Conventional Arms Research Articles

Impact of Conservative Versus Conventional Oxygenation on Outcomes of Patients in Intensive Care Units: A Systematic Review and Meta-analysis.

Background: There is mixed evidence in the superiority of conservative versus conventional approach to oxygen therapy among patients admitted into the intensive care unit (ICU). The purpose of this study was to determine if conservative versus conventional oxygenation results in a statistically significant difference in outcomes in ICU patients.Methods: A systematic review was registered with the International Prospective Register of Systematic Reviews (PROSPERO) and performed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Inclusion criteria consisted of Level I-IV investigations of conservative versus conventional oxygenation among ICU patients. ICU mortality, 28-day mortality, in-hospital mortality, ICU length-of-stay, hospital length-of-stay, rate of new infections, and rate of new non-respiratory organ failure were compared using two-sample Z-tests using p-value less than 0.05.Results: Three thousand four hundred thirty-three articles were screened. Four articles were included in the analysis. Three hundred seventy-two patients under the conservative oxygenation arm (Minimum target SpO2: 88-94%) and 370 patients under the conventional oxygenation arm (Minimum target SpO2: 96-97%) were analyzed. ICU mortality (16.7 ± 9.5% vs. 22.7 ± 6.0%; P<0.01), 28-day mortality (34.6 ± 26.4% vs. 41.6 ± 14.6%; P=0.02), and in-hospital mortality (30.2 ± 22.5% vs. 37.7 ± 14.2%; P<0.01) were all significantly lower in the conservative oxygenation arm versus the conventional oxygenation arm, respectively. Rate of new non-respiratory organ failure was also significantly lower in the conservative oxygenation arm (20.0 ± 8.5% vs. 29.7 ± 11.7%; P<0.01).Conclusion: The authors conclude that conservative oxygenation therapy could result in significantly lower rates of ICU mortality, 28-day mortality, in-hospital mortality, and new-onset non-respiratory organ failure. Further randomized controlled studies that show clinical outcome improvement in multiple parameters may be worthwhile to assess the true efficacy of this practice.

Rectal Wall vs. Whole Rectum Dose: Which Volume Better Predicts Gastrointestinal Toxicity from Prostate External Beam Radiotherapy?

Radiation-induced gastrointestinal (GI) toxicity is an important complication of prostate cancer (PCa) radiotherapy (RT) that radiation oncologists seek to minimize by respecting dose constraints for the rectum. It remains unclear whether dose to the rectal wall or whole rectum better predicts GI toxicity. This study used prospectively collected toxicity data from a registered phase III randomized trial to address this question. Dose-volume histogram (DVH) data was extracted from patients enrolled in PCS V, a multi-institutional phase III trial that compared conventionally fractionated (76 Gy in 38 fractions) to hypofractionated RT (68 Gy in 25 fractions) in PCa patients. Acute and late GI toxicity was assessed at 0-6 months and 6-24 months, respectively, using the Common Terminology Criteria for Adverse Events (CTCAE v.4). Rectal wall and whole volumes were collected prospectively. Dosimetric values evaluated were the whole rectum and rectal wall V50, V60, V60, V65, V70, V75, Dmax, and Dmean. Spearman’s rho (ρ) was used to correlate each DVH point of both rectum contours to acute and late GI toxicity. A Fisher’s z-transformation was then performed to test the significance of the difference between the rectal wall and whole rectum ρ’s for individual DVH points. Wilcoxon signed rank test was used to determine whether paired differences of the GI toxicity grade associated with rectal wall vs. whole rectum were significant. In total, DVH data was obtained from 155 patients, with 83 patients having been treated conventionally and 72 with hypofractionation. Spearman’s ρ correlation test revealed a strong association between the whole rectum DVH points and acute GI toxicity, namely for V60 (p=0.04), V65 (p=0.01), V70 (p=0.01) and Dmax (p=0.04). When the same analysis was conducted for late toxicity, only the V50 and Dmean points yielded a marginally significant correlation (p=0.049 and 0.042, respectively). These findings were not observed in the hypofractionated arm. There was no significant association between the rectal wall’s DVH points with either acute nor late GI toxicity in both arms. While the Fisher’s z-transformation analysis did not reveal any significant differences between the correlations of individual DVH points obtained from the rectal wall and whole rectum with acute or late GI toxicity, the distribution of Spearman’s ρ was significantly higher for the whole rectum, compared to its wall for acute toxicity (p=0.047) in the conventional arm. Our data suggests that the whole rectum DVH profile better correlates with acute GI toxicity than that of the rectal wall. Furthermore, the whole rectum’s DVH distribution rather than individual DVH points correlated more reliably with acute GI toxicity. Set-up protocols aiming to minimize rectal wall inter- and intra-fractional movement to improve the accuracy of rectal wall dosimetric values to predict toxicity are thus worthy of future study.

