findings suggest that although the early goals for the clinic had been exceeded, these may have been limited in terms of true 'partnership' working.   Early Explorer clinics appeared to have enhanced the service provided within traditional child health clinics and to have provided practitioners with access to hard-to-reach families and parents with access to services that are consistent with the broader policy aims of improving parent-infant interaction. However, questions remain as to whether the benefit of 'partnership' working was fully

Clinical signs of early osteoarthritis: reproducibility and relation to x ray changes in 541 women in the general population.

PubMed Central

Hart, D J; Spector, T D; Brown, P; Wilson, P; Doyle, D V; Silman, A J

1991-01-01

The definition and classification of early clinically apparent osteoarthritis both in clinical situations and in epidemiological surveys remains a problem. Few data exist on the between-observer reproducibility of simple clinical methods of detecting hand and knee osteoarthritis in the population and their sensitivity and specificity as compared with radiography. Two observers first studied the reproducibility of a number of clinical signs in 41 middle aged women. Good rates of agreement were found for most of the clinical signs tested (kappa = 0.54-1.0). The more reproducible signs were then tested on a population of 541 women, aged 45-65, drawn from general practice, screening centres, and patients previously attending hospital for non-rheumatic problems. The major clinical signs used had a high specificity (87-99%) and lower sensitivity (20-49%) when compared with radiographs graded on the Kellgren and Lawrence scale (2+ = positive). When analysis was restricted to symptomatic radiographic osteoarthritis, levels of sensitivity were increased and specificity was lowered. These data show that certain physical signs of osteoarthritis are reproducible and may be used to identify clinical disease. They are not a substitute for radiographs, however, if radiographic change is regarded as the 'gold standard' of diagnosis. As the clinical signs tested seemed specific for osteoarthritis they may be of value in screening populations for clinical disease. PMID:1877852

The long-term consequences of early childhood trauma: a case study and discussion.

PubMed

Kaplow, Julie B; Saxe, Glenn N; Putnam, Frank W; Pynoos, Robert S; Lieberman, Alicia F

2006-01-01

There is a great need to better understand the impact of traumatic events very early in life on the course of children's future development. This report focuses on the intriguing case of a girl who witnessed the murder of her mother by her father at the age of 19 months and seemed to have no recollection of this incident until the age of 11, when she began to exhibit severe symptoms of posttraumatic stress disorder (PTSD) in response to a traumatic reminder. The case presentation serves as the basis for a discussion regarding pertinent issues involved in early childhood trauma. This case and accompanying discussion were originally presented at the 19th Annual Meeting of the International Society for Traumatic Stress Studies and were transcribed and revised for use in this article. Specific topics include early childhood memory and trauma, learning and the appraisal of danger, and PTSD and traumatic grief in early childhood. Clinical and public health implications are also discussed. This case illustrates the dramatic impact that "preverbal" traumatic memories can have on children's later functioning and speaks to the importance of assisting very young children in the immediate aftermath of traumatic events.

Early experimental and clinical experience with a focal implant for lower extremity post-angioplasty dissection.

PubMed

Schneider, Peter A; Giasolli, Robert; Ebner, Adrian; Virmani, Renu; Granada, Juan F

2015-02-01

This study provides preliminary data on the safety and feasibility of the use of a novel focal implant for managing post-percutaneous transluminal balloon angioplasty (post-PTA) dissection. Post-PTA dissection of the lower extremity arteries is managed with stent placement. This provides an acceptable post-intervention result but has long-term disadvantages, such as in-stent restenosis. Focal treatment of post-PTA dissection and avoidance of stents are the objectives of the Tack-It (Intact Vascular, Inc., Wayne, Pennsylvania) device. A preclinical study and first-in-human data are presented. Seven swine underwent superficial femoral artery device placement, with a self-expanding nitinol stent on 1 side and a series of 4 Tack-It devices on the other side. Specimens were harvested at 28 days. The clinical study included 15 limbs that underwent revascularization for critical limb ischemia (n = 9) or claudication (n = 6). Twenty-five lesions were treated in the superficial femoral (n = 8), popliteal (n = 7), and tibial (n = 10) arteries. The preclinical study demonstrated a reduction in stenosis with the Tack-It (16.8 ± 2.6%) compared with stents (46.4 ± 9.8%). Neointimal thickness and injury score decreased with the Tack-It. Clinically, Tack-It placement resulted in acute technical success with resolution of the post-PTA dissection in 100% of lesions. There were no device-related complications or major amputations. Eighteen of the 25 lesions were available for angiographic follow-up at 1-year, and patency was 83.3%. Preclinical data suggest that the Tack-It device causes minimal vessel injury. Clinical use of the Tack-It to manage post-PTA dissection was safe and feasible in this early study and resulted in apposition of dissection flaps without stent placement. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Early identification and high-risk strategies for bipolar disorder.

PubMed

Correll, Christoph U; Penzner, Julie B; Lencz, Todd; Auther, Andrea; Smith, Christopher W; Malhotra, Anil K; Kane, John M; Cornblatt, Barbara A

2007-06-01

To describe and compare the relative merits of different identification strategies for individuals at risk for bipolar disorder (BPD). Selective review of data that support early identification in BPD, with a particular focus on emerging clinical high-risk strategies. Early detection of individuals at risk for BPD can utilize genetic, endophenotypic and clinical methods. Most published work focuses on genetic familial endophenotypic risk markers for BPD. However, despite encouraging results, problems with specificity and sensitivity limit the application of these data to early prevention programs. In addition, offspring studies of BPD patients systematically exclude the majority of subjects without a first-degree bipolar relative. On the other hand, emerging work in the clinical-high-risk arena has already produced encouraging results. Although still preliminary, the identification of individuals in subsyndromal or attenuated symptom 'prodromal' stages of BPD seems to be an under-researched area that holds considerable promise deserving increased attention. Required next steps include the development of rating tools for attenuated and subsyndromal manic and depressive symptoms and of prodromal criteria that will allow prodromal symptomatology to be systematically studied in patients with recent-onset bipolar, as well as in prospective population-based phenomenology trials and attenuated symptom-based high-risk studies. Given the current limitations of each early identification method, combining clinical, endophenotypic and genetic strategies will increase prediction accuracy. Since reliable biological markers for BPD have not been established and since most patients with BPD lack a first-degree relative with this disorder, clinical high-risk approaches have great potential to inform early identification and intervention programs.

Treatment of Early-stage Extracranial Arteriovenous Malformations with Intralesional Interstitial Bleomycin Injection: A Pilot Study.

PubMed

Jin, Yunbo; Zou, Yun; Hua, Chen; Chen, Hui; Yang, Xi; Ma, Gang; Chang, Lei; Qiu, Yajing; Lyu, Dongze; Wang, Tianyou; Chang, Shih-Jen; Qiao, Congzhen; Luo, Chunfen; Tremp, Mathias; Lin, Xiaoxi

2018-04-01

Purpose To assess the efficacy and safety of intralesional interstitial bleomycin injection in the treatment of early-stage (Schobinger stage I or II) extracranial arteriovenous malformations (AVMs). Materials and Methods This prospective study involved 34 patients with early-stage AVMs, as defined by the Schobinger staging system. The patients received intralesional interstitial bleomycin injected at a maximum dose of 15 000 IU or 1000 IU per kilogram of body weight for children who weighed less than 15 kg per procedure for a total of 6 months (once every month). Therapeutic outcome was evaluated by the degree of devascularization at angiography and the clinical outcome 3 months after the last treatment. Further follow-up was evaluated based on further clinical outcome. Adverse events were recorded according to the Society of Interventional Radiology classification. Results Of the 34 patients with early-stage AVM, 32 (mean age, 20.5 years; 24 female [75%]) completed the study. The results showed that 27 (84.4%, 95% confidence interval [CI]: 71.1, 97.7) patients were responsive to bleomycin injection, including nine (28.1%) with a complete response. Four (12.5%) patients showed no response, and one (3.1%) patient experienced worsening 3 months after the last treatment. During further follow-up (mean follow-up time, 20.7 months; range, 5-28 months), the outcome remained stable in 31 (96.9%) of the 32 patients. A major complication, anaphylactic shock, was observed in one (3.1%, 95% CI: 0, 9.5) patient. Common minor complications included hyperpigmentation, nausea, pruritus, and bullae. Conclusion Intralesional interstitial bleomycin injection is a feasible approach for early-stage AVMs and yields safe and effective outcomes. © RSNA, 2017.

Clinical Manifestation and Risk Factors of Tuberculosis Infection in Malaysia: Case Study of a Community Clinic

PubMed Central

Shanmuganathan, Rohan; Shanmuganathan, Indra Devi

2015-01-01

Introduction: The main aim of this study was to describe the clinical manifestation of tuberculosis infection cases in Malaysia and to determine the individual risk factors for their occurrence. Methodology: The study adopted a quantitative research approach with use of descriptive statistical approach. The study setting was a community clinic which treats walk in patients who are mainly living and working in the surrounding areas. The study was conducted for a period of one year. All tuberculosis patients who sought treatment in the clinic during the time were included in this study. The total number of cases was 40. Data was collected from the medical records of the tuberculosis patients. The risk factors selected for investigation were demographic characteristics of age and sex, personal habits such as smoking, drug use and alcohol and presence of diseases such as human immunodeficiency virus positive (HIV+), diabetes mellitus, cancer, cyanotic heart disease, renal failure and steroid use. Results: Patients in the age group ranging from 41 to 50 years had the highest incidence of the infection. Smoking appears to be the most important risk factor for contracting followed by drug abuse, HIV+ infection and diabetes mellitus. Conclusions: People with diseases such as diabetes mellitus and HIV that are high risk factors for TB should be screened for TB so that early detection and intervention is possible. Educational programs should be carried out to create awareness among the at risk groups. PMID:25946947

Clinical manifestation and risk factors of tuberculosis infection in Malaysia: case study of a community clinic.

PubMed

Shanmuganathan, Rohan; Subramaniam, Indra Devi

2015-01-01

The main aim of this study was to describe the clinical manifestation of tuberculosis infection cases in Malaysia and to determine the individual risk factors for their occurrence. The study adopted a quantitative research approach with use of descriptive statistical approach. The study setting was a community clinic which treats walk in patients who are mainly living and working in the surrounding areas. The study was conducted for a period of one year. All tuberculosis patients who sought treatment in the clinic during the time were included in this study. The total number of cases was 40. Data was collected from the medical records of the tuberculosis patients. The risk factors selected for investigation were demographic characteristics of age and sex, personal habits such as smoking, drug use and alcohol and presence of diseases such as human immunodeficiency virus positive (HIV+), diabetes mellitus, cancer, cyanotic heart disease, renal failure and steroid use. Patients in the age group ranging from 41 to 50 years had the highest incidence of the infection. Smoking appears to be the most important risk factor for contracting followed by drug abuse, HIV+ infection and diabetes mellitus. People with diseases such as diabetes mellitus and HIV that are high risk factors for TB should be screened for TB so that early detection and intervention is possible. Educational programs should be carried out to create awareness among the at risk groups.

78 FR 69690 - Draft Guidance for Industry: Considerations for the Design of Early-Phase Clinical Trials of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-20

... and Gene Therapy Products; Extension of Comment Period AGENCY: Food and Drug Administration, HHS...: Considerations for the Design of Early-Phase Clinical Trials of Cellular and Gene Therapy Products'' that... sponsors of Investigational New Drug Applications for cellular therapy (CT) and gene therapy (GT) products...

Water T2 as an early, global and practical biomarker for metabolic syndrome: an observational cross-sectional study.

