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Annals of Surgery Sep 2018Massive burns induce a hypermetabolic response that leads to total body wasting and impaired physical and psychosocial recovery. The administration of propranolol or... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Massive burns induce a hypermetabolic response that leads to total body wasting and impaired physical and psychosocial recovery. The administration of propranolol or oxandrolone positively affects postburn metabolism and growth. The combined administration of oxandrolone and propranolol (OxProp) for 1 year restores growth in children with large burns. Here, we investigated whether the combined administration of OxProp for 1 year would reduce scarring and improve quality of life compared with control.
STUDY DESIGN
Children with large burns (n = 480) were enrolled into this institutional review board-approved study; patients were randomized to control (n = 226) or administration of OxProp (n = 126) for 1 year postburn. Assessments were conducted at discharge and 6, 12, and 24 months postburn. Scar biopsies were obtained for histology. Physical scar assessments and patient reported outcome measures of physical and psychosocial function were obtained.
RESULTS
Reductions in cellularity, vascular structures, inflammation, and abnormal collagen (P < 0.05) occurred in OxProp-treated scars. With OxProp, scar severity was attenuated and pliability increased (both P < 0.05). Analyses of patient-reported outcomes showed improved general and emotional health within the OxProp-treated group (P < 0.05).
CONCLUSIONS
Here, we have shown improvements in objective and subjective measures of scarring and an increase in overall patient-reported physical function. The combined administration of OxProp for up to a year after burn injury should be considered for the reduction of postburn scarring and improvement of long-term psychosocial outcomes in children with massive burns.
Topics: Adolescent; Anabolic Agents; Biomarkers; Biopsy; Burns; Child; Cicatrix, Hypertrophic; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Female; Humans; Immunoenzyme Techniques; Male; Oxandrolone; Propranolol; Prospective Studies; Quality of Life; Recovery of Function; Treatment Outcome; Vasodilator Agents
PubMed: 30048322
DOI: 10.1097/SLA.0000000000002926 -
The Journal of Clinical Endocrinology... Sep 2018Klinefelter syndrome (KS) is a common genetic condition in which males have an extra X chromosome. KS is associated with testosterone deficiency, neurodevelopmental... (Randomized Controlled Trial)
Randomized Controlled Trial
CONTEXT
Klinefelter syndrome (KS) is a common genetic condition in which males have an extra X chromosome. KS is associated with testosterone deficiency, neurodevelopmental delays, and cardiometabolic disorders. There has been recent interest in prepubertal androgen treatment; however, the effects on puberty and gonadal function are unknown.
OBJECTIVE
To compare onset of puberty and testicular function in prepubertal boys treated with 2 years of oxandrolone (Ox) vs placebo (Pl).
DESIGN
Double-blind, randomized, controlled trial.
SETTING
Single tertiary care referral center.
PARTICIPANTS
Eighty prepubertal boys with KS; mean age: 8.0 ± 2.2 years (range: 4 to 12).
INTERVENTIONS
Ox 0.05 mg/kg vs identical-appearing Pl capsule given for 2 years.
OUTCOME MEASURES
Onset of gonadarche (testicular volume ≥4 mL) and onset of pubarche (Tanner 2 pubic hair); change in testicular hormone concentrations.
RESULTS
Ox-treated group had 20.5 times higher odds of reaching gonadarche (OR 95% CI: 6.5, 77.8) and 28.1 times higher odds of reaching pubarche (OR 95% CI: 8.8, 110.4) during the 2-year study period after adjusting for baseline age. Gonadarche and pubarche both occurred at a younger age in the Ox group (gonadarche: 9.8 ± 1.5 vs 12.1 ± 1.0 years, P < 0.001; pubarche: 10.2 ± 1.1 vs 11.6 ± 1.3 years, P = 0.02). Serum concentrations of testicular hormones and gonadotropins were not different between groups.
CONCLUSIONS
Two years of Ox treatment in prepubertal boys with KS results in an increased risk of early gonadarche, on average 2 years earlier than in Pl-treated boys. Ox did not affect serum concentrations of testicular hormones.
