Intranasal hydromorphone for treatment of acute pain in children: A pilot study

ObjectivesWe aimed to describe the analgesic efficacy, duration of analgesia, and adverse event profile associated with intranasal hydromorphone in children with acute pain presenting to an emergency department.MethodsProspective dose titration pilot study of otherwise healthy children 4 to 17-years-old with moderate to severe pain who required a parenteral opioid. All patients received an initial intranasal hydromorophone dose of 0.03 mg/kg. The need for additional analgesia was assessed at 15 and 30 min; an additional 0.015 mg/kg was given at each assessment, if required. Need for rescue analgesic, pain intensity and adverse events were assessed until 6 h after hydromorphone administration or until patients were discharged, underwent a procedure to treat their painful condition, or received a rescue analgesic.ResultsWe enrolled 35 children. Fifteen, 11, and 9 children required a total dose of 0.03, 0.045, and 0.06 mg/kg, respectively. Patients in each dose group experienced an absolute decrease in pain score of ≥3/10 and percent reduction >40% within 5–15 min of completing dose-titration administration of hydromorphone. Duration of analgesia (i.e. time until rescue analgesic administered) >1 h was observed in 85.7% of patients. Patients not requiring rescue analgesics had mild or no pain until discharged or their painful conditions were treated. Three (8.6%) patients required a rescue analgesic <1 h after hydromorphone administration. There were no major adverse events.ConclusionsIntranasal hydromorphone led to rapid, clinically significant and frequently sustained decreases in pain intensity in children. No major adverse events were observed in this preliminary sample.Clinical Trials Registration Number: NCT02437669     

Human subjects exploit a cognitive map for credit assignment

An influential reinforcement learning framework proposes that behavior is jointly governed by model-free (MF) and model-based (MB) controllers. The former learns the values of actions directly from past encounters, and the latter exploits a cognitive map of the task to calculate these prospectively. Considerable attention has been paid to how these systems interact during choice, but how and whether knowledge of a cognitive map contributes to the way MF and MB controllers assign credit (i.e., to how they revaluate actions and states following the receipt of an outcome) remains underexplored. Here, we examine such sophisticated credit assignment using a dual-outcome bandit task. We provide evidence that knowledge of a cognitive map influences credit assignment in both MF and MB systems, mediating subtly different aspects of apparent relevance. Specifically, we show MF credit assignment is enhanced for those rewards that are related to a choice, and this contrasted with choice-unrelated rewards that reinforced subsequent choices negatively. This modulation is only possible based on knowledge of task structure. On the other hand, MB credit assignment was boosted for outcomes that impacted on differences in values between offered bandits. We consider mechanistic accounts and the normative status of these findings. We suggest the findings extend the scope and sophistication of cognitive map-based credit assignment during reinforcement learning, with implications for understanding behavioral control.

