What are the outcomes of acupuncture for back pain? According to well-regarded trials, acupuncture is little better for back pain than biomedicine, and active acupuncture is no better than sham acupuncture. These trials occurred in the West. Patients are inside the clinic a miniscule amount of time in relation to the time they are outside the clinic and enmeshed in the wider sociocultural context. Nevertheless, trials have largely overlooked potential effects of sociocultural context. The main objective of this article is to draw attention to designated features of sociocultural context that, as compared with outcomes obtained in the West, may enhance outcomes of acupuncture for back pain in China. Additional objectives of the article are to reconceptualize “sociocultural context” so that it is measurable, and to measure pre-existing acquaintance with acupuncture and other forms of Traditional Chinese Medicine (TCM) within the sociocultural context of China.
Back pain patients (N=86) were recruited from the Acupuncture Clinic and Pain Clinic of West China Hospital (Chengdu, Sichuan Province). Patients completed questionnaires on their use of TCM before they came to the Acupuncture Clinic and their families' use of TCM.
Most patients had used TCM, and those who did so likely used it repeatedly, which indicated substantial acquaintance with TCM beliefs in the cultural context. Patients whose families used TCM were also likely to use it themselves, which indicated that TCM use was anchored in the social context of the family.
Although multiple studies substantiate biologic mechanisms of acupuncture, there is not necessarily a fixed relationship between those mechanisms and people's experience of them. Rather, sociocultural context may interact with biologic mechanisms and mediate this experience. The theory proposed here explains why outcomes of acupuncture for back pain will potentially be more pronounced in the sociocultural context of China than in the West.
Acute otitis media (AOM) occurs as a complication of viral upper respiratory tract infections in young children. AOM and respiratory viruses both display seasonal variation. Our objective was to examine the temporal association between circulating respiratory viruses and the occurrence of pediatric ambulatory care visits for AOM.
This retrospective study included 9 seasons of respiratory viral activity (2002-2010) in Utah. We used Intermountain Healthcare's electronic medical records to assess community respiratory viral activity via laboratory-based active surveillance and to identify children <18 years with outpatient visits and ICD-9 codes for AOM. We assessed the strength of the association between AOM and individual respiratory viruses using interrupted time series analyses.
During the study period, 96,418 respiratory viral tests were performed; 46,460 (48%) were positive. The most commonly identified viruses were: RSV (22%), rhinovirus (8%), influenza (8%), parainfluenza (4%), human metapneumovirus (3%), and adenovirus (3%). AOM was diagnosed during 271,268 ambulatory visits. There were significant associations between peak activity of RSV, human metapneumovirus, influenza A, and office visits for AOM. Adenovirus, parainfluenza, and rhinovirus were not associated with visits for AOM.
Seasonal RSV, human metapneumovirus, and influenza activity were temporally associated with increased diagnoses of AOM among children. These findings support the role of individual respiratory viruses in the development AOM. These data also underscore the potential for respiratory viral vaccines to reduce the burden of AOM.
respiratory tract infection; influenza; RSV; human metapneumovirus; pediatrics
While the role of the macular pigment carotenoids in the prevention of age-related macular degeneration has been extensively studied in adults, comparatively little is known about the physiology and function of lutein and zeaxanthin in the developing eye. We therefore developed a protocol using a digital video fundus camera (RetCam) to measure macular pigment optical density (MPOD) and distributions in premature infants and in children.
We used blue light reflectance to image the macular pigment in premature babies at the time of retinopathy of prematurity (ROP) screening and in children aged under 7 years who were undergoing examinations under anesthesia for other reasons. We correlated the MPOD with skin carotenoid levels measured by resonance Raman spectroscopy, serum carotenoids measured by HPLC, and dietary carotenoid intake.
We enrolled 51 infants and children ranging from preterm to age 7 years. MPOD correlated significantly with age (r = 0.36; P = 0.0142), with serum lutein + zeaxanthin (r = 0.44; P = 0.0049) and with skin carotenoid levels (r = 0.42; P = 0.0106), but not with dietary lutein + zeaxanthin intake (r = 0.13; P = 0.50). All premature infants had undetectable macular pigment, and most had unusually low serum and skin carotenoid concentrations.
