Qualitative interviews of patients with COPD and muscle weakness enrolled in a clinical trial evaluating a new anabolic treatment: patient perspectives of disease experience, trial participation and outcome assessments.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) and muscle weakness can cause impaired physical function, significantly impacting patients' health-related quality of life (HRQoL). Loss of muscle strength is usually assessed through clinical and performance outcome (PerfO) assessments, which consists of tasks performed in a standardized manner, providing evidence of a patient's functional ability. However, evidence documenting the patient experience of COPD and muscle weakness is limited. METHODS: This two-stage qualitative study used semi-structured interviews in patients aged 45-80 years with COPD (post-bronchodilator forced expiratory volume in 1s [FEV1]/forced vital capacity ratio < 0.70, and FEV1% predicted of 30-80%) and muscle weakness. In Stage 1, 30-minute concept elicitation interviews were conducted with participants recruited across three US sites to explore impacts on physical functioning and activities of daily living. In Stage 2, interviews were performed with participants exiting a Phase IIa trial investigating the efficacy of a selective androgen receptor modulator (GSK2881078) on leg strength, whereby PerfOs were used to evaluate strength and physical functioning endpoints. These participants completed either 60-minute in-depth (n = 32) or 15-minute confirmatory (n = 35) interviews exploring trial experience, completion of outcome measures, disease experience and treatment satisfaction. RESULTS: In Stage 1 (n = 20), most participants described their muscles as weak (83.3%). Difficulties with walking (100%) and lifting heavy objects (90%) were reported. In Stage 2, 60-minute interviews, all participants (n = 32) reported a positive trial experience. Most participants reported that the home exercise program was easy to fit into daily life (77.8%), the PROactive daily diary was easy to complete (100%) and wearable sensors were easy to use (65.6%). However, technical issues were reported (71%), and few participants (19.4%) found physical assessments easy to complete. Improvements in muscle strength and functional limitations were reported by most participants. The shorter 15-minute confirmatory interviews (n = 35) supported the in-depth interview results. CONCLUSION: The qualitative interviews generated in-depth evidence of key concepts relevant to patients with COPD and muscle weakness and support the assessments of patient strength and physical function as outcome measures in this population in future studies. TRIAL NUMBER: GSK Stage 1: 206869; Stage 2: 200182, NCT03359473; Registered December 2, 2017, https://clinicaltrials.gov/ct2/show/NCT03359473 .

Ile105Val polymorphism in the GSTP1 gene is associated with susceptibility to acute myeloid leukemia: an updated systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Several genetic variations are associated with acute myeloid leukemia (AML) susceptibility, including the GSTP1 Ile105Val polymorphism. Even with the existing meta-analysis conducted on the topic, no consensus has been reached since none of the studies available performed in-depth data analysis. Hence, we performed an updated systematic review and meta-analysis in this paper to obtain more precise estimates. MATERIALS AND METHODS: We searched various databases and calculated the odds ratio (OR) and 95% confidence interval (CI) to examine whether the GSTP1 Ile105Val polymorphism is associated with AML susceptibility. Further statistical analysis was also done to obtain more accurate and reliable findings. RESULTS: A total of 15 studies are included in the systematic review, but only 9 were included in the meta-analysis due to the studies deviating from the Hardy-Weinberg equilibrium. The analysis showed significantly increased susceptibility to AML in the allelic, co-dominant, and recessive models. Furthermore, subgroup analysis noted increased AML susceptibility in the non-Asian population. Comparing the proportions of the genotypes and alleles showed a significantly higher proportion of the Val/Val genotype and Val allele in the non-Asian cohort. CONCLUSION: The GSTP1 Ile105Val polymorphism is significantly associated with AML susceptibility, especially among non-Asians. Further investigation should be performed to strengthen the current results.

Effects of Acute Caffeine Ingestion on Cognitive Performance before and after Repeated Small-Sided Games in Professional Soccer Players: A Placebo-Controlled, Randomized Crossover Trial.

