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Introduction Several treatment options are available for the management of older adults with newly diagnosed patients with Multiple Myeloma (MM) who are ineligible for hematopoietic cell transplantation (tiMM). We aimed to identify treatment options that provide the best balance in terms of efficacy and safety. Methods We searched bibliographic databases and meeting libraries for search terms reflecting newly diagnosed and older and/or transplant-ineligible patients from inception to October 21, 2018. Phase II/III randomized trials comparing at least two first line treatment regimens for newly diagnosed tiMM were included. We extracted data on efficacy (progression free survival, PFS, overall survival and overall response rate) and safety (grade ¾ toxicities) and conducted network meta-analysis using Bayesian methods and random effects models. Relative ranking of treatment regimens was assessed using Surface under the cumulative ranking (SUCRA) probabilities. Results We identified 27 trials involving 12,194 patients. For PFS, the four most effective regimens were: Daratumumab, Bortezomib, Melphalan and Prednisone (SUCRA 0.960) followed by Daratumumab, lenalidomide and dexamethasone (Dara_RD, SUCRA 0.847), Bortezomib, melphalan, prednisone, thalidomide maintenance with bortezomib-thalidomide (SUCRA 0.834) and Bortezomib, Lenalidomide and Dexamethasone (SUCRA 0.739). Among these four most efficacious regimens, toxicity profile was most favorable for Dara_RD (median additional AEs per patient vs dexamethasone = 0.74; 95% CrI 0.51–1.17; SUCRA 0.430). Conclusion Among first line tiMM regimens, increasing efficacy is associated with increased toxicity. We provide relative ranking of these regimens for both efficacy and safety. Future studies should incorporate geriatric assessments and frailty biomarkers to refine treatment decision-making for each individual patient.

Background Several new treatment options have been approved for relapsed and/or refractory multiple myeloma (RRMM). In this systematic review, associations of the efficacy of each approved regimen with adverse events (AEs) and the total cost per cycle were compared with a Bayesian network meta-analysis (NMA) of phase 3 randomized controlled trials (RCTs). Methods Scopus, Cochrane, PubMed Publisher, and Web of Science were searched from January 1999 to July 2018 for phase 3 RCTs of regimens (approved by the US Food and Drug Administration) used in RRMM. The relative ranking of agents was assessed with surface under the cumulative ranking (SUCRA) probabilities. The primary efficacy, safety, and cost outcomes were progression-free survival with the regimen, grade 3 to 4 AEs, and the total cost per cycle (regimen cost plus average cost of managing AEs). Results Fifteen studies including 7718 patients and evaluating 14 different regimens were identified. Daratumumab, lenalidomide, and dexamethasone were ranked highest for reducing progression (hazard ratio, 0.13; 95% credible interval, 0.09-0.19; SUCRA, 1) but carried the highest probability of total cost per cycle ($41,420; 95% Credible Interval [CrCl], $58,665-$78,041; SUCRA, 0.02). Panobinostat, bortezomib, and dexamethasone were the least effective and least safe (SUCRA, 0.24), whereas bortezomib, thalidomide, and dexamethasone emerged as least effective with the highest total cost per cycle (SUCRA, 0.33). Carfilzomib and dexamethasone emerged as the winner when this regimen was considered in terms of efficacy and safety (SUCRA, 0.61) and efficacy and total cost per cycle (SUCRA, 0.60). Conclusions The results of this NMA can provide additional guidance for the decision-making process when one is choosing the most appropriate regimen for RRMM.

Background Randomized clinical trials comparing the efficacy and safety of direct oral anticoagulants (DOAC) with vitamin K antagonist (VKA) or low molecular weight heparin (LMWH) for the treatment of venous thromboembolism (VTE) generally exclude patients who are morbidly obese (body mass index ≥ 40 kg/m2 or weight ≥ 120 kg). Recently, smaller studies have compared DOACs with warfarin or low molecular weight heparin (LMWH) in morbidly obese patients with VTE. We aim to systematically review and do a meta-analysis of the studies that directly compared DOACs with VKAs or LMWH in morbidly obese patients. Methods Studies comparing DOAC with warfarin or LMWH in patients with acute VTE were identified through electronic literature searches of MEDLINE, EMBASE, Scopus, clinicaltrials.gov, and the Cochrane Library up to March 2020. The primary efficacy outcome was recurrent VTE and the primary safety outcome was major bleeding as defined by the International Society on Thrombosis and Haemostasis (ISTH) guidelines. Study-specific odds ratios (OR) were calculated and combined using a random-effects model meta-analysis. Result Five studies were identified. Recurrent VTE occurred in 95 of 3207 (2.96%) patients in the DOAC group and 81 of 3181 (2.54%) patients in the VKA and LMWH group (OR: 1.17; 95% CI 0.87 to 1.59, p=.30). Major bleeding occurred in 63 of 3316 (1.89%) patients in the DOAC group, and 83 of 3259(2.54%) patients in the VKA or LMWH group (OR: 0.74; 95% CI: 0.53 to 1.03, p=.08). Sensitivity analysis comparing factor Xa inhibitors apixaban and rivaroxaban to warfarin also yielded consistent findings. Conclusion DOACs showed similar efficacy and safety in the prevention of recurrent VTE risk and major bleeding events in morbidly obese patients when compared to warfarin/LMWH. Our study underscores the need for further modifications of therapy to reduce the high VTE recurrence rate irrespective of whether the patient is on a DOAC or VKA. This might be possible through a very large multi-institutional randomized clinical trial.

Noonan syndrome (NS) is an autosomal dominant disorder with multisystem involvement. NS can be associated with bleeding disorders due to defects in platelet function or coagulation factors and diagnosis can be challenging. Factor XIII (FXIII) deficiency is uncommon in patients with NS. We present a case of NS who presented with bleeding in both thighs and was diagnosed to have deficiency in FXIII.

