Simulation Study of the Effect of Influenza and Influenza Vaccination on Risk of Acquiring Guillain-Barré Syndrome

It is unclear whether seasonal influenza vaccination results in a net increase or decrease in the risk for Guillain-Barré syndrome (GBS). To assess the effect of seasonal influenza vaccination on the absolute risk of acquiring GBS, we used simulation models and published estimates of age- and sex-specific risks for GBS, influenza incidence, and vaccine effectiveness. For a hypothetical 45-year-old woman and 75-year-old man, excess GBS risk for influenza vaccination versus no vaccination was −0.36/1 million vaccinations (95% credible interval −1.22 to 0.28) and −0.42/1 million vaccinations (95% credible interval, –3.68 to 2.44), respectively. These numbers represent a small absolute reduction in GBS risk with vaccination. Under typical conditions (e.g. influenza incidence rates >5% and vaccine effectiveness >60%), vaccination reduced GBS risk. These findings should strengthen confidence in the safety of influenza vaccine and allow health professionals to better put GBS risk in context when discussing influenza vaccination with patients.     

Comparison of azithromycin and clarithromycin in triple therapy regimens for the eradication of Helicobacter pylori

OBJECTIVE: We sought to compare an azithromycin-based regimen with an already established clarithromycin-based regimen in the eradication of Helicobacter pylori infection. METHODS: A prospective, randomized, blinded comparative analysis was performed on 56 patients with upper GI symptoms who presented to the Gastroenterology Department at the Naval Medical Center Portsmouth. All patients had documented H. pylori infection on endoscopy via rapid urease test and histopathology. Patients were randomized to a treatment arm, which consisted of bismuth, clarithromycin, amoxicillin, and lansoprazole (B-LAC) or one consisting of bismuth, azithromycin, amoxicillin, and lansoprazole (B-LAA). To assess eradication, patients then received repeat endoscopy at 8 wk from entrance into the study. Rapid urease test and histopathology were again used to evaluate infection. Patients recorded all side effects. Comparison between the two groups was made using the chi2 method. RESULTS: Of the 56 patients included in the study, 27 went on to receive B-LAC, whereas 29 received B-LAA. The per protocol eradication rate was 84.6% with B-LAC and 55.5% with B-LAA (p = 0.021). Under intention to treat analysis, the eradication rates for B-LAC and B-LAA were 81% and 52%, respectively (p = 0.019). There was a significant difference between the two groups in number of subjects using nonsteroidal anti-inflammatory drugs (NSAIDs) (p = 0.013) and a trend toward a difference in histamine-2 (H2) blocker use (p = 0.066). Taking these two variables into account, a logistical regression was performed and continued to show a significant superiority in the B-LAC regimen (p = 0.03). CONCLUSIONS: The results of our study suggest that B-LAC is superior to B-LAA in the eradication of Helicobacter pylori. Our results also suggest that B-LAA is not a suitable regimen in the treatment of H. pylori because of its substandard eradication rate.     

Influence of a Methanogenic Flora on the Breath H2 and Symptom Response to Ingestion of Sorbitol or Oat Fiber

Background and Objectives: We investigated the possibility that a variant of the normal colonic flora, a high concentration of methanogeas, influences the host's response to ingestion of nonabsorbable, fermentable materials. Methods: To better evaluate symptomatic and breath H₂ and methane (CH₄) responses, subjects were placed on a basal diet (primarily rice and hamburger) that contained minimal amounts of nonabsorbable, fermentable substrate. A breath CH₄/H₂ ratio of greater or less than 1 on the second day of the basal diet was used to categorize subjects as high (N = 9) or low (N = 25) CH₄ producers. After stabilization of the breath gas excretion (day 3 or 4 on the basal diet), the subjects ingested either sorbitol (8.8 g) or oat fiber (10.2 g). Results: The low CH₄ producers had a signficantly higher ( p < 0.05) breath H₂ concentration than the high producers on the basal diet and after ingestion of sorbitol (27.1 ± 2.7 ppm vs 15.8 ± 3.6 ppm) or oat fiber (13.1 ± 0.08 ppm vs 9.6 ± 1.2 ppm). Low producers of methane reported significantly increased bloating and cramping after sorbitol ingestion and increased bloating after fiber ingestion, whereas high CH₄ producers reported no signficant increase in these symptoms. Conclusion: The presence of a methanogenic flora is associated with a reduced symptomatic response to ingestion of nonabsorbable, fermentable material in healthy subjects. Manipulation of the normal flora could be of therapeutic value in nonmethanogenic patients with irritable bowel syndrome.     

