A randomized controlled clinical evaluation of desensitization efficacy of a newly developed toothpaste with highly stabilized SnF2.

PURPOSE: To assess the relief of dentin hypersensitivity of the new toothpaste with stabilized stannous fluoride (SnF2) versus a marketed standard fluoride toothpaste as a negative control and a marketed anhydrous SnF2 toothpaste as a positive control. METHODS: This was a single-centered, randomized, controlled, double blind, clinical trial. 96 participants with hypersensitivity were enrolled in this 4-week clinical study. Electrical stimulation and evaporative air tests were performed to evaluate the desensitization efficacy. Clinical assessments were made at baseline, and after 3 days, 1 week, 2 weeks and 4 weeks of twice-daily brushing. Additionally, the influence of Sn² ⁺ species on desensitization was evaluated using bovine dentin specimens treated with toothpaste. RESULTS: All 96 enrolled participants were randomized. 96 participants completed all evaluations. Participants had an average age (SD) of 47.0 (10.5) years; 45% of participants were female. Both SnF2 toothpastes showed superior desensitization efficacy compared to the negative control toothpaste, the conventional sodium monofluorophosphate (SMFP) toothpaste, after a week. The new stabilized SnF2 toothpaste demonstrated improved electrical stimulation benefits compared to the negative control toothpaste, with increases of 15.1% after 3 days, 34.2% after 1 week, 66.3% after 2 weeks, and 111.6% after 4 weeks. Additionally, it showed relative verbal evaluation scale (VES) benefits of 14.2% after 3 days, 37.6% after 1 week, 28.9% after 2 weeks, and 37.4% after 4 weeks. The stabilized SnF2 toothpaste exhibited desensitization properties comparable to those of a commercial anhydrous SnF2 toothpaste, which typically produces undesirable side effects in the mouth. Toothpastes containing 0.454 % SnF2 exhibited perfect occlusion of dentin tubules. CLINICAL SIGNIFICANCE: The stabilized 0.454% SnF2 toothpaste exhibited significantly greater dentin hypersensitivity relief within only a week and comparable property to commercial anhydrous SnF2 toothpaste.

Tooth wear and cleaning effect of an abrasive-free dentifrice.

BACKGROUND/PURPOSE: To evaluate the degree of wear on human teeth and the cleaning effect of abrasive-free dentifrice. A sodium pyrophosphate and cellulose-containing abrasive-free dentifrice and calcium carbonate-containing control dentifrice were evaluated. MATERIALS AND METHODS: Dentin and enamel specimens were subjected to 109,500 successive double strokes and 5480 double strokes in pH-cycling condition. A profilometer measured abrasion depth. The cleaning effect of dentifrices on artificial stain was evaluated by cleaning power (modified Stookey method) and by removal of colored stain on artificial tooth. RESULTS: The experimental results were evaluated using Mann-Whitney U test. The abrasion depth in dentin specimens was 13.97-26.73 times smaller with abrasive-free dentifrice than with control dentifrice. The abrasion depth of enamel specimen was 2.17 ± 0.66 µm with control dentifrice. The values for abrasive-free dentifrice were too small to measure. In pH-cycling conditions using dentin specimens, abrasion depth was 14.28-19.00 times smaller with abrasive-free dentifrice than with control dentifrice. The cleaning power and removing effect of colored stain were statistically insignificant between abrasive-free dentifrice and control dentifrice (P > 0.05). CONCLUSION: The abrasive-free dentifrice was as effective as control dentifrice in its cleaning effect on artificial stain and can significantly reduce tooth wear more than control dentifrice.

Disruptive mood dysregulation disorder and chronic irritability in youth at familial risk for bipolar disorder.

