Association between trunk pain and lower extremity pain among youth soccer players: a cross-sectional study

Background

Soccer is a high-intensity sport with a high injury rate. Among youth soccer players, lower extremity pain is a major problem that could be associated with trunk function. This study investigated the association between lower extremity pain and trunk pain among youth soccer players.

Methods

A cross-sectional study involving youth soccer players participating in the Miyagi Amateur Sports Association was conducted using a self-reported questionnaire. A multiple logistic regression analysis was used to examine the association between trunk pain and lower extremity pain. Covariates were sex, age, body mass index, height increase, number of days of training per week, practice time per day on weekdays or weekends, competition levels, frequency of participation in games, and previous injuries.

Results

The final study population comprised 1139 youth soccer players (age, 6–15 years; male, 94.2%). Lower extremity pain with concomitant trunk pain occurred in 61.8% (42/68). Trunk pain was significantly associated with lower extremity pain (adjusted odds ratio [OR], 6.82; 95% confidence interval [CI], 3.99–11.67). Back pain and hip pain were significantly associated with knee pain (adjusted OR [95% CI]: 7.63 [3.70–15.76] and 3.84 [1.89–7.83], respectively), ankle pain (adjusted OR [95% CI]: 9.03 [4.42–18.44] and 5.43 [2.77–10.62], respectively), and both knee and ankle pain (adjusted OR [95% CI]: 13.67 [6.01–31.09] and 5.98 [2.56–13.97], respectively).

Conclusions

Trunk pain was associated with lower extremity pain among youth soccer players. Clinicians and coaches should consider comorbidities while treating those players.

     

Video-assisted Thoracoscopic surgery (VATS) lobectomy for lung cancer does not induce a procoagulant state

Background

Changes in the coagulation system in patients undergoing surgery for lung cancer have been sparsely investigated and the impact of the surgical trauma on the coagulation system is largely unknown in these patients. An increased knowledge could potentially improve the thromboprophylaxis regimes. The aim of this study was to assess the coagulation profile evoked in patients undergoing curative surgery by Video-Assisted Thoracoscopic Surgery (VATS) lobectomy for primary lung cancer.

Methods

Thirty-one patients diagnosed with primary lung cancer undergoing VATS lobectomy were prospectively included. The coagulation profile was assessed preoperatively and in the first two days postoperatively using a wide range of standard coagulation tests, dynamic whole blood coagulation measured by rotational thromboelastometry (ROTEM®) and thrombin generation evaluated by calibrated automated thrombography. Patients did not receive thromboprophylactic treatment. Data was analyzed using repeated measures one-way ANOVA.

Results

The standard coagulation parameters displayed only subtle changes after surgery and the ROTEM® and thrombin generation results remained largely unchanged.

Conclusions

Patients undergoing VATS lobectomy are normocoagulable in the preoperative state and a VATS lobectomy does not significantly influence the coagulation.

Trial registration

The trial is registered at ClinicalTrials.gov (Identifier: NCT01741506) and at EudraCTno. 2012–002409-23. Registered December 2012.

     

Questions to improve family–staff communication in the ICU: a randomized controlled trial

Purpose

Relatives of intensive care unit (ICU) patients suffer emotional distress that impairs their ability to acquire the information they need from the staff. We sought to evaluate whether providing relatives with a list of important questions was associated with better comprehension on day 5.

Methods

Randomized, parallel-group trial. Relatives of mechanically ventilated patients were included from 14 hospitals belonging to the FAMIREA study group in France. A validated list of 21 questions was handed to the relatives immediately after randomization. The primary endpoint was comprehension on day 5. Secondary endpoints were satisfaction (Critical Care Family Needs Inventory, CCFNI) and symptoms of anxiety and depression (Hospital Anxiety and Depression Scale, HADS).

Results

Of 394 randomized relatives, 302 underwent the day-5 assessment of all outcomes. Day-5 family comprehension was adequate in 68 (44.2%) and 75 (50.7%) intervention and control group relatives (P?=?0.30), respectively. Over the first five ICU days, median number of family–staff meetings/patient was 6 [3–9], median total meeting time was 72.5 [35–110] min, and relatives asked a median of 20 [8–33] questions including 11 [6–13] from the list, with no between-group difference. Satisfaction and anxiety/depression symptoms were not significantly different between groups. The only variable significantly associated with better day-5 comprehension by multivariable analysis was a higher total number of questions asked before day 5.

