Carbon dioxide levels in neonates: what are safe parameters?

There is no consensus on the optimal pCO2 levels in the newborn. We reviewed the effects of hypercapnia and hypocapnia and existing carbon dioxide thresholds in neonates. A systematic review was conducted in accordance with the PRISMA statement and MOOSE guidelines. Two hundred and ninety-nine studies were screened and 37 studies included. Covidence online software was employed to streamline relevant articles. Hypocapnia was associated with predominantly neurological side effects while hypercapnia was linked with neurological, respiratory and gastrointestinal outcomes and Retinpathy of prematurity (ROP). Permissive hypercapnia did not decrease periventricular leukomalacia (PVL), ROP, hydrocephalus or air leaks. As safe pCO2 ranges were not explicitly concluded in the studies chosen, it was indirectly extrapolated with reference to pCO2 levels that were found to increase the risk of neonatal disease. Although PaCO2 ranges were reported from 2.6 to 8.7 kPa (19.5-64.3 mmHg) in both term and preterm infants, there are little data on the safety of these ranges. For permissive hypercapnia, parameters described for bronchopulmonary dysplasia (BPD; PaCO2 6.0-7.3 kPa: 45.0-54.8 mmHg) and congenital diaphragmatic hernia (CDH; PaCO2 ≤ 8.7 kPa: ≤65.3 mmHg) were identified. Contradictory findings on the effectiveness of permissive hypercapnia highlight the need for further data on appropriate CO2 parameters and correlation with outcomes. IMPACT: There is no consensus on the optimal pCO2 levels in the newborn. There is no consensus on the effectiveness of permissive hypercapnia in neonates. A safe range of pCO2 of 5-7 kPa was inferred following systematic review.

A longitudinal evaluation of the impact of the COVID-19 pandemic on patients with pre-existing anxiety disorders.

OBJECTIVES: To examine if the COVID-19 pandemic is associated with a differential effect over time in relation to its psychological and social impact on patients with established anxiety disorders. METHODS: Semi-structured interviews were conducted with 24 individuals attending the Galway-Roscommon Mental Health Services with an International Classification of Diseases (ICD)-10 diagnosis of an anxiety disorder at two time points (six months apart) to determine the impact of the COVID-19 restrictions on anxiety and depressive symptoms, social and occupational functioning and quality of life. RESULTS: No statistical difference in symptomatology was noted between the two time points in relation to anxiety symptoms as measured by utilising psychometric rating scales (BAI and HARS) or utilising a Likert scale. The greatest impact of COVID-19 at both time points is related to social functioning and quality of life. Significant variability was noted for individual participants. Qualitative analysis noted social isolation, concern for the participants' future and increased difficulty managing anxiety with ongoing restrictions. CONCLUSIONS: No significant overall change in symptomatology or functioning over time was noted for individuals with pre-existing anxiety disorders. Variability was, however, demonstrated between individuals, with some individuals describing ongoing anxiety, social isolation and concern for their future. Identifying those with ongoing symptoms or distress and providing multidisciplinary support to this cohort is suggested.

Impact of the COVID-19 pandemic on patients with pre-existing anxiety disorders attending secondary care.

OBJECTIVES: To examine the psychological and social impact of the COVID-19 pandemic on patients with established anxiety disorders during a period of stringent mandated social restrictions. METHODS: Semi-structured interviews were conducted with 30 individuals attending the Galway-Roscommon Mental Health Services with an International Classification of Diseases diagnosis of an anxiety disorder to determine the impact of the COVID-19 restrictions on anxiety and mood symptoms, social and occupational functioning and quality of life. RESULTS: Twelve (40.0%) participants described COVID-19 restrictions as having a deleterious impact on their anxiety symptoms. Likert scale measurements noted that the greatest impact of COVID-19 related to social functioning (mean = 4.5, SD = 2.9), with a modest deleterious effect on anxiety symptoms noted (mean = 3.8, SD = 2.9). Clinician rated data noted that 8 (26.7%) participants had disimproved and 14 (46.7%) participants had improved since their previous clinical review, prior to commencement of COVID-19 restrictions. Conditions associated with no 'trigger', such as generalised anxiety disorder, demonstrated a non-significant increase in anxiety symptoms compared to conditions with a 'trigger', such as obsessive compulsive disorder. Psychiatric or physical comorbidity did not substantially impact on symptomatology secondary to COVID-19 mandated restrictions. CONCLUSIONS: The psychological and social impact of COVID-19 restrictions on individuals with pre-existing anxiety disorders has been modest with only minimal increases in symptomatology or social impairment noted.

