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1.  UCH-L1 and GFAP Serum Levels in Neonates with Hypoxic–Ischemic Encephalopathy: A Single Center Pilot Study 
Objective: We examined two potential biomarkers of brain damage in hypoxic–ischemic encephalopathy (HIE) neonates: glial fibrillary acidic protein (GFAP; a marker of gliosis) and ubiquitin C-terminal hydrolase L1 (UCH-L1; a marker of neuronal injury). We hypothesized that the biomarkers would be measurable in cord blood of healthy neonates and could serve as a normative reference for brain injury in HIE infants. We further hypothesized that higher levels would be detected in serum samples of HIE neonates and would correlate with brain damage on magnetic resonance imaging (MRI) and later developmental outcomes.?
Study Design: Serum UCH-L1 and GFAP concentrations from HIE neonates (n = 16) were compared to controls (n = 11). The relationship between biomarker concentrations of HIE neonates and brain damage (MRI) and developmental outcomes (Bayley-III) was examined using Pearson correlation coefficients and a mixed model design.
Result: Both biomarkers were detectable in cord blood from control subjects. UCH-L1 concentrations were higher in HIE neonates (p < 0.001), and associated with cortical injury (p < 0.055) and later motor and cognitive developmental outcomes (p < 0.05). The temporal change in GFAP concentrations during (from birth to 96 h of age) predicted motor developmental outcomes (p < 0.05) and injury to the basal ganglia and white matter.
Conclusion: Ubiquitin C-terminal hydrolase L1 and GFAP should be explored further as promising serum biomarkers of brain damage and later neurodevelopmental outcomes in neonates with HIE.
PMCID: PMC4271579  PMID: 25566179
biomarkers; HIE; UCH-L1; GFAP
2.  Stakeholder Perspectives on Barriers for Healthy Living for Low-Income African American Families 
Background: Childhood obesity is a growing problem for children in the United States, especially for children from low-income, African American families.
Objective: The purpose of this qualitative study was to understand facilitators and barriers to engaging in healthy lifestyles faced by low-income African American children and their families.
Methods: This qualitative study used semi-structured focus group interviews with eight African American children clinically identified as overweight or obese (BMI ≥ 85) and their parents. An expert panel provided insights in developing culturally appropriate intervention strategies.
Results: Child and parent focus group analysis revealed 11 barriers and no definitive facilitators for healthy eating and lifestyles. Parents reported confusion regarding what constitutes nutritional eating, varying needs of family members in terms of issues with weight, and difficulty in engaging the family in appropriate and safe physical activities; to name a few themes. Community experts independently suggested that nutritional information is confusing and, often, contradictory. Additionally, they recommended simple messaging and practical interventions such as helping with shopping lists, meal planning, and identifying simple and inexpensive physical activities.
Conclusion: Childhood obesity in the context of low-resource families is a complex problem with no simple solutions. Culturally sensitive and family informed interventions are needed to support low-income African American families in dealing with childhood obesity.
PMCID: PMC4255506  PMID: 25538931
childhood obesity; qualitative methods; poverty; African American; United States
4.  Evaluating an audit and feedback intervention for reducing antibiotic prescribing behaviour in general dental practice (the RAPiD trial): a partial factorial cluster randomised trial protocol 
Antibiotic prescribing in dentistry accounts for 9% of total antibiotic prescriptions in Scottish primary care. The Scottish Dental Clinical Effectiveness Programme (SDCEP) published guidance in April 2008 (2nd edition, August 2011) for Drug Prescribing in Dentistry, which aims to assist dentists to make evidence-based antibiotic prescribing decisions. However, wide variation in prescribing persists and the overall use of antibiotics is increasing.
RAPiD is a 12-month partial factorial cluster randomised trial conducted in NHS General Dental Practices across Scotland. Its aim is to compare the effectiveness of individualised audit and feedback (A&F) strategies for the translation into practice of SDCEP recommendations on antibiotic prescribing. The trial uses routinely collected electronic healthcare data in five aspects of its design in order to: identify the study population; apply eligibility criteria; carry out stratified randomisation; generate the trial intervention; analyse trial outcomes.