Effectiveness of Acute Asthma Care Among Inner-city Adults

BACKGROUND: Acute asthma often requires expensive emergency department visits and hospitalizations, especially among economically disadvantaged inner-city adults. However, few studies have examined approaches for improving acute asthma care in this population. METHODS: We conducted a cohort study involving patients who were discharged from a public hospital emergency department following acute asthma care between March 31, 1997, and August 5, 1999, to identify processes of care effective for improving peak expiratory flow rate at a 2- to 3-week follow-up. Adult patients who met the predetermined criteria for asthma, who underwent a baseline peak expiratory flow rate reading, and who did not have concurrent acute sinusitis or pneumonia were eligible (N = 448). Of the 365 patients enrolled in the study, 309 (84.7%) completed it. We used a multiple linear regression analysis adjusted for patient risk to assess the association between acute asthma care processes derived from the National Asthma Education Prevention Program guidelines (inhaled beta2-agonists, inhaled corticosteroids, systemic corticosteroids, asthma care follow-up, and patient asthma education) and percentage peak expiratory flow rate change at follow-up. RESULTS: Systemic corticosteroids had a significant effect for increasing percentage peak expiratory flow rate change at the 2- to 3-week follow-up for all asthma exacerbation severity levels (beta = 26.1; 95% confidence interval, 1.8-50.5; P =.04) and severity levels specified by the National Asthma Education Prevention Program guidelines (beta = 31.6; 95% confidence interval, 8.1-55.1; P =.01). CONCLUSION: Outpatient systemic corticosteroids were effective for improving lung function 2 to 3 weeks after acute asthma care, and their use should reduce asthma-related morbidity, especially among economically disadvantaged inner-city adults.     

Purging of acute myeloid leukemic cells by ether lipids and hyperthermia

Ether lipids (EL) and hyperthermia have been shown to possess a relatively selective cytotoxicity to leukemic cells. In this study, the combined effects of EL (ET-18-OCH3, ET-16-NHCOCH3, or BM 41.440) and hyperthermia on the growth of hematopoietic progenitors, myeloid leukemic cell lines, and leukemic cells obtained from patients with acute myeloid leukemia (AML) were examined to determine if this combination resulted in a greater selective killing of leukemic cells than that achieved by either EL or heat alone. When the cells were treated simultaneously with EL (50 micrograms/mL) and hyperthermia (42 degrees C) for one hour, the killing of leukemic cell line cells was enhanced considerably. Among the three EL, however, the combination of ET-18-OCH3 and heat seemed to be the most cytotoxic to leukemic cell line cells with no effect on the growth of hematopoietic progenitors. An increase in the duration of treatment with ET-18-OCH3 to four hours with heat added during the last hour resulted in a further reduction of leukemic cell line cells while sparing 50% of hematopoietic progenitors after cryopreservation. The combined treatment with ET-18-OCH3 and heat also inhibited the growth of leukemic progenitors obtained from AML patients by 97% to 100%. These data indicate that the combined treatment with EL and hyperthermia might offer an efficient means to eliminate myeloid leukemic cells in vitro.     

Validity of standard gamble estimated quality of life in acute venous thrombosis

Introduction

The standard gamble is considered the ‘gold standard’ technique for measuring quality of life. We recently used the standard gamble to estimate quality of life in acute venous thrombosis, and found unexpected variability in the responses. The current study aimed to explore the reasons for variability by comparing the standard gamble technique in patients with acute venous thrombosis to other quality of life measurement tools.

Materials and Methods

Thrombosis clinic patients treated for venous thrombosis were eligible to participate. Patients evaluated their current health state by performing a standard gamble interview, reporting on a visual analogue scale, completing the SF-36 and disease specific questionnaires (PEmb-Qol and VEINES-QOL/Sym). Validity was assessed by correlating the standard gamble utilities with the other methods. Test-retest reliability, responsiveness and acceptability were also assessed.

Results

Forty-four patients were interviewed, with 16 attending for a repeat interview. The median standard gamble utility was 0.97 (0.84-1.0), SF-6D 0.64 (0.59 - 0.80) and visual analogue score 70 (60 - 80). Participants with pulmonary embolism had lower standard gamble estimates than those with deep vein thrombosis. There was good discriminant validity in that the standard gamble estimates were not associated with risk taking behavior, negative outlook, sex or education. Test-retest reliability with the standard gamble was moderate and there was evidence of a ceiling effect.

