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1.  Periodontal Disease as a Risk Factor for Bisphosphonate-Related Osteonecrosis of the Jaw 
Journal of periodontology  2013;85(2):226-233.
Background
Previous case reports and animal studies suggest periodontitis is associated with bisphosphonate-related osteonecrosis of the jaw (BRONJ). We conducted a case-control study to evaluate the association between clinical and radiographic measures of periodontal disease and BRONJ.
Methods
25 BRONJ patients were matched with 48 controls. Trained examiners measured probing depth (PD), clinical attachment level (CAL), and bleeding on probing (BOP) on all teeth except third molars, and gingival and plaque indices on six index teeth. Alveolar bone height was measured from orthopantomograms. Most BRONJ cases were using antibiotics (48%) or a chlorhexidine mouthrinse (84%) at enrollment. Adjusted comparisons of cases vs. controls used multiple linear regression.
Results
The average number of BP infusions was significantly higher in BRONJ cases compared to controls (38.4 vs 18.8, p=0.0001). In unadjusted analyses, BRONJ cases had more missing teeth (7.8 vs 3.1, p=0.002) and high average CAL (2.18 vs 1.56 mm, p=0.047) and percent of sites with CAL ≥3 mm (39.0 vs 23.3, p=0.039) than controls. Also, BRONJ cases had lower average bone height (as a fraction of tooth length, 0.59 vs 0.62, p=0.004) and more teeth with bone height under half of tooth length (20% vs 6%, p=0.001). These differences remained significant after adjusting for age, sex, smoking, and number of bisphosphonate infusions.
Conclusions
BRONJ patients have fewer teeth, greater CAL, and less alveolar bone support compared to controls after adjusting for number of bisphosphonate infusions. Group differences in antibiotics and chlorhexidine rinse usage may have masked differences in the other clinical measures.
doi:10.1902/jop.2013.130017
PMCID: PMC3972496  PMID: 23786404
Bisphosphonates; Periodontitis; Periodontal Disease; Alveolar Bone Loss; Osteonecrosis; Bisphosphonate-related osteonecrosis of the jaw
2.  Blunted Response to a Growth Hormone Stimulation Test is Associated with Unfavorable Cardiovascular Risk Factor Profile in Childhood Cancer Survivors 
Pediatric blood & cancer  2012;60(3):467-473.
Background
Childhood cancer survivors (CCS) are at risk for growth hormone (GH) deficiency. CCS are also at increased risk for early mortality from cardiovascular (CV) disease, but the association between GH levels and CV risk remains poorly understood. The goal of this study was to examine the cross-sectional association between stimulated GH levels and CV risk factors in CCS younger than 18 years.
Procedure
276 CCS (147 males, 14.4±2.6 years) ≥5 years after cancer diagnosis, and 208 sibling controls (112 males, 13.6±2.4 years) participated in this cross-sectional study, which included anthropometry, body composition, and metabolic studies. Blunted response (BR) was defined as peak GH level <7 μg/L after clonidine and arginine. Insulin sensitivity (Mlbm) was measured by euglycemic hyperinsulinemic clamp. Statistical analyses used linear and logistic regression accounting for sibling clustering, adjusted for age, sex, Tanner stage, and adiposity.
Results
34 (12%) CCS showed BR to GH stimulation. BR CCS were shorter and had a lower IGF-1 than controls; only 6 of 34 received cranial radiation therapy. CCS with normal stimulated GH response were similar to controls for CV risk factors. Conversely, BR CCS had greater adiposity, higher lipids, and lower Mlbm than controls. Differences in lipids and Mlbm between BR CCS and controls remained significant after adjustment for BMI or visceral fat.
