Safety and reactogenicity of the adjuvanted recombinant zoster vaccine: experience from clinical trials and post-marketing surveillance.

An adjuvanted recombinant zoster vaccine (RZV) is licensed for the prevention of herpes zoster. This paper reviews its safety and reactogenicity. A pooled analysis of two pivotal randomized Phase-3 trials (NCT01165177, NCT01165229) in adults ⩾50 years found that more solicited adverse events (AEs) were reported with RZV than placebo. Injection site pain was the most common solicited AE (RZV: 78.0% participants; placebo: 10.9%). Grade-3 pain occurred in 6.4% of RZV and 0.3% of placebo recipients. Myalgia, fatigue, and headache were the most commonly reported general solicited AEs (RZV: 44.7%, 44.5%, and 37.7%, respectively; placebo: 11.7%, 16.5%, and 15.5%, respectively). Most symptoms were mild to moderate in intensity with a median duration of 2-3 days. The intensity of reactogenicity symptoms did not differ substantially after the first and second vaccine doses. The pooled analysis of the pivotal Phase-3 trials did not identify any clinically relevant differences in the overall incidence of serious adverse events (SAEs), fatal AEs or potential immune-mediated diseases (pIMDs) between RZV and placebo. Reactogenicity in five studies of immunocompromised patients ⩾18 years (autologous stem cell transplant, human immunodeficiency virus, solid tumors, hematological malignancies, and renal transplant; NCT01610414, NCT01165203, NCT01798056, NCT01767467, and NCT02058589) was consistent with that observed in the pivotal Phase-3 trials. There were no clinically relevant differences between RZV and placebo in the immunocompromised populations with regard to overall incidence of SAEs, fatal AEs, pIMDs, or AEs related to patients' underlying condition. Post-marketing surveillance found that the most commonly reported AEs were consistent with the reactogenicity profile of the vaccine in clinical trials. Overall, the clinical safety data for RZV are reassuring.

A systematic literature review to assess the burden of herpes zoster disease in China.

INTRODUCTION: Herpes zoster (HZ) or shingles occurs as a result of reactivation after a primary infection with varicella zoster virus (chickenpox). The burden of HZ in older adults in China is not well understood. We conducted a systematic literature review to understand the burden of disease related to HZ, its complications, and associated costs in China. AREAS COVERED: Using publications retrieved from Chinese and English literature databases, we described incidence and prevalence of HZ, occurrence of HZ-related complications, and costs associated with HZ in mainland China, Taiwan, and Hong Kong. EXPERT OPINION: The data, although limited, indicate that the burden of disease due to HZ is substantial in China, with incidence rates that are comparable to the rest of the world. Recently, an adjuvanted recombinant HZ vaccine was approved for use in China. Disease prevention is likely to reduce the burden of disease, with potentially significant economic benefits. However, understanding the public health impact of vaccination in China will require extensive baseline information about incidence, complication rates, and associated costs. This review gives an overview of available research, but also reveals existing gaps. Well-designed observational studies are needed to quantify the total burden of disease and potential impact of prevention through vaccination.

PLAIN LANGUAGE SUMMARY What is the context? Although Herpes zoster (shingles) is a common disease of older age, the burden of disease in China is not well described. 32% of the Chinese population is aged 50 years and Older and this proportion is increasing. As a result of the ageing population, the public burden associated with shingles is expected to increase over time. What is new? We accessed published studies in the English and Chinese language literature to explore available information describing shingles in China. The incidence of shingles in Taiwan, Hong Kong and mainland China appears to be similar to other countries, although reliable population-based data are currently sparse in Hong Kong and mainland China. What is the impact? Data describing the disease burden due to shingles are currently heterogeneous throughout China. This review is a first step to determine those populations which could benefit most from shingles vaccination. Preventing shingles through vaccination could benefit the individual as well as provide potentially significant economic benefits for the individual, the employer and the economy.

Time trial performance in normal and high ambient temperature: is there a role for 5-HT?