Soccer is a team sport that requires players to process a significant amount of information quickly and respond with both speed and accuracy to the ever-changing demands of the game. As such, success in soccer depends not only on physical attributes but also on cognitive abilities such as perception and decision-making. The aim of the current study was to investigate the acute effects of caffeine ingestion on Stroop test performance before and after repeated small-sided games (SSG) in professional soccer players. Twelve professional male soccer players (29 ± 4.1 years; 78.1 ± 7.7 kg body mass) participated in this study. A randomized crossover double-blind placebo-controlled trial was used. Caffeine (5 mg.kg-1) or a placebo was ingested 45 min before a protocol consisting of five 5 min SSG with 1 min rest intervals. A computerized version of the colour Stroop test was completed immediately before and after the exercise protocol. During the Stroop test, words appeared on the computer screen in three different ways: (i) neutral words (neutral condition); (ii) correspondent colour (i.e., "red" painted in red; congruent condition), or; (iii) different colour (i.e., "red" painted in green; incongruent condition). The incongruent condition aimed to cause the interference effect, as the colour and the word did not match. Ratings of perceived exertion (RPE) were assessed after each SSG. RPE increased during the five sets of the SSG protocol (p < 0.001), without differences between the caffeine and placebo trials. The soccer-specific exercise protocol promoted a faster response during the Stroop test (two-way ANOVA main effect for SSG protocol: p < 0.05), with no differences in accuracy (p > 0.05). Caffeine ingestion resulted in slower reaction time during the Stroop test during the congruent and neutral trials but not during the incongruent trial (two-way ANOVA main effect for supplementation: p = 0.009, p = 0.045, and p = 0.071, respectively). Accuracy was lower in the caffeine trial in congruent and incongruent trials (p < 0.05 caffeine vs. placebo both on the pre- and post-SSG protocol). In conclusion, a soccer-specific exercise protocol improved the Stroop test performance in professional soccer players, but acute caffeine ingestion (5 mg.kg-1) was detrimental.

Exercise improves depression through positive modulation of brain-derived neurotrophic factor (BDNF). A review based on 100 manuscripts over 20 years.

The aim of this review was to explore the relevant neurobiology and the association between peripheral levels of brain-derived neurotrophic factor (BDNF) and acute and short to long-term exercise regimes, as well as its relation to depression and antidepressant treatment. A 20-year literature search was conducted. The screening process resulted in 100 manuscripts. Antidepressants as well as acute exercise, particularly high-intensity, elevates BDNF in healthy humans and clinical populations, as evidenced from aerobic and resistance-based studies. Although exercise is increasingly recognised in the management of depression, acute and short-term exercise studies have failed to establish a relationship between the severity of depression and changes in peripheral BDNF. The latter rapidly returns to baseline, possibly indicating a quick re-uptake by the brain, aiding its neuroplasticity functions. The timescale of administration needed for the antidepressants to stimulate biochemical changes is longer than similar increases with acute exercise.

Selective androgen receptor modulation for muscle weakness in chronic obstructive pulmonary disease: a randomised control trial.