Conclusions

Providing relatives with a list of questions did not improve day-5 comprehension, secondary endpoints, or information time. Further research is needed to help families obtain the information they need.

Trial registration

ClinicalTrials.gov Identifier: NCT02410538.

     

Differential Protein Expression Profiles in Glaucomatous Trabecular Meshwork: An Evaluation Study on a Small Primary Open Angle Glaucoma Population

Introduction

Primary open angle glaucoma (POAG) is a progressive optic neuropathy characterized by impaired aqueous outflow and extensive remodeling in the trabecular meshwork (TM). The aim of this study was to characterize and compare the expression patterns of selected proteins belonging to the tissue remodeling, inflammation and growth factor pathways in ex vivo glaucomatous and post-mortem TMs using protein-array analysis.

Methods

TM specimens were collected from 63 white subjects, including 40 patients with glaucoma and 23 controls. Forty POAG TMs were collected at the time of surgery and 23 post-mortem specimens were from non-glaucomatous donor sclerocorneal tissues. Protein profiles were evaluated using a chip-based array consisting of 60 literature-selected antibodies.

Results

A different expression of some factors was observed in POAG TMs with respect to post-mortem specimens, either in abundance (interleukin [IL]10, IL6, IL5, IL7, IL12, IL3, macrophage inflammatory protein [MIP]1δ/α, vascular endothelial growth factor [VEGF], transforming growth factor beta 1 [TGFβ1], soluble tumor necrosis factor receptor I [sTNFRI]) or in scarcity (IL16, IL18, intercellular adhesion molecule 3 [ICAM3], matrix metalloproteinase-7 [MMP7], tissue inhibitor of metalloproteinase 1 [TIMP1]). MMP2, MMP7, TGFβ1, and VEGF expressions were confirmed by Western blot, zymography, and polymerase chain reaction. No difference in protein profile expression was detected between glaucomatous subtypes.

Conclusion

The analysis of this small TM population highlighted some proteins linked to POAG, some previously reported and others of new detection (IL7, MIPs, sTNFαRI). A larger POAG population is required to select promising disease-associated biomarker candidates.

Funding

This study was partially supported by the Fondazione Roma, the Italian Ministry of Health and the “National 5xMille 2010 tax donation to IRCCS-G.B. Bietti Foundation”.

     

Respiratory variations in aortic blood flow predict fluid responsiveness in ventilated children

Objective

To investigate whether respiratory variations in aortic blood flow velocity (ΔVpeak ao), systolic arterial pressure (ΔPS) and pulse pressure (ΔPP) could accurately predict fluid responsiveness in ventilated children.

Design and setting

Prospective study in a 18-bed pediatric intensive care unit.

Patients

Twenty-six children [median age 28.5 (16–44) months] with preserved left ventricular (LV) function.

Intervention

Standardized volume expansion (VE).

Measurements and main results

Analysis of aortic blood flow by transthoracic pulsed-Doppler allowed LV stroke volume measurement and on-line ΔVpeak ao calculation. The VE-induced increase in LV stroke volume was >?15% in 18 patients (responders) and p?=?0.001], whereas ΔPP and ΔPS did not significantly differ between groups. The prediction of fluid responsiveness was higher with ΔVpeak ao [ROC curve area 0.85 (95% IC 0.99–1.8), p?=?0.001] than with ΔPS (0.64) or ΔPP (0.59). The best cut-off for ΔVpeak ao was 12%, with sensitivity, specificity, and positive and negative predictive values of 81.2%, 85.7%, 93% and 66.6%, respectively. A positive linear correlation was found between baseline ΔVpeak ao and VE-induced gain in stroke volume (rho?=?0.68, p?=?0.001).

Conclusions

While respiratory variations in aortic blood flow velocity measured by pulsed Doppler before VE accurately predict the effects of VE, ΔPS and ΔPP are of little value in ventilated children.

     

Clinical spectrum and short-term outcome of adult patients with purpura fulminans: a French multicenter retrospective cohort study

Purpose

Data on purpura fulminans (PF) in adult patients are scarce and mainly limited to meningococcal infections. Our aim has been to report the clinical features and outcomes of adult patients admitted in the intensive care unit (ICU) for an infectious PF, as well as the predictive factors for limb amputation and mortality.