Conclusions
Blunted response to GH stimulation is prevalent in CCS youth and is associated with an unfavorable CV risk factor profile. Further studies are needed to establish the mechanisms of these associations.
doi:10.1002/pbc.24308
PMCID: PMC3529966  PMID: 23002034
cardiovascular risk; growth hormone deficiency; cancer survivors; chemotherapy; insulin resistance; children
3.  Superior methadone treatment outcome in Hmong compared to non-Hmong patients 
The Hmong are a distinct ethnic group from Laos. Little is known about how opiate addicted Hmong respond to methadone maintenance treatment. Therefore, opium addicted Hmong (exclusive route of administration: smoking) attending an urban methadone maintenance program in Minneapolis, Minnesota were matched by gender and date of admission with predominately heroin addicted non-Hmong (predominant route of administration: injection) attending the same program and both groups were evaluated for 1-year treatment retention, stabilization dose of methadone, and urine drug screen results. Hmong had greater 1-year treatment retention (79.8%) than non-Hmong (63.5%; p<0.01). In both groups, methadone dose was significantly associated with retention (p=0.005). However, Hmong required lower doses of methadone for stabilization (mean 49.0 mg versus 77.1 mg; p<0.0001). For both groups, positive urine drug screens were associated with stopping treatment. Further research to determine levels of tolerance, psychosocial, and pharmacogenetic factors contributing to differences methadone treatment outcome and dosing in Hmong may provide further insight into opiate addiction and its treatment.
doi:10.1016/j.jsat.2011.12.006
PMCID: PMC3340471  PMID: 22285835
Methadone; opiate dependence; treatment outcome; ethnicity; Hmong
4.  Quality of Care for Gout in the US Needs Improvement 
Arthritis and rheumatism  2007;57(5):822-829.
Objective
To examine evidence-based quality indicators (QIs) in US veterans with gout diagnosis, and to examine the effect of demographics, heath care utilization/access, comorbid conditions, or physican characteristics as predictors of quality of gout care.
Methods
Using the Minneapolis Veterans Affairs electronic medical record system, we identified a cohort of veterans receiving medication to treat gout between January 1, 1999 and December 31, 2003, and evaluated 3 recently published evidence-based QIs for gout management: QI 1 = allopurinol dose <300 mg in gout patients with renal insufficiency, QI 2 = uric acid check within 6 months of starting a new allopurinol prescription, and QI 3 = complete blood count and creatine kinase check every 6 months for gout patients receiving prolonged colchicine therapy. We calculated the proportion of patients whose therapy adhered to each QI and to all applicable indicators (overall physician adherence). Logistic regression analysis examined association of overall physician adherence with sociodemographics, health care utilization, comorbidity, and provider characteristics.
Results
Of 3,658 patients with a diagnosis of gout, 663 patients qualified for examination of ≥1 QI. Of these 663 patients, therapy in only 144 (22%) adhered to all applicable QIs; 59 (78%) of 76 adhered to QI 1, 155 (24%) of 643 adhered to QI 2, and 18 (35%) of 52 adhered to QI 3. Overall physician adherence to QIs was significantly lower in older veterans and in those with more inpatient visits per year, but was higher in those with more primary care visits or more health care providers.
Conclusion
Suboptimal physician adherence to QIs was seen for all 3 QIs tested in this cohort of veterans with gout. These findings can guide quality improvement efforts.
doi:10.1002/art.22767
PMCID: PMC3619972  PMID: 17530682
Gout; Veterans; Quality of care; Quality indicators; Physician adherence
5.  The Association between Cognition and Academic Performance in Ugandan Children Surviving Malaria with Neurological Involvement 
PLoS ONE  2013;8(2):e55653.
Background
The contribution of different cognitive abilities to academic performance in children surviving cerebral insult can guide the choice of interventions to improve cognitive and academic outcomes. This study's objective was to identify which cognitive abilities are associated with academic performance in children after malaria with neurological involvement.
Methods
62 Ugandan children with a history of malaria with neurological involvement were assessed for cognitive ability (working memory, reasoning, learning, visual spatial skills, attention) and academic performance (reading, spelling, arithmetic) three months after the illness. Linear regressions were fit for each academic score with the five cognitive outcomes entered as predictors. Adjusters in the analysis were age, sex, education, nutrition, and home environment. Exploratory factor analysis (EFA) and structural equation models (SEM) were used to determine the nature of the association between cognition and academic performance. Predictive residual sum of squares was used to determine which combination of cognitive scores was needed to predict academic performance.