BACKGROUND: Selective androgen receptor modulators (SARMs) increase muscle mass via the androgen receptor. This phase 2A trial investigated the effects of a SARM, GSK2881078, in conjunction with exercise, on leg strength in patients with chronic obstructive pulmonary disease (COPD) and impaired physical function. METHODS: 47 postmenopausal women and 50 men with COPD (forced expiratory volume in 1 s 30%-65% predicted; short physical performance battery score: 3-11) were enrolled into a randomised double-blind, placebo control trial. Patients were randomised 1:1 to once daily placebo or oral GSK2881078 (females: 1.0 mg; males: 2.0 mg) for 13 weeks with a concurrent home-exercise programme, involving strength training and physical activity. Primary endpoints were change from baseline in leg strength at 90 days (one-repetition maximum; absolute (kg) and relative (% change)) and multiple safety outcomes. Secondary endpoints included lean body mass, physical function and patient-reported outcomes. RESULTS: GSK2881078 increased leg strength in men. The difference in adjusted mean change from baseline and adjusted mean percentage change from baseline between treatment and placebo were: for women, 8.0 kg (90% CI -2.5 to 18.4) and 5.2% (90% CI -4.7 to 15.0), respectively; for men, 11.8 kg (90% CI -0.5 to 24.0) and 7.0% (90% CI 0.5 to 13.6), respectively. Lean body mass increased, but no changes in patient-reported outcomes were observed. Reversible reductions in high-density lipoprotein-cholesterol and transient elevations in hepatic transaminases were the main treatment-related safety findings. CONCLUSIONS: GSK2881078 was well tolerated and short-term treatment increased leg strength, when expressed as per cent predicted, in men with COPD more than physical training alone. TRIAL REGISTRATION NUMBER: NCT03359473.

Effect of Caffeine Ingestion on Indirect Markers of Exercise-Induced Muscle Damage: A Systematic Review of Human Trials.

The effect of caffeine on mitigating exercise-induced muscle damage (EIMD) is still poorly understood, but it was hypothesized that caffeine could contribute to decreasing delayed onset muscle soreness, attenuating temporary loss of strength, and reducing circulating levels of blood markers of muscle damage. However, evidence is not conclusive and beneficial effects of caffeine ingestion on EIMD are not always observed. Factors, such as the type of exercise that induces muscle damage, supplementation protocol, and type of marker analyzed contribute to the differences between the studies. To expand knowledge on the role of caffeine supplementation in EIMD, this systematic review aimed to investigate the effect of caffeine supplementation on different markers of muscle damage. Fourteen studies were included, evaluating the effect of caffeine on indirect muscle damage markers, including blood markers (nine studies), pain perception (six studies), and MVC maximal voluntary contraction force (four studies). It was observed in four studies that repeated administration of caffeine between 24 and 72 h after muscle damage can attenuate the perception of pain in magnitudes ranging from 3.9% to 26%. The use of a single dose of caffeine pre-exercise (five studies) or post-exercise (one study) did not alter the circulating blood levels of creatine kinase (CK). Caffeine supplementation appears to attenuate pain perception, but this does not appear to be related to an attenuation of EIMD, per se. Furthermore, the effect of caffeine supplementation after muscle damage on strength recovery remains inconclusive due to the low number of studies found (four studies) and controversial results for both dynamic and isometric strength tests.

The Effect of Acute Caffeine Ingestion on Tactical Performance of Professional Soccer Players.

In soccer, physical, tactical, and decision-making processes are highly important facets of successful performance. Caffeine has well established effects for promoting both physical and cognitive performance, but the translation of such benefits specifically for soccer match play is not well established. This study examined the effects of acute caffeine ingestion on tactical performance during small-sided games (SSG) in professional soccer players. Nineteen soccer players (22 ± 4 years) underwent a randomized, counterbalanced, crossover, double-blind placebo-controlled trial. The protocol consisted of 5 bouts of 5-min SSG with 3 players plus a goalkeeper in each team (3 + GK × 3 + GK) with each SSG separated by 1 min rest intervals. Tactical performance was assessed using the system of tactical assessment in soccer (FUT-SAT). Prior to each experimental trial, participants ingested caffeine (5 mg·kg-1) or a placebo 60 min before the protocol. Overall, caffeine ingestion resulted in an increased ball possession time when compared to the placebo. When the offensive and defensive core principles were analyzed, the results were equivocal. Caffeine resulted in positive effects on some tactical decisions during the protocol, but it was deleterious or promoted no observed effect on other of the core tactical principles. Caffeine ingestion resulted in less offensive (during SSG3) and defensive (SSG 2, SSG3, and SSG4) errors. Caffeine ingestion also resulted in higher total offensive success during SSG 1 and SSG2, but it was detrimental during SSG3. Additionally, total defensive success was lower for the caffeine conditions during SSG 2 and SSG5 when compared to the placebo. In conclusion, caffeine influenced aspects of tactical decisions in soccer, resulting in fewer offensive and defensive errors, although it may be deleterious considering other tactical parameters. Future studies may clarify the effects of caffeine ingestion on specific decision-making parameters in soccer.

