scholarly journals Advanced Diabetic Nephropathy with Nephrotic Range Proteinuria: A Pilot Study of the Long-Term Efficacy of Subcutaneous ACTH Gel on Proteinuria, Progression of CKD, and Urinary Levels of VEGF and MCP-1

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
J. A. Tumlin ◽  
C. M. Galphin ◽  
B. H. Rovin
Keyword(s):  
Diabetic Nephropathy ◽  
Dose Group ◽  
Low Dose ◽  
Pilot Trial ◽  
Unit Group ◽  
Urinary Protein ◽  
High Dose ◽  
Open Label ◽  
Nephrotic Range Proteinuria

Background and Objective.Adrenocorticotropic hormone (ACTH) is able to reduce proteinuria in nondiabetic glomerulopathies through activation of melanocortin receptors (MCR) expressed in the podocyte. To determine the efficacy of ACTH, we conducted a randomized, open-label pilot trial of ACTH gel in patients with advanced diabetic nephropathy.Study Design.Twenty-three (23) patients with diabetic nephropathy were randomized to daily subcutaneous (SQ) injections of 16 or 32 units of ACTH gel for six months.Outcome.The primary endpoint was the percentage of patients achieving a complete remission (<300 mg/24 hours) within 6 months. Exploratory endpoints included the percentage of partial (50% reduction) remissions, changes in Cr, and urinary cytokine markers.Results.After 6 months of ACTH gel therapy, 8 of 14 (57%) patients achieved a complete (n=1) or partial (n=7) remission. In the low-dose ACTH gel group (16 units), urinary protein fell from6709+953to2224+489 mg/24 hrs (P<0.001). In contrast, 2 of 6 patients in the 32-unit group achieved partial remission, but aggregate proteinuria (5324+751to5154+853 mg/24 hours) did not change. Urinary VEGF increased from 388 to 1346 pg/mg urinary creatinine (P<0.02) in the low-dose group but remained unchanged in the high-dose group.Conclusion.ACTH gel stabilizes renal function and reduces urinary protein for up to 6 months after treatment. The ClinTrials.gov identifier isNCT01028287.

Effects of long-term continuous GnRH administration on the pituitary–gonadal axis in Eld's deer stags (Cervus eldi thamin)

1995 ◽  
Vol 73 (9) ◽  
pp. 1609-1619 ◽  
Author(s):  
S. L. Monfort ◽  
J. L. Brown ◽  
T. C. Wood ◽  
M. Bush ◽  
L. R. Williamson ◽  
...  
Keyword(s):  
Dose Group ◽  
Low Dose ◽  
High Dose ◽  
Fertile Period ◽  
Nonbreeding Season ◽  
Testosterone Secretion ◽  
High Doses ◽  
Seasonal Decline ◽  
Seasonally Breeding

Eld's deer stags (Cervus eldi thamin) (in groups of three) were continuously administered gonadotropin-releasing hormone (GnRH) in control, low, medium, or high doses (0, 20.1 ± 0.7, 83.3 ± 2.6, and 292.9 ± 4.9 ng∙kg−1∙d−1, respectively) via osmotic minipumps for ~80 d to investigate the potential for precociously reactivating the pituitary–testicular axis during the nonbreeding season. Secretory patterns of LH, FSH, and testosterone concentrations were qualitatively similar among treatments. However, in the low-dose group, basal LH and FSH concentrations were both increased (p < 0.05) and pituitary responsiveness to a superimposed GnRH challenge was augmented (p < 0.05) after 12 weeks of treatment compared with all other groups. Despite these endocrine changes, continuous low-dose GnRH administration was not effective for precociously inducing testicular activity in this seasonally breeding species. High-dose GnRH administration initially induced a transient increase in LH, FSH, and testosterone secretion and delayed, but did not prevent, the seasonal decline in spermatogenesis. After 6–12 weeks of high-dose GnRH administration, however, attenuated pituitary responsiveness appeared to delay the normal seasonal reactivation of the pituitary–gonadal axis. In conclusion, prolonged, continuous low-dose GnRH administration did not effectively translate into a precocious onset of testicular activity; therefore, this specific approach is unlikely to be useful for prolonging the fertile period in this seasonally breeding species.

