Nurses' attitudes, behaviours, and enablers of intravenous to oral switching (IVOS) of antibiotics: a mixed-methods survey of nursing staff in secondary care hospitals across the Midlands region of England.

BACKGROUND: Intravenous (IV) antibiotic use in secondary care in England is widespread. Timely appropriate intravenous to oral switch (IVOS) has the potential to deliver significant clinical and operational benefits. To date, antimicrobial stewardship (AMS) efforts around IVOS have not focused on the nursing staff who administer antibiotics, which represents a significant gap in AMS programmes. AIM: To determine the involvement of bedside nurses in acute trusts in the Midlands region of England in IVOS in their organizations and describe their views regarding how to improve IVOS. METHODS: An anonymous self-administered mixed-methods online survey was developed and distributed to nursing staff in acute trusts via antimicrobial stewardship networks between March and May 2023. Quantitative data was analysed to describe participant demographics and behaviours, whereas barriers and enablers to IVOS were explored through thematic content analysis of responses to open-ended questions. FINDINGS: A total of 545 nursing staff responded to the survey. The majority (65.3%) routinely suggested IVOS to clinicians, despite only 50.6% being aware of local IVOS policies. One-third (34.7%) did not suggest IVOS, relying on doctors, believing their patients needed IV treatment, or lacked knowledge and skills to request IVOS. Content analysis of suggestions for improving the rate of IVOS proposed three major themes (People, Process, System) and identified that education and training, improved confidence and interprofessional relationships, and prompts were important drivers. CONCLUSION: Nursing staff suggest IVOS to other clinicians, but more education and resources are needed to enable and empower them in this role.

Dendritic cell and T cell responses in children with food allergy.

BACKGROUND: Food allergy (FA) and eosinophilic oesophagitis (EE) are increasingly common clinical problems. Dendritic cells (DCs) are key regulators of the sensitization and effector phases of allergic immune responses, but their role in these diseases is largely unknown. OBJECTIVE: To evaluate for alterations in the phenotype and function of DCs in children with IgE-mediated milk allergy or EE compared with their non-affected siblings. METHODS: Plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) were prepared from peripheral blood of children with milk allergy (FA), EE, and non-affected siblings (CON). Purified pDCs and mDCs were cultured alone or with autologous CD4(+) lymphocytes. Cytokine levels in plasma, or culture supernatants following stimulation, were measured using multiplex array immunoassay. Cell-surface molecule expression was determined by flow cytometry. RESULTS: DCs from FA subjects produced greater levels of pro-inflammatory cytokines (IL-6, TNF-α), granulocyte macrophage-colony forming factor, and mDC-derived IL-10 compared with controls following allergen exposure. T(H) 2 but not T(H) 1 cytokines were spontaneously produced in DC-CD4(+) T cell co-cultures from children with FA and were not significantly increased after stimulation with milk extract, suggesting an ongoing activation in vivo. This hypothesis was further supported by evidence for elevated IL-5 and IL-13 protein in the plasma of children with both FA and EE. The only significant DC phenotypic differences were: (1) reduced levels of CD80 in EE subjects and (2) FcɛRI expression that correlated with serum IgE levels in both groups of subjects. CONCLUSION: This study suggests that DCs from children with FA and EE produce more pro-inflammatory cytokines, and that their CD4(+) T cells are spontaneously activated to produce T(H) 2 cytokines in the presence of FcɛRI-bearing DCs.

Harnessing the wisdom of crowds can improve guideline compliance of antibiotic prescribers and support antimicrobial stewardship.

Antibiotic overprescribing is a global challenge contributing to rising levels of antibiotic resistance and mortality. We test a novel approach to antibiotic stewardship. Capitalising on the concept of "wisdom of crowds", which states that a group's collective judgement often outperforms the average individual, we test whether pooling treatment durations recommended by different prescribers can improve antibiotic prescribing. Using international survey data from 787 expert antibiotic prescribers, we run computer simulations to test the performance of the wisdom of crowds by comparing three data aggregation rules across different clinical cases and group sizes. We also identify patterns of prescribing bias in recommendations about antibiotic treatment durations to quantify current levels of overprescribing. Our results suggest that pooling the treatment recommendations (using the median) could improve guideline compliance in groups of three or more prescribers. Implications for antibiotic stewardship and the general improvement of medical decision making are discussed. Clinical applicability is likely to be greatest in the context of hospital ward rounds and larger, multidisciplinary team meetings, where complex patient cases are discussed and existing guidelines provide limited guidance.

Cardiac function in mice overexpressing the beta-adrenergic receptor kinase or a beta ARK inhibitor.

