Pirfenidone improves the survival of patients with idiopathic pulmonary fibrosis hospitalized for acute exacerbation

Objective: To examine the effect of pirfenidone on the survival of patients hospitalized due to acute exacerbation of idiopathic pulmonary fibrosis (AE–IPF).

Methods: The outcomes of 11 consecutive AE–IPF patients who were receiving pirfenidone treatment when they were admitted to a respiratory intensive care unit (RICU) for acute respiratory failure (ARF) (treatment group) were retrospectively compared with those of 9 patients who were not on pirfenidone treatment at admission (control group). The study’s primary outcome measure was survival following RICU admission; the patients’ mortality rate and the length of time spent in the RICU were also assessed.

Results: The treatment group had significantly longer survival than the control group (median survival time: 137.0 [95% CI, 39.0–373.0] versus 16.0 [95% CI, 14.0–22.0] days; p?=?.0009); the hazard ratio for death was 0.2896 (95% CI, 0.09541–0.8791). The treatment group also tended to have a lower RICU mortality rate (3/11 vs. 7/9; p?=?.0698).

Conclusions: Pirfenidone significantly improved survival in IPF patients hospitalized for severe acute exacerbation compared to controls.     

An evaluation of peripapillar choroidal thickness in patients receiving systemic isotretinoin treatment

Purpose: Oral isotretinoin (13-cis retinoic acid, 13-cis RA) was approved for severe acne treatment by the FDA in 1982. The ocular side effects associated with oral isotretinoin use are mostly dose-dependent. Numerous ocular pathologies affect peripapillary choroidal layer primarily or indirectly.

Objective: Evaluation of the peripapillary choroidal layer in the patients receiving oral isotretinoin therapy may aid in explaining the pathophysiology of ocular side effects.

Methods: In this study, peripapillary choroidal thickness was assessed in the patients receiving oral isotretinoin treatment via optical coherent tomography technique.

Results: Significant difference was found in the superotemporal and temporal areas.

Conclusion: Oral isotretinoin treatment may affect the thickness of the peripapillary choroidal layer.     

Adenocarcinoma histology is a poor prognostic factor in locally advanced cervical cancer

Objective: This retrospective study aimed to compare prognostic factors and survival between adenocarcinoma (AC) and squamous cell carcinoma (SCC) in locally advanced cervical cancer treated at a single center.

Methods: All medical records of cervical cancer patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIB or IIIA,B, treated between 2004 and 2012, were reviewed. We treated patients with chemoradiotherapy (CRT) followed by brachytherapy (BT). Multivariate logistic regression and Cox proportional hazard models were used to analyze clinicopathological characteristics, patterns of care and outcomes.

Results: We included in the analysis 161 patients (52 AC; 109 SCC). Patients with AC were younger (age 50 vs. 55?years), more likely to die from the disease (HR: 1.60; 95% CI: 1.26–2.58; p?=?.001) and to have disease recurrence (HR: 1.69; 95% C.I: 1.21–2.12; p?=?.004) than those with SCC. The other significant prognostic factors for overall survival (OS) and recurrence-free survival (RFS) in AC were FIGO stage (p?=?.001; p?=?.002), WHO status (0 vs. 1–3; p?=?.003; p?=?.04), and hemoglobin level (<12?g/dl>; p?=?.04; p?=?.02). The 5?year overall survival for stage II of AC and SCC was 63% and 82% (p?=?.03), and for IIIA,B it was 33.6% and 73% (p?=?.0005). The 5?year RFS for AC and SCC stage FIGO IIIA,B was 24% and 57% (p?=?.001).

Conclusions: Adenocarcinoma histology negatively impacts OS and RFS for advanced cervical cancer. Histology-specific therapy may be an opportunity for survival improvement in these women.     

Outcomes of spironolactone treatment in patients in Northeast China suffering from heart failure with mid-range ejection fraction

Aim: The treatment effects of spironolactone on heart failure with reduced (HFrEF LVEF <40%) and preserved (HFpEF LVEF ≥50%) ejection fraction are well characterized. It is not clear whether heart failure patients with mid-range ejection fraction (HFmrEF, LVEF 40–49%) benefit from spironolactone. The present study aims to evaluate the efficacy of spironolactone in HFmrEF patients.

Method: This study compared a high dosage of spironolactone (50?mg daily), a low dosage of spironolactone (25?mg daily), and an untreated group for the prevention of major adverse cardiovascular events (MACE) in 279 patients admitted to hospital diagnosed with HFmrEF.

