Use of Immunization Information Systems in Ascertainment of COVID-19 Vaccinations for Claims-Based Vaccine Safety and Effectiveness Studies.

Importance: Safety and effectiveness studies of COVID-19 vaccines are being conducted using clinical data, including administrative claims. However, claims data only partially capture administered COVID-19 vaccine doses for numerous reasons, such as vaccination at sites that do not generate claims for reimbursement. Objective: To evaluate the extent to which Immunization Information Systems (IIS) data linked to claims data enhances claims-based COVID-19 vaccine capture for a commercially insured population and to estimate the magnitude of misclassification of vaccinated individuals as having unvaccinated status in the linked IIS and claims data. Design, Setting, and Participants: This cohort study used claims data from a commercial health insurance database and obtained vaccination data from IIS repositories in 11 US states. Participants were individuals younger than 65 years who resided in 1 of 11 states of interest and who were insured in health plans from December 1, 2020, through December 31, 2021. Main Outcomes and Measures: Estimated proportion of individuals with at least 1 dose of any COVID-19 vaccine and proportion of individuals with a completed vaccine series based on general population guidelines. Vaccination status estimates were calculated and compared using claims data alone and linked IIS and claims data. Remaining misclassification of vaccination status was assessed by comparing linked IIS and claims data estimates with estimates from external surveillance data sources (Centers for Disease Control and Prevention [CDC] and state Department of Health [DOH]) and capture-recapture analysis. Results: This cohort study included 5 112 722 individuals (mean [SD] age, 33.5 [17.6] years; 2 618 098 females [51.2%]) from 11 states. Characteristics of those who received at least 1 vaccine dose and those who completed a vaccine series were similar to the overall study population. The proportion with at least 1 vaccine dose increased from 32.8% using claims data alone to 48.1% when the data were supplemented with IIS vaccination records. Vaccination estimates using linked IIS and claims data varied widely by state. The percentage of individuals who completed a vaccine series increased from 24.4% to 41.9% after the addition of IIS vaccine records and varied across states. The percentages of underrecording using linked IIS and claims data were 12.1% to 47.1% lower than those using CDC data, 9.1% to 46.9% lower than the state DOH, and 9.2% to 50.9% lower than capture-recapture analysis. Conclusion and Relevance: Results of this study suggested that supplementing COVID-19 claims records with IIS vaccination records substantially increased the number of individuals who were identified as vaccinated, yet potential underrecording remained. Improvements in reporting vaccination data to IIS infrastructures could allow frequent updates of vaccination status for all individuals and all vaccines.

Prevalence of hereditary tubulointerstitial kidney diseases in the German Chronic Kidney Disease study.

Hereditary chronic kidney disease (CKD) appears to be more frequent than the clinical perception. Exome sequencing (ES) studies in CKD cohorts could identify pathogenic variants in ~10% of individuals. Tubulointerstitial kidney diseases, showing no typical clinical/histologic finding but tubulointerstitial fibrosis, are particularly difficult to diagnose. We used a targeted panel (29 genes) and MUC1-SNaPshot to sequence 271 DNAs, selected in defined disease entities and age cutoffs from 5217 individuals in the German Chronic Kidney Disease cohort. We identified 33 pathogenic variants. Of these 27 (81.8%) were in COL4A3/4/5, the largest group being 15 COL4A5 variants with nine unrelated individuals carrying c.1871G>A, p.(Gly624Asp). We found three cysteine variants in UMOD, a novel missense and a novel splice variant in HNF1B and the homoplastic MTTF variant m.616T>C. Copy-number analysis identified a heterozygous COL4A5 deletion, and a HNF1B duplication/deletion, respectively. Overall, pathogenic variants were present in 12.5% (34/271) and variants of unknown significance in 9.6% (26/271) of selected individuals. Bioinformatic predictions paired with gold standard diagnostics for MUC1 (SNaPshot) could not identify the typical cytosine duplication ("c.428dupC") in any individual, implying that ADTKD-MUC1 is rare. Our study shows that >10% of selected individuals carry disease-causing variants in genes partly associated with tubulointerstitial kidney diseases. COL4A3/4/5 genes constitute the largest fraction, implying they are regularly overlooked using clinical Alport syndrome criteria and displaying the existence of phenocopies. We identified variants easily missed by some ES pipelines. The clinical filtering criteria applied enriched for an underlying genetic disorder.

