The PAX LC Trial: A Decentralized, Phase 2, Randomized, Double-Blind Study of Nirmatrelvir/Ritonavir Compared with Placebo/Ritonavir for Long COVID.

BACKGROUND: Individuals with long COVID lack evidence-based treatments and have difficulty participating in traditional site-based trials. Our digital, decentralized trial investigates the efficacy and safety of nirmatrelvir/ritonavir, targeting viral persistence as a potential cause of long COVID. METHODS: The PAX LC trial (NCT05668091) is a Phase 2, 1:1 randomized, double-blind, superiority, placebo-controlled trial in 100 community-dwelling, highly symptomatic adult participants with long COVID residing in the 48 contiguous US states to determine the efficacy, safety, and tolerability of 15 days of nirmatrelvir/ritonavir compared with placebo/ritonavir. Participants are recruited via patient groups, cultural ambassadors, and social media platforms. Medical records are reviewed through a platform facilitating participant-mediated data acquisition from electronic health records nationwide. During the drug treatment, participants complete daily digital diaries using a web-based application. Blood draws for eligibility and safety assessments are conducted at or near participants' homes. The study drug is shipped directly to participants' homes. The primary endpoint is the PROMIS-29 Physical Health Summary Score difference between baseline and Day 28, evaluated by a mixed model repeated measure analysis. Secondary endpoints include PROMIS-29 (Mental Health Summary Score and all items), Modified GSQ-30 with supplemental symptoms questionnaire, COVID Core Outcome Measures for Recovery, EQ-5D-5L (Utility Score and all items), PGIS 1 and 2, PGIC 1 and 2, and healthcare utilization. The trial incorporates immunophenotyping to identify long COVID biomarkers and treatment responders. CONCLUSION: The PAX LC trial uses a novel decentralized design and a participant-centric approach to test a 15-day regimen of nirmatrelvir/ritonavir for long COVID.

A structured approach to EHR surveillance of diagnostic error in acute care: an exploratory analysis of two institutionally-defined case cohorts.

OBJECTIVES: To test a structured electronic health record (EHR) case review process to identify diagnostic errors (DE) and diagnostic process failures (DPFs) in acute care. METHODS: We adapted validated tools (Safer Dx, Diagnostic Error Evaluation Research [DEER] Taxonomy) to assess the diagnostic process during the hospital encounter and categorized 13 postulated e-triggers. We created two test cohorts of all preventable cases (n=28) and an equal number of randomly sampled non-preventable cases (n=28) from 365 adult general medicine patients who expired and underwent our institution's mortality case review process. After excluding patients with a length of stay of more than one month, each case was reviewed by two blinded clinicians trained in our process and by an expert panel. Inter-rater reliability was assessed. We compared the frequency of DE contributing to death in both cohorts, as well as mean DPFs and e-triggers for DE positive and negative cases within each cohort. RESULTS: Twenty-seven (96.4%) preventable and 24 (85.7%) non-preventable cases underwent our review process. Inter-rater reliability was moderate between individual reviewers (Cohen's kappa 0.41) and substantial with the expert panel (Cohen's kappa 0.74). The frequency of DE contributing to death was significantly higher for the preventable compared to the non-preventable cohort (56% vs. 17%, OR 6.25 [1.68, 23.27], p<0.01). Mean DPFs and e-triggers were significantly and non-significantly higher for DE positive compared to DE negative cases in each cohort, respectively. CONCLUSIONS: We observed substantial agreement among final consensus and expert panel reviews using our structured EHR case review process. DEs contributing to death associated with DPFs were identified in institutionally designated preventable and non-preventable cases. While e-triggers may be useful for discriminating DE positive from DE negative cases, larger studies are required for validation. Our approach has potential to augment institutional mortality case review processes with respect to DE surveillance.

Analyzing diagnostic errors in the acute setting: a process-driven approach.

