Defining conditions where long-term glucocorticoid treatment has an acceptably low level of harm to facilitate implementation of existing recommendations: viewpoints from an EULAR task force

2016 ◽  
Vol 75 (6) ◽  
pp. 952-957 ◽  
Author(s):  
Cindy Strehl ◽  
Johannes W J Bijlsma ◽  
Maarten de Wit ◽  
Maarten Boers ◽  
Nele Caeyers ◽  
...  

There is convincing evidence for the known and unambiguously accepted beneficial effects of glucocorticoids at low dosages. However, the implementation of existing recommendations and guidelines on the management of glucocorticoid therapy in rheumatic diseases is lagging behind. As a first step to improve implementation, we aimed at defining conditions under which long-term glucocorticoid therapy may have an acceptably low level of harm. A multidisciplinary European League Against Rheumatism task force group of experts including patients with rheumatic diseases was assembled. After a systematic literature search, breakout groups critically reviewed the evidence on the four most worrisome adverse effects of glucocorticoid therapy (osteoporosis, hyperglycaemia/diabetes mellitus, cardiovascular diseases and infections) and presented their results to the other group members following a structured questionnaire for final discussion and consensus finding. Robust evidence on the risk of harm of long-term glucocorticoid therapy was often lacking since relevant study results were often either missing, contradictory or carried a high risk of bias. The group agreed that the risk of harm is low for the majority of patients at long-term dosages of ≤5 mg prednisone equivalent per day, whereas at dosages of >10 mg/day the risk of harm is elevated. At dosages between >5 and ≤10 mg/day, patient-specific characteristics (protective and risk factors) determine the risk of harm. The level of harm of glucocorticoids depends on both dose and patient-specific parameters. General and glucocorticoid-associated risk factors and protective factors such as a healthy lifestyle should be taken into account when evaluating the actual and future risk.

2019 ◽  
Vol 26 (3-4) ◽  
pp. 50-54
Author(s):  
Uma A. Bhosale ◽  
Radha Yegnanarayan ◽  
Akhil Agrawal ◽  
Ashwini Patil

Background: Epilepsy is a chronic medical condition that requires long-term therapy with antiepileptic drugs (AEDs). However, long-term employment of AEDs may lead to the onset of hyperhomocysteinemia, which has been found to modulate imperative metabolic mechanisms and induce cardiovascular disorders (CVDs). Therefore, adolescent population that have been diagnosed with epilepsy and utilize AEDs are among the most vulnerable, exhibiting higher risks of developing CVDs. Purpose: The present study was designed to explore the effects of folic acid (FA) supplementation on AED-induced hyperhomocysteinemia and CVD risk factors in adolescent epileptics. Methods: The randomized clinical trial included adolescent epileptics (i.e., 10–19 years of age) of either sex, on antiepileptic therapy for > 6 months with high homocysteine levels (i.e., >10.9 µmol/L). At the time of enrolment, their baseline BP, lipid and homocysteine levels were recorded. Participants were randomly assigned to either treatment or placebo groups and received the respective treatments. At the end of the first month, BP, lipid and homocysteine levels were recorded and compared to determine the effect of FA on these parameters. Results and conclusion: A significant fall in homocysteine levels was observed with FA supplementation ( P < 0.05). However, this fall was significantly high in valproic acid treated epileptic patients. In addition, we observed an improvement in high-density lipoprotein levels, a risk factor for CVDs, but the change was statistically insignificant ( P > 0.05). The study results suggest that FA supplementation in epileptic patients receiving AED therapy may minimize AED-induced hyperhomocysteinemia and other CVD risk factors.


