Lehigh Valley Hospital-Pocono

According to the World Health Organization (WHO), viral diseases continue to emerge and represent a serious issue to public health In the last twenty years, several viral epidemics such as the severe acute respiratory syndrome (SARS-CoV) in 2002 to 2003, and H1N1 influenza in 2009, have been recorded Most recently, the Middle East respiratory syndrome (MERS-CoV) was first identified in Saudi Arabia in 2012 In a timeline that reaches the present day, an epidemic of cases with unexplained low respiratory infections detected in Wuhan, the largest metropolitan area in China's Hubei province, was first reported to the WHO Country Office in China, on December 31, Published literature can trace the beginning of symptomatic individuals back to the beginning of December As they were unable to identify the causative agent, these first cases were classified as pneumonia of unknown etiology The Chinese Center for Disease Control and Prevention (CDC) and local CDCs organized an intensive outbreak investigation program The etiology of this illness is now attributed to a novel virus belonging to the (CoV) family, COVID-19 On February 11, 2020, the WHO Director-General, Dr Tedros Adhanom Ghebreyesus, announced that the disease caused by this new CoV was a which is the acronym of coronavirus disease 2019 In the past twenty years, two additional epidemics have occurred  SARS-CoV provoked a large-scale epidemic beginning in China and involving two dozen countries with approximately 8000 cases and 800 deaths, and the MERS-CoV that began in Saudi Arabia and has approximately 2,500 cases and 800 deaths and still causes as sporadic cases This new virus seems to be contagious and has quickly spread globally In a meeting on January 30, 2020, per the International Health Regulations (IHR, 2005), the outbreak was declared by the WHO a Public Health Emergency of International Concern (PHEIC) as it had spread to 18 countries with four countries reporting human-to-human transmission An additional landmark occurred on February 26, 2020, as the first case of the disease, not imported from China, was recorded in the United States Initially, the new virus was called 2019-nCoV Subsequently, the task of experts of the International Committee on Taxonomy of Viruses (ICTV) termed it the SARS-CoV-2 virus as it is similar to the one that caused the SARS outbreak (SARS-CoVs) The CoVs have become the major pathogens of emerging respiratory disease outbreaks They are a large family of single-stranded RNA viruses (+ssRNA) that can be isolated in different animal species  For reasons yet to be explained, these viruses can cross species barriers and can cause, in humans, illness ranging from the common cold to more severe diseases such as MERS and SARS  Interestingly, these latter viruses have probably originated from bats and then moving into other mammalian hosts — the Himalayan palm civet for SARS-CoV, and the dromedary camel for MERS-CoV — before jumping to humans The dynamics of SARS-Cov-2 are currently unknown, but there is speculation that it also has an animal origin The potential for these viruses to grow to become a pandemic worldwide seems to be a serious public health risk Concerning COVID-19, the WHO raised the threat to the CoV epidemic to the very high level, on February 28, 2020 Probably, the effects of the epidemic caused by the new CoV has yet to emerge as the situation is quickly evolving World governments are at work to establish countermeasures to stem possible devastating effects Health organizations coordinate information flows and issues directives and guidelines to best mitigate the impact of the threat At the same time, scientists around the world work tirelessly, and information about the transmission mechanisms, the clinical spectrum of disease, new diagnostics, and prevention and therapeutic strategies are rapidly developing Many uncertainties remain with regard to both the virus-host interac ion and the evolution of the epidemic, with specific reference to the times when the epidemic will reach its peak At the moment, the therapeutic strategies to deal with the infection are only supportive, and prevention aimed at reducing transmission in the community is our best weapon Aggressive isolation measures in China have led to a progressive reduction of cases in the last few days In Italy, in geographic regions of the north of the peninsula, political and health authorities are making incredible efforts to contain a shock wave that is severely testing the health system In the midst of the crisis, the authors have chosen to use the Statpearls platform because, within the PubMed scenario, it represents a unique tool that may allow them to make updates in real-time  The aim, therefore, is to collect information and scientific evidence and to provide an overview of the topic that will be continuously updated