Results
In regressions of a single academic score on all five cognitive outcomes and adjusters, only Working Memory was associated with Reading (coefficient estimate = 0.36, 95% confidence interval = 0.10 to 0.63, p<0.01) and Spelling (0.46, 0.13 to 0.78, p<0.01), Visual Spatial Skills was associated with Arithmetic (0.15, 0.03 to 0.26, p<0.05), and Learning was associated with Reading (0.06, 0.00 to 0.11, p<0.05). One latent cognitive factor was identified using EFA. The SEM found a strong association between this latent cognitive ability and each academic performance measure (P<0.0001). Working memory, visual spatial ability and learning were the best predictors of academic performance.
Conclusion
Academic performance is strongly associated with the latent variable labelled “cognitive ability” which captures most of the variation in the individual specific cognitive outcome measures. Working memory, visual spatial skills, and learning together stood out as the best combination to predict academic performance.
doi:10.1371/journal.pone.0055653
PMCID: PMC3562187  PMID: 23383342
6.  Decreased Prevalence of Anemia in Highland Areas of Low Malaria Transmission After a 1-Year Interruption of Transmission 
In 2 highland areas of Kenya with low malaria transmission, interruption of malaria transmission led to a 34% reduction in anemia prevalence in children <5 years of age.
Background. Malaria control campaigns have reduced malaria transmission to very low levels in many areas of Africa. Yet the extent to which malaria interruption or elimination might decrease the prevalence of anemia in areas of low malaria transmission is unknown.
Methods. Kapsisiywa and Kipsamoite, highland areas of Kenya with low, unstable malaria transmission, experienced a 12-month interruption in malaria transmission from April 2007 to May 2008, following high-level coverage (>70% of households) with indoor residual insecticide spraying in 2007. Hemoglobin levels were tested in 1697 randomly selected asymptomatic residents of Kapsisiywa (n = 910) and Kipsamoite (n = 787) at the beginning of a 12-month period of interrupted transmission (in May 2007) and 14 months later (in July 2008).
Results. From May 2007 to July 2008, only 1 of 1697 study cohort members developed clinical malaria. In this period, the prevalence of anemia decreased in Kapsisiywa in all age groups (from 57.5% to 37.9% in children aged <5 years [P < .001], from 21.7% to 10.5% in children aged 5–14 years [P < .001], and from 22.7% to 16.6% in individuals aged ≥15 years [P = .004]). The prevalence of anemia in Kipsamoite also decreased in children aged <5 years (from 47.2% to 31.3%; P = .001) but was unchanged in children aged 5–14 years and in individuals aged ≥15 years. Among children <5 years, anemia prevalence was reduced by 34% in both Kapsisiywa (95% confidence interval [CI], 21%–45%) and Kipsamoite (95% CI, 16%–48%).
Conclusions. Successful malaria elimination or interruption may lead to substantial reductions in anemia prevalence even in areas of very low transmission.
doi:10.1093/cid/cir768
PMCID: PMC3245725  PMID: 22052892
7.  Effects of a Home-Based Walking Intervention on Mobility and Quality of Life in People With Diabetes and Peripheral Arterial Disease 
Diabetes Care  2011;34(10):2174-2179.
OBJECTIVE
Determine the efficacy of a home-based walking intervention to improve walking ability and quality of life in people with diabetes and peripheral arterial disease (PAD).
RESEARCH DESIGN AND METHODS
We conducted a randomized, controlled, single-blind trial within university-affiliated clinics in our local community. We randomized 145 participants (45 women) with diabetes and PAD to our intervention—a 6-month behavioral intervention targeting levels of readiness to engage in routine walking for exercise—versus attention control. Our primary outcome was 6-month change in maximal treadmill walking distance. Secondary outcomes included 3-month change in maximal walking distance, lower limb function (i.e., walking impairment scores), quality of life (Medical Outcomes Short Form Survey), exercise behaviors, depressive symptoms, and self-efficacy at 3 and 6 months.
