Risk factors for sporadic Giardia infection in the USA: a case-control study in Colorado and Minnesota.

Giardia duodenalis is the most common intestinal parasite of humans in the USA, but the risk factors for sporadic (non-outbreak) giardiasis are not well described. The Centers for Disease Control and Prevention and the Colorado and Minnesota public health departments conducted a case-control study to assess risk factors for sporadic giardiasis in the USA. Cases (N = 199) were patients with non-outbreak-associated laboratory-confirmed Giardia infection in Colorado and Minnesota, and controls (N = 381) were matched by age and site. Identified risk factors included international travel (aOR = 13.9; 95% CI 4.9-39.8), drinking water from a river, lake, stream, or spring (aOR = 6.5; 95% CI 2.0-20.6), swimming in a natural body of water (aOR = 3.3; 95% CI 1.5-7.0), male-male sexual behaviour (aOR = 45.7; 95% CI 5.8-362.0), having contact with children in diapers (aOR = 1.6; 95% CI 1.01-2.6), taking antibiotics (aOR = 2.5; 95% CI 1.2-5.0) and having a chronic gastrointestinal condition (aOR = 1.8; 95% CI 1.1-3.0). Eating raw produce was inversely associated with infection (aOR = 0.2; 95% CI 0.1-0.7). Our results highlight the diversity of risk factors for sporadic giardiasis and the importance of non-international-travel-associated risk factors, particularly those involving person-to-person transmission. Prevention measures should focus on reducing risks associated with diaper handling, sexual contact, swimming in untreated water, and drinking untreated water.

Mortality from selected diseases that can be transmitted by water - United States, 2003-2009.

Diseases spread by water are caused by fecal-oral, contact, inhalation, or other routes, resulting in illnesses affecting multiple body systems. We selected 13 pathogens or syndromes implicated in waterborne disease outbreaks or other well-documented waterborne transmission (acute otitis externa, Campylobacter, Cryptosporidium, Escherichia coli (E. coli), free-living ameba, Giardia, Hepatitis A virus, Legionella (Legionnaires' disease), nontuberculous mycobacteria (NTM), Pseudomonas-related pneumonia or septicemia, Salmonella, Shigella, and Vibrio). We documented annual numbers of deaths in the United States associated with these infections using a combination of death certificate data, nationally representative hospital discharge data, and disease-specific surveillance systems (2003-2009). We documented 6,939 annual total deaths associated with the 13 infections; of these, 493 (7%) were caused by seven pathogens transmitted by the fecal-oral route. A total of 6,301 deaths (91%) were associated with infections from Pseudomonas, NTM, and Legionella, environmental pathogens that grow in water system biofilms. Biofilm-associated pathogens can cause illness following inhalation of aerosols or contact with contaminated water. These findings suggest that most mortality from these 13 selected infections in the United States does not result from classical fecal-oral transmission but rather from other transmission routes.

Prevalence and direct costs of emergency department visits and hospitalizations for selected diseases that can be transmitted by water, United States.

National emergency department (ED) visit prevalence and costs for selected diseases that can be transmitted by water were estimated using large healthcare databases (acute otitis externa, campylobacteriosis, cryptosporidiosis, Escherichia coli infection, free-living ameba infection, giardiasis, hepatitis A virus (HAV) infection, Legionnaires' disease, nontuberculous mycobacterial (NTM) infection, Pseudomonas-related pneumonia or septicemia, salmonellosis, shigellosis, and vibriosis or cholera). An estimated 477,000 annual ED visits (95% CI: 459,000-494,000) were documented, with 21% (n = 101,000, 95% CI: 97,000-105,000) resulting in immediate hospital admission. The remaining 376,000 annual treat-and-release ED visits (95% CI: 361,000-390,000) resulted in $194 million in annual direct costs. Most treat-and-release ED visits (97%) and costs ($178 million/year) were associated with acute otitis externa. HAV ($5.5 million), NTM ($2.3 million), and salmonellosis ($2.2 million) were associated with next highest total costs. Cryptosporidiosis ($2,035), campylobacteriosis ($1,783), and NTM ($1,709) had the highest mean costs per treat-and-release ED visit. Overall, the annual hospitalization and treat-and-release ED visit costs associated with the selected diseases totaled $3.8 billion. As most of these diseases are not solely transmitted by water, an attribution process is needed as a next step to determine the proportion of these visits and costs attributable to waterborne transmission.

