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Timothy Deer,1 Ankur A Patel,2 Dawood Sayed,3 Ashley Bailey-Classen,4 Ashley Comer,1 Benjamin Gill,5 Kiran Patel,6 Alaa Abd-Elsayed,7 Natalie Strand,8 Jonathan M Hagedorn,9 Zohra Hussaini,3 Nasir Khatri,10 Ryan Budwany,1 Melissa Murphy,11 Dan Nguyen,12 Vwaire Orhurhu,13 Morteza Rabii,14 Douglas Beall,15 Stephen Hochschuler,16 Michael E Schatman,17,18 Timothy Lubenow,19 Richard Guyer,16,20 Ahmed M Raslan21 1The Spine and Nerve Center of the Virginias, Charleston, WV, USA; 2Weill Cornell Tri-Institutional Pain Medicine Program, Department of Anesthesiology, Weill Medical College of Cornell University, New York, NY, USA; 3Department of Anesthesiology and Pain Medicine, the University of Kansas Medical Center, Kansas City, KS, USA; 4Trinity Pain Medicine Associates, Fort Worth, TX, USA; 5Department of Physical Medicine and Rehabilitation, University of Missouri, Columbia, MO, USA; 6Lenox Hill Hospital, Northwell Health, New York, NY, USA; 7Department of Anesthesiology, University of Wisconsin, Madison, WI, USA; 8Interventional Pain Management, Mayo Clinic, Scottsdale, AZ, USA; 9Department of Anesthesiology and Perioperative Medicine, Division of Pain Medicine, Mayo Clinic, Rochester, MN, USA; 10Novant Health Spine Specialists, Charlotte, NC, USA; 11North Texas Orthopedics and Spine Center, Grapevine, TX, USA; 12Neuroradiology and Pain Solutions of Oklahoma, Oklahoma City, OK, USA; 13Department of Anesthesia, University of Pittsburgh Medical Center, Susquehanna, PA, USA; 14Crimson Pain Management, Overland Park, Kansas, KS, USA; 15Comprehensive Specialty Care, Edmond, OK, USA; 16Texas Back Institute, Plano, TX, USA; 17Department of Anesthesiology, Perioperative Care and Pain Medicine, NYU Grossman School of Medicine, New York, NY, USA; 18Department of Population Health – Division of Medical Ethics, NYU Grossman School of Medicine, New York, NY, USA; 19Department of Anesthesiology, Rush University Medical Center, Chicago, IL, USA; 20Department of Orthopedic Surgery, University of Texas Southwestern Medical School, Dallas, TX, USA; 21Department of Neurological Surgery, Oregon Health and Science University, Portland, OR, USACorrespondence: Dawood Sayed, The University of Kansas Health System, 3901 Rainbow Blvd, Kansas City, KS, 66160, USA, Tel +1 913-588-5521, Email dsayed@kumc.eduIntroduction: The evolution of treatment options for painful spinal disorders in diverse settings has produced a variety of approaches to patient care among clinicians from multiple professional backgrounds. The American Society of Pain and Neuroscience (ASPN) Best Practice group identified a need for a multidisciplinary guideline regarding appropriate and effective informed consent processes for spine procedures.Objective: The ASPN Informed Consent Guideline was developed to provide clinicians with a comprehensive evaluation of patient consent practices during the treatment of spine pathology.Methods: After a needs assessment, ASPN determined that best practice regarding proper informed consent for spinal procedures was needed and a process of selecting faculty was developed based on expertise, diversity, and knowledge of the subject matter. A comprehensive literature search was conducted and when appropriate, evidence grading was performed. Recommendations were based on evidence when available, and when limited, based on consensus opinion.Results: Following a comprehensive review and analysis of the available evidence, the ASPN Informed Consent Guideline group rated the literature to assist with specification of best practice regarding patient consent during the management of spine disorders.Conclusion: Careful attention to informed consent is critical in achieving an optimal outcome and properly educating patients. This process involves a discussion of risks, advantages, and alternatives to treatment. As the field of interventional pain and spine continues to grow, it is imperative that clinicians effectively educate patients and obtain comprehensive informed consent for invasive procedures. This consent should be tailored to the patient’s specific needs to ensure an essential recognition of patient autonomy and reasonable expectations of treatment.Keywords: informed consent, best practice, clinical guideline, pain medicine, spine intervention, spine surgery

