US Food and Drug Administration regulatory pesticide residue monitoring of human foods: 2009-2017.

Pesticides such as insecticides, fungicides, and herbicides can protect crops from insects, fungi, weeds, and other pests but must be applied following label instructions so that the pesticide residues in human and animal foods do not exceed maximum residue limits (MRLs, known in the US as pesticide tolerances). The US Food and Drug Administration (FDA) collects and tests foods for pesticide residues to enforce compliance with tolerances and publishes annual reports on pesticide testing results. In this study, results for over 56,000 human food samples collected and analysed under the FDA pesticide residue monitoring programme between fiscal years (FY) 2009 to 2017 were reviewed to identify trends not apparent in annual reports. The overwhelming majority of these samples, 98.0% of domestic and 90.9% of import human foods, were compliant with federal standards. Although herbicides may be more widely used, the 10 most frequently detected residues were insecticides and fungicides. On a yearly basis, the violation rate for imported samples is 3-5 times higher than the rate for domestic samples. The import violation rate increased over time, as did the number of residues detected. Targeted sampling of foods with higher commodity-specific violation rates appears to be a major contributor to the increased violation rate. Mismatches between US tolerances and international MRLs can lead to violations; this was especially marked for rice. Overall, the majority of violations are due to residues of pesticides not authorised for use in the US (lack of tolerances). While DDT continues to persist in the environment and was found in 2.2% of domestic samples and 0.6% of imported samples, 42.3% of DDT-positive samples were below the limit of quantitation. The trends and analyses identified in this paper may help FDA plan future sampling and continue to protect the food supply.

Prevalence of Cronobacter spp. and Salmonella in Milk Powder Manufacturing Facilities in the United States.

ABSTRACT: The U.S. Food and Drug Administration (FDA) conducted a sampling assignment in 2014 to ascertain the prevalence of Cronobacter spp. and Salmonella in the processing environment of facilities manufacturing milk powder. Cronobacter was detected in the environment of 38 (69%) of 55 facilities. The average prevalence of Cronobacter in 5,671 subsamples (i.e., swabs and sponges from different facility locations) was 4.4%. In the 38 facilities where Cronobacter was detected, the average prevalence of positive environmental subsamples was 6.25%. In 20 facilities where zone information of the sampling location was complete, Cronobacter was most frequently detected in zone 4, followed by zone 3, then zone 2, with zone 1 yielding the lowest percentage of positive samples. The prevalence of Cronobacter across the zones was statistically different (P < 0.05). There was no significant association between product type (i.e., lactose, whey products, buttermilk powder, and nonfat dried milk) and prevalence of Cronobacter in the facility. Salmonella was detected in the environment of three (5.5%) of the 55 facilities; all three facilities produced dried whey product. The overall prevalence of Salmonella in 5,714 subsamples was 0.16%. In facilities in which Salmonella was detected, the average prevalence was 2.5%. Salmonella was most frequently detected in zone 4, followed by zone 3. Salmonella was not detected in zone 1 or zone 2. The disparity between Salmonella and Cronobacter prevalence indicates that additional measures may be required to reduce or eliminate Cronobacter from the processing environment.

Cervicomedullary tumors in children.

OBJECT: Cervicomedullary tumors (CMTs) represent a heterogeneous group of intrinsic neoplasms that are typically low grade and generally carry a good prognosis. This single-institution study was undertaken to document the outcomes and current treatment philosophy for these challenging neoplasms. METHODS: The charts of all pediatric patients with CMTs who received treatment at St. Jude Children's Research Hospital between January 1988 and May 2013 were retrospectively reviewed. Demographic, surgical, clinical, radiological, pathological, and survival data were collected. Treatment-free survival and overall survival were estimated, and predictors of recurrence were analyzed. RESULTS: Thirty-one children (16 boys, 15 girls) with at least 12 months of follow-up data were identified. The median age at diagnosis was 6 years (range 7 months-17 years) and the median follow-up was 4.3 years. Low-grade tumors (Grade I or II) were present in 26 (84%) patients. Thirty patients underwent either a biopsy alone or resection, with the majority of patients undergoing biopsy only (n = 12, 39%) or subtotal resection (n = 14, 45%). Only 4 patients were treated solely with resection; 21 patients received radiotherapy alone or in combination with other treatments. Recurrent tumor developed in 14 children (45%) and 4 died as a result of their malignancy. A high-grade pathological type was the only independent variable that predicted recurrence. The 5- and 10-year treatment-free survival estimates are 64.7% and 45.3%, respectively. The 5- and 10-year overall survival estimate is 86.7%. CONCLUSIONS: Children with CMTs typically have low-grade neoplasms and consequently long-term survival, but high risk of recurrence. Therapy should be directed at achieving local tumor control while preserving and even restoring neurological function.

