The natural course of unruptured cerebral aneurysms in a Japanese cohort.

BACKGROUND: The natural history of unruptured cerebral aneurysms has not been clearly defined. METHODS: From January 2001 through April 2004, we enrolled patients with newly identified, unruptured cerebral aneurysms in Japan. Information on the rupture of aneurysms, deaths, and the results of periodic follow-up examinations were recorded. We included 5720 patients 20 years of age or older (mean age, 62.5 years; 68% women) who had saccular aneurysms that were 3 mm or more in the largest dimension and who initially presented with no more than a slight disability. RESULTS: Of the 6697 aneurysms studied, 91% were discovered incidentally. Most aneurysms were in the middle cerebral arteries (36%) and the internal carotid arteries (34%). The mean (±SD) size of the aneurysms was 5.7±3.6 mm. During a follow-up period that included 11,660 aneurysm-years, ruptures were documented in 111 patients, with an annual rate of rupture of 0.95% (95% confidence interval [CI], 0.79 to 1.15). The risk of rupture increased with increasing size of the aneurysm. With aneurysms that were 3 to 4 mm in size as the reference, the hazard ratios for size categories were as follows: 5 to 6 mm, 1.13 (95% CI, 0.58 to 2.22); 7 to 9 mm, 3.35 (95% CI, 1.87 to 6.00); 10 to 24 mm, 9.09 (95% CI, 5.25 to 15.74); and 25 mm or larger, 76.26 (95% CI, 32.76 to 177.54). As compared with aneurysms in the middle cerebral arteries, those in the posterior and anterior communicating arteries were more likely to rupture (hazard ratio, 1.90 [95% CI, 1.12 to 3.21] and 2.02 [95% CI, 1.13 to 3.58], respectively). Aneurysms with a daughter sac (an irregular protrusion of the wall of the aneurysm) were also more likely to rupture (hazard ratio, 1.63; 95% CI, 1.08 to 2.48). CONCLUSIONS: This study showed that the natural course of unruptured cerebral aneurysms varies according to the size, location, and shape of the aneurysm. (Funded by the Ministry of Health, Labor, and Welfare in Japan and others; UCAS Japan UMIN-CTR number, C000000418.).

qAC2, a novel QTL that interacts with Wx and controls the low amylose content in rice (Oryza sativa L.).

KEY MESSAGE: This manuscript reports the fine mapping of a novel QTL, qAC2 controlling the low amylose in rice. The action mechanism of the qAC2 is also investigated by the analysis of genetic interactions to Wx (a), Wx (b), du1, du2 and du3. Amylose content of the rice (Oryza sativa L.) endosperm greatly affects starch properties and eating quality of cooked rice. Seeds of japonica rice cultivar Kuiku162 have low amylose content (AC) and good eating quality. Our analysis revealed a novel QTL, designated as qAC2 that contributed to the low AC of Kuiku162. qAC2 was fine mapped within a 74.9-kb region between two insertion and deletion markers, KID3001 and KID5101, on the long arm of chromosome 2. Seven genes are predicted in this region, but none of them is known to be related to the regulation of AC. The AC of a near-isogenic line (NIL110) carrying qAC2 (Kuiku), the Kuiku162 allele of qAC2, in the genetic background of japonica cultivar Itadaki was lower by 1.1% points than that of Itadaki. The chain length distributions of amylopectin were similar in NIL110 and Itadaki; therefore, the low AC of NIL110 was caused by a decrease in the actual AC, but not by a difference in the amylopectin structure. The interaction analyses revealed that qAC2 (Kuiku) has epistatic interaction with Wx (a). The qAC2 (Kuiku) has epistatic interactions with two loci, du1 and du2, on Wx (b), whereas the genetic effect of qAC2 (Kuiku) has additive to that of du3 on Wx (b). Thus, similar to du1 and du2, qAC2 may have a function related to Wx (b) mRNA splicing.

Using Time Series Analysis to Predict Cardiac Arrest in a PICU.

