Median Infection Rate Research Articles

In-vitro Replication Competence of Three Modified-live Canine Distemper Vaccines

Over the past several years, there have been a number of severe canine distemper virus (CDV) outbreaks in shelters involving adult dogs that were considered fully vaccinated with modified live vaccine prior to exposure. Shelters vaccinating large numbers of animals during admission or high-volume public vaccine clinics may reconstitute modified live vaccines (MLV) hours ahead of use and store them under non-ideal cold chain conditions. There is little guidance regarding the durability of MLV potency, and viral components may degrade under storage conditions (both pre- and post-reconstitution) employed by shelters in the name of efficiency. This study aimed to generate a model for examining the effect of vaccine husbandry on the in-vitro replication competence of MLV CDV. Shelters were surveyed to determine the most common vaccine brands and the maximum duration between reconstitution and use of CDV MLV to guide the time/temperature conditions in our in vitro study. CDV-susceptible Madin-Darby canine kidney (MDCK) cells were grown in Dulbecco’s modified Eagle’s medium containing fetal bovine serum, penicillin/streptomycin, and l-glutamine, seeded into a 96-well plate, and inoculated with CDV MLV. There were 3 replicates per time/temperature condition. Viral replication was allowed to proceed for 72 hours. Fluorescently labeled anti-CDV antibodies were used to identify cells infected with vaccine-derived CDV via flow cytometry. A Kruskal-Wallis test was used to test differences in medians between the groups. Three quadrivalent CDV vaccine brands were assessed in our model system to examine virus replication competency in vitro. Two commercial vaccines, including the most reported brand in our survey, did not produce infection beyond baseline uninoculated controls, while a third showed robust infect rates. This brand was used for subsequent trials of different storage conditions. Immediate reconstitution infected a median of 14% (IQR 10, 18) of cells. In comparison, 10 min at room temperature (RT) pre-reconstitution (PreR), 10 min at RT post-reconstitution (PostR), 10 min at 4 °C PostR, 60 min at RT PreR, 60 min at RT PostR, and 60 min at °4C PostR infected a median of 15% (IQR 10,20), 14% (IQR 8,23) 14% (11, 24), 11% (8, 21), 13% (9, 26), and 10% (7, 20), respectively. Similarly, 120 min at RT PreR, 120 min at RT PostR, 120 min at 4 °C PostR, 120 min RT PreR followed by 60 min 4 °C, and 1440 min at RT PreR followed by 1440 min at RT PostR infected a median of 9% (8, 17), 10% (8, 20), (9% (8, 22), 8% (9, 22), and 9% (10, 23) of cells, respectively. There was no difference between conditions. Our in-vitro model demonstrated no significant difference in median cell infection rates between time/temperature conditions up to an extreme of 24 hours pre-reconstitution/24 hours post-reconstitution at room temperature.

Infectivity of symptomatic Plasmodium vivax cases to different generations of wild-caught and laboratory-adapted Anopheles arabiensis using a membrane feeding assay, Ethiopia

When measuring human to mosquito transmission of Plasmodium spp., laboratory-adapted (colony) mosquitoes can be utilized. To connect transmission studies to the local epidemiology, it can be important to comprehend the relationship between infectivity in laboratory-adapted (colony) and wild-caught (wild) mosquitoes of the same species. Microscopically confirmed Plasmodium vivax cases were recruited from health facilities in Arba Minch town, and a nested polymerase chain reaction (nPCR) was used for subsequent confirmation. We performed paired membrane-feeding assays using colony An. arabiensis and three generations of wild origin An. arabiensis. Anopheles arabiensis aged 3–6 days were fed after being starved for 8–14 h. Microscopically, the oocyst development was evaluated at day 7 after feeding. Circumsporozoite proteins (CSPs) assay was carried out by enzyme-linked immunosorbent assay (ELISA). In 19 paired feeding experiments, the feeding efficiency was more than doubled in colony (median: 62.5%; interquartile range, IQR: 35–78%) than in wild mosquitoes (median: 28.5%; IQR: 17.5–40%; P < 0.001). Among the 19 P. vivax gametocyte-positive blood samples, 63.2% (n = 12) were infective to wild An. arabiensis and 73.7% (n = 14) were infective to colony An. arabiensis. The median infection rate was twice as high (26%) in the colony than in the wild (13%) An. arabiensis, although the difference was marginally insignificant (P = 0.06). Although the observed difference was not statistically significant (P = 0.19), the median number of oocysts per midgut was more than twice as high (17.8/midgut) in colony than in wild (7.2/midgut) An. arabiensis. The median feeding efficiency was 26.5% (IQR: 18–37%) in F1, 29.3% (IQR: 28–40%) in F2 and 31.2% (IQR: 30–37%) in F3 generations of wild An. arabiensis. Also, no significant difference was observed in oocyst infection rate and load between generations of wild An. arabiensis. CSP rate of P. vivax was 3.1% (3/97; 95% CI: 0.6–8.8%) in wild and 3.6% (3/84; 95% CI: 0.7–10.1%) in colony An. arabiensis. The results of the present study revealed that oocyst infection and load/midgut, and CSP rate were roughly comparable, indicating that colony mosquitoes can be employed for infectivity studies, while larger sample sizes may be necessary in future studies.