BACKGROUND: Alternative therapies for Staphylococcus aureus bacteremia and endocarditis are needed. METHODS: We randomly assigned 124 patients with S. aureus bacteremia with or without endocarditis to receive 6 mg of daptomycin intravenously per kilogram of body weight daily and 122 to receive initial low-dose gentamicin plus either an antistaphylococcal penicillin or vancomycin. The primary efficacy end point was treatment success 42 days after the end of therapy. RESULTS: Forty-two days after the end of therapy in the modified intention-to-treat analysis, a successful outcome was documented for 53 of 120 patients who received daptomycin as compared with 48 of 115 patients who received standard therapy (44.2 percent vs. 41.7 percent; absolute difference, 2.4 percent; 95 percent confidence interval, -10.2 to 15.1 percent). Our results met prespecified criteria for the noninferiority of daptomycin. The success rates were similar in subgroups of patients with complicated bacteremia, right-sided endocarditis, and methicillin-resistant S. aureus. Daptomycin therapy was associated with a higher rate of microbiologic failure than was standard therapy (19 vs. 11 patients, P=0.17). In 6 of the 19 patients with microbiologic failure in the daptomycin group, isolates with reduced susceptibility to daptomycin emerged; similarly, a reduced susceptibility to vancomycin was noted in isolates from patients treated with vancomycin. As compared with daptomycin therapy, standard therapy was associated with a nonsignificantly higher rate of adverse events that led to treatment failure due to the discontinuation of therapy (17 vs. 8, P=0.06). Clinically significant renal dysfunction occurred in 11.0 percent of patients who received daptomycin and in 26.3 percent of patients who received standard therapy (P=0.004). CONCLUSIONS: Daptomycin (6 mg per kilogram daily) is not inferior to standard therapy for S. aureus bacteremia and right-sided endocarditis. (ClinicalTrials.gov number, NCT00093067 [ClinicalTrials.gov].).

OBJECTIVE: To systematically review the current preoperative diagnostic modalities, surgical treatments, and glandular pathologies associated with primary hyperparathyroidism. STUDY DESIGN: A systematic literature review. RESULTS: Of the 20,225 cases of primary hyperparathyroidism reported, solitary adenomas (SA), multiple gland hyperplasia disease (MGHD), double adenomas (DA), and parathyroid carcinomas (CAR) occurred in 88.90%, 5.74%, 4.14%, and 0.74% of cases respectively. Tc 99m -sestamibi and ultrasound were 88.44% and 78.55% sensitive, respectively, for SA, 44.46% and 34.86% for MGHD, and 29.95% and 16.20% for DA, respectively. Postoperative normocalcemia was achieved in 96.66%, 95.25%, and 97.69% of patients offered minimally invasive radio-guided parathyroidectomy (MIRP), unilateral, and bilateral neck exploration (BNE). Intraoperative PTH assays (IOPTH) were helpful in approximately 60% of bilateral neck exploration conversion (BNEC) surgeries. CONCLUSION: The overall prevalence of multiple gland disease (MGD and DA) was lower than often suggested by conventional wisdom. Furthermore, preoperative imaging was less accurate than it is often perceived for accurately imaging MGD. MIRP and UNE were more successful in achieving normocalcemia than is typically quoted. IOPTH was a helpful but not "fool-proof" adjunct in parathyroid exploration surgery. SIGNIFICANCE: These results support a greater role for the treatment of primary hyperparathyroidism using less invasive approaches. EMB rating: B-3.

PURPOSE Nivolumab received US Food and Drug Administration approval as a single agent or in combination with ipilimumab in patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC) that progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan based on CheckMate 142. Presented are results of nivolumab plus low-dose ipilimumab in the first-line therapy cohort from the phase II CheckMate 142 study. PATIENTS AND METHODS Patients with no prior treatment in the metastatic setting for MSI-H/dMMR CRC were treated with nivolumab every 2 weeks plus low-dose ipilimumab every 6 weeks until disease progression. The primary end point was objective response rate (investigator assessment; RECIST v1.1). RESULTS Median age of treated patients was 66 years (N = 45). Median follow-up was 29.0 months. Objective response rate and disease control rate were 69% (95% CI, 53 to 82) and 84% (95% CI, 70.5 to 93.5), respectively, with 13% complete response rate. Median duration of response was not reached; 74% of responders had ongoing responses at data cutoff. Median progression-free survival and median overall survival were not reached with minimum follow-up of 24.2 months (24-month rates, 74% and 79%, respectively). Clinical benefit was observed regardless of baseline demographic and tumor characteristics, including BRAF or KRAS mutation status. In a post hoc analysis, of 14 patients who discontinued treatment and did not receive subsequent therapy, 10 remained progression-free. Patient-reported outcomes were stable over the treatment period. Grade 3-4 treatment-related adverse events occurred in 22% of patients; 13% discontinued because of any-grade treatment-related adverse events. CONCLUSION Nivolumab plus low-dose ipilimumab demonstrated robust and durable clinical benefit and was well tolerated as a first-line treatment for MSI-H/dMMR mCRC. Based on these promising data, randomized studies are warranted.

