Ebola Virus Disease Sensitization: Community-Driven Efforts in Sierra Leone.

The 2014-2016 West Africa Ebola outbreak was the largest in history, resulting in approximately 11,000 deaths. Despite the outbreak's eventual end, national and international health sensitization and containment efforts were subject to criticism. This study investigates disease-related knowledge and beliefs, as well as trusted sources of health information among EVD-survivors and their family members, highlighting the importance of community-informed public health responses. Participants (n = 134) were adults who were either EVD-infected, affected families/caregivers, or community leaders. In-depth interviews and focus groups explored EVD-related experiences, including health effects, stigma, and community relationships. Using a grounded theory and thematic content analysis approach, transcripts were coded for evidence of health sensitization, as well as compliance with mitigation measures and trusted sources of information. Participants displayed a high level of knowledge around EVD and reported compliance with mandated and personal prevention measures. Levels of health sensitization and subsequent reintegration of survivors were reported to be largely the products of community-based efforts, rather than the top-down, national public health response. Primary sources of trusted information included EVD survivors acting as peer educators; local leaders; and EVD sensitization by community health workers. This study highlights the importance of a community-based response for increasing the effectiveness of public health campaigns. Participants expressed that relying on the experiences of trusted cultural insiders led to a deeper understanding of Ebola compared to top-down public health campaigns, and helped infected and affected community members reintegrate. Future public health efforts should incorporate community-based participatory approaches to address infectious disease outbreaks.

A scoping review of dental practitioners' perspectives on perceived barriers and facilitators to preventive oral health care in general dental practice.

BACKGROUND: Oral health has an important role in the general health and well-being of individuals. Dental teams are ideally placed to support patients in preventing ill-health. Understanding the barriers and facilitators to the adoption, promotion and facilitation of preventive advice and treatment is key to improving oral health services. The Theoretical Domains Framework (TDF) is a useful psychological framework to help identify individual, interpersonal and environmental issues which could be impacting clinicians' ability to provide preventive advice and care. The aim of this review was to identify the perceived barriers and facilitators to preventive oral health care from the perspectives of the oral healthcare team within the general dental practice. METHODS: A search strategy was developed, piloted, and run in: Medline via Ovid, PsycInfo, Web of Science, SCOPUS, EMBASE, Conference Proceedings Citation Index- Science, Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews and followed PRISMA guidelines. Identified records were screened independently by two researchers. Data were coded using the Theoretical Domains Framework (TDF) and analysed using narrative data synthesis. RESULTS: 5610 papers were identified, and 19 included in this review. Thirteen papers focussed on dentists. Of the 106 items mapped onto the TDF, 48 were facilitators. The domains most frequently represented were, environmental context and resources, beliefs about consequences, social professional role and identity, skills, beliefs about capabilities and knowledge. Six studies focussed on dental hygienists. There were 47 items mapped onto the TDF, 18 were facilitators. The domains most frequently represented were environmental context and resources, social influences, beliefs about consequences and knowledge. CONCLUSIONS: The review identified that the delivery of preventive activities did not focus solely on the patient and dental professional interaction as many previous studies have highlighted. The review found that multiple factors influence whether prevention is delivered to patients. The largest barrier and facilitator for the dental professionals identified in this review was the environmental context and resources. Further research is needed to evaluate the effectiveness of interventions that aim to promote preventive oral health care in primary care settings to understand whether they address the barriers identified in this review.

Explanatory variables for women's increased risk for mental health problems in Vietnam.

