Character-space-limited online prescription drug communications: Four experimental studies.

BACKGROUND: Character-space-limited (CSL) communications (e.g., tweets) present a challenge for maintaining fair balance between risks and benefits in direct-to-consumer prescription drug promotion. Current FDA guidance advises incorporating risk information within the CSL communication. Because space is limited, others suggest only linking to risk information. OBJECTIVES: The primary objectives were to examine the effects of (1) including substantive risk information in CSL communications versus only providing a link to risk information and (2) including risks and benefits versus only risks on the linked landing page. METHODS: Four experimental studies (N = 469 per study) were conducted. Participants self-reported migraine (Studies 1 and 2) or being overweight (Studies 3 and 4). Participants were instructed to either browse or search a mock Google (Studies 1 and 3) or Twitter (Studies 2 and 4) search page that included the study CSL communication. The CSL communication either did or did not include risk information, and its linked landing page either did or did not include benefit information. Half the participants used a mobile device and half used a desktop/laptop. Participants viewed the search page once without prompting to pay attention to the CSL communication and a second time with prompting. RESULTS: Including the risk in the CSL communication increased the likelihood that participants would recognize the risk after the first viewing (three studies) and second viewing (four studies). However, after the second viewing, including the risk decreased the likelihood that participants would click the landing-page link (three studies), and decreased the number of landing-page-only risks recognized (three studies). Including the drug's benefit on the landing page increased benefit recognition (four studies) without negatively affecting risk recognition or risk perceptions (three studies). CONCLUSIONS: The results provide a first look at the tradeoffs for consumer understanding of drug risks and benefits when drugs are promoted in CSL communications.

Posterior resection of sacral osteosarcoma utilizing cement-infused chest tube interbody reconstruction and lumbopelvic fusion.

BACKGROUND: Primary osteosarcoma (OS) of the spine is very rare. En bloc resection of spinal OS is challenging due to anatomical constraints. Surgical planning must balance the benefits of en bloc resection with its potential risks of causing a significant neurological deficit. In this case, we successfully performed a posterior-only approach for decompression with S1 reconstruction via a cement-infused chest tube interbody device, along with a navigated L4 to pelvis fusion. CASE DESCRIPTION: A 49-year-old female presented with a primary sacral OS. Computed tomography (CT) and magnetic resonance (MR) imaging revealed an S1 lytic vertebral body lesion with severe stenosis and progressive L5 on S1 anterior subluxation. Surgical decompression with tumor resection and S1 corpectomy with S1 reconstruction via a cement-infused 32-French chest tube interbody device accompanied by L4 -pelvis fusion utilizing S2-alar-iliac screws was completed. 6 months postoperatively, the patient continues to have significant pain relief and the instrumentation remains intact. CONCLUSION: A 49-year-old female with an S1 OS successfully underwent a posterior-only approach that included an S1 corpectomy with anterior column reconstruction via a cement-infused chest tube interbody plus a navigated L4 to pelvis fusion.

A phase II randomized controlled trial of tiopronin for aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Delayed cerebral ischemia (DCI) is a significant contributor to poor outcomes after aneurysmal subarachnoid hemorrhage (aSAH). The neurotoxin 3-aminopropanal (3-AP) is upregulated in cerebral ischemia. This phase II clinical trial evaluated the efficacy of tiopronin in reducing CSF 3-AP levels in patients with aSAH. METHODS: In this prospective, randomized, double-blind, placebo-controlled, multicenter clinical trial, 60 patients were assigned to receive tiopronin or placebo in a 1:1 ratio. Treatment was commenced within 96 hours after aSAH onset, administered at a dose of 3 g daily, and continued until 14 days after aSAH or hospital discharge, whichever occurred earlier. The primary efficacy outcome was the CSF 3-AP level at 7 ± 1 days after aSAH. RESULTS: Of the 60 enrolled patients, 29 (97%) and 27 (93%) in the tiopronin and placebo arms, respectively, received more than one dose of the study drug or placebo. At post-aSAH day 7 ± 1, CSF samples were available in 41% (n = 12/29) and 48% (n = 13/27) of patients in the tiopronin and placebo arms, respectively. No difference in CSF 3-AP levels at post-aSAH day 7 ± 1 was observed between the study arms (11 ± 12 nmol/mL vs 13 ± 18 nmol/mL; p = 0.766). Prespecified adverse events led to early treatment cessation for 4 patients in the tiopronin arm and 2 in the placebo arm. CONCLUSIONS: The power of this study was affected by missing data. Therefore, the authors could not establish or refute an effect of tiopronin on CSF 3-AP levels. Additional observational studies investigating the role of 3-AP as a biomarker for DCI may be warranted prior to its use as a molecular target in future clinical trials.Clinical trial registration no.: NCT01095731 (ClinicalTrials.gov).

