Novel paradigm enables accurate monthly gestational screening to prevent congenital toxoplasmosis and more.

Background: Congenital toxoplasmosis is a treatable, preventable disease, but untreated causes death, prematurity, loss of sight, cognition and motor function, and substantial costs worldwide. Methods/Findings: In our ongoing USA feasibility/efficacy clinical trial, data collated with other ongoing and earlier published results proved high performance of an Immunochromatographic-test(ICT) that enables accurate, rapid diagnosis/treatment, establishing new paradigms for care. Overall results from patient blood and/or serum samples tested with ICT compared with gold-standard-predicate-test results found ICT performance for 4606 sera/1876 blood, 99.3%/97.5% sensitive and 98.9%/99.7% specific. However, in the clinical trial the FDA-cleared-predicate test initially caused practical, costly problems due to false-positive-IgM results. For 58 persons, 3/43 seronegative and 2/15 chronically infected persons had false positive IgM predicate tests. This caused substantial anxiety, concerns, and required costly, delayed confirmation in reference centers. Absence of false positive ICT results contributes to solutions: Lyon and Paris France and USA Reference laboratories frequently receive sera with erroneously positive local laboratory IgM results impeding patient care. Therefore, thirty-two such sera referred to Lyon's Reference laboratory were ICT-tested. We collated these with other earlier/ongoing results: 132 of 137 USA or French persons had false positive local laboratory IgM results identified correctly as negative by ICT. Five false positive ICT results in Tunisia and Marseille, France, emphasize need to confirm positive ICT results with Sabin-Feldman-Dye-test or western blot. Separate studies demonstrated high performance in detecting acute infections, meeting FDA, CLIA, WHO ASSURED, CEMark criteria and patient and physician satisfaction with monthly-gestational-ICT-screening. Conclusions/Significance: This novel paradigm using ICT identifies likely false positives or raises suspicion that a result is truly positive, rapidly needing prompt follow up and treatment. Thus, ICT enables well-accepted gestational screening programs that facilitate rapid treatment saving lives, sight, cognition and motor function. This reduces anxiety, delays, work, and cost at point-of-care and clinical laboratories. Author's Summary: Toxoplasmosis is a major health burden for developed and developing countries, causing damage to eyes and brain, loss of life and substantial societal costs. Prompt diagnosis in gestational screening programs enables treatment, thereby relieving suffering, and leading to > 14-fold cost savings for care. Herein, we demonstrate that using an ICT that meets WHO ASSURED-criteria identifying persons with/without antibody to Toxoplasma gondii in sera and whole blood with high sensitivity and specificity, is feasible to use in USA clinical practice. We find this new approach can help to obviate the problem of detection of false positive anti- T.gondii IgM results for those without IgG antibodies to T.gondii when this occurs in present, standard of care, predicate USA FDA cleared available assays. Thus, this accurate test facilitates gestational screening programs and a global initiative to diagnose and thereby prevent and treat T.gondii infection. This minimizes likelihood of false positives (IgG and/or IgM) while maintaining maximum sensitivity. When isolated IgM antibodies are detected, it is necessary to confirm and when indicated continue follow up testing in ∼2 weeks to establish seroconversion. Presence of a positive ICT makes it likely that IgM is truly positive and a negative ICT makes it likely that IgM will be a false positive without infection. These results create a new, enthusiastically-accepted, precise paradigm for rapid diagnosis and validation of results with a second-line test. This helps eliminate alarm and anxiety about false-positive results, while expediting needed treatment for true positive results and providing back up distinguishing false positive tests.

Comparison of the Respiratory Resistomes and Microbiota in Children Receiving Short versus Standard Course Treatment for Community-Acquired Pneumonia.

