scholarly journals Tolerability and Efficacy of Long-Term Medical Therapy in Primary Aldosteronism

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A301-A302
Author(s):  
Troy Puar ◽  
Fengjie Tang ◽  
Lih-Ming Loh ◽  
Roger Foo ◽  
Wann Jia Loh ◽  
...  
Keyword(s):  
Side Effects ◽  
Medical Therapy ◽  
Primary Aldosteronism ◽  
Male Gender ◽  
Monitoring Strategy ◽  
Biochemical Control ◽  
Duration Of Treatment ◽  
Limited Efficacy ◽  
Dose Dependent

Abstract Introduction: Patients with primary aldosteronism (PA) have increased cardiovascular risk and studies have found that medical therapy fails to ameliorate this. This may be due to side effects and limited efficacy of medications at tolerable doses. Methods: We conducted a retrospective study on 201 patients with PA treated with medical therapy (spironolactone, eplerenone or amiloride) for PA from 2000–2020 at two tertiary centres. Patients were assessed for efficacy to achieve clinical and biochemical control, and for side effects. Results: 53.7% of patients achieved blood pressure <140/90mmHg, 44.6% achieved serum potassium ≥4.3mmol/L, and 63.2% achieved renin levels >1ng/ml/hr. Concordance between biochemical control as assessed by potassium and renin levels was 49%. 45.3% of patients experienced side effects, with 8.5% switching to another medication, 18.9% decreasing dose, and 10.0% stopping medications altogether. Risk factors for side effects were spironolactone use, dose ≥50mg, duration of treatment ≥1 year, male gender and unilateral PA. Patients with unilateral PA, compared to bilateral PA, used higher median doses of spironolactone, 75mg vs 50mg, P<0.001, but more had persistent hypokalemia, 20.5% versus 6.4%, P=0.007. 44 patients with unilateral PA underwent surgery after initial medical therapy, which further improved systolic and diastolic BP, from 142 to 134mmHg, P<0.001, and from 85 to 79mmHg, P<0.001, respectively. Conclusion: Dose-dependent side effects limit the efficacy of medical therapy in PA. Future prospective studies should assess the best monitoring strategy for biochemical control during long-term medical therapy. In patients with unilateral PA, surgery remains a better option compared to life-long medications.

scholarly journals Tolerability and Efficacy of Long-term Medical Therapy in Primary Aldosteronism

2021 ◽  
Author(s):  
Fengjie Tang ◽  
Lih M Loh ◽  
Roger S Foo ◽  
Wann J Loh ◽  
Dawn S T Lim ◽  
...  
Keyword(s):  
Side Effects ◽  
Medical Therapy ◽  
Primary Aldosteronism ◽  
Treatment Duration ◽  
Male Gender ◽  
Monitoring Strategy ◽  
Biochemical Control ◽  
Limited Efficacy ◽  
Dose Dependent

Abstract Introduction Patients with primary aldosteronism (PA) have increased cardiovascular risk, and some studies find medical therapy less effective than surgery. This may be due to side effects and limited efficacy of medications at tolerable doses. Methods We conducted a retrospective study on 201 patients with PA treated with medical therapy (spironolactone, eplerenone or amiloride) for PA from 2000-2020 at two tertiary centres. Patients were assessed for efficacy to achieve clinical and biochemical control, and for side effects. Results Amongst 155 patients on long-term medications, 57.4% achieved blood pressure <140/90mmHg, 90.1% achieved normokalemia(48.0% achieved potassium≥4.3mmol/L), and 63.2% achieved renin>1ng/ml/hr. Concordance of biochemical control using potassium and renin levels was 49.1%. 52.3% of patients experienced side effects, with 10.3% switching to another medication, 22.6% decreasing dose, and 11.0% stopping medications. Risk factors for side effects were spironolactone use, dose≥50mg, treatment duration ≥1year, male gender and unilateral PA. Patients with unilateral PA, compared to bilateral PA, used higher spironolactone doses, 57mg vs 50mg, P<0.001, and had more side effects, 63.2% versus 41.8%, P=0.008. Amongst 46 patients with unilateral PA who underwent surgery after initial medical therapy, surgery further improved systolic and diastolic BP, from 141 to 135mmHg, P=0.045, and from 85 to 79mmHg, P=0.002, respectively. Conclusion Dose-dependent side effects limit the efficacy of medical therapy in PA. Future prospective studies should assess the best monitoring strategy for biochemical control during long-term medical therapy. For unilateral PA, surgery remains preferable to medications, as surgery leads to better control with less long-term side-effects.

scholarly journals P709 Is azathioprine safe as long-term treatment in paediatric patients with inflammatory bowel disease?

