Low-pathogenicity Mycoplasma spp. alter human monocyte and macrophage function and are highly prevalent among patients with ventilator-acquired pneumonia.

BACKGROUND: Ventilator-acquired pneumonia (VAP) remains a significant problem within intensive care units (ICUs). There is a growing recognition of the impact of critical-illness-induced immunoparesis on the pathogenesis of VAP, but the mechanisms remain incompletely understood. We hypothesised that, because of limitations in their routine detection, Mycoplasmataceae are more prevalent among patients with VAP than previously recognised, and that these organisms potentially impair immune cell function. METHODS AND SETTING: 159 patients were recruited from 12 UK ICUs. All patients had suspected VAP and underwent bronchoscopy and bronchoalveolar lavage (BAL). VAP was defined as growth of organisms at >10(4) colony forming units per ml of BAL fluid on conventional culture. Samples were tested for Mycoplasmataceae (Mycoplasma and Ureaplasma spp.) by PCR, and positive samples underwent sequencing for speciation. 36 healthy donors underwent BAL for comparison. Additionally, healthy donor monocytes and macrophages were exposed to Mycoplasma salivarium and their ability to respond to lipopolysaccharide and undertake phagocytosis was assessed. RESULTS: Mycoplasmataceae were found in 49% (95% CI 33% to 65%) of patients with VAP, compared with 14% (95% CI 9% to 25%) of patients without VAP. Patients with sterile BAL fluid had a similar prevalence to healthy donor BAL fluid (10% (95% CI 4% to 20%) vs 8% (95% CI 2% to 22%)). The most common organism identified was M. salivarium. Blood monocytes from healthy volunteers incubated with M. salivarium displayed an impaired TNF-α response to lipopolysaccharide (p=0.0003), as did monocyte-derived macrophages (MDMs) (p=0.024). MDM exposed to M. salivarium demonstrated impaired phagocytosis (p=0.005). DISCUSSION AND CONCLUSIONS: This study demonstrates a high prevalence of Mycoplasmataceae among patients with VAP, with a markedly lower prevalence among patients with suspected VAP in whom subsequent cultures refuted the diagnosis. The most common organism found, M. salivarium, is able to alter the functions of key immune cells. Mycoplasmataceae may contribute to VAP pathogenesis.

Comparison of caregivers' assessments of clinical outcome in dogs with idiopathic epilepsy administered levetiracetam, zonisamide, or phenobarbital monotherapy.

OBJECTIVE: To investigate caregivers' assessments of outcome in dogs with idiopathic epilepsy (IE) administered levetiracetam (LEV), zonisamide (ZNS), or phenobarbital (PB) monotherapy. ANIMALS: 100 dogs with IE administered LEV (n = 34), ZNS (31), or PB (35) monotherapy between January 1, 2003, and February 6, 2019, and survey responses from their caregivers. PROCEDURES: Information on duration of therapy, adverse effects (AEs), and outcome was obtained from medical record review and caregiver questionnaire. RESULTS: A significant improvement in mean quality of life score was reported during monotherapy (7.7; SD, 2.14) compared to before treatment (6.25; SD, 2.63; P < .0001), with no difference identified between monotherapy groups. Compared to ZNS monotherapy, dogs prescribed PB monotherapy had a significantly younger median age at seizure onset (2.6 vs 4.3 years; P = .024). A significant relationship was identified between the occurrence of reported AEs and monotherapy group, with a higher prevalence in the PB group (77% [27/35]) and a lower prevalence in the ZNS group (39% [12/31]; P = .0066). Treatment failure rates for PB, LEV, and ZNS monotherapy were 51%, 35%, and 45%, respectively, with failure attributed most commonly to inadequate seizure control. No significant difference was identified between groups with respect to rate of or time to failure. CLINICAL RELEVANCE: Most caregivers reported a favorable outcome with administration of LEV, ZNS, or PB monotherapy to dogs with IE. Phenobarbital is associated with the highest prevalence of AEs but no difference in quality of life score. Prospective controlled studies are needed to further compare the efficacy and safety of these monotherapies in dogs with IE.

Management of Group B streptococcal sepsis risk in well, term newborns.

