Development of an Insulin-Prescribing Chart for Paediatric Diabetes

Aim Our aim was to design a new insulin prescribing tool in compliance with the Irish Medicines Safety Network recommendations. Methods In 2015, we undertook a review of the existing paediatric subcutaneous insulin-prescribing sheet introduced to Cork University Hospital in 2013. This involved a retrospective analysis of 15 consecutive in-patient insulin prescribing charts and a questionnaire distributed to health professionals. Following this a new insulin prescribing chart was designed and implemented in 2016 and a re-audit was performed in 2017. Results The 2017 re-audit demonstrated that the new insulin chart was viewed as easier (95% of previous users n=18) and safer (n=16) to use. There was less confusion (2017: 28%, n=11/39 vs 2015: 50%, n=17/34 2015) and the ALERT system helped staff standardise hypo/hyperglycaemia management (71%, n=28). Conclusion The new paediatric insulin prescribing chart has improved safety and ease of prescribing insulin. The colour coded quasi graph and ALERT system has made it easier to appreciate capillary blood glucose trends and manage them safely.

Observation of the Leggett-Rice effect in a unitary Fermi gas.

We observe that the diffusive spin current in a strongly interacting degenerate Fermi gas of (40)K precesses about the local magnetization. As predicted by Leggett and Rice, precession is observed both in the Ramsey phase of a spin-echo sequence, and in the nonlinearity of the magnetization decay. At unitarity, we measure a Leggett-Rice parameter γ=1.08(9) and a bare transverse spin diffusivity D(0)(⊥)=2.3(4)ℏ/m for a normal-state gas initialized with full polarization and at one-fifth of the Fermi temperature, where m is the atomic mass. One might expect γ=0 at unitarity, where two-body scattering is purely dissipative. We observe γ→0 as temperature is increased towards the Fermi temperature, consistent with calculations that show the degenerate Fermi sea restores a nonzero γ. Tuning the scattering length a, we find that a sign change in γ occurs in the range 0<(k(F)a)(-1)≲1.3, where k(F) is the Fermi momentum. We discuss how γ reveals the effective interaction strength of the gas, such that the sign change in γ indicates a switching of branch between a repulsive and an attractive Fermi gas.

Detection of Language Lateralization Using Spectral Analysis of EEG.

PURPOSE: Language lateralization relies on expensive equipment and can be difficult to tolerate. We assessed if lateralized brain responses to a language task can be detected with spectral analysis of electroencephalography (EEG). METHODS: Twenty right-handed, neurotypical adults (28 ± 10 years; five males) performed a verb generation task and two control tasks (word listening and repetition). We measured changes in EEG activity elicited by tasks (the event-related spectral perturbation [ERSP]) in the theta, alpha, beta, and gamma frequency bands in two language (superior temporal and inferior frontal [ST and IF]) and one control (occipital [Occ]) region bilaterally. We tested whether language tasks elicited (1) changes in spectral power from baseline (significant ERSP) at any region or (2) asymmetric ERSPs between matched left and right regions. RESULTS: Left IF beta power (-0.37±0.53, t = -3.12, P = 0.006) and gamma power in all regions decreased during verb generation. Asymmetric ERSPs (right > left) occurred between the (1) IF regions in the beta band (right vs. left difference of 0.23±0.37, t(19) = -2.80, P = 0.0114) and (2) ST regions in the alpha band (right vs. left difference of 0.48±0.63, t(19) = -3.36, P = 0.003). No changes from baseline or hemispheric asymmetries were noted in language regions during control tasks. On the individual level, 16 (80%) participants showed decreased left IF beta power from baseline, and 16 showed ST alpha asymmetry. Eighteen participants (90%) showed one of these two findings. CONCLUSIONS: Spectral EEG analysis detects lateralized responses during language tasks in frontal and temporal regions. Spectral EEG analysis could be developed into a readily available language lateralization modality.

Novel quantitative digital image analysis methodology for assessment of inflammatory changes in MRI data in a post-hoc analysis of data acquired from a phase IIb study of baricitinib in patients with active rheumatoid arthritis.