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S573-S573
Author(s):  
M A Martínez Ibeas ◽  
I Bacelo Ruano ◽  
S Rodríguez Manchón ◽  
M Velasco Rodríguez-Belvís ◽  
J F Viada Bris ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Side Effects ◽  
Adverse Effects ◽  
Term Treatment ◽  
Tpmt Activity ◽  
Duration Of Treatment ◽  
Median Dosage ◽  
Long Term Treatment ◽  
Inflammatory Bowel

Abstract Background The toxicity of azathioprine (AZA) includes myelosuppression, infections, pancreatitis, photosensitivity, and hepatotoxicity. The aim of this study was to describe the adverse effects profile of azathioprine as long-term treatment in paediatric inflammatory bowel disease (IBD). Methods An observational, descriptive and retrospective study was performed in the paediatric IBD Unit of a tertiary care hospital from September 2008 to December 2018. It was included patients under 18 diagnosed with IBD who were treated with AZA during their follow-up. We recorded epidemiological data, thiopurine methyltransferase (TPMT) enzyme activity, AZA side effects, and the dosage the patients were receiving when these effects took place. Bone marrow suppression (BMS) was defined as leukopenia, thrombocytopenia and/or anaemia. Acute pancreatitis (AP) induced by azathioprine was considered when two of these criteria (Atlanta 2012) were met: lipase increase (> 3 times normal value), congruent signs and symptoms and/or echographic findings, without other possible aetiology and with complete recovery after AZA withdrawal. Results We included 52 patients, being 31 men (59.6%). They were diagnosed with Crohn′s disease (CD) (73%), ulcerative colitis (UC) (21%) and IBD-unclassified (6%). The median TPMT activity was 17 U/ml (14.2–19.2). Up to 63.5% developed adverse effects by AZA with a median time from the beginning of treatment of 11.4 months (2.6–26.4) and a median dosage of 2 mg/kg/day (1.7–2.3). The most frequent side effect was BMS (52%). These patients had a median TPMT activity of 16.9 U/ml (14.2–18.9), the median duration of treatment was 14 months (3.9–27.7), and the median dosage was 2 mg/kg/d (1.8–2.5). BMS was more frequent in patients with UC (p 0.04) and longer treatment (p 0.08). No differences were found according to age, sex or TPMT activity. Up to 11.5% developed AP, the median duration of treatment until its appearance was 1.5 months (0.7–43.3) and the median dosage was 2 mg/kg/d (1.5–2.5). No differences were found related to age, sex, diagnosis or dosage. Other side effects were: 3 flu-like symptoms, 3 opportunistic infections, 2 hypertransaminasemia, and 1 patient with elevated pancreatic enzymes and hyperbilirubinemia. AZA was discontinued in 14 patients (43.8%): in 6 due to AP, in 4 due to severe lymphopenia, in 2 because of Epstein-Barr virus infection, in 1 due to flu-like symptoms and in 1 with several adverse effects. Conclusion More than half of the patients treated with AZA presented side effects, mainly BMS, although most of them were mild and temporary, and the withdrawal of the drug was not necessary. It seems that TPMT activity is not useful to predict BMS, but this adverse effect could be related to a longer treatment.

scholarly journals Positive and Negative Effects of Antipsychotic Medication: An International Online Survey of 832 Recipients

2019 ◽  
Vol 14 (3) ◽  
pp. 173-181 ◽  
Author(s):  
John Read ◽  
James Williams
Keyword(s):  
Side Effects ◽  
Adverse Effects ◽  
Antipsychotic Medication ◽  
Online Survey ◽  
Negative Effects ◽  
Duration Of Treatment ◽  
Direct To Consumer ◽  
Poor Outcomes

