Effectiveness of Fludrocortisone Plus Hydrocortisone versus Hydrocortisone Alone in Septic Shock: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

Rationale: The use of hydrocortisone in adult patients with septic shock is controversial, and the effectiveness of adding fludrocortisone to hydrocortisone remains uncertain. Objectives: To assess the comparative effectiveness and safety of fludrocortisone plus hydrocortisone, hydrocortisone alone, and placebo or usual care in adults with septic shock. Methods: A systematic review and a Bayesian network meta-analysis of peer-reviewed randomized trials were conducted. The primary outcome was all-cause mortality at last follow-up. Treatment effects are presented as relative risks (RRs) with 95% credible intervals (CrIs). Placebo or usual care was the reference treatment. Measurements and Main Results: Among 7,553 references, we included 17 trials (7,688 patients). All-cause mortality at last follow-up was lowest with fludrocortisone plus hydrocortisone (RR, 0.85; 95% CrI, 0.72-0.99; 98.3% probability of superiority, moderate-certainty evidence), followed by hydrocortisone alone (RR, 0.97; 95% CrI, 0.87-1.07; 73.1% probability of superiority, low-certainty evidence). The comparison of fludrocortisone plus hydrocortisone versus hydrocortisone alone was based primarily on indirect evidence (only two trials with direct evidence). Fludrocortisone plus hydrocortisone was associated with a 12% lower risk of all-cause mortality compared with hydrocortisone alone (RR, 0.88; 95% CrI, 0.74-1.03; 94.2% probability of superiority, moderate-certainty evidence). Conclusions: In adult patients with septic shock, fludrocortisone plus hydrocortisone was associated with lower risk of all-cause mortality at last follow-up than placebo and hydrocortisone alone. The scarcity of head-to-head trials comparing fludrocortisone plus hydrocortisone versus hydrocortisone alone led our network meta-analysis to rely primarily on indirect evidence for this comparison. Although we undertook several sensitivity analyses and assessments, these findings should be considered while also acknowledging the heterogeneity of included trials.

The genetic effects of hormones modulated by the Pituitary-Thyroid/Adrenal/Gonadal axis on the risk of developing venous thromboembolism: a mendelian randomization study.

BACKGROUND: The aim of this study was to explore the genetic effects of hormones modulated through the pituitary-thyroid/adrenal/gonadal axis on the risk of developing venous thromboembolism (VTE) and to investigate the potentially causal relationships between them. METHODS: A two-sample Mendelian randomization (MR) design was used. The single-nucleotide polymorphisms (SNPs) used as instrumental variables for various hormones and hormone-mediated diseases were derived from published genome-wide association studies (GWASs). Summary statistics for the risk of developing VTE (including deep venous thrombosis [DVT] and pulmonary embolism [PE]) were obtained from the UK Biobank and the FinnGen consortium. Inverse-variance weighting (IVW) was applied as the primary method to analyse causal associations. Other MR methods were used for supplementary estimates and sensitivity analysis. RESULTS: A genetic predisposition to greater free thyroxine (FT4) concentrations was associated with a greater risk of developing DVT (OR = 1.0007, 95%CI [1.0001-1.0013], p = 0.0174) and VTE (OR = 1.0008, 95%CI [1.0002-1.0013], p = 0.0123). Genetically predicted hyperthyroidism was significantly associated with an increased risk of developing DVT (OR = 1.0685, 95%CI [1.0139-1.1261], p = 0.0134) and VTE (OR = 1.0740, 95%CI [1.0165-1.1348], p = 0.0110). According to the initial MR analysis, testosterone concentrations were positively associated with the risk of developing VTE (OR = 1.0038, 95%CI [1.004-1.0072], p = 0.0285). After sex stratification, estradiol concentrations were positively associated with the risk of developing DVT (OR = 1.0143, 95%CI [1.0020-1.0267], p = 0.0226) and VTE (OR = 1.0156, 95%CI [1.0029-1.0285], p = 0.0158) in females, while the significant relationship between testosterone and VTE did not persist. SHBG rs858518 was identified as the only SNP that was associated with an increased risk of developing VTE, mediated by estradiol, in females. CONCLUSIONS: Genetically predicted hyperthyroidism and increased FT4 concentrations were positively associated with the risk of developing VTE. The effects of genetically predicted sex hormones on the risk of developing VTE differed between males and females. Greater genetically predicted estradiol concentrations were associated with an increased risk of developing VTE in females, while the SHBG rs858518 variant may become a potential prevention and treatment target for female VTE.

