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Burns & Trauma 2024Prospective randomized trials in severely burned children have shown the positive effects of oxandrolone (OX), beta blockers (BB) and a combination of the two (BBOX) on...
BACKGROUND
Prospective randomized trials in severely burned children have shown the positive effects of oxandrolone (OX), beta blockers (BB) and a combination of the two (BBOX) on hypermetabolism, catabolism and hyperinflammation short- and long-term post-burn. Although data on severely burned adults are lacking in comparison, BB, OX and BBOX appear to be commonly employed in this patient population. In this study, we perform a secondary analysis of an international prospective randomized trial dataset to provide descriptive evidence regarding the current utilization patterns and potential treatment effects of OX, BB and BBOX.
METHODS
The RE-ENERGIZE (RandomizEd Trial of ENtERal Glutamine to minimIZE Thermal Injury, NCT00985205) trial included 1200 adult patients with severe burns. We stratified patients according to their receipt of OX, BB, BBOX or none of these drugs (None) during acute hospitalization. Descriptive statistics describe the details of drug therapy and unadjusted analyses identify predisposing factors for drug use per group. Association between OX, BB and BBOX and clinical outcomes such as time to discharge alive and 6-month mortality were modeled using adjusted multivariable Cox regressions.
RESULTS
More than half of all patients in the trial received either OX (n = 138), BB (n = 293) or BBOX (n = 282), as opposed to None (n = 487, 40.6%). Per study site and geographical region, use of OX, BB and BBOX was highly variable. Predisposing factors for the use of OX, BB and BBOX included larger total body surface area (TBSA) burned, higher acute physiology and chronic health evaluation (APACHE) II scores on admission and younger patient age. After adjustment for multiple covariates, the use of OX was associated with a longer time to discharge alive [hazard ratio (HR) 0.62, confidence interval (CI) (0.47-0.82) per 100% increase, = 0.001]. A higher proportion of days on BB was associated with lower in-hospital-mortality (HR: 0.5, CI 0.28-0.87, = 0.015) and 6-month mortality (HR: 0.44, CI 0.24-0.82, = 0.01).
CONCLUSIONS
The use of OX, BB and BBOX is common within the adult burn patient population, with its use varying considerably across sites worldwide. Our findings found mixed associations between outcomes and the use of BB and OX in adult burn patients, with lower acute and 6-month-mortality with BB and longer times to discharge with OX. Further research into these pharmacological modulators of the pathophysiological response to severe burn injury is indicated.
PubMed: 38650969
DOI: 10.1093/burnst/tkad063 -
British Journal of Anaesthesia Mar 2024Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PICS) is a clinical endotype of chronic critical illness. PICS consists of a self-perpetuating cycle... (Review)
Review
Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PICS) is a clinical endotype of chronic critical illness. PICS consists of a self-perpetuating cycle of ongoing organ dysfunction, inflammation, and catabolism resulting in sarcopenia, immunosuppression leading to recurrent infections, metabolic derangements, and changes in bone marrow function. There is heterogeneity regarding the definition of PICS. Currently, there are no licensed treatments specifically for PICS. However, findings can be extrapolated from studies in other conditions with similar features to repurpose drugs, and in animal models. Drugs that can restore immune homeostasis by stimulating lymphocyte production could have potential efficacy. Another treatment could be modifying myeloid-derived suppressor cell (MDSC) activation after day 14 when they are immunosuppressive. Drugs such as interleukin (IL)-1 and IL-6 receptor antagonists might reduce persistent inflammation, although they need to be given at specific time points to avoid adverse effects. Antioxidants could treat the oxidative stress caused by mitochondrial dysfunction in PICS. Possible anti-catabolic agents include testosterone, oxandrolone, IGF-1 (insulin-like growth factor-1), bortezomib, and MURF1 (muscle RING-finger protein-1) inhibitors. Nutritional support strategies that could slow PICS progression include ketogenic feeding and probiotics. The field would benefit from a consensus definition of PICS using biologically based cut-off values. Future research should focus on expanding knowledge on underlying pathophysiological mechanisms of PICS to identify and validate other potential endotypes of chronic critical illness and subsequent treatable traits. There is unlikely to be a universal treatment for PICS, and a multimodal, timely, and personalised therapeutic strategy will be needed to improve outcomes for this growing cohort of patients.
