Efficacy and safety of a supplement combination on hand pain among people with symptomatic hand osteoarthritis an internet-based, randomised clinical trial the RADIANT study.

OBJECTIVE: The RADIANT study aimed to investigate the efficacy and safety of a complementary medicine supplement combination in people with hand osteoarthritis (HOA). METHOD: This was an internet-based, double-blind, randomised, placebo-controlled trial. Participants aged over 40 years with symptomatic HOA with radiographic confirmation (Kellgren Lawrence grade ≥ 2) throughout Australia were recruited and randomly assigned (1:1) to receive either a supplement combination composed of Boswellia serrata extract 250 mg/day, pine bark extract 100 mg/day, methylsulfonylmethane 1,500 mg/day and curcumin 168 mg/day or placebo for 12 weeks. The primary outcome was change in hand pain assessed using a visual analogue scale (VAS 0-100) from baseline to week 12. A range of secondary outcomes and additional measures were recorded. Adverse events were monitored weekly. RESULTS: One hundred and six participants were included with mean age 65.6 years and 81% were women. 45% of the participants were graded as KLG 4, 40% KLG three and 39 (37%) had erosive OA. There was no significant difference in pain VAS reduction between groups. The adjusted between group difference in means (95%CI) was 5.34 (-2.39 to 13.07). Five participants (10%) in the supplement combination group discontinued study treatment due to AE vs four participants (7%) in the placebo group. CONCLUSION: There were no significant differences in symptomatic relief between the two groups over 12 weeks. These findings do not support the use of the supplement combination for treating hand pain in people with HOA. REGISTRATION: Prospectively registered (Australian New Zealand Clinical Trials Registry ACTRN12619000835145, 31/05/2019).

Abdominal functional electrical stimulation to improve respiratory function after spinal cord injury: a systematic review and meta-analysis.

OBJECTIVES: Abdominal functional electrical stimulation (abdominal FES) is the application of a train of electrical pulses to the abdominal muscles, causing them to contract. Abdominal FES has been used as a neuroprosthesis to acutely augment respiratory function and as a rehabilitation tool to achieve a chronic increase in respiratory function after abdominal FES training, primarily focusing on patients with spinal cord injury (SCI). This study aimed to review the evidence surrounding the use of abdominal FES to improve respiratory function in both an acute and chronic manner after SCI. SETTINGS: A systematic search was performed on PubMed, with studies included if they applied abdominal FES to improve respiratory function in patients with SCI. METHODS: Fourteen studies met the inclusion criteria (10 acute and 4 chronic). Low participant numbers and heterogeneity across studies reduced the power of the meta-analysis. Despite this, abdominal FES was found to cause a significant acute improvement in cough peak flow, whereas forced exhaled volume in 1 s approached significance. A significant chronic increase in unassisted vital capacity, forced vital capacity and peak expiratory flow was found after abdominal FES training compared with baseline. CONCLUSIONS: This systematic review suggests that abdominal FES is an effective technique for improving respiratory function in both an acute and chronic manner after SCI. However, further randomised controlled trials, with larger participant numbers and standardised protocols, are needed to fully establish the clinical efficacy of this technique.

Non-intrusive real-time breathing pattern detection and classification for automatic abdominal functional electrical stimulation.

Abdominal Functional Electrical Stimulation (AFES) has been shown to improve the respiratory function of people with tetraplegia. The effectiveness of AFES can be enhanced by using different stimulation parameters for quiet breathing and coughing. The signal from a spirometer, coupled with a facemask, has previously been used to differentiate between these breath types. In this study, the suitability of less intrusive sensors was investigated with able-bodied volunteers. Signals from two respiratory effort belts, positioned around the chest and the abdomen, were used with a Support Vector Machine (SVM) algorithm, trained on a participant by participant basis, to classify, in real-time, respiratory activity as either quiet breathing or coughing. This was compared with the classification accuracy achieved using a spirometer signal and an SVM. The signal from the belt positioned around the chest provided an acceptable classification performance compared to the signal from a spirometer (mean cough (c) and quiet breath (q) sensitivity (Se) of Se(c)=92.9% and Se(q)=96.1% vs. Se(c)=90.7% and Se(q)=98.9%). The abdominal belt and a combination of both belt signals resulted in lower classification accuracy. We suggest that this novel SVM classification algorithm, combined with a respiratory effort belt, could be incorporated into an automatic AFES device, designed to improve the respiratory function of the tetraplegic population.

