Outcomes and Health Care Resource Utilization of Adult Bacterial Meningitis in the United States.

OBJECTIVE: To examine the longitudinal health care resource utilization, in-hospital mortality, and incidence of downstream complications of bacterial meningitis in the United States. METHODS: Using IBM MarketScan, we retrieved data on adult patients with a diagnosis of bacterial meningitis admitted to a US hospital between 2008 and 2015. Patients were stratified into groups (1) with/without prior head trauma/neurosurgical complications, (2) nosocomial/community acquisition, and (3) Gram-negative/positive bacteria. Cost data were collected for up to 2 years and analyzed with descriptive statistics and longitudinal modeling. RESULTS: Among 4,496 patients with bacterial meningitis, 16.5% and 4.6% had preceding neurosurgical complications and head injuries, respectively. Lumbar punctures were performed in 37.3% of patients without prior trauma/complications who went on to develop nosocomial meningitis, and those with prior head injuries or complications had longer initial hospital stays (17.0 days vs 8.0 days). Within a month of diagnosis, 29.2% of patients with bacterial meningitis had experienced downstream complications, most commonly hydrocephalus (12.7%). The worst 30-day mortality was due to tuberculous (12.3%) and streptococcal meningitis (7.2%). Overall, prior head trauma and complications were associated with higher costs. Community-acquired bacterial meningitis had lower median baseline costs relative to the nosocomial group (no head trauma/complication: $17,152 vs $82,778; head trauma/complication: $92,428 vs $168,309) but higher median costs within 3 months of diagnosis (no head trauma/complication: $47,911 vs $34,202; head trauma/complication: $89,207 vs $58,947). All costs demonstrated a sharp decline thereafter. CONCLUSIONS: Bacterial meningitis remains costly and devastating, especially for those who experience traumatic head injuries or have a complicated progress after neurosurgery.

Deep brain stimulation and electromagnetic interference.

Deep brain stimulation (DBS) has evolved into an approved and efficacious treatment for movement, obsessive-compulsive, and epilepsy disorders that are refractory to medical therapy, with current investigation into other disease conditions. However, there are unintentional and intentional sources of external electromagnetic interference (EMI) that can lead to either malfunctioning or damaged DBS devices, as well as injury to human tissue. Comprehensive studies and guidelines on such topics in the medical literature are scarce. Herein, we review the principles behind EMI, as well as the various potential sources of interference, both unintentional (e.g. stray EMI fields) and intentional (e.g. MRI scans, "brainjacking"). Additionally, we employ the Manufacturer and User Device Facility Experience (MAUDE) database to assess real-world instances of EMI (e.g., airport body scanners, magnetic resonance imaging (MRI), and electrosurgery) affecting DBS devices commonly implanted in the United States (US).

Paediatric bacterial meningitis in the USA: outcomes and healthcare resource utilization of nosocomial versus community-acquired infection.