PURPOSE: The United Nations Sustainable Development Goals include gender equality for women, including health, as one of seventeen targets. Within this broad domain, a wide range of research indicates that being female is associated with increased risk for mental health problems, particularly in low- and middle-income countries (LMIC). What is less clear are the trans-diagnostic demographic and environmental risk factors in LMIC that may underlie this increased risk. The purpose of the present study was to identify socio-economic and related disadvantages potentially underlying increased risk for women for mental health-related problems in the Southeast Asian LMIC of Vietnam. METHODS: Nine hundred and seventy-seven adults were randomly selected from five provinces in central coastal Vietnam. Individuals were assessed cross-sectionally for depression (PHQ-9), anxiety (GAD-7), post-traumatic stress disorder symptoms (PDS), somatic syndrome (SCL-90-R), alcohol dependence (ICD-10), functional impairment (PDS life functioning section), and self-perceived general physical health (SF-36). Trans-diagnostic risk factors assessed included financial stress, education level, exposure to traumatic events, and others. RESULTS: At the multivariate level, gender explained approximately 5% of the variance in mental health symptoms, with women significantly higher in all mental health domains except alcohol dependency. The trans-diagnostic risk factors explained slightly over half of this variance, with financial stress and lower education levels the two strongest individual explanatory variables for women's increased risk for mental health problems. CONCLUSIONS: These results suggest that support for gender equality including in regard to economic stability and education may be critical for reducing broad gender disparities in mental health functioning.

Barriers and facilitators to health visiting teams delivering oral health promotion to families of young children: a mixed methods study with vignettes.

OBJECTIVE: To explore the potential barriers and facilitators to health visiting (HV) teams delivering oral health promotion during the 9-12-month old child mandated visit in Ealing, England. BACKGROUND: HV schemes and their counterparts worldwide share similar priorities to discuss oral health at 6-12 months of age. The HV programme in England stipulates at 9-12 months old, diet and dental health should be discussed. HVs believe dental decay is important however oral health knowledge is varied. Further, little is understood about what drives HVs to deliver oral health advice. An appropriate theoretical model to explore these factors is the Theoretical Domains Framework (TDF). METHODS: An opportunistic sample of HV team members was drawn from three hubs to allow for maximum variation. First, participants completed a questionnaire to establish baseline knowledge. Secondly, participants were invited to take part in focus groups (FGs) with vignettes. Thirdly, face-to-face interviews were conducted. FGs were subject to thematic analysis and the interviews to framework analysis. RESULTS: Thirty-six participants provided written informed consent and completed baseline questionnaires. Three FGs were conducted with an average of seven participants (n=21) followed by 13 interviews. Perceived facilitators: good levels of knowledge and skills, sense of professional role, emotions, belief in capability, organisational structure and resources. Perceived barriers: gaps in knowledge, conflicting advice from other professionals, conflicting issues for parents/ carers, use of interpreters. CONCLUSIONS: These findings can be harnessed to support oral health promotion delivered by HV teams.

Assessing the perceived impact of post Minamata amalgam phase down on oral health inequalities: a mixed-methods investigation.

BACKGROUND: Data from countries that have implemented a complete phase out of dental amalgam following the Minamata agreement suggest increased costs and time related to the placement of alternatives with consumers absorbing the additional costs. This aim of this study was to investigate the impact of a complete phase out of dental amalgam on oral health inequalities in particular for countries dependent on state run oral health services. METHODS: A mixed methods component design quantitative and qualitative study in the United Kingdom. The quantitative study involved acquisition and analysis of datasets from NHS Scotland to compare trends in placement of dental amalgam and a survey of GDPs in Yorkshire, UK. The qualitative study involved analysis of the free text of the survey and a supplementary secondary analysis of semi-structured interviews and focus groups with GDPs (private and NHS), dental school teaching leads and NHS dental commissioners to understand the impact of amalgam phase down on oral health inequalities. RESULTS: Time-trends for amalgam placement showed that there was a significant (p < 0.05) reduction in amalgam use compared with composites and glass ionomers. However dental amalgam still represented a large proportion (42%) of the restorations (circa 1.8 million) placed in the 2016-2017 financial year. Survey respondents suggest that direct impacts of a phase down were related to increased costs and time to place alternative restorations and reduced quality of care. This in turn would lead to increased tooth extractions, reduced access to care and privatisation of dental services with the greatest impact on deprived populations. CONCLUSION: Amalgam is still a widely placed material in state run oral health services. The complete phase down of dental amalgam poses a threat to such services and threatens to widen oral health inequalities. Our data suggest that a complete phase out is not currently feasible unless appropriate measures are in place to ensure cheaper, long-lasting and easy to use alternatives are available and can be readily adopted by primary care oral health providers.

Identifying the barriers and facilitators for homeless people to achieve good oral health.