Genetic risk factors for spontaneous intracerebral haemorrhage.

Intracerebral haemorrhage (ICH) is associated with the greatest morbidity and mortality of all stroke subtypes. Established risk factors for ICH include hypertension, alcohol use, current cigarette smoking, and use of oral anticoagulants and/or antiplatelet agents. Familial aggregation of ICH has been observed, and the heritability of ICH risk has been estimated at 44%. Few genes have been found to be associated with ICH at the population level, and much of the evidence for genetic risk factors for ICH comes from single studies conducted in relatively small and homogenous populations. In this Review, we summarize the current knowledge of genetic variants associated with primary spontaneous ICH. Two variants of the gene encoding apolipoprotein E (APOE) - which also contributes to the pathogenesis of cerebral amyloid angiopathy - are the most likely candidates for variants that increase the risk of ICH. Other promising candidates for risk alleles in ICH include variants of the genes ACE, PMF1/SLC25A44, COL4A2, and MTHFR. Other genetic variants, related to haemostasis, lipid metabolism, inflammation, and the CNS microenvironment, have been linked to ICH in single candidate gene studies. Although evidence for genetic contributions to the risk of ICH exists, we do not yet fully understand how and to what extent this information can be utilized to prevent and treat ICH.

Partner Facilitation and Partner Interference in Individuals' Weight Loss Goals.

Drawing on the logic of the relational turbulence model, this study examined the ways in which romantic partners facilitate and interfere with individuals' weight loss goals. Participants (N = 122) described the ways in which their romantic partner had recently helped or hindered their weight loss at four times over the course of 2 months. We conducted a content analysis of responses to identify themes of partner facilitation (Research Question 1 [RQ1]) and partner interference (RQ2) in individuals' weight loss goals. Results revealed seven themes of partner facilitation: (a) partner enabling diet, (b) motivation and encouragement, (c) emotional support and positive reinforcement, (d) exercising together, (e) partner enabling exercise, (f) dieting together, and (g) relationship influence and priorities. Four themes of partner interference emerged in the data: (a) inability to plan for healthy meals, (b) inability to control the food environment, (c) preventing or discouraging exercise, and (d) emotional or relational discouragement.

Variability in outcome after elective cerebral aneurysm repair in high-volume academic medical centers.

BACKGROUND AND PURPOSE: Unruptured intracranial aneurysm repair is the most commonly performed procedure for the prevention of hemorrhagic stroke. Despite efforts to regionalize care in high-volume centers, overall results have improved little. This study aims to determine the effectiveness in improving outcomes of previous efforts to regionalize unruptured intracranial aneurysm repair to high-volume centers and to recommend future steps toward that goal. METHODS: Using data obtained via the New York Statewide Planning and Research Cooperative System, this study included all patients admitted to any of the 10 highest volume centers in New York state between 2005 and 2010 with a principal diagnosis of unruptured intracranial aneurysm who were treated either by microsurgical or endovascular repair. Mixed-effects logistic regression was used to determine the degree to which hospital-level and patient-level variables contributed to observed variation in good outcome, defined as discharge to home, between hospitals. RESULTS: Of 3499 patients treated during the study period, 2692 (76.9%) were treated at the 10 highest volume centers, with 2198 (81.6%) experiencing a good outcome. Good outcomes varied widely between centers, with 44.6% to 91.1% of clipped patients and 75.4% to 92.1% of coiled patients discharged home. Mixed-effects logistic regression revealed that procedural volume accounts for 85.8% of the between-hospital variation in outcome. CONCLUSIONS: There is notable interhospital heterogeneity in outcomes among even the largest volume unruptured intracranial aneurysm referral centers. Although further regionalization may be needed, mandatory participation in prospective, adjudicated registries will be necessary to reliably identify factors associated with superior outcomes.

Volume-dependent effect of perihaematomal oedema on outcome for spontaneous intracerebral haemorrhages.