The original central fatigue hypothesis suggested that fatigue during prolonged exercise might be due to higher 5-HT activity. Therefore, we examined the effects of acute administration of a selective 5-HT reuptake inhibitor (SSRI) on performance and thermoregulation. Eleven healthy trained male cyclists completed four experimental trials (two in 18 degrees C, two in 30 degrees C) in a double-blind randomised crossover design. Subjects ingested either a placebo (PLA: lactose 2 x 10 mg) or citalopram (CITAL 2 x 10 mg) on the evening before and the morning of the trial. Subjects cycled for 60 min at 55% W(max), immediately followed by a time trial (TT) to measure performance. The significance level was set at P < 0.05. Acute SSRI did not significantly change performance on the TT (18 degrees C P = 0.518; 30 degrees C P = 0.112). During recovery at 30 degrees C, core temperature was significantly lower in the CITAL trial (P < 0.012). At 30 degrees C heart rate was significantly lower after exercise in CITAL (P = 0.013). CITAL significantly increased cortisol concentrations at rest (P = 0.016), after the TT (P = 0.006) and after 15-min recovery (P = 0.041) at 30 degrees C. 5-HT reuptake inhibition did not cause significant reductions in performance. Core temperature was significantly lower only after the time trial in heat after CITAL administration. The present work failed to prove whether or not 5-HT has an exclusive role in the onset of centrally mediated fatigue during prolonged exercise in both normal and high ambient temperature.

VIBE MRI: an alternative to CT in the imaging of sports-related osseous pathology?

MRI is an excellent diagnostic tool in the imaging of sports-related musculoskeletal pathology; however, standard slice thickness acquisitions can lack the spatial resolution to accurately define and characterise osseous abnormalities. Standard MRI sequences may be supplemented with CT to reduce diagnostic uncertainty. We provide a clinical perspective, in the form of pictorial review, on the potential applications of 3D MRI sequences, specifically using volumetric interpolated breath-hold examination in the characterisation of various musculoskeletal osseous pathologies. The potential to negate the requirement for CT in a young radiation sensitive cohort is a clinically significant concept and suggests the requirement for further studies comparing the performance of volumetric MRI to CT.

Heat and cold : what does the environment do to the marathon runner?

The marathon poses a considerable physical challenge for athletes of all levels. When combined with high heat and humidity, not only is performance potentially compromised, but health and well-being are also at risk. There are well recognised effects of heat and hydration status on the cardiovascular and thermoregulatory systems that can account for the decreased performance and increased sensation of effort that are experienced when competing in the heat. Elevated exercise heart rate and core temperature at the same absolute exercise intensity are commonly reported. Dehydration occurring during exercise in the heat and results in reductions in stroke volume, cardiac output and blood pressure, as well as a marked decline in blood flow to the working muscles. Recent work suggests that hyperthermia may have a direct affect on the CNS and the brain may contribute to fatigue during prolonged exercise in a warm environment. At present, evidence supports a significant role of catecholaminergic neurotransmission, but there are a number of metabolic and circulatory perturbations occurring within the brain that may also be important in the fatigue process.

Discrepant illness perceptions, affect and expressed emotion in people with psychosis and their carers.

BACKGROUND: Illness perception, a measure of illness representations developed from physical medicine, has recently been applied to psychosis. We investigated how illness perceptions relate to affect and expressed emotion (EE) in carer-patient dyads, particularly if their perceptions differed. METHOD: We interviewed 82 carer-patient dyads, after a relapse of psychosis. Carers were assessed for illness perceptions, distress, self-esteem and EE; patients for illness perceptions, depression, anxiety and self-esteem, in a cross sectional study. RESULTS: Carers were more pessimistic than patients about illness persistence and consequences, and carers with low mood were particularly pessimistic about persistence and controllability. Discrepant views about illness consequences were related to greater anxiety, depression, and lower self-esteem in patients, while discrepant views on controllability were associated with greater distress, depression, and lower self-esteem in carers. Illness perceptions did not relate directly to EE. CONCLUSIONS: In this sample, meta-cognitive carer representations of illness in psychosis are related to negative affective reactions in carers, but not to EE. Resolving discrepant illness perceptions between carers and patients might provide a way of improving family reactions to the health threat of psychosis.

Amino acids and the brain: do they play a role in "central fatigue"?

It is clear that the cause of fatigue is complex, influenced by both events occurring in the periphery and the central nervous system (CNS). It has been suggested that exercise-induced changes in serotonin (5-HT), dopamine (DA), and noradrenaline (NA) concentrations contribute to the onset of fatigue during prolonged exercise. Serotonin has been linked to fatigue because of its documented role in sleep, feelings of lethargy and drowsiness, and loss of motivation, whereas increased DA and NA neurotransmission favors feelings of motivation, arousal, and reward. 5-HT has been shown to increase during acute exercise in running rats and to remain high at the point of fatigue. DA release is also elevated during exercise but appears to fall at exhaustion, a response that may be important in the fatigue process. The rates of 5-HT and DA/NA synthesis largely depend on the peripheral availability of the amino acids tryptophan (TRP) and tyrosine (TYR), with increased brain delivery increasing serotonergic and DA/NA activity, respectively. TRP, TYR, and the branched-chained amino acids (BCAAs) use the same transporter to pass through the blood-brain barrier, meaning that the plasma concentration ratio of these amino acids is thought to be a very important marker of neurotransmitter synthesis. Pharmacological manipulation of these neurotransmitter systems has provided support for an important role of the CNS in the development of fatigue. Work conducted over the last 20 y has focused on the possibility that manipulation of neurotransmitter precursors may delay the onset of fatigue. Although there is evidence that BCAA (to limit 5-HT synthesis) and TYR (to elevate brain DA/NA) ingestion can influence perceived exertion and some measures of mental performance, the results of several apparently well-controlled laboratory studies have yet to demonstrate a clear positive effect on exercise capacity or performance. There is good evidence that brain neurotransmitters can play a role in the development of fatigue during prolonged exercise, but nutritional manipulation of these systems through the provision of amino acids has proven largely unsuccessful.