Methods

A 17-year national multicenter retrospective cohort study in 55 ICUs in France from 2000 to 2016, including adult patients admitted for an infectious PF defined by a sudden and extensive purpura, together with the need for vasopressor support. Primary outcome variables included hospital mortality and amputation during the follow-up period (time between ICU admission and amputation, death or end of follow-up).

Results

Among the 306 included patients, 126 (41.2%; 95% CI 35.6–46.9) died and 180 (58.8%; 95% CI 53.3–64.3) survived during the follow-up period [13 (3–24) days], including 51/180 patients (28.3%, 95% CI 21.9–35.5) who eventually required limb amputations, with a median number of 3 (1–4) limbs amputated. The two predominantly identified microorganisms were Neisseria meningitidis (63.7%) and Streptococcus pneumoniae (21.9%). By multivariable Cox model, SAPS II [hazard-ratio (HR)?=?1.03 (1.02–1.04); p?<?0.001], lower leucocytes [HR 0.83 (0.69–0.99); p?=?0.034] and platelet counts [HR 0.77 (0.60–0.91); p?=?0.007], and arterial blood lactate levels [HR 2.71 (1.68–4.38); p?<?0.001] were independently associated with hospital death, while a neck stiffness [HR?0.51 (0.28–0.92); p?=?0.026] was a protective factor. Infection with Streptococcus pneumoniae [sub-hazard ratio 1.89 (1.06–3.38); p?=?0.032], together with arterial lactate levels and ICU admission temperature, was independently associated with amputation by a competing risks analysis.

Conclusion

Purpura fulminans carries a high mortality and morbidity. Pneumococcal PF leads to a higher risk of amputation.

Trials registration

NCT03216577.

     

Strain Differences Determine the Suitability of Animal Models for Noninvasive <Emphasis Type="Italic">In Vivo</Emphasis> Beta Cell Mass Determination with Radiolabeled Exendin

Purpose

Noninvasive beta cell mass (BCM) quantification is a crucial tool to understand diabetes development and progression. [¹¹¹In]exendin is a promising agent for in vivo beta cell imaging, but tracer testing has been hampered by the lack of well-defined rodent models.

Procedures

Biodistribution and pancreatic uptake of [¹¹¹In]exendin were compared in rats and mice. In selected models, the amount of [¹¹¹In]exendin accumulation in the pancreas and other organs was determined using a model of alloxan-induced beta cell loss. GLP-1R expression levels were analyzed by RT-PCR and immunohistochemistry.

Results

Namely Brown Norway rats showed beta-cell-specific tracer accumulation and favorable pancreas-to-background ratios for noninvasive BCM determination. Mice displayed receptor-mediated [¹¹¹In]exendin uptake in endocrine and exocrine pancreas, in spite of very low GLP-1R expression in exocrine tissue.

Conclusions

Rats display better characteristics for in vivo BCM determination than mice and are suggested as a more adequate model for humans.

     

The Prevalence of Suicidal Ideation in Adolescents and Associated Risk Factors: An Example from Turkey

Introduction

Identifying risk factors is important in intervening in suicide, which is a preventable cause of death in adolescents. The aim of the present study was to evaluate the prevalence of suicidal ideation and risk factors for suicidal thought in high school students aged 15–18 years.

Methods

The data were obtained from questionnaire forms administered to 2438 high school students aged 15–18 years. Risk factors that might be associated with suicidal thought were identified using logistic regression analysis.

Results

The prevalence of suicidal ideation in adolescents in the last 12 months was 17.9%. Being female [OR 1.95, (CI 95% 1.47–2.59)], use of alcohol [OR 2.44, (CI 95% 1.63–3.68)] and addictive drugs [OR 1.78, (CI 95% 1.07–2.97)], being in physical fights [OR 1.76, (CI 95% 1.34–2.32)], having no close friends [OR 2.17, (CI 95% 1.34–3.52)], bullying(victimization) [OR 1.99, (CI 95% 1.43–2.77)], and other psychosocial distress were significant risk factors in the development of suicidal ideation.

Conclusions

Solutions for decreasing risky behaviors for health, particularly the use of alcohol and addictive drugs, prevention of violence between peers, and strengthening of social relationships, must be developed.