OBJECTIVE: Disruptive mood dysregulation disorder (DMDD) is a new diagnosis in the DSM-5. Youth with a family history of bipolar disorder (BD) are at increased risk for BD and non-bipolar psychopathology. No studies to date have examined rates of DMDD among offspring of parents with BD. This study examines the risk for DMDD in offspring of parents with BD compared to community controls and considers rates of chronic irritability (independent of a DMDD diagnosis) across diagnoses in youth with parents with BD. METHOD: Modified DMDD criteria were applied post hoc to 375 offspring of parents with BD and 241 offspring, aged 6 to 17 years, of community control parents. We calculated odds ratios using generalized linear mixed models. In addition, we explored associations with a severe chronic irritability phenotype and various diagnoses in the high-risk cohort. RESULTS: Offspring of parents with BD were more likely to meet criteria for DMDD than were the offspring of community control parents (Odds ratio [OR] = 8.3, 6.7% vs. 0.8%), even when controlling for demographic variables and comorbid parental diagnoses (OR = 5.4). They also had higher rates of chronic irritability compared to community controls (12.5% vs. 2.5%, χ(2) = 18.8, p < .005). Within the offspring of parents with BD, the chronic irritability phenotype was frequently present in offspring with diagnoses of BD, depression, attention-deficit/hyperactivity disorder, and disruptive behavior disorders. CONCLUSIONS: Like other non-BD diagnoses, family history of BD increases the risk for DMDD. Severe chronic irritability and temper tantrums are the core features of DMDD, and are associated with mood and behavioral disorders in youth at risk for BD.

Effects of comorbid anxiety disorders on the longitudinal course of pediatric bipolar disorders.

OBJECTIVE: To examine the longitudinal effects of comorbid anxiety disorders in youth with bipolar spectrum disorder (BP). METHOD: As part of the Course and Outcome of Bipolar Youth study, 413 youth, who were 7 through 17 years or age and who met criteria for DSM-IV BP-I (n = 244), BP-II (n = 28), and operationally defined bipolar disorder not otherwise specified (BP-NOS) (n = 141) were included. Subjects were followed on average 5 years using the Longitudinal Interval Follow-up Evaluation. Effects of anxiety on the time to mood recovery and recurrence and percentage of time with syndromal and subsyndromal mood symptomatology during the follow-up period were analyzed. RESULTS: At intake and during the follow-up, 62% of youth with BP met criteria for at least 1 anxiety disorder. About 50% of the BP youth with anxiety had ≥2 anxiety disorders. Compared to BP youth without anxiety, those with anxiety had significantly more depressive recurrences and significantly longer median time to recovery. The effects of anxiety on recovery disappeared when the severity of depression at intake was taken into account. After adjusting for confounding factors, BP youth with anxiety, particularly those with ≥2 anxiety disorders, spent significantly less follow-up time asymptomatic and more time with syndromal mixed/cycling and subsyndromal depressive symptomatology compared to those without anxiety. CONCLUSIONS: Anxiety disorders are common and adversely affect the course of BP in youth, as characterized by more mood recurrences, longer time to recovery, less time euthymic, and more time in mixed/cycling and depressive episodes. Prompt recognition and the development of treatments for BP youth with anxiety are warranted.

Predictors of first-onset substance use disorders during the prospective course of bipolar spectrum disorders in adolescents.

