Using Clinical Narratives in Program and Curriculum Evaluation.

Background: Using personal experience stories as teaching tools, clinical narratives are an effective means for sharing the art of nursing practice and provide insight into nurses' critical thinking and clinical proficiency. Using clinical narratives to assess curriculum effectiveness provides important insights into changed practice and learning beyond the classroom. Aim: This article provides an example of using clinical narratives in the evaluation of the Department of Veterans Health Affairs Office of Nursing Services (ONS) Evidence Based Practice Curriculum (EBPC). Methods: As part of a larger mixed-method evaluation of the EBPC, clinical narrative methods were employed to describe one incident where participants (n=3) applied at least two of three evidence based practice components (best available evidence; clinical expertise; patient preference). Results: Examination of clinical narratives demonstrated successful application of key components of evidence based practice and an integration into individual nursing practice beyond data obtained from other evaluation methods. Conclusions: Incorporating rich clinical narratives into a rigorous mixed-method program evaluation protocol provides insights beyond information uptake, satisfaction, efficacy, or competency assessment scores.

Emergency biventricular assist device implantation in a patient with suspected COVID-19 disease.

Severe coronavirus disease 2019 (COVID-19) is a multisystem inflammatory disorder and knowledge and experience with severe acute respiratory failure in infected patients has grown considerably since reports of the first few cases. Little is known about the effect of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) virus on the heart, and it has been suggested that fulminant cardiac failure, with or without respiratory failure, may occur several weeks following infection. A young man presented after a recent viral illness. He was in severe cardiogenic shock and was implanted with an emergency biventricular assist device, which also incorporated an extracorporeal membrane oxygenator. He stabilised soon after and, despite an intracerebral haemorrhage which resolved and bleeding into the trachea following percutaneous tracheostomy, he survived to explant and was successfully stepped down to a rehabilitation unit on postoperative day 50. He tested positive for SARS-CoV-2 antibodies when the test became available on postoperative day 33. We envisage there will be many more such presentations of acute COVID-19-associated cardiogenic shock and we recommend clinicians consider this diagnosis when presented with an acutely unwell patient with an unclear diagnosis following a viral illness. These patients should be discussed as early as possible with a transplant/mechanical circulatory support team.

Second line options for hyperlipidemia management after cardiac transplantation.

Despite widespread statin therapy, 91% of cardiac transplant patients have hyperlipidemia within 5 years from cardiac transplantation. The implications of this are profound, particularly given that coronary allograft vasculopathy is a leading cause of death. Unfortunately the solution is not easy, with problems of toleration at higher statin doses and a lack of good quality evidence for second line agents. We review the literature and discuss some of the key issues transplant physicians are faced with when considering alternatives to statin therapy.

The pathophysiology of chronic graft failure in the cardiac transplant patient.

Following cardiac transplantation, many patients develop chronic deterioration of graft function, which may lead to a clinical syndrome similar to native chronic heart failure (CHF). This condition of chronic cardiac graft failure (CGF) may also share pathophysiological processes comparable with that of CHF. However, the unique environment following cardiac transplantation may also contribute with a variety of unique mechanisms, deserved of special attention. This review article discusses the complex pathophysiology of CGF after cardiac transplantation, an important yet neglected condition of transplant medicine.

BNP directly immunoregulates the innate immune system of cardiac transplant recipients in vitro.

BACKGROUND: The innate immune system plays an important role in cardiac allograft rejection. BNP has frequently been reported to elevate during acute cardiac rejection, yet the explanation behind this phenomenon is unclear. We hypothesized that BNP might interact with the innate immune system in cardiac transplant recipients and devised a series of in vitro culture experiments to explore this phenomena. METHODS: PBMCs were isolated from whole blood of (total n = 40) cardiac transplant recipients. Short (24h, n = 20) and long term (72h, n = 20) co-cultures of innate cells in the presence or absence of BNP were performed. BNP was added at two specific concentrations and compared to placebo control. Innate cells were immunophenotyped using flow cytometry. RESULTS: BNP dose dependently reduced the total number of monocytes, B cells and NK cells. Furthermore, BNP co-culture impaired NK cell cytotoxicity and adhesion of non-classical monocytes (via down-regulation of CD11c). DISCUSSION: BNP has an additional physiological role of moderating components of the innate immune system. Although speculative, this could be beneficial to cardiac transplant recipients as the innate immune system is involved in allograft rejection. Further investigation is required to elucidate the mechanism behind how BNP affects immune cells and whether the same effects are consistent with the adaptive immune system.