OBJECTIVES: To build and test cardiac arrest prediction models in a PICU, using time series analysis as input, and to measure changes in prediction accuracy attributable to different classes of time series data. DESIGN: Retrospective cohort study. SETTING: Thirty-one bed academic PICU that provides care for medical and general surgical (not congenital heart surgery) patients. SUBJECTS: Patients experiencing a cardiac arrest in the PICU and requiring external cardiac massage for at least 2 minutes. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred three cases of cardiac arrest and 109 control cases were used to prepare a baseline dataset that consisted of 1,025 variables in four data classes: multivariate, raw time series, clinical calculations, and time series trend analysis. We trained 20 arrest prediction models using a matrix of five feature sets (combinations of data classes) with four modeling algorithms: linear regression, decision tree, neural network, and support vector machine. The reference model (multivariate data with regression algorithm) had an accuracy of 78% and 87% area under the receiver operating characteristic curve. The best model (multivariate + trend analysis data with support vector machine algorithm) had an accuracy of 94% and 98% area under the receiver operating characteristic curve. CONCLUSIONS: Cardiac arrest predictions based on a traditional model built with multivariate data and a regression algorithm misclassified cases 3.7 times more frequently than predictions that included time series trend analysis and built with a support vector machine algorithm. Although the final model lacks the specificity necessary for clinical application, we have demonstrated how information from time series data can be used to increase the accuracy of clinical prediction models.

Use of self-tapping metal screws for temporary fixation of a resorbable plate system in maxillofacial surgery.

Resorbable plate systems have been used in maxillofacial surgery to obviate the need for plate removal. However, resorbable plates and screws are very costly, and refixation with additional screws may be necessary when reduction or repositioning of the bone segment is inaccurate. Here we report the use of self-tapping metal screws for temporary fixation of a resorbable plating system in maxillofacial surgery to avoid the use of additional screws following inaccurate fixation or the reuse of resorbable screws, which may result in loosening.

Validation of the FIB4 index in a Japanese nonalcoholic fatty liver disease population.

BACKGROUND: A reliable and inexpensive noninvasive marker of hepatic fibrosis is required in patients with nonalcoholic fatty liver disease (NAFLD). FIB4 index (based on age, aspartate aminotransferase [AST] and alanine aminotransferase [ALT] levels, and platelet counts) is expected to be useful for evaluating hepatic fibrosis. We validated the performance of FIB4 index in a Japanese cohort with NAFLD. METHODS: The areas under the receiver operating characteristic curves (AUROC) for FIB4 and six other markers were compared, based on data from 576 biopsy-proven NAFLD patients. Advanced fibrosis was defined as stage 3-4 fibrosis. FIB4 index was assessed as: age (yr) × AST (IU/L)/(platelet count (10(9)/L) × âˆšALT (IU/L)) RESULTS: Advanced fibrosis was found in 64 (11%) patients. The AUROC for FIB4 index was superior to those for the other scoring systems for differentiating between advanced and mild fibrosis. Only 6 of 308 patients with a FIB4 index below the proposed low cut-off point (< 1.45) were under-staged, giving a high negative predictive value of 98%. Twenty-eight of 59 patients with a FIB4 index above the high cut-off point (> 3.25) were over-staged, giving a low positive predictive value of 53%. Using these cutoffs, 91% of the 395 patients with FIB-4 values outside 1.45-3.25 would be correctly classified. Implementation of the FIB4 index in the Japanese population would avoid 58% of liver biopsies. CONCLUSION: The FIB4 index was superior to other tested noninvasive markers of fibrosis in Japanese patients with NAFLD, with a high negative predictive value for excluding advanced fibrosis. The small number of cases of advanced fibrosis in this cohort meant that this study had limited power for validating the high cut-off point.

[Shared web-based data center for multi-institutional clinical trials: evaluation of UMIN-INDICE (university hospital medical information network-internet data and information center for medical research)in clinical trials of JIVROSG (Japan interventional radiology in oncology study group)].

A patient registration system is mandatory for establishing the scientific credibility of the multi-center clinical trials. The Japan Interventional Radiology in Oncology Study Group (JIVROSG) was organized in 2002 to establish evidence supporting the procedures used in interventional radiology. The Internet Data and Information Center for Medical Research (INDICE), provided by the University Hospital Medical Information Network(UMIN), has been utilized for patient registration in the clinical trials of JIVROSG. In this study, the safety and efficacy of UMIN-INDICE were evaluated. From 2002 to 2010, 18 clinical trials, including one international trial, were conducted. A total of 736 patients were enrolled from 51 institutions. No significant trouble was encountered during this period. A questionnaire survey demonstrated that 90% of participating researchers could use this system without difficulties. UMIN-INDICE may contribute to promoting clinical trials as an infrastructure of multicenter studies.

