The Effect of the Relationship of APOE Polymorphisms and Cerebral Vasospasm on Functional Outcomes in Children With Traumatic Brain Injury.

BACKGROUND: Pediatric traumatic brain injury (TBI) is a leading cause of death and disability. Polymorphisms in the apolipoprotein E ( APOE) gene have been linked to cerebral vasospasm (CV) and poor outcomes in adults with TBI, yet these associations remain poorly defined in children. OBJECTIVE: We examined the effect of the relationship between APOE polymorphisms and CV on functional outcomes in children with a TBI. METHOD: This prospective, descriptive study examined 60 children (aged 10 days to 15 years) with a TBI. Data included demographic information, genetic sampling for the APOE gene and single-nucleotide polymorphisms (SNPs; rs405509, rs429358, rs7412), and daily transcranial Doppler ultrasounds to evaluate for CV. We examined Glasgow Outcome Scale-Extended Pediatrics (GOS-E Peds) scores at the time of discharge and 4-6 weeks after discharge. RESULTS: More than half (56.7%) of the 60 children ( Mage = 5.9 years) were male. Twenty-six participants (43.3%) experienced an occurrence of CV. There were significant differences in injury mechanism (unadjusted p = .048) and age (unadjusted p = .02) between those with and without CV. Also, the noncoding promoter SNP rs405509 T/T, when considered with injury severity, appeared to modify the relationship of APOE genotype to CV. The relationship between APOE and CV had no significant effect on GOS-E Peds scores. CONCLUSION: Injury severity and the APOE noncoding promoter SNP rs405509 may modify the relationship between APOE and CV in children with TBI. More studies are needed to understand the role of APOE polymorphisms in outcomes in children with TBI.

Expanded Medicaid Provides Access to Substance Use, Mental Health, and Physician Visits to Homeless and Precariously Housed Persons.

To describe the Medicaid costs associated with persons who are homeless or unstably housed. A retrospective secondary data analysis linked Medicaid recipient data with a statewide homeless management information system. A total of 19,950 persons received a housing service between 2012 and 2015 including 14,136 persons with Medicaid. Five of the most frequent diagnoses were substance abuse or mental health conditions in 42.83% of all diagnoses. The most frequent service was outpatient mental health and emergency department physician services. These costs totaled $166,653,689 with prescription drug costs at $62,800,463, with a total cost of $672,242,449, averaging $14,632.42 per 12-month period per person. The potential changes in Medicaid could lead to cost transfers or a reduction in services. Recognizing these are significant costs by homeless and unstably housed persons only, these high costs warrant the determination of points in care where effective cost saving interventions may be employed.

Healthcare Utilization and Costs During the Initial Phase of Care Among Elderly Women With Breast Cancer.

Background: Understanding the patterns of healthcare utilization and costs during the initial phase of care (12 months after breast cancer [BC] diagnosis) in older women (aged ≥65 years) is crucial in the allocation of Medicare resources. The objective of this study was to determine healthcare utilization and costs during the initial phase of care in older, female, Medicare fee-for-service beneficiaries diagnosed with BC, and to determine the factors associated with higher costs. Methods: A retrospective observational study using the SEER-Medicare linked database was conducted in 69,307 women aged ≥66 years diagnosed with primary incident BC in 2003-2009 to determine healthcare utilization, average costs, and costs for specific services during the initial phase of care. Generalized linear model regression was conducted to identify the factors associated with higher costs in a multivariate framework. Results: A total of 96% of women were treated with surgery during the initial phase of BC care, whereas 21% and 54% underwent chemotherapy and radiotherapy, respectively. Costs during the initial phase of care totalled $28,075 in 2012 USD, comprising $13,344 for physician services and $7,456 for outpatient services. Factors associated with higher costs during the initial phase of care were younger age (66-69 years), African American race, higher household income, advanced stages of BC, initial BC treatment, higher number of primary care physician visits, and presence of comorbidities and/or a mental condition. Conclusions: The economic burden of BC is substantial during the initial phase of care. Physician and outpatient services accounted for the highest proportion of costs. Predisposing factors, need-related factors, healthcare use, and external environmental healthcare factors significantly predicted costs during the initial phase of care.

Designing an Effective, Small-Scope Practice-based Study.

