Clinical performance of the infant nutrition early warning score in routine practice across four international clinical settings in Europe: A study by the ESPGHAN special interest group in clinical malnutrition.

There is a scarcity of nutritional screening tools for use in infants (<1 year). The infant Nutrition Early Warning Score (iNEWS) has been developed to identify infants who need further dietetic review. We introduced the iNEWS into clinical practice and evaluated its performance in Scotland, Belgium, Athens and Bulgaria. Of the 352 infants screened, 72 (20%) were placed in the high iNEWS category, and of these, 70 (97%) were reviewed by a hospital dietitian. iNEWS produced a true positive rate of 80% which increased to 96% after accounting for anticipated misclassified cases due to prematurity. In Belgium, false positive screens had a shorter length of stay (p = 0.014). Otherwise, misclassification was not related to a specific iNEWS component. This study corroborates previous research, underscoring the validity of iNEWS as a dietetic referral tool and demonstrating that it can be integrated into "real-world" clinical practice across international settings with diverse healthcare resources.

Human amniotic membranes as an allogenic biological dressing for the treatment of burn wounds: Protocol for a randomized-controlled study.

Background: Burn wounds pose significant challenges in medical treatment due to their devastating nature and resource-intensive requirements. Temporary coverage of burn wounds using synthetic or biological dressings allows for reepithelization before definitive skin grafting. Allogenic skin grafts have been widely used but come with drawbacks such as rejection and disease transmission. The use of amniotic membranes (AMs) offers a promising alternative for temporary coverage, as they possess biological properties that promote faster healing and improved scar quality. The various components of the amniotic membrane, including pluripotent stem cells, extracellular matrix proteins, and regenerative factors, contribute to cell growth, migration, and differentiation, as well as preservation of the original epithelial phenotype. Objective: Reliable information on the treatment of burn wounds with AM is needed. The knowledge gained in this project may help to include this advantageous modern concept of biological dressings in clinical practice. The purpose of this study is to use human amniotic membranes from our in hospital laboratory, as an allogenic biological dressing after enzymatic debridement in superficial partial thickness, deep partial thickness or full thickness burn wounds. Methods: We will include 30 patients in a randomized-controlled trial with each patient receiving the study intervention and the control intervention. Two 7 × 7 cm burn wound areas will be compared regarding percentage of skin graft take, healing time, healing percentage value and total healing time. Human amniotic membranes will be compared to allogenic skin grafts.

Physician-Pharmacist Collaborative Drug Therapy Management in Pediatric Hypertension.

OBJECTIVE: Pediatric hypertension affects 2% to 5% of children and adolescents in the United States and is frequently undertreated. The increasing prevalence of pediatric hypertension and worsening physician shortage create difficulties in closing this treatment gap. Physician-pharmacist collaborations have been shown to improve patient outcomes in adult patients. Our aim was to demonstrate a similar benefit for pediatric hypertension. METHODS: Pediatric patients whose hypertension was managed at a single pediatric cardiology clinic from January 2020 to December 2021 were enrolled in collaborative drug therapy management (CDTM). Patients whose hypertension was managed in the same clinic from January 2018 to December 2019 were used as a comparison group. The primary outcomes were achievement of at-goal blood pressure at 3, 6, and 12 months and time to control of hypertension. Secondary outcomes were appointment adherence and serious adverse events. RESULTS: A total of 151 patients were included in the CDTM group, and 115 patients were included in the traditional care group. Of those, 100 CDTM patients and 78 traditional care patients were assessed for the primary outcome. Fifty-four (54%) CDTM patients and 28 (36%) traditional care patients achieved at-goal blood pressure at 12 months (OR, 2.09; 95% CI, 1.14-3.85). Appointment non-adherence was 9.4% for CDTM and 16% for traditional care (OR, 0.54; 95% CI, 0.35-0.82). Adverse events were similar between groups. CONCLUSIONS: CDTM increased rates of at-goal blood pressure without increased adverse events. Physician-pharmacist collaboration may improve treatment of hypertension in pediatric patients.

Autistic young people's experiences of remote psychological interventions during COVID-19.