Eligibility was determined on contract status and a minimum level of recent NHS treatment provision. All eligible dental practices in Scotland were simultaneously randomised at baseline either to current audit practice or to an intervention group. Randomisation was stratified by single-handed/multi-handed practices. General dental practitioners (GDPs) working at intervention practices will receive individualised graphical representations of their antibiotic prescribing rate from the previous 14 months at baseline and an update at six months. GDPs could not be blinded to their practice allocation. Intervention practices were further randomised using a factorial design to receive feedback with or without: a health board comparator; a supplementary text-based intervention; additional feedback at nine months. The primary outcome is the total antibiotic prescribing rate per 100 courses of treatment over the year following delivery of the baseline intervention.
A concurrent qualitative process evaluation will apply theory-based approaches using the Consolidated Framework for Implementation Research to explore the acceptability of the interventions and the Theoretical Domains Framework to identify barriers and enablers to evidence-based antibiotic prescribing behaviour by GDPs.
RAPiD will provide a robust evaluation of A&F in dentistry in Scotland. It also demonstrates that linked administrative datasets have the potential to be used efficiently and effectively across all stages of an randomised controlled trial.
Trial registration
Current Controlled Trials ISRCTN49204710
PMCID: PMC4108126  PMID: 24758164
Prescribing; Antibiotics; Dental
6.  IQuaD dental trial; improving the quality of dentistry: a multicentre randomised controlled trial comparing oral hygiene advice and periodontal instrumentation for the prevention and management of periodontal disease in dentate adults attending dental primary care 
BMC Oral Health  2013;13:58.
Periodontal disease is the most common oral disease affecting adults, and although it is largely preventable it remains the major cause of poor oral health worldwide. Accumulation of microbial dental plaque is the primary aetiological factor for both periodontal disease and caries. Effective self-care (tooth brushing and interdental aids) for plaque control and removal of risk factors such as calculus, which can only be removed by periodontal instrumentation (PI), are considered necessary to prevent and treat periodontal disease thereby maintaining periodontal health. Despite evidence of an association between sustained, good oral hygiene and a low incidence of periodontal disease and caries in adults there is a lack of strong and reliable evidence to inform clinicians of the relative effectiveness (if any) of different types of Oral Hygiene Advice (OHA). The evidence to inform clinicians of the effectiveness and optimal frequency of PI is also mixed. There is therefore an urgent need to assess the relative effectiveness of OHA and PI in a robust, sufficiently powered randomised controlled trial (RCT) in primary dental care.
This is a 5 year multi-centre, randomised, open trial with blinded outcome evaluation based in dental primary care in Scotland and the North East of England. Practitioners will recruit 1860 adult patients, with periodontal health, gingivitis or moderate periodontitis (Basic Periodontal Examination Score 0–3). Dental practices will be cluster randomised to provide routine OHA or Personalised OHA. To test the effects of PI each individual patient participant will be randomised to one of three groups: no PI, 6 monthly PI (current practice), or 12 monthly PI.
Baseline measures and outcome data (during a three year follow-up) will be assessed through clinical examination, patient questionnaires and NHS databases.
The primary outcome measures at 3 year follow up are gingival inflammation/bleeding on probing at the gingival margin; oral hygiene self-efficacy and net benefits.
IQuaD will provide evidence for the most clinically-effective and cost-effective approach to managing periodontal disease in dentate adults in Primary Care. This will support general dental practitioners and patients in treatment decision making.
Trial registration
Protocol ID: ISRCTN56465715
PMCID: PMC4015981  PMID: 24160246
Oral hygiene advice; Scale and polish; Prevention; Toothbrushing advice; Periodontal instrumentation; RCT; Primary care
7.  Drug use and treatment success among gang and non-gang members in El Salvador: a prospective cohort study 
This article focuses on examining drug abuse treatment (DAT) in El Salvador highlighting gang vs. non-gang membership differences in drug use and treatment outcomes.
Cross-sectional and prospective cohort designs were employed to examine the study aims. The 19 centers that met the study’s inclusion criteria of one year or less in planned treatment offered varying treatment services: individual, group, family, and vocational therapy, dual diagnosis treatment, psychological testing, 12-step program, and outreach and re-entry aftercare. Most directors describe their treatment approach as “spiritual.” Data were collected from 625 patients, directors, and staff from the 19 centers at baseline, of which 34 patients were former gang members. Seventy-two percent (72%) of the former patients (448) were re-interviewed six-months after leaving treatment and 48% were randomly tested for drug use.