The Vasarhelyi Method of Child Art Psychotherapy in Child and Adolescent Mental Health Services: a stakeholder survey of clinical supervisors.

OBJECTIVES: The Vasarhelyi Method of Child Art Psychotherapy (CAP) is a largely understudied psychotherapeutic modality. This study aims to describe the Vasarhelyi Method of CAP and to describe a stakeholder survey of the views and attitudes of CAP placement supervisors towards CAP among various Child and Adolescent Mental Health Services (CAMHS) teams nationwide. METHODS: A phone- and letter-based survey of 17 CAP placement supervisors who oversee CAP masters students attached to CAMHS teams was performed. A questionnaire was designed enquiring about their experiences with CAP in their clinic and their thoughts on the validity of CAP in various conditions/patient demographics. Participants received written correspondence and were asked to return the survey by post; this was followed up by a telephone call to complete missing surveys. RESULTS: In all, 12 (70.6%) complete surveys were returned. Of the 12 respondents, all considered the CAP student to be a valuable member of the team. In total, 10 respondents (83.33%) stated they would make regular use of the service if it were made available to them. With regard to the therapy itself, nine respondents (75%) believed it was better for internalising symptoms than externalising symptoms. Depression, anxiety, attachment difficulties, trauma, deliberate self-harm and possible psychosomatic illnesses are the conditions viewed as receiving the most benefit from CAP. No gender difference was reported. CONCLUSION: CAP is considered an effective modality and valuable addition to a psychotherapeutic repertoire. Further, more extensive studies are needed in this field.

Can Early Changes in Vital signs Predict Duration of Antibiotic Therapy in Suspected Neonatal Sepsis?

Aims Suspected sepsis remains a leading causes of Neonatal Intensive Care Unit admission, with infants often receiving 48-72 hours of empirical antibiotic therapy. Early in treatment it is difficult to predict infants who will require prolonged antibiotic therapy. Our aim was to assess if vital sign measurements in the initial period of treatment can predict those neonates requiring prolonged antibiotic therapy in term and late-preterm infants. Methods Data was retrospectively collected over 1 year on neonates admitted to our institute for antibiotics. Infants were classified as standard (<48hours duration) or prolonged (>48hours duration) antibiotic therapy. Results Respiratory rate on admission and 12 hours after initiation of therapy correlated significantly with duration of antibiotic therapy and infants requiring prolonged therapy were more likely to have one or more abnormal vital signs 12 hours after initiation of treatment (p<0.05). Conclusion Respiratory rate shows a weak positive correlation with antibiotic duration. Infants requiring prolonged therapy were more likely to have abnormal vital signs 12 hours after initiating antibiotic therapy. Changes in vital signs maybe useful in detecting infants who will require prolonged antibiotic therapy.

Doubling immunochemistry laboratory testing efficiency with the cobas e 801 module while maintaining consistency in analytical performance.

OBJECTIVES: The new immunochemistry cobas e 801 module (Roche Diagnostics) was developed to meet increasing demands on routine laboratories to further improve testing efficiency, while maintaining high quality and reliable data. DESIGN AND METHODS: During a non-interventional multicenter evaluation study, the overall performance, functionality and reliability of the new module was investigated under routine-like conditions. It was tested as a dedicated immunochemistry system at four sites and as a consolidator combined with clinical chemistry at three sites. RESULTS: We report on testing efficiency and analytical performance of the new module. Evaluation of sample workloads with site-specific routine request patterns demonstrated increased speed and almost doubled throughput (maximal 300 tests per h), thus revealing that one cobas e 801 module can replace two cobas e 602 modules while saving up to 44% floor space. Result stability was demonstrated by QC analysis per assay throughout the study. Precision testing over 21 days yielded excellent results within and between labs, and, method comparison performed versus the cobas e 602 module routine results showed high consistency of results for all assays under study. In a practicability assessment related to performance and handling, 99% of graded features met (44%) or even exceeded (55%) laboratory expectations, with enhanced reagent management and loading during operation being highlighted. CONCLUSION: By nearly doubling immunochemistry testing efficiency on the same footprint as a cobas e 602 module, the new module has a great potential to further consolidate and enhance laboratory testing while maintaining high quality analytical performance with Roche platforms.

Parental Decisions regarding pre-hospital therapy and costing of the Emergency Department Visit.

