Can facial emotion recognition be rapidly improved in children with disruptive behavior? A targeted and preventative early intervention study.

An impairment in recognizing distress is implicated in the development and severity of antisocial behavior. It has been hypothesized that a lack of attention to the eyes plays a role, but supporting evidence is limited. We developed a computerized training to improve emotion recognition in children and examined the role of eye gaze before and after training. Children referred into an intervention program to prevent antisocial outcomes completed an emotion recognition task with concurrent eye tracking. Those with emotion recognition impairments (n = 54, mean age: 8.72 years, 78% male) completed the training, while others (n = 38, mean age: 8.95 years, 84% male) continued with their usual interventions. Emotion recognition and eye gaze were reassessed in all children 8 weeks later. Impaired negative emotion recognition was significantly related to severity of behavioral problems at pretest. Children who completed the training significantly improved in emotion recognition; eye gaze did not contribute to impairment or improvement in emotion recognition. This study confirms the role of emotion recognition in severity of disruptive behavior and shows that a targeted intervention can quickly improve emotion impairments. The training works by improving children's ability to appraise emotional stimuli rather than by influencing their visual attention.

Improving emotion recognition is associated with subsequent mental health and well-being in children with severe behavioural problems.

Impaired emotion recognition is a transdiagnostic risk factor for a range of psychiatric disorders. It has been argued that improving emotion recognition may lead to improvements in behaviour and mental health, but supportive evidence is limited. We assessed emotion recognition and mental health following a brief and targeted computerised emotion recognition training in children referred into an intervention program because of severe family adversity and behavioural problems (n = 62; aged 7-10). While all children continued to receive their usual interventions, only children impaired in emotion recognition (n = 40) received the emotion training. Teachers blind to whether or not children had received the training rated children's mental health problems before and 6 months after the training. Participants who received the emotion training significantly improved their recognition of negative and neutral facial expressions. Although both groups showed improved behaviour at follow-up, the reduction in behavioural problems was only significant in children who received the emotion training. Post-training emotion recognition scores predicted mental health problems 6 months later independently of initial emotion recognition ability and severity of behavioural problems. The results are consistent with the view that targeting emotion recognition can improve longer term functioning in individuals with disruptive behaviour, although further research using fully randomised designs is needed before causal conclusions can be drawn with confidence.

The nature and extent of emotion recognition and empathy impairments in children showing disruptive behaviour referred into a crime prevention programme.

Childhood disruptive behaviour has been linked to later antisocial and criminal behaviour. Emotion recognition and empathy impairments, thought to be caused by inattention to the eye region, are hypothesised to contribute to antisocial and criminal behaviour. This is the first study to simultaneously examine emotion recognition and empathy impairments, their relationship, and the mechanism behind these impairments, in children with disruptive behaviour. We hypothesised that children with disruptive behaviour would exhibit negative emotion recognition and cognitive and affective empathy impairments, but that these impairments would not be due to reduced attention to the eye region. We expected these emotion impairments to be driven by disruptive behaviour. We also expected a relationship between emotion recognition and cognitive empathy only. Ninety-two children with disruptive behaviour, who were participating in a police crime prevention programme and rated by their schoolteacher using the Strengths and Difficulties Questionnaire (DB; mean age 8.8 years, 80% male), took part. There was a comparison group of 58 typically developing children (TD; mean age 9.7 years, 78% male). All children completed emotion recognition and empathy tasks, both with concurrent eye tracking to assess social attention. Not only were DB children significantly impaired in negative emotion and neutral emotion recognition, and in cognitive and affective empathy compared to the TD children, but severity of disruptive behaviour also predicted intensity of emotion impairments. There were no differences in social attention to the eye region. Negative emotion recognition and empathy impairments are already present in an identifiable group of children displaying disruptive behaviour. These findings provide evidence to encourage the use of targeted interventions.

Attitudes toward prevention of mtDNA-related diseases through oocyte mitochondrial replacement therapy.