OBJECTIVES: We describe an approach for analyzing failures in diagnostic processes in a small, enriched cohort of general medicine patients who expired during hospitalization and experienced medical error. Our objective was to delineate a systematic strategy for identifying frequent and significant failures in the diagnostic process to inform strategies for preventing adverse events due to diagnostic error. METHODS: Two clinicians independently reviewed detailed records of purposively sampled cases identified from established institutional case review forums and assessed the likelihood of diagnostic error using the Safer Dx instrument. Each reviewer used the modified Diagnostic Error Evaluation and Research (DEER) taxonomy, revised for acute care (41 possible failure points across six process dimensions), to characterize the frequency of failure points (FPs) and significant FPs in the diagnostic process. RESULTS: Of 166 cases with medical error, 16 were sampled: 13 (81.3%) had one or more diagnostic error(s), and a total of 113 FPs and 30 significant FPs were identified. A majority of significant FPs (63.3%) occurred in "Diagnostic Information and Patient Follow-up" and "Patient and Provider Encounter and Initial Assessment" process dimensions. Fourteen (87.5%) cases had a significant FP in at least one of these dimensions. CONCLUSIONS: Failures in the diagnostic process occurred across multiple dimensions in our purposively sampled cohort. A systematic analytic approach incorporating the modified DEER taxonomy, revised for acute care, offered critical insights into key failures in the diagnostic process that could serve as potential targets for preventative interventions.

Research, Clinical, and Sociological Aspects of Autism.

The concept of autism continues to evolve. Not only have the central diagnostic criteria that define autism evolved but understanding of the label and how autism is viewed in research, clinical and sociological terms has also changed. Several key issues have emerged in relation to research, clinical and sociological aspects of autism. Shifts in research focus to encompass the massive heterogeneity covered under the label and appreciation that autism rarely exists in a diagnostic vacuum have brought about new questions and challenges. Diagnostic changes, increasing moves towards early diagnosis and intervention, and a greater appreciation of autism in girls and women and into adulthood and old age have similarly impacted on autism in the clinic. Discussions about autism in socio-political terms have also increased, as exemplified by the rise of ideas such as neurodiversity and an increasingly vocal dialogue with those diagnosed on the autism spectrum. Such changes are to be welcomed, but at the same time bring with them new challenges. Those changes also offer an insight into what might be further to come for the label of autism.

Colonic Migration of a Nephroureteral Stent Through a Colovesical Fistula.

Description We describe a case of a patient with a two-year history of prostate cancer who underwent placement of nephroureteral stents. He subsequently presented to the hospital with complications from prolonged retention of the stents, which ultimately lead to a secondary diagnosis of adenocarcinoma of the rectum. A colonoscopy performed approximately two weeks after a bilateral nephroureteral tube exchange demonstrated what was believed to be locoregional metastatic disease and a fistulous connection with the distal nephroureteral stents. Radiographic features of this complication are discussed together with proper management and possible complications of distal nephroureteral stents. Both nephroureteral stents were explanted, and nephrostomy catheters were sequentially replaced to allow for healing of the fistula.

Mechanical Revascularization in the Era of the Field Assessment Stroke Triage for Emergency Destination (FAST-ED): A Retrospective Cohort Assessment in a Community Stroke Practice.

BACKGROUND: Endovascular mechanical revascularization has become the mainstay acute stroke management secondary to emergent large vessel occlusions. In patients who can benefit from mechanical revascularization, the ability to intervene in a timely manner directly correlates with improved outcomes. The field assessment for stroke triage (FAST-ED) prehospital triage tool, is one of many stroke severity scales designed to decrease time to diagnosis in the field and optimize patient triage to comprehensive stroke centers. It is however unclear what impact if any, this tool has on time to activation of hospital stroke intervention teams. We set out to assess the impact of the implementation of the FAST-ED triage tool on the activation of the stroke intervention team in a community stroke treatment practice. METHODS: We retrospectively reviewed institutional records for consecutive admissions with reported stroke alerts between March 2017 and September 2018, and selected patients who presented via Emergency Medical Services (EMS). The association between FAST-ED scores and impact on time to revascularization as well as the association between FAST-ED scores and the presence of emergent large vessel occlusion were analyzed. RESULTS: There was a statistically significant improvement in interventional team activation times in favor of the FAST-ED cohort, (P < .05). CONCLUSIONS: FAST-ED implementation demonstrates a statistically significant improvement on stroke team activation times for patients who are candidates for mechanical revascularization. Larger cohort analysis is needed to fully evaluate the magnitude of this effect.