LAY ABSTRACT: Recently, therapy has been delivered at a distance (i.e. remotely) to help control the spread of coronavirus. Clinicians have voiced concerns that remote delivery is unsuitable for certain individuals, including those who are autistic, but they have also highlighted potential benefits for autistic individuals. Benefits include some individuals feeling more comfortable receiving therapy at home. This is the first study to interview autistic individuals about their experience of remote therapy. Participants were six young people aged 15-18 years and eight clinicians. Participants described their experience of remote delivery, including challenges, benefits, and suggestions. Most of these supported previous research findings, but some were new or provided further insight into those already identified. A newly identified challenge was knowing online social etiquette. All participants found aspects of the experience challenging, but all identified benefits and most voiced that remote sessions should be offered to young people. Participants further identified individual characteristics that may make someone less suited to remote delivery (e.g. shyness). They also identified ways of making the experience of remote delivery easier (e.g. sitting with a pet). Young people's and clinicians' views were similar overall, with only subtle differences. For example, young people uniquely voiced that remote delivery was similar to in-person, that benefits were hard to identify, and provided distinct reasons for the social interaction feeling less intense remotely. Findings may be used to improve remote delivery, for guiding future research, and as a case for continuing to offer it to those who may most benefit.

Impact of interprofessional geriatric teamwork on students' perceptions of older persons and collaborative practice.

Health professions programs lack sufficient exposure to geriatric education in curricula. The Seniors Assisting in Geriatric Education (SAGE) Program exposes interprofessional (IP) teams of health professions students to older adults. To determine the impact of an interprofessional geriatric educational experience on student perceptions of team collaboration and older adults. IP teams of three or four students (n = 662) representing eight disciplines from two institutions were paired with an older adult to promote person-centered care over three semesters. Students completed two online questionnaires (pre- and post-SAGE Program, ~10 min). 136 students completed both questionnaires. Three IP collaborative practice sub-competencies under the Roles & Responsibilities and Interprofessional Communication Core Competencies increased significantly from pre- to post-SAGE Program (p ≤ 0.002). Comparison of the means for attitudes toward geriatric patients revealed statistically significant improvement in one item, Compassion (p < .002). The SAGE Program had a positive impact on IP collaborative practice and attitudes toward older people in some, but not all, areas.

Disruption of Endosomal Sorting in Schwann Cells Leads to Defective Myelination and Endosomal Abnormalities Observed in Charcot-Marie-Tooth Disease.

Endosomal sorting plays a fundamental role in directing neural development. By altering the temporal and spatial distribution of membrane receptors, endosomes regulate signaling pathways that control the differentiation and function of neural cells. Several genes linked to inherited demyelinating peripheral neuropathies, known as Charcot-Marie-Tooth (CMT) disease, encode proteins that directly interact with components of the endosomal sorting complex required for transport (ESCRT). Our previous studies demonstrated that a point mutation in the ESCRT component hepatocyte growth-factor-regulated tyrosine kinase substrate (HGS), an endosomal scaffolding protein that identifies internalized cargo to be sorted by the endosome, causes a peripheral neuropathy in the neurodevelopmentally impaired teetering mice. Here, we constructed a Schwann cell-specific deletion of Hgs to determine the role of endosomal sorting during myelination. Inactivation of HGS in Schwann cells resulted in motor and sensory deficits, slowed nerve conduction velocities, delayed myelination and hypomyelinated axons, all of which occur in demyelinating forms of CMT. Consistent with a delay in Schwann cell maturation, HGS-deficient sciatic nerves displayed increased mRNA levels for several promyelinating genes and decreased mRNA levels for genes that serve as markers of myelinating Schwann cells. Loss of HGS also altered the abundance and activation of the ERBB2/3 receptors, which are essential for Schwann cell development. We therefore hypothesize that HGS plays a critical role in endosomal sorting of the ERBB2/3 receptors during Schwann cell maturation, which further implicates endosomal dysfunction in inherited peripheral neuropathies.SIGNIFICANCE STATEMENT Schwann cells myelinate peripheral axons, and defects in Schwann cell function cause inherited demyelinating peripheral neuropathies known as CMT. Although many CMT-linked mutations are in genes that encode putative endosomal proteins, little is known about the requirements of endosomal sorting during myelination. In this study, we demonstrate that loss of HGS disrupts the endosomal sorting pathway in Schwann cells, resulting in hypomyelination, aberrant myelin sheaths, and impairment of the ERBB2/3 receptor pathway. These findings suggest that defective endosomal trafficking of internalized cell surface receptors may be a common mechanism contributing to demyelinating CMT.