The first complete mitochondrial genome of the Indian Tent Turtle, Pangshura tentoria (Testudines: Geoemydidae): Characterization and comparative analysis.

The characterization of a complete mitogenome is widely used in genomics studies for systematics and evolutionary research. However, the sequences and structural motifs contained within the mitogenome of Testudines taxa have rarely been examined. The present study decodes the first complete mitochondrial genome of the Indian Tent Turtle, Pangshura tentoria (16,657 bp) by using next‐generation sequencing. This denovo assembly encodes 37 genes: 13 protein‐coding genes (PCGs), 22 transfer RNA (tRNAs), two ribosomal RNA, and one control region (CR). Most of the genes were encoded on majority strand, except for one PCG (NADH dehydrogenase subunit 6) and eight tRNAs. Most of the PCGs were started with an ATG initiation codon, except for Cytochrome oxidase subunit 1 with “GTG” and NADH dehydrogenase subunit 5 with “ATA.” The termination codons, “TAA” and “AGA” were observed in two subunits of NADH dehydrogenase gene. The relative synonymous codon usage analysis revealed the maximum abundance of alanine, isoleucine, leucine, and threonine. The nonsynonymous/synonymous ratios were <1 in all PCGs, which indicates strong negative selection among all Geoemydid species. The study also found the typical cloverleaf secondary structure in most of the tRNA genes, except for serine with the lack of the conventional DHU arm. The comparative study of Geoemydid mitogenomes revealed the occurrence of tandem repeats was frequent in the 3′ end of CR. Further, two copies of a unique tandem repeat “TTCTCTTT” were identified in P. tentoria. The Bayesian and maximum‐likelihood phylogenetic trees using concatenation of 13 PCGs revealed the close relationships of P. tentoria with Batagur trivittata in the studied dataset. All the Geoemydid species showed distinct clustering with high bootstrap support congruent with previous evolutionary hypotheses. We suggest that the generations of more mitogenomes of Geoemydid species are required, to improve our understanding of their in‐depth phylogenetic and evolutionary relationships.

Comparing the effect of STan (cardiotocographic electronic fetal monitoring (CTG) plus analysis of the ST segment of the fetal electrocardiogram) with CTG alone on emergency caesarean section rates: study protocol for the STan Australian Randomised controlled Trial (START)