PubMed

Robinson, Michelle D; Mishra, Ina; Deodhar, Sneha; Patel, Vipulkumar; Gordon, Katrina V; Vintimilla, Raul; Brown, Kim; Johnson, Leigh; O'Bryant, Sid; Cistola, David P

2017-12-19

Metabolic syndrome (MetS) is a highly prevalent condition that identifies individuals at risk for type 2 diabetes mellitus and atherosclerotic cardiovascular disease. Prevention of these diseases relies on early detection and intervention in order to preserve pancreatic β-cells and arterial wall integrity. Yet, the clinical criteria for MetS are insensitive to the early-stage insulin resistance, inflammation, cholesterol and clotting factor abnormalities that characterize the progression toward type 2 diabetes and atherosclerosis. Here we report the discovery and initial characterization of an atypical new biomarker that detects these early conditions with just one measurement. Water T 2 , measured in a few minutes using benchtop nuclear magnetic resonance relaxometry, is exquisitely sensitive to metabolic shifts in the blood proteome. In an observational cross-sectional study of 72 non-diabetic human subjects, the association of plasma and serum water T 2 values with over 130 blood biomarkers was analyzed using bivariate, multivariate and logistic regression. Plasma and serum water T 2 exhibited strong bivariate correlations with markers of insulin, lipids, inflammation, coagulation and electrolyte balance. After correcting for confounders, low water T 2 values were independently and additively associated with fasting hyperinsulinemia, dyslipidemia and subclinical inflammation. Plasma water T 2 exhibited 100% sensitivity and 87% specificity for detecting early insulin resistance in normoglycemic subjects, as defined by the McAuley Index. Sixteen normoglycemic subjects with early metabolic abnormalities (22% of the study population) were identified by low water T 2 values. Thirteen of the 16 did not meet the harmonized clinical criteria for metabolic syndrome and would have been missed by conventional screening for diabetes risk. Low water T 2 values were associated with increases in the mean concentrations of 6 of the 16 most abundant acute phase proteins and

Early, Accurate Diagnosis and Early Intervention in Cerebral Palsy: Advances in Diagnosis and Treatment.

PubMed

Novak, Iona; Morgan, Cathy; Adde, Lars; Blackman, James; Boyd, Roslyn N; Brunstrom-Hernandez, Janice; Cioni, Giovanni; Damiano, Diane; Darrah, Johanna; Eliasson, Ann-Christin; de Vries, Linda S; Einspieler, Christa; Fahey, Michael; Fehlings, Darcy; Ferriero, Donna M; Fetters, Linda; Fiori, Simona; Forssberg, Hans; Gordon, Andrew M; Greaves, Susan; Guzzetta, Andrea; Hadders-Algra, Mijna; Harbourne, Regina; Kakooza-Mwesige, Angelina; Karlsson, Petra; Krumlinde-Sundholm, Lena; Latal, Beatrice; Loughran-Fowlds, Alison; Maitre, Nathalie; McIntyre, Sarah; Noritz, Garey; Pennington, Lindsay; Romeo, Domenico M; Shepherd, Roberta; Spittle, Alicia J; Thornton, Marelle; Valentine, Jane; Walker, Karen; White, Robert; Badawi, Nadia

2017-09-01

Cerebral palsy describes the most common physical disability in childhood and occurs in 1 in 500 live births. Historically, the diagnosis has been made between age 12 and 24 months but now can be made before 6 months' corrected age. To systematically review best available evidence for early, accurate diagnosis of cerebral palsy and to summarize best available evidence about cerebral palsy-specific early intervention that should follow early diagnosis to optimize neuroplasticity and function. This study systematically searched the literature about early diagnosis of cerebral palsy in MEDLINE (1956-2016), EMBASE (1980-2016), CINAHL (1983-2016), and the Cochrane Library (1988-2016) and by hand searching. Search terms included cerebral palsy, diagnosis, detection, prediction, identification, predictive validity, accuracy, sensitivity, and specificity. The study included systematic reviews with or without meta-analyses, criteria of diagnostic accuracy, and evidence-based clinical guidelines. Findings are reported according to the PRISMA statement, and recommendations are reported according to the Appraisal of Guidelines, Research and Evaluation (AGREE) II instrument. Six systematic reviews and 2 evidence-based clinical guidelines met inclusion criteria. All included articles had high methodological Quality Assessment of Diagnostic Accuracy Studies (QUADAS) ratings. In infants, clinical signs and symptoms of cerebral palsy emerge and evolve before age 2 years; therefore, a combination of standardized tools should be used to predict risk in conjunction with clinical history. Before 5 months' corrected age, the most predictive tools for detecting risk are term-age magnetic resonance imaging (86%-89% sensitivity), the Prechtl Qualitative Assessment of General Movements (98% sensitivity), and the Hammersmith Infant Neurological Examination (90% sensitivity). After 5 months' corrected age, the most predictive tools for detecting risk are magnetic resonance imaging (86

Logistical challenges and design considerations for studies using acute anterior cruciate ligament injury as a potential model for early posttraumatic osteoarthritis.

PubMed

Lattermann, Christian; Jacobs, Cale A; Bunnell, Mary Proffitt; Jochimsen, Kate N; Abt, John P; Reinke, Emily K; Gammon, Lee G; Huebner, Janet L; Kraus, Virginia B; Spindler, Kurt P

2017-03-01

Anterior cruciate ligament (ACL) injuries are common and lead to posttraumatic osteoarthritis (PTOA) in a high percentage of patients. Research has been ineffective in identifying successful treatment options for people suffering from symptomatic PTOA resulting in a shift of focus toward the young, ACL injured patients at risk of developing PTOA. Randomized clinical trials examining the very early phase after ACL injury are ideal to study this population; however, these trials face significant challenges regarding recruitment as well as reproducibility of patient-reported outcomes (PROs) and inflammatory and/or chondrodegenerative biomarkers associated with early PTOA. The aim of this work was to develop an approach to allow for early recruitment into an RCT for early treatment following ACL injury and to analyze the variability of commonly used measures and biomarkers at various time points after injury. This paper reports the study design and data related to the first month of treatment for the placebo group of an ongoing 2-year clinical trial to evaluate the effect of an early intra-articular intervention after ACL injury. The results of this study suggest that acute ACL injury results in early changes of both inflammatory and chondrodegenerative biomarkers. These results also provide vital information for researchers to consider when developing future protocols, both related to the logistics of early patient enrollment as well as the appropriate timing of biomarker and patient-reported outcome collection. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:641-650, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Clinical Prediction and Diagnosis of Neurosyphilis in HIV-Infected Patients with Early Syphilis

PubMed Central

Langevin, Stéphanie; Gagnon, Simon; Serhir, Bouchra; Deligne, Benoît; Tremblay, Cécile; Tsang, Raymond S. W.; Fortin, Claude; Coutlée, François; Roger, Michel

2013-01-01

The diagnosis of neurosyphilis (NS) is a challenge, especially in HIV-infected patients, and the criteria for deciding when to perform a lumbar puncture (LP) in HIV-infected patients with syphilis are controversial. We retrospectively reviewed demographic, clinical, and laboratory data from 122 cases of HIV-infected patients with documented early syphilis who underwent an LP to rule out NS, and we evaluated 3 laboratory-developed validated real-time PCR assays, the Treponema pallidum particle agglutination (TPPA) assay, the fluorescent treponemal antibody absorption (FTA-ABS) assay, and the line immunoassay INNO-LIA Syphilis, for the diagnosis of NS from cerebrospinal fluid (CSF) samples of these patients. NS was defined by a reactive CSF-VDRL test result and/or a CSF white blood cell (WBC) count of >20 cells/μl. Thirty of the 122 patients (24.6%) had early NS. Headache, visual symptoms, a CD4 cell count of <500 cells/μl, and viremia, as defined by an HIV-1 RNA count of ≥50 copies/ml, were associated with NS in multivariate analysis (P = <0.001 for each factor). Blood serum rapid plasma reagin (RPR) titers were not associated with early NS (P = 0.575). For the diagnosis of NS, the PCR, FTA-ABS, TPPA, and INNO-LIA assays had sensitivities of 58%, 100%, 68%, and 100%, specificities of 67%, 12%, 49%, and 13%, and negative predictive values of 85%, 100%, 84%, and 100%, respectively. Visual disturbances, headache, uncontrolled HIV-1 viremia, and a CD4 cell count of <500 cells/μl were predictors of NS in HIV-infected patients with early syphilis, while blood serum RPR titers were not; therefore, RPR titers should not be used as the sole criterion for deciding whether to perform an LP in early syphilis. When applied to CSF samples, the INNO-LIA Syphilis assay easily helped rule out NS. PMID:24088852

Clinical prediction and diagnosis of neurosyphilis in HIV-infected patients with early Syphilis.

PubMed

Dumaresq, Jeannot; Langevin, Stéphanie; Gagnon, Simon; Serhir, Bouchra; Deligne, Benoît; Tremblay, Cécile; Tsang, Raymond S W; Fortin, Claude; Coutlée, François; Roger, Michel

2013-12-01

The diagnosis of neurosyphilis (NS) is a challenge, especially in HIV-infected patients, and the criteria for deciding when to perform a lumbar puncture (LP) in HIV-infected patients with syphilis are controversial. We retrospectively reviewed demographic, clinical, and laboratory data from 122 cases of HIV-infected patients with documented early syphilis who underwent an LP to rule out NS, and we evaluated 3 laboratory-developed validated real-time PCR assays, the Treponema pallidum particle agglutination (TPPA) assay, the fluorescent treponemal antibody absorption (FTA-ABS) assay, and the line immunoassay INNO-LIA Syphilis, for the diagnosis of NS from cerebrospinal fluid (CSF) samples of these patients. NS was defined by a reactive CSF-VDRL test result and/or a CSF white blood cell (WBC) count of >20 cells/μl. Thirty of the 122 patients (24.6%) had early NS. Headache, visual symptoms, a CD4 cell count of <500 cells/μl, and viremia, as defined by an HIV-1 RNA count of ≥50 copies/ml, were associated with NS in multivariate analysis (P = <0.001 for each factor). Blood serum rapid plasma reagin (RPR) titers were not associated with early NS (P = 0.575). For the diagnosis of NS, the PCR, FTA-ABS, TPPA, and INNO-LIA assays had sensitivities of 58%, 100%, 68%, and 100%, specificities of 67%, 12%, 49%, and 13%, and negative predictive values of 85%, 100%, 84%, and 100%, respectively. Visual disturbances, headache, uncontrolled HIV-1 viremia, and a CD4 cell count of <500 cells/μl were predictors of NS in HIV-infected patients with early syphilis, while blood serum RPR titers were not; therefore, RPR titers should not be used as the sole criterion for deciding whether to perform an LP in early syphilis. When applied to CSF samples, the INNO-LIA Syphilis assay easily helped rule out NS.

Postnatal Psychosocial Assessment and Clinical Decision-Making, a Descriptive Study.