AIM: To investigate how clinically well, term newborns at risk of early-onset Group B streptococcal (EOGBS) disease are currently managed in the United Kingdom (UK). METHODS: Review of guidelines of UK neonatal units. RESULTS: One hundred and twenty-five guidelines covering 157 neonatal units were received (71% of UK units), three of which were excluded from the review. We found great variation in every aspect for the management of EOGBS disease risk including the following: definition of risk factors; management of at-risk newborns; choice of antibiotics. CONCLUSION: Our findings highlight the need for national consensus guidelines and clinical trials into the management of risk babies at risk of EOGBS disease.

Measuring the development of insight by dental health professionals in training using workplace-based assessment.

INTRODUCTION: For health professionals, the development of insight into their performance is vital for safe practice, professional development and self-regulation. This study investigates whether the development of dental trainees' insight, when provided with external feedback on performance, can be assessed using a single criterion on a simple global ratings form such as the Longitudinal Evaluation of Performance or Mini Clinical Evaluation Exercise. METHODS: Postgraduate dental trainees (N = 139) were assessed using this tool on a weekly basis for 6 months. Regression analysis of the data was carried out using SPSS, and a short trainer questionnaire was implemented to investigate feasibility. RESULTS: Ratings for insight were shown to increase with time in a similar manner to the growth observed in other essential skills. The gradient of the slope for growth of insight was slightly less than that of the other observed skills. Trainers were mostly positive about the new criterion assessing trainees' insight, although the importance of training for trainers in this process was highlighted. DISCUSSION: Our data suggest that practitioners' insight into their performance can be developed with experience and regular feedback. However, this is most likely a complex skill dependent on a number of intrinsic and external factors. CONCLUSION: The development of trainees' insight into their performance can be assessed using a single criterion on a simple global ratings form. The process involves no additional burden on evaluators in terms of their time or cost, and promotes best practice in the provision of feedback for trainees.

Challenges of Developing Robust AI for Intrapartum Fetal Heart Rate Monitoring.

Background: CTG remains the only non-invasive tool available to the maternity team for continuous monitoring of fetal well-being during labour. Despite widespread use and investment in staff training, difficulty with CTG interpretation continues to be identified as a problem in cases of fetal hypoxia, which often results in permanent brain injury. Given the recent advances in AI, it is hoped that its application to CTG will offer a better, less subjective and more reliable method of CTG interpretation. Objectives: This mini-review examines the literature and discusses the impediments to the success of AI application to CTG thus far. Prior randomised control trials (RCTs) of CTG decision support systems are reviewed from technical and clinical perspectives. A selection of novel engineering approaches, not yet validated in RCTs, are also reviewed. The review presents the key challenges that need to be addressed in order to develop a robust AI tool to identify fetal distress in a timely manner so that appropriate intervention can be made. Results: The decision support systems used in three RCTs were reviewed, summarising the algorithms, the outcomes of the trials and the limitations. Preliminary work suggests that the inclusion of clinical data can improve the performance of AI-assisted CTG. Combined with newer approaches to the classification of traces, this offers promise for rewarding future development.

Revalidation of general dental practitioners in Scotland: the results of a pilot study. Part 1--feasibility of operation.

AIM: To devise and operate a pilot scheme of revalidation for general dental practitioners. METHOD: A representative group of dental practitioners was convened to advise on an approach to piloting revalidation. Ten general dental practitioners volunteered and completed portfolios of evidence of fitness to practise. The portfolios were assessed by a panel of three calibrated experts, using a specially developed assessment tool. A single decision "evidence presented allowed revalidation to be recommended" was made. A timesheet was used to record the time spent producing the portfolio. RESULTS: Eight portfolios were assessed as sufficient for revalidation purposes. Two dentists were required to make supplementary submissions of evidence before they were found to be acceptable. An average of eight hours of dentist time and six hours of delegated time was spent producing the portfolios. CONCLUSIONS: The small number of dentists in this pilot were able to use the portfolio satisfactorily. The dentists were all volunteers and so may not necessarily be fully representative of the profession. The time spent completing the portfolio was not considered excessive. The assessors were adequately prepared and calibrated for their work.

