Favorable Treatment Effect Research Articles

The INVEST trial: a randomised feasibility trial of psychologically informed vestibular rehabilitation versus current gold standard physiotherapy for people with Persistent Postural Perceptual Dizziness

BackgroundPersistent postural perceptual dizziness (PPPD) is a common and disabling functional neuro-vestibular disorder. We aimed to determine the feasibility and acceptability of conducting a randomised controlled trial of cognitive-behavioural therapy informed vestibular rehabilitation (INVEST intervention) designed for persistent dizziness.MethodsA two-armed parallel groups randomised feasibility study of INVEST vs. a time-matched gold standard vestibular rehabilitation (VRT) control. Participants with PPPD were recruited from a specialist vestibular clinic in London, UK. Participants were individually randomised using a minimisation procedure with allocation concealment. Measures of feasibility and clinical outcome were collected and assessed at 4 months.ResultsForty adults with PPPD were randomised to six sessions of INVEST (n = 20) or gold standard VRT (n = 20). Overall, 59% of patients screened met the inclusion criteria, of which 80% enrolled. Acceptability of INVEST, as assessed against the theoretical framework of acceptability (TFA), was excellent and 80% adhered to all 6 sessions. There were small to moderate treatment effects in favour of INVEST across all measures, including dizziness handicap, negative illness perceptions, symptom focussing, fear avoidance, and distress (standardised mean difference [SMD]g = 0.45; SMDg = 0.77; SMDg = 0.56; SMDg = 0.50, respectively). No intervention-related serious adverse events were reported.ConclusionsThe study results give strong support for the feasibility of a full-scale trial. Both arms had high rates of recruitment, retention, and acceptability. There was promising support of the benefits of integrated cognitive-behavioural therapy-based vestibular rehabilitation compared to gold standard vestibular rehabilitation. The study fulfilled all the a-priori criteria to advance to a full-scale efficacy trial.Trial registration numberISRCTN10420559.

Immediate results of using both internal thoracic arteries for coronary artery bypass surgery in patients with ischemic artery disease

Objective: To compare direct results of «in situ» and Y-graft bimammary autoarterial bypass in patients having coronary artery disease.Methods: From January 2018 to November 2020, 107 patients having ischemic artery disease undergone coronary artery bypass surgery in the Cardiac Surgery Department No.1 of the Federal State Budgetary Institution "Federal Center for Cardiovascular Surgery" of the Ministry of Health of the Russian Federation (Krasnoyarsk). The distribution of the groups was carried out in a 3:1 ratio: in the first group (24 patients) both internal thoracic arteries were used for myocardial revascularization according to the «in situ» technique, in the second group (composite bypass surgery) (83 patients) the right internal thoracic artery was anastomosed with a free graft with the left internal thoracic artery (Y- graft).Results: There were no cases of hospital mortality. The duration of operations in the composite bypass group was significantly higher than in the «in situ» group (126.4 minutes ± 20.1 minutes versus 172.3 minutes ± 27.1 minutes, p = 0.038). The reason for extra time is the necessity to put a large number of distal anastomoses. Bleeding in the early postoperative period was observed only in one case (1.2%) in the composite bypass group. Perioperative myocardial infarctions, neurological complications, and deep wound infection of the sternum weren't observed in any group. One patient from the «in situ» group (4.2%) and one patient from the composite bypass grafting group (1.2%), experienced the postoperative period complicated by a superficial wound infection in the area of the sternotomy access (p = 0.649). In the «in situ» group, average blood flow velocity according to flowmetry data was 32 ml / min ± 8.1 ml / min, and in the composite shunting group it counted 51.8 ml / min ± 12.3 ml / min, p = 0.001.Conclusions. Using both internal thoracic arteries for coronary artery bypass surgery provides a favorable effect of surgical treatment in the postoperative period. This operation technique can be safely performed with low mortality rate and less complications. It may be associated with improved long-term patient survival; but this requires further analysis of the study results in a longer period.