Topics: Androgens; Child; Child, Preschool; Double-Blind Method; Humans; Klinefelter Syndrome; Male; Oxandrolone; Puberty; Testicular Hormones; Testis; Treatment Outcome
PubMed: 29931143
DOI: 10.1210/jc.2018-00682 -
Journal of Clinical Research in... Jul 2018A comprehensive survey was conducted to evaluate the shortcomings of clinical care in patients with Turner syndrome (TS) in Turkey.
OBJECTIVE
A comprehensive survey was conducted to evaluate the shortcomings of clinical care in patients with Turner syndrome (TS) in Turkey.
METHODS
A structured questionnaire prepared by the Turner study group in Turkey, which covered relevant aspects of patient care in TS was sent to 44 pediatric endocrinology centers.
RESULTS
Eighteen centers (41%) responded to the questionnaire. In the majority of the centers, diagnostic genetic testing, screening for Y chromosomal material, protocols regarding the timing and posology of growth hormone (GH) and estrogen, thrombophilia screening, fertility information and screening for glucose intolerance, thyroid, and coeliac diseases in patients with TS were in line with the current consensus. Thirteen centers (72.2%) performed GH stimulation tests. Only four centers (22.2%) used oxandrolone in patients with TS with very short stature. The majority of the centers relied on bone age and breast development to assess estrogen adequacy, though together with variable combinations of oestrogen surrogates. Two centers (11.1%) reported performing serum estradiol measurements. Eight centers (44.4%) routinely conducted cardiac/thoracic aorta magnetic resonance imaging. Screening for hearing, dental and ophthalmologic problems were performed by thirteen (72.2%), six (33.3%) and ten (55.6%) centers, respectively. Psychiatric assessments were made by four centers (22.2%) at diagnosis, with only one center (5.6%) requiring annual reassessments.
CONCLUSION
Although we found some conformity between the current consensus and practice of the participating centers in Turkey regarding TS, further improvements are mandatory in the multi-disciplinary approach to address co-morbidities, which if unrecognized, may be associated with reduced quality of life and even mortality.
Topics: Adolescent; Adult; Child; Female; Humans; Surveys and Questionnaires; Turkey; Turner Syndrome; Young Adult
PubMed: 29699389
DOI: 10.4274/jcrpe.0003 -
Endocrine Connections Apr 2018This study sought to determine the effect of the recombinant human growth hormone (rhGH) treatment of Turner syndrome (TS) on height outcome.
OBJECTIVE
This study sought to determine the effect of the recombinant human growth hormone (rhGH) treatment of Turner syndrome (TS) on height outcome.
METHODS
We searched in MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews. A literature search identified 640 records. After screening and full-text assessment, 11 records were included in the systematic review. Methodological quality was assessed using the Cochrane Risk of Bias tool. RevMan 5.3 software was used for meta-analysis. We also assessed the quality of evidence with the GRADE system.
RESULTS
Compared with controls, rhGH therapy led to increased final height (MD = 7.22 cm, 95% CI 5.27-9.18, < 0.001, 2 = 4%; = 0.18), height standard deviation (HtSDS) (SMD = 1.22, 95% CI 0.88-1.56, < 0.001, 2 = 49%; = 0.14) and height velocity (HV) (MD 2.68 cm/year; 95% CI 2.34, 3.02; < 0.001, 2 = 0%; = 0.72). There was a small increase in bone age (SMD 0.32 years; 95% CI 0.1, 0.54; = 0.004, 2 = 73%; = 0.02) after rhGH therapy for 12 months. What is more, the rhGH/oxandrolone combination therapy suggested greater final height (MD 2.46 cm; 95% CI 0.73, 4.18; = 0.005, 2 = 32%; = 0.22), increase and faster HV (SMD 1.67 cm/year; 95% CI 1.03, 2.31; < 0.03, 2 = 80%; < 0.001), with no significant increase in HtSDS and bone maturation compared with rhGH therapy alone.
CONCLUSIONS
For TS patients, rhGH alone or with concomitant use of oxandrolone treatment had advantages on final height.
