Is Using the Harmonic Scalpel Better than Conventional Hemostasis in Neck Dissection? A Meta-Analysis.

Study Design: Systematic review and meta-analysis. Objective: The clinical decision to pursue harmonic scalpel (HS) method vs conventional hemostasis to treat head and neck cancers has been arguably predicated on the clinical outcomes observed. This study aims to evaluate the surgical outcomes of neck dissection between both techniques and perform an updated meta-analysis using the available literature. Methods: We searched PubMed, Scopus, and Cochrane Library through 31st December 2021, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Outcome metrics included operative time and intraoperative blood loss. Secondary outcomes consisted of length of hospital stay, length of drain stay, total drain output, and postoperative complications. A meta-analysis was conducted using Review Manager Version 5.3 (RevMan) software employing the Random Effects Model. Results: We identified 114 articles, out of which 10 randomized control trials (RCTs) analyzing a combined total of 558 patients met the inclusion criteria after title and full-text screening. Meta-analysis shows the group treated with HS had a significantly shorter operative time. [MD = -23.21, 95% CI (-34.30, -12.12) P value <.0001 I2 = 92%] but an insignificant lesser intraoperative blood loss [MD = -61.53, 95% CI (-88.61, -34.45) P < .00001 I2 = 79%]. Conclusions: This study confirms that that HS use in neck dissection yields a reduced operative time and intra operative blood loss relative to conventional hemostasis. Furthermore, our paper shows no superiority of HS method over conventional hemostasis where length of hospital stays, length of drain stays, and postoperative complications are concerned. Future RCTs with high-level evidence may further elucidate the relative effectiveness of HS method over conventional hemostasis in treating head and neck cancers.

Is endovascular treatment alone as effective and safe as that with preceding intravenous thrombolysis for acute ischemic stroke? A meta-analysis of randomized controlled trials.

INTRODUCTION: This meta-analysis aimed to evaluate the safety and efficacy of direct endovascular therapy (EVT) and bridging therapy (EVT with preceding intravenous thrombolysis i.e. IVT), in acute anterior circulation, large vessel occlusion stroke. EVIDENCE ACQUISITION: Following the PRISMA guidelines, a systematic literature review of the English language literature was conducted using PubMed, Cochrane CENTRAL, SCOPUS and ClinicalTrials.gov. Outcomes of interest were measured by the modified Rankin Scale (mRS), and included: no disability (mRS0), no significant disability despite some symptoms (mRS1), slight disability (mRS2), moderate disability (mRS3), moderately severe disability (mRS4), severe disability (mRS5), mortality (mRS6). Additionally, we inspected patients having excellent outcome, functional independence outcome, and poor outcome, along with successful reperfusion and intracranial hemorrhage. We calculated pooled risk ratios (RRs) and their corresponding 95% confidence intervals (CI). EVIDENCE SYNTHESIS: A total of seven RCTs involving 2,392 patients were finally included. The chances of achieving successful reperfusion were significantly more with IVT+EVT as compared to EVT alone (RR: 0.97; 95% CI: 0.94, 1.00; P=0.03) (I2=0%). There was no significant difference in the number of patients having outcomes ranging from mRS0 to mRS6, excellent outcome, functional independence, poor outcome or incidence of intracranial hemorrhage, who underwent either EVT alone or IVT+EVT. CONCLUSIONS: Additional trials are needed to determine if the absence of significant differences is due to insufficient sample size or if the combination therapy is truly not beneficial.

Effect of vitamin D on postoperative atrial fibrillation in patients who underwent coronary artery bypass grafting: A systematic review and meta-analysis.