Diverse molecular causes of unsolved autosomal dominant tubulointerstitial kidney diseases.

Autosomal Dominant Tubulointerstitial Kidney Disease (ADTKD) is caused by mutations in one of at least five genes and leads to kidney failure usually in mid adulthood. Throughout the literature, variable numbers of families have been reported, where no mutation can be found and therefore termed ADTKD-not otherwise specified. Here, we aim to clarify the genetic cause of their diseases in our ADTKD registry. Sequencing for all known ADTKD genes was performed, followed by SNaPshot minisequencing for the dupC (an additional cytosine within a stretch of seven cytosines) mutation of MUC1. A virtual panel containing 560 genes reported in the context of kidney disease (nephrome) and exome sequencing were then analyzed sequentially. Variants were validated and tested for segregation. In 29 of the 45 registry families, mutations in known ADTKD genes were found, mostly in MUC1. Sixteen families could then be termed ADTKD-not otherwise specified, of which nine showed diagnostic variants in the nephrome (four in COL4A5, two in INF2 and one each in COL4A4, PAX2, SALL1 and PKD2). In the other seven families, exome sequencing analysis yielded potential disease associated variants in novel candidate genes for ADTKD; evaluated by database analyses and genome-wide association studies. For the great majority of our ADTKD registry we were able to reach a molecular genetic diagnosis. However, a small number of families are indeed affected by diseases classically described as a glomerular entity. Thus, incomplete clinical phenotyping and atypical clinical presentation may have led to the classification of ADTKD. The identified novel candidate genes by exome sequencing will require further functional validation.

Impact of the Comprehensive Care for Joint Replacement model on patient-reported outcomes.

OBJECTIVE: To determine whether the Comprehensive Care for Joint Replacement (CJR) model, a mandatory episode-based payment program for knee and hip replacement surgery, affected patient-reported measures of quality. DATA SOURCES: Surveys of Medicare fee-for-service beneficiaries who had hip or knee replacement surgery, collected between July 2018 and March 2019, secondary Medicare administrative data, the Provider of Services file, CJR and Bundled Payments for Care Improvement participant lists from the Centers for Medicare & Medicaid Services, and the Area Health Resource Files. STUDY DESIGN: In 2018, participation in the CJR model was mandatory for nearly all hospitals in 34 randomly selected, metropolitan statistical areas (MSAs) that had high historical Medicare payments for lower-extremity joint replacements surgery. The control group included 47 high-payment MSAs randomly assigned as controls. We estimated risk-adjusted differences in self-reported measures of functional status and pain, satisfaction with care, and caregiver help between respondents in CJR hospitals and respondents in hospitals located in the control group. DATA COLLECTION: We selected a census of CJR patients and an equal number of control patients to survey. We fielded two waves of surveys using a mail and phone protocol, yielding 8433 CJR and 9014 control respondents. PRINCIPAL FINDINGS: CJR respondents were slightly more likely to depend on caregivers for certain activities of daily living when they got home (either directly from the hospital or after an institutional post-acute care stay). On a 100-point scale, differences ranged from -2.6 points (p < 0.01) for help needed bathing to -1.7 points (p < 0.05) for help needed using the toilet. However, differences in eight measures of self-reported functional status approximately 90-120 days after hospital discharge were not statistically significant, ranging from -1.1% (p = 0.087) to 0.7% (p = 0.437). CONCLUSIONS: CJR did not harm patient health or affect patient satisfaction on average but did increase reliance on caregivers during recovery.

A noninvasive diagnostic approach to retrospective donor HLA typing in kidney transplant patients using urine.

