Early rapid naming longitudinally predicts shared variance in reading and arithmetic fluency.

A number of cognitive factors have been suggested to underlie development in reading and arithmetic skills. Although the two domains are strongly linked, only a few studies have investigated the processes that are shared between them during the early school years. Rapid automatized naming (RAN) has been identified as a strong predictor of a common fluency factor in reading and arithmetic. In the current study with 232 Norwegian children, we examined how RAN in preschool and Grade 1 relates to the shared and nonshared variance in arithmetic fluency and reading fluency in Grade 3. Furthermore, we examined whether related processing skills (phoneme awareness, working memory, speed of processing, and symbol knowledge) can account for the relationship between RAN and shared fluency-or if they predict variance that is unique to each domain. Our results show that RAN in both preschool and Grade 1 is a strong predictor of shared variance between reading fluency and arithmetic fluency measured several years later, whereas other predictors mainly relate to the nonshared parts of variance in the fluency outcomes. That is, control variables with the theoretical potential to explain some of RAN's relation to the overlap between reading and arithmetic fluency do not in fact account for this relationship. Our findings provide a starting point for future investigations of the mechanisms of rapid naming.

Positiva upplevelser av dopning: En kvalitativ studie av AAS-bruk och reflexiva kroppar [Positive experiences of doping: A qualitative study of AAS-use and reflexive bodies].

Research on doping usually has focused on social and individual problems, such as AAS-use in relations to substance abuse, criminality and health issues. The purpose of this study was to analyze the meaning of positive experiences of doping with Anabolic Androgenic Steroids (AAS), outside the traditional sports competition context. Eight respondents with own AAS-experiences were interviewed. The theoretical framework was elaborated from Giddens' discussion on individuals' self-reflexivity and the construction of the self-identity in the late modern age. The respondents' narratives were analyzed in four themes: (1) To be big and strong - masculine self-identity; (2) Revenge and to become a part of a community; (3) AAS and training as an "exit" from risk behavior and substance use; (4) Euphoria generator and anxiety reducer. The themes were analyzed as different processes of the respondents' constructions of new self-identities and lifestyles using their reflexive bodies in body regimes where weight training and use of AAS were crucial.

Intrathecal Methotrexate Containing the Preservative Benzyl Alcohol Erroneously Administered in Pediatric Leukemia Patients: Clinical Course and Preventive Process.

Administration of intrathecal chemotherapy for leukemia is a common procedure in pediatric oncology. The direct delivery of drug into the cerebral spinal fluid requires that no preservative be used. Preserved drugs administered in error can result in significant neurotoxicity. A case series is described where preservative-containing methotrexate was incidentally administered intrathecally. All patients were treated at Children's Hospitals and Clinics of Minnesota. Medical records of the patients affected were reviewed and abstracted for this report. Four children with acute lymphoblastic leukemia received 1 dose of intrathecal methotrexate that contained 0.07% benzyl alcohol in January 2019. Overall, minimal to no symptoms were seen after dosing. The error was traced to a drug shortage in which benzyl alcohol-containing methotrexate was obtained and incorrectly stocked. A novel replacement drug procurement process was developed within our institution. The process includes sequestered queues where a drug awaits evaluation and independent double check of entry accuracy in the electronic health record and pharmacy parenteral dose preparation software prior to release and use. In contrast to IV administration, intrathecal benzyl alcohol at concentrations ≥ 0.9% can cause significant neurotoxicity. Although minimal, if any, neurotoxicity was seen in patients who received a 10-fold lower concentration of benzyl alcohol than previously associated with complications, all institutions should recognize the potential for this error and implement similar safety precautions to ensure that this type of error will not occur.

Key Potentially Inappropriate Drugs in Pediatrics: The KIDs List.

