Tyrosine Kinase Inhibitor-Induced Hypertension.

PURPOSE OF REVIEW: The purpose of this paper is to identify commonly used tyrosine kinase inhibitors (TKIs) that are associated with hypertension, primarily, vascular endothelial growth factor (VEGF) signaling pathway (VSP) inhibitors. We review the incidence, mechanism, and strategies for management of TKI-induced HTN. We hope to provide clinicians with guidance on how to manage similar clinical scenarios. RECENT FINDINGS: Many of the newer VSP inhibitors are reviewed here, including cediranib, axitinib, pazopanib, and ponatinib. Trials utilizing prophylactic treatment with angiotensin system inhibitors (ASIs) are discussed as well as recent data showing an improvement in overall survival and progression-free survival in patients on ASIs and TKI-induced hypertension. The incidence of TKI-induced HTN among the VEGF inhibitors ranges from 5 to 80% and is dose dependent. Newer generation small-molecule TKIs has a lower incidence. The mechanism of action involves VSP inhibition, leading to decreased nitric oxide and increased endothelin production, which causes vasoconstriction, capillary rarefaction, and hypertension. ASIs and calcium channel blockers are first-line therapy for treatment and are associated with improved overall survival. Nitrates and beta-blockers are associated with in vitro cancer regression; however, there is a paucity of trials regarding their use as an anti-hypertensive agent in the TKI-induced HTN patient population.

Clinical, Serological, and Molecular Observations from a Case Series Study during the Asian Lineage Zika Virus Outbreak in Grenada during 2016.

This paper describes the spatial and temporal distribution of cases, demographic characteristics of patients, and clinical manifestations of Zika virus (ZIKV) during the 2016 outbreak in Grenada. The first reported case was recorded in St. Andrew Parish in April, and the last reported case was seen in November, with peak transmission occurring in the last week of June, based on test results. Data were collected from a total of 514 patients, of whom 207 (40%) tested positive for ZIKV. No evidence was found that testing positive for ZIKV infection was related to age, gender, or pregnancy status. Clinical presentation with rash (OR = 2.4, 95% CI = 1.5 to 3.7) or with lymphadenopathy (OR = 1.7, 95% CI = 1.0 to 2.9) were the only reported symptoms consistent with testing positive for ZIKV infection. During the Zika outbreak, the infection rate was 20 clinical cases per 10,000 in the population compared to 41 cases per 10,000 during the chikungunya outbreak in Grenada in 2014 and 17 cases per 10,000 during the dengue outbreak in 2001-2002. Even though the country has employed vector control programs, with no apparent decrease in infection rates, it appears that new abatement approaches are needed to minimize morbidity in future arbovirus outbreaks.

Public health response and lessons learned from the 2014 chikungunya epidemic in Grenada.

In June 2014, the first cases of chikungunya virus (CHIKV) were diagnosed on the island of Carriacou, part of the tri-island state of Grenada. In the three months that followed, CHIKV spread rapidly, with conservative estimates of the population infected of at least 60%. Multiple challenges were encountered in the battle to manage the spread and impact of this high-attack rate virus, including 1) limited indigenous laboratory diagnostic capabilities; 2) an under-resourced health care system; 3) a skeptical general public, hesitant to accept facts about the origin and mode of transmission of the new virus; and 4) resistance to the vector control strategies used. Lessons learned from the outbreak included the need for 1) a robust and reliable epidemiological surveillance system; 2) effective strategies for communicating with the general population; 3) exploration of other methods of mosquito vector control; and 4) a careful review of all health care policies and protocols to ensure that effective, organized responses are triggered when an infectious outbreak occurs.

Vibration for Pain Reduction in a Plastic Surgery Clinic.

Patients can experience significant pain during routine procedures in the plastic surgery clinic. Methods for clinical pain reduction are often impractical, time-consuming, or ineffective. Vibration is a safe, inexpensive, and highly applicable modality for pain reduction that can be readily utilized for a wide variety of procedures. This study evaluated the use of vibration as a viable pain-reduction strategy in the clinical plastic surgery setting. Patients requiring at least 2 consecutive procedures that are considered painful were enrolled in the study. These included injections, staple removal, and suture removal. In the same patient, one half of the procedures were performed without vibration and the other half with vibration. After completing the procedures, the patients rated their pain with vibration and without vibration. The patient and the researcher also described the experience with a short questionnaire. Twenty-eight patients were enrolled in the study. Patients reported significantly less pain on the Numeric Rating Scale pain scale when vibration was used compared with the control group (p < .001). The average pain score was 3.46 without vibration and 1.93 with vibration, and vibration with injections resulted in the greatest improvement. Eighty-six percent of the patients claimed that vibration significantly reduced their pain. Vibration is an effective method of pain reduction. It significantly reduces the pain experienced by patients during minor office procedures. Given its practicality and ease of use, it is a welcome tool in the plastic surgery clinic.