Antibody-mediated rejection (AMR) is a major obstacle to long-term kidney transplantation. AMR is mostly caused by donor specific HLA antibodies, which can arise before or any time after transplantation. Incomplete donor HLA typing and unavailability of donor DNA regularly preclude the assessment of donor-specificity of circulating anti-HLA antibodies. In our centre, this problem arises in approximately 20% of all post-transplant HLA-antibody assessments. We demonstrate that this diagnostic challenge can be resolved by establishing donor renal tubular cell cultures from recipient´s urine as a source of high-quality donor DNA. DNA was then verified for genetic origin and purity by fluorescence in situ hybridization and short tandem repeat analysis. Two representative cases highlight the diagnostic value of this approach which is corroborated by analysis of ten additional patients. The latter were randomly sampled from routine clinical care patients with available donor DNA as controls. In all 12 cases, we were able to perform full HLA typing of the respective donors confirmed by cross-comparison to results from the stored 10 donor DNAs. We propose that this noninvasive diagnostic approach for HLA typing in kidney transplant patients is valuable to determine donor specificity of HLA antibodies, which is important in clinical assessment of suspected AMR.

An evaluation of manual tidal volume and respiratory rate delivery during simulated resuscitation.

INTRODUCTION: Excessive minute ventilation during cardiac arrest may cause lung injury and decrease the effectiveness of cardiopulmonary resuscitation (CPR). However, little is known about how clinicians deliver tidal volumes and respiratory rates during CPR. METHODS: In this cross-sectional study, licensed practitioners attending an American Heart Association (AHA) Advanced Cardiac Life Support (ACLS) course performed CPR and manual ventilation on a high-fidelity simulator during the megacode portion of the course. Delivered tidal volumes and respiratory rates were measured on a monitor. During the first scenario, results were not displayed to participants, but were displayed during the second scenario. RESULTS: Fifty-two clinicians participated in this study. Average height was 169 (157,178) cm. Pre-monitor display tidal volumes delivered were larger in male participants compared to female participants (684.6 ± 134.4 vs 586.7 ± 167.6 ml, P = 0.05). Those using medium-sized gloves delivered smaller tidal volumes than those using small or large gloves. Twenty-two (42.3%) delivered tidal volume in the range of 5-8 ml/kg of predicted body weight for the simulation manikin, and 35 (67.3%) delivered tidal volumes with >20% variability among breaths. All participants met the target respiratory rate around 10 breaths/min. CONCLUSION: Tidal volume delivery varied greatly during manual ventilation and fewer than half participants delivered tidal volume at 5-8 ml/kg to the manikin. Sex and glove size appeared to impact tidal volume delivery when the participants were unaware of what they were delivering. Participants were able to meet the target respiratory rate around 10 without audio or visual feedback.

Developing a Sustainable Need-Based Pediatric Acute Care Training Curriculum in Solomon Islands.

BACKGROUND: The Johns Hopkins Hospital Pediatric Emergency Department (PED) was invited to collaborate with the National Referral Hospital (NRH), Solomon Islands, to establish an acute care pediatric education program for the country's inaugural class of national medical graduate trainees. OBJECTIVE: To develop and evaluate a sustainable, need-based post-graduate training curriculum in pediatric acute care, resuscitation, and point-of-care ultrasound. METHODS: A need-based training curriculum was developed utilizing the ADDIE model and was implemented and revised over the course of 2 years and two site visits. Implementation followed a train-the-trainer model. The curriculum consisted of high-yield didactics including workshops, simulations, hands-on ultrasound sessions, and lectures at the NRH. A mixed-methods design was used to evaluate the curriculum, including pre/posttesting, qualitative group discussions, and individual surveys. The curriculum was revised in response to ongoing learner evaluations and needs assessments. Continuing educational sessions after the site visit demonstrated sustainability. RESULTS: The curriculum included 19 core topics with 42 teaching sessions during the two site visits. A total of 135 pre/posttests and 366 individual surveys were collected from 46 trainees. Completion rates were 78.2% for surveys and 71.3% for pre/posttests. Pre/posttest scores increased from 44 to 63% during the first site visit and 69.6 to 77.6% during the second. Learners reported a mean 4.81/5 on a standard Likert scale for curriculum satisfaction. Group discussions and surveys highlighted key areas of knowledge growth, important clinical care advances, and identified further needs. Initial sustainability was demonstrated by continued ultrasound sessions led by local graduate trainees. CONCLUSION: A collaborative team including Johns Hopkins PED staff, Solomon Islands' graduate trainees, and NRH administration initiated a professional education curriculum for the first class of Solomon Islands' medical graduates. Knowledge growth and positive impacts of the program were reflected in learner survey and test scores. Graduate trainees were identified as local champions to continue as course instructors. This innovative curriculum was developed, revised, and initially sustained on site. It has been successful in introducing life-saving pediatric acute care and graduate training in Solomon Islands.