Pediatric community-acquired pneumonia (CAP) is often treated with 10 days of antibiotics. Shorter treatment strategies may be effective and lead to less resistance. The impact of duration of treatment on the respiratory microbiome is unknown. Data are from children (n = 171), ages 6 to 71 months, enrolled in the SCOUT-CAP trial (NCT02891915). Children with CAP were randomized to a short (5 days) versus standard (10 days) beta-lactam treatment strategy. Throat swabs were collected at enrollment and the end of the study and used for shotgun metagenomic sequencing. The number of beta-lactam and multidrug efflux resistance genes per prokaryotic cell (RGPC) was significantly lower in children receiving the short compared to standard treatment strategy at the end of the study (Wilcoxon rank sum test, P < 0.05 for each). Wilcoxon effect sizes were small for beta-lactam (r: 0.15; 95% confidence interval [CI], 0.01 to 0.29) and medium for multidrug efflux RGPC (r: 0.23; 95% CI, 0.09 to 0.37). Analyses comparing the resistome at the beginning and end of the trial indicated that in contrast to the standard strategy group, the resistome significantly differed in children receiving the short course strategy. Relative abundances of commensals such as Neisseria subflava were higher in children receiving the standard strategy, and Prevotella species and Veillonella parvula were higher in children receiving the short course strategy. We conclude that children receiving 5 days of beta-lactam therapy for CAP had a significantly lower abundance of antibiotic resistance determinants than those receiving standard 10-day treatment. These data provide an additional rationale for reductions in antibiotic use when feasible. IMPORTANCE Antibiotic resistance is a major threat to public health. Treatment strategies involving shorter antibiotic courses have been proposed as a strategy to lower the potential for antibiotic resistance. We examined relationships between the duration of antibiotic treatment and its impact on resistance genes and bacteria in the respiratory microbiome using data from a randomized controlled trial of beta-lactam therapy for pediatric pneumonia. The randomized design provides reliable evidence of the effectiveness of interventions and minimizes the potential for confounding. Children receiving 5 days of therapy for pneumonia had a lower prevalence of two different types of resistance genes than did those receiving the 10-day treatment. Our data also suggest that children receiving longer durations of therapy have a greater abundance of antibiotic resistance genes for a longer period of time than do children receiving shorter durations of therapy. These data provide an additional rationale for reductions in antibiotic use.

Comparison of forces acting on maxillary incisors during tracheal intubation with different laryngoscopy techniques: a blinded manikin study.

Dental trauma is a common complication of tracheal intubation. As existing evidence is insufficient to validly assess the impact of different laryngoscopy techniques on the incidence of dental trauma, the force exerted onto dental structures during tracheal intubation was investigated. An intubation manikin was equipped with hidden force sensors in all maxillary incisors. Dental force was measured while 104 anaesthetists performed a series of tracheal intubations using direct laryngoscopy with a Macintosh blade, and videolaryngoscopy with a C-MAC® , or the hyperangulated GlideScope® or KingVision® laryngoscopes in both normal and difficult airway conditions. A total of 624 tracheal intubations were analysed. The median (IQR [range]) peak force of direct laryngoscopy in normal airways was 21.1 (14.0-32.8 [2.3-127.6]) N and 29.3 (17.7-44.8 [3.3-97.2]) N in difficult airways. In normal airways, these were lower with the GlideScope and KingVision hyperangulated laryngoscopes, with a reduction of 4.6 N (p = 0.006) and 10.9 N (p < 0.001) compared with direct laryngoscopy, respectively. In difficult airways, these were lower with the GlideScope and KingVision hyperangulated laryngoscopes, with a reduction of 9.8 N (p < 0.001) and 17.6 N (p < 0.001) compared with direct laryngoscopy, respectively. The use of the C-MAC did not have an impact on the median peak force. Although sex of anaesthetists did not affect peak force, more experienced anaesthetists generated a higher peak force than less experienced providers. We conclude that hyperangulated videolaryngoscopy was associated with a significantly decreased force exerted on maxillary incisors and might reduce the risk for dental injury in clinical settings.

Suture button reconstruction of the central band of the interosseous membrane in Essex-Lopresti lesions: a comparative biomechanical investigation.

Surgical reconstruction of the interosseous membrane may restore longitudinal forearm stability in Essex-Lopresti lesions. This study aimed to compare the longitudinal stability of the intact forearm with a single-bundle and a double-bundle reconstruction of the central band of the interosseous membrane using digital image correlation with a three-dimensional camera system. Single and cyclic axial loading of eight fresh-frozen forearm specimens was carried out in the intact state, after creation of an Essex-Lopresti lesion, after a single-bundle and after a double-bundle reconstruction of the central band using a TightRope® (Arthrex GmbH, Munich, Germany) construct. Instability significantly increased after creation of an Essex-Lopresti lesion. The stability of intact specimens was similar to both reconstruction techniques. The results of this study suggest that TightRope® reconstruction of the central band restores longitudinal forearm stability. However, the single-bundle technique may be less reliable than double-bundle reconstruction. LEVEL OF EVIDENCE: Basic Science Study.

Influence of a freeze-thaw cycle on the stress-stretch curves of tissues of porcine abdominal organs.

The paper investigates both fresh porcine spleen and liver and the possible decomposition of these organs under a freeze-thaw cycle. The effect of tissue preservation condition is an important factor which should be taken into account for protracted biomechanical tests. In this work, tension tests were conducted for a large number of tissue specimens from twenty pigs divided into two groups of 10. Concretely, the first group was tested in fresh state; the other one was tested after a freeze-thaw cycle which simulates the conservation conditions before biomechanical experiments. A modified Fung model for isotropic behavior was adopted for the curve fitting of each kind of tissues. Experimental results show strong effects of the realistic freeze-thaw cycle on the capsule of elastin-rich spleen but negligible effects on the liver which virtually contains no elastin. This different behavior could be explained by the autolysis of elastin by elastolytic enzymes during the warmer period after thawing. Realistic biomechanical properties of elastin-rich organs can only be expected if really fresh tissue is tested. The observations are supported by tests of intestines.