OBJECTIVE: Present a methodology to promote good practices in designing small-scale, practice-based studies. STUDY DESIGN: We propose the following methods to assist clinicians and other practice-based researchers in designing and conducting good quality, small-scale studies in a clinical setting. METHODS: Research projects applied to a limited, practice-based study may require modification to increase the consistency of patient research. RESULTS: Although common requests to collaborative methodologists mirror methods for experimental design, clinic-based studies may face different limitations. Each participant enrolled consumes resources, including time, and personnel. If practice-based studies have a different goal, to learn about the health outcomes of patients in a medical practice with limited intent for generalization, should the same methods be used? CONCLUSIONS: When limitations are clearly stated and the findings are described within the study context, these limitations may not be so severe to discourage the research. We propose a systematic method to conduct practice-based research intended for small-scale study use. Relying heavily on existing research from similar areas, the incorporation of data from the practice, and the a priori defined timelines and resources, we set forth some guiding principles to assist clinic-based investigators. Individualized focus and small-scale studies are growing in use and acceptance especially given the focus on personalized health.

Smartphone assessment of knee flexion compared to radiographic standards.

BACKGROUND: Measuring knee range of motion (ROM) is an important assessment for the outcomes of total knee arthroplasty. Recent technological advances have led to the development and use of accelerometer-based smartphone applications to measure knee ROM. The purpose of this study was to develop, standardize, and validate methods of utilizing smartphone accelerometer technology compared to radiographic standards, visual estimation, and goniometric evaluation. METHODS: Participants used visual estimation, a long-arm goniometer, and a smartphone accelerometer to determine range of motion of a cadaveric lower extremity; these results were compared to radiographs taken at the same angles. RESULTS: The optimal smartphone position was determined to be on top of the leg at the distal femur and proximal tibia location. Between methods, it was found that the smartphone and goniometer were comparably reliable in measuring knee flexion (ICC=0.94; 95% CI: 0.91-0.96). Visual estimation was found to be the least reliable method of measurement. CONCLUSIONS: The results suggested that the smartphone accelerometer was non-inferior when compared to the other measurement techniques, demonstrated similar deviations from radiographic standards, and did not appear to be influenced by the person performing the measurements or the girth of the extremity.

Retrospective cross-sectional pilot study of rifaximin dosing for the prevention of recurrent hepatic encephalopathy.

Standard treatment for hepatic encephalopathy (HE) includes medications that reduce ammonia and bacterial translocation in the gut. Rifaximin can be used off-label for the reduction of overt HE. The study purpose was to determine efficacy of traditional rifaximin dosing (400 mg three times daily) compared with newer dosing (550 mg twice daily) via readmission rates for the prevention of recurrent HE. This was a retrospective, observational, cross-sectional pilot study conducted in a tertiary medical center. A total of 226 patients 18-89 years of age with documentation of HE via ICD-9 code who started rifaximin therapy while inpatient between April 2009 and June 2014 were evaluated. Data collected included rifaximin dosing, other medications used to treat HE, duration of therapy, time to readmission, and various laboratory values. There were no differences in readmission rates at 30 days, 60 days, or 6 months between treatment groups. Additionally, there was no difference in the odds of readmission between the treatment groups (OR = 0.77, 95% CI: [0.201, 4.365], P = 0.718). Patients had a low overall probability of readmission over the observational period. Based on average wholesale price data, the cost for a 9-day supply of rifaximin for the 400-mg dosing regimen is $952.56 versus $605.16 for the 550-mg dosing regimen. The rifaximin 550-mg dosing strategy should be utilized in hospitalized patients for the prevention of recurrent HE as there was no difference in readmission rate or time to readmission between dosing groups. The 550-mg regimen had a lower acquisition cost for a 9-day duration of treatment in the studied institution.