Metabolic profiling shows pre-existing mitochondrial dysfunction contributes to muscle loss in a model of ICU-acquired weakness.

BACKGROUND: Surgery can lead to significant muscle loss, which increases recovery time and associates with increased mortality. Muscle loss is not uniform, with some patients losing significant muscle mass and others losing relatively little, and is likely to be accompanied by marked changes in circulating metabolites and proteins. Determining these changes may help understand the variability and identify novel therapeutic approaches or markers of muscle wasting. METHODS: To determine the association between muscle loss and circulating metabolites, we studied 20 male patients (median age, 70.5, interquartile range, 62.5-75) undergoing aortic surgery. Muscle mass was determined before and 7 days after surgery and blood samples were taken before surgery, and 1, 3, and 7 days after surgery. The circulating metabolome and proteome were determined using commercial services (Metabolon and SomaLogic). RESULTS: Ten patients lost more than 10% of the cross-sectional area of the rectus femoris (RFCSA ) and were defined as wasting. Metabolomic analysis showed that 557 circulating metabolites were altered following surgery (q < 0.05) in the whole cohort and 104 differed between wasting and non-wasting patients (q < 0.05). Weighted genome co-expression network analysis, identified clusters of metabolites, both before and after surgery, that associated with muscle mass and function (r = -0.72, p = 6 × 10-4 with RFCSA on Day 0, P = 3 × 10-4 with RFCSA on Day 7 and r = -0.73, P = 5 × 10-4 with hand-grip strength on Day 7). These clusters were mainly composed of acyl carnitines and dicarboxylates indicating that pre-existing mitochondrial dysfunction contributes to muscle loss following surgery. Surgery elevated cortisol to the same extent in wasting and non-wasting patients, but the cortisol:cortisone ratio was higher in the wasting patients (Day 3 P = 0.043 and Day 7 P = 0.016). Wasting patients also showed a greater increase in circulating nucleotides 3 days after surgery. Comparison of the metabolome with inflammatory markers identified by SOMAscan® showed that pre-surgical mitochondrial dysfunction was associated with growth differentiation factor 15 (GDF-15) (r = 0.79, P = 2 × 10-4 ) and that GDF-15, interleukin (IL)-8), C-C motif chemokine 23 (CCL-23), and IL-15 receptor subunit alpha (IL-15RA) contributed to metabolic changes in response to surgery. CONCLUSIONS: We show that pre-existing mitochondrial dysfunction and reduced cortisol inactivation contribute to muscle loss following surgery. The data also implicate GDF-15 and IL-15RA in mitochondrial dysfunction.

Assessment and determinants of global outcomes among 445 mass-casualty burn survivors: A 2-year retrospective cohort study in Taiwan.

