Glucocorticoid Medication Research Articles

Clinical practice pattern of Pneumocystis pneumonia prophylaxis in systemic lupus erythematosus: a cross-sectional study from lupus registry of nationwide institutions (LUNA)

BackgroundPneumocystis jirovecii pneumonia (PCP) is an opportunistic infection in patients undergoing immunosuppressive therapy, such as glucocorticoid (GC) medication, for systemic autoimmune diseases like systemic lupus erythematosus (SLE). Despite the confirmed effectiveness of PCP prophylaxis, its clinical administration, especially in conjunction with GC dosage, remains unclear. We aimed to describe the clinical practice of PCP prophylaxis in association with SLE in Japan, evaluate the relationship between GC dosage and PCP prophylaxis, and explore the practice patterns associated with PCP prophylaxis.MethodsThis cross-sectional study used data from the Lupus Registry of Nationwide Institutions in Japan from 2016 to 2021 and included patients diagnosed with SLE. Using descriptive statistics, multivariate analysis, and decision tree analysis, we examined the prevalence of PCP prophylaxis and its association with the GC dosage.ResultsOut of 1,460 patients, 21% underwent PCP prophylaxis. The frequency of prophylaxis decreased with a decrease in GC dosage. After adjusting for confounders, logistic regression revealed the odds ratio of PCP prophylaxis increased with higher prednisolone (PSL) doses: 3.7 for 5 ≤ PSL < 7.5 mg, 5.2 for 7.5 ≤ PSL < 10 mg, 9.0 for 10 ≤ PSL < 20 mg, and 43.1 for PSL ≥ 20 mg, using PSL < 5 mg as the reference. Decision tree analysis indicated that a PSL dosage of < 11 mg/day and immunosuppressant use were key determinants of PCP prophylaxis.ConclusionThis study provides valuable insights into PCP prophylaxis practices in patients with SLE in Japan, underscoring the importance of GC dosage and concomitant immunosuppressant use.

Hair and nail cortisol levels are associated and affected by glucocorticoid use

Hair and nail cortisol is increasingly studied as a physiologic proxy for chronic stress response. Glucocorticoid use is an expected confounder for cortisol measurement, yet there remains little evidence of whether external cortisol use should be subject to exclusion in study subjects. In a group of 209 youth (15–22 year-olds), we analyzed hair and fingernail cortisol concentrations. We assessed topical, nasal, oral, and injectable glucocorticoid use via a questionnaire. Extensively validated methods were used for hair and nail cortisol extraction and measurements. The median value of hair cortisol was 10.2 pg/mg (n=200), and the median value of nail cortisol was 7.06 pg/mg (n=203). Topical glucocorticoid use significantly increased hair and nail cortisol concentrations (p<0.005). Hair and nail cortisol concentrations were positively associated (p<0.0001, n=194). Spearman correlation coefficients demonstrated that the positive correlation between hair and nail cortisol values was higher in participants who used external glucocorticoids. Topical glucocorticoids moderated the association between hair and nail cortisol values (p=0.006). Based on these findings, we recommend that the assessment of topical glucocorticoid use must be performed when collecting hair/nail samples and that subjects reporting glucocorticoid use should be excluded from all future hair and nail cortisol studies; also, all outliers must be excluded to account for glucocorticoid medication underreporting and yet-unknown confounders.

Prescription glucocorticoid medication and iridocyclitis are associated with an increased risk of senile cataract occurrence: a Mendelian randomization study.

Iridocyclitis and the use of glucocorticoid medication have been widely studied as susceptibility factors for cataracts. However, the causal relationship between them remains unclear. This study aimed to investigate the causal relationship between the development of iridocyclitis and the genetic liability of glucocorticoid medication use on the risk of senile cataracts occurrence by performing Two-sample Mendelian randomization (MR) analyses. Instrumental variables (IVs) significantly associated with exposure factors (P < 5 × 10-8) were identified using published genome-wide association data from the FinnGen database and UK Biobank. Reliability analyses were conducted using five approaches, including inverse-variance weighted (IVW), MR-Egger regression, simple median, weighted median, and weighted mode. A sensitivity analysis using the leave-one-out method was also performed. Genetic susceptibility to glucocorticoid use was associated with an increased risk of developing senile cataracts (OR, 1.10; 95% CI, 1.02-1.17; P < 0.05). Moreover, iridocyclitis was significantly associated with a higher risk of developing senile cataracts (OR, 1.03; 95% CI, 1.01-1.05; P < 0.05). Nonetheless, some heterogeneity in the IVs was observed, but the MR results remained consistent after penalizing for outliers. The estimates were consistent in multivariate analyses by adjusting for body mass index (BMI) and diabetes mellitus type 2 (T2DM). This study provides new insights into the prevention and management of senile cataracts by highlighting the increased risk associated with iridocyclitis and the use of glucocorticoids.

