A multicenter audit of the use of bronchoscopy during open and thoracoscopic repair of esophageal atresia with tracheoesophageal fistula.

BACKGROUND: Esophageal atresia (EA) with tracheoesophageal fistula is usually repaired in the neonatal period. Preferential ventilation through the fistula can lead to gastric distension. Bronchoscopy has a role in defining the site and size of the fistula, and may be carried out by the surgeon or the anesthetist. The use of bronchoscopy varies across different institutions. METHODS: This is a multicenter case note review of infants with EA with tracheoesophageal fistula who underwent surgery between January 2010 and December 2015. This retrospective audit aims primarily to document the use of bronchoscopy during open and thoracoscopic repair at a selection of United Kingdom centers. Respiratory complications, that is relating to airway management, the respiratory system, and difficulty with ventilation, at induction and during surgery, are recorded. The range of techniques for anesthesia and analgesia in these centers is noted. RESULTS: Bronchoscopy was carried out in 52% of cases. The incidence of respiratory complications was 7% at induction and 21% during surgery. Thoracoscopic repair usually took longer. One center used high-frequency oscillatory ventilation, on an elective basis during thoracoscopic repair, to facilitate surgical access and address concerns about hypoxemia and hypercarbia. CONCLUSION: The use of bronchoscopy varies considerably between institutions. Infants undergoing tracheoesophageal fistula repair are at risk of perioperative respiratory morbidity. The advent of thoracoscopic repair has introduced further variation.

Recent outbreaks of infectious syphilis, United Kingdom, January 2012 to April 2014.

Six outbreaks of infectious syphilis in the United Kingdom, ongoing since 2012, have been investigated among men who have sex with men (MSM) and heterosexual men and women aged under 25 years. Interventions included case finding and raising awareness among healthcare professionals and the public. Targeting at-risk populations was complicated as many sexual encounters involved anonymous partners. Outbreaks among MSM were influenced by the use of geospatial real-time networking applications that allow users to locate other MSM within close proximity.

Lyophilized (freeze-dried) human milk for preterm infants: a scoping review.

Freeze-drying (FD), or lyophilization, is commonly used to preserve foods. FD offers potential to create a human milk-derived human milk fortifier, and an alternative to freeze-storing human milk. However, processing human milk is known to affect its components. This scoping review explores the effect of FD on the; macronutrient, micronutrient, vitamin, bioactive components, microbes and anti-microbial factors in human milk, and studies where lyophilized human milk has been given to newborn infants. 48 articles were identified after full text review. FD human milk reduces the fat globule size and as well as the quantity of enzymes, vitamin C and immunoglobulin. Common serum electrolyte disturbances have been reported when preterm infants' are fed FD human milk however it appears a promising method to avoid exposure of preterm infants' to cows' milk. Due to limited data, further studies exploring the safety and efficacy of FD human milk in preterm infants are needed.

Gestational Development of the Human Immune System.

Building an immune system is a monumental task critical to the survival of the fetus and newborn. A functional fetal immune system must complement the maternal immune system in handling in utero infection; abstain from damaging non-self-reactions that would compromise the materno-fetal interface; mobilize in response to infection and equip mucosal tissues for pathogen exposure at birth. There is growing appreciation that immune cells also have noncanonical roles in development and specifically may contribute to tissue morphogenesis. In this review we detail how hematopoietic and lymphoid organs jointly establish cellular constituents of the immune system; how these constituents are organized in 2 mucosal sites-gut and lung-where early life immune function has long-term consequences for health; and how exemplar diseases of prematurity and inborn errors of immunity reveal dominant pathways in prenatal immunity.

A Quality Improvement Initiative to Reduce Necrotizing Enterocolitis in Very Preterm Infants.

