Assessment of cardiopulmonary point-of-care ultrasound objective structured clinical examinations in graduating anesthesiology residents across multiple residency programs.

STUDY OBJECTIVE: To implement and assess a cardiopulmonary point-of-care ultrasound (POCUS) objective structured clinical examination (OSCE) in a large cohort of graduating anesthesia residents. DESIGN: Observational cohort study. SETTING: University-affiliated hospitals. SUBJECTS: 150 graduating anesthesia residents in their last nine months of training. INTERVENTIONS: A standardized cardiopulmonary OSCE was administered to each resident. MEASUREMENTS: The cardiac views evaluated were parasternal long axis (PLAX), apical 4 chamber (A4C), and parasternal short axis (PSAX). The pulmonary views evaluated were pleural effusion (PLE) and pneumothorax (PTX). In addition, a pre- and post-exam survey scored on a 5-point Likert scale was administered to each resident. MAIN RESULTS: A4C view (mean 0.7 ± 0.3) scored a lower mean, compared to PSAX (mean 0.8 ± 0.3) and PLAX (mean 0.8 ± 0.4). Residents performed well on the PTX exam (mean 0.9 ± 0.3) but more poorly on the PLE exam (mean 0.6 ± 0.4). Structural identification across cardiac and pulmonary views were mostly high (means >0.7), but advanced interpretive skills and maneuvers had lower mean scores. Pre- and post- OSCE survey results were positive with almost all questions scoring >4 on the Likert scale. CONCLUSION: Our study demonstrates that a cardiopulmonary POCUS OSCE can be successfully implemented across multiple anesthesia training programs. While most residents were able to perform basic ultrasound views and identify structures, advanced interpretive skills and maneuvers performed lower.

Cardiogenic Shock Complicating ST-Segment Elevation Myocardial Infarction: An 18-Year Analysis of Temporal Trends, Epidemiology, Management, and Outcomes.

BACKGROUND: There are limited data on the temporal trends, incidence, and outcomes of ST-segment-elevation myocardial infarction-cardiogenic shock (STEMI-CS). METHODS: Adult (>18 years) STEMI-CS admissions were identified using the National Inpatient Sample (2000-2017) and classified by tertiles of admission year (2000-2005, 2006-2011, 2012-2017). Outcomes of interest included temporal trends, acute organ failure, cardiac procedures, in-hospital mortality, hospitalization costs, and length of stay. RESULTS: In ∼4.3 million STEMI admissions, CS was noted in 368,820 (8.5%). STEMI-CS incidence increased from 5.8% in 2000 to 13.0% in 2017 (patient and hospital characteristics adjusted odds ratio [aOR] 2.45 [95% confidence interval {CI} 2.40-2.49]; P < 0.001). Multiorgan failure increased from 55.5% (2000-2005) to 74.3% (2012-2017). Between 2000 and 2017, coronary angiography and percutaneous coronary intervention use increased from 58.8% to 80.1% and 38.6% to 70.6%, whereas coronary artery bypass grafting decreased from 14.9% to 10.4% (all P < 0.001). Over the study period, the use of intra-aortic balloon pump (40.6%-37.6%) decreased, and both percutaneous left ventricular assist devices (0%-12.9%) and extra-corporeal membrane oxygenation (0%-2.8%) increased (all P < 0.001). In hospital mortality decreased from 49.6% in 2000 to 32.7% in 2017 (aOR 0.29 [95% CI 0.28-0.31]; P < 0.001). During the 18-year period, hospital lengths of stay decreased, hospitalization costs increased and use of durable left ventricular assist device /cardiac transplantation remained stable (P > 0.05). CONCLUSIONS: In the United States, incidence of CS in STEMI has increased 2.5-fold between 2000 and 2017, while in-hospital mortality has decreased during the study period. Use of coronary angiography and PCI increased during the study period.

Temporal Trends, Clinical Characteristics, and Outcomes of Emergent Coronary Artery Bypass Grafting for Acute Myocardial Infarction in the United States.