Eighty-nine percent (89%) of the DAT patients at baseline were classified as heavy alcohol users and 40% were using illegal drugs, i.e., crack, marijuana, cocaine, tranquilizers, opiates, and amphetamines. There were large decreases after treatment in heavy alcohol and illegal drug use, crime, and gang related risk activities. Gang members reported illegal drug use, crime, and gang related risk activity more than non-gang members, yet only 5% of the study participants were gang members; further, positive change in treatment outcomes among gang members were the same or larger as compared to non-gang members.
Alcohol use is the drug of choice among DAT patients in El Salvador with gang member patients having used illegal drugs more than non-gang members. The study shows that DAT centers successfully reduced the use of illegal drugs and alcohol among gang and non-gang members. Although our study could not include a control group, we believe that the DAT treatment centers in El Salvador contributed to producing this treatment success among former patients. These efforts should be continued and complemented by funding support from the Salvadoran government for DAT centers that obtain certification. In addition, tailored/alternative treatment modalities are needed for gang members in treatment for heavy drinking.
PMCID: PMC3682862  PMID: 23734635
Gangs; El Salvador; Drug abuse treatment; Outcome evaluation
8.  Examining human rights and mental health among women in drug abuse treatment centers in Afghanistan 
Denial of human rights, gender disparities, and living in a war zone can be associated with severe depression and poor social functioning, especially for female drug abusers. This study of Afghan women in drug abuse treatment (DAT) centers assesses (a) the extent to which these women have experienced human rights violations and mental health problems prior to entering the DAT centers, and (b) whether there are specific risk factors for human rights violations among this population. A total of 176 in-person interviews were conducted with female patients admitted to three drug abuse treatment centers in Afghanistan in 2010. Nearly all women (91%) reported limitations with social functioning. Further, 41% of the women indicated they had suicide ideation and 27% of the women had attempted suicide at least once 30 days prior to entering the DAT centers due to feelings of sadness or hopelessness. Half of the women (50%) experienced at least one human rights violation in the past year prior to entering the DAT centers. Risk factors for human rights violations among this population include marital status, ethnicity, literacy, employment status, entering treatment based on one’s own desire, limited social functioning, and suicide attempts. Conclusions stemming from the results are discussed.
PMCID: PMC3333825  PMID: 22532779
Afghanistan; women; human rights; mental health; drug abuse treatment
9.  RNA-seq: technical variability and sampling 
BMC Genomics  2011;12:293.
RNA-seq is revolutionizing the way we study transcriptomes. mRNA can be surveyed without prior knowledge of gene transcripts. Alternative splicing of transcript isoforms and the identification of previously unknown exons are being reported. Initial reports of differences in exon usage, and splicing between samples as well as quantitative differences among samples are beginning to surface. Biological variation has been reported to be larger than technical variation. In addition, technical variation has been reported to be in line with expectations due to random sampling. However, strategies for dealing with technical variation will differ depending on the magnitude. The size of technical variance, and the role of sampling are examined in this manuscript.
In this study three independent Solexa/Illumina experiments containing technical replicates are analyzed. When coverage is low, large disagreements between technical replicates are apparent. Exon detection between technical replicates is highly variable when the coverage is less than 5 reads per nucleotide and estimates of gene expression are more likely to disagree when coverage is low. Although large disagreements in the estimates of expression are observed at all levels of coverage.
Technical variability is too high to ignore. Technical variability results in inconsistent detection of exons at low levels of coverage. Further, the estimate of the relative abundance of a transcript can substantially disagree, even when coverage levels are high. This may be due to the low sampling fraction and if so, it will persist as an issue needing to be addressed in experimental design even as the next wave of technology produces larger numbers of reads. We provide practical recommendations for dealing with the technical variability, without dramatic cost increases.
PMCID: PMC3141664  PMID: 21645359
10.  The translation research in a dental setting (TRiaDS) programme protocol 
It is well documented that the translation of knowledge into clinical practice is a slow and haphazard process. This is no less true for dental healthcare than other types of healthcare. One common policy strategy to help promote knowledge translation is the production of clinical guidance, but it has been demonstrated that the simple publication of guidance is unlikely to optimise practice. Additional knowledge translation interventions have been shown to be effective, but effectiveness varies and much of this variation is unexplained. The need for researchers to move beyond single studies to develop a generalisable, theory based, knowledge translation framework has been identified.