BackgroundCardiotocography is almost ubiquitous in its use in intrapartum care. Although it has been demonstrated that there is some benefit from continuous intrapartum fetal monitoring using cardiotocography, there is also an increased risk of caesarean section which is accompanied by short-term and long-term risks to the mother and child. There is considerable potential to reduce unnecessary operative delivery with up to a 60% false positive diagnosis of fetal distress using cardiotocography alone. ST analysis of the fetal electrocardiogram is a promising adjunct to cardiotocography alone, and permits detection of metabolic acidosis of the fetus, potentially reducing false positive diagnosis of fetal distress.MethodsThis study will be a single-centre, parallel-group, randomised controlled trial, conducted over 3 years. The primary hypothesis will be that the proportion of women with an emergency caesarean section on ST analysis will not equal that for women on cardiotocography monitoring alone. Participants will be recruited at the Women’s and Children’s Hospital, a high-risk specialty facility with approximately 5000 deliveries per annum. A total of 1818 women will be randomised to the treatment or conventional arm with an allocation ratio of 1:1, stratified by parity. The primary outcome is emergency caesarean section (yes/no). Statistical analysis will follow standard methods for randomised trials and will be performed on an intention-to-treat basis. Secondary maternal and neonatal outcomes will also be analysed. Additional study outcomes include psychosocial outcomes, patient preferences and cost-effectiveness.DiscussionApproximately 20% of Australian babies are delivered by emergency caesarean section. This will be the first Australian trial to examine ST analysis of the fetal electrocardiogram as an adjunct to cardiotocography as a potential method for reducing this proportion. The trial will be among the first to comprehensively examine ST analysis, taking into account the impact on psychosocial well-being as well as cost-effectiveness. This research will provide Australian evidence for clinical practice and guideline development as well as for policy-makers and consumers to make informed, evidence-based choices about care in labour.Trial registrationANZCTR, ACTRN1261800006268. Registered on 19 January 2018.

Western Gunrunners, (Middle-)Eastern Casualties: Unlawfully Trading Arms with States Engulfed in Yemeni Civil War?

Abstract According to the United Nations Secretary-General, Yemen today constitutes the worst man-made humanitarian crisis in the world. It is fuelled by extensive third-state involvement, with none of the warring parties championing respect for international human rights and humanitarian law (to put it mildly). Conversely, primary rules of international law already prohibit arms transfers from the moment there is a significant risk that they could be used to commit or facilitate grave breaches, with the recipient’s past and present record of respect for international law qualifying as the crucial factor to predict future transgressions. From that perspective, it appears deeply disingenuous for western states to continue transferring military equipment to members of the multilateral coalition in Yemen while maintaining adherence to the international legal framework. This article thus aims to examine whether the legal framework lives up to its noble goals or rather serves to defend state decisions that primarily serve their economic interests. It is structured as follows: Section 1 starts with an overview of the facts, and the focus and aim of this article. Section 2 then sets out the international legal framework as it applies to the trade in conventional arms with states that are involved in a non-international armed conflict. Section 3 analyses key domestic judgments (in the UK, Canada, Belgium and France) to test the available facts against the legal framework as elaborated. Finally, Section 4 concludes.

Conventional and Chemically Programmed Asymmetric Bispecific Antibodies Targeting Folate Receptor 1.

T-cell engaging bispecific antibodies (biAbs) can mediate potent and specific tumor cell eradication in liquid cancers. Substantial effort has been invested in expanding this concept to solid cancers. To explore their utility in the treatment of ovarian cancer, we built a set of asymmetric biAbs in IgG1-like format that bind CD3 on T cells with a conventional scFv arm and folate receptor 1 (FOLR1) on ovarian cancer cells with a conventional or a chemically programmed Fab arm. For avidity engineering, we also built an asymmetric biAb format with a tandem Fab arm. We show that both conventional and chemically programmed CD3 × FOLR1 biAbs exert specific in vitro and in vivo cytotoxicity toward FOLR1-expressing ovarian cancer cells by recruiting and activating T cells. While the conventional T-cell engaging biAb was curative in an aggressive mouse model of human ovarian cancer, the potency of the chemically programmed biAb was significantly boosted by avidity engineering. Both conventional and chemically programmed CD3 × FOLR1 biAbs warrant further investigation for ovarian cancer immunotherapy.

Long-term neurocognitive and other side effects of radiotherapy, with or without chemotherapy, for glioma.

Long-term neurocognitive and other side effects of radiotherapy, with or without chemotherapy, for glioma.

Comparative evaluation of minimally invasive ‘tibial tuberoplasty’ surgical technique versus conventional open surgery for Schatzker II–III tibial plateau fractures: design of a multicentre, randomised, controlled and blinded trial (TUBERIMPACT study)

IntroductionFractures of the tibial plateau are in constant progression. They affect an elderly population suffering from a number of comorbidities, but also a young population increasingly practicing high-risk sports. The...