Results: With a mean follow-up duration of 1 year, the death and HF-rehospitalization rate demonstrated significantly lower incidence in those taking spironolactone, compared with the untreated group (21.3% vs 34.5%, p?=?.014, respectively). Further analysis showed no difference between two spironolactone groups (21.8% vs 20.7%, p?=?.861). Kaplan-Meier analysis of outcome-free survival illustrated a significant difference in survival rate among three groups (log-rank testing, p?=?.045). Compared with the baseline level, patients receiving 25?mg spironolactone had a lower physical score (p?<?.05) at 1-year follow-up. MLHFQ total scores in the two spironolactone groups markedly improved compared with the untreated group (p?<?.001); similar results were observed in the MLHFQ physical scores (p?=?.025, .001, respectively) and emotional sub-scale (p?=?.023, .011, respectively); however, paired comparison between the two spironolactone groups showed no difference.

Conclusions: In patients with HFmrEF, treatment with spironolactone significantly reduced the incidence of the primary composite outcomes of all-cause death, and rehospitalization for the management of heart failure compared with placebo, and a high dosage of spironolactone did not show trends of reduction in MACE.     

Clinical profile of the functionally selective glucocorticoid receptor agonist BI 653048 in healthy male subjects

Background: An efficacious anti-inflammatory corticosteroid with reduced side effects has been long sought. We report the pooled results from three clinical proof-of-mechanism Phase I studies of BI 653048 in healthy subjects, a functionally selective, nonsteroidal glucocorticoid (GC).

Research design and methods: Three Phase I trials were conducted: a single rising-dose study and a multiple rising-dose study to evaluate the safety, tolerability, and pharmacokinetics of BI 653048, and a multiple parallel-arm-dose study with intravenous lipopolysaccharide challenge to assess in vivo pharmacodynamics. The pharmacodynamics, efficacy, and safety of BI 653048 and prednisolone were compared.

Results: Treatment with 200 mg BI 653048 was associated with a reduced expression of IL1R2, ITGB3, and SDPR versus 20 mg prednisolone; comparable levels of FKBP5, ZBTB16, and DDIT4 expression were observed. Changes in C-peptide, glucose, insulin, and cortisol were moderate compared with prednisolone. A greater reduction of osteocalcin was observed with 200 mg BI 653048 versus 20 mg prednisolone. Comparable anti-inflammatory efficacy was demonstrated for 200 mg BI 653048 and 20 mg prednisolone. BI 653048 was well tolerated in healthy subjects.

Conclusion: BI 653048 demonstrated the desired anti-inflammatory effects of the nonsteroidal GC; however, the undesirable side-effect profile associated with GC steroids could not be disassociated from BI 653048.

Trial registration: ClinicalTrials.gov identifiers NCT02217644, NCT02217631, and NCT02224105.     

Vitamin D deficiency is associated with dyslipidemia: a cross-sectional study in 3788 subjects

Background: Previously we reported on severe vitamin D deficiency in a large-scale cohort in the Tangshan area in northern China. However, whether vitamin D deficiency is associated with cardiovascular risk factors has not been systematically examined in the cohort.

Objective: We aimed to determine the correlation between serum vitamin D status and lipid levels in circulation via an observational study.

Methods: Serum 25-hydroxyvitamin D (25[OH]D) was measured. Based on the measurement subjects were classified into quintiles. Dyslipidemia was defined as having one of the following: elevated serum total cholesterol, LDL cholesterol, triglycerides or decreased HDL cholesterol, under lipid-control treatment.

Results: The study was conducted in a total of 3788 adults in northern China during their routine health examinations. When the highest quintile of the 25(OH)D level was set as reference, the risk of having dyslipidemia increased progressively across the highest to the lowest 25(OH)D with ORs of 1 (reference), 1.232 (95% CI, 1.005–1.509), 1.235 (95% CI, 1.007–1.513), 1.403 (95% CI, 1.143–1.735) and 1.494 (95% CI, 1.217–1.833), respectively (P_trend < .0001) after adjustment for age. This trend was unchanged after further adjustment for several potential confounders. In linear regression analysis, we found an inverse significant correlation between 25(OH)D and triglycerides (β coefficient = ?0.077, p?<?.05) and LDL cholesterol (β coefficient = ?0.245, p < .05), and positive correlation with HDL cholesterol (β coefficient = 0.038, p = .018).

