Comparative efficacy of chemoimmunotherapy versus immunotherapy for advanced non-small cell lung cancer: A network meta-analysis of randomized trials.

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] <1%), NMA comparing chemoimmunotherapy with dual-agent ICI failed to demonstrate a statistically significant difference with regard to OS, PFS, or the ORR. In patients with low PD-L1 (TPS 1%-49%), there was no statistically significant difference observed between chemoimmunotherapy compared with either single-agent ICI or dual-agent ICI with regard to OS or the ORR. In patients with high PD-L1 (TPS ≥50%), chemoimmunotherapy was found to be associated with an improved PFS and ORR compared with single-agent ICI, but not with dual-agent ICI. No differences in OS were observed with chemoimmunotherapy when compared with either single-agent or dual-agent ICIs. CONCLUSIONS: Although chemoimmunotherapy appears to improve the ORR and PFS in patients with PD-L1-high tumors when compared with single-agent ICI, it does not appear to confer an OS benefit over single-agent or dual-agent ICI for patients with advanced NSCLC regardless of PD-L1 status. Prospective trials are needed to validate these findings.

Efficacy and safety of frontline regimens for older transplant-ineligible patients with multiple myeloma: A systematic review and meta-analysis.

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.

Venous Thromboembolism in COVID-19: Towards an Ideal Approach to Thromboprophylaxis, Screening, and Treatment.

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. 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.

Systematic review and meta-analysis of the efficacy and safety of apixaban compared to rivaroxaban in acute VTE in the real world.

Both apixaban and rivaroxaban have been approved for use in acute venous thromboembolism (VTE). Although indirect comparison through network meta-analyses of randomized trials have been performed to compare the efficacy and safety of these agents, further comparison between these agents was lacking until recently. We sought to systematically review and carry out a meta-analysis of studies to further compare apixaban with rivaroxaban from multiple studies done in the real-world settings. Studies comparing rivaroxaban with apixaban in patients with acute VTE were identified through electronic literature searches of MEDLINE, EMBASE, Scopus, and the Cochrane library up to May 2019. Study-specific risk ratios (RRs) were calculated and combined using a random-effects model meta-analysis. In an analysis involving 24 041 patients, recurrent VTE within 6 months occurred in 56 of 4897 patients (1.14%) in the apixaban group and 258 of 19 144 patients (1.35%) in the rivaroxaban group (RR, 0.89; 95% confidence interval [CI], 0.67-1.19; P = .45). Clinically relevant major bleeding occurred in 85 of 11 559 patients (0.74%) in the apixaban group and 350 of 33 909 patients (1.03%) in the rivaroxaban group (RR, 0.73; 95% CI, 0.58-0.93; P = .01). Clinically relevant nonmajor bleeding occurred in 169 of 3417 patients (4.95%) in the apixaban group and 1094 of 12 475 patients (8.77%) in the rivaroxaban group (RR, 0.59; 95% CI, 0.50-0.70; P < .01). Apixaban shows equivalent efficacy in prevention of recurrent VTE but decreased risk of major and minor bleeding events compared with rivaroxaban.

Medical and Economic Burden of Heparin-Induced Thrombocytopenia: A Retrospective Nationwide Inpatient Sample (NIS) Study.

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.

Hypertriglyceridemic pancreatitis associated with confounding laboratory abnormalities.

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 pancreatitis.

Seasonal variation in acute gouty arthritis: data from Nationwide Inpatient Sample.

INTRODUCTION: Studies describing seasonal variations in acute gouty arthritis note seasonal variation, but disagree on timing, with most showing a peak in spring months while 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 primary diagnosis of acute gouty arthritis (International Classification of Diseases, 9th Revision, Clinical Modification code 274.01) from 2009-2011 during hospitalization. We used the Edwards recognition and estimation of cyclic trend method to study the seasonal variation of the incidence of acute gout and z-test to compare the seasonal 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 < 0.05). The highest number of hospitalizations was observed in autumn months while the lowest incidence was observed in spring (28.12 vs. 23.13 %, p < 0.001). CONCLUSION: The peak incidence of acute gout seems to be in the fall with its peak in the month of November. This seasonality may shed light into the pathophysiology of acute attacks and better management of patients with gout who are at risk of acute attacks.

Use of Varenicline in Smokeless Tobacco Cessation: A Systematic Review and Meta-Analysis.