Regulatory effects of microRNAs on monocytic HLA-DR surface expression.

Decreased monocytic HLA-DR expression is the most studied biomarker of immune competency in critically ill and autoimmune disease patients. However, the underlying regulatory mechanisms remain largely unknown. One probable HLA-DR dysregulation is through microRNAs. The aim of this study was to investigate the effects of specific microRNAs on HLA-DR expression in human monocytic cells. Four up- and four down-HLA-DR-regulating microRNAs were identified, with hsa-miR-let-7f-2-3p showing the most significant upregulation and hsa-miR-567 and hsa-miR-3972 downregulation. Anti-inflammatory glucocorticoid medication Dexamethasone-decreased HLA-DR was significantly restored by hsa-miR-let-7f-2-3p and hsa-miR-5693. Contrarily, proinflammatory cytokines IFN-γ and TNF-α-increased HLA-DR were significantly reversed by hsa-miR-567. Clinically, paired plasma samples from patients before and one day after cardiac surgery revealed up-regulated expression of hsa-miR-5693, hsa-miR-567, and hsa-miR-3972, following the major surgical trauma. In silico approaches were applied for functional microRNA-mRNA interaction prediction and candidate target genes were confirmed by qPCR analysis. In conclusion, novel monocytic HLA-DR microRNA modulators were identified and validated in vitro. Moreover, both the interaction between the microRNAs and anti- and proinflammatory molecules and the up-regulated microRNAs identified in cardiac surgery highlight the potential clinical relevance of our findings.

Multiple brain abscess in systemic lupus erythematosus patients

Introduction: Because SLE patients receive immunosuppressive and glucocorticoid medication, they are more susceptible to opportunistic infections. Multiple brain abscesses are an extremely uncommon side effect of systemic lupus erythematosus (SLE). Case description: The purpose of this case study is to raise awareness of the 14-year-old girl who reported experiencing weakness in her limbs. A year ago, she received a diagnosis of systemic lupus erythematosus. Upon physical examination, nervus VII central paresis was discovered; the lower extremities' muscular strength was 3333/2222 and the upper extremities' 3333/2222. A head CT scan revealed findings that were consistent with lupus cerebritis. Multiple ring lesions with extensive edoema were detected by magnetic resonance imaging, raising the possibility of multiple brain abscesses. For six weeks, the patient had intravenous metronidazole and ceftriaxone. The patient was allowed to go home with instructions to keep taking corticosteroids and mycophenolic acid as well as to schedule routine outpatient appointments. This case study aims to raise awareness about the 14-year-old girl who reported experiencing weakness in her limbs. Her condition was identified by specialists as systemic lupus erythematosus a year ago. Upon physical examination, nervus VII central paresis was discovered; the lower extremities' muscular strength was 3333/2222 and the upper extremities' 3333/2222. A head CT scan revealed findings that were consistent with lupus cerebritis. Multiple ring lesions with extensive edoema were detected by magnetic resonance imaging, raising the possibility of multiple brain abscesses. For six weeks, the patient received metronidazole and ceftriaxone intravenously. We sent the patient home with instructions to keep taking mycophenolic acid and corticosteroids and to make routine outpatient appointments. This case study aims to raise awareness about the 14-year-old girl who reported experiencing weakness in her limbs. Her condition was identified by specialists as systemic lupus erythematosus a year ago. Upon physical examination, nervus VII central paresis was discovered; the lower extremities' muscular strength was 3333/2222 and the upper extremities' 3333/2222. A head CT scan revealed findings that were consistent with lupus cerebritis. Multiple ring lesions with extensive edoema were detected by magnetic resonance imaging, raising the possibility of multiple brain abscesses. For six weeks, the patient received metronidazole and ceftriaxone intravenously. We sent the patient home with instructions to keep taking mycophenolic acid and corticosteroids and to make routine outpatient visits. Conclusion: It is critical to being aware that individuals with impaired immune systems should always be suspected of having an opportunistic central nervous system infection when they experience new neurologic symptoms. A brain abscess is a chronic infection of the central nervous system that can arise from a number of risk factors and infection sources. A brain abscess is one of the uncommon side effects of SLE.

Medication and bone health in multiple sclerosis: A systematic review and meta-analysis.