OBJECTIVE: A qualitative exploration of the barriers and facilitators for people experiencing homelessness achieving good oral health. PARTICIPANTS: Adults using two homeless centres in Leeds. METHODS: Focus group discussions were convened with homeless people using support services. Both an inductive and deductive approach to data analysis was taken. Themes were identified and then a framework applied to analysis using Nvivo software. RESULTS: Three focus group discussions with 16 participants were conducted with people experiencing homelessness. The barriers identified were insufficient information on local dental services, negative attitudes of oral health professionals, low priority of dental care, anxiety and cost of dental treatments. Facilitators included single dental appointments, accessible dental locations and being treated with respect. CONCLUSIONS: Despite the barriers that prevent people experiencing homelessness from maintaining and improving their oral health, the participants were aware that they needed oral healthcare and requested that dental services were made available to them and were accessible in line with their socioeconomic status and needs.

Barriers and facilitators for prevention in Danish dental care.

Objective: To explore barriers and facilitators to oral disease prevention in Danish dental care from a multi-stakeholder perspective. Methods: Eleven semi-structured focus groups and interviews about Danish oral healthcare were conducted with 27 stakeholders (general public, dental teams, dental policy makers) in Copenhagen. Transcripts were analyzed using deductive thematic analysis independently by KR and HL, supervised by JC and KVC. Results: Seven broad themes were identified, including both barriers and facilitators: Knowledge and attitudes, Education and training, Regulation, Incentivization, Multidisciplinary approach, Access to care and the Dental professional-patient relationship. Whilst all themes were relevant to each group of stakeholders, the salient driver within each theme was different for each group. Conclusions: Stakeholder perspectives on the Danish Oral health care system suggest the following are important features for a preventively focused system: (a) Involving all stakeholders in oral healthcare planning. (b) Securing sufficient and ongoing briefing regarding disease prevention for all stakeholders. (c) Regulatory support and creation of incentives to promote and facilitate implementation of disease prevention. (d) Appropriate prevention for disadvantaged groups within society which may be possible to a higher degree by means of multidisciplinary collaboration. (e) Personal relations between the patient and the professional based on mutual trust.

Feeding fodder beet (Beta vulgaris L.) with either barley straw or pasture silage to non-lactating dairy cows.

AIMS: To determine the suitability of diets containing either approximately 85% fodder beet (Beta vulgaris L.) with barley straw or 65% fodder beet with pasture silage when fed to non-lactating dairy cows, by measuring intakes, digestibility, rumen function including microbial growth, and N excretion. METHODS: Holstein-Friesian cows fitted with permanent rumen fistulae were fed either 65% fodder beet with pasture silage (Silage; n=8) or 85% fodder beet with barley (Hordeum vulgare L.) straw (Straw; n=8) in an indoor facility over a 9-day period, for measurement of intakes, digestibility, rumen function and urine production. The cows were adapted to the diets over 2 weeks before the indoor measurements. Feed was available for about 6 hours/day, as practiced commercially for wintering non-lactating cows. RESULTS: Five cows fed the Straw diet had to be removed from the trial because of acute acidosis; four on Day 1 of the measurement period and one on Day 7. One cow allocated to the Silage diet refused to eat fodder beet bulbs and was also removed from the trial. Two cows fed the Silage diet were also treated for acidosis. DM intakes were lower with the Straw than Silage diets (6.4 (SE 0.4) vs. 8.3 (SE 0.5) kg/day) and organic matter (OM) digestibility was lower with the Straw than Silage diets (77 (SE 1) vs. 83 (SE 1) g/100g). The N content of the two diets was 1.14 and 1.75 g/100 g DM and there was a net loss of N by cows fed the Straw diet (-22.7 (SE 7) g/day). Rumen microbial N production was much lower in cows fed the Straw than the Silage diet (6.6 (SE 1.3) vs. 15.8 (SE 0.7) g microbial N/kg digestible OM intake). Concentrations of ammonia in rumen liquid collected on Days 5-6 were below detection limits (<0.1 mmol/L) in 36/48 (75%) samples collected from cows fed the Straw diet and in 27/48 (56%) cows fed the Silage diet. Mean urinary N excretion was lower in cows fed the Straw than the Silage diet (52.0 (SE 5.8) vs. 87.7 (SE 5.9) g/day). CONCLUSION AND CLINICAL RELEVENCE: An over-wintering diet for dry cows comprising about 65% fodder beet with 35% pasture silage provided adequate nutrition, although there was some risk of acidosis. In contrast, the diet containing about 85% fodder beet with barley straw resulted in lower DM intakes, poor rumen function, negative N balance so that both nutrition and welfare were compromised.