PubMed

Sims, Deborah; Fowler, Cathrine

2018-05-18

The aim of this study is to describe experienced child and family health nurses' clinical decision-making during a postnatal psychosocial assessment. Maternal emotional wellbeing in the postnatal year optimises parenting and promotes infant development. Psychosocial assessment potentially enables early intervention and reduces the risk of a mental disorder occurring during this time of change. Assessment accuracy, and the interventions used are determined by the standard of nursing decision-making. A qualitative methodology was employed to explore decision-making behaviour when conducting a postnatal psychosocial assessment. This study was conducted in an Australian early parenting organisation. Twelve experienced child and family health nurses were interviewed. A detailed description of a postnatal psychosocial assessment process was obtained using a critical incident technique. Template analysis was used to determine the information domains the nurses accessed, and content analysis was used to determine the nurses' thinking strategies, to make clinical decisions from this assessment. The nurses described 24 domains of information and used 17 thinking strategies, in a variety of combinations. The four information domains most commonly used were parenting, assessment tools, women-determined issues and sleep. The seven thinking strategies most commonly used were searching for information, forming relationships between the information, recognising a pattern, drawing a conclusion, setting priorities, providing explanations for the information and judging the value of the information. The variety and complexity of the clinical decision-making involved in postnatal psychosocial assessment confirms that the nurses use information appropriately and within their scope of nursing practice. The standard of clinical decision-making determines the results of the assessment and the optimal access to care. Knowledge of the information domains and the decision-making strategies

The Relationship between Early Language, Cognitive and Social Development through a Longitudinal Study of Autistic Children.

ERIC Educational Resources Information Center

Ogura, Tamiko

The development of and relationship between early language, symbolic play, sensorimotor skills, and social development were examined in a longitudinal study conducted in Japan with two young autistic males who were observed from the approximate ages of 2 to 4 years in clinic, day care, and home settings. One child acquired speech; the other did…

[Early diagnosis of autism: Phenotype-endophenotype].

PubMed

Kotsopoulos, S

2015-01-01

Autism Spectrum Disorders have for some time been the focus of intense interest for clinicians and researchers because of the high prevalence of the disorders among children in the community (approximately 1%), their severity and pervasiveness. Particular attention has been paid to the early diagnosis of the disorder and to the intensive therapeutic intervention. Currently the best prognosis for autism lays in the early diagnosis and intervention. Postponing the diagnosis and the intervention beyond infancy is considered loss of precious time. The diagnosis of autism, which begins early in life, was until recently considered that could be reliability made at the age of 3 years. Recent follow up studies however on children at risk for autism (children who had an older sibling with autism) have shown that the clinical signs of autism emerge at the end of the first year and become distinct by the end of the second year when the diagnosis can reliably be made. From a clinical perspective it is noted that the early clinical signs of risk for autism are related to social communication (e.g. limited or absent response when calling his/her name and to joint attention), stereotype behaviours and body movements or unusual handling of objects (e.g. intensive observation of objects and stereotype movements of hands and tapping or spinning), incongruent regulation of emotions (reduced positive and increased negative emotion). There is also delay in developmental characteristics such as the language (both receptive and expressive) and motor (particularly in postural control - characteristic is the drop of the head backwards when the infant is held in horizontal position). Studies on various aspects of the endophenotype of certain clinical signs among infants at risk for Autism Spectrum Disorders, such as avoidance of eye contact, delay in verbal communication and increase of the head circumference, may provide useful information and may assist the clinician on follow up in the

An Early Model for Value and Sustainability in Health Information Exchanges: Qualitative Study

PubMed Central

2018-01-01

Background The primary value relative to health information exchange has been seen in terms of cost savings relative to laboratory and radiology testing, emergency department expenditures, and admissions. However, models are needed to statistically quantify value and sustainability and better understand the dependent and mediating factors that contribute to value and sustainability. Objective The purpose of this study was to provide a basis for early model development for health information exchange value and sustainability. Methods A qualitative study was conducted with 21 interviews of eHealth Exchange participants across 10 organizations. Using a grounded theory approach and 3.0 as a relative frequency threshold, 5 main categories and 16 subcategories emerged. Results This study identifies 3 core current perceived value factors and 5 potential perceived value factors—how interviewees predict health information exchanges may evolve as there are more participants. These value factors were used as the foundation for early model development for sustainability of health information exchange. Conclusions Using the value factors from the interviews, the study provides the basis for early model development for health information exchange value and sustainability. This basis includes factors from the research: fostering consumer engagement; establishing a provider directory; quantifying use, cost, and clinical outcomes; ensuring data integrity through patient matching; and increasing awareness, usefulness, interoperability, and sustainability of eHealth Exchange. PMID:29712623

An Early Model for Value and Sustainability in Health Information Exchanges: Qualitative Study.

PubMed

Feldman, Sue S

2018-04-30

The primary value relative to health information exchange has been seen in terms of cost savings relative to laboratory and radiology testing, emergency department expenditures, and admissions. However, models are needed to statistically quantify value and sustainability and better understand the dependent and mediating factors that contribute to value and sustainability. The purpose of this study was to provide a basis for early model development for health information exchange value and sustainability. A qualitative study was conducted with 21 interviews of eHealth Exchange participants across 10 organizations. Using a grounded theory approach and 3.0 as a relative frequency threshold, 5 main categories and 16 subcategories emerged. This study identifies 3 core current perceived value factors and 5 potential perceived value factors-how interviewees predict health information exchanges may evolve as there are more participants. These value factors were used as the foundation for early model development for sustainability of health information exchange. Using the value factors from the interviews, the study provides the basis for early model development for health information exchange value and sustainability. This basis includes factors from the research: fostering consumer engagement; establishing a provider directory; quantifying use, cost, and clinical outcomes; ensuring data integrity through patient matching; and increasing awareness, usefulness, interoperability, and sustainability of eHealth Exchange. ©Sue S Feldman. Originally published in JMIR Medical Informatics (http://medinform.jmir.org), 30.04.2018.

Recognizing the clinical manifestations of acromegaly: case studies.

PubMed

Iuliano, Sherry L; Laws, Edward R

2014-03-01

To present case studies of a 36-year-old woman and a 73-year-old man who presented with the syndrome of acromegaly, and to provide primary care nurse practitioners (NPs) with the understanding of the clinical and laboratory features needed for early recognition and treatment of this fascinating disease. A comprehensive review of published literature on acromegaly is presented. The findings discussed include the history, physical examination, and diagnostic studies of two patients presenting in different ways. They both saw multiple healthcare providers, and had symptoms and signs eventually leading to the diagnosis of acromegaly. Acromegaly is the result of excessive amounts of growth hormone (GH) and insulin-like growth factor type 1 (IGF-1), almost always caused by a benign adenoma of the pituitary gland. This leads to coarse facial features, soft tissue swelling (including the tongue), enlargement of the hands and feet, respiratory problems, hypertension, diabetes mellitus, carpal tunnel syndrome, and osteoarthritis. Early recognition and appropriate referral can reverse some of the signs and symptoms over time, and lead to decreased mortality and a markedly improved quality of life. These cases exemplify the challenges faced by NPs and other healthcare providers in diagnosing patients with acromegaly. ©2013 The Author(s) ©2013 American Association of Nurse Practitioners.

Myoxinol (Hydrolyzed Hibiscus esculentus Extract) in the Cure of Chronic Anal Fissure: Early Clinical and Functional Outcomes

PubMed Central

Renzi, Adolfo; Di Sarno, Giandomenico; D'Aniello, Francesco; Ziccardi, Stefania; Paladino, Fiorella

2015-01-01

Objective. This study was designed to evaluate the early results of the topical application of Hydrolyzed Hibiscus esculentus Extract 3% ointment (Myoxinol 3%), a novel local product with Botox-like activity, in the conservative treatment of chronic anal fissure (CAF). Methods. Among all patients with CAF observed during the study period, 31 subjects met the inclusion criteria and underwent medical therapy with Myoxinol 3% ointment every 12 hours for 6 weeks. Two patients were lost to follow-up. Clinical and manometric follow-up was carried out eight weeks after treatment. Results. At follow-up the success rate was 72.4% (21/29); median VAS score and mean anal resting pressure were significantly lower if compared with respective baseline data. The only one adverse effect of the topical application of Myoxinol 3% ointment was perianal itch, which was reported by 3,4% (1/29) of the patients available for the analysis. However, in this case this symptom did not cause interruption of the treatment. Conclusions. The topical application of Myoxinol 3% ointment in the cure of CAF shows encouraging early results. Further researches with a larger series and a longer follow-up are needed to confirm these data. PMID:25861259

Clinical evaluation of C-reactive protein and procalcitonin for the early detection of postoperative complications after laparoscopic sleeve gastrectomy.

PubMed

Frask, Agata; Orłowski, Michał; Dowgiałło-Wnukiewicz, Natalia; Lech, Paweł; Gajewski, Krzysztof; Michalik, Maciej

2017-06-01

Among the most common early complications after bariatric surgery are anastomosis leak and bleeding. In order to react quickly and perform accurate treatment before the clinical signs appear, early predictors should be found. In the study C-reactive protein (CRP) and procalcitonin (PCT) levels were investigated. Characterized by a relatively short half-life, they can predict surgical complications. To develop and implement certain standards for early detection of complications. The study involved 319 adults who underwent laparoscopic sleeve gastrectomy (LSG) as a surgical intervention for morbid obesity at the Department of General Surgery of Ceynowa Hospital in Wejherowo. Every patient had CRP and PCT levels measured before the surgery and on the 1 st and 2 nd postoperative day (POD). Early postoperative complications occurred in 19 (5.96%) patients. Septic and non-septic complications occurred in 3 and 16 patients respectively. Among the patients with septic postoperative complications CRP level increased significantly on the 2 nd POD compared to the remainder (p = 0.0221). Among the patients with non-septic postoperative complications CRP level increased significantly on the 1 st and 2 nd POD compared to the remainder. Among the patients with septic and non-septic postoperative complications PCT level increased significantly on the 2 nd POD compared to the remainder. The CRP and PCT level are supposed to be relevant diagnostic markers to predict non-septic and septic complications after LSG.

Clinical evaluation of C-reactive protein and procalcitonin for the early detection of postoperative complications after laparoscopic sleeve gastrectomy

PubMed Central

Frask, Agata; Orłowski, Michał; Lech, Paweł; Gajewski, Krzysztof; Michalik, Maciej

2017-01-01

Introduction Among the most common early complications after bariatric surgery are anastomosis leak and bleeding. In order to react quickly and perform accurate treatment before the clinical signs appear, early predictors should be found. In the study C-reactive protein (CRP) and procalcitonin (PCT) levels were investigated. Characterized by a relatively short half-life, they can predict surgical complications. Aim To develop and implement certain standards for early detection of complications. Material and methods The study involved 319 adults who underwent laparoscopic sleeve gastrectomy (LSG) as a surgical intervention for morbid obesity at the Department of General Surgery of Ceynowa Hospital in Wejherowo. Every patient had CRP and PCT levels measured before the surgery and on the 1st and 2nd postoperative day (POD). Results Early postoperative complications occurred in 19 (5.96%) patients. Septic and non-septic complications occurred in 3 and 16 patients respectively. Among the patients with septic postoperative complications CRP level increased significantly on the 2nd POD compared to the remainder (p = 0.0221). Among the patients with non-septic postoperative complications CRP level increased significantly on the 1st and 2nd POD compared to the remainder. Among the patients with septic and non-septic postoperative complications PCT level increased significantly on the 2nd POD compared to the remainder. Conclusions The CRP and PCT level are supposed to be relevant diagnostic markers to predict non-septic and septic complications after LSG. PMID:28694902

Nationwide epidemiological survey of early chronic pancreatitis in Japan.

