Embedding electronic growth charts into clinical practice at a children's hospital.

Embedding electronic growth charts (EGCs) into clinical practice in a children's hospital. We employed initial implementation in the outpatient setting and subsequently extended this across inpatients with the growth chart following the child's records through both settings and significantly increasing growth data documentation.

Apixaban or Warfarin in Patients with an On-X Mechanical Aortic Valve.

BACKGROUND: Vitamin K antagonists are the only oral anticoagulants approved to prevent valve thrombosis and valve-related thromboembolism in patients with mechanical heart valves. Whether patients with an On-X mechanical aortic valve can be safely anticoagulated with apixaban is unknown. METHODS: Patients with an On-X aortic valve implanted at least 3 months before enrollment were randomly assigned to receive apixaban 5 mg twice daily or warfarin (target international normalized ratio 2.0 to 3.0). The primary efficacy end point was the composite of valve thrombosis or valve-related thromboembolism with coprimary analyses comparing apixaban with warfarin for noninferiority and comparing the apixaban event rate with an objective performance criterion (OPC). RESULTS: The trial was stopped after 863 participants were enrolled owing to an excess of thromboembolic events in the apixaban group. Most (94%) participants took aspirin. A total of 26 primary end-point events occurred, 20 (in 16 participants) in the apixaban group (4.2%/patient-year; 95% confidence interval [CI], 2.3 to 6.0) and 6 (in 6 participants) in the warfarin group (1.3%/patient-year; 95% CI, 0.3 to 2.3). The difference in primary end-point rates between the apixaban and warfarin groups was 2.9 (95% CI, 0.8 to 5.0); noninferiority and OPC success criteria were not met. Major bleeding rates were 3.6%/patient-year with apixaban and 4.5%/patient-year with warfarin. CONCLUSIONS: Apixaban did not demonstrate noninferiority to warfarin and is less effective than warfarin for the prevention of valve thrombosis or thromboembolism in patients with an On-X mechanical aortic valve. (Funded by Artivion; ClinicalTrials.gov number, NCT04142658.)

New life for old cellular pathology: a transformational approach to the upcycling of historic e-pathology records for contemporary clinical uses.

AIMS: Cellular pathology ('e-pathology') record sets are a rich data resource with which to populate the electronic patient record (EPR). Accessible reports, even decades old, can be of great value in contemporary clinical decision making and as a resource for longitudinal clinical research. The aim of this short paper is to describe a solution in a major UK University Hospital which gives immediate visibility and clinical utility to 30 years of e-pathology records METHODS: Over the past decade, we have created a timeline structured and iconographic data framework for the 'whole-of-life' visualisation of the entirety of an EPR. We have enhanced this interface with the sequential extraction of 373 342 e-pathology reports from legacy Ferranti (1990-1997) and Masterlab (1997-2004) files. They have been uploaded into our SQL file servers, following appropriate data quality and patient identity reconciliation checks. RESULTS: We have restored a large repository of previously inaccessible e-pathology records to clinical use and to immediacy of access as a foundation element of our timeline structured EPR. This process has also allowed us to populate and validate an EPR-integral breast cancer data system of 20 000 cases with e-pathology records dating back to 1990. CONCLUSIONS: The revitalisation of old e-pathology reports into a timeline structured EPR creates preserves and upcycles the investment in pathology reporting which is otherwise progressively lost to clinical use. E-pathology records provide reliable, life-long evidence of critical transition points in individual lives and disease progression for clinical and research use, when they can be instantly accessed.

Can routine blood tests be modelled to detect advanced liver disease in the community: model derivation and validation using UK primary and secondary care data.