Background: Antipsychotic medication is currently the treatment of choice for psychosis, but few studies directly survey the first-hand experience of recipients. Objective: To ascertain the experiences and opinions of an international sample of users of antipsychotic drugs, regarding positive and negative effects. Methods: An online direct-to-consumer questionnaire was completed by 832 users of antipsychotics, from 30 countries – predominantly USA, UK and Australia. This is the largest such sample to date. Results: Over half (56%) thought, the drugs reduced the problems they were prescribed for, but 27% thought they made them worse. Slightly less people found the drugs generally ‘helpful’ (41%) than found them ‘unhelpful’ (43%). While 35% reported that their ‘quality of life’ was ‘improved’, 54% reported that it was made ‘worse’. The average number of adverse effects reported was 11, with an average of five at the ‘severe’ level. Fourteen effects were reported by 57% or more participants, most commonly: ‘Drowsiness, feeling tired, sedation’ (92%), ‘Loss of motivation’ (86%), ‘Slowed thoughts’ (86%), and ‘Emotional numbing’ (85%). Suicidality was reported to be a side effect by 58%. Older people reported particularly poor outcomes and high levels of adverse effects. Duration of treatment was unrelated to positive outcomes but significantly related to negative outcomes. Most respondents (70%) had tried to stop taking the drugs. The most common reasons people wanted to stop were the side effects (64%) and worries about long-term physical health (52%). Most (70%) did not recall being told anything at all about side effects. Conclusion: Clinical implications are discussed, with a particular focus on the principles of informed consent, and involving patients in decision making about their own lives.

Combination of Prednisolone and Azathioprine for Steroid-Responsive Meningitis-Arteritis Treatment in Dogs

2020 ◽  
Vol 57 (1) ◽  
pp. 1-7
Author(s):  
Lucile Giraud ◽  
Maud Girod ◽  
Laurent Cauzinille
Keyword(s):  
Side Effects ◽  
Relapse Rate ◽  
Primary Treatment ◽  
Immunosuppressive Drug ◽  
Duration Of Treatment ◽  
Glucocorticoid Treatment ◽  
Immune Mediated

ABSTRACT Treatment with high corticosteroid dosages for steroid-responsive meningitis-arteritis (SRMA) is correlated with severe adverse effects and worse quality of life. In order to improve immunosuppression and decrease dosage and duration of glucocorticoid treatment, a second immunosuppressive drug is commonly used in most of the immune-mediated diseases. The objective of this retrospective study was to evaluate the efficacy, tolerability, and occurrence of relapse for the combination of prednisolone and azathioprine. All dogs received azathioprine 2 mg/kg q 24 hr for 1 mo and then 2 mg/kg every other day for 2 mo; prednisolone was started at an immunosuppressive dosage and tapered off gradually during a mean of 3 mo. Twenty-six dogs met inclusion criteria. Twenty-one dogs (81%) were in clinical remission with no relapse observed within the 2 yr follow-up period. Treatment was well tolerated in all dogs and side effects were most of the time mild and self-limiting. The relapse rate (19%) was lower than most published rates. A prednisolone and azathioprine combination appeared to be effective for primary treatment of dogs with SRMA and allows a quicker tapering in prednisolone dosage, a decrease in long-term side effects of steroids, a shorter duration of treatment, and a low relapse rate.

scholarly journals Corticosteroid-Sparing Effect of Chromoglycate Sodium and Nedocromil

1994 ◽  
Vol 3 (7) ◽  
pp. S25-S30 ◽  
Author(s):  
A. F. Capristo ◽  
M. Miraglia del Giudice Jr ◽  
C. Alfaro ◽  
N. Maiello
Keyword(s):  
Side Effects ◽  
Combined Treatment ◽  
Provocation Test ◽  
Double Bind ◽  
Hypertonic Solution ◽  
Inflammatory Drugs ◽  
Bronchial Hyper Responsiveness ◽  
Sparing Effect ◽  
Dose Dependent