PURPOSE: To evaluate a novel quantitative methodology to assess inflammatory changes in magnetic resonance imaging (MRI) data from patients with rheumatoid arthritis (RA) and the impact of image quality on imaging outcomes compared to the RA Magnetic Resonance Imaging Score (RAMRIS). METHODS: Three-dimensional, T1-weighted, fat-suppressed MRI sequences of the hand/wrist before and after intravenous Gadolinium contrast from patients with RA in a placebo-controlled clinical trial (NCT01185353) were re-evaluated post hoc. The methodology was integrated into proprietary software (DYNAMIKA®) and assessed inflammation through pixelated measurements of the contrast-enhancing (inflammatory) volume. A semi-automatic approach outlined contrast-enhancing synovial tissue in the wrist and second to fifth metacarpophalangeal joints with a rough region of interest (ROI); quantitative imaging biomarkers were generated by means of quantitative total volume of inflammation and quantitative degree of inflammation relative to the signal in a 1 cm in diameter ROI in the center of the thenar or lumbrical muscle for internal reference. The time from Gadolinium injection to finalization of the post-contrast images was calculated from the images' Digital Imaging and Communications in Medicine header. An experienced reader graded image quality as poor, acceptable, or good. RESULTS: Results from this quantitative methodology, especially when excluding images with poor quality scores (14-32%), provided a more pronounced and monotonically increasing dose-response than the original RAMRIS results on synovitis and osteitis. CONCLUSIONS: This computer-aided quantitative scoring method provided continuous measures of inflammatory changes relative to muscle and may be more sensitive and interpretable concerning dose/response separation between RA treatment groups.

Pre-Transplant Marital Status and Hematopoietic Cell Transplantation Outcomes

Background: Evidence about the impact of marital status before hematopoietic cell transplantation (hct) on outcomes after hct is conflicting. Methods: We identified patients 40 years of age and older within the Center for International Blood and Marrow Transplant Research registry who underwent hct between January 2008 and December 2015. Marital status before hct was declared as one of: married or living with a partner, single (never married), separated or divorced, and widowed. We performed a multivariable analysis to determine the association of marital status with outcomes after hct. Results: We identified 10,226 allogeneic and 5714 autologous hct cases with, respectively, a median follow-up of 37 months (range: 1-102 months) and 40 months (range: 1-106 months). No association between marital status and overall survival was observed in either the allogeneic (p = 0.58) or autologous (p = 0.17) setting. However, marital status was associated with grades 2-4 acute graft-versus-host disease (gvhd), p < 0.001, and chronic gvhd, p = 0.04. The risk of grades 2-4 acute gvhd was increased in separated compared with married patients [hazard ratio (hr): 1.13; 95% confidence interval (ci): 1.03 to 1.24], and single patients had a reduced risk of grades 2-4 acute gvhd (hr: 0.87; 95% ci: 0.77 to 0.98). The risk of chronic gvhd was lower in widowed compared with married patients (hr: 0.82; 95% ci: 0.67 to 0.99). Conclusions: Overall survival after hct is not influenced by marital status, but associations were evident between marital status and grades 2-4 acute and chronic gvhd. To better appreciate the effects of marital status and social support, future research should consider using validated scales to measure social support and patient and caregiver reports of caregiver commitment, and to assess health-related quality of life together with health care utilization.

Patient eligibility for hematopoietic stem cell transplantation: a review of patient-associated variables.

Assessing patient eligibility for hematopoietic stem cell transplantation (HSCT) remains a complex, multifaceted challenge. Among these challenges, the paucity of comprehensive clinical data to guide decision making remains problematic coupled with unclear trade-offs between patient, disease and local HSCT center factors. Moreover, it is unclear that the modification of poor patient characteristics will improve post-HSCT outcomes. However, the use of Comorbidity Indices and Comprehensive Geriatric Assessments helps meet this challenge, but may be limited by overlapping patient characteristics. The increasing consideration for pre-HSCT psychosocial assessments and interventions remains to be studied. Ultimately, the decision to proceed with a HSCT remains interdisciplinary while considering the available evidence discussed in this review.

Towards High Capacity Li-ion Batteries Based on Silicon-Graphene Composite Anodes and Sub-micron V-doped LiFePO4 Cathodes.

Lithium iron phosphate, LiFePO4 (LFP) has demonstrated promising performance as a cathode material in lithium ion batteries (LIBs), by overcoming the rate performance issues from limited electronic conductivity. Nano-sized vanadium-doped LFP (V-LFP) was synthesized using a continuous hydrothermal process using supercritical water as a reagent. The atomic % of dopant determined the particle shape. 5 at. % gave mixed plate and rod-like morphology, showing optimal electrochemical performance and good rate properties vs. Li. Specific capacities of >160 mAh g-1 were achieved. In order to increase the capacity of a full cell, V-LFP was cycled against an inexpensive micron-sized metallurgical grade Si-containing anode. This electrode was capable of reversible capacities of approximately 2000 mAh g-1 for over 150 cycles vs. Li, with improved performance resulting from the incorporation of few layer graphene (FLG) to enhance conductivity, tensile behaviour and thus, the composite stability. The cathode material synthesis and electrode formulation are scalable, inexpensive and are suitable for the fabrication of larger format cells suited to grid and transport applications.

