Functional abilities, respiratory and cardiac function in a large cohort of adults with Duchenne muscular dystrophy treated with glucocorticoids.

BACKGROUND AND PURPOSE: The transition to adult services, and subsequent glucocorticoid management, is critical in adults with Duchenne muscular dystrophy. This study aims (1) to describe treatment, functional abilities, respiratory and cardiac status during transition to adulthood and adult stages; and (2) to explore the association between glucocorticoid treatment after loss of ambulation (LOA) and late-stage clinical outcomes. METHODS: This was a retrospective single-centre study on individuals with Duchenne muscular dystrophy (≥16 years old) between 1986 and 2022. Logistic regression, Cox proportional hazards models and survival analyses were conducted utilizing data from clinical records. RESULTS: In all, 112 individuals were included. Mean age was 23.4 ± 5.2 years and mean follow-up was 18.5 ± 5.5 years. At last assessment, 47.2% were on glucocorticoids; the mean dose of prednisone was 0.38 ± 0.13 mg/kg/day and of deflazacort 0.43 ± 0.16 mg/kg/day. At age 16 years, motor function limitations included using a manual wheelchair (89.7%), standing (87.9%), transferring from a wheelchair (86.2%) and turning in bed (53.4%); 77.5% had a peak cough flow <270 L/min, 53.3% a forced vital capacity percentage of predicted <50% and 40.3% a left ventricular ejection fraction <50%. Glucocorticoids after LOA reduced the risk and delayed the time to difficulties balancing in the wheelchair, loss of hand to mouth function, forced vital capacity percentage of predicted <30% and forced vital capacity <1 L and were associated with lower frequency of left ventricular ejection fraction <50%, without differences between prednisone and deflazacort. Glucocorticoid dose did not differ by functional, respiratory or cardiac status. CONCLUSION: Glucocorticoids after LOA preserve late-stage functional abilities, respiratory and cardiac function. It is suggested using functional abilities, respiratory and cardiac status at transition stages for adult services planning.

Effect of a Single Dose of Deflazacort on Postoperative Pain, Swelling, and Trismus after Impacted Lower Third Molar Surgery: Randomised Clinical Trial.

Background and Objectives: The aim of this study was to investigate the efficacy of a single preoperative dose of deflazacort on pain, swelling, and trismus after impacted lower third molar surgery. Materials and Methods: This randomised, prospective, double-blind, split-mouth clinical study included 26 healthy individuals with bilaterally impacted lower third molars. Group 1 was given a placebo (single-dose vitamin C tablet), and group 2 was given a single 30 mg dose of deflazacort 1 h prior to surgery. Pain was evaluated using the visual analogue scale for 1 week postoperatively. Oedema (in mm) and trismus (in mm) were evaluated preoperatively and on postoperative days 2 and 7. The Mann-Whitney U test was applied for group analyses. p values < 0.05 were considered statistically significant. Results: Postoperative pain scores were significantly lower in the deflazacort group at the 6th and 12th hours after surgery (p < 0.05). There were no significant differences in trismus between the groups at any time point (p > 0.05). There was less oedema in the deflazacort group on postoperative days 2 and 7, without any statistically significant difference (p > 0.05). Conclusions: A single preoperative dose of 30 mg deflazacort was found to be clinically effective in reducing pain and oedema after extraction of impacted lower third molars.

Repurposing of FDA-Approved Drugs for Treating Iatrogenic Botulism: A Paired 3D-QSAR/Docking Approach†.