For dentistry in Scotland, the production of clinical guidance is the responsibility of the Scottish Dental Clinical Effectiveness Programme (SDCEP). TRiaDS (Translation Research in a Dental Setting) is a multidisciplinary research collaboration, embedded within the SDCEP guidance development process, which aims to establish a practical evaluative framework for the translation of guidance and to conduct and evaluate a programme of integrated, multi-disciplinary research to enhance the science of knowledge translation.
Set in General Dental Practice the TRiaDS programmatic evaluation employs a standardised process using optimal methods and theory. For each SDCEP guidance document a diagnostic analysis is undertaken alongside the guidance development process. Information is gathered about current dental care activities. Key recommendations and their required behaviours are identified and prioritised. Stakeholder questionnaires and interviews are used to identify and elicit salient beliefs regarding potential barriers and enablers towards the key recommendations and behaviours. Where possible routinely collected data are used to measure compliance with the guidance and to inform decisions about whether a knowledge translation intervention is required. Interventions are theory based and informed by evidence gathered during the diagnostic phase and by prior published evidence. They are evaluated using a range of experimental and quasi-experimental study designs, and data collection continues beyond the end of the intervention to investigate the sustainability of an intervention effect.
The TRiaDS programmatic approach is a significant step forward towards the development of a practical, generalisable framework for knowledge translation research. The multidisciplinary composition of the TRiaDS team enables consideration of the individual, organisational and system determinants of professional behaviour change. In addition the embedding of TRiaDS within a national programme of guidance development offers a unique opportunity to inform and influence the guidance development process, and enables TRiaDS to inform dental services practitioners, policy makers and patients on how best to translate national recommendations into routine clinical activities.
PMCID: PMC2920875  PMID: 20646275
11.  Can't do it, won't do it! Developing a theoretically framed intervention to encourage better decontamination practice in Scottish dental practices 
Guidance on the cleaning of dental instruments in primary care has recently been published. The aims of this study are to determine if the publication of the guidance document was enough to influence decontamination best practice and to design an implementation intervention strategy, should it be required.
A postal questionnaire assessing current decontamination practice and beliefs was sent to a random sample of 200 general dental practitioners.
Fifty-seven percent (N = 113) of general dental practitioners responded. The survey showed large variation in what dentists self-reported doing, perceived as necessary or practical to do, were willing to do, felt able to do, as well as what they planned to change. Only 15% self-reported compliance with the five key guideline-recommended individual-level decontamination behaviours; only 2% reported compliance with all 11 key practice-level behaviours. The results also showed that our participants were almost equally split between dentists who were completely unmotivated to implement best decontamination practice or else highly motivated. The results suggested there was scope for further enhancing the implementation of decontamination guidance, and that an intervention with the greatest likelihood of success would require a tailored format, specifically targeting components of the theory of planned behaviour (attitude, perceived behavioural control, intention) and implementation intention theory (action planning).
Considerable resources are devoted to encouraging clinicians to implement evidence-based practice using interventions with erratic success records, or no known applicability to a specific clinical behaviour, selected mainly by means of researchers' intuition or optimism. The methodology used to develop this implementation intervention is not limited to decontamination or to a single segment of primary care. It is also in accordance with the preliminary stages of the framework for evaluating complex interventions suggested by the medical research council. The next phases of this work are to test the intervention feasibility and evaluate its effectiveness in a randomised control trial.
PMCID: PMC2701915  PMID: 19500342
12.  Therapeutic community drug treatment success in Peru: a follow-up outcome study 
The purpose of this study was to assess the impact of drug abuse treatment in Peru that used the therapeutic community (TC) model. Program directors and several staff members from all study treatment facilities received two to eight weeks of in-country training on how to implement the TC treatment model prior to the follow-up study.
