Supplementing electronic health records through sample collection and patient diaries: A study set within a primary care research database.

PURPOSE: To describe a novel observational study that supplemented primary care electronic health record (EHR) data with sample collection and patient diaries. METHODS: The study was set in primary care in England. A list of 3974 potentially eligible patients was compiled using data from the Clinical Practice Research Datalink. Interested general practices opted into the study then confirmed patient suitability and sent out postal invitations. Participants completed a drug-use diary and provided saliva samples to the research team to combine with EHR data. RESULTS: Of 252 practices contacted to participate, 66 (26%) mailed invitations to patients. Of the 3974 potentially eligible patients, 859 (22%) were at participating practices, and 526 (13%) were sent invitations. Of those invited, 117 (22%) consented to participate of whom 86 (74%) completed the study. CONCLUSIONS: We have confirmed the feasibility of supplementing EHR with data collected directly from patients. Although the present study successfully collected essential data from patients, it also underlined the requirement for improved engagement with both patients and general practitioners to support similar studies.

Use of a Risk-Stratification Tool in Identification of Potential Adrenal Suppression Preceding Steroid Injection Therapy in Chronic Pain Patients.

BACKGROUND: Patients who present for steroid injections are not routinely screened for potential hypothalamic-pituitary-adrenal (HPA) axis suppression from previous steroid exposure. Patients often receive various steroid therapies that are not reported by the patient or recorded in available medical records. Yet, HPA axis suppression has been reported with a single intra-articular injection. METHODS: An IRB-approved quality improvement questionnaire was implemented to comprehensively screen patients for risk of HPA axis suppression secondary to prior and/or concurrent corticosteroid use. This questionnaire was given to adult patients seen in a University Pain Management Clinic, who were being considered for a steroid injection, to define the extent of exposure to corticosteroids either by mouth, topically, inhaled, or systemic/local injection within the past 6 months. RESULTS: Two hundred patients completed the questionnaire. Eighty-nine patients (44.5%) screened positive for significant steroid exposure with a screen score of three or above. The average score for the screen positive group was 6.31 ± 3.47 (range 3-22). Women were 1.9 times more likely to screen positive than men (53.4% vs 27.5%, P < 0.0004). Otherwise, the screen positive and screen negative groups were similar in demographic characteristics (age, BMI, and diabetes status). CONCLUSIONS: Our results suggest that patients receive steroids from many sources and may be at risk for HPA axis suppression. Further testing is necessary to determine if these patients indeed have biochemical evidence of adrenal suppression. Utilization of a screening questionnaire might help identify patients who should be considered for HPA axis testing prior to steroid injections.

Monitoring adrenal insufficiency through salivary steroids: a pilot study.

BACKGROUND: Various glucocorticoid replacement therapies (GRTs) are available for adrenal insufficiency (AI). However, their effectiveness in restoring glucocorticoid rhythm and exposure lacks adequate biochemical markers. We described the diurnal salivary cortisol (SalF) and cortisone (SalE) rhythm among different GRTs and analysed the associations between saliva-derived parameters and life quality questionnaires. METHODS: Control subjects (CSs, n = 28) and AI patients receiving hydrocortisone (HC, n = 9), cortisone acetate (CA, n = 23), and dual-release hydrocortisone once (DRHC-od, n = 10) and twice a day (DRHC-td, n = 6) collected 9 saliva samples from 07:00 to 23:00. Patients compiled Pittsburgh Sleep Quality Index, Hospital Anxiety and Depression Scale, and Addison disease-specific quality-of-life questionnaires. SalE and SalF were measured by liquid chromatography-mass spectrometry. Exposure was monitored using SalE for HC and DRHC and SalF for CA. Area under the curve (AUC) was computed. Different GRTs were compared by Z-scores calculated from saliva-derived parameters. Questionnaire results predictors were evaluated with multiple regression analysis. RESULTS: Compared with controls, all GRTs resulted in glucocorticoid overexposure in the morning. Hydrocortisone, CA, and DRHC-td caused overexposure also in afternoon and evening. Compared with other treatments, CA determined increased Z-score-07:00 (P < .001), DRHC-td determined increased Z-score-AUC07:00→14:00 (P = .007), and DRHC-od induced lower Z-score-AUC14:00→23:00 (P = .015). Z-scores-AUC14:00→16:00 ≥ .619 best predicted questionnaire scores. CONCLUSIONS: None of the GRTs mimics normal glucocorticoid rhythmicity and exposure. SalE, SalF, and Z-score may be useful markers for monitoring and comparing different GRTs. Excess glucocorticoid in early afternoon best associated with depressive symptoms and worse life and sleep quality.

Corticosteroid administration in oral and orthognathic surgery: a systematic review of the literature and meta-analysis.