PubMed: 29581156
DOI: 10.1530/EC-18-0115 -
Cureus Nov 2017Nonprescription drug use is increasingly prevalent in the United States. We report a case of a 31-year-old male who presented with hallucinations and was found to have...
Nonprescription drug use is increasingly prevalent in the United States. We report a case of a 31-year-old male who presented with hallucinations and was found to have rhabdomyolysis. He was consuming oxandrolone for six weeks and ingested methamphetamine the night prior to presentation. With supportive treatment, including intravenous hydration, the patient's mental status returned to baseline and rhabdomyolysis resolved. Our case illustrates the need to understand the interaction between different illicit substances. More research needs to be done to further understand the reactions between different medications as patients consume different combinations of substances.
PubMed: 29344437
DOI: 10.7759/cureus.1843 -
Biosensors Dec 2017We have studied the Fourier Transform Infrared (FT-IR) and the Fourier transform Raman (FT-Raman) spectra of stanozolol and oxandrolone, and we have performed quantum...
We have studied the Fourier Transform Infrared (FT-IR) and the Fourier transform Raman (FT-Raman) spectra of stanozolol and oxandrolone, and we have performed quantum chemical calculations based on the density functional theory (DFT) with a B3LYP/6-31G (d, p) level of theory. The FT-IR and FT-Raman spectra were collected in a solid phase. The consistency between the calculated and experimental FT-IR and FT-Raman data indicates that the B3LYP/6-31G (d, p) can generate reliable geometry and related properties of the title compounds. Selected experimental bands were assigned and characterized on the basis of the scaled theoretical wavenumbers by their total energy distribution. The good agreement between the experimental and theoretical spectra allowed positive assignment of the observed vibrational absorption bands. Finally, the calculation results were applied to simulate the Raman and IR spectra of the title compounds, which show agreement with the observed spectra.
Topics: Anabolic Agents; Oxandrolone; Quantum Theory; Spectroscopy, Fourier Transform Infrared; Spectrum Analysis, Raman; Stanozolol
PubMed: 29278383
DOI: 10.3390/bios8010002 -
Medicine and Science in Sports and... Mar 2018Severe burns result in prolonged hypermetabolism and skeletal muscle catabolism. Rehabilitative exercise training (RET) programs improved muscle mass and strength in... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Severe burns result in prolonged hypermetabolism and skeletal muscle catabolism. Rehabilitative exercise training (RET) programs improved muscle mass and strength in severely burned children. The combination of RET with β-blockade or testosterone analogs showed improved exercise-induced benefits on body composition and muscle function. However, the effect of RET combined with multiple drug therapy on muscle mass, strength, cardiorespiratory fitness, and protein turnover are unknown. In this placebo-controlled randomized trial, we hypothesize that RET combined with oxandrolone and propranolol (Oxprop) will improve muscle mass and function and protein turnover in severely burned children compared with burned children undergoing the same RET with a placebo.
METHODS
We studied 42 severely burned children (7-17 yr) with severe burns over 30% of the total body surface area. Patients were randomized to placebo (22 control) or to Oxprop (20) and began drug administration within 96 h of admission. All patients began RET at hospital discharge as part of their standardized care. Muscle strength (N·m), power (W), V˙O2peak, body composition, and protein fractional synthetic rate and fractional breakdown rate were measured pre-RET (PRE) and post-RET (POST).
RESULTS
Muscle strength and power, lean body mass, and V˙O2peak increased with RET in both groups (P < 0.01). The increase in strength and power was significantly greater in Oxprop versus control (P < 0.01), and strength and power was greater in Oxprop over control POST (P < 0.05). Fractional synthetic rate was significantly higher in Oxprop than control POST (P < 0.01), resulting in improved protein net balance POST (P < 0.05).
CONCLUSIONS
Rehabilitative exercise training improves body composition, muscle function, and cardiorespiratory fitness in children recovering from severe burns. Oxprop therapy augments RET-mediated improvements in muscle strength, power, and protein turnover.