OBJECTIVES: The safe use of medications in pediatric patients requires practitioners to consider the unique pharmacokinetics and pharmacodynamics of drugs prescribed in this age group. In an effort to create a standard of care for the safe use of medications in this population, a list of drugs that are potentially inappropriate for use in pediatric patients has been developed and titled the "KIDs List." METHODS: A panel of 7 pediatric pharmacists from the Pediatric Pharmacy Association were recruited to evaluate primary, secondary, and tertiary literature; FDA Pediatric Safety Communications; the Lexicomp electronic database; and product information for drugs that should be considered potentially inappropriate for use in pediatric patients. Information was rated using predefined criteria. A PubMed search was conducted using the following terms: adverse drug events OR adverse drug reactions. The search was limited to humans; age <18 years; case reports, observational studies, or clinical trials; and English language. No date range was used. Results were used to create an evidence-based list of candidate drugs that was then peer-reviewed and subjected to a 30-day public comment period prior to being finalized. RESULTS: A PubMed search yielded 4049 unique titles, of which 210 were deemed relevant for full review. Practitioner recommendations highlighted an additional 77 drugs. FDA Pediatric Safety Communications and the Lexicomp database yielded 22 and 619 drugs, respectively. After critical analysis, peer review, and public review the final KIDs List contains 67 drugs and/or drug classes and 10 excipients. CONCLUSIONS: This extensive effort led to compilation of the first list of drugs that are potentially inappropriate for prescribing in all or in a select subgroup of pediatric patients. If avoidance is not clinically possible, the drug should be used with caution and accompanied by appropriate monitoring.

Effects of sodium thiosulfate versus observation on development of cisplatin-induced hearing loss in children with cancer (ACCL0431): a multicentre, randomised, controlled, open-label, phase 3 trial.

BACKGROUND: Sodium thiosulfate is an antioxidant shown in preclinical studies in animals to prevent cisplatin-induced hearing loss with timed administration after cisplatin without compromising the antitumour efficacy of cisplatin. The primary aim of this study was to assess sodium thiosulfate for prevention of cisplatin-induced hearing loss in children and adolescents. METHODS: ACCL0431 was a multicentre, randomised, open-label, phase 3 trial that enrolled participants at 38 participating Children's Oncology Group hospitals in the USA and Canada. Eligible participants aged 1-18 years with newly diagnosed cancer and normal audiometry were randomly assigned (1:1) to receive sodium thiosulfate or observation (control group) in addition to their planned cisplatin-containing chemotherapy regimen, using permuted blocks of four. Randomisation was initially stratified by age and duration of cisplatin infusion. Stratification by previous cranial irradiation was added later as a protocol amendment. The allocation sequence was computer-generated centrally and concealed to all personnel. Participants received sodium thiosulfate 16 g/m2 intravenously 6 h after each cisplatin dose or observation. The primary endpoint was incidence of hearing loss 4 weeks after final cisplatin dose. Hearing was measured using standard audiometry and reviewed centrally by audiologists masked to allocation using American Speech-Language-Hearing Association criteria but treatment was not masked for participants or clinicians. Analysis of the primary endpoint was by modified intention to treat, which included all randomly assigned patients irrespective of treatment received but restricted to those assessable for hearing loss. Enrolment is complete and this report represents the final analysis. This trial is registered with ClinicalTrials.gov, number NCT00716976. FINDINGS: Between June 23, 2008, and Sept 28, 2012, 125 eligible participants were randomly assigned to either sodium thiosulfate (n=61) or observation (n=64). Of these, 104 participants were assessable for the primary endpoint (sodium thiosulfate, n=49; control, n=55). Hearing loss was identified in 14 (28·6%; 95% CI 16·6-43·3) participants in the sodium thiosulfate group compared with 31 (56·4%; 42·3-69·7) in the control group (p=0·00022). Adjusted for stratification variables, the likelihood of hearing loss was significantly lower in the sodium thiosulfate group compared with the control group (odds ratio 0·31, 95% CI 0·13-0·73; p=0·0036). The most common grade 3-4 haematological adverse events reported, irrespective of attribution, were neutropenia (117 [66%] of 177 participant cycles in the sodium thiosulfate group vs 145 [65%] of 223 in the control group), whereas the most common non-haematological adverse event was hypokalaemia (25 [17%] of 147 vs 22 [12%] of 187). Of 194 serious adverse events reported in 26 participants who had received sodium thiosulfate, none were deemed probably or definitely related to sodium thiosulfate; the most common serious adverse event was decreased neutrophil count: 26 episodes in 14 participants. INTERPRETATION: Sodium thiosulfate protects against cisplatin-induced hearing loss in children and is not associated with serious adverse events attributed to its use. Further research is needed to define the appropriate role for sodium thiosulfate among emerging otoprotection strategies. FUNDING: US National Cancer Institute.