Our most remarkable finding is the undetectable MPOD in premature infants. This may be due in part to foveal immaturity, but the very low levels of serum and skin carotenoids suggest that these infants are carotenoid insufficient as a consequence of low dietary intake and/or severe oxidative stress. The potential value of carotenoid supplementation in the prevention of ROP and other disorders of prematurity should be a fruitful direction for further investigation.
Little is known about the physiology and function of lutein and zeaxanthin in the developing eye. We therefore developed a protocol using a digital fundus camera (RetCam) to measure macular pigment optical density (MPOD) and distributions in premature infants and in children.
macular pigment; carotenoid; imaging; lutein; zeaxanthin
The induction of autophagy in the mammalian heart during the perinatal period is an essential adaptation required to survive early neonatal starvation; however, the mechanisms that mediate autophagy suppression once feeding is established are not known. Insulin signaling in the heart is transduced via insulin and IGF-1 receptors (IGF-1Rs). We disrupted insulin and IGF-1R signaling by generating mice with combined cardiomyocyte-specific deletion of Irs1 and Irs2. Here we show that loss of IRS signaling prevented the physiological suppression of autophagy that normally parallels the postnatal increase in circulating insulin. This resulted in unrestrained autophagy in cardiomyocytes, which contributed to myocyte loss, heart failure, and premature death. This process was ameliorated either by activation of mTOR with aa supplementation or by genetic suppression of autophagic activation. Loss of IRS1 and IRS2 signaling also increased apoptosis and precipitated mitochondrial dysfunction, which were not reduced when autophagic flux was normalized. Together, these data indicate that in addition to prosurvival signaling, insulin action in early life mediates the physiological postnatal suppression of autophagy, thereby linking nutrient sensing to postnatal cardiac development.
Febrile infants in the first 90 days may have life-threatening serious bacterial infection (SBI). Well-appearing febrile infants with SBI cannot be distinguished from those without by examination alone. Variation in care resulting in both undertreatment and overtreatment is common.
We developed and implemented an evidence-based care process model (EB-CPM) for the management of well-appearing febrile infants in the Intermountain Healthcare System. We report an observational study describing changes in (1) care delivery, (2) outcomes of febrile infants, and (3) costs before and after implementation of the EB-CPM in a children’s hospital and in regional medical centers.
From 2004 through 2009, 8044 infants had 8431 febrile episodes, resulting in medical evaluation. After implementation of the EB-CPM in 2008, infants in all facilities were more likely to receive evidence-based care including appropriate diagnostic testing, determination of risk for SBI, antibiotic selection, decreased antibiotic duration, and shorter hospital stays (P < .001 for all). In addition, more infants had a definitive diagnosis of urinary tract infection or viral illness (P < .001 for both). Infant outcomes improved with more admitted infants positive for SBI (P = .011), and infants at low risk for SBI were more often managed without antibiotics (P < .001). Although hospital admissions were shortened by 27%, there were no cases of missed SBI. Health Care costs were also reduced, with the mean cost per admitted infant decreasing from $7178 in 2007 to $5979 in 2009 (−17%, P < .001).
The EB-CPM increased evidence-based care in all facilities. Infant outcomes improved and costs were reduced, substantially improving value.
fever; infant; outcomes; cost
Few prospective cohort studies of workplace low back pain (LBP) with quantified job physical exposure have been performed. There are few prospective epidemiological studies for LBP occupational risk factors and reported data generally have few adjustments for many personal and psychosocial factors.