Target temperature management following cardiac arrest: a systematic review and Bayesian meta-analysis

BackgroundTemperature control with target temperature management (TTM) after cardiac arrest has been endorsed by expert societies and adopted in international clinical practice guidelines but recent evidence challenges the use of hypothermic TTM.MethodsSystematic review and Bayesian meta-analysis of clinical trials on adult survivors from cardiac arrest undergoing TTM for at least 12 h comparing TTM versus no TTM or with a separation > 2 °C between intervention and control groups using the PubMed/MEDLINE, EMBASE, CENTRAL databases from inception to 1 September 2021 (PROSPERO CRD42021248140). All randomised and quasi-randomised controlled trials were considered. The risk ratio and 95% confidence interval for death (primary outcome) and unfavourable neurological recovery (secondary outcome) were captured using the original study definitions censored up to 180 days after cardiac arrest. Bias was assessed using the updated Cochrane risk-of-bias for randomised trials tool and certainty of evidence assessed using the Grading of Recommendation Assessment, Development and Evaluation methodology. A hierarchical robust Bayesian model-averaged meta-analysis was performed using both minimally informative and data-driven priors and reported by mean risk ratio (RR) and its 95% credible interval (95% CrI).ResultsIn seven studies (three low bias, three intermediate bias, one high bias, very low to low certainty) recruiting 3792 patients the RR by TTM 32–34 °C was 0.95 [95% CrI 0.78—1.09] for death and RR 0.93 [95% CrI 0.84—1.02] for unfavourable neurological outcome. The posterior probability for no benefit (RR ≥ 1) by TTM 32–34 °C was 24% for death and 12% for unfavourable neurological outcome. The posterior probabilities for favourable treatment effects of TTM 32–34 °C were the highest for an absolute risk reduction of 2–4% for death (28–53% chance) and unfavourable neurological outcome (63–78% chance). Excluding four studies without active avoidance of fever in the control arm reduced the probability to achieve an absolute risk reduction > 2% for death or unfavourable neurological outcome to ≤ 50%.ConclusionsThe posterior probability distributions did not support the use of TTM at 32–34 °C compared to 36 °C also including active control of fever to reduce the risk of death and unfavourable neurological outcome at 90–180 days. Any likely benefit of hypothermic TTM is smaller than targeted in RCTs to date.

English

This article studies the potential use of the Rosemarry (REO) microemulsion with/without chitosan to assess the growth inhibition of Gram-positive and Gram-negative pathogenic bacteria represented by Listeria monocytogenes and Escherichia coli. The chicken samples were divided into four groups after inoculation of E. coli and L. monocytogenes separately: control group (without treatment), 1% chitosan nanoparticle treatment group, 0.5% REO microemulsion treatment group, and 0.5% REO + 1% chitosan microemulsion treatment group. Chicken samples were dipped into the treatments for 15 days of refrigerated storage at 4°C. All groups were kept refrigerated, and bacterial counts were taken on days 0, 1, 3, 6, 9, 12 and 15. Chitosan nanoparticle and REO microemulsion with/without chitosan were spherical shape and showed a narrow size distribution of 23.98 ± 0.83, 34.24 ± 2.2 and 28.01 ± 1.36 nm with a polydispersity index (PDI) of 0.86, 0.33 and 0.54, respectively indicating that greater homogeneity was achieved. REO chitosan microemulsion has 12 components detected by GC-Mass as follows: pinene (22.21%), borneol (21.32%), 1-(4-methoxyphenyl) ethanoneoxime (3.48%), oxocamphor (0.49%), camphor (2.99%), limonene (0.29%), cis-linalool oxide (0.87), 2-(5-chloro-methoxyphenyl) pyrrole (2.19%), homofarnesol (0.27%), levoverbenone (0.45%), peruviol (0.73%) and campesterol (1.22%). The results showed a substantial reduction in L. monocytogenes and E. coli count in all treatment groups when compared to the control group, with the greatest inhibitory efficacy in the 0.5% REO chitosan microemulsion group. A favorable effect of chitosan treatment on chicken acceptability during refrigerated storage was reported, with an improvement in the sensory qualities of the products. Thus, REO chitosan microemulsion is advised to be used in chicken to enhance resistance to harmful microorganisms. © 2022 Friends Science Publishers

Systemic effects of oral appliance treatment for sleep related breathing disorders

Sleep related breathing disorders (SRBDs) are a spectrum of diseases characterized by difficulties in airflowduring sleep. Central sleep apnea, obstructive sleep apnea (OSA), sleep-related hypoventilation, and hypoxemiadisorder are included in this disease entity. OSA is known to be the most common SRBDs and studies show its significant correlation with general health issues including hypertension, arrhythmia, diabetes, and metabolicsyndrome. The relationship between cardiovascular risk and OSA is especially significant with systemic inflammation, intermittent hypoxia, and increased oxidative stress considered as the underlying mechanism. Previous studies show that oral appliance treatment for OSA has a positive impact on lowering blood pressure and such an effect is non-inferior to that of continuous positive airway pressure therapy. More recent studies also support the favorable effect of oral appliance treatment for OSA patients in the aspect of endocrine, psychologic disorders, and cogni-tive function. Furthermore oral appliance treatment for OSA is known to improve the overall quality of life and daytime sleepiness levels of the patient.The dentist who is experienced in dental sleep medicine can easily identify patients with the risk of OSA andprovide appropriate treatment. The dentist should play an important part in the diagnosis and treatment of OSAwhich is inevitably connected to the well-being of the patient and better treatment results for various conditions. So the objective of this article is to assist dental professionals in gaining knowledge and insight of the systemic effects of oral appliance treatment for OSA.