People with multiple sclerosis (MS) are often prescribed medications associated with adverse effects on bone health. However, it is unclear whether these medications incur decreases in areal bone mineral density (aBMD) and higher fracture risk in this population. To investigate the effects of commonly used medications on aBMD and fracture risk among people with MS. MEDLINE, Embase, Scopus, CINAHL, and Web of Science were searched from their inception until February 5, 2023. We included randomized controlled trials as well as cross-sectional, retrospective, and prospective studies investigating whether glucocorticoids, immunomodulators, antidepressants, anticonvulsants, anxiolytics, opioids, or antipsychotics influenced aBMD or fracture risk in people with MS. Data were pooled using random effects meta-analyses to determine hazard ratios (HRs) and 95% CIs. We included 22 studies (n = 18,193). Six studies were included in the meta-analyses of glucocorticoid use and aBMD, whereas 2 studies were included in the medication use and fracture risk meta-analyses. No studies assessed the effect of antidepressants, anxiolytics, anticonvulsants, opioids, and antipsychotics on aBMD, and no studies assessed the effect of immunomodulators on fracture risk. Glucocorticoid use was significantly negatively associated with femoral neck aBMD (correlation = -0.21 [95% CI = -0.29 to -0.13]), but not with lumbar spine aBMD (correlation = -0.21 [95% CI = -0.50 to 0.12]). There were no differences in fracture risk between users of glucocorticoids (HR = 1.71 [95% CI = 0.04 to 76.47]), antidepressants (HR = 1.84 [95% CI = 0.09 to 38.49]), or anxiolytics (HR = 2.01 [95% CI = 0.06 to 64.22]), compared with nonusers. The available evidence is insufficient to support a relationship between greater fracture risk for people with MS taking glucocorticoid, antidepressant, or anxiolytic medication, compared with nonusers, and it is unclear whether these medications are associated with bone loss in people with MS, beyond that in the general population. Additional high-quality studies with homogenous methodology exploring how medications influence aBMD and fracture risk in people with MS are required.

Appraisal, recent advancement, and impacts of nanomedicine in cardiac asthma

Cardiopulmonary asthma is a type of coughing, not an external appearance of asthma. Depending on persistent symptoms, this full-to-the-brim situation can be used to survive a therapeutic emergency. Liquid composition in the lungs and the area around the airways may result from heart failure. This demonstrates how the direction causes symptoms such as shortness of breath, coughing, and bursting at the seams which are likecipher and asthma symptoms. The common condition known as asthma is brought on by airway sensitivity, which can lead to constrictions, most noticeably leading to breathing difficulty. Heart failure treatment is trained to ease the effects of cardiac asthma and heart failure symptoms. Current developments in nano science and nanotechnology point towards a wealth of novel ideas for understanding and treating cardiovascular, pulmonary, and hematological conditions. Asthma is a common complaint that provokes the airways through various causes. Additionally, these instances consistently run into issues with their management schedule pertinent to the collection of the complaints. Asthma quantifiable treatment currently relies primarily on glucocorticoid medication therapy; however, the development of more effective treatments is hampered by glucocorticoid conflict as well as numerous elevated possessions due to deprived drug delivery. Our fundamental understanding of cardiac asthma nano medicine therapy is updated in this review.

Genetic glucocorticoid receptor variants differ between ethnic groups but do not explain variation in age of diabetes onset, metabolic and inflammation parameters in patients with type 2 diabetes.

The effect of excess glucocorticoid receptor (GR) stimulation through glucocorticoid medication or cortisol on glucose metabolism is well established. There are genetic GR variants that result in increased or decreased GR stimulation. We aimed to determine the prevalence of genetic GR variants in different ethnic groups in a cohort of patients with type 2 diabetes, and we aimed to determine their association with age of diabetes onset and metabolic and inflammation parameters. A cross-sectional analysis was performed in a multiethnic cohort (n = 602) of patients with established type 2 diabetes. Polymorphisms in the GR gene that have previously been associated with altered glucocorticoid sensitivity (TthIIII, ER22/23EK N363S, BclI and 9β) were determined and combined into 6 haplotypes. Associations with age of diabetes onset, HbA1c, hs-CRP and lipid values were evaluated in multivariate regression models. The prevalence of the SNPs of N363S and BclI was higher in Dutch than in non-Dutch patients. We observed a lower prevalence of the SNP 9β in Dutch, South(East) Asian and Black African patients versus Turkish and Moroccan patients. We did not detect an association between SNPs and diabetes age of onset or metabolic parameters. We only found a trend for lower age of onset and higher HbA1c in patients with 1 or 2 copies of haplotype 3 (TthIIII + 9β). The prevalence of genetic GR variants differs between patients of different ethnic origins. We did not find a clear association between genetic GR variants and age of diabetes onset or metabolic and inflammation parameters. This indicates that the clinical relevance of GR variants in patients with established type 2 diabetes is limited.