BACKGROUND: Vitamin D insufficiency/deficiency has been identified as a risk factor for postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG). This is associated with significantly increased morbidity and mortality leading to not only prolonged hospital and intensive care unit (ICU) stay, but increased risk of stroke, heart failure, dementia, and long-term atrial fibrillation. This analysis aims to evaluate the efficacy of vitamin D supplementation in preventing POAF in patients undergoing CABG. METHODS: We searched PubMed, Cochrane Central Register of Controlled Trials and SCOPUS from inception to June 2022 for randomized controlled trials (RCTs). The outcome of interest was the incidence of POAF. Secondarily, we analyzed the length of ICU stay, length of hospital stay, cardiac arrest, cardiac tamponade, and blood transfusion. Results were pooled using a random-effect model. Three RCTs consisting of 448 patients were included. RESULTS: Our results suggest that vitamin D significantly reduced the incidence of POAF (RR: 0.60; 95 % CI: 0.40, 0.90; p = 0.01; I2 = 8 %). It was also observed that vitamin D significantly reduced the duration of ICU stay (WMD: -1.639; 95 % CI: -1.857, -1.420; p < 0.00001). Furthermore, the length of hospital stay (WMD: -0.85; 95 % CI: -2.14, 0.43; p = 0.19; I2 = 87 %) was also reduced, however, the result was not significant. CONCLUSION: Our pooled analysis suggests that vitamin D prevents POAF. Future large-scale randomized trials are needed to confirm our results.

Comparison of sodium-glucose cotransporter-2 inhibitors and thiazolidinediones for management of non-alcoholic fatty liver disease: A systematic review and meta-analysis.

BACKGROUND: The pharmacologic treatment of non-alcoholic fatty liver disease (NAFLD) remains unclear. METHODS: Two reviewers searched PubMed, SCOPUS, Cochrane Central and clinicaltrials.gov for randomized controlled trials (RCTs) of patients with NAFLD with or without type 2 diabetes mellitus (T2DM) receiving TZDs vs SGLT2 inhibitors. The primary outcomes were change in alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transferase (GGT) and improvement in steatosis and fibrosis. The secondary outcomes were changes in lipid profile, body weight and glycated hemoglobin (HbA1c). Random effects models with continuous outcomes as weighted mean differences (WMD) with 95% confidence intervals (CI) were used. RESULTS: Five studies (n = 311 NAFLD patients) were included. Patients treated with SGLT2 inhibitors (n = 156) showed significant decrease in visceral fat area (VFA; WMD 23.45, p < 0.00001) and body weight (WMD 4.22, p < 0.00001) as compared to those treated with TZDs (n = 155). Patients from both groups showed improvement in AST (WMD 1.21, p = 0.40), ALT (WMD -0.46, p = 0.81), GGT (WMD -0.47, p = 0.84), hepatic fibrosis (WMD 0.11, p = 0.52), LDL (WMD 2.19, p = 0.35), HbA1c (WMD -0.16%, p = 0.20), HOMA-IR (WMD: -0.04, p = 0.91) and FPG (WMD -7.37, p = 0.28) which was equivalent and non-significant. CONCLUSION: The improvement in liver enzymes, steatosis and fibrosis caused by SGLT2 inhibitors and TZDs was similar. SGLT2 inhibitors, however, resulted in a significant decrease in VFA and body weight. As weight loss is found to have a positive effect on the resolution of steatosis and fibrosis in NAFLD patients, SGLT2 inhibitors may have the potential to be considered for long-term management, however, further research needs to be conducted to determine the utility of SGLT2 inhibitor class of antidiabetic drugs for effectively treating NAFLD.

Is it safe and effective to administer COVID-19 vaccines during pregnancy? A systematic review and meta-analysis.

