Impact of loading protocol of a mandibular single implant-supported complete denture on oral health-related quality of life over a period of 5 years: A randomized controlled trial.

OBJECTIVES: The aim of the present study was to assess the long-term course of OHRQoL and the impact of the loading protocol in patients receiving a single mandibular implant supporting a complete denture over a period of five years. METHODS: In this multicenter RCT, a total of 158 edentulous patients were initially included and were randomly allocated immediately after placement of a mandibular midline implant to either immediate loading (IL) or to conventional loading (CL) with submerged healing. The assessment of OHRQoL was performed with the 49-item Oral Health Impact Profile (OHIP) at baseline and 1, 4, 12, 24, and 60 months after loading. At 5-year follow-up, 100 patients (mean age: 69.2 years; 45.0% female) with completed OHIP were available for analyses. A mixed-effects model with patients as random effect and an unstructured covariance matrix was developed to address repeated outcome measurement. RESULTS: The OHRQoL improved substantially after loading, indicated by a decrease of mean OHIP summary scores from 51.0 points at baseline, by 14.2 (95%-CI: 9.4 - 19.1; p<0.001) points to 37.2 points at 1-month follow-up, and by continuous improvement to 20.4 OHIP points at final follow-up. Considering constant treatment effects, the loading protocol had no significant effect on OHIP scores (-3.7, 95%-CI: -9.4 - 2.2; p = 0.204). Time effect was statistically significant with -0.21 (95%-CI: -0.28 - -0.15; p<0.001) points per month. CONCLUSION: Both the immediate and conventional loading of a single mandibular midline implant supporting a complete denture offer long-lasting high levels of OHRQoL, with no significant or clinically relevant long-term differences. CLINICAL SIGNIFICANCE: The study firstly presents long-term data for OHRQoL by investigating the loading protocol of single mandibular implant-supported complete dentures. Since immediate loading has been associated with a reduced implant survival rate for this concept, information on patient benefits is essential for evidence-based decision making.

Generic Dry-Contact Ear-EEG.

Generic dry-contact ear-EEG allows for discreet, user-friendly, unobtrusive, cost-effective and convenient recordings of EEG in real-life settings. In this study we introduce a new generic earpiece design with larger internal ear electrode distances, resulting in an increased spatial coverage compared to previous generic earpiece designs. The signal quality of ear-Fpz, within-ear (the measuring and reference electrode located in the same ear) and cross-ear (the measuring electrodes located in one ear and the reference electrode in the opposite ear) electrode configurations of the developed generic earpiece was evaluated with auditory steady-state responses (ASSR) and compared to dry-contact cEEGrid. Ten subjects with different ear sizes were included. The recordings were performed in a sleep setup, where the subjects were lying on a bed and the effect of sleeping position (back vs. sides) was investigated. We found that the generic earpiece attained statistically significant ASSRs with ear-Fpz, within-ear and cross-ear electrode configurations. However, the dry-contact cEEGrid achieved significantly higher average ASSR signal-to-noise ratio (SNR) compared to the generic earpiece. Additionally, this study showed no significant difference between back and side positions for the ear-EEG.

Auditory Steady-State Responses Across Chirp Repetition Rates For Ear-EEG And Scalp EEG.

Measurement of auditory steady-state responses (ASSR) using ear-EEG potentially enables objective audiometry out of the clinic in the everyday life of hearing aid users. As ear-EEG are measured from electrodes placed within the ear, electrode distances are inherently small and consequently the potential differences, and thereby signal amplitudes, are also small. Because the detection of the ASSR is based on the signalto-noise ratio (SNR), it is of fundamental interest to know the inherent SNR of the ASSR as a function of the stimulus repetition rate. In this study, ASSRs were recorded using both scalp and ear-EEG in response to broadband chirp stimuli with repetition rates from 20 to 95 Hz. The results showed that in general ear-EEG and scalp EEG SNR was on par across repetition rates; an exception to this was at rates around 40 Hz where the SNR was significantly lower for ear-EEG as compared to scalp EEG. For ear-EEG, the ASSR was relatively constant across repetition rates, whereas the noise showed a 1/f characteristic. In consequence, there was a tendency to increased SNR as a function of repetition rate. This suggests that use of relatively high repetition rates may be beneficial in earEEG applications.

Survival and Complications of Single Dental Implants in the Edentulous Mandible Following Immediate or Delayed Loading: A Randomized Controlled Clinical Trial.