Resolution of a periapical lesion in an autoimmune pancreatitis patient treated with long-term low-dose glucocorticoids: a case report

BackgroundPatients diagnosed with an autoimmune disease are often systemically medicated with glucocorticoids. Autoimmune pancreatitis (AIP) Type 1 is considered a rare autoimmune disease, which is very well responsive to glucocorticoids and hence can be treated optionally on a long-term basis using low dose of the drug. Apical lesions of root canal-treated teeth can be solved by retreatment of the preexisting root canal obturation or via surgical approaches.Case presentationThis case report relates to a 76-year-old male patient, whose symptomatic acute apical periodontitis was treated nonsurgically by root canal treatment. However, overtime both roots of tooth 46 were associated with asymptomatic apical lesions. Despite progression of the lesions, due to a painless situation, the patient refrained from proceeding with any further treatment options after explaining the pathological pathway with all its consequences. A few years later the patient was prescribed 2.5 mg glucocorticoid prednisone daily for long-term therapy due to an AIP Type 1. Six years later under strict glucocorticoid therapy the apical lesions healed nearly completely and the patient remained free of symptoms without any further interventions.ConclusionsThese observations suggest that prospective clinical studies are required to further elucidate the potential healing effect of systemic long-term low-dose glucocorticoid medication on lesions of endodontic origin.

Prevalence and factors associated with polypharmacy among patients with rheumatoid arthritis: a single-centre, cross-sectional study.

This study aimed to identify factors associated with polypharmacy, including social aspects, among patients with rheumatoid arthritis. We conducted this single-centre, cross-sectional study at a 715-bed regional tertiary care teaching hospital in Japan from 1 September to 30 November 2020. Polypharmacy was defined as having five or more medications administered orally regularly, and excessive polypharmacy was defined as having 10 or more medications administered orally regularly. The prevalence of polypharmacy and excessive polypharmacy, distribution of medication types, and factors associated with polypharmacy and excessive polypharmacy were investigated among patients with rheumatoid arthritis. The proportions of polypharmacy and excessive polypharmacy were 61% and 15%, respectively, in 991 patients. Polypharmacy and excessive polypharmacy were associated with older age (odds ratio, 1.03 and 1.03, respectively), high Health Assessment Questionnaire Disability Index (odds ratio, 1.45 and 2.03, respectively), medication with glucocorticoids (odds ratio, 5.57 and 2.42, respectively), high Charlson comorbidity index (odds ratio, 1.28 and 1.36, respectively), and a history of hospitalisation in internal medicine (odds ratio, 1.92 and 1.87, respectively) and visits to other internal medicine clinics (odds ratio, 2.93 and 2.03, respectively). Moreover, excessive polypharmacy was associated with the presence of public assistance (odds ratio, 3.80). Considering that polypharmacy and excessive polypharmacy are associated with a history of hospitalisation and glucocorticoid medication in patients with rheumatoid arthritis, medications during hospitalisation should be monitored, and glucocorticoids should be discontinued. Key points • The proportion of polypharmacy (five or more medications administered orally regularly) was 61%. • The proportion of excessive polypharmacy (10 or more medications administered orally regularly) was 15%. • Medications during hospitalisation should be reviewed and examined, and glucocorticoids should be discontinued.

Clinical course of patients with adrenal incidentalomas and cortisol autonomy: a German retrospective single center cohort study.

Adrenal incidentalomas with cortisol autonomy are associated with increased cardiovascular morbidity and mortality. Specific data on the clinical and biochemical course of affected patients are lacking. Retrospective study from a tertiary referral centre in Germany. After exclusion of overt hormone excess, malignancy and glucocorticoid medication, patients with adrenal incidentalomas were stratified according to serum cortisol after 1 mg dexamethasone: autonomous cortisol secretion (ACS), >5.0; possible ACS (PACS), 1.9-5.0; non-functioning adenomas (NFA), ≤1.8 µg/dl. A total of 260 patients were enrolled (147 women (56.5%), median follow-up 8.8 (2.0-20.8) years). At initial diagnosis, median age was 59.5 (20-82) years, and median tumour size was 27 (10-116) mm. Bilateral tumours were more prevalent in ACS (30.0%) and PACS (21.9%) than in NFA (8.1%). Over time, 40/124 (32.3%) patients had a shift of their hormonal secretion pattern (NFA to PACS/ACS, n=15/53; PACS to ACS, n=6/47; ACS to PACS, n=11/24; PACS to NFA, n=8/47). However, none of the patients developed overt Cushing's syndrome. Sixty-one patients underwent adrenalectomy (NFA, 17.9%; PACS, 24.0%; ACS, 39.0%). When non-operated patients with NFA were compared to PACS and ACS at last follow-up, arterial hypertension (65.3% vs. 81.9% and 92.0%; p<0.05), diabetes (23.8% vs. 35.6% and 40.0%; p<0.01), and thromboembolic events (PACS: HR 3.43, 95%-CI 0.89-13.29; ACS: HR 5.96, 95%-CI 1.33-26.63; p<0.05) were significantly less frequent, along with a trend towards a higher rate of cardiovascular events in case of cortisol autonomy (PACS: HR 2.23, 95%-CI 0.94-5.32; ACS: HR 2.60, 95%-CI 0.87-7.79; p=0.1). Twenty-five (12.6%) of the non-operated patients died, with higher overall mortality in PACS (HR 2.6, 95%-CI 1.0-4.7; p=0.083) and ACS (HR 4.7, 95%-CI 1.6-13.3; p<0.005) compared to NFA. In operated patients, prevalence of arterial hypertension decreased significantly (77.0% at diagnosis to 61.7% at last follow-up; p<0.05). The prevalence of cardiovascular events and mortality did not differ significantly between operated and non-operated patients, whereas thromboembolic events were significantly less frequent in the surgical treatment group. Our study confirms relevant cardiovascular morbidity in patients with adrenal incidentalomas (especially those with cortisol autonomy). These patients should therefore be monitored carefully, including adequate treatment of typical cardiovascular risk factors. Adrenalectomy was associated with a significantly decreased prevalence of hypertension. However, more than 30% of patients required reclassification according to repeated dexamethasone suppression tests. Thus, cortisol autonomy should ideally be confirmed before making any relevant treatment decision (e.g. adrenalectomy).