Pressure-specified sensory device versus electrodiagnostic testing in brachial plexus upper trunk injury.

Brachial plexus upper trunk injury is associated with winged scapula owing to the close anatomical course of the long thoracic nerve and upper trunk. Needle electromyography is a common diagnostic test for this injury; however, it does not detect injury in most patients with upper trunk damage. The pressure-specified sensory device may be an alternative to needle electromyography. Thirty patients with winged scapula and upper trunk injury were evaluated with needle electromyography (EMG) and pressure-specified sensory device (PSSD) tests. EMG testing of the biceps muscle was compared with PSSD testing of the dorsal hand skin (C6 damage), and EMG testing of the deltoid and spinati muscles was compared with PSSD testing of the deltoid skin (C5 damage). PSSD pressure values were significantly higher on the affected arm. On the basis of published and calculated threshold values the PSSD was found to be significantly more sensitive than EMG. The PSSD tests consistently identified injuries that were not detected by needle EMG tests. These findings provide strong evidence that the PSSD is more effective than needle EMG in the detection of brachial plexus upper trunk injury.

Pre and postnatal exposure to Chikungunya virus does not affect child neurodevelopmental outcomes at two years of age.

BACKGROUND: The 2005-06 chikungunya virus (CHIKV) outbreak in La Réunion suggested that mothers could transmit CHIKV to their neonates while viremic during the intrapartum period, and more than half of the infected neonates showed impaired neurodevelopment at two years of age. However, data sparsity precluded an overview of the developmental impact of vertical infection within the whole prenatal period. OBJECTIVE & METHODS: The current study assessed two-year old children born to mothers who were infected during the 2014 CHIKV outbreak in Grenada to determine the neurodevelopmental impact of perinatal CHIKV infection throughout gestation. Mother and child infection status were confirmed by serologic testing (IgG and IgM) for CHIKV. Cognitive, fine motor, gross motor, language and behavioral outcomes were assessed at two years of age on the INTERGROWTH-21st Neurodevelopment Assessment (INTER-NDA). RESULTS: No differences in neurodevelopmental outcomes were observed between two-year-old children born to mothers infected with CHIKV during gestation (n = 149) and those born to mothers not infected with CHIKV (n = 161). No differences were found in INTER-NDA scores between children infected with CHIKV (n = 47) and children not infected with CHIKV (n = 592). Likewise, there were no differences between children infected with CHIKV post-partum (n = 19) versus children not infected with CHIKV (n = 592). CONCLUSION: Our findings suggest that children exposed and/or infected with CHIKV outside of the intrapartum period experience no significant neurodevelopmental delay at two years of age, as measured by the INTER-NDA, compared to their unexposed and/or uninfected peers. These results complement those of previous studies which showed a neurodevelopmental risk only for children infected during the intrapartum period, while the mother was highly viremic. These results might be reassuring for women of childbearing age and public health officials in CHIKV-endemic regions.

Prevalence of sickle cell disease among Grenadian newborns.

Objective To establish the birth prevalence of sickle cell disease in Grenada, with a view to assess the requirement for a population-based neonatal screening programme. Methods A two-year pilot neonatal screening programme, involving the Ministry of Health of Grenada, the Sickle Cell Association of Grenada, and the diagnostic laboratory of hemoglobinopathies of the University Hospital of Guadeloupe, was implemented in 2014-2015 under the auspices of the Caribbean Network of Researchers on Sickle Cell Disease and Thalassemia. Results Analysis of 1914 samples processed identified the following abnormal phenotypes: 10 FS, 2 FSC, 183 FAS, 63 FAC. These data indicate ßs and ßc allele frequencies of 0.054 and 0.018, respectively. Conclusion Neonatal screening conducted in the framework of this Caribbean cooperation can allow rapid detection and earlier management of affected children.

The Identification of Risk Factors for Chronic Chikungunya Arthralgia in Grenada, West Indies: A Cross-Sectional Cohort Study.