Pharmacodynamic interaction of warfarin with cranberry but not with garlic in healthy subjects.

BACKGROUND AND PURPOSE: Patients commonly take complementary medicines in conjunction with warfarin yet evidence supporting the safety or the risk of a herb-drug interaction is lacking. The aim of this study was to investigate the possible impact of two commonly used herbal medicines, garlic and cranberry, on the pharmacokinetics and pharmacodynamics of warfarin in healthy male subjects. EXPERIMENTAL APPROACH: An open-label, three-treatment, randomized crossover clinical trial was undertaken and involved 12 healthy male subjects of known CYP2C9 and VKORC1 genotype. A single dose of 25 mg warfarin was administered alone or after 2 weeks of pretreatment with either garlic or cranberry. Warfarin enantiomer concentrations, INR, platelet aggregation and clotting factor activity were measured to assess pharmacokinetic and pharmacodynamic interactions between warfarin and herbal medicines. KEY RESULTS: Cranberry significantly increased the area under the INR-time curve by 30% when administered with warfarin compared with treatment with warfarin alone. Cranberry did not alter S- or R-warfarin pharmacokinetics or plasma protein binding. Co-administration of garlic did not significantly alter warfarin pharmacokinetics or pharmacodynamics. Both herbal medicines showed some evidence of VKORC1 (not CYP2C9) genotype-dependent interactions with warfarin, which is worthy of further investigation. CONCLUSIONS AND IMPLICATIONS: Cranberry alters the pharmacodynamics of warfarin with the potential to increase its effects significantly. Co-administration of warfarin and cranberry requires careful monitoring.

Effects of St John's wort and CYP2C9 genotype on the pharmacokinetics and pharmacodynamics of gliclazide.

BACKGROUND AND PURPOSE: Patients commonly take complementary medicines in conjunction with conventional drugs without clear evidence of safety or the risk of herb-drug interactions. The aim of this study was to assess potential pharmacokinetic (PK) and pharmacodynamic (PD) interactions between St John's wort and gliclazide in healthy subjects with different cytochrome P450 2C9 (CYP2C9) genotypes. EXPERIMENTAL APPROACH: A crossover controlled study was conducted in 21 healthy subjects. Each received gliclazide (80 mg) either alone or during 15 days treatment with St John's wort. The area under the plasma concentration-time curve (AUC(0-infinity)), apparent clearance (CL/F) and elimination half-life (t 1/2) of gliclazide and incremental changes in glucose and insulin AUC(0-4) were compared. CYP2C9*2 and CYP2C9*3 alleles were identified using PCR followed by restriction enzyme digestion analysis. KEY RESULTS: St John's wort significantly altered gliclazide pharmacokinetics in all except for four healthy subjects. The mean ratio and 90% confidence interval (CI) of gliclazide AUC(0-infinity) and CL/F were 0.67 (0.55-0.81) and 1.50 (1.24-1.81), respectively, after St John's wort treatment. St John's wort decreased gliclazide t (1/2), with mean ratio and 90% CI of 0.85 (0.74-0.93). There were no significant changes in glucose or insulin AUC(0-4) after St John's wort treatment and no significant differences according to CYP2C9 genotype. CONCLUSIONS AND IMPLICATIONS: Treatment with St John's wort significantly increases the apparent clearance of gliclazide which is independent of CYP2C9 genotype. People with diabetes receiving this combination should be closely monitored to evaluate possible signs of reduced efficacy.

Herb-drug interactions: an evidence based approach.

The increasing use of herbal medicinal products (HMPs) in the community where people are also receiving prescription medicines suggests that adverse herb-drug interactions may be of significant public health consequence. The evidence available to guide practitioners in decision making is complex and consists of a range of sources including adverse event database entries, spontaneous or case reports, in vivo and in vitro drug metabolism studies, and in vivo drug interaction studies in healthy subjects and patients. In the absence of further rigorous studies to assess the clinical significance of herb-drug interactions, an evidence-based appraisal of the current literature is essential to guide practitioners involved in patient care.