The most appropiate management for bronchial asthma is the control of airway inflammation. Corticosteroids are the most effective anti-inflammatory drugs available, but they have a number of side effects; most of these are dose-dependent. In children, asthma control should be accomplished with low steroid doses possibly given by inhalation. In a double-bind placebo-controlled crossover study a group of children with mild to moderate asthma received NED 16 mg/day or BDP 400 μg/day. Values for FEV1, PEF, symptoms use ofbronchodilators overlapped, whereas bronchial hyper-responsiveness assessed by histamine bronchoprovocation challenge was better with BDP than NED. In another case, one boy with high bronchial hyper-reactivity assessed by provocation test with hypertonic solution, experienced a significant improvement only after 2 weeks of therapy with Deflazacort (2 mg/Kg/day) followed by 4 months on combined treatment with NED (16 mg/day) and BDP (300 μ/day). Authors conclude that NED could have a steroidsparing effect over long-term use.

scholarly journals Biochemical Control in Acromegaly With Multimodality Therapies: Outcomes From a Pituitary Center and Changes Over Time

2019 ◽  
Vol 105 (3) ◽  
pp. e532-e543 ◽  
Author(s):  
Alireza Ghajar ◽  
Pamela S Jones ◽  
Francisco J Guarda ◽  
Alex Faje ◽  
Nicholas A Tritos ◽  
...  
Keyword(s):  
Pituitary Surgery ◽  
Male Gender ◽  
Multimodality Therapy ◽  
Therapeutic Interventions ◽  
Biochemical Control ◽  
Adjuvant Therapies ◽  
Changes Over Time ◽  
Term Analysis ◽  
Over Time

Abstract Purpose To determine the prevalence of insulin-like growth factor-1 (IGF-1) normalization with long-term multimodality therapy in a pituitary center and to assess changes over time. Methods Patients with acromegaly (N = 409), with ≥1 year of data after surgery and at least 2 subsequent clinic visits were included in long-term analysis (N = 266). Biochemical data, clinical characteristics, and therapeutic interventions were reviewed retrospectively. Results At diagnosis, mean [standard deviation] age was 43.4 [14.3] years, body mass index was 28.5 (24.9–32.1) kg/m2 (median, interquartile range), serum IGF-1 index (IGF-1 level/upper limit of normal) was 2.3 [1.7–3.1], and 80.5% had macroadenomas. Patients with transsphenoidal surgery after 2006 were older [46.6 ± 14.3 vs 40.0 ± 13.4 years; P < 0.001]. Age and tumor size correlated inversely. Overall (N = 266), 93.2% achieved a normal IGF-1 level during 9.9 [5.0–15.0] years with multimodality therapy. The interval to first normal IGF-1 level following failed surgical remission was shorter after 2006: 14.0 (95% confidence interval, 10.0–20.0) versus 27.5 (22.0–36.0) months (P = 0.002). Radiation therapy and second surgery were rarer after 2006: 28 (22%) versus 62 (47.0%); P < 0.001 and 12 (9.4%) versus 28 (21.2%); P = 0.010, respectively. Age at diagnosis increased over time periods, possibly reflecting increased detection of acromegaly in older patients with milder disease. Male gender, older age, smaller tumor and lower IGF-1 index at diagnosis predicted long-term sustained IGF-1 control after surgery without adjuvant therapies. Conclusion The vast majority of patients with acromegaly can be biochemically controlled with multimodality therapy in the current era. Radiotherapy and repeat pituitary surgery became less frequently utilized over time. Long-term postoperative IGF-1 control without use of adjuvant therapies has improved.

scholarly journals Long-term re-evaluation of primary aldosteronism after medical treatment reveals high proportion of normal mineralocorticoid secretion

2013 ◽  
Vol 168 (4) ◽  
pp. 525-532 ◽  
Author(s):  
Barbara Lucatello ◽  
Andrea Benso ◽  
Isabella Tabaro ◽  
Elena Capello ◽  
Mirko Parasiliti Caprino ◽  
...  
Keyword(s):  
Medical Treatment ◽  
Primary Aldosteronism ◽  
Cross Sectional Study ◽  
Term Treatment ◽  
Duration Of Treatment ◽  
Cross Sectional ◽  
Long Term Treatment ◽  
Suppression Test ◽  
Mineralocorticoid Antagonists