Purpose of Review Novel coronavirus disease 2019 (COVID-19) has been associated with an increased risk of arterial and venous thromboembolic (VTE) diseases. However, there is a limited amount of data regarding the prevention and management of VTE in severe hospitalized COVID-19 patients. Recent Findings In this article, we review currently available clinical data, and mechanisms for COVID-associated coagulopathy, and propose algorithms for screening, prevention (including extended-duration prophylaxis), and treatment of these patients. Summary Although these recommendations are subject to change given rapidly evolving data, we provide a framework that can guide clinicians in managing thrombotic complications in this challenging condition.

BACKGROUND To the authors' knowledge, in the absence of head-to-head trials, it is unclear whether chemoimmunotherapy provides an additional overall survival (OS) benefit compared with immunotherapy alone in the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC). The authors conducted a systematic literature review and network meta-analysis (NMA) to compare the efficacy of chemoimmunotherapy versus ICI. METHODS MEDLINE, Excerpta Medica dataBASE (EMBASE), Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from inception to April 2020. Phase 3 trials evaluating the efficacy of first-line ICI or chemoimmunotherapy and reporting efficacy outcomes (OS, progression-free survival [PFS], and the overall response rate [ORR]) stratified by programmed death-ligand 1 (PD-L1) status were included. NMA with a Bayesian random effects model was performed. RESULTS A total of 12 eligible trials comprising 7845 patients were included. In patients who were negative for PD-L1 (tumor proportion score [TPS]

Heparin-induced thrombocytopenia (HIT) syndrome is an immune-mediated disorder producing thrombocytopenia and thrombosis, with or without prior exposure to heparin. Although avoidance of heparin products and nonheparin anticoagulants are used, immune-based therapies including intravenous immunoglobulin (IVIg) have been tried when the thrombocytopenia persists or there is breakthrough thrombosis. We sought to systematically review and analyze the published literature on use of IVIg in the treatment of HIT. A systematic search of PubMed, Google Scholar, EMBASE and SCOPUS for all study designs and reports were carried out from inception until April 2019. Statistical analysis was done using Microsoft Excel and Stata version 13. In 34 patients with HIT, the mean age was 60 years. About 70% cases were by unfractionated heparin exposure and 30% by low-molecular weight heparin. The most common precipitant in the patients without heparin exposure was recent surgery. Average nadir platelet count for which IVIg was used was 28 000/μl. Time from resolution of the thrombocytopenia after IVIg treatment was 3 days with average platelet count recovery to 159 000/μl. Mean time from diagnosis to administration of IVIg was day 18. Thrombosis was identified in 32% of patients. About 77% patients improved (platelet count >100 000/μl or cessation of thrombosis) following use of IVIg. Logistic regression did not identify any factors that predicted IVIg response (P > 0.05). No thrombotic events or other adverse events were noted with use of IVIg. IVIg appears to be a safe and effective treatment option for HIT-related thrombocytopenia and for refractory thrombosis.

The risk of venous thromboembolism (VTE) increases with age. New oral anticoagulants (NOACs) have been increasingly studied for VTE prophylaxis in patients with elective postarthroplasty. Although the elderly population accounts for a significant proportion of patients requiring VTE prophylaxis, safety and efficacy of NOACs in this subgroup for VTE prophylaxis has not been well studied. Relevant studies were identified through electronic literature searches of MEDLINE, EMBASE, Cochrane Library, and ClinicalTrials.gov (from inception to 12 August 2014). Phase III randomized controlled trials that compared NOACs against low-molecular-weight heparin (LMWH) in the prevention of VTE prophylaxis in patients with elective postarthroplasty were included. We defined our elderly population as adults of at least 75 years and assessed the reported safety and efficacy outcomes with NOACs in this population. Study-specific odds ratios (ORs) were calculated and between-study heterogeneity was assessed using the I statistic. In nine trials involving 29 403 patients, the risk of VTE or VTE-related deaths in elderly patients with elective postarthroplasty was similar with NOACs compared with LMWH (OR 0.62, 95% confidence interval 0.30-1.26; P = 0.18; I = 44%) but bleeding risk was significantly lower (OR 0.71, 95% confidence interval 0.53-0.94; P = 0.02; I = 0%). Analysis of individual NOACs showed superior efficacy but similar safety for apixaban when compared with LMWH. Efficacy and safety profiles of rivaroxaban and dabigatran were similar to LMWH. In elderly patients with elective postarthroplasty, NOACs have similar efficacy but superior safety when compared with enoxaparin for VTE prophylaxis.

Apixaban is a novel oral anticoagulant which is approved for the management of atrial fibrillation and venous thromboembolism prophylaxis. There have been concerns regarding bleeding risks with apixaban in patients with renal impairment. We performed a systematic review and meta-analysis to evaluate the risk of bleeding with apixaban in these patients. Relevant studies were identified through electronic literature searches of MEDLINE, EMBASE, Cochrane library, and clinicaltrials.gov (from inception to February 24, 2014). Phase III randomized controlled trials that compared apixaban with conventional agents (vitamin K antagonist and/or warfarin, low molecular weight heparin, aspirin, and placebo) were included. We defined mild renal impairment as creatinine clearance of 50 to 80 ml/min and moderate to severe renal impairment as creatinine clearance50 ml/min. Study-specific risk ratios were calculated, and between-study heterogeneity was assessed using the I(2) statistics. In 6 trials involving 40,145 patients, the risk of bleeding with apixaban in patients with mild renal impairment was significantly less (risk ratio 0.80, 95% confidence interval 0.66 to 0.96, I(2) = 13%) compared with conventional anticoagulants. In patients with moderate to severe renal impairment, the risk of bleeding with was found to be similar (risk ratio 1.01, 95% confidence interval 0.49 to 2.10, I(2) = 72%). In conclusion, compared with the conventional agents, bleeding risk with apixaban in patients with mild and moderate to severe renal insufficiency is lower and similar, respectively.

