An investigation of the effects of procalcitonin testing on antimicrobial prescribing in respiratory tract infections in an Irish university hospital setting: a feasibility study.

BACKGROUND: Diagnostic uncertainty and a high prevalence of viral infections present unique challenges for antimicrobial prescribing for respiratory tract infections (RTIs). Procalcitonin (PCT) has been shown to support prescribing decisions and reduce antimicrobial use safely in patients with RTIs, but recent study results have been variable. METHODS: We conducted a feasibility study of the introduction of PCT testing in patients admitted to hospital with a lower RTI to determine if PCT testing is an effective and worthwhile intervention to introduce to support the existing antimicrobial stewardship (AMS) programme and safely decrease antimicrobial prescribing in patients admitted with RTIs. RESULTS: A total of 79 patients were randomized to the intervention PCT-guided treatment group and 40 patients to the standard care respiratory control group. The addition of PCT testing led to a significant decrease in duration of antimicrobial prescriptions (mean 6.8 versus 8.9 days, P = 0.012) and decreased length of hospital stay (median 7 versus 8 days, P = 0.009) between the PCT and respiratory control group. PCT did not demonstrate a significant reduction in antimicrobial consumption when measured as DDDs and days of therapy. CONCLUSIONS: PCT testing had a positive effect on antimicrobial prescribing during this feasibility study. The successful implementation of PCT testing in a randomized controlled trial requires an ongoing comprehensive education programme, greater integration into the AMS programme and delivery of PCT results in a timely manner. This feasibility study has shown that a larger randomized controlled trial would be beneficial to further explore the positive aspects of these findings.

Follow-up interval for small untreated pulmonary arteriovenous malformations in hereditary haemorrhagic telangiectasia.

AIM: To investigate the natural history of untreated small (<3 mm) and microscopic pulmonary arteriovenous malformations (PAVMs) in hereditary haemorrhagic telangiectasia (HHT) in order to discern the optimal frequency of follow-up thoracic computed tomography (CT). MATERIALS AND METHODS: A retrospective analysis was performed on the follow-up data for definite and suspected HHT patients with untreated PAVMs. RESULTS: For small PAVMs in definite HHT (n=13), PAVM enlargement was identified in one patient (1/13, 7.7%) after 10.7 years follow-up and was successfully treated using transcatheter embolisation (TCE). For microscopic PAVMs in definite HHT (n=28), two patients (2/28, 7%) developed small asymptomatic PAVMs, which did not meet the size criteria for TCE after 6.8 years of follow-up. For small PAVMs in suspected HHT (n=5), feeding artery enlargement was seen in one patient (1/5, 20%) after 7.9 years, but again, this did not meet the size criteria for embolisation. No macroscopic PAVM development was identified after a median follow-up of 5.4 years in suspected HHT with microscopic PAVMs (n=20). CONCLUSION: For small and microscopic PAVMs in HHT, PAVM enlargement was found to be more infrequent than would be expected based on current guidelines; therefore, potentially challenging the current surveillance imaging recommendation of a repeat thoracic CT every 5 years.

Feasibility of an obesity intervention for paediatric primary care targeting parenting and children: Helping HAND.

BACKGROUND: The primary care setting offers the opportunity to reach children and parents to encourage healthy lifestyle behaviours, and improve weight status among children. OBJECTIVE: Test the feasibility of Helping HAND (Healthy Activity and Nutrition Directions), an obesity intervention for 5- to 8-year-old children in primary care clinics. METHODS: A randomized controlled pilot study of Helping HAND, a 6-month intervention, targeted children with body mass index 85-99%tile and their parents. Intervention group attended monthly sessions and self-selected child behaviours and parenting practices to change. Control group received regular paediatric care and was wait-listed for Helping HAND. Session completion, participant satisfaction, child anthropometrics, dietary intake, physical activity, TV viewing and behaviour-specific parenting practices were measured pre and post intervention. RESULTS: Forty parent-child dyads enrolled: 82.5% were Hispanic, 80% had a girl and 65% reported income ≤ $30, 000/year. There was 20% attrition from Helping HAND (attended <4/6 sessions). Families self-selected 4.35 (SD 1.75) behaviours to target during the 6-month programme and each of the seven behaviours was selected by 45-80% of the families. There were no between group differences in the child's body mass index z-score, dietary intake or physical activity post intervention. Intervention group viewed 14.9 (SE 2.3) h/week of TV post intervention versus control group 23.3 (SE 2.4) h/week (P < 0.05). CONCLUSION: Helping HAND is feasible, due to low attrition, good programme attendance, and clinically relevant improvements in some child and parenting behaviours.

