Evaluation of efficacy and safety of doxofylline 800mg sustained release tablet in treatment of patients with COPD: an open label, prospective and RCT

Background: COPD is a major cause of health care burden worldwide and leading cause of death that is increasing in prevalence. Methylxanthines are used in the treatment of patients with asthma and COPD. Doxofylline (methylxanthine) shows improved disease control, reduced total daily dose of inhaled b2 agonists and improved patient compliance.Methods: This was a prospective, open labelled, randomized, two-arm, parallel group, controlled, clinical trial. 115 patients were randomized to two groups. Patients in group A received tablet doxofylline 400mg BD whereas patients in group B received tablet doxofylline 800mg SR for 4 weeks. Primary outcome measure of trial was change in FEV1 and secondary outcome measure were change in FVC/FEV1, change in symptoms score, effect on health-related quality of life (HRQOL) and safety of study medication.Results: At 4 week the FEV1increase by 13.028% and 17.647% in group A and B respectively. In group A FEV1/FVC increase by 5.79% and in group B it increases by 9.57% at 4 weeks. The symptom score of cough decrease by 77.35% and 97.43% in group A and group B respectively at 4 weeks. In group A shortness of breath decrease by 77.60% and in group B it decreases by 95.90% at 4 weeks. Tightness in chest decrease by 86.29% and 98.40% in group A and group B respectively at 4 weeks.Conclusions:Doxofylline 800mg sustained release tablet provided significantly greater improvement in FEV1, symptomatic control and health related quality of life compared to doxofylline 400mg.

Comparative study of safety and efficacy of pregabalin and gabapentin in management of neuropathic pain associated with chronic lumbar radiculopathy

Background: Chronic lumbar radiculopathy a clinical condition in which there is back and leg pain associated with sensory, reflex, or motor deficits in the area of nerve root distribution lasting for more than 12 weeks. The prevalence of lumbar radiculopathy has been reported to be 5.3% in men and 3.7% in women. Pregabalin and gabapentin, which fit in to a new category of drugs called as alpha-2-delta (α2δ) modulators, have been discovered to be effective in the treatment of neuropathic pain related with multiple conditions. So this study was done to compare safety and efficacy of pregabalin and gabapentin in management of pain associated with chronic lumbar radiculopathy.Methods: This was a randomized two arm comparative prospective study. Total 160 patients were enrolled and randomized equally into 2 groups. Group A patients were given capsule pregabalin 75 mg two times a day orally, Group B patients were given tablet gabapentin 300 mg two times a day. Pain intensity was assessed at the start of study i.e. at baseline (0 week), at 6 weeks and at 12 weeks of starting the treatment using numeric pain rating scale.Results: There was significant reduction in pain at the end of 12 weeks in both the groups (p<0.0001), but there was no significant difference between these two groups. The incidence of adverse effects was also more in group A.Conclusions: Both the drugs are having comparable efficacy but gabapentin is more tolerable in such cases

Evaluation of efficacy and tolerability of eperisone and thiocolchicoside in treatment of low back pain associated with muscle spasm: An open label, prospective, randomized controlled trial

Background: Low back pain has a high prevalence in adult population. Because of reflex muscle spasm, muscle relaxants are frequently used either alone or in combination with analgesics. Eperisone inhibits voltage gated sodium channels in brain stem and Thiocolchicoside acts via GABA-mediated mechanism to relax muscle spasm and relieves pain.Methods: This was a prospective; open labeled, randomized, two-arm, parallel group, controlled, clinical trial. 113 patients were randomised to two groups. Patients in group A received Tablet Eperisone 100 mg whereas patients in group B received Tablet Thiocolchicoside 8 mg for seven days along with Tablet Paracetamol 500 mg. The outcome measures of trial were the improvement in finger to floor distance (FFD) and pain in lumbar region, relief of spasm and tenderness of paravertebral muscles on day 4 and 7.Results: At the end of the study FFD reduced by 18 cm in group A (p < 0.0001*) and 17.36 cm in group B (p<0.0001*) from baseline. Mean score of pain on day 7 reduced by 5.64 scale in group A as compared to 5.42 scale in group B (p<0.0001* in both groups). Paravertebral tenderness reduced by 92.6% in group A and 94.6% in group B at the end of the trial. On day 7, the spasm relief was 87% in group A and 88% in group B.Conclusions: Eperisone is an effective muscle relaxant with equivalent efficacy compared to Thiocolchicoside, and has a better tolerability in treatment of low back pain with muscle spasm