Examining clinicians' concerns delivering telemental health interventions directly to autistic individuals during COVID-19.

Background: The COVID-19 pandemic necessitated the adoption of telemental health (TMH). Pre-pandemic, clinicians had voiced many TMH concerns, but these had not been investigated with respect to autism spectrum disorder (ASD) even with it being known that there are distinct ASD-associated challenges for in-person mental health interventions. Method: A convenience sample of (n = 55) clinicians completed an online survey regarding their perspectives of adopting TMH interventions in ASD, with closed- and open-answered questions. Quantitative and qualitative data were analysed descriptively/inferentially and via Content Analysis, respectively. Results: Multiple clinicians endorsed each TMH challenges/barrier previously identified as concerns in the non-ASD literature. However, overall levels of concern over challenges/barriers were low, and challenges were more likely to be predicted than experienced and considered to be case/presentation specific. Challenges that were considered ASD-specific included the exacerbation of those associated with in-person delivery in ASD, alongside difficulties with trust and appropriate remote social behaviour. On average, clinicians indicated a preference for 50% TMH interventions post-pandemic. Clinicians' perceived technological competence and extent of professional experience with ASD were not significantly associated with levels of concern, nor number of experienced challenges, with TMH interventions in ASD. Conclusion: In support of the existing TMH literature, challenges/barriers were more likely to be predicted than experienced and were considered to be case/presentation-specific, though this may be more variable in ASD owing to the well-established marked heterogeneity in this population. Remote provision of interventions exacerbated in-person ASD-associated challenges, as predicted, but clinician-level factors appeared not to impact TMH perceptions.

Collective Perceptions of Aging and Older Persons Held by Students From Eight Healthcare Professions.

In order to increase the number of students entering the geriatric workforce, an understanding of factors influencing career preference and what may prevent students from pursuing geriatric careers is necessary. Using a convergent parallel mixed methods approach, the aim of this study was to provide insight for geriatric educators regarding the collective perceptions of aging and older persons held by 864 students from eight healthcare professions. Quantitative questions assessed students' attitudes (Geriatric Attitudes Scale). Student responses to four open-ended questions were assessed using conventional content analysis. Results included rich narrative examples of healthcare professions students' perceptions and understanding of the aging process, as well as myths and misconceptions of aging and older persons that can be used to inform geriatric curricula across multiple health professions training and education programs. Geriatric education is a critical avenue to correct misperceptions, quell ageism and address the current shortage in the geriatrician workforce.

Tramadol in seized drugs containing non-pharmaceutical fentanyl: Crime lab data from Ohio, USA.

Introduction: Non-pharmaceutical fentanyl and related drugs (NPF) have contributed to increases in drug-related overdose mortality in the U.S. More data are needed to track the shifting composition of fentanyl-containing drug mixtures. The key aims of the study are to characterize the crime lab data from Montgomery County, Ohio on the increased cases of seized drugs containing mixtures of NPF and tramadol. Methods: Crime lab data on seized drugs in Montgomery County, Ohio (2015 - 2020) were analyzed to extract information on cases that tested positive for NPF and tramadol. Descriptive statistics are provided to characterize NPF/tramadol mixtures in terms of the quantity, weight, form of the drug seized (powder, tablet, capsule, residue), and the types of fentanyl analogs and other drugs identified. Results: In December 2017, the first case of NPF/tramadol mixture was identified in the amount of 0.2 g. Sub-sequently, cases containing NPF/tramadol increased significantly to 149 cases in 2018, 102 in 2019, and 134 in 2020. The total yearly amounts of seized NPF/tramadol mixtures increased to 373.27 g in 2018, 2,601.82 g in 2019, and 13,487.62 g in 2020. The majority (72.6%) of the cases were in powder form. There were 15 other drugs identified along with fentanyl with tramadol mixtures, including heroin (38.8%), 5.7% cocaine (5.7%), and methamphetamine (4.9%). Conclusions: The addition of tramadol to NPF may be viewed as a harm mitigation strategy but contributes to the overall unpredictability of the illicit drug supply. According to Ohio legal statutes, identification of schedule IV drugs such as tramadol with fentanyl (schedule II) may provide a reduction in drug-related charges from a felony to a misdemeanor. More research is needed to characterize potential sources of tramadol in NPF-containing drugs.

Trends in gabapentinoid prescribing, co-prescribing of opioids and benzodiazepines, and associated deaths in Scotland.