BACKGROUND: It is unknown whether warfarin or aspirin therapy is superior for patients with heart failure who are in sinus rhythm. METHODS: We designed this trial to determine whether warfarin (with a target international normalized ratio of 2.0 to 3.5) or aspirin (at a dose of 325 mg per day) is a better treatment for patients in sinus rhythm who have a reduced left ventricular ejection fraction (LVEF). We followed 2305 patients for up to 6 years (mean [±SD], 3.5±1.8). The primary outcome was the time to the first event in a composite end point of ischemic stroke, intracerebral hemorrhage, or death from any cause. RESULTS: The rates of the primary outcome were 7.47 events per 100 patient-years in the warfarin group and 7.93 in the aspirin group (hazard ratio with warfarin, 0.93; 95% confidence interval [CI], 0.79 to 1.10; P=0.40). Thus, there was no significant overall difference between the two treatments. In a time-varying analysis, the hazard ratio changed over time, slightly favoring warfarin over aspirin by the fourth year of follow-up, but this finding was only marginally significant (P=0.046). Warfarin, as compared with aspirin, was associated with a significant reduction in the rate of ischemic stroke throughout the follow-up period (0.72 events per 100 patient-years vs. 1.36 per 100 patient-years; hazard ratio, 0.52; 95% CI, 0.33 to 0.82; P=0.005). The rate of major hemorrhage was 1.78 events per 100 patient-years in the warfarin group as compared with 0.87 in the aspirin group (P<0.001). The rates of intracerebral and intracranial hemorrhage did not differ significantly between the two treatment groups (0.27 events per 100 patient-years with warfarin and 0.22 with aspirin, P=0.82). CONCLUSIONS: Among patients with reduced LVEF who were in sinus rhythm, there was no significant overall difference in the primary outcome between treatment with warfarin and treatment with aspirin. A reduced risk of ischemic stroke with warfarin was offset by an increased risk of major hemorrhage. The choice between warfarin and aspirin should be individualized. (Funded by the National Institute of Neurological Disorders and Stroke; WARCEF ClinicalTrials.gov number, NCT00041938.).

PURPOSE: Patients with centrally located early-stage non-small-cell lung cancer (NSCLC) are at a higher risk of toxicity from high-dose ablative radiotherapy. NRG Oncology/RTOG 0813 was a phase I/II study designed to determine the maximum tolerated dose (MTD), efficacy, and toxicity of stereotactic body radiotherapy (SBRT) for centrally located NSCLC. MATERIALS AND METHODS: Medically inoperable patients with biopsy-proven, positron emission tomography-staged T1 to 2 (≤ 5 cm) N0M0 centrally located NSCLC were accrued into a dose-escalating, five-fraction SBRT schedule that ranged from 10 to 12 Gy/fraction (fx) delivered over 1.5 to 2 weeks. Dose-limiting toxicity (DLT) was defined as any treatment-related grade 3 or worse predefined toxicity that occurred within the first year. MTD was defined as the SBRT dose at which the probability of DLT was closest to 20% without exceeding it. RESULTS: One hundred twenty patients were accrued between February 2009 and September 2013. Patients were elderly, there were slightly more females, and the majority had a performance status of 0 to 1. Most cancers were T1 (65%) and squamous cell (45%). Organs closest to planning target volume/most at risk were the main bronchus and large vessels. Median follow-up was 37.9 months. Five patients experienced DLTs; MTD was 12.0 Gy/fx, which had a probability of a DLT of 7.2% (95% CI, 2.8% to 14.5%). Two-year rates for the 71 evaluable patients in the 11.5 and 12.0 Gy/fx cohorts were local control, 89.4% (90% CI, 81.6% to 97.4%) and 87.9% (90% CI, 78.8% to 97.0%); overall survival, 67.9% (95% CI, 50.4% to 80.3%) and 72.7% (95% CI, 54.1% to 84.8%); and progression-free survival, 52.2% (95% CI, 35.3% to 66.6%) and 54.5% (95% CI, 36.3% to 69.6%), respectively. CONCLUSION: The MTD for this study was 12.0 Gy/fx; it was associated with 7.2% DLTs and high rates of tumor control. Outcomes in this medically inoperable group of mostly elderly patients with comorbidities were comparable with that of patients with peripheral early-stage tumors.

