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Recovery After Adenotonsillectomy-Do Steroids Help? Outcomes From a Randomized Controlled Trial.
Greenwell, AG, Isaiah, A, Pereira, KD
Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. 2021;(1):83-88
Abstract
OBJECTIVES The primary objective was to compare pain control following adenotonsillectomy (AT) in children with and without a single postoperative dose of oral dexamethasone in addition to standard analgesic medication. The secondary objective was to compare changes in caregiver-reported snoring, return to normal diet and baseline function, and the number of phone calls and emergency department (ED) visits. STUDY DESIGN Prospective randomized controlled trial. SETTING Tertiary care university hospital. METHODS Children aged 3 to 10 years with sleep-disordered breathing who were scheduled to undergo AT were randomized to receive standard analgesia with or without dexamethasone (0.6 mg/kg) administered on the third postoperative day. Standard analgesia was defined as alternating weight-based doses of ibuprofen and acetaminophen. A nurse practitioner blinded to the study condition performed telephone surveys postoperatively, and the electronic medical record was reviewed. RESULTS Enrollment comprised 149 children, of whom 119 were included. When compared with the control group (n = 61, 51%), children who received dexamethasone (n = 58, 49%) had a greater decrease in reported pain score on day 4 (mean ± SD, 2.5 ± 3.1 vs 1.1 ± 3.5, P < .001). Additionally, steroid use was associated with fewer caregiver phone calls (18 [29.5%] vs 6 [10%]) and ED visits (6 [10%] vs 1 [2%]). CONCLUSION A single dose of dexamethasone administered on day 3 after adenotonsillectomy significantly improved pain control. There were fewer phone calls and ED visits in the steroid arm. These results support the use of oral steroids as an adjunct for postoperative pain control in children undergoing AT.
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Prophylactic metformin after antenatal corticosteroids (PROMAC): a double blind randomized controlled trial.
Hong, JGS, Tan, PC, Kamarudin, M, Omar, SZ
BMC pregnancy and childbirth. 2021;(1):138
Abstract
BACKGROUND Antenatal corticosteroids (ACS) are increasingly used to improve prematurity-related neonatal outcome. A recognized and common adverse effect from administration of antenatal corticosteroid is maternal hyperglycemia. Even normal pregnancy is characterized by relative insulin resistance and glucose intolerance. Treatment of maternal hyperglycemia after ACS might be indicated due to the higher risk of neonatal acidosis which may coincide with premature birth. Metformin is increasingly used to manage diabetes mellitus during pregnancy as it is effective and more patient friendly. There is no data on prophylactic metformin to maintain euglycemia following antenatal corticosteroids administration. METHODS A double blind randomized trial. 103 women scheduled to receive two doses of 12-mg intramuscular dexamethasone 12-hour apart were separately randomized to take prophylactic metformin or placebo after stratification according to their gestational diabetes (GDM) status. First oral dose of allocated study drug was taken at enrolment and continued 500 mg twice daily for 72 hours if not delivered. Six-point blood sugar profiles were obtained each day (pre- and two-hour post breakfast, lunch and dinner) for up to three consecutive days. A hyperglycemic episode is defined as capillary glucose fasting/pre-meal ≥ 5.3 mmol/L or two-hour post prandial/meal ≥ 6.7 mmol/L. Primary outcome was hyperglycemic episodes on Day-1 (first six blood sugar profile points) following antenatal corticosteroids. RESULTS Number of hyperglycemic episodes on the first day were not significantly different (mean ± standard deviation) 3.9 ± 1.4 (metformin) vs. 4.1 ± 1.6 (placebo) p = 0.64. Hyperglycemic episodes markedly reduced on second day in both arms to 0.9 ± 1.0 (metformin) vs. 1.2 ± 1.0 (placebo) p = 0.15 and further reduced to 0.6 ± 1.0 (metformin) vs. 0.7 ± 1.0 (placebo) p = 0.67 on third day. Hypoglycemic episodes during the 3-day study period were few and all other secondary outcomes were not significantly different. CONCLUSIONS In euglycemic and diet controllable gestational diabetes mellitus women, antenatal corticosteroids cause sustained maternal hyperglycemia only on Day-1. The magnitude of Day-1 hyperglycemia is generally low. Prophylactic metformin does not reduce antenatal corticosteroids' hyperglycemic effect. TRIAL REGISTRATION The trial is registered in the ISRCTN registry on May 4 2017 with trial identifier https://doi.org/10.1186/ISRCTN10156101 .