Topics: Animals; Humans; Critical Illness; Syndrome; Immunosuppression Therapy; Inflammation; Chronic Disease; Research
PubMed: 38177003
DOI: 10.1016/j.bja.2023.11.052 -
Current Opinion in Clinical Nutrition... Mar 2011The hypermetabolic response in critically ill patients is characterized by hyperdynamic circulatory, physiologic, catabolic and immune system responses. Failure to... (Review)
Review
PURPOSE OF REVIEW
The hypermetabolic response in critically ill patients is characterized by hyperdynamic circulatory, physiologic, catabolic and immune system responses. Failure to satisfy overwhelming energy and protein requirements after, and during critical illness, results in multiorgan dysfunction, increased susceptibility to infection, and death. Attenuation of the hypermetabolic response by various pharmacologic modalities is emerging as an essential component of the management of severe burn patients. This review focuses on the more recent advances in therapeutic strategies to attenuate the hypermetabolic response and its associated insulin resistance postburn.
RECENT FINDINGS
At present, beta-adrenergic blockade with propranolol represents probably the most efficacious anticatabolic therapy in the treatment of burns. Other pharmacological strategies include growth hormone, insulin-like growth factor, oxandrolone and intensive insulin therapy.
SUMMARY
Novel approaches to the management of critical illness by judicious glucose control and the use of pharmacologic modulators to the hypercatabolic response to critical illness have emerged. Investigation of alternative strategies, including the use of metformin, glucagon-like-peptide-1 and the PPAR-γ agonists are under current investigation.
Topics: Anabolic Agents; Blood Glucose; Burns; Growth Hormone; Humans; Insulin; Insulin Resistance; Insulin-Like Growth Factor I; Oxandrolone; Propranolol
PubMed: 21157309
DOI: 10.1097/MCO.0b013e3283428df1 -
Archives of Disease in Childhood Jan 2021The UK Turner syndrome (TS) study examined the effect on final height of oxandrolone 0.05 mg/kg/day (maximum dose 2.5 mg) versus placebo from 9 years of age; and... (Randomized Controlled Trial)
Randomized Controlled Trial
The UK Turner syndrome (TS) study examined the effect on final height of oxandrolone 0.05 mg/kg/day (maximum dose 2.5 mg) versus placebo from 9 years of age; and delaying ethinylestradiol induction of puberty by 2 years from 12 (E12) to 14 (E14) years in growth hormone-treated girls with TS. The study ran from 1999 to 2013. By 2011, eighty-two of 92 participants had reached final height and an interim analysis using the Super-Imposition by Translation And Rotation model showed significant increases in final height with both oxandrolone and E14. The analysis has been repeated now that all 92 patients have reached final height. Oxandrolone still significantly increased final height by 4.1 cm (95% CI 1.6 to 6.6, n=92) compared with 4.6 cm previously. However, the E14 effect was no longer significant at 2.7 cm (95% CI -0.8 to 6.1, n=56) compared with 3.8 cm previously.
Topics: Anabolic Agents; Body Height; Child; Drug Administration Schedule; Female; Humans; Male; Oxandrolone; Treatment Outcome; Turner Syndrome; United Kingdom
PubMed: 31862699
DOI: 10.1136/archdischild-2019-317695 -
Frontiers in Endocrinology 2023To study the impact of GH dose and age at GH start in girls with Turner syndrome (TS), aiming for normal height and age at pubertal onset (PO) and at adult height (AH)....
OBJECTIVE
To study the impact of GH dose and age at GH start in girls with Turner syndrome (TS), aiming for normal height and age at pubertal onset (PO) and at adult height (AH). However, age at diagnosis will limit treatment possibilities.
METHODS
National multicenter investigator-initiated studies (TNR 87-052-01 and TNR 88-072) in girls with TS, age 3-16 years at GH start during year 1987-1998, with AH in 2003-2011. Of the 144 prepubertal girls with TS, 132 girls were followed to AH (intention to treat), while 43 girls reduced dose or stopped treatment prematurely, making n=89 for Per Protocol population. Age at GH start was 3-9 years (young; n=79) or 9-16 years (old; n=53). Treatment given were recombinant human (rh)GH (Genotropin Kabi Peptide Hormones, Sweden) 33 or 67 µg/kg/day, oral ethinyl-estradiol (2/3) or transdermal 17β-estradiol (1/3), and, after age 11 years, mostly oxandrolone. Gain in height, AH, and age at PO and at AH were evaluated.
RESULTS
At GH start, height was -2.8 (versus non-TS girls) for all subgroups and mean age for young was 5.7 years and that of old was 11.6 years. There was a clear dose-response in both young and old TS girls; the mean difference was (95%CI) 0.66 (-0.91 to -0.26) and 0.57 (-1.0 to -0.13), respectively. The prepubertal gain (1.3-2.1) was partly lost during puberty (-0.4 to -2.1). Age/height at PO ranged from 13 years/-0.42 for GH to 15.2 years/-1.47 for GH. At AH, GH group became tallest (17.2 years; 159.9 cm; -1.27 SDS; total gain, 1.55) compared to GH group being least delayed (16.1 years; 157.1 cm; -1.73 SDS; total, 1.08). The shortest was the GH group (17.3 years; 153.7 cm: -2.28 SDS; total gain, 0.53), and the most delayed was the GH group, (18.5 years; 156.5 cm; -1.82 SDS; total gain, 0.98).