It was the aim of this 24-mo randomized controlled clinical trial to investigate whether the survival of a single median implant placed in the edentulous mandible to retain a complete denture is not compromised by immediate loading. Secondary outcomes were differences in prosthetic complications between the loading principles. Each of the 158 patients who received an implant was randomly assigned to the immediate loading group ( n = 81) or the delayed loading group ( n = 77). Recall visits were performed 1 mo after implant placement (for only the delayed loading group) and 1, 4, 12, and 24 mo after implant loading. Nine implants failed in the immediate loading group, all within the first 3 mo of implant loading, and 1 implant failed in the delayed loading group prior to loading. Noninferiority of implant survival of the immediate loading group, as compared with the delayed loading group, could not be shown ( P = 0.81). Consistent with this result, a secondary analysis with Fisher exact test revealed that the observed difference in implant survival between the treatment groups was indeed statistically significant ( P = 0.019). The most frequent prosthetic complications and maintenance interventions in the mandible were retention adjustments, denture fractures, pressure sores, and matrix exchanges. There was only 1 statistically significant difference between the groups regarding the parameter "fracture of the denture base in the ball attachment area" ( P = 0.007). The results indicate that immediate loading of a single implant in the edentulous mandible reveals inferior survival than that of delayed loading and therefore should be considered only in exceptional cases (German Clinical Trials Register: DRKS00003730).

Pain and discomfort following immediate and delayed loading by overdentures in the single mandibular implant study (SMIS).

OBJECTIVES: This randomized clinical trial compares immediate and delayed loading of single implants to support mandibular overdentures. The aim of this preliminary analysis is to test the hypothesis whether patients with immediate loading will experience less pain and discomfort through the intervention than patients with delayed loading. MATERIALS AND METHODS: Edentulous patients in nine German dental schools received a midline implant with a length of 11 mm. Implants with a minimum insertion torque of 30 Ncm and an implant stability quotient of ≥60 were randomly allocated to group A for immediate loading using ball attachments or to group B for delayed loading after 3 months. Patients completed questionnaires with 100-mm visual analogue scales about the items pain, pain during chewing, swelling, bleeding, and perception of the intervention at the day of surgery and 1, 2, 3, and 7 days, thereafter. Groups were compared by Wilcoxon-Mann-Whitney tests (P ≤ 0.05). RESULTS: The questionnaires of 81 patients in group A and 74 patients in group B were completed. The medians for pain and discomfort were moderate (<30). Participants of group A felt significantly more pain from the first day and more swelling from the third day after implantation than participants of group B. The individual perception of interventions showed no significant differences between groups. CONCLUSIONS: Immediate loading evoked more postoperative pain and swelling than the two stages of delayed loading. CLINICAL RELEVANCE: Immediate loading of a single mandibular midline implant supporting overdentures should be carefully considered.

Assessing the TP53 marker type in patients treated with or without neoadjuvant chemotherapy for resectable colorectal liver metastases: a p53 Research Group study.

The type of a biomarker - whether it is prognostic or predictive - is frequently not known, although such information is crucial for assessing the clinical value of a marker. In order to evaluate the type of marker TP53 is, we identified a cohort of 76 patients with colorectal liver metastases (CLM), homogeneously staged as resectable, who had been treated either with or without fluorouracil-based neoadjuvant chemotherapy. The TP53 genotype was assessed retrospectively from paraffin-embedded, diagnostic tumour biopsies using a standardised, p53 gene-specific sequencing protocol (mark53(®) kit). The overall median survival was 44.2 months, and the overall TP53 mutation frequency was 55%. A significant interaction was observed between chemotherapy and TP53 status (P = 0.045). To illustrate this effect, the 51 patients with and the 25 patients without neoadjuvant chemotherapy were described separately. In patients with neoadjuvant chemotherapy, mutated TP53 was significantly associated with poor survival (P = 0.0025), resulting in five-year survival rates of 22%, compared to 60% in patients with normal TP53. The hazard ratio was 3.12 (95% confidence intervals (CI): 1.46-6.95) to the disadvantage of TP53-mutated patients and 5.49 (P = 0.0001; 95% CI: 2.28-13.24) after adjustment for known prognostic factors. In patients treated with surgery alone, a mutated TP53 did not have a negative effect on survival (P = 0.54). A mutated TP53 status independently predicted survival disadvantage in CLM patients in the presence, but not in the absence, of neoadjuvant chemotherapy. Our data suggest that TP53 might be a pure predictive marker.

Evaluation strategies for isotope ratio measurements of single particles by LA-MC-ICPMS.