VP.60 Every breath counts! Inspiratory muscle training in children with neuromuscular diseases: a cross-over randomised controlled trial

Progressive respiratory muscle weakness and ineffective cough contributes to morbidity and mortality in children with neuromuscular diseases (NMD). Inspiratory muscle training (IMT) aims to preserve or improve respiratory muscle strength and reduce respiratory morbidity. This study aimed to determine the safety and efficacy of IMT in children with NMD. A randomised cross-over study compared three-month intervention (IMT) with control periods. During the intervention, children with NMD (5-18 years) from two provinces in South Africa performed 30 breaths (at 30% of inspiratory muscle strength (Pimax)) with an electronic threshold device, twice daily. During the control period participants did not perform any IMT. Twenty-three participants (median (IQR) age of 12.33 (10.03-14.17) years), mostly male (n=20) and non-ambulant (n=14) were included. No adverse events related to IMT were reported. There was no evidence of a difference in median patient hospitalisation and respiratory tract infection rates between control and intervention periods (p=0.60; p=0.21). During IMT, Pimax and peak cough flow improved with a mean (SD) of 14.57 (±15.67) cmH2O and 32.27 (±36.60) L/min, compared to a change of 3.04(±11.93)cmH2O (p=0.01) and -16.59 (±48.29) L/min (p=0.0005) during the control period. There was no evidence of change in spirometry, functional ability and total health-related quality of life scores following intervention. Patient satisfaction with IMT was high (median 8/10 (IQR 5-10)) and adherence was good. A three-month IMT programme in children with NMD is well tolerated, appears to be safe and is associated with a significant improvement in respiratory muscle strength and cough efficacy.

The Geographical Correlation Between Historical Preterm Birth Disparities and COVID-19 Burden.

Similar to obstetric outcomes, rates of SARS-CoV-2 (COVID-19) infection are not homogeneously distributed among populations; risk factors accumulate in discrete locations. This study aimed to investigate the geographical correlation between pre-COVID-19 regional preterm birth (PTB) disparities and subsequent COVID-19 disease burden. We performed a retrospective, ecological cohort study of an upstate New York birth certificate database from 2004 to 2018, merged with publicly available community resource data. COVID-19 rates from 2020 were used to allocate ZIP codes to “low-,” “moderate-,” and “high-prevalence” groups, defined by median COVID-19 diagnosis rates. COVID-19 cohorts were associated with poverty and educational attainment data from the US Census Bureau. The dataset was analyzed for the primary outcome of PTB using ANOVA. GIS mapping visualized PTB rates and COVID-19 disease rates by ZIP code. Within 38 ZIP codes, 123,909 births were included. The median COVID-19 infection rate was 616.5 (per 100 K). PTB (all) and COVID-19 were positively correlated, with high- prevalence COVID-19 ZIP codes also being the areas with the highest prevalence of PTB (F = 11.06, P = .0002); significance was also reached for PTB < 28 weeks (F = 15.87, P < .0001) and periviable birth (F = 16.28, P < .0001). Odds of PTB < 28 weeks were significantly higher in the “high-prevalence” COVID-19 cohort compared to the “low-prevalence” COVID 19 cohort (OR 3.27 (95% CI 2.42–4.42)). COVID-19 prevalence was directly associated with number of individuals below poverty level and indirectly associated with median household income and educational attainment. GIS mapping demonstrated ZIP code clustering in the urban center with the highest rates of PTB < 28 weeks overlapping with high COVID-19 disease burden. Historical disparities in social determinants of health, exemplified by PTB outcomes, map community distribution of COVID-19 disease burden. These data should inspire socioeconomic policies supporting economic vibrancy to promote optimal health outcomes across all communities.Supplementary InformationThe online version contains supplementary material available at 10.1007/s43032-022-01076-w.

Centre-specific differences in short-term outcomes in neonates with hypoxic-ischaemic encephalopathy.

To investigate and compare the centre-specific short-term outcome indicators seizures, arterial hypotension, infection and mortality during therapeutic hypothermia until discharge from the neonatal/paediatric intensive care unit in term and near-term neonates with hypoxic-ischaemic encephalopathy (HIE) registered in the Swiss National Asphyxia and Cooling Register between 2011 and 2018. Retrospective analysis of prospectively collected national register data between 1 January 2011 and 31 December 2018. Pregnancy, maternal, delivery and neonatal characteristics were compared between the centres. Four short-term outcomes were defined: seizures, arterial hypotension, infection and mortality. The outcome indicators were defined as stated in the protocol of the Swiss National Asphyxia and Cooling Register. Descriptive analyses of the de-identified centre to centre analysis were performed, and standardised observed-to-expected values (risk adjusted for male sex, small for gestational age, Sarnat score on admission, pregnancy/delivery complications) of each centre were compared using with the entire network indirectly standardised mortality/morbidity ratio charts. 570 cooled neonates with HIE receiving therapeutic hypothermia in 10 different centres were included. Clinical or subclinical seizures were reported in a median of 32% (range 17&ndash;49%). Arterial hypotension occurred in a median of 62% (range 30&ndash;90%). Median infection rate was 10% (range 0&ndash;31%). Median mortality rate until discharge was 14% (range 0&ndash;25%). Short-term outcome indicators of seizures, arterial hypotension, infection and mortality showed significant differences in incidence between the centres. These data will help to establish benchmarks for the assessed outcome measures. Benchmarking is a continuous need with the ultimate goal of improving modifiable short-term outcomes in neonates with HIE.

