Qualitative analysis of healthcare provider perspectives to evaluating beta-lactam allergies.

BACKGROUND: There is a lack of understanding of the barriers reported by healthcare providers when evaluating beta-lactam allergies, but knowledge of these barriers is required for practical and effective implementation interventions. METHODS: Twenty-five healthcare providers, consisting of physicians, nurses and pharmacists practicing in the areas of intensive care, emergency medicine, infectious disease and general hospital practice, were interviewed between September 2021 and July 2023. Twenty-three of these providers were practising in the USA. A semi-structured interview guide grounded in the Theoretical Domain Framework was used for the interviews. Deductive and inductive analysis was performed on the interview transcripts, and translated into intervention recommendations using the Behaviour Change Wheel. RESULTS: Widely held beliefs included a lack of clear policy for the evaluation of allergies, confusing or missing documentation of allergy information, confidence in their own and their colleagues' ability to evaluate allergies when information is available, and pharmacists as the provider most equipped to evaluate beta-lactam allergies. CONCLUSIONS: Health systems should adopt and disseminate policies for the evaluation of beta-lactam allergies, and promote the use of pharmacists in the evaluation of drug allergies when possible. Allergy sections of electronic health records should be reworked to encourage unambiguous documentation of allergy reactions and support using previously tolerated beta-lactam antibiotics.

The behavior of dairy cattle in late gestation: Effects of parity and dystocia.

The aim of this study was to objectively assess, using an automated behavioral monitoring system, any behavioral differences between primiparous and multiparous cows before calving, and to quantify any behavioral differences between assisted (dystocic) and unassisted (eutocic) calvings. Data were collected from 32 multiparous and 12 primiparous Holstein dairy cattle to describe normal calving behavior and parity differences. To quantify behavior related to calving difficulty, the data from 14 animals that had dystocia at calving were matched to cows that had an eutocic calving based on parity, locomotion score, calf breed, calf sex, month, and year of calving. An IceQube (IceRobotics Ltd., South Queensferry, United Kingdom) was fitted to the right hind leg of cows 4 wk before their expected calving date. Data for lying time, standing time, number of steps, motion index (total motion), and the total number of standing and lying bouts (postural transitions) were automatically collected and summed into 15-min blocks. Behavioral variables were summarized into 2-h periods and 24-h periods before analyses. Mixed-effect models were used to analyze cow behavior in the last 4 d before calving (d -4 to -1), and on the day of calving. In the 4 d before calving, compared with multiparous cows, primiparous cows lay down an average 2.8 h/d less, had 9.1 more postural transitions/d (37.7 ± 1.2 vs. 27.6 ± 0.7), walked 172 more steps/d, and had a higher motion index (2,673.2 vs. 1,981.5 units/d). There was an effect of 2-h period on all behavioral variables on the day of calving. No indicator of calving difficulty was found on the day of calving, nor the days leading up to calving. These findings suggest that parity should be considered when predicting the day of calving, and changes in cow behavior on the day of calving could be used to identify calving cows, and to predict the time of calving.

Implementing Genomic Clinical Decision Support for Drug-Based Precision Medicine.

The explosive growth of patient-specific genomic information relevant to drug therapy will continue to be a defining characteristic of biomedical research. To implement drug-based personalized medicine (PM) for patients, clinicians need actionable information incorporated into electronic health records (EHRs). New clinical decision support (CDS) methods and informatics infrastructure are required in order to comprehensively integrate, interpret, deliver, and apply the full range of genomic data for each patient.

Accuracy of an automated knowledge base for identifying drug adverse reactions.