Transgenic mice were created with cardiac-specific overexpression of the beta-adrenergic receptor kinase-1 (beta ARK1) or a beta ARK inhibitor. Animals overexpressing beta ARK1 demonstrated attenuation of isoproterenol-stimulated left ventricular contractility in vivo, dampening of myocardial adenylyl cyclase activity, and reduced functional coupling of beta-adrenergic receptors. Conversely, mice expressing the beta ARK inhibitor displayed enhanced cardiac contractility in vivo with or without isoproterenol. These animals demonstrate the important role of beta ARK in modulating in vivo myocardial function. Because increased amounts of beta ARK1 and diminished cardiac beta-adrenergic responsiveness characterize heart failure, these animals may provide experimental models to study the role of beta ARK in heart disease.

Enhanced myocardial relaxation in vivo in transgenic mice overexpressing the beta2-adrenergic receptor is associated with reduced phospholamban protein.

To assess the effect of targeted myocardial beta-adrenergic receptor (AR) stimulation on relaxation and phospholamban regulation, we studied the physiological and biochemical alterations associated with overexpression of the human beta2-AR gene in transgenic mice. These mice have an approximately 200-fold increase in beta-AR density and a 2-fold increase in basal adenylyl cyclase activity relative to negative littermate controls. Mice were catheterized with a high fidelity micromanometer and hemodynamic recordings were obtained in vivo. Overexpression of the beta2-AR altered parameters of relaxation. At baseline, LV dP/dt(min) and the time constant of LV pressure isovolumic decay (Tau) in the transgenic mice were significantly shorter compared with controls, indicating markedly enhanced myocardial relaxation. Isoproterenol stimulation resulted in shortening of relaxation velocity in control mice but not in the transgenic mice, indicating maximal relaxation in these animals. Immunoblotting analysis revealed a selective decrease in the amount of phospholamban protein, without a significant change in the content for either sarcoplasmic reticulum Ca2+ ATPase or calsequestrin, in the transgenic hearts compared with controls. This study indicates that myocardial relaxation is both markedly enhanced and maximal in these mice and that conditions associated with chronic beta-AR stimulation can result in a selective reduction of phospholamban protein.

Determination of mean valproic acid serum level by assay of a single pooled sample.

Determinations of single serum drug concentrations are useful in monitoring drug therapy. A mean serum level would supply more information but is expensive and laborious because of the multiple blood samples and assays, calculation of area under the curve (AUC) by the trapezoidal rule, and division of the AUC by the time interval during which the samples were drawn. A method was devised that pools aliquots from individual serum samples taken during the testing period to form on composite sample. A single assay of this sample provides the mean serum level of the testing period. The method was successfully tested with amaranth and then applied to valproic acid serum levels. AUC and mean serum levels were determined by the standard procedure of assays of multiple samples and the trapezoidal rule. Mean serum level was also determined by the pooled sample technique. The correlation coefficient for the comparison of the mean serum levels determined by the two techniques is 0.907 (p less than 0.001). There was no difference between the estimates of the mean serum levels by Student's paired t test (t = 0.693, p greater than 0.2). The good correlation and lack of difference between the conventional method and the pooled sample method indicates that the method is valid.

Effect of the acetylator phenotype on amrinone pharmacokinetics.

Ten healthy male subjects were phenotyped with isoniazid for their acetylator status and then received intravenous amrinone at a dose of 75 mg during a period of 10 minutes. Blood samples were drawn at specified times during a 24-hour period after dosing. Plasma concentrations of amrinone were determined by a specific HPLC method. The plasma concentration data were fitted to a biexponential model by nonlinear regression. The mean apparent first-order elimination t1/2 for amrinone in the slow acetylators was 4.4 hours, whereas it was 2.0 hours in the fast acetylators (P less than 0.05). There was little difference in the volume of distribution at steady state. Clearance was lower in the slow acetylators, 16.6 L/hr, than in the fast acetylators, 37.2 L/hr (P less than 0.05). The AUC was higher for the slow acetylators, 4.96 micrograms X hr X ml-1, than for the fast acetylators, 2.20 micrograms X hr X ml-1 (P less than 0.01). Concentrations of amrinone and its N-acetyl metabolite in the urine from each volunteer were determined. The ratio of N-acetylamrinone to amrinone was calculated and, as expected, the fast acetylators had a higher ratio than did the slow acetylators (P less than 0.01).

Frequency of hospitalization after exposure to known drug-drug interactions in a Medicaid population.