Is Autism Inborn And Lifelong For Everyone?

Autism or autism spectrum disorder (ASD) is described as a lifelong condition with core behavioural symptoms appearing during infancy or early childhood. Genetic and other effects occurring during the earliest times of life are thought to play a significant contributory role to the presentation of autism, denoting that autism is typically seen as an innate or inborn condition. Such descriptions have, and continue to, define autism research and clinical practice. Inspection of the existing research literature, however, suggests that within the vast heterogeneity of autism, not everyone experiences autism in such a prescribed way. Various reports have observed the presentation of "acquired autism" following a period of typical development. Other findings have documented an abatement of clinically relevant autistic features and related comorbid pathology for some. Such reports offer important insights into the heterogeneity and complexity of autism.

MRI myelography for diagnosis and targeted blood patching of multilevel thoracic spine CSF leaks: Report of 2 cases.

In patients with occult cerebrospinal fluid (CSF) leaks or CSF leak syndrome, orthostatic headaches are a common presenting symptom. Although computed tomography (CT) myelography has historically been the gold standard for diagnosis with radioisotope cisternography as a diagnostic alternative, magnetic resonance imaging (MRI) myelography using intrathecal gadolinium has reported sensitivity of 80%-87%. Two patients with spontaneous orthostatic headaches lasting for several days were diagnosed with CSF leaks at multiple thoracic segments using MRI myelogram with intrathecal gadolinium (Gadavist, Bayer, Whippany, NJ). This allowed for subsequent targeted treatment with CT fluoroscopy guidance, resulting in therapeutic responses within 1-2 treatment with targeted blood patching. Although intrathecal gadolinium is an off-label use, the superior contrast resolution and lack of radiation exposure makes MRI myelography an excellent imaging modality for diagnosing CSF leak, targeting treatment, and monitoring outcomes compared to CT myelography and radioisotope cisternography.

Endovascular aspiration of a symptomatic free-floating common carotid artery thrombus.

Free-floating thrombi of the common carotid artery (CCA) are a very rare cause of ischemic stroke. To date, only a few reports have been described in the academic literature. Revascularization is indicated due to the risk of thromboembolic disease and hemodynamic-related stroke syndromes. Medical treatment typically includes anticoagulation and, in some circumstances, open surgical thrombectomy is an additional option. Although rarely described in the literature, endovascular thrombectomy is a viable treatment alternative in these patients.

Malignant stroke in a ticagrelor non-responder as a complication following aneurysm treatment with the Pipeline Embolization Device™.

The Pipeline Embolization Device™ (PED; Covidien Neurovascular Inc, Irvine, CA, USA) is a flow-diverting stent often used for the endovascular treatment of large or giant, wide-necked intracranial aneurysms of the internal carotid artery. Because of the inherent thrombogenicity of intracranial stents, dual-antiplatelet therapy is initiated after placement, which has been shown to decrease morbidity and mortality related to perioperative ischemic events in neurointerventional procedures. However, in some series, as much as 50% of patients demonstrate clopidogrel non-responsiveness. In these non-responders, alternate agents such as ticagrelor can be used to achieve adequate anticoagulation. Compared with clopidogrel, a prodrug requiring Cytochrome P450 enzymolysis for activation, ticagrelor directly and reversibly inhibits the P2Y12 ADP receptor. The absorption of the prodrug and the formation of its active metabolite is comparatively quicker ( tmax 1.3-2 hours; 1.5-3 hours, respectively). To date, there have been no documented cases of ticagrelor non-responsiveness involving patients undergoing placement of flow-diverting stents or other endovascular neuro-interventional procedures.

Posterior fossa syndrome with delayed MR evidence of unilateral superior cerebellar peduncle (SCP) damage.

Posterior fossa syndrome (PFS) is a well-known sequela of midline posterior fossa tumor resection. Patients typically exhibit transient behavioral, motor, and oculomotor disturbances that resolve within a few weeks to several months after surgery. The underlying pathophysiology of PFS is not completely understood, but contemporary literature has implicated injury to the dentate nucleus and/or exiting dentatothalamocortical fiber bundles as a causative factor. The authors present a case of a young male who developed a delayed variant of PFS typified by motor deficits and demonstrated diffusion restriction in the ipsilateral superior cerebellar peduncle. Because the correlation between PFS and the superior cerebellar peduncle injury is poorly described in the literature, particularly with regard to relevant radiographic imaging, the authors of this report hope their findings will contribute to that insufficient body of evidence.