Background There are limited contemporary data on the use of emergent coronary artery bypass grafting (CABG) in acute myocardial infarction. Methods and Results Adult (aged >18 years) acute myocardial infarction admissions were identified using the National (Nationwide) Inpatient Sample (2000-2017) and classified by tertiles of admission year. Outcomes of interest included temporal trends of CABG use; age-, sex-, and race-stratified trends in CABG use; in-hospital mortality; hospitalization costs; and hospital length of stay. Of the 11 622 528 acute myocardial infarction admissions, emergent CABG was performed in 1 071 156 (9.2%). CABG utilization decreased overall (10.5% [2000] to 8.7% [2017]; adjusted odds ratio [OR], 0.98 [95% CI, 0.98-0.98]; P<0.001), in ST-segment-elevation myocardial infarction (10.2% [2000] to 5.2% [2017]; adjusted OR, 0.95 [95% CI, 0.95-0.95]; P<0.001) and non-ST-segment-elevation myocardial infarction (10.8% [2000] to 10.0% [2017]; adjusted OR, 0.99 [95% CI, 0.99-0.99]; P<0.001), with consistent age, sex, and race trends. In 2012 to 2017, compared with 2000 to 2005, admissions receiving emergent CABG were more likely to have non-ST-segment-elevation myocardial infarction (80.5% versus 56.1%), higher rates of noncardiac multiorgan failure (26.1% versus 8.4%), cardiogenic shock (11.5% versus 6.4%), and use of mechanical circulatory support (19.8% versus 18.7%). In-hospital mortality in CABG admissions decreased from 5.3% (2000) to 3.6% (2017) (adjusted OR, 0.89; 95% CI, 0.88-0.89 [P<0.001]) in the overall cohort, with similar temporal trends in patients with ST-segment-elevation myocardial infarction and non-ST-segment-elevation myocardial infarction. An increase in lengths of hospital stay and hospitalization costs was seen over time. Conclusions Utilization of CABG has decreased substantially in acute myocardial infarction admissions, especially in patients with ST-segment-elevation myocardial infarction. Despite an increase in acuity and multiorgan failure, in-hospital mortality consistently decreased in this population.

The Direct Healthcare Cost of Stargardt Disease: A Claims-Based Analysis.

Purpose: Stargardt disease (SD) is the most common juvenile macular degeneration and a leading cause of uncorrectable childhood blindness. The progressive and incurable nature of this chronic condition entails a long-term financial burden on affected individuals. The economic costs of SD have not been characterized in detail, so we aimed to estimate the direct healthcare cost of SD.Methods: Outpatient administrative claims data (2010-2014) for patients with SD were analyzed from the IBM® MarketScan® Commercial Claims and Encounters Database. Two comparison groups were selected: nonexudative age-related macular degeneration (AMD) and bilateral sensorineural hearing loss (SHL). Gross median payments per year of insurance coverage were calculated.Results: A total of 472,428 patients were analyzed (5,015 SD, 369,750 SHL and 97,663 AMD patients respectively). The payment per year of insurance coverage for SD (median: 105.58 USD, IQR: 50.53 USD-218.71 USD) was higher than that of SHL (median: 51.01 USD, IQR: 25.66 USD-121.66 USD, p < .001) and AMD (median: 76.20 USD, IQR: 38.00 USD-164.86 USD, p < .001). When adjusted for age, sex, year of first service, and type of benefit plan, the annual payment for SD was 47.83 USD higher than SHL (p < .001) and 17.34 USD higher than AMD (p < .001).Conclusions: There is a significant direct healthcare cost associated with SD. The annual per-patient cost of SD was higher than SHL, another condition that causes sensory impairment in people of all ages, and nonexudative AMD which causes a similar pattern of visual loss that typically begins later in life. The total lifetime per-patient cost of SD may exceed that of nonexudative AMD.

Toxicity studies of highly bioavailable isoniazid loaded solid lipid nanoparticles as per Organisation for Economic Co-operation and Development (OECD) guidelines.

