Nocturnal Medications Dosing: Does It Really Make a Difference in Blood Pressure Control Among Patients with Chronic Kidney Disease?

Ambulatory blood pressure (BP) monitoring is superior to clinic BP monitoring in predicting long-term consequences of hypertension. This has raised interest in diurnal variation in BP and elevation in nighttime BP as a prognostic and therapeutic target. Several studies have identified prevalence of nocturnal hypertension in patients with accelerated progression of chronic kidney disease and target organ damage. Some studies suggest that nocturnal BP can be lowered by changing administration of antihypertensive medication to bed time; whether that results in retarding kidney disease progression is not very clear. Further research is needed to determine if certain classes of medications or interventions are superior in controlling nocturnal hypertension, and protocols need to be developed to screen patients for monitoring nocturnal BP. Further studies are needed to evaluate long-term renal outcomes of evening dosing in patients with nocturnal hypertension and chronic kidney disease.     

Poststroke acute dysexecutive syndrome,a disorder resulting from minor stroke due to disruption of network dynamics

Stroke patients with small central nervous system infarcts often demonstrate an acute dysexecutive syndrome characterized by difficulty with attention, concentration, and processing speed, independent of lesion size or location. We use magnetoencephalography (MEG) to show that disruption of network dynamics may be responsible. Nine patients with recent minor strokes and eight age-similar controls underwent cognitive screening using the Montreal cognitive assessment (MoCA) and MEG to evaluate differences in cerebral activation patterns. During MEG, subjects participated in a visual picture–word matching task. Task complexity was increased as testing progressed. Cluster-based permutation tests determined differences in activation patterns within the visual cortex, fusiform gyrus, and lateral temporal lobe. At visit 1, MoCA scores were significantly lower for patients than controls (median [interquartile range] = 26.0 [4] versus 29.5 [3], P = 0.005), and patient reaction times were increased. The amplitude of activation was significantly lower after infarct and demonstrated a pattern of temporal dispersion independent of stroke location. Differences were prominent in the fusiform gyrus and lateral temporal lobe. The pattern suggests that distributed network dysfunction may be responsible. Additionally, controls were able to modulate their cerebral activity based on task difficulty. In contrast, stroke patients exhibited the same low-amplitude response to all stimuli. Group differences remained, to a lesser degree, 6 mo later; while MoCA scores and reaction times improved for patients. This study suggests that function is a globally distributed property beyond area-specific functionality and illustrates the need for longer-term follow-up studies to determine whether abnormal activation patterns ultimately resolve or another mechanism underlies continued recovery.

Advances in acute stroke treatment have significantly reduced motor and language deficits, converting highly morbid large hemispheric lesions into smaller infarcts with better overall long-term outcomes (1, 2). Prior work has shown that the majority of individuals presenting for follow-up 4- to 6-wk postinfarct now exhibit what would be classified as “minor symptoms,” (3) with low stroke severity measured by the NIH Stroke Scale (NIHSS) (4) and modified Rankin Scale (mRS) (5) scores. Although these individuals lack a dense hemiparesis or aphasia, over half endorse some degree of cognitive impairment that significantly impacts their recovery. Interestingly, these symptoms are typically found to be independent of stroke size, location, or coexisting depression (6, 7).Poststroke cognitive decline has a substantial presence in the literature (8–13). However, we find that rather than memory impairment or confusion, patients without prior cognitive disability report immediate difficulty with executive function, focus, concentration, and attention after a minor stroke, hereafter referred to as poststroke acute dysexecutive syndrome (PSADES) (3). Dysexecutive syndrome has been previously described in individuals with anatomic lesions (14) as well as disorders, such as schizophrenia (15) and Alzheimer’s disease (14), affecting the frontal lobes. When mild, the syndrome can be hard for others to appreciate, particularly, in previously high-functioning individuals, but poststroke, these deficits are detectable on screening tests, such as the Montreal cognitive assessment (MoCA) (16) and other scales of activities of daily living compared to age-matched controls (3). Despite the fact that following stroke, symptoms typically improve over the first 3–6 mo of recovery, PSADES impedes many successful well-educated individuals from returning to cognitively driven professions given the uncertainty of their prognosis. These decisions affect lifestyle and quality of life, resulting in lasting long-term consequences.The pathophysiology underlying PSADES is poorly understood, as many times the inciting infarct is small and does not involve an area of the brain classically thought to be important for cognitive processing. Cognitive change due to deep white matter lesions (in multiplicity) has been well described (17), but there is no clear unifying physiological explanation regarding how a single small cortical or subcortical lesion may cause significant generalized cortical dysfunction. Some posit a “network” hypothesis suggesting that an individual requires an extensive system of neuronal connectivity, involving numerous cortical and subcortical regions, in order to complete a task (18). We propose that the cognitive dysfunction of PSADES may be the result of a disruption of general network dynamics due to lesions of the subcortical white matter tracts, which would, in turn, interfere with basic network function.This study was designed as a first step in evaluating the role of network dynamics during tasks requiring attention, concentration, speed, and accuracy; all skills difficult for patients poststroke. We used magnetoencephalography (MEG) to determine the differences in cerebral activation patterns in nine individuals with small strokes versus a group of eight age-similar controls by measuring the amplitude and latency of cerebral responses during a visual comprehension task at two time points: ∼1- and 6-mo postinfarct. Our analysis focused on the early visual, M170, and M400 components of the event-related potential from the occipital lobe, fusiform gyrus, and lateral temporal lobe given their importance in visual recognition and language processing (19–22).     