Can pharmacological, psychological and non-invasive brain stimulation interventions prevent depression after stroke? A cochrane review summary with commentary.

Depression is very common in patients after a stroke and it can impact recovery. The Cochrane Review aimed to determine whether psychological therapy, pharmacological interventions, non-invasive brain stimulation, or their combination can prevent depression after stroke. The population addressed were patients who suffered from a stroke and had no previous diagnosis of depressive disorders. Studies comparing pharmacological intervention to placebo, psychological therapy to usual care, and non-invasive brain stimulation to sham stimulation or usual care were included. Outcome information was available for nine pharmacological and two psychological trials, showing favorable treatment effects. The available evidence suggests that pharmacological interventions and psychological therapy may prevent depression and improve mood after stroke. Although, the current evidence is of very low quality resulting in serious uncertainties about the estimates of effect observed.

Demonstrative Experiment on the Favorable Effects of Static Electric Field Treatment on Vitamin D3-Induced Hypercalcemia

Simple SummaryStatic electric field (SEF) treatment by high-voltage alternating current is a traditional complementary medicine in Japan. Although it is believed that the SEF-induced electric current serves to regulate cellular or humoral responses in patients, the mechanism for SEF treatment remains poorly understood. There have been very few experimental reports on the biological action with SEF treatment. The aim of this study was to elucidate the effects of SEF treatment on vitamin D3 (Vit D3)-induced abnormalities in mice. SEF treatment improved the abnormalities in the renal function tests and the imbalance of serum electrolytes. In addition, this treatment remarkably attenuated the Vit D3-induced tissue injuries (severe tissue calcification in the kidneys, hearts, and stomachs). It was likely that the SEF treatment had some favorable effects on the metabolism of calcium. In conclusion, this study provides important evidence that SEF treatment can reduce hypercalcemia and remove calcium deposits from the renal, cardiac, and gastric tissues. SEF treatment is useful in the regulation of disorders caused by an imbalance of serum electrolytes. This study experimentally demonstrates the favorable effects of SEF treatment on Vit D3-induced hypercalcemia. For small animals, the larger the body surface area per body weight becomes, the higher the therapeutic efficacy with SEF treatment.The purpose of this study was to elucidate the effects of static electric field (SEF) treatment on vitamin D3 (Vit D3)-induced hypercalcemia and renal calcification in mice. The mice were assigned to three groups: Vit D3-treated mice, mice treated with Vit D3 and SEF (Vit D3 + SEF), and untreated mice. After the administration of Vit D3, the Vit D3 + SEF-treated mice were exposed to SEF treatment by a high-voltage alternating current over five days. Serum biochemical examinations revealed that both the creatinine and blood urea nitrogen concentrations were significantly higher in the Vit D3-treated group. Significantly, decreased Cl concentrations, and increased Ca and inorganic phosphorus concentrations, were found in the Vit D3-treated group. In the Vit D3 + SEF-treated group, these parameters returned to the levels of the untreated group. In the Vit D3-treated group, histopathological examinations showed marked multifocal calcification in the lumens of the renal tubules and the renal parenchyma. The myocardium was replaced by abundant granular mineralization (calcification), with degeneration and necrosis of the calcified fibers. The stomach showed calcification of the cardiac mucosa. SEF treatment remarkably attenuated the Vit D3-induced hypervitaminotic injuries. In conclusion, this study provides important evidence that SEF treatment can reduce hypercalcemia and remove calcium deposits from the renal, cardiac, and gastric tissues. SEF treatment is useful in the regulation of disorders caused by an imbalance of serum electrolytes.