Potential immunologic effects of statins in cancer following transplantation.

3-hydroxy-3-methyglutaryl CoA reductase inhibitors (statins) are frequently used following organ transplantation and have well reported pleiotropic effects, including immunomodulation, which may be of benefit in preventing graft rejection. However, the immunomodulatory effects of statins on cell transformation and malignancy, combined with the immunologic processes and administration of immunosuppression are almost completely unknown. The administration of immunosuppression is well recognised as the main cause of cancer following transplantation, so the addition of an immunomodulatory agent should be associated with an increased incidence of cancer, as immune surveillance and response may be suppressed, allowing cellular transformation and proliferation combined with lack of recognition to occur. This hypothetical review attempts to delineate the mode of action of statins in terms of pro/anti-carcinogenic mechanisms, while considering graft rejection and the presence of immunosuppression.

HMG-CoA reductase inhibitors deplete circulating classical and non-classical monocytes following human heart transplantation.

BACKGROUND: Monocytes mediate immune responses following solid organ transplantation via cytokine secretion and differentiation to macrophage/dendritic cell lineages. To date, the pleiotropic immunomodulatory effect of statins on human monocytes following human heart transplantation has yet to be elucidated. This study was designed to assess the effects of statin administration on the monocyte repertoire. METHODS: 108 patients were recruited into the study. Clinical data were collected from patients' notes. Peripheral blood immunophenotype was determined via flow cytometry (using CD11c, CD14, CD16, CD49d, CD64, CD80 and CD195). RESULTS: There were fewer circulating classical (p=0.0001) and non-classical (p=0.0013) monocytes in patients treated with a statin. CD64 expression was down-regulated (p=0.011 and p=0.049) whereas CD49d expression was up-regulated (p=0.004 and p=0.022) on classical and non-classical monocytes in this group. Patients receiving Atorvastatin had fewer circulating classical monocytes (p=0.001) compared to patients administered Pravastatin. Patients receiving Pravastatin had fewer circulating non-classical monocytes (p=0.029) compared to patients administered Atorvastatin. DISCUSSION: Statin administration alters the circulating monocyte repertoire following heart transplantation, including population size, FcgammaRI and VLA-4 adhesion molecule expression. Furthermore, different statin treatments are associated with a selective depletion of macrophage or DC (re)generating monocytes.

Surgical aspects of cardiac resynchronisation therapy.

Despite significant advances in the pharmacological treatment of heart failure, rates of mortality and morbidity from the condition remain a concern. The introduction of cardiac resynchronisation therapy (CRT) has been a welcome addition to the treatment strategy of patients who display ventricular dyssynchrony. Several control studies have shown significant benefits from this intervention in particular improved mortality and reduction in symptom burden. In this short review, we focus on several concepts of CRT and discuss the implications of surgical implantation of the left ventricular (LV) lead as compared to the standard transvenous approach.

Mitochondrial inhibitors evoke catecholamine release from pheochromocytoma cells.

Quantal catecholamine secretion evoked from individual pheochromocytoma (PC12) cells by exposure to mitochondrial inhibitors and uncouplers was monitored in real time using amperometry. Cyanide (0.05-5 mM) caused a concentration-dependent increase in the frequency of amperometric events. This secretory response was abolished by removal of extracellular Ca(2+) and by the application of Cd(2+) (200 microM), a nonselective blocker of voltage-gated Ca(2+) channels. Secretion was also inhibited by ca. 75% following pretreatment of cells with omega-conotoxin GVIA to inhibit N-type Ca(2+) channels selectively. Secretion was also detected when cells were exposed to rotenone (10 microM), dinitrophenol (250 microM) and p-trifluoromethoxyphenyl hydrazone (1 microM) and, as for cyanide, these secretory responses were abolished by removal of extracellular Ca(2+) or application of 200 microM Cd(2+). These results indicate that, like hypoxia, mitochondrial inhibitors and uncouplers evoke catecholamine secretion from PC12 cells which is wholly dependent on Ca(2+) influx through voltage-gated Ca(2+) channels.

A non-invasive isotope dilution technique for quantifying hepatic blood flow using radiolabelled red blood cells.