Compared to Vitamin K antagonists (VKA), novel oral anticoagulants (NOACs) appear to be safer in terms of major bleeding risks with added advantage of having fixed dosing schedules when used in patients with non-valvular atrial fibrillation (AF). We sought to study the differences as sources and severity of anticoagulant-associated haemorrhage in patients with AF in the year preceding introduction of NOACs (first cohort) as compared to post approval of the NOACs (second cohort) by retrospectively reviewing the hospital admissions, as well as the pharmacodynamic and pharmacokinetic interactions between time periods. There were 359 patients for the first cohort and 405 patients for the second cohort, including 57 patients prescribed NOACs. There was no significant difference in age, deaths, source of bleeding, or rate of pharmacokinetic or pharmacodynamic interaction between the two time periods. Comparing all VKA patients to patients prescribed NOAC's, there were non-significant but higher rates of intracerebral bleed, significantly higher rates of pharmacokinetic (194 (25.4%) versus 0 (0%), p.001) and similar rates of pharmacodynamic interactions (505 (66.1%) versus 39 (68.4%), p=.70). Drug-renal interactions were seen in 7 of the 57 (12.3%) NOAC-treated patients, in which all seven had acute renal failure that may have prolonged the effects of the anticoagulants. NOACs hold promise in that drug interactions are far less common than those seen in VKAs, and intracerebral bleeds appear to be less common in randomised trials as well as our review. For patients on dabigatran or rivaroxaban, consideration should be given to serial monitoring of renal function.

Purpose Central venous catheterization is a commonly used procedure to gain access to the central circulation. Although ultrasound guidance decreases the complication rates, arterial puncture may still occur. Failure to recognize this early may lead to devastating complications such as thrombosis and embolic stroke. We discuss the factors associated with increased risk of arterial puncture, techniques to detect them early and the management of established carotid artery cannulation. Methods We report a case of internal jugular catheterization complicated by carotid artery puncture leading to embolic stroke. Result Arterial catheterization in the patient went unrecognized for 2 days. During this period, the patient developed catheter-related thrombus in the carotid artery, ultimately resulting in embolic stroke. Emergent open surgical repair of the vessels with thrombectomy was performed. Conclusion Even with ultrasound-guided central venous catheterization, it is essential to remain vigilant for the early detection of vascular complications. Clinical suspicion combined with diagnostic modalities such as chest radiograph, transduction and manometry can increase the detection rates.

Objective To review efficacy of percutaneous closure of patent foramen ovale compared with medical therapy in prevention of recurrent strokes in patients with cryptogenic stroke. Methods and Results Electronic databases; PUBMED, EMBASE, Cochrane registry and web of knowledge were searched for relevant studies. In three randomised clinical trials involving 2303 participants, risk of the recurrent strokes (pooled HR 0.62, 95% CI = 0.36-1.07, P = 0.09, I2 =10%) did not show benefit with device closure when compared with medical therapy group on meta-analysis of all three trials. However, on sensitivity analysis in trials using Amplatzer PFO occluder device, the closure of PFO was associated with significantly lower recurrent strokes (pooled HR = 0.44, 95% CI = 0.21-0.94, P = 0.03, I2 = 0%) compared with medical therapy. Conclusion The closure of PFO with Amplatzer PFO occluder device was associated with significant reduction in recurrent strokes in patients with cryptogenic stroke and patent foramen ovale. The better outcome in prevention of secondary stroke in patients with cryptogenic stroke and PFO may be associated with type of closure device used.

Background: Several options exist for front-line treatment of previously untreated patients with Multiple Myeloma (MM) ineligible for hematopoietic cell transplant (HCT). Many of these have not been evaluated in head to head clinical trials. Since these patients are often old and frail, treatment regimens should have dual goals: a) maximize clinical efficacy b) minimize therapy related toxicity. However, published network meta-analysis (NMA) till date have ignored the equally important safety outcome. In this systematic review, we provide an updated comparative efficacy and safety data of various front-line treatment regimens for HCT ineligible MM patients, using a Bayesian framework. Methods: We searched Medline, Embase, Web of Science Core Collection and the Cochrane library for published phase II/phase III RCTs from inception to October 2018 comparing at least two frontline regimens for the treatment of HCT ineligible MM patients. The primary efficacy outcome was progression free survival (PFS) whereas secondary outcomes included overall response rate (ORR) and overall Survival (OS). We defined safety as rate of all-cause and common grade 3 or higher adverse events (AE) in each arm. Risk of bias was assessed using Cochrane Risk of Bias Assessment Tool. Using aggregate data, a Bayesian random-effect hierarchical model was fit with non-informative priors and adjusting for correlation between effects in multi-arm trials. Assessment of inconsistency was performed by node-splitting approach. For toxicity, a multivariate Bayesian probit-normal regression model was fitted to the observed number of adverse events for each toxicity in an arm based meta-analytic approach. The relative ranking of agents was assessed using surface under the cumulative ranking (SUCRA) probabilities. (PROSPERO # CRD42018115364) Results: After screening 5587 publications, we selected 27 clinical trials involving 12,194 patients comparing 25 different regimens for final analysis (table 1). 26 of these studies were incorporated into one network geometry. The median age of study participants ranged from 63 to 79 years and 47% were females (table 1). Our NMA showed that for PFS, the three most effective regimens were: Daratumumab, Bortezomib, Melphalan and Prednisone (Dara-VMP, SUCRA 0.960) followed by Daratumumab, lenalidomide and dexamethasone (Dara-RD, SUCRA 0.847) and Bortezomib, melphalan, prednisone, thalidomide followed by maintenance with bortezomib-thalidomide (VMPT-VT, SUCRA 0.834), with results consistent for ORR and OS (table 2). For safety, we extracted data on 33 different grade ¾ AEs, 7 of which were reported by >50% of studies (anemia, neutropenia, thrombocytopenia, infections, neuropathy, thrombosis and gastrointestinal AEs) and used for further analyses. Among the three most efficacious regimens, the toxicity profile was most favorable for Dara-RD (median additional AEs per patient vs dexamethasone=0.74; 95% CrI 0.51-1.17; SUCRA 0.430) followed by Dara-VMP (median additional AE 0.91; 95% CrI 0.65-1.34; SUCRA 0.279) and VMPT-VT (median additional AE 0.98; 95% CrI 0.79-1.24; SUCRA 0.224) (figure 3). Conclusion: We provide direct/indirect comparison of efficacy and safety of various frontline regimens for HCT ineligible MM patients. While Dara-VMP was most likely to be the most efficacious regimen, Dara-RD provided the best balance between efficacy and safety. The results of our analysis should provide guidance to clinicians and patients in choosing the right regimen tailored to individual patient needs. Disclosures Huntington: Celgene: Consultancy, Research Funding; Genentech: Consultancy; Bayer: Consultancy, Honoraria; DTRM Biopharm: Research Funding; Pharmacyclics: Honoraria; AbbVie: Consultancy. Dhakal:Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria; Sanofi: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees.