Improvement of Sprint Performance in Wheelchair Sportsmen With Caffeine Supplementation.

PURPOSE: Caffeine can be beneficial during endurance and repeated-sprint exercise in able-bodied individuals performing leg or whole-body exercise. However, little evidence exists regarding its effects during upper-body exercise. This study therefore aimed to investigate the effects of caffeine on sprint (SPR) and 4-min maximal-push (PUSH) performance in wheelchair sportsmen. METHODS: Using a double-blind, placebo-controlled, crossover design, 12 male wheelchair rugby players (age 30.0 ± 7.7 y, body mass 69.6 ± 15.3 kg, training 11.1 ± 3.5 h/wk) completed 2 exercise trials, separated by 7-14 d, 70 min after ingestion of 4 mg/kg caffeine (CAF) or dextrose placebo (PLA). Each trial consisted of four 4-min PUSHes and 3 sets of 3 × 20-m SPRs, each separated by 4 min rest. Participants responded to the Felt Arousal (a measure of perceived arousal), Feeling (a measure of the affective dimension of pleasure/displeasure), and rating-of-perceived-exertion (RPE) scales. Salivary caffeine secretion rates were measured. RESULTS: Average SPR times were faster during CAF than PLA during SPR 1 and SPR 2 (P = .037 and .016). There was no influence of supplementation on PUSHes 2-4 (P > .099); however, participants pushed significantly farther during PUSH 1 after CAF than after PLA (mean ± SD 677 ± 107 and 653 ± 118 m, P = .047). There was no influence of CAF on arousal or RPE scores (P > .132). Feeling scores improved over the course of the CAF trial only (P = .017) but did not significantly differ between trials (P > .167). Pre-warm-up (45 min postingestion) salivary CAF secretion rates were 1.05 ± 0.94 and 0.08 ± 0.05 µg/min for CAF and PLA, respectively. CONCLUSION: Acute CAF supplementation can improve both 20-m-sprint performance and a 1-off bout of short-term endurance performance in wheelchair sportsmen.

Conclusions of the II International and IV Spanish Hydration Congress. Toledo, Spain, 2nd-4th December, 2015.

Water is the major component of our organism representing about 60% of total body weight in adults and has to be obtained through the consumption of different foods and beverages as part of our diet. Water is an essential nutrient performing important functions, including transport of other nutrients, elimination of waste products, temperature regulation, lubrication and structural support. In this context, hydration through water has an essential role in health and wellness, which has been highly acknowledged in recent years among the health community experts such as nutritionists, dietitians, general practitioners, pharmacists, educators, as well as by physical activity and sport sciences experts and the general population.

Intensity of a training session during Ramadan in fasting and non-fasting Tunisian youth football players.

Heart rate was measured in 79 young male soccer players during training in the third week of Ramadan. Forty-eight players were practising Ramadan fasting, while the other 31 players were eating normally. All participants trained for 60-80 min at an ambient temperature of 25-28 degrees C and relative humidity of 50-53%. Heart rate, which was measured throughout the training session, was marginally higher in the fasting (mean 144 beats . min(-1), s = 25) than in the non-fasting (139 beats . min(-1), s = 23) group (P < 0.001). When assessed as the percentage of heart rate reserve utilized, however, the training load was similar for both groups (62%, s = 8). No difference was detected in training intensity for the fasting and non-fasting groups when quantified by either training impulse (253, s = 139 and 253, s = 108, respectively) or training load indicator (222, s = 123 and 179, s = 49, respectively). The overall subjective rating of perceived exertion of the training session reported 20 min after finishing training was similar for the fasting (12, range 6-17) and non-fasting (12, range 7-17) groups, which was comparable (P = 0.16) to the mean value for the entire week (13, range 8-16). A similar finding was observed in the players' subjective appraisal of the difficulty of training of the individual session and for the whole week's training. Overall exercise load measures indicated that there was no biologically significant difference between the fasting and non-fasting groups during training in the third week of Ramadan.