BACKGROUND: Chikungunya virus (CHIKV) is a re-emerging arboviral pathogen. In 2014, an explosive CHIKV outbreak occurred in Grenada, West Indies, infecting approximately 60% of the population. In approximately 50% of cases, CHIKV infection transitions to painful arthralgia that can persist for years. Elucidation of the risk factors for chronic disease is imperative to the development of effective risk management strategies and specific therapeutics. METHODS: We conducted a cross-sectional study of 240 people who were tested for CHIKV during the outbreak. We administered questionnaires to examine demographic, behavioral, psychological, social, and environmental factors to identify associations with chronic disease. Physical examinations were performed and persistent symptoms were recorded. RESULTS: Ethnicity and socioeconomic status were not associated with risk of chronic joint pain. Female sex increased risk, and age was demonstrated to be predictive of chronic CHIKV sequelae. Mosquito avoidance behaviors did not reduce risk. Patients suffering joint pains, generalized body ache, and weakness in the extremities during acute infection were more likely to develop chronic arthralgia, and an increased duration of acute disease also increased risk. CONCLUSIONS: These data demonstrate that chronic CHIKV affects people across the ethnic and socioeconomic spectrum, and it is not reduced by vector avoidance activity. Increased duration of acute symptoms, in particular acute joint pain, was strongly correlated with the risk of persistent arthralgia, thus effective clinical management of acute CHIKV disease could reduce burden of chronic CHIKV.

Clinical and Serological Insights from the Asian Lineage Chikungunya Outbreak in Grenada, 2014: An Observational Study.

Chikungunya virus (CHIKV) spread rapidly throughout the Caribbean region in 2014, and the first serologically confirmed case was seen in Grenada in July. This study investigated the outbreak of CHIKV in Grenada to identify the distinguishing clinical manifestations and the symptoms that corresponded the closest with serological test results. Sera were tested by IgM enzyme-linked immunosorbent assay and polymerase chain reaction to distinguish between cases positive or negative for CHIKV. Of 493 cases, 426 (86%) tested positive for CHIKV. The diagnostic decision rule, "Define as CHIKV positive a patient presenting with joint pain and any combination of fever, body pain, or rash," produced the closest agreement (85%) with the serological test results (Cohen's kappa, k = 0.289, P value < 0.001). When laboratory facilities are not available for diagnostic confirmation, syndromic surveillance using these four symptoms could be useful to define cases during a CHIKV outbreak when CHIKV is the predominant circulating arbovirus.

A survey of anthelmintic resistant nematode parasites in Scottish sheep flocks.

The state of anthelmintic resistance in Scottish sheep flocks was evaluated during April-August 2000 using in vitro bioassays, egg hatch assays for detecting thiabendazole (TBZ) resistance and larval development assays for levamisole, ivermectin and TBZ resistance. Anaerobic sampling kits and detailed questionnaires outlining farm demographics and current management practices were mailed to 227 Moredun Foundation member farms, replies were received from 98 farms. Kits received from 90 farms contained sufficient material to conduct one or more of the assays. A majority of the farms examined (64%) exhibited TBZ resistance but there were both farm locality and regional variations in the percentage of resistant farms. Teladorsagia was the predominant genera detected from farms. No resistance to levamisole or ivermectin was detected in any of the samples. There was no strong evidence from this survey that any of the management practices examined greatly affected TBZ resistance.

Radiation coronary arteritis refractory to surgical and percutaneous revascularization culminating in orthotopic heart transplantation.

BACKGROUND: Hodgkin's lymphoma (HL) comprises of 4% of malignancies diagnosed in children from birth to 14 years of age. While overall survival rates have increased, HL survivors can be at risk of late cardiovascular complications from radiotherapy. HL survivors with a history of mediastinal RT have been found to have an increased incidence of myocardial infarction, angina, congestive heart failure, and valvular disorders compared to the general population. METHODS: A 33 year old female with a history of HL status post chemotherapy and mediastinal radiation 11 years ago became symptomatic with multivessel coronary artery disease with aggressive progression of her disease despite coronary bypass graft surgery, patch angioplasty of the left main coronary artery (LMCA) with an extracellular bioscaffold, and repeated percutaneous coronary intervention of the LMCA. She eventually underwent orthotopic heart transplant and did well postoperatively. RESULTS: Histopathological analysis of the explanted heart revealed a variety of sequelae of radiation arteritis, including thrombosis of both native vessels and arterial grafts, intimal hyperplasia and involvement of the bioscaffold in the left main coronary vasculature. The bioscaffold did not contribute significantly to the stenosis within the LMCA. CONCLUSION: Our case demonstrates an unusual indication for OHT due to severe refractory radiation induced CAD, as well the wide spectrum of the histopathologic manifestations of radiation induced arteritis.

