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Two letters to the editor are presented in response to the article in previous issues including "Three-dimensional plating system in the management of mandibular fracture," by Puneet Puri in the December, 2011 issue and "Biophosphonates," by Vijay Raghavan in the December, 2011 issue.

A young male in his late 20s presented with brownish discolouration of the conjunctiva and periocular area of both eyes. He was diagnosed as a case of lepromatous leprosy with recurrent type II lepra reaction 4 years ago and was started on multidrug therapy-multi bacillary, which included clofazimine. The best-corrected visual acuity was 20/20 in both eyes. Examination revealed reddish-brown discolouration of the facial skin including the periorbital area and the eyelids, brownish discolouration of the conjunctiva with shiny sub-conjunctival deposits and multiple polychromatic refractile crystalline corneal deposits. Both eyes had clear lenses with normal fundus. On follow-up after 4 months of discontinuing clofazimine and again after 1 year, the deposits had decreased than previous visits, but they had not totally disappeared. Few studies documented similar ocular side effects of this drug. When diagnosing crystalline deposits in the cornea and conjunctiva, one should rule out clofazimine-induced crystalline keratopathy especially in a leprosy patient., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

A newly formatted enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies to bluetongue virus (BTV) was developed and validated for bovine and ovine sera and plasma. Validation of the new sandwich ELISA (sELISA) was achieved with 949 negative bovine and ovine sera from BTV endemic and non-endemic areas of Australia and 752 BTV positive (field and experimental) sera verified by VNT and/or PCR. The test diagnostic sensitivity (DSe) and diagnostic specificity (DSp) were 99.70% and 99.20%, respectively, for bovine sera, and 97.80% and 99.50%, respectively, for ovine sera. Comparable diagnostic performances were noted for the sELISA compared to four competition ELISAs. While the sensitivity of the sELISA remained unaffected by BTV-15 positive sera, the cELISAs were not as sensitive. BTV-15 is endemic to Australia, and early warning depends on sensitive diagnoses of all serotypes: endemic or incurring. The sELISA failed to discriminate against epizootic hemorrhagic disease virus (EHDV) antibodies, the most serologically related orbivirus to BTV. The ACDP cELISA and the IDEXX kit showed cross-reactivity with some EHDV serotypes, with the least cross-reactive being the VMRD and the IDVet kits. Cross-reactivities, however, were also detected in sera raised experimentally from 10 isolates of the 21 known non-BTV orbiviruses. In this case, the sELISA was the least affected, followed equally by the VMRD and IDVet kits, and the IDEXX kit and the ACDP cELISA were the least discriminatory. In addition to exclusivity assessment of the ELISAs, an inclusivity assessment was made for all ELISAs using well characterized reference sera positive for antibodies to all serotypes BTV-1 to BTV-24.