Corticosteroid Injection Methods for Frozen Shoulder: A Network Meta-analysis.

OBJECTIVE: To investigate the efficacy of corticosteroid (CS) injection methods for frozen shoulder. DATA SOURCES: PubMed, Embase, and Cochrane Library were searched up to May 6, 2023. STUDY SELECTION: Randomized controlled trials (RCTs) that investigated CS injection methods for frozen shoulder were included. DATA EXTRACTION: Data were extracted independently by 2 authors. Risk of bias was assessed using the RoB 2 tool. DATA SYNTHESIS: A random-effects network meta-analysis was performed within a frequentist framework. The certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations approach. A total of 66 RCTs involving 4491 patients were included. For short-term outcomes, 4-site injection (vs placebo [PLA]: standardized mean difference [SMD]=-2.20, 95% confidence interval [CI], -2.81 to -1.59 in pain; SMD=2.02; 95% CI, 1.39-2.65 in global function) was the most effective (low certainty). Rotator interval injection was the optimal treatment with moderate to high certainty (vs PLA: SMD=-1.07, 95% CI, -1.51 to -0.64 in pain; SMD=0.94, 95% CI, 0.49-1.40 in global function). For midterm outcomes, 4-site injection was most effective (vs PLA: SMD=-1.71, 95% CI, -2.41 to -1.01 in pain; SMD=2.22, 95% CI, 1.34-3.09 in global function; low certainty). Distension via rotator interval (D-RI) was the optimal treatment with moderate to high certainty (vs PLA: SMD=-1.10, 95% CI, -1.69 to -0.51 in pain; SMD=1.46, 95% CI, 0.73-2.20 in global function). Distension and intra-articular injection via anterior or posterior approaches produced effects equivalent to those of rotator interval injection and D-RI. CONCLUSIONS: Rotator interval injection, distension, and intra-articular injection had equivalent effects on symptom relief. More RCTs are required to validate the superiority of multisite injections.

Musculoskeletal corticosteroid injection and risk of acute coronary syndrome: a case control study.

BACKGROUND: Musculoskeletal corticosteroid injection (CSI) is a frequently used treatment, considered safe with a low incidence of minor side effects. OBJECTIVE: To investigate whether the incidence of acute coronary syndrome (ACS) is increased following corticosteroid injection for musculoskeletal conditions. METHODS: Data were reviewed from 41,276 patients aged over 40 years and hospitalised with ACS between January 2015 and December 2019. Each ACS case was allocated up to 10 control patients from their primary care clinic, matched for age and sex. The cases and controls were reviewed for orthopaedic or rheumatological consultation including a CSI procedure and occurring prior to the hospital admission date. The incidence of CSI was compared between the case and control groups. RESULTS: Data from a total of 413,063 patients were reviewed, 41,276 ACS cases and 371,787 controls. The mean age was 68.1, standard deviation (SD) = 13.1, 69.4% male. In the week prior to their hospital admission, 118 ACS patients were treated with CSI compared with 495 patients in the control group; odds ratio (OR) = 1.95 (1.56-2.43). In total, 98% of CSI procedures were carried out by orthopaedic specialists. An association between ACS and prior CSI was strongest in the days immediately prior to hospitalisation: OR = 3.11 (2.10-4.61) for patients who were injected 1 day before ACS. The association between ACS and CSI declined with increasing time between injection and hospital admission: at 90 days OR = 1.08 (0.98-1.18). The association remained robust when cardiovascular risk factors, history of rheumatological disease, and other co-morbidity were taken into consideration. CONCLUSIONS: Musculoskeletal corticosteroid injection appears to substantially increase the risk of acute coronary syndrome.

Technical Update No. 439: Antenatal Corticosteroids at Late Preterm Gestation.