OBJECTIVE: To reduce the incidence of necrotizing enterocolitis (NEC) among very preterm infants in the Calgary Health Region to ≤2% within 2 years. METHODS: A multidisciplinary team developed key drivers for NEC. Targeted interventions included strategies to increase mothers' own milk (MOM), improve compliance with feeding regimens, standardize management of feeding intolerance, prevent intestinal microbial aberrations, and feed conservatively during blood transfusion and the treatment of patent ductus arteriosus. The outcome measure was NEC (≥ stage 2). Changes in NEC rates were examined among racial and ethnic groups. Process measures included MOM feeding at discharge, the difference between actual and expected time to reach full feeds, lowest hemoglobin, and the duration of empirical antibiotics. Growth, the rate of blood transfusion, and the duration of parenteral nutrition were balancing measures. The preintervention, intervention, and sustainment periods were January 2013 to June 2016, July 2016 to December 2018, and December 2018 to December 2021, respectively. RESULTS: We included 2787 infants born at ≤326/7 weeks' gestation (1105 preintervention, 763 during intervention, and 919 in sustainment). NEC decreased from 5.6% to 1.9%. Process measures indicated increased MOM feeding at discharge, improved compliance with feeding regimens, increased lowest hemoglobin levels, and shorter durations of empirical antibiotics. Balancing measures revealed improved weight Z-scores, shorter durations on parenteral nutrition, and increased rates of blood transfusion. CONCLUSIONS: Quality improvement initiatives to increase MOM, improve compliance with feeding regimens, feed conservatively during blood transfusion and treatment of patent ductus arteriosus, and prevent intestinal microbial aberrations were associated with reduced NEC.

Laboratory-based surveillance of Campylobacter and Salmonella infection and the importance of denominator data.

Laboratory data are the cornerstone in surveillance of infectious disease. We investigated whether changes in reported incidence of Campylobacter and Salmonella infection might be explained by changes in stool sampling rates. Data were extracted from a national database on 585 843 patient stool samples tested by microbiology laboratories in Wales between 1998 and 2008. Salmonella incidence fell from 43 to 19 episodes/100 000 population but Campylobacter incidence after declining from 111/100 000 in 1998 to 84/100 000 in 2003 rose to 119/100 000 in 2008. The proportion of the population sampled rose from 2·0% in 1998 to 2·8% in 2008, mostly due to increases in samples from hospital patients and older adults. The proportion of positive samples declined for both Salmonella and Campylobacter from 3·1% to 1·1% and from 8·9% to 7·5%, respectively. The decline in Salmonella incidence is so substantial that it is not masked even by increased stool sampling, but the recent rise in Campylobacter incidence may be a surveillance artefact largely due to the increase in stool sampling in older people.

Two waves of pandemic influenza A(H1N1) 2009 in Wales--the possible impact of media coverage on consultation rates, April-December 2009.

In the United Kingdom, the influenza A(H1N1) 2009 pandemic had a distinct two-wave pattern of general practice consultations for influenza-like illness (ILI). We describe the epidemiology of the influenza pandemic in Wales between April and December 2009 using integrated data from a number of independent sources: GP surveillance, community virology surveillance, hospital admissions and deaths, and media enquiries monitoring. The first wave peaked in late July at 100 consultations per 100,000 general practice population and attracted intensive media coverage. The positivity rate for the A(H1N1)2009 influenza did not exceed 25% and only 44 hospitalisations and one death were recorded. By contrast, the second wave peaked in late October and although characterised by lower ILI consultation rates (65 consultations per 100,000 general practice population) and low profile media activity, was associated with much higher positivity rates for pandemic influenza A(H1N1)2009 (60%) and substantially more hospital admissions (n=379) and deaths (n=26). The large number of ILI-related consultations during the first wave in Wales probably reflected the intensive media activity rather than influenza virus circulating in the community. Data from community surveillance schemes may therefore have considerably overestimated the true incidence of influenza. This has implications for the future interpretation of ILI surveillance data and their use in policy making, and underlines the importance of using integrated epidemiological, virological and hospital surveillance data to monitor influenza activity.

Why has oral health promotion and prevention failed children requiring general anaesthesia for dental extractions?

