Showing papers by "Jewish Hospital published in 2019"

Risk of Suicide and Self-harm Is Increased After Bariatric Surgery—a Systematic Review and Meta-analysis

Abstract: Bariatric surgery is endorsed by multiple societies as the most effective treatment for obesity. Psychosocial functioning has also been noted to improve for most patients after bariatric surgery. However, some studies have shown an increase in post-operative suicide risk. The aim of this study was to review the published literature and evaluate the association of bariatric surgery with suicide events and suicide/self-harm attempts in patients who have undergone weight loss surgery. MEDLINE and Embase were searched from inception through January 2018 for retrospective or prospective studies reporting mortality outcomes and self-harm or suicide rates after bariatric procedures. The primary outcome was the pooled event rate with 95% confidence interval (95% CI) for suicide. Secondary outcomes were suicide/self-harm attempts after bariatric surgery compared to same population prior to surgery and to matched control subjects, with the respective calculated odds ratios (OR) and 95% CI. From 227 citations, 32 studies with 148,643 subjects were eligible for inclusion. The patients were predominantly females (76.9%). Roux-en-Y gastric bypass (RYGB) was the most commonly performed procedure (58.9%). The post-bariatric suicide event rate was 2.7/1000 patients (95% CI 0.0019–0.0038), while the suicide/self-harm attempt event rate was 17/1000 patients (95% CI 0.01–0.03). The self-harm/suicide attempt risk was higher after bariatric surgery within the same population with OR of 1.9 (95% CI 1.23–2.95), and compared to matched control subjects, OR 3.8 (95% CI, 2.19–6.59). Post-bariatric surgery patients had higher self-harm/suicide attempt risk compared to age-, sex-, and BMI-matched controls. Various pre- and post-surgical psychosocial, pharmacokinetic, physiologic, and medical factors may be involved.

Symptomatology and symptomatic treatment in multiple sclerosis: Results from a nationwide MS registry.

Abstract: Background:Multiple sclerosis (MS) is a neuroinflammatory and neurodegenerative disease. Over time, symptoms accumulate leading to increased disability of patients.Objective:The objective of this a...

Review of gait, cognition, and fall risks with implications for fall prevention in older adults with dementia

Abstract: Background Older people with cognitive impairment are at increased risk of falls; however, fall prevention strategies have limited success in this population. The aim of this paper is to review the literature to inform a theoretical framework for fall prevention in older adults with dementia. Summary A narrative review was conducted on fall risk factors in people with cognitive impairment, the relationship between cognition and gait, and their joint impact on the risk of falls. This was used to develop a theoretical framework for fall prevention for people with dementia. Executive function and motor function are closely related as they share neuroanatomy. This close relationship has been confirmed by observational studies including neuroimaging and intervention studies. Executive function is the cognitive domain most commonly associated with gait dysfunction. Attention, sensory integration, and motor planning are the sub-domains of executive function associated with risk of falls through gait dysfunction, whereas cognitive flexibility, judgement, and inhibitory control affect risk of falls through risk-taking behaviour. Key Messages: Gait, cognition, and falls are closely related. The comorbidity and interaction between gait abnormality and cognitive impairment may underpin the high prevalence of falls in older adults with dementia. Gait assessment and cognitive assessment, particularly executive function, should be integrated in fall risk screening. Assessment results should be interpreted and utilised using a multidisciplinary approach; specific strategies such as customised gait training and behavioural modulation should be considered as part of falls prevention for people with dementia.

ALS blood expression profiling identifies new biomarkers, patient subgroups, and evidence for neutrophilia and hypoxia