A multi-center prospective cohort study has been incepted to quantify risk factors for LBP and potentially develop improved methods for designing and analyzing jobs. Due to the subjectivity of LBP, six measures of LBP are captured: 1) any LBP, 2) LBP ≥ 5/10 pain rating, 3) LBP with medication use, 4) LBP with healthcare provider visits, 5) LBP necessitating modified work duties and 6) LBP with lost work time. Workers have thus far been enrolled from 30 different employment settings in 4 diverse US states and performed widely varying work. At baseline, workers undergo laptop-administered questionnaires, structured interviews, and two standardized physical examinations to ascertain demographics, medical history, psychosocial factors, hobbies and physical activities, and current musculoskeletal disorders. All workers’ jobs are individually measured for physical factors and are videotaped. Workers are followed monthly for the development of low back pain. Changes in jobs necessitate re-measure and re-videotaping of job physical factors. The lifetime cumulative incidence of low back pain will also include those with a past history of low back pain. Incident cases will exclude prevalent cases at baseline. Statistical methods planned include survival analyses and logistic regression.
Data analysis of a prospective cohort study of low back pain is underway and has successfully enrolled over 800 workers to date.
Epidemiology; Ergonomics; Cohort; Low back pain; NIOSH lifting equation
Age-Related Eye Disease Study 2 (AREDS2) is a randomized, placebo-controlled study designed to determine whether supplementation with 10 mg of lutein and 2 mg of zeaxanthin per day can slow the rate of progression of age-related macular degeneration (AMD). Although some biomarkers of response to carotenoid supplementation such as serum concentrations are part of the AREDS2 protocol, measurement of carotenoid concentrations in the eye and other tissues is not. In this approved ancillary study, macular pigment optical density (MPOD), macular pigment distributions, and skin carotenoid levels at enrollment and at each annual visit were measured to assess baseline carotenoid status and to monitor response to assigned interventions.
All subjects enrolled at the Moran Eye Center had MPOD and macular pigment spatial distributions measured by dual-wavelength autofluorescence imaging and total skin carotenoids measured by resonance Raman spectroscopy.
Baseline MPOD in enrolled subjects was unusually high relative to an age-matched control group that did not consume carotenoid supplements regularly, consistent with the high rate of habitual lutein and zeaxanthin consumption in Utah AREDS2 subjects prior to enrollment. MPOD did not correlate with serum or skin carotenoid measurements.
Useful information is provided through this ancillary study on the ocular carotenoid status of AREDS2 participants in the target tissue of lutein and zeaxanthin supplementation: The macula. When treatment assignments are unmasked at the conclusion of the study, unique tissue-based insights will be provided on the progression of AMD in response to long-term, high-dose carotenoid supplementation versus diet alone. (ClinicalTrials.gov number, NCT00345176.)
Baseline macular pigment measurements at the Utah AREDS2 site were unusually high relative to an age-matched control group that did not consume carotenoid supplements regularly, consistent with the high rate of habitual lutein and zeaxanthin consumption in Utah AREDS2 subjects prior to enrollment.
Neural tube defects (NTDs) are one of the most common birth defects caused by a combination of genetic and environmental factors. Currently, little is known about the genetic basis of NTDs although up to 70% of human NTDs were reported to be attributed to genetic factors. Here we performed genome-wide copy number variants (CNVs) detection in a cohort of Chinese NTD patients in order to exam the potential role of CNVs in the pathogenesis of NTDs.
The genomic DNA from eighty-five NTD cases and seventy-five matched normal controls were subjected for whole genome CNVs analysis. Non-DGV (the Database of Genomic Variants) CNVs from each group were further analyzed for their associations with NTDs. Gene content in non-DGV CNVs as well as participating pathways were examined.
Fifty-five and twenty-six non-DGV CNVs were detected in cases and controls respectively. Among them, forty and nineteen CNVs involve genes (genic CNV). Significantly more non-DGV CNVs and non-DGV genic CNVs were detected in NTD patients than in control (41.2% vs. 25.3%, p<0.05 and 37.6% vs. 20%, p<0.05). Non-DGV genic CNVs are associated with a 2.65-fold increased risk for NTDs (95% CI: 1.24–5.87). Interestingly, there are 41 cilia genes involved in non-DGV CNVs from NTD patients which is significantly enriched in cases compared with that in controls (24.7% vs. 9.3%, p<0.05), corresponding with a 3.19-fold increased risk for NTDs (95% CI: 1.27–8.01). Pathway analyses further suggested that two ciliogenesis pathways, tight junction and protein kinase A signaling, are top canonical pathways implicated in NTD-specific CNVs, and these two novel pathways interact with known NTD pathways.
