In children aged >18 months with cerebral malaria, elevated erythropoietin levels were associated with increased mortality, prolonged coma duration, and a lack of neuroprotection. Caution is warranted in the use of systemic erythropoietin as adjunctive therapy in cerebral malaria.
Background. Elevated endogenous plasma erythropoietin (EPO) levels have been associated with protection from acute neurologic deficits in Kenyan children with cerebral malaria (CM). Based on these findings and animal studies, clinical trials of recombinant human EPO (rHuEPO) have been started in children with CM. Recent clinical trials in adults with acute ischemic stroke have demonstrated increased mortality with rHuEPO treatment. We conducted a study in children with CM to assess the relationship of endogenous plasma and cerebrospinal fluid (CSF) EPO levels with mortality and acute and long-term neurologic outcomes.
Methods. A total of 210 children between 18 months and 12 years of age with a diagnosis of CM, were enrolled at Mulago Hospital, Kampala, Uganda. Plasma (n = 204) and CSF (n = 147) EPO levels at admission were measured by radioimmunoassay and compared with mortality and neurologic outcomes.
Results. After adjustment for age and hemoglobin level, a 1-natural-log increase in plasma EPO level was associated with a 1.74-fold increase in mortality (95% confidence interval, 1.09–2.77, P = .02). Plasma and CSF EPO levels also correlated positively with coma duration (P = .05 and P = .02, respectively). Plasma and CSF EPO levels did not differ in children with vs those without acute or long-term neurologic deficits. Plasma EPO levels correlated positively with markers of endothelial and platelet activation and histidine-rich protein-2 levels, but remained associated with mortality after adjustment for these factors.
Conclusions. High endogenous plasma EPO levels are associated with prolonged coma duration and increased mortality in children >18 months of age with CM.
erythropoietin; cerebral malaria; mortality; neurologic deficits
One year after illness, children with severe malarial anemia demonstrated significantly lower scores in cognitive ability than community children. Severe malarial anemia may contribute to long-term cognitive impairment in children in sub-Saharan Africa.
Background. Cerebral malaria (CM) is associated with long-term neurocognitive impairment in children ≥5 years of age. No prospective studies to date have assessed neurocognitive impairment in children with CM <5 years of age, or in children with severe malarial anemia (SMA), a form of severe malaria estimated to affect as many as 5 million children annually.
Methods. Children <5 years of age presenting to Mulago Hospital, Kampala, Uganda, with CM (n = 80) or SMA (n = 86) were assessed for overall cognitive ability, attention, and associative memory 1 week after discharge and 6 and 12 months later. The z scores for each domain were computed based on scores of 61 healthy community children (CC), who were also tested at enrollment and 6 and 12 months later. Groups were compared using mixed linear models, adjusted for age, weight for age, and child's education.
Results. At 12 months, children with CM had lower adjusted scores than CC in cognitive ability (P < .001), attention (P = .02), and associative memory, (P = .002). Children with SMA had lower scores than CC in cognitive ability (P = .01) but not attention or associative memory. Cognitive ability scores in children with CM and SMA did not differ significantly.
Conclusions. In children <5 years of age, SMA is associated with long-term impairment in cognitive ability, whereas CM is associated with additional impairment in the areas of attention and associative memory. SMA may be a major contributor to long-term neurocognitive impairment in children in sub-Saharan Africa.
severe malarial anemia; cerebral malaria; cognitive; impairment
Despite well-recognized recommendations to reduce human exposure to zoonotic pathogens, the use of personal and herd-level protective practices is inconsistent in communities where human interactions with animals are common. This study assessed household-level participation in rodent- (extermination, proper food storage, trash disposal), occupational- (preventive veterinary care, boot-wearing, glove-wearing), and garden-associated (restricting animal access, boot-wearing, glove-wearing) protective practices in farms, villages, and slums in the Los Rios region, Chile, where zoonotic pathogens are endemic.
Questionnaires administered at 422 households across 12 communities recorded household-level socio-demographic characteristics and participation in nine protective practices. Household inclusion in the analysis of occupational practices required having livestock and a household member with occupational exposure to livestock (n = 127), and inclusion in analysis of garden practices required having a garden and at least one animal (n = 233). The proportion of households participating in each protective practice was compared across community types through chi-square analyses. Mixed effects logistic regression assessed household-level associations between socio-demographic characteristics and participation in each protective practice.
Most households (95.3 %) reported participation in rodent control, and a positive association between the number of rodent signs in a household and rodent extermination was observed (OR: 1.75, 95 % CI: 1.41, 2.16). Occupational protective practices were reported in 61.8 % of eligible households; household size (OR: 1.63, 95 % CI: 1.17, 5.84) and having children (OR: 0.22, 95 % CI: 0.06, 0.78) were associated with preventive veterinary care. Among eligible households, 73.8 % engaged in protective practices when gardening, and species diversity was positively associated with wearing boots (OR: 1.27, 95 % CI: 1.03, 1.56). Household-level participation in all three protective practices within any exposure category was limited (<10.4 %) and participation in any individual protective practice varied considerably within and across community types.
