Comparison of once-daily atazanavir with efavirenz, each in combination with fixed-dose zidovudine and lamivudine, as initial therapy for patients infected with HIV

BACKGROUND: Atazanavir, an azapeptide protease inhibitor (PI), has pharmacokinetics that allow once-daily dosing, and it is not associated with significant PI-associated dyslipidemia. METHODS: A randomized, double-blind, double-dummy, active-controlled, 2-arm study comparing the antiviral efficacy and safety of atazanavir 400 mg administered once daily with efavirenz 600 mg administered once daily in combination with open-label fixed-dose zidovudine plus lamivudine twice daily. The 810 treatment-naive patients were stratified by HIV RNA level. The primary efficacy end point was the proportion of treated patients with HIV RNA levels <400 copies/mL through week 48. RESULTS: At week 48, HIV RNA levels were <400 copies/mL in 70% of patients receiving atazanavir and 64% of patients receiving efavirenz (intent-to-treat, difference; 95% confidence interval: 5.2%; -1.2%, 11.7%). Median CD4 cell counts increased at comparable magnitudes and rates in the 2 treatment arms (mean change at week 48: 176 cells/mm with atazanavir, 160 cells/mm with efavirenz). Atazanavir-treated patients relative to comparator-treated patients did not demonstrate significant increases in total cholesterol, fasting low-density lipoprotein cholesterol, or fasting triglycerides over 48 weeks of therapy. Atazanavir-linked bilirubin elevations infrequently resulted in treatment discontinuation (<1%). Atazanavir treatment did not increase fasting glucose or insulin levels. CONCLUSIONS: For initial HIV treatment, a highly active antiretroviral therapy regimen of atazanavir/zidovudine/lamivudine is as efficacious and well tolerated as the combination of efavirenz/zidovudine/lamivudine.     

Language barriers between nurses and patients: A scoping review

ObjectiveGlobal migration and linguistic diversity are at record highs, making healthcare language barriers more prevalent. Nurses, often the first contact with patients in the healthcare system, can improve outcomes including safety and satisfaction through how they manage language barriers. This review aimed to explore how research has examined the nursing workforce with respect to language barriers.MethodsA systematic scoping review of the literature was conducted using four databases. An iterative coding approach was used for data analysis. Study quality was appraised using the CASP checklists.Results48 studies representing 16 countries were included. Diverse healthcare settings were represented, with the inpatient setting most commonly studied. The majority of studies were qualitative. Coding produced 4 themes: (1) Interpreter Use/Misuse, (2) Barriers to and Facilitators of Quality Care, (3) Cultural Competence, and (4) Interventions.ConclusionGenerally, nurses noted like experiences and applied similar strategies regardless of setting, country, or language. Language barriers complicated care delivery while increasing stress and workload.Practice ImplicationsThis review identified gaps which future research can investigate to better support nurses working through language barriers. Similarly, healthcare and government leaders have opportunities to enact policies which address bilingual proficiency, workload, and interpreter use.     

Radiotherapy for melanotic freckles

Five patients who received radiotherapy (RT) for 7 melanotic freckles (MF, also known as Hutchinson's freckles, lentigo maligna) were reviewed 8 to 37 months after their treatment by RT. Local control and a favourable cosmetic result occurred in all patients. Treatment toxicity was minimal. Few reports about the use of RT for MF exist. Many other treatments including observation alone have been associated with high rates of recurrence, and in some cases conversion to invasive melanoma has occurred. RT appears to be a safe and effective treatment for this condition, providing that doses equivalent to 44 Gy in 11 fractions or more are given.     

Lissencephaly: fetal pattern of glucose metabolism on positron emission tomography?

BACKGROUND: In classical lissencephaly, the cerebral cortex is four-layered, containing neurons that have failed to complete their migration between 12 and 16 weeks of gestation. METHODS: The authors studied the functional activity of lissencephalic cortex using 2-deoxy-2[(18)F]fluoro-D-glucose PET (FDG PET) in eight patients (six girls and two boys, mean age 7.5 years) with isolated lissencephaly sequence. RESULTS: The PET scans revealed a remarkably similar and bilaterally symmetric pattern of glucose metabolism in all eight patients. The cerebral cortex of lissencephaly showed two layers that could be differentiated based on metabolic activity. The inner layer, which probably corresponds to the inner cellular layer of lissencephalic cortex, showed 8 to 63% higher glucose utilization rate than the outer layer, which probably represents a composite of the molecular, outer cellular, and cell-sparse layers. Patients with a higher metabolic ratio between the cortical layers (inner/outer) showed greater delay in communication (p = 0.007) and socialization (p = 0.03). CONCLUSIONS: These findings are consistent with [(14)C]-2-deoxyglucose autoradiography studies in fetal sheep that have shown that before the development of significant numbers of axons, dendrites, and synapses, glucose metabolism appears to be highest in regions with the highest density of cell bodies, compared to the more mature state when glucose metabolism is highest in areas of greatest dendritic arborization. FDG PET studies of classical lissencephaly provide a different perspective in the analysis of brain gyral anomalies than those with traditional neuroanatomic imaging techniques.     