Evgenii Belykh,1 Arpan A Patel,1 Eric J Miller,1 Baran Bozkurt,1 Kaan Yağmurlu,1 Eric C Woolf,2 Adrienne C Scheck,2 Jennifer M Eschbacher,3 Peter Nakaji,1 Mark C Preul1 1Department of Neurosurgery, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, AZ, USA; 2Neuro-Oncology Research, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, AZ, USA; 3Department of Neuropathology, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, AZ, USA Background: Confocal laser endomicroscopy (CLE) is used during fluorescence-guided brain tumor surgery for intraoperative microscopy of tumor tissue with cellular resolution. CLE could augment and expedite intraoperative decision-making and potentially aid in diagnosis and removal of tumor tissue.Objective: To describe an extension of CLE imaging modality that produces Z-stack images and three-dimensional (3D) pseudocolored volumetric images.Materials and methods: Hand-held probe-based CLE was used to collect images from GL261-luc2 gliomas in C57BL/6 mice and from human brain tumor biopsies. The mice were injected with fluorescein sodium (FNa) before imaging. Patients received FNa intraoperatively, and biopsies were imaged immediately in the operating room. Some specimens were counterstained with acridine orange, acriflavine, or Hoechst and imaged on a benchtop confocal microscope. CLE images at various depths were acquired automatically, compiled, rendered into 3D volumes using Fiji software and reviewed by a neuropathologist and neurosurgeons.Results: CLE imaging, Z-stack acquisition, and 3D image rendering were performed using 19 mouse gliomas and 31 human tumors, including meningiomas, gliomas, and pituitary adenomas. Volumetric images and Z-stacks provided additional information about fluorescence signal distribution, cytoarchitecture, and the course of abnormal vasculature.Conclusion: 3D and Z-stack CLE imaging is a unique new option for live intraoperative endomicroscopy of brain tumors. The 3D images afford an increased spatial understanding of tumor cellular architecture and visualization of related structures compared with two-dimensional images. Future application of specific fluorescent probes could benefit from this rapid in vivo imaging technology for interrogation of brain tumor tissue. Keywords: 3D microscopy, confocal laser endomicroscopy, fluorescein sodium, fluorescence-guided brain tumor resection, glioma, brain tumor, volumetric imaging

Jagruti B Prajapati, Sneha D Verma, Amit A Patel Department of Ppharmaceutics and Ppharmaceutical Technology, Rramanbhai Patel College of Ppharmacy, Charotar University of Science and Technology, Changa, Gujarat, India Abstract: Agomelatine (AGM) is a new antidepressant drug with a novel mechanism of action and fewer side effects compared with older antidepressants. AGM is a melatonin receptor (MT1 and MT2) agonist and 5-hydroxytryptamine receptor (5-HT2C) antagonist. In the present study, the enhancement of the oral bioavailability of AGM was formulated and loaded into nanostructured lipid carriers (NLCs), using ultrasonication method. In vitro and ex vivo drug release was performed using a dialysis bag and rat duodenum, respectively. Our pharmacodynamic study showed that AGM–NLCs are more efficacious than a pure drug and marketed product, and confocal microscopy revealed lymphatic uptake of AGM–NLCs. The present study concluded that the NLCs enhanced the oral bioavailability of AGM (6.5-fold) by avoiding its first-pass metabolism by way of lymphatic uptake. Keywords: agomelatine, nanostructured lipid carriers, antidepressant drug

Raj B Padalia,1 Corey J Reeves,2 Neal Shah,1 Ankur A Patel,3 Devang M Padalia4 1Pain Medicine, University of South Florida, Tampa, FL, USA; 2Physical Medicine and Rehabilitation, University of South Florida, Tampa, FL, USA; 3Edward Via College of Osteopathic Medicine, Blacksburg, VA, USA; 4Interventional Pain, Moffitt Cancer Center, University of South Florida, Tampa, FL, USA Objective: Unilateral analgesia often occurs with epidural analgesia. Traditional methods of troubleshooting this problem can be insufficient in obtaining adequate pain relief in a timely manner for terminal cancer patients. This case report demonstrates a safe and effective solution which can be utilized in these circumstances.Case report: A 55-year-old female with stage IV pancreatic cancer and life expectancy of a few weeks presented to the interventional pain clinic with intractable sacral pain. The decision to place an epidural catheter and external pump for analgesia was made. An epidural catheter placed at the L5-S1 level showed contrast spread only along the right nerve roots and a test dose produced only right-sided analgesia. Suspecting compartmentalization of the epidural space, a second left-sided epidural catheter was placed and bilateral analgesia was achieved by using both catheters. This dual catheter technique gave the patient effective bilateral analgesia until she passed away several weeks later. Conclusion: The bilateral epidural catheter technique is safe and effective in patients who present with persistent unilateral epidural analgesia despite exhausting traditional solutions. Keywords: pain management, palliative care, cancer, regional techniques

Ashfaq Ahmad Patel, Abdul Rahman Arabi, Hakam Alzaeem, Jassim Al Suwaidi, Rajvir Singh, Hajar A Al BinaliDepartment of Cardiology, Heart Hospital, Hamad Medical Corporation, Doha, QatarBackground: There is limited information regarding the clinical characteristics and outcome of out of hospital cardiac arrest (OHCA) in Middle Eastern patients. The aim of this study was to evaluate clinical characteristics, treatment, and outcomes in patients admitted following OHCA at a single center in the Middle East over a 20-year period.Methods: The data used for this hospital-based study were collected for patients hospitalized with OHCA in Doha, Qatar, between 1991 and 2010. Baseline clinical characteristics, in-hospital treatment, and outcomes were studied in comparison with the rest of the admissions.Results: A total of 41,453 consecutive patients were admitted during the study period, of whom 987 (2.4%) had a diagnosis of OHCA. Their average age was 57±15 years, and 72.7% were males, 56.5% were Arabs, and 30.9% were South Asians. When compared with the rest of the admissions taken as a reference, patients with OHCA were more likely to have diabetes mellitus (42.8% versus 39.1%, respectively, P=0.02), prior myocardial infarction (21.8% versus 19.2%, P=0.04), and chronic renal failure (7.4% versus 3.9%, P=0.001), but were less likely to have dyslipidemia (16.9% versus 25.4%, P=0.001). Further, 52.6% of patients had preceding symptoms, the most common of which was chest pain (27.2%) followed by dyspnea (24.8%). An initially shockable rhythm (ventricular fibrillation or ventricular tachycardia) was present in 25.1% of OHCA patients, with ST segment elevation myocardial infarction documented in 30.0%. Severely reduced left ventricular systolic function (ejection fraction ≤35%) was present in 53.2% of OHCA patients; 42.9% had cardiogenic shock requiring use of inotropes at presentation. An intra-aortic balloon pump was inserted in 3.6% of cases. Antiarrhythmic medications were used in 27.4% and thrombolytic therapy in 13.9%, and 10.8% underwent a percutaneous coronary procedure (coronary angiography ± percutaneous coronary intervention). The in-hospital mortality rate was 59.8%.Conclusion: OHCA was associated with higher incidences of diabetes, prior myocardial infarction, and chronic kidney disease as compared with the remaining admissions. Approximately half of the patients had no preceding symptoms. In-hospital mortality was high (59.8%), but similar to the internationally published data.Keywords: out of hospital cardiac arrest, cardiogenic shock, in-hospital mortality