PURPOSE: This study evaluated the effect of corticosteroid (CS) administration on edema, analgesia, and neuroregeneration in conjunction with surgical dental extraction, orthognathic surgery, and the risk of developing side effects. MATERIALS AND METHODS: A systematic search of the literature was made. The primary predictor variable was CS administration and the outcome variables were edema, pain, and infection. A meta-analysis was performed. The risk of other side effects was evaluated through a simple review. RESULTS: In oral surgery, most clinical trials showed a significant decrease in edema (P < .0001) after CS, and local injection of methylprednisolone > or =25 mg was expected to result in a significant decrease in edema. Regarding the analgesic effect, several clinical trials showed a decrease in pain after CS (P < .0001). Further, CS administration resulted in a slightly higher risk of infection (relative risk, 1.0041), but with a P value of .89. CS could be administered with no increased risk of infection. In orthognathic surgery, methylprednisolone > or =85 mg administered intravenously seemed sufficient to produce a significant decrease in edema, and several trials pointed toward a neuroregeneration effect, but no statistical analysis could be performed. Regarding the risk of other side effects, in oral surgery, a minimal risk of chronic adrenal suppression was seen; in orthognathic surgery, an elevated risk of avascular osteonecrosis, steroid-induced psychosis, and adrenal suppression was seen. There were no reports of decreased healing. CONCLUSION: These findings suggest that the administration of CS in oral surgery decreases edema and pain significantly, with no higher risk of infection and with a minimum risk of other side effects.

Relationship Between Epidural Steroid Dose and Suppression of Hypothalamus-Pituitary-Adrenal Axis.

BACKGROUND: The suppression of hypothalamic-pituitary-adrenal (HPA) axis is a common complication associated with epidural steroid injections (ESIs). However, the effect of different doses is unknown. OBJECTIVES: The primary objective was to compare the differences in the duration of HPA suppression following treatment with different doses of ESI; triamcinolone acetate (TA) 40 mg and TA 20 mg. The secondary objectives were to compare the extent of salivary cortisol (SC) reduction, the incidence of adrenal insufficiency (AI), and the differences in a numeric rating scale (NRS) depending on the varying levels of TA dose used for ESI. STUDY DESIGN: A double-blind, parallel-group, randomized controlled trial. SETTING: Pain clinics in a university hospital. METHODS: The patients were treated with TA epidurally and divided into 2 groups (T20 and T40) depending on the dose of TA (20 mg and 40 mg). The SC concentration was measured before and after ESI to calculate the duration of HPA axis suppression, the extent of SC concentration reduction, and the SC recovery rate. Additionally, NRS and adrenocorticotropic hormone stimulation tests were used. RESULTS: Thirty patients were analyzed. The T40 group showed longer HPA suppression (19.7 ± 3.1 days) compared with that of the T20 group (8.0 ± 2.4 days). The recovery rate of the T40 group was lower than that of the T20 group (P < 0.015). However, there was no difference in the extent of reduction in SC concentration after ESI, the occurrence of AI, and pain reduction. LIMITATIONS: There were selection bias and no placebo control. CONCLUSIONS: Although the difference in pain relief according to the ESI dose is not significant, the HPA suppression is prolonged with a higher dose than a lower dose, and the recovery is slower. Therefore, the time interval between consecutive ESIs should be adjusted depending on the steroid dose to ameliorate the adverse effects of steroids.

Efficacy and systemic tolerability of mometasone furoate and betamethasone sodium phosphate.

This study evaluates the efficacy and systemic tolerability of licensed doses of mometasone furoate (Nasonex) and betamethasone sodium phosphate (Betnesol) in allergic chronic rhinosinusitis patients. It also assesses the diagnostic accuracy of morning salivary cortisol (MSC) concentrations to screen for adrenal suppression in these patients. Forty-eight patients were prospectively randomized to two treatment limbs. Symptom scores and adrenal function assessments were performed immediately prior to commencement and at the end of treatment. One (4 per cent) mometasone furoate and 14 (58 per cent) betamethasone sodium phosphate patients developed biochemical evidence of adrenal suppression. There were statistically significant (p < 0.005) reductions in symptom scores following treatment, but no significant difference (p > 0.05) between the drug groups regarding post-treatment symptom scores. As a screening tool for iatrogenic adrenal suppression, MSC had a sensitivity of 100 per cent and a specificity of 97 per cent. This study demonstrates the high risk of developing adrenal suppression secondary to betamethasone sodium phosphate therapy. The salivary cortisol assay is an accurate tool for monitoring adrenal function and is ideally suited to the out-patient setting.

Assessment of salivary free cortisol levels by liquid chromatography with tandem mass spectrometry (LC-MS/MS) in patients treated with mitotane.