Clinically significant changes in hepatic haemodynamics accompany the development of portal hypertension, hepatocellular carcinoma, liver metastases and liver cirrhoses, and after major liver resection. Hepatic blood flow parameters, such as hepatic arterial flow (HAF), hepatic portal flow (HPF), total hepatic blood flow (THBF) and hepatic perfusion index (HPI), are useful adjuncts to the diagnosis of liver pathology, the evaluation of disease progress and prognostication. Here, we describe a non-invasive method that combines the measurement of these parameters in a single study in real time. Red blood cells from eight pigs were labelled with 99Tc(m) using an in-vitro method and re-injected into the pigs. Data acquisition over the heart, lungs, liver and kidneys was started immediately and a blood sample was obtained 15 min post-injection. Hepatic arterial flow was determined from the ratio of the maximum gradients between the integrated time-activity curve of the left ventricle and the first-pass time-activity curve of the liver before the peak of the kidneys time-activity curve. The hepatic perfusion index was determined by comparing the slope of the liver time-activity curve before and after the kidney peak. Hepatic portal flow was determined from the hepatic arterial flow and the hepatic perfusion index, and total hepatic blood flow was determined as the sum of arterial and portal flow. The results were compared against those obtained from a clearance method using 99Tc(m)-DISIDA. The average hepatic perfusion index was 0.38, and the average hepatic arterial flow and hepatic portal flow were 168.3 +/- 52.9 and 274.6 +/- 60.1 ml x min(-1) respectively. The average total hepatic blood flow was 442.8 +/- 53.5 ml x min(-1), while the total hepatic flow determined by 99Tc(m)-DISIDA clearance was 419.7 +/- 62.6 ml x min(-1). No significant difference in total hepatic blood flow was found between the two methods. The results of this study show that it is possible to obtain all hepatic haemodynamics data in a single study using a non-invasive method.

Nuclear pharmacy, Part I: Emergence of the specialty of nuclear pharmacy.

OBJECTIVE: Nuclear pharmacy was the first formally recognized area in pharmacy designated as a specialty practice. The events leading to nuclear pharmacy specialty recognition are described in this article. After reading this article the nuclear medicine technologist or nuclear pharmacist should be able to: (a) describe the status of nuclear pharmacy before recognition as a specialty practice; (b) describe the events that stimulated pharmacists to organize a professional unit to meet the needs of nuclear pharmacists; and (c) identify the steps by which nuclear pharmacists become board certified in nuclear pharmacy.

The impact of eating disorders on family relationships.

Having a child in crisis with an eating disorder impacts the entire family as well as the child. The family's emotional involvement, as well as such changes in routine involving appointments with thera-pists and support groups, all cause disruption to normal patterns and to family relationships. The purpose of this study was to investigate the challenges that parents face and the changes that occur, particularly in relationships, when a child is diagnosed with an eating disorder, and how parents cope with these changes. A detailed questionnaire using both quantitative and qualitative questions was completed by 52 mothers in Ontario. The findings indicated that there is a significant impact on relationships correlated with age of child, personal leisure, and level of confusion in the family. The findings also showed contrasts in the way families cope with having a child in crisis, either very negatively or very positively. The qualitative anecdotes describe the tremendous strains and changes in patterns within families particularly during the initial period of diagnosis. The parents provide helpful recommendations for researchers, practitioners, and service providers.

Evidence of a glycemic threshold for the development of cataracts in diabetic rats.

PURPOSE: This study was aimed to establish a possible correlation between the levels of plasma glucose and degree of lens opacification. Levels of glycation- and glycoxidation-products in different lens protein fractions were also estimated with an aim to determine the involvement of these products in lens opacification. METHODS: A wide range of hyperglycemia was induced by injecting different doses of streptozotocin to 1 month old rats and lenses were examined on the 75th, 90th and 150th day post-injection. Lens opacification was measured by Scheimpflug imaging and densitometry. Levels of plasma glucose and glycated hemoglobin were measured after overnight fasting. On 90th day, levels of Amadori products in lens water soluble (WS) fraction were measured by affinity chromatography. Similarly, advanced glycation end products (AGEs) in lens WS, urea soluble (US) and alkali soluble (AS) fractions were measured immunochemically using a monoclonal antibody against the major glycoxidation product, carboxymethyl lysine (CML). RESULTS: Different dosages of streptozotocin injection resulted in a broad range of plasma glucose levels in the rats which were grouped into three groups on the basis of their plasma glucose levels: mildly diabetic (< 170 mg/dl plasma glucose), moderately diabetic (190-350 mg/dl) and severely diabetic (> 400 mg/dl). On the 75th, 90th and 150th day post-injection, only the moderately and severely diabetic rats developed cataracts whereas lenses of the mildly diabetic rats remained clear. As seen on 90th day, levels of glycated hemoglobin and Amadori products in lens WS fraction increased significantly in the moderately and severely diabetic groups whereas in the mildly diabetic rats these levels remained more or less same as in the control group. Levels of CML in WS fractions remained unchanged between control rats and different diabetic groups, while US fractions showed a decrease in CML in both the moderately and severely diabetic groups compared to the controls and the mildly diabetic group. Interestingly, AS fractions contained the highest level of CML; the moderately and severely diabetic groups showed about 2-fold higher levels than the controls and the mildly diabetic group. CONCLUSIONS: This study strongly supports the existence of plasma glycemic threshold above which incidence of diabetic cataract formation increases exponentially. This threshold level seems to be at approximately 180 mg/dl or 10 mM plasma glucose. Significant increase in the levels of glycation and glycoxidation products mainly in cataract lenses suggests that glycation and glycation-mediated oxidation play an important role in the development of diabetic cataracts.