The importance of children and young person involvement in scoping the need for a paediatric glucocorticoid-associated patient reported outcome measure

BackgroundFor many children and young people (CYP) with paediatric rheumatic conditions, glucocorticoid medications and their associated side-effects have a substantial impact on disease experience. Whilst there are physician-rated measures of glucocorticoid toxicity, no parallel patient reported measure has been developed to date for CYP with rheumatic disease. This manuscript describes a series of public patient involvement (PPI) events to inform the development of a future paediatric glucocorticoid-associated patient reported outcome measure (PROM).MethodsOne large group PPI event was advertised to CYP with experience of glucocorticoid medication use and their parents through clinicians, charities and existing PPI groups. This featured education on the team’s research into glucocorticoid medication and interactive polls/structured discussion to help participants share their experiences. Further engagement was sought for PPI group work to co-develop future glucocorticoid studies, including development of a glucocorticoid associated PROM. Quantitative and qualitative feedback was collected from online questionnaires. The initiative was held virtually due to the Covid-19 pandemic.ResultsNine families (n = 15) including 6 CYP joined the large group PPI event. Online pre-attendance and post-attendance questionnaires showed improvement in mean self-reported confidence [1 = not at all confident, 5 = very confident] in the following: what steroid medications are (pre = 3.9, post = 4.8), steroid side effects (pre = 3.8, post = 4.6), patient-reported outcome measures (pre = 2.0, post = 4.5), available research on steroids (pre = 2.2, post = 3.5). Five families (n = 7) were involved in a monthly PPI group who worked alongside the research team to identify priorities in glucocorticoid research, produce age-appropriate study materials, identify barriers to study participation (e.g. accessibility & convenience) and recommend appropriate modalities for dissemination. The participants found discussing shared experiences and learning about research to be the most enjoyable aspects of the initiative.ConclusionsThis PPI initiative provided a valuable forum for families, including young children, to share their perspectives. Here, the authors explore the effective use of PPI in a virtual setting and provide a unique case study for the involvement of CYP in PROM development. The monthly PPI group also identified a need for the development of a new PROM related to glucocorticoid medication use and provided unique insights into how such a study could be structured.

Association between use of systemic and inhaled glucocorticoids and changes in brain volume and white matter microstructure: a cross-sectional study using data from the UK Biobank

ObjectiveTo test the hypothesis that systemic and inhaled glucocorticoid use is associated with changes in grey matter volume (GMV) and white matter microstructure.DesignCross-sectional study.SettingUK Biobank, a prospective population-based cohort study...

Associations of Prior Chronic Use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and Glucocorticoids With Cachexia Incidence and Survival.