Solid lipid nanoparticles (SLNs) are presently being promoted to improve bioavailability of encapsulated drugs. These are well tolerated in living systems, as they are made from biocompatible material. Despite finding extensive applicability, these systems have not been sufficiently investigated for the toxicity so far. We have reported use of SLNs to improve plasma bioavailability of isoniazid (INH), a hepatotoxic, antitubercular drug. Presently we evaluate acute and repeated (28-day) oral dose toxicity, with satellite group, of developed INH loaded COMBI-SLN. In addition to high bioavailability, the COMBI-SLN exhibited 3 times higher LD50 (2000 mg/kg BW) versus 650 mg/kg BW for free INH. Results were complemented with histopathological evidence in brain, sciatic nerve and liver tissue all of which indicated enhanced safety of INH upon incorporation into SLNs. In the repeated dose study at doses selected as per Organisation for Economic Co-operation and Development (OECD) guidelines, a series of behavioural and haematological tests, clinical biochemistry (kidney and liver function, lipid profile) and histopathological studies were performed to evaluate the effect of low (250 mg/kg BW), medium (500 mg/kg BW) and high oral dose (1000 mg/kg BW). Absence of adverse effects like hepatotoxicity and peripheral neuropathy observed in rats at an oral intake level of 500 and 1000 mg/kg BW of COMBI-SLN, that is 20-40 folds above the anticipated human intake levels (after normalizing the surface area correction for rats), supports the conclusion that SLN are an intrinsically safe nanocarrier system that improves both the efficacy and the safety of INH.

Influence of primary payer status on the management and outcomes of ST-segment elevation myocardial infarction in the United States.

BACKGROUND: There are limited contemporary data on the influence of primary payer status on the management and outcomes of ST-segment elevation myocardial infarction (STEMI). OBJECTIVE: To assess the influence of insurance status on STEMI outcomes. METHODS: Adult (>18 years) STEMI admissions were identified using the National Inpatient Sample database (2000-2017). Expected primary payer was classified into Medicare, Medicaid, private, uninsured and others. Outcomes of interest included in-hospital mortality, use of coronary angiography and percutaneous coronary intervention (PCI), hospitalization costs, hospital length of stay and discharge disposition. RESULTS: Of the 4,310,703 STEMI admissions, Medicare, Medicaid, private, uninsured and other insurances were noted in 49.0%, 6.3%, 34.4%, 7.2% and 3.1%, respectively. Compared to the others, the Medicare cohort was older (75 vs. 53-57 years), more often female (46% vs. 20-36%), of white race, and with higher comorbidity (all p<0.001). The Medicare and Medicaid population had higher rates of cardiogenic shock and cardiac arrest. The Medicare cohort had higher in-hospital mortality (14.2%) compared to the other groups (4.1-6.7%), p<0.001. In a multivariable analysis (Medicare referent), in-hospital mortality was higher in uninsured (adjusted odds ratio (aOR) 1.14 [95% confidence interval {CI} 1.11-1.16]), and lower in Medicaid (aOR 0.96 [95% CI 0.94-0.99]; p = 0.002), privately insured (aOR 0.73 [95% CI 0.72-0.75]) and other insurance (aOR 0.91 [95% CI 0.88-0.94]); all p<0.001. Coronary angiography (60% vs. 77-82%) and PCI (45% vs. 63-70%) were used less frequently in the Medicare population compared to others. The Medicare and Medicaid populations had longer lengths of hospital stay, and the Medicare population had the lowest hospitalization costs and fewer discharges to home. CONCLUSIONS: Compared to other types of primary payers, STEMI admissions with Medicare insurance had lower use of coronary angiography and PCI, and higher in-hospital mortality.

Cost-effectiveness Analysis of Preoperative Screening Strategies for Obstructive Sleep Apnea among Patients Undergoing Elective Inpatient Surgery.