Topics: Adolescent; Basal Metabolism; Body Composition; Burns; Cardiorespiratory Fitness; Child; Exercise Therapy; Female; Heart Rate; Humans; Male; Muscle Strength; Muscle, Skeletal; Oxandrolone; Oxygen Consumption; Propranolol
PubMed: 29040226
DOI: 10.1249/MSS.0000000000001459 -
Burns & Trauma 2017Trauma and related sequelae result in disturbance of homeostatic mechanisms frequently leading to cellular dysfunction and ultimately organ and system failure.... (Review)
Review
Trauma and related sequelae result in disturbance of homeostatic mechanisms frequently leading to cellular dysfunction and ultimately organ and system failure. Regardless of the type and severity of injury, gender dimorphism in outcomes following trauma have been reported, with females having lower mortality than males, suggesting that sex steroid hormones (SSH) play an important role in the response of body systems to trauma. In addition, several clinical and experimental studies have demonstrated the effects of SSH on the clinical course and outcomes following injury. Animal studies have reported the ability of SSH to modulate immune, inflammatory, metabolic and organ responses following traumatic injury. This indicates that homeostatic mechanisms, via direct and indirect pathways, can be maintained by SSH at local and systemic levels and hence result in more favourable prognosis. Here, we discuss the role and mechanisms by which SSH modulates the response of the body to injury by maintaining various processes and organ functions. Such properties of sex hormones represent potential novel therapeutic strategies and further our understanding of current therapies used following injury such as oxandrolone in burn-injured patients.
PubMed: 28920065
DOI: 10.1186/s41038-017-0093-9 -
The Cochrane Database of Systematic... Jun 2017Pressure ulcers, also known as bed sores, pressure sores or decubitus ulcers develop as a result of a localised injury to the skin or underlying tissue, or both. The... (Review)
Review
BACKGROUND
Pressure ulcers, also known as bed sores, pressure sores or decubitus ulcers develop as a result of a localised injury to the skin or underlying tissue, or both. The ulcers usually arise over a bony prominence, and are recognised as a common medical problem affecting people confined to a bed or wheelchair for long periods of time. Anabolic steroids are used as off-label drugs (drugs which are used without regulatory approval) and have been used as adjuvants to usual treatment with dressings, debridement, nutritional supplements, systemic antibiotics and antiseptics, which are considered to be supportive in healing of pressure ulcers. Anabolic steroids are considered because of their ability to stimulate protein synthesis and build muscle mass. Comprehensive evidence is required to facilitate decision making, regarding the benefits and harms of using anabolic steroids.
OBJECTIVES
To assess the effects of anabolic steroids for treating pressure ulcers.
SEARCH METHODS
In March 2017 we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE (including In-Process & Other Non-Indexed Citations); Ovid Embase and EBSCO CINAHL Plus. We also searched clinical trials registries for ongoing and unpublished studies, and scanned reference lists of relevant included studies as well as reviews, meta-analyses and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication or study setting.
SELECTION CRITERIA
Published or unpublished randomised controlled trials (RCTs) comparing the effects of anabolic steroids with alternative treatments or different types of anabolic steroids in the treatment of pressure ulcers.
DATA COLLECTION AND ANALYSIS
Two review authors independently carried out study selection, data extraction and risk of bias assessment.