The patient-centered medical home (PCMH) is four things: 1) the fundamental tenets of primary care: first contact access, comprehensiveness, integration/coordination, and relationships involving sustained partnership; 2) new ways of organizing practice; 3) development of practices' internal capabilities, and 4) related health care system and reimbursement changes. All of these are focused on improving the health of whole people, families, communities and populations, and on increasing the value of healthcare. The value of the fundamental tenets of primary care is well established. This value includes higher health care quality, better whole-person and population health, lower cost and reduced inequalities compared to healthcare systems not based on primary care. The needed practice organizational and health care system change aspects of the PCMH are still evolving in highly related ways. The PCMH will continue to evolve as evidence comes in from hundreds of demonstrations and experiments ongoing around the country, and as the local and larger healthcare systems change. Measuring the PCMH involves the following: Giving primacy to the core tenets of primary care. Assessing practice and system changes that are hypothesized to provide added value Assessing development of practices' core processes and adaptive reserve. Assessing integration with more functional healthcare system and community resources. Evaluating the potential for unintended negative consequences from valuing the more easily measured instrumental features of the PCMH over the fundamental relationship and whole system aspects. Recognizing that since a fundamental benefit of primary care is its adaptability to diverse people, populations and systems, functional PCMHs will look different in different settings. Efforts to transform practice to patient-centered medical homes must recognize, assess and value the fundamental features of primary care that provide personalized, equitable health care and foster individual and population health.

BACKGROUND: Heart failure with preserved ejection fraction (HFPEF) is common and characterized by exercise intolerance and lack of proven effective therapies. Exercise training has been shown to be effective in improving cardiorespiratory fitness (CRF) in patients with systolic heart failure. In this meta-analysis, we aim to evaluate the effects of exercise training on CRF, quality of life, and diastolic function in patients with HFPEF. METHODS AND RESULTS: Randomized controlled clinical trials that evaluated the efficacy of exercise training in patients with HFPEF were included in this meta-analysis. Primary outcome of the study was change in CRF (measured as change in peak oxygen uptake). Effect of exercise training on quality of life (estimated using Minnesota living with heart failure score), and left ventricular systolic and diastolic function was also assessed. The study included 276 patients who were enrolled in 6 randomized controlled trials. In the pooled data analysis, patients with HFPEF undergoing exercise training had significantly improved CRF (mL/kg per min; weighted mean difference, 2.72; 95% confidence interval, 1.79-3.65) and quality of life (weighted mean difference, -3.97; 95% confidence interval, -7.21 to -0.72) when compared with the control group. However, no significant change was observed in the systolic function (EF-weighted mean difference, 1.26; 95% confidence interval, -0.13% to 2.66%) or diastolic function (E/A-weighted mean difference, 0.08; 95% confidence interval, -0.01 to 0.16) with exercise training in patients with HFPEF. CONCLUSIONS: Exercise training in patients with HFPEF is associated with an improvement in CRF and quality of life without significant changes in left ventricular systolic or diastolic function.

BACKGROUND: Animal and limited human studies have raised concerns as to the safety of in utero exposure to mycophenolate mofetil (MMF) and sirolimus (SRL) in transplant recipients. This study examined the outcomes of pregnancies with exposure to MMF or SRL from 30 female transplant recipients (39 pregnancies) who have reported pregnancies to the National Transplantation Pregnancy Registry. METHODS: Data were collected via questionnaires, phone interviews and medical records. RESULTS: There were 18 kidney recipients reporting 26 pregnancies with exposure to MMF: 15 livebirths (LB), 11 spontaneous abortions (SA). Structural malformations were reported in four of the 15 children (26.7%) including: hypoplastic nails and shortened fifth fingers (one), microtia with cleft lip and palate (one), microtia alone (one), and neonatal death with multiple malformations (one). One kidney/pancreas (K/P) recipient reported one SA. Three liver recipients reported three pregnancies; two LB (no malformations), and one second trimester SA. Two heart recipients reported one LB (no malformations) and two SA. SRL exposures included seven recipients (four kidney, one K/P and two liver) reporting four LB (one infant whose mother was switched from MMF to SRL during late pregnancy had cleft lip and palate and microtia) and three SA. CONCLUSIONS: A higher incidence of structural malformations was seen with MMF exposures during pregnancy compared to the overall kidney transplant recipient offspring, while no structural defects have as yet been reported with early pregnancy sirolimus exposures. Centers are encouraged to report all pregnancy exposures in transplant recipients.

