A three-point time series study of antibiotic usage on an intensive care unit, following an antibiotic stewardship programme, after an outbreak of multi-resistant Acinetobacter baumannii.

Antibiotic use in intensive care units (ICUs) can promote antimicrobial resistance. Outbreaks of multi-resistant bacteria significantly affect patient outcomes and delivery of care. Antibiotic stewardship programmes (ASPs), combining root-cause analyses and multi-faceted prevention strategies, are necessary, often at significant cost and time. Which elements of such strategies have the largest impact on antibiotic usage following an outbreak is unclear. The aim of this study was to investigate how antibiotic usage in a university hospital ICU changed with a non-protocolised ASP following a disruptive outbreak of multi-resistant Acinetobacter baumannii (MRAB). This was a three time-period observational cohort study. The primary endpoint was the change in overall antibiotic usage (daily defined dose, DDD, antibiotic-days, antibiotic-courses) for consecutive ICU patients staying >48 h, over three 6-month study time periods pre-MRAB (2008, n = 84) and post-MRAB (2010, n = 88; 2012, n = 122). Secondary endpoints were changes in antibiotic usage and patient demographics, in predefined admission categories (Medical Emergency, ME; Surgical Elective, SEL; and Surgical Emergency, SE). The mean age (54.6 ± 17.7, 58.1 ± 17.9, 62.8 ± 19.1 years*) and severity of illness (APACHE 14.8 ± 8.0, 16.7 ± 6.8, 18.3 ± 6.1*) increased, particularly medical admissions. There was a sustained reduction in DDD antibiotic usage [1895.1 (2008), 1224.2 (2010), 1236.6 (2012) per 1000 patient-days] but no overall change in antibiotic-days or antibiotic-courses. Antibiotic usage (antibiotic-days) fell significantly in surgical emergency admissions [20.2 ± 32.1, 4.6 ± 7.4*, 5.9 ± 7.3]. There was a sustained drop in beta-lactam, quinolone, glycopeptide and macrolide usage. Following an MRAB outbreak, and subsequent operational changes including enhanced ASPs (non-protocolised), there was a sustained overall fall in antibiotic usage in spite of an increase in disease severity over 5 years.

Five-hour fatty acid elevation increases muscle lipids and impairs glycogen synthesis in the rat.

Insulin-mediated muscle glycogen synthesis is impaired after several weeks of high-fat feeding in rats, but not by short-term (2-hour) nonesterified fatty acids (NEFA) elevation induced by intravenous triglyceride/heparin infusion (TG/H). We examined whether a longer TG/H infusion induces defective glycogen synthesis. Five-hour hyperinsulinemic (700 pmol/L) euglycemic clamps with either TG/H or saline infusion were performed. TG/H-infused rats developed insulin resistance, but only after 2 to 3 hours. Red gastrocnemius glycogen synthesis rate decreased by 50% (P < .01 v saline) associated with decreased glycogen synthase activity (GSa; assessed at several glucose-6-phosphate [G-6-P] levels; two-way ANOVA, P=.02) and increased muscle TG and total long-chain acyl coenzyme A (LCAC) content (twofold; P < .05 v saline). Thus a 3- to 5-hour NEFA elevation in the rat produced significant impairment of insulin-stimulated muscle glycogen synthesis, associated with muscle lipid accumulation. These effects were similar to those observed after several weeks of fat feeding. The 5-hour TG/H-infused rat is a useful model for studying lipid-induced muscle insulin resistance.

The use of microfilters as an alternative to centrifugation in radioimmunoassay.

A microfilter was designed, together with a mechanical filtration apparatus for the separation of "antibody-bound" and "free" antigen in radioimmunoassay. A comparison of the results obtained using both filtration and centrifugation was carried out and the optimum incubation times, reaction conditions and washing volume for use with the microfilter were studied. The use of microfilters in radioimmunoassay gave reproducible results and offered a convenient means of automating the separation procedure.

Dietary intake of Al, Ca, Cu, Fe, Pb, and Zn in infants.

