Mortality, neurodevelopmental impairments, and economic outcomes after invasive group B streptococcal disease in early infancy in Denmark and the Netherlands: a national matched cohort study.

BACKGROUND: Group B Streptococcus (GBS) disease is a leading cause of neonatal death, but its long-term effects have not been studied after early childhood. The aim of this study was to assess long-term mortality, neurodevelopmental impairments (NDIs), and economic outcomes after infant invasive GBS (iGBS) disease up to adolescence in Denmark and the Netherlands. METHODS: For this cohort study, children with iGBS disease were identified in Denmark and the Netherlands using national medical and administrative databases and culture results that confirmed their diagnoses. Exposed children were defined as having a history of iGBS disease (sepsis, meningitis, or pneumonia) by the age of 89 days. For each exposed child, ten unexposed children were randomly selected and matched by sex, year and month of birth, and gestational age. Mortality data were analysed with the use of Cox proportional hazards models. NDI data up to adolescence were captured from discharge diagnoses in the National Patient Registry (Denmark) and special educational support records (the Netherlands). Health care use and household income were also compared between the exposed and unexposed cohorts. FINDINGS: 2258 children-1561 in Denmark (born from Jan 1, 1997 to Dec 31, 2017) and 697 in the Netherlands (born from Jan 1, 2000 to Dec 31, 2017)-were identified to have iGBS disease and followed up for a median of 14 years (IQR 7-18) in Denmark and 9 years (6-11) in the Netherlands. 366 children had meningitis, 1763 had sepsis, and 129 had pneumonia (in Denmark only). These children were matched with 22 462 children with no history of iGBS disease. iGBS meningitis was associated with an increased mortality at age 5 years (adjusted hazard ratio 4·08 [95% CI 1·78-9·35] for Denmark and 6·73 [3·76-12·06] for the Netherlands). Any iGBS disease was associated with an increased risk of NDI at 10 years of age, both in Denmark (risk ratio 1·77 [95% CI 1·44-2·18]) and the Netherlands (2·28 [1·64-3·17]). A history of iGBS disease was associated with more frequent outpatient clinic visits (incidence rate ratio 1·93 [95% CI 1·79-2·09], p<0·0001) and hospital admissions (1·33 [1·27-1·38], p<0·0001) in children 5 years or younger. No differences in household income were observed between the exposed and unexposed cohorts. INTERPRETATION: iGBS disease, especially meningitis, was associated with increased mortality and a higher risk of NDIs in later childhood. This previously unquantified burden underlines the case for a maternal GBS vaccine, and the need to track and provide care for affected survivors of iGBS disease. FUNDING: The Bill & Melinda Gates Foundation. TRANSLATIONS: For the Dutch and Danish translations of the abstract see Supplementary Materials section.

Hospital utilization for orbital and intracranial complications of pediatric acute rhinosinusitis.

BACKGROUND: Orbital and intracranial complications of pediatric acute rhinosinusitis (ARS) are uncommon. With a risk of significant morbidity, hospital utilization and the financial burden of these entities are often high. We sought to assess utilization trends for complicated ARS and elucidate which factors influence cost. METHODOLOGY: Analysis of Kids' Inpatient Database (2006, 2009 and 2012). Children were selected based on diagnosis codes for ARS and grouped as: uncomplicated ARS, orbital complications (OC), or intracranial complications (IC). Patients with IC were subdivided into abscess (ICa), meningitis, or sinus thrombosis. Length of stay (LOS), cost and management information were analysed. Data presented as median [IQR]. RESULTS: A weighted total of 20,775 children were included. OC and IC were observed in 10.9% and 2.7% of these patients. LOS was longer for IC compared to OC (9 [8] v 4 [3]days, p < 0.001). Daily cost for IC was greater than OC ($2861 [4044] v $1683 [1187], p < 0.001), likely due to differences in need for surgery (IC 66.3% v OC 37.1%, p < 0.001). Within the ICa group, patients who received both otolaryngologic (ENT) and neurosurgery, compared to neurosurgery alone, had higher total cost ($41,474 [41,976] v $32,299 [18,235], p < 0.001) but similar LOS (12 [10] v 11 [9] days, p = 0.783). CONCLUSIONS: Children with IC required more surgery than their OC counterparts, resulting in a longer LOS and increased cost. Within the ICa group, the addition of ENT surgery to neurosurgery resulted in higher costs, but with a similar LOS. Considering the increased costs, the additional benefit of ENT surgery to those with children with IC should be investigated further.