Large dentigerous cyst associated with the maxillary impacted supernumerary teeth: A rare occurrence and literature review.

Dentigerous cysts are common odontogenic cysts of the jaw but are rarely associated with supernumerary teeth. Few cases of large dentigerous cysts associated with anterior maxillary supernumerary teeth have been reported. The English literature has documented only four cases of dentigerous cysts>40 mm in diameter associated with supernumerary teeth. A 47-year-old man was referred to our hospital, complaining of minor pain in the maxillary gingiva. Computed tomography revealed a well-defined oval unilocular radiolucent lesion (50×45×35 mm) in the right maxilla, including two impacted supernumerary teeth. A dentigerous cyst associated with impacted anterior maxillary supernumerary teeth was diagnosed. The two impacted teeth were surgically removed, and the cyst was enucleated using the Caldwell-Luc approach. Histopathology confirmed the diagnosis of a large dentigerous cyst associated with impacted anterior maxillary supernumerary teeth. The postoperative course has been uneventful for two years. We also reviewed the relevant English literature.

Efficacy and cost-effectiveness of consensus interferon monotherapy with high-dose induction for hepatitis C patients with genotype 2.

OBJECTIVE: Several treatment strategies for patients with chronic hepatitis C have been compared mainly in terms of their efficacy, and it has been found that pegylated interferon (IFN) plus ribavirin has become the standard therapy, but aged patients may not tolerate ribavirin and the cost-effectiveness of treatment should also be further considered. We conducted a study to evaluate the efficacy, safety, and cost-effectiveness of consensus IFN monotherapy with high-dose induction for patients with chronic hepatitis C in clinical practice. MATERIAL AND METHODS: We consecutively enrolled 104 patients with chronic hepatitis C. Patients were scheduled to receive 12 or 18 µg of consensus IFN daily for 2 weeks, then three times a week for 22 weeks. Efficacy, safety, and cost-effectiveness were assessed. A Markov model was developed to investigate cost-effectiveness in patients with chronic hepatitis C treated by different IFN-based treatment strategies. RESULTS: Of the 104 study patients, a sustained virological response (SVR) was achieved in 66 (63%). Logistic regression analysis revealed that genotype 2, lower hepatitis C virus RNA levels, and patient age were independently associated with SVR. The response rate was significantly higher in patients with genotype 2 (51/66, 77%) versus genotype 1 (15/38, 40%). Cost-effectiveness analysis in patients with genotype 2 revealed that high-dose induction with consensus IFN monotherapy was as highly cost-effective as pegylated IFN plus ribavirin. CONCLUSION: Consensus IFN monotherapy with high-dose induction shows high efficacy and cost-effectiveness in chronic hepatitis C patients with genotype 2 infection. Thus, it may be a reliable alternative in aged patients and for those excluded from standard combination therapy.

The impact of an emergency telephone consultation service on the use of ambulances in Tokyo.

INTRODUCTION: The increasing demands made on emergency ambulance services contribute to inefficient, clinically inappropriate health care, and may delay the provision of emergency care to life-threatening cases. The hypothesis of this study was that the activity for the first year of operation of an emergency telephone consultation service contributed to a reduction in ambulance use in non-urgent cases and a decrease in the cost associated with despatching ambulances. METHODS: The numbers of ambulance use and the emergency hospitalisation of ambulance cases were compared before and after the introduction of the Tokyo Emergency Telephone Consultation Centre (the #7119 centre). Public awareness of the #7119 centre in each region of Tokyo and the cost related to despatching ambulances were also investigated. RESULTS: A total of 26,138 consultations was performed in the initial year. Compared with the previous year, the number of ambulance uses per 1 million people decreased (before 46,846, after 44,689, p<0.0001). The emergency hospitalisation rate (EHR) of ambulance cases increased significantly because of the decreased proportion of non-urgent cases (before 36.5%, after 37.8%, p<0.0001). There was a statistical correlation between the awareness rate in each region and the change of after-hours EHR in adults (R=0.333, p=0.025). The total cost related to despatching ambulances was reduced by approximately ¥678,000,000 (£4,520,000) in the initial year. CONCLUSION: To date, the emergency telephone consultation service has contributed to the appropriate use of ambulances and a reduction of its cost in Tokyo.

