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PubMed2026

Brainstem Disconnection Syndrome in a Patient With Respiratory Failure and Failed Weaning From Oxygen: A Case Report.

BACKGROUND: Brainstem disconnection syndrome (BDS) is an exceedingly rare congenital malformation of the hindbrain characterized by disconnection of the brainstem, often presenting with severe neurological deficits and early neonatal mortality. Whereas previous cases have documented isolated neurological anomalies, this report delineates a distinctive presentation of BDS associated with a specific constellation of multisystem vascular and extracerebral skeletal malformations. CASE PRESENTATION: A 4-month-old female infant, born from a discordant twin pregnancy, exhibited persistent neonatal respiratory failure, failure to wean from oxygen therapy, global tonic-clonic seizures, and severe hypotonia. Magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) of the brain demonstrated a complete absence of the pons, a slender tissue cord connecting the midbrain and medulla oblongata, extensive cerebellar hypoplasia, and nonopacification or aplasia of the basilar and distal vertebral arteries. Whole exome sequencing did not reveal any standard inherited neurodevelopmental mutations; however, genomic analysis identified carrier status for a biologically plausible frameshift variant in TMEM67, a gene heavily implicated in ciliary hindbrain morphogenesis. The implementation of targeted supportive care allowed the patient to survive beyond the typical early neonatal period, with the patient remaining alive at a 12-month follow-up. CONCLUSION: This case broadens the known phenotypic and radiological range of BDS by reporting new multilevel skeletal and vascular co-occurring conditions. The notable phenotypic differences seen in this twin pregnancy support the theory of early embryonic vascular disruption. Additionally, the detection of the TMEM67 variant indicates that ciliary gene mutations could be important genetic factors or modifiers in BDS.

MRI neonate↗
PubMed1992

Lineage-specific methylation of the c-fms gene in blood cells and macrophages.

DNA methylation belongs to the multilevel genetic control system regulating differentiation processes and gene expression. The extent to which DNA methylation contributes to the differentiation of hematopoietic cells is elusive. In the present study we investigated the methylation state of the c-fms/M-CSF receptor gene in normal human blood cells and tissue macrophages. The methylation pattern of the c-fms gene as detected by isoschizomeric restriction analysis with MspI/HpaII showed only slight interindividual variations in normal donors, whereas constant differences were found between granulocytes and monocytes from the same donor. The second intron of the c-fms gene contains several CpG loci which were found to be hypomethylated on both alleles in monocytes and tissue macrophages. By contrast, these positions were methylated in granulocytes and lymphocytes that did not express the c-fms gene. In comparison to monocytes alveolar and peritoneal macrophages revealed an enhanced demethylation. There were constant differences in c-fms gene methylation between alveolar and peritoneal macrophages with a higher degree of demethylation in alveolar macrophages. We conclude that c-fms gene demethylation is involved in the differentiation of monocytes and macrophages from immature precursors and that the demethylation of lineage-specific growth factor receptor genes might provide an important step in lineage commitment of hematopoietic cells.

Alleles↗
PubMed2000

Implementing multilevel dynamic scheduling for a highly flexible 5-rail high throughput screening system.

As automation solves the bottleneck involved in drug screening, new bottlenecks present themselves. Some of these bottlenecks include sample management, hit picking and confirmation, and reagents lost as a result of incomplete runs. To keep up with the demands of a large HTS department, scientists spend a disproportionate amount of time simply feeding these systems with samples and reagents. Automating the sample management functions directly on the screening systems would solve this problem. With the use of online data analysis, an integrated sample store permits automated hit picking and confirmation. In addition to these issues, other bottlenecks are often caused by instrument malfunctions. A single lost run can now mean a loss of hundreds of plates and the reagents associated with their testing. A system was designed to include four assaying systems that are fed by an automated online sample repository system. Redundancy between the assaying systems allows for an extra level of error handling in case of a malfunction. The control of such a system requires a sophisticated scheduler/controller software package capable of coordinating the interaction between multiple systems and reacting to changes in the robotic environment in realtime. This paper discusses the design of the system as well as the requirements and selection of an appropriate scheduler/controller package.

Drug Evaluation, Preclinical↗
PubMed2006

Multilevel modeling was a convenient alternative to common regression designs in longitudinal suicide research.