BACKGROUND: Obstructive sleep apnea is underdiagnosed in surgical patients. The cost-effectiveness of obstructive sleep apnea screening is unknown. This study's objective was to evaluate the cost-effectiveness of preoperative obstructive sleep apnea screening (1) perioperatively and (2) including patients' remaining lifespans. METHODS: An individual-level Markov model was constructed to simulate the perioperative period and lifespan of patients undergoing inpatient elective surgery. Costs (2016 Canadian dollars) were calculated from the hospital perspective in a single-payer health system. Remaining model parameters were derived from a structured literature search. Candidate strategies included: (1) no screening; (2) STOP-Bang questionnaire alone; (3) STOP-Bang followed by polysomnography (STOP-Bang + polysomnography); and (4) STOP-Bang followed by portable monitor (STOP-Bang + portable monitor). Screen-positive patients (based on STOP-Bang cutoff of at least 3) received postoperative treatment modifications and expedited definitive testing. Effectiveness was expressed as quality-adjusted life month in the perioperative analyses and quality-adjusted life years in the lifetime analyses. The primary outcome was the incremental cost-effectiveness ratio. RESULTS: In perioperative and lifetime analyses, no screening was least costly and least effective. STOP-Bang + polysomnography was the most effective strategy and was more cost-effective than both STOP-Bang + portable monitor and STOP-Bang alone in both analyses. In perioperative analyses, STOP-Bang + polysomnography was not cost-effective compared to no screening at the $4,167/quality-adjusted life month threshold (incremental cost-effectiveness ratio $52,888/quality-adjusted life month). No screening was favored in more than 90% of iterations in probabilistic sensitivity analyses. In contrast, in lifetime analyses, STOP-Bang + polysomnography was favored compared to no screening at the $50,000/quality-adjusted life year threshold (incremental cost-effectiveness ratio $2,044/quality-adjusted life year). STOP-Bang + polysomnography was favored in most iterations at thresholds above $2,000/quality-adjusted life year in probabilistic sensitivity analyses. CONCLUSIONS: The cost-effectiveness of preoperative obstructive sleep apnea screening differs depending on time horizon. Preoperative screening with STOP-Bang followed by immediate confirmatory testing with polysomnography is cost-effective on the lifetime horizon but not the perioperative horizon. The integration of preoperative screening based on STOP-Bang and polysomnography is a cost-effective means of mitigating the long-term disease burden of obstructive sleep apnea.

Comprehensive Geriatric Assessment in the Management of Older Patients With Cardiovascular Disease.

Cardiovascular disease (CVD) disproportionately affects older adults. It is expected that by 2030, one in five people in the United States will be older than 65 years. Individuals with CVD now live longer due, in part, to current prevention and treatment approaches. Addressing the needs of older individuals requires inclusion and assessment of frailty, multimorbidity, depression, quality of life, and cognition. Despite the conceptual relevance and prognostic importance of these factors, they are seldom formally evaluated in clinical practice. Further, although these constructs coexist with traditional cardiovascular risk factors, their exact prevalence and prognostic impact remain largely unknown. Development of the right decision tools, which include these variables, can facilitate patient-centered care for older adults. These gaps in knowledge hinder optimal care use and underscore the need to rigorously evaluate the optimal constructs for providing care to older adults. In this review, we describe available tools to examine the prognostic role of age-related factors in patients with CVD.

The Predictive Capacity of American Society of Anesthesiologists Physical Status (ASA PS) Score in Burn Patients.

Advances in burn care continues to improve survival rates and patient outcomes. There are several burn prognostic tools used to predict mortality and outcomes; however, none include patient comorbidities. We used the American Society of Anesthesiologists physical status score as a surrogate measure for comorbidities, and evaluated its role in predicting mortality and outcomes in adult burn patients undergoing surgery. A retrospective analysis was performed on data collected from a single burn center in the United States, which was comprised of 183 patients. We evaluated the American Society of Anesthesiologists physical status score as an independent predictor of mortality and outcomes, including intensive care unit (ICU) length of stay (LOS), hospital LOS, mechanical ventilator (MV) days, and complications. We compared the American Society of Anesthesiologists physical status score to other prognostic models which included the revised Baux score, Belgian Outcome in Burn Injury, and the Abbreviated Burn Severity Index. Our results demonstrated that the revised Baux and American Society of Anesthesiologists physical status scores could be used to determine the mortality risk in adult burn patients. The revised Baux was the best predictor of mortality, ICU LOS, and MV days, while the Abbreviated Burn Severity Index was the best predictor of total LOS.