Evidence from the genome-wide CNV study suggests that genic CNVs, particularly ciliogenic CNVs are associated with NTDs and two ciliogenesis pathways, tight junction and protein kinase A signaling, are potential pathways involved in NTD pathogenesis.
Few prospective cohort studies of distal upper extremity musculoskeletal disorders have been performed. Past studies have provided somewhat conflicting evidence for occupational risk factors and have largely reported data without adjustments for many personal and psychosocial factors.
A multi-center prospective cohort study was incepted to quantify risk factors for distal upper extremity musculoskeletal disorders and potentially develop improved methods for analyzing jobs. Disorders to analyze included carpal tunnel syndrome, lateral epicondylalgia, medial epicondylalgia, trigger digit, deQuervain’s stenosing tenosynovitis and other tendinoses. Workers have thus far been enrolled from 17 different employment settings in 3 diverse US states and performed widely varying work. At baseline, workers undergo laptop administered questionnaires, structured interviews, two standardized physical examinations and nerve conduction studies to ascertain demographic, medical history, psychosocial factors and current musculoskeletal disorders. All workers’ jobs are individually measured for physical factors and are videotaped. Workers are followed monthly for the development of musculoskeletal disorders. Repeat nerve conduction studies are performed for those with symptoms of tingling and numbness in the prior six months. Changes in jobs necessitate re-measure and re-videotaping of job physical factors. Case definitions have been established. Point prevalence of carpal tunnel syndrome is a combination of paraesthesias in at least two median nerve-served digits plus an abnormal nerve conduction study at baseline. The lifetime cumulative incidence of carpal tunnel syndrome will also include those with a past history of carpal tunnel syndrome. Incident cases will exclude those with either a past history or prevalent cases at baseline. Statistical methods planned include survival analyses and logistic regression.
A prospective cohort study of distal upper extremity musculoskeletal disorders is underway and has successfully enrolled over 1,000 workers to date.
Epidemiology; Ergonomics; Cohort; Carpal tunnel syndrome; Strain index; TLV for HAL
Pneumonia; Bacterial complications; epidemiology; Pneumococcal Empyema; Streptococcus pneumoniae; Polymerase chain reaction (PCR); Molecular Diagnostics
To describe the cerebrospinal fluid (CSF) profiles of febrile infants 1–90 days with negative bacterial cultures and negative testing for enteroviruses by polymerase chain reaction.
Statistical analysis of a retrospective cohort.
CSF profiles from 823 infants with negative evaluations for infection were analyzed. For 677 with atraumatic lumbar punctures (RBC < 1,000/mm3), the mean and median CSF WBC counts were 4.3/mm3 and 3.0/mm3 respectively with a range from 0–12/mm3. Mean CSF WBC counts (6.1/mm3 vs. 3.1/mm3 and 3.0/mm3) and protein levels (75.4 mg/dl vs. 58.9 mg/dl and 39.2 mg/dl) were higher in the first month compared with months two and three, respectively (p<0.001 for all). CSF glucose levels were lower in the first month compared with month three (45.3 mg/dl vs. 48.0 mg/dl and 57.7 mg/dl) (p< 0.001). Increasing RBC counts were statistically associated with increasing WBC counts (p< 0.001). However, the contribution of RBC < 10,000/mm3 was small and the normal range for WBC in uninfected infants with traumatic lumbar punctures was 0–16/mm3.
CSF WBC counts in febrile infants without evidence of bacterial or enteroviral infection, even in those with traumatic lumbar puncture, are lower than reported in pediatric references.
Low 25-hydroxyvitamin D (25OHD) concentrations have been associated with tumors and osteopenia/fractures in adults with neurofibromatosis type 1 (NF1). We report 25OHD concentrations in 109 children with NF1 and 218 age, sex, geographic location, and time-of-year matched controls.
Children with NF1 were recruited (n=109; 2–17yr), and clinical data and dual energy x-ray absorptiometry measurements obtained. 25OHD concentrations were measured in subjects and controls.