Association Between Relative Anemia and Early Functional Recovery After Severe Traumatic Brain Injury (TBI).

BACKGROUND: Severe traumatic brain injury is associated with a multi-systemic response and changes in metabolic demand. Patients requiring intracranial pressure monitoring or cerebrospinal fluid diversion, often signifies a greater severity of injury. For this group, the association between RBC transfusion, transfusion thresholds, and clinical recovery is unknown. In this study, we studied the association between transfusion and clinical recovery for severe traumatic brain injury patients requiring external ventricular drain or intracranial pressure monitor placement. METHODS: Eighty-nine patients with a primary diagnosis of traumatic brain injury requiring implantation of either an intracranial pressure monitor or external ventricular drainage device were identified. All patients were managed in a Level 1 Trauma facility by board-certified neuro-intensive care practitioners for the course of their intensive care unit duration. The correlation between transfusion and clinical recovery, defined by change in Glasgow Coma Scale was assessed. RESULTS: Thirty-four patients required surgical decompression, and 56.18 % of the cumulative cohort were transfused during admission. Overall, transfusion was not associated with significant clinical recovery (change in GCS > 3) for Hgb threshold of 7 mg/dL (<3, 29.03 vs. ≥3, 37.93 %; p = 0.49), nor for higher stratifications (8 mg/dL, p = 0.63; 9 mg/dL, p = 0.79, 10 mg/dL, p = 1). For patients who required transfusions at thresholds ≥8 mg/dL, there was a positive association with decreased length of hospitalization, [p = 0.01; <8 mg/dL: 22 (12-33), ≥8 mg/dL: 14 (7.75-20)] [median (IQR)]. Similarly, length of ICU stay was shorter for patients transfused at thresholds ≥9 mg/dL, (p = 0.02). CONCLUSIONS: From our studies, we demonstrate no significant clinical benefit associated with stratified transfusion goals; however, there was a decrease in length of hospitalization for patients with transfusion thresholds of Hgb ≥ 8 mg/dL. Larger, randomized controlled trials may be required to more accurately assess outcomes in this patient population. In patients admitted for primary severe traumatic brain injury, we demonstrate no significant clinical benefit associated with stratified transfusion goals; however, there was a noticeable decrease in length of hospitalization for patients with transfusion thresholds of Hgb ≥ 8 mg/dL. Larger, randomized controlled trials may be required to more accurately assess outcomes in this patient population.

Response of silent corticotroph pituitary carcinoma to chemotherapy: case report.

Silent pituitary corticotroph carcinomas are rare, with only six previously described cases in the literature. We report a patient with a silent pituitary corticotroph adenoma treated with multiple trans-sphenoidal resections. Twelve years after her initial presentation, she returned with leptomeningeal metastases to the posterior fossa, foramen magnum, and numerous other subarachnoid locations involving the spine. Histopathology obtained from the metastatic foci was identical to previous trans-sphenoidal specimens - consistent with the diagnosis of corticotroph pituitary carcinoma. A carboplatin and etoposide chemotherapy regimen successfully arrested disease progression and produced regression of multiple radiographically documented leptomeningeal deposits. To the authors' knowledge, this is the first report of a patient with silent pituitary carcinoma treated successfully with chemotherapy.

Exocarp Properties and Transcriptomic Analysis of Cucumber (Cucumis sativus) Fruit Expressing Age-Related Resistance to Phytophthora capsici.