The Association between Educational Attainment and Patterns of Emergency Department Utilization among Adults with Sickle Cell Disease.

PURPOSE: Patients with low educational attainment may be at increased risk for unplanned health care utilization. This study aimed to determine what factors are related to emergency department (ED) visits in hopes of guiding treatments and early interventions. METHODS: At two medical centers in the Mid-Atlantic United States, 258 adults with sickle cell disease aged 19-70 years participated in a retrospective study where we examined whether education level is independently associated with ED visits after accounting for other socioeconomic status (SES) variables, such as pain and disease severity and psychosocial functioning. RESULTS: The data showed that patients without a high school education visited the ED three times as frequently as patients with post secondary education. Controlling for poverty and employment status decreased the effect of education on ED visits by 33.24 %. Further controlling for disease severity and/or psychosocial functioning could not account for the remaining association between education and ED visits, suggesting that education is independently associated with potentially avoidable emergency care. CONCLUSIONS: Early interventions addressing disparities in academic performance, especially for those children most at risk, may lead to improved long-term health outcomes in this population.

A three-point time series study of antibiotic usage on an intensive care unit, following an antibiotic stewardship programme, after an outbreak of multi-resistant Acinetobacter baumannii.

Antibiotic use in intensive care units (ICUs) can promote antimicrobial resistance. Outbreaks of multi-resistant bacteria significantly affect patient outcomes and delivery of care. Antibiotic stewardship programmes (ASPs), combining root-cause analyses and multi-faceted prevention strategies, are necessary, often at significant cost and time. Which elements of such strategies have the largest impact on antibiotic usage following an outbreak is unclear. The aim of this study was to investigate how antibiotic usage in a university hospital ICU changed with a non-protocolised ASP following a disruptive outbreak of multi-resistant Acinetobacter baumannii (MRAB). This was a three time-period observational cohort study. The primary endpoint was the change in overall antibiotic usage (daily defined dose, DDD, antibiotic-days, antibiotic-courses) for consecutive ICU patients staying >48 h, over three 6-month study time periods pre-MRAB (2008, n = 84) and post-MRAB (2010, n = 88; 2012, n = 122). Secondary endpoints were changes in antibiotic usage and patient demographics, in predefined admission categories (Medical Emergency, ME; Surgical Elective, SEL; and Surgical Emergency, SE). The mean age (54.6 ± 17.7, 58.1 ± 17.9, 62.8 ± 19.1 years*) and severity of illness (APACHE 14.8 ± 8.0, 16.7 ± 6.8, 18.3 ± 6.1*) increased, particularly medical admissions. There was a sustained reduction in DDD antibiotic usage [1895.1 (2008), 1224.2 (2010), 1236.6 (2012) per 1000 patient-days] but no overall change in antibiotic-days or antibiotic-courses. Antibiotic usage (antibiotic-days) fell significantly in surgical emergency admissions [20.2 ± 32.1, 4.6 ± 7.4*, 5.9 ± 7.3]. There was a sustained drop in beta-lactam, quinolone, glycopeptide and macrolide usage. Following an MRAB outbreak, and subsequent operational changes including enhanced ASPs (non-protocolised), there was a sustained overall fall in antibiotic usage in spite of an increase in disease severity over 5 years.

Preventing community-wide transmission of Cryptosporidium: a proactive public health response to a swimming pool-associated outbreak--Auglaize County, Ohio, USA.

The incidence of recreational water-associated outbreaks in the United States has significantly increased, driven, at least in part, by outbreaks both caused by Cryptosporidium and associated with treated recreational water venues. Because of the parasite's extreme chlorine tolerance, transmission can occur even in well-maintained treated recreational water venues (e.g. pools) and a focal cryptosporidiosis outbreak can evolve into a community-wide outbreak associated with multiple recreational water venues and settings (e.g. childcare facilities). In August 2004 in Auglaize County, Ohio, multiple cryptosporidiosis cases were identified and anecdotally linked to pool A. Within 5 days of the first case being reported, pool A was hyperchlorinated to achieve 99·9% Cryptosporidium inactivition. A case-control study was launched to epidemiologically ascertain the outbreak source 11 days later. A total of 150 confirmed and probable cases were identified; the temporal distribution of illness onset was peaked, indicating a point-source exposure. Cryptosporidiosis was significantly associated with swimming in pool A (matched odds ratio 121·7, 95% confidence interval 27·4-∞) but not with another venue or setting. The findings of this investigation suggest that proactive implementation of control measures, when increased Cryptosporidium transmission is detected but before an outbreak source is epidemiologically ascertained, might prevent a focal cryptosporidiosis outbreak from evolving into a community-wide outbreak.

