Disruption of Pharmacotherapy During the Transition from Adolescence to Early Adulthood in Patients with Attention-Deficit/Hyperactivity Disorder: A Claims Database Analysis Across the USA.

BACKGROUND AND OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) treatment rates in adults are low, possibly owing to discontinuation of pediatric care due to various circumstances (including inadequate health insurance coverage, poor disease insight, and patient/family resistance, as well as those who manage their ADHD independent of pharmacologic intervention) during the transition from adolescence to adulthood. To improve the understanding of treatment patterns during this transition, this study characterized pharmacotherapy use in patients with ADHD aged 16-21 years. METHODS: A retrospective claims analysis of the IBM® MarketScan® Commercial Databases, which represent all census regions of the USA, included patients aged 16-21 years with two or more ADHD diagnoses between 1/1/2008 and 12/31/2017 (one or more diagnoses during the year of age 17) who were continuously enrolled from ages 16-21 years and prescribed ADHD medication for ≥ 6 months at age 17 years. Pharmacotherapy use was assessed longitudinally. Comparisons between ages were conducted using Wilcoxon signed-rank tests and McNemar tests. Treatment discontinuation was estimated using Kaplan-Meier analyses. RESULTS: The analysis included 10,292 patients. The overall percentage of patients receiving pharmacotherapy significantly decreased (p < 0.001, regardless of treatment type and presence of co-occurring psychiatric disorders) as patients aged, with a median time to treatment discontinuation of 2.94 years. Among patients using pharmacotherapy at the age of 17 years, more than 30% were no longer using pharmacotherapy at age 21 years. As patients aged, the percentage using long-acting amphetamines or methylphenidates decreased, and the percentage receiving no treatment increased. The percentage of patients with disrupted treatment from age 18 to 21 years ranged from 17.9 to 24.1%. After transitioning to disrupted treatment or no treatment, low percentages of patients returned to pharmacotherapy use (disrupted treatment: 15.7-21.5% per year; no treatment, 2.7-3.8% per year). Across all age groups, statistically significantly greater (p < 0.05) percentages of patients with co-occurring psychiatric disorders used lisdexamfetamine, dextroamphetamine-amphetamine mix short acting, and non-stimulants compared with patients without co-occurring psychiatric disorders. Patients with co-occurring psychiatric disorders remained on ADHD pharmacotherapy longer and switched or augmented their pharmacotherapy more frequently than patients without co-occurring psychiatric comorbidities. CONCLUSIONS: Patients rarely reinitiated treatment after pharmacotherapy was disrupted or discontinued, emphasizing the need for increased focus on the management of ADHD as patients transition from adolescence to adulthood.

Effects of hyperglycemia and aging on the healing of colonic anastomoses in rats.

INTRODUCTION: Despite the significant advances in the knowledge of the healing process, there is a limited number of studies demonstrating the relationships of this healing with ageing and elevated levels of glycemia. PURPOSE: To evaluate the effects of ageing and hyperglycemia on the healing of colonic anastomosis. METHODS: 138 young and old male rats were utilized. Some of them were normoglycemic and others had hyperglycemia induced by streptozocin (50mg/kg). They were maintained under control for 90 days. They were then submitted to a termino-terminal anastomosis in the left colon. On the third, seventh and fourteenth days after surgery, their resistance was evaluated and a histopathological study of the anastomosis was carried out. RESULTS: Gain in resistance was similar for both groups. The additive effect of age with hyperglycemia made a significant difference to the collagen I (p<0.001), III (p=0.022) and total (p<0.001). Among the old animals, the glycemia was a determining factor for the occurrence of a significant difference in total collagen (p=0.029) and collagen I (p=0.013). Among the normoglycemics, age determined a lower density of collagen I (p=0.002). CONCLUSION: There is delayed collagen synthesis and maturation of the scars of older animals, a situation that becomes more serious in older hyperglycemic animals, but insufficient to adversely affect the gain in resistance.

Effects of hyperglycemia and ageing on the healing of colonic anastomoses in rats / Efeitos da hiperglicemia e do envelhecimento na cicatrização de anastomoses colônicas, em ratos

INTRODUCTION: Despite the significant advances in the knowledge of the healing process, there is a limited number of studies demonstrating the relationships of this healing with ageing and elevated levels of glycemia. PURPOSE: To evaluate the effects of ageing and hyperglycemia on the healing of colonic anastomosis. METHODS: 138 young and old male rats were utilized. Some of them were normoglycemic and others had hyperglycemia induced by streptozocin (50mg/kg). They were maintained under control for 90 days. They were then submitted to a termino-terminal anastomosis in the left colon. On the third, seventh and fourteenth days after surgery, their resistance was evaluated and a histopathological study of the anastomosis was carried out. RESULTS: Gain in resistance was similar for both groups. The additive effect of age with hyperglycemia made a significant difference to the collagen I (p<0.001), III (p=0.022) and total (p<0.001). Among the old animals, the glycemia was a determining factor for the occurrence of a significant difference in total collagen (p=0.029) and collagen I (p=0.013). Among the normoglycemics, age determined a lower density of collagen I (p=0.002). CONCLUSION: There is delayed collagen synthesis and maturation of the scars of older animals, a situation that becomes more serious in older hyperglycemic animals, but insufficient to adversely affect the gain in resistance.