OBJECTIVES: Most patients are unaware they have liver cirrhosis until they present with a decompensating event. We therefore aimed to develop and validate an algorithm to predict advanced liver disease (AdvLD) using data widely available in primary care. DESIGN, SETTING AND PARTICIPANTS: Logistic regression was performed on routinely collected blood result data from the University Hospital Southampton (UHS) information systems for 16 967 individuals who underwent an upper gastrointestinal endoscopy (2005-2016). Data were used to create a model aimed at detecting AdvLD: 'CIRRhosis Using Standard tests' (CIRRUS). Prediction of a first serious liver event (SLE) was then validated in two cohorts of 394 253 (UHS: primary and secondary care) and 183 045 individuals (Care and Health Information Exchange (CHIE): primary care). PRIMARY OUTCOME MEASURES: Model creation dataset: cirrhosis or portal hypertension. Validation datasets: SLE (gastro-oesophageal varices, liver-related ascites or cirrhosis). RESULTS: In the model creation dataset, 931 SLEs were recorded (5.5%). CIRRUS detected cirrhosis or portal hypertension with an area under the curve (AUC) of 0.90 (95% CI 0.88 to 0.92). Overall, 3044 (0.8%) and 1170 (0.6%) SLEs were recorded in the UHS and CHIE validation cohorts, respectively. In the UHS cohort, CIRRUS predicted a first SLE within 5 years with an AUC of 0.90 (0.89 to 0.91) continuous, 0.88 (0.87 to 0.89) categorised (crimson, red, amber, green grades); and AUC 0.84 (0.82 to 0.86) and 0.83 (0.81 to 0.85) for the CHIE cohort. In patients with a specified liver risk factor (alcohol, diabetes, viral hepatitis), a crimson/red cut-off predicted a first SLE with a sensitivity of 72%/59%, specificity 87%/93%, positive predictive value 26%/18% and negative predictive value 98%/99% for the UHS/CHIE validation cohorts, respectively. CONCLUSION: Identification of individuals at risk of AdvLD within primary care using routinely available data may provide an opportunity for earlier intervention and prevention of liver-related morbidity and mortality.

Automated data cleaning of paediatric anthropometric data from longitudinal electronic health records: protocol and application to a large patient cohort.

'Big data' in healthcare encompass measurements collated from multiple sources with various degrees of data quality. These data require quality control assessment to optimise quality for clinical management and for robust large-scale data analysis in healthcare research. Height and weight data represent one of the most abundantly recorded health statistics. The shift to electronic recording of anthropometric measurements in electronic healthcare records, has rapidly inflated the number of measurements. WHO guidelines inform removal of population-based extreme outliers but an absence of tools limits cleaning of longitudinal anthropometric measurements. We developed and optimised a protocol for cleaning paediatric height and weight data that incorporates outlier detection using robust linear regression methodology using a manually curated set of 6,279 patients' longitudinal measurements. The protocol was then applied to a cohort of 200,000 patient records collected from 60,000 paediatric patients attending a regional teaching hospital in South England. WHO guidelines detected biologically implausible data in <1% of records. Additional error rates of 3% and 0.2% for height and weight respectively were detected using the protocol. Inflated error rates for height measurements were largely due to small but physiologically implausible decreases in height. Lowest error rates were observed when data was measured and digitally recorded by staff routinely required to do so. The protocol successfully automates the parsing of implausible and poor quality height and weight data from a voluminous longitudinal dataset and standardises the quality assessment of data for clinical and research applications.

Asymmetric dimethylarginine endogenous inhibition of nitric oxide synthase causes differential vasculature effects.