Cost-effectiveness of the surveillance program of hepatocellular carcinoma depends on the medical circumstances.

BACKGROUND AND AIM: The clinical features of hepatocellular carcinoma (HCC) and the medical environment are diverse in different geographic areas. The aim of this study is to evaluate the cost-effectiveness of the surveillance of HCC in different medical circumstances. METHODS: The Markov model focused on variables that differ from country to country and may change in the future, especially in regards to the proportion of small HCC detected incidentally. The target population was 45-year-old patients with Child-Pugh class A cirrhosis, and the intervention was surveillance with ultrasonography every 6 months. RESULTS: The additional cost of the surveillance was $US15 100, the gain in quality-adjusted life years (QALYs) was 0.50 years, and the incremental cost-effectiveness ratio (ICER) was $US29 900/QALY in a base-case analysis (annual incidence of HCC = 4%). If 40% of small HCC were detected incidentally without surveillance, the gain in QALY decreased to 0.15 and the ICER increased to $US47 900/QALY. The increase in the annual incidence of HCC to 8% resulted in the increase of QALYs to 0.81, and the decrease of the ICER to $US25 400/QALY. The adoption of liver transplantation increased the gain in QALYs and the ICER to 0.84 and $US59 900/QALY, respectively. CONCLUSIONS: The gain in QALYs and the ICER due to the surveillance of HCC varies between different patient subgroups and it critically depends on the rate of small HCC detected incidentally without surveillance, as well as the annual incidence of HCC and the adoption of liver transplantation.

Risk stratification after successful coronary revascularization.

BACKGROUND: Clinicians treating coronary revascularization patients need to be able to identify those who require more intensive medical therapy or follow-up. However, predictors of survival after coronary revascularization are often reported in terms of hazard ratios, which are accurate but difficult to convert to concrete values. We sought to develop a more practical and user-friendly method of predicting long-term survival in revascularization patients. METHODS: We used a decision-tree induction algorithm to retrospectively examine all-cause mortality during 3-year follow-up in 3331 consecutive patients with multivessel or single proximal left anterior descending coronary artery disease who underwent an isolated first revascularization by either coronary stenting or coronary artery bypass graft between 1995 and 1999. RESULTS: Recursive partitioning of the derivation cohort by the algorithm indicated that the best single predictor of long-term mortality was history of congestive heart failure, followed by age greater than 65 years and the presence of renal insufficiency. With these three variables, patients were readily stratified into low-, intermediate-, and high-risk groups whose 3-year mortality risks ranged from 2.0% to 18.8%. Logistic regression revealed nine significant predictors of 3-year mortality, including two interaction terms. Areas under the receiver operation characteristic curve for prediction of 3-year mortality were not significantly different between the decision tree and the logistic regression models [0.72 (95% confidence interval, 0.69 to 0.75) vs. 0.76 (95% confidence interval, 0.73 to 0.80)]. CONCLUSIONS: Long-term mortality risk in coronary revascularization patients can be estimated from three predictors that are easily obtained in clinical settings.

An introduction to the theory of constraint and how it can be applied to medical management.

This overview of a new way of thinking about medical management problems could help physicians executives think about those problems differently.

Lateral Bone Window Approach with Micross Mini Bone Scraper for Sinus Floor Elevation.

OBJECTIVE: The purpose of this article is to describe a technique with a mini bone scraper for lateral bone window approach and simultaneous bone harvesting during sinus floor elevation. METHODS: This study included five consecutive patients with the atrophic posterior maxilla. After elevation of mucoperiosteal flap, a bone window was then opened safely using a Micross Mini Bone Scraper® with small shape and easy handling. Data were recorded on the residual alveolar bone height, number of implants, site of implant placement, collected particulate bone volume, and bone harvesting time. RESULTS: There was no injury of the Schneiderian membrane, and one to two implants of 11.5 mm length were placed simultaneously after sinus floor elevation in all cases. Mean residual bone height was 4.6 mm. The mean volume of particulate bone collected from the anterior wall of the maxilla using this technique was 0.74 cm3. Supplementary allogeneic materials were not required in all cases. Mean bone harvesting time was 4.6 min. CONCLUSIONS: Our technique with Micross Mini Bone Scraper® is a simple and safe procedure in lateral bone window approach and simultaneous bone harvesting during sinus floor elevation, because it is performed under better visualization of the membrane without irrigation.