Assessing Mental Healthcare Worker Experiences of Workplace Fairness and Organizational Value: A National Survey of Peer-Support Specialists.

BACKGROUND: Peer-support specialists-individuals with diagnosed mental illnesses who provide support services to other adults with diagnosed mental health issues-often feel stigmatized and undervalued at work, leading to negative personal- and job-related outcomes. Given their important link to positive service user outcomes, this study assessed how peer-support specialists perceive fairness and feel valued in the workplace. METHODS: Peer-support specialists (N = 274) were recruited online from peer-support specialist listservs, social media groups, and patient-run organizations to take a cross-sectional survey that included a 14-item scale on how workplace fairness relates to job satisfaction and four questions on how valued they felt by administrators, clinicians, the people they serve, and fellow peer-support specialists. Descriptive and bivariate statistics were used to assess total scores and differences by gender and race. FINDINGS: Ranging in age from 20 to 77 years and identifying predominantly as White (81.0%) and female (62.9%), respondents noted that fair practices in the workplace would increase their job satisfaction, with no significant differences observed by gender or race. Most peer-support specialists felt valued by the people they serve (97.1%) and fellow peer-support specialists (92.7%). However, fewer reported feeling valued by administrators (64.6%) and clinicians (60.6%). CONCLUSIONS/APPLICATION TO PRACTICE: Peer-support specialists value fairness at the workplace and feel undervalued by some staff. This study highlights peer-support specialists' important role in behavioral health services and suggests that healthcare professionals, including occupational health specialists, are important stakeholders in creating fairer workplaces and increasing peer-support specialists' sense of being valued, leading to improved personal and organizational outcomes.

SciComm Optimizer for Policy Engagement: a randomized controlled trial of the SCOPE model on state legislators' research use in public discourse.

BACKGROUND: While prior work has revealed conditions that foster policymakers' use of research evidence, few studies have rigorously investigated the effectiveness of theory-based practices. Specifically, policymakers are most apt to use research evidence when it is timely, relevant, brief, and messaged appropriately, as well as when it facilitates interactive engagement. This study sought to experimentally evaluate an enhanced research dissemination intervention, known as the SciComm Optimizer for Policy Engagement (SCOPE), implemented during the COVID-19 pandemic among US state legislators. METHODS: State legislators assigned to health committees and their staff were randomized to receive the SCOPE intervention. This involved providing academic researchers with a pathway for translating and disseminating research relevant to current legislative priorities via fact sheets emailed directly to officials. The intervention occurred April 2020-March 2021. Research language was measured in state legislators' social media posts. RESULTS: Legislators randomized to receive the intervention, relative to the control group, produced 24% more social media posts containing research language related to COVID-19. Secondary analyses revealed that these findings were driven by two different types of research language. Intervention officials produced 67% more COVID-related social media posts referencing technical language (e.g., statistical methods), as well as 28% more posts that referenced research-based concepts. However, they produced 31% fewer posts that referenced creating or disseminating new knowledge. CONCLUSIONS: This study suggests that strategic, targeted science communication efforts may have the potential to change state legislators' public discourse and use of evidence. Strategic science communication efforts are particularly needed in light of the role government officials have played in communicating about the pandemic to the general public.

Social distancing, community stigma, and implications for psychological distress in the aftermath of Ebola virus disease.