Paediatric patients represent a large percentage of Emergency Department (ED) visits and there is often a perception that the acuity of these presentations is low. The decision-making process that results in parents attending the ED is poorly understood. We designed a cross-sectional cohort study to explore the reasons for attendance, the treatment initiated at home and to assess parental perception of the economic cost of attendance. Data was collected on 200 patients using a survey administered to parents in ED with a follow-up phone call 4-6 weeks later. Our results suggest that attendances are often prompted by parental anxiety rather than clinical deterioration and that prior ED usage is common among those presenting for assessment. Many parents had attempted community therapy with 128/200 patients (64%) having been referred by a healthcare professional and medical therapy at home having been employed by 114/200 (57%) parents before attendance. Parental knowledge of the safety of over-the-counter medications was variable the economic cost of an ED visit was poorly understood by participants. The results of our study suggest that parental desire for control over worrisome symptoms drives much of their management strategy prior to hospital attendance. Strategies in the ED may need to focus more on managing parental expectations than on managing the illness itself and management strategies employed should focus not only on medical therapy of the child's illness but on educating and empowering the parent.

Novel COL4A2 variant in a large pedigree: Consequences and dilemmas.

Pathogenic COL4A2 variants cause abnormalities in collagen production and can have serious implications for a range of organ systems, most notably the brain. Herein, we describe a large family of first-degree relatives affected by a novel heterozygous variant in COL4A2 (c.3490G.A). A wide disease spectrum is described, from asymptomatic to symptomatic, including 2 children with porencephaly and co-existing juvenile idiopathic polyarthritis. During a subsequent pregnancy, antenatal testing identified a positive fetus. In view of the literature, we review management and genetic counselling dilemmas.

Comparative dosimetry study of three UK centres implementing total skin electron treatment through external audit.

OBJECTIVE: This article describes the external audit measurements conducted in two UK centres implementing total skin electron beam therapy (TSEBT) and the results obtained. METHODS: Measurements of output, energy, beam flatness and symmetry at a standard distance (95 or 100 cm SSD) were performed using a parallel plate chamber in solid water. Similarly, output and energy measurements were also performed at the treatment plane for single and dual fields. Clinical simulations were carried out using thermoluminescent dosemeters (TLDs) and Gafchromic® film (International Specialty Products, Wayne, NJ) on an anthropomorphic phantom. RESULTS: Extended distance measurements confirmed that local values for the beam dosimetry at Centres A and B were within 2% for outputs and 1-mm agreement of the expected depth at which the dose is 50% of the maximum for the depth-dose curve in water (R50,D) value. Clinical simulation using TLDs) showed an agreement of -1.6% and -6.7% compared with the expected mean trunk dose for each centre, respectively, and a variation within 10% (±1 standard deviation) across the trunk. The film results confirmed that the delivery of the treatment technique at each audited centre complies with the European Organisation for Research and Treatment of Cancer recommendations. CONCLUSION: This audit methodology has proven to be a successful way to confirm the agreement of dosimetric parameters for TSEBT treatments at both audited centres and could serve as the basis for an audit template to be used by other audit groups. ADVANCES IN KNOWLEDGE: TSEBT audits are not established in the UK owing to a limited number of centres carrying out the treatment technique. This article describes the audits performed at two UK centres prior to their clinical implementation.

Operative surgical yield from general surgical outpatient clinics; time to change the way we practice?

The aim of this study was to compare the number of patients attending surgical outpatient clinics in a general hospital to the number of resulting elective procedures scheduled in a single year. Patients initially assessed at private consulting rooms are not included in this study. The number of surgical outpatient appointments issued in 2011 totalled 6503 with non-attendances running at 1489 (22.9%). The number of elective surgical theatre cases performed in 2011 (i.e. the surgical yield from that period) came to 1078 with an additional 1470 patients referred for endoscopy and 475 patients referred for minor operations. Operative surgical yield from the currently structured outpatient clinic model is low, with the number of theatre cases coming to only 16.58% of the original number of outpatient appointments issued. Recommendations for the improvement of outpatient services are made. These findings are relevant in the context of streamlining access to surgical services.

An MRI rating scale for amyloid-related imaging abnormalities with edema or effusion.