PubMed

Masamune, Atsushi; Kikuta, Kazuhiro; Nabeshima, Tatsuhide; Nakano, Eriko; Hirota, Morihisa; Kanno, Atsushi; Kume, Kiyoshi; Hamada, Shin; Ito, Tetsuhide; Fujita, Motokazu; Irisawa, Atsushi; Nakashima, Masanori; Hanada, Keiji; Eguchi, Takaaki; Kato, Ryusuke; Inatomi, Osamu; Shirane, Akio; Takeyama, Yoshifumi; Tsuji, Ichiro; Shimosegawa, Tooru

2017-08-01

The world's first diagnostic criteria for early CP were proposed in 2009 in Japan. This study aimed to clarify the clinico-epidemiological features of early CP in Japan. Patients with early CP who were diagnosed according to the diagnostic criteria for early CP and had visited the selected hospitals in 2011 were surveyed. The study consisted of two-stage surveys: the number of patients with early CP was estimated by the first questionnaire and their clinical features were assessed by the second questionnaire. The estimated number of early CP patients was 5410 (95% confidence interval 3675-6945), with an overall prevalence of 4.2 per 100,000 persons. The number of patients who were newly diagnosed with early CP was estimated to be 1330 (95% confidence interval 1058-1602), with an annual incidence of 1.0 per 100,000 persons. Detailed clinical information was obtained in 151 patients in the second survey. The male-to-female sex ratio was 1.32:1. The mean age was 60.4 and the mean age at disease onset was 55.4. Idiopathic (47.7%) and alcoholic (45.0%) were the two most common etiologies. Proportions of female and idiopathic cases were higher in early CP than in definite CP. Hyperechoic foci without shadowing and stranding were the most common findings on endoscopic ultrasonography. The clinical profiles of early CP patients who showed lobularity with honeycombing on endoscopic ultrasonography or previous episodes of acute pancreatitis were similar to those of definite CP patients. We clarified the current status of early CP in Japan.

[A Critical Condition of Clinical Studies in Japan -- A Battle of Clinical Study Groups].

PubMed

Furukawa, Hiroshi

2016-04-01

The post-marketing clinical study groups have been losing their activity due to stop of financial support. As the result, clinical study groups cannot achieve any EBM for treatment guidelines. Financial supports should be restarted immediately not to extinguish the post-marketing clinical studies and study groups.

Challenges in early clinical development of adjuvanted vaccines.

PubMed

Della Cioppa, Giovanni; Jonsdottir, Ingileif; Lewis, David

2015-06-08

A three-step approach to the early development of adjuvanted vaccine candidates is proposed, the goal of which is to allow ample space for exploratory and hypothesis-generating human experiments and to select dose(s) and dosing schedule(s) to bring into full development. Although the proposed approach is more extensive than the traditional early development program, the authors suggest that by addressing key questions upfront the overall time, size and cost of development will be reduced and the probability of public health advancement enhanced. The immunogenicity end-points chosen for early development should be critically selected: an established immunological parameter with a well characterized assay should be selected as primary end-point for dose and schedule finding; exploratory information-rich end-points should be limited in number and based on pre-defined hypothesis generating plans, including system biology and pathway analyses. Building a pharmacodynamic profile is an important aspect of early development: to this end, multiple early (within 24h) and late (up to one year) sampling is necessary, which can be accomplished by sampling subgroups of subjects at different time points. In most cases the final target population, even if vulnerable, should be considered for inclusion in early development. In order to obtain the multiple formulations necessary for the dose and schedule finding, "bed-side mixing" of various components of the vaccine is often necessary: this is a complex and underestimated area that deserves serious research and logistical support. Copyright © 2015 Elsevier Ltd. All rights reserved.

Influence of Clinical and Sociodemographic Characteristics on Early Intervention Enrollment after NICU Discharge

ERIC Educational Resources Information Center

Litt, Jonathan S.; Perrin, James M.

2014-01-01

This study aims to characterize participation of neonatal intensive care unit (NICU) graduates in early intervention (EI). We used data from the National Early Intervention Longitudinal Study. We fit models of days from referral to Individualized Family Service Plan creation (plan time), days from referral to initiation of services (service time),…

The History of Parkinson's Disease: Early Clinical Descriptions and Neurological Therapies

PubMed Central

Goetz, Christopher G.

2011-01-01

Although components of possible Parkinson's disease can be found in very early documents, the first clear medical description was written in 1817 by James Parkinson. In the mid-1800s, Jean-Martin Charcot was particularly influential in refining and expanding this early description and in disseminating information internationally about Parkinson's disease. He separated Parkinson's disease from multiple sclerosis and other disorders characterized by tremor, and he recognized cases that later would likely be classified among the Parkinsonism-plus syndromes. Early treatments of Parkinson's disease were based on empirical observation, and anticholinergic drugs were used as early as the nineteenth century. The discovery of dopaminergic deficits in Parkinson's disease and the synthetic pathway of dopamine led to the first human trials of levodopa. Further historically important anatomical, biochemical, and physiological studies identified additional pharmacological and neurosurgical targets for Parkinson's disease and allow modern clinicians to offer an array of therapies aimed at improving function in this still incurable disease. PMID:22229124

Evaluation of the effects of implementing an electronic early warning score system: protocol for a stepped wedge study.

PubMed

Bonnici, Timothy; Gerry, Stephen; Wong, David; Knight, Julia; Watkinson, Peter

2016-02-09

An Early Warning Score is a clinical risk score based upon vital signs intended to aid recognition of patients in need of urgent medical attention. The use of an escalation of care policy based upon an Early Warning Score is mandated as the standard of practice in British hospitals. Electronic systems for recording vital sign observations and Early Warning Score calculation offer theoretical benefits over paper-based systems. However, the evidence for their clinical benefit is limited. Previous studies have shown inconsistent results. The majority have employed a "before and after" study design, which may be strongly confounded by simultaneously occurring events. This study aims to examine how the implementation of an electronic early warning score system, System for Notification and Documentation (SEND), affects the recognition of clinical deterioration occurring in hospitalised adult patients. This study is a non-randomised stepped wedge evaluation carried out across the four hospitals of the Oxford University Hospitals NHS Trust, comparing charting on paper and charting using SEND. We assume that more frequent monitoring of acutely ill patients is associated with better recognition of patient deterioration. The primary outcome measure is the time between a patient's first observations set with an Early Warning Score above the alerting threshold and their subsequent set of observations. Secondary outcome measures are in-hospital mortality, cardiac arrest and Intensive Care admission rates, hospital length of stay and system usability measured using the System Usability Scale. We will also measure Intensive Care length of stay, Intensive Care mortality, Acute Physiology and Chronic Health Evaluation (APACHE) II acute physiology score on admission, to examine whether the introduction of SEND has any effect on Intensive Care-related outcomes. The development of this protocol has been informed by guidance from the Agency for Healthcare Research and Quality (AHRQ

RNA-seq analysis of clinical-grade osteochondral allografts reveals activation of early response genes.

PubMed

Lin, Yang; Lewallen, Eric A; Camilleri, Emily T; Bonin, Carolina A; Jones, Dakota L; Dudakovic, Amel; Galeano-Garces, Catalina; Wang, Wei; Karperien, Marcel J; Larson, Annalise N; Dahm, Diane L; Stuart, Michael J; Levy, Bruce A; Smith, Jay; Ryssman, Daniel B; Westendorf, Jennifer J; Im, Hee-Jeong; van Wijnen, Andre J; Riester, Scott M; Krych, Aaron J

2016-11-01

Preservation of osteochondral allografts used for transplantation is critical to ensure favorable outcomes for patients after surgical treatment of cartilage defects. To study the biological effects of protocols currently used for cartilage storage, we investigated differences in gene expression between stored allograft cartilage and fresh cartilage from living donors using high throughput molecular screening strategies. We applied next generation RNA sequencing (RNA-seq) and real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR) to assess genome-wide differences in mRNA expression between stored allograft cartilage and fresh cartilage tissue from living donors. Gene ontology analysis was used to characterize biological pathways associated with differentially expressed genes. Our studies establish reduced levels of mRNAs encoding cartilage related extracellular matrix (ECM) proteins (i.e., COL1A1, COL2A1, COL10A1, ACAN, DCN, HAPLN1, TNC, and COMP) in stored cartilage. These changes occur concomitantly with increased expression of "early response genes" that encode transcription factors mediating stress/cytoprotective responses (i.e., EGR1, EGR2, EGR3, MYC, FOS, FOSB, FOSL1, FOSL2, JUN, JUNB, and JUND). The elevated expression of "early response genes" and reduced levels of ECM-related mRNAs in stored cartilage allografts suggests that tissue viability may be maintained by a cytoprotective program that reduces cell metabolic activity. These findings have potential implications for future studies focused on quality assessment and clinical optimization of osteochondral allografts used for cartilage transplantation. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1950-1959, 2016. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

[The early pregnancy factor (EPF) as an early marker of disorders in pregnancy].

PubMed

Straube, W; Römer, T; Zeenni, L; Loh, M

1995-01-01

The early pregnancy factor (EPF) seems to be very helpful in clinical applications such as early detection of pregnancy, differential diagnosis of failure of fertilization or implementation and prognosis of a fertilized ovum. Our purpose was to investigate the diagnostic value of single and serial measurement of EPF, especially in the differential diagnosis of abortion and extrauterine pregnancy. Women with a history of 6-16 weeks amenorrhoea with/without vaginal bleeding were included in the prospective study. The EPF-test system was carried out by means of the rosette inhibition method. EPF proved to be always positive in normal pregnant women and always negative in nonpregnant controls. In case of threatened abortion the prognosis was good, when the EPF values were positive, and poor when they became negative. Patients suffering from spontaneous and missed abortion mostly showed negative EPF-values. This was also true in ectopic pregnancies. The sensitivity and specificity of EPF-test system were 83%. The positive predictive value was observed to be 54% and the negative predictive value 95%. The EPF as an early embryonic signal may be a suitable parameter for the clinical use detecting pregnancy disturbances very early.

The Clinical Utility of Informants' Appraisals on Prospective and Retrospective Memory in Patients with Early Alzheimer's Disease

PubMed Central

Hsu, Yen-Hsuan; Huang, Ching-Feng; Tu, Min-Chien; Hua, Mau-Sun

2014-01-01

Increasing studies suggest the importance of including prospective memory measures in clinical evaluation of dementia due to its sensitivity and functional relevance. The Prospective and Retrospective Memory Questionnaire (PRQM) is originally a self-rated memory inventory that offers a direct comparison between prospective and episodic memory. However, the informant's report has been recognized as a more valid source of cognitive complaints. We thus aimed to examine the validity of the informant-rated form of the PRMQ in assessing memory function of the patients and in detecting individuals with early dementia. The informants of 140 neurological outpatients with memory complaints completed the Taiwan version of the PRMQ. Tests of prospective memory, short-term memory, and general cognitive ability were also administered to non-demented participants and patients with early stages of Alzheimer's disease (AD). Results showed significant relationships between the PRMQ ratings and objective cognitive measures, and showed that higher ratings on the PRMQ were associated with increasing odds of greater dementia severity. Receiver operative characteristic (ROC) curves showed an adequate ability of the PRMQ to identify patients with dementia (93% sensitivity and 84% specificity). Hierarchical regression revealed that the PRMQ has additional explanatory power for dementia status after controlling for age, education and objective memory test results, and that the prospective memory subscale owns predictive value for dementia beyond the retrospective memory subscale. The present study demonstrated the external validity and diagnostic value of informants' evaluation of their respective patients' prospective and retrospective memory functioning, and highlighted the important role of prospective memory in early dementia detection. The proxy-version of the PRMQ is a useful tool that captures prospective and episodic memory problems in patients with early AD, in combination with

Clinical features and hormonal profiles of cloprostenol-induced early abortions in heifers monitored by ultrasonography

PubMed Central

Lobago, Fikre; Gustafsson, Hans; Bekana, Merga; Beckers, Jean-François; Kindahl, Hans

2006-01-01

Background The present study describes the clinical features and plasma profiles of bovine pregnancy-associated glycoprotein 1 (bPAG1), the main metabolite of prostaglandin F2α (PG metabolite) and progesterone (P4) in heifers in which early abortions were induced. Methods Early abortions were induced in four heifers with cloprostenol and monitored by ultrasonography. Blood samples were collected and the plasma were analyzed for bPAG 1, P4 and PG metabolite. Results The foetal heartbeat rates varied from 170–186 beats per minute for all foetuses up to the date of cloprostenol treatment. Foetal death was confirmed within two days after cloprostenol treatment. Prior to cloprostenol injection, blood plasma concentrations of bPAG1, PG metabolite and P4 varied from 8.4 – 40.0 ng/mL, 158 – 275 pmol/L and 20.7 – 46.9 nmol/L, respectively. After the foetus expelled, the plasma level of bPAG1 began to decrease but the decrease was small and gradual. The estimated half-life of bPAG1 was 1.8 – 6.6 days. The plasma level of the PG metabolite started to have short lasting peaks (above 300 pmol/L) within three hours after cloprostenol treatment. The plasma concentrations of P4 dropped sharply to less than 4 nmol/L after 24 hours of cloprostenol injection. Conclusion The current findings indicated that after early closprostenol-induced foetal death, the plasma concentration of bPAG1 decreased gradually and showed a tendency of variation with the stages of pregnancy. PMID:17121683

Microperimetry and fundus autofluorescence in diabetic macular edema: subthreshold micropulse diode laser versus modified early treatment diabetic retinopathy study laser photocoagulation.