BACKGROUND: The National Cardiogenic Shock Initiative is a single-arm, prospective, multicenter study to assess outcomes associated with early mechanical circulatory support (MCS) in patients presenting with acute myocardial infarction and cardiogenic shock (AMICS) treated with percutaneous coronary intervention (PCI). METHODS: Between July 2016 and February 2019, 35 sites participated and enrolled into the study. All centers agreed to treat patients with AMICS using a standard protocol emphasizing invasive hemodynamic monitoring and rapid initiation of MCS. Inclusion and exclusion criteria mimicked those of the "SHOCK" trial with an additional exclusion criteria of intra-aortic balloon pump counter-pulsation prior to MCS. RESULTS: A total of 171 consecutive patients were enrolled. Patients had an average age of 63 years, 77% were male, and 68% were admitted with AMICS. About 83% of patients were on vasopressors or inotropes, 20% had a witnessed out of hospital cardiac arrest, 29% had in-hospital cardiac arrest, and 10% were under active cardiopulmonary resuscitation during MCS implantation. In accordance with the protocol, 74% of patients had MCS implanted prior to PCI. Right heart catheterization was performed in 92%. About 78% of patients presented with ST-elevation myocardial infarction with average door to support times of 85 ± 63 min and door to balloon times of 87 ± 58 min. Survival to discharge was 72%. Creatinine ≥2, lactate >4, cardiac power output (CPO) <0.6 W, and age ≥ 70 years were predictors of mortality. Lactate and CPO measurements at 12-24 hr reliably predicted overall mortality postindex procedure. CONCLUSION: In contemporary practice, use of a shock protocol emphasizing best practices is associated with improved outcomes.

BACKGROUND: The combination of daclatasvir, a hepatitis C virus (HCV) NS5A inhibitor, and the NS5B inhibitor sofosbuvir has shown efficacy in patients with HCV monoinfection. Data are lacking on the efficacy and safety of this combination in patients coinfected with human immunodeficiency virus type 1 (HIV-1). METHODS: This was an open-label study involving 151 patients who had not received HCV treatment and 52 previously treated patients, all of whom were coinfected with HIV-1. Previously untreated patients were randomly assigned in a 2:1 ratio to receive either 12 weeks or 8 weeks of daclatasvir at a standard dose of 60 mg daily (with dose adjustment for concomitant antiretroviral medications) plus 400 mg of sofosbuvir daily. Previously treated patients were assigned to undergo 12 weeks of therapy at the same doses. The primary end point was a sustained virologic response at week 12 after the end of therapy among previously untreated patients with HCV genotype 1 who were treated for 12 weeks. RESULTS: Patients had HCV genotypes 1 through 4 (83% with genotype 1), and 14% had compensated cirrhosis; 98% were receiving antiretroviral therapy. Among patients with genotype 1, a sustained virologic response was reported in 96.4% (95% confidence interval [CI], 89.8 to 99.2) who were treated for 12 weeks and in 75.6% (95% CI, 59.7 to 87.6) who were treated for 8 weeks among previously untreated patients and in 97.7% (95% CI, 88.0 to 99.9) who were treated for 12 weeks among previously treated patients. Rates of sustained virologic response across all genotypes were 97.0% (95% CI, 91.6 to 99.4), 76.0% (95% CI, 61.8 to 86.9), and 98.1% (95% CI, 89.7 to 100), respectively. The most common adverse events were fatigue, nausea, and headache. There were no study-drug discontinuations because of adverse events. HIV-1 suppression was not compromised. CONCLUSIONS: Among previously untreated HIV-HCV coinfected patients receiving daclatasvir plus sofosbuvir for HCV infection, the rate of sustained virologic response across all genotypes was 97.0% after 12 weeks of treatment and 76.0% after 8 weeks. (Funded by Bristol-Myers Squibb; ALLY-2 ClinicalTrials.gov number, NCT02032888.).