OBJECTIVES: Many children in the UK still require dental treatment under general anaesthesia (DGA). Why oral health promotion and prevention, in this cohort of children, has failed is poorly understood. By questioning the parents/carers of children undergoing DGA this study aimed to establish: 1 previous exposure to oral health education and promotion activities; 2 beliefs and behaviours about dental caries and prevention; and 3 what parents perceive useful in preventing dental caries. BASIC RESEARCH DESIGN: A cross-sectional questionnaire based study. CLINICAL SETTING: Dental general anaesthetic centres in Wales, UK. PARTICIPANTS: 207 consecutively attending parents of children aged < 10 years requiring a DGA. RESULTS: In total, 150 (76%) parents/carers claimed to have received previous oral health advice and 103 (52%) had received toothbrushing instruction from a dentist. Only 18 (9%) reported the application of topical fluoride. Sixty seven (34%) believed "tooth decay runs in families" and 53 (27%) it was simply bad luck that their child had dental decay. The majority (89%) believed that information leaflets on oral health would be useful and 133 (67%) would find information on a website helpful. CONCLUSIONS: This study suggests that there is a significant scope for increasing the exposure of high risk children to fluoride. A sense of fatalism and erroneous beliefs were evident amongst some parents/carers of children needing DGA. These issues need to be addressed in the future design of oral health promotion/prevention activities.

Stimulus control in pigeons based on proprioceptive stimuli from floor inclination.

Two groups of pigeons trained to peck a dimly illuminated disc in an otherwise dark experimental chamber with the floor horizontal (0 degrees tilt) or inclined 30 degrees to the left, respectively, show decremental generalization gradients of response rate when the floor inclination is varied from its training position. Discrimination training in which food reinforcement is available under one floor tilt condition but not under another steepens the slope of such gradients. In a secondv experiment, pigeons reinforced for pecking when the floor was tilted 10 degrees or 20 degrees and not reinforced under the alternative condition showed steep gradients with maximal responding displaced from the reinforced stimulus.

Acquisition of Key-Pecking via Autoshaping as a Function of Prior Experience: "Learned Laziness"?

A group of pigeons that had previously received noncontingent food delivery acquired the key-peck response (in autoshape training) more slowly than did a naive control group; key-peck acquisition was most rapid for a group given operant treadle-press training in the initial phase.

The Big Four: Functional Assessment Research Informs Preventative Behavior Analysis.

Current practice guidelines suggest that the assessment and treatment of challenging behavior should consist of conducting a functional behavior assessment following the onset of problem behavior. This assessment process can include indirect and direct assessment, as well as manipulation of variables to determine function. The purpose of this article is to outline a proposal that would add prevention practices to early intervention guidelines for problem behavior. Based on decades of research, the suggestion is to proactively teach children at risk for problem behavior to navigate four of the most common conditions that have been demonstrated to occasion problem behavior. Prevention is made a possibility because a large body of research examining the conditions under which challenging behavior occurs has been reliably replicated. Preventative approaches are an emerging phenomenon and reflect a progression in the practice of behavior analysis. Prevention may lead to acquisition of prosocial behavior before problems arise, to expedited and enhanced treatment, to increased access to favorable learning environments, and, we hope, to improvement in the quality of life for many children at risk for the development of problem behavior.

Systemic inflammatory markers in older persons: the effect of oral nutritional supplementation with prebiotics.

OBJECTIVE: To evaluate the effect of oral nutritional supplementation with and without oligosaccharides on gut bacteriology, in particular the bifidogenic flora, and on immunology and inflammatory parameters in older persons at risk of malnutrition. DESIGN: Prospective, randomized, double-blind, controlled study. SETTING: Division of Geriatric Medicine, St. Louis University, Missouri, United States. PARTICIPANTS: Seventy-four community dwelling elderly and/or nursing home subjects (age superior 70 y; 84 +/- 7 years) either undernourished or at risk of undernutrition. INTERVENTION: Daily liquid supplements, with (1.3 g/250 ml) and without oligosaccharides (OS) for 12 weeks. MEASUREMENTS: Nutritional evaluation, serum immunoglobulins, lymphocyte subsets, various cytokines and the endotoxin soluble receptor CD14 (sCD14) in serum, and cytokines specific mRNA in peripheral blood mononuclear cells at baseline and 12 weeks, and fecal bacteriologicy. RESULTS: Specific mRNA extracted from blood leucocytes showed a different level of pro-inflammatory gene activation: TNF-alpha mRNA and IL-6 mRNA diminished in the OS group after 12 weeks, while no changes were detected in the control group (P=0.05 and P=0.04 respectively). Serum levels of sCD14, a product shed by activated macrophages, decreased only in the OS group without reaching statistical significance (P=0.08). No significant differences were detected in the fecal gut flora or in the nutritional parameters. CONCLUSIONS: This study shows that the administration of supplements in older persons at risk of malnutrition may benefit from the addition of prebiotics that can improve the low noise inflammatory process frequently observed in this population.