The short-term impact of atrial fibrillation (AF) on cardiac surgery hospitalizations has been previously reported in cohorts of various sizes, but results have been variable. Using the 2005-2014 National Inpatient Sample, we identified all adult hospitalizations for cardiac surgery using the International Classification of Diseases, Ninth Revision, Clinical Modification as any procedure code and AF as any diagnosis code. We estimated the impact of AF on inpatient mortality, length of stay (LOS), and cost of hospitalization using survey-weighted, multivariable logistic, accelerated failure-time log-normal, and log-transformed linear regressions, respectively. Additionally, we exact-matched AF to non-AF hospitalizations on various confounders for the same outcomes. A total of 1,269,414 hospitalizations were noted for cardiac surgery during the study period. Coexistent AF was found in 44.9% of these hospitalizations. Overall mean age was 65.6 years, 40.9% were female, mean LOS was 11.6 days, and inpatient mortality was 4.5%. Stroke rate was lower in AF hospitalizations (1.8% vs 2.1%, p<0.001). Mortality was lower in the AF (3.9%) versus the non-AF (5%) group (exact-matched OR or emOR=0.48, 95% CI 0.29 to 0.80, p<0.001; 987 matched pairs, n=2423), with similar results after procedural stratification: isolated valve replacement/repair (emOR=0.38, p<0.001), isolated coronary artery bypass graft (CABG) (emOR=0.33, p<0.001), and CABG with valve replacement/repair (emOR=0.55, p<0.001). A 12% increase was seen in LOS in the AF subgroup (exact-matched time ratio=1.12, 95% CI 1.10 to 1.14, p<0.001) among hospitalizations which underwent valve replacement/repair with or without CABG. Hospitalizations for cardiac surgery which had coexistent AF were found to have lower inpatient mortality risk and stroke prevalence but higher LOS and hospitalization costs compared with hospitalizations without AF., Competing Interests: Competing interests: None declared., (© American Federation for Medical Research 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Middle Point orbivirus (MPOV) is an Australian arbovirus, belongs to the Yunnan orbivirus species found in China. First detected and reported from Beatrice Hill, Northern Territory (NT), MPOV has to date, only been exclusively reported from the NT, Australia. Whilst genetic characterization of MPOV has been previously described, only restricted to sequence information for segments 2 and 3 coding core protein VP2 and outer capsid protein VP3, respectively. This study presents for the first time nearly full-length genome sequences of MPOV, which represent 24 isolates collected over a span of more than 20 years from 1997 to 2018. Whilst the majority of isolates were sampled at Beatrice Hill, NT where MPOV is most frequently isolated, this report also describes the first two isolations of MPOV from Queensland (QLD), Australia. One of which is the first non-bovine isolate obtained from the mosquito vector Aedes vittiger . We further compared these MPOV sequences with known sequences of the Yunnan orbivirus and other known orbivirus sequences of mosquito origin found in Australia. The phylogenetic analyses indicate the Australian MPOV sequences are more closely related to each other than other known sequences of Yunnan orbivirus. Furthermore, MPOV sequences are closely related to sequences from the Indonesian isolate JKT-8650. The clustering of Australian sequences in the phylogenetic tree suggests the monophyletic lineage of MPOV circulating in Australia. Further, ongoing surveillance is required to assess the existence and prevalence of this or other yet undetected lineages of MPOV and other orbiviruses in Australia.

Background: The use of cardiac telemetry in the inpatient setting is widespread and has become integral in managing hospitalized patients. Telemetry is used to monitor patients with brady- and tachyarrhythmias. While most of the focus is on the rhythm strip data, a significant utility remains in analyzing the graphic heart rate trends. We specifically focused on the shape of the curve (rectangle or bell) of the heart rate over time to differentiate sinus tachycardia (ST) and supraventricular tachycardia (SVT). We hypothesized that identifying the shape of the graphic trend would improve the accuracy of diagnosis., Methods: To demonstrate the simplicity of employing this method for improving the diagnosis of arrhythmia, we had senior medical students evaluate the telemetry strips and graphical trends. We gathered data from the medical student interpretation of 82 strips of in-hospital cardiac telemetry and asked them to differentiate ST and SVT based on the shape of the graphic trend. Each rhythm strip and the graphic trend was interpreted by two clinical cardiac electrophysiology attending physicians and confirmed on a 12‑lead electrocardiogram., Results: When students were asked to choose between ST and SVT based on the telemetry rhythm strip without graphic trends, 73% of their answers were correct. Diagnostic accuracy improved to 96% correct with the addition of the graphic trend. Depending on the telemetry rhythm strip alone, sensitivity to detect SVT was 75%, with 68% specificity. With the addition of the graphical trend, sensitivity improved to 98% and specificity 100%., Conclusion: Review of graphical trends, specifically the analysis of onset and offset, allows novice ECG readers to improve the ability to distinguish between ST and SVT., (Published by Elsevier Inc.)

In 2018, an outbreak resulting in deaths of 28 breeding pigeons was reported north of Brisbane, Australia. The affected birds had runny nasal discharge and poor body condition. Two birds were submitted to Biosecurity Sciences Laboratory, Brisbane, for investigation. A range of diagnostic tests excluded a number of known pathogens, and no virus was isolated in cell culture. Histopathological examination revealed severe acute multifocal necrosis in the liver with eosinophilic intranuclear inclusions in hepatocytes and Kupffer cells. High-throughput sequencing (HTS) revealed full-length sequences for pigeon adenovirus 1 (PiAd-A) and pigeon torque teno virus (PTTV). This report indicates concomitant PiAd-1and PTTV infections in Australian pigeons.