Botulinum neurotoxin (BoNT) is widely used for the treatment of spasticity, focal dystonia, chronic migraine, facial hemispasm, and facial aesthetic treatments. Generally, treatment with botulinum toxin is a safe procedure when conducted by clinicians with expertise, and local side effects are rare and transient. However, occasionally adverse effects can occur due to the spread of the drug to nontargeted muscles and organs, producing dry mouth, fatigue, and flu-like symptoms, up to signs of systemic botulism, which appears to be more frequent in children treated for spasticity than in adults. In silico 3D-QSAR and molecular docking studies were performed to build a structure-based model on selected potent known botulinum neurotoxin type A inhibitors; this was used to screen the US Food and Drug Administration (FDA) database. Thirty molecules were identified as possible light-chain BoNT/A inhibitors. In this study, we applied a well-established ligand- and structure-based methodology for the identification of hit compounds among a database of FDA-approved drugs. The identification of budesonide, protirelin, and ciclesonide followed by other compounds can be considered a starting point for investigations of selected compounds that could bypass much of the time and costs involved in the drug approval process.

Granulomatous facial reaction to injected cosmetic fillers--a presentation of five cases.

The use of substances to augment soft tissues as aesthetic purpose is associated with, among other undesirable effects, the appearance of foreign body granulomas. The improvements made to these substances have reduced the incidence of adverse reactions, but not eliminated them. We present five cases of foreign body reactions to three different products, dimethylpolysiloxane (silicone), bovine collagen, and polylactic acid, which were injected into the subcutaneous cellular tissue of the patients (all five were women), between two and sixteen years before the appearance of the foreign body reaction. All five presented painless, diffuse facial tumefaction, of firm, elastic consistency. The magnetic resonance image (MRI) studies showed signs of intense inflammatory reaction in the affected areas. The histology revealed the presence of foreign body granulomas with giant multi-nucleated cells. The patients were treated with systemically administered corticoids, except in one case which did not require pharmacological treatment.

A comparative study of amcinonide and halcinonide in the treatment of eczematous dermatitis.

Thirty-three patients with acute or subacute eczematous dermatitis were treated for two weeks in a double-blind, parallel-group study to compare the efficacy and cosmetic acceptability of 0.1 percent amcinonide cream and 0.1 percent halcinonide cream. Patients in both treatment groups showed significant (p less than 0.05) improvement from baseline for most signs and symptoms at the three evaluation times (days 3, 7, and 14). Comparisons between groups showed no significant differences at any evaluation except at day 14, when the amicinonide-treated patients had significantly (p = 0.04) less edema. The physician's evaluations were not significantly different except at day 7, when the halcinonide patients showed significantly (p = 0.04) more overall improvement. The patients' overall evaluations were not significantly different at any time. In general, both creams were cosmetically acceptable. At day 3, seven amcinonide patients noted skin tightening compared to one halcinonide patient; four halcinonide patients (as well as two at day 7 and one at day 14) reported stinging compared to only one amcinonide patient. In addition, two halcinonide patients reported a burning sensation at one or more evaluations compared to no such reports from amcinonide patients. One other side effect, a metallic taste in the mouth, occurred in a halcinonide-treated patient.

Rapid periapical bone destruction during endodontic treatment of a patient with rheumatoid arthritis.

Rheumatoid arthritis is an autoimmune disease with an unknown etiology. Azathioprine is an immunosuppressive drug that is used to treat rheumatoid arthritis. This case report describes the rapid periapical bone destruction that occurred during the endodontic treatment of a rheumatoid arthritis patient taking azathioprine and a corticosteroid. The cause of the rapid destruction is unclear. However, severe side effects can occur after administering azathioprine to rheumatoid arthritis patients. Therefore, dentists should check the patient's medical state thoroughly in order to prevent side effects when performing endodontic treatment.

A metal aerosol holding chamber devised for young children with asthma.