Association of Infection Rate in Heart Transplant Recipients with Combined Tacrolimus and Sirolimus at High versus Low Concentration

<h3>Purpose</h3> Assess the impact of tacrolimus-sirolimus (TAC/SRL) concentration on infection rate in heart transplant recipients (HTR). <h3>Methods</h3> A retrospective review of HTR on TAC/SRL for > 1 year from 01/2006-08/2019 was conducted. Drug concentrations were defined as high (≥ 15 ng/mL) or low (<15 ng/mL), calculated as the summation of individual medication's annual average concentration for every year of therapy. The primary outcome was median rate of infection per year, defined as positive culture or other documented clinical finding treated with a course of antimicrobial. Secondary outcomes included incidence of infection, biopsy-proven acute rejection (BPAR), clinically evident cellular rejection treated with high-dose corticosteroids, and reason for SRL initiation and discontinuation. <h3>Results</h3> A total of 22 patients were included, 9 vs. 13 in the high and low TAC/SRL groups, respectively. Baseline characteristics were similar between groups. HTR in the high TAC/SRL group had higher median infection rate per year of therapy compared to those in the low group (1.67 vs 0.75, p<0.001). Numerically there were more patients with any cellular rejection (Grade 0R, 1R, 2R or 3R) in the high (100%) compared to the low group (77%). There were no cases of antibody mediated rejection in either group. <h3>Conclusion</h3> Higher combined concentrations of TAC/SRL in HTR resulted in increased infections per year. Due to the retrospective nature of this study, it is difficult to conclude the association between high TAC/SRL level and rejection severity. Given the small sample size and retrospective design, additional studies are warranted to confirm infection rates and to prospectively assess the association of high combined TAC/SRL concentrations on allograft rejection.

Modeling intra-mosquito dynamics of Zika virus and its dose-dependence confirms the low epidemic potential of Aedes albopictus.

Originating from African forests, Zika virus (ZIKV) has now emerged worldwide in urbanized areas, mainly transmitted by Aedes aegypti mosquitoes. Although Aedes albopictus can transmit ZIKV experimentally and was suspected to be a ZIKV vector in Central Africa, the potential of this species to sustain virus transmission was yet to be uncovered until the end of 2019, when several autochthonous transmissions of the virus vectored by Ae. albopictus occurred in France. Aside from these few locally acquired ZIKV infections, most territories colonized by Ae. albopictus have been spared so far. The risk level of ZIKV emergence in these areas remains however an open question. To assess Ae. albopictus' vector potential for ZIKV and identify key virus outbreak predictors, we built a complete framework using the complementary combination of (i) dose-dependent experimental Ae. albopictus exposure to ZIKV followed by time-dependent assessment of infection and systemic infection rates, (ii) modeling of intra-human ZIKV viremia dynamics, and (iii) in silico epidemiological simulations using an Agent-Based Model. The highest risk of transmission occurred during the pre-symptomatic stage of the disease, at the peak of viremia. At this dose, mosquito infection probability was estimated to be 20%, and 21 days were required to reach the median systemic infection rates. Mosquito population origin, either temperate or tropical, had no impact on infection rates or intra-host virus dynamic. Despite these unfavorable characteristics for transmission, Ae. albopictus was still able to trigger and yield large outbreaks in a simulated environment in the presence of sufficiently high mosquito biting rates. Our results reveal a low but existing epidemic potential of Ae. albopictus for ZIKV, that might explain the absence of large scale ZIKV epidemics so far in territories occupied only by Ae. albopictus. They nevertheless support active surveillance and eradication programs in these territories to maintain the risk of emergence to a low level.

Variation in COVID-19 Diagnosis by Zip Code and Race and Ethnicity in Indiana.

Objectives: To describe variations in coronavirus disease 2019 (COVID-19) diagnosis by zip code race and ethnicity in Indiana.Methods: Cross-sectional evaluation of subjects with SARS-CoV-2 at Indiana University Health. We performed two separate analyses, first evaluating likelihood of COVID-19 diagnosis by race (Caucasian, African American, Asian, or other) and ethnicity (Hispanic vs. non-Hispanic) in the cohort encompassing the entire state of Indiana. Subsequently, patient data was geolocated with zip codes in Marion County and the immediate surrounding counties, and descriptive statistical analyses were used to calculate the number of COVID-19 cases per 10,000 persons for each of these zip codes.Results: Indiana had a total of 3,892 positive COVID-19 cases from January 1 to April 30, 2020. The odds of testing positive for COVID-19 were four-fold higher in African Americans than non-African Americans (OR 4.58, 95% CI 4.25–4.94, P < 0.0001). Increased COVID-19 cases per 10,000 persons were seen in zip codes with higher percentage of African American (median infection rate of 17.4 per 10,000 population in zip codes above median % African American compared to 6.7 per 10,000 population in zip codes below median % African American, with an overall median infection rate 9.9 per 10,000 population, P < 0.0001) or Hispanic residents (median infection rate of 15.9 per 10,000 population in zip codes above median % Hispanic compared to 7.0 per 10,000 population in zip codes below median % Hispanic, overall median infection rate 9.6 per 10,000 population, P < 0.0001).Conclusions: Individuals from zip codes with higher percentages of African American, Hispanic, foreign-born, and/or residents living in poverty are disproportionately affected by COVID-19. Urgent work is needed to understand and address the disproportionate burden of COVID-19 in minority communities and when economic disparities are present.