BACKGROUND AND OBJECTIVE: The prospective investigation of repetitive nonfatal suicidal behavior is associated with two methodological problems. Due to the commonly used definitions of nonfatal suicidal behavior, clinical samples usually consist of patients with a considerable between-person variability. Second, repeated nonfatal suicidal episodes of the same subjects are likely to be correlated. We examined three regression techniques to comparatively evaluate their efficiency in addressing the given methodological problems. STUDY DESIGN AND SETTING: Repeated episodes of nonfatal suicidal behavior were assessed in two independent patient samples during a 2-year follow-up period. The first regression design modeled repetitive nonfatal suicidal behavior as a summary measure. The second regression model treated repeated episodes of the same subject as independent events. The third regression model represented a hierarchical linear model. RESULTS: The estimated mean effects of the first model were likely to be nonrepresentative for a considerable part of the study subjects. The second regression design overemphasized the impact of the predictor variables. The hierarchical linear model most appropriately accounted for the heterogeneity of the samples and the correlated data structure. CONCLUSION: The nonhierarchical regression designs did not provide appropriate statistical models for the prospective investigation of repetitive nonfatal suicidal behavior. Multilevel modeling provides a convenient alternative.

Adolescent↗
PubMed2003

Surgery for aortic stenosis in children: a 40-year experience.

BACKGROUND: Aortic stenosis (AS) is encountered in approximately 5% of children with heart disease. The indications for surgery and the surgical techniques for AS are well established. This report focuses on the early and long-term outcomes in children with AS over a 40-year period. METHODS: Included in this study were 508 patients ranging in ages from 1 day to 19 years, who were operated on for AS between 1960 and 2002. Eighty-one percent (414 of 508) of the patients had left ventricular outflow tract obstruction (LVOTO) at a single level: 40 supravalvar, 242 valvar (critical AS in 85 neonates and young infants and in 157 older children), and 132 subvalvar. Nineteen percent (94 of 508) of the patients had LVOTO at more than one level. Associated congenital cardiac defects were found in 32% of the patients. RESULTS: The overall hospital mortality rate was 8% (40/508) with neonates with critical AS having the highest mortality (33%). The late mortality was 4% for the entire group. Follow-up was 95% complete. The mean follow-up was 8.5 +/- 7.1 years. In the subgroup with multilevel LVOTO (n = 94), the average intraoperative peak systolic left ventricular-aortic gradient decreased from 80 to 22 mm Hg after repair but increased progressively to 74 +/- 36 mm Hg (p < 0.05) before reintervention was required. One hundred twenty-one patients (24%) underwent 151 reoperations for recurrent or residual LVOTO or aortic regurgitation. Actuarial curves predict a 20-year survival of 88% and 62% freedom from reoperation for all patients with AS. Symptomatic improvement in survivors was excellent (90% New York Heart Association class I). CONCLUSIONS: Surgical relief of LVOTO in infants and children can be accomplished with low mortality and morbidity. Neonates with critical AS have significantly higher mortality and morbidity due to their complex anatomy and their critical presentation that affects outcome. Aortic valvotomy delays valve replacement in a significant percentage of children. The Ross procedure and mechanical aortic valve replacements have had a low mortality and morbidity in our series. Valve replacement will eventually be required in most children presenting with valvar AS and multilevel LVOTO while repair of discrete subaortic stenosis and supravalvar AS may not require reoperation in most patients. Children with LVOTO should have lifetime follow-up.

Adolescent↗
PubMed1999

Reconstruction after multilevel corpectomy in the cervical spine. A sagittal plane biomechanical study.