OBJECTIVE: To update recommendations for administration of antenatal corticosteroids in the late preterm period. TARGET POPULATION: Pregnant individuals at risk of preterm birth from 340 to 366 weeks gestation. OPTIONS: Administration or non-administration of a single course of antenatal corticosteroids at 340 to 366 weeks gestation. OUTCOMES: Neonatal morbidity (respiratory distress, hypoglycemia), long-term neurodevelopment, and other long-term outcomes (growth, cardiac/metabolic, respiratory). BENEFITS, HARMS, AND COSTS: Administration of antenatal corticosteroids from 340 to 366 weeks gestation decreases the risk of neonatal respiratory distress but increases the risk of neonatal hypoglycemia. The long-term impacts of antenatal corticosteroid administration from 340 to 366 weeks gestation are uncertain. EVIDENCE: For evidence on the neonatal effects of antenatal corticosteroid administration at late preterm gestation, we summarized evidence from the 2020 Cochrane review of antenatal corticosteroids and combined this with evidence from published randomized trials identified by searching Ovid MEDLINE from January 1, 2020, to May 11, 2022. Given the absence of direct evidence on the impact of late preterm antenatal corticosteroid administration on neurodevelopmental outcomes, we summarized evidence on the impact of antenatal corticosteroids across gestational ages on neurodevelopmental outcomes using the following sources: (1) the 2020 Cochrane review; and (2) evidence obtained by searching Ovid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases from inception to January 5, 2022. We did not apply date or language restrictions. Given the absence of direct evidence on the impact of late preterm antenatal corticosteroid administration on other long-term outcomes, we summarized evidence on the impact of antenatal corticosteroids across gestational ages on other long-term outcomes by combining findings from the 2020 Cochrane review with evidence obtained by searching Ovid MEDLINE for observational studies related to long-term cardiometabolic, respiratory, and growth effects of antenatal corticosteroids from inception to October 22, 2021. We reviewed reference lists of included studies and relevant systematic reviews for additional references. See Appendix A for search terms and summaries. VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix B (Tables B1 for definitions and B2 for interpretations of strong and conditional [weak] recommendations). INTENDED AUDIENCE: Maternity care providers, including midwives, family physicians, and obstetricians. SUMMARY STATEMENTS: RECOMMENDATIONS.

Evidence of off-label inhalation therapy on pediatric asthma practice in Japan.

BACKGROUND: In Japan, many asthma inhalers do not have formal approval for use in the pediatric population because of the lack of domestic data. In real-world settings, however, numerous off-label medications are prescribed. Currently, the nature of off-label prescriptions of asthma inhalers on pediatric patients in Japan remains unclear. METHODS: Using public open-source national medical claims data, we investigated the real-world descriptive epidemiology of off-label prescriptions for asthma inhalers for pediatric patients. We obtained the number of off-label prescriptions of formulations for patients aged 0-14 years from anonymously summarized prescription data for a 7-year period starting from April 2014. The actual prescription numbers and their chronology over time were then analyzed. RESULTS: In 2019, 143,439 asthma inhalers were used off label in children and adolescents. Overall, 96.1% were inhaled corticosteroids (ICSs) or long-acting beta stimulants (LABAs), and 3.9% were high-dose ICS. Of ICSs and LABAs, 18.8% were off-label prescriptions. The total number of off-label ICS/LABA prescriptions and their percentage relative to the overall formulations gradually decreased but a notable disparity was observed among inhaler types. CONCLUSIONS: There was a surprisingly large number of off-label prescriptions of asthma inhalers in the pediatric population in Japan. The proper use of ICSs/LABAs and expansion of insurance coverage should be advocated to reduce off-label use.

Real-world impact of dupilumab on asthma disease burden in Japan: The CROSSROAD study.

BACKGROUND: Dupilumab, a human monoclonal anti-interleukin (IL)-4Ra antibody blocks the shared receptor component of IL-4 and IL-13, drivers of type 2 inflammation. Dupilumab is approved for severe/refractory asthma inadequately controlled by existing therapies, but knowledge of its effect on real-world disease burden is lacking. This study investigates real-world effects of dupilumab on asthma exacerbation risk and oral corticosteroid (OCS) use in Japanese individuals with asthma. METHODS: This retrospective, cohort study used a Japanese insurance claims database to identify patients who started dupilumab between 26 March 2019-31 May 2020. Patients were followed for ±365 days from dupilumab initiation. The study primarily assessed the annual incidence rate of severe asthma exacerbations occurring simultaneously with hospitalizations or OCS bursts. Secondary and exploratory endpoints assessed OCS dosage and duration, and healthcare resource utilization (HRU), respectively. RESULTS: At dupilumab initiation (N = 215), mean age was 57.2 years, 41.9% of patients were aged ≥65 years, and 59.5% were female. Dupilumab significantly reduced the annual incidence of severe asthma exacerbations from 1.29 to 0.74 (95% confidence interval, 0.44-0.76) per patient per year. Mean OCS dosage decreased from 10.4 to 7.2 mg/day in chronic OCS users; median frequency of OCS bursts decreased from 3 to 0. Both unscheduled outpatient visits (35.8% vs 29.8%) and hospitalizations (21.9% vs 12.1%) decreased. Mean (standard deviation) duration of hospitalization also decreased from 6.7 (27.6) to 2.2 (8.1) days. CONCLUSIONS: Japanese patients with asthma who received dupilumab had reduced incidence rates of severe asthma exacerbations, OCS use, and HRU over 12 months.