STUDY QUESTION: Among women who carry pathogenic mitochondrial DNA (mtDNA) point mutations and healthy oocyte donors, what are the levels of support for developing oocyte mitochondrial replacement therapy (OMRT) to prevent transmission of mtDNA mutations? SUMMARY ANSWER: The majority of mtDNA carriers and oocyte donors support the development of OMRT techniques to prevent transmission of mtDNA diseases. WHAT IS KNOWN ALREADY: Point mutations of mtDNA cause a variety of maternally inherited human diseases that are frequently disabling and often fatal. Recent developments in (OMRT) as well as pronuclear transfer between embryos offer new potential options to prevent transmission of mtDNA disease. However, it is unclear whether the non-scientific community will approve of embryos that contain DNA from three people. STUDY DESIGN, SIZE, DURATION: Between 1 June 2012 through 12 February 2015, we administered surveys in cross-sectional studies of 92 female carriers of mtDNA point mutations and 112 healthy oocyte donors. PARTICIPANTS/MATERIALS, SETTING, METHODS: The OMRT carrier survey was completed by 92 female carriers of an mtDNA point mutation. Carriers were recruited through the North American Mitochondrial Disease Consortium (NAMDC), the United Mitochondrial Disease Foundation (UMDF), patient support groups, research and private patients followed at the Columbia University Medical Center (CUMC) and patients' referrals of maternal relatives. The OMRT donor survey was completed by 112 women who had donated oocytes through a major ITALIC! in vitro fertilization clinic. MAIN RESULTS AND THE ROLE OF CHANCE: All carriers surveyed were aware that they could transmit the mutation to their offspring, with 78% (35/45) of women, who were of childbearing age, indicating that the risk was sufficient to consider not having children, and 95% (87/92) of all carriers designating that the development of this technique was important and worthwhile. Of the 21 surveyed female carriers considering childbearing, 20 (95%) considered having their own biological offspring somewhat or very important and 16 of the 21 respondents (76%) were willing to donate oocytes for research and development. Of 112 healthy oocyte donors who completed the OMRT donor survey, 97 (87%) indicated that they would donate oocytes for generating a viable embryo through OMRT. LIMITATIONS, REASONS FOR CAUTION: Many of the participants were either patients or relatives of patients who were already enrolled in a research-oriented database, or who sought care in a tertiary research university setting, indicating a potential sampling bias. The survey was administered to a select group of individuals, who carry, or are at risk for carrying, mtDNA point mutations. These individuals are more likely to have been affected by the mutation or have witnessed first-hand the devastating effects of these mutations. It has not been established whether the general public would be supportive of this work. This survey did not explicitly address alternatives to OMRT. WIDER IMPLICATIONS OF THE FINDINGS: This is the first study indicating a high level of interest in the development of these methods among women affected by the diseases or who are at risk of carrying mtDNA mutations as well as willingness of most donors to provide oocytes for the development of OMRT. STUDY FUNDING/COMPETING INTERESTS: This work was conducted under the auspices of the NAMDC (Study Protocol 7404). NAMDC (U54NS078059) is part of the NCATS Rare Diseases Clinical Research Network (RDCRN). RDCRN is an initiative of the Office of Rare Diseases Research (ORDR) and NCATS. NAMDC is funded through a collaboration between NCATS, NINDS, NICHD and NIH Office of Dietary Supplements. The work was also supported by the Bernard and Anne Spitzer Fund and the New York Stem Cell Foundation (NYSCF). Dr Hirano has received research support from Santhera Pharmaceuticals and Edison Pharmaceuticals for studies unrelated to this work. None of the other authors have conflicts of interest. TRIAL REGISTRATION NUMBER: Not applicable.

Implementation and Assessment of a Proning Protocol for Nonintubated Patients With COVID-19.

INTRODUCTION: The COVID-19 pandemic has caused over 1,250,000 deaths worldwide. With limited therapeutic options, proning nonintubated patients emerged as a safe and affordable intervention to manage hypoxemia. METHODS: A proning protocol to identify and prone eligible patients was implemented. Patients were encouraged to self-prone for 2-3 hours, 3 times daily. Investigators created educational materials for nurses and patients and developed a COVID-19-specific proning order within the electronic health record (EHR). Investigators completed an 800-person retrospective chart review to study the implementation of this protocol. RESULTS: From March 22, 2020, to June 5, 2020, 586 patients were admitted to the COVID-19 floor. Of these patients, 42.8% were eligible for proning. Common contraindications were lack of hypoxia, altered mental status, and fall risk. The proning protocol led to a significant improvement in provider awareness of patients appropriate for proning, increasing from 12% to 83%, as measured by placement of a proning order into the EHR. There was a significant improvement in all appropriate patients documented as proned, increasing from 18% to 45% of eligible patients. CONCLUSIONS: The creation of an effective hospital-wide proning protocol to address the exigencies of the COVID-19 pandemic is possible and may be accomplished in a short period of time.

Children with Behavioural Problems Misinterpret the Emotions and Intentions of Others.