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3.
Pharmacological prevention of fractures in patients undergoing glucocorticoid therapies: a systematic review and network meta-analysis.
Deng, J, Silver, Z, Huang, E, Zheng, E, Kavanagh, K, Wen, A, Cheng, W, Dobransky, J, Sanger, S, Grammatopoulos, G
Rheumatology (Oxford, England). 2021;(2):649-657
Abstract
OBJECTIVE To perform a network meta-analysis (NMA) on the efficacy of antiosteoporotic interventions in the prevention of vertebral and non-vertebral fractures in adult patients taking glucocorticoids (GCs). METHODS We performed NMAs based on a prospectively developed protocol. A librarian-assisted database search of MEDLINE, EMBASE, Web of Science, Cumulative Index of Nursing and Allied Health Literature (CINAHL), the Cochrane Central Register of Controlled Trials (CENTRAL) and Chinese databases was conducted for randomized controlled trials (RCTs) comparing antiosteoporotic interventions in adult patients taking GCs. Outcomes were vertebral and non-vertebral fracture incidences. RESULTS We included 56 RCTs containing 6479 eligible patients in our analysis. We found that alendronate and teriparatide were associated with decreased odds of both vertebral and non-vertebral fractures. Denosumab and risedronate were associated with decreased odds of vertebral fractures, while etidronate, ibandronate and alfacalcidol were associated with decreased odds of non-vertebral fractures. We observed low network heterogeneity as indicated by the I2 statistic, and we did not detect evidence of publication bias. All outcomes were based on a moderate quality of evidence according to GRADE. CONCLUSION Bisphosphonates, teriparatide and denosumab are associated with decreased odds of fracture in patients undergoing GC therapy. Vitamin D metabolites and analogues (e.g. alfacalcidol) may have greater anti-fracture efficacy compared with plain vitamin D. SYSTEMATIC REVIEW REGISTRATION The International Prospective Register of Systematic Reviews (PROSPERO)-CRD42019127073.
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Therapies for Preventing Bone Loss with Glucocorticoid Treatment.
Agarwal, A, Adachi, JD
Current osteoporosis reports. 2021;(1):34-39
Abstract
PURPOSE OF REVIEW We aim to critically review recent recommendations regarding preventative strategies for glucocorticoid-induced osteoporosis and provide a summary of key evidence regarding available interventions. RECENT FINDINGS Lifestyle optimization remains the hallmark of bone health preservation. Early initiation of anti-osteoporotic agents in the setting of glucocorticoid exposure is essential, guided by appropriate risk stratification. Recommendations for calcium and vitamin D intake optimization are well-supported across all risk strata. Bisphosphonates are the mainstay of pharmacological therapy. Newer agents such as denosumab and teriparatide have demonstrated comparative benefit in terms of incident fracture risk reduction and bone mineral density preservation, with comparable adverse events. With due consideration to cost, resource availability, and patient values and preferences, these agents may warrant use as the first-line agents in this setting. Glucocorticoid-induced osteoporosis remains preventable and warrants early and targeted evidence-based therapy.
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Beneficial effect of low-dose radioiodine ablation for Graves' orbitopathy: results of a retrospective study.