Data evaluation is a crucial step when it comes to the determination of accurate and precise isotope ratios computed from transient signals measured by multi-collector-inductively coupled plasma mass spectrometry (MC-ICPMS) coupled to, for example, laser ablation (LA). In the present study, the applicability of different data evaluation strategies (i.e. 'point-by-point', 'integration' and 'linear regression slope' method) for the computation of (235)U/(238)U isotope ratios measured in single particles by LA-MC-ICPMS was investigated. The analyzed uranium oxide particles (i.e. 9073-01-B, CRM U010 and NUSIMEP-7 test samples), having sizes down to the sub-micrometre range, are certified with respect to their (235)U/(238)U isotopic signature, which enabled evaluation of the applied strategies with respect to precision and accuracy. The different strategies were also compared with respect to their expanded uncertainties. Even though the 'point-by-point' method proved to be superior, the other methods are advantageous, as they take weighted signal intensities into account. For the first time, the use of a 'finite mixture model' is presented for the determination of an unknown number of different U isotopic compositions of single particles present on the same planchet. The model uses an algorithm that determines the number of isotopic signatures by attributing individual data points to computed clusters. The (235)U/(238)U isotope ratios are then determined by means of the slopes of linear regressions estimated for each cluster. The model was successfully applied for the accurate determination of different (235)U/(238)U isotope ratios of particles deposited on the NUSIMEP-7 test samples.

Aspergillus fumigatus Majocchi's granuloma in a patient with acquired immunodeficiency syndrome.

Majocchi's granuloma, also known as nodular granulomatous perifolliculitis, is an uncommon fungal infection of the skin and subcutaneous tissue. It can occur in healthy and immunocompromised patients. The most common cause of Majocchi's granuloma is Trichophyton rubrum. We report a case of a Majocchi's granuloma caused by Aspergillus fumigatus in a patient with acquired immunodeficiency syndrome.

Functional categories of TP53 mutation in colorectal cancer: results of an International Collaborative Study.

BACKGROUND: Loss of TP53 function through gene mutation is a critical event in the development and progression of many tumour types including colorectal cancer (CRC). In vitro studies have found considerable heterogeneity amongst different TP53 mutants in terms of their transactivating abilities. The aim of this work was to evaluate whether TP53 mutations classified as functionally inactive (< or=20% of wildtype transactivation ability) had different prognostic and predictive values in CRC compared with mutations that retained significant activity. MATERIALS AND METHODS: TP53 mutations within a large, international database of CRC (n = 3583) were classified according to functional status for transactivation. RESULTS: Inactive TP53 mutations were found in 29% of all CRCs and were more frequent in rectal (32%) than proximal colon (22%) tumours (P < 0.001). Higher frequencies of inactive TP53 mutations were also seen in advanced stage tumours (P = 0.0003) and in tumours with the poor prognostic features of vascular (P = 0.006) and lymphatic invasion (P = 0.002). Inactive TP53 mutations were associated with significantly worse outcome only in patients with Dukes' stage D tumours (RR = 1.71, 95%CI 1.25-2.33, P < 0.001). Patients with Dukes' C stage tumours appeared to gain a survival benefit from 5-fluorouracil-based chemotherapy regardless of TP53 functional status for transactivation ability. CONCLUSIONS: Mutations that inactivate the transactivational ability of TP53 are more frequent in advanced CRC and are associated with worse prognosis in this stage of disease.

Contralateral breast cancer: molecular differentiation between metastasis and second primary cancer.

Previous cancer in one breast is a strong known risk factor for cancer in the contralateral breast. Differences in tumor histology and nuclear grading are applied to distinguish between a metastatic spread and a second primary cancer, although cancers of the breast often share the same histological features. Comparison of genetic alterations in paired tumors may provide the most reliable approach for discerning clonal relationships, hence uncovering the presence or absence of multiple primary cancers. We compared tumors from 33 patients with cancer in both breasts for mutations in the p53 gene. With this molecular approach, we were able to define the relationship within paired tumors in 13 patients. The paired tumors of two patients shared the same mutation, revealing the second lesion in one case as a contralateral metachronous lymph node metastasis appearing 29 months after first surgery, and in the other as a spread to the opposite breast. In 11 patients, mutations were either discordant or solely present in one of the lesions, confirming the diagnosis of bilateral breast cancer. Histopathological evaluation had failed to provide firm diagnosis in nine out of 11 instances on account of concordances in pathological parameters such as histological type and grading. In our study, we could show that bilateral breast malignancies most frequently represent two primary breast cancers. We could also demonstrate that contralateral breast cancer spread does occur. Standard pathological assessment allowed a firm diagnosis only in the presence of different histological types.

