Tonabersat, a gap-junction modulator: efficacy and safety in two randomized, placebo-controlled, dose-ranging studies of acute migraine

Tonabersat is a novel benzopyran derivative that blocks the cortical spreading depression proposed to be associated with migraine attacks. The ability of single oral doses of 15, 25, 40 and 80 mg of tonabersat to relieve the symptoms of moderate to severe migraine was evaluated in 859 migraineurs enrolled in two dose-ranging, double-blind, randomized, placebo-controlled, parallel-group trials, one international and the other North American. In the international study, significantly more patients given tonabersat than given placebo experienced relief of headache pain at 2 h (15 mg, 36.8%; 40 mg, 40.7%), the principal efficacy variable, and at 4 h (40 mg, 63.0%) and complete abolition of headache at 4 h (40 mg, 34.3%). None of the primary or secondary efficacy variables indicated significant differences between tonabersat and placebo in the North American study. Tonabersat was generally well tolerated, with dizziness and nausea the most common side-effects. Serious adverse events were uncommon, and no patient withdrew from either study because of adverse events. These results suggest a possible interplay between tonabersat pharmacokinetics (the relatively long time required to reach maximum plasma concentrations) and patient characteristics (previous triptan exposure) in the management of acute migraine attacks. Based on the pharmacokinetics and actions on cortical spreading depression, tonabersat may have potential value in migraine prophylaxis.     

The effect of casein phosphopeptide-amorphous calcium phosphate on erosive dentine wear

Background:  Erosive tooth wear is a growing concern in clinical dentistry. Our aims were to assess the effect of Tooth Mousse (TM) in managing erosive dentine wear in vitro .
Methods:  Opposing enamel and dentine specimens from 36 third molar teeth were worn under a load of 100 N for 75 000 cycles in electromechanical tooth wear machines. In experiment 1, TM was applied continuously at the wear interface and the mean dentine wear rate was compared with those of specimens subjected to continuous application of hydrochloric acid (HCl, pH 3.0) and deionized water (DW, pH 6.1) as lubricants. In experiment 2, specimens were subjected to TM application every 1600 cycles at both pH 3.0 and 6.1, and the mean dentine wear rates were compared with those of specimens worn with continuous application of HCl and DW lubricants.
Results:  Dentine wear was reduced significantly with continuous application of TM compared with HCl and DW lubricants. Specimens prepared with continuous TM application displayed smooth wear facets, whereas more pronounced microwear details were observed with HCl and DW lubricants.
Conclusions:  Both remineralization and lubrication seem to contribute to reduction in dentine wear associated with TM application, although lubrication appears to have a more pronounced effect.     

VEGF and MVD expression in sinus augmentation with autologous bone and several graft materials

Objective:  The aim of this study was to assess vascular endothelial growth factor (VEGF) expression and microvessel density (MVD) in maxillary sinus augmentation with autogenous bone and different graft materials for evaluating their angiogenic potential.
Methods:  Biopsies were harvested 10 months after sinus augmentation with a combination of autogenous bone and different graft materials: hydroxyapatite (HA, n  =   6 patients), demineralized freeze-dried bone allograft (DFDBA, n  =   5 patients), calcium phosphate (CP, n  =   5 patients), Ricinus communis polymer ( n  =   5 patients) and control group – autogenous bone only ( n  =   13 patients).
Results:  In all the samples, higher intensities of VEGF expression were prevalent in the newly formed bone, while lower intensities of VEGF expression were predominant in the areas of mature bone. The highest intensity of VEGF expression in the newly formed bone was expressed by HA ( P  < 0.001) and CP in relation to control ( P  < 0.01) groups. The lowest intensities of VEGF expression in newly formed bone were shown by DFDBA and polymer groups ( P  <   0.05). When comparing the different grafting materials, higher MVD were found in the newly formed bone around control, HA and CP ( P  <   0.001).
Conclusion:  Various graft materials could be successfully used for sinus floor augmentation; however, the interactions between bone formation and angiogenesis remain to be fully characterized.     