Abstract: Amyotrophic lateral sclerosis (ALS) is a debilitating disease with few treatment options. Progress towards new therapies requires validated disease biomarkers, but there is no consensus on which fluid-based measures are most informative. This study analyzed microarray data derived from blood samples of patients with ALS (n = 396), ALS mimic diseases (n = 75), and healthy controls (n = 645). Goals were to provide in-depth analysis of differentially expressed genes (DEGs), characterize patient-to-patient heterogeneity, and identify candidate biomarkers. We identified 752 ALS-increased and 764 ALS-decreased DEGs (FDR 10% expression change). Gene expression shifts in ALS blood broadly resembled acute high altitude stress responses. ALS-increased DEGs had high exosome expression, were neutrophil-specific, associated with translation, and overlapped significantly with genes near ALS susceptibility loci (e.g., IFRD1, TBK1, CREB5). ALS-decreased DEGs, in contrast, had low exosome expression, were erythroid lineage-specific, and associated with anemia and blood disorders. Genes encoding neurofilament proteins (NEFH, NEFL) had poor diagnostic accuracy (50–53%). However, support vector machines distinguished ALS patients from ALS mimics and controls with 87% accuracy (sensitivity: 86%, specificity: 87%). Expression profiles were heterogeneous among patients and we identified two subgroups: (i) patients with higher expression of IL6R and myeloid lineage-specific genes and (ii) patients with higher expression of IL23A and lymphoid-specific genes. The gene encoding copper chaperone for superoxide dismutase (CCS) was most strongly associated with survival (HR = 0.77; P = 1.84e−05) and other survival-associated genes were linked to mitochondrial respiration. We identify a 61 gene signature that significantly improves survival prediction when added to Cox proportional hazard models with baseline clinical data (i.e., age at onset, site of onset and sex). Predicted median survival differed 2-fold between patients with favorable and risk-associated gene expression signatures. Peripheral blood analysis informs our understanding of ALS disease mechanisms and genetic association signals. Our findings are consistent with low-grade neutrophilia and hypoxia as ALS phenotypes, with heterogeneity among patients partly driven by differences in myeloid and lymphoid cell abundance. Biomarkers identified in this study require further validation but may provide new tools for research and clinical practice.

Interventions to Improve Gait in Older Adults with Cognitive Impairment: A Systematic Review.

Abstract: Objectives To review intervention programs that measure gait to investigate what features of the intervention may contribute to improving gait in older adults with cognitive impairment or dementia. Design Systematic review using Medline, Cinahl, Scopus, PsychInfo, Amed, Embase, Web of Science, and PubMed for original research published in English between January 1, 2000, and July 23, 2018, to identify interventional controlled trials. Narrative synthesis was undertaken. Results Of 6,379 citations, 36 articles met inclusion criteria. Interventions were categorized as medication or medical devices (8 studies), exercise (19 studies), and exercise plus cognitive training (9 studies). Antidementia medication may improve gait variability in people with Alzheimer's disease. Exercise programs focusing on strength and balance training, especially when combined with functional mobility training, improve gait in people with mild cognitive impairment or dementia. Exercise plus cognitive training programs combining strength and balance training, functional mobility training, and training on attention and executive function also improve gait. Conlusion Physical and cognitive factors affect gait performance, and both should be addressed in intervention programs. Physical exercises including functional mobility training, especially walking, have better results than physical programs with only static, resistance, and flexibility training. Cognitive intervention should be concomitant with physical exercises rather than separate, with a focus on attention and executive function. Combining physical training with cognitive training in a functional context may assist older adults with cognitive impairment generalize from training to everyday activity. J Am Geriatr Soc 67:381–391, 2019.

BAL Cell Gene Expression in Severe Asthma Reveals Mechanisms of Severe Disease and Influences of Medications.

Abstract: Rationale: Gene expression of BAL cells, which samples the cellular milieu within the lower respiratory tract, has not been well studied in severe asthma.Objectives: To identify new biomolecular me...

Not all primary total hip arthroplasties are equal—so is there a difference in reimbursement?

Abstract: Background: Relative value units (RVUs) are a physician reimbursement model based on the effort required, or value, in providing a procedure or service for a patient Procedures such as conversion total hip arthroplasties (THAs) can be compared to primary THAs, but many studies have revealed increased difficulties in conversion cases Despite the increased time and effort for conversion THA, it is unknown if this is reflected in the RVU compensation model Therefore, the purpose of this study was to compare the: (I) mean operative times; (II) mean RVUs; (III) RVU/minute for primary and conversion THAs; and (IV) perform an individualized idealized surgeon annual cost difference analysis Methods: A total of 103,702 primary THA patients were identified using CPT code 27130 and 2,986 conversion THA patients were identified using CPT code 27132 using the National Surgical Quality Improvement Program (NSQIP) database The mean RVUs, operative times (minutes), and RVU/minute were calculated and compared An annualize cost analysis of dollar amounts per case, day, and the year was also performed Results: The mean operative times for the primary and conversion THA cohorts were 94 vs 146 minutes (P vs 2568 (P vs 021, P vs conversion THAs Conclusions: Even though conversion THA can be considered to a more complex and demanding procedure, based on RVUs per minute of surgery, orthopaedic surgeons are reimbursed better for primary THA cases This data could be used by orthopaedic surgeons to administer their practices better to yield the highest return on time

A randomized trial of three novel regimens for recurrent acute myeloid leukemia demonstrates the continuing challenge of treating this difficult disease.