BACKGROUND: Gabapentinoid drugs (gabapentin and pregabalin) are effective in neuropathic pain, which has a prevalence of ∼7%. Concerns about increased prescribing have implications for patient safety, misuse, and diversion. Drug-related deaths (DRDs) have increased and toxicology often implicates gabapentinoids. We studied national and regional prescribing rates (2006-2016) and identified associated sociodemographic factors, co-prescriptions and mortality, including DRDs. METHODS: National data from the Information Service Division, NHS Scotland were analysed for prescribing, sociodemographic, and mortality data from the Health Informatics Centre, University of Dundee. DRDs in which gabapentinoids were implicated were identified from National Records of Scotland and Tayside Drug Death Databases. RESULTS: From 2006 to 2016, the number of gabapentin prescriptions in Scotland increased 4-fold (164 630 to 694 293), and pregabalin 16-fold (27 094 to 435 490). In 2016 'recurrent users' (three or more prescriptions) had mean age 58.1 yr, were mostly females (62.5%), and were more likely to live in deprived areas. Of these, 60% were co-prescribed an opioid, benzodiazepine, or both (opioid 49.9%, benzodiazepine 26.8%, both 17.1%). The age-standardised death rate in those prescribed gabapentinoids was double that in the Scottish population (relative risk 2.16, 95% confidence interval 2.08-2.25). Increases in gabapentinoids contributing to cause of DRDs were reported regionally and nationally (gabapentin 23% vs 15%; pregabalin 21% vs 7%). In Tayside, gabapentinoids were implicated in 22 (39%) of DRDs, 17 (77%) of whom had not received a prescription. CONCLUSIONS: Gabapentinoid prescribing has increased dramatically since 2006, as have dangerous co-prescribing and death (including DRDs). Older people, women, and those living in deprived areas were particularly likely to receive prescriptions. Their contribution to DRDs may be more related to illegal use with diversion of prescribed medication.

Thyroid function in preterm infants and neurodevelopment at 2 years.

OBJECTIVES: Postnatal thyroid dysfunction is common in preterm infants but the relationship between mild dysfunction and neurodevelopment is unclear. Our aim is to describe the relationship between thyroid function and neurodevelopment. DESIGN: Cohort analysis. PATIENTS: 1275 infants born under 31 weeks' gestation; there were no exclusion criteria. SETTING: The infants were part of a UK daily iodine supplementation trial. MAIN OUTCOMES: Thyroid-stimulating hormone, thyroid-binding globulin and total thyroxine levels were measured in dried blood spots on postnatal days 7, 14, 28 and the equivalent of 34 weeks' gestation. Neurodevelopment was measured using the Bayley-III Scales of infant development at 2 years of age. RESULTS: No infant was identified as hypothyroid through routine screening. The 3% of infants consistently in the top decile of gestationally age-adjusted thyroid-stimulating hormone levels had a reduction in cognitive score of 7 Bayley units when compared with those not in the top decile (95% CI -13 to -1). A reduction in motor composite score of 6 units (95% CI -12 to <-0.1) and fine motor score of 1 unit (95% CI -2 to -0.1) was also identified. The 0.7% of infants consistently in the bottom decile of age-adjusted thyroxine levels had a reduction in motor composite score of 14 units (95% CI -25 to -2) and its two subset scores, fine and gross motor, of 2 units (95% CI respectively -4.5 to <-0.1 and -4.3 to -0.3). CONCLUSIONS: Preterm infants with consistent 'mild' thyroid dysfunction score less on neurodevelopmental tests at 2 years of age. Many of these infants will not be detected by current clinical protocols or screening programmes.

Direct intraoperative assessment of total mesorectal excision specimens by expert pathologists in patients with very low rectal cancer prevents unnecessary abdominoperineal resections.