Radionuclide studies of articular cartilage in the early diagnosis of arthritis in the rabbit.

The compound Se-75 bis[beta-(N,N,N-trimethylamino-)ethyl]selenide diiodide (Se-75 BISTAES) has been synthesized and its biodistribution in rabbits studied. A high uptake of radioactivity is found in the knee cartilage. Good scans of the knee are obtained by nuclear scintigraphy at 15 minutes after the injection of Se-75 BISTAES. The results of an equilibrium dialysis study show that Se-75 BISTAES binds to chondroitin sulfate and the binding is directly proportional to the chondroitin concentration. It appears that Se-75 BISTAES or its derivative should have potential as an articular imaging agent.

The effect of formulation on radioiodide thyroid uptake in the hyperthyroid cat.

This investigation was designed to compare in vitro dissolution profiles from sodium iodide capsules with radioiodide thyroid uptake in hyperthyroid cats using sodium iodide capsules prepared with a formulation exhibiting a complete release of radioiodide (I-123) in vitro and a formulation with an incomplete release of radioiodide. In vitro dissolution profiles for I-123 sodium iodide capsules with two different formulations were determined using the USP XXIII dissolution test. The two formulations studied in vitro were sodium phosphate dibasic powder with 1% magnesium stearate and calcium phosphate dibasic powder with 3% magnesium stearate. By 20 min after initiation of the dissolution test, over 95% of the I-123 was released from capsules of sodium phosphate dibasic powder. The capsules of calcium phosphate dibasic powder reached 75% at 65 min, with no further release occurring thereafter. There was a statistically significant difference in the dissolution profiles of the two formulations. The thyroid uptake of I-123 from capsules exhibiting complete release and incomplete release of radioiodide was determined in hyperthyroid cats. At 4 hr, the mean percentage thyroid uptake value for sodium phosphate dibasic powder with 1% magnesium stearate (complete release formulation) was 12.0% compared to 9.4% for calcium phosphate dibasic powder with 3% magnesium stearate (incomplete release formulation); at 24 hr, the values were 34.4% compared to 23.7%. The data suggest that the incomplete dissolution profile observed in vitro may correlate with a reduction in the bioavailability of the radioiodide in vivo. However, using the Wilcoxon signed rank test, statistically significant differences did not occur between the complete release formulation and incomplete release formulation at either 4 hr or 24 hr (p > .05). The results of the in vivo study with five hyperthyroid cats were not conclusive due to the variability in response between individual cats.

Influence of iodine-131 solution volume and storage time on in vitro dissolution.

OBJECTIVE: This investigation was conducted to determine the influence of 131I solution volume and storage time on the in vitro release of radioiodide from capsules. METHODS: In vitro dissolution profiles for 131I sodium iodide capsules compounded in a centralized nuclear pharmacy were determined using the USP XXIII Dissolution Test. Iodine-131 solution volumes of 0.05, 0.15 and 0.25 ml and storage times of 2, 5, 7 and 9 days were considered. RESULTS: By 80 min after initiation of the dissolution test, more than 95% of the 131I was released from capsules prepared with 0.15 and 0.25 ml of the 131I solution. The 0.05-ml capsules reached 95% at 55 min. Capsules prepared with 0.05 ml of solution and stored 2, 5, 7 or 9 days released over 95% of the radioactivity within 65 min. Capsules prepared with 0.25 ml of solution and stored for 2, 5, 7 or 9 days released over 95% of the 131I by 55 min after initiation of the dissolution test. CONCLUSION: Neither the different volume of radioactive sodium iodide solution used in the preparation of capsules nor the time of storage greatly influenced the release of 131I from the capsules. Based on dissolution profiles, it appears that the bioavailability of 131I would not be influenced by factors studied in this investigation.