OBJECTIVE: To evaluate the safety and efficacy of COVID-19 vaccines in pregnant women performing an updated meta-analysis. METHODS: We searched PubMed, Cochrane Central, and SCOPUS from inception to March 2022. Outcomes of interest were incidence of adverse maternal, fetal and neonatal consequences pertaining to safety of the vaccines. Secondarily, we analyzed the number of SARS-CoV-2 infections, hospitalization for COVID-19, and admission to the I.C.U. for COVID-19 assessing the effectiveness of vaccines. Results were pooled using a random effects model. RESULTS: Ten observational studies (n=326,499) analyzing pregnant women were included. Our results suggest that COVID-19 vaccination prevents infection (OR: 0.56, 95% CI: 0.47, 0.67; P = <0.00001) and related hospitalizations (OR: 0.50, 95% CI: 0.31, 0.82; P = 0.006) effectively. It was also observed that vaccination does not change adverse outcomes in pregnancy, namely preeclampsia or eclampsia, stroke (four weeks of delivery), meconium-stained amniotic fluid, spontaneous vaginal delivery, operative vaginal delivery, cesarean delivery, postpartum hemorrhage, and blood transfusions. Furthermore, the vaccine was observed to be protective against neonatal COVID-19 I.C.U. admissions (OR: 0.85; 95% CI: 0.81, 0.90; P = <0.00001). CONCLUSION: Our pooled analysis suggests that the COVID-19 vaccination in pregnant women prevents infection effectively and has no adverse outcomes. Future large-scale trials in a randomized fashion are needed to confirm our results.

Transaxillary Versus Transaortic Transcatheter Aortic Valve Implantation in the Treatment of Aortic Stenosis: An Updated Systematic Review and Meta-Analysis.

Transcatheter aortic valve replacement (TAVR) is a technique that can be performed through multiple approaches, and the benefits of one approach over another are still being evaluated to make sure patients receive the best possible care. Our meta-analysis aims to compare clinical and procedural outcomes of the transaxillary (TAx) and transaortic (TAo) approaches to validate the more optimal procedure. The systematic literature search was done via PubMed/MEDLINE, Embase, and the Cochrane Central databases from inception to December 2021, to identify articles reporting data on both TAx TAVR and TAo TAVR. In addition, we checked ClinicalTrials.gov for more published or unpublished trials. Baseline patient characteristics, procedure results, and clinical results were extracted from the article and pooled for analysis. A quantitative meta-analysis was conducted using Review Manager (RevMan) version 5.3 (Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark). The outcomes extracted included blood transfusion, conversion to sternotomy, tamponade, contrast amount, procedure time, bleeding incidents (minor, major, or life-threatening), length of stay (LOS), vascular complications (minor or major), acute kidney injury (AKI), paravalvular leak (PVL), permanent pacemaker (PPM) implantation, 30-day mortality, one-year mortality, 30-day stroke, and device success. The final analysis included 11 articles, consisting of 10 observational studies and a pivotal trial. Cumulative results revealed that the TAo approach had a significantly lower incidence of vascular complications (RR = 2.30; 95% CI = 1.22 to 4.35), and the need for implantation of a permanent pacemaker (RR = 1.82; 95% CI = 1.30 to 2.54) along with a lower amount of contrast (mean difference (MD) = 27.40; 95% CI = 3.73 to 51.08) needed to be used. The TAx group was associated with a significantly lower 30-day mortality (RR = 0.46; 95% CI = 0.31 to 0.69), AKI (RR = 0.47; 95% CI = 0.33 to 0.67), and length of hospital stay (MD = -1.95; 95% CI = -2.51 to -1.38). No significant difference was observed between the outcomes of 30-day stroke (RR = 1.38; 95% CI = 0.81 to 2.33), PVL (RR = 1.05; 95% CI = 0.50 to 2.18), tamponade (RR = 0.71; 95% CI = 0.12 to 4.03), conversion to sternotomy (RR = 0.51; 95% CI = 0.06 to 4.30), device success (RR = 0.97; 95% CI = 0.88 to 1.07), the incidence of bleeding (RR = 0.75; 95% CI = 0.51 to 1.10), and procedure time (MD = 4.44; 95% CI = -96.30 to 105.17). Both the procedures were associated with their benefits and risks. Although most of the outcomes favored TAx transcatheter aortic valve implantation (TAVI), it is too early to say if it would be better than TAo TAVI. To authenticate the findings concluded in this meta-analysis and further improve our understanding of the efficacy, safety, and risk profile between TAx and TAo approaches for TAVI, large sample randomized clinical trials are required on a wide scale.