Background Clinical investigations of shock in cardiac intensive care units (CICUs) have primarily focused on acute myocardial infarction (AMI) complicated by cardiogenic shock (AMICS). Few studies have evaluated the full spectrum of shock in contemporary CICUs. Methods and Results The Critical Care Cardiology Trials Network is a multicenter network of advanced CICUs in North America. Anytime between September 2017 and September 2018, each center (n=16) contributed a 2-month snap-shot of all consecutive medical admissions to the CICU. Data were submitted to the central coordinating center (TIMI Study Group, Boston, MA). Shock was defined as sustained systolic blood pressure <90 mm Hg with end-organ dysfunction ascribed to the hypotension. Shock type was classified by site investigators as cardiogenic, distributive, hypovolemic, or mixed. Among 3049 CICU admissions, 677 (22%) met clinical criteria for shock. Shock type was varied, with 66% assessed as cardiogenic shock (CS), 7% as distributive, 3% as hypovolemic, 20% as mixed, and 4% as unknown. Among patients with CS (n=450), 30% had AMICS, 18% had ischemic cardiomyopathy without AMI, 28% had nonischemic cardiomyopathy, and 17% had a cardiac cause other than primary myocardial dysfunction. Patients with mixed shock had cardiovascular comorbidities similar to patients with CS. The median CICU stay was 4.0 days (interquartile range [IQR], 2.5-8.1 days) for AMICS, 4.3 days (IQR, 2.1-8.5 days) for CS not related to AMI, and 5.8 days (IQR, 2.9-10.0 days) for mixed shock versus 1.9 days (IQR, 1.0-3.6) for patients without shock ( P<0.01 for each). Median Sequential Organ Failure Assessment scores were higher in patients with mixed shock (10; IQR, 6-13) versus AMICS (8; IQR, 5-11) or CS without AMI (7; IQR, 5-11; each P<0.01). In-hospital mortality rates were 36% (95% CI, 28%-45%), 31% (95% CI, 26%-36%), and 39% (95% CI, 31%-48%) in AMICS, CS without AMI, and mixed shock, respectively. Conclusions The epidemiology of shock in contemporary advanced CICUs is varied, and AMICS now represents less than one-third of all CS. Despite advanced therapies, mortality in CS and mixed shock remains high. Investigation of management strategies and new therapies to treat shock in the CICU should take this epidemiology into account.

OBJECTIVE: To review the success rate of embolization in stopping hemorrhage for unstable patients with severe pelvic fractures, to calculate the time to achieve embolization, and to determine the yield from angiography. DESIGN: Retrospective review of patients admitted to a Level I trauma center with pelvic fractures during a 5-year period. MATERIALS AND METHODS: Charts were reviewed for Injury Severity Score, age, blood pressure, prothrombin time/partial thromboplastin time, pelvic fracture type, mortality, time to reach the angiography suite, time to achieve embolization, and mechanism of injury. MEASUREMENTS AND MAIN RESULTS: Of 806 patients admitted with pelvic fractures, 35 underwent pelvic angiography, and 15 (1.9%) required embolization. Embolization was successful for all patients. No deaths resulted from ongoing hemorrhage. Angiography yield in initially unstable patients was 64%. The mean age and initial hemodynamic instability were significantly greater in nonsurvivors. The time from arrival in the trauma bay to arrival in the angiography suite ranged from 50 to 1,140 minutes, and the time spent in the angiography suite performing embolization ranged from 50 to 140 minutes, with an average time of 90 minutes. Patients who were embolized within 3 hours of arrival had a significantly greater survival rate. CONCLUSION: Only a small percentage of patients with pelvic fractures require embolization, but when it is used, embolization can be 100% effective. Age, time to achieve embolization, and initial hemodynamic instability appear to be important factors in survival.