Author(s):  
Gary H. Lyman

Appropriate use of myeloid growth factors may reduce the risk of neutropenic complications including febrile neutropenia (FN) in patients receiving cancer chemotherapy. The recently updated American Society of Clinical Oncology (ASCO) Guidelines on the Use of the White Blood Cell Growth Factors recommends routine prophylaxis with these agents starting in the first cycle when the risk of FN is 20% or greater. However, the risks for neutropenic complications and the risk of serious adverse consequences from FN vary considerably with different chemotherapy regimens as well as other disease-, treatment-, and patient-specific risk factors. Considerably more information is now available on the major risk factors for FN. Multivariable risk models combining factors look promising but require further validation. Most clinical studies of myeloid growth factor prophylaxis assessed relative risk (RR) of FN but were not powered to evaluate the effect of prophylaxis on disease-free or overall survival. Accumulating evidence suggests, however, that the appropriate use of these agents in selected patients may improve both short-term and long-term survival by reducing the immediate risk of mortality accompanying patients with high-risk disease developing FN as well as improving disease-free and overall survival by enabling the delivery of full dose intensity chemotherapy and reducing the risk of disease recurrence in patients treated with curative intent. Further studies to evaluate risk factors and models for FN are needed to guide clinical and shared decision making for the optimal personalized use of these agents and offer patients at increased risk the best chance of long-term disease control.


Author(s):  
V Munro ◽  
B Tugwell ◽  
S Doucette ◽  
DB Clarke ◽  
A Lacroix ◽  
...  

Background: Patients with pituitary disorders may be placed on steroid replacement for secondary adrenal insufficiency (SAI), generally after pituitary surgery; however, data regarding recovery of long-term SAI are lacking. We conducted a study to assess the longer term recovery rate of SAI in patients with pituitary disorders. Methods: We identified all SAI patients from prospectively entered data in the Halifax Neuropituitary Database from November 1, 2005 to September 30, 2014, who had required glucocorticoid therapy for >3 months, and a minimum follow-up of 6 months. Exclusion: ACTH-secreting adenomas; peri-operative glucocorticoid treatment only; glucocorticoids for non-pituitary conditions. Results: 55 patients fulfilled the criteria, 41 (75%) of which had transsphenoidal surgery. Nine (16.4%) patients had complete recovery of SAI over a median of 20 months (range: 8–51). Smaller tumour size and initial cortisol >175 nmol/L had increased likelihood of recovery; those with secondary hypogonadism or growth hormone deficiency were less likely to recover. Conclusions: This is the first study to examine long-term recover of SAI in patients with pituitary disorders: approximately 1 in 6 patients recover adrenal function, up to 5 years after diagnosis. Consequently, patients with SAI should undergo regular testing to prevent unnecessary chronic glucocorticoid therapy.


2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
F Mendonca ◽  
M I Mendonca ◽  
M Temtem ◽  
M Santos ◽  
J A Sousa ◽  
...  

Abstract Introduction Coronary Heart Disease (CAD) is a multifactorial disease, including environmental and genetic risk factors. Current smoking, dyslipidemia and diabetes have a significant impact in long- term mortality and morbidity. However, several genetic variants associated with CAD but not with traditional risk factors (TRFs) has been reported to improve prediction of events and extended mortality, in younger CAD people. Aim To evaluate the clinical utility of a GRS composed by variants from GWAS associated to CAD but not with TRF to predict life-long residual risk in patients under 55 years old and a low level of TRFs. Methods We conducted a prospective study with 573 consecutive patients aged &lt;55 years presenting with AMI and a low level of TRFs (without diabetes and with LDL cholesterol &gt;150 mg/ml). We analysed several biochemical markers and performed a GRS with variants not associated with TRFs (TCF21 rs12190287, CDKN2B-AS1 rs1333049, CDKN2B rs4977574, PHACTR1 rs1332844, MIA3 rs17465637, ADAMTS7 rs3825807, ZC3HC1 rs11556924, SMAD3 rs17228212 and GJA4 rs618675). We studied the GRS association with a primary composite endpoint of all-cause vascular morbidity and mortality including recurrent acute coronary syndrome (myocardial infarct and unstable angina), coronary revascularization (coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI), re-hospitalization for heart failure, ischemic stroke and cardiovascular dead. Results A total of 573 patients were studied and followed up for a mean of 4.7±4.0 years. There were 169 recurrent cardiovascular events. The GRS was sub-divided into terciles, verifying that patients in the third tercile (high risk) had a higher number of risk alleles. Compared with the low-risk GRS tercile, the multivariate-adjusted HR for recurrences was 1.520 (95% CI 1.011–2.286); p=0.044 for the intermediate-risk group and was 2.051 (95% CI 1.382–3.044); p&lt;0.0001 for the high-risk group. Inclusion of the GRS in the model with TRFs alone (low risk) improved the C-statistic analysis (C-statistic = 0.030; p=0.004), cNRI (continuous net reclassification improvement) (30.8%), and the IDI (integrated discrimination improvement index) (0.022). Conclusions A multilocus GRS may identify young coronary disease patients with a low level of TRFs but at significant risk of long-term events recurrence. The genetic information may improve prediction discrimination, and reclassification over the conventional risk factors alone, providing better cost-effective therapeutic strategies. FUNDunding Acknowledgement Type of funding sources: None. Figure 1


