Effect of Eurycoma longifolia standardised aqueous root extract-Physta® on testosterone levels and quality of life in ageing male subjects: a randomised, double-blind, placebo-controlled multicentre study.

BACKGROUND: Low testosterone levels cause physiological changes that compromise the quality of life in ageing men. A standardised water extract from the root of Eurycoma longifolia (EL), known as Physta®, is known to increase testosterone levels. OBJECTIVE: To evaluate the safety and efficacy of Physta® in improving the testosterone levels and quality of life in ageing male subjects. DESIGN: This randomised, double-blind, placebo-controlled study enrolled 105 male subjects aged 50-70 years with a testosterone level <300 ng/dL, BMI ≥ 18 and ≤30.0 kg/m2. The subjects were given either Physta® 100 mg, 200 mg or placebo daily for 12 weeks. The primary endpoints were changes in serum total and free testosterone levels. The secondary endpoints included changes in the level of sex hormone-binding globulin (SHBG), dihydroepiandrosterone (DHEA), glycated haemoglobin (HbA1c), insulin-like growth factor-1 (IGF-1), thyroid function tests (T3, T4, TSH and Free T3) and cortisol. Changes in Ageing Male Symptoms (AMS) score, Fatigue Severity Scale (FSS) score and muscle strength are other secondary endpoints. The safety of the intervention products was measured by complete blood count, lipid profile, liver and renal function tests. RESULTS: There was a significant increase in the total testosterone levels at week 12 (P < 0.05) in the Physta® 100 mg group and at weeks 4 (P < 0.05), 8 (P < 0.01) and 12 (P < 0.001) in the Physta® 200 mg group compared to placebo. No significant between-group differences in free testosterone levels were observed but a significant within-group increase occurred at weeks 4 (P < 0.01), 8 (P < 0.001) and 12 (P < 0.001) in the Physta®100 mg group and at weeks 2 (P < 0.01), 4 (P < 0.01), 8 (P < 0.001) and 12 (P < 0.001) in the Physta® 200 mg group. The AMS and FSS showed significant reduction (P < 0.001) in total scores at all time-points within- and between-group in both Physta® groups. DHEA levels significantly increased (P < 0.05) within-group in both Physta® groups from week 2 onwards. Cortisol levels significantly (P < 0.01) decreased in the Physta® 200 mg group, while muscle strength significantly (P < 0.001) increased in both Physta® groups at week 12 in the within-group comparison. There were no significant changes in SHBG. No safety related clinically relevant changes were observed. CONCLUSION: Supplementation of Physta® at 200 mg was able to increase the serum total testosterone, reduce fatigue and improve the quality of life in ageing men within 2 weeks' time. TRIAL REGISTRATION: This clinical study has been registered in ctri.nic.in (CTRI/2019/03/017959).

Monitoring of inhaler use at home with a smartphone video application in a pilot study.

Inhalation therapy is the basis of the pharmacological management of asthma and COPD. Most patients are trained on the correct use of inhalers by health professionals but after that do patients continue to take them correctly at home remains largely unknown. Video recording of the inhalation technique using a smartphone can be used to evaluate the inhaler technique at home. Through this pilot study, we aimed to understand whether inhaler training given to patients in the outpatient clinic translates into good inhalation practices at home by a video application platform using a smartphone. We recruited 70 newly diagnosed asthma and COPD patients and a pulmonologist trained them to use their inhaler until they were able to use it correctly. Videos of inhaler use were captured by a relative or a friend at home and then sent to an independent reviewer via WhatsApp on Days 1, 7, 14 and 28 (±2). Each step of the inhaler technique was evaluated based on a predetermined checklist with a rating scale of 0 to 10 (10 for all steps done correctly). Out of 70 patients recruited, 30 (42%) sent all videos. We found that, although all patients performed all the steps correctly in the clinic, none of them performed all steps correctly at home even on Day 1 itself of the inhaler use. On Day 1, the steps score reduced from 10 to 6.9 with a downward trend until Day 28. The most common mistakes from Day 1 onwards were incorrect inspiratory flow rates and not gargling after the inhaler use. Also, most patients showed partially effective inhalation as per our scoring method. Remote video monitoring of inhaler use in the home environment is possible with a mobile video application that gives us a better insight into the most common inhaler mistakes performed by patients at home. Inhaler errors start appearing immediately on Day 1 after the training, and incorrect inspiratory flow rates and forgetting to do gargles are common errors. Early detection of inhaler errors at home may be possible through this method.

Systemic Immuno-metabolic alterations in chronic obstructive pulmonary disease (COPD).

BACKGROUND: Metabolic adaptation in immune cells is necessary to modulate immune cell function as it is intricately coupled with intracellular metabolism. We aimed to characterize the metabolic state of human peripheral blood mononuclear cells (PBMCs) after long-term exposure to tobacco smoke in smokers with preserved lung function and COPD subjects. METHODS: PBMCs were isolated from healthy non-smokers (HNS), healthy smokers (HS) and COPD subjects, cultured and the mitochondrial respiration while utilizing glucose (glycolysis), fatty acids (ß-oxidation) or pyruvate (direct Krebs' cycle substrate) was measured using the XFp Extracellular Flux Analyzer. Plasma levels of inflammatory cytokines IFN-γ, IL-17, TNF-α, IL-5, IL-9 and IFN-α were measured using flow cytometry. RAW264.7 cells were exposed to cigarette smoke condensate (CSC) for 1 h and its effect on cell viability, cellular metabolism and phagocytosis ability were also studied. Patient's data was analyzed using the Mann Whitney U test, whereas Student's t test was performed to analyze the in-vitro data. RESULTS: PBMCs from COPD subjects showed a significant decrease in extracellular acidification rate (ECAR) while utilizing glucose as compared to HNS (151.9 Vs 215%). Mitochondrial oxygen consumption rate (OCR) on palmitate or pyruvate was also found to be significantly lower in COPD subjects as compared to HS and a strong positive correlation between palmitate OCR in PBMCs and FEV1 (r = 0.74, p < 0.05) and FVC (r = 0.79, p < 0.05) values in HS was observed. The metabolic shift towards fatty acid metabolism in healthy smokers promoted an inflammatory cytokine response with a greater increase in the levels of IL-5, IL-9 and IFN-α as compared to IFN-γ, IL-17 and TNF-α. In-vitro experiments with RAW 264.7 cells showed similar metabolic alterations and a reduced ability to phagocytose Streptococcus pneumonia and Haemophilus influenza after cigarette smoke exposure in the presence of glucose or palmitate. CONCLUSIONS: These findings indicate a metabolic basis for the inflammatory response in COPD and could suggest a new therapeutic target for controlling the immune response and delaying the onset of disease. TRIAL REGISTRATION: This observational study was retrospectively registered in the Clinical Trails Registry - India (ICMR - NIMS) on 19th January 2018 with the registration number CTRI/2018/01/011441 .