Intact-Brain Analyses Reveal Distinct Information Carried by SNc Dopamine Subcircuits.

Recent progress in understanding the diversity of midbrain dopamine neurons has highlighted the importance--and the challenges--of defining mammalian neuronal cell types. Although neurons may be best categorized using inclusive criteria spanning biophysical properties, wiring of inputs, wiring of outputs, and activity during behavior, linking all of these measurements to cell types within the intact brains of living mammals has been difficult. Here, using an array of intact-brain circuit interrogation tools, including CLARITY, COLM, optogenetics, viral tracing, and fiber photometry, we explore the diversity of dopamine neurons within the substantia nigra pars compacta (SNc). We identify two parallel nigrostriatal dopamine neuron subpopulations differing in biophysical properties, input wiring, output wiring to dorsomedial striatum (DMS) versus dorsolateral striatum (DLS), and natural activity patterns during free behavior. Our results reveal independently operating nigrostriatal information streams, with implications for understanding the logic of dopaminergic feedback circuits and the diversity of mammalian neuronal cell types.

Dynamic synchronization between hippocampal representations and stepping.

The hippocampus is a mammalian brain structure that expresses spatial representations1 and is crucial for navigation2,3. Navigation, in turn, intricately depends on locomotion; however, current accounts suggest a dissociation between hippocampal spatial representations and the details of locomotor processes. Specifically, the hippocampus is thought to represent mainly higher-order cognitive and locomotor variables such as position, speed and direction of movement4-7, whereas the limb movements that propel the animal can be computed and represented primarily in subcortical circuits, including the spinal cord, brainstem and cerebellum8-11. Whether hippocampal representations are actually decoupled from the detailed structure of locomotor processes remains unknown. To address this question, here we simultaneously monitored hippocampal spatial representations and ongoing limb movements underlying locomotion at fast timescales. We found that the forelimb stepping cycle in freely behaving rats is rhythmic and peaks at around 8 Hz during movement, matching the approximately 8 Hz modulation of hippocampal activity and spatial representations during locomotion12. We also discovered precisely timed coordination between the time at which the forelimbs touch the ground ('plant' times of the stepping cycle) and the hippocampal representation of space. Notably, plant times coincide with hippocampal representations that are closest to the actual position of the nose of the rat, whereas between these plant times, the hippocampal representation progresses towards possible future locations. This synchronization was specifically detectable when rats approached spatial decisions. Together, our results reveal a profound and dynamic coordination on a timescale of tens of milliseconds between central cognitive representations and peripheral motor processes. This coordination engages and disengages rapidly in association with cognitive demands and is well suited to support rapid information exchange between cognitive and sensory-motor circuits.

Hierarchical neural architecture underlying thirst regulation.

Neural circuits for appetites are regulated by both homeostatic perturbations and ingestive behaviour. However, the circuit organization that integrates these internal and external stimuli is unclear. Here we show in mice that excitatory neural populations in the lamina terminalis form a hierarchical circuit architecture to regulate thirst. Among them, nitric oxide synthase-expressing neurons in the median preoptic nucleus (MnPO) are essential for the integration of signals from the thirst-driving neurons of the subfornical organ (SFO). Conversely, a distinct inhibitory circuit, involving MnPO GABAergic neurons that express glucagon-like peptide 1 receptor (GLP1R), is activated immediately upon drinking and monosynaptically inhibits SFO thirst neurons. These responses are induced by the ingestion of fluids but not solids, and are time-locked to the onset and offset of drinking. Furthermore, loss-of-function manipulations of GLP1R-expressing MnPO neurons lead to a polydipsic, overdrinking phenotype. These neurons therefore facilitate rapid satiety of thirst by monitoring real-time fluid ingestion. Our study reveals dynamic thirst circuits that integrate the homeostatic-instinctive requirement for fluids and the consequent drinking behaviour to maintain internal water balance.

Evaluation of an early childhood caries preventive programme starting during pregnancy-Results after 3 and 6 years.