Accidental Epidural Injection of Rocuronium in a Pediatric Patient: A Case Report and Literature Review.

Accidental administration of non-epidural drugs into the epidural or subarachnoid spaces may be associated with unexpected pain, morbidity, adverse effects, increased level of care, prolonged hospital stay, and mortality. We describe a 12-month-old admitted for secondary-stage hypospadias reconstruction. General anesthesia was induced with sevofiurane and a peripheral catheter was placed. Instead of ropivacaine, rocuronium (80 mg; 6.3 mg/kg) was injected into the epidural space by the caudal route. Surgery was uneventful and was completed 160 minutes after rocuronium was given. The patient exhibited paralysis with 1 of 4 twitches to the train-of-four with some posttetanic potentiation at the end of surgery. He was transferred to the pediatric intensive care unit for supportive ventilation and recovery. He did not experience oxygen desaturation or hypoventilation between the time of rocuronium administration and intubation. He was hemodynamically stable, without respiratory insufficiency, and his neurologic exam was normal, without motor or sensorial block. The patient was discharged home on the morning of the first postoperative day. Clinical examination 1 week after surgery revealed no lasting sequelae from the error.

Higher Pretreatment Blood Pressure Is Associated With Greater Posttraumatic Stress Disorder Symptom Reduction in Soldiers Treated With Prazosin.

BACKGROUND: In a previously reported positive randomized controlled trial of the α1-adrenoreceptor (α1AR) antagonist prazosin for combat posttraumatic stress disorder (PTSD) in 67 active duty soldiers, baseline symptoms did not predict therapeutic response. If increased brain α1AR activation in PTSD is the target of prazosin treatment action, higher brain α1AR activation should predict greater prazosin efficacy. Although brain α1AR activation is not measurable, coregulated peripheral α1AR activation could provide an estimate of brain α1AR activation. Standing blood pressure (BP) is an accessible biological parameter regulated by norepinephrine activation of α1ARs on peripheral arterioles. METHODS: Effects of baseline standing systolic and other BP parameters on PTSD outcome measures from the previously reported randomized controlled trial were analyzed using linear mixed-effects models. Prazosin participants (n = 32) and placebo participants (n = 35) were analyzed separately. RESULTS: In prazosin participants, each 10-mm Hg higher baseline standing systolic BP increment resulted in an additional 14-point reduction (improvement) of Clinician-Administered PTSD Scale total score at end point (p = .002). All other combinations of baseline BP parameters and PTSD outcome measures were similarly significant or demonstrated trends in the predicted direction. In placebo participants, there was no signal for a baseline BP effect on PTSD outcome measures. CONCLUSIONS: These findings suggest that higher standing BP is a biomarker that helps identify persons with combat PTSD who are likely to benefit from prazosin. These results also are consistent with α1AR activation contributing to PTSD pathophysiology in a subgroup of patients.

Fish Oil Lipid Emulsion-Associated Sea-Blue Histiocyte Syndrome in a Pediatric Patient.