COPD exacerbations -- a comparison of Irish data with European data from the ERS COPD Audit.

The European Respiratory Society COPD audit was a cross-sectional, multicentre study that analysed outcomes for COPD patients admitted to hospital with an exacerbation across Europe. We present the data on patients admitted to 11 Irish hospitals that participated in the audit. Among 237 patients (123 Male), the median age was 71 years and 79 (33%) patients were current smokers. 82 (35%) patients received high-flow oxygen before admission and 43 (18%) were cared for in a dedicated respiratory ward. 54 (23%) patients required ventilatory support. Median length of stay was 7 days, 98 (41%) patients were readmitted and 211 (89%) patients were alive at the 90 day follow up point. Irish patients were more likely to receive high-flow oxygen before admission, less likely to be managed in a dedicated respiratory ward and had a higher likelihood of readmission or death within 90 days than the European average.

Pulmonary arterial hypertension in hereditary hemorrhagic telangiectasia associated with ACVRL1 mutation: a case report.

INTRODUCTION: Hereditary hemorrhagic telangiectasia is an autosomal dominant condition with an estimated prevalence of 1 in 5000. It is characterized by the presence of abnormalities of vascular structures, and may affect many organ systems, including the lungs, brain, spinal cord, gastrointestinal tract, and liver. A causative mutation is identified in approximately 97% of patients with definite hereditary hemorrhagic telangiectasia in one of three genes including a mutation in endoglin, a mutation in a locus mapped to chromosome 5, and an activin receptor-like kinase-1 (ACVRL1) mutation that is associated with an increased incidence of primary pulmonary hypertension. Pulmonary arterial hypertension is a rare (15-25 cases per million people) but severe vascular disorder. Heritable pulmonary arterial hypertension is associated with several gene mutations, with 75% having a mutation in the bone morphogenetic protein receptor 2 (BMPR2). However, the remaining 25% of patients have other associated genetic mutations including ACVLR1, which is also associated with hereditary hemorrhagic telangiectasia. Pulmonary arterial hypertension is a rare complication in patients with hereditary hemorrhagic telangiectasia (< 1% of the hereditary hemorrhagic telangiectasia population). We describe a case report with this rare occurrence. CASE PRESENTATION: A 70-year-old white/caucasian Irish male presented for screening for hereditary hemorrhagic telangiectasia due to a history of recurrent epistaxis (once/week) and a family history suggestive of pulmonary hypertension. Genetic testing confirmed an ACVRL1 mutation, while an echocardiogram and right heart catheterization confirmed pulmonary arterial hypertension. On examination, he had several mucocutaneous telangiectasia across his face. He was commenced on tadalafil and macitentan. However, this led to increased iron deficiency anemia and pedal edema. Selexipag was also added to his drug regime. He continues to require intermittent admissions for diuresis and blood transfusions. CONCLUSION: The association of hereditary hemorrhagic telangiectasia and pulmonary arterial hypertension is rare (< 1%). Here we describe a case of hereditary hemorrhagic telangiectasia complicated with pulmonary arterial hypertension as a result of an ACVRL1 mutation. We also describe the clinical challenges of treating these two conditions together, as treatment options for pulmonary arterial hypertension tend to worsen hereditary hemorrhagic telangiectasia symptoms.

Comparison of arterial and venous blood gases and the effects of analysis delay and air contamination on arterial samples in patients with chronic obstructive pulmonary disease and healthy controls.