INTRODUCTION: It is still unknown whether subsequent perihaematomal oedema (PHE) formation further increases the odds of an unfavourable outcome. METHODS: Demographic, clinical, radiographic and outcome data were prospectively collected in a single large academic centre. A multiple logistic regression model was then developed to determine the effect of admission oedema volume on outcome. RESULTS: 133 patients were analysed in this study. While there was no significant association between relative PHE volume and discharge outcome (p=0.713), a strong relationship was observed between absolute PHE volume and discharge outcome (p=0.009). In a multivariate model incorporating known predictors of outcome, as well as other factors found to be significant in our univariate analysis, absolute PHE volume remained a significant predictor of poor outcome only in patients with intracerebral haemorrhage (ICH) volumes ≤30 cm(3) (OR 1.123, 95% CI 1.021 to 1.273, p=0.034). An increase in absolute PHE volume of 10 cm(3) in these patients was found to increase the odds of poor outcome on discharge by a factor of 3.19. CONCLUSIONS: Our findings suggest that the effect of absolute PHE volume on functional outcome following ICH is dependent on haematoma size, with only patients with smaller haemorrhages exhibiting poorer outcome with worse PHE. Further studies are needed to define the precise role of PHE in driving outcome following ICH.

Effectiveness and safety of nicardipine and labetalol infusion for blood pressure management in patients with intracerebral and subarachnoid hemorrhage.

BACKGROUND: Nicardipine and labetalol are two commonly used antihypertensives for treating elevated blood pressures in the setting of intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH). There are no studies comparing these two agents as continuous infusions. METHODS: A retrospective chart review was conducted of patients admitted between November 2009 and January 2011 with ICH and SAH to compare effectiveness and safety between both agents. Percent time spent at goal was set as the primary outcome. The secondary outcomes included blood pressure variability, time to goal, incidence of bradycardia, tachycardia, and hypotension. RESULTS: A total of 81 patients were available for analysis, 10 initiated on labetalol (LAB), 57 on nicardipine (NIC), and 14 required the combination of these agents (COMB) to reach goal. We found no difference between NIC, LAB, and the COMB groups in the median percent time at goal [88 % (61-98); 93 % (51-99); 66 % (25-95), (p = NS)]. Median percentage of blood pressure variability, hypotension, and bradycardia were also comparable between groups, however, more tachycardia was observed in the COMB group versus both LAB and NIC groups (45 vs. 0 vs. 3 %; p < 0.001). Mean time to goal SBP in 24 patients who had BP readings available at 1st h of initiation was 32 ± 34 min in the NIC group and 53 ± 42 min in the LAB group (p = 0.03). CONCLUSIONS: Both agents appear equally effective and safe for blood pressure control in SAH and ICH during the initial admission hours. A prospective study is needed to validate these findings.

Epidemiological trends in the neurological intensive care unit from 2000 to 2008.

Intensive care units (ICU) specializing in the treatment of patients with neurological diseases (Neuro-ICU) have become increasingly common. However, there are few data on the longitudinal demographics of this patient population. Identifying admission trends may provide targets for improving resource utilization. We performed a retrospective analysis of admission logs for primary diagnosis, age, sex, and length of stay, for all patients admitted to the Neuro-ICU at Columbia University Medical Center (CUMC) between 2000 and 2008. From 2000 to 2008, inclusive, the total number of Neuro-ICU admissions increased by 49.9%. Overall mean patient age (54.6 ± 17.4 to 56.2 ± 18.0 years, p=0.041) and gender (55.9-50.3% female, p=0.005) changed significantly, while median length of stay (2 days) did not. When comparing the time period prior to construction of a larger Neuro-ICU (2000-2004) to that after completion (2005-2008), patient age (56.0 ± 17.6 compared to 56.9 ± 17.5 years, p=0.012) and median length of stay (1 compared to 2 days, p<0.001) both significantly increased. Construction of a newer, larger Neuro-ICU at CUMC led to a substantial increase in admissions and changes in diagnoses from 2000 to 2008. Advances in neurocritical care, neurosurgical practices, and the local and global expansion and utilization of ICU resources likely led to differences in lengths of stay.

Predictors of long-term shunt-dependent hydrocephalus in patients with intracerebral hemorrhage requiring emergency cerebrospinal fluid diversion.