BACKGROUND AND PURPOSE: Immune therapy against amyloid-ß appears to be a promising target in Alzheimer disease. However, a dose-related risk for ARIA on FLAIR images thought to represent parenchymal vasogenic edema or sulcal effusion (termed "ARIA-E"), has been observed in clinical trials. To assess the intensity of ARIA-E presentation, an MR imaging scale that is both reproducible and easily implemented would assist in monitoring and evaluating this adverse event. MATERIALS AND METHODS: On the basis of a review of existing cases from a phase II bapineuzumab study, a scale was constructed with a 6-point score for the 6 regions on each side of the brain (range, 0-60). Scores would be obtained for both parenchymal and sulcal hyperintensities and frequently co-occurring gyral swelling. Inter-rater reliability between 2 neuroradiologists was evaluated in 20 patients, 10 with known ARIA-E and 10 without, by using the intraclass correlation coefficient. RESULTS: The 2 raters had excellent agreement in the identification of ARIA-E cases. A high inter-rater agreement was observed for scores of parenchymal hyperintensity (ICC = 0.83; 95% CI, 48-96) and sulcal hyperintensity (ICC = 0.89; 95% CI, 63-97) and for the combined scores of the 2 ARIA-E findings (ICC = 0.89; 95% CI, 62-97). Gyral swelling scores were observed to have lower inter-rater agreement (ICC = 0.54; 95% CI, -0.06-0.86). CONCLUSIONS: The proposed rating scale provides a reliable and easily implemented instrument to grade ARIA-E imaging findings. We currently do not recommend including swelling.

Culture Positivity of CVCs Used for TPN: Investigation of an Association with Catheter-Related Infection and Comparison of Causative Organisms between ICU and Non-ICU CVCs.

A relationship between central venous catheter (CVC) tip colonisation and catheter-related blood-stream infection (CRBSI) has been suggested. We examined culture positivity of CVC tips (colonised and infected CVCs) in a total parenteral nutrition (TPN) population. Our aims were to define the relationship between culture positivity and CRBSI, and to compare causative organisms between culture positive and CRBSI CVCS, and between ward and ICU CVCs. All patients receiving TPN via non-tunnelled CVCs during the study (1997-2009) were included. All CVC tips were analysed. Data were collated contemporaneously. A TPN audit committee determined whether CVC tip culture positivity reflected colonisation/CRBSI using CDC criteria. 1,392 patients received TPN via 2,565 CVCs over 15,397 CVC days. 25.4% of CVCs tips were culture positive, of these 32% developed CRBSI. There was a nonsignificant trend of higher Gram negative Bacilli isolation in ICU CVCs (P = 0.1), ward CVCs were associated with higher rates of staphylococcal isolation (P = 0.01). A similar pattern of organisms were cultured from CRBSI and culture positive CVCs. The consistent relationship between CRBSI and culture positive CVCs, and similar pattern of causative organisms further supports an aetiological relationship between culture positive CVC tips and CRBSI, supporting the contention that CVC culture-positivity may be a useful surrogate marker for CRBSI rates.

Thermo-optic locking of a semiconductor laser to a microcavity resonance.

We experimentally demonstrate thermo-optic locking of a semiconductor laser to an integrated toroidal optical microcavity. The lock is maintained for time periods exceeding twelve hours, without requiring any electronic control systems. Fast control is achieved by optical feedback induced by scattering centers within the microcavity, with thermal locking due to optical heating maintaining constructive interference between the cavity and the laser. Furthermore, the optical feedback acts to narrow the laser linewidth, with ultra high quality microtoroid resonances offering the potential for ultralow linewidth on-chip lasers.

Introduction of a new incentive and target-based contract for family physicians in the UK: good for older patients with diabetes but less good for women?

AIMS: To determine whether the recording of diabetes-related health indicators has increased and differences diminished between age, gender and deprivation groups, following the introduction of the new General Medical Services contract (nGMS), an incentive- and target-based contract for UK family physicians. METHODS: A serial cross-sectional study set in 310 primary care practices in Scotland serving a population of 1.5 million registered patients, focussing on diabetic patients. Data were taken immediately before the introduction of the nGMS and after it had been in place for 1 year. RESULTS: One year after the introduction of the nGMS contract, there was a 54.2% relative increase in the number of patients electronically recorded as having diabetes. In addition, measurement of the quality indicators glycated haemoglobin (HbA(1c)), blood pressure, serum creatinine and cholesterol significantly increased (P < 0.05). Women were less likely than men to have HbA(1c)[odds ratio (OR) 0.85, 95% confidence intervals (CI) 0.80-0.91], serum creatinine (OR 0.90, 95% CI 0.84-0.96) and cholesterol recorded (OR 0.83, 95% CI 0.77-0.90) or achieve HbA(1c) (

Aspirin reduces cutaneous flushing after administration of an optimized extended-release niacin formulation.