An exploratory study of salivary calcitonin gene-related peptide levels relative to acute interventions and preventative treatment with onabotulinumtoxinA in chronic migraine.

OBJECTIVE: To determine if baseline/interictal saliva calcitonin gene-related peptide (CGRP) levels would be lower in subjects with chronic migraine receiving onabotulinumtoxinA compared with those receiving saline. BACKGROUND: CGRP is considered central to the pathogenesis of episodic migraine, but its relationship to chronic migraine is less understood. OnabotulinumtoxinA is an effective treatment for chronic migraine and has been demonstrated to inhibit the vesicular release of CGRP. METHODS: This was an exploratory, randomized, placebo-controlled, crossover pilot study of 20 subjects that received onabotulinumtoxinA and saline injection (placebo). The amount of CGRP in saliva samples collected on a nonheadache or low headache day, and prior to and after treatment of a headache exacerbation was measured. Daily headache records, medications, and response to treatment were recorded in a diary. RESULTS: A decrease in baseline/interictal saliva CGRP levels for subjects receiving onabotulinumtoxinA from 39.4 ± 7.5 pg CGRP/mg total protein after the first month to 25.5 ± 4.1 pg after the third month was observed. However, this difference did not reach significance nor was it significant when compared to the saline treatment. There was a reduction in the number of headache days for both onabotulinumtoxinA and saline over baseline throughout the active phases of the study. However, there was no statistical difference in headache days between groups. Subjects with a greater than 50% response to onabotulinumtoxinA had better 2-hour pain relief with acute treatment than non-responders to onabotulinumtoxinA or saline. CONCLUSION: While CGRP levels were not elevated during a migraine attack in chronic migraine subjects as has been reported in episodic migraine, there was an overall decrease in the baseline/interictal levels in response to onabotulinumtoxinA.

Treatment of chronic migraine: a 3-month comparator study of naproxen sodium vs SumaRT/Nap.

OBJECTIVE: To compare the use of a combination of 85 mg sumatriptan plus 500 mg naproxen sodium in a combination tablet with 500 mg naproxen sodium in an identically appearing tablet when used as a daily preventative and acute treatment for 1 month and episodic acute treatment for an additional 2 months in patients with chronic migraine. BACKGROUND: To date, there has been minimal study of acute medications for patients with chronic migraine. Consequently, there is a paucity of study methodology or evidence-based guidance on the use of acute treatment medications in patients with chronic migraine. METHODS: This two-center, double-blind, randomized, parallel-group, comparator pilot trial of 28 subjects, 18 to 65 years of age, with ICHD-II defined chronic migraine, was designed to generate hypotheses about the efficacy of 2 established acute migraine medications used both as a daily preventive treatment (month 1) and episodic acute treatment (months 1, 2, and 3). Subjects were randomized 1:1 to treat daily with SumaRT/Nap (85 mg sumatriptan + 500 mg naproxen sodium) (group A) or naproxen sodium (500 mg) (group B) in a prophylactic strategy for 1 month followed by 2 months of the same medications used for episodic acute treatment. RESULTS: The combination of SumaRT/Nap used over a 3-month period did not appear to significantly reduce the number of migraine headache days. In the subset of subjects using naproxen sodium and completing the study per protocol, there was a marked reduction in migraine headache days (P < .02 vs 0.25, respectively). Duration of migraine from treatment to pain free decreased in both groups, but was more robust in group B from baseline to month 3. Subjects in group B completing the study per protocol reported a 56% reduction in headache days vs 8% for group A. Subjects in group A and group B completing the study per protocol had considerably better 2-hour headache relief than subjects withdrawing early from the study. More subjects in group B prematurely withdrew from the study because of lack of efficacy (5 vs 1, respectively). Despite using significant quantities of acute medication during month 1, there was a reduction of acute medication in month 2 and 3 vs baseline vs month 1, particularly in the naproxen group. CONCLUSION: A combination of SumaRT/Nap (group A) did not appear to reduce migraine headache frequency over a 3-month period. Subjects using naproxen sodium (group B) alone and completing the study per protocol had a marked statistically significant reduction in migraine headache days. Both groups completing the study per protocol had experienced clinically meaningful 2-hour headache relief. This suggests there may be a subset of patients with chronic migraine that are responsive to high doses of naproxen as an acute intervention with a significant prophylactic benefit. Subjects randomized to SumaRT/Nap experience benefit, primarily as an acute intervention. This hypothesis may warrant future larger scale clinical trials. Frequent dosing of SumaRT/Nap or naproxen sodium was well tolerated in this study.