2021 ◽  
Vol 25 (3) ◽  
pp. 17-26
Author(s):  
Irina B. Belyaeva ◽  
Vadim I. Mazurov ◽  
Lyubov E. Sarantseva ◽  
Evgeny A. Trofimov

The review presents the results of scientific studies devoted to the features of the course and outcomes of a new coronavirus infection COVID-19 in patients with immuno-inflammatory rheumatic diseases (IIRD). It was noted that the risk of developing COVID-19 for patients with IVR, apparently, is similar to the population or slightly increased and mostly depends on the presence of established risk factors for its severe course (old age, obesity, diabetes mellitus, cardiovascular diseases). Patients receiving long-term immunosuppressive therapy and high doses of glucocorticoids may have a long period of positive viral replication and isolation of a viable virus, which requires dynamic monitoring of such patients and correction of anti-rheumatic therapy. The issues of post-COVID-19 joint syndrome, which can occur within the framework of post-viral arthritis or be the debut of an immuno-inflammatory rheumatic disease, are highlighted. The draft recommendations of the All-Russian Public Organization Association of Rheumatologists of Russia on the management and temporary recommendations of V.A. Nasonova Research Institute of Rheumatology for vaccination of patients with rheumatic diseases in the conditions of the COVID-19 pandemic are presented.


2021 ◽  
Vol 10 (29) ◽  
pp. 2166-2170
Author(s):  
Gargi Nitin Babar ◽  
Sana Imtiyaj Bagwan ◽  
Govindhan Varadharajulu

BACKGROUND The objective of the study was to assess and determine the level of awareness regarding cerebral palsy and its risk factors in young adults and provide a statistical data showing the level of awareness in young adults. Cerebral palsy is one of the most commonly occurring neurological disorders in children with having lifelong abnormalities. Increasing prevalence of cerebral palsy needs attention as this is the leading cause of disability in children. The age group of 18 - 35 years is known as the reproductive age group; it is important to assess the level of awareness to educate them about the preventive measures during pregnancy. Due to this, the percentage of occurrence of cerebral palsy will drop significantly. METHODS The research was completed by survey method. It is an observational study including 192 participants. Sample size was calculated by the formula n = 4pq/l2. Both males and females in the age group of 18 to 35 were included. A structured questionnaire comprising of cerebral palsy and risk factor questions was used. Ethical approval from institutional ethical committee, permission from respective authorities were taken. After the protocol and ethical clearance, the procedure was started. Results were obtained from statistical analysis. RESULTS The obtained results revealed significantly low level of awareness about cerebral palsy in younger adults which was 29.17 % of the sample size 192 (100 %) which made 70.83 % unaware about the condition with an extreme low level of awareness regarding the risk factors causing cerebral palsy. Only 9.38 % were aware about risks causing cerebral palsy. CONCLUSIONS Study results concluded that there is lack of awareness about cerebral palsy and its risk factors in young adults. KEY WORDS Awareness, Cerebral Palsy, Disability, Risk Factors, Young Adults, Pregnancy


Endocrinology ◽  
2017 ◽  
Vol 159 (2) ◽  
pp. 579-596 ◽  
Author(s):  
Isabella Finco ◽  
Antonio M Lerario ◽  
Gary D Hammer