Toxicity Profile of Double-agent Adjuvant Chemotherapy after Concurrent Chemoradiation and Brachytherapy in Locally Advanced Cervical Cancer: Comparison with Standard Chemoradiation Protocol

Abstract Introduction: Carcinoma cervix is the most common gynecological malignancy in India and a major cause of cancer mortality and morbidity in the females despite Concurrent chemoradiotherapy (CCRT). Attempts are on to improved overall survival by addition of adjuvant chemotherapy (ACT) to CCRT. Aim: The aim of this study is to establish toxicity profile of double-agent ACT after CCRT and ICRT in locally advanced cervical cancer (LACC) and to compare it with standard chemoradiation protocol. Materials and Methods: Patients were randomized into two arms: in conventional arm (Arm 1, n = 23), patients received a standard protocol of weekly injection cisplatin 40 mg/m2 concurrently with pelvic external beam radiotherapy (5040cGy/28 fractions) followed by ICRT (03 fractions of 7 Gy each). In interventional arm (Arm 2, n = 24), patients received CCRT/ICRT protocol; and were further offered ACT with three cycles of consolidation chemotherapy using injection paclitaxel and injection carboplatin every 3 weeks after CCRT and ICRT. Results: The incidence of anemia was 14/23 (50% Grade 1) in Arm 1 and 12/24 in Arm 2 (17% Grade 1, rest higher grade). In Arm 2, 37% of patients had ≥Grade 2 neuropathy and 16% of patients had Grade 1 alopecia, whereas nil incidence was reported in Arm 1 (P = 0.005 and 0.04, respectively). Grade 3 neutropenia was observed in 4/23 (17%) patients of Arm 1 and 8/24 patients (33%) of Arm 2. None of the patients in Arm 1 required indoor supportive care while 4/24 patients (17%) were managed as an indoor patient. Among late toxicities, in Arm 2, the incidence of Grade 2 and Grade 3 anemia was 42%, whereas in Arm 1, its incidence was 22%. In Arm 1, no patient exhibited features of neuropathy, whereas, in Arm 2, 12/24 (50%) of the patients had neuropathy (P value for these two late events was &lt;0.05 statistically significant). No therapy-induced mortality was noted. Conclusion: Exhibition of ACT with injection Paclitaxel and injection carboplatin in locally advanced carcinoma cervix is a technically viable option with manageable toxicity.

Art of the arms deal: Reagan, AWACS, and the rhetorical presidency

ABSTRACTDuring his first year in office President Reagan sought to authorize the sale of the Airborne Warning and Control System (AWACS), an advanced weapons system, to Saudi Arabia over strong congressional opposition. The Reagan administration employed a range of strategies to ensure congressional approval of the deal, including tactics of deferring and promoting and rhetorically leveraging the presidential office. By overtly breaking from Jimmy Carter’s rhetoric of arms control, Reagan’s rhetoric reconstituted the bounds of accepted political action regarding conventional arms transfers, in the process setting new precedents in presidential rhetoric, US–Saudi relations, and the discourse of arms control.

Randomized Prospective Study Comparing Conventional Versus Hypofractionated Adjuvant Radiotherapy in Node-Positive Breast Cancer