Mitigation strategies for time-resolved x-ray diagnostic data degradation due to high neutron yield of ICF experiments at the NIF.

Inertial confinement fusion experiments taking place at the National Ignition Facility are generating ever increasing amounts of fusion energy, with the deuterium tritium fusion neutron yield growing a hundredfold over the past ten years. Strategies must be developed to mitigate this harsh environment's deleterious effects on the operation and the performance of the time-resolved x-ray imagers deployed in the National Ignition Facility target bay to record the dynamics of the implosions. We review the evolution of these imagers in recent years and detail some of the past and present efforts undertaken to maintain or improve the quality of the experimental data collected on high neutron yield experiments. These include the use of a dump-and-read electronic backend, the selection of photographic film with a low background sensitivity, and the optical filtering of Cherenkov radiation.

Identification and analysis of murine pancreatic islet enhancers.

AIMS/HYPOTHESIS: The paucity of information on the epigenetic barriers that are blocking reprogramming protocols, and on what makes a beta cell unique, has hampered efforts to develop novel beta cell sources. Here, we aimed to identify enhancers in pancreatic islets, to understand their developmental ontologies, and to identify enhancers unique to islets to increase our understanding of islet-specific gene expression. METHODS: We combined H3K4me1-based nucleosome predictions with pancreatic and duodenal homeobox 1 (PDX1), neurogenic differentiation 1 (NEUROD1), v-Maf musculoaponeurotic fibrosarcoma oncogene family, protein A (MAFA) and forkhead box A2 (FOXA2) occupancy data to identify enhancers in mouse islets. RESULTS: We identified 22,223 putative enhancer loci in in vivo mouse islets. Our validation experiments suggest that nearly half of these loci are active in regulating islet gene expression, with the remaining regions probably poised for activity. We showed that these loci have at least nine developmental ontologies, and that islet enhancers predominately acquire H3K4me1 during differentiation. We next discriminated 1,799 enhancers unique to islets and showed that these islet-specific enhancers have reduced association with annotated genes, and identified a subset that are instead associated with novel islet-specific long non-coding RNAs (lncRNAs). CONCLUSIONS/INTERPRETATIONS: Our results indicate that genes with islet-specific expression and function tend to have enhancers devoid of histone methylation marks or, less often, that are bivalent or repressed, in embryonic stem cells and liver. Further, we identify a subset of enhancers unique to islets that are associated with novel islet-specific genes and lncRNAs. We anticipate that these data will facilitate the development of novel sources of functional beta cell mass.

Variation in access to sugar-sweetened beverages in vending machines across rural, town and urban high schools.

OBJECTIVES: The 2010 Dietary Guidelines for Americans include reducing consumption of sugar-sweetened beverages. Among the many possible routes of access for youth, school vending machines provide ready availability of sugar-sweetened beverages. The purpose of this study was to determine variation in high school student access to sugar-sweetened beverages through vending machines by geographic location - urban, town or rural - and to offer an approach for analysing school vending machine content. STUDY DESIGN: Cross-sectional observational study. METHODS: Between October 2007 and May 2008, trained coders recorded beverage vending machine content and machine-front advertising in 113 machines across 26 schools in New Hampshire and Vermont, USA. RESULTS: Compared with town schools, urban schools were significantly less likely to offer sugar-sweetened beverages (P = 0.002). Rural schools also offered more sugar-sweetened beverages than urban schools, but this difference was not significant. Advertisements for sugar-sweetened beverages were highly prevalent in town schools. CONCLUSIONS: High school students have ready access to sugar-sweetened beverages through their school vending machines. Town schools offer the highest risk of exposure; school vending machines located in towns offer up to twice as much access to sugar-sweetened beverages in both content and advertising compared with urban locations. Variation by geographic region suggests that healthier environments are possible and some schools can lead as inspirational role models.