Research indicates that the misinterpretation of other's emotions or intentions may lead to antisocial behaviour. This study investigated emotion and intention recognition in children with behavioural problems and examined their relationship and relations with behaviour problem severity. Participants were 7-11 year old children with behavioural problems (n = 93, mean age: 8.78, 82.8% male) who were taking part in an early intervention program and typically developing controls (n = 44, mean age: 9.82, 79.5% male). Participants completed emotion recognition and Theory of Mind tasks. Teachers and parents rated children's emotional and behavioural problems. Children with behavioural problems showed impaired emotion and intention recognition. Emotion recognition and intention recognition were positively related and inversely associated with behavioural problem severity and, independently of one another, predicted behavioural problems. This study is the first to show that children with behavioural problems are impaired in identifying others' emotions as well as intentions. These social cognitive processes were found to be related and inversely associated with severity of behavioural problems. This has important implications for intervention and prevention programmes for children with behavioural difficulties.

Obesity is Associated with Increased Risk for Mortality Among Hospitalized Patients with COVID-19.

OBJECTIVE: Obesity has been identified as a risk factor for severe coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 virus. This study sought to determine whether obesity is a risk factor for mortality among patients with COVID-19. METHODS: The study was a retrospective cohort that included patients with COVID-19 between March 1 and April 18, 2020. RESULTS: A total of 238 patients were included; 218 patients (91.6%) were African American, 113 (47.5%) were male, and the mean age was 58.5 years. Of the included patients, 146 (61.3%) had obesity (BMI > 30 kg/m2 ), of which 63 (26.5%), 29 (12.2%), and 54 (22.7%) had class 1, 2, and 3 obesity, respectively. Obesity was identified as a predictor for mortality (odds ratio [OR] 1.7 [1.1-2.8], P = 0.016), as was male gender (OR 5.2 [1.6-16.5], P = 0.01) and older age (OR 3.6 [2.0-6.3], P < 0.0005). Obesity (OR 1.7 [1.3-2.1], P < 0.0005) and older age (OR 1.3 [1.0-1.6], P = 0.03) were also risk factors for hypoxemia. CONCLUSIONS: Obesity was found to be a significant predictor for mortality among inpatients with COVID-19 after adjusting for age, gender, and other comorbidities. Patients with obesity were also more likely to present with hypoxemia.

Effectiveness of long-term infliximab use and impact of treatment adherence on disease control in refractory, non-infectious pediatric uveitis.

BACKGROUND: Refractory non-infectious uveitis is a serious condition that leads to ocular complications and vision loss and requires effective systemic treatment to control disease. The effectiveness of long-term infliximab [IFX] in refractory non-infectious childhood uveitis and the impact of treatment adherence on disease control were evaluated. METHODS: Retrospective, single-center study between December 2002 and April 2016 of 27 children with refractory non-infectious uveitis [17 with juvenile idiopathic arthritis, JIA] treated with long-term IFX [9+ months]. Disease activity was assessed prior to and while on IFX using the Standardization of Uveitis Nomenclature [SUN]. Number of visits per year with active uveitis was analyzed by repeated measures logistic regression analysis from 2 years prior to IFX initiation or from onset of uveitis until most recent visit on IFX. Incomplete treatment adherence was assessed for each visit and defined as any deviance in corticosteroid use, prescribed infusion frequency, and/or follow-up examination frequency. RESULTS: Primary outcomes were sustained uveitic and systemic disease control prior to and during IFX treatment and the impact of incomplete adherence on uveitic disease control while on IFX. Secondary outcomes included corticosteroid and glaucoma medication requirement, ocular complications and need for surgical intervention. Mean age at IFX initiation was 10.4 ± 4.5 years; initial mean dose was 6.6 ± 2.2 mg/kg [and given at weeks 0, 2, 4 and q4 weeks thereafter for 93%]. Median duration on IFX was 35 [range 9-128] months. Prior to IFX, 14/27 patients had failed adalimumab ± methotrexate [MTX]; 21/27 failed MTX. IFX led to uveitis control in 89% and arthritis control in 76% (13/17). The odds ratio of having controlled disease after IFX was 4.1 (2.6, 6.4) compared to pre-treatment visits. Topical corticosteroids and glaucoma medications were statistically decreased (p = 0.007 right eye [OD], 0.003 left eye [OS] and p = 0.001 OD, p = 0.028 OS respectively). Incomplete adherence to treatment showed 10.3 times greater odds (7.1, 15.0) of having disease activity than full adherence. CONCLUSIONS: This study adds significantly to the IFX literature by documenting outstanding uveitis control with long-term IFX treatment in non-infectious pediatric uveitis patients. Higher dosage and shorter interval were utilized without adverse effects. Importantly, this is the first study, to our knowledge, to document the significant impact of treatment adherence on uveitis control.