The brain and fatigue: new opportunities for nutritional interventions?

It is clear that the cause of fatigue is complex, influenced by events occurring in both the periphery and the central nervous system. Work conducted over the last 20 years has focused on the role of brain serotonin and catecholamines in the development of fatigue, and the possibility that manipulation of neurotransmitter precursors may delay the onset of fatigue. While there is some evidence that branched-chain amino acid and tyrosine ingestion can influence perceived exertion and some measures of mental performance, the results of several apparently well-controlled laboratory studies have not demonstrated a positive effect on exercise capacity or performance under temperate conditions. As football is highly reliant upon the successful execution of motor skills and tactics, the possibility that amino acid ingestion may help to attenuate a loss in cognitive function during the later stages of a game would be desirable, even in the absence of no apparent benefit to physical performance. There are several reports of enhanced performance of high-intensity intermittent exercise with carbohydrate ingestion, but at present it is difficult to separate the peripheral effects from any potential impact on the central nervous system. The possibility that changes in central neurotransmission play a role in the aetiology of fatigue when exercise is performed in high ambient temperatures has recently been examined, although the significance of this in relation to the pattern of activity associated with football has yet to be determined.

Why do older people not get immunised against influenza? A community survey.

Many older people who would benefit from influenza vaccine do not get immunised. We carried out a postal questionnaire survey of people aged 65 years and over living in the community to explore views about influenza vaccine and identify ways of improving uptake. Completed questionnaires were returned by 1468/2553 (57.5%). Vaccine coverage for 1998-1999 season was 50.5% (95% confidence interval (CI) 47.9-53.1%). Important predictor variables for non-uptake included absence of medical risk factors, perceived good health, lack of advice from a doctor or nurse, and negative views on vaccine efficacy and safety. Most people had to request vaccination, only one in five got a reminder from their general practitioner. There is scope for improving influenza vaccine coverage in older people by placing more emphasis in patient information materials on vaccine efficacy and safety and by greater use of reminders.

Effects of caspase inhibition on the progression of experimental glomerulonephritis.

BACKGROUND: Caspase-3 has a central role in the execution of apoptosis. In a nephrotoxic nephritis (NTN) model, we previously demonstrated an up-regulation of caspase-3 that was associated with inappropriate renal apoptosis, inflammation, tubular atrophy, and renal scarring. METHODS: We applied a pan caspase inhibitor, Boc-Asp (OMe)-fluoro-methyl-ketone (B-D-FMK), directly to rat NTN kidney using an intrarenal cannula fed from an osmotic pump. Animals were treated either for the first 7 days (acutely) to determine the effects on renal inflammation (ED-1 staining) and apoptosis (in situ end labeling of fragmented DNA), or for 28 days commencing 15 days after NTN (chronically) to observe the effects on cell death and renal fibrosis. Changes of caspase-3 and caspase-1 activity were detected by fluorometric substrate cleavage assay. Changes in caspase-3 and caspase-1, interleukin-1 beta (IL-1 beta), and collagen I, III, and IV proteins and mRNA were detected by Western blotting and Northern blotting, respectively. RESULTS: In both treated groups, caspase-3 activity was inhibited, and 17 and 24 kD active caspase-3 proteins were reduced significantly. A compensatory increase of caspase-3 mRNA occurred in the acutely treated group, but decreased in the chronically treated group (P < 0.05). Although there were no significant changes in caspase-1 activity and its active protein, the observed decrease in its precursor in the chronic group was increased by treatment (P < 0.05). Further, IL-1 beta precursor and its mRNA were significantly reduced by treatment only in the chronically treated group. Apoptosis was decreased in the glomeruli of acutely treated rats, and in the tubules and interstitium of chronically treated animals (P < 0.05). Glomerular inflammation was decreased only in the acutely treated group, whereas tubulointerstitial inflammation was lowered in both treated groups (P < 0.05). Glomerulosclerosis was reduced in both inhibitor groups, with a reduction in tubulointerstitial fibrosis and collagen I, III, and IV mRNA restricted to chronically treated animals (P < 0.05). Proteinuria was significantly decreased with caspase inhibition in both treated groups, but not serum creatinine level. CONCLUSION: This study clearly indicates that caspase inhibition reduces renal apoptosis, ameliorates inflammation and fibrosis, and improves proteinuria in experimental glomerulonephritis, which may mainly be related to changes in the caspase enzymatic system.