HIV-infected patients are known to be at risk for premature coronary artery disease. This emerging paradigm is a rising concern for clinicians. Due to advances in the treatment of HIV, this once fatal infection has been transformed into a chronic illness. Traditional risk factors paired with the long-term use of antiretroviral therapy (ART) and chronic inflammation leads to premature atherosclerosis, particularly progression of atherosclerotic plaque. This population of patients requires early recognition of subclinical atherosclerosis, as well aggressive primary and secondary prevention strategies among the multi-disciplinary team of physicians caring for them. We sought to present a comprehensive review of the available literature related to HIV and atherosclerosis and cardiovascular risk.

The mechanistic link between ER stress, autophagy, and resultant cell death was investigated by the use of drugs Thapsigargin (Tg) and Chloroquine (CQ) with prior induction and or blockade of autophagy and apoptosis which modulated the ER stress response and resultant form of cell death. All these biological processes can be measured flow cytometrically allowing the determination of the type of cell death, G1 cell cycle arrest, cell cycle dependent measurement of ER stress transducer PERK, misfolded proteins, reticulophagy, and autophagy marker LC3B. Jurkat cells after Tg or CQ treatment became necrotic and apoptotic, showed G1 cell cycle arrest, autophagy, and ER stress. Prior induction of autophagy before ER stress increased levels of necrotic and apoptotic cell death. Autophagy was further up‐regulated, while PERK was reduced or abrogated. CQ showed reduced levels of misfolded proteins and reticulophagy, while Tg showed no change in misfolded protein levels but increased reticulophagy and thus displayed more ER stress. Prior blockade of apoptosis before induction of ER stress resulted in cell survival except with high Tg levels which induced necrosis. Autophagy was up‐regulated with modulation of PERK and reticulophagy levels with an abrogation of the misfolded protein response. Blockade of apoptosis with induction of autophagy before ER stress showed death by necrosis with high dose drugs and cell survival with low doses of drugs. CQ induced reduced levels G1 cell cycle arrest while it was maintained with Tg. Autophagy was also maintained with reduced levels of ER stress. These data demonstrates a profound link between the processes of ER stress, autophagy, and the resultant form of cell death all of which can be modulated depending upon the sequence and concentration of drugs employed. © 2018 International Society for Advancement of Cytometry [ABSTRACT FROM AUTHOR]

Objective: Although low HDL cholesterol (HDL-C) is an established risk factor for atherosclerosis, data on HDL-C and the risk of microvascular disease are limited. We tested the association between HDL-C and microvascular disease in a cohort of patients with type 2 diabetes.Research Design and Methods: A total of 11,140 patients with type 2 diabetes and at least one additional vascular risk factor were followed a median of 5 years. Cox proportional hazards models were used to assess the association between baseline HDL-C and the development of new or worsening microvascular disease, defined prospectively as a composite of renal and retinal events.Results: The mean baseline HDL-C level was 1.3 mmol/L (SD 0.45 mmol/L [range 0.1-4.0]). During follow-up, 32% of patients developed new or worsening microvascular disease, with 28% experiencing a renal event and 6% a retinal event. Compared with patients in the highest third, those in the lowest third had a 17% higher risk of microvascular disease (adjusted hazard ratio 1.17 [95% CI 1.06-1.28], P = 0.001) after adjustment for potential confounders and regression dilution. This was driven by a 19% higher risk of renal events (1.19 [1.08-1.32], P = 0.0005). There was no association between thirds of HDL-C and retinal events (1.01 [0.82-1.25], P = 0.9).Conclusions: In patients with type 2 diabetes, HDL-C level is an independent risk factor for the development of microvascular disease affecting the kidney but not the retina. [ABSTRACT FROM AUTHOR]