BackgroundCachexia is an inflammatory and metabolic syndrome of unintentional weight loss through depletion of muscle and adipose tissue. There is limited knowledge of how chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids affect cachexia development. The purpose of this study was to investigate associations between prior long-term use of NSAIDs or glucocorticoids with cachexia incidence and post-diagnosis weight loss progression in a retrospective cancer patient cohort.MethodsOf 3,802 lung or gastrointestinal cancer patient records, 3,180 comprised our final cohort. Patient demographic information, tumor qualities, medication histories, and comorbidities were assessed. Cachexia was defined as having developed prior to oncologic treatment. Statistical evaluations included categorical, multivariate logistic regression, and log-rank survival analyses. Development of substantial post-diagnosis weight loss was calculated and interpreted for patients without cachexia at diagnosis.ResultsChronic prior use of any NSAID or glucocorticoid medication was associated with approximate absolute and relative reductions in cachexia incidence at diagnosis of 10 and 25 percent (P<0.0001). In multivariate analyses, NSAID medications demonstrated a 23 percent reduction in cachexia incidence likelihood (OR=0.770; 95% CI=0.594, 0.998; P=0.0481). Patients without cachexia at diagnosis were significantly more likely to develop substantial post-diagnosis weight loss from pre-diagnosis use groups of glucocorticoids (OR= 1.452; 95% CI=1.065, 1.979; P=0.0183) or NSAIDs (OR=1.411; 95% CI=1.082, 1.840; P=0.011).ConclusionsOur findings suggest a protective effect of prior anti-inflammatory medications, primarily NSAIDs, against manifestations of the cachexia phenotype at cancer diagnosis. These observations support further exploration of potential therapeutic benefits from anti-inflammatory medications early in cancer management.

Critical Influenza and COVID-19-A Comparative Nationwide Case-Control Study.

IMPORTANCE:Refined knowledge of risk factors for critical influenza and COVID-19 may lead to improved understanding of pathophysiology and better pandemic preparedness.OBJECTIVES:To compare risk-factor profiles of patients admitted to intensive care with critical influenza and COVID-19.DESIGN, SETTING, AND PATIENTS:A nationwide retrospective matched case-control study, including all adults admitted to an ICU in Sweden with influenza or COVID-19 between 2014 and September 2020 and a matched control population (ratio 1:5, patients:controls).MEASUREMENTS AND MAIN RESULTS:Admission to an ICU. The study included 1,873 influenza and 2,567 COVID-19 ICU patients, and 9,365 and 12,835 controls, respectively, matched on sex, age, and geographical region. Influenza patients were older and less likely male, and carried a larger burden of comorbidity and a higher Simplified Acute Physiology Score III score, whereas short-term mortalities were similar when compared to COVID-19 patients. The risk-factor profiles at ICU admission were largely comparable including socioeconomic, psychiatric, and several somatic variables. Hypertension was a strong risk factor in critical COVID-19 patients compared with influenza. Nonglucocorticoid immunosuppressive therapy was associated with critical influenza but not COVID-19. Premorbid medication with statins and renin-angiotensin-aldosterone system inhibitors reduced the risk for both conditions, the opposite was a seen for glucocorticoid medication. Notably, medication with betablockers, oral anticoagulation, and platelet inhibitors reduced the risk of critical COVID-19 but not influenza.CONCLUSIONS:The risk-factor profiles for critical influenza and COVID-19 were largely comparable; however, some important differences were noted. Hypertension was a stronger risk factor for developing critical COVID-19, whereas the use of betablockers, oral anticoagulants, and platelet inhibitors all reduced the risk of ICU admission for COVID-19 but not influenza. Findings possibly reflected differences in pathophysiological mechanisms between these conditions.

Treatment of congenital adrenal hyperplasia in children aged 0-3 years: a retrospective multicenter analysis of salt supplementation, glucocorticoid and mineralocorticoid medication, growth and blood pressure.

ObjectivesInternational guidelines recommend additional salt supplementation during infancy in classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. The influence of corticoid medication and growth has not been assessed.AimTo investigate the current use of salt supplementation, fludrocortisone (FC) and hydrocortisone (HC) dosage as well as weight, height, BMI and blood pressure (BP) in CAH children aged 0–3 years.MethodsRetrospective multicentre analysis using data from the I-CAH registry. Salt-treated (ST) and non-salt-treated (NST) children were compared regarding FC and HC dosage, weight, height and BP at 0, 3, 6, 9, 12, 18, 24, 30, and 36 months.ResultsWe analysed 2483 visits of 331 patients born after year 2000 in 13 countries (male, n = 145) with 203 ST patients (61%). NST children had significantly higher FC dosages at 1.5–4.5 months and higher HC dosages until 1.5 months of age. No differences in weight, length and BP between subgroups were observed. Children of the whole cohort showed increased BMI-SDS during the study period and about half of the reported BP readings were >P95.ConclusionIn children treated with additional salt supplementation, FC and HC dosages are lower during the first months of life but without differences in weight, length and BP until 3 years of age compared to NST children. All children showed an increase in BMI-SDS and a high rate of BP readings >P95 until 3 years, indicating the start of weight gain and negative effects on blood pressure already in very early life.

High prevalence of hypertension and target organ damage in patients with 11β-hydroxylase deficiency.