Conclusion: Vitamin D deficiency is found to be associated with dyslipidemia in a cohort of 3788 subjects. Specifically, serum 25(OH)D is inversely correlated with LDL cholesterol and triglycerides levels, and positively correlated with HDL cholesterol level.     

Stress-related upper gastrointestinal bleeding in adult neurocritical care patients: a Chinese multicenter,retrospective study

Objective: China has limited data on stress-related gastrointestinal ulcers in patients admitted for neurosurgical care. This study evaluated the incidence of upper gastrointestinal bleeding (UGIB) and use of stress ulcer prophylaxis (SUP) in Chinese neurocritical care patients (Glasgow Coma Scale [GCS] score ≤10).

Methods: This multicenter, retrospective study was performed from January 2015 to July 2015. Medical records of 1468 patients hospitalized during 2014 were reviewed. An estimated UGIB incidence rate of 4.4% was considered for precision of 1.3% for estimation of UGIB. The primary endpoint was evaluation of overall incidence of any overt UGIB in ≤14 days after cerebral lesion. Secondary endpoints included incidence of UGIB with or and without clinically significant complications, time to UGIB, associated risk factors and SUP used.

Results: We analyzed 1416 patients (mean age: 53.7?±?14.00 years; males: 62.4%) with cerebral lesions. Overall incidence rate of UGIB ≤14 days was 12.9% (95% CI: 11.2%–14.7%), 0.76% with and 12.1% without significant clinical complications. Average time and duration of bleeding were 2.9?±?3.37 days and 4.2?±?8.4 days, respectively. The most significant risk factors for UGIB were mechanical ventilation for >48?hours (p?<?.0001), UGIB history (p?=?.0026) and use of anticoagulants (p?<?.0001). Acid-suppression drugs were administered for SUP in 79.0% of the patients, whereas 40.5% received hemostatic drugs.

Conclusions: The rate of UGIB incidence was higher than the estimated rate in neurocritical care patients in China, suggesting the need for better management and treatment for stress-related mucosal disease in China. History of UGIB, mechanical ventilation and/or anticoagulants significantly affected UGIB.

ClinicalTrials registry number: NCT02316990.     

Secondary cannabis use among London drug treatment service clients

Background: Cannabis is the second most commonly used substance after alcohol among people seeking treatment for other drug use, but no statistics are available regarding secondary cannabis use among drug treatment clients.

Objectives: To investigate levels of secondary cannabis use among drug treatment clients and perceived need for support addressing this use among clients and staff.

Methods: Cross-sectional surveys of clients (N?=?295) and staff (N?=?33) were conducted in 2015 at four London drug and alcohol treatment services. Client measures included recent drug use, type of cannabis used, Severity of Dependence Scale for cannabis, and views on secondary cannabis use treatment. Staff measures included definition of problem cannabis use, importance and timing for addressing secondary cannabis use.

Results: Among clients, 39.7% reported recent secondary cannabis use, with 30.8% of these clients meeting criteria for problem use. Problem users were more likely to be interested in receiving treatment for cannabis use than non-problem users (51.4% versus 10.8%, p?<?.001). Nearly half of staff (48.5%) thought secondary cannabis use should be addressed early in treatment.

Conclusions: Two out of five drug treatment clients used cannabis and a third experienced cannabis-related problems. Many are willing to address cannabis use, but defined treatment pathways are needed.     

Optimisation of the microencapsulation of lavender oil by spray drying

Background: Lavender oil consists of around 100 components and is susceptible to volatilisation and degradation reactions.

Aim: Microencapsulate lavender oil by spray drying using a biocompatible polymeric blend of gum acacia and maltodextrin to protect the oil components. Effect of total polymer content, oil loading, gum acacia, and maltodextrin proportions on the size, yield, loading, and encapsulation efficiency of the microparticles was investigated.

Methods: Morphology and oil localisation within microparticles were assessed by confocal laser scanning electron microscope. Structural preservation and compatibility were assessed using Fourier transform infra-red spectroscopy, differential scanning calorimetry, and gas chromatography–mass spectrometry.

Results: Lavender microparticles of size 12.42?±?1.79?µm prepared at 30 w/w% polymer concentration, 16.67 w/w% oil loading, and 25w/w% gum acacia showed maximum oil protection at high loading (12?mg w/w%), and encapsulation efficiency (77.89 w/w%).