This outcome study involved 33 TC treatment facilities and 509 former clients in Lima and other cities in five providences across Peru. A retrospective pre-test (RPT) follow-up design was employed in which 30-day use of illegal drugs and alcohol to intoxication was measured at baseline retrospectively, at the same time of the six-month follow-up. In-person interview data were collected from directors of 73 percent of the eligible TC organizations in January and February 2003 and from former 58 percent of the eligible TC former clients between October 2003 and October 2004. Drug testing was conducted on a small sample of former clients to increase the accuracy of the self-reported drug use data.
Medium to large positive treatment effects were found when comparing 30-day illegal drug and alcohol use to intoxication before and six months after receiving treatment. As a supplemental analysis, we assumed the 42 percent of the former clients who were not interviewed at the six month assessment had returned to drugs. These results showed medium treatment effects as well. Hierarchical Generalized Linear Modeling (HGLM) results showed higher implementation fidelity, less stigma after leaving treatment, and older clients, singly or in combination are key predictors of treatment success.
This study found that former clients of drug and alcohol treatment in facilities using the TC model reported substantial positive change in use of illegal drugs and alcohol to intoxication at a six-month follow-up. The unique contribution of this study is that the results also suggest attention should be placed on the importance of implementing the TC drug abuse treatment model with fidelity. Further, the results strongly suggest that TC drug abuse treatment programs should incorporate follow-up activities that attempt to neutralize community negative reactions (perceived stigma) independent of other factors.
PMCID: PMC2631528  PMID: 19055774
13.  Laboratory Safety Monitoring of Chronic Medications in Ambulatory Care Settings 
To evaluate laboratory safety monitoring in patients taking selected chronic prescription drugs.
Retrospective study using 1999–2001 claims data to calculate rates of missed laboratory tests (potential laboratory monitoring errors). Eleven drugs/drug groups and 64 laboratory tests were evaluated.
Two staff/network model health maintenance organizations.
Continuously enrolled health plan members age≥19 years taking ≥1 chronic medications.
Among patients taking chronic medications (N=29,823 in 1999, N=32,423 in 2000, and N=36,811 in 2001), 47.1% in 1999, 45.0% in 2000, and 44.0% in 2001 did not receive ≥1 test recommended for safety monitoring. Taking into account that patients were sometimes missing more than 1 test for a given drug and that patients were frequently taking multiple drugs, the rate of all potential laboratory monitoring errors was 849/1,000 patients/year in 1999, 810/1,000 patients/year in 2000, and 797/1,000 patients/year in 2001. Rates of potential laboratory monitoring errors varied considerably across individual drugs and laboratory tests.
Lapses in laboratory monitoring of patients taking selected chronic medications were common. Further research is needed to determine whether, and to what extent, this failure to monitor patients is associated with adverse clinical outcomes.
PMCID: PMC1490088  PMID: 15857489
patient safety; laboratory testing; chronic medications; medical errors; medication safety
14.  A randomised controlled trial to explore attitudes to routine scale and polish and compare manual versus ultrasonic scaling in the general dental service in Scotland [ISRCTN99609795] 
BMC Oral Health  2005;5:3.
To investigate, within general dental practice, patients' and vocational dental practitioners' (VDP) attitudes towards the benefits and costs of a simple scale and polish and to compare the experience of using manual versus ultrasonic instruments to scale teeth.
28 VDPs and 420 patients participated. Patients were randomly allocated to either group. Patients' and VDPs' attitudes towards, and experience of, the scale and polish were elicited by means of self-administered questionnaires.
The majority of patients (99%) believed a scale and polish was beneficial. VDPs considered ultrasonic treatment to be appropriate on significantly more occasions than they did for manual scale and polish (P < 0.001). Patient discomfort: with ultrasonic scaling 69.2% felt 'a little uncomfortable' or worse compared with 60% of those undergoing manual treatment (P = 0.072). VDPs considered treatment charges were appropriate for 77% of patients.
Routine scaling and polishing is considered beneficial by both patients and vocational trainees. The majority of patients, regardless of treatment method, experience some degree of discomfort when undergoing a scale and polish. VDPs showed a preference for the ultrasonic treatment method.
PMCID: PMC1183219  PMID: 15975140
15.  Processes Involved in Reading Imaging Studies: Workflow Analysis and Implications for Workstation Development  
Journal of Digital Imaging  2003;15(3):171-177.