Surgically Managed Ovarian Masses at the Royal Children’s Hospital,Melbourne –19 Year Experience

Background/PurposeTo describe the clinicopathological characteristics and management of surgically removed ovarian masses at the Royal Children’s Hospital, Melbourne from 1993 to 2012.MethodsMedical records were reviewed retrospectively. Data regarding clinical findings, imaging and surgical management were evaluated.ResultsThere were 266 ovarian masses found in 258 surgeries (eight had bilateral masses). Most were benign (246/266, 92.5%), 2.3% (6/266) were borderline, and 5.3% (14/266) were malignant. The most common presenting symptom was abdominal pain for benign masses (169/246, 68.7%), and a palpable mass for borderline and malignant masses (12/20, 60.0%).Sensitivity and specificity of ultrasound for detection of malignancy was 64.7% and 52.9% respectively. Ovarian torsion occurred in 22.1% (n = 57), none with malignancy, with seven cases diagnosed under one year of age. Sensitivity and specificity of ultrasound for ovarian torsion was 22.0% and 91.9%, respectively.The proportion undergoing ovarian cystectomy rather than oophorectomy has increased from 56.3% during 1993-1997 to 93.8% during 2008-2012 (p < 0.005). Ovarian torsion was managed with ovarian conservation in 82.6% of cases between 2008-2012.ConclusionThe majority of pediatric and adolescent ovarian masses were benign. Sensitivity of ultrasound was fair for detection of malignancy, and poor for ovarian torsion. Conservative surgeries are increasingly common.Level of EvidenceLevel IV – case series with no comparison groupType of StudyRetrospective Study     

Blood pressure,executive function,and network connectivity in middle-aged adults at risk of dementia in late life

Midlife blood pressure is associated with structural brain changes, cognitive decline, and dementia in late life. However, the relationship between early adulthood blood pressure exposure, brain structure and function, and cognitive performance in midlife is not known. A better understanding of these relationships in the preclinical stage may advance our mechanistic understanding of vascular contributions to late-life cognitive decline and dementia and may provide early therapeutic targets. To identify resting-state functional connectivity of executive control networks (ECNs), a group independent components analysis was performed of functional MRI scans of 600 individuals from the Coronary Artery Risk Development in Young Adults longitudinal cohort study, with cumulative systolic blood pressure (cSBP) measured at nine visits over the preceding 30 y. Dual regression analysis investigated performance-related connectivity of ECNs in 578 individuals (mean age 55.5 ± 3.6 y, 323 female, 243 Black) with data from the Stroop color–word task of executive function. Greater connectivity of a left ECN to the bilateral anterior gyrus rectus, right posterior orbitofrontal cortex, and nucleus accumbens was associated with better executive control performance on the Stroop. Mediation analyses showed that while the relationship between cSBP and Stroop performance was mediated by white matter hyperintensities (WMH), resting-state connectivity of the ECN mediated the relationship between WMH and executive function. Increased connectivity of the left ECN to regions involved in reward processing appears to compensate for the deleterious effects of WMH on executive function in individuals across the burden of cumulative systolic blood pressure exposure in midlife.

Vascular risk factors (VRF) such as hypertension in midlife are associated with cognitive decline in late life (1–4). Notably, deficits in executive function, such as cognitive flexibility or inhibitory control, are early and “prominent” in vascular-related neurocognitive disorders (5). VRF are also associated with structural MRI brain changes such as white matter hyperintensities (WMH) (6), gray matter atrophy (7), and subcortical morphological changes (8), which may not be reversible. However, functional MRI (fMRI) changes may be detectable prior to irreversible structural damage. fMRI studies have shown that VRF are associated with reduced functional connectivity of brain networks and that this reduced network connectivity is associated with cognitive decline (9, 10). Understanding these relationships in midlife individuals and prior to the clinical onset of cognitive decline could provide significant insight into imaging markers that may identify individuals at risk of cognitive impairment and mechanisms for targeted interventions.In this study, we examined the relationship between blood pressure (BP), executive performance, and resting-state fMRI (rsfMRI) connectivity in participants from the brain substudy of the Coronary Artery Disease in Young Adults (CARDIA) longitudinal cohort study. We hypothesized that greater rsfMRI connectivity of executive control networks (ECN) would be related to better performance in an out-of-scanner executive control (Stroop) task. We further hypothesized that while the previously established relationship of systolic BP (SBP) to Stroop performance (11) would be mediated by WMH, the established relationship between WMH and executive function (12, 13) would be mediated by ECN connectivity.     