Introduction. Paediatric bacterial meningitis remains a costly disease, both financially and clinically.Hypothesis/Gap Statement. Previous epidemiological and cost studies of bacterial meningitis (BM) have largely focused on adult populations or single pathogens. There have been few recent, large-scale studies of pediatric BM in the USA.Aim. We examined healthcare resource utilization (HCRU) and associated morbidity and mortality of community-acquired versus nosocomial bacterial infections in children across the USA.Methodology. The IBM MarketScan Research databases were used to identify patients <18 years old admitted to USA hospitals from 2008 to 2015 with a primary diagnosis of BM. Cases were categorized as either community-acquired or nosocomial. HCRU, post-diagnosis neurosurgical procedures, 30-day in-hospital mortality, and complications were compared between groups. Multivariable regression adjusted for sex, age and Gram staining was used to compare costs of nosocomial versus community-acquired infections over time.Results. We identified 1928 cases of paediatric BM without prior head trauma or neurological/systemic complications. Of these, 15.4 % were nosocomial and 84.6 % were community-acquired infections. After diagnostic lumbar puncture (37.1 %), the most common neurosurgical procedure was placement of ventricular catheter (12.6 %). The 30-day complication rates for nosocomial and community-acquired infections were 40.5 and 45.9 %, respectively. The most common complications were hydrocephalus (20.8 %), intracranial abscess (8.8 %) and cerebral oedema (8.1 %). The 30-day in-hospital mortality rates for nosocomial and community-acquired infections were 2.7 and 2.8 %, respectively.Median length of admission was 14.0 days (Q1: 7 days, Q3: 26 days). Median 90-day cost was $40 861 (Q1: $11 988, Q3: $114,499) for the nosocomial group and $56 569 (Q1: $26 127, Q3: $142 780) for the community-acquired group. In multivariable regression, the 90-day post-diagnosis total costs were comparable between groups (cost ratio: 0.89; 95 % CI: 0.70 to 1.13), but at 2 years post-diagnosis, the nosocomial group was associated with 137 % higher costs (CR: 2.37, 95 % CI: 1.51 to 3.70).Conclusion. In multivariable analysis, nosocomial infections were associated with significantly higher long-term costs up to 2 years post-infection. Hydrocephalus, intracranial epidural abscess and cerebral oedema were the most common complications, and lumbar punctures and ventricular catheter placement were the most common neurosurgical procedures. This study represents the first nation-wide, longitudinal comparison of the outcomes and considerable HCRU of nosocomial versus community-acquired paediatric BM, including characterization of complications and procedures contributing to the high costs of these infections.

Health care resource utilization and treatment of leptomeningeal carcinomatosis in the United States.

BACKGROUND: The economic burden of cancer in the United States is substantial, and better understanding it is essential in informing health care policy and innovation. Leptomeningeal carcinomatosis (LC) represents a late complication of primary cancer spreading to the leptomeninges. METHODS: The IBM MarketScan Research databases were queried for adults diagnosed with LC from 2001 to 2015, secondary to 4 primary cancers (breast, lung, gastrointestinal, and melanoma). Health care resource utilization (HCRU) and treatment utilization were quantified at baseline (1-year pre-LC diagnosis) and 30, 90, and 365 days post-LC diagnosis. RESULTS: We identified 4961 cases of LC (46.3% breast cancer, 34.8% lung cancer, 13.5% gastrointestinal cancer, and 5.4% melanoma). The median age was 57.0 years, with 69.7% female and 31.1% residing in the South. Insurance status included commercial (71.1%), Medicare (19.8%), and Medicaid (9.1%). Median follow-up was 66.0 days (25th percentile: 24.0, 75th percentile: 186.0) and total cumulative costs were highest for the gastrointestinal subgroup ($167 768) and lowest for the lung cancer subgroup ($145 244). There was considerable variation in the 89.6% of patients who used adjunctive treatments at 1 year, including chemotherapy (64.3%), radiotherapy (57.6%), therapeutic lumbar puncture (31.5%), and Ommaya reservoir (14.5%). The main cost drivers at 1 year were chemotherapy ($62 026), radiation therapy ($37 076), and specialty drugs ($29 330). The prevalence of neurologic impairments was 46.9%, including radiculopathy (15.0%), paresthesia (12.3%), seizure episode/convulsive disorder not otherwise specified (11.0%), and ataxia (8.0%). CONCLUSIONS: LC is a devastating condition with an overall poor prognosis. We present the largest study of LC in this real-world study, including current treatments, with an emphasis on HCRU. There is considerable variation in the treatment of LC and significant health care costs.

Impact of Spinal Cord Stimulation on Opioid Dose Reduction: A Nationwide Analysis.