ObjectiveIn most cases of primary aldosteronism (PA), an adrenal aldosterone-secreting tumor cannot be reasonably proven, so these patients undergo medical treatment. Controversial data exist about the evolution of PA after medical therapy: long-term treatment with mineralocorticoid antagonists has been reported to normalize aldosterone levels but other authors failed to find remission of mineralocorticoid hypersecretion. Thus, we planned to retest aldosterone secretion in patients with medically treated PA diagnosed at least 3 years before.DesignRetrospective, cross-sectional study.MethodsThe same workup for PA as at diagnosis (basal aldosterone to renin activity ratio (ARR) and aldosterone suppression test) was performed after stopping interfering drugs and low-salt diet, in 34 subjects with PA diagnosed between 3 and 15 years earlier, by case finding from subgroups of hypertensive patients at high risk for PA. Criteria for persistence of PA were the same as at diagnosis (ARR (pg/ml per ng per ml per h) >400, aldosterone >150 pg/ml basally, and >100 pg/ml after saline infusion) or less restrictive.ResultsPA was not confirmed in 26 (76%) of the patients and also not in 20 (59%) using the least restrictive criteria suggested by international guidelines. Unconfirmed PA was positively associated with female sex, higher potassium levels, longer duration of hypertension, and follow-up, but not with adrenal mass, aldosterone levels at diagnosis, and treatment with mineralocorticoid antagonists.ConclusionsThis study suggests that mineralocorticoid hyperfunction in patients with PA after medical treatment may decline spontaneously. Higher potassium concentration and duration of treatment seem to increase the probability of this event.

scholarly journals A review study of targeting of AAK1 and JAK1/2 using baricitinib in COVID-19 infected human cells

2020 ◽  
Vol 16 (supplement) ◽  
pp. 9-15
Author(s):  
Abeer M Al-Humaidhi
Keyword(s):  
Side Effects ◽  
Inhibitory Effect ◽  
Term Treatment ◽  
Long Term Treatment ◽  
Pros And Cons ◽  
Experimental Trials ◽  
Pharmaceutical Agents ◽  
Dose Dependent ◽  
A Current

     The outbreak of a current public health coronavirus 2019 disease is a causative agent of a serious acute respiratory syndrome and even death. COVID-19 has exposed to multi-suggested pharmaceutical agents to control this global disease. Baricitinib, a well-known antirheumatic agent, was one of them. This article reviews the likely pros and cons of baricitinib in attenuation of COVID-19 based on the mechanism of drug action as well as its pharmacokinetics. The inhibitory effect of baricitinib on receptor mediated endocytosis promoter, AKK1, and on JAK-STAT signaling pathway is benefacial in inhibition of both viral assembling and inflammation. Also, its pharmacokinetic has encouraged the physicians toward the drug selection for COVID-19 treatment. On the other hand, most of baricitinib side effects are dose-dependent. In conclusion, targeting of AAK1 and JAK1/2 using baricitinib has predicted to be potential and effective with minimal side effects in management COVID-19 infected patients for a short therapeutic dosing period. Laboratory monitoring should be considered for some parameters. However, experimental trials are mandatory for a long-term treatment with a lower dose of baricitinib to evaluate its effectiveness and safety in patients with moderate COVID-19 infection.

scholarly journals Surgery as a Viable Alternative First-Line Treatment for Prolactinoma Patients. A Systematic Review and Meta-Analysis

2019 ◽  
Vol 105 (3) ◽  
pp. e32-e41 ◽  
Author(s):  
Amir H Zamanipoor Najafabadi ◽  
Ingrid M Zandbergen ◽  
Friso de Vries ◽  
Leonie H A Broersen ◽  
M Elske van den Akker-van Marle ◽  
...  
Keyword(s):  
Side Effects ◽  
Dopamine Agonist ◽  
Transsphenoidal Surgery ◽  
Dopamine Agonists ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Sensitivity Analyses ◽  
Biochemical Control ◽  
Disease Remission