Lanzolla, G, Menconi, F, Nicolì, F, Posarelli, C, Maglionico, MN, Figus, M, Nardi, M, Marcocci, C, Marinò, M
Journal of endocrinological investigation. 2021;(12):2575-2579
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Abstract
OBJECTIVE Graves' orbitopathy (GO) reflects an autoimmune response against antigens expressed by the thyroid and orbital tissues. Elimination of thyroid antigens may be beneficial for GO. Total thyroid ablation (TTA) [thyroidectomy (Tx), followed by 30 mCi of radioiodine] was shown to exert a beneficial effect on GO following intravenous glucocorticoids (ivGC) compared with Tx alone. Here, we investigated retrospectively whether TTA performed with a 15 mCi of radioiodine still maintains advantages over Tx. METHODS Thirty-two subjects, 13 treated with TTA (performed with 15 mCi of radioiodine) and 19 with Tx alone, all with moderately severe, active GO, treated with ivGC, were studied. The primary objective was the outcome of GO at 24 weeks based on a composite evaluation. RESULTS The two groups did not differ at baseline in terms of sex, age, smoking habits, TSH, anti-TSH receptor autoantibodies, GO duration and eye features. The proportion of GO responders at 24 weeks was greater in the TTA (61.5%) than in the Tx group (26.3%, P = 0.046). In contrast, GO outcome at 48 weeks did not differ between the two groups (69.2% vs 52.6% of responder in TTA and Tx group, respectively). The outcome of the individual GO features did not differ between the two groups both a 24 and 48 months. CONCLUSIONS The advantage of total thyroid ablation seems to be a more rapid response for GO to ivGC treatment. Prospective, randomized studies in a larger number of subjects are needed to confirm our findings.
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Comparison of Therapeutic Results with/without Additional Hyperbaric Oxygen Therapy in Idiopathic Sudden Sensorineural Hearing Loss: A Randomized Prospective Study.
Tong, B, Niu, K, Ku, W, Xie, W, Dai, Q, Hellström, S, Duan, M
Audiology & neuro-otology. 2021;(1):11-16
Abstract
OBJECTIVE To assess the efficacy of the combination of hyperbaric oxygen (HBO) and pharmacological treatment in patients with idiopathic sudden sensorineural hearing loss (ISSNHL) and define patients amenable for HBO therapy. METHODS Prospective, randomized, trial involving 136 cases with unilateral ISSNHL that were randomly divided into 2 groups: the pharmacological treatment (P) group and HBO + pharmacological treatment (HBO+P) group, which received additional HBO for 14 days besides the pharmacological treatments. Pure tone audiometry gain larger than 15 dBHL was defined as success, and the success rate of each group was calculated. RESULTS The overall success rate of the HBO+P group and the P group is 60.6% (40/66) and 42.9% (30/70), respectively (p < 0.05). Furthermore, patients with mild-moderate baseline hearing loss, aged ≤50 years, receiving treatment in ≤14 days, or without accompanied dizziness/vertigo in the HBO+P group had higher success rate than the P group (p < 0.05). CONCLUSIONS HBO combined with pharmacological treatments leads to better hearing recovery than pharmacological treatments alone.
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Eosinophilic Esophagitis: Etiology and Therapy.
Patel, RV, Hirano, I, Gonsalves, N
Annual review of medicine. 2021;:183-197
Abstract
Eosinophilic esophagitis (EoE) is a relatively recently identified but now frequently encountered antigen/immune-mediated disease which places significant burden on patients and the healthcare system. With its growing prevalence and recognition by healthcare providers in multiple disciplines, substantial progress has been made regarding the diagnostic criteria, clinical evaluation, tools for disease assessment, and immune pathways related to pathogenesis. Current treatment goals focus on the amelioration of inflammation and prevention of remodeling consequences using proton pump inhibitors, swallowed topical steroids, elimination diets, and esophageal dilation. Ongoing research holds promise for more efficacious and targeted therapies as well as a personalized approach to the care of patients with EoE.
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Bone density and bone health alteration in boys with Duchenne Muscular Dystrophy: a prospective observational study.