A syndrome of hepatosplenomegaly, thrombocytopenia, and anemia and the presence of sea-blue histiocytes in bone marrow has been associated with parenteral soybean oil administration in patients receiving long-term total parenteral nutrition (TPN). A case is described here where this syndrome was observed in a pediatric patient who received long-term parenteral fish oil nutrition.

Retrospective analysis of large-dose intrapleural alteplase for complicated pediatric parapneumonic effusion and empyema.

OBJECTIVES: Medical treatment of complicated parapneumonic effusion or empyema in pediatric patients includes antibiotics and pleural space drainage. Intrapleural fibrinolysis may facilitate pleural drainage; however, there is a lack of consensus regarding the optimal dosing regimen. The primary purpose of this study was to evaluate the efficacy and safety of a large-dose intrapleural alteplase regimen in pediatric patients. Secondarily, this investigation sought to differentiate the clinical characteristics of responders and non-responders to intrapleural alteplase therapy. METHODS: All patients with parapneumonic effusions treated with intrapleural alteplase between June 2003 and December 2011 were reviewed retrospectively. Efficacy was assessed by comparing chest tube output, in mL/hr and mL/kg/hr, for 24 hours before and after the first dose of alteplase. Additional efficacy outcomes included duration of in situ chest tubes, a need for surgical intervention for pleural effusion, and length of hospital stay. Safety was assessed by frequency and severity of adverse events. Non-responders and responders were compared based on demographic and disease characteristics. Responders were defined as patients who did not require surgical intervention after intrapleural alteplase therapy. RESULTS: Seventy-three patients, aged 0.5 to 22.5 years, received intrapleural alteplase to facilitate pleural drainage. Median alteplase dose was 7 mg (range, 3 to 10 mg; median 0.38 mg/kg). Chest tube output increased from 10.7 to 24.2 mL/hr (p = 0.006), and median length of hospital stay was 9 days. Eighty-four percent of patients were responders. The most common adverse events were pain (20.5%) and oxygen desaturation greater than 10% from baseline (16.4%). High-flow nasal cannula was the most common intervention for oxygen desaturation to 80% to 90%. Nine patients (12%) required a blood transfusion during the study. CONCLUSION: Large-dose intrapleural alteplase is effective in facilitating pleural drainage in pediatric patients with complicated parapneumonic effusion or empyema. Common adverse effects include pain and oxygen desaturation. The potential for bleeding warrants clinical monitoring.

Neuroimaging, behavioral, and psychological sequelae of repetitive combined blast/impact mild traumatic brain injury in Iraq and Afghanistan war veterans.

Abstract Whether persisting cognitive complaints and postconcussive symptoms (PCS) reported by Iraq and Afghanistan war veterans with blast- and/or combined blast/impact-related mild traumatic brain injuries (mTBIs) are associated with enduring structural and/or functional brain abnormalities versus comorbid depression or posttraumatic stress disorder (PTSD) remains unclear. We sought to characterize relationships among these variables in a convenience sample of Iraq and Afghanistan-deployed veterans with (n=34) and without (n=18) a history of one or more combined blast/impact-related mTBIs. Participants underwent magnetic resonance imaging of fractional anisotropy (FA) and macromolecular proton fraction (MPF) to assess brain white matter (WM) integrity; [(18)F]-fluorodeoxyglucose positron emission tomography imaging of cerebral glucose metabolism (CMRglu); structured clinical assessments of blast exposure, psychiatric diagnoses, and PTSD symptoms; neurologic evaluations; and self-report scales of PCS, combat exposure, depression, sleep quality, and alcohol use. Veterans with versus without blast/impact-mTBIs exhibited reduced FA in the corpus callosum; reduced MPF values in subgyral, longitudinal, and cortical/subcortical WM tracts and gray matter (GM)/WM border regions (with a possible threshold effect beginning at 20 blast-mTBIs); reduced CMRglu in parietal, somatosensory, and visual cortices; and higher scores on measures of PCS, PTSD, combat exposure, depression, sleep disturbance, and alcohol use. Neuroimaging metrics did not differ between participants with versus without PTSD. Iraq and Afghanistan veterans with one or more blast-related mTBIs exhibit abnormalities of brain WM structural integrity and macromolecular organization and CMRglu that are not related to comorbid PTSD. These findings are congruent with recent neuropathological evidence of chronic brain injury in this cohort of veterans.