Conclusion: Lavender oil was successfully microencapsulated into stable microparticles by spray drying using gum acacia/maltodextrin polymeric blend.     

Gender,subclinical organ damage and cardiovascular risk stratification in hypertensive patients

Background: The aims of the study were to assess subclinical organ damage in men and women with hypertension and its subsequent effect on cardiovascular risk, and use of new statistical methods for more precise estimation of cardiovascular risk using vascular cardiovascular risk factors: ankle–brachial index (ABI), intima–media thickness (IMT) and pulse wave velocity (PWV).

Methods: We studied 200 patients: 100 hypertensive and 100 normotensive. The parameters we evaluated included: patient age, ABI, IMT, PWV, serum uric acid and serum C-reactive protein (CRP). In addition, the cardiovascular risk according to the SCORE and Framingham scales was assessed.

Results: In the hypertensive group, there were significant correlations between ABI and the Framingham scale in both sexes. In hypertensive women, there were also significant correlations between IMT and the SCORE scale risk, and IMT and the Framingham scale risk.

In normotensive women, there were significant correlations between ABI and the SCORE scale risk, and between ABI and the Framingham scale risk. In normotensive men, there were significant correlations between PWV and the SCORE scale risk, and between PWV and the Framingham scale risk. Lastly, in the group of normotensive men, there were significant correlations between IMT and the SCORE scale risk, and IMT and the Framingham scale risk.

The possibility of correctly classifying a patient into the high-risk category by a logistic regression model using synchronous ABI, IMT and PWV was high – 74% for the risk according to the SCORE scale (66% in men, 88% in women), and 98% for the Framingham scale.

Conclusions: The addition of recognized subclinical target organ damage tests to the estimation of cardiovascular risk can significantly strengthen the prevention of cardiovascular disease.

Cardiovascular risk estimation follow-up with ABI, PWV and IMT increased the probability of correctly classifying people, especially women, into an at least high-risk category according to the SCORE scale, which has valuable therapeutic implications.     

Preclinical pharmacokinetics of a novel anti-c-Met antibody–drug conjugate,SHR-A1403, in rodents and non-human primates

1. The in vivo pharmacokinetics (PK) profiles of a novel c-Met antibody–drug conjugate (ADC), SHR-A1403, were investigated and characterized in mice, rats and monkeys.

2. Serum concentrations of ADC and total antibody were detected using validated ELISA methods. The results showed low systemic clearance of both ADC and total antibody in all three species as reflected by gradual decrease in serum concentrations. Half-life (t_1/2) of ADC ranged from 4.6 to 11.3?days in the three species.

3. Tissue distribution study in tumor-bearing mice showed high accumulation of ¹²⁵I-SHR-A1403 in tumor tissues over the other organs/tissues, indicating the favorable safety of SHR-A1403 and characteristics of an ADC drug.

4. Relatively low grade of anti-drug antibody (ADA) in monkeys had no impact on PK profile of the ADC.

5. During discovery stage, undesirable exposure and/or ADA incidence were observed for SHR-A1403 with high or low drug-antibody ratio (DAR), which was DAR?=?5 to 6 and DAR?=?1, respectively, and therefore prompted selection of an appropriate DAR value (DAR?=?2) for SHR-A1403 used in preclinical development and clinical trials.

6. In conclusion, our work demonstrated favorable PK characterization of SHR-A1403, and supported for investigational new drug application (IND) and the ongoing first-in-human trial in the US.     

Alosetron versus traditional pharmacotherapy in clinical practice: effects on resource use,health-related quality of life,safety and symptom improvement in women with severe diarrhea-predominant irritable bowel syndrome

Objective: Severe diarrhea-predominant irritable bowel syndrome (IBS-D) is associated with decreased health-related quality of life (HRQOL) and increased health care costs. Treatment recommendations for IBS-D often start with traditional pharmacotherapy (TP), with escalation to alosetron, rifaximin or eluxadoline if there is no success. There has been no previous head-to-head clinical trial comparing IBS-D treatment outcome for alosetron versus TP. This study, GSK protocol S3B30020, evaluated resource use, work productivity, health-related quality of life and global symptom response in women with IBS-D who were treated with alosetron or TP.

Methods: A total of 1956 patients who met criteria for severe IBS-D were randomized to treatment with alosetron 1?mg twice daily (BID) or only TP for up to 24 weeks. Work productivity and resource use were evaluated by standard questionnaires, HRQOL by the IBSQOL instrument and IBS symptoms by the Global Improvement Scale (GIS).