RESULTS
The mean age of participants was 66.5 (SD 10.1) years. Intervention and control groups did not differ significantly in 6-month change in maximal treadmill walking distance (average [SE] 24.5 [19.6] meters vs. 39.2 [19.6] meters; P = 0.60). Among secondary outcomes, for the intervention and control groups, respectively, average walking speed scores increased by 5.7 [2.2] units and decreased by 1.9 [2.8] units (P = 0.03); the mental health quality of life subscale score increased by 3.2 [1.5] and decreased by 2.4 [1.5] units (P = 0.01).
CONCLUSIONS
A home-based walking intervention did not improve walking distance but did improve walking speed and quality of life in people with diabetes and PAD. Clinicians should consider recommending home-based walking therapy for such patients.
doi:10.2337/dc10-2399
PMCID: PMC3177730  PMID: 21873560
8.  Noninvasive quantification of ascorbate and glutathione concentration in the elderly human brain 
NMR in biomedicine  2011;24(7):888-894.
In this study, ascorbate (Asc) and glutathione (GSH) concentrations were quantified noninvasively using double-edited 1H MRS at 4 T in the occipital cortex of healthy young [age (mean ± standard deviation) = 20.4 ± 1.4 years] and elderly (age = 76.6 ± 6.1 years) human subjects. Elderly subjects had a lower GSH concentration than younger subjects (p < 0.05). The Asc concentration was not significantly associated with age. Furthermore, the lactate (Lac) concentration was higher in elderly than young subjects. Lower GSH and higher Lac concentrations are indications of defective protection against oxidative damage and impaired mitochondrial respiration. The extent to which the observed concentration differences could be associated with physiological differences and methodological artifacts is discussed. In conclusion, GSH and Asc concentrations were compared noninvasively for the first time in young vs elderly subjects.
doi:10.1002/nbm.1646
PMCID: PMC3118919  PMID: 21834011
ascorbate; glutathione; lactate; brain; human; aging; MEGA-PRESS; MRS
9.  Noninvasive quantification of human brain antioxidant concentrations after an intravenous bolus of vitamin C 
Nmr in Biomedicine  2010;24(5):521-528.
Until now, the lack of a means to detect a deficiency or to measure the pharmacologic effect in the human brain in situ has been a hindrance to the development of antioxidant-based prevention and treatment of dementia. In this study, a recently developed 1H MRS approach was applied to quantify key human brain antioxidant concentrations throughout the course of an aggressive antioxidant-based intervention. The concentrations of the two most abundant central nervous system chemical antioxidants, vitamin C and glutathione, were quantified noninvasively in the human occipital cortex prior to and throughout 24 h after bolus intravenous delivery of 3 g of vitamin C. Although the kinetics of the sodium-dependent vitamin C transporter and physiologic blood vitamin C concentrations predict theoretically that brain vitamin C concentration will not increase above its homeostatically maintained level, this theory has never been tested experimentally in the living human brain. Therefore, human brain vitamin C and glutathione concentrations were quantified noninvasively using MEGA-PRESS double-edited 1H MRS and LCModel. Healthy subjects (age, 19–63 years) with typical dietary consumption, who did not take vitamin supplements, fasted overnight and then reported for the measurement of baseline antioxidant concentrations. They then began controlled feeding which they adhered to until after vitamin C and glutathione concentrations had been measured at 2, 6, 10 and 24 h after receiving intravenous vitamin C. Two of the twelve studies were sham controls in which no vitamin C was administered. The main finding was that human brain vitamin C and glutathione concentrations remained constant throughout the protocol, even though blood serum vitamin C concentrations spanned from the low end of the normal range to very high.
doi:10.1002/nbm.1619
PMCID: PMC3335753  PMID: 21674654
antioxidants; ascorbate; glutathione; MRS; noninvasive; human; brain; intravenous
10.  Maternal Periodontitis Treatment and Child Neurodevelopment at 24 to 28 Months of Age 
Pediatrics  2011;127(5):e1212-e1220.