INTRODUCTION: Drug safety researchers seek to know the degree of certainty with which a particular drug is associated with an adverse drug reaction. There are different sources of information used in pharmacovigilance to identify, evaluate, and disseminate medical product safety evidence including spontaneous reports, published peer-reviewed literature, and product labels. Automated data processing and classification using these evidence sources can greatly reduce the manual curation currently required to develop reference sets of positive and negative controls (i.e. drugs that cause adverse drug events and those that do not) to be used in drug safety research. METHODS: In this paper we explore a method for automatically aggregating disparate sources of information together into a single repository, developing a predictive model to classify drug-adverse event relationships, and applying those predictions to a real world problem of identifying negative controls for statistical method calibration. RESULTS: Our results showed high predictive accuracy for the models combining all available evidence, with an area under the receiver-operator curve of ⩾0.92 when tested on three manually generated lists of drugs and conditions that are known to either have or not have an association with an adverse drug event. CONCLUSIONS: Results from a pilot implementation of the method suggests that it is feasible to develop a scalable alternative to the time-and-resource-intensive, manual curation exercise previously applied to develop reference sets of positive and negative controls to be used in drug safety research.

A survey of nursing home physicians to determine laboratory monitoring adverse drug event alert preferences.

OBJECTIVE: We conducted a survey of nursing home physicians to learn about (1) the laboratory value thresholds that clinical event monitors should use to generate alerts about potential adverse drug events (ADEs); (2) the specific information to be included in the alerts; and (3) the communication modality that should be used for communicating them. METHODS: Nursing home physician attendees of the 2010 Conference of AMDA: The Society for Post-Acute and Long-Term Care Medicine. RESULTS: A total of 800 surveys were distributed; 565 completed surveys were returned and seven surveys were excluded due to inability to verify that the respondents were physicians (a 70% net valid response rate). Alerting threshold preferences were identified for eight laboratory tests. For example, the majority of respondents selected thresholds of ≥5.5 mEq/L for hyperkalemia (63%) and ≤3.5 without symptoms for hypokalemia (54%). The majority of surveyed physicians thought alerts should include the complete active medication list, current vital signs, previous value of the triggering lab, medication change in the past 30 days, and medication allergies. Most surveyed physicians felt the best way to communicate an ADE alert was by direct phone/voice communication (64%), followed by email to a mobile device (59%). CONCLUSIONS: This survey of nursing home physicians suggests that the majority prefer alerting thresholds that would generally lead to fewer alerts than if widely accepted standardized laboratory ranges were used. It also suggests a subset of information items to include in alerts, and the physicians' preferred communication modalities. This information might improve the acceptance of clinical event monitoring systems to detect ADEs in the nursing home setting.

Autism-specific maternal autoantibodies recognize critical proteins in developing brain.

Autism spectrum disorders (ASDs) are neurodevelopmental in origin, affecting an estimated 1 in 88 children in the United States. We previously described ASD-specific maternal autoantibodies that recognize fetal brain antigens. Herein, we demonstrate that lactate dehydrogenase A and B (LDH), cypin, stress-induced phosphoprotein 1 (STIP1), collapsin response mediator proteins 1 and 2 (CRMP1, CRMP2) and Y-box-binding protein to comprise the seven primary antigens of maternal autoantibody-related (MAR) autism. Exclusive reactivity to specific antigen combinations was noted in 23% of mothers of ASD children and only 1% of controls. ASD children from mothers with specific reactivity to LDH, STIP1 and CRMP1 and/or cypin (7% vs 0% in controls; P<0.0002; odds ratios of 24.2 (95% confidence interval: 1.45-405)) had elevated stereotypical behaviors compared with ASD children from mothers lacking these antibodies. We describe the first panel of clinically significant biomarkers with over 99% specificity for autism risk thereby advancing our understanding of the etiologic mechanisms and therapeutic possibilities for MAR autism.

Bacillus thuringiensis israelensis (Bti) for the control of dengue vectors: systematic literature review.