Two center, randomized pilot study of migraine prophylaxis comparing paradigms using pre-emptive frovatriptan or daily topiramate: research and clinical implications.

OBJECTIVE: To compare the efficacy and clinical benefit of 2 paradigms of migraine prevention using pre-emptive frovatriptan and daily topiramate. The study compares the paradigms of pre-emptive use of frovatriptan, a drug approved for acute migraine, and the daily use of topiramate, a Federal Drug Administration-approved and -accepted standard for migraine prophylaxis. BACKGROUND: Traditionally, preventive treatment of migraine required daily medication. However, recent studies suggest that pre-emptive prophylaxis may be beneficial to those migraineurs who can predict an attack of migraine based on premonitory symptoms and treat during that phase. METHODS: A total of 76 adult subjects with a diagnosis of migraine were screened for the study. During a 1-month baseline period, subjects demonstrated through a daily diary that they predicted at least 50% of migraine attacks during the premonitory phase and treated with their usual medication. Of these, 55 were randomized to either Group A (daily topiramate) or Group B (frovatriptan during premonitory symptoms); 44 completed the study. The treatment period lasted 2 months. The subjects answered the Migraine-Specific Quality of Life Questionnaire at randomization, and at Weeks 4 and 8. The revised Patient Perception of Migraine Questionnaire was answered 24 hours after taking frovatriptan (Group A, for break-through headaches; Group B, treatment during premonitory symptoms). RESULTS: The number of migraine attacks and headache days per month decreased significantly from baseline for both Groups A and B. Subjects in Group A had considerably more adverse events leading to study withdrawal than in Group B (18% vs 4%). Though this study was not powered to directly compare the efficacy of the 2 drugs, topiramate showed superiority over frovatriptan at Month 2 in reduction of headache days, which was a secondary end point in the study (P = .036). CONCLUSIONS: This pilot study demonstrated that statistical benefit for reduction of headache days over baseline for both pre-emptive frovatriptan and daily topiramate. Subjects utilizing pre-emptive frovatriptan experienced fewer adverse events leading to study withdrawal. Subjects utilizing daily topiramate had fewer headache days at Month 2.

The development of a survey to measure completeness of response to migraine therapy.

OBJECTIVE: To assess the psychometric properties of a new patient-reported migraine instrument, the Completeness of Response Survey (CORS), which measures a comprehensive set of factors important to patients' decisions regarding the initiation and continuation of treatment. BACKGROUND: Traditionally, migraine treatments and the instruments used to demonstrate their efficacy have focused on the relief of headache pain. As new treatments emerge with the potential for more complete and consistent migraine relief, more comprehensive tools are needed to demonstrate these benefits. The CORS includes 2 modules, the static CORS, which comprehensively evaluates one treatment at one time point, and the comparative CORS, which provides a more global comparison between 2 treatments at one time point. Together, the 2 modules can measure unmet treatment needs and improvements over the course of a clinical study. METHODS: Data from an 8-site study comparing 147 patients' recent experiences with their current triptan therapy and 2 months of study treatment with a single-tablet formulation of sumatriptan/naproxen sodium were used to conduct a preliminary psychometric evaluation of the CORS. The study included both modules of the CORS, the Headache Impact Test, the revised Patient Perception of Migraine Questionnaire, and a migraine diary. RESULTS: The CORS response categories in both the static and comparative modules demonstrated limited floor or ceiling effects and few missing values (<3%). Inter-item correlations, principal components analysis (component loading range: 0.62 to 0.95), and high estimates of internal consistency (alpha range: 0.88 to 0.94) for each composite score supported the structure and proposed scoring algorithm for the static module. The pattern of correlations between the CORS static and comparative items and composites with the revised Patient Perception of Migraine Questionnaire items and subscales, as well as the relationships between responses to selected static CORS items and the migraine diary, supported the construct validity of the CORS. CONCLUSIONS: The CORS is capable of demonstrating advantages of more comprehensive migraine therapies over traditional therapies, which are primarily focused on the resolution of headache pain, by addressing the frequency and speed with which the most common migraine symptoms are resolved and patients' return to normal functioning. This research shows evidence for the value and utility for the CORS static and comparative items and components, and further evaluation is underway.