Revalidation of general dental practitioners in Scotland: the results of a pilot study. Part 2 - acceptability to practitioners.

AIM: To investigate the acceptablility of a pilot scheme of revalidation to general dental practitioners. METHOD: Ten general dental practitioners completed portfolios of evidence of being up to date and fit to practise. This portfolio was assessed by a panel of three experts, using an assessment tool developed specifically for that purpose. An action research methodology was used to evaluate participants' perceptions, consisting of a focus group and semi-structured interviews. The views of the assessors on the portfolio and its assessment were collected using a questionnaire. RESULTS: The views of the participants on revalidation, the pilot scheme portfolio and its use, who should assess it and how its use could be supported were collected. Also areas of difficulty in using the portfolio were identified, along with suggestions for improving it and alternative ways of evidencing competence. Assessors noted that the quality of evidence was adequate, but also made suggestions for improvement of the portfolio. CONCLUSIONS: The pilot scheme appears to have been acceptable to the dentists in this scheme, given some caveats. The assessors felt that appraisal would significantly enhance any substantive scheme.

Anaesthesia for elective inguinal hernia repair in rural Ghana - appeal for local anaesthesia in resource-poor countries.

Local anaesthesia has been identified as the most favourable anaesthesia for elective inguinal hernia repair with respect to complication rate, cost-effectiveness, and overall patient satisfaction. Operation theatre notes in all seven hospitals in the Northern Region in Ghana over the period of 1 year were reviewed. Only 22.4% out of 1038 repairs were performed under local anaesthesia while predominantly spinal and general anaesthesia were used (48.0 and 29.6%, respectively). African surgeons chose local anaesthesia far less frequently than visiting overseas surgeons (15.6 versus 27.7%, respectively). All surgeons in resource-poor countries should be encouraged to use local anaesthesia more frequently for elective inguinal hernia repair. Valuable resources in sub-Saharan African hospitals could be saved, especially if used in combination with outpatient surgery. The technique should be taught in teaching institutions. A simple step-by-step technique is described.

In-depth performance analysis of an EEG based neonatal seizure detection algorithm.

OBJECTIVE: To describe a novel neurophysiology based performance analysis of automated seizure detection algorithms for neonatal EEG to characterize features of detected and non-detected seizures and causes of false detections to identify areas for algorithmic improvement. METHODS: EEGs of 20 term neonates were recorded (10 seizure, 10 non-seizure). Seizures were annotated by an expert and characterized using a novel set of 10 criteria. ANSeR seizure detection algorithm (SDA) seizure annotations were compared to the expert to derive detected and non-detected seizures at three SDA sensitivity thresholds. Differences in seizure characteristics between groups were compared using univariate and multivariate analysis. False detections were characterized. RESULTS: The expert detected 421 seizures. The SDA at thresholds 0.4, 0.5, 0.6 detected 60%, 54% and 45% of seizures. At all thresholds, multivariate analyses demonstrated that the odds of detecting seizure increased with 4 criteria: seizure amplitude, duration, rhythmicity and number of EEG channels involved at seizure peak. Major causes of false detections included respiration and sweat artefacts or a highly rhythmic background, often during intermediate sleep. CONCLUSION: This rigorous analysis allows estimation of how key seizure features are exploited by SDAs. SIGNIFICANCE: This study resulted in a beta version of ANSeR with significantly improved performance.

Developmental outcome of the use of etamsylate for prevention of periventricular haemorrhage in a randomised controlled trial.

OBJECTIVE: To compare neurodevelopmental outcome of survivors of the multicentre trial of etamsylate (the iRNN for ethamsylate) for prevention of periventricular haemorrhage in very low birthweight infants. DESIGN: Double blind, single observer, prospective follow up of placebo controlled study. SETTING: Six neonatal intensive care units in the United Kingdom. Neurodevelopmental outcome was assessed in health premises or children's homes. SUBJECTS: 268 of 276 survivors of the original study were seen between 3.5 and 4.2 years of age. All were inborn and weighed 1500 g or less at birth. INTERVENTION: Etamsylate 12.5 mg/kg or placebo six hourly from within one hour of delivery for four days. MAIN OUTCOME MEASURES: McCarthy scales of children's abilities, standardised neurological examination, full physical examination, functional assessment, seven letter Stycar vision test, and audiometry. RESULTS: There was no difference between the groups in neuromotor outcome (cerebral palsy) or in the general cognitive index (GCI) of the McCarthy scales (mean GCI was 93.3 for the etamsylate group (n = 133) and 89.7 for the placebo group (n = 131); p = 0.10). There were more children with GCI < 70 (9 v 19; p = 0.047) or

Educational needs and employment status of Scottish dental hygienists.