The pulmonary valve is the least affected site for valvular papillary fibroelastoma. With increasing use of routine echocardiography and other modalities of imaging, pulmonary valve papillary fibroelastomas (PVPFE) are being recognized more frequently. PVPFE is more often an incidental diagnosis and symptomatic patients usually present with shortness of breath. Embolic phenomena and right ventricular outflow tract obstruction are the most serious complications of PVPFE. Since PVPFE is rare, the purpose of this systematic review is to address demographic characteristics, the clinical presentation, management, and outcome of this benign tumor of the pulmonary valve.

Objectives Large licensing trials did not find any association between the use of fondaparinux and the development of heparin-induced thrombocytopenia (HIT). Fondaparinux is in fact recommended as an option for the management of HIT. Since the first report of fondaparinux-associated HIT in 2007, additional reports have been published. However, the rarity of these cases, differences in case definition, and lack of larger case series have prevented better understanding of this disease. The objective of this study was to determine the clinical manifestations of fondaparinux-associated HIT, the predictive value of pretest probability (4Ts) scoring system, and the outcomes associated with current management. Methods Using several search terms, we reviewed all cases of fondaparinux-associated HIT reported and indexed in PubMed till May 2013. All references were also checked for additional reports. We categorized the cases of fondaparinux-associated HIT as confirmed, probable, and possible based on our case definition. Results A total of eight cases of fondaparinux-associated HIT were identified. Fondaparinux-associated HIT occurred in the setting of pro-inflammatory state, prior HIT, or exposure to heparin products. Bilateral adrenal hemorrhage or infarct, reflecting hypercoagulability or disseminated intravascular coagulation, was seen in 25% of patients. The pretest probability (4Ts) scoring system used for HIT appears to correctly risk stratify all the cases. Although functional assays can be used for the diagnosis, in the presence of recent exposure to heparin products, only the demonstration of fondaparinux-dependent platelet activation should be considered confirmatory. Non-heparin anticoagulants are effective therapy; however, one-third of the patients had poor outcomes. Conclusion The risk of fondaparinux-associated HIT, although low is real, which along with documented cases of fondaparinux failure mandate its cautious use in the management of HIT.

In recent years, US hospitals have switched from use of unfractionated heparin to use of low-molecular-weight heparin, which is associated with lower risk of heparin-induced thrombocytopenia (HIT). In the study reported here, we retrospectively searched the Nationwide Inpatient Sample (NIS) for patients who were at least 18 years old and received a diagnosis of HIT between 2009 and 2011. Our goal was to get an updated perspective on the incidence and economic impact of HIT. We calculated the incidence of HIT overall and in subgroups of patients who underwent cardiac, vascular, or orthopedic surgery. We compared characteristics of patients with and without HIT and compared characteristics of patients with HIT with thrombosis (HITT) and HIT patients without thrombosis. Of 98,636,364 hospitalizations, 72,515 (0.07%) involved HIT. Arterial and venous thromboses were identified in 24,880 (34.3%) of HIT cases. Men were slightly more likely to have a HIT diagnosis (50.1%), but women had higher rates of HIT after cardiac surgery (odds ratio [OR], 1.41; 95% confidence interval [CI], 1.26-1.58) and vascular surgery (OR, 1.42; 95% CI, 1.29-1.57). Rates of HIT were 0.53% (95% CI, 0.51%-0.54%) after cardiac surgery, 0.28% (95% CI, 0.28%-0.29%) after vascular surgery, and 0.05% (95% CI, 0.05%-0.06%) after orthopedic surgery. HIT and HITT cases were significantly (P ⟨ 0.001) more likely than non-HIT cases to be fatal (9.63% and 12.28% vs 2.19%), and they had significantly higher costs and longer inpatient stays. HIT and especially HITT are associated with increased mortality, costs, and length of stay. Journal of Hospital Medicine 2017;12:94-97.

Background: Statins modify inflammatory cell signaling during the immune response to infection. This has been considered as a pleotropic effect. Effects of statins in inflammatory conditions such as bacteremia have been found to be controversial. Aims: We examined the effect of statins on the mortality of bacteremia patients. Materials and Methods: Major databases were searched for the pertinent clinical trials. Results: Six cohort studies comprising 7553 patients were included. Hospital mortality was lower (15.36% vs 22.28%) in patients on statin. Conclusions: There may be a potential role of statins in similar inflammatory and infective conditions.