School and neuropsychological performance of evacuated children in Kyiv 11 years after the Chornobyl disaster

This paper examines the cognitive and neuropsychological functioning of children who were in utero to age 15 months at the time of the Chornobyl disaster and were evacuated to Kyiv from the 30-kilometer zone surrounding the plant. Specifically, we compared 300 evacuee children at ages 10-12 with 300 non-evacuee Kyiv classmates on objective and subjective measures of attention, memory, and school performance. The evacuee children were not significantly different from their classmates on the objective measures (grades; Symbolic Relations subtest of the Detroit Test; forms 1 and 2 of the Visual Search and Attention Test; Benton Form A; Trails A; Underline the Words Test) or on most of the subjective measures (the attention subscale of the Child Behavior Checklist completed by mothers; the attention items of the Iowa Conners Teacher's Rating Scale; mother and child perceptions of school performance). The one exception was that 31.3% of evacuee mothers compared to 7.4% of classmate mothers indicated that their child had a memory problem. However, this subjective measure of memory problems was not significantly related to neuropsychological or school performance. No significant differences were found in comparisons of evacuees and classmates who were in utero at the time of the explosion, children from Pripyat vs. other villages in the 30-kilometer zone, and children manifesting greater generalized anxiety. For both groups, children with greater Chornobyl-focused anxiety performed significantly worse than children with less Chornobyl-focused anxiety on measures of attention. The results thus fail to confirm two previous reports that relatively more children from areas contaminated by radiation had cognitive deficits compared to controls. Possible reasons for the differences in findings among the studies are discussed.     

Ionic control of beta cell function in nesidioblastosis. A possible therapeutic role for calcium channel blockade.

A preterm female infant presented with intractable hypoglycaemia within 10 minutes of delivery. Normoglycaemia could be maintained only by the intravenous infusion of glucose at a rate of 20-22 mg/kg/min. Persistent hyperinsulinaemic hypoglycaemia of infancy was diagnosed from an inappropriately raised plasma insulin concentration (33 mU/l) at the time of hypoglycaemia (blood glucose < 0.5 mmol/l). Medical treatment with glucagon, somatostatin, and diazoxide led to only a modest reduction in the intravenous glucose requirement; a 95% pancreatectomy was performed and histological ''nesidioblastosis'' confirmed. In vitro electrophysiological studies using patch clamp techniques on isolated pancreatic beta cells characterised the ionic basis for insulin secretion in nesidioblastosis. The beta cells were depolarised in low ambient glucose concentrations with persistently firing action potentials; these were blocked reversibly by the calcium channel blocking agent verapamil. Persistent postoperative hyperinsulinaemic hypoglycaemia was treated with oral nifedipine. This increased median blood glucose concentrations from 3.5 to 4.8 mmol/l and increased in duration the child''s tolerance to fasting from 3 to 10.5 hours. These data allude to an abnormality in the ionic control of insulin release in nesidioblastosis and offer a new logical approach to treatment which requires further evaluation.     

Aerobic fitness: II. Orthostasis and VO2peak following head-down tilt.

To determine whether endurance exercise trained (ET) subjects would experience greater reductions in peak oxygen delivery and orthostatic tolerance (OT) than untrained (UT) subjects, both peak oxygen uptake (VO2peak) during upright bicycle ergometry and tolerance time during 70 degrees head-up tilt (HUT) were compared within and between groups before and after 4 h of -6 degrees head-down tilt (HDT). Eight ET subjects with a mean VO2peak of 61.7 +/- 1.6 ml.kg-1.min-1 were matched for age, height, and weight with eight UT subjects (VO2peak = 38.4 +/- 1.7 ml.kg-1.min-1). Following HDT, decreases in plasma volume (PV) were larger for ET subjects (-3.7 +/- 0.5 ml.kg-1) than for UT subjects (-2.3 +/- 0.3 ml.kg-1), P less than 0.03. Reductions in VO2peak for ET subjects (-5.4 +/- 1.1 ml.kg-1.min-1) were also greater than for UT subjects (-2.4 +/- 0.8 ml.kg-1.min-1), P less than 0.05. The ET (N = 6) subjects also had a significant decrease in OT time (-13.0 +/- 4.2 min) during post-HDT HUT, which was not observed for the UT group (N = 6). A significant inverse correlation was found pre-HDT VO2peak and the change in OT time, r = -0.74, P less than 0.01. The decrease in OT was also significantly correlated to the PV decrease, r = 0.59, P less than 0.04. The UT subjects had significantly augmented pressor responses to HUT manifested by the increases in both HR and MAP following HDT.(ABSTRACT TRUNCATED AT 250 WORDS)