     

Factors and Regional Differences Associated with Endometriosis: A Multi-Country,Case–Control Study

Introduction

The present study aimed to investigate clinical, lifestyle, and environmental factors associated with endometrioma (OMA) and/or deep infiltrating endometriosis (DIE) as determined by case–control comparison [women with superficial peritoneal endometriosis (SUP) or no endometriosis], and compare differences between factor associated with endometriosis at a national level.

Methods

This was three countries (China, Russia, and France), case–control study in 1008 patients. Patients were identified and enrolled during their first routine appointment with their physician post-surgery for a benign gynecologic indication, excluding pregnancy. Retrospective information on symptoms and previous medical history was collected via face-to-face interviews; patients also completed a questionnaire to provide information on current habits. For every DIE patient recruited (n = 143), two women without endometriosis (n = 288), two SUP patients (n = 288), and two OMA patients (n = 288) were recruited.

Results

For the overall population, factors significantly associated (P ≤ 0.05) with DIE or OMA [Odds ratio (OR) >1] were: previous use of hormonal treatment for endometriosis [OR 6.66; 95% confidence interval (CI) 4.05–10.93]; previous surgery for endometriosis (OR 1.95; 95% CI 1.11–3.43); and living or working in a city or by a busy area (OR 1.66; 95% CI 1.09–2.52). Differences between regions with regard to the diagnosis, symptomatology, and treatment of endometriosis exist.

Conclusion

The findings provide insight into potential risk factors for endometriosis and differences between regions in terms of endometriosis management and symptomatology. Further investigations are required to confirm the associations found in this study.

Trial registration

ClinicalTrials.gov identifier, NCT01351051.

Funding

Ipsen.

     

Is the cardiac output obtained from a Swan–Ganz catheter always zero?

Objective

By means of a Swan–Ganz catheter cardiac output is calculated using the Stewart–Hamilton thermodilution equation. Assuming the body as a thermally isolated inert system, this equation theoretically always results in zero cardiac output.

Methods

Using the first and second law of thermodynamics together with a few lines simple analysis this statement is proven.

Conclusion

It is at least a necessary condition for the application of the Stewart–Hamilton equation, that core body temperature is kept constant in a thermo- regulatory steady state.

     

A Comparison of microCT and microPET for Evaluating Lymph Node Metastasis in a Rat Model

Purpose

The demand to optimize multidisciplinary treatment strategies in patients with benign and malignant diseases of the lung and other organs has led to the increased need of mechanistic proof-of-concept studies in preclinical small animal models using new non-invasive imaging methods. Therefore, we evaluated the role of microPET and microCT for mediastinal lymph node staging in an orthotopic lung cancer model in rats.

Procedures

Human lung cancer cells (NCI-H460) were injected transthoracically in nude rats (NIH-RNU). After 2 weeks of tumour growth, animals underwent multiphase contrast-enhanced microCT using ExiTron nano 12000 as a contrast agent and dynamic microPET using the tracer 2-deoxy-2-[¹⁸F]fluoro-d-glucose ([¹⁸F]FDG). Thereafter, animals were sacrificed for histological analysis.

Results

Late phase micro X-ray computed tomography (microCT) revealed the best delineation of lymph node metastases, as compared to earlier scans. In terms of an increased [¹⁸F]FDG uptake over time, dynamic micro positron emission tomography (microPET) delineated lymph node metastases and enabled metabolic examinations of the induced lung cancer metastases.

Conclusion

The combination of contrast-enhanced microCT and dynamic microPET is feasible in rats for the visualization of mediastinal lymph node metastases.

     

Early PREdiction of sepsis using leukocyte surface biomarkers: the ExPRES-sepsis cohort study

Purpose

Reliable biomarkers for predicting subsequent sepsis among patients with suspected acute infection are lacking. In patients presenting to emergency departments (EDs) with suspected acute infection, we aimed to evaluate the reliability and discriminant ability of 47 leukocyte biomarkers as predictors of sepsis (Sequential Organ Failure Assessment score?≥?2 at 24 h and/or 72 h following ED presentation).

Methods

In a multi-centre cohort study in four EDs and intensive care units (ICUs), we standardised flow-cytometric leukocyte biomarker measurement and compared patients with suspected acute infection (cohort-1) with two comparator cohorts: ICU patients with established sepsis (cohort-2), and ED patients without infection or systemic inflammation but requiring hospitalization (cohort-3).