BACKGROUND: The 2013-2016 Ebola virus disease (EVD) epidemic resulted in more infections and deaths than all prior outbreaks in the 40-year history of this virus combined. This study examines how experiences of EVD infection, and preventive measures such as social distancing, were linked to experiences of stigma and social exclusion among those reintegrating into their communities. METHODS: Key informant interviews (n = 42) and focus group discussions (n = 27) were conducted in districts with a high prevalence of EVD and representing geographical and ethnic diversity (n = 228 participants). The final sample was composed of adults (52%) and children (48%) who were EVD-infected (46%) and -affected (42%) individuals, and community leaders (12%). Data were coded using a Grounded Theory approach informed by Thematic Content Analysis, and analyzed using NVivo. Interrater reliability was high, with Cohen's κ = 0.80 or higher. FINDINGS: Participants described two main sources of EVD-related stress: isolation from the community because of social distancing and other prevention measures such as quarantine, and stigma related to infected or affected status. Participants linked experiences of social isolation and stigma to significant distress and feelings of ostracization. These experiences were particularly pronounced among children. Sources of support included community reintegration over time, and formal community efforts to provide education and establish protection bylaws. INTERPRETATION: This study found that social distancing and EVD-related stigma were each prominent sources of distress among participants. These results suggest that isolation because of infection, and the enduring stigmatization of infected individuals and their families, demand coordinated responses to prevent and mitigate additional psychosocial harm. Such responses should include close engagement with community leaders to combat misinformation and promote community reintegration.

Whose Responsibility Is It Anyway? Exploring Barriers to Prevention of Oral Diseases across Europe.

INTRODUCTION: Dental caries, gum disease, and tooth loss are all preventable conditions. However, many dental care systems remain treatment oriented rather than prevention oriented. This promotes the treatment of oral diseases over preventive treatments and advice. Exploring barriers to prevention and understanding the requirements of a paradigm shift are the first steps toward delivering quality prevention-focused health care. OBJECTIVES: To qualitatively explore perceived barriers and facilitators to oral disease prevention from a multistakeholder perspective across 6 European countries. METHODS: A total of 58 interviews and 13 focus groups were undertaken involving 149 participants from the United Kingdom, Denmark, Germany, the Netherlands, Ireland, and Hungary. Interviews and focus groups were conducted in each country in its native language between March 2016 and September 2017. Participants were patients (n = 50), dental team members (n = 39), dental policy makers(n = 33), and dental insurers (n = 27). The audio was transcribed, translated, and analyzed via deductive thematic analysis. RESULTS: Five broad themes emerged that were both barriers and facilitators: dental regulation, who provides prevention, knowledge and motivation, trust, and person-level factors. Each theme was touched on in all countries; however, cross-country differences were evident surrounding the magnitude of each theme. CONCLUSION: Despite the different strengths and weaknesses among the systems, those who deliver, organize, and utilize each system experience similar barriers to prevention. The findings suggest that across all 6 countries, prevention in oral health care is hindered by a complex interplay of factors, with no particular dental health system offering overall greater user satisfaction. Underlying the themes were sentiments of blame, whereby each group appeared to shift responsibility for prevention to other groups. To bring about change, greater teamwork is needed in the commissioning of prevention to engender its increased value by all stakeholders within the dental system. KNOWLEDGE TRANSFER STATEMENT: The results from this study provide an initial first step for those interested in exploring and working toward the paradigm shift to preventive focused dentistry. We also hope that these findings will encourage more research exploring the complex relationship among dental stakeholders, with a view to overcoming the barriers. In particular, these findings may be of use to dental public health researchers, dentists, and policy makers concerned with the prevention of oral diseases.

Stimulation of the rat subthalamic nucleus is neuroprotective following significant nigral dopamine neuron loss.

Deep brain stimulation of the subthalamic nucleus (STN-DBS) is efficacious in treating the motor symptoms of Parkinson's disease (PD). However, the impact of STN-DBS on the progression of PD is unknown. Previous preclinical studies have demonstrated that STN-DBS can attenuate the degeneration of a relatively intact nigrostriatal system from dopamine (DA)-depleting neurotoxins. The present study examined whether STN-DBS can provide neuroprotection in the face of prior significant nigral DA neuron loss similar to PD patients at the time of diagnosis. STN-DBS between 2 and 4 weeks after intrastriatal 6-hydroxydopamine (6-OHDA) provided significant sparing of DA neurons in the SN of rats. This effect was not due to inadvertent lesioning of the STN and was dependent upon proper electrode placement. Since STN-DBS appears to have significant neuroprotective properties, initiation of STN-DBS earlier in the course of PD may provide added neuroprotective benefits in addition to its ability to provide symptomatic relief.