Multidisciplinary approach for treatment of a dentigerous cyst - marsupialization, orthodontic treatment, and implant placement: a case report.

BACKGROUND: Dentigerous cysts are common odontogenic cysts associated with unerupted teeth. We describe a previously unreported case of a multidisciplinary approach using surgical, orthodontic, and implant treatment to establish the occlusion for a patient with a maxillary dentigerous cyst. CASE PRESENTATION: An 18-year-old Japanese woman visited our hospital with a chief complaint of gingival swelling in her anterior maxillary region, midline diastema, and tooth crowding. Her main symptom was this gingival swelling. A panoramic radiograph revealed a radiolucent area, 30 mm in diameter, round in shape, and with well-demarcated margins including the maxillary canine. Computed tomography revealed a cystic cavity filled with homogeneous fluid of the same density as water, and a distolingually inclined canine. Our clinical diagnosis was maxillary dentigerous cyst with an unerupted distolingually inclined canine. The selected treatment was marsupialization of the dentigerous cyst, followed by orthodontic traction of the unerupted canine, and simultaneous orthodontic treatment of the midline diastema and tooth crowding. The orthodontic traction failed because the canine did not erupt completely, and the canine was extracted. The treatment plan was then changed to implant treatment after the tooth crowding and midline diastema had been improved. Because the alveolar ridge width was inadequate, the implant was placed after a two-stage implant treatment; therefore, a satisfactory occlusion could be achieved. Our patient did not experience any complications, and the cyst has not recurred. A radiograph taken 7 years after marsupialization of the dentigerous cyst revealed that the cystic cavity had been replaced by new bone. CONCLUSIONS: In general, orthodontic traction of an unerupted tooth after marsupialization should be the best option. However, if orthodontic traction fails, a multidisciplinary approach involving implant treatment may be necessary. We describe a case in which a multidisciplinary approach involving surgical, orthodontic, and implant treatment was used to establish a satisfactory occlusion for a patient with a dentigerous cyst.

Cost-effectiveness analysis of telemedicine to evaluate diabetic retinopathy in a prison population.

OBJECTIVE: A cost-effectiveness analysis was conducted to investigate the clinical and economic impact of teleophthalmology in evaluating diabetic retinopathy in prison inmates with type 2 diabetes. RESEARCH DESIGN AND METHODS: Based on a hypothetical teleophthalmology system to evaluate diabetic retinopathy patients with type 2 diabetes in a prison care setting, a Markov decision model was developed with probability and cost data derived primarily from published epidemiological and outcome studies. A 40-year-old African-American man with type 2 diabetes was used as a reference case subject. The number of quality-adjusted life-years (QALYs) gained was used as the clinical outcome, and the cost in U.S. dollars from the year 2003 was used as the economic outcome. Teleophthalmology and nonteleophthalmology strategies were compared using an expected QALYs calculation and two types of sensitivity analyses: probabilistic and traditional n-way sensitivity analyses. RESULTS: The teleophthalmology strategy dominates in the cost-effectiveness analysis for the reference case subject: 16,514/18.73 dollars QALYs for teleophthalmology and 17,590/18.58 dollars QALYs for nonteleophthalmology. Ninety percent of the Monte Carlo simulations showed cost effectiveness (annual cost/QALYs < or = 50,000 dollars) in the teleophthalmology strategy based on an assumed inmate population. Teleophthalmology is the better strategy if the number of diabetic inmates in the prison community is >500. CONCLUSIONS: Our cost-effectiveness analysis demonstrates that teleophthalmology holds great promise to reduce the cost of inmate care and reduce blindness caused by diabetic retinopathy in type 2 diabetic patients.

Removal of migrated dental implants from maxillary sinus 4 years 10 months after implant placement.