PURPOSE: In patients with low rectal cancer, the intraoperative assessment of sufficient distal resection margins can be challenging. The assessment determines whether reconstruction can be performed or whether permanent colostomy is required. The goal of the present study was to evaluate intraoperative assessment of the total mesorectal excision (TME) specimen during an interruption of the operation. METHODS: The intraoperative strategy of eight patients with low rectal cancer was evaluated. In all cases, intraoperative pathological assessment of the TME specimen by an expert pathologist together with the surgeon was performed. Assessment of the distance of the tumor to the resection margin was measured macroscopically as well as microscopically. RESULTS: All patients underwent neoadjuvant chemoradiation. The tumor was located at an average 4.8 ± 1.4 cm from the anal verge. In all cases, preoperative MRI revealed mrT3 tumors. The intraoperative assessment showed a median distal resection margin of 10 mm (2-15 mm). In six patients, sufficient margins allowed for reconstruction while in two patients APR was needed. In three patients (37.5%), the pathological assessment changed the operative strategy: In one patient APR could be avoided while two patients required APR instead of the anticipated TME. CONCLUSION: The intraoperative assessment of the TME specimen by an expert pathologist together with the surgeon is a valuable tool to avoid unnecessary APR or R1 resections. We therefore suggest routine intraoperative pathological assessment in all operations for borderline low rectal cancers.

Student clinicians' and clients' perceptions of the therapeutic alliance and outcomes in stuttering treatment.

PURPOSE: The purpose of this study was to examine how the therapeutic alliances (TA) of graduate student clinicians and adult clients who stutter relate to perceived treatment outcomes. METHODS: Student clinicians (N = 42) and adult clients who stutter (N = 22) completed a survey assessing their TA strength and perception of treatment outcomes. Responses were analyzed to determine similarities and differences in how clinicians and clients relate the TA to perceptions of treatment effectiveness, progress, and outcome satisfaction. RESULTS: Results suggest that clinicians and clients who stutter both relate the TA to treatment outcome, but in different ways. While clinicians associate the TA most with treatment effectiveness and client progress, clients relate the TA most to outcome satisfaction. CONCLUSION: Clinicians should be aware that for adult clients who stutter, outcome satisfaction is related to the degree of shared understanding, agreement on daily tasks, and bond they experience with their clinician. To ensure a strong TA and client satisfaction, clinicians should actively seek their clients' perspective regarding TA status.

Supplemental Iodide for Preterm Infants and Developmental Outcomes at 2 Years: An RCT.

BACKGROUND: The recommendation for enteral iodide intake for preterm infants is 30 to 40 µg/kg per day and 1 µg/kg per day for parenteral intake. Preterm infants are vulnerable to iodide insufficiency and thyroid dysfunction. The hypothesis tested whether, compared with placebo, iodide supplementation of preterm infants improves neurodevelopment. METHODS: A randomized controlled trial of iodide supplementation versus placebo in infants <31 weeks' gestation. Trial solutions (sodium iodide or sodium chloride; dose 30 µg/kg per day) were given within 42 hours of birth to the equivalent of 34 weeks' gestation. The only exclusion criterion was maternal iodide exposure during pregnancy or delivery. Whole blood levels of thyroxine, thyrotropin, and thyroid-binding globulin were measured on 4 specific postnatal days. The primary outcome was neurodevelopmental status at 2 years of age, measured by using the Bayley Scales of Infant Development-III. The primary analyses are by intention-to-treat, and data are presented also for survivors. RESULTS: One thousand two hundred seventy-three infants (637 intervention, 636 placebo) were recruited from 21 UK neonatal units. One hundred thirty-one infants died, and neurodevelopmental assessments were undertaken in 498 iodide and 499 placebo-supplemented infants. There were no significant differences between the intervention and placebo groups in the primary outcome: mean difference cognitive score, -0.34, 95% confidence interval (CI) -2.57 to 1.89; motor composite score, 0.21, 95% CI -2.23 to 2.65; and language composite score, -0.05, 95% CI -2.48 to 2.39. There was evidence of weak interaction between iodide supplementation and hypothyroxinemic status in the language composite score and 1 subtest score. CONCLUSIONS: Overall iodide supplementation provided no benefit to neurodevelopment measured at 2 years of age.

Outcomes of a single-center experience with classification and treatment of endothermal heat-induced thrombosis after endovenous ablation.