STUDY DESIGN: An in vitro biomechanical study of reconstruction techniques used after multilevel cervical corpectomy. OBJECTIVES: To determine the biomechanical behavior of the cervical spine after a multilevel corpectomy and reconstruction with a strut graft and supplementation of the graft with anterior and posterior plates. SUMMARY OF BACKGROUND DATA: Reconstruction of the spine after multilevel corpectomy represents a significant challenge, with nonunion or graft dislodgment being relatively common. Anterior and posterior plate fixation have increased the possibilities for supplemental stabilization. Although some clinical studies have been performed to examine multilevel corpectomies reconstructed with plates, biomechanical studies are few and are limited to single-segment models. METHODS: Flexibility testing was performed on 11 intact cervical spine preparations. Flexibility testing was also conducted on the spine preparations after reconstruction with a strut graft, after supplementation of the graft with an anterior plate, and after supplementation of the graft with lateral mass plates. Physiologic moments were applied dynamically, and the three-dimensional motion of the specimen was recorded with stereophoto-grammetry. Failure testing was performed on the plated specimens in compression. Load displacement curves and failure modes were analyzed. RESULTS: The range of motion after reconstruction compared with the control was decreased 24% after strut grafting, 43% after application of an anterior plate, and 62% after application of posterior plates. Similarly, flexibility coefficients showed that the posterior plate technique was the least flexible, followed by the anterior plate technique, with the graft alone being the most flexible reconstruction construct. Load to initial failure tended to be higher in posterior than in anterior plate specimens, and screw pullout was the predominant failure mode. CONCLUSIONS: The application of plates to the cervical spine as an adjunct to bone graft may improve the surgeon's ability to stabilize the spine after multilevel corpectomy. Understanding the biomechanics of these devices and the potential mode of failure is important in their use.

Adult↗
PubMed2006

An intervention to decrease catheter-related bloodstream infections in the ICU.

BACKGROUND: Catheter-related bloodstream infections occurring in the intensive care unit (ICU) are common, costly, and potentially lethal. METHODS: We conducted a collaborative cohort study predominantly in ICUs in Michigan. An evidence-based intervention was used to reduce the incidence of catheter-related bloodstream infections. Multilevel Poisson regression modeling was used to compare infection rates before, during, and up to 18 months after implementation of the study intervention. Rates of infection per 1000 catheter-days were measured at 3-month intervals, according to the guidelines of the National Nosocomial Infections Surveillance System. RESULTS: A total of 108 ICUs agreed to participate in the study, and 103 reported data. The analysis included 1981 ICU-months of data and 375,757 catheter-days. The median rate of catheter-related bloodstream infection per 1000 catheter-days decreased from 2.7 infections at baseline to 0 at 3 months after implementation of the study intervention (P< or =0.002), and the mean rate per 1000 catheter-days decreased from 7.7 at baseline to 1.4 at 16 to 18 months of follow-up (P<0.002). The regression model showed a significant decrease in infection rates from baseline, with incidence-rate ratios continuously decreasing from 0.62 (95% confidence interval [CI], 0.47 to 0.81) at 0 to 3 months after implementation of the intervention to 0.34 (95% CI, 0.23 to 0.50) at 16 to 18 months. CONCLUSIONS: An evidence-based intervention resulted in a large and sustained reduction (up to 66%) in rates of catheter-related bloodstream infection that was maintained throughout the 18-month study period.

Adult↗
PubMed2005

Shared help seeking behaviour within families: a retrospective cohort study.

OBJECTIVE: To examine the extent to which the family influences individual use of general practitioner care. DESIGN: Retrospective cohort study of all consultations in one calendar year. Multilevel modelling was used to analyse contact frequencies of individuals within families within practices. SETTING: General practice in the Netherlands. PARTICIPANTS: 42 262 families with children aged 2-21 years registered in 96 practices. MAIN OUTCOME MEASURES: Family influence on individual frequency of contact with general practice and correlation in frequency of contacts between parents and children. RESULTS: After correction for patients' age and sex, analysis of siblings indicates that 22% of the variance in frequencies of contact can be ascribed to influence of the family. This means that contact frequencies of family members within families resemble each other, whereas differences in contact frequencies exist between families. Almost 6% of the variance refers to differences between practices and 73% of the variance refers to individual differences. The strongest correlations were found between mothers and children and between children. CONCLUSIONS: The extent of shared help seeking behaviour within families has considerable implications in the context of the practice.

Adolescent↗
PubMed2001

C-reactive protein in febrile children 1 to 36 months of age with clinically undetectable serious bacterial infection.