Coronavirus disease 2019 (COVID-19), the illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had a devastating effect on the world's population resulting in more than 2 8 million deaths worldwide and emerging as the most significant global health crisis since the influenza pandemic of 1918 Since being declared a global pandemic by the World Health Organization (WHO) on March 11, 2020, the virus continues to cause devastation, with many countries enduring a second or a third wave of outbreaks of this viral illness Adaptive mutations in the viral genome can alter the virus's pathogenic potential Even a single amino acid exchange can drastically affect a virus's ability to evade the immune system and complicate the vaccine development progress against the virus [1] SARS-CoV-2, like other RNA viruses, is prone to genetic evolution while adapting to their new human hosts with the development of mutations over time, resulting in the emergence of multiple variants that may have different characteristics compared to its ancestral strains Periodic genomic sequencing of viral samples helps detect any new genetic variants of SARS-CoV-2 circulating in communities, especially in a global pandemic setting The genetic evolution of SARS-CoV-2 was minimal during the early phase of the pandemic with the emergence of a globally dominant variant called D614G, which was associated with higher transmissibility but without increased disease severity of its ancestral strain [2] Another variant was identified in humans, attributed to transmission from infected farmed mink in Denmark, which was not associated with increased transmissibility [3] Since then, multiple variants of SARS-CoV-2 have been described, of which a few are considered variants of concern (VOCs), given their impact on public health VOCs are associated with enhanced transmissibility or virulence, reduction in neutralization by antibodies obtained through natural infection or vaccination, the ability to evade detection, or a decrease in therapeutics or vaccination effectiveness The first VOC, the B 1 1 7 lineage (or VOC 202012), was described in the United Kingdom (UK) in late December 2020, followed shortly by the detection of the B 1 351 lineage (or 501Y V2) in South Africa In early January 2021, a new VOC, B 1 1 248/B1 1 28/P1 (or 501Y V3), was reported in Brazil, and more recently, the B 1 427/B 1 429 lineage was identified in California The B 1 427/B 1 429 lineage is classified as VOC by the US Centers for Disease Control and Prevention (CDC) but is considered a variant of interest by the WHO All three reported VOCs (B 1 1 7 variant, B 1 351 variant, and P 1 variant) harbor mutations in the receptor-binding domain (RBD) and the N-terminal domain (NTD), of which the N501Y mutation located on the RBD is common to all variants RBD plays a vital role in facilitating viral entry into the host cell by binding to the host cell angiotensin-converting enzyme-2 (ACE-2) receptors Along with NBD, it is the dominant neutralization target and facilitates antibody production in response to antisera or vaccines [4] Two recent preprint studies (not peer-reviewed) reported that a single mutation of N501Y alone increases the affinity between RBD and ACE2 approximately ten times more than the ancestral strain (N501-RBD) Interestingly the binding affinity of B 1 351 variant and P 1 variant with mutations N417/K848/Y501-RBD and ACE2 was much lower than that of N501Y-RBD and ACE2 [5][6] Despite the extraordinary speed of vaccine development against COVID-19 and continued mass vaccination efforts across the world, the emergence of these new variant strains of SARS-CoV-2 threatens to overturn the significant progress made so far in halting the spread of SARS-CoV-2 This review article aims to comprehensively describe these new variants of concern, the latest therapeutics available in managing COVID-19 in adults, and the efficacy of different available vaccines against this virus and its new variants SARS-CoV-2 Variant

Mindfulness-based Stress Reduction, a stress-reduction program, has increasing empirical support as a patient-care intervention. Its emphasis on self-care, compassion, and healing makes it relevant as an intervention for helping nurses manage stress and reduce burnout. This article describes the implementation of Mindfulness-based Stress Reduction in a hospital system as a way to lower burnout and improve well-being among nurses, using both quantitative and qualitative data.

BACKGROUND: This study attempts to validate the American Association for the Surgery of Trauma (AAST) Organ Injury Scale (OIS) for spleen, liver, and kidney injuries using the National Trauma Data Bank (NTDB). STUDY DESIGN: All NTDB entries with Abbreviated Injury Scale codes for spleen, liver, and kidney were classified by OIS grade. Injuries were stratified either as an isolated intraabdominal organ injury or in combination with other abdominal injuries. Isolated abdominal solid organ injuries were additionally stratified by presence of severe head injury and survival past 24 hours. The patients in each grading category were analyzed for mortality, operative rate, hospital length of stay, ICU length of stay, and charges incurred. RESULTS: There were 54,148 NTDB entries (2.7%) with Abbreviated Injury Scale-coded injuries to the spleen, liver, or kidney. In 35,897, this was an isolated abdominal solid organ injury. For patients in which the solid organ in question was not the sole abdominal injury, a statistically significant increase (p < or = 0.05) in mortality, organ-specific operative rate, and hospital charges was associated with increasing OIS grade; the exception was grade VI hepatic injuries. Hospital and ICU lengths of stay did not show substantial increase with increasing OIS grade. When isolated organ injuries were examined, there were statistically significant increases (p < or = 0.05) in all outcomes variables corresponding with increasing OIS grade. Severe head injury appears to influence mortality, but none of the other outcomes variables. Patients with other intraabdominal injuries had comparable quantitative outcomes results with the isolated abdominal organ injury groups for all OIS grades. CONCLUSIONS: This study validates and quantifies outcomes reflective of increasing injury severity associated with increasing OIS grades for specific solid organ injuries alone, and in combination with other abdominal injuries.