The levels of participation in protective practices reported in this study are consistent with descriptions in the literature of imperfect use of methods that reduce human exposure to zoonotic pathogens. The wide differences across communities in the proportion of households participating in protective practices against human exposure to zoonotic pathogens, suggests that future research should identify community-level characteristics that influence household participation in such practices.
Electronic supplementary material
The online version of this article (doi:10.1186/s12889-015-1964-2) contains supplementary material, which is available to authorized users.
Zoonoses; Prevention; Education programs; Social ecology; Community type; Chile
Evaluate the association of abdominal visceral and subcutaneous fat, independent of total body fat, with cardiometabolic risk factors and insulin resistance among youth.
Visceral and subcutaneous fat, percent total body fat, insulin resistance (adjusted for lean body mass: Mlbm), blood pressure, glucose, insulin, and lipids were obtained in 472 youth ages 6–18 years. Linear regression, adjusted for age, sex, race, Tanner stage, and percent total body fat, was used to evaluate associations of visceral and subcutaneous fat with cardiometabolic risk factors.
Visceral fat was associated inversely with Mlbm (p=0.003) and positively with fasting insulin (p=0.002) and triglycerides (p=0.002). Visceral fat levels above the mean were associated inversely with HDL cholesterol (p=0.002), and positively systolic blood pressure (p<0.0001) and non-HDL cholesterol (p<0.0001). Subcutaneous fat was associated inversely with Mlbm (p=0.003) and HDL cholesterol (p<0.05), and positively with fasting glucose (p<0.05), fasting insulin (p=0.0003), systolic blood pressure (p=0.005), and triglycerides (p=0.003). Subcutaneous fat levels above the mean were associated with non-HDL cholesterol (p=0.0002).
These findings suggest that there may be a threshold level of visceral and subcutaneous fat (regardless of total body fat), that when exceeded in childhood, is more likely to be associated with many cardiometabolic risk factors. Triglycerides and insulin resistance appear to be associated with these fat depots at even lower thresholds of abdominal adiposity.
visceral; subcutaneous; cardiometabolic risk factors; insulin resistance
Our previous studies reported on the obstetric, periodontal, and microbiologic outcomes of women participating in the Obstetrics and Periodontal Therapy (OPT) Study. This article describes the systemic antibody responses to selected periodontal bacteria in the same patients.
Serum samples, obtained from pregnant women at baseline (13 to 16 weeks; 6 days of gestation) and 29 to 32 weeks, were analyzed by enzyme-linked immunosorbent assay for serum immunoglobulin G (IgG) antibody to Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans), Campylobacter rectus, Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia (previously T. forsythensis), and Treponema denticola.
At baseline, women who delivered live preterm infants had significantly lower total serum levels of IgG antibody to the panel of periodontal pathogens (P = 0.0018), to P. gingivalis (P = 0.0013), and to F. nucleatum (P = 0.0200) than women who delivered at term. These differences were not significant at 29 to 32 weeks. Changes in IgG levels between baseline and 29 to 32 weeks were not associated with preterm birth when adjusted for treatment group, clinical center, race, or age. In addition, delivery of low birth weight infants was not associated with levels of antibody at baseline or with antibody changes during pregnancy.
Live preterm birth is associated with decreased levels of IgG antibody to periodontal pathogens in women with periodontitis when assessed during the second trimester. Changes in IgG antibody during pregnancy are not associated with birth outcomes.
Antibody; bacteria; periodontitis; pregnancy; preterm birth
Low bone mineral density (BMD) has been reported in recipients of
pediatric hematopoietic cell transplantation (HCT), but it is unclear whether
age at HCT plays a role. The objective of this cross-sectional study was to
determine if patients treated with HCT before age 10 years have long-term BMD
deficits compared to patients transplanted at an older age and to sibling
controls. The study included 151 HCT recipients (87 males), age at study
24.7±8.6 years treated with HCT for hematologic malignancies at age
10.9±6.4 years, and 92 healthy sibling controls (49 males), age at study
22.3±8.0 years. Dual-energy x-ray absorptiometry was performed to
measure BMD Z-scores for total body (TBMD), lumbar spine (LBMD), and femoral
neck (FNBMD, for subjects ≥20 years at study visit). Patients <10
years at HCT had significantly lower TBMD and FNBMD Z-scores (by 0.5 and 0.8 SD,
respectively) compared to controls (P=0.003 and
P=0.0001, respectively) and patients >18 years
at HCT (P=0.04 and P=0.004,
respectively) at an average of 14 years after HCT. In conclusion, this study
identified young age at transplant as an important risk factor for bone deficits
in young adulthood, suggesting that efforts to reduce bone loss should focus on
this patient population.