Interleukin-10-deficient mice and inflammatory bowel disease associated cancer development.

Interleukin-10-deficient mice develop colitis and colorectal cancer similar to the inflammatory bowel disease associated cancer in humans. The aim of this study was to identify possible mutations of oncogenes and tumour suppressor genes involved in tumorigenesis in Interleukin-10 (IL-10)-deficient mice. Twenty colon carcinomas from IL-10-deficient mice were screened for mutations in the K-ras and p53 genes by 'cold' single-strand-conformation polymorphism. Immunohistochemical staining was performed to detect mutations in the proteins P53, APC and MSH2, and the transforming growth factor beta type II receptor. Microsatellite instability was analysed at eight chromosomal loci and plasma levels of transforming growth factor beta1 (TGF-beta1) were also measured. At 9 weeks, 14% of the animals developed colorectal cancer, and at 10-31 weeks the incidence of carcinoma was 65%. No mutations were detected in the analysed oncogene and tumour suppressor genes. Plasma TGF-beta1 levels in IL-10-deficient mice 10-31 weeks old were higher than in wild-type littermates e.g. 45.7 +/- 4.6 ng/ml versus 19.8 +/- 4.5 ng/ml (P<0.01). No alterations in K-ras, p53, APC: and Msh2 genes suggests that other genes are involved in the development of these tumours. Elevated TGF-beta1 plasma levels correspond to the high incidence of dysplasia and cancer. Normal expression of the TGF-beta II receptors hints at genetic alterations in other members of the TGF-beta receptor signal transduction pathway.

TP53 mutation and p53 overexpression for prediction of response to neoadjuvant treatment in breast cancer patients.

The value of p53 to predict the cytotoxic effect of two commonly used chemotherapy regimens was assessed in patients with advanced breast cancer. Response to a DNA-damaging combination therapy [fluorouracil, epirubicin, cyclophosphamide (FEC] considered to induce p53-dependent apoptosis was compared with a microtubule stabilizing therapy (paclitaxel) expected to be independent of p53 function. The p53 status of the patients' breast tumors was assessed using both immunohistochemistry (IHC) and direct sequencing of the entire p53 gene. p53 findings were correlated with treatment response, and linkage between p53 function and cellular response was assessed by terminal deoxynucleotidyl transferase-mediated nick end labeling assay. In a series of 67 breast tumors, 19% had TP53 gene mutations, 40% had a positive p53 IHC, and 12% had both. In the FEC group, treatment failure was related to both the presence of TP53 gene mutations (P = 0.0029) and a positive IHC (P < 0.0001). Apoptosis was almost exclusively found in tumors having normal p53 in both parameters (P < 0.0001). In the paclitaxel group, treatment response was neither related to apoptosis nor to normal p53. Combination of sequencing and IHC results revealed a significant association between abnormal p53 and response to paclitaxel (P = 0.011). We found TP53 mutations, as well as p53 protein overexpression, to be associated with response to chemotherapy. Whereas clinical response to FEC was found to be dependent on normal p53, the cytotoxicity of paclitaxel was related to defective p53. The efficiency of paclitaxel during mitosis might be supported by lack of G1 arrest due to p53 deficiency. Therefore, patients with p53-deficient tumors may benefit from paclitaxel.

The TP53 genotype but not immunohistochemical result is predictive of response to cisplatin-based neoadjuvant therapy in stage III non-small cell lung cancer.

BACKGROUND: The cytotoxic effects of cisplatin and anthracyclins have been attributed to apoptosis induction, which has been recognized as a major function of the TP53 gene. The TP53 gene appears to be mutated in about 50% of cases of non-small cell lung cancer. A possible dependence of chemotherapy response on TP53 genotype was evaluated retrospectively in a group of patients with advanced non-small cell lung cancer and induction treatment. METHODS: Patients with complete or partial remission were compared with those with stable or progressive disease with respect to TP53 genotype and overall survival. Mutations in the TP53 gene were detected by complete direct sequencing (exons 2-11). RESULTS: A normal TP53 genotype proved to be significantly associated with major response to chemotherapy (P <.001). Overall, no association was found between p53 protein expression and TP53 genotype. A normal TP53 genotype was found to be highly sensitive in predicting response to treatment, whereas a mutant genotype was revealed to be specific in predicting lack of response. The difference in overall length of survival was significant between patients exhibiting a normal TP53 genotype (corresponding to those whose disease responded to chemotherapy) and patients showing mutant TP53 genotype (corresponding to those who had disease resistant to chemotherapy, P =.027). CONCLUSIONS: In a small cohort of patients with advanced non-small cell lung cancer we found a direct link between normal TP53 genotype and response to cisplatin-based induction treatment and also between mutant genotype and resistance to treatment, whereas p53 immunohistochemical result was predictive of neither.