Febrile neutropenia is a potentially life threatening complication of breast cancer chemotherapy associated with a significant amount of morbidity, mortality, and health care resource utilization. Recent data on the national estimates of mortality rate, length of stay, and health care costs among the subpopulation of febrile neutropenia admissions with breast cancer are lacking.We used the Nationwide Inpatient Sample database to identify patients with breast cancer hospitalized for febrile neutropenia from 2009 to 2011. We derived data on inhospital mortality rate, length of stay, and mean health care costs and compared it with previous studies.The average inhospital mortality rate during 2009-2011 was 2.6 % (n = 685). Advanced age (≥ 65 years) was found to be significantly associated with a higher odds of mortality (4.4 vs 1.7 %, OR 2.7, 95 % CI 2.3-3.1, p0.01). The mean length of stay was 5.7 days (95 % CI 5.5-5.9 days), whereas the mean cost of hospitalization was $37,087 (95 % CI $34,009-$40,165).Febrile neutropenia-related hospitalizations continue to account for significant morbidity, mortality, and health care resource utilization among patients with breast cancer. Further efforts should be focused on curtailing the rising health care costs without compromising the quality of care.

Toxocariasis is a zoonotic infection caused by Toxocara canis, or less commonly, Toxocara cati, which is one of the most common zoonotic infections worldwide. It commonly affects the pediatric and immunocompromised population; however, it has rarely been reported in the immunocompetent adults. Two of the well-recognized syndromes in children are visceral larva migrans and ocular larva migrans. Infection in adults usually ranges from asymptomatic to non-specific symptoms which makes the diagnosis challenging. A case of 36 year-old male was presented with disseminated toxocariasis with pulmonary and hepatic involvement and striking peripheral eosinophilia.

Background Patients with immune thrombocytopenia (ITP) may be at increased risk of thromboembolism related to different causes, including the use of thrombopoietin receptor agonists and splenectomy. Patients with ITP who develop coronary artery disease (CAD) can be a further challenge given their risk of both thromboembolism and bleeding, which may significantly increase the risk of mortality and length of stay (LOS) compared to patients who do not have ITP. We aimed to study the impact of ITP in hospital outcomes of patients with CAD. Methods We utilized the National Inpatient Sample database from years 2009 - 2011. We selected non-pregnant inpatients over the age of 18 with history of CAD. We selected patients with CAD and ITP based on International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). We used STATA version 13.0 (College Station, TX) for database analysis. Results A total of 4,777 cases of ITP with CAD were identified compared to 2,614,008 without ITP (Table 1). Logistic multivariable analyses found that patients with ITP had higher in-hospital mortality (95% CI: 1.21 to 1.55, p=0.0001) and LOS (95% CI: 1.32 to 1.72, p Conclusion: Our study shows that in patients with coronary artery disease-associated ITP, adjusted LOS and mortality was significantly higher compared to patients without ITP. Disclosures No relevant conflicts of interest to declare.

Association between sarcoidosis and antiphospholipid syndrome (APS) is rare with few reported cases. We sought to systematically review the published cases of APS with sarcoidosis to better characterize the demographics, clinical characteristics, treatment, and the outcome of this association. Systematic electronic search for case report, case series, and related articles published until May 2014 was carried out and relevant data were extracted and analyzed. Four cases of APS with sarcoidosis were identified exclusively in females. These cases were seen in the sixth decade of life. Pulmonary embolism and central retinal artery occlusion were the presenting thrombotic events. All the patients were treated with lifelong anticoagulation with warfarin. During the median follow-up period of 5.5 months, additional thrombotic events were not observed. Although rare, sarcoidosis may be associated with APS. Further reporting of the cases will help to better establish this association, elucidate pathogenesis, and define clinical characteristics and outcomes.

Background: The current West Africa epidemic of Ebola virus disease (EVD), which began from Guinea in December 2013, has been the longest and deadliest Ebola outbreak to date. With the propagation of the internet, public health officials must now compete with other official and unofficial sources of information to get their message out. Aims: This study aimed at critically appraising videos available on one popular internet video site (YouTube) as a source of information for Ebola virus disease (EVD). Materials and Methods: Videos were searched in YouTube (http://www.youtube.com) using the keyword “Ebola outbreak” from inception to November 1, 2014 with the default “relevance” filter. Only videos in English language under 10 min duration within first 10 pages of search were included. Duplicates were removed and the rest were classified as useful or misleading by two independent reviewers. Video sources were categorized by source. Inter-observer agreement was evaluated with kappa coefficient. Continuous and categorical variables were analyzed using the Student t-test and Chi-squared test, respectively. Results: One hundred and eighteen out of 198 videos were evaluated. Thirty-one (26.27%) videos were classified as misleading and 87 (73.73%) videos were classified as useful. The kappa coefficient of agreement regarding the usefulness of the videos was 0.68 (P < 0.001). Independent users were more likely to post misleading videos (93.55% vs 29.89%, OR = 34.02, 95% CI = 7.55-153.12, P < 0.001) whereas news agencies were most likely to post useful videos (65.52% vs 3.23%, OR = 57.00, 95% CI = 7.40-438.74, P < 0.001). Conclusions: This study demonstrates that majority of the internet videos about Ebola on YouTube were characterized as useful. Although YouTube seems to generally be a useful source of information on the current outbreak, increased efforts to disseminate scientifically correct information is desired to prevent unnecessary panic among the among the general population.