A transition-state analogue inhibitor of human renin (H.261): test in vitro and a comparison with captopril in the anaesthetized baboon.

H.261, a new transition state inhibitor of human renin with an IC50 of 6.9 X 10(-10) M, was given by intravenous infusion to six anaesthetized baboons. The inhibitor was infused first at 0.1 mumol/kg/h for 15 min, then at 1.0 mumol/kg/h for a further 15 min. After a recovery period of 2 h in which the animals received 5% dextrose, they were infused with captopril, 25 mumol/kg/h for 15 min. At both rates of infusion H.261 markedly and significantly reduced the enzymatic action of renin in plasma, the blood concentration of angiotensin I, the plasma concentration of angiotensin II and mean arterial pressure. All changes reverted towards or to control values in the subsequent control period. Captopril also lowered plasma angiotensin II concentration and mean arterial pressure markedly and significantly but, as expected for an inhibitor of the angiotensin I-converting enzyme, plasma active renin concentration and blood angiotensin I concentration increased. The changes of angiotensin II and arterial pressure were similar with captopril and H.261.

Short report: short-term triple therapy for H. pylori-associated duodenal ulcer disease.

Thirty consecutive patients with endoscopically proven duodenal ulceration who had Helicobacter pylori infection on culture and histology, were treated with tripotassium dicitrato bismuthate (1 tablet q.d.s., 400 mg metronidazole t.d.s. and 500 mg tetracycline t.d.s. for one week, followed by the bismuth salt for a further 3 weeks. All patients were endoscoped at entry and 4 weeks after cessation of treatment, to check for ulcer healing and H. pylori eradication. Two antral biopsies were taken at each endoscopy for histological and microbiological evidence of H. pylori infection. Complete healing of duodenal ulcers was observed in 27/30 patients (90%). Gastritis improved or completely resolved in 26 patients. Eradication of H. pylori was achieved in 27 patients. Of the three patients who failed to heal, two were H. pylori-positive at follow-up and one was H. pylori-negative.

Short report: high-dose omeprazole and amoxycillin in the treatment of Helicobacter pylori-associated duodenal ulcer.

Thirteen consecutive patients with active duodenal ulcer disease were assigned to a treatment schedule with high-dose omeprazole and amoxycillin. Duodenal ulcer was diagnosed endoscopically in all patients, at which time antral biopsies were taken for culture and histology. All were positive for Helicobacter pylori and histological gastritis. Treatment was for 2 weeks: 80 mg omeprazole daily plus 500 mg amoxycillin syrup t.d.s. in the first week, followed by 40 mg omeprazole daily in the second week. Repeat gastroscopy was performed 4 weeks after completion of treatment in all patients. Duodenal ulcer healing occurred in 4/13 patients. H. pylori eradication was achieved in 2/4 patients with healed ulcers and in 3/9 patients with persistent ulceration. This study suggests that a short period of treatment with high-dose omeprazole and amoxycillin achieves low rates of ulcer healing and H. pylori eradication.

Short report: treatment of Helicobacter pylori-associated duodenal ulcer with omeprazole plus antibiotics.

Omeprazole heals most duodenal ulcers after 4 weeks of treatment but relapse is common. Eradication of Helicobacter pylori is associated with reduced rate of ulcer relapse. This study investigates the effect of omeprazole with antibiotics in H. pylori-associated duodenal ulceration. Forty-three patients with endoscopically proven duodenal ulcer and H. pylori entered this study. Treatment consisted of 20 mg omeprazole daily (four weeks) and seven days (first week) treatment with 400 mg metronidazole t.d.s. and 500 mg tetracycline t.d.s. Four weeks after completing the treatment, 81% (35/43) had a healed duodenal ulcer, and 58% (25/43) had H. pylori eradication. In those who healed, at one year 21 remained H. pylori-negative, 12 had persistent H. pylori infection and 2 had re-infection. The ulcer relapse rate at one year was 26%: of the 9 who relapsed, 6 had persistent infection, 2 were re-infected, and only 1 was H. pylori-negative. This combination therapy of antibiotics with omeprazole successfully eradicates Helicobacter pylori and has a lower ulcer relapse than omeprazole alone.