OBJECT: Intracerebral hemorrhage (ICH) is frequently complicated by acute hydrocephalus, necessitating emergency CSF diversion with a subset of patients, ultimately requiring long-term treatment via placement of permanent ventricular shunts. It is unclear what factors may predict the need for ventricular shunt placement in this patient population. METHODS: The authors performed a retrospective analysis of a prospective database (ICH Outcomes Project) containing patients with nontraumatic ICH admitted to the neurological ICU at Columbia University Medical Center between January 2009 and September 2011. A multiple logistic regression model was developed to identify independent predictors of shunt-dependent hydrocephalus after ICH. The following variables were included: patient age, admission Glasgow Coma Scale score, temporal horn diameter on admission CT imaging, bicaudate index, admission ICH volume and location, intraventricular hemorrhage volume, Graeb score, LeRoux score, third or fourth ventricle hemorrhage, and intracranial pressure (ICP) and ventriculitis during hospital stay. RESULTS: Of 210 patients prospectively enrolled in the ICH Outcomes Project, 64 required emergency CSF diversion via placement of an external ventricular drain and were included in the final cohort. Thirteen of these patients underwent permanent ventricular CSF shunting prior to discharge. In univariate analysis, only thalamic hemorrhage and elevated ICP were significantly associated with the requirement for permanent CSF diversion, with p values of 0.008 and 0.033, respectively. Each remained significant in a multiple logistic regression model in which both variables were present. CONCLUSIONS: Of patients with ICH requiring emergency CSF diversion, those with persistently elevated ICP and thalamic location of their hemorrhage are at increased odds of developing persistent hydrocephalus, necessitating permanent ventricular shunt placement. These factors may assist in predicting which patients will require permanent CSF diversion and could ultimately lead to improvements in the management of this disorder and the outcome in patients with ICH.

Acute effects of nimodipine on cerebral vasculature and brain metabolism in high grade subarachnoid hemorrhage patients.

BACKGROUND: Nimodipine is the only medication shown to improve outcomes after aneurysmal subarachnoid hemorrhage (SAH). Preliminary theories regarding the mechanism by which it prevents vasospasm have been challenged. The acute physiologic and metabolic effects of oral Nimodipine have not been examined in patients with poor-grade SAH. METHODS: This is an observational study performed in 16 poor-grade SAH patients undergoing multimodality monitoring who received oral Nimodipine as part of routine clinical care. A total of 663 doses of Nimodipine were observed. Changes in physiologic measurements including MAP, CPP, ICP, P(bt)O(2), and CBF were examined. RESULTS: Administration of oral Nimodipine was associated with a 1.33 mmHg decrease in MAP (P < 0.001) and a 1.22 mmHg decrease in CPP (P < 0.001). When administration of Nimodipine was associated with MAP decreases, P(bt)O(2) (1.03 mmHg; P < 0.001) and CBF (0.39 ml/100 g/min; P = 0.002) also decreased. CONCLUSIONS: Despite CPP targeted therapy with vasopressor medication, oral Nimodipine was associated with a decrease in MAP and CPP. When Nimodipine administration was associated with a decrease in MAP, there were concomitant drops in P(bt)O(2) and CBF. These findings suggest that MAP support after oral Nimodipine may be important to maintain adequate CBF in patients with poor-grade subarachnoid hemorrhage.

Evaluation of intraventricular hemorrhage assessment methods for predicting outcome following intracerebral hemorrhage.

OBJECT: Intraventricular hemorrhage (IVH) associated with intracerebral hemorrhage (ICH) is an independent predictor of poor outcome. Clinical methods for evaluating IVH, however, are not well established. This study sought to determine the best IVH grading scale by evaluating the predictive accuracies of IVH, Graeb, and LeRoux scores in an independent cohort of ICH patients with IVH. Subacute IVH dynamics as well as the impact of external ventricular drain (EVD) placement on IVH and outcome were also investigated. METHODS: A consecutive cohort of 142 primary ICH patients with IVH was admitted to Columbia University Medical Center between February 2009 and February 2011. Baseline demographics, clinical presentation, and hospital course were prospectively recorded. Admission CT scans performed within 24 hours of onset were reviewed for ICH location, hematoma volume, and presence of IVH. Intraventricular hemorrhage was categorized according to IVH, Graeb, and LeRoux scores. For each patient, the last scan performed within 6 days of ictus was similarly evaluated. Outcomes at discharge were assessed using the modified Rankin Scale (mRS). Receiver operating characteristic analysis was used to determine the predictive accuracies of the grading scales for poor outcome (mRS score ≥ 3). RESULTS: Seventy-three primary ICH patients (51%) had IVH. Median admission IVH, Graeb, and LeRoux scores were 13, 6, and 8, respectively. Median IVH, Graeb and LeRoux scores decreased to 9 (p = 0.005), 4 (p = 0.002), and 4 (p = 0.003), respectively, within 6 days of ictus. Poor outcome was noted in 55 patients (75%). Areas under the receiver operating characteristic curve were similar among the IVH, Graeb, and LeRoux scores (0.745, 0.743, and 0.744, respectively) and within 6 days postictus (0.765, 0.722, 0.723, respectively). Moreover, the IVH, Graeb, and LeRoux scores had similar maximum Youden Indices both at admission (0.515 vs 0.477 vs 0.440, respectively) and within 6 days postictus (0.515 vs 0.339 vs 0.365, respectively). Patients who received EVDs had higher mean IVH volumes (23 ± 26 ml vs 9 ± 11 ml, p = 0.003) and increased incidence of Glasgow Coma Scale scores < 8 (67% vs 38%, p = 0.015) and hydrocephalus (82% vs 50%, p = 0.004) at admission but had similar outcome as those who did not receive an EVD. CONCLUSIONS: The IVH, Graeb, and LeRoux scores predict outcome well with similarly good accuracy in ICH patients with IVH when assessed at admission and within 6 days after hemorrhage. Therefore, any of one of the scores would be equally useful for assessing IVH severity and risk-stratifying ICH patients with regard to outcome. These results suggest that EVD placement may be beneficial for patients with severe IVH, who have particularly poor prognosis at admission, but a randomized clinical trial is needed to conclusively demonstrate its therapeutic value.