Obesity is an independent risk factor for venous thromboembolism (VTE), and the risk rises further in the postarthroplasty period. Although medication doses often require adjustment for the altered pharmacokinetic profile in obese patients, the efficacy and safety of a fixed-dose regimen of new oral anticoagulants (NOACs) in overweight and obese patients remain unclear. Relevant studies were identified through searches of major databases. Phase III randomized controlled trials that compared NOACs against low-molecular-weight heparin (LMWH) in the prevention of VTE in postarthroplasty patients were included. Efficacy and safety outcomes with NOACs in overweight (BMI 25-29 kg/m) and obese (BMI ≥ 30 kg/m) patients were assessed. In five trials involving 16 674 patients, NOACs were found similar to LMWH in preventing VTE and VTE-related deaths after arthroplasty in both overweight and obese patients [odds ratio (OR) 0.64, P = 0.19 and OR 0.76, P = 0.43, respectively]. Similarly, the risk of major or clinically relevant bleeding was similar to LMWH in overweight patient with a trend toward lower bleeding in obese patients (OR 0.83, P = 0.54 and OR 0.44, P = 0.07 respectively). Apixaban was found to be more effective than LMWH in obese patients (OR 0.54, P = 0.01) with the lower dose of dabigatran (150 mg) being less effective (OR 1.81, P = 0.02). Our study suggests that a fixed-dose regimen of dabigatran might be ineffective in severe obesity. However, apixaban at the currently recommended dose seems to be superior to LMWH in obese patients with noninferior bleeding risk.

Prior studies in the USA and elsewhere have suggested a distinct seasonal pattern in the incidence of immune thrombocytopenic purpura (ITP) among children [Kuhne et al. 2001; Moussalem and Yassine, 2003; Watts, 2004; Zeller et al. 2005; Yong et al. 2010]. However, it remains unknown if such a seasonal trend exists among adults with ITP-related hospitalizations. We utilized the Nationwide Inpatient Sample (NIS) database to study the seasonal pattern of ITP-related hospitalizations among adults in the US. NIS is the largest inpatient database in the USA and is sponsored by the Agency for Healthcare Research and Quality. International Classification of Diseases ninth revision, Clinical Modification code 287.31 was used to identify all patients discharged with a principal diagnosis of ITP between 1 January 2005 and 31 December 2011. We stratified each hospitalization with a primary diagnosis of ITP by the month of presentation. Walter and Elwood modification of the Edwards test was used to determine the monthly variation in the frequency of hospitalizations. Statistical analysis was conducted using STATA-MP 13.0 (StataCorp LP, College Station, TX, USA). ITP accounted for a total of 69,981 hospitalizations between 2005 and 2011. No significant monthly variation in ITP-related hospitalizations was seen during the study period (Figure 1). There was a nonsignificant trend towards peak hospitalization during the month of September (peak/low ratio of 1.01, 95% confidence interval 1.0–1.03). Figure 1. Monthly frequency distribution of immune thrombocytopenic purpura (ITP)-related hospitalizations in the USA based on the Nationwide Inpatient Sample database 2005–2011. Our study shows a lack of a seasonal trend among ITP-related hospitalizations among adults in the USA. This is in contrast to childhood ITP, for which a distinct seasonal trend has been shown [Kuhne et al. 2001; Moussalem and Yassine, 2003; Zeller et al. 2005; Yong et al. 2010]. The seasonal pattern among children with ITP likely reflects the seasonality of viral infections such as influenza, which is responsible for the majority of cases of ITP in children [Yong et al. 2010]. Unlike in children, ITP in adults has an insidious onset and a chronic course with no preceding viral illness or other infection [Liu et al. 2013]. The large sample size and inclusion of different regions of the USA are the main strengths of our study. However, our study has several limitations. It was a retrospective study based on discharge-level patient data with limited clinical information. NIS is a deidentified administrative database and is prone to errors in coding of diagnoses that cannot be individually verified.

To the editor: In recent years, there has been growing evidence that hospital volume affects survival among patients undergoing a variety of surgical procedures and medical treatments.[1][1],[2][2] Whether case volume affects outcomes after chemotherapy among patients with acute myeloid leukemia (

Background Two different needle gauges (21 and 22 G) are currently used for endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). Few studies have compared the diagnostic utility of EBUS-TB107NA using 21 versus 22 G needles. We aimed to systematically analyze all existing literature comparing the diagnostic benefit of these 2 needles. Methods A systematic search for the identification of all relevant studies comparing 21 and 22 G needles in EBUS-TBNA was performed using the MEDLINE, EMBASE, SCOPUS databases up to September 21, 2014. All the extracted data underwent meta-analysis using Review Manager 5.3 and Comprehensive Meta-analysis 3.3. Study-specific odds ratios (OR) were calculated and combined using random-effects model. Between study heterogeneity was assessed using the I statistic. Results A total of 5 studies involving 1720 patients were identified. The sample adequacy rate was 89.1% in the 21 G group and 90.0% in the 22 G group and this difference was not statistically significant [OR, 0.94; 95% confidence interval (CI), 0.56-1.59; P=0.82]. Similarly, there was no significant difference in the diagnostic yield (73.7% vs. 58.5%; OR, 1.04; 95% CI, 0.80-1.35; P=0.80) or the mean number of needle passes (mean difference -0.31; 95% CI, -1.1 to 0.47; P=0.44). There were no major complications reported in any of these studies. Conclusions There were no differences in the diagnostic yield, sample adequacy, or the mean number of needle passes between the 21 and 22 G groups during EBUS-TBNA. Similarly, the complication rates were low and similar between the 2 groups.