Background: The lateral transpsoas approach to the lumbar spine was developed to eliminate the need for an anterior-approach surgeon and retraction of the great vessels and has the potential for shorter operative times. However, the reported complications associated with this approach vary.Questions/purposes: We identified the incidence of complications associated with the lateral transpsoas approach to the lumbar spine.Patients and Methods: We retrospectively reviewed 45 patients who underwent a lateral transpsoas approach to the spine for various diagnoses between January 1, 2006, and October 31, 2010. The patients' average age was 63.3 years. Sixteen (35.6%) patients had prior lumbar spinal surgery. Twenty-one patients (46.7%) underwent supplemental posterior instrumentation. Minimum followup was 0 months (mean, 11 months; range, 0-34 months).Results: Eighteen of the 45 patients (40%) had complications: 10 (22.2%) developed postoperative iliopsoas weakness, three had quadriceps weakness, and one experienced foot drop. Eight patients (17.8%) developed anterior thigh hypoesthesia, which did not fully resolve in seven of the eight patients at an average of 9 months' followup. Three patients had postoperative radiculopathies, one a durotomy, and one died postoperatively from a pulmonary embolism.Conclusions: We found a 40% incidence of complications and a nontrivial frequency and severity of postoperative weakness, numbness, and radicular pain in patients who underwent a lateral transpsoas approach to the spine. Given the expanding use of the approach, a thorough understanding of the risks associated with it is essential for patient education, medical decision making, and identifying methods of reducing such complications.Level Of Evidence: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Objective: To examine the perception and management of cardiovascular disease (CVD) risk in Australian primary care.Design, Setting and Participants: The Australian Hypertension and Absolute Risk Study (AusHEART) was a nationally representative, cluster-stratified, cross-sectional survey of 322 general practitioners. Each GP was asked to collect data on CVD risk factors and their management in 15-20 consecutive patients aged >or= 55 years who presented between April and June 2008, and to estimate each patient's absolute risk of a cardiovascular event in the next 5 years.Main Outcome Measures: Estimated 5-year risk of a cardiovascular event, proportion of patients receiving appropriate treatment.Results: Among 5293 patients, 29% (1548) had established CVD. A further 22% (1145), when categorised according to the 2009 National Vascular Disease Prevention Alliance guideline, to 42% (2211), when categorised according to National Heart Foundation (NHF) 2004 guideline, had a high (>or= 15%) 5-year risk of a cardiovascular event. Of the 1548 patients with established CVD, 50% were prescribed a combination of a blood pressure (BP)-lowering medication, a statin and an antiplatelet agent, and 9% were prescribed a BP-lowering medication and a statin but not an antiplatelet agent. Among high-risk patients without established CVD, categorised using NHF 2004 adjustments, 34% were prescribed a combination of a BP-lowering medication and a statin. GPs estimated 60% of patients with established CVD as having a risk of less than 15%. The GPs' estimates of risk among patients without established CVD agreed with the centrally calculated estimate (according to the NHF 2004 guideline) in 48% of instances (Kappa = 0.21).Conclusions: These data confirm substantial undertreatment of patients who are at high risk of a cardiovascular event. We recommend that GPs assess absolute risk for older patients and ensure that high-risk patients receive evidence-based pharmacotherapy. [ABSTRACT FROM AUTHOR]

Background: To perform a meta analysis of randomised placebo-controlled trials evaluating the use of dopamine agonist (DA) or placebo to preexisting levodopa therapy for the treatment of advanced Parkinson's disease (PD). We focused on clinically important efficacy [Unified Parkinson's Disease Rating Scale (UPDRS) activities of daily living (ADL) and motor scores as well as change in 'off' time and levodopa dose] and safety outcomes (withdrawal because of adverse drug events (ADEs), dyskinesias, hallucinations and mortality). Methods: A systematic literature search was performed between January 1990 and July 2007. The primary outcome measures assessed were the reduction in scores of Unified Parkinson's Disease Rating Scale (UPDRS) activities of daily living (ADL) and motor scores as well as reduction in 'off' time and reductions in levodopa dose from baseline. Safety end-points were also evaluated. Results: A total of 15 trials ( n = 4380 subjects) were included in the meta analysis. Adjunctive DA use resulted in greater improvement as measured by the UPDRS ADL [weighted mean difference (WMD) -2.20, 95% confidence interval (CI) -2.64 to -1.76; p < 0.0001] and motor score reduction (WMD -5.56, 95% CI -6.82 to -4.31; p < 0.0001) as well as reduction in 'off' time measured in hours/day (WMD -1.20, 95% CI -1.78 to -0.62; p < 0.0001) and reduction in levodopa dose (WMD -128.5 mg, 95% CI -175.0 to -82.1; p < 0.0001) vs. placebo. Incidence of dyskinesia and hallucinations was higher with DAs [odds ratio (OR) 3.27, 95% CI 2.65-4.03; p < 0.0001] and (OR 3.34, 95% CI 2.44-4.58; p < 0.0001). Non-ergot DAs were qualitatively better, although both ergot and non-ergot DAs showed statistically significant improvements in all UPDRS scores. Conclusion: Adjunctive DA use to levodopa is superior to levodopa alone in reducing PD symptoms in patients not controlled with monotherapy. DAs seem especially useful amongst PD patients with wearing-off phenomenon from levodopa therapy, but can cause some adverse events. [ABSTRACT FROM AUTHOR]