OBJECTIVE: To systematically review the literature on the effectiveness of Bacillus thuringiensis israelensis (Bti), when used as a single agent in the field, for the control of dengue vectors. METHOD: Systematic literature search of the published and grey literature was carried out using the following databases: MEDLINE, EMBASE, Global Health, Web of Science, the Cochrane Library, WHOLIS, ELDIS, the New York Academy of Medicine Gray Literature Report, Africa-Wide and Google. All results were screened for duplicates and assessed for eligibility. Relevant data were extracted, and a quality assessment was conducted using the CONSORT 2010 checklist. RESULTS: Fourteen studies satisfied the eligibility criteria, incorporating a wide range of interventions and outcome measures. Six studies were classified as effectiveness studies, and the remaining eight examined the efficacy of Bti in more controlled settings. Twelve (all eight efficacy studies and 4 of 6 effectiveness studies) reported reductions in entomological indices with an average duration of control of 2-4 weeks. The two effectiveness studies that did not report significant entomological reductions were both cluster-randomised study designs that utilised basic interventions such as environmental management or general education on environment control practices in their respective control groups. Only one study described a reduction in entomological indices together with epidemiological data, reporting one dengue case in the treated area compared to 15 dengue cases in the untreated area during the observed study period. CONCLUSION: While Bti can be effective in reducing the number of immature Aedes in treated containers in the short term, there is very limited evidence that dengue morbidity can be reduced through the use of Bti alone. There is currently insufficient evidence to recommend the use of Bti as a single agent for the long-term control of dengue vectors and prevention of dengue fever. Further studies examining the role of Bti in combination with other strategies to control dengue vectors are warranted.

Phaeohyphomycosis due to Alternaria species in transplant recipients.

Alternaria species are members of a heterogeneous group of dematiaceous fungi that rarely cause opportunistic infections in transplant recipients. During a 20-year period from 1989 to 2008, 8 solid organ transplant recipients (63% males; median age, 48 years) developed Alternaria species infections at the Mayo Clinic. All patients were highly immunocompromised as evidenced by their receipt of multiple transplants, treatment of acute and chronic allograft rejection, and occurrence of other opportunistic infections. All patients presented with non-tender erythematous or violaceous skin papules, nodules, or pustules in exposed areas of the extremities. No case of visceral dissemination was observed. Itraconazole was the most common drug used for treatment, although voriconazole, posaconazole, and caspofungin could potentially be useful based on our limited clinical data and in vitro antifungal susceptibility testing. One patient was treated with voriconazole, while another patient who was refractory to itraconazole had rapid resolution of lesions after the addition of caspofungin. Attempts at antifungal therapy alone were unsuccessful; all patients eventually required surgical excision of lesions. In conclusion, Alternaria species are rare but increasingly recognized opportunistic infections among highly immunocompromised transplant recipients. Wide excisional surgery combined with prolonged systemic antifungal therapy and reduction in immunosuppressive regimens provided the best chance of cure. Although itraconazole remains the most common drug for treatment, this case series highlights the potential clinical utility of caspofungin, voriconazole, and posaconazole as alternative regimens.

Potential for estimation of body condition scores in dairy cattle from digital images.

Body condition scoring, an indirect measure of the level of subcutaneous fat in dairy cattle, has been widely adopted for research and field assessment or for management purposes on farms. The feasibility of utilizing digital images to determine body condition score (BCS) was assessed for lactating dairy cows at the Scottish Agricultural College Crichton Royal Farm. Two measures of BCS were obtained by using the primary systems utilized in the United Kingdom (UK-BCS) and the United States (USBCS). Means were 2.12 (+/-0.35) and 2.89 (+/-0.40), modes were 2.25 and 2.75, and ranges were 1.0 to 3.5 and 1.5 to 4.5 for the UKBCS (n = 2,346) and USBCS (n = 2,571), respectively. Up to 23 anatomical points were manually identified on images captured automatically as cows passed through a weigh station. Points around the hooks were easier to identify on images than points around pins and the tailhead. All identifiable points were used to define and formulate measures describing the cow's contour. For both BCS systems, hook angle, posterior hook angle, and tailhead depression were significant predictors of BCS. When the full data set testing only the angles around the hooks was used, 100% of predicted BCS were within 0.50 points of actual USBCS and 92.79% were within 0.25 points; and 99.87% of predicted BCS were within 0.50 points of actual UKBCS and 89.95% were within 0.25 points. In a reduced data set considering only observations in which the tailhead depression angle was available, adding the tailhead depression to models did not improve model predictions. The relationships of the calculated angles with USBCS were stronger than those with UKBCS. This research demonstrates the potential for using digital images for assessing BCS. Future efforts should explore ways to automate this process by using a larger number of animals to predict scores accurately for cows across all levels of body condition.