OBJECTIVE: To determine the diagnostic properties of quantitative C-reactive protein (CRP) associated with clinically undetectable serious bacterial infection (SBI) in febrile children 1 to 36 months of age. METHODS: Febrile children presenting to a pediatric emergency department (ED) with ages ranging from 1 to 36 months, temperatures > or =39 degrees C, and clinically undetectable source of fever were enrolled in this prospective cohort study. Demographic information, ED temperature, duration of fever, and clinical evaluation using the Yale observation scale were recorded at the time of the initial evaluation. The white blood cell count (WBC), band count, absolute neutrophil count (ANC), and CRP concentration were measured at the same time. All patients received blood cultures and either a screening urinalysis or urine culture. A chest radiograph was obtained at the discretion of the ED physician. Patients with history of using antibiotics within 1 week of their presentation to the ED were excluded. The main outcome result was the presence of laboratory or radiographically proven SBI (bacteremia, meningitis, urinary tract infection, pneumonia, septic arthritis, and osteomyelitis). RESULTS: Seventy-seven patients were enrolled in the study. Fourteen (18%) had a SBI (6 urinary tract infection; 4 pneumonia, including 1 patient with Streptococcus pneumoniae bacteremia; and 4 occult S pneumoniae bacteremia), and 63 had no SBI. The 2 groups were indistinguishable in age, sex, ED temperature, duration of fever, and Yale observation scale. CRP concentration, WBC, and ANC were significantly different between the 2 groups. In a multivariate logistic regression analysis, only CRP remained as a predictor of SBI (Beta = 0.76, 95% confidence interval [CI]: 0.64, 0.89). Receiver-operating characteristic analysis demonstrated CRP (area under curve [AUC] 0.905, standard error [SE] 0.05, 95% CI: 0.808, 1.002) to be superior to ANC (AUC 0.805, SE 0.051, 95% CI: 0.705, 0.905) and to WBC (AUC 0.761, SE 0.068, 95% CI: 0.628, 0.895). A CRP cutoff point of 7 was determined to maximize both sensitivity and specificity (sensitivity 79%, specificity 91%, likelihood ratio 8.3, 95% CI: 3.8, 27.3). Multilevel likelihood ratios and posttest probabilities were calculated for a variety of CRP levels. A CRP concentration of <5 mg/dL effectively ruled out SBI (likelihood ratio 0.087, 95% CI: 0.02, 0.38, posttest probability of SBI 1.9%). CONCLUSIONS: Quantitative CRP concentration is a valuable laboratory test in the evaluation of febrile young children who are at risk for occult bacteremia and SBI, with a better predictive value than the WBC or ANC.

Arthritis, Infectious↗
PubMed2005

Spatial analysis of air pollution and mortality in Los Angeles.

BACKGROUND: The assessment of air pollution exposure using only community average concentrations may lead to measurement error that lowers estimates of the health burden attributable to poor air quality. To test this hypothesis, we modeled the association between air pollution and mortality using small-area exposure measures in Los Angeles, California. METHODS: Data on 22,905 subjects were extracted from the American Cancer Society cohort for the period 1982-2000 (5,856 deaths). Pollution exposures were interpolated from 23 fine particle (PM2.5) and 42 ozone (O3) fixed-site monitors. Proximity to expressways was tested as a measure of traffic pollution. We assessed associations in standard and spatial multilevel Cox regression models. RESULTS: After controlling for 44 individual covariates, all-cause mortality had a relative risk (RR) of 1.17 (95% confidence interval=1.05-1.30) for an increase of 10 mug/m PM2.5 and a RR of 1.11 (0.99-1.25) with maximal control for both individual and contextual confounders. The RRs for mortality resulting from ischemic heart disease and lung cancer deaths were elevated, in the range of 1.24-1.6, depending on the model used. These PM results were robust to adjustments for O3 and expressway exposure. CONCLUSION: Our results suggest the chronic health effects associated with within-city gradients in exposure to PM2.5 may be even larger than previously reported across metropolitan areas. We observed effects nearly 3 times greater than in models relying on comparisons between communities. We also found specificity in cause of death, with PM2.5 associated more strongly with ischemic heart disease than with cardiopulmonary or all-cause mortality.

Air Pollution↗
PubMed2026

Multilevel genomic, transcriptomic, and epidemiologic evidence linking diabetic retinopathy to Alzheimer disease.