OBJECTIVE: Substance use disorders (SUD) are common and problematic in bipolar disorder (BP). We prospectively examined predictors of first-onset SUD among adolescents with BP. METHOD: Adolescents (12-17 years old; N = 167) in the Course and Outcome of Bipolar Youth (COBY) study fulfilling criteria for BP-I, BP-II, or operationalized BP not otherwise specified, without SUD at intake, were included. Baseline demographic, clinical, and family history variables, and clinical variables assessed during follow-up, were examined in relation to first-onset SUD. Participants were prospectively interviewed every 38.5 ± 22.2 weeks for an average of 4.25 ± 2.11 years. RESULTS: First-onset SUD developed among 32% of subjects, after a mean of 2.7 ± 2.0 years from intake. Lifetime alcohol experimentation at intake most robustly predicted first-onset SUD. Lifetime oppositional defiant disorder and panic disorder, family history of SUD, low family cohesiveness, and absence of antidepressant treatment at intake were also associated with increased risk of SUD, whereas BP subtype was not. Risk of SUD increased with increasing number of these 6 predictors: 54.7% of subjects with 3 or more predictors developed SUD vs. 14.1% of those with fewer than 3 predictors (hazard ratio = 5.41 95% confidence interval = 2.7-11.0 p < .0001). Greater hypo/manic symptom severity in the preceding 12 weeks predicted greater likelihood of SUD onset. Lithium exposure in the preceding 12 weeks predicted lower likelihood of SUD. CONCLUSIONS: This study identifies several predictors of first-onset SUD in the COBY sample that, if replicated, may suggest targets for preventive interventions for SUD among youth with BP. Treatment-related findings are inconclusive and must be interpreted tentatively, given the limitations of observational naturalistic treatment data. There is a substantial window of opportunity between BP and SUD onset during which preventive strategies may be used.

Mood lability among offspring of parents with bipolar disorder and community controls.

OBJECTIVES: Early identification of bipolar disorder (BP) symptomatology is crucial for improving the prognosis of this illness. Increased mood lability has been reported in BP. However, mood lability is ubiquitous across psychiatric disorders and may be a marker of severe psychopathology and not specific to BP. To clarify this issue, this study examined the prevalence of mood lability and its components in offspring of BP parents and offspring of community control parents recruited through the Pittsburgh Bipolar Offspring Study. METHODS: Forty-one school-age BP offspring of 38 BP parents, 257 healthy or non-BP offspring of 174 BP parents, and 192 offspring of 117 control parents completed a scale that was developed to evaluate mood lability in youth, i.e., the Children's Affective Lability Scale (CALS). RESULTS: A factor analysis of the parental CALS, and in part the child CALS, revealed Irritability, Mania, and Anxiety/Depression factors, with most of the variance explained by the Irritability factor. After adjusting for confounding factors (e.g., parental and offspring non-BP psychopathology), BP offspring of BP parents showed the highest parental and child total and factor scores, followed by the non-BP offspring of BP parents, and then the offspring of the controls. CONCLUSIONS: Mood lability overall and mania-like, anxious/depressed, and particularly irritability symptoms may be a prodromal phenotype of BP among offspring of parents with BP. Prospective studies are warranted to clarify whether these symptoms will predict the development of BP and/or other psychopathology. If confirmed, these symptoms may become a target of treatment and biological studies before BP develops.

Predictors of prospectively examined suicide attempts among youth with bipolar disorder.

CONTEXT: Individuals with early onset of bipolar disorder are at high risk for suicide. Yet, no study to date has examined factors associated with prospective risk for suicide attempts among youth with bipolar disorder. OBJECTIVE: To examine past, intake, and follow-up predictors of prospectively observed suicide attempts among youth with bipolar disorder. DESIGN: We interviewed subjects, on average, every 9 months over a mean of 5 years using the Longitudinal Interval Follow-up Evaluation. SETTING: Outpatient and inpatient units at 3 university centers. PARTICIPANTS: A total of 413 youths (mean [SD] age, 12.6 [3.3] years) who received a diagnosis of bipolar I disorder (n=244), bipolar II disorder (n=28), or bipolar disorder not otherwise specified (n=141). MAIN OUTCOME MEASURES: Suicide attempt over prospective follow-up and past, intake, and follow-up predictors of suicide attempts. RESULTS: Of the 413 youths with bipolar disorder, 76 (18%) made at least 1 suicide attempt within 5 years of study intake; of these, 31 (8% of the entire sample and 41% of attempters) made multiple attempts. Girls had higher rates of attempts than did boys, but rates were similar for bipolar subtypes. The most potent past and intake predictors of prospectively examined suicide attempts included severity of depressive episode at study intake and family history of depression. Follow-up data were aggregated over 8-week intervals; greater number of weeks spent with threshold depression, substance use disorder, and mixed mood symptoms and greater number of weeks spent receiving outpatient psychosocial services in the preceding 8-week period predicted greater likelihood of a suicide attempt. CONCLUSIONS: Early-onset bipolar disorder is associated with high rates of suicide attempts. Factors such as intake depressive severity and family history of depression should be considered in the assessment of suicide risk among youth with bipolar disorder. Persistent depression, mixed presentations, and active substance use disorder signal imminent risk for suicidal behavior in this population.