Suthar, R, Reddy, BVC, Malviya, M, Sirari, T, Attri, SV, Patial, A, Tageja, M, Didwal, G, Khandelwal, NK, Saini, AG, et al
Journal of pediatric endocrinology & metabolism : JPEM. 2021;(5):573-581
Abstract
OBJECTIVES Boys with Duchenne Muscular Dystrophy (DMD) are at increased risk for compromised bone health, manifesting as low-impact trauma long bone fractures and vertebral compression fractures. METHODS In a prospective observational study, we studied bone health parameters in North Indian boys with DMD. We consecutively enrolled ambulatory boys with DMD on glucocorticoid therapy. Bone health was evaluated with X-ray spine, Dual-energy X-ray absorptiometry (DXA), serum calcium, vitamin D3 (25[OH]D), 1,25-dihyroxyvitamin D3 (1,25[OH]2D3), serum osteocalcin, osteopontin, and N terminal telopeptide of type 1 collagen (Ntx) levels. RESULTS A total of 76 boys with DMD were enrolled. The median age was 8.5 (interquartile range [IQR] 7.04-10.77) years. Among these, seven (9.2%) boys had long bone fractures, and four (5.3%) had vertebral compression fractures. Fifty-four (71%) boys underwent DXA scan, and among these 31 (57%) had low bone mineral density (BMD, ≤-2 z-score) at the lumbar spine. The mean BMD z-score at the lumbar spine was -2.3 (95% confidence interval [CI] = -1.8, -2.8), and at the femoral neck was -2.5 (95% CI = -2, -2.9). 25(OH)D levels were deficient in 68 (89.5%, n=76) boys, and 1,25(OH)2D3 levels were deficient in all. Mean serum osteocalcin levels were 0.68 ± 0.38 ng/mL (n=54), serum osteopontin levels were 8.6 ± 4.6 pg/mL (n=54) and serum Ntx levels were 891 ± 476 nmol/L (n=54). Boys with low BMD received glucocorticoids for longer duration, in comparison to those with normal BMD (median, IQR [16.9 (6-34) months vs. 7.8 (4.8-13.4) months]; p=0.04). CONCLUSIONS Bone health is compromised in North Indian boys with DMD. BMD at the lumbar spine is reduced in more than half of boys with DMD and nearly all had vitamin D deficiency on regular vitamin D supplements. Longer duration of glucocorticoid therapy is a risk factor for low BMD in our cohort.
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Lung macrophages drive mucus production and steroid-resistant inflammation in chronic bronchitis.
Andelid, K, Öst, K, Andersson, A, Mohamed, E, Jevnikar, Z, Vanfleteren, LEGW, Göransson, M
Respiratory research. 2021;(1):172
Abstract
BACKGROUND Patients with chronic obstructive pulmonary disease (COPD) frequently suffer from chronic bronchitis (CB) and display steroid-resistant inflammation with increased sputum neutrophils and macrophages. Recently, a causal link between mucus hyper-concentration and disease progression of CB has been suggested. METHODS In this study, we have evaluated the steroid sensitivity of purified, patient-derived sputum and alveolar macrophages and used a novel mechanistic cross-talk assay to examine how macrophages and bronchial epithelial cells cross-talk to regulate MUC5B production. RESULTS We demonstrate that sputum plug macrophages isolated from COPD patients with chronic bronchitis (COPD/CB) are chronically activated and only partially respond to ex vivo corticosteroid treatment compared to alveolar macrophages isolated from lung resections. Further, we show that pseudo-stratified bronchial epithelial cells grown in air-liquid-interface are inert to direct bacterial lipopolysaccharide stimulation and that macrophages are able to relay this signal and activate the CREB/AP-1 transcription factor complex and subsequent MUC5B expression in epithelial cells through a soluble mediator. Using recombinant protein and neutralizing antibodies, we identified a key role for TNFα in this cross-talk. CONCLUSIONS For the first time, we describe ex vivo pharmacology in purified human sputum macrophages isolated from chronic bronchitis COPD patients and identify a possible basis for the steroid resistance frequently seen in this population. Our data pinpoint a critical role for chronically activated sputum macrophages in perpetuating TNFα-dependent signals driving mucus hyper-production. Targeting the chronically activated mucus plug macrophage phenotype and interfering with aberrant macrophage-epithelial cross-talk may provide a novel strategy to resolve chronic inflammatory lung disease.
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Experience of SARS-CoV-2 infection in two kidney transplant recipients living with HIV-1 infection.
Chowdary, P, Shetty, S, Booth, J, Khurram, MA, Yaqoob, M, Mohamed, IH
Transplant infectious disease : an official journal of the Transplantation Society. 2021;(2):e13500
Abstract
There is still no consensus on the optimal management of COVID-19 within the general population due to the emerging evidence base. High-risk groups, including kidney transplant recipients living with HIV present unique additional challenges. Here we discuss two kidney transplant recipients living with HIV with SARS-CoV-2 infection and their clinical course, and review the existing literature for this subset of challenging patients.