Systematic Review on the Acute Cost-of-illness of Sepsis and Meningitis in Neonates and Infants.

BACKGROUND: Sepsis and meningitis in neonates and infants are a source of substantial morbidity, mortality and economic loss. The objective of this review is to estimate the acute costs associated with treating sepsis, meningitis and meningococcal septicemia, in neonates and infants, worldwide. METHODS: The electronic databases Medline, Embase and EconLit were searched and exported on November 24, 2018. Studies that reported an average hospitalization cost for confirmed cases of sepsis, meningitis or meningococcal septicemia were eligible for our review. Descriptive data were extracted and reported costs were inflated and converted. A narrative synthesis of the costs was conducted. RESULTS: Our review identified 20 studies reporting costs of sepsis, meningitis and/or meningococcal septicemia. Costs ranged from $55 to $129,632 for sepsis and from $222 to $33,635 for meningitis (in 2017 US dollars). One study estimated the cost of meningococcal septicemia to be $56,286. All reported costs were estimated from the perspective of the healthcare provider or payer. Most studies were from the United States, which also had the highest costs. Only a few studies were identified for low- and middle-income countries, which reported lower costs than high-income countries for both sepsis and meningitis. CONCLUSIONS: Sepsis and meningitis in neonates and infants are associated with substantial costs to the healthcare system and showed a marked difference across global income groups. However, more research is needed to inform costs in low- and middle-income settings and to understand the economic costs borne by families and wider society.

Acute Otitis Media and Associated Complications in United States Emergency Departments.

OBJECTIVE: Complications due to acute otitis media (AOM), while rare, are associated with significant morbidity and are not well characterized from an epidemiological perspective. We analyze the pattern of presentation and emergency department (ED) utilization in patients with AOM and associated complications. STUDY DESIGN: Retrospective analysis of the Nationwide Emergency Department Sample (NEDS) from 2009 to 2011. SETTING: Emergency Department. PATIENTS: Patients who presented with a primary diagnosis of AOM or acute mastoiditis. INTERVENTION: Diagnostic. MAIN OUTCOME MEASURES: NEDS was queried for patient encounters with a diagnosis of AOM or acute mastoiditis based on ICD-9 codes. Complications of severe infection, including petrositis, Gradenigo's syndrome, facial paresis, labyrinthitis, meningitis, intracranial abscess, venous sinus thrombosis, and cerebrospinal fluid leak, were assessed. Weighted estimates for demographics, types of complications, socioeconomic status, and trends over time were extracted. RESULTS: A weighted total of 5,811,127 ED visits were identified. The majority of patients were less than 18 years old (79.9%) with an average age of 10.1 years. Most were discharged (99.4%). There were 15,243 (0.26%) patients who presented with a complication. The most common complications were acute mastoiditis (0.16%), labyrinthitis (0.06%), and facial paresis (0.03%). Compared with patients with uncomplicated AOM, patients with complicated AOM were older (37 vs. 10-yr old), insured by Medicare (18% vs. 2.1%), and more likely to be admitted (43.6% vs. 0.4%) (p < 0.0001, for all comparisons). CONCLUSIONS: ED visits related to AOM or mastoiditis are common and complications are rare. An in-depth analysis on a national level is useful for assessing healthcare utilization trends.

An evidence-based approach to managing acute otitis media.

Acute otitis media is one of the most common pediatric illnesses; however, there is considerable controversy in its management. While most cases are treated with antibiotics, there is a growing concern regarding antibiotic overuse and subsequent drug resistance. Researchers in the Netherlands have developed a "watchful waiting" (ie, an observation approach) that has been successful in treating acute otitis media, although it has not gained widespread popularity in the United States. This review will summarize the latest research on diagnosing acute otitis media as well as different treatment regimens, including the efficacy of the watchful-waiting approach.

[Risk management in spinal anesthesia].