Trends and Factors Associated with Nebulized Therapy Prescription in Older Adults with Chronic Obstructive Pulmonary Disease from 2008 to 2015.

Background: Medical management of patients with chronic obstructive pulmonary disease (COPD) includes nebulized therapy as an option for inhalational drug delivery. A broad variety of short- and long-acting bronchodilators and inhaled corticosteroids in the nebulized form are available. Despite this, limited information exists on the pattern and predictors of nebulized prescription. We examined the trend and factors associated with prescription of nebulized therapy among Medicare beneficiaries with COPD. Methods: A retrospective cross-sectional study of 5% Medicare beneficiaries with COPD (n = 66,032) who were enrolled in parts A, B, and D and received nebulized prescription from 2008 to 2015 was conducted. This sample has shown to be representative of the entire fee-for-service Medicare population. The primary outcome was a prescription of nebulized medications. Reliever nebulized medications included short-acting beta agonist (SABA), short-acting muscarinic agents (SAMAs), and a combination of SABA and SAMA, while maintenance nebulized medications included long-acting beta agonists, long-acting muscarinic agents, and corticosteroid solutions as well as combinations of these agents. The secondary outcome was prescription of other inhaler respiratory medications not administered with a nebulizer. Results: Overall, 38.9% patients were prescribed nebulized medication and their prescription significantly declined from 42.4% in 2008 to 35.1% in 2015, majority of which was related to decreased prescriptions of nebulized relievers. Factors associated with the prescription of nebulized medications include female gender (odds ratio [OR] = 1.06; 95% confidence interval [CI] = 1.02-1.09), dual eligibility or low-income subsidy beneficiaries (OR = 1.49; CI = 1.44-1.53), hospitalization for COPD in the previous year (OR = 1.29; CI = 1.25-1.34), home oxygen therapy (OR = 2.29; CI = 2.23-2.36), pulmonary specialist visit (OR = 1.24; CI = 1.20-1.27), and moderate (OR = 1.61; CI = 1.57-1.65) or high (OR = 1.52; CI = 1.46-1.59) severity of COPD. Conclusion: Between 2008 and 2015, prescriptions for nebulized therapy for COPD declined among Medicare beneficiaries, probably related to increase in use of maintenance non-nebulized medications.

Routine Continuous Electrocardiographic Monitoring Following Percutaneous Coronary Interventions.

BACKGROUND: The clinical utility of routine electrocardiographic monitoring following percutaneous coronary interventions (PCI) is not well studied. METHODS: We prospectively evaluated the incidence, cost, and the clinical implications of actionable arrhythmia alarms on telemetry monitoring following PCI. One thousand three hundred fifty-eight PCI procedures (989 [72.8%] for acute coronary syndrome and 369 [27.2%] for stable angina) on patients admitted to nonintensive care unit were identified and divided into 2 groups; group 1, patients with actionable alarms (AA) and group 2, patients with non-AA. AA included (1) ≥3 s electrical pause or asystole; (2) high-grade Mobitz type II atrioventricular block or complete heart block; (3) ventricular fibrillation; (4) ventricular tachycardia (>15 beats); (5) atrial fibrillation with rapid ventricular response; (6) supraventricular tachycardia (>15 beats). Primary outcomes were 30-day all-cause mortality. Cost-savings analysis was performed. RESULTS: Incidence of AA was 2.2% (37/1672). Time from end of procedure to AA was 5.5 (0.5, 24.5) hours. Patients with AA were older, presented with acute congestive heart failure or non-ST-segment-elevation myocardial infarction, and had multivessel or left main disease. The 30-day all-cause mortality was significantly higher in patients with AA (6.5% versus 0.3% in non-AA [P<0.001]). Applying the standardized costing approach and tailored monitoring per the American Heart Association guidelines lead to potential cost savings of $622 480.95 for the entire population. CONCLUSIONS: AA following PCI were infrequent but were associated with increase in 30-day mortality. Following American Heart Association guidelines for monitoring after PCI can lead to substantial cost saving.