A comparative evaluation of existing grading scales in intracerebral hemorrhage.

BACKGROUND: In recent years, a multitude of clinical grading scales have been created to help identify patients at greater risk of poor outcome following ICH. We sought to validate and compare eight of the most frequently used ICH grading scales in a prospective cohort. METHODS: Eight grading scales were calculated for 67 patients with non-traumatic ICH enrolled in the prospective intracerebral hemorrhage outcomes project (ICHOP) database. Receiver operating characteristic (ROC) analysis, including area under the curve (AUC) and maximum Youden Index were used to assess the ability of each score to predict in-hospital mortality, long-term (3 months) mortality, and functional outcome at 3 months (mRS ≥ 3). RESULTS: All scales demonstrated excellent to outstanding discrimination for in-hospital and long-term mortality, with no significant differences between them after controlling for the false discovery rate. All scales demonstrated acceptable to outstanding discrimination for functional outcome at 3 months, with the new ICH score demonstrating significantly lower AUC than 6 of the 8 scores. Essen ICH score was the only score to demonstrate outstanding discrimination for each outcome measure. CONCLUSION: Though significant differences were minimal in our cohort, we showed the existing selection of ICH grading scales to be useful in stratifying patients according to risk of mortality and poor functional outcome. Continued validation and comparison in large prospective cohorts will bring the goal of a singular prognostic model for ICH closer to fruition.

Prevention of shivering during therapeutic temperature modulation: the Columbia anti-shivering protocol.

BACKGROUND: As the practice of aggressive temperature control has become more commonplace, new clinical problems are arising, of which shivering is the most common. Treatment for shivering while avoiding the negative consequences of many anti-shivering therapies is often difficult. We have developed a stepwise protocol that emphasizes use of the least sedating regimen to achieve adequate shiver control. METHODS: All patients treated with temperature modulating devices in the neurological intensive care unit were prospectively entered into a database. Baseline demographic information, daily temperature goals, best daily GCS, and type and cumulative dose of anti-shivering agents were recorded. RESULTS: We collected 213 patients who underwent 1388 patient days of temperature modulation. Eighty-nine patients underwent hypothermia and 124 patients underwent induced normothermia. In 18% of patients and 33% of the total patient days only none-sedating baseline interventions were needed. The first agent used was most commonly dexmeditomidine at 50% of the time, followed by an opiate and increased doses of propofol. Younger patients, men, and decreased BSA were factors associated with increased number of anti-shivering interventions. CONCLUSIONS: A significant proportion of patients undergoing temperature modulation can be effectively treated for shivering without over-sedation and paralysis. Patients at higher risk for needing more interventions are younger men with decreased BSA.

Clinical grading scales in intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) carries higher risk of long-term disability and mortality than any other form of stroke. Despite greater understanding of ICH pathophysiology, treatment options for this devastating condition remain limited. Moreover, a lack of a standard, universally accepted clinical grading scale for ICH has contributed to variations in management protocols and clinical trial designs. Grading scales are essential for standardized assessment and communication among physicians, selecting optimized treatment regiments, and designing effective clinical trials. There currently exist a number of ICH grading scales and prognostic models that have been developed for mortality and/or functional outcome, particularly 30 days after the ICH onset. Numerous reliable scales have been externally validated in heterogeneous populations. We extensively reviewed the inherent strengths and limitations of all the existing clinical ICH grading scales based on their development and validation methodology. For all ICH grading scales, we carefully observed study design and the definition and timing of outcome assessment to elucidate inconsistencies in grading scale derivation and application. Ultimately, we call for an expansive, prospective, multi-center clinical outcome study to clearly define all aspects of ICH, establish ideal grading scales, and standardized management protocols to enable the identification of novel and effective therapies in ICH.