Software development for imaging workstations has lagged behind hardware availability. To guide development and to analyze work flow involved in interpretation of cross-sectional imaging studies, we assessed the cognitive and physical processes. We observed the performance and interpretation of body computed tomography (CT scans and recorded the events that occurred during this process. We studied work flow using a bottleneck analysis. Twenty-four of a total of 54 cases (44%) involved comparing the images with those of prior scans. Forty-seven of 54 scans (87%) were viewed using windows other than soft tissue, or compared with precontrast scans. In 46 cases (85%), the interpretation stopped to return to a previous level for review. Measurement of lesions was performed in 24 of 54 (44%) cases, and in 15 (63%) of these cases, measurements were taken of lesions on old studies for comparison. Interpretation was interrupted in 14 of 54 cases (26%) by referring clinicians desiring consultation. The work flow analysis showed film folder retrieval by the film room to be the bottleneck for interpretation by film. For picture archiving and communication system (PACS) reading, the CT examination itself proved to be the bottleneck. We conclude that workstations for CT interpretation should facilitate movement within scans, comparison with prior examinations, and measuring lesions on these scans. Workstation design should consider means of optimizing time currently not used between interpretation sessions, minimizing interruptions and providing more automated functions currently requiring physician interaction.
PMCID: PMC3613257  PMID: 12641097
16.  Processes involved in reading imaging studies: Workflow analysis and implications for workstation development 
Journal of Digital Imaging  1997;10(1):40-45.
Software development for imaging workstations has lagged behind hardware availability. To guide development and to analyze work flow involved in interpretation of cross-sectional imaging studies, we assessed the cognitive and physical processes. We observed the performance and interpretation of body computed tomography (CT) scans and recorded the events that occurred during this process. We studied work flow using a bottleneck analysis. Twenty-four of a total of 54 cases (44%) involved comparing the images with those of prior scans. Forty-seven of 54 scans (87%) were viewed using windows other than soft tissue, or compared with precontrast scans. In 46 cases (85%), the interpretation stopped to return to a previous level for review. Measurement of lesions was performed in 24 of 54 (44%) cases, and in 15 (63%) of these cases, measurements were taken of lesions on old studies for comparison. Interpretation was interrupted in 14 of 54 cases (26%) by referring clinicians desiring consultation. The work flow analysis showed film folder retrieval by the film room to be the bottleneck for interpretation by film. For picture archiving and communication system (PACS) reading, the CT examination itself proved to be the bottleneck. We conclude that workstations for CT interpretation should facilitate movement within scans, comparison with prior examinations, and measuring lesions on these scans. Workstation design should consider means of optimizing time currently not used between interpretation sessions, minimizing interruptions and providing more automated functions currently requiring physician interaction.
PMCID: PMC3453185  PMID: 9147527
PACS; workstation design; time and motion analysis; radiology; computers
17.  Effects of Physicochemical Factors and Bacterial Colony Morphotype on Association of Vibrio vulnificus with Hemocytes of Crassostrea virginica 
Vibrio vulnificus is a naturally occurring marine bacterium that causes invasive disease of immunocompromised humans following the consumption of raw oysters. It is a component of the natural microbiota of Gulf Coast estuaries and has been found to inhabit tissues of oysters, Crassostrea virginica (Gmelin 1791). The interaction of V. vulnificus with oyster host defenses has not been reported in detail. We examined the interaction of V. vulnificus with phagocytic oyster hemocytes as a function of time, temperature, bacterial concentration, pretreatment with hemolymph, and V. vulnificus translucent and opaque colony morphotypes. Within these experimental parameters, the results showed that the association of V. vulnificus with hemocytes increased with time, temperature, and initial V. vulnificus/hemocyte ratio. Pretreatment of V. vulnificus with serum or an increased serum concentration did not enhance V. vulnificus-hemocyte associations, a result suggesting the absence of opsonic activity. More than 50% of hemocytes bound the translucent, avirulent morphotype, whereas 10 to 20% were associated with the opaque, virulent form, a result indicating that the degree of encapsulation was related to resistance to phagocytosis, as previously described for mammalian phagocytes. Understanding these cellular interactions may, in part, explain the persistence of V. vulnificus in oyster tissues and the ecology of V. vulnificus in estuarine environments.
PMCID: PMC202230  PMID: 16348903

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