Early Blood Transfusions in Sepsis: Unchanged Survival and Increased Costs.

BACKGROUND: Early red blood cell transfusions are a common treatment for adults hospitalized for sepsis without shock. However, their utility and association with mortality and costs have not been well studied. OBJECTIVES: To examine early transfusion rates for patients with sepsis treated outside intensive care units, and to find a correlation between transfusion rates and survival rates and costs. METHODS: Data were obtained from hospital members of the Premier Healthcare Alliance that admitted at least 50 adults with sepsis between January 1, 2006, and December 31, 2010. Early transfusion rates at each hospital were calculated as the observed incidence of allogeneic red blood cells administered by hospital day 2. A multivariable logistic regression model was constructed to estimate the expected or risk-adjusted transfusion rates, mortality rates, and costs. RESULTS: A total of 256 396 adults were hospitalized with sepsis without major bleeding or surgery at 364 US hospitals. Approximately 84% of all patients admitted with sepsis, without vasopressor therapy, were treated outside the intensive care unit (by day 2). The mean institutional early transfusion rate was 6.9%. After risk standardization, the median (interquartile range) transfusion rate was 6.7% (5.8%-7.6%), mortality rate was 15.5% (13.1%-18.1%), and costs were $13 333 ($11 939-$14 986). Early transfusion rates were not correlated with mortality but were modestly positively correlated with costs (Spearman ρ = 0.157; P = .003). CONCLUSIONS: Early transfusion rates during hospitalization for sepsis without shock varied widely across the hospitals. Transfusion rates were associated with increased costs but not with mortality rates.

Sex Differences in Long-Term Cause-Specific Mortality After Percutaneous Coronary Intervention: Temporal Trends and Mechanisms.

BACKGROUND: Women have higher rates of all-cause mortality after percutaneous coronary intervention. Whether this is because of greater age and comorbidity burden or a sex-specific factor remains unclear. METHODS AND RESULTS: We retrospectively assessed cause-specific long-term mortality after index percutaneous coronary intervention over 3 time periods (1991-1997, 1998-2005, and 2006-2012). Cause of death was determined using telephone interviews, medical records, and death certificates. We performed competing risks analyses of cause-specific mortality. A total of 6847 women and 16 280 men survived index percutaneous coronary intervention hospitalization 1991 to 2012. Women were older (mean±SD: 69.4±12 versus 64.8±11.7 years; P<0.001) with more comorbidities (mean±SD: Charlson index 2.1±2.1 versus 1.9±2.1; P<0.001). Across the 3 time periods, both sexes exhibited a decline in cardiac deaths at 5 years (26% relative decrease in women, 17% in men, trend P<0.001 for each). Although women had higher all-cause mortality compared with men in all eras, the excess mortality was because of noncardiac deaths. In the contemporary era, only a minority of deaths were cardiac (33.8% in women, 38.0% in men). After adjustment, there was no evidence for a sex-specific excess of risk for cardiac or noncardiac mortality. The commonest causes of death were chronic diseases and heart failure in women (5-year cumulative mortality, 5.4% and 3.9%) but cancer and myocardial infarction/sudden death in men (5.4% and 4.3%). CONCLUSIONS: The higher mortality after percutaneous coronary intervention in women is because of death from noncardiac causes. This is accounted for by baseline age and comorbidities rather than an additional sex-specific factor. These findings have implications for sex-specific clinical care and trial design.

Duration of Dual Antiplatelet Therapy in Patients with an Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.