Background: Hypofractionated radiotherapy in early breast cancer yields equivalent or better outcome in terms of efficacy, toxicity, cosmesis and cost-effectiveness. However, its role in node-positive breast cancer is less clear. Aim: To compare between adjuvant conventional and hypofractionated radiotherapy in node-positive breast cancer. Methods: Prospective pilot study of 66 node-positive breast cancer patients recruited over 1 year in a single institution. Patients were randomized to receive adjuvant conventional radiotherapy 200 cGy x 25 fractions with 200 cGy x 5 fractions boost to the tumor bed in case of breast conservation (control arm) or hypofractionated radiotherapy 266 cGy x 16 fractions with 266 cGy x 4 fractions boost to the tumor bed in case of breast conservation (intervention arm). The end points were disease-free survival, cosmetic outcome, ipsilateral arm lymphedema and acute skin reactions. Results: Disease-free survival did not differ significantly between the two treatment arms (p = 0.6) and the 2-year disease-free survival rate was 87% and 89% in the hypofractionated and conventional arms. The rate of excellent/good cosmetic score was higher in the hypofractionated arm than the conventional as rated by patients (71% vs. 46%, p = 0.182) and physicians (29% vs. 8%, p = 0.32). Hypofractionation, when compared to conventional fractionation, was associated with less arm lymphedema (22% vs. 40%, p = 0.149), dry desquamation (28% vs. 53%, p = 0.04), skin darkness (0% vs. 15%, p = 0.054) and wet desquamation (16% vs. 21%, p = 0.601). Conclusion: Hypofractionated adjuvant radiotherapy in node-positive breast cancer patients is equivalent to conventional fractionation as regards disease-free survival, cosmetic outcome and arm lymphedema with less early skin reactions.

Body Mass Index and Mortality in Subjects With ARDS: Post-hoc Analysis of the OSCILLATE Trial

Studies on the association of obesity with mortality in subjects with ARDS have yielded inconsistent results. In a sub-analysis of the Oscillation for ARDS Treated Early (OSCILLATE) randomized controlled trial, 451 subjects were divided into 5 strata based on their body mass index (BMI) using the World Health Organization definitions: underweight < 18.5 kg/m2; normal weight 18.5-24.99 kg/m2; overweight 25-29.99 kg/m2; obese 30-39.99 kg/m2; severely obese > 40 kg/m2. The primary outcome was all-cause hospital mortality across BMI strata for all subjects and for the 2 study arms (high-frequency oscillatory ventilation [HFOV] vs conventional ventilation) separately using multivariable logistic regression adjusting for potential confounding variables. Hospital mortality was not different across the BMI strata for all subjects (P = .86), for the HFOV arm (P = .94) or for the conventional ventilation arm (P = .59). After risk adjustment, BMI was not associated with increased risk for hospital mortality (odds ratio 1.01, 95% CI 0.97-1.04, P = .67), whereas HFOV was independently associated with increased mortality (odds ratio 1.74, 95% CI 1.11-2.72, P = .02) with no effect modification by BMI strata (for this interaction, P = .56). Although there was no difference in the use of rescue therapies or in the number of days on sedation or analgesia, higher daily doses of fentanyl and midazolam were administered as BMI increased. There was no difference in adjusted hospital mortality across BMI strata in subjects with moderate to severe ARDS. Processes of care were not different across BMI strata except for higher daily doses of fentanyl as BMI increased. (ClinicalTrials.gov registration NCT0150640).

Torque Minimized Design of a Light Weight 3 DoF Planar Manipulator

The main objective of this paper is to design a robotic arm with all the motors located at the base so that the arm becomes lighter than the conventional arms where each motor is set on the links themselves which will lead to an extra weight of the motor to be held by previous motors. The main advantage of this development is to decrease the torque required to control the arm. The motion of motors transferred to links via aluminum pulleys, bearings, and timing belts that yield to the need of lighter motors and hence a lighter manipulator. The maximum torque of each joint has been calculated then compared with the torque required using conventional structures. The proposed arm has been built and tested. The simulation and experimental results reveal a noticeable improvement in the required maximum torque, which was reduced to less than half in some links.