Associations between Inhaled Corticosteroid Use in the First 6 Years of Life and Obesity-related Traits.

Rationale: Infants and young children might be particularly likely to experience the potential clinical side effects of inhaled corticosteroids (ICSs) on body mass index (BMI), adiposity rebound (AR), and body composition, but this has rarely been studied in long-term studies in this age group. Objectives: To determine the association between ICS exposure in the first 6 years of life and the BMI, AR, body composition, and blood lipid concentrations. Methods: Children from the two mother-child cohorts of the COPSAC (Copenhagen Prospective Studies on Asthma in Childhood) were included. ICS use was registered prospectively to age 6 years, and the cumulative dose was calculated. Multiple linear regression models were used for analysis. Measurements and Main Results: A total of 932 (84%) of the 1,111 children from the COPSAC cohorts had BMI data, 786 (71%) had dual-energy X-ray absorptiometry scan data at the age of 6 years, and 815 (73%) had an AR age calculated. Two hundred ninety-one children (31%) received a cumulative ICS dose higher than that from 10 weeks of standard treatment before the age of 6. ICS treatment during 0-6 years of age was associated with an increased BMI z-score (0.05 [95% confidence interval, 0.005 to 0.09] SDs per each year of standard treatment; P = 0.03) an earlier age at AR (-0.18 [95% confidence interval, -0.28 to -0.08] yr; P = 0.0006), and a 2% increased geometric mean android fat percentage (P = 0.05). ICS exposure and dual-energy X-ray absorptiometry scan data were not associated. Conclusions: ICS use in early childhood was associated with an increased BMI z-score at age 6, an earlier AR, and a trend of association with an increased android body fat percentage.

Platelet-rich plasma vs. corticosteroid injections for the treatment of recalcitrant lateral epicondylitis: a cost-effectiveness Markov decision analysis.

BACKGROUND: Both platelet-rich plasma (PRP) and corticosteroid injections may be used to treat lateral epicondylitis. We evaluated the cost-effectiveness of PRP injections vs. corticosteroid injections for the treatment of recalcitrant lateral epicondylitis. METHODS: Markov modeling was used to analyze the base-case 45-year-old patient with recalcitrant lateral epicondylitis, unresponsive to conservative measures, treated with a single injection of PRP or triamcinolone 40 mg/mL. Transition probabilities were derived from randomized controlled trials, quality-of-life (QOL) values from the Tufts University Cost-Effectiveness Analysis Registry reported using Disabilities of the Arm, Shoulder, and Hand (DASH) scores, and costs from institution financial records. Analyses were performed from health care and societal perspectives. Outcomes were incremental cost-effectiveness ratios (ICERs), reported as US dollars / quality-adjusted life-year (USDs/QALY) and net monetary benefit (NMB) to represent the values of an intervention in monetary terms. Willingness-to-pay thresholds were set at $50,000 and $100,000. Deterministic and probabilistic sensitivity analyses were performed over 10,000 iterations. RESULTS: Both PRP and triamcinolone 40-mg/mL injections were considered cost-effective interventions from a health care and societal perspective below the WTP threshold of $50,000. From a health care perspective, PRP injections were dominant compared with triamcinolone 40-mg/mL injections, with an ICER of -$5846.97/QALY. PRP injections provided an NMB of $217,863.98, whereas triamcinolone 40 mg/mL provided an NMB of $197,534.18. From a societal perspective, PRP injections were dominant compared to triamcinolone 40-mg/mL injections, with an ICER of -$9392.33/QALY. PRP injections provided an NMB of $214,820.16, whereas triamcinolone 40 mg/mL provided an NMB of $193,199.75. CONCLUSIONS: Both PRP and triamcinolone 40-mg/mL injections provided cost-effective treatments from health care and societal perspectives. Overall, PRP injections were the dominant treatment, with the greatest NMB for recalcitrant lateral epicondylitis over the time horizon of 5 years.

Steroidogenesis in patients with adrenal incidentalomas: Extended steroid profile measured by liquid chromatography-mass spectrometry after ACTH stimulation and dexamethasone suppression.