Bibliometric evaluation of pediatric neurosurgery in North America.

OBJECT: The application of bibliometric techniques to academic neurosurgery has been the focus of several recent publications. The authors provide here a detailed analysis of all active pediatric neurosurgeons in North America and their respective departments. METHODS: Using Scopus and Google Scholar, a bibliometric profile for every known active pediatric neurosurgeon in North America was created using the following citation metrics: h-, contemporary h-, g-, and e-indices and the m-quotient. Various subgroups were compared. Departmental productivity from 2008 through 2013 was measured, and departments were ranked on the basis of cumulative h- and e-indices and the total number of publications and citations. Lorenz curves were created, and Gini coefficients were calculated for all departments with 4 or more members. RESULTS: Three hundred twelve pediatric neurosurgeons (260 male, 52 female) were included for analysis. For the entire group, the median h-index, m-quotient, contemporary h-, g-, and e-indices, and the corrected g- and e-indices were 10, 0.59, 7, 18, 17, 1.14, and 1.01, respectively; the range for each index varied widely. Academic pediatric neurosurgeons associated with fellowship programs (compared with unassociated neurosurgeons), academic practitioners (compared with private practitioners), and men (compared with women) had superior measurements. There was no significant difference between American and Canadian pediatric neurosurgeons. The mean Gini coefficient for publications was 0.45 (range 0.18-0.70) and for citations was 0.53 (range 0.25-0.80). CONCLUSIONS: This study represents the most exhaustive evaluation of academic productivity for pediatric neurosurgeons in North America to date. These results should serve as benchmarks for future studies.

A meta-analysis of spinal surgical site infection and vancomycin powder.

OBJECT: Surgical site infection (SSI) is a serious and costly complication of spinal surgery. There have been several conflicting reports on the use of intrawound vancomycin powder in decreasing SSI in spine surgery. The purpose of this study is to answer the question: "Does intrawound vancomycin powder reduce the rate of SSIs in spine surgery?" METHODS: A comprehensive search of multiple electronic databases and bibliographies was conducted to identify clinical studies that evaluated the rates of SSI with and without the use of intrawound vancomycin powder in spine surgery. Independent reviewers extracted data and graded the quality of each paper that met inclusion criteria. A random effects meta-analysis was then performed. RESULTS: The search identified 9 retrospective cohort studies (Level III evidence) and 1 randomized controlled trial (Level II evidence). There were 2574 cases and 106 infections in the control group (4.1%) and 2518 cases and 33 infections (1.3%) in the treatment group, yielding a pooled absolute risk reduction and relative risk reduction of 2.8% and 68%, respectively. The meta-analysis revealed the use of vancomycin powder to be protective in preventing SSI (relative risk = 0.34, 95% confidence interval 0.17-0.66, p = 0.021). The number needed to treat to prevent 1 SSI was 36. A subgroup analysis found that patients who had implants had a reduced risk of SSI with vancomycin powder (p = 0.023), compared with those who had noninstrumented spinal operations (p = 0.226). CONCLUSIONS: This meta-analysis suggests that the use of vancomycin powder may be protective against SSI in open spinal surgery; however, the exact population in which it should be used is not clear. This benefit may be most appreciated in higher-risk populations or in facilities with a high baseline rate of infection.

Case-control studies in neurosurgery.