북핵 협상과 남북 재래식 군비통제 평가 및 과제

북핵 협상과 남북 재래식 군비통제 평가 및 과제

Low Risk of Variceal Bleeding in Patients With Cirrhosis After Variceal Screening Stratified by Liver/Spleen Stiffness

We previously demonstrated the possible noninferiority of a screening strategy for varices guided by liver and spleen stiffness measurement (LSSM) compared to universal endoscopic screening in detecting clinically significant varices in patients with cirrhosis. We now report the long-term outcome of the patients recruited in this trial for incident variceal bleeding and other hepatic events. This was a prospective follow-up study of a noninferiority, open-label, randomized controlled trial (NCT02024347) of 548 adult patients with known chronic liver diseases, radiological evidence of liver cirrhosis, and compensated liver function. The primary outcome of this prospective study was incident variceal bleeding confirmed with upper endoscopy. Between October 2013 and June 2016, 548 patients were randomized to an LSSM arm (n = 274) and a conventional arm (n = 274). Patients in both study arms were predominantly middle-aged men (mean age 59 years, male 68.9%) with viral hepatitis-related cirrhosis (85%). Upper endoscopy examination was performed in 127 (46.4%) patients in the LSSM arm and 263 (96.0%) in the conventional arm. During the follow-up period of 41.3 ± 12.6 months, 12/274 patients in the LSSM arm (4.4%) and 11/274 in the conventional arm (4.0%) developed incident variceal bleeding (log-rank test P = 0.724). The incident rates of hepatic events were also similar in both arms (P = 0.327). Conclusions: Patients with liver cirrhosis who had undergone LSSM-guided variceal screening were at similarly low risk of incident variceal bleeding in the future; patients with cirrhosis may first have LSSM measured to save up to half of the upper endoscopy examinations.

Main Technological Competences of Organizations of the Conventional Arms Industry of the Russian Federation

Рассмотрены основные технологические компетенции предприятий ОПК РФ, производящих обычные вооружения. В исследовании были использованы обобщение, систематизация, формализация, логические методы, а также методы сравнительного анализа для изучения основных технологических компетенций предприятий ОПК РФ, производящих обычные вооружения. Производство обычных вооружений относится к числу высокотехнологичных отраслей российской экономики, обеспечивающих оборонно-промышленную безопасность страны. С переходом сферы производства обычных вооружений к инновационному развитию и достижению максимального уровня технологических компетенций возрастает необходимость выявления достигнутых технологических компетенций организаций отрасли. Рассмотрены основные технологические компетенции предприятий ОПК, производящих обычные вооружения: проектирование и инжиниринг, производство и сборка продукции, связи и управление. Описана динамика изменения технологических компетенций за период 2014-2017 гг. и проведена их оценка. Выявлены основные направления развития технологических компетенций, способствующие переходу отрасли к инновационному развитию и достижению максимального уровня технологических компетенций. Для обеспечения дальнейшего инновационного развития предприятий ОПК РФ, производящих обычные вооружения, представляется целесообразным продолжить разработку, модернизацию и производство перспективной номенклатуры высокотехнологичной гражданской продукции. Практическая значимость проведенного автором анализа достигнутых технологических компетенций и основных направлений развития технологических компетенций предприятий ОПК, производящих обычные вооружения, способствует повышению эффективности управления деятельностью организаций отрасли.

Deep Learning and Handcrafted Method Fusion: Higher Diagnostic Accuracy for Melanoma Dermoscopy Images.

This paper presents an approach that combines conventional image processing with deep learning by fusing the features from the individual techniques. We hypothesize that the two techniques, with different error profiles, are synergistic. The conventional image processing arm uses three handcrafted biologically inspired image processing modules and one clinical information module. The image processing modules detect lesion features comparable to clinical dermoscopy information-atypical pigment network, color distribution, and blood vessels. The clinical module includes information submitted to the pathologist-patient age, gender, lesion location, size, and patient history. The deep learning arm utilizes knowledge transfer via a ResNet-50 network that is repurposed to predict the probability of melanoma classification. The classification scores of each individual module from both processing arms are then ensembled utilizing logistic regression to predict an overall melanoma probability. Using cross-validated results of melanoma classification measured by area under the receiver operator characteristic curve (AUC), classification accuracy of 0.94 was obtained for the fusion technique. In comparison, the ResNet-50 deep learning based classifier alone yields an AUC of 0.87 and conventional image processing based classifier yields an AUC of 0.90. Further study of fusion of conventional image processing techniques and deep learning is warranted.