Impact of Tissue Plasminogen Activator Dosing on Patients Weighing More Than 100 kg on 3-Month Outcomes in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: The landmark National Institute of Neurological Disorders and Stroke (NINDS) tissue plasminogen activator (tPA) trial established the effectiveness and dosing of intravenous tPA for acute ischemic stroke (AIS) at .9 mg/kg with a maximum dose of 90 mg. Since the publication of the NINDS trial in 1995, there has been a drastic increase in the amount of obesity and the average weight of adults in the United States, which has caused an increase in the number of patients receiving 90 mg of alteplase for AIS. This retrospective trial was an attempt to see if reduced-dose tPA is as effective as full .9 mg/kg dosing. METHODS: We performed a single-center retrospective analysis to assess the dosing rate and 90-day outcomes comparing maximum dosage (90 mg) and standard dosage (.9 mg/kg) of tPA. RESULTS: A total of 301 patients were included in the analysis with 64 (21%) receiving less than .9 mg/kg dosing. The adjusted binary logistic regression model showed a statistically significant association toward a good outcome for increases in tPA dose rate (odds ratio = 1.7, P = .027) when compared against a poor outcome. Our analysis showed that patients receiving doses of alteplase closer to .9 mg/kg had a higher likelihood of a modified Rankin Scale score of 0-1 at 90 days. CONCLUSIONS: With the growth of obesity in the United States and the lack of data supporting dose capping of alteplase, it remains unclear if this dosing practice should continue to be accepted without question. Further studies are needed to assess optimum dosing practices particularly given the obesity epidemic.

The Orthogonally Partitioned EM Algorithm: Extending the EM Algorithm for Algorithmic Stability and Bias Correction Due to Imperfect Data.

We propose an extension of the EM algorithm that exploits the common assumption of unique parameterization, corrects for biases due to missing data and measurement error, converges for the specified model when standard implementation of the EM algorithm has a low probability of convergence, and reduces a potentially complex algorithm into a sequence of smaller, simpler, self-contained EM algorithms. We use the theory surrounding the EM algorithm to derive the theoretical results of our proposal, showing that an optimal solution over the parameter space is obtained. A simulation study is used to explore the finite sample properties of the proposed extension when there is missing data and measurement error. We observe that partitioning the EM algorithm into simpler steps may provide better bias reduction in the estimation of model parameters. The ability to breakdown a complicated problem in to a series of simpler, more accessible problems will permit a broader implementation of the EM algorithm, permit the use of software packages that now implement and/or automate the EM algorithm, and make the EM algorithm more accessible to a wider and more general audience.

Long-term pharmacotherapy for elevated low density lipoprotein levels in children: A retrospective analysis.

BACKGROUND: There is limited research detailing low-density lipoprotein cholesterol (LDL-C) trends over the long term in children on various lipid-lowering medications. OBJECTIVES: This study sought to assess factors associated with stability of LDL-C levels in children on long-term pharmacotherapy and their ability to reach the LDL-C goal of ≤130 mg/dL while on pharmacotherapy. METHODS: Medical records of children seen in a university pediatric cholesterol clinic between 1998 and 2012 treated with a statin, ezetimibe, or both were reviewed. Aggregate data were obtained to determine the number of children able to reach an LDL-C level of ≤130 mg/dL while on pharmacotherapy. Kaplan-Meier curve and proportional hazard regression analysis were used to examine the propensity for LDL-C levels to stabilize over time while on pharmacotherapy as well as factors affecting this propensity. RESULTS: Overall, 76 patients who contributed 864 total visits were included. Of the 76 patients, 56 developed a stable LDL-C with median time to stability of 28 months on pharmacotherapy. Younger age at first visit and higher medication potencies/doses were associated with an increased propensity to stabilize. Only 36 patients were able to reach an LDL-C of ≤130 mg/dL, with only 11 of 38 patients with probable familial hypercholesterolemia reaching this goal. CONCLUSIONS: Most children reached LDL-C stability on pharmacotherapy after a median 28-month interval. However, most children had difficulty in reaching the LDL-C goal of ≤130 mg/dL even with aggressive medication titration. This was specifically true for those with probable familial hypercholesterolemia.

Lung Pathology in U.S. Coal Workers with Rapidly Progressive Pneumoconiosis Implicates Silica and Silicates.