BACKGROUND: Arterial blood gases (ABGs) are often sampled incorrectly, leading to a 'mixed' or venous sample. Delays in analysis and air contamination are common. OBJECTIVES: We measured the effects of these errors in patients with chronic obstructive pulmonary disease (COPD) exacerbations and controls. METHODS: Arterial and venous samples were analyzed from 30 patients with COPD exacerbation and 30 controls. Venous samples were analysed immediately and arterial samples separated into non-air-contaminated and air-contaminated specimens and analysed at 0, 30, 60, 90 and 180 min. RESULTS: Mean venous pH was 7.371 and arterial pH was 7.407 (p < 0.0001). There was a correlation between venous and arterial pH (r = 0.5347, p < 0.0001). The regression equation to predict arterial pH was: arterial pH = 4.2289 + 0.43113 · venous pH. There were no clinically significant differences in arterial PO2 associated with analysis delay. A statistically significant decline in pH was detected at 30 min in patients with COPD exacerbation (p = 0.0042) and 90 min in controls (p < 0.0001). A clinically significant decline in pH emerged at 73 min in patients with COPD exacerbation and 87 min in controls. Air contamination was associated with a clinically significant increase in PO2 in all samples, including those that were immediately analyzed. CONCLUSIONS: Arterial and venous pH differ significantly. Venous pH cannot accurately replace arterial pH. Temporal delays in ABG analysis result in a significant decline in measured pH. ABGs should be analysed within 30 min. Air contamination leads to an immediate increase in measured PO2, indicating that air-contaminated ABGs should be discarded.

Cell death in the embryonic chick spinal cord.

The events which occur in the death of visceromotor neurons of the cervical region of the chick embryo's spinal cord have been analyzed by electron microscopy. These normal degenerative events are compared with those in the lumbosacral cord where nerve cell death was induced by removal of peripheral organs. The initial set of degenerative changes include a decrease in nuclear size, the clumping of chromatin beneath the nuclear envelope, an increase in electron opacity of the cells, the disappearance of Golgi bodies, and the disaggregation of polysomes. These events are followed by the loss of the nuclear envelope and most of the endoplasmic reticulum, the appearance of bundles of filaments, and the formation of many ribosome crystals. Ribosome crystals are seen only in the dying cells. Their abundance may indicate a drastic reduction in RNA synthesis as one of the initial events which lead to the death of these neurons. The neurons are finally subdivided and engulfed by cells of the normal glial population, and further breakdown of the cell fragments occurs in large phagocytic vesicles of the gliocytes.

Characteristics of patients presenting with erythema nodosum and sarcoidosis.

We explored the relationship between erythema nodosum (EN) and sex, age, serum angiotensin converting enzyme (ACE), bronchoalveolar lavage lymphocytosis (BAL-I), interstitial granulomas and radiological stage in patients presenting with pulmonary sarcoidosis in Ireland. Sixty-nine patients diagnosed with sarcoidosis between 2003 and 2006 were studied. Forty one patients (59%) were male. Sixteen patients (23%) presented with EN. Forty one patients of 65 (63%) had transbronchial biopsies demonstrating non-caseating granulomas. Patients with sarcoidosis presenting with EN were more likely to be female (p=0.042), younger (p=0.012) and have earlier stage pulmonary disease (p=0.02). There were no correlations between serum ACE, interstitial granulomas and disease stage. BAL-I did however predict increasing disease radiological stage (p=0.042). In this study, one quarter of patients with sarcoidosis presented with EN among their presenting features. These patients were more likely to be young females with early stage radiological disease.

Interrelationships of child appetite, weight and snacking among Hispanic preschoolers.

BACKGROUND: Snacking among US preschoolers has increased in recent decades, raising questions about whether snacking contributes to dietary excess. OBJECTIVES: This research aimed to characterize snacking contributions to dietary excess and to evaluate associations with appetite and weight among preschool-aged children. METHODS: This study is a cross-sectional, observational study of 187 Hispanic low-income preschoolers. Three 24-h dietary recalls were used to assess snacking frequency and parameters of dietary excess including energy, saturated fat, trans fats and added sugars. Parental reports of child satiety responsiveness, food responsiveness, and enjoyment of food were obtained. Child height and weight were measured. RESULTS: Children consumed 28% (395 kcal) of daily energy from snacks eaten at 2.3 ± 1.0 occasions per day. Greater snacking frequency was associated with greater daily intakes of energy (p < 0.05) and added sugars (p < 0.001). Among overweight/obese children, higher enjoyment of food was associated with more frequent snacking and greater energy intake from snacks (p = 0.01). Inverse associations of enjoyment of food with snacking frequency and energy intake were seen among normal weight children (p < 0.05). CONCLUSIONS: More frequent snacking among low-income Hispanic preschoolers may contribute to excessive intakes of energy and added sugars, particularly among overweight/obese children with greater motivation to eat.