Results

Between January 2014 and February 2016, we recruited 272, 59 and 75 patients to cohorts 1, 2, and 3, respectively. Of 47 leukocyte biomarkers, 14 were non-reliable, and 17 did not discriminate between the three cohorts. Discriminant analyses for predicting sepsis within cohort-1 were undertaken for eight neutrophil (cluster of differentiation antigens (CD) CD15; CD24; CD35; CD64; CD312; CD11b; CD274; CD279), seven monocyte (CD35; CD64; CD312; CD11b; HLA-DR; CD274; CD279) and a CD8 T-lymphocyte biomarker (CD279). Individually, only higher neutrophil CD279 [OR 1.78 (95% CI 1.23–2.57); P?=?0.002], higher monocyte CD279 [1.32 (1.03–1.70); P?=?0.03], and lower monocyte HLA-DR [0.73 (0.55–0.97); P?=?0.03] expression were associated with subsequent sepsis. With logistic regression the optimum biomarker combination was increased neutrophil CD24 and neutrophil CD279, and reduced monocyte HLA-DR expression, but no combination had clinically relevant predictive validity.

Conclusions

From a large panel of leukocyte biomarkers, immunosuppression biomarkers were associated with subsequent sepsis in ED patients with suspected acute infection.

Clinical trial registration

NCT02188992.

     

Olanzapine vs haloperidol: treating delirium in a critical care setting

Objective

To compare the safety and estimate the response profile of olanzapine, a second-generation antipsychotic, to haloperidol in the treatment of delirium in the critical care setting.

Design

Prospective randomized trial

Setting

Tertiary care university affiliated critical care unit.

Patients

All admissions to a medical and surgical intensive care unit with a diagnosis of delirium.

Interventions

Patients were randomized to receive either enteral olanzapine or haloperidol.

Measurements

Patient’s delirium severity and benzodiazepine use were monitored over 5 days after the diagnosis of delirium.

Main results

Delirium Index decreased over time in both groups, as did the administered dose of benzodiazepines. Clinical improvement was similar in both treatment arms. No side effects were noted in the olanzapine group, whereas the use of haloperidol was associated with extrapyramidal side effects.

Conclusions

Olanzapine is a safe alternative to haloperidol in delirious critical care patients, and may be of particular interest in patients in whom haloperidol is contraindicated.

     

Toxicity and Pharmacokinetics of Sustained-Release Dexamethasone in Beagle Dogs

Introduction

The purpose of the present study was to examine the potential ocular and systemic toxicity and toxicokinetics/pharmacokinetics of sustained-release dexamethasone in canines.

Methods

In this non-randomized study, intracanalicular depots (dexamethasone-loaded or placebo vehicle) were inserted into both eyes of 33 beagles. Tear fluid and plasma were collected for toxicokinetic/pharmacokinetic analysis of dexamethasone, ophthalmic examinations were performed for signs of toxicity, and urine and blood samples were collected for urinalysis, hematology, clinical chemistry, and coagulation analysis. Animals were observed daily for signs of toxicity. Macroscopic and microscopic evaluations were performed.

Results

Mean dexamethasone tear fluid concentration from the dexamethasone group decreased from 4245 ng/mL 6-h post-insertion to 1044 ng/mL on Day 35. All plasma dexamethasone levels were below the limit of quantitation. No systemic or ocular toxicities were attributed to the dexamethasone depot.

Conclusion

Sustained-release dexamethasone produced no identifiable ocular or systemic toxicity in this animal model, and pharmacokinetics demonstrated a tapered, sustained drug release.

Funding

Ocular Therapeutix.

     

A novel ultrasonic method for evaluation of blood clotting parameters

Purpose

For long time, blood clot retraction was measured only by thromboelastographic or platelet contractile force measurement techniques. The purpose of the present study was development of a novel ultrasonic method based on simultaneous monitoring of variations in the ultrasound velocity and the frequency spectrum of the signal propagating in clotting blood and its application for automatic evaluation of blood clotting parameters.

Methods

Simultaneous measurement of ultrasound velocity and variations in the frequency spectrum of wideband ultrasonic signals in clotting blood samples was performed. All measurements were performed in pulse-echo mode. Standard clinical data were obtained using routine clinical laboratory methods.