Abstract: To improve the outcome of relapsed/refractory acute myeloid leukemia (AML), a randomized phase II trial of three novel regimens was conducted. Ninety patients were enrolled and were in first relapse or were refractory to induction/re-induction chemotherapy. They were randomized to the following regimens: carboplatin-topotecan (CT), each by continuous infusion for 5 days; alvocidib (formerly flavopiridol), cytarabine, and mitoxantrone (FLAM) in a timed sequential regimen; or sirolimus combined with mitoxantrone, etoposide, and cytarabine (S-MEC). The primary objective was attainment of a complete remission (CR). A Simon two-stage design was used for each of the three arms. The median age of the patients in the FLAM arm was older at 62 years compared with 55 years for the CT arm and the S-MEC arm. The overall response was 14% in the CT arm (5/35, 90% CI 7%-35%), 28% in the FLAM arm (10/36, 90% CI, 16%-43%), and 16% in the S-MEC arm (3/19, 90% CI, 4%-36%). There were nine treatment-related deaths, seven of which occurred in the FLAM arm with four of these in elderly patients. We conclude that the FLAM regimen had an encouraging response rate and should be considered for further clinical development but should be used with caution in elderly patients.

Proteomic Analysis Reveals Novel Mechanisms by Which Polychlorinated Biphenyls Compromise the Liver Promoting Diet-Induced Steatohepatitis.

Abstract: Environmental pollution contributes to fatty liver disease pathogenesis. Polychlorinated biphenyl (PCB) exposures have been associated with liver enzyme elevation and suspected steatohepatitis in cohort studies. Male mice treated with the commercial PCB mixture, Aroclor 1260 (20 mg/kg), and fed high fat diet (HFD) for 12 weeks developed steatohepatitis. Receptor-based modes of action including inhibition of the epidermal growth factor (EGF) receptor were previously proposed, but other mechanisms likely exist. Objectives were to identify and validate the pathways, transcription factors, and mechanisms responsible for the steatohepatitis associated with PCB and HFD coexposures. Comparative proteomics analysis was performed in archived mouse liver samples from the aforementioned chronic exposure study. Pathway and transcription factor analysis (TFA) was performed, and selected results were validated. Liver proteomics detected 1103 unique proteins. Aroclor 1260 upregulated 154 and downregulated 93 of these. Aroclor 1260 + HFD coexposures affected 55 pathways including glutathione metabolism, intermediary metabolism, and cytoskeletal remodeling. TFA of Aroclor 1260 treatment demonstrated alterations in the function of 42 transcription factors including downregulation of NRF2 and key nuclear receptors previously demonstrated to protect against steatohepatitis (e.g., HNF4α, FXR, PPARα/δ/γ, etc.). Validation studies demonstrated that Aroclor 1260 significantly reduced HNF4α protein levels, while Aroclor 1260 + HFD reduced expression of the HNF4α target gene, albumin, in vivo. Aroclor 1260 attenuated EGF-dependent HNF4α phosphorylation and target gene activation in vitro. Aroclor 1260 reduced levels of NRF2, its target genes, and glutathione in vivo. Aroclor 1260 attenuated EGF-dependent NRF2 upregulation, in vitro. Aroclor 1260 indirectly activated hepatic stellate cells in vitro via induction of hepatocyte-derived TGFβ. PCB exposures adversely impacted transcription factors regulating liver protection, function, and fibrosis. PCBs, thus, compromised the liver by reducing its protective responses against nutritional stress to promote diet-induced steatohepatitis. The identified mechanisms by which environmental pollutants influence fatty liver disease pathogenesis require confirmation in humans.