BACKGROUND: Diabetic retinopathy (DR) and Alzheimer disease (AD) share metabolic and vascular dysfunctions, but the extent to which they reflect overlapping genetic susceptibility and neurovascular-metabolic regulatory pathways remains unclear. We combined multi-omics analyses with population-based data to examine the genetic convergence, cellular pathways, and longitudinal association between DR and AD. METHODS: We performed a two-sample Mendelian randomisation (MR) to estimate the association between genetically predicted DR liability and AD risk. We used Bayesian colocalisation analysis to identify shared genomic loci, and summary-data-based MR (SMR) to detect expression-mediated genes jointly associated with DR and AD. We analysed single-cell RNA sequencing data to characterise shared cellular features and related biological pathways. We also conducted an MR-based mediation analysis to explore whether lipid-related, metabolic, or inflammatory traits mediated the observed DR-AD association, and a longitudinal analysis of the UK Biobank cohort to assess the association between DR and incident AD. RESULTS: With the MR analysis, we found that genetically predicted liability to DR was associated with a modest increase in AD risk. Colocalisation analysis supported a shared genetic signal. We identified three genes with shared expression-mediated associations across DR and AD through SMR. Functional enrichment analyses revealed partially overlapping neurovascular and metabolic pathways. Using MR-based mediation analysis, we found no significant intermediary traits linking DR and AD. Findings from the UK Biobank cohort were directionally consistent with the genetic analyses. CONCLUSIONS: Genetic liability to DR is associated with an increased risk of AD and is accompanied by shared expression-mediated effects and convergent neurovascular-metabolic pathways. These findings support the possibility that DR may serve as a clinically accessible indicator of increased neurodegenerative vulnerability.

Humans↗
PubMed2001

Cadaveric fibula, locking plate, and allogeneic bone matrix for anterior cervical fusions after cervical discectomy for radiculopathy or myelopathy.

OBJECT: The authors have previously reported that the results of using cadaveric fibula and locking plate (CF/LP) fusion following anterior cervical discectomy (ACD) for cervical spondylotic radiculopathy and myelopathy are superior to those obtained using autologous iliac crest (AIC) grafts in the short term. The long-term results of using this construct are important in substantiating this improvement. The authors report on 246 consecutive patients (54% smokers) who underwent ACD with CF/LP fusion (175 with allogeneic bone matrix [ABM]) and compare them with 111 consecutive patients in whom AIC fusions (49% smokers) were performed by the same surgeons. METHODS: The study is a retrospective nonrandomized analysis, and chi-square statistics were used. Bone densitometric studies of AIC grafts and CF grafts were performed. A paired t-test was used for statistical analysis of the results. Disease in the group of patients undergoing CF/LP fusion included soft-disc herniation with radiculopathy in 14, soft-disc hemiation with myelopathy in seven, cervical spondylotic radiculopathy in 144, cervical spondylotic myelopathy in 75, AIC graft collapse pseudarthrosis in five, and ACD with no fusion collapse/kyphosis in one. Operations consisted of single-level CF/LP fusion in 142 patients and multilevel CF/LP fusion in 104. Perioperative complications in the CF/LP group included three cases of transient hoarseness. There were no transfusions, infections, neurological injuries, or deaths. The mean hospital length of stay was 1.2 days (28% outpatient and 66% 23-hour stay). The mean follow-up period was 60 months (range 12-94 months). Ten patients were lost to follow up after 1 year. Long-term complications included one traumatic plate fracture and one symptomatic pseudarthrosis with plate fracture. At 1 year and beyond, in 245 (99.6%) of 246 patients radiographically documented fusion with no motion at the fused level on flexion-extension films was demonstrated. There was no kyphosis, no symptomatic screw plate backout, and no CF/LP graft collapse (100% in the ABM group). In the 111 consecutive patients with AIC fusions, however, there was a 17% graft-related complication rate. There were significantly fewer graft-related complications in the CF/LP group (p < 0.001). There was no difference in neurological outcome for any of the groups. In the groups undergoing single-level ACD there was a significantly greater chance of complete relief of neck pain CF/LP fusion compared with those undergoing AIC fusion (p < 0.02). There was a significantly greater chance of AIC collapse with the passage of time compared with CF graft (p < 0.02). Time until return to work was shorter for the CF/LP group by 5 to 6 weeks (p < 0.02). There was a higher rate of radiographically documented pseudarthrosis in the AIC group (p < 0.006). The mean bone densitometry for the CF/LP group was 0.7 g/cm2, significantly greater than that of the AIC group, which was 0.2 g/cm2 (paired t-test p < 0.001). CONCLUSIONS: When fusion is necessary following ACD, the results of CF/LP fusion are significantly superior in the first 5 years after surgery compared with those for AIC fusions. It remains to be determined if demineralized ABM has a significant effect in enhancing fusion.