OBJECTIVE: Describe the secretion and profile of adrenal steroids in patients with adrenal incidentalomas compared to control subjects. DESIGN, SETTING AND PARTICIPANTS: A prospective study, 73 patients with adrenal incidentalomas, 21 bilateral and 52 unilateral and 34 matched controls in University Hospital. METHODS: Collect fasting blood sample before and 60 min after ACTH test (250 µg IV). One week later, perform overnight 1 mg dexamethasone test. The following steroids were measured by liquid chromatography-mass spectrometry (LC-MS): pregnenolone, 17-OH pregnenolone, 17-OH progesterone, 11-deoxycorticosterone, 11-deoxyortisol, 21-deoxycortisol, corticosterone, cortisol, androstenedione and aldosterone. RESULTS: Mean baseline serum cortisol was higher in incidentalomas, bilateral 361 ± 124, (range 143-665) nmol/L,(p < .0001), unilateral 268 ± 89 3.2 (range 98-507) nmol/L (p < .019) compared to controls 207 ± 100 (range 72-502) nmol/L. ACTH stimulation showed significantly higher levels in bilateral and unilateral cases compared to controls. After dexamethasone, mean serum cortisol levels suppressed in bilaterals 89 ± 69 (range 30-3) nmol/L (p < .0001), 58 ± 52 (range 16-323) nmol/L in unilateral (p < .01) compared to 26 ± 9 (range 7-46) nmol/L in controls. Mean baseline serum corticosterone was higher in bilateral 9.3 ± 4.8 (range 2.4-18.4) nmol/L (p < .005) and unilateral 7.3 ± 5.7 (range 0.1-30.3) nmol/L (p < .01) compared to controls 4.2 ± 2.4 (range 1.1-10.2) nmol/L, after ACTH stimulation significantly increased to higher levels in bilateral (p < .0002) and unilateral cases (p < .044) compared to controls. After dexamethasone, mean levels were 2.5 ± 2.6 (range 0.5-12.5) nmol/L in bilateral (p < .0006), 1.5 ± 1.6 (range 0.3-9.3) nmol/L in unilateral (p < .09) and 0.75 ± 0.46 (range 0.1-2.1) nmol/L in controls. Mean baseline serum 11-deoxycorticosterone (DOC) was higher in bilaterals 0.32 ± 0.23 (range 0.08-1.1) nmol/L (p < .03) compared to controls 0.15 ± 0.21 (range 0.08-1.1) nmol/L. ACTH stimulation increased levels to 3.27 ± 1.72 (range 0.5-7.4) nmol/L in bilateral cases compared to controls 1.369 ± 1.53 (range 0.1-7.1) nmol/L (p < .0001). Dexamethasone decreased levels to baseline (p ns). There were significant differences in serum 21-deoxycortisol (p < .0002) and serum pregnenolone (p < .004) only after ACTH stimulation. CONCLUSIONS: There is increased activity in several steroid biosynthesis pathways and higher steroid levels in bilateral compared to unilateral cases and evidence of hypercortisolism in 30% unilateral and 62% of bilateral incidentalomas.

Sustained Remission After Treatment Withdrawal in Autoimmune Hepatitis: A Multicenter Retrospective Study.

BACKGROUND: In patients with autoimmune hepatitis (AIH), relapse rates between 25 and 100% after treatment withdrawal have been reported. The optimal strategy for immunosuppressive treatment withdrawal is controversial. AIM: To identify the predictive factors of histological remission and to assess the relapse rate after treatment withdrawal in AIH patients with prolonged biochemical response. METHODS: Patients with AIH and sustained biochemical remission on first-line treatment were retrospectively included. Histological response was defined as complete regression of interface hepatitis and lobular necrosis and no or minimal portal inflammation and relapse as any elevation of serum aminotransferase or gammaglobulin/IgG levels. RESULTS: Sixty-two patients were included. Forty-seven had a biopsy after a median biochemical response of 49.7 months. Twenty-five of them were histological responders. Independent predictors of histological remission were older age (OR = 1.1; CI 95%: 1.0; 1.2), mild-to-moderate fibrosis at diagnosis (OR = 8; CI: 1.4; 47.6) and aspartate aminotransferases < 0.6 × ULN (OR = 7.1; CI: 1.3; 36.7). Thirty-nine patients stopped therapy after a median biochemical response of 48.6 months. Twenty-four of them had a biopsy before treatment withdrawal: 21 were histological responders. The cumulative rate of relapse was 25% at 64 months. CONCLUSIONS: This study indicates that older age, mild-to-moderate fibrosis at diagnosis and serum aspartate aminotransferases in the lower range of normal are independent predictors of histological response in AIH with prolonged biochemical response. The relapse rate after treatment withdrawal may be limited to 25% at 64 months when patients are selected on the basis of prolonged biochemical remission and, when available, histological response.