The dietary intake of six elements--Al, Ca, Cu, Fe, Pb, and Zn--was measured in 39 normal healthy children aged 17-61 (mean 35.5) weeks. There was a downward trend with age in daily intake of fluid, Pb and Fe, in contrast to an increase in solid intake, Ca and Zn throughout the study. The geometric mean total daily element intake (mg) was: Al 1.12; Ca 446; Cu 0.6; Fe 4.5; Pb 0.020; Zn 2.8. The geometric mean daily element intake (mg) from milks only was as follows: Formula milk (n = 14): Al 0.26; Ca 184; Cu 0.24; Fe 1.85; Pb 0.005; Zn 1.6. Cows' milk (n = 6): Al 0.27; Ca 384; Cu 0.04; Fe 0.21; Pb 0.004; Zn 1.3. Breast milk (n = 12): Al 0.77; Ca 116; Cu 0.15; Fe 0.38; Pb 0.012; Zn 0.4. Additionally, levels of aluminium were investigated in some packaged infant foodstuffs, including four soya milk formulae. The soya-based formulae had a mean concentration of 1.09 +/- 0.37 micrograms/g, which was not significantly different from the mean of 0.83 +/- 0.28 microgram/g for six cows' milk formulae.

Assessment of clinical risk in the out of hours hospital prior to the introduction of Hospital at Night.

Overnight medical cover in hospital is less than during daylight hours. We aimed to quantify the numbers of patients deteriorating overnight and their clinical outcome. Data was collected in real time on use of the Standardised Early Warning Score (SEWS), 'time to doctor', seniority of medical review and clinical outcome. 136 incidents of clinical concern were noted on the general wards with a median response time of 5 minutes for SEWS>4 and 10 minutes if SEWS<4. 159 incidents were recorded in critical care. There was significant inter-speciality variation in median response times and seniority of responding staff, particularly within critical care, which recorded the slowest times across the hospital. This will be reassessed following the establishment of Hospital at Night.

Improvement in out-of-hours outcomes following the implementation of Hospital at Night.

BACKGROUND: Hospital at Night (H@N) is a Department of Health (England) driven programme being widely implemented across UK. It aims to redefine how medical cover is provided in hospitals during the out-of-hours period. AIM: To investigate whether the implementation of H@N is associated with significant change in system or clinical outcomes. DESIGN: An observational study for 14 consecutive nights before, and 14 consecutive nights after the implementation of H@N. Data were collected from the Combined surgical and medical Assessment Unit (CAU), the 18 medical/surgical wards (The Ward Arc) and the four High Dependency Units (The Critical Care corridor) within the Royal Infirmary of Edinburgh. METHODS: Following an overnight episode of clinical concern, data were gathered on response time, seniority of reviewing staff, patient outcome and the use of Standardized Early Warning Score (SEWS). RESULTS: Two hundred and nine episodes of clinical concern were recorded before the implementation of H@N and 216 episodes afterwards. There was no significant change in response time in the CAU, Ward Arc or Critical Care corridor. However, significant inter-speciality differences in response time were eradicated, particularly in the Critical Care corridor. Following the implementation of H@N, patients were reviewed more frequently by senior medical staff in CAU (28% vs. 4%, P < 0.05) and the Critical Care corridor (50% vs. 22%, P < 0.001). Finally there was a reduction in adverse outcome (defined as unplanned transfer to critical care/cardiac arrest) in the Ward Arc and CAU from 17% to 6% of patients reviewed overnight (P < 0.01). SEWS was more frequently and accurately recorded in CAU. CONCLUSION: This is the first study that we are aware of directly comparing out-of-hours performance before and after the implementation of H@N. Significant improvements in both patient and system outcomes were observed, with no adverse effects noted.

Cushing's syndrome from an inhaled glucocorticoid.

OBJECTIVE: To report a case of significant systemic side effects from an inhaled glucocorticoid at a reported dose in the upper recommended therapeutic range. CLINICAL FEATURES: A 25-year-old white man with asthma treated with inhaled glucocorticoid (beclomethasone 1500 micrograms daily), and primary testicular failure with inadequate androgen replacement, was referred with back pain. He was found to have osteoporosis, clinical features of Cushing's syndrome and complete suppression of endogenous adrenocorticotrophic hormone adrenal function. INTERVENTION AND OUTCOME: He was recommended to receive adequate androgen replacement and to use a spacer device with the inhaled beclomethasone, or to change to budesonide via a Turbuhaler (AB Astra, Sweden). CONCLUSIONS: Inhaled glucocorticoids should not be regarded as entirely safe, as serious systemic side effects may occur at doses at the upper level of the recommended therapeutic range.