Adult↗
PubMed1998

Occupation-centered assessment of children.

The past 5 years have seen increasing calls to reexamine our assessment and intervention practices to ensure that they reflect the profession's basic focus on occupation. Although a number of noteworthy efforts in this direction have been presented for adult practice areas, implementation of occupation-centered assessment in pediatric has been hampered by the lack of a consistent framework to guide this process. This article will present an adaptation of the functional assessment model proposed by Trombly (1993) designed to better reflect the unique needs and situations of children. It is a multilevel model that examines the pattern of a child's occupations in a particular environment as well as the performance of important tasks and activities that are part of these occupations. It is proposed that this model can serve as an organizing framework for an occupation-centered assessment process by helping to identify the critical questions that need to be addressed at each level of analysis and the kinds of measures that might be used to obtain relevant information. The newly completed School Function Assessment will be used to illustrate application of the framework to examine occupational performance of children in elementary school.

Child↗
PubMed2001

High-performance liquid chromatographic analysis of the tyrphostin AG1478, a specific inhibitor of the epidermal growth factor receptor tyrosine kinase, in mouse plasma.

The tyrphostin 4-(3-chloroanilino)-6,7-dimethoxyquinazoline (AG1478) is undergoing evaluation as a potential new anticancer agent. We have developed a specific and sensitive reversed-phase HPLC assay for AG1478 in mouse plasma. The method involves a rapid and simple extraction process followed by separation on a Symmetry C8 stationary phase with a gradient of acetonitrile in ammonium acetate buffer. A linear response was achieved over the concentration range of 0.2-100 microM using multilevel calibration with internal standard method of calculation. Inter- and intra-assay accuracy and precision were better than +/-10%. The limit of quantitation was 0.2 microM. We have used this method to study the preclinical pharmacokinetics of this new agent in mice.

Animals↗
PubMed2000

Follow-up of coping skills training in adults with sickle cell disease: analysis of daily pain and coping practice diaries.

This study examined the 3-month follow-up effects of a pain coping skills intervention in African American adults with sickle cell disease. Sixty-seven participants were randomly assigned to either a coping skills condition or a disease-education control condition. Multivariate analyses applied to summary measures of coping, laboratory pain perception, and clinical measures indicated that participants in the coping intervention reported significantly lower laboratory pain and significantly higher coping attempts at 3-month follow-up in comparison with the control condition. Multilevel random effects models applied to prospective daily diaries of daily pain, health care contacts, and coping practice indicated that on pain days when participants practiced their strategies, they had less major health care contacts in comparison with days when they did not use strategies.

Adaptation, Psychological↗
PubMed2006

Guided tissue regeneration for periodontal infra-bony defects.