Cryosurgery as a Single Agent and in Combination with Intralesional Corticosteroids Is Effective on Young, Small Keloids and Induces Characteristic Histological and Immunohistological Changes: A Prospective Randomized Trial.

BACKGROUND: As the pathogenesis of keloids is poorly understood, there is no sound biological basis of keloid management. Few controlled therapeutic studies have been published, and recurrences are a major reason for treatment failure. OBJECTIVE: To detect efficacy and safety of cryosurgery regimens on keloids and the occurring biological changes caused by the treatment. METHODS: This prospective randomized study compared efficacy and tolerability as well as histological/immunohistochemical effects of liquid nitrogen contact cryosurgery as a single regimen (group A) and combined with intralesional corticosteroids (group B) on young (<2 years old), small (≤10 cm2) keloids in 40 patients (2-sided effect, α-error 1%, power 95%). RESULTS: Marked flattening of the lesions was achieved by both regimens. Median lesional volumes decreased from 106 to 7 mm3 in group A (p = 0.001) and from 138 to 6 mm3 in group B (p < 0.0001; ns, between groups). Good to excellent responses were registered in 83.3 and 90% of patients in groups A and B, respectively, by evaluating the lesional volume, in 80 and 95% of patients by the physician's evaluation and in 95% of patients in either group by the patient's assessment. Follow-up of 6-36 months revealed no further significant changes. Cryosurgery was generally well tolerated, with minor pain during treatment not requiring (27.5%) or requiring local anaesthesia (5%) - but not analgesics -, and hypopigmentation (25%). Histological examination showed increased vessel number and lumen dilatation after treatment in group B and reduction of rete ridge length in both groups with more prominent changes in group A. Tenascin C staining demarcated keloids from normal skin before therapy, while after therapy the entire treated tissue was labelled. Interferon-γ expression was significantly decreased after therapy both regarding positively stained cells and intensity in both groups. CONCLUSION: Cryosurgery without and with intralesional corticosteroids is effective and safe on young, small keloids not only as a destructive physical procedure, but also by inducing biochemical and immunological scar rejuvenation.

Focus group parental opinions regarding treatment with topical corticosteroids on children with atopic dermatitis.

INTRODUCTION AND OBJECTIVES: Atopic dermatitis is common among children of 0-5 years old. Treatment consists of emollients and topical corticosteroids. Due to corticophobia, however, adherence to topical corticosteroids is low. Our aim was to find factors that influence opinions about topical corticosteroids among parents of children with atopic dermatitis. METHODS: A qualitative focus group study in secondary care with parents of children with atopic dermatitis. Questions concerned opinions, attitude, sources of information, and the use of topical corticosteroids. RESULTS: The parents indicated that they lack knowledge about the working mechanism and side effects of topical corticosteroids. Dermatologists and paediatricians emphasise the beneficial effects, whereas other healthcare workers and lay people often express a negative attitude. CONCLUSIONS: This study gives a complete overview of factors influencing adherence. Treatment with topical corticosteroids can be improved by better informing parents about the working mechanisms, the use, and how to reduce the dose. Healthcare professionals need to be aware of the consequences of their negative attitude concerning topical corticosteroids.

SUCCESSFUL TREATMENT OF ACUTE DISSEMINATED ENCEPHALOMYELITIS (ADEM) BY PROMPT USAGE OF IMMUNOGLOBULINS - CASE REPORT AND REVIEW OF THE LITERATURE.

Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the central nervous system that usually affects children and young adults. It most commonly has a monophasic course, although relapses are reported. Clinical presentation of the disease includes encephalopathy and multifocal neurological deficits. There are no established reliable criteria for diagnosis of ADEM and sometimes it is difficult to distinguish it from first attack of multiple sclerosis, especially in adults. The diagnosis of ADEM is based on clinical, radiological and laboratory findings. In the treatment of ADEM, high doses of corticosteroids, plasmapheresis and immunoglobulins are used. We report a case of a young adult female patient with ADEM who fully recovered after prompt administration of high dose methylprednisolone and immunoglobulins.

Steroid administration after anaesthetic induction with etomidate does not reduce in-hospital mortality or cardiovascular morbidity after non-cardiac surgery.