Three dimensional reconstruction of a human breast carcinoma using routine laboratory equipment and immunohistochemistry.

AIMS: To establish a three dimensional reconstruction of an invasive breast carcinoma using basic laboratory equipment to evaluate and characterise the spatial arrangement of the parenchymal cells of the breast. METHODS: One hundred and twenty eight sequential 4 microm sections (20 microm apart) of the tumour were stained immunohistochemically with an epithelial specific marker (AE1/AE3) or tumour specific marker (c-erbB-2) to reconstruct two different three dimensional images of the normal and malignant parenchymal cells. Sections were digitally imaged using a microscope, scanner, and digital camera linked to a conventional personal computer. Accurate alignment of the digitalised images was carried out using a semiautomatic graphical method of manual interaction, using the cross correlation coefficient as a goodness of fit measure, and an automatic search algorithm using the Fibonacci search algorithm for automatic alignment. The volume was reconstructed using maximum, minimum point projection and "back to front" opacity blending. RESULTS: The quality of the reconstructed images was distinct and perfect, providing a comprehensive and explicit view of the normal and malignant parenchymal tissues of the breast that is not possible by viewing two dimensional histological sections. Specifically, this approach showed the spatial arrangement of the tumour cells and their relation to the surrounding tissues at a high resolution. CONCLUSION: This simple and reproducible approach enables the spread and infiltration of invasive carcinoma to be understood and could also be used to analyse the spatial relation between atypical hyperplastic and malignant in situ lesions of the breast.

Hypothermic machine perfusion of liver grafts for transplantation: technical development in human discard and miniature swine models.

INTRODUCTION: Cold storage (CS) is the standard preservation technique for liver transplantation (LTx). Hypothermic machine perfusion (HMP) is an alternative preservation technique that provides a continuous supply of substrates and removes waste products. HMP improves early graft function in kidney transplantation, especially for marginal organs: To our knowledge there have been no reports HMP in human LTx. The aim of this study was to develop a reproducible technique for liver HMP prior to initiating a clinical trial. METHODS: For the discard protocol, between May 2001 and March 2002, 10 nontransplantable human livers were obtained. We designed a model of atraumatic, centrifugal HMP of the portal vein (PV) and hepatic artery (HA) via donor vascular conduit. Livers were perfused at 3 degrees C to 5 degrees C with Vasosol solution for 5 to 10 hours using a modified Medtronic Portable Bypass System. Perfusion variables (temp, flow, pressure) where recorded every 30 minutes. During the study, we also validated our techniques in an animal model. For the animal protocol; six swine were used as liver donors and randomized to 12 hours of CS in UW (n = 3) or 12 hours of HMP using Vasosol solution (n = 3). LTx was performed in six swine. Animals survived until postoperative day 5. RESULTS: For the discard protocol, mean HMP time was 6.7 +/- 1.8 hours. Target flow was 0.7 mL/g liver/min. PV and HA pressure ranged from 3 to 5 and 12 to 18 mm Hg, respectively. All grafts were maintained at 3 degrees C to 5 degrees C during HMP. For the animal protocol, all recipients had good liver function and survived to postoperative day 5. AST and TBili were similar between CS and HMP. CONCLUSIONS: Our method of liver HMP appears to be a safe and reliable method to preserve livers. A clinical trial is now underway to evaluate this technique in human LTx.