Detecting Asymmetric Patterns and Localizing Cancers on Mammograms.

One in eight women develops invasive breast cancer in her lifetime. The frontline protection against this disease is mammography. While computer-assisted diagnosis algorithms have made great progress in generating reliable global predictions, few focus on simultaneously producing regions of interest (ROIs) for biopsy. Can we combine ROI-oriented algorithms with global classification of cancer status, which simultaneously highlight suspicious regions and optimize classification performance? Can the asymmetry of breasts be adopted in deep learning for finding lesions and classifying cancers? We answer the above questions by building deep-learning networks that identify masses and microcalcifications in paired mammograms, exclude false positives, and stepwisely improve performance of the model with asymmetric information regarding the breasts. This method achieved a co-leading place in the Digital Mammography DREAM Challenge for predicting breast cancer. We highlight here the importance of this dual-purpose process that simultaneously provides the locations of potential lesions in mammograms.

Anti-human TREM2 induces microglia proliferation and reduces pathology in an Alzheimer's disease model.

TREM2 is a receptor for lipids expressed in microglia. The R47H variant of human TREM2 impairs ligand binding and increases Alzheimer's disease (AD) risk. In mouse models of amyloid ß (Aß) accumulation, defective TREM2 function affects microglial response to Aß plaques, exacerbating tissue damage, whereas TREM2 overexpression attenuates pathology. Thus, AD may benefit from TREM2 activation. Here, we examined the impact of an anti-human TREM2 agonistic mAb, AL002c, in a mouse AD model expressing either the common variant (CV) or the R47H variant of TREM2. Single-cell RNA-seq of microglia after acute systemic administration of AL002c showed induction of proliferation in both CV- and R47H-transgenic mice. Prolonged administration of AL002c reduced filamentous plaques and neurite dystrophy, impacted behavior, and tempered microglial inflammatory response. We further showed that a variant of AL002c is safe and well tolerated in a first-in-human phase I clinical trial and engages TREM2 based on cerebrospinal fluid biomarkers. We conclude that AL002 is a promising candidate for AD therapy.

Neonatal danger signs and healthcare seeking behaviours: A cross-sectional study in Karachi amongst pregnant females.

OBJECTIVE: To assess knowledge among pregnant women regarding neonatal danger signs and to evaluate their healthcare seeking behaviour. METHODS: The cross-sectional study was conducted at Civil Hospital, Karachi, from February to April 2018, and comprised pregnant females presenting to the hospital. They were interviewed through a structured questionnaire. Participants' knowledge regarding 12 neonatal danger signs was assessed. Those who could identify 3 or more such signs were considered to have a good knowledge. Data was analysed using SPSS 23. RESULTS: There were 468 subjects with a mean age of 25.17±5.18 years. Of the total, 416(88.9%) women were aged 18-35 years. Overall, 72(15%) subjects had good knowledge, while 366(78%) could identify at least one danger sign. Also, 318(82%) participants preferred visiting a hospital / clinic to seek healthcare. CONCLUSIONS: There was a severe lack of knowledge among pregnant women regarding neonatal danger signs. However, most participants realised the necessity of taking their neonate to a hospital / clinic for proper healthcare.

Joint learning improves protein abundance prediction in cancers.