RATIONALE: Recent reports of progressive massive fibrosis and rapidly progressive pneumoconiosis in U.S. coal miners have raised concerns about excessive exposures to coal mine dust, despite reports of declining dust levels. OBJECTIVES: To evaluate the histologic abnormalities and retained dust particles in available coal miner lung pathology specimens, and to compare these findings with those derived from corresponding chest radiographs. METHODS: Miners with severe disease and available lung tissue were identified through investigator outreach. Demographic as well as smoking and work history information was obtained. Chest radiographs were interpreted according to the International Labor Organization classification scheme to determine if criteria for rapidly progressive pneumoconiosis were confirmed. Pathology slides were scored by three expert pulmonary pathologists using a standardized nomenclature and scoring system. MEASUREMENTS AND MAIN RESULTS: Thirteen cases were reviewed, many of which had features of accelerated silicosis and mixed dust lesions. Twelve had progressive massive fibrosis, and 11 had silicosis. Only four had classic lesions of simple coal workers' pneumoconiosis. Four had diffuse interstitial fibrosis with chronic inflammation, and two had focal alveolar proteinosis. Polarized light microscopy revealed large amounts of birefringent mineral dust particles consistent with silica and silicates; carbonaceous coal dust was less prominent. On the basis of chest imaging studies, specimens with features of silicosis were significantly associated (P = 0.047) with rounded (type p, q, or r) opacities, whereas grade 3 interstitial fibrosis was associated (P = 0.02) with the presence of irregular (type s, t, or u) opacities. CONCLUSIONS: Our findings suggest that rapidly progressive pneumoconiosis in these miners was associated with exposure to coal mine dust containing high concentrations of respirable silica and silicates.

The Role of Arginase 1 in Post-Stroke Immunosuppression and Ischemic Stroke Severity.

A balanced immune system response plays an important role in acute ischemic stroke (AIS) recovery. Our laboratory has previously identified several immune-related genes, including arginase 1 (ARG1), with altered expression in human AIS patients. The neutrophil-lymphocyte ratio (NLR) may be a marker of the degree of immune dysregulation following AIS; however, the molecular mechanisms that may mediate the NLR are unknown. The purpose of this study was to (1) examine the relationship between ARG1, NLR, and AIS severity and (2) to utilize principal component analysis (PCA) to statistically model multiple gene expression changes following AIS. AIS patients and stroke-free control subjects were recruited, and blood samples were collected from AIS patients within 24 h of stroke symptom onset. White blood cell differentials were obtained at this time to calculate the NLR. Gene expression was measured using real-time PCR. PCA with varimax rotation was used to develop composite variables consisting of a five-gene profile. ARG1 was positively correlated with NLR (r = 0.57, p = 0.003), neutrophil count (r = 0.526, p = 0.007), NIHSS (r = 0.607, p = 0.001), and infarct volume (r = 0.27, p = 0.051). PCA identified three principal components that explain 84.4 % of variation in the original patient gene dataset comprised of ARG1, LY96, MMP9, s100a12, and PC1 was a significant explanatory variable for NIHSS (p < 0.001) and NLR (p = 0.005). Our study suggests a novel relationship between ARG1, NLR, and stroke severity, and the NLR is an underutilized clinically available biomarker to monitor the post-stroke immune response.

Gait parameters associated with balance in healthy 2- to 4-year-old children.

The use of validated measurements of gait and balance are crucial to establish baseline function and assess effectiveness of therapeutic interventions. Gait in children changes with motor development requiring frequent observations to effectively track progress. Standardized baseline spatiotemporal measurements and a greater understanding of the relationship between gait and balance would provide important feedback to clinicians regarding the effectiveness of rehabilitation and guide treatment modifications. 84 subjects (2.0-4.9 years) walked along the GAITRite(®), a walkway that records spatiotemporal parameters. The Pediatric Balance Scale (PBS) was administered to assess balance. Comparison of spatiotemporal parameter means between age groups showed trends associated with motor development similar to the ones described in the literature such as decreased cadence and increased step/stride length with increasing age. However, no significant differences in normalized spatiotemporal parameters were found between age groups. Age, leg length, cadence, step/stride length, step/stance time, and single/double support time showed significant correlation with balance scores. When the parameters were grouped into spatial, temporal, and age-related components using principal components analysis and included in a multiple regression model, they significantly predicted 51% of the balance score variance. Age-related components most strongly predicted balance outcomes. We suggest that balance can potentially be evaluated by assessment of spatial, temporal, and age-related characteristics of gait such as step length, cadence, and leg length. This suggests the possibility of developing new gait measurement technology that could provide functional assessment and track improvements during rehabilitation regimens. If the same model can be applied to monitor treatment efficacy in children with gait abnormalities remains to be addressed.

Can We Predict Functional Outcome in Neonates with Hypoxic Ischemic Encephalopathy by the Combination of Neuroimaging and Electroencephalography?