OBJECTIVE: Endothermal heat-induced thrombosis (EHIT) is a known complication of endothermal venous ablation procedures. EHIT can lead to deep vein thrombosis/pulmonary embolism, which cause significant disability and, rarely, death. Other studies have evaluated risk factors for EHIT. There is an accepted grading system for EHIT, but there is no consensus on treatment type, duration, or follow-up. We retrospectively evaluated all cases of EHIT after radiofrequency ablation or endovenous laser ablation at our institution during a 7-year period, focusing on classification, treatment, and outcomes of EHIT. METHODS: The analysis included all patients aged >18 years who underwent radiofrequency ablation or endovenous laser ablation at our institution, Spectrum Health Hospital Vein Solutions (Grand Rapids, Mich), between January 1, 2008, and December 31, 2014. Electronic medical records were queried retrospectively to identify patients with EHIT during the study interval by International Classification of Diseases-Ninth Revision code. Demographic data, including age, gender, comorbidities (eg, history of deep venous thrombosis, hypercoagulable state, family history of blood clots, etc), body mass index, Clinical, Etiology, Anatomy, and Pathophysiology (CEAP) classification, and use of preoperative anticoagulation were collected for each patient in the registry. Each patient had a required postoperative duplex ultrasound (US) examination within 1 to 2 weeks of the procedure. Preoperative and postoperative US imaging data and procedure-specific data were also recorded for each patient. EHIT was graded from 1 to 4 by review of the US studies. Each patient's treatment course was reviewed for type of anticoagulation, duration of treatment, follow-up imaging, and outcome. RESULTS: From 2008 to 2014, 4799 ablations were performed at Spectrum Health Hospital Vein Center, and EHIT was identified in 70 patients. At presentation, 87% of patients were asymptomatic, 10% reported pain, and 2.9% reported swelling. Patients with EHIT grades 1 or 2 were treated with daily aspirin, and most of those with grades 3 or 4 were treated with systemic anticoagulation. Repeat US imaging was performed at 1 to 2 weeks to evaluate progression. Progression was not seen in any patients treated with systemic anticoagulation (grades 3-4). Thrombus progression occurred in two patients with grades 1 or 2 EHIT treated with aspirin. A bleeding complication occurred in one patient. CONCLUSIONS: EHIT after endovenous ablation occurred in ∼1.5% of patients, which is similar to that reported in the literature. Our review shows that systemic anticoagulation is effective in the prevention of progression with a low risk of bleeding complications. Patients with EHIT grades 1 or 2 can be treated with aspirin alone with a low risk of progression (3%).

Cosmetic sclerotherapy.

Telangiectasias and spider veins are considered a common cosmetic concern for both women and men. Sclerotherapy is a frequently used, low-risk, and highly successful method to treat these venous problems. This article reviews the pathophysiology and diagnosis of telangiectasias and reticular veins as well as the currently available agents and techniques of sclerotherapy. The possible complications and adverse outcomes of sclerotherapy are described. Standard care and follow-up for patients after the procedure are outlined. Also included are tips and tricks found to be valuable in a busy vein practice.

Thyroid dysfunction in preterm neonates exposed to iodine.

BACKGROUND: Infants <32 weeks' gestation should not be exposed to topical iodine and its avoidance is recommended during pregnancy and breast feeding. Exposure to contrast media and topical iodine is frequently used in many preterm neonates. AIM: To determine whether thyrotropin levels in preterm infants are affected by exposure to intrapartum/neonatal topical iodine and/or the use of iodinated contrast media. DESIGN: Infants <32 weeks' gestation were recruited. Maternal and neonatal exposures to iodinated contrast media and topical iodine were recorded; levels of thyrotropin and thyroxine were measured from blood-spot cards on postnatal days 7, 14, 28 and the equivalent of 36 weeks' gestation. RESULTS: One hundred and twenty-five infants were exposed to topical iodine/contrast media and 48 infants were unexposed. No infants were treated for hypothyroidism; three infants (exposed group) had transient hyperthyrotropinaemia. Mean thyrotropin levels were significantly higher on postnatal days 7, 14 and 28 in infants exposed to topical iodine prior to caesarean section compared to unexposed infants, a relationship which persisted after adjustment. CONCLUSIONS: In the context of this study, neonatal thyroid dysfunction was seen following exposure to iodine via caesarean section but not via exposure to contrast media.

Identification of novel macrolides with antibacterial, anti-inflammatory and type I and III IFN-augmenting activity in airway epithelium.