MAIN RESULTS
The review contains only one trial with a total of 212 participants, all with spinal cord injury and open pressure ulcers classed as stage III and IV. The participants were mainly male (98.2%, 106/108) with a mean age of 58.4 (standard deviation 10.4) years in the oxandrolone group and were all male (100%, 104/104) with a mean age of 57.3 (standard deviation 11.6) years in the placebo group. This trial compared oxandrolone (20 mg/day, administered orally) with a dose of placebo (an inactive substance consisting of 98% starch and 2% magnesium stearate) and reported data on complete healing of ulcers and adverse events. There was very low-certainty evidence on the relative effect of oxandrolone on complete ulcer healing at the end of a 24-week treatment period (risk ratio RR) 0.81, 95% confidence interval (CI) 0.52 to 1.26) (downgraded twice for imprecision due to an extremely wide 95% CI, which spanned both benefit and harm, and once for indirectness, as the participants were mostly male spinal cord injury patients). Thus, we are uncertain whether oxandrolone improves or reduces the complete healing of pressure ulcers, as we assessed the certainty of the evidence as very low.There was low-certainty evidence on the risk of non-serious adverse events reported in participants treated with oxandrolone compared with placebo (RR 3.85, 95% CI 1.12 to 13.26) (downgraded once for imprecision and once for indirectness, as the participants were mostly male spinal cord injury patients). Thus, the treatment with oxandrolone may increase the risk of non-serious adverse events reported in participants.There was very low-certainty evidence on the risk of serious adverse events reported in participants treated with oxandrolone compared with placebo (RR 0.54, 95% CI 0.25 to 1.17) (downgraded twice for imprecision due to an extremely wide 95% CI, which spanned both benefit and harm, and once for indirectness, as the participants were mostly male spinal cord injury patients). Of the five serious adverse events reported in the oxandrolone-treated group, none were classed by the trial teams as being related to treatment. We are uncertain whether oxandrolone increases or decreases the risk of serious adverse events as we assessed the certainty of the evidence as very low.Secondary outcomes such as pain, length of hospital stay, change in wound size or wound surface area, incidence of different type of infection, cost of treatment and quality of life were not reported in the included trial.Overall the evidence in this study was of very low quality (downgraded for imprecision and indirectness). This trial stopped early when the futility analysis (interim analysis) in the opinion of the study authors showed that oxandrolone had no benefit over placebo for improving ulcer healing.
AUTHORS' CONCLUSIONS
There is no high quality evidence to support the use of anabolic steroids in treating pressure ulcers.Further well-designed, multicenter trials, at low risk of bias, are necessary to assess the effect of anabolic steroids on treating pressure ulcers, but careful consideration of the current trial and its early termination are required when planning future research.
Topics: Female; Humans; Male; Middle Aged; Off-Label Use; Oxandrolone; Pressure Ulcer; Starch; Stearic Acids; Testosterone Congeners; Wound Healing
PubMed: 28631809
DOI: 10.1002/14651858.CD011375.pub2 -
The Journal of Pediatrics Jun 2017To examine the effects of early low-dose androgen on motor, cognitive, and behavioral function in prepubertal boys with Klinefelter syndrome (47,XXY). (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
To examine the effects of early low-dose androgen on motor, cognitive, and behavioral function in prepubertal boys with Klinefelter syndrome (47,XXY).
STUDY DESIGN
Double-blind trial of 84 boys, ages 4-12 years, randomized to oxandrolone (Ox; 0.06?mg/kg daily; n?=?43) or placebo (Pl; n?=?41) for 24 months. Standardized assessments were performed at baseline and every 12 months for 24 months evaluating motor, cognitive, and behavioral function.
RESULTS
The 24-month outcomes were better in the Ox vs. Pl group on 1 of 5 primary endpoints (motor function/strength): Bruininks Visual-Motor scale (P?=?.005), without significant differences between the 2 groups for the other 4 components. Secondary analyses suggested improvement in the Ox vs. Pl group in the anxiety/depression (P?=?.03) and social problems (P?=?.01) scales on the Child Behavior Checklist, anxiety (P?=?.04) on the Piers Harris Self Concept Scale, and interpersonal problems (P?=?.02) on the Children's Depression Inventory, without significant differences in hyperactive or aggressive behaviors.
CONCLUSIONS
This double-blind, randomized trial demonstrates that 24 months of childhood low-dose androgen treatment in boys with Klinefelter syndrome benefited 1 of 5 primary endpoints (visual-motor function). Secondary analyses demonstrated positive effects of androgen on aspects of psychosocial function (anxiety, depression, social problems), without significant effects on cognitive function, or hyperactive or aggressive behaviors.
TRIAL REGISTRATION
ClinicalTrials.gov: NCT00348946.
Topics: Androgens; Anxiety; Child; Child Behavior; Child, Preschool; Cognition; Depression; Double-Blind Method; Humans; Interpersonal Relations; Klinefelter Syndrome; Male; Muscle Strength; Neuropsychological Tests; Oxandrolone
PubMed: 28285751
DOI: 10.1016/j.jpeds.2017.02.036