OBJECTIVE: Niacin is an effective treatment for dyslipidemia due to its favorable effects on multiple lipid parameters. Clinical utility of niacin is sometimes limited, however, because of cutaneous flushing. A once-daily, extended-release (ER) niacin formulation has been shown to significantly reduce flushing compared to immediate-release niacin. An optimized (reformulated) version of niacin ER has recently been developed and was shown in a previous study to significantly reduce flushing intensity (severity) compared to the non-optimized (commercial) formulation. The current study was designed to evaluate the effect of aspirin on various indices of flushing when administered with the optimized niacin ER formulation. METHOD: This was a randomized, double-blind, double-dummy, placebo-controlled flush provocation crossover study in healthy males. To increase the probability of flushing, subjects received a single dose of reformulated niacin ER 2,000 mg, which is the upper limit of the approved dosage range. Subjects received 650 mg aspirin orally either 30 minutes before or concomitantly with niacin ER, or placebo with niacin ER, in 3-way crossover fashion. The primary endpoint was the number of subjects who reported at least one flushing event. Secondary endpoints included the perceived intensity and duration of flushing symptoms. RESULTS: In the 148 men who completed all treatments, aspirin significantly reduced flushing incidence (the primary endpoint) following administration of niacin ER compared with placebo. Among subjects receiving placebo, 77% of subjects reported flushing with niacin ER. Among subjects receiving aspirin, 53-61% of subjects reported flushing (pretreatment and concomitant treatment, respectively, both p < 0.001 compared with placebo) with niacin ER. Aspirin also significantly reduced intensity and duration of flushing (by 30-40%) compared with no aspirin. The two aspirin-containing treatments (i.e. pre- or concomitant treatment) were similar in their effects on flushing incidence, intensity and duration. Median intensity on a 100 mm visual analogue scale (VAS) was reduced from 33 mm with placebo to 19-23 mm with aspirin. Median duration was reduced from approximately 1 hour with placebo to 37-48 minutes with aspirin. CONCLUSION: Aspirin significantly reduced the incidence, intensity and duration of flushing associated with reformulated niacin ER. These results support the administration of aspirin prophylactically to decrease niacin-induced cutaneous flushing and to improve patient adherence and acceptability of chronic niacin treatment at therapeutic doses.

Natural history of Type A Niemann-Pick disease: possible endpoints for therapeutic trials.

OBJECTIVE: To describe the disease course and natural history of Type A Niemann-Pick disease (NPD). METHODS: Ten patients with NPD-A (six male, four female; age range at entry: 3 to 6 months) were serially evaluated including clinical neurologic, ophthalmologic, and physical examinations, and assessment of development. Laboratory analyses, abdominal and brain ultrasounds, and chest radiographs also were obtained and information on intercurrent illnesses and cause of mortality was collected. RESULTS: All affected infants had a normal neonatal course and early development. The first symptom detected in all patients was hepatosplenomegaly. Developmental age did not progress beyond 10 months for adaptive behavior, 12 months for expressive language, 9 months for gross motor skills, and 10 months for fine motor skills. Non-neurologic symptoms included frequent vomiting, failure to thrive, respiratory infections, irritability, and sleep disturbance. Neurologic examination at the time of presentation was normal in most patients. Later neurologic examinations revealed progressive hypotonia with loss of the deep tendon reflexes. All patients had cherry red spots by 12 months. The median time from diagnosis to death was 21 months. The cause of death was respiratory failure in nine patients and complications from bleeding in the tenth. CONCLUSIONS: The clinical course in Type A Niemann-Pick disease is similar among affected patients and is characterized by a relentless neurodegenerative course that leads to death, usually within 3 years.

Causes of apparent life threatening events in infants: a systematic review.

AIMS: To determine the most likely diagnoses when infants first present with an apparent life threatening event (ALTE). METHODS: Medline (1966-2002), Embase (1980-2002), and Cinahl (1982-2002) were searched. Primary authors and content experts were contacted to identify further studies. Bibliographies from studies, reviews, and textbooks were searched. Foreign language studies were translated. Articles were included if the ALTE was clearly defined and if the evaluation recorded was from the initial contact. Case reports and studies focusing on single conditions or non-clinical data were excluded. RESULTS: From an initial 2912 papers, eight studies involving 643 infants (aged 0-13 months) were included. All studies were non-randomised and methodological quality varied. All diagnoses were made after evaluation in hospital but investigation protocols varied widely. There were 728 diagnoses assigned overall. Some infants had multiple diagnoses. The most common diagnoses were gastro-oesophageal reflux (n = 227), seizure (n = 83), lower respiratory tract infection (n = 58), and "unknown" (n = 169). Five deaths were noted in total. CONCLUSIONS: There is a wide range of diagnoses reported after evaluation of an ALTE. Differing management protocols contributed to variations in the frequency of the diagnoses. The development and validation of an evidence based management plan may contribute to the care of this common condition.