The effect of name-based reporting and partner notification on HIV testing in New York State

Objectives. We examined the effect of New York’s HIV Reporting and Partner Notification law on HIV testing levels and on the HIV testing decisions of high-risk individuals.Methods. In-person interviews were administered to 761 high-risk individuals to assess their knowledge, attitudes, and behaviors regarding HIV testing and reporting. Trends in HIV testing were also assessed in publicly funded HIV counseling and testing programs, Medicaid, and New York’s Maternal Pediatric Newborn Prevention and Care Program.Results. High-risk individuals had limited awareness of the reporting and notification law, and few cited concern about named reporting as a reason for avoiding or delaying HIV testing. HIV testing levels, posttest counseling rates, and anonymous-to-confidential conversion rates among those who tested HIV positive were not affected by the law. Medicaid-related HIV testing rates also remained stable. HIV testing during pregnancy continued to trend upward following implementation of the law. Findings held true within demographic and risk-related subgroups.Conclusions. HIV reporting has permitted improved monitoring of New York’s HIV/AIDS epidemic. This benefit has not been offset by decreases in HIV testing behavior, including willingness to test among those at high risk of acquiring HIV.New York State leads the nation in AIDS cases, with more than 170000 AIDS cases diagnosed through 2005.1 Prior to 2000, public health surveillance in New York State was carried out exclusively through the reporting of AIDS cases. AIDS case surveillance, however, reflects disease transmission patterns in the distant past: historically, it has taken 10 years on average for persons to progress from HIV infection to AIDS. The advent of highly active antiretroviral therapy in the mid-1990s significantly slowed progression from HIV infection to AIDS, further reducing the value of AIDS case surveillance in tracking the HIV epidemic.2 In 1998 the Centers for Disease Control and Prevention (CDC) recommended that all states and local surveillance programs undertake name-based HIV reporting.A primary concern with name-based HIV reporting is that it might deter HIV testing behavior. Research from other states has yielded conflicting findings. In the late 1980s and early 1990s, several surveys of HIV testing behavior in at-risk populations suggested a deterrent effect of HIV reporting.3^–6 More recent studies have found fewer or no deterrent effects. The HIV Testing Survey7 was conducted in 9 states with differing HIV reporting policies in the mid-1990s. Results indicated a low awareness of states’ reporting laws among high-risk individuals in general and little evidence that HIV testing decisions were being strongly influenced by a concern about name-based HIV reporting.8^–11 However, people who lived in states with name-based HIV reporting were more likely to delay—rather than completely avoid—HIV testing,8 and concerns about name-based reporting were expressed by some men who have sex with men and intravenous drug users.8^,9In the late 1990s, the Multistate Evaluation of Surveillance for HIV project studied a probability sample of nearly 2000 AIDS patients in 8 states.12 The percentage of study participants obtaining timely medical care differed only slightly in states with and without name-based HIV reporting, with fear of being reported to the health department given as a reason for delaying care by 9% of respondents; none cited this as the main reason.A few studies have addressed prenatal HIV testing and found no evidence that maternal HIV testing is affected by the initiation of name-based HIV reporting.13^,14 A 1998 study by Nakashima et al. examined HIV testing levels in publicly funded HIV testing sites in 6 states before and after the introduction of HIV reporting.15 The authors found no decreases in the total number of HIV tests reported after HIV reporting laws took effect in any state; however, statistically significant changes in testing levels were found among select HIV-risk and demographic groups across states. This study has been criticized for failing to use data from states with high HIV prevalence16 and for not further investigating the subgroup differences.17New York State’s HIV Reporting and Partner Notification (HIVRPN) law became effective June 1, 2000.18 The law requires named reporting of persons with HIV infection, HIV-related illness, and AIDS by physicians and laboratories. Physicians also are required to report known partners of infected individuals, but individuals testing HIV positive are not required to name partners for the purpose of partner notification. An intimate partner violence screening tool must be applied for each identified partner, and partner notification may be deferred in cases where a risk of violence exists (on the part of the partner or the infected individual). Consistent with CDC guidelines for HIV case surveillance,19 New York’s law retains anonymous HIV counseling and testing to offset potential deterrent effects of HIV reporting on test-seeking behavior. Several studies have addressed the need for anonymous HIV counseling and testing, with many studies suggesting that anonymous counseling and testing may be an important component to HIV prevention, especially for certain subgroups.11^,20^–24Previous examinations of HIV reporting laws were largely limited to states with lower prevalences of HIV. In addition, concern was expressed that the formal integration of HIV partner notification and intimate partner violence screening into New York’s law might affect HIV testing behavior. The implementation of the HIVRPN law provided an opportunity to assess the effect of the law, including the partner notification and intimate partner violence screening requirements, on HIV testing behaviors in a high–HIV prevalence state.