Context: An outbreak of a novel, zoonotic coronavirus occurred in December 2019 in the city of Wuhan, China and has now affected almost the entire world, with the maximum confirmed cases being 1 521 252 as of April 10, 2020. The WHO named this coronavirus 2019-nCoV, with COVID-19 being the name for diseases allied with it., Objective: The study intended to examine the features and characteristics of existing human coronaviruses and identify their resemblance to the newly identified 2019-nCoV., Design: The research team performed a literature review, searching relevant literature databases. We searched four databases, PubMed, EMBASE, Web of Science and CNKI (Chinese Database), to identify studies reporting COVID-19. Articles published on or before April 10, 2020 were eligible for inclusion. We used the following search terms: "Coronavirus" or "2019-nCoV" or "COVID-19" or "SARS-CoV" or "MERS-CoV" or "Bat SARS-CoV" or "ACE2 receptor"., Setting: This study was take place in School of Pharmacy, Suresh Gyan Vihar University, Jaipur, India., Results: The undistinguishable similarity of the genomic sequences of Severe Respiratory Syndrome (SARS)-CoV, Middle East Respiratory Syndrome (MERS)-CoV, and Bat SARS-CoV-bat-SL-CoVZC45 and bat-SL-CoVZXC21-to nCoV-2019 has facilitated the process of identifying primary treatment measures. Researchers are presuming the existence of angiotensin-converting enzyme 2 (ACE2) receptor binding in nCoV-2019, as in SARS-CoV. Researchers have been examining human-to-human transmission, the possibility of an intermediate host between bats and humans, and the existence of asymptomatic cases. An incubation period of 0 to 14 days has been reported, with acute to chronic symptoms being cough, nasal congestion, high fever, dyspnea, pneumonia, invasive lesions in both lungs, respiratory failure, and even death, including in pediatric cases. Mechanical ventilation, extracorporeal membrane oxygenation, repurposing of antivirals, and plasma infusion have proven to be somewhat effective. Several countries have started clinical trials to evaluate the safety and effectiveness of some drugs, but the ability to vaccinate people with existing or new molecules will require time. Previously learned lessons from SARS and MERS have led some areas to be well equipped in terms of the ability to take speedy action., Conclusions: First-level treatments include repurposing antivirals and antimalarials, and plasma infusion should help, but development of existing or new molecules into vaccines will take time. The unpredictable trajectory of this outbreak demands careful surveillance to monitor the situation, draw strategies, implement control measures, and create proper ethical laws and medical guidelines.

In November 2017, two groups of P. conspicillatus pups from separate locations in Far North Queensland presented with neurological signs consistent with Australian bat lyssavirus (ABLV) infection. These pups (n = 11) died over an 11-day period and were submitted to a government laboratory for testing where ABLV infection was confirmed. Over the next several weeks, additional ABLV cases in flying foxes in Queensland were also detected. Brain tissue from ABLV-infected flying foxes during this period, as well as archived brain tissue, was selected for next-generation sequencing. Phylogenetic analysis suggests that the two groups of pups were each infected from single sources. They were likely exposed while in crèche at night as their dams foraged. This study identifies crèche-age pups at a potentially heightened risk for mass ABLV infection., (© 2020 Blackwell Verlag GmbH.)