Abstract Context The improved remission and complication rates of current transsphenoidal surgery warrant reappraisal of the position of surgery as a viable alternative to dopamine agonists in the treatment algorithm of prolactinomas. Objective To compare clinical outcomes after dopamine agonist withdrawal and transsphenoidal surgery in prolactinoma patients. Methods Eight databases were searched up to July 13, 2018. Primary outcome was disease remission after drug withdrawal or surgery. Secondary outcomes were biochemical control and side effects during dopamine agonist treatment and postoperative complications. Fixed- or random-effects meta-analysis was performed to estimate pooled proportions. Robustness of results was assessed by sensitivity analyses. Results A total of 1469 articles were screened: 55 (10 low risk of bias) on medical treatment (n = 3564 patients) and 25 (12 low risk of bias) on transsphenoidal surgery (n = 1836 patients). Long-term disease remission after dopamine agonist withdrawal was 34% (95% confidence interval [CI], 26-46) and 67% (95% CI, 60-74) after surgery. Subgroup analysis of microprolactinomas showed 36% (95% CI, 21-52) disease remission after dopamine agonist withdrawal, and 83% (95% CI, 76-90) after surgery. Biochemical control was achieved in 81% (95% CI, 75-87) of patients during dopamine agonists with side effects in 26% (95% CI, 13-41). Transsphenoidal surgery resulted in 0% mortality, 2% (95% CI, 0-5) permanent diabetes insipidus, and 3% (95% CI, 2-5) cerebrospinal fluid leakage. Multiple sensitivity analyses yielded similar results. Conclusions In the majority of prolactinoma patients, disease remission can be achieved through surgery, with low risks of long-term surgical complications, and disease remission is less often achieved with dopamine agonists.

scholarly journals Long-term treatment of acromegalic patients resistant to somatostatin analogues with the GH receptor antagonist pegvisomant: its efficacy in relation to gender and previous radiotherapy

2009 ◽  
Vol 160 (4) ◽  
pp. 535-542 ◽  
Author(s):  
Mónica Marazuela ◽  
Tomás Lucas ◽  
Cristina Alvarez-Escolá ◽  
Manel Puig-Domingo ◽  
Nuria Garcia de la Torre ◽  
...  
Keyword(s):  
Insulin Dose ◽  
Male Gender ◽  
Diabetic Patients ◽  
Somatostatin Analogue ◽  
University Hospitals ◽  
Duration Of Treatment ◽  
Cross Sectional ◽  
Long Term Treatment ◽  
The Mean

ContextPegvisomant is an effective treatment for somatostatin analogue-resistant acromegaly, but the determinants defining the response to this treatment are largely unknown.ObjectiveTo investigate the efficacy of pegvisomant treatment in resistant acromegalic patients (e.g. serum IGF1 at least 1.25×upper normal limit) in a clinical setting and the factors conditioning this response.Design and settingA retrospective cross-sectional study performed in six Spanish University hospitals from 2004 to 2007.PatientsForty-four acromegalic patients (61.4% female, mean age: 49±14), 95% of whom had undergone pituitary surgery and 61% having received pituitary radiotherapy. The mean follow-up was 22.7±11.2 months.Main outcome measuresIGF1 levels reflected treatment efficacy, and the influence of gender, age, weight, previous radiotherapy and duration of treatment was assessed.ResultsIGF1 normalisation was achieved in 84% of the patients. Male gender (P<0.05), previous irradiation (P<0.05) and the treatment duration (r=0.364, P<0.02) were associated with a better response to pegvisomant therapy. There was a significant decrease in HbA1c (P<0.001) and in the mean insulin dose (P<0.01) in acromegalic diabetic patients. Although 25% of patients experienced mild adverse events, pegvisomant was only withdrawn in four patients due to side effects (two cases of tumour growth, one liver dysfunction and one headache).ConclusionsLong-term pegvisomant is a very effective therapy in resistant acromegaly. Male gender and prior radiotherapy influence the therapeutic response rate.

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