Finite element modelling of stapled colorectal end-to-end anastomosis: advantages of variable height stapler design.

The impact of surgical staplers on tissues has been studied mostly in an empirical manner. In this paper, finite element method was used to clarify the mechanics of tissue stapling and associated phenomena. Various stapling modalities and several designs of circular staplers were investigated to evaluate the impact of the device on tissues and mechanical performance of the end-to-end colorectal anastomosis. Numerical simulations demonstrated that a single row of staples is not adequate to resist leakage due to non-linear buckling and opening of the tissue layers between two adjacent staples. Compared to the single staple row configuration, significant increase in stress experienced by the tissue at the inner staple rows was observed in two and three rows designs. On the other hand, adding second and/or third staple row had no effect on strain in the tissue inside the staples. Variable height design with higher staples in outer rows significantly reduced the stresses and strains in outer rows when compared to the same configuration with flat cartridge.

Hypothermic machine perfusion of kidney grafts: which pressure is preferred?

To assess the effect of the perfusion pressure (PP) during machine perfusion (MP) on the preservation quality of kidney grafts, we compared mean PPs of 25 and 30 mmHg using a porcine autotransplantation model. After assessment of the microcirculation, animals underwent left nephrectomy. Thereafter, kidneys were washed out followed by 20 h of MP at 25 mmHg (MP25, n = 7) or 30 mmHg (MP30, n = 7) using a novel MP system for hypothermic pulsatile perfusion. After MP preservation, the contralateral kidneys were removed and the preserved kidneys heterotopically autotransplanted. Ten minutes after reperfusion, the microcirculation was reassessed. Seven days posttransplant, animals were euthanized and the kidney grafts removed for histological analysis. MP using a mean PP of 25 mmHg resulted in higher capillary blood flow after reperfusion. In the MP30 group, 6 out of 7 animals survived, whereas in the MP25 group all animals survived. Overall, improvement in recovery of renal function and a better preservation of structural integrity were seen in the MP25 group compared to the MP30 group. Using a novel system for hypothermic MP, a mean PP of 25 mmHg is preferred over a mean PP of 30 mmHg.

A new model for blunt liver injuries in the swine.

BACKGROUND: To elaborate the impact of new haemostatic agents we developed an instrument for the pressure-controlled induction of blunt liver injuries in a porcine animal model. MATERIALS AND METHODS: A dilutional coagulopathy of 80% of animal blood volume was induced in 9 anaesthetized pigs. Animals were randomly assigned to be injured with a force of 112 Newton (N) (n = 1), 224 +/- 19 N (n = 4) or 355 +/- 35 N (n = 4). The impact of injury was measured by blood loss, survival time and coagulation parameters. Liver histology was obtained to evaluate the degree of liver injury. RESULTS: The profound haemodilution resulted in a significant alteration of all coagulation parameters. After inflicting the injury with 355 +/- 35 N, both the survival time (30 +/- 9 min; p = 0.006) and blood loss (68 +/- 16 ml min(-1), p = 0.002) were significantly different as compared to injuries with 224 +/- 19 N (survival time: 76 +/- 20 min, blood loss: 23 +/- 4 ml min(-1)). In contrast, an injury with 112 N led to an insignificant blood loss of only 239 ml. CONCLUSION: We developed a pressure-controlled clamp that allows for the induction of blunt liver traumas with highly reproducible injuries with a positive correlation with blood loss and survival.

Estimating the undetected burden of influenza hospitalizations in children.

During the 2004-2005 influenza season two independent influenza surveillance systems operated simultaneously in three United States counties. The New Vaccine Surveillance Network (NVSN) prospectively enrolled children hospitalized for respiratory symptoms/fever and tested them using culture and RT-PCR. The Emerging Infections Program (EIP) and a similar clinical-laboratory surveillance system identified hospitalized children who had positive influenza tests obtained as part of their usual medical care. Using data from these systems, we applied capture-recapture analyses to estimate the burden of influenza related-hospitalizations in children aged<5 years. During the 2004-2005 influenza season the influenza-related hospitalization rate estimated by capture-recapture analysis was 8.6/10,000 children aged<5 years. When compared to this estimate, the sensitivity of the prospective surveillance system was 69% and the sensitivity of the clinical-laboratory based system was 39%. In the face of limited resources and an increasing need for influenza surveillance, capture-recapture analysis provides better estimates than either system alone.

Tungiasis in North America: a report of 2 cases in internationally adopted children.