More than one hundred years have passed since Bier first succeeded in spinal anesthesia. Spinal anesthesia now spreads all over the world because it has many advantages. Spinal anesthesia requires both a simple technique and a small volume of drug, produces profound analgesia, and is devoid of systemic pharmacologic side effects. However, several complications after spinal anesthesia have been reported. Although some of them rarely occur, they cause serious consequences once they happen. Those include cardiac arrest, meningitis, intracranial subdural hematoma, spinal epidural hematoma and cauda equina syndrome. Patients should be informed in detail of the incidence, severity, and outcome of these complications, especially when alternative analgesic methods can be chosen. The prediction, early detection and prompt start of the treatment of the complications after spinal anesthesia are important to minimize the risk of adverse outcome.

Combined spinal epidural analgesia is the preferred technique for labour analgesia.

To justify its place as the preferred method of pain relief in labour, CSE must demonstrated a clear superiority over epidural analgesia. Looking at the relative efficacy of the two techniques failure rates appear to be equal. Speed of onset may be faster with an initial spinal injection although perhaps only clinically relevant in advanced labour where the quality of analgesia may sometimes be better. CSE would not seem to offer significant advantage in terms of mode of delivery or the ability to ambulate. The side effects of the technique are somewhat more concerning as CSE would appear to carry slightly greater risk than epidural analgesia, most notably in neurological sequelae and the effects of intrathecal opioids. Certainly CSE confers no benefit in terms of cost. What then is the place of CSE in labour analgesia? Its potential benefit makes it a reasonable option when there is a clear clinical advantage such as requests for analgesia in late labour or where maternal distress is extreme or where epidural analgesia has been ineffective. However even in such situations the slight increase in risk must be weighed against the possible advantage. Consequently the CSE cannot at the present time be recommended as the preferred option for labour analgesia.

Practice guideline for the treatment of coccidioidomycosis. Infectious Diseases Society of America.

Management of patients diagnosed with coccidioidomycosis involves defining the extent of infection and assessing host factors that predispose to disease severity. Patients with relatively localized acute pulmonary infections and no risk factors for complications often require only periodic reassessment to demonstrate resolution of their self-limited process. On the other hand, patients with extensive spread of infection or at high risk of complications because of immunosuppression or other preexisting factors require a variety of treatment strategies that may include antifungal therapy, surgical debridement, or both. Amphotericin B is often selected for treatment of patients with respiratory failure due to Coccidioides immitis or rapidly progressive coccidioidal infections. With other more chronic manifestations of coccidioidomycosis, treatment with fluconazole, itraconazole, or ketoconazole is common. Duration of therapy often ranges from many months to years, and, for some patients, chronic suppressive therapy is needed to prevent relapses.

[Review of claims from the Patient Insurance: spinal anesthesia is not completely without risks]. / Fallgenomgång från patientförsäkringen: ryggbedövning inte helt komplikationsfri.

The Patient Injury Claims Department in Sweden grants compensation to patients who have incurred injury in the national health service system. All claims involving spinal and epidural anaesthesia were studied during the period 1997-1999. Serious neurological complications were behind 29 out of 65 claims. These occurred more frequently after epidural anaesthesia (1:4,000) than after spinal anaesthesia (1:13,000) with the exclusion of obstetric epidural anaesthesia (1:40,000). Epidural haematoma occurred in 1:30,000 after epidural anaesthesia, in 1:200,000 after spinal anaesthesia. One epidural abscess occurred in 60,000 epidural anaesthesias, while five cases of meningitis occurred after spinal anaesthesia (1:40,000).

The learning curve in vestibular schwannoma surgery.