Alterations in Anatomical Covariance in the Prematurely Born.

Preterm (PT) birth results in long-term alterations in functional and structural connectivity, but the related changes in anatomical covariance are just beginning to be explored. To test the hypothesis that PT birth alters patterns of anatomical covariance, we investigated brain volumes of 25 PTs and 22 terms at young adulthood using magnetic resonance imaging. Using regional volumetrics, seed-based analyses, and whole brain graphs, we show that PT birth is associated with reduced volume in bilateral temporal and inferior frontal lobes, left caudate, left fusiform, and posterior cingulate for prematurely born subjects at young adulthood. Seed-based analyses demonstrate altered patterns of anatomical covariance for PTs compared with terms. PTs exhibit reduced covariance with R Brodmann area (BA) 47, Broca's area, and L BA 21, Wernicke's area, and white matter volume in the left prefrontal lobe, but increased covariance with R BA 47 and left cerebellum. Graph theory analyses demonstrate that measures of network complexity are significantly less robust in PTs compared with term controls. Volumes in regions showing group differences are significantly correlated with phonological awareness, the fundamental basis for reading acquisition, for the PTs. These data suggest both long-lasting and clinically significant alterations in the covariance in the PTs at young adulthood.

Cost analysis of magnetically controlled growing rods compared with traditional growing rods for early-onset scoliosis in the US: an integrated health care delivery system perspective.

PURPOSE: Traditional growing rod (TGR) for early-onset scoliosis (EOS) is effective but requires repeated invasive surgical lengthenings under general anesthesia. Magnetically controlled growing rod (MCGR) is lengthened noninvasively using a hand-held magnetic external remote controller in a physician office; however, the MCGR implant is expensive, and the cumulative cost savings have not been well studied. We compared direct medical costs of MCGR and TGR for EOS from the US integrated health care delivery system perspective. We hypothesized that over time, the MCGR implant cost will be offset by eliminating repeated TGR surgical lengthenings. METHODS: For both TGR and MCGR, the economic model estimated the cumulative costs for initial implantation, lengthenings, revisions due to device failure, surgical-site infections, device exchanges (at 3.8 years), and final fusion, over a 6-year episode of care. Model parameters were estimated from published literature, a multicenter EOS database of US institutions, and interviews. Costs were discounted at 3.0% annually and represent 2015 US dollars. RESULTS: Of 1,000 simulated patients over 6 years, MCGR was associated with an estimated 270 fewer deep surgical-site infections and 197 fewer revisions due to device failure compared with TGR. MCGR was projected to cost an additional $61 per patient over the 6-year episode of care compared with TGR. Sensitivity analyses indicated that the results were sensitive to changes in the percentage of MCGR dual rod use, months between TGR lengthenings, percentage of hospital inpatient (vs outpatient) TGR lengthenings, and MCGR implant cost. CONCLUSION: Cost neutrality of MCGR to TGR was achieved over the 6-year episode of care by eliminating repeated TGR surgical lengthenings. To our knowledge, this is the first cost analysis comparing MCGR to TGR - from the US provider perspective - which demonstrates the efficient provision of care with MCGR.

Functional magnetic resonance connectivity studies in infants born preterm: suggestions of proximate and long-lasting changes in language organization.

Sophisticated neuroimaging strategies demonstrate alterations in functional connectivity at school age, adolescence, and young adulthood in individuals born preterm. Recent data suggest these alterations are present in the postnatal period prior to term-equivalent age in neonates born preterm. Likewise, functional organization increases across development, but the influence of preterm birth on this fundamental infrastructure is immediate and unchanging. This article briefly reviews the current methods of measuring functional connectivity throughout development in those born preterm, and the association of functional connectivity with language disorders. Taken together, these data suggest that the effects of preterm birth on the functional organization of language in the developing brain are both proximate and long-lasting.