Study Design: A retrospective review. Objective: The purpose of this study is to document a series of cases of neurologic deficit following percutaneous vertebral stabilization, to identify patterns of neurologic injury, and to describe potential methods for avoiding these injuries. Summary Of Background Data: Percutaneous vertebral stabilization procedures, including vertebroplasty and kyphoplasty, have become a widely used for the treatment of osteoporotic vertebral compression fractures, primary and metastatic vertebral tumors, and traumatic burst fractures. Despite an increasing array of indications, there have been few reports of adverse events. Neurologic complications associated with vertebroplasty and kyphoplasty have been described previously as case reports and have generally been considered as infrequent and minor in severity. Methods: The clinical course of 14 patients with documented loss of neurologic function following percutaneous vertebral cement augmentation was retrospectively reviewed. Results: The average patient age was 74.9 years (range, 46-88 years) with 3 male and 11 female patients. Four patients underwent a vertebroplasty procedure while 10 were treated with kyphoplasty. Six patients developed neurologic deficits acutely (<24 hours of procedure). The remaining 8 patients developed neurologic symptoms at an average of 37.1 days (range, 3-112 days) postprocedure. Neurologic deficits were recorded as ASIA A in 4 patients, ASIA B in 2 patients, ASIA C in 1 patient, and ASIA D in 7 patients. Twelve of 14 patients (85.7%) required revision open surgical intervention for treatment of their neurologic injury. Conclusion: Percutaneous vertebroplasty and kyphoplasty have been reported to be safe options for the treatment of painful osteoporotic vertebral fractures. Although complications are infrequent, there remains the potential for catastrophic neurologic injury. Physicians performing these procedures need to be aware of these potential complications and be prepared to respond in an emergent manner (surgically) if a need arises. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationship between statin therapy and the development of new-onset, recurrent, and postoperative atrial fibrillation (AF).Research Design and Methods: A systematic literature search was conducted through September 2006. Included studies were either randomized, controlled trials or observational studies with adjusted analyses using multivariate regression or covariate matching, compared patients receiving or not receiving a statin, and reported data on the incidence of AF. Weighted averages were reported as odds ratios with 95% confidence intervals (CIs) using a random-effects model.Main Outcome Measures: The primary outcome measured was a combined endpoint of any AF type. Secondary outcomes included new-onset, recurrent, and postoperative AF.Results: Fourteen trials reporting the results of 15 unique analyses (n = 7402) were included. There was a 20% incidence rate for any AF with varying rates depending on AF type (new-onset [11%], recurrent [56%], recurrent after cardioversion [54%], postoperative [22%]). The use of a statin reduced the odds of developing any AF by 45% (odds ratio [OR] 0.55; 95% CI 0.43-0.70); Q statistic p = 0.001). Statins reduced the odds of developing new-onset AF by 32% (OR 0.68; 95% CI 0.51-0.90), recurrent AF by 57% (OR 0.43; 95% CI 0.24-0.79), recurrent AF after cardioversion by 42% (OR 0.58; 95% CI 0.32-1.05) and postoperative AF by 58% (OR 0.42; 95% CI 0.27-0.65).Limitations: We considered studies that were observational in nature or only available in abstract form. Publication bias could not be ruled out.Conclusions: Statin therapy was associated with a reduced odds of developing AF, thus providing evidence of the benefit of statins beyond the lipid-lowering activity. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine the impact of statin therapy on the combined endpoint of cardiovascular events in women and men separately. RESEARCH DESIGN AND METHODS: A systematic literature search through May 2006 was conducted to identify randomized, controlled statin trials evaluating the gender specific incidence of cardiovascular events. Weighted averages were reported as relative risks (RRs) with 95% confidence intervals (CI) calculated via random-effects model. MAIN OUTCOME MEASURES: The primary outcome measured was a composite endpoint of all cardiovascular events. Secondary outcomes measured included death, myocardial infarction (MI), and stroke. RESULTS: Fifteen trials were included in this meta-analysis. Cardiovascular events were reduced in men (RR 0.76 [95% CI 0.70, 0.81]) and women (RR 0.79 [95% CI 0.69, 0.90]). Reductions in mortality, MI, and stroke predominantly contributed to the reduction in cardiovascular events in men taking statins. Women did not have a reduction in mortality or stroke, suggesting that the reductions in cardiac events may have been predominantly due to reductions in need for revascularization and/or unstable angina. CONCLUSIONS: Statins reduced the risk of cardiovascular events in men and women, but women on statins may not have reductions in mortality and stroke like their male counterparts. [ABSTRACT FROM AUTHOR]

Objective: Pharmacy-managed medication assistance programs (MAPS) allow patients without insurance coverage to receive medications free of charge. Improved access to medications may provide an avenue for these patients to positively affect their treatment outcomes by improving adherence. This study sought to assess the effect of a MAP on treatment outcomes in patients with type 2 diabetes. Methods: This before-and-after study was conducted with patients enrolled in the University of Connecticut School of Pharmacy's and Hartford Hospital's outpatient MAP between May 2003 and April 2005. All adult patients in whom type 2 diabetes mellitus was diagnosed and who were receiving at least 1 antihyperglycemic agent were included. Patients were excluded from the analysis if they did not have at least 1 hemoglobin A[1c] (HbA[1c]) level drawn within the 6-month period before their enrollment in the MAP. Six-month pre- and post-enrollment data on the primary end point (mean HbA[1c]) as well as other disease markers were compared. Results: Of the 143 patients enrolled in the outpatient MAP, 50 patients (mean age 59±8 years, 52% male, 82% non-Caucasian) met all study inclusion criteria. After 6 months of program enrollment, a statistically significant reduction in mean HbA[1c] levels was observed (-0.85%; 95% CI, -0.34% to -1.37%; P=.002). As a result of this reduction, there was a 33% increase in the percentage of patients in whom the goal of an HbA[1c] level of <7% (P=.008) was achieved. Significant reductions in total cholesterol (25.7 mg/dL; 95% Cl, -11.1 to -40.2; P=.001) also were demonstrated when comparing pre- and post-enrollment values. Conclusion: Enrollment in this MAP was associated with reductions in HbA[1c] levels and an increased likelihood of achieving national diabetes treatment goals in type 2 diabetic patients. [ABSTRACT FROM AUTHOR]