BACKGROUND: Opioid misuse in the USA is an epidemic. Utilization of neuromodulation for refractory chronic pain may reduce opioid-related morbidity and mortality, and associated economic costs. OBJECTIVE: To assess the impact of spinal cord stimulation (SCS) on opioid dose reduction. METHODS: The IBM MarketScan® database was retrospectively queried for all US patients with a chronic pain diagnosis undergoing SCS between 2010 and 2015. Opioid usage before and after the procedure was quantified as morphine milligram equivalents (MME). RESULTS: A total of 8497 adult patients undergoing SCS were included. Within 1 yr of the procedure, 60.4% had some reduction in their opioid use, 34.2% moved to a clinically important lower dosage group, and 17.0% weaned off opioids entirely. The proportion of patients who completely weaned off opioids increased with decreasing preprocedure dose, ranging from 5.1% in the >90 MME group to 34.2% in the ≤20 MME group. The following variables were associated with reduced odds of weaning off opioids post procedure: long-term opioid use (odds ratio [OR]: 0.26; 95% CI: 0.21-0.30; P < .001), use of other pain medications (OR: 0.75; 95% CI: 0.65-0.87; P < .001), and obesity (OR: 0.75; 95% CI: 0.60-0.94; P = .01). CONCLUSION: Patients undergoing SCS were able to reduce opioid usage. Given the potential to reduce the risks of long-term opioid therapy, this study lays the groundwork for efforts that may ultimately push stakeholders to reduce payment and policy barriers to SCS as part of an evidence-based, patient-centered approach to nonopioid solutions for chronic pain.

Painful diabetic peripheral neuropathy: Health care costs and complications from 2010 to 2015.

OBJECTIVE: To quantify health care resource utilization and risk of complications in painful diabetic peripheral neuropathy (pDPN). METHODS: Adult patients diagnosed with diabetes mellitus or diabetic peripheral neuropathy (DPN) were identified in MarketScan from January 2010 to December 2015. Subgroups (pDPN and nonpainful DPN) were based on the use of pain medications 6 months before a new indexed diagnosis and 1 year thereafter. Health care costs were collected for up to 5 years, and complications charted for those with at least 1 and 2 years of follow-up. Complication comparisons were made using χ2 or Fisher exact tests, and a multivariable regression cost model was fit with log link function using generalized estimating equations. RESULTS: Among 360,559 patients with diabetes (62 ± 14 years; 54.3% female), 84,069 (23.3%) developed pDPN, 17,267 (4.8%) experienced nonpainful DPN, and the majority (259,223, 71.9%) were controls with diabetes without neuropathy. At baseline, costs associated with pDPN patients were 20% higher than diabetic controls (95% confidence interval [CI] [1.19, 1.21], p < 0.001), which increased to 31% in the 5th year (95% CI [1.27, 1.34], p < 0.001). Patients with pDPN had 200%, 356%, and 224% of the odds of using opioids, anticonvulsants, and antidepressants, respectively, compared with diabetic controls. The amputation risk in the pDPN subgroup was 16.24 times that of diabetic controls (95% CI [2.15, 122.72], p = 0.0003), and 87% more patients with pDPN experienced lower extremity infections (95% CI [1.43, 2.46], p < 0.0001) within a year. Within 2 years, 2.2% of patients with pDPN had falls and fall-related injuries compared with 1.1% of diabetic controls (p < 0.0001). CONCLUSIONS: Our study characterizes a substantial pDPN cohort in the United States, demonstrating considerable morbidity and economic costs.

The longitudinal health economic impact of viral encephalitis in the United States.