Discrimination among Bacillus cereus, B. mycoides and B. thuringiensis and some other species of the genus Bacillus by Fourier transform infrared spectroscopy.

Fourier transform infrared spectroscopy (FTIR) in conjunction with canonical variate analysis was found to be effective in discriminating among spectra of 9 representative strains of Bacillus spp., including B. cereus, B. mycoides and B. thuringiensis. The method was also able to discriminate according to species among spectra of 14 other non-type strains of B. cereus, 12 of B. mycoides and 12 of B. thuringiensis with a success rate of > 95%, even without using a prior classification of the groups by species. FTIR spectroscopy can be used for the rapid and accurate differentiation of species in the genus Bacillus that are of importance to the food and dairy industry.

The effect of colonic site of biopsy on cell proliferation profiles using BRDU incorporation as a measure of cell proliferation.

Sigmoidal and rectal biopsies were taken from 10 patients at colonoscopy. Colonic crypt cell proliferation was measured using a monoclonal antibody to bromodeoxyuridine by an immunohistochemical technique. Labelling index and crypt cell proliferation profiles were analysed and compared between the two sites. No statistically significant difference was found in proliferation parameters. Assessment of colonic proliferation is a useful indicator for colorectal cancer risk and for determining the effects of ongoing drug treatment. Rectal biopsies are easier to take than sigmoidal biopsies. The results of this study suggest that there is no difference in cell proliferation at the two sites. Rectal biopsies are more practical for clinical studies.

Residual alkaline phosphatase activity in pasteurized milk heated at various temperatures--measurement with the fluorophos and Scharer rapid phosphatase tests.

Milk containing three levels of milkfat (skim [0.5%], lowfat [2.0%], and whole [3.25%]) were heat treated at five different temperatures (59, 61, 63, 65, and 67 degrees C) using a laboratory scale, batch pasteurization method. Heated milk samples were removed at 5-min intervals, immediately cooled, and then assayed using the quantitative fluorometric method and the qualitative Scharer rapid test. Mean alkaline phosphatase (ALP) activity values as measured with the Fluorophos method decreased in all milk preparations as the time of sampling and temperature of heating increased. Samples representing the three fat levels and heat treated at 63 degrees C for 30 min, the minimum time/temperature allowed by the 1995 pasteurized milk ordinance (PMO), had ALP activity values <100 mU/liter. All values were below the 350 mU/liter standard for fluid milk products established by the Food and Drug Administration and cited in the 1995 PMO. Evaluation of the milks for adequacy of pasteurization with the Scharer rapid method indicated that those same milks were adequately pasteurized.

The effect of grain storage conditions on the viability of Fusarium and deoxynivalenol production in infested malting barley.

A continuing outbreak of Fusarium head blight occurred on barley in the upper Midwest from 1993 to 1995. This resulted in barley with levels of the mycotoxin deoxynivalenol (DON) reaching levels of concern for maltsters and brewers. This study evaluated the effect of 7 months of storage under different conditions (ambient outdoor temperature from October to April), -20 degrees C, 4 degrees C, 24 degrees C with quiescent air, and 24 degrees C with forced air) on the viability of Fusarium and Alternaria infesting stored grain. Additionally, the ability of Fusarium to produce DON after storage and during malting was evaluated. Initial levels of infestation of barley by Fusarium and Alternaria were 85 and 75%, respectively. All storage condition reduced the viability of both molds slightly and significantly for Fusarium. Forced air ventilation at 24 degrees C was the type of storage most effective in reducing the viability of Fusarium, dropping the percentage of infected kernels to 66%. DON levels did not change after 7 months with respect to storage conditions. However, DON levels were lower in malt produced from barley stored at 24 degrees C with or without aeration. On-farm storage of infected barley at elevated temperatures may provide a means to reduce the level of DON in finished malts.

Coronary thrombosis associated with inherited protein S deficiency: a case report.

Protein S deficiency (PSD) may be associated with thrombotic events, including venous and arterial thrombosis. Most commonly, superficial and deep venous thrombosis have been noted. We report a case of acute myocardial infarction resulting from coronary thrombosis in a young male with PSD.

HpSA: assessment of a new non-invasive diagnostic assay for Helicobacter pylori infection in an Irish population.