Very young cucumber (Cucumis sativus) fruit are highly susceptible to infection by the oomycete pathogen, Phytophthora capsici. As the fruit complete exponential growth, at approximately 10-12 days post pollination (dpp), they transition to resistance. The development of age-related resistance (ARR) is increasingly recognized as an important defense against pathogens, however, underlying mechanisms are largely unknown. Peel sections from cucumber fruit harvested at 8 dpp (susceptible) and 16 dpp (resistant) showed equivalent responses to inoculation as did whole fruit, indicating that the fruit surface plays an important role in defense against P. capsici. Exocarp from 16 dpp fruit had thicker cuticles, and methanolic extracts of peel tissue inhibited growth of P. capsici in vitro, suggesting physical or chemical components to the ARR. Transcripts specifically expressed in the peel vs. pericarp showed functional differentiation. Transcripts predominantly expressed in the peel were consistent with fruit surface associated functions including photosynthesis, cuticle production, response to the environment, and defense. Peel-specific transcripts that exhibited increased expression in 16 dpp fruit relative to 8 dpp fruit, were highly enriched (P<0.0001) for response to stress, signal transduction, and extracellular and transport functions. Specific transcripts included genes associated with potential physical barriers (i.e., cuticle), chemical defenses (flavonoid biosynthesis), oxidative stress, penetration defense, and molecular pattern (MAMP)-triggered or effector-triggered (R-gene mediated) pathways. The developmentally regulated changes in gene expression between peels from susceptible- and resistant- age fruits suggest programming for increased defense as the organ reaches full size.

A transcriptome approach towards understanding the development of ripening capacity in 'Bartlett' pears (Pyrus communis L.).

BACKGROUND: The capacity of European pear fruit (Pyrus communis L.) to ripen after harvest develops during the final stages of growth on the tree. The objective of this study was to characterize changes in 'Bartlett' pear fruit physico-chemical properties and transcription profiles during fruit maturation leading to attainment of ripening capacity. RESULTS: The softening response of pear fruit held for 14 days at 20 °C after harvest depended on their maturity. We identified four maturity stages: S1-failed to soften and S2- displayed partial softening (with or without ET-ethylene treatment); S3 - able to soften following ET; and S4 - able to soften without ET. Illumina sequencing and Trinity assembly generated 68,010 unigenes (mean length of 911 bp), of which 32.8 % were annotated to the RefSeq plant database. Higher numbers of differentially expressed transcripts were recorded in the S3-S4 and S1-S2 transitions (2805 and 2505 unigenes, respectively) than in the S2-S3 transition (2037 unigenes). High expression of genes putatively encoding pectin degradation enzymes in the S1-S2 transition suggests pectic oligomers may be involved as early signals triggering the transition to responsiveness to ethylene in pear fruit. Moreover, the co-expression of these genes with Exps (Expansins) suggests their collaboration in modifying cell wall polysaccharide networks that are required for fruit growth. K-means cluster analysis revealed that auxin signaling associated transcripts were enriched in cluster K6 that showed the highest gene expression at S3. AP2/EREBP (APETALA 2/ethylene response element binding protein) and bHLH (basic helix-loop-helix) transcripts were enriched in all three transition S1-S2, S2-S3, and S3-S4. Several members of Aux/IAA (Auxin/indole-3-acetic acid), ARF (Auxin response factors), and WRKY appeared to play an important role in orchestrating the S2-S3 transition. CONCLUSIONS: We identified maturity stages associated with the development of ripening capacity in 'Bartlett' pear, and described the transcription profile of fruit at these stages. Our findings suggest that auxin is essential in regulating the transition of pear fruit from being ethylene-unresponsive (S2) to ethylene-responsive (S3), resulting in fruit softening. The transcriptome will be helpful for future studies about specific developmental pathways regulating the transition to ripening.

Incidence and morbidity of craniocervical arterial dissections in atraumatic subarachnoid hemorrhage patients who underwent aneurysmal repair.