AIMS AND OBJECTIVES: To investigate the educational needs and employment status of registered dental hygienists in Scotland. SUBJECTS: Three hundred and eighty one registered dental hygienists with postal addresses in Scotland. DESIGN: Structured questionnaire. RESULTS: A 76% response rate was achieved following two mailings. Of the respondents, 43% were in full-time employment albeit in more than one setting, mostly in the 'central belt' of Scotland. It was reported that 41% were employed in general dental practice with both NHS and private lists and 39% worked in a purely private setting. The introduction of extended clinical duties had been well received and 59% of subjects were interested in additional training in dental therapy, should this become available. Absence of funding for CPD was raised repeatedly, with only 41% reporting a degree of financial assistance. Greater accessibility to continuing education via distance learning, particularly in remote and rural settings, was requested by 73% of hygienists. CONCLUSIONS: This study identifies a number of issues in relation to this increasingly important group of healthcare professionals, which will inform the providers of oral healthcare. Although hygienists' involvement in CPD was commendable, results indicated that despite commitment to their profession, respondents did not always feel respected in terms of their employment status or support for continuing professional development.

In vivo effect of 1,25-dihydroxycholecalciferol on the proliferation and differentiation of avian chondrocytes.

A combination of immunocytochemistry and in situ biochemistry has been used to determine the in vivo effects of 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] on the proliferation and differentiation of chondrocytes. Chicks were fed a diet supplemented with 1,25-(OH)2D3 (2.5, 5, or 10 micrograms/kg diet) for 3 weeks, and measurements were made in sections of growth plate of chondrocyte proliferation and rate of maturation through the growth plate [using bromodeoxyuridine (BrdUrd) labeling] and also chondrocyte differentiation [assessed by alkaline phosphatase (ALP) activity]. The labeling indices of the control and supplemented chicks were similar (23.1 +/- 1.3 versus 23.2 +/- 1.6%); however, within a 21 h period the BrdUrd-positive cells of the supplemented chicks had moved down the growth plate significantly farther than in the control chicks (71.0 +/- 2.8 versus 52.6 +/- 1.8%). Greater ALP (mean integrated absorbance) activity higher up the growth plate of the supplemented chicks indicated a more differentiated phenotype in cells closer to the epiphyseal junction. Within individual transitional chondrocytes ALP activity in the 10 micrograms/kg supplemented chicks was 26.6 +/- 0.85, which was significantly higher (p < 0.01) than that of the control chicks (19.2 +/- 0.9). These results suggest that 1,25-(OH)2D3 in vivo does not increase the rate of chondrocyte proliferation but accelerates the onset of maturation.

Platelet adhesiveness and fibrinolysis after recent cerebro-vascular accidents and their relationship with subsequent deep venous thrombosis of the legs.

In fifteen patients with a cerebro-vascular accident resulting in an acute hemiplegia there was a subsequent rise in the platelet count and plasma fibrinogen level. There were no significant alterations in platelet adhesiveness, plasminogen activator, plasminogen, FR-antigen and haematocrit. Patients diagnosed as developing deep venous thrombosis with the 125I-fibrinogen technique had a significantly lower platelet adhesiveness and plasminogen level than those who were not.

In vivo and in vitro effect of 1,25-dihydroxyvitamin D3 and 1,25-dihydroxy-16-ene-23-yne-vitamin D3 on the proliferation and differentiation of avian chondrocytes: their role in tibial dyschondroplasia.