A matched-pair case-control analysis of Medicaid claims was performed to determine the risks of hospitalization associated with drug-drug interactions. Patients were hospitalized and controls were not. They were randomly matched based on contemporaneous eligibility for Medicaid benefits. Odds ratios for hospitalization in patients exposed to known drug-drug interactions were compared with those in patients exposed to one of the interacting agents. When confidence intervals did not overlap, the odds ratio was considered to be significantly increased. Odds ratios were significantly increased for many interacting drug pairs, and were associated with commonly recognized interactions as well as less widely recognized ones. Cimetidine interactions achieved significance only with theophylline. In the Medicaid population, exposure to a number of drug-drug interactions was associated with a significantly increased risk of hospitalization.

Cholesterol and glycemic effects of Niaspan in patients with type 2 diabetes.

STUDY OBJECTIVE: To determine the effect of Niaspan--a niacin preparation with both immediate- and extended-release characteristics--on lipid and glycemic control in patients with type 2 diabetes. DESIGN: Retrospective study SETTING: Private-practice endocrinology group. PATIENTS: Thirty-two patients (mean age 60 yrs; 72% men) with type 2 diabetes identified by a computerized text search. INTERVENTION: Patients received Niaspan 1000, 1500, or 2000 mg/day (median daily dosage 1000 mg). MEASUREMENTS AND MAIN RESULTS: Total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, hemoglobin A1c, and transaminase levels were compared for each patient before and 6 months after initiation of Niaspan. Niaspan therapy was associated with a significant 34% increase in HDL (p=0.033), a significant 36% reduction of triglycerides (p=0.049), and no significant change in LDL (p=0.236) or total cholesterol (p=0.122). Mean hemoglobin A1c levels significantly decreased from baseline by 0.5 +/- 0.3% (p=0.032), even though dosages and treatment with antidiabetic agents remained constant. There were no significant changes in transaminase levels. Seven patients (21.9%) discontinued Niaspan; one of them experienced an increase in blood glucose while receiving the agent. CONCLUSION: For most patients with type 2 diabetes, Niaspan is a safe and effective therapy for dyslipidemia and does not exacerbate glycemic control.

Home care pharmacy: extending clinical pharmacy services beyond infusion therapy.

A clinical pharmacy program was developed at an established home health care (HHC) agency to demonstrate the need for clinical pharmacy services in the HHC population and to explore opportunities for providing pharmaceutical care beyond infusion-related therapies. Initial experiences of this pilot project are described. Patients were found to be primarily elderly (mean age, 70 years) and to use a substantial number of medications. While only 11% of patients referred to the agency required infusion therapy, multiple opportunities for pharmacist involvement in patient care were identified and a variety of projects were undertaken. A drug information service was developed, a retrospective evaluation of patients with congestive heart failure led to an interventional study, a cisapride intervention was implemented, home vancomycin monitoring was assessed, pharmaceutical care services were provided to patients enrolled in a long-term home care program, a pain management initiative was begun, adverse drug reactions were identified and reported, and pharmacists participated in agency policy development. Preliminary data suggest that pharmacist involvement positively affected patient care. Drug information was provided on 232 occasions. Cisapride was discontinued in five patients with contraindications to the agent. Comprehensive pharmacotherapy assessments were performed on 29 long-term-care patients, generating 129 therapy recommendations of which 33% were accepted. Pharmacists working with a home care agency identified numerous opportunities for improving patient care. Many of the patients receiving home care services were elderly, took a substantial number of medications, and were at risk for drug-related problems and suboptimal therapy.

The management of bleeding in early pregnancy.

Ultrasound scan findings were analysed for 187 women referred to an emergency gynaecological scanning clinic during a seven month period, with bleeding in early pregnancy. One sixth of the women were not pregnant, one third had non-viable pregnancies and one half had viable pregnancies; 9% of this latter group subsequently miscarried. For the majority of women referred to the clinic, bed rest would have been inappropriate. In this study the value of bed rest and hospitalisation was considered uncertain for women with viable singleton pregnancies of 7-14 weeks gestation and bleeding in the previous 24 hours. Only 23 women with otherwise uncomplicated pregnancies met these criteria and consented to recruitment to a randomized controlled trial: three subsequently miscarried. Emergency scanning as a routine part of the gynaecological service is recommended, thus confining bed rest to those women with viable pregnancies. Reliable evaluation of bed rest and hospitalisation for such women will require a multicentre study.

Neural tube defects--prenatal diagnosis and management.