Prevention of Postoperative Pneumonia in Noncardiac Surgical Patients: A Prospective Study Using the National Surgical Quality Improvement Program Database.

Abstract: Postoperative pneumonia increases morbidity, length of stay, and hospital readmission rates. Current data support the use of perioperative chlorhexidine gluconate in elective cardiac surgery patients to prevent postoperative pneumonia. The objectives of this study were to implement a resident-driven quality improvement project and determine the efficacy of an oral care bundle in preventing postoperative pneumonia among noncardiac surgical patients. A retrospective review of postoperative pneumonia occurrences at our hospital captured by the NSQIP database from 2014 to 2016 was conducted. A pre- and postoperative pulmonary care bundle was implemented in all surgical patients undergoing general anesthesia and outcomes were tracked by NSQIP for up to 90 days postoperatively for calendar year 2017. The NSQIP-reported incidence of postoperative pneumonia at our hospital was reduced from 0.8 to 0 per cent (P = 0). The risk-adjusted smoothed rate fell from 1.17 (95% confidence interval 0.77-1.66) in 2014 to 0.33 (95% confidence interval 0.03-0.98) in 2017. We encountered multiple systematic issues while conducting this study, which led to an imbalanced compliance to the preoperative (90%) and postoperative (31%) bundle; however, there was no significant difference between these two groups. Successful implementation of a resident-driven quality project resulted in a decreased rate of postoperative pneumonia.

Anterior Cruciate Ligament Graft Conditioning Required to Prevent an Abnormal Lachman and Pivot Shift After ACL Reconstruction: A Robotic Study of 3 ACL Graft Constructs.

Abstract: Background:Anterior cruciate ligament (ACL) graft conditioning protocols to decrease postoperative increases in anterior tibial translation and pivot-shift instability have not been established.Pur...

High‐resolution diffusion‐weighted imaging identifies ischemic lesions in a majority of transient ischemic attack patients

Abstract: Transient ischemic attack (TIA) is defined as focal neurological deficit caused by ischemia resolving within 24 hours. In a secondary analysis of a large monocentric cohort of 446 TIA patients, we explored the frequency and determinants of diffusion-weighted imaging (DWI) lesions on high-resolution magnetic resonance imaging. Overall, 240 (54%) of all TIA patients presented with DWI lesions. These patients had higher National Institute of Health Stroke Scale and ABCD2 scores and presented more frequently with vessel occlusion and perfusion deficits, but had similar functional outcome at 3 months. Taken together, high-resolution DWI provides evidence of ischemic brain injury in the majority of TIA patients. ANN NEUROL 2019;86:452-457.

Related peripheral blood stem cell donors experience more severe symptoms and less complete recovery at one year compared to unrelated donors

Abstract: Unlike unrelated donor registries, transplant centers lack uniform approaches to related donor assessment and deferral. To test whether related donors are at increased risk for donation-related toxicities, we conducted a prospective observational trial of 11,942 related and unrelated donors aged 18-60 years. Bone marrow (BM) was collected at 37 transplant and 78 National Marrow Donor Program centers, and peripheral blood stem cells (PBSC) were collected at 42 transplant and 87 unrelated donor centers in North America. Possible presence of medical comorbidities was verified prior to donation, and standardized pain and toxicity measures were assessed pre-donation, peri-donation, and one year following. Multivariate analyses showed similar experiences for BM collection in related and unrelated donors; however, related stem cell donors had increased risk of moderate [odds ratios (ORs) 1.42; P<0.001] and severe (OR 8.91; P<0.001) pain and toxicities (OR 1.84; P<0.001) with collection. Related stem cell donors were at increased risk of persistent toxicities (OR 1.56; P=0.021) and non-recovery from pain (OR 1.42; P=0.001) at one year. Related donors with more significant comorbidities were at especially high risk for grade 2-4 pain (OR 3.43; P<0.001) and non-recovery from toxicities (OR 3.71; P<0.001) at one year. Related donors with more significant comorbidities were at especially high risk for grade 2-4 pain (OR 3.43; P<0.001) and non-recovery from toxicities (OR 3.71; P<0.001) at one year. Related donors reporting grade ≥2 pain had significant decreases in Health-Related Quality of Life (HR-QoL) scores at one month and one year post donation (P=0.004). In conclusion, related PBSC donors with comorbidities are at increased risk for pain, toxicity, and non-recovery at one year after donation. Risk profiles described in this study should be used for donor education, planning studies to improve the related donor experience, and decisions regarding donor deferral. Registered at clinicaltrials.gov identifier:00948636.