OBJECT: Observational studies, such as cohort and case-control studies, are valuable instruments in evidence-based medicine. Case-control studies, in particular, are becoming increasingly popular in the neurosurgical literature due to their low cost and relative ease of execution; however, no one has yet systematically assessed these types of studies for quality in methodology and reporting. METHODS: The authors performed a literature search using PubMed/MEDLINE to identify all studies that explicitly identified themselves as "case-control" and were published in the JNS Publishing Group journals (Journal of Neurosurgery, Journal of Neurosurgery: Pediatrics, Journal of Neurosurgery: Spine, and Neurosurgical Focus) or Neurosurgery. Each paper was evaluated for 22 descriptive variables and then categorized as having either met or missed the basic definition of a case-control study. All studies that evaluated risk factors for a well-defined outcome were considered true case-control studies. The authors sought to identify key features or phrases that were or were not predictive of a true case-control study. Those papers that satisfied the definition were further evaluated using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist. RESULTS: The search detected 67 papers that met the inclusion criteria, of which 32 (48%) represented true case-control studies. The frequency of true case-control studies has not changed with time. Use of odds ratios (ORs) and logistic regression (LR) analysis were strong positive predictors of true case-control studies (for odds ratios, OR 15.33 and 95% CI 4.52-51.97; for logistic regression analysis, OR 8.77 and 95% CI 2.69-28.56). Conversely, negative predictors included focus on a procedure/intervention (OR 0.35, 95% CI 0.13-0.998) and use of the word "outcome" in the Results section (OR 0.23, 95% CI 0.082-0.65). After exclusion of nested case-control studies, the negative correlation between focus on a procedure/intervention and true case-control studies was strengthened (OR 0.053, 95% CI 0.0064-0.44). There was a trend toward a negative association between the use of survival analysis or Kaplan-Meier curves and true case-control studies (OR 0.13, 95% CI 0.015-1.12). True case-control studies were no more likely than their counterparts to use a potential study design "expert" (OR 1.50, 95% CI 0.57-3.95). The overall average STROBE score was 72% (range 50-86%). Examples of reporting deficiencies were reporting of bias (28%), missing data (55%), and funding (44%). CONCLUSIONS: The results of this analysis show that the majority of studies in the neurosurgical literature that identify themselves as "case-control" studies are, in fact, labeled incorrectly. Positive and negative predictors were identified. The authors provide several recommendations that may reverse the incorrect and inappropriate use of the term "case-control" and improve the quality of design and reporting of true case-control studies in neurosurgery.

Methodology and reporting of meta-analyses in the neurosurgical literature.

OBJECT: Neurosurgeons are inundated with vast amounts of new clinical research on a daily basis, making it difficult and time-consuming to keep up with the latest literature. Meta-analysis is an extension of a systematic review that employs statistical techniques to pool the data from the literature in order to calculate a cumulative effect size. This is done to answer a clearly defined a priori question. Despite their increasing popularity in the neurosurgery literature, meta-analyses have not been scrutinized in terms of reporting and methodology. METHODS: The authors performed a literature search using PubMed/MEDLINE to locate all meta-analyses that have been published in the JNS Publishing Group journals (Journal of Neurosurgery, Journal of Neurosurgery: Pediatrics, Journal of Neurosurgery: Spine, and Neurosurgical Focus) or Neurosurgery. Accepted checklists for reporting (PRISMA) and methodology (AMSTAR) were applied to each meta-analysis, and the number of items within each checklist that were satisfactorily fulfilled was recorded. The authors sought to answer 4 specific questions: Are meta-analyses improving 1) with time; 2) when the study met their definition of a meta-analysis; 3) when clinicians collaborated with a potential expert in meta-analysis; and 4) when the meta-analysis was the only focus of the paper? RESULTS: Seventy-two meta-analyses were published in the JNS Publishing Group journals and Neurosurgery between 1990 and 2012. The number of published meta-analyses has increased dramatically in the last several years. The most common topics were vascular, and most were based on observational studies. Only 11 papers were prepared using an established checklist. The average AMSTAR and PRISMA scores (proportion of items satisfactorily fulfilled divided by the total number of eligible items in the respective instrument) were 31% and 55%, respectively. Major deficiencies were identified, including the lack of a comprehensive search strategy, study selection and data extraction, assessment of heterogeneity, publication bias, and study quality. Almost one-third of the papers did not meet our basic definition of a meta-analysis. The quality of reporting and methodology was better 1) when the study met our definition of a meta-analysis; 2) when one or more of the authors had experience or expertise in conducting a meta-analysis; 3) when the meta-analysis was not conducted alongside an evaluation of the authors' own data; and 4) in more recent studies. CONCLUSIONS: Reporting and methodology of meta-analyses in the neurosurgery literature is excessively variable and overall poor. As these papers are being published with increasing frequency, neurosurgical journals need to adopt a clear definition of a meta-analysis and insist that they be created using checklists for both reporting and methodology. Standardization will ensure high-quality publications.

An analysis of publication productivity for 1225 academic neurosurgeons and 99 departments in the United States.