Corrigendum

AndrologiaVolume 53, Issue 9 e14205 CORRIGENDUMFree Access Corrigendum This article corrects the following: Favourable effect of β-glucan treatment against cisplatin-induced reproductive system damage in male rats Kürşat Kaya, Osman Ciftci, Muhterem Aydın, Aslı Cetin, Neşe Basak, Volume 51Issue 9Andrologia First Published online: July 5, 2019 First published: 10 September 2021 https://doi.org/10.1111/and.14205AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat In the article (Kaya et al., 2019), it has come to our attention that the published version of Table 1 is incorrect. This table has now been corrected as follows: TABLE 1 The levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione (GSH) and thiobarbituric acid-reactive substances (TBARS) in testis tissue of rats Groups TBARS nmol/g tissue Reduced GSH nmol/g tissue CAT k/mg protein SOD U/mg protein GPx U/mg protein Control 11.1 ± 2.27a 245.5 ± 9.68a 0.050 ± 0.003a 38.13 ± 2.12a 2.75 ± 0.19a CP 19.6 ± 1.14b 134.3 ± 7.7b 0.031 ± 0.002b 29.27 ± 2.18b 1.88 ± 0.14b Β-Glucan 10.7 ± 1.19a 234.6 ± 10.5ac 0.049 ± 0.001ac 40.43 ± 1.96a 2.65 ± 0.18a CP plus β-Glucan 13.4 ± 2.06c 216.8 ± 9.9c 0.045 ± 0.002c 37.35 ± 2.19a 2.23 ± 0.17c Note: The data are expressed in mean ± SD for seven animals per group. Means bearing different superscripts within same column were significantly different (P < 0.01). REFERENCE Kaya, K., Ciftci, O., Aydın, M., Cetin, A., & Basak, N. (2019). Favourable effect of β-glucan treatment against cisplatin-induced reproductive system damage in male rats. Andrologia., 51, e13342. https://doi.org/10.1111/and.13342Wiley Online LibraryPubMedWeb of Science®Google Scholar Volume53, Issue9October 2021e14205 ReferencesRelatedInformation

Integrated Bioinformatics Analysis of Potential mRNA and miRNA Regulatory Networks in Mice With Ischemic Stroke Treated by Electroacupuncture.

Background: The complicated molecular mechanisms underlying the therapeutic effect of electroacupuncture (EA) on ischemic stroke are still unclear. Recently, more evidence has revealed the essential role of the microRNA (miRNA)–mRNA networks in ischemic stroke. However, a systematic analysis of novel key genes, miRNAs, and miRNA–mRNA networks regulated by EA in ischemic stroke is still absent.Methods: We established a middle cerebral artery occlusion (MCAO) mouse model and performed EA therapy on ischemic stroke mice. Behavior tests and measurement of infarction area were applied to measure the effect of EA treatment. Then, we performed RNA sequencing to analyze differentially expressed genes (DEGs) and functional enrichment between the EA and control groups. In addition, a protein–protein interaction (PPI) network was built, and hub genes were screened by Cytoscape. Upstream miRNAs were predicted by miRTarBase. Then hub genes and predicted miRNAs were verified as key biomarkers by RT-qPCR. Finally, miRNA–mRNA networks were constructed to explore the potential mechanisms of EA in ischemic stroke.Results: Our analysis revealed that EA treatment could significantly alleviate neurological deficits in the affected limbs and reduce infarct area of the MCAO model mice. A total of 174 significant DEGs, including 53 upregulated genes and 121 downregulated genes, were identified between the EA and control groups. Functional enrichment analysis showed that these DEGs were associated with the FOXO signaling pathway, NF-kappa B signaling pathway, T-cell receptor signaling pathway, and other vital pathways. The top 10 genes with the highest degree scores were identified as hub genes based on the degree method, but only seven genes were verified as key genes according to RT-qPCR. Twelve upstream miRNAs were predicted to target the seven key genes. However, only four miRNAs were significantly upregulated and indicated favorable effects of EA treatment. Finally, comprehensive analysis of the results identified the miR-425-5p-Cdk1, mmu-miR-1186b-Prc1, mmu-miR-434-3p-Prc1, and mmu-miR-453-Prc1 miRNA–mRNA networks as key networks that are regulated by EA and linked to ischemic stroke. These networks might mainly take place in neuronal cells regulated by EA in ischemic stroke.Conclusion: In summary, our study identified key DEGs, miRNAs, and miRNA–mRNA regulatory networks that may help to facilitate the understanding of the molecular mechanism underlying the effect of EA treatment on ischemic stroke.

Comparison of Accelerated Resolution Therapy for PTSD Between Veterans With and Without Prior PTSD Treatment.