PubMed

Vujosevic, Stela; Bottega, Elisa; Casciano, Margherita; Pilotto, Elisabetta; Convento, Enrica; Midena, Edoardo

2010-06-01

The purpose of this study was to evaluate and compare microperimetry and fundus autofluorescence (FAF) after subthreshold micropulse diode laser versus modified Early Treatment Diabetic Retinopathy Study photocoagulation for clinically significant diabetic macular edema. A prospective randomized clinical trial including 62 eyes (50 patients) with untreated, center-involving, clinically significant diabetic macular edema was performed. All patients underwent best-corrected visual acuity determination (logarithm of the minimum angle of resolution), slit-lamp biomicroscopy, FAF, optical coherence tomography, microperimetry (macular sensitivity), and fluorescein angiography before and after treatment. Best-corrected visual acuity, optical coherence tomography, microperimetry, and FAF were repeated at 1-, 3-, 6-, 9-, and 12-month follow-up examinations. Fluorescein angiography was performed at baseline and at 6 and 12 months. Before treatment, demographic and macular parameters were not different between the two treatment groups. At 12 months, best-corrected visual acuity remained stable in both groups (P = 0.41 and P = 0.82), mean central retinal thickness decreased in both groups (P = 0.0002 and P < 0.0001), and mean central 4 degrees and 12 degrees retinal sensitivity increased in the micropulse diode laser group (P = 0.02 and P = 0.0075) and decreased in the Early Treatment Diabetic Retinopathy Study group (P = 0.2 and P = 0.0026). There was no significant difference in either best-corrected visual acuity or central retinal thickness between the 2 treatment groups (P = 0.48 and P = 0.29), whereas there was a significant difference in 4 degrees and 12 degrees retinal sensitivity (P = 0.04 and P < 0.0001). Fundus autofluorescence never changed in the micropulse diode laser group even after retreatment. In the Early Treatment Diabetic Retinopathy Study group, FAF increased up to 9 months and decreased in 6 eyes (20%) at 12 months. Micropulse diode laser seems to be as

Early- versus Late-Onset Dysthymia

PubMed Central

Sansone, Lori A.

2009-01-01

In the current Diagnostic and Statistical Manual of Mental Disorders, dysthymic disorder is categorized as either early-onset or late-onset, based upon the emergence of symptoms before or after the age of 21, respectively. Does this diagnostic distinction have any meaningful clinical implications? In this edition of The Interface, we present empirical studies that have, within a single study, compared individuals with early-versus late-onset dysthymia. In this review, we found that, compared to those with late-onset dysthymia, early-onset patients are more likely to harbor psychiatric comorbidity both on Axis I and II, exhibit less psychological resilience, and have more prominent family loadings for mood disorders. These findings suggest that this distinction is meaningful and that the early-onset subtype of dysthymia is more difficult to effectively treat. PMID:20049145

Early neuroprotection after cardiac arrest.

PubMed

Dell'anna, Antonio M; Scolletta, Sabino; Donadello, Katia; Taccone, Fabio S

2014-06-01

Many efforts have been made in the last decades to improve outcome in patients who are successfully resuscitated from sudden cardiac arrest. Despite some advances, postanoxic encephalopathy remains the most common cause of death among those patients and several investigations have focused on early neuroprotection in this setting. Therapeutic hypothermia is the only strategy able to provide effective neuroprotection in clinical practice. Experimental studies showed that therapeutic hypothermia was even more effective when it was started immediately after the ischemic event. In human studies, the use of prehospital hypothermia was able to reduce the time to target temperature but did not result in higher survival rate or neurological recovery in patients with out-of-hospital cardiac arrest, when compared with standard in-hospital therapeutic hypothermia. Thus, intra-arrest hypothermia (i.e., initiated during cardiopulmonary resuscitation) may be a valid alternative to improve the effectiveness of therapeutic hypothermia in this setting; however, more clinical data are needed to demonstrate any potential benefit of such intervention on neurological outcome. Together with cooling, early hemodynamic optimization should be considered to improve cerebral perfusion in cardiac arrest patients and minimize any secondary brain injury. Nevertheless, only scarce data are available on the impact of early hemodynamic optimization on the development of organ dysfunction and neurological recovery in such patients. Some new protective strategies, including inhaled gases (i.e., xenon, argon, nitric oxide) and intravenous drugs (i.e., erythropoietin) are emerging in experimental studies as promising tools to improve neuroprotection, especially when combined with therapeutic hypothermia. Early cooling may contribute to enhance neuroprotection after cardiac arrest. Hemodynamic optimization is mandatory to avoid cerebral hypoperfusion in this setting. The combination of such

Changes in pathology test ordering by early career general practitioners: a longitudinal study.

PubMed

Magin, Parker J; Tapley, Amanda; Morgan, Simon; Henderson, Kim; Holliday, Elizabeth G; Davey, Andrew R; Ball, Jean; Catzikiris, Nigel F; Mulquiney, Katie J; van Driel, Mieke L

2017-07-17

To assess the number of pathology tests ordered by general practice registrars during their first 18-24 months of clinical general practice. Longitudinal analysis of ten rounds of data collection (2010-2014) for the Registrar Clinical Encounters in Training (ReCEnT) study, an ongoing, multicentre, cohort study of general practice registrars in Australia. The principal analysis employed negative binomial regression in a generalised estimating equations framework (to account for repeated measures on registrars).Setting, participants: General practice registrars in training posts with five of 17 general practice regional training providers in five Australian states. The registrar participation rate was 96.4%. Number of pathology tests requested per consultation. The time unit for analysis was the registrar training term (the 6-month full-time equivalent component of clinical training); registrars contributed data for up to four training terms. 876 registrars contributed data for 114 584 consultations. The number of pathology tests requested increased by 11% (95% CI, 8-15%; P < 0.001) per training term. Contrary to expectations, pathology test ordering by general practice registrars increased significantly during their first 2 years of clinical practice. This causes concerns about overtesting. As established general practitioners order fewer tests than registrars, test ordering may peak during late vocational training and early career practice. Registrars need support during this difficult period in the development of their clinical practice patterns.

Pronounced Structural and Functional Damage in Early Adult Pediatric-Onset Multiple Sclerosis with No or Minimal Clinical Disability.

PubMed

Giorgio, Antonio; Zhang, Jian; Stromillo, Maria Laura; Rossi, Francesca; Battaglini, Marco; Nichelli, Lucia; Mortilla, Marzia; Portaccio, Emilio; Hakiki, Bahia; Amato, Maria Pia; De Stefano, Nicola

2017-01-01

Pediatric-onset multiple sclerosis (POMS) may represent a model of vulnerability to damage occurring during a period of active maturation of the human brain. Whereas adaptive mechanisms seem to take place in the POMS brain in the short-medium term, natural history studies have shown that these patients reach irreversible disability, despite slower progression, at a significantly younger age than adult-onset MS (AOMS) patients. We tested for the first time whether significant brain alterations already occurred in POMS patients in their early adulthood and with no or minimal disability ( n  = 15) in comparison with age- and disability-matched AOMS patients ( n  = 14) and to normal controls (NC, n  = 20). We used a multimodal MRI approach by modeling, using FSL, voxelwise measures of microstructural integrity of white matter tracts and gray matter volumes with those of intra- and internetwork functional connectivity (FC) (analysis of variance, p  ≤ 0.01, corrected for multiple comparisons across space). POMS patients showed, when compared with both NC and AOMS patients, altered measures of diffusion tensor imaging (reduced fractional anisotropy and/or increased diffusivities) and higher probability of lesion occurrence in a clinically eloquent region for physical disability such as the posterior corona radiata. In addition, POMS patients showed, compared with the other two groups, reduced long-range FC, assessed from resting functional MRI, between default mode network and secondary visual network, whose interaction subserves important cognitive functions such as spatial attention and visual learning. Overall, this pattern of structural damage and brain connectivity disruption in early adult POMS patients with no or minimal clinical disability might explain their unfavorable clinical outcome in the long term.

Early full weight-bearing versus 6-week partial weight-bearing after open wedge high tibial osteotomy leads to earlier improvement of the clinical results: a prospective, randomised evaluation.

PubMed

Schröter, S; Ateschrang, A; Löwe, W; Nakayama, H; Stöckle, U; Ihle, C

2017-01-01

Open wedge high tibial osteotomy is a widespread treatment option in patients with varus malalignment and medial compartment osteoarthritis. There is no standardised protocol for post-operative rehabilitation available. The purpose of this study was to compare two post-operative rehabilitation protocols and to evaluate the clinical outcome of early full weight-bearing after open wedge HTO. One hundred and twenty consecutive patients with varus malalignment and medial compartment osteoarthritis received an open wedge HTO using an angular locking plate fixation between December 2008 and December 2011. All patients were assigned randomly into one of two groups with different post-operative rehabilitation protocols (11-day vs. 6-week 20-kg partial weight-bearing). Clinical outcome was evaluated using established instruments (Lequesne, Lysholm, HSS and IKDC scores) preoperatively, 6, 12 and 18 months post-operatively. Deformity analysis was performed preoperatively and during follow-up. All clinical scores showed a significant pre- to post-operative improvement. After 6 months, there was a higher improvement in the group of early full weight-bearing. The difference between preoperative and 6-month follow-up for the group with early full weight-bearing and for the group with 20-kg PWB for 6 weeks was 28 ± 26 and 18 ± 22, respectively, for the Lysholm score and -5.0 ± 5.1 and -3.0 ± 3.6, respectively, for the Lequesne score. Early full weight-bearing (11-day 20-kg partial weight-bearing) after open wedge HTO without bone graft leads to earlier improvement of the clinical results and can be recommended for post-operative rehabilitation after open wedge HTO and fixation with an angular locking plate. Therapeutic study, Level I.

A simplified clinical risk score predicts the need for early endoscopy in non-variceal upper gastrointestinal bleeding.