A trial of prazosin for combat trauma PTSD with nightmares in active-duty soldiers returned from Iraq and Afghanistan.

OBJECTIVE: The authors conducted a 15-week randomized controlled trial of the alpha-1 adrenoreceptor antagonist prazosin for combat trauma nightmares, sleep quality, global function, and overall symptoms in active-duty soldiers with posttraumatic stress disorder (PTSD) returned from combat deployments to Iraq and Afghanistan. METHOD: Sixty-seven soldiers were randomly assigned to treatment with prazosin or placebo for 15 weeks. Drug was titrated based on nightmare response over 6 weeks to a possible maximum dose of 5 mg midmorning and 20 mg at bedtime for men and 2 mg midmorning and 10 mg at bedtime for women. Mean achieved bedtime doses were 15.6 mg of prazosin (SD=6.0) and 18.8 mg of placebo (SD=3.3) for men and 7.0 mg of prazosin (SD=3.5) and 10.0 mg of placebo (SD=0.0) for women. Mean achieved midmorning doses were 4.0 mg of prazosin (SD=1.4) and 4.8 mg of placebo (SD=0.8) for men and 1.7 mg of prazosin (SD=0.5) and 2.0 mg of placebo (SD=0.0) mg for women. Primary outcome measures were the nightmare item of the Clinician-Administered PTSD Scale (CAPS), the Pittsburgh Sleep Quality Index, and the change item of the Clinical Global Impressions Scale anchored to functioning. Secondary outcome measures were the 17-item CAPS, the Hamilton Depression Rating Scale, the Patient Health Questionnaire-9, and the Quality of Life Index. Maintenance psychotropic medications and supportive psychotherapy were held constant. RESULTS: Prazosin was effective for trauma nightmares, sleep quality, global function, CAPS score, and the CAPS hyperarousal symptom cluster. Prazosin was well tolerated, and blood pressure changes did not differ between groups. CONCLUSIONS: Prazosin is effective for combat-related PTSD with trauma nightmares in active-duty soldiers, and benefits are clinically meaningful. Substantial residual symptoms suggest that studies combining prazosin with effective psychotherapies might demonstrate further benefit.

Recommendations for meeting the pediatric patient's need for a clinical pharmacist: a joint opinion of the Pediatrics Practice and Research Network of the American College of Clinical Pharmacy and the Pediatric Pharmacy Advocacy Group.

Children warrant access to care from clinical pharmacists trained in pediatrics. The American College of Clinical Pharmacy Pediatrics Practice and Research Network (ACCP Pediatrics PRN) released an opinion paper in 2005 with recommendations for improving the quality and quantity of pediatric pharmacy education in colleges of pharmacy, residency programs, and fellowships. Although progress has been made in increasing the availability of pediatric residencies, there is still much to be done to meet the direct care needs of pediatric patients. The purpose of this joint opinion paper is to outline strategies and recommendations for expanding the quality and capacity of pediatric clinical pharmacy practitioners by elevating the minimum expectations for pharmacists entering pediatric practice, standardizing pediatric pharmacy education, expanding the current number of pediatric clinical pharmacists, and creating an infrastructure for development of pediatric clinical pharmacists and clinical scientists. These recommendations may be used to provide both a conceptual framework and action items for schools of pharmacy, health care systems, and policymakers to work together to increase the quality and quantity of pediatric training, practice, and research initiatives.