Impact of selection of post-implant technique on dosimetry parameters for permanent prostate implants.

PURPOSE: To investigate the variability of prostate implant quality indices between three different methods of calculating the post-implant dose distribution. METHODS AND MATERIALS: In a study of 9 permanent prostate implant patients, post-implant dosimetry was carried out using three methods of identifying seed positions within the prostate volume: (1) prostate volumes defined by transrectal ultrasound (TRUS) immediately following implant were registered with shift-film defined seed positions, (2) seeds were identified directly from the post-implant TRUS images, and (3) CT was used to define seed positions and prostate volumes from images acquired at 41-65 days post-implant. For each method, the volume of prostate receiving 90%, 100%, and 150% of the prescribed dose (V90, V100, V150) and the dose delivered to 90% of the prostate volume (D90) were calculated. RESULTS: Post-implant TRUS volumes were within 15% of the preimplant TRUS volumes in 8 of the 9 patients investigated. The post-implant CT volume was within 15% of the preimplant (TRUS) volume in only 3 of the 9 cases. The value of the dosimetry parameters was dependent on the method used and varied by 5-25% for V90, 5-30% for V100, 42-134% for V150, and 9-60% for D90. No simple relationship was found between change in volume and the resultant change in dosimetry parameter. Differences in dosimetry parameters due to source localization uncertainties was found to be small (< or = 10% for V100) when comparing methods (1) and (2). CONCLUSIONS: There are many uncertainties in the calculation of parameters that are commonly used to describe the quality of a permanent prostate implant. Differences in the parameters calculated were most likely a result of a combination of factors including uncertainties in delineating the prostate with different imaging modalities, differences in source identification techniques, and intraobserver variability.

A novel mutation in PNPLA2 leading to neutral lipid storage disease with myopathy.

BACKGROUND: Mutations in PNPLA2, a gene encoding adipose triglyceride lipase, lead to neutral lipid storage disease with myopathy. OBJECTIVE: To report the clinical and molecular features of a case of neutral lipid storage disease with myopathy resulting from a novel mutation in PNPLA2. DESIGN: Case report. SETTING: University hospital. PATIENT: A 65-year-old man with progressive muscle weakness and high serum creatine kinase levels. INTERVENTION: Direct sequencing of the PNPLA2 gene. RESULTS: Identification of a novel homozygous mutation in the patient's PNPLA2 gene confirmed the suspected diagnosis of neutral lipid storage disease with myopathy. CONCLUSION: Screening of the PNPLA2 gene should be considered for patients presenting with high levels of creatine kinase, progressive muscle weakness, and systemic lipid accumulation. The presence of Jordans anomaly can be a strong diagnostic clue.

Prostate-specific antigen relapse-free survival in patients with localized prostate cancer treated by brachytherapy.

OBJECTIVE: To report the clinical outcome after permanent implantation of (125)iodine seeds (brachytherapy) for early prostate cancer, after 8.2 years of follow-up. PATIENTS AND METHODS: Between March 1995 and December 2001, 667 men (mean age 63 years, range 42-77) were treated with brachytherapy at the one cancer centre; 346 (51.9%) had a short course of neoadjuvant hormone therapy. The prescribed minimum peripheral dose was 145 Gy. No patient received external beam radiation. RESULTS: The median (range) follow-up was 31 (18-98.2) months; 41 patients were lost to follow-up. The actuarial biochemical relapse-free survival was 74.9%; 100 patients had biochemical relapse (international definition). In all, 20 patients had clinical relapse, and 24 died (10 from prostate cancer). The prostate-specific antigen (PSA) relapse-free survival was 78.3%, 66.5% and 56.4% for patients with Gleason scores of <7, 7 and > 7, respectively, and was 81.4%, 69.8% and 36.3% for those with PSA levels of <10, 10-20 and > 20 ng/mL, respectively (both P < 0.001). There was a strong cohort effect depending on year of implant, with progressive annual improvements in relapse-free survival (P < 0.001). Hormone therapy, tumour stage, prostate volume before implantation, age and D90 dose had no significant effect on the outcome. CONCLUSION: The overall relapse-free survival for all patients was 75%; the initial PSA, Gleason score and risk group were significant factors predicting the outcome. Increasing clinical experience was associated with a better outcome but neoadjuvant hormone therapy had no effect.