Relation of Dietary Factors with Infection and Mortality Rates of COVID-19 across the World

ObjectivePoor dietary habits are considered to be the second-leading risk factors for mortality and disability-adjusted life-years (DALYs) in the world. Dietary patterns are different based on cultural, environmental, technological, and economic factors. Nutritional deficiencies of energy, protein, and specific micronutrients have been shown to contribute to depressed immune function and increased susceptibility to infections. We aimed to explore the relation of dietary factors with global infection and mortality rates of COVID-19 in this study.DesignIn the current ecological study, the countries that had national dietary data from the Global Dietary Databases of the United Nations and Coronavirus disease statistics from the World Health Organization (WHO) were included. The countries that had Coronavirus disease statistics from the WHO were consecutively checked for the recent data of the dietary factors.SettingWorld.Participants158 countries across the world.Measurementsinfection and mortality rates of COVID-19; dietary factors.ResultsThe median crude infection and mortality rates by COVID-19 were 87.78 (IQR: 468.03) and 0.0015 (IQR: 0.0059), respectively. The two highest percentage of the crude infection rate were between 0 and 500 (75.9%) and 500–1000 (8.9%) per one million persons. The regression analysis showed that the crude infection rate has been increased by raising consuming fruits (Beta: 0.237; P=0.006) and calcium (Beta: 0.286; P=0.007) and was decreased with rising consuming beans and legumes (Beta: −0.145; P=0.038). The analysis showed that the crude mortality rate was increased by raising consuming sugar-sweetened beverages (Beta: 0.340; P<0.001). Whereas, the crude mortality rate by COVID-19 has been decreased by increasing fruits consuming (Beta: −0.226; P=0.047) and beans and legumes (Beta: −0.176; P=0.046).ConclusionThe present study showed the higher intake of fruits and sugar-sweetened beverages had a positive effect on infection and mortally rates by COVID-19, respectively. In contrast, the higher intake of beans and legumes had a negative effect on both increasing infection and mortality rates.

Relation of Dietary Factors with Infection and Mortality Rates of COVID-19 across the World.

ObjectivePoor dietary habits are considered to be the second-leading risk factors for mortality and disability-adjusted life-years (DALYs) in the world. Dietary patterns are different based on cultural, environmental, technological, and economic factors. Nutritional deficiencies of energy, protein, and specific micronutrients have been shown to contribute to depressed immune function and increased susceptibility to infections. We aimed to explore the relation of dietary factors with global infection and mortality rates of COVID-19 in this study.DesignIn the current ecological study, the countries that had national dietary data from the Global Dietary Databases of the United Nations and Coronavirus disease statistics from the World Health Organization (WHO) were included. The countries that had Coronavirus disease statistics from the WHO were consecutively checked for the recent data of the dietary factors.SettingWorld.Participants158 countries across the world.Measurementsinfection and mortality rates of COVID-19; dietary factors.ResultsThe median crude infection and mortality rates by COVID-19 were 87.78 (IQR: 468.03) and 0.0015 (IQR: 0.0059), respectively. The two highest percentage of the crude infection rate were between 0 and 500 (75.9%) and 500–1000 (8.9%) per one million persons. The regression analysis showed that the crude infection rate has been increased by raising consuming fruits (Beta: 0.237; P=0.006) and calcium (Beta: 0.286; P=0.007) and was decreased with rising consuming beans and legumes (Beta: −0.145; P=0.038). The analysis showed that the crude mortality rate was increased by raising consuming sugar-sweetened beverages (Beta: 0.340; P<0.001). Whereas, the crude mortality rate by COVID-19 has been decreased by increasing fruits consuming (Beta: −0.226; P=0.047) and beans and legumes (Beta: −0.176; P=0.046).ConclusionThe present study showed the higher intake of fruits and sugar-sweetened beverages had a positive effect on infection and mortally rates by COVID-19, respectively. In contrast, the higher intake of beans and legumes had a negative effect on both increasing infection and mortality rates.

Estimating COVID-19 Prevalence in the United States: A Sample Selection Model Approach

Background: Public health efforts to determine population infection rates from coronavirus disease 2019 (COVID-19) have been hampered by limitations in testing capabilities and the large shares of mild and asymptomatic cases. We developed a methodology that corrects observed positive test rates for non-random sampling to estimate population infection rates across U.S. states from March 31 to April 7. Methods: We adapted a sample selection model that corrects for non-random testing to estimate population infection rates. The methodology compares how the observed positive case rate vary with changes in the size of the tested population, and applies this gradient to infer total population infection rates. Model identification requires that variation in testing rates be uncorrelated with changes in underlying disease prevalence. To this end, we relied on data on day-to-day changes in completed tests across U.S. states for the period March 31 to April 7, which were primarily influenced by immediate supply-side constraints. We used this methodology to construct predicted infection rates across each state over the sample period. We also assessed the sensitivity of the results to controls for state-specific daily trends in infection rates. Results: The median population infection rate over the period March 31 to April 7 was 0.9% (IQR 0.64 1.77). The three states with the highest prevalence over the sample period were New York (8.5%), New Jersey (7.6%), and Louisiana (6.7%). Estimates from models that control for state-specific daily trends in infection rates were virtually identical to the baseline findings. The estimates imply a nationwide average of 12 population infections per diagnosed case. We found a negative bivariate relationship (corr. = -0.51) between total per capita state testing and the ratio of population infections per diagnosed case. Interpretation: The effectiveness of the public health response to the coronavirus pandemic will depend on timely information on infection rates across different regions. With increasingly available highly frequency data on COVID-19 testing, our methodology could be used to estimate population infection rates for a range of countries and subnational districts. In the United States, we found widespread undiagnosed COVID-19 infection. Expansion of rapid diagnostic and serological testing will be critical in preventing recurrent unobserved community transmission and identifying the large numbers individuals who may have some level of viral immunity. Funding Statement: This study was supported by funding from the Social Sciences and Humanities Research Council (Grant: SSHRC 430-2017-00307). Declaration of Interests: The authors declare no competing interests.