Abstract The atrophy and hypofunction of the adrenal cortex following long-term pharmacologic glucocorticoid therapy is a major health problem necessitating chronic glucocorticoid replacement that often prolongs the ultimate return of endogenous adrenocortical function. Underlying this functional recovery is anatomic regeneration, the cellular and molecular mechanisms of which are poorly understood. Investigating the lineage contribution of cortical Sonic hedgehog (Shh)+ progenitor cells and the SHH–responsive capsular Gli1+ cells to the regenerating adrenal cortex, we observed a spatially and temporally bimodal contribution of both cell types to adrenocortical regeneration following cessation of glucocorticoid treatment. First, an early repopulation of the cortex is defined by a marked delamination and expansion of capsular Gli1+ cells, recapitulating the establishment of the capsular-cortical homeostatic niche during embryonic development. This rapid repopulation is promptly cleared from the cortical compartment only to be supplanted by repopulating cortical cells derived from the resident long-term-retained zona glomerulosa Shh+ progenitors. Pharmacologic and genetic dissection of SHH signaling further defines an SHH-dependent activation of WNT signaling that supports regeneration of the cortex following long-term glucocorticoid therapy. We define the signaling and lineage relationships that underlie the regeneration process.


Rheumatology ◽  
2020 ◽  
Author(s):  
María A Martín-Martínez ◽  
Santos Castañeda ◽  
Fernando Sánchez-Alonso ◽  
Carmen García-Gómez ◽  
Carlos González-Juanatey ◽  
...  

Abstract Objectives To determine cardiovascular (CV) mortality and incidence of the first CV event (CVE) in patients with chronic inflammatory rheumatic diseases (CIRD) after 5 years of follow-up. Methods This is an analysis of the CARdiovascular in rheMAatology (CARMA) study after 5 years of follow-up. It includes patients with RA (n = 775), AS (n = 738) and PsA (n = 721), and individuals without CIRD (n = 677) attending outpatient rheumatology clinics from 67 public hospitals in Spain. Descriptive analyses were performed for the CV mortality at 5 years. The Systematic COronary Risk Evaluation (SCORE) function at 5 years was calculated to determine the expected risk of CV mortality. Poisson models were used to estimate the incidence rates of the first CVE. Hazard ratios of the risk factors involved in the development of the first CVE were evaluated using the Weibull proportional hazard model. Results Overall, 2382 subjects completed the follow-up visit at 5 years. Fifteen patients died due to CVE. CV deaths observed in the CIRD cohort were lower than that predicted by SCORE risk charts. The highest incidence rate of CVE [7.39 cases per 1000 person-years (95% CI 4.63, 11.18)] was found in PsA patients. However, after adjusting for age, sex and CV risk factors, AS was the inflammatory disease more commonly associated with CVE at 5 years [hazard ratio 4.60 (P =0.02)], compared with those without CIRD. Conclusions Cardiovascular mortality in patients with CIRD at 5 years of follow-up is lower than estimated. Patients with AS have a higher risk of developing a first CVE after 5 years of follow-up.


2013 ◽  
Vol 2013 ◽  
pp. 1-4 ◽  
Author(s):  
Mieko Yamagata ◽  
Koichi Hirose ◽  
Kei Ikeda ◽  
Hiroshi Nakajima

AlthoughNocardiosishas considerable recurrence and mortality rates, characteristics and risk factors ofNocardiainfection have not been assessed in patients with rheumatic diseases. Here, we examined the characteristics and risk factors ofNocardiainfection in rheumatic disease patients in our hospital. Ten rheumatic disease patients who developedNocardiainfection were identified by retrospectively reviewing the medical records. Possible predisposing factors forNocardiainfection were high-dose glucocorticoid treatment, concomitant use of immunosuppressants, preexisting pulmonary diseases, and diabetes mellitus. All patients had pulmonaryNocardiosis, and six of them had disseminatedNocardiosiswhen their pulmonary lesions were identified.


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