Neural tube defects rank second to congenital heart disease as a major cause of congenital malformation. Recent developments in ultrasound have improved prenatal diagnosis. Due to anomaly scans at 18 weeks gestation and the availability of a genetic clinic, prenatal diagnosis of neural tube defects at the Royal Maternity Hospital was 91.2% during 1987-1989. However, only 50% of parents accept termination of pregnancy and it is questionable if prenatal diagnosis is of benefit to those who wish to continue with the pregnancy. Parents may accept the situation better at birth, having had time to come to terms with it, helped with support from the obstetrician, clinical geneticist, paediatrician, genetic nurse and social worker. For some affected fetuses who have better muscle function and leg movement at term it appears from the literature that the outcome may be improved by caesarean section delivery. In Ireland fetuses with neural tube defects will continue to be delivered, as termination is unacceptable to many, but despite this there may be a positive benefit from prenatal diagnosis of neural tube defects. Prospective randomised controlled trials are needed to confirm benefit from delivery by caesarean section for fetuses with a good prognosis. As a result of prenatal diagnosis of a neural tube lesion the fetus should enjoy benefit in terms of physical morbidity, and the parents should benefit in terms of psychological morbidity.

A prospective evaluation of cimetidine drug use.

A drug utilization evaluation (DUE) of cimetidine surveyed use, dose, route of administration, indications, and safety in five New York hospitals. Drug use and patient information were recorded on cimetidine data collection forms; data on indications were noted on physician response forms. In addition to FDA-approved indications, cimetidine was frequently used for non-approved indications substantiated by the H2-antagonist literature. Prophylaxis accounted for 42.5% of total use, followed by nonulcer (25.5%), ulcer (18.8%), and other indications (13.1%). Appropriateness of dosage could not be determined in 42 (16.1%) patients with insufficient creatinine clearance data. One hundred and thirty patients (49.8%) whose renal function could be estimated were within dosage guidelines; 89 (34.1%) were above or below dosage recommendations. The incidence of adverse effects was low (3.83%), although many patients were "at risk" of untoward events or drug-drug interactions.

The NIF x-ray spectrometer calibration campaign at Omega.

The calibration campaign of the National Ignition Facility X-ray Spectrometer (NXS) was carried out at the Omega laser facility. Spherically symmetric, laser-driven, millimeter-scale x-ray sources of K-shell and L-shell emission from various mid-Z elements were designed for the 2-18 keV energy range of the NXS. The absolute spectral brightness was measured by two calibrated spectrometers. We compare the measured performance of the target design to radiation hydrodynamics simulations.

Health care data and the MHA.

One area experiencing perhaps more change than any other at the MHA is data management. This article places these changes in perspective and outlines the current agenda for data management initiatives at the association.

Incidence and cost of hospital admissions secondary to drug interactions involving theophylline.

OBJECTIVE: To determine the incidence and cost of hospital admissions for theophylline toxicity, which occurred as a result of the concurrent use of one of the following medications: cimetidine, erythromycin, or ciprofloxacin. DESIGN: Retrospective chart review (18 months, between June 1989 and November 1990). SETTING: A Department of Veterans Affairs Medical Center. PARTICIPANTS: All patients who were receiving theophylline chronically (913 patients) and also had a prescription for cimetidine (124 patients with 140 treatment courses), erythromycin (66 patients with 93 treatment courses), or ciprofloxacin (39 patients with 59 treatment courses) dispensed. INTERVENTIONS: Each patient's medical record was reviewed to identify hospital admissions within 30 days following the dispensing of the interacting drug. MAIN OUTCOME MEASURES: Admissions were considered to be related to theophylline toxicity if appropriate signs and symptoms were present and the theophylline concentration was above 20 micrograms/mL or had increased significantly from the concentration obtained prior to introduction of the interacting drug. RESULTS: One patient who received cimetidine and one who received ciprofloxacin were admitted for theophylline toxicity (2 of 292 potential interactions, 0.81 percent). Admissions were for 16 and 13 days, respectively, and total costs for the two admissions were $12,864.22 or $44.00, respectively, per potential interaction. The entire admission was not for theophylline toxicity; it appeared that iatrogenic factors contributed to the duration. CONCLUSIONS: The incidence of hospital admissions secondary to theophylline drug interactions with cimetidine, ciprofloxacin, or erythromycin is low, but the admissions represent considerable expense, even when distributed among all patients at risk for the interactions.

The effects of food on methotrexate absorption.

OBJECTIVE: To determine the effects of food on methotrexate (MTX) absorption in patients receiving MTX for the treatment of rheumatoid arthritis (RA). METHODS: Standard pharmacokinetic variables were determined in patients with RA after their usual maintenance dose of MTX, under fasting conditions and after they ate a standard breakfast. RESULTS: No significant differences in area under the serum concentration versus time curve, maximal MTX concentration after dosing (Cmax), time to Cmax), bioavailability, urinary MTX, renal clearance of MTX, or creatinine clearance were observed between the 2 dosing conditions. CONCLUSION: We observed no significant effect of food on MTX absorption or bioavailability. Patients may consume MTX without regard to meals.