Tungiasis is a cutaneous infestation caused by the gravid female sand flea, Tunga penetrans. We describe 2 cases of tungiasis that occurred in siblings who recently emigrated as international adoptees from Liberia to the United States. Both patients had infectious complications as a result of the infestation with T penetrans.

The protective effectiveness of natural rotavirus infection in an American Indian population.

The degree of protection conferred by natural rotavirus infection was estimated through analyses of data gathered as part of a 2-year rotavirus vaccine study of 1185 Native American infants. In 292 placebo recipients with complete serum sample sets, rotavirus IgA antibody indicative of infection before 2 months of age was associated with a 58% decrease in symptomatic infections throughout the trial. In all 391 placebo recipients, the preventive effectiveness of an initial symptomatic infection was 72% overall and 94% within 6 months following the infection. In contrast to studies conducted at other sites in the United States, serotype G3 was the predominant serotype associated with gastrointestinal episodes (80%). The effectiveness of an initial serotype G3 episode with respect to preventing subsequent serotype G3 episodes was 91%.

Susceptibility to vaccine-preventable diseases in a sexually transmitted disease clinic population.

BACKGROUND AND OBJECTIVE: Sexually transmitted disease (STD) clinics often serve a population that has low medical care utilization. The objective of this study was to determine the susceptibility of an STD clinic population to vaccine-preventable diseases. STUDY DESIGN: A cross-sectional study of immunization practices and susceptibility to vaccine-preventable diseases was undertaken by enrolling consecutive patients attending an STD clinic. Demographic information and a history of disease or immunization was assessed by interview. Immunity to measles and rubella was determined by measuring IgG antibodies by ELISA assays. RESULTS: Of the 288 patients evaluated, the mean age was 28 years and 70.5% were male. Serologically, 16.3% were susceptible to rubella and 8% to measles. Only 8% reported hepatitis B immunization. Although measles protection was high, nearly one in six was susceptible to rubella. Hepatitis B immunization was severely underused. CONCLUSION: Baltimore STD clinic patients may benefit from an enhanced rubella and hepatitis B prevention strategy.

A population-based serologic survey of Helicobacter pylori infection in children and adolescents in the United States.

To provide more accurate estimates of Helicobacter pylori infection in the US population, IgG antibody levels were measured in serum from 2581 persons aged 6-19 years examined during phase 1 of the third National Health and Nutrition Examination Survey. Overall, 24.8% of participants had evidence of H. pylori infection. Infection was strongly associated with increasing age (chi 2 trend, P < .01) and being nonwhite (17.0% of non-Hispanic whites vs. 40.1% of non-Hispanic blacks and 42.0% of Mexican Americans infected). In a multivariate logistic regression model, H. pylori infection was significantly associated with increasing age (odds ratio [OR] = 1.07/year), being nonwhite (non-Hispanic black OR = 2.6 or Mexican American OR = 1.8), poverty (OR = 1.5), crowding (OR = 5.6), and head of household education level (OR = 1.8). In Mexican Americans, infection was associated with birth outside the United States or Canada in the univariate analyses but was not significantly associated after adjustment for age, poverty, crowding, and head of household education level.

Lone mothers: a review.

"This paper briefly reviews recent empirical studies on the economic behavior of lone mothers concentrating on the duration of lone motherhood, on labour supply, and on the determinants of their welfare participation. We start out by sketching some stylised facts about lone-mother-families in various countries. With this background we give a guided tour through the empirical literature followed by a summary of the policy implications of the results presented."

Diarrhea in children newly enrolled in day-care centers in Houston.

Diarrhea is a common illness among children in day-care centers (DCC). We hypothesized that the incidence of diarrhea was greater among children in their first 1 or 2 months after enrollment in a DCC than in any subsequent period in day care. We followed 442 children younger than 2 years of age enrolled in 13 randomly selected DCCs for the occurrence of diarrhea during a 14 1/2-month period. Parents completed standardized baseline questionnaires and research nurses visited the DCC twice weekly to record the occurrence of diarrhea and to collect stool specimens. Incidence rates, rate ratios, chi square statistics and 95% confidence intervals were calculated for crude and stratified analyses. The diarrheal incidence rate of 4.4 cases/child-year in the first 4 weeks in the centers was significantly (rate ratio, 1.6; confidence interval, 1.3 to 2.1; P less than 0.01) higher than the 2.7 cases/child-year incidence rate of diarrhea in subsequent weeks. The effects of gender, ethnicity, age, DCC size, previous DCC attendance and season were examined and did not account for the association observed between recent enrollement and risk of diarrheal illness. Rotavirus was identified in 18% of cases of diarrhea, but no association was seen with recent enrollment in DCC. A significantly higher incidence of diarrhea occurred in males compared with females (P less than 0.002) and in younger children (P less than 0.001) compared with older children. Diarrhea is common in children in DCCs and occurs significantly more frequently in children during their first 4 weeks in a DCC.