OBJECT: Bibliometrics is defined as the study of statistical and mathematical methods used to quantitatively analyze scientific literature. The application of bibliometrics in neurosurgery is in its infancy. The authors calculate a number of publication productivity measures for almost all academic neurosurgeons and departments within the US. METHODS: The h-index, g-index, m-quotient, and contemporary h-index (hc-index) were calculated for 1225 academic neurosurgeons in 99 (of 101) programs listed by the Accreditation Council for Graduate Medical Education in January 2013. Three currently available citation databases were used: Google Scholar, Scopus, and Web of Science. Bibliometric profiles were created for each surgeon. Comparisons based on academic rank (that is, chairperson, professor, associate, assistant, and instructor), sex, and subspecialties were performed. Departments were ranked based on the summation of individual faculty h-indices. Calculations were carried out from January to February 2013. RESULTS: The median h-index, g-index, hc-index, and m-quotient were 11, 20, 8, and 0.62, respectively. All indices demonstrated a positive relationship with increasing academic rank (p < 0.001). The median h-index was 11 for males (n = 1144) and 8 for females (n = 81). The h-index, g-index and hc-index significantly varied by sex (p < 0.001). However, when corrected for academic rank, this difference was no longer significant. There was no difference in the m-quotient by sex. Neurosurgeons with subspecialties in functional/epilepsy, peripheral nerve, radiosurgery, neuro-oncology/skull base, and vascular have the highest median h-indices; general, pediatric, and spine neurosurgeons have the lowest median h-indices. By summing the manually calculated Scopus h-indices of all individuals within a department, the top 5 programs for publication productivity are University of California, San Francisco; Barrow Neurological Institute; Johns Hopkins University; University of Pittsburgh; and University of California, Los Angeles. CONCLUSIONS: This study represents the most detailed publication analysis of academic neurosurgeons and their programs to date. The results for the metrics presented should be viewed as benchmarks for comparison purposes. It is our hope that organized neurosurgery will adopt and continue to refine bibliometric profiling of individuals and departments.

A correlation between National Institutes of Health funding and bibliometrics in neurosurgery.

OBJECTIVE: The relationship between metrics, such as the h-index, and the ability of researchers to generate funding has not been previously investigated in neurosurgery. This study was performed to determine whether a correlation exists between bibliometrics and National Institutes of Health (NIH) funding data among academic neurosurgeons. METHODS: The h-index, m-quotient, g-index, and contemporary h-index were determined for 1225 academic neurosurgeons from 99 (of 101) departments. Two databases were used to create the citation profiles, Google Scholar and Scopus. The NIH Research Portfolio Online Reporting Tools Expenditures and Reports tool was accessed to obtain career grant funding amount, grant number, year of first grant award, and calendar year of grant funding. RESULTS: Of the 1225 academic neurosurgeons, 182 (15%) had at least 1 grant with a fully reported NIH award profile. Bibliometric indices were all significantly higher for those with NIH funding compared to those without NIH funding (P < .001). The contemporary h-index was found to be significantly predictive of NIH funding (P < .001). All bibliometric indices were significantly associated with the total number of grants, total award amount, year of first grant, and duration of grants in calendar years (bivariate correlation, P < .001) except for the association of m-quotient with year of first grant (P = .184). CONCLUSIONS: Bibliometric indices are higher for those with NIH funding compared to those without, but only the contemporary h-index was shown to be predictive of NIH funding. Among neurosurgeons with NIH funding, higher bibliometric scores were associated with greater total amount of funding, number of grants, duration of grants, and earlier acquisition of their first grant.

Pediatric hydrocephalus: systematic literature review and evidence-based guidelines. Part 6: Preoperative antibiotics for shunt surgery in children with hydrocephalus: a systematic review and meta-analysis.

OBJECT: The objective of this systematic review and meta-analysis was twofold: to answer the question "What is the evidence for the effectiveness of prophylactic intravenous antibiotics for infection prevention in shunt surgery?" and to make treatment recommendations based on the available evidence. METHODS: The US National Library of Medicine PubMed/MEDLINE database and the Cochrane Database of Systematic Reviews were queried using MeSH headings and key words relevant to prophylactic antibiotic use in children undergoing a shunt operation. Abstracts were reviewed to identify which studies met the inclusion criteria. An evidentiary table was assembled summarizing the studies and the quality of evidence (Classes I-III). A meta-analysis was conducted using a random-effects model to calculate a cumulative estimate of treatment effect using risk ratio (RR). Heterogeneity was assessed using chi-square and I(2) statistics. A sensitivity analysis was also conducted. Based on the quality of the literature and the result of the meta-analysis, a recommendation was rendered (Level I, II, or III). RESULTS: Nine studies (4 Class I, 3 Class II, and 2 Class III) met our inclusion criteria. Of 7 randomized controlled trials (RCTs), 3 were downgraded from Class I to Class II because of significant quality issues, and all RCTs were potentially underpowered. In only 2 Class in retrospective cohort studies were preoperative antibiotic agents found to be protective against shunt infection. When data from the individual studies were pooled together, the infection rate in the prophylactic antibiotics group was 5.9% compared with 10.7% in the control group. Using a random-effects model, the cumulative RR was 0.55 (95% CI 0.38-0.81), indicating a protective benefit of prophylactic preoperative intravenous antibiotics. A sensitivity analysis of RCTs only (n = 7) also demonstrated a statistical benefit, but an analysis of higher-quality RCTs only (n = 4) did not. Conclusions Within the limits of this systematic review and meta-analysis, administration of preoperative antibiotic agents for shunt surgery in children was found to lower the infection risk (quality of evidence: Class II; strength of recommendation, Level II). RECOMMENDATION: The use of preoperative antibiotic agents can be recommended to prevent shunt infection in patients with hydrocephalus. It was only by combining the results of the various underpowered studies (meta-analysis) that the use of preoperative antibiotics for shunt surgery in children was shown to lower the risk of shunt infection. STRENGTH OF RECOMMENDATION: Level II, moderate degree of clinical certainty.