More NF1 individuals (50%) were in the 25OHD insufficient/deficient range (<30ng/ml) compared to controls (36%) (p=0.0129). 25OHD concentrations were higher in individuals with neurofibromas after controlling for age (p=0.0393), and negatively associated with whole body subtotal bone mineral density (BMD) z-scores (p=0.0385).
More children with NF1 had 25OHD concentrations <30ng/ml, potentially due to increased pigmentation and/or decreased sunlight exposure. In contrast to adults, decreased 25OHD concentrations were not associated with neurofibromas, and there was not a positive association of 25OHD with BMD.
neurofibromatosis; vitamin D; neurofibromas; bone dysplasia; bone health
Hospitalized children are perceived to be increasingly medically complex, but no such trend has been documented. The objective of this study was to determine whether the proportion of pediatric inpatient use that is attributable to patients with a diagnosis of one or more complex chronic condition (CCC) has increased over time and to assess the degree to which CCC hospitalizations are associated with attributes that are consistent with heightened medical complexity.
A retrospective observational study that used the 1997, 2000, 2003, and 2006 Kids Inpatient Databases examined US hospitalizations for children. Attributes of medical complexity included hospital admissions, length of stay, total charges, technology-assistance procedures, and mortality risk.
The proportion of inpatient pediatric admissions, days, and charges increased from 1997 to 2006 for any CCC and for every CCC group except hematology. CCCs accounted for 8.9% of US pediatric admissions in 1997 and 10.1% of admissions in 2006. These admissions used 22.7% to 26.1% of pediatric hospital days, used 37.1% to 40.6% of pediatric hospital charges, accounted for 41.9% to 43.2% of deaths, and (for 2006) used 73% to 92% of different forms of technology-assistance procedures. As the number of CCCs for a given admission increased, all markers of use increased.
CCC-associated hospitalizations compose an increasing proportion of inpatient care and resource use. Future research should seek to improve methods to identify the population of medically complex children, monitor their increasing inpatient use, and assess whether current systems of care are meeting their needs.
child health services; health care delivery/access; health services research; hospitalization; children with special needs
Utah had a high rate of pediatric pneumococcal empyema (PPE) prior to licensure of the pneumococcal conjugate vaccine (PCV-7) in 2000. The majority (62%) of PPE cases was due to nonvaccine serotypes, primarily Streptococcus pneumoniae serotype 1, multilocus sequence type (MLST) 227. PPE in Utah children has increased over the last decade. It is unclear whether the increase was due to serotype replacement or switch. In this study, we describe the incidence and molecular epidemiology of PPE by MLST in Utah children after the licensure of PCV-7. Empyema rates increased from 8.5/100,000 children in the state of Utah in 2001 to 12.5/100,000 children in 2007 (P = 0.006). Ninety-eight percent was due to nonvaccine serotypes (P < 0.001 when compared to the pre-PCV-7 period). PPE was primarily due to serotypes 1, 3, 19A, and 7F, with MLST demonstrating sequence types (ST) that were commonly present in the United States prior to licensure of PCV-7. Serotype switch was not documented. Replacement disease with common ST of serotypes 1,3, 7F, and 19A rather than serotype switch was responsible for the increase in PPE in Utah children.
Lower leg bowing with tibial pseudarthrosis is associated with neurofibromatosis type 1 (NF1). The objective of the study is to determine if the geometry of the lower limb in individuals with neurofibromatosis type 1 (NF1) differs from controls, and to characterize the osseous components of the tibia in NF1.
Peripheral quantitative computed tomography (pQCT) of the lower limb was performed (90 individuals with NF1 without tibial and/or fibular dysplasia: 474 healthy individuals without NF1). Subjects were 4–18 years of age. Individuals with NF1 were compared to controls using an analysis-of-covariance with a fixed set of covariates (age, weight, height, Tanner stage, and gender).
Using pQCT, NF1 individuals without bowing of the lower leg have smaller periosteal circumferences (p<0.0001), smaller cortical area (p<0.0001), and decreased tibial cortical and trabecular bone mineral content (BMC) (p<0.0001) compared to controls.