Post-traumatic stress disorder (PTSD) is a psychiatric disorder commonly caused by a traumatic event(s) and prevalent among service members and veterans. Accelerated Resolution Therapy (ART) is an emerging "mind-body" psychotherapy for PTSD that is generally briefer and less expensive than current first-line treatments, such as cognitive processing therapy (CPT) and prolonged exposure (PE) therapy. This study examined the results of ART for treatment of military-related PTSD, with stratification by prior PTSD treatment types, including service members/veterans with reported residual PTSD symptoms following receipt of first-line recommended psychotherapy. Four groups were constructed and compared based on self-reported prior PTSD treatment history: treatment-naïve (n = 33), pharmacotherapy only (n = 40), first-line psychotherapy (CPT and/or PE) (n = 33), and other psychotherapy (n = 42). Participants were assessed for PTSD symptoms at baseline, post-treatment, and 6-month follow-up using the 17-item Military PTSD Checklist (PCL-M), as well as assessment of depressive, anxiety, and sleep symptoms. The study was approved by the Institutional Review Board at University of South Florida. Among 148 veterans/service members who enrolled and started treatment with ART, 106 (71.6%) completed treatment in a mean of 3.5 treatment sessions, and 55 (51.9%) provided 6-month follow-up data. Mean age was 43.8 years, 95% were male, and 84% were of white race. Within-group standardized effect sizes for pre-to-post changes in PTSD scores (PCL-M) were large at 1.48, 1.11, 1.88, and 1.03 for the treatment-naïve, pharmacotherapy only, first-line psychotherapy, and other psychotherapy groups, respectively. Among treatment completers, the clinically significant treatment response rate (reduction of ≥10 points on the PCL-M) was highest in the treatment-naïve (83%) and first-line psychotherapy (88%) groups. Similar significant symptom reductions were observed for measures of depression and anxiety, and favorable treatment effects were generally sustained at 6-month follow-up. In a brief treatment period, ART appears to result in substantial reductions in symptoms of PTSD among veterans, including those with residual PTSD symptoms after prior treatment with first-line psychotherapies endorsed by the U.S. Department of Defense and Veterans Affairs. These results suggest that ART be considered as a potential first-line treatment modality for veterans with PTSD.

Effect of surgical treatment on myocardial strain in patients with pheochromocytoma and paraganglioma: a mini-review and meta-analysis.

Information on systolic dysfunction, as assessed by left-ventricular (LV) mechanics, in patients with pheochromocytoma after surgical treatment is scanty. We performed a systematic meta-analysis of speckle tracking echocardiographic studies to provide an updated comprehensive information on this issue. The PubMed, OVID-MEDLINE, and Cochrane library databases were analyzed to search for articles published from the inception up to May 31st 2021. Studies were identified using MeSH terms and crossing the following search items: "myocardial strain" "left ventricular mechanics", "speckle tracking echocardiography", "systolic dysfunction", "pheochromocytoma", and "paraganglioma". A total of 92 surgically treated patients with pheochromocytoma/paraganglioma were included in 3 longitudinal studies. Successful surgical treatment was associated with a decrease in relative wall thickness (SMD -0.25 ± 0.10, CI -0.45/-0.05, p < 0.01) and an improvement in global longitudinal strain (SMD -0.45 ± 0.10, CI -0.66/-0.24, p < 0.0001). The favorable effects of treatment on LV geometry and mechanics were not accompanied by significant changes in ejection fraction (SMD -0.07 ± 0.10, CI -0.27/0.12, p = 0.44). This meta-analysis adds a new piece of evidence, suggesting that surgical treatment of patients with pheochromocytoma impacts favorably on LV geometry and LV mechanics, and, more importantly, the assessment of LV changes in this setting can no longer rely on conventional echocardiographic parameters such as ejection fraction.

A Systematic Review of the Efficacy and Safety of Direct Oral Anticoagulants in Atrial Fibrillation Patients with Diabetes Using a Risk Index.

Diabetes mellitus (DM) represents an independent risk factor for chronic AF and is associated with unfavorable outcomes. We aimed to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF), with and without diabetes mellitus (DM), using a new risk index (RI) defined as: RI . In particular, an RI lower than 1 suggests a favorable treatment effect. We searched MEDLINE, MEDLINE In-Process, EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials. The risk index (RI) was calculated in terms of efficacy (rate of stroke/systemic embolism (stroke SEE)/rate of patients with and without DM; rate of cardiovascular death/rate of patients with and without DM) and safety (rate of major bleeding/rate of patients with and without DM) outcomes. AF patients with DM (n = 22,057) and 49,596 without DM were considered from pivotal trials. DM doubles the risk index for stroke/SEE, major bleeding (MB), and cardiovascular (CV) death. The RI for stroke/SEE, MB, and CV death was comparable in patients treated with warfarin or DOACs. The lowest RI was in DM patients treated with Rivaroxaban (stroke/SEE, RI = 0.08; CV death, RI = 0.13). The RIs for bleeding were higher in DM patients treated with Dabigatran (RI110 = 0.32; RI150 = 0.40). Our study is the first to use RI to homogenize the efficacy and safety data reported in the DOACs pivotal studies against warfarin in patients with and without DM. Anticoagulation therapy is effective and safe in DM patients. DOACs appear to have a better efficacy and safety profile than warfarin. The use of DOACs is a reasonable alternative to vitamin-K antagonists in AF patients with DM. The RI can be a reasonable tool to help clinicians choose between DOACs or warfarin in the peculiar set of AF patients with DM.