BACKGROUND: The classic central dogma in biology is the information flow from DNA to mRNA to protein, yet complicated regulatory mechanisms underlying protein translation often lead to weak correlations between mRNA and protein abundances. This is particularly the case in cancer samples and when evaluating the same gene across multiple samples. RESULTS: Here, we report a method for predicting proteome from transcriptome, using a training dataset provided by NCI-CPTAC and TCGA, consisting of transcriptome and proteome data from 77 breast and 105 ovarian cancer samples. First, we establish a generic model capturing the correlation between mRNA and protein abundance of a single gene. Second, we build a gene-specific model capturing the interdependencies among multiple genes in a regulatory network. Third, we create a cross-tissue model by joint learning the information of shared regulatory networks and pathways across cancer tissues. Our method ranked first in the NCI-CPTAC DREAM Proteogenomics Challenge, and the predictive performance is close to the accuracy of experimental replicates. Key functional pathways and network modules controlling the proteomic abundance in cancers were revealed, in particular metabolism-related genes. CONCLUSIONS: We present a method to predict proteome from transcriptome, leveraging data from different cancer tissues to build a trans-tissue model, and suggest how to integrate information from multiple cancers to provide a foundation for further research.

Prevalence of pain in atypical parkinsonism: a systematic review and meta-analysis.

Pain is common in atypical parkinsonism such as multiple system atrophy (MSA), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and dementia with Lewy bodies (LBD). In this study, a systematic review and meta-analysis was conducted and peer-reviewed literature was searched to determine the prevalence and types of pain in four atypical parkinsonism syndromes: MSA, PSP, CBD and LBD. The results show that pain was prevalent mainly in MSA patients in comparison to PSP and CBD patients. Pain was reported at an early stage and was found in females, with limb pain being the most common, followed by neck and back pain. In comparison to PSP, pain locations were similar to MSA patients. CBD patients experienced pain the least in comparison to MSA, PSP and LBD patients.

Chromosome 17 Missing Proteins: Recent Progress and Future Directions as Part of the neXt-MP50 Challenge.

The Chromosome-centric Human Proteome Project (C-HPP), announced in September 2016, is an initiative to accelerate progress on the detection and characterization of neXtProt PE2,3,4 "missing proteins" (MPs) with a mandate to each chromosome team to find about 50 MPs over 2 years. Here we report major progress toward the neXt-MP50 challenge with 43 newly validated Chr 17 PE1 proteins, of which 25 were based on mass spectrometry, 12 on protein-protein interactions, 3 on a combination of MS and PPI, and 3 with other types of data. Notable among these new PE1 proteins were five keratin-associated proteins, a single olfactory receptor, and five additional membrane-embedded proteins. We evaluate the prospects of finding the remaining 105 MPs coded for on Chr 17, focusing on mass spectrometry and protein-protein interaction approaches. We present a list of 35 prioritized MPs with specific approaches that may be used in further MS and PPI experimental studies. Additionally, we demonstrate how in silico studies can be used to capture individual peptides from major data repositories, documenting one MP that appears to be a strong candidate for PE1. We are close to our goal of finding 50 MPs for Chr 17.

Association of the frequency of pre-end-stage renal disease medical care with post-end-stage renal disease mortality and hospitalization.

Background: Previous studies have demonstrated that early pre-end-stage renal disease (ESRD) nephrology care could improve postdialysis prognosis. However, less is known about the specific types of interventions responsible for the improved outcomes. We hypothesized that more frequent predialysis laboratory testing is associated with better postdialysis outcomes in incident ESRD patients. Methods: In all, 23 089 patients with available outpatient laboratory tests performed during the 2-year predialysis (i.e. prelude) period were identified from a total of 52 172 American veterans with chronic kidney disease (CKD) transitioning to dialysis between October 2007 and September 2011. The associations between the frequency of combined laboratory tests, including serum creatinine, serum potassium and hemoglobin (test trio), with postdialysis mortality and hospitalization were examined in multivariable adjusted Cox and logistic regression models. Results: When entering the 2-year prelude period, the mean age (Standard Deviation) of the patients was 66.2 (SD 11.3) years and the mean estimated glomerular filtration rate was 46.8 (SD 23.9) mL/min/1.73 m2. In all, 14% of patients had the test trio performed less than twice in 24 months and 8.9% had the trio measured more often than every other month. Over a 2.5-year median postdialysis follow-up period, 15 303 (66.3%) patients died (mortality rate 260/1000 patient-years). The adjusted hazard ratio of all-cause mortality and adjusted odds ratio of the composite of hospitalization or death associated with lab testing done >12/24 months compared with 2-≤4/24 months were 0.68 [95% confidence interval (CI) 0.65-0.73] and 0.70 (95% CI 0.62-0.79), respectively. Conclusions: More frequent laboratory testing in patients with advanced CKD is associated with better clinical outcomes after dialysis. Further examination in clinical trials is needed before the implementation of more frequent laboratory testing in clinical practice.