INTRODUCTION: Dental implant treatment has been applied widely in recent years. However, several complications sometimes have been reported. Although displacement of dental implants into the maxillary sinus commonly occurs during surgery, the migration of dental implants after a period of function, especially several years after dental implant placement, is very rare. CASE REPORT: We report here removal of migrated dental implants from the maxillary sinus 4 years and 10 months after dental implant placement.

A novel epithelial keratin, hK6irs1, is expressed differentially in all layers of the inner root sheath, including specialized huxley cells (Flügelzellen) of the human hair follicle.

In this study we have characterized a novel human type II keratin, hK6irs1, which is specifically expressed in the inner root sheath of the hair follicle. This keratin represents the ortholog of the recently described mouse inner root sheath keratin mK6irs. The two keratins were highly related and migrated at the same height as keratin 6 in two-dimensional gel electrophoresis. Both RNA in situ hybridization and indirect immunofluorescence studies of human hair follicles demonstrated hK6irs1 expression in the Henle and Huxley layers as well as in the cuticle of the inner root sheath. In all three layers, the expression of hK6irs1 mRNA and protein began simultaneously in adjacent cells of the lowermost bulb above the germinative cell pool. Higher up in the follicle, the detection limits for both hK6irs1 mRNA and protein precisely coincided with the asynchronous onset of abrupt terminal differentiation of the Henle layer, inner root sheath cuticle, and Huxley layer. Mainly above the level of terminal Henle cell differentiation, both indirect immunofluorescence and immunoelectron microscopy revealed the occurrence of distinct Huxley cells that developed pseudopodal hK6irs1-positive extensions passing through the fully keratinized Henle layer. These outwardly protruding foot processes abutted upon cells of the companion layer, with which they were connected by numerous desmosomes. These specialized Huxley cells have previously been termed "Flügelzellen", which means "winged cells", with reference to their characteristic foot processes. We provide evidence that, together with Henle cells, Flügelzellen ensure the maintenance of a continuous desmosomal anchorage of the companion layer along the entire inner root sheath. This tightly connected companion layer/inner root sheath unit provides an optimal molding and guidance of the growing hair shaft.

hKAP1.6 and hKAP1.7, two novel human high sulfur keratin-associated proteins are expressed in the hair follicle cortex.

Hair fiber differentiation involves the expression of both hair keratin intermediate filament proteins and their associated proteins, termed keratin-associated proteins. In this study, cDNA clones encoding two novel keratin-associated proteins were isolated from human hair follicle mRNA. The predicted amino acid sequence derived from these clones revealed that these proteins represent members of the human keratin-associated protein 1 family. They show strong sequence homology to two previously described keratin-associated protein 1 family members hKAP1.1 A and hKAP1.1B. We have called these new proteins hKAP1.6 and hKAP1.7, respectively. RNA in situ hybridization studies of human anagen hair follicles using a conserved probe for these four keratin-associated protein 1 members demonstrated the expression of this group in the differentiated portions of the hair cortex.

Gene expression of Sh3d19, a novel adaptor protein with five Src homology 3 domains, in anagen mouse hair follicles.

BACKGROUND: Sh3yl1, which contains one Src homology (SH) 3 domain, has been previously identified from mouse skin and considered to play an important role in hair follicle formation by interacting with other proteins. OBJECTIVE: We performed this study to identify proteins capable of associating with Sh3yl1. METHODS: We screened a mouse skin cDNA library using the SH3 domain of Sh3yl1 as bait in the yeast two-hybrid system. RESULTS: We identified a 420-amino acid-long protein containing a proline-rich stretch and five carboxyl-terminal SH3 domains, which we have termed Sh3d19. We confirmed the interactions between Sh3yl1 and Sh3d19 by in vitro binding assays. Northern blot analysis showed that Sh3d19 transcripts in mouse skin were expressed in accordance with the hair cycle. Furthermore, RNA in situ hybridization studies demonstrated that its transcripts were detected predominantly in the medulla cells at the level corresponding to the keratogenous zone of the hair follicles during the mid and late anagen phases. CONCLUSION: Sh3d19 is a novel adaptor protein that may be involved in the development of medulla cells during the anagen phase.