The synaptic impact of the host immune response in a parkinsonian allograft rat model: Influence on graft-derived aberrant behaviors.

Graft-induced dyskinesias (GIDs), side-effects found in clinical grafting trials for Parkinson's disease (PD), may be associated with the withdrawal of immunosuppression. The goal of this study was to determine the role of the immune response in GIDs. We examined levodopa-induced dyskinesias (LIDs), GID-like behaviors, and synaptic ultrastructure in levodopa-treated, grafted, parkinsonian rats with mild (sham), moderate (allografts) or high (allografts plus peripheral spleen cell injections) immune activation. Grafts attenuated amphetamine-induced rotations and LIDs, but two abnormal motor syndromes (tapping stereotypy, litter retrieval/chewing) emerged and increased with escalating immune activation. Immunohistochemical analyses confirmed immune activation and graft survival. Ultrastructural analyses showed increases in tyrosine hydroxylase-positive (TH+) axo-dendritic synapses, TH+ asymmetric specializations, and non-TH+ perforated synapses in grafted, compared to intact, striata. These features were exacerbated in rats with the highest immune activation and correlated statistically with GID-like behaviors, suggesting that immune-mediated aberrant synaptology may contribute to graft-induced aberrant behaviors.

Acquired Resistance to Poly (ADP-ribose) Polymerase Inhibitor Olaparib in BRCA2-Associated Prostate Cancer Resulting From Biallelic BRCA2 Reversion Mutations Restores Both Germline and Somatic Loss-of-Function Mutations.

PARP1/2 inhibitors are effective against BRCA2-deficient tumors. The PARP inhibitor (PARPi) olaparib received FDA breakthrough designation for treatment of metastatic castration-resistant prostate cancers (CRPC) carrying mutations in BRCA1/2 or ATM genes. Emergent resistance to PARPi has been associated with tumor-specific BRCA2 mutations that revert the normal open reading frame rescuing homologous recombination. We describe a case of metastatic CRPC with germline BRCA2 mutation with acquired resistance to olaparib related to biallelic BRCA2 reversion mutations of both the germline and somatic loss of function alleles detected by circulating tumor DNA testing. We also summarize a retrospective analysis of 1,534 prostate cancer cases with ctDNA analysis showing a 1.6% incidence of germline BRCA2 mutations. Within the germline BRCA2-positive cases exposed to platinum chemotherapy or PARP inhibition, the prevalence of reversion mutations was 40%. This report documents the frequency of reversion mutations in a large cohort of prostate cancer patients carrying of BRCA mutations. It also shows the potential utility of ctDNA analyses for early detection of reversion mutation driving tumor resistance.

BDNF in the Aged Brain: Translational Implications for Parkinson's Disease.

Brain Derived Neurotrophic Factor (BDNF) is a member of the neurotrophin family of secreted growth factors. BDNF signaling is known to exert both chronic, pro-survival effects related to gene expression and protein synthesis ("canonical signaling"), and acute effects as a modulator of neurotransmission ("non-canonical signaling"). BDNF has received a great deal of attention for its role in neurodegenerative diseases including Huntington's Disease (HD), Alzheimer's Disease (AD), and Parkinson's Disease (PD) and has been extensively reviewed elsewhere in this regard (e.g., [1-6]). However aging-related changes in BDNF function and expression have been studied only rarely, with the majority of studies characterizing changes in structures such as the hippocampus and neocortex. In this review, we attempt to briefly summarize the extent of the existing literature on age-related BDNF changes, and discuss the relevance of these changes as a factor potentially impacting therapeutics in aged parkinsonian subjects.

Shaping dental contract reform: a clinical and cost-effective analysis of incentive-driven commissioning for improved oral health in primary dental care.