Early Renoprotective Effect of Ruxolitinib in a Rat Model of Diabetic Nephropathy.

Diabetic kidney disease (DKD) is still one of the unresolved major complications of diabetes mellitus, which leads ultimately to end-stage renal disease in both type 1 and type 2 diabetes patients. Available drugs that suppress the renin–angiotensin system have partially minimized the disease impact. Yet, there is an unmet need for new therapeutic interventions to protect the kidneys of diabetic patients. In DN, glomerular sclerosis and tubulointerstitial fibrosis are mediated through several pathways, of which JAK/STAT is a key one. The current study explored the potential renoprotective effect of the JAK1/JAK2 inhibitor ruxolitinib (at doses of 0.44, 2.2, and 4.4 mg·kg−1) compared to that of enalapril at a dose of 10 mg·kg−1, in a rat model of streptozotocin-induced diabetes mellitus over 8 weeks. The effect of ruxolitinib was assessed by determining urinary albumin/creatinine ratio, serum level of cystatin, and levels of TGF-β1, NF-κB, and TNF-α in renal tissue homogenates by biochemical assays, the glomerular sclerosis and tubulointerstitial fibrosis scores by histological analysis, and fibronectin, TGF-β1, and Vimentin levels by immunohistochemical staining with the respective antibodies. Our results revealed a significant early favorable effect of a two-week ruxolitinib treatment on the renal function, supported by a decline in the proinflammatory biomarkers of DKD. This pre-clinical study suggests that the renoprotective effect of ruxolitinib in the long term should be investigated in animals, as this drug may prove to be a potential option for the treatment of diabetic kidney disease.

Soft tissue integration of different abutment surfaces: An experimental study with histological analysis.

To evaluate whether abutment surface and surface bio-activation have an effect on soft tissue morphogenesis. 36 patients (36 implants) were included. Abutments were randomly divided into 4 groups (n=9): Smooth Surface-MAChined (MAC), Ultrathin Threaded Microsurface (UTM), MAC Plasma of Argon activated (Plasma-MAC), and UTM Plasma of Argon activated (Plasma-UTM). After 2months of healing, soft tissue samples were collected and prepared for histological analysis. The margin of the peri-implant mucosa (PM), the apical extension of the barrier epithelium (aJE), and the apical location of the abutment (AM) were identified. Significances of differences among groups were tested by means of the Kruskal-Wallis test and between pairs of results by means of the Mann-Whitney test. The mean (SD) vertical dimension of the mucosa was 2.5mm (1.0), including a connective tissue portion (CTP) of 0.8mm (0.8) in the MAC group; 3.6mm (0.2) with a CTP of 1.6mm (0.4) in the Plasma-MAC group; 3.2mm (1.0), with a CPT of 0.5mm (0.6) in the UTM; and 3.3mm (0.8), with a CPT of 0.9mm (0.7) in the Plasma-UTM group. Statistically significant differences were observed in the aJE-AM height and PM-aJE profile among the four experimental groups (p=.042 and p=.039, respectively). The Mann-Whitney test indicated differences between the Plasma-abutments and the untreated abutments both for PM-AM (p=.025) and AjE-AM (p=.021). The differences appeared more evident when the preoperative soft tissue thickness was ≤2mm. Within its limits, the study demonstrated a favorable effect of the plasma treatment on the connective tissue portion tissues. Plasma-MAC group highlighted the best performance. This behavior appeared strictly correlated with the soft tissue thickness.

Efficacy of therapist-delivered transdiagnostic CBT for patients with persistent physical symptoms in secondary care: a randomised controlled trial