The low tidal volume and flow in preschool children may reduce the efficiency of aerosol delivery from a pressurized metered-dose inhaler (pMDI) through a traditional holding chamber. A prototype small-volume steel holding chamber with two one-way valves was devised to prolong aerosol availability in the chamber and to ensure unidirectional airflow. Dead space between the valves was minimized to less than 2 ml. The dose-delivery and rate of passive disappearance of a budesonide pMDI aerosol were compared between this prototype and the large-volume, single-valved plastic Nebuhaler, in 164 asthmatic children less than 8 yrs of age. In vitro, the half life of aerosol disappearance in the steel prototype and the plastic Nebuhaler was > 30 s and 9 s, respectively. In vivo, the prototype delivered an age-independent mean dose of 38% of the nominal dose, and the Nebuhaler delivered an age-dependent mean dose, ranging from 42% of the nominal dose in children > or = 4 yrs to 19% of the nominal dose in infants. We conclude that the use of plastic for holding chambers may influence dose-delivery, and single-valve control may cause age-dependent dose-delivery. Reproducible age-independent drug-delivery may be achieved by pMDI aerosol inhaled through a small-volume metal holding chamber with separate inlet and outlet valves and minimized dead space. This holding chamber would improve the possibilities of aerosol therapy for young children.

Glucocorticoids and asthma. Studies of resistance and systemic effects of glucocorticoids.

Glucocorticoid resistance in asthma is genetically determined in a few individuals. Preliminary data are presented from a study showing interaction with a drug as another explanation for glucocorticoid resistance. In 6 healthy individuals, prednisolone concentrations were measured during 9 h after oral intake of 15 mg before and after 10 days' intake of 450 mg of rifampicin daily. An increased clearance of prednisolone was demonstrated. Systemic effects of inhaled glucocorticoids have also been studied. Comparison in healthy individuals between beclomethasone dipropionate given as a spray and as powder showed similar systemic effects with the two modes of administration. A new glucocorticoid for inhalation therapy, budesonide, was shown to have a weaker systemic effect than beclomethasone dipropionate. By rinsing the mouth with water after inhalation, it was possible to reduce the amount of drug swallowed, and our data showed a tendency towards less systemic effects after mouth-rinsing.

Nasal inhalation of the glucocorticoid budesonide from a spacer for the treatment of patients with pollen rhinitis and asthma.

Glucocorticoid sprays are increasingly used for the treatment of allergic rhinitis and asthma. This therapy is highly effective, and side effects are few and mild. It was the aim of the present study to evaluate a physiological nasal inhalation technique, which results in airway deposition of the steroid molecule similar to that of inhaled allergen particles. Thirty adults with grass pollen-induced rhinitis and asthma inhaled the steroid molecule budesonide through the nose from a pressurized aerosol attached to a spacer device. Compared with inhalation of placebo, the treatment resulted in a significant reduction of nasal symptoms (P = 0.005), of bronchial symptoms (P = 0.005), but not of eye symptoms. In addition, nasal peak inspiratory flow (P = 0.0003) and oral peak expiratory flow (P = 0.02) increased. There was no difference between budesonide and placebo with regard to local side effects, such as nose bleeding, hoarseness, and irritation in mouth and throat. It is concluded that nasal inhalation of a steroid from a spacer offers effective therapy of pollen rhinitis and asthma without significant local side effects. This therapeutic modality may have advantages over the ordinarily used nasal and bronchial spray treatment in patients with both rhinitis and asthma, especially when conventional spray therapy is associated with local side effects.

Comparative adrenal suppression with inhaled budesonide and fluticasone propionate in adult asthmatic patients.