Atrial fibrillation-flutter (AF) has been described in 10% to 24% of patients after heart transplant (HT). Data on AF hospitalizations after HT are limited to single-center experiences. To bridge this gap, we performed an analysis of admissions for AF in HT patients from the National Inpatient Sample (NIS) years 2000 to 2014. All hospitalizations with a primary diagnosis of 427.31 or 427.32 and V42.1 were used to identify hospitalizations with AF and previous HT respectively. Among a total of 211,961 HT related hospitalizations, 1,304 (0.62%) (955 males, 349 females, mean age 59 years, median CHA 2 DS 2 Vasc score 2 [Interquartile range 1 to 3]) were admitted with a primary diagnosis AF. Most hospitalizations were nonelective (80.17%). In-hospital mortality was 2.3% and the mean length of stay (LOS) was 3.7 days. Among those patients who were discharged from hospital, 85 % were discharged to home with self-care. Most commonly reported secondary diagnoses included hypertension (57.9%), diabetes (33%), renal failure (31.3%), and congestive heart failure (22%). The event rates for ischemic stroke and gastrointestinal bleeding in the same admission with the AF hospitalization were low (1.2% and 1.2% respectively). Cardioversion was performed in 37% and ablation in 11.2% of admissions. The adjusted median cost of hospitalization was $6478.7 (IQR $3561.8 to $12352.3) and did not change significantly during the study period. AF is a relatively infrequent cause of hospitalization among HT recipients. The number of hospitalizations, ablations, cardioversions, disposition, LOS, and cost of hospitalization for AF remained stable during the study period., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Cardiovascular disease (CVD) rates in adulthood are high in premature infants; unfortunately, the underlying mechanisms are not well defined. In this review, we discuss potential pathways that could lead to CVD in premature babies. Studies show intense oxidant stress and inflammation at tissue levels in these neonates. Alterations in lipid profile, foetal epigenomics, and gut microbiota in these infants may also underlie the development of CVD. Recently, probiotic bacteria, such as the mucin-degrading bacterium Akkermansia muciniphila have been shown to reduce inflammation and prevent heart disease in animal models. All this information might enable scientists and clinicians to target pathways to act early to curtail the adverse effects of prematurity on the cardiovascular system. This could lead to primary and secondary prevention of CVD and improve survival among preterm neonates later in adult life., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Background: Mortality caused by ventricular arrhythmias (VAs) remains a problem of epidemic proportions. Understanding current trends on admission of VA, patient characteristics, morbidity, mortality, and health care utilization could help us improve allocation of health care resources and risk prediction., Objective: The purpose of this study was to investigate clinical outcomes of VA, including ventricular tachycardia (VT), implantable cardioverter-defibrillator (ICD) shocks, and sudden cardiac death (SCD); and to identify predictors of morbidity and mortality, patterns of utilization of ICD and VT ablation, and the impact of such metrics on overall health care utilization., Methods: From 2010-2015, we identified 290,998 VA hospitalizations, which were stratified into group 1: normal heart; group 2: ischemic heart disease (IHD); group 3: nonischemic heart disease (non-IHD); group 4: ICD shocks; and group 5: SCD (cardiac arrest without ICD shock)., Results: The number of admissions for VA decreased during the study period (except for patients with SCD and ICD shock, which increased); in-hospital mortality in patients admitted with VA and SCD increased; utilization of VT ablation in patients with ICD shocks and IHD increased; ICD implantation decreased in non-IHD patients and IHD patients; and admission for SCD was the strongest predictor of in-hospital mortality, followed by patients with non-IHD, patients with ICD shocks, and all patients with a Charlson comorbidity index ≥2., Conclusion: We report a decrease in admissions for VA, decreased ICD utilization, a change in pattern of VT ablation utilization, and an increase of in-hospital mortality in SCD patients. Predictors of adverse outcomes identified in our study should be considered when developing risk models for patients undergoing risk assessment for SCD., (Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: The utilization of cardiac resynchronization therapy defibrillator (CRT-D) has increased significantly, since its initial approval for use in selected patients with heart failure. Limited data exist as for current trends in implant-related in-hospital complications and cost utilization. The aim of our study was to examine in-hospital complication rates associated with CRT-D and their trends over the last decade., Methods and Results: Using the Nationwide Inpatient Sample, we estimated 378 248 CRT-D procedures from 2003 to 2012. We investigated common complications, including mechanical, cardiovascular, pericardial complications (hemopericardium, cardiac tamponade, or pericardiocentesis), pneumothorax, stroke, vascular complications (consisting of hemorrhage/hematoma, incidents requiring surgical repair, and accidental arterial puncture), and in-hospital deaths described with CRT-D, defining them by the validated International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code. Mechanical complications (5.9%) were the commonest, followed by cardiovascular (3.6%), respiratory failure (2.4%), and pneumothorax (1.5%). Age (≥65 years), female gender (OR, 95% CI; P value) (1.08, 1.03-1.13; 0.001), and the Charlson score ≥3 (1.52, 1.45-1.60; <0.001) were significantly associated with increased mortality/complications., Conclusions: The overall complication rate in patients undergoing CRT-D has been increasing in the last decade. Age (≥65), female sex, and the Charlson score ≥3 were associated with higher complications. In patients who underwent CRT-D implantation, postoperative complications were associated with significant increases in cost., (© 2018 Wiley Periodicals, Inc.)