BACKGROUND:
Some maternal infections are associated with impaired infant cognitive and motor performance. Periodontitis results in frequent bacteremia and elevated serum inflammatory mediators.
OBJECTIVE:
The purpose of this study was to determine if periodontitis treatment in pregnant women affects infant cognitive, motor, or language development.
METHODS:
Children born to women who had participated in a previous trial were assessed between 24 and 28 months of age by using the Bayley Scales of Infant and Toddler Development (Third Edition) and the Preschool Language Scale (Fourth Edition). Information about the pregnancy, neonatal period, and home environment was obtained through chart abstractions, laboratory test results, and questionnaires. We compared infants born to women treated for periodontitis before 21 weeks' gestation (treatment group) or after delivery (controls). In unadjusted and adjusted analyses, associations between change in maternal periodontal condition during pregnancy and neurodevelopment scores were tested by using Student's t tests and linear regression.
RESULTS:
A total of 411 of 791 eligible mother/caregiver-child pairs participated. Thirty-seven participating children (9.0%) were born at <37 weeks' gestation. Infants in the treatment and control groups did not differ significantly for adjusted mean cognitive (90.7 vs 91.4), motor (96.8 vs 97.2), or language (92.2 vs 92.1) scores (all P > .5). Results were similar in adjusted analyses. Children of women who experienced greater improvements in periodontal health had significantly higher motor and cognitive scores (P = .01 and .02, respectively), although the effect was small (∼1-point increase for each SD increase in the periodontal measure).
CONCLUSION:
Nonsurgical periodontitis treatment in pregnant women was not associated with cognitive, motor, or language development in these study children.
doi:10.1542/peds.2010-3129
PMCID: PMC3081189  PMID: 21482606
child neurodevelopment; periodontitis; pregnancy; treatment
11.  Frequency of Non-Odontogenic Pain After Endodontic Therapy: A Systematic Review and Meta-Analysis 
Journal of endodontics  2010;36(9):1494-1498.
Introduction
Little is known about ill-defined pain that persists following endodontic procedures, including an estimate of the problem’s magnitude. We conducted a systematic review of prospective studies that reported the frequency of non-odontogenic pain in patients who had undergone endodontic procedures.
Methods
Non-odontogenic pain was defined as dentoalveolar pain present for 6 months or more after endodontic treatment without evidence of dental pathology. Endodontic procedures reviewed were non-surgical root canal treatment, retreatment, and surgical root canal treatment. Studies were searched in four databases electronically, complemented by hand searching. A summary estimate of non-odontogenic tooth pain frequency was derived using random-effects meta-analysis.
Results
Of 770 articles retrieved and reviewed, 10 met inclusion criteria and 9 had data on both odontogenic and non-odontogenic causes of pain. A total of 3,343 teeth were included; 1,125 had follow-up information regarding pain status. We identified 48 teeth with non-odontogenic pain and estimated a 3.4% (95% CI: 1.4 to 5.5%) frequency of occurrence. In 9 articles containing data regarding both odontogenic and non-odontogenic causes of tooth pain, 56% (44/78) of all cases were thought to have a non-odontogenic cause.
Conclusions
Non-odontogenic pain is not an uncommon outcome following root canal therapy and may represent half of all cases of persistent tooth pain. These findings have implications for diagnosis and treatment of painful teeth that were previously root canal treated since therapy directed at the tooth in question would not be expected to resolve non-odontogenic pain.
doi:10.1016/j.joen.2010.06.020
PMCID: PMC2941431  PMID: 20728716
Tooth; Dentoalveolar; Pain; Root canal therapy; Systematic review
12.  Frequency of Persistent Tooth Pain Following Root Canal Therapy: A Systematic Review and Meta-Analysis 
Journal of endodontics  2010;36(2):224-230.
Introduction
Little is known about the frequency of persistent pain after endodontic procedures, even though pain is a core patient-oriented outcome. We estimated the frequency of persistent pain, regardless of etiology, following endondontic treatment.