Language at rest: A longitudinal study of intrinsic functional connectivity in preterm children.

BACKGROUND: Preterm (PT) children show early cognitive and language deficits and display altered cortical connectivity for language compared to term (T) children. Developmentally, functional connectivity networks become more segregated and integrated, through the weakening of short-range and strengthening of long-range connections. METHODS: Longitudinal intrinsic connectivity distribution (ICD) values were assessed in PT (n = 13) compared to T children (n = 12) at ages 8 vs. 16 using a Linear Mixed Effects model. Connectivity values in regions generated by the group × age interaction analysis were then correlated to scores on full IQ (FSIQ), verbal IQ (VIQ), verbal comprehension IQ (VCIQ), performance IQ (PIQ), Peabody picture vocabulary test-revised (PPVT-R), and Rapid Naming Composite (RDRL_Cmp). RESULTS: Nine regions were generated by the group × age interaction analysis. PT connectivity significantly increased over time in all but two regions, and they ultimately displayed greater relative connectivity at age 16 than Ts in all areas except the left occipito-temporal cortex (OTC). PTs underwent significant connectivity reductions in the left OTC, which corresponded with worse performance on FSIQ, VIQ, and PIQ. These findings differed from Ts, who did not undergo any significant changes in connectivity over time. CONCLUSIONS: These findings suggest that the developmental alterations in connectivity in PT children at adolescence are both pervasive and widespread. The persistent and worsening cognitive and language deficits noted in the PT subjects may be attributed to the loss of connections in the left OTC.

From Theory to Practice: Implementation of a Resource Allocation Model in Health Departments.

OBJECTIVE: To develop a resource allocation model to optimize health departments' Centers for Disease Control and Prevention (CDC)-funded HIV prevention budgets to prevent the most new cases of HIV infection and to evaluate the model's implementation in 4 health departments. DESIGN, SETTINGS, AND PARTICIPANTS: We developed a linear programming model combined with a Bernoulli process model that allocated a fixed budget among HIV prevention interventions and risk subpopulations to maximize the number of new infections prevented. The model, which required epidemiologic, behavioral, budgetary, and programmatic data, was implemented in health departments in Philadelphia, Chicago, Alabama, and Nebraska. MAIN OUTCOME MEASURES: The optimal allocation of funds, the site-specific cost per case of HIV infection prevented rankings by intervention, and the expected number of HIV cases prevented. RESULTS: The model suggested allocating funds to HIV testing and continuum-of-care interventions in all 4 health departments. The most cost-effective intervention for all sites was HIV testing in nonclinical settings for men who have sex with men, and the least cost-effective interventions were behavioral interventions for HIV-negative persons. The pilot sites required 3 to 4 months of technical assistance to develop data inputs and generate and interpret the results. Although the sites found the model easy to use in providing quantitative evidence for allocating HIV prevention resources, they criticized the exclusion of structural interventions and the use of the model to allocate only CDC funds. CONCLUSIONS: Resource allocation models have the potential to improve the allocation of limited HIV prevention resources and can be used as a decision-making guide for state and local health departments. Using such models may require substantial staff time and technical assistance. These model results emphasize the allocation of CDC funds toward testing and continuum-of-care interventions and populations at highest risk of HIV transmission.

Preterm birth alters neonatal, functional rich club organization.

Alterations in neural networks are associated with the cognitive difficulties of the prematurely born. Using functional magnetic resonance imaging, we analyzed functional connectivity for preterm (PT) and term neonates at term equivalent age. Specifically, we constructed whole-brain networks and examined rich club (RC) organization, a common construct among complex systems where important (or "rich") nodes connect preferentially to other important nodes. Both PT and term neonates showed RC organization with PT neonates exhibiting significantly reduced connections between these RC nodes. Additionally, PT neonates showed evidence of weaker functional segregation. Our results suggest that PT birth is associated with fundamental changes of functional organization in the developing brain.