An extensive body of psychological and neuroscientific literature on dual-system reinforcement learning (RL) indicates that behavior is governed by two distinct systems (1–17)—a rigid, retrospective model-free (MF) system (18, 19) and a flexible, prospective model-based (MB) system (18, 20). Unlike an MF system, which tends to repeat actions with a past history of success, an MB system relies on a cognitive map (CM) (21), that is, a model detailing the structure of a decision-making environment, including how states, actions, observations, and rewards are linked, to predict the impact of action choice on potential future rewards. Recent research highlights competitive and cooperative interactions between these systems, including speed accuracy trade-offs (22), reliability-based arbitration (1, 23), and a plan-to-habit strategy (24), with a focus on a prospective-planning role served by the MB system during choice. Recently, we demonstrated another influence of a CM (and thus, as we described it there, MB processes) in guiding credit assignment (CA) to MF action-values (i.e., affecting how MF values of actions and states are updated as reward-outcomes are received) (25). However, by design, this influence was limited to unraveling the resolution of state uncertainty for MF purposes, leaving broader aspects of the contribution of CM-based processes to CA unexplored.Here, we consider two potential complementary CM-based modulators of CA. Both concern the causal structure of the relationship between options and outcomes. One involves the “relatedness” of actual outcomes to an enacted choice, a retrospective effect of a CM on MF CA. The second involves the “importance” of potential outcomes during the deliberation process preceding a choice, a prospective effect of a CM on MB CA.“Relatedness” arises out of a complexity in assigning credit when information about streams of rewards is provided that depends only partly on the actions taken (unlike situations that involve simple lotteries, for instance, when an action is directly followed by the reward it occasions). An MF system, lacking structural causal knowledge, is disposed to assign credit naively to a choice based on the entire collection of ensuing outcomes, irrespective of whether these outcomes were caused by, or related to, an actual initiating action choice. By contrast, knowledge stored as a CM can guide MF CA to favor action-related outcomes.Take an example of a trader who deliberates purchasing one of two available mutual funds: X, which invests in companies A and B, or Y, which invests in companies A and C. Assume the trader opts for X and then later receives positive information about companies B and D. The trader might assign credit in an MF manner to her/his past action (“buy X”), updating the action’s cached value on the basis that positive consequences followed that choice. However, only one component of those positive consequences (that concerning company B) actually related to the choice of fund X. We propose that MF CA is modulated by a CM such that a change in the action’s value will be affected mostly by information about company B. More generally, relatedness depends on a causal attribution of rewards to actions (26).We consider a second modulator of CA, termed “importance,” as a form of attentional effect. When deliberating between several choice options, and taking into account their prospective outcomes, it is often the case that certain outcomes (which we dub “unimportant”) should not determine choice, as they are common to all choice options. In contrast, other (“important”) outcomes are distinctive to some choice options but not to others, and these should be the main determinants of choice. A CM will contain this type of information and direct attention to the latter alone. We consider the possibility that when the outcomes of the choice are observed, those that garnered more attention at choice are favored in learning.Consider our previous example where information about companies B and D triggers a CA process that leads to positive revaluation of these companies—a process useful for future MB financial decisions related to these companies. We propose this CA process can be biased by CM-based deliberations during choice. Notably, the values of companies B and C were “important” in the trader’s MB deliberation process (choosing a fund), as each is unique to one fund. The values of companies A and D, on the other hand, are less important, as these are either common to both choice options (A) or altogether absent (D). We hypothesize that representations of “important” components in a CM are activated more strongly during choice, leading to them being revalued more when information about choice outcomes are subsequently realized. Thus, ceteris paribus, the increase in the trader’s evaluation of company B will be higher than for company D, given the positive information. This evaluation is then exploited by MB planning processes for future choices.To test these hypotheses, we developed a variant of our previously described dual-outcome bandit task (25). Participants chose between pairs of bandits (i.e., lotteries) that led to different outcomes and received a stream of reward feedback pertaining to choice-related, choice-unrelated, important, and unimportant outcomes. Critically, there are two ways to value bandits in this task. An MF controller treats each bandit holistically, and, as described above, an MB controller predicts the values of the bandits from knowledge of the outcomes to which the bandits lead as provided by a putative CM. This distinction in the structure of evaluations can then be generalized to the apportioning of credit. We consider CA to a bandit to take the form of an MF credit assignment (MFCA; since the MF system makes decisions directly based on these values). Similarly, we consider CA to the outcomes associated with the bandits to be an MB credit assignment (MBCA). To put this another way, the main distinction between MFCA and MBCA in our task is that the former pertains to a revaluation of actions, while the latter pertains to a revaluation of latent causes for these actions (i.e., the ensuing outcomes).In support of our hypothesis that MFCA is guided by a CM, we found evidence that credit for choice-related and -unrelated outcomes is assigned to actions in a different manner. We show information about rewards actually related to chosen actions alone positively impact on the value of those actions. Information about rewards not related to chosen actions, on the other hand, have an opposite effect. Second, we found that MBCA was greater for choice outcomes that were “important” compared to “unimportant” during choice deliberations. We discuss mechanistic and normative accounts of these results.     