BACKGROUND: No studies have assessed the incidence of craniocervical arterial dissections (CCADs) and its association to mortality in hospitalized patients with a primary diagnosis of atraumatic subarachnoid hemorrhage (SAH) requiring aneurysmal repair. We hypothesize that the incidence of CCADs in these patients has increased over time as well as its association to mortality. METHODS: We conducted a 9 year retrospective assessment of the incidence of CCADs in patients hospitalized with a primary diagnosis of an SAH requiring repair and the effect of CCAD on mortality. Using the Nationwide Inpatient Sample (NIS), we queried records from 2003 to 2011 for an ICD-9 (International Classification of Diseases-9) code corresponding to admissions for atraumatic SAH. Demographical data, incidence of CCADs, type of aneurysmal repair, length of hospital stay, and hospital mortality were recorded. Multivariate logistical regression models were fitted to assess for the impact of CCAD on inhospital mortality and morbidity. RESULTS: During the period 2003-2011, of the NIS reported 18,260 patients who required aneurysmal SAH repair, 9737 (53.32%) underwent endovascular coiling and 8523 (46.48%) had surgical clipping. There were 131 patients in the cohort with reported CCADs: 94 (71.75%) of these patients had received endovascular coiling repair and 37 (28.25%) had undergone surgical clipping repair. Patients who underwent endovascular coiling had a higher rate of CCADs in this cohort (OR 2.94; 95% CI 2.00 to 4.31, p<0.0001). The incidence of CCADs in this population increased by an average rate of 9.4% per year (OR 1.14; 95% CI 1.06 to 1.23, p<0.0006), from 0.49% in 2003 to 1.10% in 2011. The diagnosis of CCAD added 3 and 6 more days to median length of hospitalization stay for surgical clipping and endovascular coiling, respectively. The unadjusted rate of mortality was 8.4% in the CCADs subgroup, and the presence of CCAD was not a predictor of mortality in our multivariate regression model (OR 0.68; 95% CI 0.36 to 1.27, p=0.2244). CONCLUSIONS: Our study indicates an annual increase in the incidence of CCADs in patients admitted with SAH who require aneurysmal repair. More than two-thirds of these patients that developed CCADs had undergone endovascular coiling repair. A diagnosis of CCAD increased the length of hospital stay but had no statistically significant association with mortality in this patient population.

Post-Traumatic brain injury (TBI) presenting with Guillain-Barré syndrome and elevated anti-ganglioside antibodies: a case report and review of the literature.

Guillain-Barré Syndrome (GBS) is a demyelinating polyneuropathy resulting in sensory, motor and autonomic symptoms. The severity of the disease can range from mild to severe but it is classically described as an ascending demyelinating process. Initially thought to be the sequelae of a bacterial or viral infection, the clinical symptoms of post-infective GBS can present up to 4 weeks after sentinel injury. A rarely defined post-surgical GBS has been since described after major cranial, cardiothoracic and gastro-intestinal surgery. Post traumatic GBS is an even more unusual presentation with very few cases reported in contemporary academic literature. We present a case of GBS presenting two weeks after non-operative traumatic brain injury (TBI) and a review of the literature.

A prospective, multi-institutional comparative effectiveness study of lumbar spine surgery in morbidly obese patients: does minimally invasive transforaminal lumbar interbody fusion result in superior outcomes?

BACKGROUND: Obese and morbidly obese patients undergoing lumbar spinal fusion surgery are a challenge to the operating surgeon. Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) and open-TLIF have been performed for many years with good results; however, functional outcomes after lumbar spine surgery in this subgroup of patients remain poorly understood. Furthermore, whether index MIS-TLIF or open-TLIF for the treatment of degenerative disc disease or spondylolisthesis in morbidly obese results in superior postoperative functional outcomes remains unknown. METHODS: A total of 148 (MIS-TLIF: n = 40, open-TLIF: n = 108) obese and morbidly obese patients undergoing index lumbar arthrodesis for low back pain and/or radiculopathy between January 2003 and December 2010 were selected from a multi-institutional prospective data registry. We collected and analyzed data on patient demographics, postoperative complications, back pain, leg pain, and functional disability over 2 years. Patients completed the Oswestry Disability Index (ODI), Medical Outcomes Study Short-Form 36 (SF-36), and back and leg pain numerical rating scores before surgery and then at 12 and 24 months after surgery. Clinical outcomes and complication rates were compared between both patient cohorts. RESULTS: Compared with preoperative status, Visual Analog Scale (VAS) back and leg pain, ODI, and SF-36 physical component score/mental component score were improved in both groups. Both MIS-TLIF and open-TLIF patients showed similar 2-year improvement in VAS for back pain (MIS-TLIF: 2.42 ± 3.81 vs. open-TLIF: 2.33 ± 3.67, P = 0.89), VAS for leg pain (MIS-TLIF: 3.77 ± 4.53 vs. open-TLIF: 2.67 ± 4.10, P = 0.18), ODI (MIS-TLIF: 11.61 ± 25.52 vs. open-TLIF: 14.88 ± 22.07, P = 0.47), and SF-36 physical component score (MIS-TLIF: 8.61 ± 17.72 vs. open-TLIF: 7.61 ± 15.55, P = 0.93), and SF-36 mental component score (MIS-TLIF: 4.35 ± 22.71 vs. open-TLIF: 5.96 ± 21.09, P = 0.69). Postoperative complications rates between both cohorts were also not significantly divergent between (12.50% vs. 11.11%, P = 0.51). CONCLUSION: MIS-TLIF is a safe and viable option for lumbar fusion in morbidly obese patients and, compared with open-TLIF, resulted in similar improvement in pain and functional disability. Postoperative complications rates between both cohorts were also not significantly divergent.