BACKGROUND: We tested the primary hypothesis that corticosteroid administration after etomidate exposure reduces a composite of in-hospital mortality and cardiovascular morbidity after non-cardiac surgery. METHODS: We evaluated ASA physical status III and IV patients who had non-cardiac surgery with general anaesthesia at the Cleveland Clinic. Amongst 4275 patients in whom anaesthesia was induced with etomidate, 804 were also given steroid intraoperatively, mostly dexamethasone at a median dose of 6 mg. We successfully matched 582 steroid patients with 1023 non-steroid patients. The matched groups were compared on composite of in-hospital mortality and cardiovascular morbidity using a generalized-estimating-equation model. Secondly, the matched groups were compared on length of hospital stay using a Cox proportional hazard model, and were descriptively compared on intraoperative blood pressures using a standardized difference. RESULTS: There was no significant association between intraoperative steroid administration after anaesthetic induction with etomidate and the composite of in-hospital mortality or cardiovascular morbidity; the estimated common odds ratio across the two components of the composite was 0.86 [95% confidence interval (CI): 0.64, 1.16] for steroid vs non-steroid, P=0.33. The duration of postoperative hospitalisation was significantly shorter amongst steroid patients [median (Q1, Q3): 6 (3, 10) days] than non-steroid patients [7 (4, 11) days], with an estimated hazard ratio of 0.89 (0.80, 0.98) for steroid vs non-steroid, P=0.01. Intraoperative blood pressures were similar in steroid and non-steroid patients. CONCLUSIONS: Steroid administration after induction of anaesthesia with etomidate did not reduce mortality or cardiovascular morbidity.

[Comparison of the effects of 0.1% bromfenac sodium eye drops and corticosteroids after small incision lenticule extraction].

Objective: To study the safety, efficacy and tolerability of the usage of 0.1% bromfenac sodium eye drops in small incision lenticule extraction (SMILE). Methods: Prospective case control study. Three groups were observed, including 60 patients (60 eyes) undergoing SMILE for myopia. After surgery, 20 patients (20 eyes) were treated with 0.1% bromfenac sodium eye drops twice daily for 10 days, 20 patients (20 eyes) were treated with topical compound tobramycin eye drops 4 times daily for 10 days, and 20 patients (20 eyes) were treated with topical compound tobramycin eye drops 4 times daily for 3 days and 0.1% bromfenac sodium eye drops twice daily thereafter for 7 days. All of the patients were examined preoperatively and at 1 day, 10 days, 1 month and 3 months postoperatively, including visual acuity, intraocular pressure, topography and adverse reactions. The differences among the 3 groups were analyzed by the single factor analysis of variance. Results: There was no significant difference among the 3 groups in the uncorrected visual acuity at 10 days, 1 month and 3 months postoperatively (F=0.77, 0.30, 0.36. P=0.47, 0.75, 0.69) . The intraocular pressure in the dexamethasone group at 10 days, 1 month and 3 months postoperatively was higher than the other two groups with no significant difference (F=0.56, 0.98, 0.63. P=0.57, 0.38, 0.54) . The surface asymmetry index of patients was 0.33±0.10, 0.50±0.17 and 0.55±0.21 in the bromfenac sodium group, 0.33±0.08, 0.49±0.16 and 0.60±0.37 in the dexamethasone-bromfenac sodium group, and 0.31±0.12, 0.52±0.23 and 0.55±0.19 in the dexamethasone group; preoperatively and at 1 and 3 months, respectively. There was no significant difference among the 3 groups in the surface asymmetry index at 1 and 3 months postoperatively (F=0.09, 0.21. P=0.91, 0.81) . The surface regularity index of patients was 0.15±0.12, 0.34±0.18 and 0.40±0.18 in the bromfenac sodium group, 0.18±0.17, 0.33±0.26 and 0.33±0.26 in the dexamethasone-bromfenac sodium group, and 0.30±0.25, 0.41±0.28 and 0.34±0.29 in the dexamethasone group preoperatively and at 1 and 3 months, respectively. There was no significant difference among the 3 groups in the surface regularity index at 1 and 3 months postoperatively (F=0.74, 0.39. P= 0.48, 0.68) . In the bromfenac sodium group, one patient complained of binocular visual fatigue at 10 days, and one patient complained of dryness in one eye at 1 and 3 months. Conclusion: Bromfenac sodium eye drops can be used to replace corticosteroids after SMILE procedure with high safety and good tolerance. Satisfactory recovery of visual acuity, intraocular pressure and ocular surface could be achieved. (Chin J Ophthalmol, 2017, 53: 18-22).

Statin Use and Adrenal Aldosterone Production in Hypertensive and Diabetic Subjects.