Direct healthcare costs of selected diseases primarily or partially transmitted by water.

Despite US sanitation advancements, millions of waterborne disease cases occur annually, although the precise burden of disease is not well quantified. Estimating the direct healthcare cost of specific infections would be useful in prioritizing waterborne disease prevention activities. Hospitalization and outpatient visit costs per case and total US hospitalization costs for ten waterborne diseases were calculated using large healthcare claims and hospital discharge databases. The five primarily waterborne diseases in this analysis (giardiasis, cryptosporidiosis, Legionnaires' disease, otitis externa, and non-tuberculous mycobacterial infection) were responsible for over 40 000 hospitalizations at a cost of $970 million per year, including at least $430 million in hospitalization costs for Medicaid and Medicare patients. An additional 50 000 hospitalizations for campylobacteriosis, salmonellosis, shigellosis, haemolytic uraemic syndrome, and toxoplasmosis cost $860 million annually ($390 million in payments for Medicaid and Medicare patients), a portion of which can be assumed to be due to waterborne transmission.

Crystal response measurement of the x-ray transmission crystals used by the Imaging Spectroscopy Snout at the National Ignition Facility.

The Imaging Spectroscopy Snout (ISS) used at the National Ignition Facility is able to simultaneously collect neutron pinhole images, 1D spatially resolved x-ray spectra, and time resolved x-ray pinhole images. To measure the x-ray spectra, the ISS can be equipped with up to four different transmission crystals, each offering different energy ranges from ∼7.5 to ∼12 keV and different resolutions. Characterizing and calibrating such instruments is of paramount importance in order to extract meaningful results from experiments. More specifically, we characterized different ISS transmission-type alpha-Quartz crystals by measuring their responses as a function of photon energy, from which we inferred the angle-integrated reflectivity for each crystal's working reflections. These measurements were made at the Lawrence Livermore National Laboratory calibration station dedicated to the characterization of x-ray spectrometers. The sources used covered a wide x-ray range-from a few to 30 keV; the source diameter was ∼0.6 mm. The experimental results are discussed alongside theoretical calculations using the pyTTE model.

HCV Infection Alters Salivary Gland Histology and Saliva Composition.

Hepatitis C virus (HCV) infection is the most common blood-borne chronic infection in the United States. Chronic lymphocytic sialadenitis and sicca syndrome have been reported in chronic HCV infection. Up to 55% of these patients may have xerostomia; the mechanisms of the xerostomia and salivary gland (SG) hypofunction remain controversial. The objectives of this project are to establish if xerostomia associates with SG and HCV infection and to characterize the structural changes in SG and saliva composition. Eighteen HCV-infected patients with xerostomia were evaluated for SG dysfunction; 6 of these patients (patients 1-6) were further evaluated for SG histopathological changes and changes in saliva composition. The techniques used include clinical and laboratory assessment, SG ultrasonography, histological evaluation, sialochemical and proteomics analysis, and RNA in situ hybridization. All the HCV patients had low saliva flow, chronic sialadenitis, and SG fibrosis and lacked Sjögren syndrome (SS) characteristic autoantibodies. Further evaluation of a subgroup of 6 HCV patients (patients 1-6) demonstrated diffuse lymphocytic infiltrates that are predominantly CD8+ T cells with a significant increase in the number of inflammatory cells. Alcian Blue/periodic acid-Schiff staining showed significant changes in the ratio and intensity of the acinar secretory units of the HCV patients' minor SG. The submandibular glands showed significant ultrasonographic abnormalities in the parenchyma relative to the parotid glands. Significant changes were also observed in the concentration of sodium and mucin 5b. Although no significant correlation was observed between the lymphocytic infiltrates and the years of HCV chronic infection, a positive correlation was observed between HCV RNA-positive epithelial cells and the years of HCV infection. Consistent with the low saliva flow and xerostomia, patients showed changes in several markers of SG acinar and ductal function. Changes in the composition of the saliva suggest that HCV infection can cause xerostomia by mechanisms distinct from SS.