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.

Upper Airway Hematoma Secondary to Warfarin Therapy: A Systematic Review of Reported Cases.

Upper airway hematoma (UAH) is a rare but life-threatening complication of oral anticoagulants requiring early recognition. However, no consensus exists regarding the best approach to treatment. We therefore, sought to systematically review the published literature on UAH to elaborate its demographic and clinical characteristics, treatment, complications, and outcomes. A systematic electronic search of PubMed and EMBASE for case reports, case series, and related articles of UAH related to warfarin published from inception (November 1950) to March 2015 was carried out. Categorical variables were expressed as percentage and continuous variables as mean ± standard deviation (SD). Statistical analysis was done using Statistical Package for the Social Sciences (SPSS) version 20.0. All cases were reported to have UAH as a complication of anticoagulation therapy with warfarin. Demographic and clinical characteristics, treatment, complications and outcomes of UAH were studied. Thirty-eight cases of UAH were identified from 34 reports in the literature. No gender preponderance (male = 52.78%) was seen and the average age of presentation was 60.11 ± 12.50 years. Dysphagia, sore throat, and neck swelling were the most common symptoms and the mean international normalized ratio (INR)at presentation was 8.07 ± 4.04. Most cases had sublingual hematoma (66.57%) followed by retropharyngeal hematoma (27.03%). Of the cases, 48.65% were managed conservatively while the rest underwent either cricothyrotomy or intubation with the time to resolution being 7.69 ± 5.44 days. UAH is a rare butpotentially serious complication of warfarin therapy. It is more common in the elderly population with supratherapeutic INR; inciting events were present in many cases. Overall, it has a good prognosis with significant morbidity present only if concomitant respiratory compromise is present. Reversal of anticoagulation with low threshold for artificial airway placement in the event of airway compromise leads to a favorable outcome in most cases.

Sarcoidosis and Antiphospholipid Syndrome: A Systematic Review of Cases.

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.

Thromboprophylaxis with apixaban and the risk of pulmonary embolism in patients undergoing knee replacement surgery.

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.

Meta-analysis on efficacy and safety of new oral anticoagulants for venous thromboembolism prophylaxis in overweight and obese postarthroplasty patients.

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.

YouTube as a Source of Information on Ebola Virus Disease.

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.

Meta-analysis on efficacy and safety of new oral anticoagulants for venous thromboembolism prophylaxis in elderly elective postarthroplasty patients.

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.

Rituximab-induced serum sickness: A systematic review.

OBJECTIVES: To report a case of rituximab-induced serum sickness (RISS) and perform a systematic review and characterize RISS in autoimmune diseases and hematological malignancies. METHODS: A comprehensive search of MEDLINE, EMBASE, ACR, and EULAR databases was performed for relevant articles of patients with RISS from inception to September 2014. Statistical analysis of demographic and clinical features was performed using Microsoft EXCEL 2007 and SPSS version 20.0. RESULTS: In the 33 patients with RISS, the mean age of presentation was 39.1 ± 17.5yr with a female preponderance (n = 23, 76.67%). The majority of cases were associated with an underlying rheumatologic condition (n = 17, 51.5%), most commonly Sjögren's syndrome (n = 8, 44.4%). The classic triad of serum sickness (fever, rash, and arthralgia) was reported in 16 (48.5%) cases. Time from drug exposure to symptom onset was significantly greater with the first doses of rituximab compared to the second dose (mean time 10.00 vs. 4.05d, P = 0.002), and time to resolution was significantly greater for rheumatologic vs. hematological indications (mean time 2.50 vs. 1.00d, P = 0.035). Corticosteroids were the most commonly used treatment (n = 21), with all cases reporting a complete resolution of symptoms in 2.15 ± 1.34d. CONCLUSION: It is important to recognize RISS clinically, as it may mimic exacerbation of various rheumatologic conditions. Although RISS is typically self-limited, further infusions of rituximab should be avoided, as it may provoke more severe symptoms.

Fibroid degeneration in a postmenopausal woman presenting as an acute abdomen.

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.

Mortality, length of stay, and health care costs of febrile neutropenia-related hospitalizations among patients with breast cancer in the United States.

PURPOSE: 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. METHODS: 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. RESULTS: 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, p < 0.01). 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). CONCLUSION: 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.