Objective: Pharmacy-managed medication assistance programs (MAP) have the potential to recoup losses incurred by the pharmacy department, but whether this offsets the personnel cost of the program has not been well-established. The purpose of this study was to conduct a cost-benefit analysis of the pharmacy-managed MAP at an urban teaching clinic at Hartford Hospital in Hartford, Conn. Methods: Patients were enrolled into a MAP at Hartford Hospital, a large urban teaching hospital, based on referrals from social workers. Patients were assisted in identifying pharmaceutical manufacturers providing free drugs and completing applications. The program's benefit was defined as the value of the drugs procured using average wholesale price (AWP) in 2005 US dollars. The costs to the pharmacy consisted of personnel cost (time administering the program times a wage rate of $18.02/h). The net benefit was calculated as the value of the drugs procured minus personnel costs. Threshold sensitivity analysis and Monte Carlo simulation were performed by varying drug value, personnel time, and wage rate. Results: Over the 24-month period (May 2003 through April 2005), 143 patients were enrolled into the program, with 328 medication shipments received. The total benefit for all drugs was $83,504. An average of 4 h/wk were spent administering the program, resulting in personnel costs of $7,496. The program yielded a net benefit of 576,008. Upon sensitivity analysis, the break-even point was reached when the drug value was reduced to 57,496, personnel lime increased to 4,634 hours (44.5 h/wk), or the wage rate increased to $200/h. When the value of the drug procured, personnel time, and wage rate were simultaneously varied within plausible ranges ($68,175-$171,584, 2 h/wk-40 h/wk, and $13.65/h-$43.60/h, respectively), Monte Carlo simulation demonstrated there was a 96.1% chance of the program being cost-beneficial. Conclusion: This study demonstrated that Hartford Hospital's pharmacy-managed MAP for indigent inpatients was cost-beneficial. The conclusions of the study were found to be robust to changes in drug value, personnel time, and wage rate. [ABSTRACT FROM AUTHOR]

Long-term glycemic control substantially reduces the risk of diabetes mellitus-related complications. Insulin is a mainstay in therapy in type 1 and later-stage type 2 diabetes mellitus. Although insulin is effective in controlling blood glucose and hemoglobin A1c concentrations, the need for subcutaneous injection can be a burden for patients, which can impact compliance. Exubera (NektarTherapeutics/Pfizer/Sanofi-Aventis) is an inhaled insulin that has demonstrated results similar to conventional short-acting insulin products while also increasing overall patient satisfaction. If approved, Exubera would be the first non-injectable insulin available in the United States. The product is administered as a dry powder fast-acting form of insulin via oral inhalation. FDA's Endocrinologic and Metabolic Drugs Advisory Committee recommended Exubera for approval in early September 2005. Exubera may offer an excellent alternative for patients suffering from diabetes who for health, personal, or societal reasons have difficulty administering subcutaneous insulin. [ABSTRACT FROM AUTHOR]

The risk of ventilator induced lung injury in mechanically ventilated (MV) critically ill patients can be mitigated by patient-specific optimisation of ventilator settings. Recent studies have shown that driving pressure, i.e. the difference between plateau pressure (Pplat) and PEEP, is a strong indicator for survival in MV patients suffering from ARDS. However, to measure Pplat, an extended end-inspiratory pause (EIP) has to be applied, possibly interrupting ventilation therapy. This study presents a method for predicting Pplat from normal breaths in MV patients.

Sarcoidosis is a systemic disease characterized by noncaseating granulomas in the involved organs. Neurologic manifestations involving the central and/or peripheral nervous system occur in about 5% of patients. Neurosarcoidosis is often refractory to conventional treatment and therefore more effective treatment options are needed. While the etiology of the disease is still unknown, there is now a better understanding of its pathogenesis on a molecular level. It is clear that tumor necrosis factor-α (TNFα) plays a pivotal role in the development of the granulomas and it is believed to be a key cytokine involved in the pathogenesis of the disease. Taking advantage of this better understanding of disease pathogenesis, anti-TNFα agents are being increasingly used to treat refractory sarcoidosis. We report a patient with refractory neurosarcoidosis who showed dramatic improvement in the clinical and radiological manifestations following treatment with infliximab; he suffered a relapse upon discontinuation of the medication.