A comparison of relative value units in revision hip versus revision knee arthroplasty.

Abstract: The purpose of this study was to compare the: 1) RVUs; 2) lengths-of-surgery; 3) RVU per minute between revision hip (THA) and knee (TKA) arthroplasties; and 4) perform an annualized surgeon cost analysis. Using the ACS-NSQIP from 2008 to 2015, 8081 revision TKAs, 7233 THAs were compared. Revision THA had greater mean RVUs (30.27 vs. 27.10 RVUs, p

Rapid Titration of Intravenous Treprostinil to Treat Severe Pulmonary Arterial Hypertension Postpartum: A Retrospective Observational Case Series Study.

Abstract: BACKGROUND:Pulmonary hypertension during pregnancy carries high mortality rate. The relatively long-acting, specific pulmonary vasodilator treprostinil has been used to improve survival in these parturients. Slow uptitration is performed in most cases, and rapid titration has not been reported in th

Adenoid cystic carcinoma of the breast - Discordant size on imaging and pathology: A case report and review of literature.

Abstract: Introduction Adenoid cystic carcinoma (ACC) is an uncommon tumour of the breast. It is known for its rare lymph node involvement and distant metastasis. A triple-negative breast cancer that has a favorable prognosis compared to other triple negative ductal carcinomas, it accounts for approximately 0.1–1% of all breast cancers. Presentation of case We report a case of a 69-year-old female with a palpable left breast mass who underwent multiple imaging modalities with significant size variance between the studies. Breast conserving therapy (BCT) was performed with axillary sentinel lymph node biopsy (SLNB) followed by radiation therapy (RT). Pathological examination confirmed the tumour as ACC. Discussion ACC, known as an persistent if low-grade malignant tumour of salivary gland, is considered to have low-malignant potential in the breast. It is a very rare subtype and from this scant data, there is minimal mention about size discrepancy between imaging modalities such as ultrasound and MRI. No consistent MRI features have been demonstrated, with the exception of T2 hyperintensity in larger lesions and T2 iso-intensity in smaller lesions. Ultrasound demonstrates primarily a hypoechoic or heterogenous mass with minimum vascularity, consistent with our radiographic findings. Conclusion ACC is a rare entity in breast cancer pathology. Its size can be highly variable as measured by various radiographic modalities, and final Pathology from the surgical specimen is, as always, required for an accurate tumoral diameter. With that caveat, careful utilization of pre-operative imaging modalities is critical in pre-surgical planning to choose the appropriate surgery.

Nonmosaic somatic HIF2A mutations associated with late onset polycythemia-paraganglioma syndrome: Newly recognized subclass of polycythemia-paraganglioma syndrome.

Abstract: BACKGROUND Somatic mutations in hypoxia-inducible factor 2α (HIF2A) are associated with polycythemia-paraganglioma syndrome. Specifically, the classic presentation of female patients with recurrent paragangliomas (PGLs), polycythemia (at birth or in early childhood), and duodenal somatostatinomas has been described. Studies have demonstrated that somatic HIF2A mutations occur as postzygotic events and some to be associated with somatic mosaicism affecting hematopoietic and other tissue precursors. This phenomenon could explain the development of early onset of polycythemia in the absence of erythropoietin-secreting tumors. METHODS Correlation analysis was performed between mosaicism of HIF2A mutant patients and clinical presentations. RESULTS Somatic HIF2A mutations (p.A530V, p.P531S, and p.D539N) were identified in DNA extracted from PGLs of 3 patients. No somatic mosaicism was detected through deep sequencing of blood genomic DNA. Compared with classic syndrome, both polycythemia and PGL in all 3 patients developed at an advanced age with polycythemia at age 30, 30, and 17 years and PGLs at age 34, 30, and 55 years, respectively. Somatostatinomas were not detected, and 2 patients had ophthalmic findings. The biochemical phenotype in all 3 patients was noradrenergic with 18 F-fluorodopa PET/CT as the most sensitive imaging modality. All patients demonstrated multiplicity, and none developed metastatic disease. CONCLUSION These findings suggest that newer techniques need to be developed to detect somatic mosaicism in patients with this syndrome. Absence of HIF2A mosaicism in patients with somatic HIF2A mutations supports association with late onset of the disease, milder clinical phenotype, and an improved prognosis compared with patients who have HIF2A mosaicism.