CONCLUSION
For both young and old TS girls, there was a GH-dose growth response, and for the young, there was less delayed age at PO and at AH. All four groups reached an AH within normal range, despite partly losing the prepubertal gain during puberty. Depending on age at diagnosis, low age at start with higher GH dose resulted in greater prepubertal height gain, permitting estrogen to start earlier at normal age and attaining normal AH at normal age, favoring physiological treatment and possibly also bone health, hearing, uterine growth and fertility, psychosocial wellbeing during adolescence, and the transition to adulthood.
Topics: Female; Adolescent; Humans; Adult; Child, Preschool; Child; Human Growth Hormone; Growth Hormone; Turner Syndrome; Sweden; Body Height; Puberty; Estradiol
PubMed: 37529614
DOI: 10.3389/fendo.2023.1197897 -
The Cochrane Database of Systematic... Sep 2014Recombinant human growth hormone (rhGH) increases protein synthesis, therefore it is used in burns with a total body surface area (TBSA) greater than 40%, where there is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Recombinant human growth hormone (rhGH) increases protein synthesis, therefore it is used in burns with a total body surface area (TBSA) greater than 40%, where there is frequently an increase in protein breakdown and a decrease in protein synthesis. This change in protein metabolism correlates with poor wound healing of the burn and donor sites.
OBJECTIVES
To determine the effects of rhGH on the healing rate of burn wounds and donor sites in people with burns.
SEARCH METHODS
For this first update we searched the Cochrane Wounds Group Specialised Register (searched 04 September 2014); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 8); Database of Abstracts of Reviews of Effects (DARE) (The Cochrane Library 2014, Issue 3); Ovid MEDLINE (1950 to September Week 4 2014); Ovid MEDLINE (In-Process & Other Non-Indexed Citations September 8, 2014); Ovid EMBASE (1980 to 2014 Week 35); and EBSCO CINAHL (1982 to 8 September 2014).
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing rhGH with any comparator intervention, e.g. oxandrolone or placebo, in adults or children with burns.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies, assessed trial quality and extracted data. The primary outcomes were the healing of the burn wound and donor sites and the occurrence of wound infections. The secondary outcomes were mortality rate, length of hospital stay, scar assessment, and adverse events: hyperglycaemia and septicaemia.
MAIN RESULTS
We included 13 RCTs (701 people). Six of the RCTs included only children aged 1 to 18 years and seven involved only adults (from 18 to 65 years of age). The mean TBSA of the included participants was greater than 49%. Twelve studies compared rhGH with placebo and one study compared rhGH with oxandrolone. Two trials found that compared with placebo, burn wounds in adults treated with rhGH healed more quickly (by 9.07 days; 95% confidence interval (CI) 4.39 to 13.76, I² = 0%). The donor site healing time was significantly shorter in rhGH-treated adults compared with placebo-treated participants (by 3.15 days; 95% CI 1.54 to 4.75, I² = 0%). Two studies in children with the outcome of donor site healing time could be pooled and the donor site healing time was shorter in the rhGH-treated children (by 1.70 days; 95% CI 0.87 to 2.53, I² = 0%). No studies reporting the outcome of wound infection were found. The incidence of hyperglycaemia was higher in adults during rhGH treatment compared with placebo (risk ratio (RR) 2.43; 95% CI 1.54 to 3.85), but not in children. Pooling the studies of adults and children yielded a significantly higher incidence of hyperglycaemia in the rhGH-treated participants (RR 2.65; 95% CI 1.68 to 4.16).
AUTHORS' CONCLUSIONS
There is some evidence that using rhGH in people with large burns (more than 40% of the total body surface area) could result in more rapid healing of the burn wound and donor sites in adults and children, and in reduced length of hospital stay, without increased mortality or scarring, but with an increased risk of hyperglycaemia. This evidence is based on studies with small sample sizes and risk of bias and requires confirmation in higher quality, adequately powered trials.
Topics: Adolescent; Adult; Aged; Anabolic Agents; Body Surface Area; Burns; Child; Child, Preschool; Human Growth Hormone; Humans; Infant; Middle Aged; Oxandrolone; Randomized Controlled Trials as Topic; Recombinant Proteins; Transplant Donor Site; Wound Healing; Young Adult
PubMed: 25222766
DOI: 10.1002/14651858.CD008990.pub3 -
Hormone Research in Paediatrics 2010This mini review summarizes papers presented in a Joint Symposium between the Bone, Growth Plate and Turner Syndrome Working Groups of the European Society for... (Review)
Review
This mini review summarizes papers presented in a Joint Symposium between the Bone, Growth Plate and Turner Syndrome Working Groups of the European Society for Paediatric Endocrinology (ESPE) that was held on September 9, 2009, in New York.The program had been composed to give an update on hormones and genes of importance in bone physiology and their influence on bone mineralization and growth in Turner syndrome. This paper summarizes the data and highlights the main topics and discussions related to each presentation.
