Post-mortem magnetic resonance imaging in patients with suspected prion disease:Pathological confirmation, sensitivity, specificity and observer reliability. A national registry

<div><p>The relationship between magnetic resonance imaging (MRI) and clinical variables in patients suspected to have Creutzfeldt-Jakob Disease (CJD) is uncertain. We aimed to determine which MRI features of CJD (positive or negative), previously described in vivo, accurately identify CJD, are most reliably detected, vary with disease duration, and whether combined clinical and imaging features increase diagnostic accuracy for CJD. Prospective patients suspected of having CJD were referred to the National CJD Research and Surveillance Unit between 1994–2004; post-mortem, brains were sent for MRI and histopathology. Two neuroradiologists independently assessed MRI for atrophy, white matter hyperintensities, and caudate, lentiform and pulvinar signals, blind to histopathological diagnosis and clinical details. We examined differences in variable frequencies using Fisher’s exact tests, and associations between variables and CJD in logistic regression models. Amongst 200 cases, 118 (59%) with a histopathological diagnosis of CJD and 82 (41%) with histopathological diagnoses other than CJD, a logistic regression model including age, disease duration at death, atrophy, white matter hyperintensities, bright or possibly bright caudate, and present pulvinar sign correctly classified 81% of cases as CJD versus not CJD. Pulvinar sign alone was not independently associated with an increased likelihood of histopathologically-confirmed CJD (of any subtype) or sporadic CJD after adjustment for age at death, disease duration, atrophy, white matter hyperintensities or caudate signal; despite the large sample, data sparsity precluded investigation of the association of pulvinar sign with variant CJD. No imaging feature varied significantly with disease duration. Of the positive CJD signs, neuroradiologists most frequently agreed on the presence or absence of atrophy (agreements in 169/200 cases [84.5%]). Combining patient age, and disease duration, with absence of atrophy and white matter hyperintensities and presence of increased caudate signal and pulvinar sign predicts CJD with good accuracy. Autopsy remains essential.</p></div

The putamen intensity gradient in CJD diagnosis

The deep grey matter structures of the brain have been reported to show MR hyperintensity in the sporadic form of Creutzfeldt-Jakob disease (sCJD), but the criteria for visual judgment of this are not well defined. We carried out a quantitative study of T2 weighted and proton density scans comparing 10 sCJD patients with 10 non-CJD dementia controls (NCD) and also with I I patients suffering from the new variant form of CID (vCJD). Scans were acquired in a clinical context and came from many hospitals. Absolute intensities varied widely and did not allow any useful discrimination. In all groups the putamen had a gradient of reducing, intensity from anterior to posterior on T2 scans. In both s- and v- CJD patients this gradient was increased. Sensitivity and specificity (S&S) for sCJD against NCD were 89%. The T2 and PD intensities of the putamen relative to the other grey matter structures studied were not useful for distinguishing between any of the patient groups. The ratio of putamen to frontal white matter T2 intensity was significantly increased in vCJD compared to NCD and also to sCJD, while sCJD and NCD were indistinguishable by this test. We conclude that: (1) in our preliminary study, the putamen gradient appears to be important diagnostically for sCJD; (2) intensities of deep grey matter structures vary systematically and intensity-based segmentation methods used in patients and normals should take account of this

Treatments for hypersensitive noncarious cervical lesions: A Practitioners Engaged in Applied Research and Learning (PEARL) Network randomized clinical effectiveness study

BACKGROUND: The Practitioners Engaged in Applied Research and Learning (PEARL) Network conducted a three-armed randomized clinical study to determine the comparative effectiveness of three treatments for hypersensitive noncarious cervical lesions (NCCLs): use of a potassium nitrate dentifrice for treatment of hypersensitivity, placement of a resin-based composite restoration and placement of a sealant. METHODS: Seventeen trained practitioner-investigators (P-Is) in the PEARL Network enrolled participants (N = 304) with hypersensitive posterior NCCLs who met enrollment criteria. Participants were assigned to treatments randomly. Evaluations were conducted at baseline and at one, three and six months thereafter. Primary outcomes were the reduction or elimination of hypersensitivity as measured clinically and by means of patient-reported outcomes. RESULTS: Lesion depth and pretreatment sensitivity (mean, 5.3 on a 0- to 10-point scale) were balanced across treatments, as was sleep bruxism (present in 42.2 percent of participants). The six-month participant recall rate was 99 percent. Treatments significantly reduced mean sensitivity (P < .01), with the sealant and restoration groups displaying a significantly higher reduction (P < .01) than did the dentifrice group. The dentifrice group’s mean (standard deviation) sensitivity at six months was 2.1 (2.1); those of the sealant and restoration groups were 1.0 (1.6) and 0.8 (1.4), respectively. Patient-reported sensitivity (to cold being most pronounced) paralleled clinical measurements at each evaluation. CONCLUSIONS: Sealing and restoration treatments were effective overall in reducing NCCL hypersensitivity. The potassium nitrate dentifrice reduced sensitivity with increasing effectiveness through six months but not to the degree offered by the other treatments. PRACTICAL IMPLICATIONS: Sealant or restoration placement is an effective method of immediately reducing NCCL sensitivity. Although a potassium nitrate dentifrice did reduce sensitivity slowly across six months, at no time was the reduction commensurate with that of sealants or restorations