PubMed

Tammaro, Leonardo; Buda, Andrea; Di Paolo, Maria Carla; Zullo, Angelo; Hassan, Cesare; Riccio, Elisabetta; Vassallo, Roberto; Caserta, Luigi; Anderloni, Andrea; Natali, Alessandro

2014-09-01

Pre-endoscopic triage of patients who require an early upper endoscopy can improve management of patients with non-variceal upper gastrointestinal bleeding. To validate a new simplified clinical score (T-score) to assess the need of an early upper endoscopy in non variceal bleeding patients. Secondary outcomes were re-bleeding rate, 30-day bleeding-related mortality. In this prospective, multicentre study patients with bleeding who underwent upper endoscopy were enrolled. The accuracy for high risk endoscopic stigmata of the T-score was compared with that of the Glasgow Blatchford risk score. Overall, 602 patients underwent early upper endoscopy, and 472 presented with non-variceal bleeding. High risk endoscopic stigmata were detected in 145 (30.7%) cases. T-score sensitivity and specificity for high risk endoscopic stigmata and bleeding-related mortality was 96% and 30%, and 80% and 71%, respectively. No statistically difference in predicting high risk endoscopic stigmata between T-score and Glasgow Blatchford risk score was observed (ROC curve: 0.72 vs. 0.69, p=0.11). The two scores were also similar in predicting re-bleeding (ROC curve: 0.64 vs. 0.63, p=0.4) and 30-day bleeding-related mortality (ROC curve: 0.78 vs. 0.76, p=0.3). The T-score appeared to predict high risk endoscopic stigmata, re-bleeding and mortality with similar accuracy to Glasgow Blatchford risk score. Such a score may be helpful for the prediction of high-risk patients who need a very early therapeutic endoscopy. Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

The Ontario Birth Study: A prospective pregnancy cohort study integrating perinatal research into clinical care.

PubMed

Anderson, Laura N; Knight, Julia A; Hung, Rayjean J; Hewko, Sheryl L; Seeto, Ryan A; Martin, Mary-Jean; Fleming, Alison; Maguire, Jonathon L; Matthews, Stephen G; Murphy, Kellie E; Okun, Nan; Jenkins, Jennifer M; Lye, Stephen J; Bocking, Alan

2018-05-01

Pregnancy and early childhood represent critical periods that impact health throughout the life-course. The Ontario Birth Study (OBS) is a pregnancy cohort study designed as a platform for research on pregnancy complications, maternal and infant health, and the developmental origins of health and disease. Pregnant women <17 weeks gestational age were recruited between 2013 and 2015 from antenatal clinics at Mount Sinai Hospital, Toronto, Canada. Life style and diet questionnaires, biospecimens, and clinical data were collected throughout the pregnancy and postpartum period at the time of clinical care. The OBS was integrated into clinical care to reduce participant burden, improve efficiency, and increase research potential. There were 3181 eligible women approached for recruitment and 1374 (43%) participated in the study. Among the 1374 participants, 1272 (93%) delivered a liveborn infant and were followed to 6-10 weeks postpartum. Of the 1272 women who completed the study, 98% had at least one pregnancy blood sample collected, 97% had vaginal swabs collected, 90% completed the prenatal life style questionnaires, and 78% completed the Diet History Questionnaire. Most women (88%) were ≥30 years of age, 55% had no previous children, 24% were overweight or obese pre-pregnancy and 78% of parents had postsecondary education. Most pregnancies were singleton (3% twins), 34% delivered by caesarean section, and 6% preterm (<37 weeks gestation). The OBS is a contemporary cohort with detailed data including banked biospecimens for studies of pregnancy health and the gene-environment interactions that establish developmental trajectories to health, learning, and social functioning. © 2018 John Wiley & Sons Ltd.

OCT for early quality evaluation of tooth-composite bond in clinical trials.

PubMed

Haak, Rainer; Schmidt, Patrick; Park, Kyung-Jin; Häfer, Matthias; Krause, Felix; Ziebolz, Dirk; Schneider, Hartmut

2018-06-19

To evaluate early quality of composite restorations with a universal adhesive in different application modes clinically and with optical coherence tomography (OCT). 22 patients with four non-carious cervical lesions each received composite restorations (Filtek Supreme TM XTE, 3 M). The universal adhesive Scotchbond Universal TM (SBU, 3 M) was applied with three etching protocols: self-etch (SE), selective-enamel-etch (SEE) and etch-and-rinse (ER). The etch-and-rinse adhesive OptiBond TM FL (OFL, Kerr) served as a control. Restorations were imaged by OCT (Thorlabs) directly after application (t 0 ). After 14 days (t 1 ) and 6 month (t 2 ) OCT imaging (interfacial adhesive defects) was repeated combined with clinical assessment (FDI criteria). Groups were compared by Friedman-/Wilcoxon- and McNemar-Test. No differences were seen clinically between groups (p i ≥ 0.500). OCT assessment revealed more adhesive defects at the enamel interface with SBU/SE at t 0- t 2 compared to all groups (p i ≤ 0.016). OFL showed more defects than SBU/ER (t 1 : p = 0.01; t 2 : p = 0.083). At dentin/cementum interface OFL exhibited more adhesive defects than SBU with all conditioning modes (t 0 , t 1 , p i ≤ 0.003) and at t 2 to SBU/SE and SBU/ER (p < 0.001). Since t 1 defects with SBU were detected more frequently in the SE and SEE modes compared to ER (p i ≤ 0.037). In contrast to SBU defects increased with OFL up to t 2 (p i ≤ 0.007). In contrast to clinical evaluation, OCT revealed subtle adhesive defects directly after application that might interfere with clinical success. It was demonstrated that ER doesn't decrease initial adhesion of SBU to dentin. Copyright © 2018. Published by Elsevier Ltd.

Clinical implications in laboratory parameter values in acute Kawasaki disease for early diagnosis and proper treatment.

PubMed

Seo, Yu-Mi; Kang, Hyun-Mi; Lee, Sung-Churl; Yu, Jae-Won; Kil, Hong-Ryang; Rhim, Jung-Woo; Han, Ji-Whan; Lee, Kyung-Yil

2018-05-01

This study aimed to analyse laboratory values according to fever duration, and evaluate the relationship across these values during the acute phase of Kawasaki disease (KD) to aid in the early diagnosis for early-presenting KD and incomplete KD patients. Clinical and laboratory data of patients with KD (n=615) were evaluated according to duration of fever at presentation, and were compared between patients with and without coronary artery lesions (CALs). For evaluation of the relationships across laboratory indices, patients with a fever duration of 5 days or 6 days were used (n=204). The mean fever duration was 6.6±2.3 days, and the proportions of patients with CALs was 19.3% (n=114). C-reactive proteins (CRPs) and neutrophil differential values were highest and hemoglobin, albumin, and lymphocyte differential values were lowest in the 6-day group. Patients with CALs had longer total fever duration, higher CRP and neutrophil differential values and lower hemoglobin and albumin values compared to patients without CALs. CRP, albumin, neutrophil differential, and hemoglobin values at the peak inflammation stage of KD showed positive or negative correlations each other. The severity of systemic inflammation in KD was reflected in the laboratory values including CRP, neutrophil differential, albumin, and hemoglobin. Observing changes in these laboratory parameters by repeated examinations prior to the peak of inflammation in acute KD may aid in diagnosis of early-presenting KD patients.

Early traumatic events in psychopaths.

PubMed

Borja, Karina; Ostrosky, Feggy

2013-07-01

The relationship between diverse early traumatic events and psychopathy was studied in 194 male inmates. Criminal history transcripts were revised, and clinical interviews were conducted to determine the level of psychopathy using the Psychopathy Checklist-Revised (PCL-R) Form, and the Early Trauma Inventory was applied to assess the incidence of abuse before 18 years of age. Psychopathic inmates presented a higher victimization level and were more exposed to certain types of intended abuse than sociopathic inmates, while the sum of events and emotional abuse were associated with the PCL-R score. Our studies support the influence of early adverse events in the development of psychopathic offenders. © 2013 American Academy of Forensic Sciences.

Early College, Early Success: Early College High School Initiative Impact Study

ERIC Educational Resources Information Center

Berger, Andrea; Turk-Bicakci, Lori; Garet, Michael; Song, Mengli; Knudson, Joel; Haxton, Clarisse; Zeiser, Kristina; Hoshen, Gur; Ford, Jennifer; Stephan, Jennifer; Keating, Kaeli; Cassidy, Lauren

2013-01-01

In 2002, the Bill & Melinda Gates Foundation launched the Early College High School Initiative (ECHSI) with the primary goal of increasing the opportunity for underserved students to earn a postsecondary credential. To achieve this goal, Early Colleges provide underserved students with exposure to, and support in, college while they are in…

Hormone-Balancing Effect of Pre-Gelatinized Organic Maca (Lepidium peruvianum Chacon): (III) Clinical responses of early-postmenopausal women to Maca in double blind, randomized, Placebo-controlled, crossover configuration, outpatient study

PubMed Central

Meissner, H. O.; Mscisz, A.; Reich-Bilinska, H.; Mrozikiewicz, P.; Bobkiewicz-Kozlowska, T.; Kedzia, B.; Lowicka, A.; Barchia, I.

2006-01-01

This is the second, conclusive part of the clinical study on clinical responses of early-postmenopausal women to standardized doses of pre-Gelatinized Organic Maca (Maca-GO). Total of 34 Caucasian women volunteers participated in a double-blind, randomized, four months outpatient crossover configuration Trial. After fulfilling the criteria of being early-postmenopausal: blood Estrogen (E2<40 pg/ml) and Follicle Stimulating Hormone (FSH>30 IU/ml) at admission, they were randomly allocated to Placebo (P) and Maca-GO (M) treatments (2 groups of 11 participants each). Two 500 mg vegetable hard gel capsules with Maca-GO or Placebo powder were self-administered twice daily with meals (total 2 g/day). At admission and follow-up monthly intervals, body mass index (BMI), blood pressure, levels of gonadal, pituitary, thyroid and adrenal hormones, lipids and key minerals were measured. Bone markers were determined after four months M and P use in 12 participants. Menopausal symptoms were assessed according to Greene’s Score (GMS) and Kupperman’s Index (KMI). Data were analyzed using multivariate technique on blocs of monthly. Results and canonical variate technique was applied to GMS and KMI matrices. Two months application of Maca-GO stimulated (P<0.05) production of E2, suppressed (P<0.05) blood FSH, Thyroid (T3) and Adrenocorticotropic hormones, Cortisol, and BMI, increased (P<0.05) low density lipoproteins, blood Iron and alleviated (P<0.001) menopausal symptoms. Maca-GO noticeably increased bone density markers. In conclusion, Maca-GO applied to early-postmenopausal women (i) acted as a toner of hormonal processes along the Hypothalamus-Pituitary-Ovarian axis, (ii) balanced hormone levels and (iii) relieved symptoms of menopausal discomfort, (hot flushes and night sweating in particular), thus, (iv) exhibited a distinctive function peculiar to adaptogens, providing an alternative non-hormonal plant option to reduce dependence on hormone therapy programs (HRT). PMID

Hormone-Balancing Effect of Pre-Gelatinized Organic Maca (Lepidium peruvianum Chacon): (III) Clinical responses of early-postmenopausal women to Maca in double blind, randomized, Placebo-controlled, crossover configuration, outpatient study.