1233. Surveillance Quality Correlates with SSI Rates in Prosthetic Hip and Knee Surgery: A Call to Action to Adjust Reporting of SSI rates

BackgroundSurgical site infections (SSIs) are rather infrequent following knee and hip surgery, but can have profound consequences for the patient. SSI data from a large network of Swiss hospitals has routinely been collected in a nationwide SSI surveillance system since 2009. The aim of the study was to investigate whether SSI rates are correlated with the quality of surveillance.MethodsWe calculated the weighted mean NNIS adjusted infection rates for hip and knee surgeries for the years in which audits occurred in each hospital. The 50-point score per audit is an amalgamation of quantitative and qualitative information from both structured interviews and a random selection of reviewed patient records, including (amongst others) an evaluation of completeness of medical documentation, follow-up, data quality, and training.ResultsThe analysis included 30’696 knee and hip surgeries from 92 hospitals (excluding those institutions with <50 procedures in the audit year), with median infection rate 1% (IQR [1–2%]) and median audit score 35 (IQR [32–39]). The Figure plots the NNIS adjusted infection rate against audit score along with the linear fit (solid red) and 95% confidence intervals (gray). There is large variability in rates and scores, with a noticeable increasing trend (P = 0.01). Using the median of both metrics to divide the plot into 4 quadrants, those hospitals in the lower left quadrant have both low infection rates and low audit scores (predominantly private hospitals), whereas those in the upper right quadrant have both higher SSI rates and audit scores (mostly public hospitals). Those in the lower right quadrant represent the ideal situation with both low rates and high-quality surveillance.ConclusionIn this national surveillance of nosocomial SSI hip and knee infections, there was a wide range of SSI rates and surveillance quality, with discernible clustering of hospital types. Those hospitals with low infection rate correlated with low-quality audit scores. Surveillance systems without routine evaluation of validity may underestimate the true incidence of SSIs. Audit quality should be taken into account when interpreting SSI rates, perhaps by infection rates for those hospitals with lower audit scores. Disclosures All authors: No reported disclosures.

A randomised single-centre trial of inhaled liposomal cyclosporine for bronchiolitis obliterans syndrome post-lung transplantation.

IntroductionNo proven treatments exist for bronchiolitis obliterans syndrome (BOS) following lung transplantation. Inhaled liposomal cyclosporine (L-CsA) may prevent BOS progression.MethodsA 48-week phase IIb randomised clinical trial was conducted in 21 lung transplant patients with BOS assigned to either L-CsA with standard-of-care (SOC) oral immunosuppression (L-CsA group) or SOC (SOC-alone group). Efficacy end-points were BOS progression-free survival (defined as absence of ≥20% decline in forced expiratory volume in 1 s (FEV1) from randomisation, re-transplantation or death) and BOS grade change.ResultsBOS progression-free survival was 82% for L-CsA versus 50% for SOC-alone (p=0.1) and BOS grade worsened in 18% for L-CsA versus 60% for SOC-alone (p=0.05). Mean changes in ΔFEV1 and forced vital capacity, respectively, stabilised with L-CsA: +0.005 (95% CI −0.004– +0.013) and −0.005 (95% CI −0.015– +0.006) L·month−1, but worsened with SOC-alone: −0.023 (95% CI −0.033– −0.013) and −0.026 (95% CI −0.039– −0.014) L·month−1 (p<0.0001 and p=0.009). Median survival (4.1 versus 2.9 years; p=0.03) and infection rate (45% versus 60%; p=0.7) improved with L-CsA versus SOC-alone; creatinine and tacrolimus levels were similar.ConclusionsL-CsA was well tolerated and stabilised lung function in lung transplant recipients affected by BOS without systemic toxicity, providing a basis for a global phase III trial using L-CsA.

Clinical, Laboratory, and Molecular Characteristics and Remission Status in Children With Severe Congenital and Non-congenital Neutropenia.