Background : Apixaban, a novel oral anticoagulant, is also used for deep vein thrombosis (DVT) prophylaxis. In this study, we sought to critically evaluate the differences in the rates of symptomatic DVT and bleeding, and analyze the rates of pulmonary embolism (PE) in subgroups of patients from ADVANCE I and II trials given their similar indication and design. Methods : Studies were identified through electronic literature searches of MEDLINE, clinicaltrial.gov, SCOPUS, and EMBASE up to January 2014. Phase III RCTs involving use of apixaban and enoxaparin for thromboprophylaxis in patients undergoing total knee or hip replacement were included. Study-specific odds ratios were calculated and between-study heterogeneity was assessed using the I 2 statistics. Results : In three studies involving 11,659 patients, the risk of symptomatic DVT (pooled OR 0.38, 95% CI 0.16–0.90, I 2 =0%, p =0.03) and bleeding (pooled OR 0.87, 95% CI 0.77–0.99, I 2 =0%, p =0.03) was less in apixaban group compared to the enoxaparin group. However, it was interesting to note that on subgroup analysis, the risk of PE was higher with apixaban when used for thromboprophylaxis in knee replacement surgery (pooled OR 2.58, 95% CI 1.10–6.04, I 2 =0%, p =0.03). Conclusion : Apixaban was found to be associated with lower risk of symptomatic DVT and bleeding compared to enoxaparin when used for thromboprophylaxis in patients undergoing knee and hip replacement surgeries. However, it was associated with higher risk of PE in patients undergoing knee replacement. Keywords: apixaban; arthroplasty; knee replacement; hip replacement; meta-analysis (Published: 1 September 2015) To access the supplementary material for this article, please see Supplementary files in the column to the right (under ‘Article Tools’) Citation: Journal of Community Hospital Internal Medicine Perspectives 2015, 5 : 27889 - http://dx.doi.org/10.3402/jchimp.v5.27889

Thrombotic thrombocytopenic purpura (TTP) is uncommon in the postoperative setting, even more so after vascular surgery. We present a case of thrombocytopenia after aortofemoral bypass, which highlights the importance of a high index of suspicion for postoperative TTP to avoid life-threatening consequences.Keywords: postoperative thrombotic thrombocytopenic purpura; aortofemoral bypass; plasmapheresis(Published: 7 January 2013)Citation: Journal of Community Hospital Internal Medicine Perspectives 2012, 2: 19797 - http://dx.doi.org/10.3402/jchimp.v2i4.19797

We present the case of a 36-year-old woman who presented to our hospital with epigastric abdominal pain and tenderness. Laboratory evaluation identified high lipase, normal amylase, pseudohyponatremia, and relatively falsely low triglyceride levels (initial value of 2,329 mg/dl which on repeat was found to have corrected value of >10,000 mg/dl). The overall clinical picture was consistent with acute pancreatitis due to hypertriglyceridemia. The patient was commenced on IV insulin and eventually required plasmapheresis with good clinical outcome. This case highlights the importance of being cognizant of falsely low amylase and TG levels that can be present in patients with hypertriglycereidemic pancreatitisKeywords: hypertriglyceride; pancreatitis; epigastric pain(Published: 6 July 2016)Citation: Journal of Community Hospital Internal Medicine Perspectives 2016, 6: 31808 - http://dx.doi.org/10.3402/jchimp.v6.31808

Uterine fibroid, one of the most common tumors in women, is estrogen dependent, which commonly regresses after menopause. Fibroid degeneration after menopause, therefore, is rare. Here the authors report a case of 56-year-old postmenopausal woman who presented with acute abdominal pain, low grade fever, and leukocytosis as a result of fibroid degeneration. Keywords: post-menopause; uterine fibroid; degeneration; acute abdomen (Published: 3 February 2015) Citation: Journal of Community Hospital Internal Medicine Perspectives 2015, 5 : 25917 - http://dx.doi.org/10.3402/jchimp.v5.25917

Fulminant hepatic failure (FHF) is a relatively rare manifestation of Hodgkin’s lymphoma. Clinical features, laboratory findings, and imaging of the liver are usually inconclusive, and liver biopsy may be required for confirmation. We present a case of an FHF in a woman 1 week after the diagnosis of Hodgkin’s lymphoma. Chemotherapy could not be instituted due to hepatic encephalopathy and other complications. Autopsy revealed diffuse infiltration of the liver parenchyma. This case illustrates the importance of early diagnosis and institution of chemotherapy, which may reverse the liver failure.Keywords: failure; acute liver; fulminating hepatic failure; Hodgkin’s disease; Hodgkin’s lymphoma(Published: 25 November 2014)Citation: Journal of Community Hospital Internal Medicine Perspectives 2014, 4: 25821 - http://dx.doi.org/10.3402/jchimp.v4.25821

Introduction Studies describing seasonal variations in acute gouty arthritis note seasonal variation, but disagree on timing, withmost showing a peakin springmonthswhile others show peaks later in the year. Various theories on the effect of weather and immune system changes on the chronobiology of monosodium urate crystals’ equilibrium and precipitation have been proposed. We aimed to shed light on this question by examining the seasonal variation in the incidence of acute gouty arthritis in the USA using a large inpatient database. Methods We used the Nationwide Inpatient Sample (NIS) database to identify patients aged ≥18 years with primarydiagnosis of acute gouty arthritis (International Classification of Diseases, 9th Revision, Clinical Modificationcode 274.01) from 2009–2011 during hospitalization. We used the Edwards recognition and estimation ofcyclic trend method to study the seasonal variation of the incidence of acute gout and z-test to compare theseasonal incidences. Results A total of 28,172 hospitalizations with primary diagnosis of acute gouty arthritis were reported in the USA from 2009–2011. The peak incidence of acute gout was seen in November (peak/low ratio 1.34, 95 % CI 1.29– 1.38, p

OBJECTIVE Conduct a systematic review and meta-analysis on the effectiveness and safety of varenicline in smokeless tobacco (SLT) cessation. METHODS PubMed, EMBASE, clinicaltrials.gov, and the Cochrane Registry were searched up to February 1, 2014, for randomized clinical trials (RCTs) comparing varenicline to placebo. Random effects Mantel-Haenszel summary relative risks (RRs), risk difference (RD), and 95% CIs were used for analysis and reporting of outcomes. Primary and secondary outcomes were the 7-day point prevalence of SLT abstinence at the end of 12 and 26 weeks, respectively. Adverse events reported include nausea, sleep disturbance, and mood disorders. RESULTS Three published RCTs involving 744 SLT users with a mean age of 39.7 years, of which greater than 88% were males, were randomized to varenicline (n = 370) and placebo (n = 374). Subjects in the varenicline arm had a significantly higher 7-day point prevalence of SLT abstinence at 12 weeks (48% vs. 33%; RR = 1.45, 95% CI = 1.22-1.72, p < .0001, I2 = 0%; RD = 13%, 95% CI = 4%-23%, p = .008) but not at 26 weeks (49% vs. 39%; RR = 1.38, 95% CI = 0.93-2.03, p = .11, I2 = 51%). There were no statistically significant differences in the incidences of adverse events between the 2 arms but interpretation is limited by high heterogeneity. CONCLUSION This pooled analysis suggests that varenicline is effective in achieving a 7-day point prevalence of SLT abstinence at 12 weeks but showed that this effect was not sustained at 26 weeks.