Measurement of vitamin D3 metabolites in smelter workers exposed to lead and cadmium.

OBJECTIVES: To investigate the effects of lead and cadmium on the metabolic pathway of vitamin D3. METHODS: Blood and urinary cadmium and urinary total proteins were measured in 59 smelter workers occupationally exposed to lead and cadmium. In 19 of these workers, the plasma vitamin D3 metabolites, (25-hydroxycholecalciferol (25 OHD3), 24R, 25-dihydroxycholecalciferol (24R,25(OH)2D3) and 1 alpha,25-dihydroxycholecalciferol (1 alpha, 25(OH)2D3)) were measured together with blood lead. Vitamin D3 metabolites were measured by radioimmunoassay, (RIA), lead and cadmium by atomic absorption spectrophotometry, and total proteins with a test kit. RESULTS: Ranges for plasma 25(OH)D3, 24R,25(OH)2D3 and 1 alpha,25(OH)2D3 were 1.0-51.9 ng/ml, 0.6-5.8 ng/ml, and 0.1-75.7 pg/ml, respectively. Ranges for blood lead were 1-3.7 mumol/l, (21-76 micrograms/dl), blood cadmium 6-145 nmol/l, and urinary cadmium 3-161 nmol/l. Total proteins in random urine samples were 2.1-32.6 mg/dl. Concentrations of lead and cadmium in blood showed no correlation (correlation coefficient -0.265) but there was a highly significant correlation between blood and urinary cadmium. Concentrations for 24R,25(OH)2D3 were depressed below the normal range as blood and urinary cadmium increased, irrespective of lead concentrations. High cadmium concentrations were associated with decreased plasma 1 alpha,25(OH)2D3 when lead concentrations were < 1.9 mumol/l and with above normal plasma 1 alpha,25(OH)2D3 when lead concentrations were > 1.9 mumol/l, Kruskal-Wallis analysis of variance (K-W ANOVA) chi 2 = 10.3, p = 0.006. Plasma 25(OH)D3 was negatively correlated with both urinary total proteins and urinary cadmium, but showed no correlation with plasma 24R,25(OH)2D3, 1 alpha,25(OH)2D3, blood lead, or blood cadmium. CONCLUSION: Continuous long term exposure to cadmium may result in a state of equilibrium between blood and urinary cadmium. Cadmium concentrations in blood could be predicted from the cadmium concentration of the urine, (regression coefficient +0.35 SE 0.077). Exposure to cadmium alone decreased the concentrations of 1 alpha,25(OH)2D3 and 24R,25(OH)2D3, whereas exposure to both cadmium and lead increased the concentrations of 1 alpha,25(OH)2D3. It has been suggested that cadmium and lead interact with renal mitochondrial hydroxylases of the vitamin D3 endocrine complex. Perturbation of the vitamin D metabolic pathway by cadmium may result in health effect, such as osteoporosis or osteomalacia, risks which are possibly increased in the presence of lead.

Blood lead in U.K. children--time for a lower action level?

1. Blood lead measurements in samples collected from 660 London schoolchildren during 1991 to 1992 suggest that the blood lead values in children in the U.K. are decreasing. 2. Geometric mean values for blood lead were 0.18 (range 0.05-0.71) micromol/l [3.7 (1. 0-15.0) microgram/dl]. Analysis of variance showed differences between ethnic groups, sex and schools. An age-matched subset of 148 children was compared with 136 children from an earlier study in 1986 and 1987. Trend analysis of the geometric mean lead values showed a negative slope (b=-0.484, P<0.0001), with maximum values of 0.81, 1.00, 0.71 and 0.43 micromol/l (17, 21, 15 and 9 microgram/dl) for the years 1986, 1987, 1991 and 1992 respectively. 3. It is recommended that children in the U.K. being investigated for anaemia, pica, recurrent abdominal pain or a high-risk environment should have blood lead values measured and that the action level for blood lead in children should be decreased from 1.19 micromol/l to 0.48 micromol/l (from 25 microgram/dl to 10 microgram/dl). 4. Guidance is offered to clinicians and other health professionals investigating excessive lead exposure.