BACKGROUND: Early childhood caries (ECC) has been found to be up to five times more common among children living in areas of low socio-economic status (SES) than among children in areas of higher SES. AIM: To evaluate an ECC prevention programme from pregnancy to 3 and 6 years of age. DESIGN: A prospective, controlled, intervention cohort study was initiated in 2013 in a low-SES area in Sweden. The intervention group received an individual interdisciplinary ECC prevention programme starting pre-birth, consisting of supportive oral health-promoting talks using motivational interviewing techniques and individual ECC preventive actions. A control group, consisting of pregnant women living in a comparable area, received ordinary routines. RESULTS: Of the 336 pregnant women, 64 mothers (with 64 children) completed the programme, and 394 children were born in the control group. At the sixth year examination, the proportion of children with no caries was similar between the groups (53% resp. 52%, p = .976), whereas the proportion with decayed, missed, filled primary teeth (dmft = 1-5) was slightly lower (23% resp. 36%, p = .063), and the proportion with severe caries disease (dmft > 5) was higher (p = .013) in the intervention group (25%) than in the control group (12%). CONCLUSION: No preventive effect regarding caries can be demonstrated at sixth year of age. Maternal behavioural change in dental care was not sufficient to even out inequalities in oral health in children, eventually due to difficulties in reaching the target group and the lack of effects among the families reached.

Cost-effectiveness of different exercise intensities during oncological treatment in the Phys-Can RCT.

BACKGROUND: Cost-effectiveness is important in the prioritisation between interventions in health care. Exercise is cost-effective compared to usual care during oncological treatment; however, the significance of exercise intensity to the cost-effectiveness is unclear. In the present study, we aimed to evaluate the long-term cost-effectiveness of the randomised controlled trial Phys-Can, a six-month exercise programme of high (HI) or low-to-moderate intensity (LMI) during (neo)adjuvant oncological treatment. METHODS: A cost-effectiveness analysis was performed, based on 189 participants with breast, colorectal, or prostate cancer (HI: n = 99 and LMI: n = 90) from the Phys-Can RCT in Sweden. Costs were estimated from a societal perspective, and included cost of the exercise intervention, health care utilisation and productivity loss. Health outcomes were assessed as quality-adjusted life-years (QALYs), using EQ-5D-5L at baseline, post intervention and 12 months after the completion of the intervention. RESULTS: At 12-month follow-up after the intervention, the total cost per participant did not differ significantly between HI (€27,314) and LMI exercise (€29,788). There was no significant difference in health outcome between the intensity groups. On average HI generated 1.190 QALYs and LMI 1.185 QALYs. The mean incremental cost-effectiveness ratio indicated that HI was cost effective compared with LMI, but the uncertainty was large. CONCLUSIONS: We conclude that HI and LMI exercise have similar costs and effects during oncological treatment. Hence, based on cost-effectiveness, we suggest that decision makers and clinicians can consider implementing both HI and LMI exercise programmes and recommend either intensity to the patients with cancer during oncological treatment to facilitate improvement of health.

Measuring the predictability of life outcomes with a scientific mass collaboration.

How predictable are life trajectories? We investigated this question with a scientific mass collaboration using the common task method; 160 teams built predictive models for six life outcomes using data from the Fragile Families and Child Wellbeing Study, a high-quality birth cohort study. Despite using a rich dataset and applying machine-learning methods optimized for prediction, the best predictions were not very accurate and were only slightly better than those from a simple benchmark model. Within each outcome, prediction error was strongly associated with the family being predicted and weakly associated with the technique used to generate the prediction. Overall, these results suggest practical limits to the predictability of life outcomes in some settings and illustrate the value of mass collaborations in the social sciences.

A cost analysis of orthodontic space closure and implant treatment in patients missing maxillary lateral incisors with a long-term perspective.