Pediatric hydrocephalus: systematic literature review and evidence-based guidelines. Part 7: Antibiotic-impregnated shunt systems versus conventional shunts in children: a systematic review and meta-analysis.

OBJECT: The objective of this systematic review and meta-analysis was to answer the following question: Are antibiotic-impregnated shunts (AISs) superior to standard shunts (SSs) at reducing the risk of shunt infection in pediatric patients with hydrocephalus? METHODS: Both the US National Library of Medicine PubMed/MEDLINE database and the Cochrane Database of Systematic Reviews were queried using MeSH headings and key words relevant to AIS use in children. Abstracts were reviewed, after which studies meeting the inclusion criteria were selected. An evidentiary table was assembled summarizing the studies and the quality of their evidence (Classes I-III). A meta-analysis was conducted using a random-effects model to calculate a cumulative estimate of treatment effect using risk ratio (RR). Heterogeneity was assessed using the chi-square and I(2) statistics. Based on the quality of the literature and the result of the meta-analysis, a recommendation was rendered (Level I, II, or III). RESULTS: Six studies, all Class III, met our inclusion criteria. All but one study focused on a retrospective cohort and all but one were conducted at a single institution. Four of the studies failed to demonstrate a lowered infection rate with the use of an AIS. However, when the data from individual studies were pooled together, the infection rate in the AIS group was 5.5% compared with 8.6% in the SS group. Using a random-effects model, the cumulative RR was 0.51 (95% CI 0.29-0.89, p < 0.001), indicating that a shunt infection was 1.96 times more likely in patients who received an SS. CONCLUSIONS: We recommend AIS tubing because of the associated lower risk of shunt infection compared to the use of conventional silicone hardware (quality of evidence: Class III; strength of recommendation: Level III). RECOMMENDATION: Antibiotic-impregnated shunt (AIS) tubing may be associated with a lower risk of shunt infection compared with conventional silicone hardware and thus is an option for children who require placement of a shunt. STRENGTH OF RECOMMENDATION: Level III, unclear degree of clinical certainty.

Part I: The application of the h-index to groups of individuals and departments in academic neurosurgery.

OBJECTIVE: The h-index was introduced as a means of quantifying the contribution a researcher makes to the scientific literature. We evaluated the h-index for academic neurosurgeons to assess the various methods of calculation and to determine whether the h-index can be used to differentiate groups of individuals by various classifications. METHODS: The h-index was calculated for all neurosurgeons from 10 institutions ranked highly by 2012 U.S. News & World Report plus the authors' institution via Scopus. The h-index also was calculated manually to evaluate its accuracy. The average h-index was calculated for groups on the basis of sex, academic rank, years in practice, institution, and subspecialty. Cumulative and mean h-indices were calculated for each department. RESULTS: The median h-index for the 188 neurosurgeons was 16 (mean, 19.71; range, 0-61). There was a positive association between the h-index, academic rank, and years posttraining. There was a significant difference between the "manually calculated" and automated h-indices, particularly for more senior physicians. The difference in h-index between men and women was not statistically significant. Among subspecialties, vascular surgeons had the greatest average h-index and general neurosurgeons had the lowest. There were significant shifts in departmental rankings when the cumulative or mean departmental indices were compared with the U.S. News & World Report rankings. CONCLUSION: Application of the h-index as a bibliometric in neurosurgery can distinguish academic productivity on the basis of academic rank, years posttraining, and neurosurgical subspecialties. The application of the h-index to compare departments is problematic and, at this time, not reliable.