Abstract Background Generic Medicines are an important policy option allowing for access to affordable, essential medicines. Quality of generic medicines must be guaranteed through the activities of national medicines regulatory authorities. Existing negative perceptions surrounding the quality of generic medicines must be addressed to ensure that people use them with confidence. Campaigns to increase the uptake of generic medicines by consumers and providers of healthcare need to be informed by local norms and practices. This study sought to compare South African consumers’ and healthcare providers’ perceptions of quality of generics to the actual quality of selected products. Methods The study was conducted at the local level in three cities of South Africa: Johannesburg, Durban and Cape Town. Purposive sampling was used to recruit consumer participants (n = 73) and random sampling used to recruit healthcare providers from public and private sectors (n = 15). Data were obtained through twelve focus group discussions with consumers and semi-structured interviews (n = 15) with healthcare providers in order to gain familiarity with perceptions of quality. One hundred and thirty five products comprising paracetamol tablets (n = 47), amoxicillin capsules (n = 45) and hydrochlorothiazide tablets (n = 43) were sourced from public and private sector healthcare providers. These products were subjected to in vitro dissolution, uniformity of weight and identity (Fourier Transformed Infrared Spectroscopy) tests using prescribed methods from the British (2005) and United States Pharmacopeias (2006). Results Respondents described drug quality in relation to the effect on symptoms. Procurement and use behavior of healthcare providers was influenced by prior experience, manufacturers’ names and consumers’ ability to pay. All formulations passed the in vitro tests for quality. Conclusions This study showed clear differences between perceptions of quality and actual quality of medicines suggesting deficiencies in public engagement by government regarding the implementation of generic medicines policy. Implementation of generic medicines policy requires the involvement of consumers and healthcare providers to specifically address their information gaps and needs.

Abstract Background The use of warfarin in older patients requires special consideration because of concerns with comorbidities, interacting medications, and the risk of bleeding. Several studies have suggested that warfarin may be underused or inconsistently prescribed in long-term care (LTC); no published systematic review has evaluated warfarin use for stroke prevention in this setting. This review was conducted to summarize the body of published original research regarding the use of warfarin in the LTC population. Methods A systematic literature search of the PubMed, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Library was conducted from January 1985 to August 2010 to identify studies that reported warfarin use in LTC. Studies were grouped by (1) rates of warfarin use and prescribing patterns, (2) association of resident and institutional characteristics with warfarin prescribing, (3) prescriber attitudes and concerns about warfarin use, (4) warfarin management and monitoring, and (5) warfarin-related adverse events. Summaries of study findings and quality assessments of each study were developed. Results Twenty-two studies met the inclusion criteria for this review. Atrial fibrillation (AF) was the most common indication for warfarin use in LTC and use of warfarin for stroke survivors was common. Rates of warfarin use in AF were low in 5 studies, ranging from 17% to 57%. These usage rates were low even among residents with high stroke risk and low bleeding risk. Scored bleeding risk had no apparent association with warfarin use in AF. In physician surveys, factors associated with not prescribing warfarin included risk of falls, dementia, short life expectancy, and history of bleeding. International normalized ratio was in the target range approximately half of the time. The combined overall rate of warfarin-related adverse events and potential events was 25.5 per 100 resident months on warfarin therapy. Conclusions Among residents with AF, use of warfarin and maintenance of INR levels to prevent stroke appear to be suboptimal. Among prescribers, perceived challenges associated with warfarin therapy often outweigh its benefits. Further research is needed to explicitly consider the appropriate balancing of risks and benefits in this frail patient population.

Abstract Background The purpose of this study was to measure the impact of an educational intervention on parents of children taking methotrexate (MTX) for juvenile idiopathic arthritis (JIA). Methods This study was conducted using a pre- and postsurvey design. The parents of 100 children with JIA taking MTX for at least 2 months were surveyed during a routine office visit. The parents completed an initial questionnaire regarding the safe use, adverse effects, and guidelines for monitoring the toxicity of MTX. An educational intervention was then administered, and an identical follow-up questionnaire was given during the next office visit. Statistical analysis using a paired t-test (critical P value < 0.05) was performed on individuals who answered both questionnaires. Results There were 100 responses to the initial questionnaire and 67 responses to the follow-up questionnaire. The mean length of time between surveys was 2.9 ± 0.9 months. In those who completed both questionnaires, the overall correct score increased significantly from 75.8% to 93.4%, respectively (P < 0.0001). Individuals scored the lowest (49%) on the question that addressed MTX's impact on pregnancy and fertility. Conclusions MTX knowledge may be less than expected in the parents of children with JIA. Brief educational interventions in the pediatric subspecialty practice can significantly affect a family's understanding of their child's medications.

Study Design: Case report; Review of Literature. Objective: To present an uncommon complication after anterior lumbar surgery as well as a treatment option and a review of the literature. Summary Of Background Data: A number of complications have been reported after anterior lumbar surgery. Common complications include vascular, ureteral, and neurologic injuries. The development of a retroperitoneal lymphocele has been previously been described, but details regarding evaluation, diagnosis, and treatment options are lacking in the literature. Methods: The case of a single patient with a postoperative retroperitoneal lymphocele was identified and retrospectively reviewed. Permission was obtained from the patient to review and publish this information. A review of literature on lymphoceles and anterior lumbar complications was also performed using PubMed and Ovid databases. Results: A 76-year-old woman underwent anterior interbody fusion from L2-L3-L4-L5, followed by posterior T11-L5 fusion for degenerative scoliosis and spinal stenosis. Six weeks after surgery, she presented with severe abdominal pain, nausea, and emesis. Examination revealed a retroperitoneal lymphocele, which was confirmed after aspiration. The patient was treated with a laparoscopic marsupialization procedure without recurrence. At 12 months, the patient had no further abdominal symptoms, noted improvements in back and leg pain scores, and had stable radiographic findings. Conclusion: Retroperitoneal lymphocele is a rare complication after anterior lumbar interbody fusion. The different diagnosis should include infectious abscess, ureteral injury with urinoma, pancreatic injury with pseudocyst formation, and spinal fluid leak with pseudomeningocele. Diagnosis can be guided by serum and cyst fluid analysis. Although treatment options exist, surgical treatment may provide the most reliable results. [ABSTRACT FROM AUTHOR]