Results: Compared to only TP, alosetron-treated patients reported: (1) fewer clinic/office visits for any health problem (p?=?.0181) or for IBS-D (p?=?.0004); (2) reduced use of over-the-counter medications for IBS-D (p < .0001); (3) fewer days of lost work productivity (p < .0001); (4) decreased restriction of social and outdoor activities (p < .0001); and (5) greater global improvement in IBS-D symptoms (p < .0001). Alosetron treatment improved HRQOL scores for all domains (p < .0001). Incidence of adverse events during alosetron use was not remarkable and was similar to that previously reported.

Conclusions: Alosetron 1?mg BID significantly reduced health care utilization and lost productivity, and significantly improved global IBS symptoms, HRQOL, and participation in outdoor and social activities compared with treatment response to TP.     

Specific hypertension smartphone application to improve medication adherence in hypertension: a cluster-randomized trial

Introduction: Digital interventions, such as smartphone applications (apps), are becoming an increasingly common way to support medication adherence and self-management in chronic illness.

Aim: To evaluate the effectiveness of the intervention in pharmacological therapeutic adherence in mild to moderate arterial hypertension (AHT), through an app installed on a mobile phone, as well as the degree of control reached by the patient with this tool.

Methods: Prospective, randomized controlled trial, full study and multicenter study. Four primary care centers participated. One hundred and fifty-four hypertensive patients under antihypertensive treatment were included. Two groups were established: a control group (CG) with usual intervention (n?=?77) and an intervention group (n?=?77) (IG), targeting hypertensive people who owned and regularly used a mobile smartphone, specifically using the app called AlerHTA to promote health education and reminder of appointments. There were three visits: initial, 6 and 12 months. Drug adherence was measured by electronic monitors (MEMSs). The primary outcomes were average daily percentage adherence between 80 and 100%, and AHT control.

Results: A total of 148 patients finished the study. Mean age was 57.5?±?9.9. Global adherence was 77.02% (CI?=?70.25–83.79) and daily adherence was 74.32% (CI?=?67.29–81.35%). Daily adherence was 93.15% and 86.3% in IG, and 70.66% and 62.66% in CG after 6 and 12 months respectively (p < .05). The percentage of uncontrolled patients was 28.3% (CI?=?21.05–35.55%). The control of high blood pressure at 12 months was 17.8% and 38.6% for IG and CG respectively (p < .05). The number of patients needed to treat to avoid non-adherence (NNT) was 4.23 patients.

Conclusions: The intervention with an app installed on the mobile phones of hypertensive patients favors pharmacological therapeutic adherence and improves the percentage of hypertensive patient control.

Trial registration: Spanish Agency of Medicine: EPA-SP UN-HTA-2015-01.     

Hospitalization risk in bipolar disorder patients treated with lurasidone versus other atypical antipsychotics

Objective: This observational study compared the risk of hospitalization for patients with bipolar disorder when treated with lurasidone versus other oral atypical antipsychotics.

Methods: This US commercial claims analysis (4 April 2010 through 24 September 2014) used the Optum Research Database to identify adult patients with bipolar disorder treated with oral atypical antipsychotics (N?=?11,132). The first claim for an atypical antipsychotic defined the index date, with pre-index and post-index periods of 180 and 360 days, respectively. Every month of the post-index period was categorized as monotherapy treatment with lurasidone, aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone, no/minimal treatment or other. Starting with the initial month of treatment, the risk of psychiatric or all-cause hospitalization in the subsequent month was examined based on treatment in the current month and pre-index covariates (age, gender, hospitalizations, emergency room visits, diagnoses for anxiety, alcohol abuse, substance abuse, hypertension, type 2 diabetes and obesity) and time-varying versions of the pre-index covariates using a marginal structural model.

Results: After controlling for covariates, relative to lurasidone, the odds of psychiatric and all-cause hospitalization, respectively, were 2–3 times higher for olanzapine (odds ratio [OR]?=?2.78, CI 1.09, 7.08, p?=?.032; OR?=?3.20, CI 1.24, 8.26, p?=?.016), quetiapine (OR?=?2.80, CI 1.13, 6.95, p?=?.026; OR?=?3.23, CI 1.29, 8.11, p?=?.013), risperidone (OR?=?2.50, CI 1.01, 6.21, p?=?.048; OR?=?2.79, CI 1.11, 7.02, p?=?.029), aripiprazole (OR?=?2.13, CI 0.87, 5.20, p?=?.097; OR?=?2.57, CI 1.04, 6.37, p?=?.041) and ziprasidone (OR =2.31, CI 0.91, 5.85, p?=?.079; OR?=?2.49, CI 0.97, 6.40, p?=?.058).