Part II: Should the h-index be modified? An analysis of the m-quotient, contemporary h-index, authorship value, and impact factor.

OBJECTIVE: The widely accepted h-index depends on the citation analysis source and does not consider the authorship position, the journal's impact factor (IF), or the age of the paper or author. We investigated these factors in citation statistics of academic neurosurgeons. METHODS: An uncorrected h-index and the m-quotient, which corrects for career length, were calculated by the use of Scopus and Google Scholar. In a subset of neurosurgeons, we computed the contemporary h-index (hc), which accounts for the age of the publications; the authorship value (AV), weighted by author position; and the journal IF. An "overall' average for AV and IF including most of an author's publications and an average for publications comprising the h-index ("h-index core") were calculated. RESULTS: When we used Google Scholar, the mean h-index was significantly greater than that calculated when we used Scopus (P = 0.0030). m-quotient and hc-index increased with academic rank, with an m-quotient >1 achieved by 69% of chairmen and 48% of professors. The effect of AV was greatest on the greater h-indices. The average IF for the h-index core was greater than the overall IF, which did not correlate with academic rank. Few neurosurgeons consistently publish in high-impact journals. CONCLUSION: Google Scholar tends to inflate the h-index. The m-quotient and hc-index allow comparisons of researchers across time. Although average journal IF did not differ significantly among neurosurgeons academic ranks, it should be noted for individuals who consistently publish in high-impact journals. We recommend the creation of individual bibliometric profiles to better compare the academic productivity of neurosurgeons.

Management and outcome of focal low-grade brainstem tumors in pediatric patients: the St. Jude experience.

OBJECT: Whereas diffuse intrinsic pontine gliomas generally have a short symptom duration and more cranial nerve involvement, focal brainstem gliomas are commonly low grade, with fewer cranial neuropathies. Although these phenotypic distinctions are not absolute predictors of outcome, they do demonstrate correlation in most cases. Because there is a limited literature on focal brainstem gliomas in pediatric patients, the objective of this paper was to report the management and outcome of these tumors. METHODS: The authors reviewed the records of all children diagnosed with radiographically confirmed low-grade focal brainstem gliomas from 1986 to 2010. Each patient underwent biopsy or resection for tissue diagnosis. Event-free survival (EFS) and overall survival were evaluated. Univariate analysis was conducted to identify demographic and treatment variables that may affect EFS. RESULTS: Fifty-two patients (20 girls, 32 boys) with follow-up data were identified. Median follow-up was 10.0 years, and the median age at diagnosis was 6.5 years (range 1-17 years). The tumor locations were midbrain (n = 22, 42%), pons (n = 15, 29%), and medulla (n = 15, 29%). Surgical extirpation was the primary treatment in 25 patients (48%). The 5- and 10-year EFS and overall survival were 59%/98% and 52%/90%, respectively. An event or treatment failure occurred in 24 patients (46%), including 5 deaths. Median time to treatment failure was 3.4 years. Disease progression in the other 19 patients transpired within 25.1 months of diagnosis. Thirteen of these patients received radiation, including 11 within 2 months of primary treatment failure. Although children with intrinsic tumors had slightly better EFS at 5 years compared with those with exophytic tumors (p = 0.054), this difference was not significant at 10 years (p = 0.147). No other variables were predictive of EFS. CONCLUSIONS: Surgery suffices in many children with low-grade focal brainstem gliomas. Radiation treatment is often reserved for disease progression but offers comparable disease control following biopsy. In the authors' experience, combining an assessment of clinical course, imaging, and tumor biopsy yields a reasonable model for managing children with focal brainstem tumors.

Antibiotic-impregnated shunt systems versus standard shunt systems: a meta- and cost-savings analysis.