Introduction. Previous studies of viral encephalitis have focused on acute costs, estimating incidence at 7.3 per 100 000 and total US annual charges at $2 billion in 2010.Aim. We aim to quantify the most updated longitudinal health economic impact of viral encephalitis in the USA from 2008 to 2015.Methodology. Data on patients diagnosed with viral encephalitis were obtained from the Truven Health Analytics MarketScan database. Patients with a primary diagnosis of viral encephalitis, from herpetic viruses and other viral aetiologies (e.g. West Nile fever) were included in the analysis. Data concerning healthcare resource utilization, inpatient mortality, length of stay and accrued healthcare costs were collected for up to 5 years.Results. Among 3985 patients with continuous enrolment for 13 months prior to the encephalitis diagnosis, more non-herpes simplex encephalitis (61.7 %) than herpes simplex encephalitis (HSE; 38.3 %) cases were recorded, with the majority concentrated in the southern USA (29.2 %). One-year inpatient mortality was 6.2 %, which over a 5-year period rose to 8.9 % for HSE and 5.8 % for all other viral encephalitides. HSE resulted in longer cumulative stays in the hospital (11 days vs. 4 days; P=0.0025), and accrued 37 % higher first-year costs, after adjusting for known confounders [P<0.001, cost ratio=1.37, 95 % confidence interval (1.20, 1.57)]. Additionally, HSE was associated with greater 5-year cumulative median charges ($125 338 vs. $82 317, P=0.0015).Conclusion. The health economic impact and long-term morbidity of viral encephalitis in the USA are substantial.

Healthcare Economics of Hydrocephalus After Aneurysmal Subarachnoid Hemorrhage in the United States.

Hydrocephalus is one of the most common sequelae after aneurysmal subarachnoid hemorrhage (aSAH), and it is a large contributor to the condition's high rates of readmission and mortality. Our objective was to quantify the healthcare resource utilization (HCRU) and health economic burden incurred by the US health system due to post-aSAH hydrocephalus. The Truven Health MarketScan® Research database was used to retrospectively quantify the prevalence and HCRU associated with hydrocephalus in aSAH patients undergoing surgical clipping or endovascular coiling from 2008 to 2015. Multivariable longitudinal analysis was conducted to model the relationship between annual cost and hydrocephalus status. In total, 2374 patients were included; hydrocephalus was diagnosed in 959 (40.4%). Those with hydrocephalus had significantly longer initial lengths of stay (median 19.0 days vs. 12.0 days, p < .001) and higher 30-day readmission rates (20.5% vs. 10.4%, p < .001). With other covariates held fixed, in the first 90 days after aSAH diagnosis, the average cost multiplier relative to annual baseline for hydrocephalus patients was 24.60 (95% CI, 20.13 to 30.06; p < .001) whereas for non-hydrocephalus patients, it was 11.52 (95% CI, 9.89 to 13.41; p < .001). The 5-year cumulative median total cost for the hydrocephalus group was $230,282.38 (IQR, 166,023.65 to 318,962.35) versus $174,897.72 (IQR, 110,474.24 to 271,404.80) for those without hydrocephalus. We characterize one of the largest cohorts of post-aSAH hydrocephalus patients in the USA. Importantly, the substantial health economic impact and long-term morbidity and costs from this condition are quantified and reviewed.

A temporal examination of calcium signaling in cancer- from tumorigenesis, to immune evasion, and metastasis.

BACKGROUND: Although the study of calcium (Ca2+) is classically associated with excitable cells such as myocytes or neurons, the ubiquity of this essential element in all cellular processes has led to interest in other cell types. The importance of Ca2+ to apoptosis, cell signaling, and immune activation is of special import in cancer. MAIN: Here we review the current understanding of Ca2+ in each of these processes vital to the initiation, spread, and drug resistance of malignancies. We describe the involvement of Ca2+, and Ca2+ related proteins in cell cycle checkpoints and Ca2+ dependent apoptosis and discuss their roles in cellular immortalization. The role of Ca2+ in inter-cellular communication is also discussed in relevance to tumor-stromal communication, angiogenesis, and tumor microinvasion. The role that Ca2+ plays in immune surveillance and evasion is also addressed. Finally, we discuss the possibility of targeting Ca2+ singling to address the most pressing topics of cancer treatment: metastatic disease and drug resistance. CONCLUSION: This review discusses the current understanding of Ca2+ in cancer. By addressing Ca2+ facilitated angiogenesis, immune evasion, metastasis, and drug resistance, we anticipate future avenues for development of Ca2+ as a nexus of therapy.