Conclusions: In this claims database analysis, lurasidone-treated patients with bipolar disorder had a significantly lower risk of psychiatric hospitalization compared to quetiapine, olanzapine and risperidone, but not aripiprazole or ziprasidone. Lurasidone-treated patients had a significantly lower risk of all-cause hospitalization compared to quetiapine, olanzapine, risperidone and aripiprazole, but not ziprasidone.     

Efficacy of istradefylline for gait disorders with freezing of gait in Parkinson’s disease: A single-arm,open-label,prospective, multicenter study

Background: Gait disorders are common in Parkinson’s disease patients who respond poorly to dopaminergic treatment. Blockade of adenosine A_2A receptors is expected to improve gait disorders. Istradefylline is a first-in-class selective adenosine A_2A receptor antagonist with benefits for motor complications associated with Parkinson’s disease.

Research design and methods: This multicenter, open-label, single-group, prospective interventional study evaluated changes in total gait-related scores of the Part II/III Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and Freezing of Gait Questionnaire (FOG-Q) in 31 Parkinson’s disease patients treated with istradefylline. Gait analysis by portable gait rhythmogram was performed.

Results: MDS-UPDRS Part III gait-related total scores significantly decreased at Weeks 4–12 from baseline with significant improvements in gait, freezing of gait, and postural stability. Significant decreases in MDS-UPDRS Part II total scores and individual item scores at Week 12 indicated improved daily living activities. At Week 12, there were significant improvements in FOG-Q, new FOG-Q, and overall movement per 48 h measured by portable gait rhythmogram. Adverse events occurred in 7/31 patients.

Conclusions: Istradefylline improved gait disorders in Parkinson’s disease patients complicated with freezing of gait, improving their quality of life. No unexpected adverse drug reactions were identified.

Trial registration: UMIN-CTR (UMIN000020288).     

Prognostic importance of the albumin to globulin ratio in metastatic gastric cancer patients

Aim: The aim of this study was to evaluate the prognostic importance of the albumin to globulin ratio (AGR) in terms of overall survival (OS) and progression free survival (PFS) in metastatic gastric cancer patients.

Methods: The patients diagnosed with metastatic gastric cancer between 2009 and April 2016 at the hospital have been studied retrospectively. The clinicopathological characteristics, laboratory, and treatment parameters have been assessed. AGR value has been calculated using the following formula (AGR?=?serum albumin/total protein???serum albumin).

Results: In total, 251 patients were included in the study population. The median value of AGR was 1.206 (range?=?0.460–3.130), and the cut-off value was set as 1.20. Based on the cut-off value, 126 patients were categorized in the low AGR group, while the remaining 125 patients were categorized in the high AGR group. ECOG (Eastern Cooperative Oncology Group) performance scores, CEA levels, CA19-9 levels, hemoglobin levels, lactate dehydrogenase levels, and liver metastasis ratios varied significantly between the low and high AGR groups (p?<?.05). The Kaplan-Meier curve has shown that, compared to the low AGR group, the high AGR group has better OS (12.2 vs 9.3 months, p?=?.002) and better PFS (8.0 vs 5.7 months, p?<?.001) rates. The univariate and multivariate analyses also proved that low AGR is an independent bad risk factor in metastatic gastric cancer patients, both in terms of OS (p?=?.019, Hazard Ratio (HR)?=?1.380, 95% Confidence Interval (CI)?=?1.055–1.805) and PFS (p?=?.002, HR?=?1.514, 95% CI?=?1.164–1.968).

Conclusion: In metastatic gastric cancer patients, AGR is an independent prognostic factor for OS and PFS. Thus, in this patient group, the low cost albumin and globulin which can be measured with routine clinical practice may be used as an appropriate prognostic tool.     

A randomized controlled trial comparing tapentadol with oxycodone in non-breastfeeding women post elective cesarean section

Background: Tapentadol may allow greater pain relief with reduced “opioid load” compared to oxycodone. Its use has not been studied in the obstetric population. The objective of this study was to compare the efficacy and side effect profile of tapentadol with oxycodone in patients who received spinal anesthesia for elective cesarean section. The trial was registered with EU Clinical Trials Register with CT number 2016-001621-33.