Global Longitudinal Strain Predicts Survival and Left Ventricular Function After Mitral Valve Surgery: A Meta-analysis

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The Association of Helicobacter pylori,Eradication, and Early Complications of Laparoscopic Sleeve Gastrectomy

Obesity Surgery - Laparoscopic sleeve gastrectomy (SG) is a common and effective bariatric surgery, with low postoperative complication rates. It is important to define modifiable risk factors for...     

Tractography of the optic radiation: a repeatability and reproducibility study

Our main objective was to evaluate the repeatability and reproducibility of optic radiation (OR) reconstruction from diffusion MRI (dMRI) data. 14 adults were scanned twice with the same 60‐direction dMRI sequence. Peaks in the diffusion profile were estimated with the single tensor (ST), Q‐ball (QSH) and persistent angular structure (PAS) methods. Segmentation of the OR was performed by two experimenters with probabilistic tractography based on a manually drawn region‐of‐interest (ROI) protocol typically employed for OR segmentation, with both standard and extended sets of ROIs. The repeatability and reproducibility were assessed by calculating the intra‐class correlation coefficient (ICC) of intra‐ and inter‐rater experiments, respectively. ICCs were calculated for commonly used dMRI metrics (FA, MD, AD, RD) and anatomical dimensions of the optic radiation (distance from Meyer's loop to the temporal pole, ML‐TP), as well as the Dice similarity coefficient (DSC) between the raters’ OR segmentation. Bland–Altman plots were also calculated to investigate bias and variability in the reproducibility measurements. The OR was successfully reconstructed in all subjects by both raters. The ICC was found to be in the good to excellent range for both repeatability and reproducibility of the dMRI metrics, DSC and ML‐TP distance. The Bland–Altman plots did not show any apparent systematic bias for any quantities. Overall, higher ICC values were found for the multi‐fiber methods, QSH and PAS, and for the standard set of ROIs. Considering the good to excellent repeatability and reproducibility of all the quantities investigated, these findings support the use of multi‐fiber OR reconstruction with a limited number of manually drawn ROIs in clinical applications utilizing either OR microstructure characterization or OR dimensions, as is the case in neurosurgical planning for temporal lobectomy. Copyright © 2015 John Wiley & Sons, Ltd.     

Dopamine Increases a Value-Independent Gambling Propensity

Although the impact of dopamine on reward learning is well documented, its influence on other aspects of behavior remains the subject of much ongoing work. Dopaminergic drugs are known to increase risk-taking behavior, but the underlying mechanisms for this effect are not clear. We probed dopamine''s role by examining the effect of its precursor L-DOPA on the choices of healthy human participants in an experimental paradigm that allowed particular components of risk to be distinguished. We show that choice behavior depended on a baseline (ie, value-independent) gambling propensity, a gambling preference scaling with the amount/variance, and a value normalization factor. Boosting dopamine levels specifically increased just the value-independent baseline gambling propensity, leaving the other components unaffected. Our results indicate that the influence of dopamine on choice behavior involves a specific modulation of the attractiveness of risky options—a finding with implications for understanding a range of reward-related psychopathologies including addiction.     

中国流感疫苗应用现状及促进预防接种的政策探讨

流感是一种疫苗可预防性疾病,每年接种流感疫苗是预防流感及其并发症的最有效手段。流感疫苗在我国是二类疫苗,年平均接种率仅2%~3%。接种率低的原因包括公众对流感和流感疫苗认知不足、医务人员极少推荐、接种服务可及性和费用等。为促进我国流感疫苗的预防接种,降低流感对公众的健康危害和经济负担,应考虑采取综合政策措施积极推动流感疫苗预防接种工作,包括采用不同筹资方式和机制,提高重点人群的接种意愿和接种率、改进免疫服务公平性的效果和效率;提高医务人员和公众对流感和疫苗预防的认识,改进临床预防实践,通过制订临床指南、路径、专家共识等多种渠道,推动临床医生对流感疫苗预防接种建议的推荐;加快预防接种工作体系建设,为公众提供更方便、可及和规范的预防接种;加大新型流感疫苗研发支持力度,加快新型流感疫苗上市应用;修订我国药典中"妊娠期妇女为流感疫苗接种禁忌"的条款。     