Reactivation of ocular toxoplasmosis in fellow unaffected eye.

PURPOSE: To report a case of reactivation of ocular toxoplasmosis in fellow unaffected eye. METHODS: Case report. RESULTS: A 15 year old girl, known to have right ocular toxoplasmosis previously, has presented with one week history of sudden left visual deterioration and pan uveitis. Her condition was improved on intensive steroid treatment. CONCLUSIONS: Reactivation of such lesion in fellow unaffected eye is quite rare. Various choices of treatment are available and there are also different techniques to treat. A review of treatment based on this pathology is briefly discussed.

In vivo myocardial protection from ischemia/reperfusion injury by the peroxisome proliferator-activated receptor-gamma agonist rosiglitazone.

BACKGROUND: Diabetes is associated with increased risk of mortality as a consequence of acute myocardial infarction. This study determined whether rosiglitazone (ROSI) could reduce myocardial infarction after ischemia/reperfusion injury. METHODS AND RESULTS: Male Lewis rats were anesthetized, and the left anterior descending coronary artery was ligated for 30 minutes. After reperfusion for 24 hours, the ischemic and infarct sizes were determined. ROSI at 1 and 3 mg/kg IV reduced infarct size by 30% and 37%, respectively (P<0.01 versus vehicle). Pretreatment with ROSI (3 mg. kg(-1). d(-1) PO) for 7 days also reduced infarct size by 24% (P<0.01). ROSI also improved ischemia/reperfusion-induced myocardial contractile dysfunction. Left ventricular systolic pressure and positive and negative maximal values of the first derivative of left ventricular pressure (dP/dt) were significantly improved in ROSI-treated rats. ROSI reduced the accumulation of neutrophils and macrophages in the ischemic heart by 40% and 43%, respectively (P<0.01). Ischemia/reperfusion induced upregulation of CD11b/CD18 and downregulation of L-selectin on neutrophils and monocytes; these effects were significantly attenuated in ROSI-treated animals. Likewise, intercellular adhesion molecule-1 expression in ischemic hearts was markedly diminished by ROSI, as was the ischemia/reperfusion-stimulated upregulation of monocyte chemoattractant protein-1. CONCLUSIONS: ROSI reduced myocardial infarction and improved contractile dysfunction caused by ischemia/reperfusion injury. The cardioprotective effect of ROSI was most likely due to inhibition of the inflammatory response.

Organisational governance structures in allied health services: a decade of change.

A ten year review of developments in the organisation and management of allied health services in Australian acute care public hospitals reveals a steady transformation away from a medically managed universal model towards more complex and contested models of governance. This article revisits early observations about the reorganisation of allied health services and presents more recent research findings to guide managerial decision-making about restructuring the diverse disciplines that constitute allied health. A new organisational model "integrated decentralization" is presented as an approach to managing allied health services which accommodates multiple stakeholder demands in the context of New Public Management (NPM) related reforms. The focus on the institutional level is complemented by examining developments in the profile and activity of allied health at the regional, state and national levels to present a more comprehensive picture of change over the decade of the 1990s.

Partial cambial mortality in high-elevation Pinus aristata (Pinaceae).

Partial cambial mortality is a growth form that is characteristic of Pinus aristata trees. To better elucidate their cambial death pattern, tree size and aspect of cambial death data were gathered from three Pinus aristata forests in central Colorado, USA. Stripping frequency tended to be higher for larger diameter classes. Partial cambial mortality exhibits significant directionality within each stand. Furthermore, cambial death was measured to be most frequent on the wind-exposed side of stripped trees in two of the three study sites and appeared to be at the third. Data presented here support the hypothesis that wind plays a role in the occurrence of partial cambial mortality in Pinus aristata. The mechanisms by which wind causes cambial mortality remain unclear.

Cloning, expression, and pharmacological characterization of a novel human histamine receptor.