BACKGROUND: Neonatal hypoxic ischemic encephalopathy (HIE) is a major cause of mortality, morbidity, and long-term neurological deficits. Despite the availability of neuroimaging and neurophysiological testing, tools for accurate early diagnosis and prediction of developmental outcome are still lacking. The goal of this study was to determine if combined use of magnetic resonance imaging (MRI) and electroencephalography (EEG) findings could support outcome prediction. METHODS: We retrospectively reviewed records of 17 HIE neonates, classified brain MRI and EEG findings based on severity, and assessed clinical outcome up to 48 months. We determined the relation between MRI/EEG findings and clinical outcome. RESULTS: We demonstrated a significant relationship between MRI findings and clinical outcome (Fisher's exact test, p = 0.017). EEG provided no additional information about the outcome beyond that contained in the MRI score. The statistical model for outcome prediction based on random forests suggested that EEG readings at 24 hours and 72 hours could be important variables for outcome prediction, but this needs to be investigated further. CONCLUSION: Caution should be used when discussing prognosis for neonates with mild-to-moderate HIE based on early MR imaging and EEG findings. A robust, quantitative marker of HIE severity that allows for accurate prediction of long-term outcome, particularly for mild-to-moderate cases, is still needed.

HIV/STI prevalence study among military conscripts in Estonia.

Risk taking behavior and sexually transmitted infections (STIs) research outcomes vary among militaries. A common theme indicates STI prevalence and risk taking among military personnel is higher than the general population. Alcohol and drug misuse is well documented. From these behaviors, high-risk sexual encounters increase. Exploring STI prevalence, knowledge, and risk behaviors among conscripted military forces, we recruited 584 conscripts from a defense force in Eastern Europe. The observed STI prevalence in the young, male conscripts was equal or less than their non-conscripted counterparts. Military entry screenings could reduce STIs, creating a healthier population. However, these findings remain informative as the notion of high STI rates among military forces is not supported. As this study was one of the first of its type in the region, it demonstrates the ability of a nation to secure their defense forces against HIV/STIs even in the face of increased prevalence within that nation.

Reported contraceptive use, risk behaviours and STIs among military conscripts in Estonian defence forces.

Limited research exists on sexually transmitted infection (STI) and risk behaviour among military personnel. Published research on condom use and types of contraceptives used yield mixed results, yet, the perception that military members are at higher risk for STIs remains. The objectives of this cross-sectional study were to measure factors such as condom use, contraceptive methods, and risky behaviours (i.e. drug use and sex with commercial sex workers) and investigate differences between ethnic groups, where culture could influence behaviour. Data were collected from a recruited population of 584 male, military conscripts in northeastern Europe. Using multinomial logistic regression models, statistically significant findings include an interaction between the use of contraceptive methods of Russians with casual partners and ethnicity, with higher odds of effective methods used among Estonians with regular partners (OR = 8.13) or casual partners (OR = 11.58) and Russians with regular partners (OR = 4.98). Effective contraceptive methods used less frequently with casual partners by ethnic Russians is important in providing education and risk reduction services to young, male conscripts. These findings may be used as a baseline to inform health education and STI prevention programmes tailored to military members in Eastern Europe in the absence of other published studies.

An inexpensive, interdisciplinary, methodology to conduct an impact study of homeless persons on hospital based services.

Homelessness is a primary concern for community health. Scientific literature on homelessness is wide ranging and diverse. One opportunity to add to existing literature is the development and testing of affordable, easily implemented methods for measuring the impact of homeless on the healthcare system. Such methodological approaches rely on the strengths in a multidisciplinary approach, including providers, both healthcare and homeless services and applied clinical researchers. This paper is a proof of concept for a methodology which is easily adaptable nationwide, given the mandated implementation of homeless management information systems in the United States and other countries; medical billing systems by hospitals; and research methods of researchers. Adaptation is independent of geographic region, budget restraints, specific agency skill sets, and many other factors that impact the application of a consistent methodological science based approach to assess and address homelessness. We conducted a secondary data analysis merging data from homeless utilization and hospital case based data. These data detailed care utilization among homeless persons in a small, Appalachian city in the United States. In our sample of 269 persons who received at least one hospital based service and one homeless service between July 1, 2012 and June 30, 2013, the total billed costs were $5,979,463 with 10 people costing more than one-third ($1,957,469) of the total. Those persons were primarily men, living in an emergency shelter, with pre-existing disabling conditions. We theorize that targeted services, including Housing First, would be an effective intervention. This is proposed in a future study.