Many commentators view the conversion of small, independent primary care practices into patient-centered medical homes as a vital step in creating a better-performing health care system. The country's first national medical home demonstration, which ran from June 1, 2006, to May 31, 2008, and involved thirty-six practices, showed that this transformation can be lengthy and complex. Among other features, the transformation process requires an internal capability for organizational learning and development; changes in the way primary care clinicians think about themselves and their relationships with patients as well as other clinicians on the care team; and awareness on the part of primary care clinicians that they will need to make long-term commitments to change that may require three to five years of external assistance. Additionally, transforming primary care requires synchronizing practice redesign with development of the health care "neighborhood," which is made up of a broad range of health and health care resources available to patients. It also requires payment reform that supports practice development and a policy environment that sets reasonable expectations and time frames for the adoption of appropriate innovations.

Hyperlipidemia is a well-established risk factor for developing cardiovascular disease (CVD). The recent American College of Cardiology and American Heart Association guidelines on lipid management emphasize treatment of individuals at increased risk for developing CVD events with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) at doses proven to reduce CVD events. However, there are limited options for patients who are either intolerant to statin therapy, develop CVD despite being on maximally tolerated statin therapy, or have severe hypercholesterolemia. Recently the Food and Drug Administration approved two novel medications for low-density lipoprotein (LDL)-cholesterol reduction: Evolocumab and Alirocumab. These agents target and inactivate proprotein convertase subtilsinkexin type 9 (PCSK9), a hepatic protease that attaches and internalizes LDL receptors into lysosomes hence promoting their destruction. By preventing LDL receptor destruction, LDL-C levels can be lowered 50%-60% above that achieved by statin therapy alone. This review explores PCSK-9 biology and the mechanisms available to alter it; clinical trials targeting PCSK9 activity, and the current state of clinically available inhibitors of PCSK9.

Abstract: A tabu search meta-heuristic has been developed and successfully demonstrated to provide solutions to the system reliability optimization problem of redundancy allocation. Tabu search is particularly well-suited to this problem and it offers distinct advantages compared to alternative optimization methods. While there are many forms of the problem, the redundancy allocation problem generally involves the selection of components and redundancy levels to maximize system reliability given various system-level constraints. This is a common and extensively studied problem involving system design, reliability engineering and operations research. It is becoming increasingly important to develop efficient solutions to this reliability optimization problem because many telecommunications (and other) systems are becoming more complex, yet with short development schedules and very stringent reliability requirements. Tabu search can be applied to a more diverse problem domain compared to mathematical programming methods, yet offers the potential of greater efficiency compared to population-based search methodologies, such as genetic algorithms. The tabu search is demonstrated on numerous variations of three different problems and compared to integer programming and genetic algorithm solutions. The results demonstrate the benefits of tabu search for solving this type of problem. Accepted to IIE Transactions

OBJECTIVES: Initial studies have shown improved reliability and validity of a new triage tool, the Emergency Severity Index (ESI), over conventional three-level scales at two university medical centers. After pilot implementation and validation, the ESI was revised to include pediatric and updated vital signs criteria. The goal of this study was to assess ESI version (v.) 2 reliability and validity at seven emergency departments (EDs) in three states. METHODS: In part 1, interrater reliability was assessed using weighted kappa analysis of written training cases and postimplementation by a random sampling of actual patient triages. In part 2, validity was analyzed using a prospective cohort with stratified random sampling at each site. The ESI was compared with outcomes including resource consumption, inpatient admission, ED length of stay, and 60-day all-cause mortality. RESULTS: Weighted kappa analysis of interrater reliability ranged from 0.70 to 0.80 for the written scenarios (n = 3289) and 0.69 to 0.87 for patient triages (n = 386). Outcomes for the validity cohort (n = 1042) included hospitalization rates by ESI triage level: level 1, 83%; 2, 67%; 3, 42%; 4, 8%; level 5, 4%. Sixty-day all-cause mortality by triage level was as follows: level 1, 25%; 2, 4%; 3, 2%; 4, 1%; and 5, 0%. CONCLUSIONS: ESI v. 2 triage produced reliable, valid stratification of patients across seven sites. ESI triage should be evaluated as an ED casemix identification system for uniform data collection in the United States and compared with other major ED triage methods.