Factors associated with the persistence and onset of new anxiety disorders in youth with bipolar spectrum disorders.

OBJECTIVE: Anxiety disorders are among the most common comorbid conditions in youth with bipolar disorder, but, to our knowledge, no studies examined the course of anxiety disorders in youth and adults with bipolar disorder. METHOD: As part of the Course and Outcome of Bipolar Youth study, 413 youth, ages 7 to 17 years who met criteria for Diagnostic and Statistical Manual, Fourth Edition (DSM-IV) bipolar I disorder (n = 244), bipolar II disorder (n = 28), and operationally defined bipolar disorder not otherwise specified (n = 141) were recruited primarily from outpatient clinics. Subjects were followed on average for 5 years using the Longitudinal Interval Follow-Up Evaluation. We examined factors associated with the persistence (> 50% of the follow-up time) and onset of new anxiety disorders in youth with bipolar disorder. RESULTS: Of the 170 youth who had anxiety at intake, 80.6% had an anxiety disorder at any time during the follow-up. Most of the anxiety disorders during the follow-up were of the same type as those present at intake. About 50% of the youth had persistent anxiety, particularly generalized anxiety disorder (GAD). Persistence was associated with multiple anxiety disorders, less follow-up time in euthymia, less conduct disorder, and less treatment with antimanic and antidepressant medications (all P values ≤ .05). Twenty-five percent of the sample who did not have an anxiety disorder at intake developed new anxiety disorders during follow-up, most commonly GAD. The onset of new anxiety disorders was significantly associated with being female, lower socioeconomic status, presence of attention-deficit/hyperactivity disorder and substance use disorder, and more follow-up time with manic or hypomanic symptoms (all P values ≤ .05) CONCLUSIONS: Anxiety disorders in youth with bipolar disorder tend to persist, and new-onset anxiety disorders developed in a substantial proportion of the sample. Early identification of factors associated with the persistence and onset of new anxiety disorders may enable the development of strategies for treatment and prevention.

Course of subthreshold bipolar disorder in youth: diagnostic progression from bipolar disorder not otherwise specified.

OBJECTIVE: To determine the rate of diagnostic conversion from an operationalized diagnosis of bipolar disorder not otherwise specified (BP-NOS) to bipolar I disorder (BP-I) or bipolar II disorder (BP-II) in youth over prospective follow-up and to identify factors associated with conversion. METHOD: Subjects were 140 children and adolescents recruited from clinical referrals or advertisement who met operationalized criteria for BP-NOS at intake and participated in at least one follow-up evaluation (91% of initial cohort). Diagnoses were assessed at follow-up interviews using the Longitudinal Interval Follow-Up Evaluation. The mean duration of follow-up was 5 years and the mean interval between assessments was 8.2 months. RESULTS: Diagnostic conversion to BP-I or BP-II occurred in 63 subjects (45%): 32 (23%) to BP-I (nine of whom had initially converted to BP-II) and 31 to only BP-II (22%). Median time from intake to conversion was 58 weeks. First- or second-degree family history of mania or hypomania was the strongest baseline predictor of diagnostic conversion (p = .006). Over follow-up, conversion was associated with greater intensity of hypomanic symptoms and with greater exposure to specialized, intensive outpatient psychosocial treatments. There was no association between conversion and exposure to treatment with particular medication classes. CONCLUSIONS: Children and adolescents referred with mood symptoms that meet operationalized criteria for BP-NOS, particularly those with a family history of BP, frequently progress to BP-I or BP-II. Efforts to identify these youth and effectively intervene may have the potential to curtail the progression of mood disorders in this high-risk population.