OBJECTIVE: Few studies within orthodontics present both economic and clinical findings. Missing maxillary lateral incisors is a frequently occurring anomaly. The treatment alternatives most used are orthodontic space closure and prosthetic replacement of the missing tooth. Our aim is to compare the total societal costs of orthodontic space closure (SC) and implant therapy (IT) in patients missing maxillary lateral incisors. METHODS: Records of 32 patients treated with SC (n = 18) or IT (n = 14) due to missing maxillary lateral incisors were retrieved from the archives. Direct costs and indirect costs in the short- and long-term were analysed using a cost analysis with a societal perspective up of to 12 years post-treatment. RESULTS: Comparing cases treated with SC and IT, the difference in direct short-term costs for treatment is €735.54, whereas SC is the least costly. There is no difference between SC and IT in short-term parent loss of productivity, long-term loss of productivity, costs for transportation, or direct long-term costs. A difference was found between SC and IT-in favour of SC-when comparing patients' loss of productivity (P = 0.007), short-term societal costs (P < 0.001), long-term societal costs (P = 0.037), and total societal costs (P < 0.001). LIMITATIONS: There is a limited number of patient records. Local factors such as subsidies, urban versus rural areas, taxes, etc. can influence monetary variables, so the transferability to other settings may be limited. CONCLUSION: Patients treated with SC have a lower total societal cost compared to patients treated with IT. There was a difference in productivity loss for patients between SC and IT; however, concerning other indirect parameters and direct long-term costs, there was no difference between the two treatments.

Long-term resource utilisation and associated costs of exercise during (neo)adjuvant oncological treatment: the Phys-Can project.

BACKGROUND: Exercise during oncological treatment is beneficial to patient health and can counteract the side effects of treatment. Knowledge of the societal costs associated with an exercise intervention, however, is limited. The aims of the present study were to evaluate the long-term resource utilisation and societal costs of an exercise intervention conducted during (neo)adjuvant oncological treatment in a randomised control trial (RCT) versus usual care (UC), and to compare high-intensity (HI) versus low-to-moderate intensity (LMI) exercise in the RCT. METHODS: We used data from the Physical Training and Cancer (Phys-Can) project. In the RCT, 577 participants were randomised to HI or to LMI of combined endurance and resistance training for 6 months, during oncological treatment. The project also included 89 participants with UC in a longitudinal observational study. We measured at baseline and after 18 months. Resource utilisation and costs of the exercise intervention, health care, and productivity loss were compared using analyses of covariance (RCT vs. UC) and t test (HI vs. LMI). RESULTS: Complete data were available for 619 participants (RCT HI: n = 269, LMI: n = 265, and UC: n = 85). We found no difference in total societal costs between the exercise intervention groups in the RCT and UC. However, participants in the RCT had lower rates of disability pension days (p < .001), corresponding costs (p = .001), and pharmacy costs (p = .018) than the UC group. Nor did we find differences in resource utilisation or costs between HI and LMI exercise int the RCT. CONCLUSION: Our study showed no difference in total societal costs between the comprehensive exercise intervention and UC or between the exercise intensities. This suggests that exercise, with its well-documented health benefits during oncological treatment, produces neither additional costs nor savings.

Changes in Water Chemistry Associated with Rainstorm Events Increase Carbon Emissions from the Inflowing River Mouth of a Major Drinking Water Reservoir.

Large reservoirs are hotspots for carbon emissions, and the continued input and decomposition of terrestrial dissolved organic matter (DOM) from upstream catchments is an important source of carbon emissions. Rainstorm events can cause a surge in DOM input; however, periodic sampling often fails to fully capture the impact of these discrete rainstorm events on carbon emissions. We conducted a set of frequent observations prior to and following a rainstorm event in a major reservoir Lake Qiandao (China; 580 km2) from June to July 2021 to investigate how rainstorms alter water chemistry and CO2 and CH4 emissions. We found that the mean CO2 efflux (FCO2) (13.2 ± 9.3 mmol m-2 d-1) and CH4 efflux (FCH4) (0.12 ± 0.02 mmol m-2 d-1) in the postrainstorm campaign were significantly higher than those in the prerainstorm campaign (-3.8 ± 3.0 and +0.06 ± 0.02 mmol m-2 d-1, respectively). FCO2 and FCH4 increased with increasing nitrogen and phosphorus levels, elevated DOM absorption (a350), specific UV absorbance SUVA254, and terrestrial humic-like fluorescence. Furthermore, FCO2 and FCH4 decreased with increasing chlorophyll-a (Chl-a), dissolved oxygen (DO), and pH. A five-day laboratory anoxic bioincubation experiment further revealed a depletion of terrestrial-DOM concurrent with increased CO2 and CH4 production. We conclude that rainstorms boost the emission of CO2 and CH4 fueled by the surge and decomposition of fresh terrestrially derived biolabile DOM in this and likely many other reservoir's major inflowing river mouths.