BACKGROUND: A study was performed to compare the adrenal suppression caused by inhaled fluticasone propionate and budesonide on a microgram equivalent basis, each given by metered dose inhaler to asthmatic patients. METHODS: Twelve asthmatic patients of mean age 29.9 years, with a forced expiratory volume in one second (FEV1) 92.9% predicted and forced expiratory flow 25-75% (FEF25-75) 69.5% predicted, on less than or equal to 400 micrograms/day inhaled corticosteroid, were studied in a double blind placebo controlled crossover design comparing single doses of inhaled budesonide 400, 1000, 1600, 2000 micrograms and fluticasone propionate 500, 1000, 1500, 2000 micrograms. Doses were administered at 22.00 hours by metered dose inhaler with mouth rinsing and measurements were made in the laboratory 10 hours later. RESULTS: Serum cortisol levels compared with placebo (mean 325.2 nmol/l) were suppressed by fluticasone at doses of 1500 micrograms (211.6 nmol/l) and 2000 micrograms (112.3 nmol/l) and by budesonide at 2000 micrograms (243.4 nmol/l). Fluticasone propionate 2000 micrograms produced lower absolute serum cortisol levels than budesonide 2000 micrograms (95% CI for difference 42.9 to 219.2). The dose ratio (geometric mean) for the relative potency was 2.89 fold (95% CI 1.19 to 7.07). In terms of percentage suppression versus placebo, fluticasone propionate also produced greater effects (means and 95% CI for difference): budesonide 1600 micrograms (16.0) versus fluticasone propionate 1500 micrograms (40.9) (95% CI -0.6 to 50.6), budesonide 2000 micrograms (26.0) versus fluticasone 2000 micrograms (65.2) (95% CI 10.5 to 67.8). Individual serum cortisol levels at the two highest doses showed 15 of 24 patients below the normal limit of the reference range (150 nmol/l) for fluticasone and five of 24 for budesonide. Fluticasone propionate also caused greater ACTH suppression than budesonide (as % versus placebo): budesonide 1600 micrograms (12.0) versus fluticasone propionate 1500 micrograms (31.9) (95% CI 7.6 to 32.1), budesonide 2000 micrograms (13.5) versus fluticasone propionate 2000 micrograms (44.4) (95% CI 13.2 to 48.7). For overnight 10 hour urinary cortisol (nmol/10 hours) there was a difference between the lowest doses of the two drugs: budesonide 400 micrograms (37.2) versus fluticasone propionate 500 micrograms (19.9) (95% CI 6.9 to 27.8). CONCLUSIONS: Like budesonide the systemic bioactivity of fluticasone propionate is mainly due to lung vascular absorption. Fluticasone propionate exhibited at least twofold greater adrenal suppression than budesonide on a microgram equivalent basis in asthmatic patients.

Adrenal suppression with chronic dosing of fluticasone propionate compared with budesonide in adult asthmatic patients.

BACKGROUND: In a previous single dosing comparison between fluticasone propionate and budesonide differences in cortisol levels measured at 08.00 hours were observed at doses in excess of 1000 micrograms. The aim of this study was to compare the adrenal suppression caused by chronic twice daily dosing with inhaled fluticasone propionate (FP) and budesonide (B) given on a microgram equivalent basis by metered dose inhaler to asthmatic patients. METHODS: Twelve stable asthmatic patients of mean age 29.7 years with forced expiratory volume in one second (FEV1) 89.0% predicted and mid forced expiratory flow (FEF25-75) 58.9% predicted, on 400 micrograms/day or less of inhaled corticosteroid, were studied in a double blind, placebo controlled, crossover design comparing inhaled budesonide and fluticasone propionate in doses of 250 micrograms, 500 micrograms, and 1000 micrograms twice daily. Each dose was given at 08.00 hours and 22.00 hours for four days by metered dose inhaler with mouth rinsing. Measurements were made of overnight urinary cortisol excretion and plasma cortisol levels at 08.00 hours, 10 hours after the eighth dose. RESULTS: The plasma cortisol levels (nmol/ l) at 08.00 hours showed that fluticasone propionate produced lower cortisol levels than budesonide at all three dose levels: F500 333.8, B500 415.2 (95% CI 28.9 to 134.0); F1000 308.3, B1000 380.3 (95% CI 10.5 to 133.5); F2000 207.3, B2000 318.5 (95% CI 5.8 to 216.7); placebo 399.9. Fluticasone produced greater effects than budesonide on the overnight urinary cortisol/creatinine ratio (nmol/mmol) at all three dose levels: F500 3.12, B500 5.55 (95% CI 0.16 to 3.79); F1000 2.54, B1000 6.12 (95% CI 1.25 to 5.91); F2000 2.07, B2000 6.09 (95% CI 0.88 to 7.18); placebo 5.23. CONCLUSIONS: With repeated dosing across a dose range of 250-1000 micrograms twice daily, fluticasone propionate produced significantly greater adrenal suppression than budesonide for both plasma and urinary cortisol. It was therefore possible to demonstrate differences between fluticasone and budesonide at lower doses with chronic dosing from those previously found with single dosing when given on a microgram equivalent basis in asthmatic patients. Factors contributing to the systemic adverse activity profile of fluticasone comprise enhanced receptor potency, prolonged receptor residency time, greater tissue retention, and a longer elimination half life.