Recommendations for Meeting the Pediatric Patient's Need for a Clinical Pharmacist: A Joint Opinion of the Pediatrics Practice and Research Network of the American College of Clinical Pharmacy and the Pediatric Pharmacy Advocacy Group.

Children warrant access to care from clinical pharmacists trained in pediatrics. The American College of Clinical Pharmacy Pediatrics Practice and Research Network (ACCP Pediatrics PRN) released an opinion paper in 2005 with recommendations for improving the quality and quantity of pediatric pharmacy education in colleges of pharmacy, residency programs, and fellowships. While progress has been made in increasing the availability of pediatric residencies, there is still much to be done to meet the direct care needs of pediatric patients. The purpose of this Joint Opinion paper is to outline strategies and recommendations for expanding the quality and capacity of pediatric clinical pharmacy practitioners by 1) elevating the minimum expectations for pharmacists entering practice to provide pediatric care; 2) standardizing pediatric pharmacy education; 3) expanding the current number of pediatric clinical pharmacists; and 4) creating an infrastructure for development of pediatric clinical pharmacists and clinical scientists. These recommendations may be used to provide both a conceptual framework and action items for schools of pharmacy, health care systems, and policymakers to work together to increase the quality and quantity of pediatric training, practice, or research initiatives.

High prevalence of chronic pituitary and target-organ hormone abnormalities after blast-related mild traumatic brain injury.

Studies of traumatic brain injury from all causes have found evidence of chronic hypopituitarism, defined by deficient production of one or more pituitary hormones at least 1 year after injury, in 25-50% of cases. Most studies found the occurrence of posttraumatic hypopituitarism (PTHP) to be unrelated to injury severity. Growth hormone deficiency (GHD) and hypogonadism were reported most frequently. Hypopituitarism, and in particular adult GHD, is associated with symptoms that resemble those of PTSD, including fatigue, anxiety, depression, irritability, insomnia, sexual dysfunction, cognitive deficiencies, and decreased quality of life. However, the prevalence of PTHP after blast-related mild TBI (mTBI), an extremely common injury in modern military operations, has not been characterized. We measured concentrations of 12 pituitary and target-organ hormones in two groups of male US Veterans of combat in Iraq or Afghanistan. One group consisted of participants with blast-related mTBI whose last blast exposure was at least 1 year prior to the study. The other consisted of Veterans with similar military deployment histories but without blast exposure. Eleven of 26, or 42% of participants with blast concussions were found to have abnormal hormone levels in one or more pituitary axes, a prevalence similar to that found in other forms of TBI. Five members of the mTBI group were found with markedly low age-adjusted insulin-like growth factor-I (IGF-I) levels indicative of probable GHD, and three had testosterone and gonadotropin concentrations consistent with hypogonadism. If symptoms characteristic of both PTHP and PTSD can be linked to pituitary dysfunction, they may be amenable to treatment with hormone replacement. Routine screening for chronic hypopituitarism after blast concussion shows promise for appropriately directing diagnostic and therapeutic decisions that otherwise may remain unconsidered and for markedly facilitating recovery and rehabilitation.

Otoacoustic emission screen results in critically ill neonates who received gentamicin in the first week of life.