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) is regarded as the most biologically active metabolite of cholecalciferol. It prevents tibial dyschondroplasia (TD) in chicks where inhibition of chondrocyte differentiation within the growth plate occurs. However, it is unclear whether its mode of action is through direct interaction with its chondrocyte receptor and its known regulatory role in cell differentiation or is mediated by increased calcium absorption and mobilisation. Synthetic analogues of 1,25(OH)2D3 such as 1,25-dihydroxy-16-ene-23-yne cholecalciferol (RO 23-7553) with increased differentiation properties but reduced calcaemic activity have been synthesised. In this study, the in vitro and in vivo effects of 1,25(OH)2D3 and RO 23-7553 on chick chondrocyte growth and differentiation were examined. In addition, the in vivo effectiveness of these steroids in preventing TD in chicks was assessed. 1,25(OH)2D3 and RO 23-7553 (10(-12)-10(-7) M) displayed biphasic concentration effects and had similar potencies in vitro in regulating chondrocyte proliferation and differentiation. However, while the incidence of TD in birds dosed with 1,25(OH)2D3 was lower (10%) than in control chicks (55%), RO 23-7553 was ineffective (50%). This may be the result of its reduced affinity (1000 times less) for the plasma vitamin D binding protein (DBP) and the chondrocyte receptor in comparison to that of 1,25(OH)2D3. A reduction in calcium supply to the chondrocyte may also result in decreased chondrocyte differentiation but blood ionised and plasma total calcium were normal in birds dosed with RO 23-7553. These data suggest that RO 23-7553 and 1,25(OH)2D3 regulate chondrocyte proliferation and differentiation similarly in vitro but not in vivo. This may be caused by differences in DBP binding and clearance rates of the two steroids in vivo.

Fibrinolytic activity in malignant disease.

Resting fibrinolytic activity and fibrinolytic capacity were compared in 31 patients with malignant disease and in 24 control subjects without malignant disease. Patients with malignant disease had a lower mean fibrinolytic activity: this was particularly marked in those with disseminated disease. In contrast, patients with malignant disease had a fibrinolytic capacity which did not differ from that of the control subjects.

Effect of local exercise and vessel occlusion on fibrinolytic activity.

Arterial occlusion of the upper limb did not affect the fibrinolytic activity in the venous blood of that limb; venous occlusion associated with venous distension resulted in a marked rise in activity. Local fibrinolytic activity was increased substantially by active exercise; passive exercise induced a smaller increase. Active exercise undertaken during arterial occlusion did not result in a rise in activator level. It is concluded from these results that blood flow into the venous system rather than accumulation of metabolites is responsible for the increased release of activator into the blood during local exercise and vessel occlusion.

Changes in protease inhibitors after acute myocardial infarction.

Plasma levels of fibrinogen, alpha1-antitrypsin, alpha2-macroglobulin, antithrombin III, and C1 inactivator were measured serially for 10 days in 11 patients after acute myocardial infarction. Both fibrinogen and alpha1-antitrypsin rose markedly to reach peak levels 5-7 days after infarction while C1 inactivator levels rose slowly with the highest observed mean level on the 10th postinfarction day. Neither antithrombin III nor alpha2-macroglobulin changed significantly after myocardial infarction. No relationship between C1 inactivator levels and either fibrinogen or alpha1-antitrypsin was found in a study of 30 patients with a variety of disorders while fibrinogen and alpha1-antitrypsin levels were significantly correlated.

Antinuclear antibody-negative systemic lupus erythematosus-how common?

A review of five years' DNA-binding antibody results in a routine service laboratory revealed 38 patients who had high DNA-binding capacity (DNA-bc) but no antinuclear antibodies (ANA). On retrospective case note analysis, 22 patients (58%) were thought to have systemic lupus erythematosus (SLE), although only six (16%) fulfilled the preliminary classification criteria of the American Rheumatism Association (ARA). Our findings indicate that ANA-negative SLE is commoner than generally realised and lead us to recommended the measurement of DNA-bc in every case where clinically appropriate.

The role of iron deficiency in experimentally-induced oral candidosis in the rat.

In comparison with normal rats, those with iron deficiency anaemia showed no significant difference in susceptibility to experimental infection with Candida albicans although anaemic rats had a significantly greater incidence of persistent infection. These findings support the suggestion that patients with chronic candidosis should be investigated for iron deficiency.