Background: We examined the effect of AF a commonly encountered arrhythmia with significant morbidity on mortality following a motor vehicle accident (MVA) related hospitalization., Methods: The Nationwide Inpatient Sample (NIS) was queried to identify patients with AF (ICD-9 CM 427.31) and MVA (ICD-9 CM E810.0-E819.9), considered separately and together, from 2003 through 2012. Baseline characteristics were identified and multilevel mixed model multivariate analysis was employed to verify the impact of AF on in-patient mortality in survivors., Results: Of an estimated 2,978,630 MVA admissions reported, 79,687 (2.6%) hospitalizations also had a diagnosis of AF. The in-hospital mortality was 2.6% in MVA alone and 7.6% in MVA and AF. In multivariate analysis, after adjustment for age, gender, Charlson Comorbidity Index (CCI), the Trauma Mortality Prediction Model (TMPM), and hospital characteristics, AF was independently associated with in-hospital mortality [Odds ratio (OR) 1.52, confidence interval (CI) 1.41-1.69, P value<0.0001]. In patients with MVA and AF, increasing age, CCI, and TMPM were associated with higher mortality. Female gender is associated with lower mortality (OR 0.84, CI 0.81-0.88, P -0.0016). Most patients with MVA and AF had a CHADS2 score of 2 (34.6%). Mortality and transfusion rates were higher in MVA and AF patients compared to patients with MVA alone across all CHADS2 scores., Conclusion: In patients with a MVA, the presence of AF is an independent risk factor for in-hospital mortality., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The distribution of bluetongue viruses (BTV) in Australia is represented by two distinct and interconnected epidemiological systems (episystems)-one distributed primarily in the north and one in the east. The northern episystem is characterised by substantially greater antigenic diversity than the eastern episystem; yet the forces that act to limit the diversity present in the east remain unclear. Previous work has indicated that the northern episystem is linked to that of island South East Asia and Melanesia, and that BTV present in Indonesia, Papua New Guinea and East Timor, may act as source populations for new serotypes and genotypes of BTV to enter Australia's north. In this study, the genomes of 49 bluetongue viruses from the eastern episystem and 13 from Indonesia were sequenced and analysed along with 27 previously published genome sequences from the northern Australian episystem. The results of this analysis confirm that the Australian BTV population has its origins in the South East Asian/Melanesian episystem, and that incursions into northern Australia occur with some regularity. In addition, the presence of limited genetic diversity in the eastern episystem relative to that found in the north supports the presence of substantial, but not complete, barriers to gene flow between the northern and eastern Australian episystems. Genetic bottlenecks between each successive episystem are evident, and appear to be responsible for the reduction in BTV genetic diversity observed in the north to south-east direction.

Objectives: The nationwide prevalence of cannabis use/abuse has more than doubled from 2002 to 2011. Whether the outpatient trend is reflected in the inpatient setting is unknown. We examined the prevalence and incidence of cannabis abuse/dependence as determined by discharge coding in a 10-year (2002-2011) National Inpatient Sample, as well as various trends among demographics, comorbidities, and hospitalization outcomes., Methods: Cannabis abuse/dependence was identified on the basis of International Classification of Diseases, 9th Revision, Clinical Modification codes 304.3* and 305.2* in adults aged 18 years or more. We excluded cases coded "in remission." National estimates of trends and matched-regression analyses were conducted., Results: Overall, 2,833,567 (0.91%) admissions with documented cannabis abuse/dependence were identified, patients had a mean age of 35.12 ± 0.06 years, 62% were male, and there was an increasing trend in prevalence from 0.52% to 1.34% (P <.001). The mean Charlson Comorbidity Index was 0.47 ± 0.006, and inpatient mortality was 0.41%. All of the above demonstrated an increasing trend (P <.001). Mean length of stay was 6.23 ± 0.06 days. The top primary discharge diagnoses were schizoaffective/mood disorders, followed by psychotic disorders and alcoholism. Asthma prevalence in nontobacco smokers had a steeper increase in the cannabis subgroup than in the noncannabis subgroup (P = .002). Among acute pancreatitis admissions, cannabis abusers had a shorter length of stay (-11%) and lower hospitalization costs (-7%) than nonabusers., Conclusion: Cannabis abuse/dependence is on the rise in the inpatient population, with an increasing trend toward older and sicker patients with increasing rates of moderate to severe disability. Psychiatric disorders and alcoholism are the main associated primary conditions. Cannabis abuse is associated with increased asthma incidence in nontobacco smokers and decreased hospital resource use in acute pancreatitis admissions., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Aortic stenosis (AS) has an increasing prevalence with age and is commonly associated with hypertension. While it has been established that hypertension is associated with increased mortality in patients with AS, further randomized control trials addressing the use of antihypertensives specifically in patients with AS are needed. The management of hypertension in patients with AS needs a cautious approach due to complex hemodynamic and structural changes involved. Comorbidities like coronary artery disease, heart failure and arrhythmias further dictate management of hypertension in patients with AS. The aim of this article is to review the various agents used in the management of hypertension in patients with AS., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Antispasmodic drugs are cheap, effective and generally safe. They may improve outcomes in colonoscopy, however their use has not been consistent or widespread. This manuscript reviews the three most commonly used antispasmodics in colonoscopy, namely, hyoscine butylbromide (and related ammonium compounds), glucagon and peppermint oil. The pharmacology, action and safety of the agents, as well as the evidence for them improving colonoscopic outcomes will be discussed. In addition to polyp detection, other colonoscopic outcome endpoints of interest include cecal and ileal intubation, and patient comfort. The drugs studied were all found to be effective gastrointestinal antispasmodics with good safety profiles. There is insufficient evidence to conclude whether antispasmodics improve cecal intubation rate, predominantly because the baseline rates are already high. Antispasmodics probably have efficacy in reducing cecal intubation time especially in those with marked colonic spasm. Antispasmodics do not offer significant benefit in polyp detection or improving patient comfort during colonoscopy. Future studies should focus on inexperienced colonoscopists as well as those with marked colonic spasm, in whom the greatest benefit seems to lie., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest.