Hormonal pattern of relapse in hyperthyroidism.

22 patients with Grave's disease were followed up for up to a year after antithyroid drug therapy was discontinued. Clinical assessment and serum T3, T4, and thyroid-stimulating-hormone (T.S.H.) estimations were done serially and simultaneously. Serum T3 or T4 concentrations may be elevated briefly in the first few weeks after antithyroid drugs are stopped, as a rebound effect not necessarily indicative of subsequent relapsf. Clinical relapse of hyperthyroidism with subsequent improvement on antithyroid drugs occurred in 13 patients. Of these 13, serum T3 concentrations became elevated before serum T4 concentrations in 5, thus predicting the subsequent development of clinical hyperthyroidism. In the remaining 8 patients who relapsed, serum T4 was elevated a month before the serum T3. Hyperthyroidism was diagnosed clinically after elevated serum T3 concentrations in 11 patients and at the same time in 2 patients. The mean period of "biochemical hyperthyroidism" in these 11 patients was 12 weeks, with a range of 1 to 56 weeks. During this period 9 of the 11 had minor clinical changes attributable to hyperthyroidism. It is concluded that serial estimations of serum T3 provide the most reliable method of monitoring relapse in hyperthyroidism.

Rat amylin-(8-37) enhances insulin action and alters lipid metabolism in normal and insulin-resistant rats.

To clarify roles of amylin, we investigated metabolic responses to rat amylin-(8-37), a specific amylin antagonist, in normal and insulin-resistant, human growth hormone (hGH)-infused rats. Fasting conscious rats were infused with saline or hGH, each with and without amylin-(8-37) (0.125 mumol/h), over 5.75 h. At 3.75 h, a hyperinsulinemic (100 mU/l) clamp with bolus 2-deoxy-D-[3H]glucose and [14C]glucose was started. hGH infusion led to prompt (2- to 3-fold) basal hyperamylinemia (P < 0.02) and hyperinsulinemia. Amylin-(8-37) reduced plasma insulin (P < 0.001) and enhanced several measures of whole body and muscle insulin sensitivity (P < 0.05) in both saline- and hGH-infused rats. Amylin-(8-37) corrected hGH-induced liver insulin resistance, increased basal plasma triglycerides and lowered plasma nonesterified fatty acids in both groups, and reduced muscle triglyceride and total long-chain acyl-CoA content in saline-treated rats (P < 0.05). In isolated soleus muscle, amylin-(8-37) blocked amylin-induced inhibition of glycogen synthesis but had no effect in the absence of amylin. Thus 1) hyperamylinemia accompanies insulin resistance induced by hGH infusion; 2) amylin-(8-37) increases whole body and muscle insulin sensitivity and consistently reduces basal insulin levels in normal and hGH-induced insulin resistant rats; and 3) amylin-(8-37) elicits a significant alteration of in vivo lipid metabolism. These findings support a role of amylin in modulating insulin action and suggest that this could be mediated by effects on lipid metabolism.

NEFA elevation during a hyperglycaemic clamp enhances insulin secretion.

Elevated non-esterified fatty acid (NEFA) levels may influence insulin secretion and contribute to the development of Type 2 DM. We investigated the effects of acute NEFA elevation in controls (n = 6) and subjects predisposed to Type 2 DM (n = 6) on basal insulin levels, and following glucose and arginine stimulation. Each subject had one study with a triglyceride (TG) plus heparin infusion (elevated NEFA levels) and another with normal saline. Twenty minutes after the TG or saline infusion began a glucose bolus was given and 10 min later a 90-min hyperglycaemic clamp (approximately 9 mmol l(-1)) was started. Intravenous arginine was given at 110 min. Elevated NEFA levels (approximately 4000 micromol l(-1)) did not enhance basal or first phase glucose stimulated insulin levels. During hyperglycaemia, NEFA elevation further increased insulin levels in both groups by 20-44% (p < 0.05) and C-peptide levels by 17-25% (p < 0.05). The post-arginine insulin levels during hyperglycaemia were increased by 45% in the Type 2 DM-risk group (p < 0.02). The glucose infusion rate maintaining matched hyperglycaemia was similar during NEFA elevation and for saline control for both groups. We conclude that acute elevation of NEFA levels enhances glucose and non-glucose-induced insulin secretion.