PURPOSE: To study outcomes among survivors of the mass-casualty powder explosion on 27 June 2015, at Formosa Fun Coast Waterpark, New Taipei City, Taiwan. METHODS: Using retrospective data on Taiwanese survivors, we analyzed prehospital management, burns assessment and prognosis, functional recovery, and medical costs, followed-up through 30 June 2017. We related outcomes to burn extent, categorized according to the percentages of total body surface area with second/third-degree burns (%TBSA) or autologous split-thickness skin grafts (%STSG), and an investigational scale: f{SASG} = (%TBSA + %STSG)/2, stratified by %STSG. Analyses included casualty dispersal, comparisons between %TBSA, %STSG and f{SASG}, and their relationships with length of hospitalization, times to rehabilitation and social/school re-entry, physical/mental disability, and medical costs. We also investigated how burn scars restricting joint mobility affected rehabilitation duration. RESULTS: 445 hospitalized casualties (excluding 16 foreigners, 23 with 0% TBSA and 15 fatalities) aged 12-38 years, had mean TBSA of 41.1%. Hospitalization and functional recovery durations correlated with %TBSA, %STSG and f{SASG} - mean length of stay per %TBSA was 1.5 days; more numerous burn scar contractures prolonged rehabilitation. Females had worse burns than males, longer hospitalization and rehabilitation, and later school/social re-entry; at follow-up, 62.3% versus 37.7% had disabilities and 57.7% versus 42.3% suffered mental trauma (all p ≤ 0.001). Disabilities affecting 225/227 people were skin-related; 34 were severely disabled but 193 had mild/moderate impairments. The prevalence of stress-related and mood disorders increased with burn extent. Treatment costs (mean USD-equivalents ∼$48,977/patient, ∼$1192/%TBSA) increased with burn severity; however, the highest %TBSA, %STSG and f{SASG} categories accounted for <10% of total costs, whereas TBSA 41-80% accounted for 73.2%. CONCLUSIONS: Besides %TBSA, skin-graft requirements and burn scar contractures are complementary determinants of medium/long-term outcomes. We recommend further elucidation of factors that influence burn survivors' recovery, long-term physical and mental well-being, and quality of life.

Efficacy of multidomain interventions to improve physical frailty, depression and cognition: data from cluster-randomized controlled trials.

BACKGROUND: Frailty is the pre-eminent exigency of aging. Although frailty-related impairments are preventable, and multidomain interventions appear more effective than unimodal ones, the optimal components remain uncertain. METHODS: We devised multidomain interventions against physical and cognitive decline among prefrail/frail community-dwelling ≥65-year-olds and evaluated these in complementary cluster-randomized trials of efficacy and participant empowerment. The Efficacy Study compared ~3-monthly telephone consultations vs. 16, 2 h sessions/year comprising communally partaken physical and cognitive training plus nutrition and disease education; the Empowerment Study compared the standard Efficacy Study multidomain intervention (Sessions 1-10) vs. an enhanced version redesigned to empower and motivate individual participants. Changes from baseline in physical, functional, and cognitive performance were measured after 6 and 12 months in the Efficacy Study and after 6 months in the Empowerment Study, with post-intervention follow-up at 9 months. Primary outcomes are as follows: Cardiovascular Health Study frailty score; gait speed; handgrip strength; and Montreal Cognitive Assessment (MoCA). Secondary outcomes are as follows: instrumental activities of daily living; metabolic equivalent of task (MET); depressed mood (Geriatric Depression Scale-5 ≥2); and malnutrition (Mini-Nutritional Assessment short-form ≤11). Intervention effects were analyzed using a generalized linear mixed model. RESULTS: Efficacy Study participants (n = 1082, 40 clusters) were 75.1 ± 6.3 years old, 68.7% women, and 64.7% prefrail/frail; analytic clusters: 19 intervention (410/549 completed) vs. 21 control (375/533 completed). Empowerment Study participants (n = 440, 14 clusters) were 75.9 ± 7.1 years old, 83.6% women, and 56.7% prefrail/frail; analytic clusters: seven intervention (209/230 completed) vs. seven control (189/210 completed). The standard and enhanced multidomain interventions both reduced frailty and significantly improved aspects of physical, functional, and cognitive performance, especially among ≥75-year-olds. Standard multidomain intervention decreased depression [odds ratio 0.56, 95% confidence interval (CI) 0.32, 0.99] and malnutrition (odds ratio 0.45, 95% CI 0.26, 0.78) by 12 months and improved concentration at Months 6 (0.23, 95% CI 0.04, 0.42) and 12 (0.46, 95% CI 0.22, 0.70). Participant empowerment augmented activity (4.67 MET/h, 95% CI 1.64, 7.69) and gait speed (0.06 m/s, 95% CI 0.00, 0.11) at 6 months, with sustained improvements in delayed recall (0.63, 95% CI 0.20, 1.06) and MoCA performance (1.29, 95% CI 0.54, 2.03), and less prevalent malnutrition (odds ratio 0.39, 95% CI 0.18, 0.84), 3 months after the intervention ceased. CONCLUSIONS: Pragmatic multidomain intervention can diminish physical frailty, malnutrition, and depression and enhance cognitive performance among community-dwelling elders, especially ≥75-year-olds; this might supplement healthy aging policies, probably more effectively if participants are empowered.