Prevalence and Predictors of Depression Amongst Hypertensive Individuals in Karachi, Pakistan.

OBJECTIVE: While studies evaluating the prevalence of depression and hypertension have been extensively carried out in high income countries, there is a paucity of information assessing the prevalence of depression within hypertensive patients in low income nations. The primary objective of this study was to investigate the prevalence of undiagnosed depression in hypertensive patients within a tertiary care facility in Karachi, Pakistan. The secondary objective was to assess factors associated with undiagnosed depression in this group. METHODS: A cross-sectional study was conducted at the Civil Hospital Karachi Outpatient Department from January 2017 to April 2017. The sample population was composed of 411 hypertensive patients. Interviews were conducted after taking informed consent, with data concerning basic demographic details and lifestyle habits gathered. Blood pressure was recorded and its severity was classified as per the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7) guidelines. Depression was evaluated and its severity classified as per the Patient Health Questionnaire-9 (PHQ-9) scale, with a score of 10 or above set as the cut-off point. Data were entered and analyzed using the IBM Statistical Package for the Social Sciences 23.0. (IBM, NY, USA). RESULTS: The prevalence of depression within 411 hypertensive patients was 40.1% (n = 165). The mean age of the sample was 45.7 ± 11.2 years, and the majority were females (72%, n = 295), unemployed (72%, n = 296), had primary or no education (67%, n = 277), and were of low socioeconomic status (78%, n = 321). The average systolic and diastolic blood pressures were 143.8 ± 21.7 and 93.3 ± 15.5 mm Hg, respectively. Factors which had a significant association with depression were gender (p = 0.009), age class (p = 0.035), educational status (p = 0.000), employment status (p = 0.003), socioeconomic status (p = 0.008), physical activity (p = 0.025), smoking (p = 0.017), and family history of hypertension (p = 0.022). CONCLUSION: With such a high prevalence rate of undiagnosed depression within hypertensive patients, it is pertinent to establish screening programs for early detection and community programs to raise awareness regarding long-term complications of untreated depression.

Secondary systemic amyloidosis in inflammatory bowel disease: a nationwide analysis.

BACKGROUND: Secondary systemic amyloidosis (SSA) is a rare but severe complication of inflammatory bowel disease (IBD). We aimed to evaluate the clinical characteristics, predictors of complications, and in-hospital mortality of patients with Crohn's disease (CD) and Ulcerative colitis (UC) who develop SSA. METHODS: Using the National Inpatient Sample, we identified patients hospitalized for IBD and SSA between 2004 and 2012. Using multivariate logistic regression, patients with CD were compared with those with UC regarding the presence or absence of SSA. IBD patients without SSA were matched in a 2:1 ratio with those with SSA using propensity matching. We analyzed the hospitalization trends of SSA in CD and UC patients using Pearson's χ2 test. Analyses were performed using SAS version 9.3. RESULTS: Among the 302,548 patients with CD and 174,057 patients with UC hospitalized between 2004 and 2012, we identified 47 (0.02%) and 36 (0.02%) cases of SSA, respectively. We noted rising annual hospitalization trends for both CD and UC patients with or without SSA. In-hospital mortality was significantly higher for both the UC+SSA group (16.7% vs. 2.1%, P<0.0001) and the CD+SSA group (6.4% vs. 1.0%, P=0.0001) before propensity matching. However, this difference was not seen for either UC+SSA (17.1% vs. 7.1%, P=0.11) or CD+SSA (6.8% vs. 2.3%, P=0.20) after matching. CONCLUSIONS: SSA rarely affects IBD patients, but when it does, it is associated with increased rates of infection, severe sepsis, and multi-organ system involvement. Despite this, SSA does not affect in-hospital mortality in IBD patients. Further studies are needed to explore this association.