OBJECTIVE: To evaluate the clinical and cost-effectiveness of a new blended dental contract incentivising improved oral health compared with a traditional dental contract based on units of dental activity (UDAs). DESIGN: Non-randomised controlled study. SETTING: Six UK primary care dental practices, three working under a new blended dental contract; three matched practices under a traditional contract. PARTICIPANTS: 550 new adult patients. INTERVENTIONS: A new blended/incentive-driven primary care dentistry contract and service delivery model versus the traditional contract based on UDAs. MAIN OUTCOME MEASURES: Primary outcome was as follows: percentage of sites with gingival bleeding on probing. Secondary outcomes were as follows: extracted and filled teeth (%), caries (International Caries Detection and Assessment System (ICDAS)), oral health-related quality of life (Oral Health Impact Profile-14 (OHIP-14)). Incremental cost-effective ratios used OHIP-14 and quality adjusted life years (QALYs) derived from the EQ-5D-3L. RESULTS: At 24 months, 291/550 (53%) patients returned for final assessment; those lost to follow-up attended 6.46 appointments on average (SD 4.80). The primary outcome favoured patients in the blended contract group. Extractions and fillings were more frequent in this group. Blended contracts were financially attractive for the dental provider but carried a higher cost for the service commissioner. Differences in generic health-related quality of life were negligible. Positive changes over time in oral health-related quality of life in both groups were statistically significant. CONCLUSIONS: This is the first UK study to assess the clinical and cost-effectiveness of a blended contract in primary care dentistry. Although the primary outcome favoured the blended contract, the results are limited because 47% patients did not attend at 24 months. This is consistent with 39% of adults not being regular attenders and 27% only visiting their dentist when they have a problem. Promotion of appropriate attendance, especially among those with high need, necessitates being factored into recruitment strategies of future studies.

Comparison of neurotoxicity following repeated administration of l-dopa, d-dopa and dopamine to embryonic mesencephalic dopamine neurons in cultures derived from Fisher 344 and Sprague-Dawley donors.

Levodopa is the most efficacious and widely used symptomatic drug for Parkinson's disease (PD). There is currently, however, a great deal of interest focused on the possibility that levodopa-induced increases in dopamine (DA) turnover may increase oxidative damage derived from the breakdown of DA. Increased oxidative damage following levodopa may contribute to the progressive degeneration of remaining host nigral neurons as well as interfere with development and function of embryonic nigral neurons in neural grafting trials. There is abundant evidence that levodopa is toxic to embryonic nigral DA neurons in both cell culture and neural grafting models. These findings have prompted a number of studies on mechanisms of levodopa toxicity to identify effective means of ameliorating potential oxidative stress related to levodopa in PD. In the current study we have utilized cultures of embryonic nigral DA neurons to address the fundamental question of whether levodopa-induced toxicity is related to DA production or whether dopa itself contributes to cell death. We compared the degree of nigral DA cell death following chronic administration of: 1) levodopa (e.g.: l-dopa); 2) its less active stereoisomer d-dopa; and 3) DA. We examined the rank order of toxicity of these compounds in two species of rats, Fisher 344 (F344) and Sprague-Dawley (SD). Results indicate a toxicity profile of: DA > l-dopa >> d-dopa. In addition, although there was no difference in response of F344 and SD cultures to l-dopa, the SD cultures were significantly more susceptible to the neurotoxic effects of DA. Taken collectively, these results suggest that levodopa-induced toxicity is related primarily to DA production rather than oxidation of dopa to toxic metabolites, and that some strain related differences do exist.

The detrimental effect of levodopa on behavioral efficacy of fetal dopamine neuron grafts in rats is reversible following prolonged withdrawal of chronic dosing.

In previous studies, we observed that chronic levodopa treatment resulted in impaired morphology and function of grafted dopamine neurons in rats. To begin to better understand how levodopa treatment might influence dopamine neurons, we examined whether subsequent discontinuation of chronic levodopa treatment might allow for recovery of graft efficacy. Function of embryonic mesencephalic tissue grafts was assessed by monitoring rotational behavior elicited by amphetamine in lesioned, grafted rats initially treated for 6 weeks with levodopa followed by a 6 week drug-free period. As observed previously, control grafted animals, but not levodopa treated animals, showed behavioral improvement. However, following a 6 week withdrawal period, the levodopa animals demonstrated a significant reduction in amphetamine rotations which was reminiscent of control animals. This suggests that grafted neurons can recover functionally after levodopa treatment is withdrawn, which may be of significance in clinical transplantation trials.