Since the introduction of new antiplatelet and anticoagulant agents in the last decade, large-scale data studying gastrointestinal bleeding (GIB) in patients undergoing percutaneous coronary intervention (PCI) are lacking. Using the Nationwide Inpatient Sample, we identified all hospitalizations from 2006 to 2012 that required PCI. Temporal trends in the incidence and multivariate predictors of GIB associated with PCI were analyzed. A total of 4,376,950 patients underwent PCI in the United States during the study period. The incidence of GIB was 1.1%. Mortality rate in the GIB group was significantly higher (9.71% vs 1.1%, p <0.0001). Although the incidence of GIB remained stable during the study period (0.97% in 2006 to 1.19% in 2012), in-hospital mortality rate increased significantly from 7.9% in 2006 to 10.78% in 2012, with a peak of 12% in 2010. The GIB group had a longer median length of stay (5.80 vs 1.57 days) and an increased median cost of hospitalization ($26,564 vs $16,879). The predictors of GIB included cardiovascular co-morbidities such as acute myocardial infarction, cardiogenic shock, atrial fibrillation, congestive heart failure, valvular heart diseases, and a history of transient ischemic attack/stroke. Gastrointestinal co-morbidities including diverticulosis, esophageal cancer, stomach cancer, small intestine cancer, large intestine cancer, rectosigmoid cancer, gastrointestinal ulcer, and liver disease were predictors of GIB. Interestingly, a lower risk of GIB was associated with obese patients and patients with private insurance. A higher risk of GIB was noted in urgent versus elective admissions and weekend versus weekday admissions. In conclusion, the incidence of GIB in patients who underwent PCI remained stable from 2006 to 2012; however, the in-hospital mortality increased significantly. Identifying patients at higher risk for GIB is critically important to develop preventive strategies to reduce morbidity and mortality., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Continued evolution of highly pathogenic H5N1 viruses causing high mortality in humans obviates need for broadly cross-reactive vaccines. For this, hemagglutinin (HA) inducing specific protective antibodies, highly conserved nucleoprotein (NP), and ectodomain of matrix (M2e) protein, either singly or in combination, were evaluated in BALB/c mice. Recombinant HA and NP (baculovirus system) and M2e (synthetic peptide) and 3 adjuvants, that is, liposomes, Mw (heat killed Mycobacterium w), and alum were utilized for the homologous virus challenge. Additional immunogens included liposome-encapsulated HA/NP proteins and corresponding DNAs. Mice groups received two doses of respective formulations given at 3-week intervals and challenged intranasally with 100LD50 of H5N1 virus strain. Dynamics of weight loss, lung viral load, titres of IgG-anti-HA, NP, and M2e antibodies (ELISA), and IgG-subtype analysis was done. Two doses of all the formulations led to 100% seroconversion against the immunogens evaluated (100% seroconversion after the first dose in majority). Antibody titres against the components were dependent on the adjuvant and combination. HA-driven Th2 response with all the adjuvants, balanced Th1/Th2 response to NP protein, and Th2-bias with alum were noted. Low anti-M2e antibody titres did not allow subtype analysis. On challenge, complete protection was observed with Mw-HA, alum-HA+NP, Lipo-HA+NP+M2e, alum-HA+NP+M2e, and HA-DP formulations with 12-fold, 8-fold, 720-fold, 17-fold, and no reduction, respectively, in lung viral load. In conclusion, the results identify several adjuvant-immunogen combinations conferring 100% protection in mice that need further evaluation in higher animals.