Toward a More Functional Analysis of Aggression

Given the substantial and oftentimes irreversible human loss resulting from aggressive acts, the need for systematic, treatment-linked assessment of aggression in school-aged children and youth cannot be overstated. Based upon recent research, the authors provide a broadly framed model for the functional analysis of aggression in school-age children and youth. Our model incorporates multi-modal data collection and data triangulation to generate credible hypotheses regarding the function(s) of aggression. Three primary data sources—record review and interviews, naturalistic observation, and analogue assessment—form the cornerstone of the model. Key features of our approach to the assessment of aggression include operational definition(s) of target behavior(s), examination of the environmental context(s) of aggression, and discovery of the function(s) of aggressive behaviors for the individual. Samples of several specific, ready-to-use data collection instruments and a basic description of the assessment procedure are presented. The assessment process assumes that a team of individuals participates in data collection, data analysis, and hypothesis generation

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Unprogrammed effects of training high-status peers to interact with severely handicapped children.

We examined the effects of a peer initiation intervention with high- and low-status nonhandicapped students on the behavior of untrained peers toward handicapped students. In the context of a counterbalanced withdrawal design, high- and low-status nonhandicapped students were taught to direct social initiations to eight severely handicapped students during recess activities. The interactions of the high-status students resulted in higher levels of initiations by untrained peers toward the handicapped students than did the interactions of the low-status students. Social response levels were also differentially affected by the status of the peer initiator

Use of descriptive and experimental analyses to identify the functional properties of aberrant behavior in school settings.

We conducted descriptive and experimental analyses of aberrant behavior in school settings with 2 children with autism, using teachers as assessors. Experimental functional analyses carried out by the investigators were followed by training teachers to conduct a descriptive analysis and a classroom experimental analysis. A comparison of the assessment procedures showed that each procedure identified negative reinforcement as a maintaining variable for aberrant behavior. The teacher implemented an intervention based on the assessment with mixed results. We then replicated the initial results by having the first teacher train a second teacher to carry out the two assessment procedures. The results of these analyses were also in agreement, again identifying negative reinforcement as a variable maintaining aberrant behavior. An intervention based on negative reinforcement was then successfully implemented. These results suggest the applicability and utility of functional analyses carried out in school settings

Use of negative reinforcement in the treatment of self-injurious behavior.

Behavioral assessment procedures were used to determine the maintaining conditions of self-injury exhibited by 2 children with severe multiple handicaps. For both children, negative reinforcement (escape from grooming activities) was determined to be the maintaining reinforcer for self-injury (hand/arm biting) within an alternating treatments design. The treatment packages involved the use of negative reinforcement (brief escape from grooming activities) contingent upon a behavior that was incompatible with self-injury (reaching and pressing a microswitch that activated a pre-recorded message of "stop"). Treatment was evaluated with a reversal design for 1 child and with a multiple baseline across grooming activities for the 2nd child. The treatment led to a marked decrease in self-injury for both children. At follow-up, high rates of self-injury were reported for the 1st child, but low rates of self-injury and an increase in task-related appropriate behavior were observed for the 2nd child

Using parents as therapists to evaluate appropriate behavior of their children: application to a tertiary diagnostic clinic.

We conducted a preliminary analysis of maintaining variables for children with conduct disorders in an outpatient clinic. Eight children of normal intelligence between the ages of 4 and 9 years were evaluated during 90-min sessions. The children's parents conducted the assessments by varying task demands (easy and difficult) and parental attention (attention and no attention) within a multielement design. The assessment focused on appropriate child behavior and was conducted to formulate hypotheses regarding maintaining contingencies. Results demonstrated that the children's appropriate behavior varied across assessment conditions and, for 7 of the 8 children, occurred at a higher rate during one condition than during other conditions. In addition, treatment integrity data demonstrated that parents were able to implement the procedures as intended. The recommended treatments were rated as being both effective and acceptable to parents for up to 6 months following the evaluation. Our results extend previous studies of functional analytic procedures conducted by trained experimenters with severely handicapped children in more controlled settings