BACKGROUND: Conventional treatment of destructive periodontal (gum) disease arrests the disease but does not usually regain the bone support or connective tissue lost in the disease process. Guided tissue regeneration (GTR) is a surgical procedure that specifically aims to regenerate the periodontal tissues when the disease is advanced and could overcome some of the limitations of conventional therapy. OBJECTIVES: To assess the efficacy of GTR in the treatment of periodontal infra-bony defects measured against conventional surgery (open flap debridement (OFD)) and factors affecting outcomes. SEARCH STRATEGY: We conducted an electronic search of the Cochrane Oral Health Group Trials Register, MEDLINE and EMBASE up to April 2004. Handsearching included Journal of Periodontology, Journal of Clinical Periodontology, Journal of Periodontal Research and bibliographies of all relevant papers and review articles up to April 2004. In addition, we contacted experts/groups/companies involved in surgical research to find other trials or unpublished material or to clarify ambiguous or missing data and posted requests for data on two periodontal electronic discussion groups. SELECTION CRITERIA: Randomised, controlled trials (RCTs) of at least 12 months duration comparing guided tissue regeneration (with or without graft materials) with open flap debridement for the treatment of periodontal infra-bony defects. Furcation involvements and studies specifically treating aggressive periodontitis were excluded. DATA COLLECTION AND ANALYSIS: Screening of possible studies and data extraction was conducted independently. The methodological quality of studies was assessed in duplicate using individual components and agreement determined by Kappa scores. Methodological quality was used in sensitivity analyses to test the robustness of the conclusions. The Cochrane Oral Health Group statistical guidelines were followed and the results expressed as mean differences (MD and 95% CI) for continuous outcomes and risk ratios (RR and 95% CI) for dichotomous outcomes calculated using random-effects models. Any heterogeneity was investigated. The primary outcome measure was change in clinical attachment. MAIN RESULTS: The search produced 626 titles, of these 596 were clearly not relevant to the review. The full text of 32 studies of possible relevance was obtained and 15 studies were excluded. Therefore 17 RCTs were included in this review, 16 studies testing GTR alone and two testing GTR+bone substitutes (one study had both test treatment arms).No tooth loss was reported in any study although these data are incomplete where patient follow up was not complete. For attachment level change, the mean difference between GTR and OFD was 1.22 mm (95% CI Random Effects: 0.80 to 1.64, chi squared for heterogeneity 69.1 (df = 15), P < 0.001, I(2) = 78%) and for GTR + bone substitutes was 1.25 mm (95% CI 0.89 to 1.61, chi squared for heterogeneity 0.01 (df = 1), P = 0.91). GTR showed a significant benefit when comparing the numbers of sites failing to gain 2 mm attachment with risk ratio 0.54 (95% CI Random Effects: 0.31 to 0.96, chi squared for heterogeneity 8.9 (df = 5), P = 0.11). The number needed to treat (NNT) for GTR to achieve one extra site gaining 2 mm or more attachment over open flap debridement was therefore 8 (95% CI 5 to 33), based on an incidence of 28% of sites in the control group failing to gain 2 mm or more of attachment. For baseline incidences in the range of the control groups of 3% and 55% the NNTs are 71 and 4. Probing depth reduction was greater for GTR than OFD: 1.21 mm (95% CI 0.53 to 1.88, chi squared for heterogeneity 62.9 (df = 10), P < 0.001, I(2) = 84%) or GTR + bone substitutes, weighted mean difference 1.24 mm (95% CI 0.89 to 1.59, chi squared for heterogeneity 0.03 (df = 1), P = 0.85). For gingival recession, a statistically significant difference between GTR and open flap debridement controls was evident (mean difference 0.26 mm (95% CI Random Effects: 0.08, 0.43, chi squared for heterogeneity 2.7 (df = 8), P = 0.95), with a greater change in recession from baseline for the control group. Regarding hard tissue probing at surgical re-entry, a statistically significant greater gain was found for GTR compared with open flap debridement. This amounted to a weighted mean difference of 1.39 mm (95% CI 1.08 to 1.71, chi squared for heterogeneity 0.85 (df = 2), P = 0.65). For GTR + bone substitutes the difference was greater, with mean difference 3.37 mm (95% CI 3.14 to 3.61). Adverse effects were generally minor although with an increased treatment time for GTR. Exposure of the barrier membrane was frequently reported with a lack of evidence of an effect on healing. AUTHORS' CONCLUSIONS: GTR has a greater effect on probing measures of periodontal treatment than open flap debridement, including improved attachment gain, reduced pocket depth, less increase in gingival recession and more gain in hard tissue probing at re-entry surgery. However there is marked variability between studies and the clinical relevance of these changes is unknown. As a result, it is difficult to draw general conclusions about the clinical benefit of GTR. Whilst there is evidence that GTR can demonstrate a significant improvement over conventional open flap surgery, the factors affecting outcomes are unclear from the literature and these might include study conduct issues such as bias. Therefore, patients and health professionals need to consider the predictability of the technique compared with other methods of treatment before making final decisions on use. Since trial reports were often incomplete, we recommend that future trials should follow the CONSORT statement both in their conduct and reporting. There is therefore little value in future research repeating simple, small efficacy studies. The priority should be to identify factors associated with improved outcomes as well as investigating outcomes relevant to patients. Types of research might include large observational studies to generate hypotheses for testing in clinical trials, qualitative studies on patient-centred outcomes and trials exploring innovative analytic methods such as multilevel modelling. Open flap surgery should remain the control comparison in these studies.