Venous thromboembolism in patients with cancer undergoing surgical exploration.

Abstract: Malignancy and surgery are both independent risk factors for venous thromboembolism (VTE) events. The current NCCN guidelines recommend VTE prophylaxis for up to 28 days after major abdominal or pelvic surgery for malignancy. We set out to evaluate the rate and timing of VTEs among patients with gastric, pancreatic, colorectal, and gynecologic malignancies who underwent surgery. We performed a retrospective review of the NSQIP database (2005–2013) focusing on patients with gastric, colorectal, pancreatic, and gynecologic malignancies. Our primary endpoint was a diagnosis of VTE within 30 days of surgery. We analyzed 128,864 patients in this study. On multivariable analysis, patients with pre-operative sepsis (OR 2.36, CI 2.04–2.76, p < 0.001), disseminated cancer (OR 1.73, CI 1.55–1.92, p < 0.001), congestive heart failure (OR 1.69, CI 1.25–2.28, p = 0.001), gastric cancer (OR 1.3, CI 1.09–1.56, p = 0.004), and pancreatic cancer (OR 1.2, CI 1.03–1.30, p = 0.021) were more likely to have a VTE. Of patients who had a VTE event, 34% occurred after discharge from surgery (gastric: 25%, colorectal 34%, pancreatic 31%, gynecologic malignancy 42%). Our study demonstrates that patients who undergo an operation for malignancy with pre-operative sepsis, disseminated cancer, congestive heart failure, gastric cancer, or pancreatic cancer are more likely to develop a VTE within 30 days of their operation. Of those patients who developed a VTE, approximately one-third occurred after discharge during a 30 day post-operative period. This data supports that further studies are needed to determine the appropriate length of post-operative VTE chemoprophylaxis in patients with cancer.

Isolated Chronic and Transient Neutropenia.

Abstract: Neutrophils are a critical part of the body's defense system to prevent serious bacterial and fungal infections. Neutropenia is a term which is defined by the absolute neutrophil counts (ANC) < 1,500 cells/µL, and it becomes clinically significant when the level falls below 500 cells/µL. The risk of morbidity and mortality increases considerably when the levels fall below 200. In some ethnicities, the neutropenia is chronic and is frequently seen on routine outpatient visits. On the other hand, transient neutropenia is associated with a transient drop in the neutrophil count and many of the underlying causes are reversible. Patients and their families, as well as some clinicians, express great concern for neutropenia, leading to a multitude of tests and emergency room visits. In this review, we discuss the causes of both chronic and transient neutropenia. Also, we have given special emphasis on the mechanism of neutropenia and management of transient neutropenia.

Infrared imaging of lymphatic function in the upper extremity of normal controls and hand transplant recipients via subcutaneous indocyanine green injection.

Abstract: Objectives:The goal of this study was to define the parameters of movement of indocyanine green in the upper extremity of normal control and hand transplant recipients The purpose was to establish

Early initiation of fingolimod reduces the rate of severe relapses over the long term: Post hoc analysis from the FREEDOMS, FREEDOMS II, and TRANSFORMS studies.