Ex vivo studies for the passive transdermal delivery of low-dose naltrexone from a cream; detection of naltrexone and its active metabolite, 6ß-naltrexol, using a novel LC Q-ToF MS assay.

Naltrexone (NTX) is a long-acting opiate antagonist. Low-dose naltrexone (LDN) therapy has shown promising results in the treatment of several autoimmune disorders. Our aim was to formulate NTX into a cream for the delivery of LDN and develop an analytical technique for the quantification of NTX and its active metabolite 6-ß-naltrexol (NTXol) during transdermal diffusion cell permeation studies. A 1% w/w NTX cream was formulated and drug permeation was examined over 24 h using static Franz diffusion cells mounted with pig skin. A Liquid Chromatography Quadrupole-Time of Flight Mass Spectrometry (LC-MS Q-ToF) method was developed for the detection of NTX and NTXol in the receptor solution, skin membrane and residual cream on the donor chamber after completion of the diffusion studies. The cream formulation exhibited steady state release of NTX over 24 h after an initial lag time of 2.74 h. The bioconversion of NTX to NTXol in the skin membrane was 1.1%. It was concluded that the cream may be an effective formulation for the sustained transdermal delivery of LDN. The novel LC Q-ToF MS method allowed the accurate measurement of NTX and NTXol levels across the diffusion cell assemblies and the quantification of NTX metabolism in the skin.

The epidemiology, risk factors, and impact on hospital mortality of status epilepticus after subdural hematoma in the United States.

INTRODUCTION: Subdural hematoma (SDH) is a well described risk factor in the development of Status Epilepticus (SE), however the epidemiology of SE after SDH is unknown. In this study, we sought to determine the epidemiology of SE, the prevalence of risk factors, and impact on hospital mortality using a large administrative dataset. METHODS: Data was derived from the Nationwide Inpatient Sample from 1988 through 2011. We queried the NIS database for patients older than 18 years, with a diagnosis of SDH and SE. Diagnoses were defined by ICD 9 CM codes 432.1, 852.2, 852.3 and 345.3 for SE. Adjusted incidence rates of admission and prevalence proportions were calculated. Multivariate logistic models were then fitted to assess for the impact of status epilepticus on hospital mortality. RESULTS: Over the 23-year period, we identified more than 1,583,255 admissions with a diagnosis of SDH. The prevalence of SE in this cohort was 0.5% (7,421 admissions). The population adjusted incidence rate of admissions of SDH increased from 13/100,000 in 1988 to 38/100,000 in 2011. The prevalence of SE in SDH, increased from 0.5% in 1988 to 0.7% in 2011. In hospital mortality of patients with SDH and without SE decreased from 17.9% to 10.3% while in hospital mortality of patients with SDH and SE did not statistically change. Mortality increased over the same period (2.3/100,000 in 1988 to 3.9/100.000 in 2011) and the diagnosis of SE increased mortality in this cohort (OR 2.17, p < 0.0001). The risk of SE remained stable throughout the study period, but was higher among older patients, blacks, and in those with respiratory, metabolic, hematological, and renal system dysfunction. CONCLUSION: Our study demonstrates that the incidence of admissions of SDH is increasing in the United States. Despite a decline in the overall SDH related mortality, SE increased the risk of in-hospital death in patients with a primary diagnosis of SDH.