OBJECTIVE: Mitotane is an adrenocytolytic agent used in adrenocortical carcinoma, inducing adrenal insufficiency, requiring replacement treatment. Such therapy is not easy to monitor because of mitotane interference. Salivary cortisol reflects a free fraction of plasma cortisol and may be useful in such patients. DESIGN: The aim of our study was to evaluate salivary cortisol by HPLC coupled to tandem-mass spectrometry (LC-MS/MS) and by an electrochemiluminescence immunoassay (ECLIA) in patients treated with mitotane. We enrolled 6 patients receiving mitotane and 2 Addison disease patients as negative controls and determined salivary cortisol rhythm. We also determined the salivary cortisol rhythm in 8 healthy subjects. Salivary samples (n=112) were assayed by ECLIA, using Roche Modular E170, and by LC-MS/MS. RESULTS: The mean values obtained by ECLIA were significantly higher than those obtained by LC-MS/MS in the mitotane group (p<0.001). In fact, in the group measured by LC-MS/MS, we observed several peaks eluting at a retention time different from the cortisol group, presumably due to cortisol-like analogues. In Addison disease, since steroidogenesis is absent, salivary cortisol values measured by the two methods did not show any significant difference (p=0.61). CONCLUSIONS: Salivary cortisol measured by LC-MS/MS is a selective method, excluding cortisol analogues accumulating in treated patients. Therefore, LC-MS/MS offers an effective system to monitor replacement therapy in mitotane treated patients.

Value of basal serum cortisol to detect corticosteroid-induced adrenal insufficiency in elite cyclists.

The frequent use of glucocorticoids by athletes necessitates testing for adrenal insufficiency because of the risk of death in cases of associated severe stress (trauma, infection). During the 2001 and 2002 sporting seasons, we assessed the value of measuring baseline serum cortisol concentrations and the frequency of corticosteroid use during compulsory medical tests carried out by the French Cycling Federation on 659 elite cyclists (585 men and 74 women); the risk of adrenal insufficiency is negatively correlated with the basal serum cortisol level. Adrenal insufficiency was suspected in 34 cyclists (5.2%; 22 in 2001 and 12 in 2002) on the basis of below normal cortisol concentrations and in three cyclists (in 2001) because they had received corticosteroid treatment. In 2001, 10 of the 25 cyclists convoked underwent baseline follow-up serum cortisol determinations and 15 underwent dynamic exploration of adrenal function with the short ACTH test. Adrenal function was found to be deficient in four of these cyclists, at the limits of the normal range in four and normal in seven. Based on these results, the FFC sent a questionnaire in 2002 to all the cyclists to assess the use of corticosteroid in this population. This survey revealed that 85 of 538 cyclists (15.8%) had received corticosteroid treatment in the previous 3 months. Moreover, 11 of the 12 cyclists (92%) with low basal serum cortisol concentrations had received corticosteroid therapy. These results show that basal serum cortisol is relevant to detect adrenal insufficiency in sportsmen, in particular in cases of values below the normal range. The high frequency of corticosteroid use among elite cyclists, and in particular road cyclists who are at risk of trauma and infection, justifies screening tests to detect adrenal insufficiency.

Preliminary results of a pilot study investigating the potential of salivary cortisol measurements to detect occult adrenal suppression secondary to steroid nose drops.

Adrenocortical suppression is a well-known risk of systemic steroids, but is thought less likely to occur with topical intranasal corticosteroids. However, the UK Committee on the Safety of Medicines (UKCSM) has expressed concern about the possibility of this complication. We assessed the prevalence of adrenal suppression in patients with rhinitis using intranasal beclomethasone and betamethasone; and the potential value of salivary cortisol as a tool for detecting this complication. Sixty-six patients (38 men: 28 women; mean age 49.6[SD 16.0] years) were prospectively screened for adrenal insufficiency using clinical assessment and salivary cortisol measurements. Abnormalities at this initial screening were confirmed with a Short Synacthen Test (SST). No patient was clinically Cushingoid. All 22 beclomethasone users had normal salivary cortisols. Eleven (25%) of 44 patients using betamethasone had subnormal salivary cortisol levels (mean morning cortisol 2.8[SD 0.9]nmol/l) suggesting adrenal suppression, which was confirmed by an impaired SST in each case. The positive predictive value of salivary cortisol measurements was 100%. Only patients with abnormal salivary cortisols had a SST, so no comment can be made about sensitivity/specificity. Topical betamethasone may produce occult adrenal insufficiency and assessment of adrenal function is recommended in these patients. Measurement of salivary cortisol is a useful, non-invasive and economical test for monitoring patients using intranasal corticosteroids.