Abstract: Background Relapse frequency is often correlated with the prognosis of multiple sclerosis (MS). In patients with relapsing-remitting MS (RRMS), relapses vary in severity and may affect activities of daily living, require steroid intervention, or hospitalization. Incomplete recovery from relapses results in increasing disability. In pivotal phase III studies of fingolimod (FREEDOMS, FREEDOMS II, and TRANSFORMS), the frequency of overall and severe relapses was significantly reduced in patients with RRMS treated with fingolimod compared with placebo or intramuscular interferon β-1a (IFN β-1a). The objective of this study was to report the effect of early initiation of fingolimod on relapse severity in patients with RRMS. Methods This is a post hoc descriptive analysis of data from the pooled placebo-controlled FREEDOMS/FREEDOMS II studies and from the active-comparator TRANSFORMS study. Patients were analyzed under 2 groups: patients initially randomized to receive fingolimod 0.5 mg during the core phase and continued fingolimod 0.5 mg in the extension phase (immediate fingolimod group), and patients initially randomized to placebo or IFN β-1a during the core phase and switched to fingolimod during the extension phase (delayed fingolimod group). Annualized relapse rate (ARR) was estimated for severe relapses (defined as Expanded Disability Status Scale increase of >1 point, or >2-point change in 1 or 2 Functional Systems, respectively, or >1-point change in >4 Functional Systems). ARR was also estimated for relapses that affected activities of daily living, required steroid use, or hospitalization. Results In the pooled FREEDOMS/FREEDOMS II extensions, the immediate fingolimod group showed sustained reductions in the proportion (core: 15.8% and extension: 9.3%) and in ARR over 4 years (0.032 and 0.015) for severe relapses, in relapses requiring steroids (0.149 and 0.123), hospitalization (0.049 and 0.039) and relapses affecting activities of daily living (0.155 and 0.112). In the TRANSFORMS extension, similar reductions were observed in the immedaite group for the proportion of severe relapses (core: 11.8% and extension: 9.8%). ARR remained low over 2 years for severe relapses (0.024 and 0.018), relapses affecting activities of daily living (0.112 and 0.109), relapses requiring steroids (0.156 and 0.161) and hospitalization (0.027 and 0.033). Results in the FREEDOMS/FREEDOMS II and TRANSFORMS extensions for the delayed group were similar. In the TRANSFORMS extension, the proportion of severe relapses were 18.0% (core) and 11.1% (extension); there were significant reductions in ARR for severe relapses (core: 0.079 and extension: 0.029), relapses requiring steroids (0.366 and 0.232), hospitalization (0.092 and 0.055), and relapses affecting activities of daily living (0.285 and 0.144) (all p Conclusions In patients with RRMS, the frequency of severe relapses and relapse severity remained low in the immedaite fingolimod group over a period of 4 years. Reductions in the proportion of severe relapses post switch from IFN β-1a or placebo to fingolimod underscore the clinical benefit and the relevance of an early initiation of fingolimod.

Intravenous Olanzapine for the Management of Agitation: Review of the Literature.

Abstract: Objective: The purpose of this review is to summarize the current evidence of the off-label use of intravenous (IV) olanzapine and discuss its risks versus benefits for the management of agitation. Data Sources: A literature search was conducted to gather relevant data regarding IV use of olanzapine for the management of acute agitation. PubMed, EMBASE, MEDLINE, and IPA were searched using the keywords and MESH terms: olanzapine, intravenous, IV, off-label, and agitation. Study Selection and Data Extraction: All case reports, and retrospective and prospective studies evaluating the efficacy and safety of IV olanzapine administration for agitation from January 2004 to December 2018 were analyzed. Data Synthesis: Doses from 2.5 to 10 mg given as an IV bolus (maximum dose of 30 mg/d) have been administered. Rescue medications such as droperidol or parenteral benzodiazepines are sometimes coadministered to assist with achieving adequate sedation. Prospective studies demonstrate efficacy similar to droperidol in achieving adequate sedation within 10 minutes and similar time to onset of sedation. Rates of respiratory depression and airway obstruction are low and similar to that of comparative agents, including intramuscular olanzapine. Relevance to Patient Care and Clinical Practice: This review evaluated the off-label use of IV olanzapine to manage agitation based on case reports, and retrospective and prospective data. Conclusions: The use of IV olanzapine remains controversial in the absence of clear evidence evaluating safety and efficacy. Future studies are warranted comparing IV olanzapine with more commonly utilized and Food and Drug Administration-approved treatment modalities for acute agitation in the emergency department and other settings.

Improving Turnaround Times through a Process Improvement Initiative Involving Barcoding, Floorplans, Dual Measuring Cells, Chemistry Analyzers, and Staff Shifts.