BACKGROUND: Exacerbations of asthma and COPD are triggered by rhinoviruses. Uncontrolled inflammatory pathways, pathogenic bacterial burden and impaired antiviral immunity are thought to be important factors in disease severity and duration. Macrolides including azithromycin are often used to treat the above diseases, but exhibit variable levels of efficacy. Inhaled corticosteroids are also readily used in treatment, but may lack specificity. Ideally, new treatment alternatives should suppress unwanted inflammation, but spare beneficial antiviral immunity. METHODS: In the present study, we screened 225 novel macrolides and tested them for enhanced antiviral activity against rhinovirus, as well as anti-inflammatory activity and activity against Gram-positive and Gram-negative bacteria. Primary bronchial epithelial cells were grown from 10 asthmatic individuals and the effects of macrolides on rhinovirus replication were also examined. Another 30 structurally similar macrolides were also examined. RESULTS: The oleandomycin derivative Mac5, compared with azithromycin, showed superior induction (up to 5-fold, EC50 = 5-11 µM) of rhinovirus-induced type I IFNß, type III IFNλ1 and type III IFNλ2/3 mRNA and the IFN-stimulated genes viperin and MxA, yet had no effect on IL-6 and IL-8 mRNA. Mac5 also suppressed rhinovirus replication at 48 h, proving antiviral activity. Mac5 showed antibacterial activity against Gram-positive Streptococcus pneumoniae; however, it did not have any antibacterial properties compared with azithromycin when used against Gram-negative Escherichia coli (as a model organism) and also the respiratory pathogens Pseudomonas aeruginosa and non-typeable Haemophilus influenzae. Further non-toxic Mac5 derivatives were identified with various anti-inflammatory, antiviral and antibacterial activities. CONCLUSIONS: The data support the idea that macrolides have antiviral properties through a mechanism that is yet to be ascertained. We also provide evidence that macrolides can be developed with anti-inflammatory, antibacterial and antiviral activity and show surprising versatility depending on the clinical need.

Depression predicts future emergency hospital admissions in primary care patients with chronic physical illness.

OBJECTIVE: More than 15 million people currently suffer from a chronic physical illness in England. The objective of this study was to determine whether depression is independently associated with prospective emergency hospital admission in patients with chronic physical illness. METHOD: 1860 primary care patients in socially deprived areas of Manchester with at least one of four exemplar chronic physical conditions completed a questionnaire about physical and mental health, including a measure of depression. Emergency hospital admissions were recorded using GP records for the year before and the year following completion of the questionnaire. RESULTS: The numbers of patients who had at least one emergency admission in the year before and the year after completion of the questionnaire were 221/1411 (15.7%) and 234/1398 (16.7%) respectively. The following factors were independently associated with an increased risk of prospective emergency admission to hospital: having no partner (OR 1.49, 95% CI 1.04 to 2.15); having ischaemic heart disease (OR 1.60, 95% CI 1.04 to 2.46); having a threatening experience (OR 1.16, 95% CI 1.04 to 1.29); depression (OR 1.58, 95% CI 1.04 to 2.40); and emergency hospital admission in the year prior to questionnaire completion (OR 3.41, 95% CI 1.98 to 5.86). CONCLUSION: To prevent potentially avoidable emergency hospital admissions, greater efforts should be made to detect and treat co-morbid depression in people with chronic physical illness in primary care, with a particular focus on patients who have no partner, have experienced threatening life events, and have had a recent emergency hospital admission.

Arterio-venous differences in cord levels of catecholamines, glucose, lactate and blood gases.

BACKGROUND: Norepinephrine (NE) and epinephrine (EPI) levels are higher in cord arterial blood relative to venous blood, consistent with active mechanisms of placental-maternal clearance. There are no contemporary studies of cord arteriovenous blood levels of sulfated and non-sulfated catechols. AIM: To assess the arteriovenous differences in cord blood levels of dopamine (DA), the sulfated catecholamines and their sulfated and non-sulfated metabolites. To correlate levels of oxygen, H+/CO2, and glucose with cord catecholamine levels. METHODS: Fifty-seven term infants, delivered by elective cesarean section, were recruited. Cord arterial and venous blood was sampled; levels of glucose, lactate, blood gases, six catechols and their sulfated conjugates were measured. RESULTS: With one exception (DOPA sulfate), mean cord arterial levels of sulfated and non-sulfated catechols were significantly higher than venous levels. Arterial lactate and glucose levels were independently associated with NE levels, but only lactate was associated with levels of EPI and DA. CONCLUSION: This study establishes that in vivo metabolic parameters of hypoxia, respiratory and metabolic acidosis are associated with catecholamine levels, a key relationship for perinatal adaptation and homeostasis, and findings that are consistent with in vitro studies of the regulators of catecholamine secretion.