Prevalence of hypertension and hypertension-mediated organ damage (HMOD) had not been well studied in patients with 11β-hydroxylase deficiency (11β-OHD). The study was to assess the prevalence and risk factors of hypertension and HMOD in patients with 11β-OHD. Retrospective cohort analysis in a single medical centre. Twenty-eight patients with 11β-OHD were recruited between January 2003 and June 2021, and their diagnosis had been confirmed by Sanger sequencing. Blood pressure and clinical indicators for the assessment of HMOD occurrence were collected from the medical records. Medication adherence of antihypertensive drugs and glucocorticoids were determined by the patients' biochemistry. Logistic regression was used to identify factors associated with HMOD. Prevalence of hypertension and HMOD in the cohort was 100% and 50%, respectively. The kidneys (71.43%) are the organ most commonly damaged by high blood pressure, followed by the heart (64.29%), eyes (57.14%) and brain (21.43%). Risk factors of HMOD were hypokalemia (odds ratio [OR]: 9.16; 95% confidence interval [CI]: 1.634-51.43; p = .012), blood pressure ≥ 180/110 mmHg (OR: 22.0, 95% CI: 3.08-157.34; p = .002) and irregular glucocorticoid use (OR: 3.18, 95% CI: 1.13-8.98; p = .021). Blood pressure ≥ 180/110 mmHg was an independent predictor for HMOD. Hypertension and HMOD are prevalent in patients with 11β-OHD in our study. These findings illustrate the importance of early HMOD evaluation and optimal glucocorticoid medication in 11β-OHD patients.

Screening for cognitive impairment in systemic lupus erythematosus: Application of the Montreal Cognitive Assessment (MoCA) in a Greek patient sample

Cognitive impairment (CI) is one of the most frequent neuropsychiatric manifestations of systemic lupus erythematosus (SLE). Given that extensive neuropsychological testing is not always feasible in routine clinical practice, brief cognitive screening tools are desirable. The aim of this study was to evaluate the Montreal Cognitive Assessment (MoCA) as a screening tool for CI in SLE. Consecutive SLE patients followed at a single centre were evaluated using MoCA and an extensive neuropsychological test battery (NPT), including the Digits Forward and Digits Backwards, Rey Auditory Verbal Learning Memory Test, Trail Making Test, Stroop Colour-Word Test, Semantic and Phonetic Verbal Fluency tests and a 25-problem version of the General Adult Mental Ability test. The criterion validity of MoCA was assessed through receiver operating characteristic (ROC) analyses using three different case definitions: i) against normative population data, ii) and iii) against average performance of a comparison group of rheumatoid arthritis (RA) patients, to adjust for possible confounding effects of chronic illness and inflammatory processes on cognitive performance. The effect of patient-related (age, years of education, anxiety, depression, fatigue and pain) and disease-related (activity, damage, age at diagnosis, disease duration, use of glucocorticoid, psychotropic and pain medication) parameters on the MoCA was examined. A total of 71 SLE patients were evaluated. MoCA significantly correlated with all NPT scores and was affected by education level (p < 0.001), but not by other demographic or clinical variables. The optimal cutoff for detecting CI, as defined on the basis of normative population data, was 23/30 points, demonstrating 73% sensitivity and 75% specificity. A cutoff of 22/30 points, using neuropsychological profiles of the RA group as inflammatory disease controls, exhibited higher sensitivity (100%, based on both definitions) and specificity (87% and 90%, depending on the definition). The standard cutoff of 26/30 points displayed excellent sensitivity (91-100%) with significant expenses in specificity (43-45%). The MoCA is an easily applied tool, which appears to be reliable for identifying CI in SLE patients. The standard cutoff score (26/30) ensures excellent sensitivity while lower cutoff scores (22-23/30) may, also, provide higher specificity.

95 Baseline body-mass-index and risk for obesity in children with rheumatic disease starting high-dose prednisone therapy