Nucleus accumbens D2R cells signal prior outcomes and control risky decision-making.

A marked bias towards risk aversion has been observed in nearly every species tested. A minority of individuals, however, instead seem to prefer risk (repeatedly choosing uncertain large rewards over certain but smaller rewards), and even risk-averse individuals sometimes opt for riskier alternatives. It is not known how neural activity underlies such important shifts in decision-making--either as a stable trait across individuals or at the level of variability within individuals. Here we describe a model of risk-preference in rats, in which stable individual differences, trial-by-trial choices, and responses to pharmacological agents all parallel human behaviour. By combining new genetic targeting strategies with optical recording of neural activity during behaviour in this model, we identify relevant temporally specific signals from a genetically and anatomically defined population of neurons. This activity occurred within dopamine receptor type-2 (D2R)-expressing cells in the nucleus accumbens (NAc), signalled unfavourable outcomes from the recent past at a time appropriate for influencing subsequent decisions, and also predicted subsequent choices made. Having uncovered this naturally occurring neural correlate of risk selection, we then mimicked the temporally specific signal with optogenetic control during decision-making and demonstrated its causal effect in driving risk-preference. Specifically, risk-preferring rats could be instantaneously converted to risk-averse rats with precisely timed phasic stimulation of NAc D2R cells. These findings suggest that individual differences in risk-preference, as well as real-time risky decision-making, can be largely explained by the encoding in D2R-expressing NAc cells of prior unfavourable outcomes during decision-making.

A review of the effects of head-worn displays on teamwork for emergency response.

Head-Worn Displays (HWD) can potentially support the mobile work of emergency responders, but it remains unclear whether teamwork is affected when emergency responders use HWDs. We reviewed studies that examined HWDs in emergency response contexts to evaluate the impact of HWDs on team performance and on team processes of situation awareness, communication, and coordination. Sixteen studies were identified through manual and systematic literature searches. HWDs appeared to improve the quality of team performance but they increased time to perform under some conditions; effects on team processes were mixed. We identify five challenges to explain the mixed results. We discuss four theoretical perspectives that might address the challenges and guide research needs-joint cognitive systems, distributed cognition, common ground, and dynamical systems. Researchers and designers should use process-based measures and apply greater theoretical guidance to uncover mechanisms by which HWDs shape team processes, and to understand the impact on team performance. Practitioner Summary: This review examines the effects of head-worn displays on teamwork performance and team processes for emergency response. Results are mixed, but study diversity challenges the search for underlying mechanisms. Guidance from perspectives such as joint cognitive systems, distributed cognition, common ground, and dynamical systems may advance knowledge in the area. Abbreviations: HWD: head-worn display; RC: remote collaboration; DD: data display; ARC: augmented remote collaboration; ACC: augmented collocated collaboration; SA: situation awareness; TSA: team situation awareness; CPR: cardiopulmonary resuscitation; SAGAT: situation awareness global assessment technique; SART: situation awareness rating technique.

The costs of human uterus transplantation: a study based on the nine cases of the initial Swedish live donor trial.