BACKGROUND: The recent American Heart Association/American College of Cardiology guidelines on duration of dual antiplatelet therapy (DAPT) recommend DAPT for 1 year in patients presenting with an acute coronary syndrome, with a Class IIb recommendation for continuation. We aim to assess the evidence for these recommendations using a meta-analytic approach. METHODS: We searched electronic databases for randomized trials comparing short-term (≤6 months) vs 12-month vs extended (>12 months) DAPT in patients with an acute coronary syndrome undergoing percutaneous coronary intervention. We evaluated all-cause mortality, cardiovascular mortality, myocardial infarction, stent thrombosis, and major bleeding. A random-effects model was used to calculate pooled relative risk (RR) and 95% confidence intervals (CI). RESULTS: We included 8 trials comprising 12,917 patients with an acute coronary syndrome; 5 trials compared short-term vs 12-month/extended DAPT, whereas 3 trials compared 12-month vs extended DAPT. There was no significant difference in cardiovascular mortality (RR 1.04; 95% CI, 0.67-1.60), myocardial infarction (RR 1.08; 95% CI, 0.79-1.47), or major bleeding (RR 0.91; 95% CI, 0.49-1.69) between short-term and 12-month/extended DAPT. However, compared with extended DAPT, 12-month DAPT showed significantly higher risk of myocardial infarction (RR 2.00; 95% CI, 1.47-2.73), but reduced risk of major bleeding (RR 0.58; 95% CI, 0.34-0.98). All-cause mortality was found to be similar between 12-month and extended DAPT. CONCLUSIONS: In acute coronary syndrome, short-term DAPT may be reasonable for some patients, whereas extended DAPT may be appropriate in select others. An individualized approach is needed, taking into account the competing risks of bleeding and ischemic events.

Issues and concerns in nanotech product development and its commercialization.

The revolutionary and ubiquitous nature of nanotechnology has fetched it a considerable attention in the past few decades. Even though its enablement and application to various sectors including pharmaceutical drug development is increasing with the enormous government aided funding for nanotechnology-based products, however the parallel commercialization of these systems has not picked up a similar impetus. The technology however does address the unmet needs of pharmaceutical industry, including the reformulation of drugs to improve their solubility, bioavailability or toxicity profiles as observed from the wide array of high-quality research publications appearing in various scientific journals and magazines. Based on our decade-long experience in the field of nanotech-based drug delivery systems and extensive literature survey, we perceive that the major hiccups to the marketing of these nanotechnology products can be categorized as 1) inadequate regulatory framework; 2) lack of support and acceptance by the public, practicing physician, and industry; 3) developmental considerations like scalability, reproducibility, characterization, quality control, and suitable translation; 4) toxicological issues and safety profiles; 5) lack of available multidisciplinary platforms; and, 6) poor intellectual property protection. The present review dwells on these issues elaborating the trends followed by the industry, regulatory role of the USFDA and their implication, and the challenges set forth for a successful translation of these products from the lab and different clinical phases to the market.

Gastrointestinal drug interactions affecting the elderly.

With the burgeoning elderly population in the United States, drug interactions are an increasing concern because of altered drug metabolism associated with age and polypharmacy. This article describes interactions between drugs used in common gastrointestinal diseases, including acid peptic disease, diarrhea, constipation, endoscopic procedural sedation, and inflammatory bowel disease, and those used to treat 5 common geriatric primary care diseases: hypertension, diabetes, hyperlipidemia, arthritis, and psychiatric illnesses.

Assessment of individual operator performance using a risk-adjustment model for percutaneous coronary interventions.