Results

The amplitudes of ultrasonic signals during native blood coagulation varied up to ten times for different frequencies. The measurement results of the start and duration of blood clot retraction differed between patient samples: different components of the blood coagulation system had significant impact on the blood clot retraction process.

Conclusions

Our results showed that during blood clotting, the ultrasound velocity and variations in frequency spectrum should be used simultaneously to determine the beginning and duration of blood clot retraction. Our results also showed that blood clot retraction is controlled by the activity of factor XIII.

     

Quantitative versus standard pupillary light reflex for early prognostication in comatose cardiac arrest patients: an international prospective multicenter double-blinded study

Purpose

To assess the ability of quantitative pupillometry [using the Neurological Pupil index (NPi)] to predict an unfavorable neurological outcome after cardiac arrest (CA).

Methods

We performed a prospective international multicenter study (10 centers) in adult comatose CA patients. Quantitative NPi and standard manual pupillary light reflex (sPLR)—blinded to clinicians and outcome assessors—were recorded in parallel from day 1 to 3 after CA. Primary study endpoint was to compare the value of NPi versus sPLR to predict 3-month Cerebral Performance Category (CPC), dichotomized as favorable (CPC 1–2: full recovery or moderate disability) versus unfavorable outcome (CPC 3–5: severe disability, vegetative state, or death).

Results

At any time between day 1 and 3, an NPi?≤?2 (n?=?456 patients) had a 51% (95% CI 49–53) negative predictive value and a 100% positive predictive value [PPV; 0% (0–2) false-positive rate], with a 100% (98–100) specificity and 32% (27–38) sensitivity for the prediction of unfavorable outcome. Compared with NPi, sPLR had significantly lower PPV and significantly lower specificity (p? <?0.001 at day 1 and 2; p ?=?0.06 at day 3). The combination of NPi?≤?2 with bilaterally absent somatosensory evoked potentials (SSEP; n?=?188 patients) provided higher sensitivity [58% (49–67) vs. 48% (39–57) for SSEP alone], with comparable specificity [100% (94–100)].

Conclusions

Quantitative NPi had excellent ability to predict an unfavorable outcome from day 1 after CA, with no false positives, and significantly higher specificity than standard manual pupillary examination. The addition of NPi to SSEP increased sensitivity of outcome prediction, while maintaining 100% specificity.

     

PET Imaging Study of S1PR1 Expression in a Rat Model of Multiple Sclerosis

Purpose

Upregulation of sphingosine-1-phosphate receptor 1 (S1PR1) expression in multiple sclerosis (MS) lesions is associated with neuroinflammatory response. This study investigated the correlation between neuroinflammation and S1PR1 expression in the spinal cord of an experimental autoimmune encephalomyelitis (EAE) rat model of MS, using the S1PR1 positron emission tomography (PET) radiotracer [¹¹C]TZ3321.

Procedures

MicroPET imaging studies of [¹¹C]TZ3321 were performed to measure uptake of [¹¹C]TZ3321 in the spinal cord of EAE rats. Immunohistochemical staining was performed to confirm the overexpression of S1PR1 and other inflammatory biomarkers.

Results

MicroPET imaging demonstrated a 20–30 % increase in [¹¹C]TZ3321 uptake in the lumbar spinal cord of EAE rats versus sham controls at 35–60 min post injection. The increased uptake of [¹¹C]TZ3321 was correlated with the overexpression of S1PR1 in the lumbar spinal cord of EAE rats that was confirmed by immunohistochemical staining. Upregulated S1PR1 expression was associated with glial cell activation and immune cell infiltration.

Conclusions

MicroPET imaging modality with a specific radioligand [¹¹C]TZ3321 is able to assess the expression of S1PR1 in EAE rat lumbar spinal cord. This may provide a new approach to the assessment of neuroinflammatory response in MS and other inflammatory diseases.

     

Long-term safety and efficacy of the recombinant human growth hormone omnitrope® in the treatment of Spanish growth hormone deficient children: Results of a phase III study

Introduction

This phase III study in growth hormone (GH) deficient (GHD) children with growth retardation was designed to demonstrate the safety and efficacy of longterm treatment with the recombinant human GH Omnitrope® (Sandoz BioPharmaceuticals, Holzkirchen, Germany).