MicroRNAs, a collection of short noncoding RNAs, are promising biomarkers for identifying cancer in its early stages and tracking the effectiveness of treatment. This is due to their critical role in regulating gene expression and other vital biological functions via cell-level epigenetic mechanisms. This review brings together data on the molecular and clinical effects of miR-765 on different types of cancer. Significant variation in miR-765 levels has been observed in a variety of cancer types, suggesting that it could have an oncogene or tumor suppressor role. A number of pathways, including PLP2/Notch, VEGFA/Akt1, PDX1, KLK4, RUNX2, DPF3, EMP3, APE1, ERK/EMT axis, and others, are impacted by the inclusion of miR-765 in their analysis. MiR-765 is an essential biomarker that shows promise as a diagnostic tool for various types of cancer. The latest research has identified them as reliable predictive markers for detecting tumor development at an early stage. Based on our study, miR-765 shows promising potential as a biomarker for prognosis in multiple types of cancer. Specifically, we suggest that miR-765 could be an early detection marker for tumor development, progression, and metastasis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Myelofibrosis (MF) in the chronic phase is a challenging disease entity to treat, and conventional treatment options are geared towards symptom palliation. In this prospective, multicenter, phase II trial, 21 patients with myelofibrosis (18 chronic-phase, 2 accelerated-phase, 1 blast-phase) were treated with a 10-day schedule of subcutaneous decitabine at 0.3 mg/kg/day. The overall response rate was 33% (95% CI, 15-57), primarily manifested as an improvement in cytopenias. The median duration of response was 7 months (range, 3-44). A high IPSS risk score, high baseline fetal hemoglobin level, and sustained decreases in circulating CD34+ cell counts were associated with response to decitabine. All patients experienced at least one grade 3 or 4 cytopenia. Non-hematologic toxicities were less frequent, with fatigue, anorexia, and hypocalcemia being the most common. Given the lack of effective therapies in myelofibrosis with severe cytopenias, this study supports further investigation into the use of hypomethylating agents as single agents or in combination therapies. NCT00095784., (Copyright © 2024 American Society of Hematology.)

Purpose: Otoacoustic emissions (OAE) are a common screening tool to evaluate cochlear function. Middle ear dysfunction has been shown to impact results of otoacoustic emission testing, but there are limited data on the effect of tympanostomy tubes on OAE. The purpose of this study was to determine whether tympanostomy tube placement significantly improved OAE., Methods: A retrospective review of charts was completed for patients younger than 18 years old who underwent tympanostomy tube placement from January 1, 2018 to September 1, 2023 and had preoperative and postoperative OAE testing within 6 months of surgery. The primary variable was presence of OAE preoperatively and postoperatively. Chi-square analysis and t test were used for statistical analysis., Results: A total of 212 ears were examined from 111 pediatric patients who underwent tympanostomy tube placement during the study period. Presence of OAE at 3000, 4000, and 5000 Hz were all noted to significantly increase following tympanostomy tube placement, with OAE presence increasing from approximately 27.8% of the sample preoperatively to 95.3% postoperatively at 3000 and 4000 Hz. Patients who noted improvement had a significantly higher proportion of type B tympanogram preoperatively, compared to a higher proportion of type A tympanogram noted in patients who did not note improvement., Conclusion: Tympanostomy tubes can significantly improve otoacoustic emissions in patients with middle ear dysfunction., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Inpatient and outpatient evaluation is important for management of temporal bone trauma due to the possible otologic complications that can result. However, there is limited literature on follow up rates following temporal bone fracture. This study aimed to determine the proportion of patients lost to follow up after sustaining temporal bone fractures and identify factors associated with loss to follow up., Methods: Retrospective review of adult patients who sustained temporal bone fractures at a level I trauma center from January 1, 2019 to January 1, 2024 was completed (IRB H-44161). The primary outcome included prevalence of patient loss to follow up. Secondary variables included initial radiographic and exam findings, otologic complications, and demographic characteristics. Patients who were seen in follow up and lost to follow up were compared, and odds of loss to follow up was calculated., Results: Sixty-nine patients met inclusion criteria for this study, of which 30 patients (43.5%) were lost to follow up. Patients who were White had a significantly lower odds of loss to follow up than those who were not White (OR = 0.2506 (95% CI: 0.0706, 0.8067, P  = .0024). While need for acute management was not significantly different between the groups, a significantly lower proportion of patients who were intubated on presentation ( P  = .0091), had abnormal otoscopic exam ( P  = .0211), and had otologic complications ( P  = .0056) were lost to follow up., Conclusion: Almost half of patients who sustained temporal bone fractures, including a significantly higher odds of minority race/ethnicity patients, were lost to follow up., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.