Exploration of antibiotic resistance risks in a veterinary teaching hospital with Oxford Nanopore long read sequencing.

The Oxford Nanopore MinION DNA sequencing device can produce large amounts of long sequences, typically several kilobases, within a few hours. This long read capacity was exploited to detect antimicrobial resistance genes (ARGs) in a large veterinary teaching hospital environment, and to assess their taxonomic origin, genetic organisation and association with mobilisation markers concurrently. Samples were collected on eight occasions between November 2016 and May 2017 (inclusive) in a longitudinal study. Nanopore sequencing was performed on total DNA extracted from the samples after a minimal enrichment step in broth. Many ARGs present in the veterinary hospital environment could potentially confer resistance to antimicrobials widely used in treating infections of companion animals, including aminoglycosides, extended-spectrum beta-lactams, sulphonamides, macrolides, and tetracyclines. High-risk ARGs, defined here as single or multiple ARGs associated with pathogenic bacterial species or with mobile genetic elements, were shared between the intensive care unit (ICU) patient cages, a dedicated laundry trolley and a floor cleaning mop-bucket. By contrast, a floor surface from an office corridor without animal contact and located outside the veterinary hospital did not contain such high-risk ARGs. Relative abundances of high-risk ARGs and co-localisation of these genes on the same sequence read were higher in the laundry trolley and mop bucket samples, compared to the ICU cages, suggesting that amplification of ARGs is likely to occur in the collection points for hospital waste. These findings have prompted the implementation of targeted intervention measures in the veterinary hospital to mitigate the risks of transferring clinically important ARGs between sites and to improve biosecurity practices in the facility.

Progress toward Equitably Managed Protected Areas in Aichi Target 11: A Global Survey.

The Convention on Biological Diversity Aichi Target 11 requires its 193 signatory parties to incorporate social equity into protected area (PA) management by 2020. However, there is limited evidence of progress toward this commitment. We surveyed PA managers, staff, and community representatives involved in the management of 225 PAs worldwide to gather information against 10 equity criteria, including the distribution of benefits and burdens, recognition of rights, diversity of cultural and knowledge systems, and processes of participation in decision-making. Our results show that more than half of the respondents indicated that there are still significant challenges to be addressed in achieving equitably managed PAs, particularly in ensuring effective participation in decision-making, transparent procedures, access to justice in conflicting situations, and the recognition of the rights and diversity of local people. Our findings are a first and fundamental contribution toward a global assessment of equitable management in PAs to report on Aichi Target 11 in 2020 and help define the next set of PA targets from 2020-2030.

Programmed knockout mutation of liver fluke granulin attenuates virulence of infection-induced hepatobiliary morbidity.