STUDY OBJECTIVE: To characterize the extent that serum gentamicin concentrations are associated with hearing loss indicated by otoacoustic emission (OAE) screen failure in critically ill neonates receiving gentamicin in accordance with a high-dose, extended-interval dosing protocol. DESIGN: Retrospective medical record review. SETTING: Two neonatal intensive care units in a pediatric tertiary care system. PATIENTS: Sequential sample of 528 critically ill neonates who were admitted between February 2003 and January 2008 and who received a gentamicin pharmacokinetic consultation during the first week of life and an OAE hearing screen before hospital discharge. Neonates were stratified into two groups: very low birth weight (VLBW [≤ 1500 g]) and non-VLBW (> 1500 g). MEASUREMENTS AND MAIN RESULTS: Gentamicin was dosed intravenously to achieve a target calculated gentamicin peak serum concentration (C(max)) of 7-10 µg/ml and a target trough serum concentration (C(min)) of less than 2 µg/ml. The dosage administered was 4 mg/kg/dose every 48 hours if the neonate's birth weight was less than 1250 g or if the neonate was receiving indomethacin. Otherwise, the dosing interval was every 24 hours. Initial OAE screen results were obtained from the medical records, and follow-up results were collected for neonates who failed the initial OAE screen. The overall rate of OAE screen failure was 13.1% (69/528 patients). The rate of OAE screen failure was 34.1% (29/85 patients) in the VLBW neonates, which was significantly higher than the failure rate in non-VLBW neonates (9.0% [40/443 patients], p=0.001). Multivariate analysis of non-VLBW neonates determined that each 1-µg/ml increase in gentamicin C(max) was associated with an increased risk of OAE screen failure (odds ratio [OR] 1.4, 95% confidence interval (CI) 1.1-1.7, p=0.003). Further, the non-VLBW neonate subpopulation had an increased rate of OAE screen failure if the gentamicin C(max) exceeded 10 µg/ml (OR 2.2, 95% CI 1.1-4.2, p=0.022) compared with neonates whose C(max) was 10 µg/ml or lower. No association between serum gentamicin concentration and OAE screen failure could be determined among the VLBW neonates. CONCLUSION: Neonates weighing more than 1500 g at birth and whose gentamicin C(max) exceeded 10 µg/ml were at an increased risk for OAE screen failure. Monitoring and maintaining gentamicin C(max) at or below 10 µg/ml may minimize hearing impairment; however, further studies are necessary.

Cerebrocerebellar hypometabolism associated with repetitive blast exposure mild traumatic brain injury in 12 Iraq war Veterans with persistent post-concussive symptoms.

Disagreement exists regarding the extent to which persistent post-concussive symptoms (PCS) reported by Iraq combat Veterans with repeated episodes of mild traumatic brain injury (mTBI) from explosive blasts represent structural or functional brain damage or an epiphenomenon of comorbid depression or posttraumatic stress disorder (PTSD). Objective assessment of brain function in this population may clarify the issue. To this end, twelve Iraq war Veterans (32.0 ± 8.5 [mean ± standard deviation (SD)] years of age) reporting one or more blast exposures meeting American Congress of Rehabilitation Medicine criteria for mTBI and persistent PCS and 12 cognitively normal community volunteers (53.0 ± 4.6 years of age) without history of head trauma underwent brain fluorodeoxyglucose positron emission tomography (FDG-PET) and neuropsychological assessments and completed PCS and psychiatric symptom rating scales. Compared to controls, Veterans with mTBI (with or without PTSD) exhibited decreased cerebral metabolic rate of glucose in the cerebellum, vermis, pons, and medial temporal lobe. They also exhibited subtle impairments in verbal fluency, cognitive processing speed, attention, and working memory, similar to those reported in the literature for patients with cerebellar lesions. These FDG-PET imaging findings suggest that regional brain hypometabolism may constitute a neurobiological substrate for chronic PCS in Iraq combat Veterans with repetitive blast-trauma mTBI. Given the potential public health implications of these findings, further investigation of brain function in these Veterans appears warranted.

Pharmacokinetic outcomes of a simplified, weight-based, extended-interval gentamicin dosing protocol in critically ill neonates.