BACKGROUND: Asymmetric dimethylarginine (ADMA), produced during protein metabolism, is an endogenous inhibitor of nitric oxide synthase, but little is known about its direct vasoactive properties in different arterial beds. MATERIAL/METHODS: Segments of canine coronary, renal, and femoral arteries were pretreated with increasing concentrations of ADMA, and endothelial function was evaluated in organ chambers. RESULTS: In precontracted canine coronary arteries, the highest concentrations of ADMA inhibited endothelium-dependent relaxation mediated by acetylcholine (n=7), but no concentration of ADMA inhibited receptor-independent relaxation mediated by calcium ionophore (n=7) (P<.001). The effect of ADMA on acetylcholine-mediated relaxation was shown to be competitive inhibition of the nitric oxide synthase pathway, because the addition of L-arginine (10(-3) M), but not D-arginine (10(-3) M), reversed the effect produced by 10-5 M ADMA. Further, ADMA did not alter endothelium-independent relaxation mediated by sodium nitroprusside (10(-9) to 10(-6) M; n=7). Femoral arteries (n=7) and renal arteries (n=7) were more sensitive to ADMA than were coronary arteries, and they demonstrated significant ADMA inhibition to receptor dependent relaxation induced by acetylcholine (P=.03 and P=.01, respectively) and to receptor-independent relaxation induced by calcium ionophore (P=.02 and P=.01, respectively). CONCLUSIONS: Endothelium-dependent relaxation mediated by ADMA is more marked in femoral and renal arteries than in coronary arteries. The response in coronary arteries may be overall protective. Considering these different effects in various artery types, the role of ADMA as a confiable and specific cardiovascular risk factor is questioned.

Design and implementation of the stacked, synchronised and iconographic timeline-structured electronic patient record in a UK NHS Global Digital Exemplar hospital.

BACKGROUND: Conventional electronic screen visualisation formats, which use tabs, dropdown menus, lists and multiple windows, present huge navigation challenges to health professionals. A unifying and intuitive interface for the electronic patient record (EPR) has been an elusive goal for software developers for decades. METHODS: Since 2009, by working in an agile way, we have built and implemented a fully operational and dynamic system, the University Hospital Southampton Lifelines (UHSL), within our clinical data estate, in a UK university hospital. UHSL permits the continuously updated display of the EPR on a single desktop computer screen in an intuitive format. During this iterative evolution, we have resolved a number of practical challenges in data display, while maintaining our core aims of end-user optimisation and radical simplification of the interface. Concurrently, we have upcycled a significant volume of clinical e-content, some from as far back as 1991, into UHSL, and at a marginal cost. OUTCOMES: UHSL went live in 2017 for all authorised staff at the hospital. It displays all e-records for 2.5 million patients and for more than 100 million documents and reports. It significantly reduces the screen time to navigate the individual EPR, and it offers substantial productivity gains in designated clinical services. CONCLUSIONS: UHSL has considerable further development potential as a National Health Service EPR interface, for the integration, display and ease of understanding of medical records across primary, secondary and community care.

Systemic thrombolytic therapy after recent abdominal aortic aneurysm repair: an absolute contraindication?

Systemic thrombolysis in the early postoperative period can cause fatal hemorrhage. Systemic thrombolysis is often considered contraindicated after major vascular procedures; thus, experience with this scenario is limited. A 67-year-old man experienced massive pulmonary embolization after his abdominal aortic aneurysm was repaired with a bifurcated, woven Dacron graft. Because systemic thrombolysis was the only option for our patient's survival, he underwent this procedure with recombinant tis-sue-type plasminogen activator just 2 weeks after the Dacron graft repair of his abdominal aortic aneurysm. After clinical stabilization, abdominal and pelvic computed tomography showed no periprosthetic graft hemorrhage. The successful systemic thrombolysis suggests that this therapy may prove useful in extreme situations.

Clustering of recurrent pericarditis with effusion and constriction in a family.

OBJECTIVE: To describe a cluster of cases of pericarditis in a midwestern family of German and Danish ancestry. PATIENTS AND METHODS: Retrospective review of available medical records identified 5 family members in 2 generations with confirmed diagnosis of pericarditis. RESULTS: Five family members, 3 males and 2 females, presented for medical evaluation of recurrent chest pain between 1969 and 1991. Physical examination resulted in the diagnosis of pericarditis with effusive and constrictive features. The age at presentation ranged from 8 to 46 years. Despite extensive investigations, an idiopathic etiology was assigned to each case. In follow-up, all 5 family members had recurrent episodes of chest pain, self-limiting or responsive to medical therapy, but the effusive component remained a notable feature of the syndrome. CONCLUSIONS: Diagnosis of pericarditis in 5 family members may represent the first description of familial clustering of isolated pericarditis. In addition, 3 other family members had symptoms of chest pain, but pericarditis remained undiagnosed. The aggregate history suggests autosomal dominant inheritance with incomplete penetrance.