PubMed

Meissner, H O; Mscisz, A; Reich-Bilinska, H; Mrozikiewicz, P; Bobkiewicz-Kozlowska, T; Kedzia, B; Lowicka, A; Barchia, I

2006-12-01

This is the second, conclusive part of the clinical study on clinical responses of early-postmenopausal women to standardized doses of pre-Gelatinized Organic Maca (Maca-GO). Total of 34 Caucasian women volunteers participated in a double-blind, randomized, four months outpatient crossover configuration Trial. After fulfilling the criteria of being early-postmenopausal: blood Estrogen (E2<40 pg/ml) and Follicle Stimulating Hormone (FSH>30 IU/ml) at admission, they were randomly allocated to Placebo (P) and Maca-GO (M) treatments (2 groups of 11 participants each). Two 500 mg vegetable hard gel capsules with Maca-GO or Placebo powder were self-administered twice daily with meals (total 2 g/day). At admission and follow-up monthly intervals, body mass index (BMI), blood pressure, levels of gonadal, pituitary, thyroid and adrenal hormones, lipids and key minerals were measured. Bone markers were determined after four months M and P use in 12 participants. Menopausal symptoms were assessed according to Greene's Score (GMS) and Kupperman's Index (KMI). Data were analyzed using multivariate technique on blocs of monthly. Results and canonical variate technique was applied to GMS and KMI matrices. Two months application of Maca-GO stimulated (P<0.05) production of E2, suppressed (P<0.05) blood FSH, Thyroid (T3) and Adrenocorticotropic hormones, Cortisol, and BMI, increased (P<0.05) low density lipoproteins, blood Iron and alleviated (P<0.001) menopausal symptoms. Maca-GO noticeably increased bone density markers. In conclusion, Maca-GO applied to early-postmenopausal women (i) acted as a toner of hormonal processes along the Hypothalamus-Pituitary-Ovarian axis, (ii) balanced hormone levels and (iii) relieved symptoms of menopausal discomfort, (hot flushes and night sweating in particular), thus, (iv) exhibited a distinctive function peculiar to adaptogens, providing an alternative non-hormonal plant option to reduce dependence on hormone therapy programs (HRT).

Clinical studies and anti-inflammatory mechanisms of treatments

PubMed Central

French, Jacqueline A.; Koepp, Matthias; Naegelin, Yvonne; Vigevano, Federico; Auvin, Stéphane; Rho, Jong M.; Rosenberg, Evan; Devinsky, Orrin; Olofsson, Peder S.; Dichter, Marc A.

2017-01-01

Summary In this exciting era, we are coming closer and closer to bringing an anti-inflammatory therapy to the clinic for the purpose of seizure prevention, modification, and/or suppression. At present, it is unclear what this approach might entail, and what form it will take. Irrespective of the therapy that ultimately reaches the clinic, there will be some commonalities with regard to clinical trials. A number of animal models have now been used to identify inflammation as a major underlying mechanism of both chronic seizures and the epileptogenic process. These models have demonstrated that specific anti-inflammatory treatments can be effective at both suppressing chronic seizures and interfering with the process of epileptogenesis. Some of these have already been evaluated in early phase clinical trials. It can be expected that there will soon be more clinical trials of both “conventional, broad spectrum” anti-inflammatory agents and novel new approaches to utilizing specific anti-inflammatory therapies with drugs or other therapeutic interventions. A summary of some of those approaches appears below, as well as a discussion of the issues facing clinical trials in this new domain. PMID:28675558

Clinical studies and anti-inflammatory mechanisms of treatments.

PubMed

French, Jacqueline A; Koepp, Matthias; Naegelin, Yvonne; Vigevano, Federico; Auvin, Stéphane; Rho, Jong M; Rosenberg, Evan; Devinsky, Orrin; Olofsson, Peder S; Dichter, Marc A

2017-07-01

In this exciting era, we are coming closer and closer to bringing an anti-inflammatory therapy to the clinic for the purpose of seizure prevention, modification, and/or suppression. At present, it is unclear what this approach might entail, and what form it will take. Irrespective of the therapy that ultimately reaches the clinic, there will be some commonalities with regard to clinical trials. A number of animal models have now been used to identify inflammation as a major underlying mechanism of both chronic seizures and the epileptogenic process. These models have demonstrated that specific anti-inflammatory treatments can be effective at both suppressing chronic seizures and interfering with the process of epileptogenesis. Some of these have already been evaluated in early phase clinical trials. It can be expected that there will soon be more clinical trials of both "conventional, broad spectrum" anti-inflammatory agents and novel new approaches to utilizing specific anti-inflammatory therapies with drugs or other therapeutic interventions. A summary of some of those approaches appears below, as well as a discussion of the issues facing clinical trials in this new domain. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Trends in Early Aspirin Use Among Patients With Acute Myocardial Infarction in China, 2001–2011: The China PEACE‐Retrospective AMI Study

PubMed Central

Gao, Yan; Masoudi, Frederick A.; Hu, Shuang; Li, Jing; Zhang, Haibo; Li, Xi; Desai, Nihar R.; Krumholz, Harlan M.; Jiang, Lixin

2014-01-01

Background Aspirin is an effective, safe, and inexpensive early treatment of acute myocardial infarction (AMI) with few barriers to administration, even in countries with limited healthcare resources. However, the rates and recent trends of aspirin use for the early treatment of AMI in China are unknown. Methods and Results Using data from the China Patient‐centered Evaluative Assessment of Cardiac Events Retrospective Study of Acute Myocardial Infarction (China PEACE‐Retrospective AMI Study), we identified a cohort of 14 041 patients with AMI eligible for early aspirin therapy. Early use of aspirin for AMI increased over time (78.4% in 2001, 86.5% in 2006, and 90.0% in 2011). However, about 15% of hospitals had a rate of use of <80% in 2011. Treatment was less likely in patients who were older, presented with cardiogenic shock at admission, presented without chest discomfort, had a final diagnosis of non‐ST‐segment elevation acute myocardial infarction, or did not receive reperfusion therapy. Hospitalization in rural regions was also associated with aspirin underuse. Conclusions Despite improvements in early use of aspirin for AMI in China, there remains marked variation in practice and opportunities for improvement that are concentrated in some hospitals and patient groups. Clinical Trial Registration URL: ClinicalTrials.gov Unique identifier: NCT01624883. PMID:25304853

Clinical Epidemiology Unit - overview of research areas

Cancer.gov

Clinical Epidemiology Unit (CEU) conducts etiologic research with potential clinical and public health applications, and leads studies evaluating population-based early detection and cancer prevention strategies

Goal-oriented cognitive rehabilitation in early-stage dementia: study protocol for a multi-centre single-blind randomised controlled trial (GREAT)

PubMed Central

2013-01-01

Background Preliminary evidence suggests that goal-oriented cognitive rehabilitation (CR) may be a clinically effective intervention for people with early-stage Alzheimer’s disease, vascular or mixed dementia and their carers. This study aims to establish whether CR is a clinically effective and cost-effective intervention for people with early-stage dementia and their carers. Methods/design In this multi-centre, single-blind randomised controlled trial, 480 people with early-stage dementia, each with a carer, will be randomised to receive either treatment as usual or cognitive rehabilitation (10 therapy sessions over 3 months, followed by 4 maintenance sessions over 6 months). We will compare the effectiveness of cognitive rehabilitation with that of treatment as usual with regard to improving self-reported and carer-rated goal performance in areas identified as causing concern by people with early-stage dementia; improving quality of life, self-efficacy, mood and cognition of people with early-stage dementia; and reducing stress levels and ameliorating quality of life for carers of participants with early-stage dementia. The incremental cost-effectiveness of goal-oriented cognitive rehabilitation compared to treatment as usual will also be examined. Discussion If the study confirms the benefits and cost-effectiveness of cognitive rehabilitation, it will be important to examine how the goal-oriented cognitive rehabilitation approach can most effectively be integrated into routine health-care provision. Our aim is to provide training and develop materials to support the implementation of this approach following trial completion. Trial registration Current Controlled Trials ISRCTN21027481 PMID:23710796

Clinical management provided by board-certificated physiatrists in early rehabilitation is a significant determinant of functional improvement in acute stroke patients: a retrospective analysis of Japan rehabilitation database.

PubMed

Kinoshita, Shoji; Kakuda, Wataru; Momosaki, Ryo; Yamada, Naoki; Sugawara, Hidekazu; Watanabe, Shu; Abo, Masahiro

2015-05-01

Early rehabilitation for acute stroke patients is widely recommended. We tested the hypothesis that clinical outcome of stroke patients who receive early rehabilitation managed by board-certificated physiatrists (BCP) is generally better than that provided by other medical specialties. Data of stroke patients who underwent early rehabilitation in 19 acute hospitals between January 2005 and December 2013 were collected from the Japan Rehabilitation Database and analyzed retrospectively. Multivariate linear regression analysis using generalized estimating equations method was performed to assess the association between Functional Independence Measure (FIM) effectiveness and management provided by BCP in early rehabilitation. In addition, multivariate logistic regression analysis was also performed to assess the impact of management provided by BCP in acute phase on discharge destination. After setting the inclusion criteria, data of 3838 stroke patients were eligible for analysis. BCP provided early rehabilitation in 814 patients (21.2%). Both the duration of daily exercise time and the frequency of regular conferencing were significantly higher for patients managed by BCP than by other specialties. Although the mortality rate was not different, multivariate regression analysis showed that FIM effectiveness correlated significantly and positively with the management provided by BCP (coefficient, .35; 95% confidence interval [CI], .012-.059; P < .005). In addition, multivariate logistic analysis identified clinical management by BCP as a significant determinant of home discharge (odds ratio, 1.24; 95% CI, 1.08-1.44; P < .005). Our retrospective cohort study demonstrated that clinical management provided by BCP in early rehabilitation can lead to functional recovery of acute stroke. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Defining Clinical Response Criteria and Early Response Criteria for Precision Oncology: Current State-of-the-Art and Future Perspectives.

PubMed

Subbiah, Vivek; Chuang, Hubert H; Gambhire, Dhiraj; Kairemo, Kalevi

2017-02-15

In this era of precision oncology, there has been an exponential growth in the armamentarium of genomically targeted therapies and immunotherapies. Evaluating early responses to precision therapy is essential for "go" versus "no go" decisions for these molecularly targeted drugs and agents that arm the immune system. Many different response assessment criteria exist for use in solid tumors and lymphomas. We reviewed the literature using the Medline/PubMed database for keywords "response assessment" and various known response assessment criteria published up to 2016. In this article we review the commonly used response assessment criteria. We present a decision tree to facilitate selection of appropriate criteria. We also suggest methods for standardization of various response assessment criteria. The relevant response assessment criteria were further studied for rational of development, key features, proposed use and acceptance by various entities. We also discuss early response evaluation and provide specific case studies of early response to targeted therapy. With high-throughput, advanced computing programs and digital data-mining it is now possible to acquire vast amount of high quality imaging data opening up a new field of "omics in radiology"-radiomics that complements genomics for personalized medicine. Radiomics is rapidly evolving and is still in the research arena. This cutting-edge technology is poised to move soon to the mainstream clinical arena. Novel agents with new mechanisms of action require advanced molecular imaging as imaging biomarkers. There is an urgent need for development of standardized early response assessment criteria for evaluation of response to precision therapy.

Ocriplasmin for treatment of stage 2 macular holes: early clinical results.