Infection with the food-borne liver fluke Opisthorchis viverrini is the principal risk factor (IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2012) for cholangiocarcinoma (CCA) in the Lower Mekong River Basin countries including Thailand, Lao PDR, Vietnam and Cambodia. We exploited this link to explore the role of the secreted growth factor termed liver fluke granulin (Ov-GRN-1) in pre-malignant lesions by undertaking programmed CRISPR/Cas9 knockout of the Ov-GRN-1 gene from the liver fluke genome. Deep sequencing of amplicon libraries from genomic DNA of gene-edited parasites revealed Cas9-catalyzed mutations within Ov-GRN-1. Gene editing resulted in rapid depletion of Ov-GRN-1 transcripts and the encoded Ov-GRN-1 protein. Gene-edited parasites colonized the biliary tract of hamsters and developed into adult flukes, but the infection resulted in reduced pathology as evidenced by attenuated biliary hyperplasia and fibrosis. Not only does this report pioneer programmed gene-editing in parasitic flatworms, but also the striking, clinically-relevant pathophysiological phenotype confirms the role for Ov-GRN-1 in virulence morbidity during opisthorchiasis.

Healthcare costs and utilization associated with muscle weakness diagnosis codes in patients with chronic obstructive pulmonary disease: a United States claims analysis.

AIMS: Muscle weakness (MW)-attributable healthcare resource utilization (HCRU) and costs in patients with chronic obstructive pulmonary disease (COPD) have not been well-characterized in US insurance claims databases. The primary objective of this study was to estimate HCRU in patients with evidence of COPD with and without MW diagnosis codes. MATERIALS AND METHODS: This retrospective analysis used the MarketScan® Commercial Claims and Encounters and Medicare Supplemental and Coordination of Benefits databases. Between January 2007 and March 2016, we identified patients aged ≥40 years with diagnosis codes for COPD (≥1 emergency department or inpatient claim or ≥2 outpatient claims within 1 year). The cohort was divided into patients with and without ≥1 MW diagnosis code. Propensity score matching was used to generate pairs of patients with and without MW (1:1). Multivariable regression analyses were used to estimate adjusted incremental costs and utilization attributable to the presence of MW diagnosis codes among patients with COPD. RESULTS: Of 427,131 patients who met the study inclusion criteria, 14% had evidence of MW. After matching, 107,420 unique patients remained equally distributed across MW status. Patients with MW diagnosis codes had greater predicted annual HCRU, $2,465 greater total predicted annual COPD-related costs, and $15,179 greater total all-cause costs than those without MW diagnosis codes. Overall, <1% of patients received COPD-related pulmonary rehabilitation services. LIMITATIONS: Study limitations include the potential for undercoding of MW and lack of information on severity of MW in claims data. CONCLUSION: The presence of MW diagnosis codes yielded higher HCRU in this COPD population and suggests that the burden of MW affects both all-cause and COPD-related care. However, utilization of pulmonary rehabilitation, a known effective treatment for MW, remains low. Future research should expand on our results by assessing data sources that allow for clinical confirmation of MW among patients with COPD.

Transoesophageal echocardiography (TOE): contra-indications, complications and safety of perioperative TOE

Transoesophageal echocardiography (TOE) has, in certain clinical situations, become an almost universal monitor and diagnostic tool. In the perioperative environment, TOE is frequently used to guide anaesthetic management and assist with surgical decision making for, but not limited to, cardiothoracic, major vascular and transplant operations. The use of TOE is not limited to the theatre environment being frequently used in outpatient clinics, emergency departments and intensive care settings. Two case reports, one of oesophageal perforation and another of TOE utilization in a patient having previously undergone an oesophagectomy, introduce the need for care while using TOE and highlight the need for vigilance. The safe use of TOE, the potential complications and the suggested contra-indications are then considered together with suggestions for improving the safety of TOE in adult and paediatric patients.

GSK2881078, a SARM, Produces Dose-Dependent Increases in Lean Mass in Healthy Older Men and Women.