osteoporosis; DXA scan; bone mineral density; bone marrow transplantation; lean body mass; children
Context. Vulvar pain level may fluctuate in women with vulvodynia even in the absence of therapy; however, there is little evidence suggesting which factors may be associated with variability. Objective. Determine the feasibility of using smartphones to collect prospective data on vulvar pain and factors that may influence vulvar pain level. Methods. 24 clinically confirmed women were enrolled from a population-based study and asked to answer five questions using their smartphones each week for one month. Questions assessed vulvar pain level (0–10), presence of pain upon wakening, pain elsewhere in their body, treatment use, and intercourse. Results. Women completed 100% of their scheduled surveys, with acceptability measures highly endorsed. Vulvar pain ratings had a standard deviation within women of 1.6, with greater variation on average among those with higher average pain levels (P < 0.001). On the weeks when a woman reported waking with pain, her vulvar pain level was higher by 1.82 on average (P < 0.001). Overall, average vulvar pain level was not significantly associated with the frequency of reporting other body pains (P = 0.64). Conclusion. Our smartphone tracking system promoted excellent compliance with weekly tracking of factors that are otherwise difficult to recall, some of which were highly associated with vulvar pain level.
Malaria in highland areas of Kenya affects children and adults. Local clinicians include symptoms other than fever when screening for malaria because they believe that fever alone does not capture all cases of malaria.
Individuals who presented to dispensaries in a highland Kenya site of low, unstable malaria transmission from 2007–2011 with 1 or more of 11 symptoms were tested by microscopy for malaria. Clinical malaria was defined as asexual Plasmodium falciparum infection on peripheral blood smear in an individual with any screening symptom. Asymptomatic P. falciparum infection was assessed in a cohort at ten time points to determine the extent to which symptomatic episodes with parasitaemia might be attributable to baseline (asymptomatic) parasitaemia in the community.
3,420 individuals were screened for malaria, 634 < 5 years of age and 2,786 ≥ 5 years of age. For the diagnosis of clinical malaria, the symptom of fever had a sensitivity and specificity of 88.9% and15.4% in children <5 years, and 55.8% and 54.4% in children ≥5 years, respectively. Adding the symptom of headache increased sensitivity to 94. 4% in children <5 years and 96.8% in individuals ≥5 years, but decreased specificity to 9.9% and 11.6%, respectively, and increased the number of individuals who would be tested by 6% and 92%, respectively. No combination of symptoms improved upon the presence fever or headache for detection of clinical malaria. In the cohort of asymptomatic individuals, P. falciparum parasitaemia was infrequent (0.1%).
In areas of low, unstable malaria transmission, fever is a sensitive indicator of clinical malaria in children <5 years, but not in older children and adults. Adding headache to fever as screening symptom increases sensitivity of detection in individuals ≥5 years old at the cost of decreased specificity. Screening for symptoms in addition to fever may be required to accurately capture all cases of clinical malaria in individuals ≥5 years old in areas of low malaria transmission.
Malaria; Plasmodium falciparum; Symptom; Fever; Highland; Unstable transmission
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.
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.
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.
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.
Bisphosphonates; Periodontitis; Periodontal Disease; Alveolar Bone Loss; Osteonecrosis; Bisphosphonate-related osteonecrosis of the jaw
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.
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.
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.
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.
cardiovascular risk; growth hormone deficiency; cancer survivors; chemotherapy; insulin resistance; children
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.
Methadone; opiate dependence; treatment outcome; ethnicity; Hmong
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.
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.
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.
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.
Gout; Veterans; Quality of care; Quality indicators; Physician adherence
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.
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.
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.
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.
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.
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.
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).
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.
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.
ascorbate; glutathione; lactate; brain; human; aging; MEGA-PRESS; MRS
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.
antioxidants; ascorbate; glutathione; MRS; noninvasive; human; brain; intravenous
Some maternal infections are associated with impaired infant cognitive and motor performance. Periodontitis results in frequent bacteremia and elevated serum inflammatory mediators.
The purpose of this study was to determine if periodontitis treatment in pregnant women affects infant cognitive, motor, or language development.
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.
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).
Nonsurgical periodontitis treatment in pregnant women was not associated with cognitive, motor, or language development in these study children.
child neurodevelopment; periodontitis; pregnancy; treatment
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.
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.
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.
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.
Tooth; Dentoalveolar; Pain; Root canal therapy; Systematic review
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.
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.
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.
Frequency of all-cause persistent tooth pain following endodontic procedures was estimated to be 5.3%, with higher report quality studies suggesting >7%.
Pain; Outcome; Root canal therapy; Frequency; Systematic review; Meta-analysis
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.
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.
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).
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.
Pregnancy; preterm birth; periodontitis; inflammation; cytokines
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.
elastic modulus; hardness; apparent density; human maxilla; mandible
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.
Analysis of variance; Bayesian inference; conditionally autoregressive model; hierarchical model; smoothing
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.
Degrees of freedom; hierarchical model; model complexity; prior distribution
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.
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).
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.
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.
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.
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.
preterm birth; low birthweight; periodontal disease; pregnancy; disease progression