Topics: Adolescent; Body Height; Bone Density; Bone Development; Bone Diseases, Metabolic; Calcification, Physiologic; Cartilage; Child; Female; Homeodomain Proteins; Humans; Oxandrolone; Oxidative Stress; Short Stature Homeobox Protein; Turner Syndrome
PubMed: 20197667
DOI: 10.1159/000284356 -
Critical Care Medicine Jun 2016ICU-acquired weakness is a common complication of critical illness and can have significant effects upon functional status and quality of life. As part of preliminary... (Review)
Review
OBJECTIVES
ICU-acquired weakness is a common complication of critical illness and can have significant effects upon functional status and quality of life. As part of preliminary work to inform the design of a randomized trial of a complex intervention to improve recovery from critical illness, we sought to identify pharmacological interventions that may play a role in this area.
DATA SOURCES
We systematically reviewed the published literature relating to pharmacological intervention for the treatment and prevention of ICU-acquired weakness.
STUDY SELECTION
We searched MEDLINE, EMBASE, CINAHL+, Web of Science, and both U.S. and European trial registries up to July 2014 alongside reviews and reference lists from populations with no age or language restrictions. We included studies that reported a measure of muscle structure or physical function as an outcome measure.
DATA EXTRACTION
We estimated pooled odds ratios and 95% CI using data extracted from published articles or where available, original data provided by the authors. Assessment of bias was performed using the Cochrane Collaboration's risk of bias tool.
DATA SYNTHESIS
Ten studies met the inclusion criteria. The current body of evidence does not support the use of any pharmacological agent in this setting, although maintaining euglycemia may reduce the prevalence of critical illness polyneuropathy.
CONCLUSIONS
At present, no pharmacological intervention can be recommended to prevent or treat ICU-acquired weakness. Further research is required into this field to include more novel agents such as myostatin inhibitors. Challenges in the conduct of research in this area are highlighted.
Topics: Adrenergic beta-Antagonists; Anabolic Agents; Critical Illness; Glutamine; Growth Hormone; Humans; Hyperglycemia; Hypoglycemic Agents; Immunoglobulins, Intravenous; Immunologic Factors; Insulin; Muscle Weakness; Oxandrolone; Polyneuropathies; Propranolol
PubMed: 26958749
DOI: 10.1097/CCM.0000000000001652 -
The American Journal of Clinical... Apr 2010This article and others that focused on the clinical features, mechanisms, and epidemiology of skeletal muscle loss and wasting in chronic diseases, which include... (Review)
Review
This article and others that focused on the clinical features, mechanisms, and epidemiology of skeletal muscle loss and wasting in chronic diseases, which include chronic kidney disease, cancer, and AIDS, were presented at a symposium entitled "Cachexia and Wasting: Recent Breakthroughs in Understanding and Opportunities for Intervention," held at Experimental Biology 2009. The clinical and anabolic efficacy of specific growth factors and anabolic steroids (eg, growth hormone, testosterone, megestrol acetate) in malnutrition and other catabolic states has been the subject of considerable research during the past several decades. Research on the effects of these agents in cachexia or wasting conditions, characterized by progressive loss of skeletal muscle and adipose tissue, focused on patients with AIDS in the early 1990s, when the devastating effects of the loss of body weight, lean body mass, and adipose tissue were recognized as contributors to these patients' mortality. These same agents have also been studied as methods to attenuate the catabolic responses observed in cancer-induced cachexia and in wasting induced by chronic obstructive pulmonary disease, congestive heart failure, renal failure, and other conditions. This article provides an updated review of recent clinical trials that specifically examined the potential therapeutic roles of growth hormone, testosterone, oxandrolone, and megestrol acetate and emerging data on the orexigenic peptide ghrelin, in human cachexia and wasting.
Topics: Anabolic Agents; Cachexia; Clinical Trials as Topic; Ghrelin; Human Growth Hormone; Humans; Megestrol Acetate; Muscular Atrophy; Oxandrolone; Steroids; Testosterone; Wasting Syndrome
PubMed: 20164318
DOI: 10.3945/ajcn.2010.28608E -
Proceedings of the Royal Society of... Jun 1974
Review
Topics: Contraceptives, Oral; Estrogens; Female; Humans; Hyperlipidemias; Lipase; Lipoproteins, VLDL; Norethindrone; Norpregnadienes; Oxandrolone; Progestins; Triglycerides
PubMed: 4368749
DOI: No ID Found