OBJECT: Infection is a serious and costly complication of CSF shunt implantation. Antibiotic-impregnated shunts (AISs) were introduced almost 10 years ago, but reports on their ability to decrease the infection rate have been mixed. The authors conducted a meta-analysis assessing the extent to which AISs reduce the rate of shunt infection compared with standard shunts (SSs). They also examined cost savings to determine the degree to which AISs could decrease infection-related hospital expenses. METHODS: After conducting a comprehensive search of multiple electronic databases to identify studies that evaluated shunt type and used shunt-related infection as the primary outcome, 2 reviewers independently evaluated study quality based on preestablished criteria and extracted data. A random effects meta-analysis of eligible studies was then performed. For studies that demonstrated a positive effect with the AIS, a cost-savings analysis was conducted by calculating the number of implanted shunts needed to prevent a shunt infection, assuming an additional cost of $400 per AIS system and $50,000 to treat a shunt infection. RESULTS: Thirteen prospective or retrospective controlled cohort studies provided Level III evidence, and 1 prospective randomized study provided Level II evidence. "Shunt infection" was generally uniformly defined among the studies, but the availability and detail of baseline demographic data for the control (SS) and treatment (AIS) groups within each study were variable. There were 390 infections (7.0%) in 5582 procedures in the control group and 120 infections (3.5%) in 3467 operations in the treatment group, yielding a pooled absolute risk reduction (ARR) and relative risk reduction (RRR) of 3.5% and 50%, respectively. The meta-analysis revealed the AIS to be statistically protective in all studies (risk ratio = 0.46, 95% CI 0.33-0.63) and in single-institution studies (risk ratio = 0.38, 95% CI 0.25-0.58). There was some evidence of heterogeneity when studies were analyzed together (p = 0.093), but this heterogeneity was reduced when the studies were analyzed separately as single institution versus multiinstitutional (p > 0.10 for both groups). Seven studies showed the AIS to be statistically protective against infection with an ARR and RRR ranging from 1.7% to 14.2% and 34% to 84%, respectively. The number of shunt operations requiring an AIS to prevent 1 shunt infection ranged from 7 to 59. Assuming 200 shunt cases per year, the annual savings for converting from SSs to AISs ranged from $90,000 to over $1.3 million. CONCLUSIONS: While the authors recognized the inherent limitations in the quality and quantity of data available in the literature, this meta-analysis revealed a significant protective benefit with AIS systems, which translated into substantial hospital savings despite the added cost of an AIS. Using previously developed guidelines on treatment, the authors strongly encourage the use of AISs in all patients with hydrocephalus who require a shunt, particularly those at greatest risk for infection.

Outcomes following single-treatment Gamma Knife surgery for trigeminal neuralgia with a minimum 3-year follow-up.

OBJECT: Gamma Knife surgery (GKS) has been shown to be effective in treating trigeminal neuralgia (TN). Existing studies have demonstrated success rates of 69.1-85% with median follow-up intervals of 19-60 months. However, series with uniform long-term follow-up data for all patients have been lacking. In the present study the authors examined outcomes in a series of patients with TN who underwent a single GKS treatment followed by a minimum follow-up of 36 months. They used a clinical scale that simplifies the reporting of outcome data for patients with TN. METHODS: Fifty-three consecutive patients with typical, intractable TN received a median maximum radiation dose of 80 Gy applied with a single 4-mm isocenter to the affected trigeminal nerve. Follow-up data were obtained by clinical examination and questionnaire. Outcome results were categorized into the following classes (in order of decreasing success): Class 1A, complete pain relief without medications; 1B, complete pain relief with either a decrease or no change in medications; 1C, > or = 50% pain relief without medications; 1D, > or = 50% pain relief with either a decrease or no change in medications; and Class 2, < 50% pain relief and/or increase in medications. Patients with Class 1A-1D outcome (equivalent to Barrow Neurological Institute Grades I-IIIb) were considered to have a good treatment outcome, whereas in patients with Class 2 outcome (equivalent to Barrow Neurological Institute Grades IV and V) treatment was considered to have failed. RESULTS: A good treatment outcome from initial GKS was achieved in 31 (58.5%) patients for whom the mean follow-up period was 48 months (range 36-66 months). Outcomes at last follow-up were reflected by class status: Class 1A, 32.1% of patients; 1B, 1.9%; 1C, 3.8%; 1D, 20.8%; and Class 2, 41.5%. Statistical analysis showed no difference in outcomes between patients previously treated with microvascular decompression or rhizotomy compared with patients with no previous surgical treatments. Thirty-six percent of patients reported some degree of posttreatment facial numbness. Anesthesia dolorosa did not develop in any patient. CONCLUSIONS: Despite a time-dependent deterioration in the success rate of GKS for medically intractable TN, the authors' study showed that > 50% of patients can be expected to have a good outcome based on their scoring system, with approximately 33% having an ideal outcome (pain free with no need for medications). Long-term data, as those presented here, are important when counseling patients on their treatment options.

Adherence and persistence with single-dosage form extended-release niacin/lovastatin compared with statins alone or in combination with extended-release niacin.