Context: GlaxoSmithKline (GSK) 2881078 is a nonsteroidal, selective androgen receptor modulator (SARM) under investigation by GSK for treatment of reduced mobility and other functional limitation in men and women with muscle weakness associated with chronic and acute illnesses. Objective: This was a phase 1b study intended to explore across a dose range the pharmacokinetics (PK)-pharmacodynamics relationship and further safety and tolerability data for GSK2881078. This study also evaluated effects of CYP3A4 inhibition on PK of GSK2881078. Methods: This was a randomized, placebo-controlled, parallel-group, repeat-dose, dose-escalation study in healthy older males and postmenopausal females. A total of three cohorts of males and three cohorts of females were studied. Dosing at each dose level was twice daily for the first 3 days followed by once daily for up to 53 days. Repeated dual-energy X-ray absorptiometry and MRI cross-sectional thigh scans were performed. The effect of CYP3A4 inhibition on GSK2881078 PK was evaluated in a separate cohort. Results: GSK2881078 was generally well tolerated and no serious adverse events were reported. Compared with placebo, there was greater lean mass accrual with all dose levels of GSK2881078. Females exhibited a greater response at lower doses than did males. Transient elevations of alanine aminotransferase were observed. The effect of CYP3A4 inhibition on GKS2881078 PK was unlikely to be of clinical significance. Conclusions: GSK2881078 yielded dose-dependent increases in lean mass with evidence of enhanced sensitivity in women. The compound was well tolerated.

Nutrition Adequacy Therapeutic Enhancement in the Critically Ill: A Randomized Double-Blind, Placebo-Controlled Trial of the Motilin Receptor Agonist Camicinal (GSK962040): The NUTRIATE Study.

BACKGROUND: Camicinal is a novel, nonmacrolide, motilin receptor agonist that accelerates gastric emptying in critically ill patients with established feed intolerance. The primary question was whether the preemptive administration of camicinal increased the provision of enteral nutrition (EN) to critically ill patients with risk factors that predisposed to feed intolerance. METHODS: This was an international, multicenter, parallel-group, blinded, randomized controlled trial. Patients at risk for feed intolerance, defined as receiving moderate to high doses of vasopressors or opiates, or admitted because of multiple traumatic injuries or with brain injury, received either enteral camicinal 50 mg or placebo daily for a maximum of 7 days, along with EN administered according to a standardized feeding protocol. The primary outcome was the daily adequacy of enteral feed delivered, as assessed by percentage of goal volume (delivered/prescribed × 100) before development of intolerance. RESULTS: Eighty-four patients participated. The administration of camicinal did not result in a statistically significant clinical difference in the daily average percentage goal volume delivered (camicinal vs placebo: 77% [95% confidence interval: 71, 83] vs 68% (58, 78); mean difference 9% [-5, 23]; P = 0.21). Similarly, there were no differences in the percentage goal calories (76% [65, 88] vs 68% [60, 77]) and protein (76% [66, 86] vs 70% [61, 80]) administered, or the incidence of feed intolerance (15% vs 14%). CONCLUSION: The incidence of feed intolerance was low in both groups. In this cohort the preemptive administration of enteral camicinal did not significantly augment the provision of goal EN.

2020 vision - An overview of prospects for diabetes management and prevention in the next decade.

After a century of medical progress, people nowadays live longer with diabetes than ever before. However, current preventative approaches, compounded in part by increased life-expectancy, are failing to reduce the prevalence of diabetes. Cardiovascular sequelae account for many of the four million deaths annually attributable to diabetes. Evidence indicates that certain glucose-lowering medications can improve vascular outcomes in some people with type 2 diabetes, which, together with better understanding of using multiple therapies concurrently, offers opportunities for beneficial personalization of medication regimens. However, further well-designed long-term studies are needed to evaluate cardiovascular benefits and safety of new and older medications, particularly in users typical of everyday diabetes care. Although there are numerous other promising advances in pharmacotherapies and biotechnology, these will probably be unaffordable for most people with diabetes globally. Therefore, effective national public health approaches will be essential to reducing the incidence of diabetes and its associated burdens; these may entail politically controversial measures to change unhealthy lifestyle behaviours. Stakeholders could learn from past failures and emulate successes in other health-care initiatives. Without early action at all levels, we face a future in which approaching one-quarter of humans will have diabetes, with more than half afflicted during their lifetime.