Porous bovine bone mineral in healing of human extraction sockets: 2. Histochemical observations at 9 months

BACKGROUND: Porous bovine bone mineral (PBBM) has been used in ridge preservation procedures following tooth extractions. The aim of this study was to investigate histochemically tissue sockets grafted with PBBM at 9 months post-extraction. By using different histochemical stainings, characteristics of the newly formed bone; i.e., lamellar/woven ratio at different socket depths, were investigated and the arrangement of bone around the grafted material, as well as the nature of the amorphous organic material found in all specimens, were examined. METHODS: After extraction of 15 single-rooted maxillary teeth from 15 patients, socket sites were grafted with PBBM particles (250 to 1,000 mu). Primary soft tissue closure of the grafted site was established using the rotated split palatal pedicle flap technique. At 9 months, a cylindrical tissue specimen, 2.5 mm in diameter, was trephined from each previously grafted site followed by placement of a screw-shaped implant. Horizontal tissue section cuts, 5 mu wide, were prepared for histological examination. Histochemical staining included alcian blue, periodic-acid Schiff, Mallory trichrome, reticulin, Van Gieson, and picrosirius red (PSR). PSR stained slides were further evaluated morphometrically, using polarized microscopy to determine the amount of lamellar versus woven bone in superficial, mid and deep specimen section cut areas. RESULTS: All staining methods revealed that newly formed bone encircled and adhered to the grafted material in most specimens. Mallory trichrome staining showed osteoblasts present within an osteoid layer, lining the interface zone of PBBM particles and the new osseous tissue. Morphometric evaluation of the PSR stained slides disclosed a constant pattern of increased osseous tissue in a coronal-apical direction. An average of 17.1% osseous tissue with 1:12.9 lamellar/woven bone ratio was calculated in the superficial area. The average bone tissue fraction was 48.3% with a lamellar/woven ratio of 1:3.8 in the mid section area and in the deep area, it increased to 63.9%, with a lamellar/woven ratio average of 1:1.7. Differences between ratios at these sites were statistically significant (P<0.001). An amorphous organic substance was noted in most grafted particles. This material usually attached cell striae and harbored glycoproteins as revealed by periodic-acid Schiff and alcian blue stainings. Mallory trichrome staining showed denatured protein within the decalcified mineral particles; reticulin, Van Gieson stainings, and polarization of PSR stained sections refuted the existence of collagen in the grafted particles. CONCLUSIONS: Cancellous PBBM is a biocompatible filler agent in extraction socket sites and an acceptable graft for edentulous ridge preservation at sites prepared to receive endosseous implants. The osteoconductivity of PBBM was determined based on promoting osseous ingrowth and close integration with the newly generated bone. Grafted particles were not significantly resorbed at 9 months. Further studies are needed to determine the resorbable capability, as well as the nature and significance of the amorphous organic substance of PBBM observed in the grafted particles.     

Developmental anomaly of permanent teeth related to traumatic injury

Abstract A case is presented where a 4-year-old girl was injured in an automobile accident. The dental injury, intrusive luxation of the maxillary deciduous incisors, seemed unimportant at the time, since the child was in critical condition. The situation was first evaluated 5 years later, when the child was referred for treatment of an apical periodontitis originating from the right central incisor. The present case reflects several important aspects that were overlooked at the time of injury: the potential of intruded luxated deciduous teeth to cause developmental anomalies to the permanent dentition; the necessity of a longer follow-up period to detect such anomalies; and the need to develop effective treatment methods.