Nitric oxide and prostacyclin-dependent pathways involvement on in vitro induced hypothermia.

Nitric oxide and prostacyclin are endogenous endothelium-derived vasodilators, but little information is available on their release during hypothermia. This study was carried out to test the hypothesis that endothelium may modulate vascular reactivity to decreased temperature changes. Segments of contracted (prostaglandin F(2alpha), 2x10(-6)M) canine coronary, femoral, and renal arteries, with and without endothelium, were in vitro ("organ chambers") exposed to progressive hypothermia (from 37 to 10 degrees C) in graded steps. The study is limited to physiological measurements of vascular tone, in the presence or absence of PGI(2) and/or NOS inhibitors, which show correlation with the relaxation. Hypothermia induced vasodilatation of vessels with intact endothelium, which became endothelium-independent below 20 degrees C. This vasodilatation began at 35 degrees C and, in the presence of indomethacin (2x10(-6)M), at 30 degrees C. Endothelium-dependent vasodilatation to hypothermia was blocked by L-NMMA or L-NOARG (10(-5)M), two competitive inhibitors of nitric oxide synthase (n=5 each, P<0.05). Oxyhemoglobin (2x10(-6)M) also inhibited vasodilatation induced by hypothermia (n=6, P<0.05). Pretreatment with either atropine or pirenzepine (10(-6)M) inhibited hypothermia-mediated vasodilatation (n=5 each, P<0.05). The present in vitro study concluded that the endothelium is sensitive to temperature variations and indicated that PGI(2) and NO-dependent pathways may be involved endothelium-dependent relaxation to hypothermia. The endothelium-dependent vasodilatation to hypothermia, in systemic and coronary arteries, is mediated by the M1 muscarinic receptor.

Prolonged exposure of canine coronary arteries to a nitric oxide donor desensitizes soluble guanylate cyclase.

BACKGROUND: This study investigated the role of soluble guanylate cyclase desensitization in the development of tolerance to organic nitrates. MATERIALS AND METHODS: In organ baths, canine coronary arteries were exposed to either sodium nitroprusside (SNP) (experimental group) or papaverine (control group) at various concentrations (10(-9), 10(-7), or 10(-5) M) for 3 h. Arteries were then compared for response to vascular agonists and for inducible cyclic guanine monophosphate (cGMP) formation. RESULTS: KCl (5 to 50 mM) and prostaglandin F(2alpha) (10(-9) to 10(-5) M) induced similar vascular contractions (n = 7, P > 0.05). Vascular relaxation in response to calcium ionophore A23187 (10(-9) to 10(-6) M) and to authentic nitric oxide (NO) (3 x 10(-9) to 10(-5) M) was attenuated in arteries exposed to SNP at 10(-7) and 10(-5) M concentrations but not at a 10(-9) M concentration (n = 7 each, P < 0.05 versus the respective papaverine group). Pretreatment of arteries with methylene blue (10(-5) M) abolished the responses to authentic NO (n = 4). In cGMP determinations, control arteries demonstrated an increase in cGMP from 364 +/- 89 to 778 +/- 175 pg/mg of protein with A23187 (3 x 10(-5) M) stimulation (n = 5). Conversely, arteries exposed to SNP (10(-5) M) demonstrated similar levels of cGMP before (562 +/- 126 pg/mg of protein) and after (641 +/- 98 pg/mg of protein) A23187 stimulation. CONCLUSIONS: Prolonged exposure of coronary arteries to SNP did not alter vascular smooth muscle function, but it markedly attenuated the relaxation in response to both A23187 and authentic NO at concentrations above 10(-9) M in a concentration-dependent fashion. The constant levels of cGMP in response to an NO donor suggest that the attenuation of relaxation is due to desensitization of soluble guanylate cyclase. Thus, this study supports the role of soluble guanylate cyclase desensitization in the development of tolerance to organic nitrates.