OBJECTIVE: To investigate the applicability of the Mayo Clinic Risk Score (MCRS) in the assessment of performance metrics of individual interventional cardiologists at 3 Mayo Clinic sites. PARTICIPANTS AND METHODS: We evaluated the risk-adjusted performance of 21 interventional cardiologists who performed 8187 percutaneous coronary intervention procedures at 3 Mayo Clinic sites from January 1, 2007, through December 31, 2010. Observed mortality, major adverse cardiac events (MACEs) (eg, death, Q-wave myocardial infarction, urgent or emergent coronary artery bypass graft, and stroke), and expected risk were estimated using the MCRS. To compare individual performance against the other operators, risk estimates were recalibrated by excluding the individual performer from logistic regression models. RESULTS: The log odds ratio for observed vs estimated risk was estimated for each interventional cardiologist, and their individual effects were then plotted on a normal probability plot to identify outliers. Observed in-hospital mortality was not different than expected (1.8% vs 1.6%; P=.24); however, the postprocedural MACE rate was lower than predicted (observed, 2.7%; expected, 3.8%; P<.001). All but one interventional cardiologist had MACE and death rates within the expected variation. Detailed assessment of that operator's risk performance produced excellent outcomes (observed vs expected MACE rate, 1.0% vs 4.4%). CONCLUSION: The MCRS can serve as a tool for the assessment of performance metrics for interventional cardiologists, and risk-adjusted outcomes may serve as a better surrogate for institutional quality metrics.

Assessment of tropism and effectiveness of new primate-derived hybrid recombinant AAV serotypes in the mouse and primate retina.

Adeno-associated viral vectors (AAV) have been shown to be safe in the treatment of retinal degenerations in clinical trials. Thus, improving the efficiency of viral gene delivery has become increasingly important to increase the success of clinical trials. In this study, structural domains of different rAAV serotypes isolated from primate brain were combined to create novel hybrid recombinant AAV serotypes, rAAV2/rec2 and rAAV2/rec3. The efficacy of these novel serotypes were assessed in wild type mice and in two models of retinal degeneration (the Abca4(-/-) mouse which is a model for Stargardt disease and in the Pde6b(rd1/rd1) mouse) in vivo, in primate tissue ex-vivo, and in the human-derived SH-SY5Y cell line, using an identical AAV2 expression cassette. We show that these novel hybrid serotypes can transduce retinal tissue in mice and primates efficiently, although no more than AAV2/2 and rAAV2/5 serotypes. Transduction efficiency appeared lower in the Abca4(-/-) mouse compared to wild type with all vectors tested, suggesting an effect of specific retinal diseases on the efficiency of gene delivery. Shuffling of AAV capsid domains may have clinical applications for patients who develop T-cell immune responses following AAV gene therapy, as specific peptide antigen sequences could be substituted using this technique prior to vector re-treatments.

Locally advanced sebaceous cell carcinoma (T3) of eyelid: incidence and pattern of nodal metastases and combined modality management approach.

BACKGROUND: Sebaceous carcinoma (SbCC) is a rare malignancy that often mimics benign conditions. Lymphatic involvement, large T3 tumors herald a dismal survival for patients. We present our series of 13 cases of locally advanced SbCC of the eyelid treated at a surgical oncology unit and describe the clinical profile, patterns of nodal spread and recurrence pattern in this subset of SbCC. METHODS: A retrospective analysis of case records was carried out for patients presenting with orbital tumors between January 1997 and April 2010 in the department of Surgical Oncology, AIIMS, New Delhi, India. All patients underwent orbital exenteration and superficial parotidectomy with neck dissection was added to patients with clinically significant lymphadenopathy. All patients who underwent OE after 2002 were advised radiotherapy as adjuvant therapy. The end point was development of recurrence or end of two year follow up period which ever occurred earlier. RESULTS: Thirteen patients underwent orbital exenteration. Eleven patients had clinically palpable lymphadenopathy. Ten patients (76.9%) had pathologically confirmed metastatic nodes. Parotid lymph node involvement was present in all patients (100%); two of these ten patients also had level II b cervical lymph node involvement. Recurrence was observed in seven patients (53.8%). All recurrences were loco-regional only and no systemic metastases was seen. There were only two recurrences in the group that received PORT. CONCLUSIONS: Eyelid SbCC is a loco-regionally aggressive malignancy and adequate disease control can be achieved with combined modality approach of radical surgery followed by post operative radiotherapy.