Objectives: Severe congenital neutropenia (SCN) is a primary immunodeficiency disease characterized by the early onset of recurrent infections and persistent severe neutropenia, with or without genetic defect. We aimed to study the different clinical features and hematological and bone marrow characteristics of patients with SCN and the non-congenital form of severe neutropenia (SN) with unknown etiology.Methods: Thirty-nine Chinese children with severe neutropenia for longer than 6 months unrelated to virus infection or autoimmune diseases were enrolled in the study to analyse the clinical, laboratory, and molecular characteristics. They were followed clinically to observe their remission status.Results: Seven patients were found to have SCN mutations, including ELANE and G6PC3. Among 26 patients with close follow-up, one died for an unknown reason, and 10 resolved spontaneously with a median neutropenia duration of 14.5 months; these patients were designated as having recovered SN. The demographic characteristics of both groups were similar, with a median infection rate of 5 times/year. SCN patients had more frequent infection than recovered SN patients (4 times/year, P = 0.039). The median absolute neutrophil count (ANC) was 0.40 × 109/L in SCN patients, which was significantly higher than 0.2 × 109/L in SN with unknown etiology and 0.21 × 109/L in recovered SN patients (P = 0.021, P = 0.017). The median monocyte count was 1.60 × 109/L in SCN patients, which was also significantly higher than 0.57 × 109/L in SN of unknown etiology and 0.55 × 109/L in recovered SN patients (P = 0.018, P = 0.001). Bone marrow examinations demonstrated myeloid maturation arrest at the myelocyte-metamyelocyte stage in SCN patients and normal findings in SN with unknown etiology and recovered SN patients.Conclusions: Patients with severe neutropenia due to gene mutations demonstrate more serious symptoms than patients with unknown etiology. Patients with relatively higher ANC and monocyte counts are more likely to have known gene mutations. Future studies should focus on more detailed laboratory investigation, prolonged follow-up and advanced molecular biology tools to facilitate accurate diagnosis and effective treatment.

Su1989 - Severe Gastrointestinal Dysmotility Related Intestinal Failure: Chronic Intestinal Pseudo-Obstruction, Enteric Dysmotility or a ‘Pragmatic’ Approach? Experience from a UK National Referral Centre

Introduction Gastrointestinal dysmotility (GID) is a recognised cause of Type 3 Intestinal Failure (IF). Diagnosis is challenging, with uncertain merits of subclassifying into chronic intestinal pseudo-obstruction (CIPO) and Enteric Dysmotility (ED) 1 . A ‘pragmatic’ algorithm for GID has been proposed to address these difficulties 2 . Retrospectively, we evaluated the performance of ED/CIPO diagnostic criteria and pragmatic GID criteria in predicting outcomes of patients with ‘dysmotility’ requiring home parenteral nutrition (HPN). Method Patients with primary dysmotility referred for HPN to a national IF Unit (1999–2015) were identified. 2 investigators reviewed casenotes for clinical histories, motility tests, imaging, full-thickness biopsies (FTB), breath tests, HPN and survival outcomes. Cases were excluded if they did not meet pragmatic GID criteria (morbidity + either >1 region abnormal motility test or positive FTB + small bowel (SB) involvement). Patients satisfying GID criteria were then sub-categorised into; ED (objective SB dysmotility), CIPO (ED criteria + non-mechanical SB dilatation) and ‘non-CIPO/ED’ if neither criteria were met. Outcomes were compared between subgroups. Results 44 patients met GID criteria (median age 40, 30 females, 18/44 with abnormal FTBs (myopathy n=12, neuropathy n=6) and median follow-up 5 years)), whereas 7 patients not meeting pragmatic criteria were excluded. HPN improved BMI (median pre 18.3 vs. post 21.2 kg/m 2 , p=0.01). HPN outcomes: survival at 1, 5 and 10 years was 95%, 77% and 47%, median catheter-related blood stream infection rate (CRBSI) 0.5/1000 days, and 18% achieved HPN independence. 25/44 (57%) met criteria for CIPO, 12/44 (27%) ED and 7/44 (16%) were ‘non-CIPO/ED’ patients that met GID criteria. CIPO was associated with bacterial overgrowth (13/25 vs. 3/19, p=0.03), and HPN dependency (1/25 weaned off HPN vs. 7/19, p=0.01) when compared to the ED and ‘non-CIPO/ED’ groups. Other factors including the yield of FTBs, opiate-dependence and HPN complications (CRBSI, IF associated liver disease and catheter related venous thromboses) did not significantly differ between the three groups. Conclusion Our data emphasise important prognostic implications of CIPO diagnosis in the IF/GID population as a predictor of HPN dependency. Combining pragmatic evidence-based criteria with imaging to exclude CIPO is likely to give the maximum diagnostic and prognostic yield across the spectrum of GID. References . Wingate, et al. Journal of Gastroenterology and Hepatology200217:S1–S14 . Paine, et al. Alimentary pharmacology & therapeutics201338(10):1209–1229. Disclosure of Interest None Declared

Advanced Neonatal Medicine in China: A National Baseline Database.