BACKGROUND: Statins substantially reduce cardiovascular mortality and appear to have beneficial effects independent of their lipid-lowering properties. We evaluated the hypothesis that statin use may modulate the secretion of aldosterone, a well-known contributor to cardiovascular disease. METHODS AND RESULTS: We measured adrenal hormones in 2 intervention studies. In study 1 in hypertensive subjects, aldosterone was analyzed at baseline and after angiotensin II stimulation on both high- and low-sodium diets (1122 observations, 15% on statins for >3 months). Statin users had 33% lower aldosterone levels in adjusted models (P<0.001). Cortisol was not modified by statins. In secondary analyses, the lowest aldosterone levels were seen with lipophilic statins and with higher doses. Statin users had lower blood pressure and reduced salt sensitivity of blood pressure (both P<0.001). In study 2, aldosterone was measured in diabetic patients on a high-sodium diet, before and after angiotensin II stimulation (143 observations, 79% statin users). Again, statin users had 26% lower aldosterone levels (P=0.006), particularly those using lipophilic statins. Ex vivo studies in rat adrenal glomerulosa cells confirmed that lipophilic statins acutely inhibited aldosterone, but not corticosterone, in response to different secretagogues. CONCLUSIONS: Statin use among hypertensive and diabetic subjects was associated with lower aldosterone secretion in response to angiotensin II and a low-sodium diet in 2 human intervention studies. This effect appeared to be most pronounced with lipophilic statins and higher doses. Future studies to evaluate whether aldosterone inhibition may partially explain the robust cardioprotective effects of statins are warranted.

The Influence of Corticosteroids on Heart Rate Variablity in Acute Cervical Spinal Cord Injury.

Heart rate variability (HRV) gives information on the sympathetic-parasympathetic autonomic balance. The aim of the study was to analyze sympathovagal balance after acute spinal cord injury (SCI), demonstrated by linear measures in time and frequency domain of HRV and to analyze the effect of corticosteroids on HRV parameters in SCI. The study included 40 tetraplegic patients with acute SCI and 40 healthy subjects as control group. In the SCI group, 29 patients received and 11 patients did not receive corticosteroid therapy. All patients underwent 24-hour Holter monitoring for evaluation of HRV. Cardiac autonomic balance was evaluated by analysis of HRV in time and frequency domain. Sympathovagal balance (LF/HF) was significantly reduced in the groups of acute SCI patients, both with and without corticosteroid therapy, as compared with controls. However, there was no statistically significant difference between the two SCI groups (1.74 (0524) with and 1.75 (0534) without corticosteroid therapy). This study showed the sympathovagal balance to be altered in the acute phase of cervical spinal cord trauma. Finally, there was no effect of corticosteroid therapy on HRV parameters in SCI patients.

Corticosteroid adulteration in proprietary Chinese medicines: a recurring problem.

OBJECTIVES: To investigate adulteration of proprietary Chinese medicines with corticosteroids in Hong Kong. DESIGN: Case series with cross-sectional analysis. SETTING: A tertiary clinical toxicology laboratory in Hong Kong. PATIENTS: All patients using proprietary Chinese medicines adulterated with corticosteroids and referred to the authors' centre from 1 January 2008 to 31 December 2012. MAIN OUTCOME MEASURES: Patients' demographic data, clinical presentation, medical history, drug history, laboratory investigations, and analytical findings of the proprietary Chinese medicines were analysed. RESULTS: The records of 61 patients who consumed corticosteroid-adulterated proprietary Chinese medicines were reviewed. The most common corticosteroid implicated was dexamethasone. Co-adulterants such as non-steroidal anti-inflammatory drugs and histamine H1-receptor antagonists were detected in the proprietary Chinese medicine specimens. Among the patients, seven (11.5%) required intensive care, two (3.3%) died within 30 days of presentation, and 38 (62.3%) had one or more complications that were potentially attributable to exogenous corticosteroids. Of 22 (36.1%) patients who had provocative adrenal function testing performed, 17 (77.3% of those tested) had adrenal insufficiency. CONCLUSION: The present case series is the largest series of patients taking proprietary Chinese medicines adulterated with corticosteroids. Patients taking these illicit products are at risk of severe adverse effects, including potentially fatal complications. Adrenal insufficiency was very common in this series of patients. Assessment of adrenal function in these patients, however, has been inadequate and routine rather than discretionary testing of adrenal function is indicated in this group of patients. The continuing emergence of proprietary Chinese medicines adulterated with western medication indicates a persistent threat to public health.