Abstract: Background: Specimen turnaround time (TAT) is an important metric for laboratory safety and quality. Various methods to improve TAT have seen success using process improvement initiatives. However, there are limited data on barcoding, pneumatic receiving proximity to modular preanalytics, 1 vs 2 measuring cells, and upgrading to Cobas 8000. The example describes the complete execution of a process improvement initiative to improve TAT within these areas over a 20-month period. The study aimed to improve specimen timeliness by decreasing the TAT for preanalytic and analytic specimen processing through a systematic process improvement initiative and to empower staff to “own” their scientific method. Methods: The primary outcome TAT was reported from a prospective quality initiative beginning January 2017 for 2 analytes: troponin and potassium. TATs for albumins from the complete metabolic panels were added to the study design retrospectively during team rounds. Mean TAT was defined as time from arrival to verified times. Process improvement tools within the study design were borrowed from Lean management. Results: After implementation of the process improvement initiative, the number of steps medical laboratory assistants and technologists performed per specimen decreased from 8 to 5. Mean TATs decreased for all analytes. Preimplementation to postimplementation comparisons from 2017 to 2018 decreased for all 3 analytes and within 2017. The number of troponin specimens verified within 60 min improved from 70% in January 2017 to 95% in August 2018, with an improvement from 64% in January 2017 to 87% in August 2018 during peak hours. Conclusions: A systematic process improvement initiative whereby employees “own” the scientific process within specimen preanalytic and analytic testing phases can significantly improve metrics for laboratory quality and safety.

Is Opioid Prescribing Driving Trauma Recidivism or Is Trauma Driving Opioid Use

Abstract: In the past 30 years, opioid prescription rates have quadrupled and hospital admissions for overdose are rising. Previous studies have focused on alcohol use and trauma recidivism, however rarely evaluating recidivism and opioid use. We hypothesized there is an association between opioid use and trauma recidivism. This is a retrospective review of patients with multiple admissions for traumatic injury. Demographics, opioid toxicology screen (TS) results, and injury characteristics were collected. Statistical analysis was performed with chi-squared and Poisson regression models. One thousand six hundred forty-nine patients (age ≥18 years) had multiple trauma admissions. Seven hundred nine patients had TS data for both admissions. Thirty-one per cent (218) were TS positive on the 1st admission compared with 34 per cent (244) on their 2nd admission. Fifty-five per cent of patients who were TS positive on the 1st admission were positive on their 2nd admission, whereas 25 per cent who were TS negative on the 1st admission were subsequently positive on their 2nd admission (P 15, 26.3% vs 22.3%, P = 0.04). The only significant risk factor for being TS positive on the 2nd admission was being TS positive on the 1st admission (relative risk = 2.18, P < 0.001). A previous history of opioid use is the strongest predictor of recurrent use in recidivists.

Serratia Liver Abscess Infection and Cardiomyopathy in a Patient with Diabetes Mellitus: A Case Report and Review of the Literature.

Abstract: BACKGROUND Liver abscesses remain difficult to diagnose and treat. Risk factors include diabetes mellitus, liver cirrhosis, and immunodeficiency. The majority are pyogenic, resulting from bacterial infection. Research identifies species in the Serratia genus as the cause of pyogenic liver abscesses in only 0.25% of cases and only 1 Serratia species in each case appears to have been identified. To the best of our knowledge, the present case report is the first to involve overlapping Serratia species in a single liver abscess infection that induced cardiomyopathy. CASE REPORT A 45-year-old woman presented to our Emergency Department (ED) for severe generalized weakness. Initial test results indicated a diagnosis of microcytic anemia, hypomagnesemia, hypokalemia, hypocalcemia, hyperglycemia, type 2 diabetes mellitus, and severe heart failure. A computed tomography scan showed a 10-cm rim-enhancing fluid collection in the right hepatic lobe. Fluid drained from the suspected abscess tested positive for Serratia marcescens and Streptococcus viridans. The patient was treated with ceftriaxone and metronidazole, which she tolerated well. The abscess decreased to less than 9.8 mm. Twenty-one weeks after discharge, the patient received a cholecystectomy. Fluid drained from the residual abscess cultured positive for a different Serratia species, S. odorifera. CONCLUSIONS Diabetes mellitus and acute cholecystitis were key factors in the initial infections and abscess. We also suspect this is a rare case of cardiomyopathy induced by a Serratia infection. The source of the Serratia odorifera is less certain, as it postdates placement of a percutaneous drain, raising the potential for a nosocomial infection but not precluding the possibility that both Serratia species were previously present.