Phase 2 Randomized Trial of the Safety and Efficacy of MHAA4549A, a Broadly Neutralizing Monoclonal Antibody, in a Human Influenza A Virus Challenge Model.

MHAA4549A, a human monoclonal antibody targeting the hemagglutinin stalk region of influenza A virus (IAV), is being developed as a therapeutic for patients hospitalized with severe IAV infection. The safety and efficacy of MHAA4549A were assessed in a randomized, double-blind, placebo-controlled, dose-ranging study in a human IAV challenge model. One hundred healthy volunteers were inoculated with A/Wisconsin/67/2005 (H3N2) IAV and, 24 to 36 h later, administered a single intravenous dose of either placebo, MHAA4549A (400, 1,200, or 3,600 mg), or a standard oral dose of oseltamivir. Subjects were assessed for safety, pharmacokinetics (PK), and immunogenicity. The intent-to-treat-infected (ITTI) population was assessed for changes in viral load, influenza symptoms, and inflammatory biomarkers. MHAA4549A was well tolerated in all IAV challenge subjects. The 3,600-mg dose of MHAA4549A significantly reduced the viral burden relative to that of the placebo as determined by the area under the curve (AUC) of nasopharyngeal virus infection, quantified using quantitative PCR (98%) and 50% tissue culture infective dose (TCID50) (100%) assays. Peak viral load, duration of viral shedding, influenza symptom scores, mucus weight, and inflammatory biomarkers were also reduced. Serum PK was linear with a half-life of ∼23 days. No MHAA4549A-treated subjects developed anti-drug antibodies. In conclusion, MHAA4549A was well tolerated and demonstrated statistically significant and substantial antiviral activity in an IAV challenge model. (This study has been registered at ClinicalTrials.gov under identifier NCT01980966.).

Early Mortality Associated with Inpatient versus Outpatient Hemodialysis Initiation in a Large Cohort of US Veterans with Incident End-Stage Renal Disease.

BACKGROUND: Mortality in the immediate post-hemodialysis transition period is extremely high. Many end-stage renal disease (ESRD) patients in the US start dialysis in an inpatient setting, but the characteristics of patients starting dialysis as inpatients, and the association of inpatient hemodialysis transition with mortality remain unclear. METHODS: We examined 48,261 US veterans who transitioned to hemodialysis between October 2007 and September 2011. Associations of inpatient hemodialysis starting with all-cause mortality were examined in Cox proportional hazard models, with adjustments for demographics, comorbidities, vascular access type, pre-dialysis nephrology care and medication use, and last pre-ESRD estimated glomerular filtration rate and hemoglobin. RESULTS: A total of 22,338 (46.3%) patients received the first hemodialysis treatment in an inpatient setting. Inpatient hemodialysis transition was associated with older age, presence of a tunneled catheter, higher comorbidity burden, and lack of pre-dialysis nephrology care. A total of 8,674 patients died (mortality rate 405/1,000 patient-years, 95% CI 397-413) during the first 6 months after transition to hemodialysis. The starting of inpatient vs. outpatient hemodialysis was associated with significantly higher crude all-cause mortality, but this association was attenuated after multivariable adjustments. CONCLUSIONS: Transition to hemodialysis in an inpatient setting is more common in older and sicker individuals, and in patients without pre-dialysis nephrology care and those who used a catheter for vascular access. Future studies are needed to determine if a higher proportion of patients could start hemodialysis treatment in outpatient clinics, through interventions targeting modifiable risk factors such as timely vascular access placement or earlier nephrology referrals.