Hirudin (desulfated, 54-65) contracts canine coronary arteries: extracellular calcium influx mediates hirudin-induced contractions.

OBJECTIVE: Although the anticoagulatory properties of hirudin are well known, its direct vasoactive effects have not been investigated extensively. Hirudin stimulates nitric oxide and prostacyclin production in noncoronary vascular beds, but its actions on coronary arteries are unknown. MATERIALS AND METHODS: Five-millimeter segments of canine left circumflex coronary arteries were obtained for organ chamber experiments. Some segments were denuded of endothelium before study. Segments were exposed to hirudin (10(-10)-10(-6) mol/L) following precontraction with prostaglandin F(2alpha) with or without pretreatment with indomethacin or calcium channel blockers (verapamil and nifedipine). RESULTS: Hirudin stimulated endothelium-independent contraction in coronary arterial segments. Maximum tension (hirudin 10(-6) mol/L) above precontraction baseline was 33.6 +/- 9.0% (n = 10, P < 0.05) for endothelium-intact and 31.8 +/- 11.5% (n = 8, P < 0.05) for endothelium-denuded arterial segments. Differences between endothelium-intact and endothelium-denuded segments were not significant. Contractile responses to hirudin were unaffected by the presence of indomethacin. Pretreatment with either verapamil or nifedipine (10(-4) mol/L) for 1 h attenuated these contractions. The maximal increase in tension above baseline (hirudin 10(-6) mol/L) for verapamil and nifedipine was only 6.2 +/- 12.4 and 3.8 +/- 7.0% (n = 6, P < 0.05 versus endothelium-intact control), respectively. CONCLUSIONS: Hirudin stimulates endothelium-independent contractions of canine coronary arteries in vitro. Pretreatment with calcium channel blockers attenuates this response, suggesting that extracellular influx of calcium has an important mechanistic role in hirudin-mediated coronary artery constriction.

Endothelium-dependent vasodilation during acute rejection in dogs.

BACKGROUND: Acute rejection, which is a major cause of death after cardiac transplantation, is associated with increased coronary artery resistance and decreased coronary blood flow, leading to congestive heart failure. MATERIALS AND METHODS: To examine the contribution of endothelium-derived vasoactive factors on coronary artery tone during acute rejection, dogs underwent orthotopic heart transplantation without immunosuppression. Plasma levels of endothelin, a potent endogenous vasoconstrictor peptide, and atrial natriuretic peptide, an endogenous coronary vasodilator of cardiac origin, were measured daily by radioimmunoassay until sacrifice. RESULTS: Over 7 days, all animals developed acute rejection accompanied by progressive increases in plasma endothelin (10 +/- 3 to 25 +/- 4 pg/ml, n = 6, P < 0.05) and atrial natriuretic peptide (57 +/- 10 to 188 +/- 42 pg/ml, n = 6, P < 0.05). However, in organ chamber experiments, coronary artery segments from rejecting hearts exhibited normal endothelium-dependent vasodilation to acetylcholine, adenosine diphosphate, and the calcium ionophore A23187. In addition, coronary arteries exhibited normal relaxation to sodium nitroprusside (cyclic guanosine monophosphate-dependent) and isoproterenol (cyclic adenosine monophosphate-dependent). CONCLUSIONS: In early, untreated acute rejection after orthotopic heart transplantation, graft dysfunction is not associated with impaired endothelium-dependent coronary artery vasodilation but may result from enhanced production of endothelin, a potent vasoconstrictor.