Level of oral health impacts among patients participating in PEARL:a dental practice-based research network

OBJECTIVES: To determine whether participants of a dental practice-based research network (PBRN) differ in their level of oral health impact as measured by the Oral Health Impact Profile (OHIP) questionnaire. METHODS: A total of 2410 patients contributed 2432 OHIP measurements (median age = 43 years; interquartile range = 28) were enrolled in four dental studies. All participants completed the Oral Health Impact Profile (OHIP-14) during a baseline visit. The main outcome of the current study was the level of oral health impact, defined as follows: no impact (“Never” reported on all items); low (“Occasionally” or “Hardly ever” as the greatest frequency score reported on any item); and high (“Fairly often” or “Very often” as the greatest frequency reported on any item). Polychotomous logistic regression was used to develop a predictive model for the level of oral health impact considering the following predictors: patient’s age, gender, race, practice location, type of dentist, and number of years the enrolling dentist has been practicing. RESULTS: A high level of oral health impacts was reported in 8% of the sample; almost a third (29%) of the sample reported a low level of impacts, and 63% had no oral health impacts. The prevalence of impacts differed significantly across protocols (P<0.001). Females were more likely to be in the high oral impact group than the no impact group compared to males (OR=1.46; 95% CI= 1.06–1.99). African-Americans were more likely to report high oral impacts when compared to other racial/ethnic groups (OR=2.11; 95% CI = 1.26–3.55). Protective effects for being in the high or in the low impact groups were observed among patients enrolled by a solo practice (P<0.001) or by more experienced dentists (P=0.01). A small but highly significant statistical association was obtained for patient age (P<0.001). In the multivariate model, patient’s age, practice size and gender were found to jointly be significant predictors of oral health impact level. CONCLUSIONS: Patients’ subjective report of oral health impact in the clinical setting is of importance for their health. In the context of a dental PBRN, the report of oral health-related quality of life (OHRQoL) was different across four dental studies. The observed findings validate the differential impact that oral health has on the patients’ perception of OHRQoL particularly among specific groups. Similar investigations to elucidate the factors associated with patient’s report of quality of life are warranted

Outcomes of implants and restorations placed in general dental practices:A retrospective study by the Practitioners Engaged in Applied Research and Learning (PEARL) Network

OBJECTIVES: The authors conducted a study to determine the types, outcomes, risk factors and esthetic assessment of implants and their restorations placed in the general practices of a practice-based research network. METHODS: All patients who visited network practices three to five years previously and underwent placement of an implant and restoration within the practice were invited to enroll. Practitioner-investigators (P-Is) recorded the status of the implant and restoration, characteristics of the implant site and restoration, presence of peri-implant pathology and an esthetic assessment by the P-I and patient. The P-Is classified implants as failures if the original implant was missing or had been replaced, the implant was mobile or elicited pain on percussion, there was overt clinical or radiographic evidence of pathology or excessive bone loss (> 0.2 millimeter per year after an initial bone loss of 2 mm). They classified restorations as failures if they had been replaced or if there was abutment or restoration fracture. RESULTS: The authors enrolled 922 implants and patients from 87 practices, with a mean (standard deviation) follow-up of 4.2 (0.6) years. Of the 920 implants for which complete data records were available, 64 (7.0 percent) were classified as failures when excessive bone loss was excluded from the analysis. When excessive bone loss was included, 172 implants (18.7 percent) were classified as failures. According to the results of univariate analysis, a history of severe periodontitis, sites with preexisting inflammation or type IV bone, cases of immediate implant placement and placement in the incisor or canine region were associated with implant failure. According to the results of multivariate analysis, sites with preexisting inflammation (odds ratio [OR] = 2.17; 95 percent confidence interval [CI], 1.41–3.34]) or type IV bone (OR = 1.99; 95 percent CI, 1.12–3.55) were associated with a greater risk of implant failure. Of the 908 surviving implants, 20 (2.2 percent) had restorations replaced or judged as needing to be replaced. The majority of P-Is and patients were satisfied with the esthetic outcomes for both the implant and restoration. CONCLUSIONS: These results suggest that implant survival and success rates in general dental practices may be lower than those reported in studies conducted in academic or specialty settings. PRACTICAL IMPLICATIONS: The results of this study, generated in the private general practice setting, add to the evidence base to facilitate implant treatment planning