Comorbid anxiety in children and adolescents with bipolar spectrum disorders: prevalence and clinical correlates.

OBJECTIVE: Anxiety disorders are among the most common comorbid conditions in youth with bipolar disorder. We aimed to examine the prevalence and correlates of comorbid anxiety disorders among youth with bipolar disorder. METHOD: As part of the Course and Outcome of Bipolar Youth study, 446 youth, ages 7 to 17 years, who met DSM-IV criteria for bipolar I disorder (n = 260) or bipolar II disorder (n = 32) or met operationalized criteria for bipolar disorder not otherwise specified (n = 154) were included. Subjects were evaluated for current and lifetime Axis I psychiatric disorders at intake using the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Aged Children-Present and Lifetime version, and standardized instruments were used to assess functioning and family history. RESULTS: Forty-four percent (n = 194) of the sample met DSM-IV criteria for at least 1 lifetime anxiety disorder, most commonly separation anxiety (24%) and generalized anxiety disorders (16%). Nearly 20% met criteria for 2 or more anxiety disorders. Overall, anxiety disorders predated the onset of bipolar disorder. Subjects with bipolar II disorder were more likely than subjects with bipolar I disorder or bipolar disorder not otherwise specified to have a comorbid anxiety disorder. After adjusting for confounding factors, youth with bipolar disorder with anxiety were more likely to have bipolar II disorder; longer duration of mood symptoms; more severe ratings of depression; and family history of depression, hopelessness, and somatic complaints during their worst lifetime depressive episode than those without anxiety. CONCLUSIONS: Comorbid anxiety disorders are common in youth with bipolar disorder, and they most often predate bipolar disorder onset. Bipolar II disorder, a family history of depression, and more severe lifetime depressive episodes distinguish youth with bipolar disorder with comorbid anxiety disorders from those without. Careful consideration should be given to the assessment of comorbid anxiety in youth with bipolar disorder.

Four-year longitudinal course of children and adolescents with bipolar spectrum disorders: the Course and Outcome of Bipolar Youth (COBY) study.

OBJECTIVE: The authors sought to assess the longitudinal course of youths with bipolar spectrum disorders over a 4-year period. METHOD: At total of 413 youths (ages 7-17 years) with bipolar I disorder (N=244), bipolar II disorder (N=28), and bipolar disorder not otherwise specified (N=141) were enrolled in the study. Symptoms were ascertained retrospectively on average every 9.4 months for 4 years using the Longitudinal Interval Follow-Up Evaluation. Rates and time to recovery and recurrence and week-by-week symptomatic status were analyzed. RESULTS: Approximately 2.5 years after onset of their index episode, 81.5% of the participants had fully recovered, but 1.5 years later 62.5% had a syndromal recurrence, particularly depression. One-third of the participants had one syndromal recurrence, and 30% had two or more. The polarity of the index episode predicted that of subsequent episodes. Participants were symptomatic during 60% of the follow-up period, particularly with subsyndromal symptoms of depression and mixed polarity, with numerous changes in mood polarity. Manic symptomatology, especially syndromal, was less frequent, and bipolar II was mainly manifested by depressive symptoms. Overall, 40% of the participants had syndromal or subsyndromal symptoms during 75% of the follow-up period, and 16% of the participants experienced psychotic symptoms during 17% the follow-up period. Twenty-five percent of youths with bipolar II converted to bipolar I, and 38% of those with bipolar disorder not otherwise specified converted to bipolar I or II. Early onset, diagnosis of bipolar disorder not otherwise specified, long illness duration, low socioeconomic status, and family history of mood disorders were associated with poorer outcomes. CONCLUSIONS: Bipolar spectrum disorders in youths are characterized by episodic illness with subsyndromal and, less frequently, syndromal episodes with mainly depressive and mixed symptoms and rapid mood changes.