Tuberculosis education in an endemic setting: application of participatory methods to video development in The Gambia.

OBJECTIVE: To produce an educational video for tuberculosis (TB) awareness in The Gambia using participatory methods and integrated formative evaluation. METHODS: A steering group was formed of key people working in TB research, health education, the health service and the media. They developed a script and commissioned local production of the video in three local languages and English. A formative participatory evaluation of the project was conducted using document review, attendance at rehearsals and semi-structured interviews. A pilot version of the video was evaluated through focus groups in Banjul and remote villages. Data were analysed using a general inductive approach. RESULTS: Five major themes emerged from evaluation of the project participatory process: collaboration, knowledge sharing, networking, ownership and a common desire to sustain the project goals for video dissemination. The video was well received and described as informative, entertaining and professional. Audiences were able to identify the key messages, prevailing attitudes about TB were challenged, and many participants expressed a desire to act on their new knowledge. CONCLUSION: A participatory approach to the development of a video in The Gambia proved to be empowering to local participants and led to the production of a resource well received by Gambian people.

The relationship of functional status, nutritional assessment, and severity of illness to in-hospital mortality.

BACKGROUND: Prediction of in-hospital mortality may direct hospital resources towards those patients most at risk. A number of single domain risk instruments have been developed, indicating that functional status, nutritional assessment, and severity of illness individually predict in-hospital mortality. The interaction among these predictors is less well described. OBJECTIVE: To determine the relationship of functional status, nutritional assessment, and severity of illness to in-hospital mortality. DESIGN, SETTING, SUBJECTS: Cohort study of 1712 consecutive admissions over a one year period to an Internal Medical Service at a tertiary university teaching hospital. MAIN OUTCOME MEASURES: Death during hospital admission. RESULTS: Dependency in activities of daily living (OR = 3.37, 95% CI 1.78 to 6.37, p = 0.0002) and body mass index less than 20 (OR = 2.38, 95% CI 1.20 to 4.74, p = 0.01) predicted in-hospital mortality after adjusting for nutritional risk assessment, and severity of illness score. CONCLUSIONS: Impairment in functional status and low body mass index produce the best predictors of inhospital mortality, after adjusting for nutritional risk and severity of illness score. Among these factors, functional impairment may be amenable to correction.

A prospective, randomized clinical study of adjunctive peripheral parenteral nutrition in adult subacute care patients.

BACKGROUND: A number of frail, older, undernourished patients cannot maintain adequate oral intake to meet protein-calorie needs after an illness, even when high-density nutritional supplements are added. Tolerance to enteral nutrition by gastric tube is poor in this group of patients. Peripheral parenteral nutrition is an effective method of administering nutritional support to patients with mild to moderate nutritional deficiencies who are unable to receive enteral nutrition or for whom enteral nutrition alone cannot meet energy needs. However, no data exists for the use of peripheral parenteral nutrition longer than two weeks and overall there are remarkably few studies on the efficacy of peripheral parenteral nutrition. METHODS: A Phase 4, single center, prospective, randomized, parallel group design clinical trial was conducted to evaluate long-term safety of peripheral parenteral nutrition in post-acute patients receiving inadequate enteral nutrition. Nutritional status was measured by the Mini-Nutritional Assessment and functional status by the Functional Inventory Measure. Subjects received a mean duration for peripheral parenteral nutrition of 15.8 +/- 6.7 days (range 8-23). RESULTS: The peripheral parenteral nutrition group demonstrated several trends towards improvement in prealbumin, CD4 cell count, and functional status compared to the untreated control group. Two patients in the peripheral parenteral nutrition group developed low-grade phlebitis; however, this did not result in discontinuing intravenous therapy. No other adverse events occurred. This study demonstrates that peripheral parenteral nutrition is feasible and safe in postacute care. CONCLUSIONS: We conclude that peripheral parenteral nutrition can be safely administered in post-acute settings with a low rate of complications.