Abstract Background Medically unexplained symptoms otherwise referred to as persistent physical symptoms (PPS) are debilitating to patients. As many specific PPS syndromes share common behavioural, cognitive, and affective influences, transdiagnostic treatments might be effective for this patient group. We evaluated the clinical efficacy and cost-effectiveness of a therapist-delivered, transdiagnostic cognitive behavioural intervention (TDT-CBT) plus (+) standard medical care (SMC) v. SMC alone for the treatment of patients with PPS in secondary medical care. Methods A two-arm randomised controlled trial, with measurements taken at baseline and at 9, 20, 40- and 52-weeks post randomisation. The primary outcome measure was the Work and Social Adjustment Scale (WSAS) at 52 weeks. Secondary outcomes included mood (PHQ-9 and GAD-7), symptom severity (PHQ-15), global measure of change (CGI), and the Persistent Physical Symptoms Questionnaire (PPSQ). Results We randomised 324 patients and 74% were followed up at 52 weeks. The difference between groups was not statistically significant for the primary outcome (WSAS at 52 weeks: estimated difference −1.48 points, 95% confidence interval from −3.44 to 0.48, p = 0.139). However, the results indicated that some secondary outcomes had a treatment effect in favour of TDT-CBT + SMC with three outcomes showing a statistically significant difference between groups. These were WSAS at 20 weeks (p = 0.016) at the end of treatment and the PHQ-15 (p = 0.013) and CGI at 52 weeks (p = 0.011). Conclusion We have preliminary evidence that TDT-CBT + SMC may be helpful for people with a range of PPS. However, further study is required to maximise or maintain effects seen at end of treatment.

POS0020 EFFICACY AND SAFETY OF SECUKINUMAB IN PATIENTS WITH ROTATOR CUFF TENDINOPATHY: A 24-WEEK, RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PHASE II PROOF-OF-CONCEPT TRIAL

Background:Rotator cuff tendinopathy (RC TP) is a multifactorial condition and one of the most common causes of musculoskeletal burden. Current standard of care (SoC) is limited to pain relief with NSAIDs and physiotherapy. Recent evidence indicates that IL-17A-expressing tendon-resident immune cells are present in human overuse tendinopathy, and IL-17A levels are increased in early human tendinopathic tissue samples [1, 2]. Secukinumab (SEC) is a fully human, monoclonal antibody that binds to and neutralises IL-17A.Objectives:To evaluate the efficacy and safety of SEC in patients with active overuse RC TP refractory to oral NSAIDs/acetaminophen, physiotherapy or corticosteroid injections.Methods:96 patients with symptomatic RC TP with no or &lt;50% rupture were randomly assigned to receive seven subcutaneous injections of SEC 300 mg or placebo (PBO) at baseline and Weeks 1, 2 and 3, followed by every 4 weeks starting at Week 4. The primary endpoint was change from baseline in the Western Ontario Rotator Cuff (WORC) index score at Week 14 for SEC vs PBO (two-sided p&lt;0.1). Secondary endpoints included, visual analogue scale (VAS) pain score, Disability of Arm, Shoulder and Hand Questionnaire (QuickDASH) score, American Shoulder and Elbow Surgeons Shoulder Evaluation Form (ASES), EQ-5D-5L score and patient global assessment (PGA) score. All endpoints were assessed through 24 weeks.Results:Clinically relevant improvement in both SEC and PBO groups on top of SoC treatment was observed, with no statistically significant difference demonstrated in the full study population on physical symptoms and function (Table 1). Similar results were observed in the secondary endpoints with marked improvement in both groups over time. Exploratory post-hoc analyses in a subpopulation of 39% of the study subjects with non-acute, moderate to severe disease, SEC provided significant and clinically relevant improvements vs PBO through Week 24 in total WORC score (overall treatment difference: 19.2, p &lt;0.01) and pain (VAS, overall treatment difference: 15, p = 0.02) with early effect observed after two weeks (Figure 1). A favourable treatment effect in the more severe subgroup was demonstrated in other patient-reported outcomes. No serious adverse events were reported.Conclusion:Although SEC did not demonstrate a significant benefit vs PBO in the overall patient population with active overuse RC TP, SEC did provide benefit in the subpopulation with non-acute, moderate to severe disease. Larger clinical trials of SEC in this area are warranted.

Treatment effects in randomised trials using routinely collected data for outcome assessment versus traditional trials: meta-research study

ObjectiveTo compare effect estimates of randomised clinical trials that use routinely collected data (RCD-RCT) for outcome ascertainment with traditional trials not using routinely collected data.DesignMeta-research study.Data sourceStudies included in the...