Novel agents in the management of Mycobacterium tuberculosis disease.

The goals of tuberculosis control are to cure active disease, prevent relapse, reduce transmission and avert the emergence of drug resistance. However, since the 1960s, there have been few developments in available therapies. Currently available agents are complicated by numerous side-effects, drug interactions and the need for a long duration of therapy. Rifampicin-containing regimes lead to hepatic enzyme induction which can complicate or preclude the use of protease inhibitors and non-nucleoside reverse transcriptase inhibitors in patients infected with the human immunodeficiency virus. Furthermore, emerging drug resistance has complicated management for many patients and clinicians. Therefore, new chemotherapeutic agents are urgently needed. Existing antimicrobials are emerging as potent antituberculous agents. Recent studies have demonstrated the antituberculous activity of newer fluoroquinolones including levofloxacin, moxifloxacin, and gatifloxacin. Their use as first line antituberculous agents is currently under investigation. Furthermore, the oxazolidinones linezolid and PNU-100480 have been shown to have antituberculous activity in addition to their antibacterial effects. Several other agents are currently being developed for the treatment of tuberculosis. These agents include diarylquinolones (R207910), nitroimidazopyrans (PA-824, OPC-67683), ethambutol analogues (SQ109), cerulenin, trans-cinnamic acid, macrolides, pyrroles (LL3858), long-acting rifamycins and inhaled interferon-gamma. Furthermore, vaccines are being explored for pre-exposure and post-exposure use. This review will describe therapeutic developments in the management of tuberculosis, highlighting mechanisms of action of new pharmacological agents and their potential for clinical use.

Predictors of mortality in adults with cystic fibrosis.

Assessment of prognostic indicators in patients with cystic fibrosis (CF) is important. The study's aim was to assess the relative contribution of gender, genetics and microbiology on survival in adults with CF. Adult patients were studied from 1995 to 2005 and data collected included FEV(1) (%predicted), body mass index (BMI), genetics, and microbiology. Data was available on 183 patients in 1995. Forty-five patients died in the subsequent 10 years. Patients who died during the study had lower mean (SD) FEV(1) %predicted in 1995 when compared to those remaining alive, 41.5 (15.2)% versus 69.8 (23.2)% predicted, respectively, P<0.001 and they had lower mean (SD) BMI in 1995, 19.2 (3.3) kg/m(2) in comparison to those remaining alive, 20.7 (3.4) kg/m(2), P=0.008. The proportion of patients infected with Pseudomonas aeruginosa and Burkholderia cepacia complex was higher in the group who died during the study compared to those remaining alive, odds ratio 20.9 P<0.0001 and 7.1 P<0.0001, respectively. The presence of the Delta F508 homozygous mutation did not alter survival, P=0.3. Patients infected with either P.aeruginosa or B.cepacia complex had reduced survival compared to those without infection, P=0.01 and P<0.0001, respectively. FEV(1)% (P<0.0001), infection with P.aeruginosa (P=0.005) or B.cepacia complex (P=0.03) were the only significant predictors of mortality. This study demonstrates adults who died were more likely to have worse lung function and be infected with either P.aeruginosa or B.cepacia complex. FEV(1)% and infection with P.aeruginosa or B.cepacia complex were the most significant predictors of survival in adults with CF.

Predictors of hepatotoxicity among patients treated with antituberculous medication.