Methods
Persistent tooth pain was defined as pain present ≥ 6 months after endodontic treatment. Endodontic procedures included in the review were pulpectomy, non-surgical root canal treatment, surgical root canal treatment, as well as retreatment. Four databases were searched electronically, complemented by hand searching. Two independent reviewers determined eligibility, abstracted data, and assessed study quality. A summary estimate of persistent all-cause tooth pain frequency was established by using a random-effects meta-analysis. Using subgroup analyses, we explored the influence of treatment approach (surgical/non-surgical), longitudinal study design (prospective/retrospective), follow-up rate, follow-up duration, initial treatment versus re-treatment, and quality of reporting (STROBE rankings) on the pain frequency estimate.
Results
Of 770 articles retrieved and reviewed, 26 met inclusion criteria. A total of 5,777 teeth were enrolled, and 2,996 had follow-up information regarding pain status. We identified 168 teeth with pain and derived a frequency of 5.3% (95%CI: 3.5–7.2%, p<0.001) for persistent all-cause tooth pain. High and statistically significant heterogeneity among studies (I2=80%) was present. In subgroup analysis, prospective studies had a higher pain frequency (7.6%) than retrospectives studies did (0.9%). Quality of study reporting was identified as the most influential reason for study heterogeneity.
Conclusions
Frequency of all-cause persistent tooth pain following endodontic procedures was estimated to be 5.3%, with higher report quality studies suggesting >7%.
doi:10.1016/j.joen.2009.11.007
PMCID: PMC2832800  PMID: 20113779
Pain; Outcome; Root canal therapy; Frequency; Systematic review; Meta-analysis
13.  Serum Inflammatory Mediators in Pregnancy: Changes Following Periodontal Treatment and Association with Pregnancy Outcomes 
Journal of periodontology  2009;80(11):1731-1741.
Objective
To determine: 1) if periodontal treatment in pregnant women before 21 weeks of gestation alters levels of inflammatory mediators in serum; and 2) if changes in these mediators are associated with birth outcomes.
Methods
823 pregnant women with periodontitis were randomly assigned to receive scaling and root planing before 21 weeks of gestation or after delivery. Serum obtained between 13 weeks and 16 weeks 6 days (study baseline) and 29–32 weeks gestation was analyzed for C-reactive protein, prostaglandin E2, matrix metalloproteinase-9, fibrinogen, endotoxin, interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor-α. Cox regression, multiple linear regression, t-tests, chi-square and Fisher’s exact tests were used to examine associations between the biomarkers, periodontal treatment, and gestational age at delivery and birthweight.
Results
796 women had baseline serum data; 620 had baseline and follow-up serum and birth data. Periodontal treatment did not significantly alter the level of any biomarker (P>0.05). Neither baseline levels nor change from baseline in any biomarker was significantly associated with preterm birth or infant birthweight (P>0.05). In treatment subjects, change in endotoxin was negatively associated with change in probing depth (P<0.05).
Conclusions
Non-surgical mechanical periodontal treatment in pregnant women delivered before 21 weeks of gestation did not reduce systemic (serum) markers of inflammation. In pregnant women with periodontitis, levels of these markers at 13–17 weeks and 29–32 weeks gestation were not associated with risk for preterm birth or with infant birthweight.
doi:10.1902/jop.2009.090236
PMCID: PMC2922720  PMID: 19905943
Pregnancy; preterm birth; periodontitis; inflammation; cytokines
14.  Elastic properties and apparent density of human edentulous maxilla and mandible 
The aim of this study aim was to determine whether elastic properties and apparent density of bone differ in different anatomical regions of the maxilla and mandible. Additional analyses assessed how elastic properties and apparent density were related. Four pairs of edentulous maxilla and mandibles were retrieved from fresh human cadavers. Bone samples from four anatomical regions (maxillary anterior, maxillary posterior, mandibular anterior, mandibular posterior) were obtained. Elastic modulus (EM) and hardness (H) were measured using the nano-indentation technique. Bone samples containing cortical and trabecular bone were used to measure composite apparent density (cAD) using Archimedes’ principle. Statistical analyses used repeated measures ANOVA and Pearson correlations. Bone physical properties differed between regions of the maxilla and mandible. Generally, mandible had higher physical property measurements than maxilla. EM and H were higher in posterior than in anterior regions; the reverse was true for cAD. Posterior maxillary cAD was significantly lower than that in the three other regions.