AIDS knowledge and attitudes among adults in Vermont.

To design a statewide educational campaign, the Vermont Department of Health attempted to measure knowledge about AIDS among residents of the State. During the period November 1986 through January 1987, the authors conducted a telephone survey of noninstitutionalized residents ages 18 and over. The results were examined in relation to age and education. The most accurate answers were given by respondents less than 45 years. In terms of educational attainment, respondents with less than a high school education had an average score of 61.4 and those with a college degree averaged 85.0. When the authors examined responses to individual questions, it became apparent that respondents were more knowledgeable about ways the virus could be transmitted than about ways it could not. A more comprehensive education program must reduce fear. One component of the current AIDS campaign in Vermont is an advertisement that addresses unfounded concern about casual transmission of AIDS.

Legionella in cooling towers.

Legionellosis (Legionnaires' disease and Pontiac fever) outbreaks have been associated with aerosols ejected from contaminated cooling towers--wet-type heat rejection units (WTHRUs) used to dissipate unwanted heat into the atmosphere. The Vermont Department of Health undertook a program to inventory, inspect, and sample all WTHRUs in Vermont from April 1981 to April 1982. All WTHRUs were sampled for Legionella pneumophila and data were obtained for location, design, construction, and operating characteristics. Of the 184 WTHRUs operating, statistical analyses were performed on those 130 which were sampled for L. pneumophila only once during the study period. Of these, 11 (8.5%) were positive for L. pneumophila. Sources of makeup water and period of operation had significant association with the recovery of L. pneumophila. Five out of 92 towers (5.4%) utilizing surface water sources for cooling were positive for L. pneumophila, in contrast to 6 positive towers of the 38 units (15.8%) which obtained makeup water from ground water sources (p = .054 by chi-square test). Nearly 15% of the 54 units which operated throughout the year were positive, compared to less than 4% of the 76 towers operating seasonally (p = .03 by chi-square test). The mean pH of the cooling water in units where L. pneumophila was recovered (8.3) was significantly higher than the mean pH of 7.9 in units testing negative (p less than .05 by t-test). In addition, the mean log-transformed turbidity of positive towers, 0.03 nephelometric units (ntu), was significantly lower than the mean of log turbidity of negative towers, 0.69 ntu (p less than .02 by t-test).

Duration of whirlpool-spa use as a risk factor for Pseudomonas dermatitis.

Pseudomonas dermatitis occurred among 16 of 49 whirlpool-spa bathers in a Vermont hotel during a weekend in November 1983. Pseudomonas aeruginosa, serotype 0:4, was isolated from a patient and the whirlpool-spa water. Since duration of whirlpool-spa use had been previously postulated as a risk factor for dermatitis, a historical cohort study was designed to test this hypothesis. Each bather was carefully interviewed about the duration in minutes of whirlpool-spa and swimming pool exposure on the weekend. Total duration of whirlpool-spa use was significantly associated with rash illness both on contingency and logistic regression analysis. Females were also found to be at increased risk, after controlling for the study hypothesis. Duration of whirlpool-spa use was an important determinant of risk for Pseudomonas dermatitis in this outbreak.

Drinking-water-induced copper intoxication in a Vermont family.

Three of four family members reported recurrent episodes of gastrointestinal illness while residing in a house in a small northwestern Vermont village. The father and two daughters repeatedly experienced episodes of emesis and abdominal pain after drinking water drawn from their kitchen faucet. One early-morning water sample taken from the family household contained a copper level of 7.8 mg/L, which is above the standard for drinking water (1.0 mg/L). Values for the second daughter's copper in hair analysis (1,200 micrograms/g) and copper in nail analysis (100 micrograms/g) were elevated (normal range 11 to 53 micrograms/g). The household was at the end of a 3/4-in (19.05-mm) copper main, and it is suspected that copper levels increased in water when the water remained stagnant in the main. All symptoms of the family resolved when they stopped drinking water in their home. This is the first report of copper-induced gastrointestinal illness attributable to a public supply of drinking water.