STUDY QUESTION: What are the costs of live donor uterus transplantation in a European setting? SUMMARY ANSWER: The total costs for preoperative investigations, including IVF, and live donor uterus transplantation including postoperative costs for 2 months, were calculated to be €74 564 (mean), with the costs of recipient being somewhat higher than for donor and the cost components of total costs distributed between sick leave (25.7%), postoperative hospitalization (17.8%), surgery (17.1%), preoperative investigations (15.7%), anaesthesia (9.7%), drugs (7.8%), tests after surgery (4.0%) and for re-hospitalization (2.2%). WHAT IS KNOWN ALREADY: Uterus transplantation has proved to be successful by demonstrations of live births, both after live donor and deceased donor procedures. The transplantation is considered as a complex and expensive infertility treatment. There exist no analyses of costs involved in uterus transplantation. STUDY DESIGN, SIZE, DURATION: This prospective cohort study included nine uterus transplantations procedures, performed in Sweden in 2013. Study duration of this health economic study included 6-12 months of pre-transplantation investigations and the time interval from transplantation to 2 months after. PARTICIPANTS/MATERIALS, SETTING, METHODS: Nine triads of uterus recipient, partner of recipient and uterus donor participated. All prospective recipients were in stable relationships and performed IVF with their partners before transplantation. The nine donors were relatives or family friends. The recipients and donors underwent pre-transplantation investigations with imaging, laboratory tests and psychological/medical screening prior to transplantation. Transplantation was by laparotomy in both donor and recipient. Standard immunosuppression and postoperative medication were used. After discharge from the hospital, the recipients were followed frequently with laboratory tests and examinations. MAIN RESULTS AND THE ROLE OF CHANCE: The mean costs for preoperative investigations, including IVF, and live donor uterus transplantation with postoperative costs for 2 months, were calculated to be €74 564 (range €50 960-€99 658), from a societal perspective. The four largest components were cost of sick leave (€19 164), cost of postoperative hospitalization (€13 246), surgery cost (€12 779) and costs for preoperative investigations, including IVF (€11 739). Smaller components were costs for anaesthesia (€7207), costs for drugs (€5821), costs for post-surgical tests (€2985) and costs for re-hospitalization (€1623). The costs of the recipient (€42 984) were somewhat higher than the costs of the donor (€31 580), but in terms of costs, they should be viewed as one entity. By using a health care perspective, excluding cost for productivity loss, the total costs would be reduced by 26%. LIMITATIONS, REASONS FOR CAUTION: A limitation is the restricted sample size and that this is in the experimental, clinical stage of development. WIDER IMPLICATIONS OF THE FINDINGS: The results provide the first information concerning the costs for pre-transplantation investigations and uterus transplantation procedures with postoperative follow-up. We consider the total estimate to be in the higher interval, because of the extensive research protocol. It is likely that the cost of live donor uterus transplantation will vary between countries and that the costs will be lower in a future clinical setting. STUDY FUNDING/COMPETING INTEREST(S): Funding was received from the Jane and Dan Olsson Foundation for Science; the Knut and Alice Wallenberg Foundation; an ALF grant from the Swedish state under an agreement between the government and the county councils; and the Swedish Research Council. None of the authors have a conflict of interest with regard to the study. TRIAL REGISTRATION NUMBER: NCT01844362.

Thalamic control of sensory selection in divided attention.

How the brain selects appropriate sensory inputs and suppresses distractors is unknown. Given the well-established role of the prefrontal cortex (PFC) in executive function, its interactions with sensory cortical areas during attention have been hypothesized to control sensory selection. To test this idea and, more generally, dissect the circuits underlying sensory selection, we developed a cross-modal divided-attention task in mice that allowed genetic access to this cognitive process. By optogenetically perturbing PFC function in a temporally precise window, the ability of mice to select appropriately between conflicting visual and auditory stimuli was diminished. Equivalent sensory thalamocortical manipulations showed that behaviour was causally dependent on PFC interactions with the sensory thalamus, not sensory cortex. Consistent with this notion, we found neurons of the visual thalamic reticular nucleus (visTRN) to exhibit PFC-dependent changes in firing rate predictive of the modality selected. visTRN activity was causal to performance as confirmed by bidirectional optogenetic manipulations of this subnetwork. Using a combination of electrophysiology and intracellular chloride photometry, we demonstrated that visTRN dynamically controls visual thalamic gain through feedforward inhibition. Our experiments introduce a new subcortical model of sensory selection, in which the PFC biases thalamic reticular subnetworks to control thalamic sensory gain, selecting appropriate inputs for further processing.