INTRODUÇÃO: Apesar dos significantes avanços no conhecimento do processo cicatricial há um restrito número de estudos demonstrando as relações deste reparo com o envelhecimento e com níveis elevados de glicemia. OBJETIVO: Avaliar os efeitos do envelhecimento e da hiperglicemia na cicatrização de anastomoses colônicas. MÉTODOS: Utilizaram-se 138 ratos machos, adultos jovens e velhos. Parte deles era normoglicêmico e parte teve hiperglicemia induzida pelo streptozocin (50mg/kg). Foram mantidos controlados por 90 dias. Após fez-se uma anastomose término-terminal no cólon esquerdo. No 3.º, 7.º e 14.º dia de pós-operatório avaliou-se a resistência e fez-se o estudo histo-patológico da anastomose. RESULTADOS: O ganho de resistência foi semelhante entre os grupos. O efeito aditivo da idade com a hiperglicemia determinou diferença significativa nos colágenos I (p<0,001), III (p=0,022) e total (p<0,001). Entre os velhos a glicemia foi determinante para ocorrer diferença significativa no colágeno total (p=0,029) e colágeno I (p=0,013). Entre os normoglicêmicos a idade determinou menor densidade de colágeno I (p=0,002). CONCLUSÃO: Existe atraso na síntese do colágeno e na maturação das cicatrizes nos animais velhos, situação que se agrava nos animais velhos e hiperglicêmicos, não suficiente para prejudicar o ganho de resistência.

Effects of hyperglycemia and aging in angiogenesis and reepithelization of colonic anastomoses in rats.

PURPOSE: To evaluate angiogenesis and reepithelization of colonic anastomoses in rats. METHODS: 82 Wistar rats, divided into: young normoglycemic, old normoglycemic and hyperglycemic. Diabetes was induced with streptozotocin. Glycemia was assessed before induction, at 24 hours and after 90 days, when a colotomy and an anastomosis were performed, assessed at days 3, 7, and 14. Samples were prepared by immuno-histochemistry (PCNA and antifactor VIII). RESULTS: Mean glycemia after 90 days streptozotocin induction was 244,95 mg/dl. Day 7, reepithelization was greater in the young group than in the old normoglycemic (p<0.0001) and old hyperglycemic (p<0.0001) groups. Day 14, the differences were significant between the young and old normoglycemic (p<0.0001) and old hyperglycemic (p<0.0001) groups. The two old groups were not significantly different. At the three periods angiogenesis was higher in the young group than in the old normoglycemic (p3=0.014; p7<0.0001; p14<0.0001) or the old hyperglycemic groups (p3=0.014, p7<0.0001; p14<0.0001). The old groups, day 3, were not different (p3=0.627), but days 7 and 14, angiogenesis was bigger in the normoglycemic group (p7=0.042; p14=0.005). CONCLUSION: Age is important in reepithelization and angiogenesis of colonic anastomoses. Hyperglycemia interferes mainly in angiogenesis.

Effects of hyperglycemia and aging in angiogenesis and reepithelization of colonic anastomoses in rats

PURPOSE: To evaluate angiogenesis and reepithelization of colonic anastomoses in rats. METHODS: 82 Wistar rats, divided into: young normoglycemic, old normoglycemic and hyperglycemic. Diabetes was induced with streptozotocin. Glycemia was assessed before induction, at 24 hours and after 90 days, when a colotomy and an anastomosis were performed, assessed at days 3, 7, and 14. Samples were prepared by immuno-histochemistry (PCNA and antifactor VIII). RESULTS: Mean glycemia after 90 days streptozotocin induction was 244,95 mg/dl. Day 7, reepithelization was greater in the young group than in the old normoglycemic (p<0.0001) and old hyperglycemic (p<0.0001) groups. Day 14, the differences were significant between the young and old normoglycemic (p<0.0001) and old hyperglycemic (p<0.0001) groups. The two old groups were not significantly different. At the three periods angiogenesis was higher in the young group than in the old normoglycemic (p3=0.014; p7<0.0001; p14<0.0001) or the old hyperglycemic groups (p3=0.014, p7<0.0001; p14<0.0001). The old groups, day 3, were not different (p3=0.627), but days 7 and 14, angiogenesis was bigger in the normoglycemic group (p7=0.042; p14=0.005). CONCLUSION: Age is important in reepithelization and angiogenesis of colonic anastomoses. Hyperglycemia interferes mainly in angiogenesis.

OBJETIVO: Avaliar a angiogênese e a reepitelização de anastomoses colônicas em ratos. MÉTODOS: 82 ratos Wistar divididos em: jovens normoglicêmicos, velhos normoglicêmicos e hiperglicêmicos. Diabetes foi induzido com estreptozotocin. Glicemia foi medida antes da indução, após 24 horas e 90 dias, quando realizou-se colotomia seguida de anastomose, a qual foi estudada no 3.°, 7.° e 14.° dia.Peças foram preparadas por imunohistoquímica (PCNA e Antifator VIII). RESULTADOS: Glicemia média após 90 dias foi de 244,95 mg/dl. No 7.° dia, a reepitelização foi maior no grupo jovem que nos grupos velho normoglicêmico (p<0,0001) e velho hiperglicêmico (p<0,0001). Dia 14, mantiveram-se as diferenças entre os grupos jovem e velhos normoglicêmico (p<0,0001) e hiperglicêmico (p<0,0001). Os dois grupos velhos não diferiram entre si. Nos três períodos a angiogênese foi maior no grupo jovem do que nos velhos normoglicêmicos (p3=0.014, p7<0.0001; p14<0.0001) e que nos velhos hiperglicêmicos (p3=0.014, p7<0.0001; p14<0.0001). No 3.° dia, os grupos velhos não foram diferentes (p3=0.627), mas no 7.° e no 14.°, a angiogênese foi maior no grupo normoglicêmico (p7=0.042; p14=0.005). CONCLUSÃO: Idade é importante para a reepitelização e angiogênese das anastomoses colônicas. Hiperglicemia interfere principalmente na angiogênese.