PubMed

Miller, John B; Kim, Leo A; Wu, David M; Vavvas, Demetrios G; Eliott, Dean; Husain, Deeba

2014-01-01

To review clinical and structural outcomes of ocriplasmin for treatment of stage 2 macular holes. A retrospective review of the first patients with stage 2 macular holes to be treated with ocriplasmin at Massachusetts Eye and Ear Infirmary. All patients were imaged with spectral-domain optical coherence tomography (SD-OCT). Eight patients with stage 2 macular holes received a single injection of 125 μg of ocriplasmin. One patient (12.5%) demonstrated macular hole closure. The posterior hyaloid separated from the macula in six eyes (75%). All seven holes that remained open showed enlargement in hole diameters (narrowest, apical, and basal) at 1 week and 1 month. All seven were successfully closed with surgery. Ellipsoid zone disruptions were observed by OCT in four eyes (50%) and persisted throughout follow-up (more than 6 months on average). In early clinical results, the authors found a lower macular hole closure rate with ocriplasmin than previously reported. Enlargement was observed in all holes that failed to close with ocriplasmin. The authors found ellipsoid zone disruptions that persisted through 6 months of follow-up after ocriplasmin injection. Further work is needed to investigate the cause for these ellipsoid zone changes. Copyright 2014, SLACK Incorporated.

Modeling naturalistic craving, withdrawal, and affect during early nicotine abstinence: A pilot ecological momentary assessment study.

PubMed

Bujarski, Spencer; Roche, Daniel J O; Sheets, Erin S; Krull, Jennifer L; Guzman, Iris; Ray, Lara A

2015-04-01

Despite the critical role of withdrawal, craving, and positive affect (PA) and negative affect (NA) in smoking relapse, relatively little is known about the temporal and predictive relationship between these constructs within the first day of abstinence. This pilot study aims to characterize dynamic changes in withdrawal, craving, and affect over the course of early abstinence using ecological momentary assessment. Beginning immediately after smoking, moderate and heavy smoking participants (n = 15 per group) responded to hourly surveys assessing craving, withdrawal, NA, and PA. Univariate and multivariate multilevel random coefficient modeling was used to describe the progression of craving, withdrawal/NA, and PA and to test correlations between these constructs at the subject level over the course of early abstinence. Heavy smokers reported greater craving from 1-4 hr of abstinence and greater withdrawal/NA after 3 or more hours as compared with moderate smokers. Level of withdrawal/NA was strongly positively associated with craving, and PA was negatively correlated with craving; however, the temporal dynamics of these correlations differed substantially. The association between withdrawal/NA and craving decreased over early abstinence, whereas the reverse was observed for PA. These findings can inform experimental studies of nicotine abstinence as well as their clinical applications to smoking cessation efforts. In particular, these results help to elucidate the role of PA in nicotine abstinence by demonstrating its independent association with nicotine craving over and above withdrawal/NA. If supported by future studies, these findings can refine experimental methods and clinical approaches for smoking cessation. (c) 2015 APA, all rights reserved).

Influence of early neurological complications on clinical outcome following lung transplant.

PubMed

Gamez, Josep; Salvado, Maria; Martinez-de La Ossa, Alejandro; Deu, Maria; Romero, Laura; Roman, Antonio; Sacanell, Judith; Laborda, Cesar; Rochera, Isabel; Nadal, Miriam; Carmona, Francesc; Santamarina, Estevo; Raguer, Nuria; Canela, Merce; Solé, Joan

2017-01-01

Neurological complications after lung transplantation are common. The full spectrum of neurological complications and their impact on clinical outcomes has not been extensively studied. We investigated the neurological incidence of complications, categorized according to whether they affected the central, peripheral or autonomic nervous systems, in a series of 109 patients undergoing lung transplantation at our center between January 1 2013 and December 31 2014. Fifty-one patients (46.8%) presented at least one neurological complication. Critical illness polyneuropathy-myopathy (31 cases) and phrenic nerve injury (26 cases) were the two most prevalent complications. These two neuromuscular complications lengthened hospital stays by a median period of 35.5 and 32.5 days respectively. However, neurological complications did not affect patients' survival. The real incidence of neurological complications among lung transplant recipients is probably underestimated. They usually appear in the first two months after surgery. Despite not affecting mortality, they do affect the mean length of hospital stay, and especially the time spent in the Intensive Care Unit. We found no risk factor for neurological complications except for long operating times, ischemic time and need for transfusion. It is necessary to develop programs for the prevention and early recognition of these complications, and the prevention of their precipitant and risk factors.

Influence of early neurological complications on clinical outcome following lung transplant

PubMed Central

Salvado, Maria; Martinez-de La Ossa, Alejandro; Deu, Maria; Romero, Laura; Roman, Antonio; Sacanell, Judith; Laborda, Cesar; Rochera, Isabel; Nadal, Miriam; Carmona, Francesc; Santamarina, Estevo; Raguer, Nuria; Canela, Merce; Solé, Joan

2017-01-01

Background Neurological complications after lung transplantation are common. The full spectrum of neurological complications and their impact on clinical outcomes has not been extensively studied. Methods We investigated the neurological incidence of complications, categorized according to whether they affected the central, peripheral or autonomic nervous systems, in a series of 109 patients undergoing lung transplantation at our center between January 1 2013 and December 31 2014. Results Fifty-one patients (46.8%) presented at least one neurological complication. Critical illness polyneuropathy-myopathy (31 cases) and phrenic nerve injury (26 cases) were the two most prevalent complications. These two neuromuscular complications lengthened hospital stays by a median period of 35.5 and 32.5 days respectively. However, neurological complications did not affect patients’ survival. Conclusions The real incidence of neurological complications among lung transplant recipients is probably underestimated. They usually appear in the first two months after surgery. Despite not affecting mortality, they do affect the mean length of hospital stay, and especially the time spent in the Intensive Care Unit. We found no risk factor for neurological complications except for long operating times, ischemic time and need for transfusion. It is necessary to develop programs for the prevention and early recognition of these complications, and the prevention of their precipitant and risk factors. PMID:28301586

Early insights into the characteristics and evolution of clinical parameters in a cohort of patients prescribed sacubitril/valsartan in Germany.

PubMed

Wachter, Rolf; Viriato, Daniel; Klebs, Sven; Grunow, Stefanie S; Schindler, Matthias; Engelhard, Johanna; Proenca, Catia C; Calado, Frederico; Schlienger, Raymond; Dworak, Markus; Balas, Bogdan; Bruce Wirta, Sara

2018-04-01

This study aimed to provide early insights into sacubitril/valsartan (sac/val) prescription patterns and the demographic and clinical characteristics of patients prescribed sac/val in primary care and cardiology settings in Germany. The study used electronic medical records from the German IMS® Disease Analyzer database. Patients with ≥1 prescription for sac/val during 1 January-31 December 2016 (n = 1643) were identified and followed up for ≤12 months from first prescription. Patients with ≥1 heart failure (HF) diagnosis during the study period, ≥1 additional HF diagnosis in the full history of the database, and ≥1 prescription for an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker and a β-blocker during the study period, without a prescription for sac/val (n = 25,264), were included as a reference cohort. Changes in clinical parameters in the 12 months before and after sac/val initiation were investigated and compared with those from the PARADIGM-HF study. The characteristics of patients prescribed sac/val more closely resembled those of patients enrolled in PARADIGM-HF (e.g. younger age, higher proportion of men than women, lower systolic blood pressure) than patients in the reference cohort. Most patients were initiated on the lowest dose of sac/val irrespective of clinical setting. Significant decreases (p < 0.001) in NT-proBNP and glycated haemoglobin levels were observed following sac/val initiation. Patients prescribed sac/val had similar baseline demographics and clinical characteristics to those from PARADIGM-HF, and most patients were initiated on the lowest dose. Changes in clinical parameters before and after initiation mirrored findings from the PARADIGM-HF study.

A socio-psychological investigation into limitations and incentives concerning reporting a clinically suspect situation aimed at improving early detection of classical swine fever outbreaks.

PubMed

Elbers, A R W; Gorgievski-Duijvesteijn, M J; van der Velden, P G; Loeffen, W L A; Zarafshani, K

2010-04-21

The aim of this study was to identify limitations and incentives in reporting clinically suspect situations, possibly caused by classical swine fever (CSF), to veterinary authorities with the ultimate aim to facilitate early detection of CSF outbreaks. Focus group sessions were held with policy makers from the veterinary authorities, and representatives of veterinary practitioners and pig farmer unions. Personal interviews with a small group of pig farmers and practitioners were held to check limitations raised and solutions proposed during the focus group sessions. An electronic questionnaire was mailed to pig farmers and practitioners to investigate perceptions and attitudes with respect to clinically suspect situations possibly caused by CSF. After triangulating the responses of veterinary authorities, veterinary practitioners and farmers, six themes emerged across all groups: (1) lack of knowledge on the early signs of CSF; (2) guilt, shame and prejudice; (3) negative opinion on control measures; (4) dissatisfaction with post-reporting procedures; (5) lack of trust in government bodies; (6) uncertainty and lack of transparency of reporting procedures. The following solutions to facilitate early detection of CSF were put forward: (a) development of a clinical decision-support system for vets and farmers, in order to get faster diagnosis and detection of CSF; (b) possibility to submit blood samples directly to the reference laboratory to exclude CSF in a clinical situation with non-specific clinical signs, without isolation of the farm and free of charge for the individual farmer; (c) decrease social and economic consequences of reporting CSF, for example by improving the public opinion on first reports; (d) better schooling of veterinary officers to deal with emotions and insecurity of farmers in the process after reporting; (e) better communication of rules and regulations, where to report, what will happen next; (f) up-to-date website with information and

Assessing progression of clinical reasoning through virtual patients: An exploratory study.

PubMed

Forsberg, Elenita; Ziegert, Kristina; Hult, Håkan; Fors, Uno

2016-01-01

To avoid test-driven learning, there have been discussions regarding the use of more formative assessments in health care education to promote students' deep learning. Feedback is important in formative assessment, but many students ignore it; therefore, interventions should be introduced which stimulate them to reflect on the new knowledge. The aim for this study was to explore if Virtual Patient (VP)-based formative assessments, in connection with self-evaluations, had an impact on postgraduate pediatric nursing students' development of clinical reasoning abilities. Students' self-evaluations served as the basis for measuring progress. Data was analysed using deductive content analysis. The findings showed a clear progression of the clinical reasoning ability of the students. After the first assessment, the students described feelings of uncertainty and that their knowledge gaps were exposed. At the mid-course assessment the awareness of improved clinical reasoning was obvious and the students were more certain of knowing how to solve the VP cases. In the final assessment, self-efficacy was expressed. VP-based assessments, in connection with self-evaluations, early in the education resulted in a gain of students' own identification of the concept of clinical reasoning, awareness of what to focus on during clinical practice and visualised expected clinical competence. Copyright © 2015 Elsevier Ltd. All rights reserved.

Anaerobic orbital cellulitis: a clinical and experimental study.

PubMed Central

Jedrzynski, M S; Bullock, J D; McGuire, T W; Elder, B L; Bullock, J D

1991-01-01

In this article we have reviewed the clinical and bacteriologic aspects of anaerobic orbital cellulitis and have presented six patients to illustrate these points. Physicians who treat patients with orbital cellulitis should have a high index of suspicion for possible instances involving anaerobes, so that appropriate management can be started early. To investigate this problem further, we created an animal model of anaerobic orbital cellulitis. This model may be useful in future studies of the pathogenesis and treatment of this serious and often devastating disease. Images FIGURE 1 FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 5 FIGURE 6 FIGURE 7 FIGURE 8 FIGURE 9 FIGURE 10 FIGURE 11 FIGURE 12 FIGURE 13 FIGURE 14 FIGURE 15 FIGURE 16 FIGURE 17 FIGURE 18 FIGURE 19 PMID:1808813