Peripheral serotoninergic receptor sensitivity in senile dementia of the Alzheimer type.

Platelet aggregation induced by 5-hydroxytryptamine (5-HT) was used as a measure of the functional responsiveness of peripheral 5-HT receptors in controls and drug-free patients suffering from senile dementia of Alzheimer type (SDAT). No significantly different aggregatory response (5-HT/ADP ratio) was noted between the two groups of subjects. If the receptor mediating this response is a 5-HT2 receptor, there is no evidence to suggest that the functional activity of this system is abnormal in SDAT.

[3H]-SB-269970 radiolabels 5-HT7 receptors in rodent, pig and primate brain tissues.

The selective 5-HT7 receptor antagonist radioligand, [3H]-SB-269970, has been reported to radiolabel the human cloned 5-HT7(a) receptor and 5-HT7 receptors in guinea pig cortex (thomas et al, 2000). Saturation analysis of [3H]-SB-269970 binding to mouse forebrain, rat cortex, pig cortex, marmoset cortex and human thalamus membranes was consistent with labelling a homogenous population of binding sites in each tissue. K(D) values for [3H]-SB-269970 binding in these tissues ranged from 0.9 to 2.3 nM, being similar to those reported for the human cloned and guinea pig cortex 5-HT7 receptors (1.3 and 1.7 nM, respectively). Bmax values for [3H]-SB-269970 binding to the mouse, rat, pig, marmoset and human brain membranes were 20, 30, 31, 14 and 68 fmoles x mg x protein(-1), respectively. For each species the profile of inhibition of [3H]-SB-269970 binding, using a number of 5-HT7 receptor agonists and antagonists, correlated well with that reported for the human cloned 5-HT7(a) receptor (correlation coefficients were 0.95, 0.94, 0.92, 0.95, 0.97 versus the mouse, rat, pig, marmoset and human tissues, respectively). In conclusion, [3H]-SB-269970 has been shown to radiolabel 5-HT7 receptors in rodent, pig and primate brain and represents a valuable tool with which to further characterise the distribution and function of 5-HT7 receptors in native tissues and elucidate their potential role in disease states.

5-CT stimulation of adenylyl cyclase activity in guinea-pig hippocampus: evidence for involvement of 5-HT7 and 5-HT1A receptors.

1. A number of compounds, including the selective 5-HT7 receptor antagonist SB-258719, were investigated for their effect on [3H]-5-carboxamidotryptamine (5-CT) radioligand binding and 5-CT-stimulated adenylyl cyclase activity in guinea-pig hippocampal membranes, in order to confirm the presence of functionally coupled 5-HT7 receptors in this tissue. 2. The [3H]-5-CT radioligand binding profile was consistent with binding predominantly to 5-HT7 receptors. The affinity of SB-258719 (pKi 7.2+/-0.1) was similar to its reported human 5-HT7 receptor affinity. 3. In the adenylyl cyclase functional assay, 5-CT was a potent and full agonist compared to 5-HT, whereas 8-hydroxy-dipropylaminotetralin (8-OH-DPAT) was a partial agonist (intrinsic activity 0.4+/-0.1). The rank order of potency for agonists (5-CT>5-HT approximately 8-OH-DPAT) was consistent with activation of 5-HT7 receptors. SB-258719 (5 microM) and methiothepin (1 microM) surmountably antagonized the response to 5-CT, consistent with competitive antagonism. The pKB for SB-258719 (7.2+/-0.1) was in good agreement with its reported antagonist potency at the human cloned 5-HT7 receptor. 4. In the functional assay, WAY-100635 (100 nM) and cyanopindolol (1 microM) induced a biphasic 5-CT response curve, consistent with selective antagonism of a component of the response to 5-CT. The estimated pKB values for WAY-100635 and cyanopindolol (9.6 and 8.4 respectively) were in good agreement with their reported 5-HT1A receptor affinities. 5. The data are consistent with the presence of 5-HT7 receptors in guinea-pig hippocampus which are positively coupled to adenylyl cyclase. In addition, 5-HT7 receptor-mediated stimulation of adenylyl cyclase activity in this tissue appears to be augmented by a mechanism involving 5-HT1A receptor activation.