Effect of denosumab or alendronic acid on the progression of aortic stenosis: A double-blind randomized controlled trial

Background: Valvular calcification is central to the pathogenesis and progression of aortic stenosis, with preclinical and observational studies suggesting that bone turnover and osteoblastic differentiation of valvular interstitial cells are important contributory mechanisms. We aimed to establish whether inhibition of these pathways with denosumab or alendronic acid could reduce disease progression in aortic stenosis. Methods: In a single-center, parallel group, double-blind randomized controlled trial, patients >50 years of age with calcific aortic stenosis (peak aortic jet velocity >2.5 m/s) were randomized 2:1:2:1 to denosumab (60 mg every 6 months), placebo injection, alendronic acid (70 mg once weekly), or placebo capsule. Participants underwent serial assessments with Doppler echocardiography, computed tomography aortic valve calcium scoring, and 18F-sodium fluoride positron emission tomography and computed tomography. The primary end point was the calculated 24-month change in aortic valve calcium score. Results: A total of 150 patients (mean age, 72±8 years; 21% women) with calcific aortic stenosis (peak aortic jet velocity, 3.36 m/s [2.93-3.82 m/s]; aortic valve calcium score, 1152 AU [655-2065 AU]) were randomized and received the allocated trial intervention: denosumab (n=49), alendronic acid (n=51), and placebo (injection n=25, capsule n=25; pooled for analysis). Serum C-terminal telopeptide, a measure of bone turnover, halved from baseline to 6 months with denosumab (0.23 [0.18-0.33 µg/L] to 0.11 µg/L [0.08-0.17 µg/L]) and alendronic acid (0.20 [0.14-0.28 µg/L] to 0.09 µg/L [0.08-0.13 µg/L]) but was unchanged with placebo (0.23 [0.17-0.30 µg/L] to 0.26 µg/L [0.16-0.31 µg/L]). There were no differences in 24-month change in aortic valve calcium score between denosumab and placebo (343 [198-804 AU] versus 354 AU [76-675 AU]; P=0.41) or alendronic acid and placebo (326 [138-813 AU] versus 354 AU [76-675 AU]; P=0.49). Similarly, there were no differences in change in peak aortic jet velocity or 18F-sodium fluoride aortic valve uptake. Conclusions: Neither denosumab nor alendronic acid affected progression of aortic valve calcification in patients with calcific aortic stenosis. Alternative pathways and mechanisms need to be explored to identify disease-modifying therapies for the growing population of patients with this potentially fatal condition. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02132026

Iterative reconstruction incorporating background correction improves quantification of [18F]-NaF PET/CT images of patients with abdominal aortic aneurysm