Alveolar Bone Loss↗
PubMed2004

Implementation of brief alcohol interventions by nurses in primary care: do non-clinical factors influence practice?

BACKGROUND: In the UK, GPs and practice nurses selectively provide brief alcohol interventions to risk drinkers. GPs' provision of a brief alcohol intervention can be predicted by patient characteristics, practitioner characteristics and structural factors such as the features of the practice and how it is organized. However, much less is known about possible modifiers of nurse practice. OBJECTIVE: Our aim was to investigate if patient characteristics, nurse characteristics and practice factors influence provision of a brief alcohol intervention by practice nurses in primary health care. METHODS: One hundred and twenty-eight practice nurses who had implemented a brief alcohol intervention programme in a previous trial based in the North of England were requested to screen adults presenting to their surgery and follow a structured protocol to give a brief intervention (5 min of advice plus an information booklet) to all 'risk' drinkers. Anonymized carbon copies of 5541 completed Alcohol Use Disorders Identification Test (AUDIT) screening questionnaires were collected after a 3-month implementation period and analysed by logistic regression analysis. RESULTS: Although AUDIT identified 1500 'risk' drinkers, only 926 (62%) received a brief intervention. Logistic regression modelling showed that patients' risk status as measured by AUDIT score was the most influential predictor of a brief intervention by practice nurses. However, risk drinkers who were most likely to receive a brief intervention were male. Patients' age or social class did not independently predict a brief intervention. The multilevel model was unable to identify any independent nurse characteristics that could predict a brief intervention, but indicated significant variation between nurses in their tendency to offer the intervention to patients. No structural factors were found to be positively associated with selective provision. CONCLUSIONS: Patient and nurse factors contributed to the selective provision of a brief intervention in primary care. If patients are to experience the beneficial effects of a brief alcohol intervention, then there is a need to improve the accuracy of delivery.

Adolescent↗
PubMed1999

The diagnostic accuracy of ultrasound scan in predicting endometrial hyperplasia and cancer in postmenopausal bleeding.

OBJECTIVE: To determine the accuracy of ultrasound scan in the diagnosis of endometrial hyperplasia and cancer in postmenopausal bleeding. DESIGN: A prospective diagnostic accuracy study (1996-97). SETTING: Minimal access surgical training centers in two large teaching hospitals. METHODS: Ultrasound scan and outpatient endometrial sampling were performed on 96 patients with postmenopausal bleeding. Patients unable to have these outpatient procedures had a formal inpatient hysteroscopy and curettage. Test performance characteristics were computed for ultrasound scan comparing its estimate of endometrial thickness with histologic diagnosis that served as a 'gold' standard. OUTCOME MEASURES: Accuracy of the ultrasonic endometrial thickness was estimated using sensitivity, specificity and predictive values for binary data. For multilevel data, the diagnostic accuracy was computed using likelihood ratios (LRs). An LR < decreased the probability that endometrial hyperplasia/cancer was present, whereas an LR > 1 increased the probability that such lesion was present. RESULTS: Using endometrial thickness > or =4 mm, the sensitivity of ultrasound to detect the endometrial malignancy was 92.9%, the specificity was 500%, and the positive and negative predictive values were 24.1% and 97.6% respectively. Analysis using likelihood ratio (LR) revealed that LR was 0.14 for endometrial thickness > or =4.0 mm, 0.94 for endometrial thickness 4.1-9.0 mm, and 3.3 for endometrial thickness >9.0 mm. CONCLUSION: In women with postmenopausal bleeding, malignancy can probably be safely excluded if sonographic endometrial thickness is < or = 4.0 mm. However, the probability of endometrial hyperplasia/cancer is not particularly altered by the knowledge that endometrial thickness on scan is >4.0 mm.

Biopsy↗