doi:10.1016/j.ijom.2009.06.025
PMCID: PMC2743800  PMID: 19647417
elastic modulus; hardness; apparent density; human maxilla; mandible
15.  SMOOTHED ANOVA WITH SPATIAL EFFECTS AS A COMPETITOR TO MCAR IN MULTIVARIATE SPATIAL SMOOTHING 
The annals of applied statistics  2009;3(4):1805-1830.
Rapid developments in geographical information systems (GIS) continue to generate interest in analyzing complex spatial datasets. One area of activity is in creating smoothed disease maps to describe the geographic variation of disease and generate hypotheses for apparent differences in risk. With multiple diseases, a multivariate conditionally autoregressive (MCAR) model is often used to smooth across space while accounting for associations between the diseases. The MCAR, however, imposes complex covariance structures that are difficult to interpret and estimate. This article develops a much simpler alternative approach building upon the techniques of smoothed ANOVA (SANOVA). Instead of simply shrinking effects without any structure, here we use SANOVA to smooth spatial random effects by taking advantage of the spatial structure. We extend SANOVA to cases in which one factor is a spatial lattice, which is smoothed using a CAR model, and a second factor is, for example, type of cancer. Datasets routinely lack enough information to identify the additional structure of MCAR. SANOVA offers a simpler and more intelligible structure than the MCAR while performing as well. We demonstrate our approach with simulation studies designed to compare SANOVA with different design matrices versus MCAR with different priors. Subsequently a cancer-surveillance dataset, describing incidence of 3-cancers in Minnesota’s 87 counties, is analyzed using both approaches, showing the competitiveness of the SANOVA approach.
doi:10.1214/09-AOAS267
PMCID: PMC2894541  PMID: 20596299
Analysis of variance; Bayesian inference; conditionally autoregressive model; hierarchical model; smoothing
16.  Partitioning degrees of freedom in hierarchical and other richly-parameterized models 
SUMMARY
Hodges & Sargent (2001) developed a measure of a hierarchical model’s complexity, degrees of freedom (DF), that is consistent with definitions for scatterplot smoothers, interpretable in terms of simple models, and that enables control of a fit’s complexity by means of a prior distribution on complexity. DF describes complexity of the whole fitted model but in general it is unclear how to allocate DF to individual effects. We give a new definition of DF for arbitrary normal-error linear hierarchical models, consistent with Hodges & Sargent’s, that naturally partitions the n observations into DF for individual effects and for error. The new conception of an effect’s DF is the ratio of the effect’s modeled variance matrix to the total variance matrix. This gives a way to describe the sizes of different parts of a model (e.g., spatial clustering vs. heterogeneity), to place DF-based priors on smoothing parameters, and to describe how a smoothed effect competes with other effects. It also avoids difficulties with the most common definition of DF for residuals. We conclude by comparing DF to the effective number of parameters pD of Spiegelhalter et al (2002). Technical appendices and a dataset are available online as supplemental materials.
doi:10.1198/TECH.2009.08161
PMCID: PMC2886314  PMID: 20559456
Degrees of freedom; hierarchical model; model complexity; prior distribution
17.  Change in Periodontitis during Pregnancy and Risk of Preterm Birth and Low Birthweight 
Aim
Determine if periodontitis progression during pregnancy is associated with adverse birth outcomes.
Materials and Methods
We used clinical data and birth outcomes from the OPT Study, which randomized women to receive periodontal treatment before 21 weeks gestation (N=413) or after delivery (410). Birth outcomes were available for 812 women and follow-up periodontal data for 722, including 75 whose pregnancies ended <37 weeks. Periodontitis progression was defined as ≥ 3mm loss of clinical attachment. Birth outcomes were compared between non-progressing and progressing groups using the log rank and t tests, separately in all women and in untreated controls.