Methods

Treatmentnaïve, prepubertal Spanish children (n=70) with isolated GHD were treated with Omnitrope 0.03 mg/kg/day subcutaneously. Changes in height, height standard deviation score (HSDS), height velocity (HV), HV standard deviation score (HVSDS), serum insulin-like growth factor (IGF)-1, and insulin-like growth factor binding protein (IGFBP)-3 levels were recorded.

Results

Omnitrope treatment provided a good growth response after 4 years, shown by a significant increase in mean body height (31.1 cm [95% CI: 29.6–32.6]), HSDS (Tanner) (1.42 [1.13–1.70]), HV (2.4 cm [1.7–3.1]), and HVSDS values (3.5 [2.7–4.3]). Mean IGF-1 and IGFBP-3 serum levels also increased significantly.

Conclusion

At a dose of 0.03 mg/kg/day, Omnitrope was safe, effective, and well tolerated during long-term treatment of children with GHD.

     

Aspirin plus tirofiban inhibit the thrombosis induced by Russell’s viper venom

Background

Thrombosis and coagulopathy are the commonest hematological manifestations of envenomation of Russell’s viper venom (RVV). Factor X is activated by a factor X-activating enzyme from Russell’s viper venom (RVV-X) to start the coagulation cascade. We established an animal model with local ischemic effects induced by RVV. We tried to treat RVV envenomation with antiplatelets and anticoagulants without recourse to antivenom.

Methods

RVV was injected into the foot pad of mice. We observed the effects at different intervals and compared local changes in ischemia with drug treatment after 30 min.

Results

A combination of aspirin plus tirofiban could prevent the ischemic change induced by RVV. The antithrombotic effects of single-use of aspirin or tirofiban were better than single-use of heparin or clopidogrel.

Conclusion

The aspirin?+?tirofiban group had a better outcome with respect to prevention of tissue ischemia and gangrene. This indicates that the activation and aggregation of platelets is the major cause of thrombosis induced by RVV.

     

Comparative Efficacy of Ibrutinib Versus Obinutuzumab + Chlorambucil in First-Line Treatment of Chronic Lymphocytic Leukemia: A Matching-Adjusted Indirect Comparison

Introduction

Ibrutinib (ibr) monotherapy and the combination of obinutuzumab plus chlorambucil (obi) are approved for previously untreated chronic lymphocytic leukemia (CLL). No trials directly comparing their efficacy are available. Therefore a matching-adjusted indirect comparison (MAIC) was performed to provide insight into their relative efficacy in terms of progression-free survival (PFS) and overall survival (OS). MAIC attempts to adjust for between-trial differences in factors known or suspected to influence treatment effects, to minimize bias.

Methods

A MAIC within a Bayesian framework was conducted using individual patient data from the RESONATE-2 study of ibr versus chlorambucil and published data from the CLL11 study of obi versus chlorambucil. Both studies were conducted in patients ineligible for full-dose fludarabine-based therapy. After matching, the reweighted adjusted relative efficacy measure of ibr versus chlorambucil from RESONATE-2 [hazard ratio (HR), 95% credible interval (CrI)] was compared with that of obi versus chlorambucil from CLL11 for each endpoint, using a Bayesian indirect comparison.

Results

Our results suggest that in a population with similar average baseline characteristics to CLL11, ibr would improve PFS and OS outcomes compared to obi. Before matching, the HRs for ibr versus obi were 0.48 [CrI = 0.22–1.02, p(HR <1) = 97%], 0.85 [CrI = 0.44–1.63, p(HR <1) = 69%], and 0.40 [CrI = 0.10–1.54, p(HR <1) = 91%] for PFS by investigator assessment, PFS by independent review committee, and OS, respectively. After matching on all available characteristics the HRs decreased to 0.12 [CrI = 0.02–0.97, p(HR <1) = 98%], 0.24 [CrI = 0.04–1.35, p(HR <1) = 95%], and 0.21 [CrI = <0.01–8.89, p(HR <1) = 79%], respectively. There was a large variance around the treatment effect for OS due to the low number of deaths.

Conclusion

Our analysis suggests that ibrutinib is highly likely to provide greater PFS benefit than obinutuzumab plus chlorambucil in older or less fit patients with previously untreated CLL. There is also an indication of improvement in OS, albeit with a higher uncertainty due to the low number of events.

Funding

Janssen-Cilag Ltd.