Massive transfusion in paediatric and adolescent trauma patients: Incidence,patient profile,and outcomes prior to a massive transfusion protocol

Objectives

The purpose of this study was to quantify the incidence, patient profile, and outcomes associated with massive transfusion in paediatric trauma patients prior to establishing a massive transfusion protocol.

Methods

We performed a retrospective review of paediatric trauma patients treated at London Heath Sciences Centre between January 1, 2006, and December 31, 2011. Inclusion criteria were Injury Severity Score (ISS) greater than 12 and age less than 18 years.

Results

435 patients met the inclusion criteria. Three hundred and fifty-six (82%) did not receive packed red blood cells in the first 24 h, 66 (15%) received a non-massive transfusion (<40 mL/kg), and 13 (3%) received a massive transfusion (>40 mL/kg). Coagulopathy of any kind was more common in massive transfusion (11/13; 85%) than non-massive (32/66; 49%) (p = 0.037). Hyperkalemia (18% versus 23%; p = 0.98) and hypocalcemia (41% versus 46%; p = 1.00) were similar in both groups. Of the 13 massively transfused patients, 9 had multisystem injuries due to a motor vehicle collision, 3 had non-accidental head injuries requiring surgical evacuation, and 1 had multiple stab wounds. In the absence of a massive transfusion protocol, only 8 of the 13 patients received both fresh frozen plasma and platelets in the first 24 h. Massive transfusion occurred in patients from across the age spectrum and was associated with severe injuries (mean ISS = 33), a higher incidence of severe head injuries (92%), longer hospital stay (mean = 36 days), and increased mortality (38%).

Conclusions

This study is the first to describe the incidence, complications, and outcomes associated with massive transfusion in paediatric trauma patients prior to a massive transfusion protocol. Massive transfusion occurred in 3% of patients and was associated with coagulopathy and poor outcomes. Protocols are needed to ensure that resuscitation occurs in a coordinated fashion and that patients are given appropriate amounts of fresh frozen plasma, platelets, and cryoprecipitate.     

Hydroxyapatite nanorods loaded with parathyroid hormone (PTH) synergistically enhance the net formative effect of PTH anabolic therapy

Parathyroid hormone (PTH) has been a major contributor to the anabolic therapy for osteoporosis, but its delivery to bone without losing activity and avoiding adverse local effects remain a challenge. Being the natural component of bone, use of hydroxyapatite for this purpose brings a major breakthrough in synergistic anabolism. This study focuses on synthesis, characterization and evaluation of in vitro and in vivo efficacy of PTH (1-34) adsorbed hydroxyapatite nanocarrier for synergistic enhancement in the anabolic activity of PTH for bone regeneration. The negative zeta potential of this nanocarrier facilitated its affinity to the Ca²⁺ rich bone tissue and solubilization at low pH enhanced specific delivery of PTH to the resorption pits in osteoporotic bone. In this process, PTH retained its anabolic effect and at the same time an increase in bone mineral content indicated enhancement of the net formative effect of the PTH anabolic therapy.