BACKGROUND: The diagnosis of Helicobacter pylori is an essential element in the management of many common gastrointestinal pathologies. Previously diagnosis was dependent on the availability of endoscopic biopsy samples. The advent of non invasive assays such as the C13Urea breath test and Elisa serology have enabled diagnosis and treatment to be undertaken in the primary care setting. The isolation of Helicobacter pylori antigen from stool has led to the development of a new non-invasive test. AIM: A prospective study was designed to assess and compare the performance of Premier Platinum HpSA with current gold standard tests. METHODS: Consecutive patients undergoing a gastroscopy for investigation of dyspepsia at the Meath and Adelaide hospitals were enrolled. At endoscopy gastric biopsies were taken for histology, microbiology and rapid urease testing. In addition all subjects had C13UBT, serology and stool tests performed. Individuals who were H. pylori positive received standard proton pump inhibitor based triple therapy. Following treatment all tests, apart from serology were repeated. RESULTS: 54 patients were enrolled, 46 per cent were H. pylori positive. HpSA had a sensitivity and specificity and positive and negative predicted values of 96 per cent, 75 per cent and 80.6 per cent, 75.8 per cent respectively and compared favourably with all other tests. The sensitivity and specificities of the other tests were, histology 79.2 per cent and 100 per cent, culture 68 per cent and 100 per cent, rapid urease test 75 per cent and 100 per cent, serology 75 per cent and 96 per cent and C13 urea breath test 100 per cent and 96.6 per cent. CONCLUSION: The detection of H. pylori antigen in stool by means of a HpSA assay is a new and effective non-invasive means of diagnosis which can be performed in a routine laboratory setting. It is simple to perform and has possible advantages over other non-invasive tests, detecting actual antigen indicating current active infection.

Prevalence of metronidazole-resistant Helicobacter pylori in dyspeptic patients.

Susceptibility to metronidazole of 213 clinical strains of H. pylori from dyspeptic patients was determined by a plate dilution method. Seventy two (33.8%) of the strains were resistant to metronidazole (MIC > 8 mg/L), 20 of these were from 24 patients who had received previously metronidazole (83.3%), giving a primary (pretreatment) resistance rate of 27.5% (52/189). The resistance rate was higher in women than in men, especially aged 50 to 59 years old (43.6% vs 23.3%, p < 0.001). The resistance rate was lower in patients at 60 or over (9.8%), but similar between the younger patients groups (38.8% - 49.0%). There was no difference in the resistance rate between peptic ulcer disease (32.6%) and nonulcer dyspepsia (34.7%). These data indicated that metronidazole resistance in H. pylori is absolutely associated with previous use of the drug, and the higher resistance rate in women may be due to the more frequent prescription of the drug for their gynaecological infection or operation. Therefore, testing of susceptibility of H. pylori to metronidazole is important. A new susceptibility testing technique, the E-test was evaluated in this study and found to give comparable results to the plate dilution method and also had the advantage of being simple to perform.

Eradicating Helicobacter pylori and symptoms of non-ulcer dyspepsia.

OBJECTIVE: To examine the effect of eradication of Helicobacter pylori on symptoms of non-ulcer dyspepsia. DESIGN: Four week prospective study. SETTING: One hospital outpatient and endoscopy department. PATIENTS: 90 adults with persistent symptoms typical of non-ulcer dyspepsia but no clinical or endoscopic evidence of other peptic, biliary, pancreatic, or malignant disease; all had histological and microbiological evidence of infection with H pylori. 83 patients completed the treatment regimen. INTERVENTION: Colloidal bismuth subcitrate 120 mg four times a day for four weeks (27 patients); metronidazole 400 mg and amoxycillin 500 mg each three times a day for one week (27); and bismuth subcitrate 120 mg four times a day for four weeks, metronidazole 400 mg three times a day for one week, plus amoxycillin 500 mg three times a day for the first week (29). MAIN OUTCOME MEASURES: Change in symptom scores determined with questionnaire; histological evidence of gastritis and microbiological evidence of presence of H pylori in biopsy specimens. RESULTS: Overall, H pylori was eradicated in 41 (49%) patients. Although gastritis scores improved significantly in only patients in whom H pylori had been eradicated (from 1.56 to 0.61, p less than 0.01 v from 1.83 to 1.07, p = 0.52) mean symptom scores after treatment were similar in patients in whom H pylori had or had not been eradicated (3.0 v 2.3, NS). Similarly the mean symptom score improved whether or not gastritis improved (2.8 v 3.1 respectively, p = 0.72). The observations were similar for treatment groups analysed individually. CONCLUSION: Antral infection with the organism does not seem to have an important aetiological role in non-ulcer dyspepsia short term.