Basomedial amygdala mediates top-down control of anxiety and fear.

Anxiety-related conditions are among the most difficult neuropsychiatric diseases to treat pharmacologically, but respond to cognitive therapies. There has therefore been interest in identifying relevant top-down pathways from cognitive control regions in medial prefrontal cortex (mPFC). Identification of such pathways could contribute to our understanding of the cognitive regulation of affect, and provide pathways for intervention. Previous studies have suggested that dorsal and ventral mPFC subregions exert opposing effects on fear, as do subregions of other structures. However, precise causal targets for top-down connections among these diverse possibilities have not been established. Here we show that the basomedial amygdala (BMA) represents the major target of ventral mPFC in amygdala in mice. Moreover, BMA neurons differentiate safe and aversive environments, and BMA activation decreases fear-related freezing and high-anxiety states. Lastly, we show that the ventral mPFC-BMA projection implements top-down control of anxiety state and learned freezing, both at baseline and in stress-induced anxiety, defining a broadly relevant new top-down behavioural regulation pathway.

Cost-effectiveness of caries preventive interventions - a systematic review.

OBJECTIVE: The primary purpose of this study was to assess the cost-effectiveness of caries preventive interventions. MATERIAL AND METHODS: A systematic review was conducted, following the PRISMA Statement. Four electronic databases were searched (final search 16 March 2020). Studies fulfilling the inclusion criteria were independently critically appraised, by two reviewers in parallel. Data from each included study were extracted and tabulated: the analysis used a narrative approach to present the results of the estimated cost-effectiveness. RESULTS AND CONCLUSIONS: Twenty-six publications fulfilled the inclusion criteria and were of low or moderate risk of bias. Ten publications were economic evaluations, directly based on empirical studies, and the other 16 were modelling studies. Most of the studies concerned interventions for children and the most common were analyses of fluoride varnish and risk-based programs. Some of the studies showed both reduced cost and improved outcomes, but most studies reported that the improved outcome came with an additional cost. The results disclosed several cost-effectiveness evaluations of caries preventive interventions in the literature, but these target primarily children at high risk. There is a scarcity of studies specifically targeting adults and especially the elderly.

Phage Display to Augment Biomaterial Function.

Biomaterial design relies on controlling interactions between materials and their biological environments to modulate the functions of proteins, cells, and tissues. Phage display is a powerful tool that can be used to discover peptide sequences with high affinity for a desired target. When incorporated into biomaterial design, peptides identified via phage display can functionalize material surfaces to control the interaction between a biomaterial and its local microenvironment. A targeting peptide has high specificity for a given target, allowing for homing a specific protein, cell, tissue, or other material to a biomaterial. A functional peptide has an affinity for a given protein, cell, or tissue, but also modulates its target's activity upon binding. Biomaterials can be further enhanced using a combination of targeting and/or functional peptides to create dual-functional peptides for bridging two targets or modulating the behavior of a specific protein or cell. This review will examine current and future applications of phage display for the augmentation of biomaterials.

Simultaneous fast measurement of circuit dynamics at multiple sites across the mammalian brain.

Real-time activity measurements from multiple specific cell populations and projections are likely to be important for understanding the brain as a dynamical system. Here we developed frame-projected independent-fiber photometry (FIP), which we used to record fluorescence activity signals from many brain regions simultaneously in freely behaving mice. We explored the versatility of the FIP microscope by quantifying real-time activity relationships among many brain regions during social behavior, simultaneously recording activity along multiple axonal pathways during sensory experience, performing simultaneous two-color activity recording, and applying optical perturbation tuned to elicit dynamics that match naturally occurring patterns observed during behavior.