Effect of early sleep apnoea treatment with adaptive servo-ventilation in acute stroke patients on cerebral lesion evolution and neurological outcomes: study protocol for a multicentre, randomized controlled, rater-blinded, clinical trial (eSATIS: early Sleep Apnoea Treatment in Stroke)

BackgroundSleep-disordered breathing (SDB) is highly prevalent in acute ischaemic stroke and is associated with worse functional outcome and increased risk of recurrence. Recent meta-analyses suggest the possibility of beneficial effects of nocturnal ventilatory treatments (continuous positive airway pressure (CPAP) or adaptive servo-ventilation (ASV)) in stroke patients with SDB. The evidence for a favourable effect of early SDB treatment in acute stroke patients remains, however, uncertain.MethodseSATIS is an open-label, multicentre (6 centres in 4 countries), interventional, randomized controlled trial in patients with acute ischaemic stroke and significant SDB. Primary outcome of the study is the impact of immediate SDB treatment with non-invasive ASV on infarct progression measured with magnetic resonance imaging in the first 3 months after stroke. Secondary outcomes are the effects of immediate SDB treatment vs non-treatment on clinical outcome (independence in daily functioning, new cardio-/cerebrovascular events including death, cognition) and physiological parameters (blood pressure, endothelial functioning/arterial stiffness). After respiratory polygraphy in the first night after stroke, patients are classified as having significant SDB (apnoea-hypopnoea index (AHI) > 20/h) or no SDB (AHI < 5/h). Patients with significant SDB are randomized to treatment (ASV+ group) or no treatment (ASV− group) from the second night after stroke. In all patients, clinical, physiological and magnetic resonance imaging studies are performed between day 1 (visit 1) and days 4–7 (visit 4) and repeated at day 90 ± 7 (visit 6) after stroke.DiscussionThe trial will give information on the feasibility and efficacy of ASV treatment in patients with acute stroke and SDB and allows assessing the impact of SDB on stroke outcome. Diagnosing and treating SDB during the acute phase of stroke is not yet current medical practice. Evidence in favour of ASV treatment from a randomized multicentre trial may lead to a change in stroke care and to improved outcomes.Trial registrationClinicalTrials.gov NCT02554487, retrospectively registered on 16 September 2015 (actual study start date, 13 August 2015), and www.kofam.ch (SNCTP000001521).

Urate, Blood Pressure, and Cardiovascular Disease: Evidence From Mendelian Randomization and Meta-Analysis of Clinical Trials.

Serum urate has been implicated in hypertension and cardiovascular disease, but it is not known whether it is exerting a causal effect. To investigate this, we performed Mendelian randomization analysis using data from UK Biobank, Million Veterans Program and genome-wide association study consortia, and meta-analysis of randomized controlled trials. The main Mendelian randomization analyses showed that every 1-SD increase in genetically predicted serum urate was associated with an increased risk of coronary heart disease (odds ratio, 1.19 [95% CI, 1.10-1.30]; P=4×10-5), peripheral artery disease (1.12 [95% CI, 1.03-1.21]; P=9×10-3), and stroke (1.11 [95% CI, 1.05-1.18]; P=2×10-4). In Mendelian randomization mediation analyses, elevated blood pressure was estimated to mediate approximately one-third of the effect of urate on cardiovascular disease risk. Systematic review and meta-analysis of randomized controlled trials showed a favorable effect of urate-lowering treatment on systolic blood pressure (mean difference, -2.55 mm Hg [95% CI, -4.06 to -1.05]; P=1×10-3) and major adverse cardiovascular events in those with previous cardiovascular disease (odds ratio, 0.40 [95% CI, 0.22-0.73]; P=3×10-3) but no significant effect on major adverse cardiovascular events in all individuals (odds ratio, 0.67 [95% CI, 0.44-1.03]; P=0.07). In summary, these Mendelian randomization and clinical trial data support an effect of higher serum urate on increasing blood pressure, which may mediate a consequent effect on cardiovascular disease risk. High-quality trials are necessary to provide definitive evidence on the specific clinical contexts where urate lowering may be of cardiovascular benefit.

Neoadjuvant immunotherapy in nonsmall cell lung cancer.

Immune-checkpoint inhibitors have improved treatment outcomes for metastatic nonsmall cell lung cancer (NSCLC). Whether this therapeutic potential might also translate into survival gains in earlier stages is an area of active research. Based on preclinical rationale the neoadjuvant administration of immunotherapeutic agents is of special interest. This review is intended to summarize the existing background, published early clinical evidence, and provide perspective on future developments regarding neoadjuvant immunotherapy in NSCLC. Preclinical data and early clinical trials suggest promising efficacy of immune-checkpoint inhibitors in early-stage NSCLC when administered in a neoadjuvant manner. Compared to historical controls, the rates of pathologic and radiographic regression seem to be improved, in particular when immunotherapy is combined with standard platinum-based chemotherapy. These favorable treatment effects are accompanied by a moderate toxicity profile without impairing surgical outcomes. Several phase III trials are underway to provide definitive evidence. Neoadjuvant immunotherapy has the potential to substantially improve outcomes in early-stage NSCLC and therefore to change daily clinical practice in the near future.