Fondaparinux therapy in a hemodialysis patient with heparin-induced thrombocytopenia type II.

PURPOSE: The successful use of fondaparinux in a hemodialysis patient with heparin-induced thrombocytopenia type II (HIT II) is reported. SUMMARY: An 85-year-old, 68-kg Caucasian woman came to the emergency department with shortness of breath and exertional chest pain radiating to the neck. Testing revealed non-ST-segment elevation myocardial infarction, severe coronary artery disease, mitral regurgitation, left ventricular dysfunction, an ejection fraction of 25-30%, and pulmonary arterial hypertension. I.V. unfractionated heparin was given for therapeutic anticoagulation per hospital protocol and discontinued on hospital day 3 before mitral valve repair and coronary bypass procedure. Postoperatively unfractionated heparin and low-molecular-weight heparin were avoided because of a reduction in the platelet count and suspicion of HIT. Instead, the patient was placed on sequential compression devices in addition to aspirin for prophylaxis of deep venous thrombosis. By postoperative day 6, the patient's platelet count dropped 76% from baseline, and the patient was found to have heparin-dependent platelet factor 4 antibodies. Argatroban infusion was initiated but discontinued after 2 days due to bleeding. Fondaparinux was ordered for anticoagulation therapy. By hospital day 8, the patient developed renal insufficiency requiring hemodialysis and adjustment of the fondaparinux regimen. During the 30-day course of fondaparinux, the patient did not experience thromboembolic events or bleeding and did not require transfusions. There was no clotting within hemodialysis membranes, and her hepatic function improved by the time of her discharge. CONCLUSION: Fondaparinux was used in a hemodialysis patient with HIT II without the development of thromboembolic, hemodialysis-clotting, thrombocytopenic, or hemorrhagic complications. The patient's platelet count remained in the normal range during the 30-day course of fondaparinux.

Clinical response to unintentionally rapid infusion of drotrecogin alfa (activated).

PURPOSE: The case of a patient with severe sepsis who received a bolus dose of 184 microg/kg of drotrecogin alfa (activated) over one hour is reported. SUMMARY: An 84-year-old woman who had undergone right total knee replacement was admitted to the hospital from a rehabilitation facility with an initial diagnosis of mental status changes and a suspected urinary tract infection. Examination of the patient's incision from her recent knee surgery revealed a discharge, and a culture was obtained. The patient was diagnosed with sepsis, intubated, and transferred to the intensive care unit. Multiple antibiotics were administered, but the patient's condition continued to deteriorate. In addition, the patient developed acute renal failure, required a ventilator, had cyanotic limbs, and had partially compensated metabolic acidosis. On hospital day 7, drotrecogin alfa (activated) was initiated. She inadvertently received an infusion of 184 microg/kg of drotrecogin alfa over 1 hour. Nine hours later, she received drotrecogin alfa 24 microg/kg/hr for 95 hours. The patient's clinical status was improved after the initial infusion. Peripheral limb cyanosis was markedly decreased, with pink, warm extremities. In addition, the patient's clinical laboratory test values improved after administration of drotrecogin alfa. However, the patient was unable to recover fully from the acute kidney failure and was discharged to hospice care. CONCLUSION: A drotrecogin alfa dose of 184 microg/kg i.v. was erroneously administered over 1 hour to a patient with sepsis. Nine hours later, a drotrecogin alfa infusion of 24 microg/kg/hr was started and continued for 95 hours. The patient improved clinically and had no apparent adverse events.

Estimating spatial patterns of effluent exposure concentrations in direct toxicity assessment studies.

Hydrodynamic models of differing scale and complexity were used to estimate spatial patterns of effluent concentration in discharge plumes in the River Esk and the Lower Tees Estuary. The output from the Tees model was used, in conjunction with measurements of toxicity determined in short-term oyster embryo tests, to predict contours/zones of toxicity in the estuary associated with effluent discharges from four chemical processing sites. One of the discharges also combined the input from a municipal sewage treatment works. The models appeared to be effective in predicting patterns of dilution and dispersion of the effluent discharges in the respective receiving environments. Confirmation of the predictive capabilities of the Tees model was achieved by comparing predicted and measured toxicity in different regions of the plumes associated with the four discharges. Differences between predicted and measured toxicity for two of the four discharges were explicable in terms of failure to take account of the effects of real-time wind conditions when test samples were collected or overlap of adjacent discharge plumes. Suggested refinements to the models and measurement of effluent toxicity would further enhance the utility of this approach for determining the extent and significance of the effects of effluent discharges in receiving environments.