Structural and molecular interrogation of intact biological systems.

Obtaining high-resolution information from a complex system, while maintaining the global perspective needed to understand system function, represents a key challenge in biology. Here we address this challenge with a method (termed CLARITY) for the transformation of intact tissue into a nanoporous hydrogel-hybridized form (crosslinked to a three-dimensional network of hydrophilic polymers) that is fully assembled but optically transparent and macromolecule-permeable. Using mouse brains, we show intact-tissue imaging of long-range projections, local circuit wiring, cellular relationships, subcellular structures, protein complexes, nucleic acids and neurotransmitters. CLARITY also enables intact-tissue in situ hybridization, immunohistochemistry with multiple rounds of staining and de-staining in non-sectioned tissue, and antibody labelling throughout the intact adult mouse brain. Finally, we show that CLARITY enables fine structural analysis of clinical samples, including non-sectioned human tissue from a neuropsychiatric-disease setting, establishing a path for the transmutation of human tissue into a stable, intact and accessible form suitable for probing structural and molecular underpinnings of physiological function and disease.

A 1-year perspective on goal-directed therapy in elderly with hip fracture: Secondary outcomes.

BACKGROUND: We have previously reported inconclusive results from a randomized controlled trial in elderly with hip-fracture comparing intra-operative goal-directed therapy with routine fluid treatment. Now we aimed to describe and compare secondary outcomes at 4 months and 1 year follow-up and to analyze the cost-effectiveness. METHODS: Patients with hip fracture (age ≥70) were randomized for GDT or routine fluid treatment (RFT). The secondary outcomes were long-term survival, complications, number of hospital readmissions, and quality of life (EQ-5D) changes. Additionally, cost effectiveness was analyzed by an analytic tool which combines the clinical effectiveness, quality of life changes and costs. RESULTS: Patient data (GDT n = 74; RFT n = 75) were analyzed on an intention to treat basis. Statistically significant differences (GDT vs RFT) were not found considering survival (RR 0.76, 95%CI 0.45-1.28) and complications (RR 0.68, 95% CI 0.4-1.10) at 12 months. No statistically significant difference was found between hospital readmissions and quality of life changes. CONCLUSION: The statistical uncertainty of risk reduction of negative outcomes and the large variability of the collected data indicate the need of further research in large sample sizes. To enable future health economic evaluation for decision support surrounding implementation of GDT, we suggest adding patient-oriented outcomes in future trials.

Cost-Effectiveness through the Dental-Health FRAMM Guideline for Caries Prevention among 12- to 15-Year-Olds in Sweden.

Since 2008, FRAMM has been a guideline for caries prevention for all 3- to 15-year-olds in the Västra Götaland Region in Sweden and a predominant part is school-based fluoride varnish applications for all 12- to 15-year-olds. The aims were to evaluate dental health-economic data among 12- to 15-year-olds, based on the approximal caries prevalence at the age of 12, and to evaluate cost-effectiveness. Caries data for 13,490 adolescents born in 1993 who did not take part and 11,321 adolescents born in 1998 who followed this guideline were extracted from dental records. Those with no dentin and/or enamel caries lesions and/or fillings on the approximal surfaces were pooled into the "low" subgroup, those with 1-3 into the "moderate" subgroup and those with ≥4 into the "high" subgroup. The results revealed that the low subgroup had a low approximal caries increment compared with the moderate and high subgroups during the 4-year study period. In all groups, there were statistically significant differences between those who took part in the guideline and those who did not. The analysis of cost-effectiveness revealed the lowest incremental cost-effectiveness ratio (ICER) for the high subgroup for decayed and/or filled approximal surfaces (DFSa) and approximal enamel lesions together and the highest ICER for the low subgroup for DFSa alone. To conclude, the FRAMM Guideline reduced the caries increment for adolescents with low, moderate and high approximal caries prevalence. The subgroup with the most favourable cost-effectiveness comprised those with a high caries prevalence at the age of 12.