Importance of android/gynoid fat ratio in predicting metabolic and cardiovascular disease risk in normal weight as well as overweight and obese children.

Numerous studies have shown that android or truncal obesity is associated with a risk for metabolic and cardiovascular disease, yet there is evidence that gynoid fat distribution may be protective. However, these studies have focused on adults and obese children. The purpose of our study was to determine if the android/gynoid fat ratio is positively correlated with insulin resistance, HOMA2-IR, and dislipidemia in a child sample of varying body sizes. In 7-13-year-old children with BMI percentiles ranging from 0.1 to 99.6, the android/gynoid ratio was closely associated with insulin resistance and combined LDL + VLDL-cholesterol. When separated by sex, it became clear that these relationships were stronger in boys than in girls. Subjects were stratified into BMI percentile based tertiles. For boys, the android/gynoid ratio was significantly related to insulin resistance regardless of BMI tertile with and LDL + VLDL in tertiles 1 and 3. For girls, only LDL + VLDL showed any significance with android/gynoid ratio and only in tertile 2. We conclude that the android/gynoid fat ratio is closely associated with insulin resistance and LDL + VLDL-, "bad," cholesterol in normal weight boys and may provide a measurement of metabolic and cardiovascular disease risk in that population.

The effect of error-in-confounders on the estimation of the causal parameter when using marginal structural models and inverse probability-of-treatment weights: a simulation study.

We performed an empirical study to evaluate the effect of mismeasured continuous confounders on the estimation of the causal parameter when using marginal structural models and inverse probability-of-treatment weighting. By executing an extensive simulation using 500 randomly generated parameter value combinations within a defined space, we observed the well-understood effects of attenuation and augmentation, and two unanticipated effects: null effects and sign reversals. We implemented a secondary empirical study to further investigate the sign reversal effect. We use the results of our study to identify conceptual similarities between the analytic and empirical results for multivariable linear and logistic regression, and our empirical results. Through this synthesis, we have been able to suggest feasible directions of research as well as outline the form of expected results.

Incidence and Pattern of Graft-versus-Host Disease in Patients Undergoing Allogeneic Transplantation after Nonmyeloablative Conditioning with Total Lymphoid Irradiation and Antithymocyte Globulin.

Nonmyeloablative (NMA) conditioning with total lymphoid irradiation and antithymocyte globulin (TLI/ATG) has been shown to protect against acute graft-versus-host disease (GVHD). We report here our institutional experience with allogeneic transplantation following NMA conditioning with TLI/ATG (n = 21). GVHD prophylaxis consisted of a combination of a calcineurin inhibitor and mycophenolate mofetil. Median patient age was 59 years. The median followup of surviving patients is 545 days. One patient experienced primary graft rejection. The median time to neutrophil engraftment was 18 days and platelet engraftment was 9.5 days. The cumulative incidence (CI) of grade II-IV acute GVHD at day +100 was 28.6% and 38.1% at day +180. The CI for grade III-IV acute GVHD was 28.6% at day +180. CI of chronic GVHD was 45.2% at 1 year. The CI of disease relapse was 9.5% at 1 year. The rate of nonrelapse mortality (NRM) was 0% at day +100 and only 9.5% at 1 year. The overall and progression free survival at 1 year was 81% and 80.4%, respectively. Our limited, retrospective data show encouraging relapse and NRM rates with TLI/ATG-based NMA conditioning, but with higher than previously reported rates of acute and chronic GVHD, underscoring the need for novel strategies designed to effectively prevent GVHD.

Lithium in the public water supply and suicide mortality in Texas.

There is increasing evidence from ecological studies that lithium levels in drinking water are inversely associated with suicide mortality. Previous studies of this association were criticized for using inadequate statistical methods and neglecting socioeconomic confounders. This study evaluated the association between lithium levels in the public water supply and county-based suicide rates in Texas. A state-wide sample of 3123 lithium measurements in the public water supply was examined relative to suicide rates in 226 Texas counties. Linear and Poisson regression models were adjusted for socioeconomic factors in estimating the association. Lithium levels in the public water supply were negatively associated with suicide rates in most statistical analyses. The findings provide confirmatory evidence that higher lithium levels in the public drinking water are associated with lower suicide rates. This association needs clarification through examination of possible neurobiological effects of low natural lithium doses.