INTRODUCTION: Hepatotoxicity in patients diagnosed with active tuberculosis (TB) is the commonest adverse effect of therapy. We sought to analyse trends in liver function in patients diagnosed with active TB and to determine predictors of hepatotoxicity. METHODS: We studied 275 patients with active TB treated at the Mercy University Hospital (Cork, Ireland) from 2009 to 2014 A retrospective review was undertaken of all patients' laboratory data and patient correspondence to determine predictors of hepatotoxicity. RESULTS: A total of 170 (62%) male and 105 (38%) female patients with active TB with a mean age of 44 years were studied. In total 15 patients (6%) required their medication to be stopped or altered as a consequence of hepatotoxicity. There was a significant difference in age between patients with hepatotoxicity (52.95 years) and those that didn't develop hepatotoxicity (41.33 years) ( P ≤ 0.01). Irish born patients were more likely to develop hepatotoxicity ( P = 0.025). There was no significant association between hepatotoxicity, illicit drug use ( P = 0.211), smoking ( P = 0.95), cavitatory disease ( P = 0.191), site of disease ( p = 0.224), alcohol use ( P = 0.088) or history of alcohol excess ( p = 0.736). Among patients with TB, peak AST values did not occur within the first 2 weeks as widely thought but later (week 10). CONCLUSION: Our study shows hepatotoxicity as a consequence of antituberculous therapy is common. Hepatotoxicity was more common in older patients and Irish born patients, and resulted in drug interruptions and treatment changes. Given the late peak in AST values at week 10 in patients treated with antituberculous therapy, the authors advocate that liver function tests should be monitored regularly throughout the course of treatment.

Rapidly changing pulmonary infiltrates.

Pulmonary eosinophilia responds very quickly to steroid treatment. Chronic pulmonary eosinophilia is common in middle aged females. We report on a patient who presented with subacute onset of shortness of breath, severe weight loss associated with a rise in the peripheral eosinophil count. She was treated successfully with steroids resulting in complete resolution of the pulmonary infiltrates.

Obesity status transitions across the elementary years: use of Markov chain modelling.

OBJECTIVE: The objective of this study was to assess overweight and obesity status transition probabilities using first-order Markov transition models applied to elementary school children. METHOD: Complete longitudinal data across 11 assessments were available from 1494 elementary school children (from 7599 students in 41 out of 45 schools in a Southeast Texas school district) from kindergarten to the beginning of the fifth grade. Heights and weights were measured by trained school nurses using standard procedures at the beginning and end of each school year for the 11 consecutive assessments. To estimate the transition probabilities, first-order three-state (healthy weight, overweight and obese) Markov transition models were fit to the longitudinal weight status data of all assessment periods. RESULTS: While there was a gradual shift to more children in the overweight or obese category over 5 years, children were most likely to stay in the same weight category as the previous assessment. A consistent seasonal difference in the probability of changing weight status category was seen, with a greater probability of becoming overweight and obese during the summer compared with the school year. The transition probabilities to obesity were higher among boys, Hispanic and non-Hispanic Black, and lower socioeconomic status children. CONCLUSIONS: This study provides the first application of a Markov transition model to child weight status data. The transitions into the overweight and obese categories were small, but persistent, with smaller percentages transitioning out of overweight or obese. Early monitoring and summer intervention strategies are needed to prevent the slow, but relentless, transition into the overweight and obese categories.

The stress response and the hypothalamic-pituitary-adrenal axis: from molecule to melancholia.

Organisms survive by maintaining equilibrium with their environment. The stress system is critical to this homeostasis. Glucocorticoids modulate the stress response at a molecular level by altering gene expression, transcription, and translation, among other pathways. The effect is the inhibition of the functions of inflammatory cells, predominantly mediated through inhibition of cytokines, such as IL-1, IL-6, and TNF-alpha. The central effectors of the stress response are the corticotrophin-releasing hormone (CRH) and locus coeruleus-norepinephrine (LC-NE)/sympathetic systems. The CRH system activates the stress response and is subject to modulation by cytokines, hormones, and neurotransmitters. Glucocorticoids also modulate the growth, reproductive and thyroid axes. Abnormalities of stress system activation have been shown in inflammatory diseases such as rheumatoid arthritis, as well as behavioural syndromes such as melancholic depression. These disorders are comparable to those seen in rats whose CRH system is genetically abnormal. Thus, the stress response is central to resistance to inflammatory and behavioural syndromes. In this review, we describe the response to stress at molecular, cellular, neuroendocrine and behavioural levels, and discuss the disease processes that result from a dysregulation of this response, as well as recent developments in their treatment.

Subclinical anaemia of chronic disease in adult patients with cystic fibrosis.