STUDY OBJECTIVE: To determine the pharmacokinetic outcomes of a simplified, weight-based, extended-interval gentamicin dosing protocol for critically ill neonates. DESIGN: Retrospective medical record review with pharmacokinetic analysis. SETTING: Two neonatal intensive care units in a pediatric tertiary care system. PATIENTS: Sequential sample of 644 critically ill neonates less than 7 days old without evidence of renal dysfunction who received gentamicin, dosed by using a simplified, weight-based, extended-interval dosing protocol, on the first day of life for suspected sepsis between February 2003 and January 2008, and who had subsequent gentamicin plasma concentrations measured during their first week of life. MEASUREMENTS AND MAIN RESULTS: Data were collected on birth weight, gestational age at birth, serum creatinine concentration during the first 10 days of life, medical conditions, and concomitant drugs. Gentamicin dosing and its pharmacokinetic parameters were noted for each patient. A mean dose of 3.96 mg/kg/dose of gentamicin was administered intravenously every 48 hours in neonates weighing less than 1250 g at birth and every 24 hours in those weighing 1250 g or more. If the neonate received concurrent indomethacin, however, gentamicin was given every 48 hours. Protocol success was defined as a peak gentamicin plasma concentration of 7-10 mg/L and a trough concentration less than 2 mg/L. Mean gentamicin peak and trough concentrations were 9.38 mg/L (95% confidence interval [CI] 9.24-9.52 mg/L) and 1.00 mg/L (95% CI 0.96-1.04 mg/L), respectively. With use of the protocol, 361 neonates (56.1%) achieved gentamicin peak plasma concentrations in the range defined as successful and 610 neonates (94.7%) achieved successful trough concentrations. The mean gentamicin apparent volume of distribution and half-life were 0.48 L/kg (95% CI 0.47-0.49 L/kg) and 8.31 hours (95% CI 8.09-8.52 hrs), respectively. CONCLUSION: This simplified, weight-based, extended-interval gentamicin dosing protocol for critically ill neonates was effective in achieving therapeutic peak plasma concentrations of gentamicin in most of the patients and, as a high proportion of patients had acceptable trough concentrations, may minimize the potential for toxicity.

Prazosin for the treatment of behavioral symptoms in patients with Alzheimer disease with agitation and aggression.

OBJECTIVES: Agitation/aggression in Alzheimer disease (AD) is a major cause of patient distress, caregiver burden, and institutionalization. Enhanced behavioral responsiveness to central nervous system norepinephrine (NE) release may contribute to the pathophysiology of agitation/aggression in AD. Prazosin, a nonsedating generic medication used for hypertension and benign prostatic hypertrophy, antagonizes NE effects at brain postsynaptic alpha-1 adrenoreceptors. This pilot study examined the efficacy and tolerability of prazosin for behavioral symptoms in patients with agitation/aggression in AD. DESIGN: Double-blind, placebo controlled, parallel group study. SETTING: A university AD center and a nursing home in Seattle, WA. PARTICIPANTS: Twenty-two nursing home and community-dwelling participants with agitation/aggression and probable or possible AD (mean age: 80.6 +/- 11.2). INTERVENTION: Randomization to placebo (N = 11) or prazosin (N = 11). Medication was initiated at 1 mg/day and increased up to 6 mg/day using a flexible dosing algorithm. MEASUREMENTS: The Brief Psychiatric Rating Scale (BPRS) and Neuropsychiatric Inventory (NPI) at Weeks 1, 2, 4, 6, and 8. The Clinical Global Impression of Change (CGIC) at Week 8. RESULTS: Participants taking prazosin (mean dose: 5.7 +/- 0.9 mg/day) had greater improvements than those taking placebo (mean dose: 5.6 +/- 1.2 mg/day) on the NPI (mean change: -19 +/- 21 versus -2 +/- 15, chi = 6.32, df = 1, p = 0.012) and BPRS (mean change: -9 +/- 9 versus -3 +/- 5, chi = 4.42, df = 1, p = 0.036) based on linear mixed effects models and the CGIC (mean: 2.6 +/- 1.0 versus 4.5 +/- 1.6, z = 2.57, p = 0.011 [Mann-Whitney test]). Adverse effects and blood pressure changes were similar between prazosin and placebo groups. CONCLUSION: Prazosin was well tolerated and improved behavioral symptoms in patients with agitation/aggression in AD.