A double-blind placebo-controlled pilot study of sublingual feverfew and ginger (LipiGesic™ M) in the treatment of migraine.

BACKGROUND: Therapeutic needs of migraineurs vary considerably from patient to patient and even attack to attack. Some attacks require high-end therapy, while other attacks have treatment needs that are less immediate. While triptans are considered the "gold standard" of migraine therapy, they do have limitations and many patients are seeking other therapeutic alternatives. In 2005, an open-label study of feverfew/ginger suggested efficacy for attacks of migraine treated early during the mild headache phase of the attack. METHODS/MATERIALS: In this multi-center pilot study, 60 patients treated 221 attacks of migraine with sublingual feverfew/ginger or placebo. All subjects met International Headache Society criteria for migraine with or without aura, experiencing 2-6 attacks of migraine per month within the previous 3 months. Subjects had <15 headache days per month and were not experiencing medication overuse headache. Inclusion required that subjects were able to identify a period of mild headache in at least 75% of attacks. Subjects were required to be able to distinguish migraine from non-migraine headache. Subjects were randomized 3:1 to receive either sublingual feverfew/ginger or a matching placebo and were instructed but not required to treat with study medication at the earliest recognition of migraine. RESULTS: Sixty subjects treated 208 evaluable attacks of migraine over a 1-month period; 45 subjects treated 163 attacks with sublingual feverfew/ginger and 15 subjects treated 58 attacks with a sublingual placebo preparation. Evaluable diaries were completed for 151 attacks of migraine in the population using feverfew/ginger and 57 attacks for those attacks treated with placebo. At 2 hours, 32% of subjects receiving active medication and 16% of subjects receiving placebo were pain-free (P= .02). At 2 hours, 63% of subjects receiving feverfew/ginger found pain relief (pain-free or mild headache) vs 39% for placebo (P= .002). Pain level differences on a 4-point pain scale for those receiving feverfew/ginger vs placebo were -0.24 vs -0.04 respectively (P= .006). Feverfew/ginger was generally well tolerated with oral numbness and nausea being the most frequently occurring adverse event. CONCLUSION: Sublingual feverfew/ginger appears safe and effective as a first-line abortive treatment for a population of migraineurs who frequently experience mild headache prior to the onset of moderate to severe headache.

Ultrasound-guided interscalene blocks: understanding where to inject the local anaesthetic.

Although ultrasound-guided regional anaesthesia has gained in popularity, few data exist describing the optimal location(s) to inject local anaesthetic. Our objective was to compare, for interscalene blocks, the effectiveness of an injection between the middle scalene muscle and brachial plexus sheath (peri-plexus) with an injection within the brachial plexus sheath (intra-plexus). We enrolled 170 patients undergoing shoulder surgery with general anaesthesia and interscalene block in this randomised, controlled trial. Our primary outcome variable was loss of shoulder abduction. Block quality was also measured and defined by an evaluation of onset time, sensory and motor loss and duration. There was no difference between the two groups in block onset times or block quality. After adjusting for sex, age and volume injected, intra-plexus blocks lasted a mean of 2.6 h (16%) longer (95% CI 0.25-5.01, p=0.03) than peri-plexus blocks.

The epidemiology of primary amoebic meningoencephalitis in the USA, 1962-2008.

Naegleria fowleri, a free-living, thermophilic amoeba ubiquitous in the environment, causes primary amoebic meningoencephalitis (PAM), a rare but nearly always fatal disease of the central nervous system. While case reports of PAM have been documented worldwide, very few individuals have been diagnosed with PAM despite the vast number of people who have contact with fresh water where N. fowleri may be present. In the USA, 111 PAM case-patients have been prospectively diagnosed, reported, and verified by state health officials since 1962. Consistent with the literature, case reports reveal that N. fowleri infections occur primarily in previously healthy young males exposed to warm recreational waters, especially lakes and ponds, in warm-weather locations during summer months. The annual number of PAM case reports varied, but does not appear to be increasing over time. Because PAM is a rare disease, it is challenging to understand the environmental and host-specific factors associated with infection in order to develop science-based, risk reduction messages for swimmers.