Background A confounding issue in [18F]-NaF PET/CT imaging of abdominal aortic aneurysms (AAA) is the spill in contamination from the bone into the aneurysm. This study investigates and corrects for this spill in contamination using the background correction (BC) technique without the need to manually exclude the part of the AAA region close to the bone. Methods Seventy-two (72) datasets of patients with AAA were reconstructed with the standard ordered subset expectation maximization (OSEM) algorithm incorporating point spread function (PSF) modelling. The spill in effect in the aneurysm was investigated using two target regions of interest (ROIs): one covering the entire aneurysm (AAA), and the other covering the aneurysm but excluding the part close to the bone (AAAexc). ROI analysis was performed by comparing the maximum SUV in the target ROI (SUVmax(T)), the corrected cSUVmax (SUVmax(T) − SUVmean(B)) and the target-to-blood ratio (TBR = SUVmax(T)/SUVmean(B)) with respect to the mean SUV in the right atrium region. Results There is a statistically significant higher [18F]-NaF uptake in the aneurysm than normal aorta and this is not correlated with the aneurysm size. There is also a significant difference in aneurysm uptake for OSEM and OSEM + PSF (but not OSEM + PSF + BC) when quantifying with AAA and AAAexc due to the spill in from the bone. This spill in effect depends on proximity of the aneurysms to the bone as close aneurysms suffer more from spill in than farther ones. Conclusion The background correction (OSEM + PSF + BC) technique provided more robust AAA quantitative assessments regardless of the AAA ROI delineation method, and thus it can be considered as an effective spill in correction method for [18F]-NaF AAA studies

Evaluation of efficacy and safety of doxofylline 800mg sustained release tablet in treatment of patients with COPD: an open label, prospective and RCT

Background: COPD is a major cause of health care burden worldwide and leading cause of death that is increasing in prevalence. Methylxanthines are used in the treatment of patients with asthma and COPD. Doxofylline (methylxanthine) shows improved disease control, reduced total daily dose of inhaled b2 agonists and improved patient compliance.Methods: This was a prospective, open labelled, randomized, two-arm, parallel group, controlled, clinical trial. 115 patients were randomized to two groups. Patients in group A received tablet doxofylline 400mg BD whereas patients in group B received tablet doxofylline 800mg SR for 4 weeks. Primary outcome measure of trial was change in FEV1 and secondary outcome measure were change in FVC/FEV1, change in symptoms score, effect on health-related quality of life (HRQOL) and safety of study medication.Results: At 4 week the FEV1increase by 13.028% and 17.647% in group A and B respectively. In group A FEV1/FVC increase by 5.79% and in group B it increases by 9.57% at 4 weeks. The symptom score of cough decrease by 77.35% and 97.43% in group A and group B respectively at 4 weeks. In group A shortness of breath decrease by 77.60% and in group B it decreases by 95.90% at 4 weeks. Tightness in chest decrease by 86.29% and 98.40% in group A and group B respectively at 4 weeks.Conclusions:Doxofylline 800mg sustained release tablet provided significantly greater improvement in FEV1, symptomatic control and health related quality of life compared to doxofylline 400mg.

First-in-human controlled inhalation of thin graphene oxide nanosheets to study acute cardiorespiratory responses

Graphene oxide nanomaterials have been developed for wide-ranging applications, but has potential safety concerns for human health. Controlled inhalation exposures in human volunteers have been a vital means to determine the effects and mechanisms of ultrafine particles in air pollution, however, few studies have used this approach to explore the effects of nanomaterials. We conducted a double-blind randomised controlled study to determine whether inhalation of graphene oxide affects pulmonary or cardiovascular function. A high purity graphene oxide was synthesised with a thickness of 1-2 layers in two sizes: ‘small’ (lateral dimensions: 100-1700 nm) and ‘ultrasmall’ (30-500 nm). Graphene oxide particles at 200 µg/m3, or filtered air, were inhaled for 2 hours by 14 young healthy volunteers on repeated visits, with measurement of cardiorespiratory parameters before and across 4 hours after exposure. Graphene oxide exposure was well-tolerated with no adverse effects. Heart rate, blood pressure, lung function and inflammatory markers were unaffected by graphene oxide irrespective of particle size. GO did not change blood biomarkers of coagulation, however, there was a mild increase in thrombus formation in an ex vivo model of arterial injury. Proteomics revealed very few differential plasma proteins. Overall, acute inhalation of graphene oxide was not associated with overt detrimental effects in healthy humans. These findings demonstrate the feasibility of carefully controlled human exposures for risk assessment of graphene nanomaterials