OBJECTIVE: This study aimed to examine the effect of surgical team experience on facial nerve function and complication rate in vestibular schwannoma surgery. STUDY DESIGN: The study design was a retrospective analysis of a case series. SETTING: The study was conducted at a tertiary referral center. PATIENTS: One hundred sixty consecutive patients undergoing vestibular schwannoma excision participated. INTERVENTION: Surgical excision of vestibular schwannoma via a translabyrinthine, middle cranial fossa, suboccipital, or combined approach was performed. MAIN OUTCOME MEASURES: Facial nerve function (House-Brackmann score) and complication rates including cerebrospinal fluid leak and meningitis compared by groups of 20 patients were measured. RESULTS: There was a statistically significant improvement in the number of patients achieving a House-Brackmann grade I result between the first 20 patients (35% House-Brackmann grade 1) and the ensuing 7 groups of 20 patients (74% House-Brackmann grade 1) by chi2 analysis. When considering House grades I and II together, there was no statistically significant difference in facial nerve function in the first 20 patients (80%) compared to the last 7 groups of 20 patients (88%) by Tukey's pairwise comparisons (p = 0.245). Mean tumor size was not significantly different in the groups studied (p = 0.54). The total cost of patient care declined over the study period; however, the wide case-to-case variance made it so that this trend was not statistically significant (p = 0.448). CONCLUSIONS: A learning curve of 20 patients was demonstrated by this study to have been necessary for attaining acceptable standards in the surgical removal of vestibular schwannomas by a new surgical team. The findings of this study may have implications for patient care and surgeon training.

Risk assessment of opportunistic bacterial pathogens in drinking water.

This study was undertaken to examine quantitatively the risks to human health posed by heterotrophic plate count (HPC) bacteria found naturally in ambient and potable waters. There is no clear-cut evidence that the HPC bacteria as a whole pose a public health risk. Only certain members are opportunistic pathogens. Using the four-tiered approach for risk assessment from the National Academy of Sciences, hazard identification, dose-response modeling, and exposure through ingestion of drinking water were evaluated to develop a risk characterization, which estimates the probability of infection for individuals consuming various levels of specific HPC bacteria. HPC bacteria in drinking water often include isolates from the following genera: Pseudomonas, Acinetobacter, Moraxella, Aeromonas, and Xanthomonas. Other bacteria that are commonly found are Legionella and Mycobacterium. All these genera contain species that are opportunistic pathogens which may cause serious diseases. For example, the three nonfermentative gram-negative rods most frequently isolated in the clinical laboratory are (1) Pseudomonas aeruginosa, (2) Acinetobacter, and (3) Xanthomonas maltophilia. P. aeruginosa is a major cause of hospital-acquired infections with a high mortality rate. Aeromonas is sometimes associated with wound infections and suspected to be a causative agent of diarrhea. Legionella pneumophila causes 4%-20% of cases of community-acquired pneumonia and has been ranked as the second or third most frequent cause of pneumonia requiring hospitalization. The number of cases of pulmonary disease associated with Mycobacterium avian is rapidly increasing and is approaching the incidence of M. tuberculosis in some areas. Moraxella can cause infections of the eye and upper respiratory tract. The oral infectious doses are as follows in animal and human test subjects: P. aeruginosa, 10(8)-10(9); A, hydrophila, > 10(10); M. avium, 10(4)-10(7); and X. maltophilia, 10(6)-10(9). The infectious dose for an opportunistic pathogen is lower for immunocompromised subjects or those on antibiotic treatment. These bacteria have been found in drinking water at the following frequencies: P. aeruginosa, < 1%-24%; Acinetobacter, 5%-38%; X. maltophilia, < 1%-2%; Aeromonas, 1%-27%; Moraxella, 10%-80%; M. avium, < 1%-50%; and L. pneumophila, 3%-33%. These data suggest that drinking water could be a source of infection for some of these bacteria. The risk characterization showed that risks of infection from oral ingestion ranged from a low of 7.3 x 10(-9) (7.3/billion) for low exposures to Aeromonas to higher risks predicted at high levels of exposure to Pseudomonas of 9 x 10(-2) (98/100). This higher risk was only predicted for individuals on antibiotics. Overall, the evidence suggests that specific members of HPC bacteria found in drinking water may be causative agents of both hospital- and community-acquired infections. However, the case numbers may be very low and the risks represent levels generally less than 1/10,000 for a single exposure to the bacterial agent. Future research needs include (1) determining the seasonal concentrations of these bacteria in drinking water, (2) conducting adequate dose-response studies in animal subjects or human volunteers, (3) determining the health risks for an individual with multiple exposures to the opportunistic pathogens, and (4) evaluating the increase in host susceptibility conferred by antibiotic use or immunosuppression.