Background : Acute mountain sickness (AMS) can occur in anyone going to a high altitude. Non-steroidal anti-inflammatory drugs (NSAIDs) have been studied for the prevention of AMS with mixed results. In this systematic review, we analyze all existing data on the use of NSAIDs to prevent AMS using the Lake Louise Scoring System (LLSS) in different randomized clinical trials (RCTs). Methods : Electronic literature searches for relevant studies were identified through MEDLINE, EMBASE, SCOPUS, and Cochrane library up to June 2013. RCTs involving NSAIDs compared to placebo in patients undergoing ascent to a height of at least 3,800 m were included. Odds ratios (OR) were calculated and combined using fixed-effect model meta-analysis if I 2 =0%. Differences between groups were calculated using the inverse variance of the standard mean differences. Between-study heterogeneity was assessed using the I 2 statistics. Results : In three clinical trials involving 349 patients, AMS using LLSS occurred in 26.92% of patients on NSAIDs and 43.71% on placebo (OR 0.43; CI [confidence interval] 0.27–0.69, I 2 =0%, p= 0.0005), NNT=6. Minor outcome of end point Spo2 was not significant in the two groups (IV=0.74; 95% CI −0.20–1.69, I 2 =81%, p= 0.12). Similarly, a change in Spo2 from baseline was also not significant in the two groups (IV=0.05; 95% CI −0.28–0.37, I 2 =44%, p= 0.78). Conclusion : NSAIDs might be a safe and effective alternative for the prevention of AMS. However, further larger population studies and studies comparing NSAIDs to acetazolamide and dexamethasone in the future may provide further data to its relative efficacy. Keywords: altitude sickness; acute mountain sickness; anti-inflammatory agents; non-steroidal; ibuprofen; headache To access the supplementary material for this article, please see Supplementary files in the column to the right (under Article Tools) (Published: 29 September 2014) Citation: Journal of Community Hospital Internal Medicine Perspectives 2014, 4 : 24927 - http://dx.doi.org/10.3402/jchimp.v4.24927

Esophageal cancer is the sixth leading cause of cancer deaths worldwide [1]. In the USA, an estimated 18,170 new cases of esophageal cancer will be detected in the year 2014 [2]. Although prior studies have shown a decline in the incidence of esophageal squamous cell carcinoma (SCC) in the USA and worldwide [3–5], it is unknown if this continues to be true in recent years. We utilized Surveillance, Epidemiology, and End Results (SEER) 18 database to determine the trend in the incidence of esophageal SCC in the USA between 2000 and 2011. SEER is a program of the National Cancer Institute that provides cancer incidence and survival data from population-based cancer registries covering 28 % of the US population. Eligible patients were identified using SEER histology codes 8050-8089. Age-adjusted rates were plotted by time period using a logarithmic scale for the ordinate. Genderand race-specific trends were also calculated. Data analysis was done using SEER*Stat 8.1.5, and trend analysis was done using Jointpoint regression program 4.1. A total of 344,408 cases of esophageal squamous cell carcinoma were identified during the study period. The study population included 57.9 % males, 82.1 % whites, and 12.1 % African-Americans (AA). The age-adjusted incidence rate steadily decreased from 40.2/100,000 in 2000 to 34.0/100,000 in 2011 (annual percentage change [APC] -1.1, p \ 0.05). The decline in incidence was observed in both sexes and all races (Fig. 1); however, the decline was most prominent in AA males (APC -3.2, p \ 0.05) (Fig. 1a). Our study demonstrates a continual decline in the incidence of esophageal SCC between 2000 and 2011. Prior studies by Trivers et al. [5] and Cook et al. [6] have shown a steady reduction in the incidence of esophageal SCC in the USA prior to 2005. This reduction has been attributed largely to a decreased prevalence of smoking [7]. Although the decline in our study was observed in both genders and all races, it was most prominent in AA males. African-Americans, compared to whites, have higher mortality rate from esophageal cancer; hence, a decrease in the incidence of esophageal SCC in AA is encouraging [2]. This is likely the result of a rapid decline in smoking rates in this population, which highlights the importance of efforts toward risk reduction. It is estimated that between the mid-1970s to early 1990s, the drop in smoking rates among AA youths was twice as much as that among whites [8, 9]. This decline has continued in the recent years as well [10]. SEER is a de-identified database; hence, the accuracy of coding cannot be verified. We were not able to compare the prevalence of risk factors for esophageal SCC among different subgroups that may have accounted for the observed racial differences.

Primary cardiac sarcomas are rare malignant tumors of the heart. Clinical features depend on the site of tumor and vary from symptoms of congestive heart failure to thromboembolism and arrhythmias. Echocardiography is helpful but definitive diagnosis is established by histopathology. Surgical resection is the mainstay of treatment, and the role of chemotherapy and radiotherapy is unclear. We report a case of primary cardiac sarcoma which presented with signs and symptoms of acute left-sided heart failure. Keywords : heart neoplasms; primary cardiac sarcoma; heart failure; left-sided heart failure (Published: 31 July 2014) Citation : Journal of Community Hospital Internal Medicine Perspectives 2014, 4 : 23057 - http://dx.doi.org/10.3402/jchimp.v4.23057