Exploring the skin-to-skin contact experience during cesarean section.

PURPOSE: To explore and describe the mother's experience of holding her neonate in skin-to-skin contact (SSC) immediately after cesarean delivery during surgical closure and recovery. DATA SOURCES: Eleven women between the ages of 23 and 38 years, who had achieved 39.1-40.2 weeks gestational age, participated in an ethnographic study using observations and interviews with the mothers conducted at 24-48 h postdelivery. Interviews were transcribed verbatim and content analysis of both observational notes and transcripts were used to analyze the data. CONCLUSIONS: Findings from this study describe the mother's experience of SSC during cesarean section. The primary theme that emerged was mutual caregiving: the mother-neonatal interaction and their shared and reciprocal relationship and benefits during SSC. Two contextual issues also were illuminated (a) the father's influence on the SSC experience and (b) the cesarean environment. IMPLICATIONS FOR PRACTICE: With cesarean section the most common surgical procedure among American women, advanced practice nurses are in a unique position to encourage and educate women on the use of SSC for their benefit and that of their newborn. Advanced practice nurses are also empowered to influence institutional policy on SSC during cesarean deliveries at the local and national level.

Adaptive mechanisms of developing brain: cerebral lateralization in the prematurely-born.

Preterm birth results in alterations in neural connectivity, but the impact of prematurity on the functional organization of the developing brain has yet to be explored. To test the hypothesis that preterm birth alters cortical organization during the late second and third trimesters of gestation, we interrogated cerebral lateralization at rest in 26 very preterm subjects (birth weight 500-1500g) with no evidence of brain injury and 25 healthy term control subjects at term equivalent age. Employing an unbiased voxel-based measure of functional connectivity, these data demonstrated that cerebral lateralization is impaired in the prematurely-born. At term equivalent age, preterm neonates showed significantly less lateralization in regions subserving both receptive and expressive language, left Brodmann (BA) areas insula-BA22-BA21 and L BA45-BA47 (p<0.05 corrected for multiple comparisons for both). Exploratory region of interest analyses demonstrated significantly less inter-hemispheric connectivity from L BA22 to R BA22 in preterm infants compared to term controls (p<0.005) and from R BA22 to its homolog (p<0.005). L BA22, Wernicke's area, was more strongly connected to R BA39, foreshadowing neural networks for language in preterm subjects at school age, adolescence and young adulthood. For these very preterm neonates born at less than 30weeks' PMA, the degree of prematurity had no influence on lateralization in these differential regions.

Cerebral Lateralization is Protective in the Very Prematurely Born.

Individuals born prematurely are at risk for developmental delay, and converging data suggest alterations in neural networks in the developing preterm brain. Nevertheless, those critical period processes such as cerebral lateralization that underlie these findings remain largely unexplored. To test the hypothesis that preterm birth alters the fundamental program of corticogenesis in the developing brain, we interrogated cerebral lateralization at rest in very prematurely born participants and term controls at young adulthood. Employing a novel, voxel-based measure of functional connectivity, these data demonstrate for the first time that cerebral lateralization of functional connectivity in right hemisphere language homologs is altered for very preterm participants. Very preterm participants with no evidence for severe brain injury exhibited a significant decrease in right hemisphere lateralization in the right parietal and temporal lobes in this data driven analysis. Further, for the very preterm participants, but not the term participants, these fundamental alterations in the cerebral lateralization for language significantly correlate with language scores. These findings provide evidence that cerebral asymmetry is both plastic and experiential, and suggest the need for further study of underlying environmental factors responsible for these changes.

Adolescents born prematurely with isolated grade 2 haemorrhage in the early 1990s face increased risks of learning challenges.