Previous surveys of neonatal medicine in China have not collected comprehensive information on workforce, investment, health care practice, and disease expenditure. The goal of the present study was to develop a national database of neonatal care units and compare present outcomes data in conjunction with health care practices and costs. We summarized the above components by extracting data from the databases of the national key clinical subspecialty proposals issued by national health authority in China, as well as publicly accessible databases. Sixty-one newborn clinical units from provincial or ministerial hospitals at the highest level within local areas in mainland China, were included for the study. Data were gathered for three consecutive years (2008–2010) in 28 of 31 provincial districts in mainland China. Of the 61 newborn units in 2010, there were 4,948 beds (median = 62 [IQR 43–110]), 1,369 physicians (median = 22 [IQR 15–29]), 3,443 nurses (median = 52 [IQR 33–81]), and 170,159 inpatient discharges (median = 2,612 [IQR 1,436–3,804]). During 2008–2010, the median yearly investment for a single newborn unit was US$344,700 (IQR 166,100–585,800), median length of hospital stay for overall inpatient newborns 9.5 (IQR 8.2–10.8) days, median inpatient antimicrobial drug use rate 68.7% (IQR 49.8–87.0), and median nosocomial infection rate 3.2% (IQR1.7–5.4). For the common newborn diseases of pneumonia, sepsis, respiratory distress syndrome, and very low birth weight (<1,500 grams) infants, their lengths of hospital stay, daily costs, hospital costs, ratios of hospital cost to per-capita disposable income, and ratios of hospital cost to per-capita health expenditure, were all significantly different across regions (North China, Northeast China, East China, South Central China, Southwest China, and Northwest China). The survival rate of extremely low birth weight (ELBW) infants (Birth weight <1,000 grams) was 76.0% during 2008–2010 in the five hospitals where each unit had more than 20 admissions of ELBW infants in 2010; and the median hospital cost for a single hospital stay in ELBW infants was US$8,613 (IQR 8,153–9,216), which was 3.0 times (IQR 2.0–3.2) the average per-capita disposable income, or 63 times (IQR 40.3–72.1) the average per-capita health expenditure of local urban residents in 2011. Our national database provides baseline data on the status of advanced neonatal medicine in China, gathering valuable information for quality improvement, decision making, longitudinal studies and horizontal comparisons.

Outcome of Minimally Invasive Open and Percutaneous Techniques for Repair of Calcaneal Fractures: A Systematic Review

Percutaneous and minimally invasive open techniques for the treatment of calcaneal fractures are now frequently used with good results, although a comparison between these different techniques has not yet been performed. The aim of the present review was to search for studies evaluating the outcomes of patients after treatment with percutaneous and minimally invasive open techniques for calcaneal fractures. A search was performed using PubMed/MEDLINE, Embase, and the Cochrane Library. Studies from the previous 15years in English were included. Data on the Sanders classification, operation technique, infection rate, American Orthopaedic Foot and Ankle Society ankle-hindfoot score, radiographic evaluation, and follow-up were extracted. The techniques were divided into 4 groups: minimally invasive open, percutaneous reduction and screw osteosynthesis, external fixation, and other. Forty-six studies were included, with 1776 patients and 2018 calcaneal fractures. Of the 2018 fractures, 924 (46%) were classified as Sanders II, 558 (28%) as Sanders III, and 245 (12%) as Sanders IV; the fractures of 291 patients(14%) were not classified or were classified as complete extra-articular. Of the 46 studies, 15 used a minimally invasive open technique, 19 evaluated the outcome of percutaneous reduction and screw osteosynthesis, 10 investigated the results of an external fixation system, and 2 studies used other operative techniques. The median infection rate was 3% (range 0% to 33%). The median American Orthopaedic Foot and Ankle Society ankle-hindfoot score was 83 (range 67 to 94). The median angle of Böhler postoperatively was 24° (range 14° to 35°) and had increased after operative treatment, with a median of 16° (range 0° to 39°). The percutaneous reduction and screw osteosynthesis and minimal invasive open technique resulted in significantly better outcomes compared with external fixation and other techniques. In conclusion, percutaneous reduction and screw osteosynthesis and minimal invasive open techniques have the best outcomes for the minimal invasive open surgical treatment of calcaneal fractures.

Increasing Incidence of Extended-Spectrum β-Lactamase-Producing Escherichia coli in Community Hospitals throughout the Southeastern United States.

OBJECTIVE To describe the epidemiology of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (ESBL-EC) and Klebsiella pneumoniae (ESBL-KP) infections DESIGN Retrospective cohort SETTING Inpatient care at community hospitals PATIENTS All patients with ESBL-EC or ESBL-KP infections METHODS ESBL-EC and ESBL-KP infections from 26 community hospitals were prospectively entered into a centralized database from January 2009 to December 2014. RESULTS A total of 925 infections caused by ESBL-EC (10.5 infections per 100,000 patient days) and 463 infections caused by ESBL-KP (5.3 infections per 100,000 patient days) were identified during 8,791,243 patient days of surveillance. The incidence of ESBL-EC infections increased from 5.28 to 10.5 patients per 100,000 patient days during the study period (P=.006). The number of community hospitals with ESBL-EC infections increased from 17 (65%) in 2009 to 20 (77%) in 2014. The median ESBL-EC infection rates among individual hospitals with ≥1 ESBL-EC infection increased from 11.1 infections/100,000 patient days (range, 2.2-33.9 days) in 2009 to 22.1 infections per 100,000 patient days (range, 0.66-134 days) in 2014 (P=.05). The incidence of ESBL-KP infections remained constant over the study period (P=.14). Community-associated and healthcare-associated ESBL-EC infections trended upward (P=.006 and P=.02, respectively), while hospital-onset infections remained stable (P=.07). ESBL-EC infections were more common in females (54% vs 44%, P<.001) and Caucasians (50% vs 40%, P<.0001), and were more likely to be isolated from the urinary tract (61% vs 52%, P<.0001) than ESBL-KP infections. CONCLUSIONS The incidence of ESBL-EC infection has increased in community hospitals throughout the southeastern United States, while the incidence of ESBL-KP infection has remained stable. Community- and healthcare-associated ESBL-EC infections are driving the upward trend. Infect. Control Hosp. Epidemiol. 2015;37(1):49-54.