BACKGROUND: Lipid-lowering therapies have been shown to reduce cardiovascular events and mortality; patient cooperation with therapy varies. A fixed-dose combination product, extended-release niacin/lovastatin (ERNL), has been shown to be beneficial in lipid management; however, little is known regarding patient behavior with ERNL therapy. OBJECTIVE: To evaluate patient adherence and persistence with ERNL, statin monotherapy (SM), extended-release niacin (ERN) monotherapy, and ERN plus a statin (ERN-S). METHODS: Prescription claims for lipid-lowering therapies were obtained from a pharmacy benefits manager between 2002 and 2003. Claims for a total of 2389 patients were analyzed for adherence and persistence, using medication possession ratios (MPRs) and proportions of days covered (PDCs). Adherence and persistence were defined, respectively, as an MPR or PDC greater than or equal to 0.80. Logistic regression was conducted to detect differences among groups. Covariates included age, gender, copay, and number of lipid-lowering therapies, a surrogate for disease severity. RESULTS: Average MPR scores were relatively high in all groups at 0.88, 0.81, 0.89, and 0.90 for ERNL, SM, ERN, and ERN-S, respectively. The adjusted odds ratio for adherence was lowest for SM (0.69), which was statistically significant compared with ERN-S (1.43), but not ERNL (1.00) or ERN (0.74). Persistence outcomes were poor in all groups. By the fourth quarter, patients receiving ERN-S (OR 1.31) had significantly greater persistence than those receiving ERN (OR 0.41) and SM (0.61), but not those receiving ERNL (OR 1.00). CONCLUSIONS: Managed care patients tended to be adherent to chronic lipid-lowering therapies, based on a mean MPR greater than 0.8. However, most patients failed to persist for at least 6 months.

Preparation of donor lamellar tissue for deep lamellar endothelial keratoplasty using a microkeratome and artificial anterior chamber system: endothelial cell loss and predictability of lamellar thickness.

BACKGROUND AND OBJECTIVE: To measure endothelial cell loss and predictability of lamellar thickness after preparing donor tissue for deep keratoplasty with an artificial anterior chamber and microkeratome. MATERIALS AND METHODS: A microkeratome set at a depth of 350 microm and a diameter of 9 mm was used to obtain ten lamellar lenticules from corneoscleral rims mounted in an artificial chamber. A punch trephine then was used to cut the donor tissue 7 mm in diameter. Specular microscopy was performed to evaluate endothelial cell density before the procedure, after cutting with the microkeratome, and after trephination. Pachymetry was performed to determine the predictability of lenticule thickness, before the procedure and after microkeratome incision. RESULTS: Mean post-microkeratome endothelial cell loss was 79 +/- 88 cells/mm2 and post-punch trephination was 85 +/- 94 cells/mm2. This represented a mean percentage loss of 3.2% and 3.5% for the respective steps of this procedure. Nine of the ten lenticules were cut within +/- 75 microm of the intended 350-microm thickness. CONCLUSIONS: Preparing donor lenticules for deep lamellar endothelial keratoplasty with a microkeratome with artificial chamber system caused a relatively small loss of endothelial cells (6.7% of the total) and a reproducible thickness. This may have advantages over manual preparation techniques.

A meta-analysis of surgery versus conventional radiotherapy for the treatment of metastatic spinal epidural disease.

Radiotherapy has been the primary therapy for managing metastatic spinal disease; however, surgery that decompresses the spinal cord circumferentially, followed by reconstruction and immediate stabilization, has also proven effective. We provide a quantitative comparison between the "new" surgery and radiotherapy, based on articles that report on ambulatory status before and after treatment, age, sex, primary neoplasm pathology, and spinal disease distribution. Ambulation was categorized as "success" or "rescue" (proportion of patients ambulatory after treatment and proportion regaining ambulatory function, respectively). Secondary outcomes were also analyzed. We calculated cumulative success and rescue rates for our ambulatory measurements and quantified heterogeneity using a mixed-effects model. We investigated the source of the heterogeneity in both a univariate and multivariate manner with a meta-regression model. Our analysis included data from 24 surgical articles (999 patients) and 4 radiation articles (543 patients), mostly uncontrolled cohort studies (Class III). Surgical patients were 1.3 times more likely to be ambulatory after treatment and twice as likely to regain ambulatory function. Overall ambulatory success rates for surgery and radiation were 85% and 64%, respectively. Primary pathology was the principal factor determining survival. We present the first known formal meta-analysis using data from nonrandomized clinical studies. Although we attempted to control for imbalances between the surgical and radiation groups, significant heterogeneity undoubtedly still exists. Nonetheless, we believe the differences in the outcomes indicate a true difference resulting from treatment. We conclude that surgery should usually be the primary treatment with radiation given as adjuvant therapy. Neurologic status, overall health, extent of disease (spinal and extraspinal), and primary pathology all impact proper treatment selection.