Methods: This was a multicenter, randomized controlled trial. Randomized patients (n?=?68) received either 50?mg tapentadol or oxycodone 10?mg 12 hourly postoperatively. The primary endpoint was the sum of pain intensity difference over the first 48?hours of treatment (SPID₄₈). Secondary outcomes included time to rescue medications, SPID₃₆, total pain relief (TOTPAR) scores, patient satisfaction scores, sum of total pain relief and pain intensity difference (SPRID) scores, time to rescue medications and side effects experienced. An analysis of covariance model with baseline pain intensity score as a covariate was used for statistical analysis.

Results: There was no significant difference in the primary endpoint of SPID₄₈ with adjusted mean difference -11.45 (95% CI -35.35, 12.45) p?=?.34). Oxycodone showed significantly greater SPID₃₆ scores compared to tapentadol with increased time to rescue medication. Side effects experienced were similar between groups.

Conclusion: Tapentadol did not provide superior pain control or improved tolerability compared to oxycodone post cesarean section. Results should be interpreted however with consideration of administration of intrathecal opioids to all patients in this study and debate over the optimal dose of tapentadol for acute pain.     

Safety concerns of biosimilar hormone products

Background: Currently, biotherapeutic medicines are the most effective options for the treatment of many severe and chronic diseases. For faster market entry of biotherapeutic products and their cost reduction, the principles of “biosimilarity” have been developed. Development and licensing of biosimilars is allowed only after the end of patent exclusivity of the original preparation period.

Purpose: Characteristics of the main safety parameters of biosimilar hormone preparations licensed by EMA.

Methods: This paper analyzes the results demonstrating the similarities and differences between biosimilar and reference hormone products indicated in the EPAR (public assessment report) for the examination of materials presented for the licensing of biosimilar products.

Results: During the development of biosimilar hormone medicines, differences in the glycosylation profile between biosimilar and reference preparations are revealed. As biotherapeutical preparations are produced by cells, the differences in glycosylation profile between biosimilar and referent preparation are predictable. While carrying out clinical studies, a high similarity of biosimilar and reference product effectiveness is shown, but some differences between them in the safety profile are revealed.

Conclusions: The study of biosimilar product safety has shown the necessity of further improvement in safety and standard approaches for the assessment of the immunogenicity of biosimilar products.     

Comparison of a twice daily injection of insulin aspart 50 with insulin aspart 30 in patients with poorly controlled type 2 diabetes

Objective: To compare the efficacy and safety of a twice daily injection of insulin aspart (BIAsp) 30 and BIAsp50 in patients with type 2 diabetes mellitus (T2DM) poorly controlled with oral hypoglycemic agents (OHAs).

Methods: In this 12 week prospective, randomized, parallel trial, a total of 80 T2DM patients, 59?±?10?years old with a disease duration of 9.3?±?6.6?years and HbA1c >7% despite large doses of metformin and sulfonylurea administration, were randomized to receive BIAsp30 (n?=?40) or BIAsp50 (n?=?40). The primary endpoint was a change in HbA1c at week 12.

Results: The changes in HbA1c from baseline were ?2.5%?±?1.0% in the BIAsp50 group and ?2.5%?±?1.2% in the BIAsp30 group (p?=?.897). No difference was observed in the rate of HbA1c target achievement (<7.0%) between BIAsp50 (42.5%) and BIAsp30 (32.5%) (p?=?.495). The change in fasting plasma glucose (FPG) in the BIAsp50 group was lower than that in the BIAsp30 group (p?<?.001), while the change in two-hour postprandial blood glucose (2hPBG) was higher and blood glucose excursion was lower in the BIAsp50 group than that in the BIAsp30 group (p?<?.001, p?<?.001). A significant improvement in HbA1c was observed with BIAsp50 in subgroups with baseline blood glucose excursion >7.8?mmol/L or 2hPBG >17.6?mmol/L compared with BIAsp30. There were no differences in hypoglycemia or body weight between groups.

Conclusions: Compared with BIAsp30, BIAsp50 showed greater efficacy in patients with baseline BG excursion >7.8?mmol/L or 2hPBG >17.6?mmol/L as well as good safety for hypoglycemia.

Clinical trial registration: ChiCTR-IIR-16008958.