Patient perceptions about chemotherapy-induced oral mucositis: implications for primary/secondary prophylaxis strategies.

GOALS: Oral mucositis (OM), the painful inflammation of oropharyngeal tissues, is an economically costly chemotherapy toxicity. Several agents to prevent chemotherapy-induced OM are in development, with most studies conducted among transplantation subjects with a brief well-defined risk period. The potential value of these preventative agents among hematology-oncology populations receiving cyclic standard-dose therapy is unknown. PATIENTS AND METHODS: Patients receiving standard-dose chemotherapy at an outpatient oncology center over a 2-week time-frame were invited to participate in an anonymous unprompted survey. The survey instrument consisted of six demographic questions and six questions regarding toxicities of chemotherapy. RESULTS: Of 514 patients providing completed surveys from among approximately 1625 patients (32% response rate), 167 (32%) reported experiencing OM. Factors associated with developing OM included number of chemotherapy cycles ( P=0.001), hematologic malignancy ( P=0.02), female gender ( P=0.03), age ( P=0.05), and treatment with anthracyclines ( P=0.001), vinca alkaloids ( P=0.001), cyclophosphamide ( P=0.001), fludarabine ( P=0.01), cis/carboplatin ( P=0.05) and radiotherapy ( P=0.005). Among patients experiencing OM, 69% considered OM to be an important toxicity with 7% rating their OM very severe, 18% severe, 36% moderate and 29% mild. Recurrent OM was reported by 87 patients (53%) and was judged similar in severity by 67%, milder by 27% and more severe by 6%. OM was considered the sixth most distressing complication behind (in descending order) fatigue, hair loss, nausea, numbness and diarrhea, and more important than anxiety and heartburn. CONCLUSIONS: OM represents a common toxicity of standard-dose chemotherapy occurring in approximately one-third of patients. High-risk populations can be identified, permitting targeting of primary prophylaxis strategies whereby all patients possessing high-risk factors are treated to prevent OM. However, since OM was self-reported by only one-third of patients receiving standard-dose chemotherapy, but over half of those experiencing OM developed recurrent episodes, secondary prophylaxis strategies targeting recurrent OM episodes may be more appropriate.

Dopamine receptor 4 (DRD4) 7-repeat allele predicts methylphenidate dose response in children with attention deficit hyperactivity disorder: a pharmacogenetic study.

OBJECTIVE: Genetic polymorphisms of the dopamine neurotransmitter system have been identified in attention deficit hyperactivity disorder (ADHD). Since stimulant medications act through this system, we sought to determine if the 48 base pair VNTR polymorphism (7- repeat allele) of dopamine receptor gene DRD4 predicts methylphenidate responsiveness. METHODS: Forty-five children, aged 7-15 years, with ADHD, confirmed by NIMH-DISC-IV, participated in this prospective pharmacogenetic study. Subjects received increasing methylphenidate doses based on serial Conners' Global Index-Parent assessments. Doses to obtain a 10-point improvement and normalization (T-score, 60) were determined. Blood and buccal screening for DRD4 7R was correlated with outcomes. RESULTS: Mean dose for a 10-point CGI-P improvement with DRD4 7R (n=20) was 30 mg (1.00 mg/kg) versus 20 mg (0.49 mg/kg) without 7R (n=25) (log rank=13.69; df=1; p=0.0002). Mean dose for CGI-P normalization for children with 7R was 47 mg (1.70 mg/kg) of methylphenidate versus 31 mg (0.79 mg/kg) of methylphenidate without 7R (log rank=14.17; df=1; p=0.0002). ADHD symptom normalization at < or =50 mg methylphenidate was achieved in 58% with 7R versus 95% without (log rank=9.45; df=1; p=0.002). CONCLUSIONS: Children with ADHD possessing the DRD4 7R allele require higher doses of methylphenidate for symptom improvement and symptom normalization. This pharmacogenetic study demonstrates that the 7-repeat allele of the DRD4 gene VNTR polymorphism correlates with treatment outcomes.

Emotional abuse in children: variations in legal definitions and rates across the United States.

Child emotional abuse has an intangible quality that has resulted in confusion regarding both medical and legal definitions. This retrospective review of emotional, physical, sexual abuse, and neglect rates reported by the National Center for Child Abuse and Neglect Data System revealed a 300-fold variation in the rate of emotional abuse across state boundaries. By contrast, the rates of physical and sexual abuses, which are much easier to define, were significantly more consistent. To better understand the potential reasons for the unique variability of emotional abuse, an analysis of sociodemographic factors was performed and no correlations were found. However, a systematic review of state laws on child emotional abuse revealed that states having inclusive civil and/or inclusive caretaker culpability statutes were more likely to report higher rates of child emotional abuse. This study supports a need for child maltreatment researchers and advocates to develop clear consensus definitions to aid the legal community in adopting uniform inclusive statutes to protect children from emotional abuse.