Outbreaks of Pseudomonas aeruginosa in pediatric patients – Clinical aspects, risk factors and management

Several outbreaks of Pseudomonas aeruginosa have been published in neonatal and pediatric patients, but no systematic analysis is available. Medline and outbreak-database search, systematic analysis of outbreak reports (confirmed by genotyping). Twenty-four studies were included. Outbreaks caused by P. aeruginosa resulted in high morbidity (median clinical infection rate: 68%; range: 0–100%), mortality (median 27%; 0–100%) and resource consumption in neonatal and pediatric inpatient facilities. In most cases, these outbreaks indicate certain breaches in basic hygienic practices or are due to the persistence of P. aeruginosa in environmental vectors and reservoirs (tap water, medical devices, and fomites). The majority of the reported isolates displayed multi-resistance to first-line antibiotics. The clinical observation of two or more temporally related cases of nosocomial P. aeruginosa infections should raise the suspicion of an outbreak particularly in high-risk pediatric patient populations (neonatal intensive care unit, pediatric intensive care unit, oncology) and when the isolate displays resistance to two or more first-line antibiotics. Strict hygienic barrier precautions should immediately be implemented, re-educated and supervised. Well-planned environmental culturing should be performed, paying special attention to water, water outlets, sinks and other wet areas, to identify environmental reservoirs. A water safety plan based on the WHO Guidelines for Drinking Water Quality must be introduced. The current strategy of empiric antibiotic treatment should be investigated by an infectious diseases' specialist. Genotyping of the isolates by pulse-field gel electrophoresis should be performed, but any interventions to interrupt further nosocomial spread should be carried out without waiting for the results.

The Use of Protocols in Obstetrics and Gynecology

There was, is, and there always will be a clamor for a protocol-based approach to treat acute conditions in Obstetrics and Gynecology. Conditions like post-partum hemorrhage, rupture of the uterus, abruptio placenta, ectopic pregnancy, and gestational trophoblastic neoplasm come to mind readily. At times, severe differences can arise when protocols of different “schools of thought” are sought to be debated, and rightly so. Questions then arise and with it some doubts. Does labor have to be “programmed?” Should epidural analgesia be administered only when the patient is in active labor? Can protocols be designed broadly for the condition and specifically altered for each individual? Should doctors be “forced” to follow protocols? Why protocols anyway? Well, protocols are intended to allow for a systematic approach to a condition, to make sure serious mistakes and variations are not made in treatment, and to ensure that correct investigations are asked for, a contemporary well-documented method of treatment is instituted, and cost effectiveness maintained. Litigation may be prevented as well. A surgical safety checklist developed by Haynes et al. [1] for the WHO is an example of a protocol that can be useful before, during, and after surgery. Protocols or checklists can and should be used when there is some leeway for a procedural approach; however, in cases of a dire emergency, resorting to such an approach may be costly in term of loss of precious time, and in such cases learned memory and a robust “common sense” approach may be best suited. Pronovost et al. [2] described a protocol to reduce infections when introducing central venous catheters due to which the median infection rate at a typical ICU dropped from 2.7 per 1,000 to zero in 3 months. The protocol consisted of seemingly a simple approach of washing hands with soap; cleaning the patient’s skin with chlorhexidine; putting sterile drapes over the whole patient; wearing sterile hat, mask, gown, and gloves; and putting a sterile dressing over the catheter site. A simple solution for a complex problem. Protocols exist for the management of eclampsia, yet after the initiation of investigations and initial treatment, the condition of the patient and any existing complications that present, e.g., renal failure, disseminated intravascular coagulation, may indicate a delay for delivery; in other cases, labor may be induced or a cesarean section may be proceeded with promptly. Similarly, in cases of obstetric hemorrhage protocols, the use of packed red blood cells, fresh frozen plasma, and cryoprecipitate in certain ratios may be advocated, yet the anesthetist/intensivist managing a particular case may ultimately decide upon how the massive transfusion protocol needs to be administered. However, institution protocols and drills go a long way to ensure that a critical obstetric case is treated competently regardless of the individual in charge at that point in time. Maintaining a well-researched and documented protocol or a checklist for the management of labor is almost mandatory. This could include recording via the history and initial findings, the raising of “red flags”—previous cesarean section, diabetes, placenta previa, pregnancy-induced hypertension—the maintenance of a partogram, the correct use of oxytocics, a recording of intrapartum monitoring when deemed necessary, and a well-timed intervention to end labor. There are several established protocols for the use of oxytocin and any of these could be followed with good results. However, a protocol of hand washing, the use of sterile gowns, and a clean environment to maintain hygiene when delivery is conducted in the labor room is almost mandatory to prevent post-partum morbidity. Protocols in the management of preterm labor could include documentation of contractions by cardiotocography, obtaining a high vaginal swab, a baseline ECG when tocolytics are considered, and the stoppage of treatment when uterine contractions are controlled. Likewise, the use of steroids in such cases is also dictated by several established protocols. An ideal protocol that can be adopted universally is non-existent. Protocols can and should vary marginally depending on local resources and work ethic. However, some standardized methodology has to be adopted in every institution or nursing home so that the essentials are kept in sight and the endpoints of treatment are achieved. Protocols have to be reviewed and altered whenever necessary to maintain a “contemporary” value to treatment. No archaic treatment based on “experience” or anecdotal evidence will be tolerated by anyone anymore.