Patients with chronic hypoxaemia develop secondary polycythaemia that improves oxygen-carrying capacity. Therefore, normal haemoglobin and haematocrit values in the presence of chronic arterial hypoxaemia in cystic fibrosis constitute 'relative anaemia'. We sought to determine the cause of this relative anaemia in patients with cystic fibrosis. We studied haematological indices and oxygen saturation in healthy volunteers (n=17) and in adult patients with cystic fibrosis (n=15). Patients with cystic fibrosis had lower resting arterial oxygen saturation when compared with normal volunteers (P<0.0001), and exercise led to a greater reduction in arterial oxygen saturation (P<0.0001). However, haemoglobin and haematocrit values in patients with cystic fibrosis did not significantly differ from normal volunteers. Serum iron (P=0.002), transferrin (P=0.02), and total iron-binding capacity (P=0.01) were lower in patients with cystic fibrosis. There were no significant differences in serum ferritin, percentage iron saturation, serum erythropoietin or red cell volume between the groups. The data presented demonstrate a characteristic picture of anaemia of chronic disease in adult patients with cystic fibrosis, except for normal haemoglobin and haematocrit values. Normal haemoglobin and haematocrit values in patients with cystic fibrosis appear to represent a combination of the effects of arterial hypoxaemia promoting polycythaemia, counterbalanced by chronic inflammation promoting anaemia of chronic disease.

Nontuberculous mycobacteria: incidence in Southwest Ireland from 1987 to 2000.

SETTING: The Southwest of Ireland (Counties Cork and Kerry) 1987-2000, average population 549,500. OBJECTIVE: Nontuberculous mycobacteria (NTM) cause significant morbidity worldwide and the study of epidemiology and characteristics helps in their prevention and treatment. This study was performed to determine the incidence of NTM disease in comparison to Mycobacterium tuberculosis (M. tuberculosis) and Mycobacterium bovis (M. bovis) in Southwest Ireland, over the above time period. DESIGN: A retrospective study was carried out in all human isolates of NTM, M. tuberculosis and M. bovis between 1987 and 2000, in the Southwest Region of Ireland. RESULTS: The mean incidence of NTM (0.4/100,000 population) has risen since 1995, principally of pulmonary Mycobacterium avium intracellulare complex (MAC). The annual incidence of M. tuberculosis in humans over 14 years in the same region was 971/100,000 population with a significant reduction since 1994 and M. bovis remained constant at 0.5/100,000 population. CONCLUSION: The increasing incidence of disease causing NTM noted in Southwest Ireland reflects global data and is surmised to be due to an ageing population, increased incidence related to chronic fibrotic lung disease, and environmental mycobacterial factors.

Aggressive management leads to improved survival in patients with small cell lung carcinoma.

BACKGROUND: Small cell lung carcinoma (SCLC) accounts for 17-25% of all cases of lung cancer, and remains the most lethal form of this disease. AIMS: We sought to determine whether an aggressive treatment policy led to an increase in median survival in patients with SCLC in our institution. METHODS: From 1985 to 1993, patients with SCLC were often treated conservatively on the basis of advanced age or poor performance status. From 1993 to 1998, a more aggressive management policy was adopted. All patients were treated with chemotherapy. Radiotherapy was administered, where appropriate, following the completion of chemotherapy. The medical records of 66 patients were analysed and clinical outcomes were compared. RESULTS: Median survival in the 1993-98 group (332 days) was significantly better compared to the 1985-93 group (194 days) (p = 0.02). In patients with limited disease, median survival in the 1993-98 group (489 days) was also significantly better compared to the 1985-93 group (254 days) (p = 0.04). The difference in median survival in extensive disease was not significant (p = 0.09). CONCLUSIONS: The presented data suggest that appropriate aggressive management of patients with SCLC leads to a significant increase in median survival. This survival benefit is most apparent in patients with limited disease.

An unusual cause of a pain in the neck: pseudoaneurysm from tuberculous lymphadenitis.

A pseudoaneurysm is a haematoma which is surrounded by connective tissue and communicates with the lumen of a ruptured blood vessel. It has no true defined capsule. We describe a case of tuberculous pseudoaneurysm. This is a rare complication of tuberculosis. The clinical presentation of these lesions is highly variable. Definitive diagnosis should consist of contrast-enhanced CT and arteriography. Treatment should include repair of the arterial wall by surgery, endovascular stent-graft insertion, or embolization followed by a full course of antituberculous chemotherapy. Our case is highly unusual in that the pseudoaneurysm arose from the subclavian vasculature in a patient with extrapulmonary tuberculosis only.