Thoracolumbar infections in penetrating injuries to the spine.

A detailed review of the TJUH experience and the published literature on gunshot and stab wounds to the spine has been presented. The following statements are supported. (1) Military (high-velocity) gunshot wounds are distinct entities, and the management of these injuries cannot be carried over to civilian (low-velocity) handgun wounds. (2) Gunshot wounds with a resultant neurologic deficit are much more common than stab wounds and carry a worse prognosis. (3) Spinal infections are rare following a penetrating wound of the spine and a high index of suspicion is needed to detect them. (4) Extraspinal infections (septic complications) are much more common than spinal infections following a gunshot or stab wound to the spine. (5) Steroids are of no use in gunshot wounds to the spine. In fact, there was an increased incidence of spinal and extraspinal infections without a difference in neurologic outcome compared with those who did not receive steroids. (6) Spinal surgery is rarely indicated in the management of penetrating wounds of the spine. The recommendations for treatment at TJUH of victims of gunshot or stab wounds with a resultant neurologic deficit are as follows. (1) Spine surgery is indicated for progressive neurologic deficits and persistent cerebrospinal fluid leaks (particularly if meningitis is present), although these situations rarely occur. (2) Consider spine surgery for incomplete neurologic deficits with radiographic evidence of neural compression. Particularly in the cauda equina region, these surgeries may be technically demanding because of frequent dural violations and nerve root injuries/extrusions. These cases must be evaluated in an individual case-by-case manner. The neurologic outcomes of patients with incomplete neurologic deficits at TJUH who underwent acute spine surgery (usually for neural compression secondary to a bullet) were worse than the outcomes for the patients who did not have spine surgery. A selection bias against the patients undergoing spine surgery was likely present as these patients had evidence of ongoing neural compression. (3) A high index of suspicion is necessary to detect spinal and extraspinal infections. (4) Do not use glucorticoid steroids for gunshot wound victims. (5) Conservative (nonoperative) treatment with intravenous broad spectrum antibiotics and tetanus prophylaxis is the sole therapy indicated in the majority of patients who sustain a penetrating wound to the thoracic or lumbar spines.

The morbidity of long-term seizure monitoring using subdural strip electrodes.

The authors report a prospective study of morbidity associated with long-term seizure monitoring using subdural strip electrodes. Three hundred fifty patients were divided into two groups: 175 patients received antibiotics intravenously during the entire period that the electrodes were implanted, and 175 patients received one dose of antibiotics on the morning of surgery. In the group given continuous antibiotic coverage there were two cases of meningitis, both treated without sequelae. In the group receiving one dose of antibiotics, one patient had a brain abscess and three had superficial wound infections. There were no other instances of major morbidity or mortality in either group of patients. The total morbidity rate for both serious and minor complications was 0.85%.

Assessment of antibiotic efficacy in acute bacterial meningitis.

Currently, antibiotic efficacy in acute bacterial meningitis is evaluated in several stages. First, animals are used to assess antibiotic penetration into cerebrospinal fluid (CSF) in the absence and presence of an inflammatory stimulus. Second, concentrations of drug are correlated to in vitro killing studies. Third, clinical evaluations compare the new drugs to currently available antimicrobic--but drug failures nevertheless occur, e.g. the experiences with cephalosporins and aminoglycosides. We propose that brain tissue levels of antibiotics are an additional parameter to be monitored. Drugs that penetrate the brain substance should yield higher ventricular concentrations than drugs that penetrate the choroid plexus alone. A protective benefit may also be afforded to brain tissue per se. Experience with chloramphenicol, which penetrates the blood-brain barrier, supports these concepts; so also, do the failures with cephalosporins and aminoglycosides which, despite high CSF concentrations of these agents, afford evidence that currently monitored parameters are inadequate predictors of therapeutic efficacy.

Amphotericin pharmacophobia.

Five cases are described in which fear of the possibly hazardous effects of giving amphotericin to patients with kidney disease resulted in death from progressive infection by an amphotericin-sensitive fungus (Cryptococcus neoformans in three cases, Blastomyces dermatitidis in one case, and Histoplasma capsulatum in one case).