Results
The distribution of gestational age at the end of pregnancy (P > 0.1) and mean birthweight (3295 versus 3184 grams, P = 0.11) did not differ significantly between women with and without disease progression. Gestational age and birthweight were not associated with change from baseline in percent of tooth sites with bleeding on probing or between those who did versus did not progress according to a published definition of disease progression (P > 0.05).
Conclusions
In these women with periodontitis and within this study’s limitations, disease progression was not associated with increased risk for delivering a preterm or low birthweight infant.
Clinical Relevance
Scientific Rationale
Maternal periodontitis and disease progression during pregnancy have been associated with elevated risk for preterm birth. We used data from a recent clinical trial to explore possible associations between progressive periodontitis and birth outcomes.
Principal Findings
The distribution of gestational age at delivery and mean birthweights did not differ significantly between women who experienced progressive periodontitis and those who did not.
Clinical Implication
While it is important to treat dental diseases, including periodontitis, during pregnancy, women whose periodontal condition worsens during pregnancy are not at elevated risk for adverse pregnancy outcomes.
doi:10.1111/j.1600-051X.2009.01385.x
PMCID: PMC2741139  PMID: 19426177
preterm birth; low birthweight; periodontal disease; pregnancy; disease progression
18.  Possible Interruption of Malaria Transmission, Highland Kenya, 2007–2008 
Emerging Infectious Diseases  2009;15(12):1917-1924.
Annual insecticide spraying and artemisinin combination therapy may stop transmission.
Highland areas where malaria transmission is unstable are targets for malaria elimination because transmission decreases to low levels during the dry season. In highland areas of Kipsamoite and Kapsisiywa, Kenya (population ≈7,400 persons), annual household indoor residual spraying with a synthetic pyrethroid was performed starting in 2005, and artemether/lumefantrine was implemented as first-line malaria treatment in October 2006. During April 2007–March 2008, no microscopy-confirmed cases of malaria occurred at the sites. In 4 assessments of asymptomatic persons during May 2007–April 2008, a total of <0.3% of persons were positive for asexual Plasmodium falciparum by microscopy or PCR at any time, and none were positive by PCR at the last 2 sample collections. Our findings show that in such areas, interruption and eventual elimination of malaria transmission may be achievable with widespread annual indoor residual spraying of households and artemisinin combination therapy.
doi:10.3201/eid1512.090627
PMCID: PMC3044531  PMID: 19961670
Malaria; transmission; Plasmodium falciparum; epidemiology; Kenya; parasites; research
19.  Should a mucoadhesive patch (DentiPatch) be used for gingival anesthesia in children? 
Anesthesia Progress  2002;49(1):3-8.
A local anesthetic-impregnated mucosal adhesive patch (DentiPatch) was compared with topical anesthetic (Hurricaine Dry Handle Swab) for gingival anesthesia before rubber dam clamp placement in children. Twenty-eight children needing sealants on their posterior teeth were enrolled in this study. Topical anesthesia was provided using either the mucoadhesive patch (20% lidocaine) or topical anesthetic (20% benzocaine). Subjects were randomized using a split mouth model. Either the patch or topical anesthetic was applied to the gingiva for 5 minutes or 1 minute, respectively. Subjects used a visual analog scale to describe their pain during the procedure. Linear regression and mixed linear models were used for data analysis. The visual analog scale results (pain scores) showed no significant difference between treatments. The mean per-child patch-sticking fraction was 29.7%. Patch adherence to oral mucosa increased with age in girls (P = .0045), but not in boys. The DentiPatch is as effective as, although not superior to, the Hurricaine Dry Handle Swab for gingival anesthesia before rubber dam clamp placement in children. These study results would not support the use of the DentiPatch for gingival anesthesia in children because of poor adherence to oral mucosa and the extra time necessary to apply and retain the device.
Images
PMCID: PMC2007396  PMID: 12779107

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