Using a genomics-based reverse pharmacological approach for screening orphan G-protein coupled receptors, we have identified and cloned a novel high-affinity histamine receptor. This receptor, termed AXOR35, is most closely related to the H3 histamine receptor, sharing 37% protein sequence identity. A multiple responsive element/cyclic AMP-responsive element-luciferase reporter assay was used to identify histamine as a ligand for AXOR35. When transfected into human embryonic kidney 293 cells, the AXOR35 receptor showed a strong, dose-dependent calcium mobilization response to histamine and H3 receptor agonists including imetit and immepip. Radioligand binding confirmed that the AXOR35 receptor was a high-affinity histamine receptor. The pharmacology of the AXOR35 receptor was found to closely resemble that of the H3 receptor; the major difference was that (R)-alpha-methylhistamine was a low potency agonist of the AXOR35 receptor. Thioperamide is an antagonist at AXOR 35. Expression of AXOR35 mRNA in human tissues is highest in peripheral blood mononuclear cells and in tissues likely to contain high concentrations of blood cells, such as bone marrow and lung. In situ hybridization analysis of a wide survey of mouse tissues showed that mouse AXOR35 mRNA is selectively expressed in hippocampus. The identification and localization of this new histamine receptor will expand our understanding of the physiological and pathological roles of histamine and may provide additional opportunities for pharmacological modification of these actions.

Intervention assessment in an Indian health service pharmacy.

OBJECTIVE: To document and evaluate pharmacists' interventions in a setting that has complete and immediate access to patient information. DESIGN: Descriptive report evaluating self-reported interventions made by pharmacists during the conduct of routine dispensing activities. The data collection period was from February 15 to April 1, 1994. SETTING: Ambulatory care facility offering medical and dental care to high school residents, Native Americans, and Alaska Natives in Northwestern Oregon. MAIN OUTCOME MEASURES: Intervention rate per 100 new prescriptions dispensed. Each intervention was evaluated with regard to the information used to initiate it, when during the dispensing process it was initiated, and the intervention type. Outside evaluators determined the clinical significance of the interventions, including potential adverse health consequences, the likelihood of their occurrence, and the level of medical care that would have been required to treat the problem. RESULTS: Of 2,535 orders screened, 104 interventions (4.1%) were collected; 71% of these occurred during chart screening. Pharmacists most often used the medication order itself (60.6%) to detect prescribing problems, followed by other records in the patient's chart (29.8%). Outside evaluators identified 47.1% of the 104 interventions as clinically significant. The most common adverse health consequence prevented was inadequate control of the patient's condition. Outside evaluators also found that the most common level of corrective care that would have been needed if the intervention had not occurred, was a scheduled physician office visit (59.2%). CONCLUSION: This information suggests that pharmacists who have access to patient information may intervene at higher rates and that more of their interventions may be deemed clinically significant. However, larger, double-blinded, case-controlled studies are needed to definitively draw these conclusions.

Dependence of winter water relations of mature high-elevation Picea engelmannii and Abies lasiocarpa on summer climate.

Water relations of Engelmann spruce (Picea engelmannii Parry) and subalpine fir (Abies lasiocarpa (Hook.) Nutt.) trees growing at an elevation of 3230 m on Mt. Evans, Colorado, USA, were studied during the winters of 1995-1996 and 1996-1997. During both winters, current-year and 1-year-old shoots were collected weekly and their relative water contents (RWC) determined. Measured meteorological parameters were used in a conifer winter water relations model, WINWAT, to simulate changes in shoot RWC of P. engelmannii and A. lasiocarpa during the winter. The model failed to predict shoot RWCs in 1996-1997 when calibrated with 1995-1996 data. The cold early summer of 1995 inhibited xylem formation, which appears to have caused lower rates of water recharge to the needles during the 1995-1996 winter than during the 1996-1997 winter. We conclude that summer climate strongly affects winter water relations in these subalpine species, and that changes in both summer and winter climate must be considered when predicting future ranges of these species.