The End of Conventional Arms Control and the Role of US Congress

ABSTRACTThe renewed conflict between Russia and NATO has brought back security concerns over nuclear and conventional deterrence and defence in Europe. Since the days of the Cold War those two elements are closely intertwined, with direct ramifications on arms control policies. This article recalls the post-Cold War history of conventional arms control in Europe. It focuses on the underexplored impact of the US legislative during the mid-to-late-1990s. Relying on open sources from US Congress, the article traces the political standstill on conventional arms control to a crucial Congressional decision in the year 1997 which ultimately tied the future of this arms control regime to the solution of two protracted conflicts in the post-Soviet space. The article challenges the mainstream view that Russia is solely to blame for the dissolution of conventional arms control and concludes that without solving the standstill, nuclear arms control for Europe will as well remain deadlocked.

Comparison of the Long-Term Remission of Rituximab and Conventional Treatment for Acquired Thrombotic Thrombocytopenic Purpura: A Systematic Review and Meta-Analysis.

The current systematic review and meta-analysis aimed to summarize the results of all available studies to compare the efficacies of rituximab and conventional treatment for acquired thrombotic thrombocytopenic purpura (TTP). Three investigators independently searched studies in the MEDLINE and EMBASE databases published before December 11, 2018. To be included in the meta-analysis, studies needed to be randomized-controlled or cohort studies comparing the efficacies of rituximab and conventional therapy for TTP treatment. The effect estimates and 95% confidence intervals (CIs) from each study were collected, and Mantel-Haenszel methods were used to pool the data. A total of 570 patients from 9 eligible studies were included in the meta-analysis (280 patients in the rituximab arm and 290 in the conventional treatment arm). Patients receiving rituximab in an acute phase to induce disease remission had a significantly lower relapse rate than those given conventional treatment (odds ratio [OR]: 0.40, 95% CI: 0.19-0.85, P = .02, I2 = 43%). Similarly, the relapse rate in the rituximab group for preemptive therapy to prevent clinical relapse was also significantly lower than in the control group (OR: 0.09, 95% CI: 0.04-0.24, P < .00001, I2 = 11%). Furthermore, the conventional treatment group had a significantly higher mortality rate than the rituximab group during the follow-up (OR: 0.41, 95% CI: 0.18-0.91, P = .03, I2 = 0%). Rituximab offered high efficacy for the prevention of relapses and lower mortality rate in cases of acquired TTP.

A Randomized Clinical Trial Evaluating the Efficacy of Colistin Loading Dose in Critically Ill Children.

Objective:Pharmacokinetic and clinical studies recommend applying loading dose of colistin for the treatment of severe infections in the critically ill adults. Pharmacokinetic studies of colistin in children also highlight the need for a loading dose. However, there are no clinical studies evaluating the effectiveness of colistin loading dose in children.Methods:In a randomized trial, children with ventilator-associated pneumonia or central line-associated bloodstream infection (CLABSI) for whom colistin was initiated, were enrolled. Patients were randomized into two groups; loading dose and conventional dose treatment arms. In the conventional treatment arm, colistimethate sodium was initiated with maintenance dose. In the loading dose group, colistimethate sodium was commenced with a loading dose of 150,000 international unit/kg, then on the maintenance dose. Both treatment arms also received meropenem as combination therapy. Primary outcomes were overall efficacy, clinical improvement and microbiological cure. Secondary outcomes were colistin-induced nephrotoxicity and development of resistance.Findings:Thirty children completed this study. There was a significantly higher overall efficacy in the group received loading dose (42.9 vs. 6.3%, P = 0.031). There weren’t any significant differences in the clinical and microbiological endpoints. In the subgroup of children with CLABSI, results illustrated a trend toward (though statistically nonsignificant) better clinical cure for patients receiving loading dose.Conclusion:This preliminary study suggests that colistin loading dose might have some benefits in critically ill children, specifically in children with CLABSI. Further trials are required to elucidate colistin best dosing strategy in critically ill children with severe infections.