[(3)H]-SB-269970--A selective antagonist radioligand for 5-HT(7) receptors.

Binding of the 5-HT(7) receptor antagonist radioligand [(3)H]-SB-269970 to human 5-HT(7(a)) receptors expressed in HEK293 cell membranes (h5-HT(7(a))/293) and to guinea-pig cerebral cortex membranes, was characterized and compared with [(3)H]-5-CT binding. [(3)H]-SB-269970 (1 nM) showed full association with h5-HT(7(a))/293 membranes after 40 min. Specific binding at equilibrium represented >90% of total binding and was fully reversible by methiothepin (10 microM), full dissociation occurring by 100 min. The association (k(+1)) and dissociation (k(-1)) rate constants were 0.05 nM(-1)min(-1) and 0.05 min(-1) respectively, giving a K(D) (k(-1)/k(+1)) of 1.0 nM. [(3)H]-SB-269970 bound saturably and apparently monophasically to both h5-HT(7(a))/293 and guinea-pig cortex membranes, with K(D) values of 1.25+/-0.05 and 1.7+/-0.3 nM respectively. The B(max) for [(3)H]-SB-269970 to both h5-HT(7(a))/293 and guinea-pig cortex membranes (5780+/-380 and 125+/-8.2 fmoles mg protein(-1) respectively) was similar to that for [(3)H]-5-CT (6190+/-940 and 143+/-19 fmoles mg protein(-1) respectively). These data suggest that, in each tissue, both radioligands labelled the same population of receptors, which appear to be present in an agonist high affinity state. The profile of compound inhibition of [(3)H]-SB-269970 binding to h5-HT(7(a))/293 and guineapig cortex membranes correlated well (corr. coeff. 0.98) with those for [(3)H]-5-CT binding and were consistent with the profiles reported previously for the human 5-HT(7(a)) and guinea-pig cortex 5-HT(7) receptors using [(3)H]-5-CT. Hill slopes for inhibition of [(3)H]-SB-269970 and [(3)H]-5-CT binding were close to 1, consistent with binding to a single receptor population in both tissues. [(3)H]-SB-269970 represents the first selective 5-HT(7) antagonist radioligand, which should aid further characterization of 5-HT(7) receptors in recombinant and native tissues and help establish their role in brain function.

Functional characterisation of the human cloned 5-HT7 receptor (long form); antagonist profile of SB-258719.

1. The functional profile of the long form of the human cloned 5-HT7 receptor (designated h5-HT7(a)) was investigated using a number of 5-HT receptor agonists and antagonists and compared with its binding profile. Receptor function was measured using adenylyl cyclase activity in washed membranes from HEK293 cells stably expressing the recombinant h5-HT7(a) receptor. 2. The receptor binding profile, determined by competition with [3H]-5-CT, was consistent with that previously reported for the h5-HT7(a) receptor. The selective 5-HT7 receptor antagonist SB-258719 ((R)-3,N-Dimethyl-N-[1-methyl-3-(4-methylpiperidin-1-yl)propyl]ben zene sulfonamide) displayed high affinity (pKi 7.5) for the receptor. 3. In the adenylyl cyclase functional assay, 5-CT and 8-OH-DPAT were both full agonists compared to 5-HT and the rank order of potency for agonists (5-CT > 5-HT > 8-OH-DPAT) was the same in functional and binding studies. 4. Risperidone, methiothepin, mesulergine, clozapine, olanzapine, ketanserin and SB-258719 antagonised surmountably 5-CT-stimulated adenylyl cyclase activity. Schild analysis of the antagonism by SB-258719 gave a pA2 of 7.2+/-0.2 and slope not significantly different from 1, consistent with competitive antagonism. 5. The same antagonists also inhibited basal adenylyl cyclase activity with a rank order of potency in agreement with those for antagonist potency and binding affinity. Both SB-258719 and mesulergine displayed apparent partial inverse agonist profiles compared to the other antagonists tested. These inhibitory effects of antagonists appear to be 5-HT7 receptor-mediated and to reflect inverse agonism. 6. It is concluded that in this expression system, the h5-HT7(a) receptor shows the expected binding and functional profile and displays constitutive activity, revealing inverse agonist activity for a range of antagonists.