Abstract Primary Subject area Rheumatology Background Prednisone is a glucocorticoid (GC) medication commonly used in moderate (&amp;gt;7.5 mg/day) to high doses (≥ 1 mg/kg/day to maximum 60 mg/day) for children with moderate to severe presentations of rheumatic disease, including systemic lupus erythematosus (SLE), juvenile idiopathic arthritis (JIA), and juvenile dermatomyositis (JDM). Adverse effects (AE) to GCs impose a significant burden on health and quality of life including frequent development of weight gain, mood changes, sleep difficulties, osteoporosis, and Cushingoid features, amongst others. Objectives We sought to evaluate a possible relationship between baseline patient body-mass-index (BMI) measure and development of select GC-mediated toxicity within the first 12 months of starting moderate or high-dose prednisone therapy using conventional weight-based dosing of prednisone. Secondary outcomes were to examine rates of GC-mediated hypertension, osteopenia, and osteoporosis. Design/Methods We performed a retrospective chart review on children with rheumatic disease aged ≤ 17 years treated with moderate and high-dose prednisone therapy at a single Canadian academic hospital between January 1, 2010 and December 31, 2019. Demographic variables collected included diagnosis, age, sex, ethnicity. Clinical variables collected include weight, height, and body-mass-index (BMI), hepatitis (AST&amp;gt;41 U/L, ALT&amp;gt;40 U/L, or GGT&amp;gt;60 U/L), proteinuria (&amp;gt;0.1 g/L), and presence of hypoalbuminemia (&amp;lt;38g/L) at baseline. We collected weight, height, and body-mass-index (BMI), at 6 and 12 months, the maximum BMI, and transformed them to z-scores according to the World Health Organization's Child Growth standards. Cumulative prednisone dose (mg/kg/12 months), total days on prednisone in the first 12 months of therapy were also obtained, in addition to bone-mineral-density cores after 12 months of prednisone therapy. Baseline characteristics, which were significant for the subsequent development of obesity during the first 12 months at the bivariate level (p &amp;lt; 0 .05), were included as predictors of obesity in separate logistic regression analyses. In each regression analysis, we also adjusted for baseline BMI, and for confounding variables of hepatitis, hypoalbuminemia (albumin less than 38 grams per litre), proteinuria and prednisone dose. We conducted a complete case analysis, and all analyses were performed using SPSS v.26 (IBM Corp., Armonk, NY, USA), and p-values &amp;lt; 0 .05 were considered statistically significant. Results Seventy-four charts were reviewed, and 72 patients met criteria for analysis. The median prednisone dose was 35 mg per day (IQR 20 to 60 mg), and median duration of therapy was 302 days (IQR 126.75 to 581.25). Thirty-five (48.6%) patients developed obesity, 33 (45.8%) hypertension, five (7.0%) osteopenia, and three (4.2%) osteoporosis. Greater BMI at baseline was associated with greater total weight gain (OR 4.04, 95% CI = [1.98-8.33], p &amp;lt; 0 .001). Conclusion Greater baseline patient BMI may be a predictor of weight gain on high-dose prednisone therapy in children with rheumatic disease requiring high-dose therapy. Further work is required to determine methods for individualized prednisone dosing and counseling and behavioral interventions to mitigate risk for weight gain.

Chemotherapy-induced peripheral neuropathy increases nontraumatic fracture risk in breast cancer survivors.

ABSTRACTChemotherapy is a common treatment for breast cancer (BrCa) and can cause chemotherapy‐induced peripheral neuropathy (CIPN). CIPN contributes to falls, and is thus a potential risk factor for nontraumatic fractures (NTFx); yet, the effect of CIPN on NTFx risk has not been examined for BrCa survivors. We therefore investigated the association between CIPN and NTFx in BrCa survivors. Data were extracted from Optum's Deidentified Clinformatics® Data Mart Database years 2010–2015 in this retrospective cohort study. Among women, three groups were derived based on BrCa and CIPN status: BrCa+/CIPN+ (primary group of interest), BrCa+/CIPN− (first comparison group), and BrCa−/CIPN− (second comparison group). After propensity score matching the comparison groups to BrCa+/CIPN+ at a ratio of 1:11 (BrCa:control) for demographics, osteoporosis, glucocorticoid medication, comorbidities, and cancer‐related variables for BrCa+/CIPN−, 1‐year incidence rate (IR) of NTFx was determined for each group. The incident rate ratio (IRR) determined if the IR for NTFx was different for BrCa+/CIPN+ compared to BrCa+/CIPN− and BrCa−/CIPN−. Cox proportional hazards regression models estimated the hazard ratios (HRs) after adjusting for covariates that were unable to be matched for. The crude IR (95% confidence interval [CI]) of NTFx was 4.54 (2.32–6.77) for BrCa+/CIPN+ (n = 359), 2.53 (2.03–3.04) for BrCa+/CIPN− (n = 3949), and 1.76 (1.35–2.18) for BrCa−/CIPN− (n = 3949). The crude IRR of NTFx was significantly elevated for BrCa+/CIPN+ as compared to BrCa+/CIPN− (IRR = 1.80; 95% CI, 1.06–3.05) and BrCa−/CIPN− (IRR = 2.58; 95% CI, 1.50–4.44). The elevated rate of NTFx for BrCa+/CIPN+ remained unchanged after adjusting for aromatase inhibitors compared to BrCa+/CIPN− (HR = 1.79; 95% CI, 1.06–3.04). Female BrCa survivors have an increased 1‐year IR of NTFx after the onset of CIPN, suggesting that CIPN is an additive burden on NTFx risk among BrCa survivors. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.