Effect of an intranasally administered corticosteroid (budesonide) on nasal obstruction, mouth breathing, and asthma.

The effect of intranasally administered corticosteroid (budesonide) on nasal symptoms, mode of respiration (nasal versus mouth breathing), and asthma was investigated in 37 asthmatic children who were mouth breathers because of chronic nasal obstruction. After a 2-wk run-in period, the children were allocated randomly to 4 wk of intranasal therapy with either budesonide (400 micrograms/day) or placebo spray. A double-blind, parallel design was used. Diaries for peak expiratory flow, asthma, and rhinitis symptom scores and degree of mouth breathing were recorded at home. Nasal eosinophilia, nasal airway resistance at a flow of 0.2 L/s (NAR0.2), and lung function at rest and after exercise challenge were assessed at the clinic immediately before and at end of the 4-wk treatment. Budesonide, when compared with placebo, significantly decreased nasal obstruction (p less than 0.05), secretion (p less than 0.01), and eosinophilia (p less than 0.02), as well as NAR0.2 (p less than 0.05) and mouth breathing (p less than 0.01). The improvement in nasal obstruction correlated closely to the changes in mouth breathing (r = 0.80, n = 17, p less than 0.001). Furthermore, intranasally administered budesonide resulted in less exercise-induced asthma (EIA) (p less than 0.02) and decreased cough and asthma severity significantly. Pulmonary mechanics were only marginally improved. The present study showed that intranasally administered budesonide is effective in the treatment of perennial allergic rhinitis. An attenuation of EIA and a tendency to less asthma after budesonide therapy suggest a decrease in bronchial reactivity, but the results gave no clear evidence of an association between nasal airway function and asthma.

Glucocorticoid-induced osteoporosis in the lumbar spine, forearm, and mandible of nephrotic patients: a double-blind study on the high-dose, long-term effects of prednisone versus deflazacort.

The long-term effects of high dose steroid treatment with either prednisone (PDN) or deflazacort (DFZ) were examined on various parts of the skeleton in 29 patients with nephrotic syndrome. All had normal skeleton at the start of the steroid treatment. At the beginning, PDN was given as 80 mg/day and tapered down to 20 mg/day for 1 year and DFZ was given in an equipotent dosage. Twenty-three patients completed 6 months of treatment, and 18 patients completed 12 months of treatment. Beside laboratory parameters to ensure the effect of treatment on the nephrotic syndrome, all had measurements of the bone mineral content (BMC) at 0, 6, and 12 months of treatment. BMC was measured by single photon absorptiometry of both forearms and by dual photon absorptiometry of the mandible, forearms, and lumbar spine. The effect of DFZ was compared to that of PDN due to a potential "calcium sparing" effect of DFZ. The therapeutical effects on the nephrotic syndrome were not different between the two drugs. Urinary 24-hour protein decreased from 9.9 to 1.1 g in the DFZ-treated patients and from 8.0 to 1.4 g in the PDN-treated patients. Plasma albumin concentration normalized in both groups. Both groups of steroid-treated patients had a significant reduction of the BMC levels in all parts of the skeleton. However, the bone decay rates per month were significantly different between different bone regions and between different drug regimes. In the forearm, the bone decay rate was 5.3%/year in the PDN group and 2.0%/year in the DFZ group (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)