Conclusions

Standard gamble utilities are higher than other methods of measuring quality of life in venous thrombosis. The choice of utility values adopted in studies will impact on future economic studies.     

Opposing roles of membrane and soluble forms of the receptor for advanced glycation end products in primary respiratory syncytial virus infection

Respiratory syncytial virus (RSV), a common respiratory pathogen in infants and the older population, causes pulmonary inflammation and airway occlusion that leads to impairment of lung function. Here, we have established a role for receptor for advanced glycation end products (RAGE) in RSV infection. RAGE-deficient (ager(-/-)) mice were protected from RSV-induced weight loss and inflammation. This protection correlated with an early increase in type I interferons, later decreases in proinflammatory cytokines, and a reduction in viral load. To assess the contribution of soluble RAGE (sRAGE) to RSV-induced disease, wild-type and ager(-/-) mice were given doses of sRAGE following RSV infection. Of interest, sRAGE treatment prevented RSV-induced weight loss and neutrophilic inflammation to a degree similar to that observed in ager(-/-) mice. Our work further elucidates the roles of RAGE in the pathogenesis of respiratory infections and highlights the opposing roles of membrane and sRAGE in modulating the host response to RSV infection.     

In vitro modeling of respiratory syncytial virus infection of pediatric bronchial epithelium, the primary target of infection in vivo

Respiratory syncytial virus (RSV) is the major viral cause of severe pulmonary disease in young infants worldwide. However, the mechanisms by which RSV causes disease in humans remain poorly understood. To help bridge this gap, we developed an ex vivo/in vitro model of RSV infection based on well-differentiated primary pediatric bronchial epithelial cells (WD-PBECs), the primary targets of RSV infection in vivo. Our RSV/WD-PBEC model demonstrated remarkable similarities to hallmarks of RSV infection in infant lungs. These hallmarks included restriction of infection to noncontiguous or small clumps of apical ciliated and occasional nonciliated epithelial cells, apoptosis and sloughing of apical epithelial cells, occasional syncytium formation, goblet cell hyperplasia/metaplasia, and mucus hypersecretion. RSV was shed exclusively from the apical surface at titers consistent with those in airway aspirates from hospitalized infants. Furthermore, secretion of proinflammatory chemokines such as CXCL10, CCL5, IL-6, and CXCL8 reflected those chemokines present in airway aspirates. Interestingly, a recent RSV clinical isolate induced more cytopathogenesis than the prototypic A2 strain. Our findings indicate that this RSV/WD-PBEC model provides an authentic surrogate for RSV infection of airway epithelium in vivo. As such, this model may provide insights into RSV pathogenesis in humans that ultimately lead to successful RSV vaccines or therapeutics.     

The Cogency of Risk Assessments

Preventive detention schemes rely on assessments of risk carried out by forensic practitioners. Corrective services departments and other organs of the state inevitably present the approaches they adopt and the tools they employ in this endeavour as being “best practice” and “evidence based”. Typically these assessments are conducted according to a bureaucratic template and are based on a selected suite of tests that are heavily biased towards actuarial assessment. The validity of this approach is gravely suspect as is the failure of many forensic professionals to properly identify the diagnostic accuracy/inaccuracy of the tests and methods they rely upon in conducting risk assessments. This article iterates the methodological and evidentiary problems with risk assessment of sexual offenders. It is concluded that common extant approaches lack scientific objectivity and fail to provide the courts with cogent evidence. As a result of these errors in investigatory processes miscarriages of justice are inevitable.     

Blastocystis: to treat or not to treat..

Parasites in the genus Blastocystis comprise several subtypes (genotypes) and have a worldwide distribution. In some surveys, these are the most common parasites found in human stool specimens. An emerging literature suggests that the pathogenicity of Blastocystis is related to specific subtypes and parasite burden, although even individuals with small numbers of cysts may be symptomatic. Some data suggest an association between infection with Blastocystis and irritable bowel syndrome. However, there are few clinical studies demonstrating a direct relationship between the presence of this parasite and disease, few animal models to explore this relationship, and no consensus as to appropriate treatment. We recommend that asymptomatic individuals with few cysts not be treated. However, those who have gastrointestinal or dermatologic signs and symptoms and many cysts in stool specimens may require treatment. Metronidazole is the drug of choice. Additional studies are required to determine pathogenicity and appropriate therapy.