Individuals with NF1 have a different geometry of the lower leg compared to healthy controls suggesting that NF1 haploinsufficiency impacts bone homeostasis although not resulting in overt anterolateral bowing of the lower leg.
neurofibromatosis type 1; tibia; peripheral quantitative computed tomography; bone; bone mineral content
Diabetes-associated cardiac dysfunction is associated with mitochondrial dysfunction and oxidative stress, which may contribute to LV dysfunction. The contribution of altered myocardial insulin action, independently of associated changes in systemic metabolism is incompletely understood. The present study tested the hypothesis that perinatal loss of insulin signaling in the heart impairs mitochondrial function.
Methods and Results
In 8-week-old mice with cardiomyocyte deletion of insulin receptors (CIRKO), inotropic reserves were reduced and mitochondria manifested respiratory defects for pyruvate that was associated with proportionate reductions in catalytic subunits of pyruvate dehydrogenase. Progressive age-dependent defects in oxygen consumption and ATP synthesis with the substrates glutamate and the fatty acid derivative palmitoyl carnitine (PC) were observed. Mitochondria were also uncoupled when exposed to PC due in part to increased ROS production and oxidative stress. Although proteomic and genomic approaches revealed a reduction in subsets of genes and proteins related to oxidative phosphorylation, no reduction in maximal activities of mitochondrial electron transport chain complexes were found. However, a disproportionate reduction in TCA cycle and FA oxidation proteins in mitochondria, suggest that defects in FA and pyruvate metabolism and TCA flux may explain the mitochondrial dysfunction observed.
Impaired myocardial insulin signaling promotes oxidative stress and mitochondrial uncoupling, which together with reduced TCA and FA oxidative capacity impairs mitochondrial energetics. This study identifies specific contributions of impaired insulin action to mitochondrial dysfunction in the heart.
Metabolism; Mitochondria; Oxidative Stress; Insulin
Vaccine strategies and antimicrobial drug stockpiling to control empyema will increase preparedness as we prepare for the next influenza pandemic.
Bacterial pneumonia with empyema is a serious complication of influenza and commonly resulted in death during the 1918 influenza pandemic. We hypothesize that deaths caused by parapneumonic empyema are increasing in Utah once again despite advances in critical care and the availability of antimicrobial drugs and new vaccines. In this study, we analyzed the historical relationship between deaths caused by empyema and influenza pandemics by using 100 years of data from Utah. Deaths caused by empyema have indeed increased from 2000–2004 when compared with the historic low death rates of 1950–1975. Vaccine strategies and antimicrobial drug stockpiling to control empyema will be important as we prepare for the next influenza pandemic.
complicated pneumonia; Spanish flu; Streptococcus pneumoniae; methicillin resistant Staphylococcus aureus; Utah Population Database; vaccine; historical review
To assess if children and adolescents with neurofibromatosis type 1 (NF1) have decreased bone mineral density (BMD).
Bone densitometry of the whole body, hip and lumbar spine was utilized in a case:control design (84 individuals with NF1: 293 healthy individuals without NF1). Subjects were 5–18 years of age. Individuals with NF1 were compared to controls using an analysis-of-covariance with a fixed set of covariates (age, weight, height, Tanner stage, and sex).
Individuals with NF1 had decreased areal bone mineral density (aBMD) of the hip (p<0.0001), femoral neck (p<0.0001), lumbar spine (p=0.0025), and whole body subtotal (p<0.0001). When individuals with NF1 were separated into groups with and without a skeletal abnormality, the NF1 individuals without a skeletal abnormality still had statistically significant decreases compared to controls (p<0.0001 for whole body subtotal aBMD) albeit less pronounced than those with osseous abnormalities.
These data suggest that individuals with NF1 have a unique generalized skeletal dysplasia, predisposing them to localized osseous defects. Dual energy x-ray absorptiometry may prove useful to identify individuals with NF1 who are at risk for clinical osseous complications, and monitoring therapeutic trials.
densitometry; bone mineral content; skeletal dysplasia; osteopenia