AIM: To compare the impact of low-grade haemorrhage on neurocognitive function in 16-year-old adolescents born preterm, by grade of intraventricular haemorrhage, and term controls. METHODS: We evaluated 338 preterm adolescents (birth weight 600-1250 g) for intelligence, executive function and memory tasks. Eleven had grade 3-4 haemorrhage, 44 had grade 2, 31 had grade 1, and 251 had no haemorrhage. Group comparisons were made with 102 term age-matched controls, and regression models used to identify the risk that low-grade haemorrhage posed for cognitive, executive function and memory deficits. RESULTS: Preterm adolescents with grade 2 haemorrhage had higher deficit rates of verbal intelligence, receptive vocabulary, phonemic fluency, cognitive flexibility and phonological fluency than preterm adolescents with grade 1 or no haemorrhage, compared with term controls. After excluding preterm adolescents with both grade 2 haemorrhage and cystic periventricular leukomalacia, those with isolated grade 2 haemorrhage remained at greater risk of cognitive and executive function deficits than term controls and of cognitive deficits than preterm adolescents with no haemorrhage. CONCLUSION: Our findings suggest that preterm adolescents born in the early 1990s with isolated grade 2 haemorrhage are at increased risk of learning challenges, including cognitive and executive function deficits.

Comparison of the costs of nonoperative care to minimally invasive surgery for sacroiliac joint disruption and degenerative sacroiliitis in a United States commercial payer population: potential economic implications of a new minimally invasive technology.

INTRODUCTION: Low back pain is common and treatment costly with substantial lost productivity and lost wages in the working-age population. Chronic low back pain originating in the sacroiliac (SI) joint (15%-30% of cases) is commonly treated with nonoperative care, but new minimally invasive surgery (MIS) options are also effective in treating SI joint disruption. We assessed whether the higher initial MIS SI joint fusion procedure costs were offset by decreased nonoperative care costs from a US commercial payer perspective. METHODS: An economic model compared the costs of treating SI joint disruption with either MIS SI joint fusion or continued nonoperative care. Nonoperative care costs (diagnostic testing, treatment, follow-up, and retail pharmacy pain medication) were from a retrospective study of Truven Health MarketScan(®) data. MIS fusion costs were based on the Premier's Perspective™ Comparative Database and professional fees on 2012 Medicare payment for Current Procedural Terminology code 27280. RESULTS: The cumulative 3-year (base-case analysis) and 5-year (sensitivity analysis) differentials in commercial insurance payments (cost of nonoperative care minus cost of MIS) were $14,545 and $6,137 per patient, respectively (2012 US dollars). Cost neutrality was achieved at 6 years; MIS costs accrued largely in year 1 whereas nonoperative care costs accrued over time with 92% of up front MIS procedure costs offset by year 5. For patients with lumbar spinal fusion, cost neutrality was achieved in year 1. CONCLUSION: Cost offsets from new interventions for chronic conditions such as MIS SI joint fusion accrue over time. Higher initial procedure costs for MIS were largely offset by decreased nonoperative care costs over a 5-year time horizon. Optimizing effective resource use in both nonoperative and operative patients will facilitate cost-effective health care delivery. The impact of SI joint disruption on direct and indirect costs to commercial insurers, health plan beneficiaries, and employers warrants further consideration.

GABA, resting-state connectivity and the developing brain.

BACKGROUND: Preclinical data demonstrate that gamma-aminobutyric acid (GABA) interneurons initiate connectivity in the developing brain. OBJECTIVES: The goal of this study was to compare GABA concentration and its relationship to functional connectivity in the brains of term and preterm infants at term-equivalent age. METHODS: Infants received both magnetic resonance spectroscopy (MRS) and functional magnetic resonance imaging (fMRI) scans at term-equivalent age. Whole brain functional connectivity MRI data using intrinsic connectivity distribution maps were compared to identify areas with differences in resting-state functional connectivity between the preterm and term control groups. MRS measured concentrations of GABA, glutamate, N-acetyl-aspartate (NAA) and choline; NAA/choline was then calculated for comparison between the 2 groups. RESULTS: Preterm infants had lower right frontal GABA and glutamate concentrations than term controls and showed a significantly different relationship between connectivity and GABA concentration in the right frontal lobe. Preterm infants had a positive correlation between GABA concentration and connectivity, while term controls demonstrated a negative correlation between these two developmentally regulated parameters. CONCLUSION: These results suggest that regional GABA concentrations are associated with normal and altered neonatal resting-state connectivity.