Long Term Efficacy and Safety Results and Analysis of Dose Correlations from the Phase I/II Peginvera Study of Ropeginterferon Alfa-2b, a Novel IFNa-2b, in Polycythemia Vera Patient

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4056-4056
Author(s):  
Heinz Gisslinger ◽  
Veronika Buxhofer-Ausch ◽  
Josef Thaler ◽  
Ernst Schlögl ◽  
Gunther Gastl ◽  
...  
Keyword(s):  
Research Funding ◽  
Dose Group ◽  
Low Dose ◽  
Term Treatment ◽  
High Dose ◽  
Individual Response ◽  
Molecular Response ◽  
Efficacy And Safety ◽  
Long Term Treatment

Abstract Background Ropeginterferon alfa-2b (AOP2014/P1101) is a novel long-acting pegylated IFN-alpha-2b, composed of mainly one isoform, resulting in longer half-life and exposure time. Reduced dosing frequencies, better tolerability, improved compliance and more favorable long-term treatment outcomes in patients with polycythemia vera (PV) are expected. The drug has Orphan designation by EMA and FDA and is currently in the phase III stage of development. Study design Efficacy and safety data are being collected in the follow-up extension stage of the study (collecting the data of both Phase I and Phase II portions of the study), after the maximum tolerated dose (MTD) of ropeginterferon alfa-2b, administered subcutaneously every 14 to 28 days, has been defined earlier. Patients with confirmed diagnosis of PV, age ≥18 years, both naïve and cytoreductively pre-treated were eligible. After establishing the MTD, an extended cohort of 25 additional patients has been planned to be recruited. Complete hematological response (CR) is defined by hematocrit (Hct)<45%, platelet count≤400*109/L, WBC count≤10*109/L, normal spleen size by sonography, and absence of thromboembolic events. Partial response (PR) is defined as Hct<45% without phlebotomy but with persistent splenomegaly or elevated (>400*109/L) platelet count, or reduction of phlebotomy requirements by at least 50%. Complete molecular response has been defined as reduction of any molecular abnormality to undetectable levels; partial molecular response as: reduction ≥ 50% in patients with < 50% mutant allele burden, or a reduction ≥ 25% in patients with > 50% mutant allele burden. The present analysis was focused on long-term tolerability and safety in correlation with the dose of ropeginterferon alfa-2b in PV. Results Data on treatment as by July, 24, 2015, are covered by the current analysis. Baseline characteristics of the study cohort during short-term treatment were already presented earlier (Gisslinger et al, ASH 2013). The full analysis set and efficacy set were composed of 51 and 47 patients, respectively. Currently, the median reported treatment duration is 138 weeks, 33 patients completed their follow up for two years, 19 for three years. Starting with the week 10, Hct-level, platelet- and WBC-counts could be constantly maintained within normal range in the majority of patients. In a group of patients with the mean administered dose of <300 µg ("low dose", n=36), CR as best individual response was achieved in 20 (56%) patients, and PR in 14 (39%) compared to the CR and PR in the high dose (>300 µg, n=11) group of 8 (73%) and 3 (27%) respectively. However, no statistical significance can be observed if correlation between the dose and response status was analyzed. 30 patients are still being treated in the study. Similarly, no association between the dose and occurrence of adverse events in the study could be observed. Complete molecular response as best individual response was observed more frequently in the high dose group 4 (36%) compared to 8 (23%) in the low dose group, while partial molecular responses were equally frequent in both dose groups (in 6/55% and 20/57%, respectively). 21 patients discontinued the study, 18 being treated with AOP2014 doses corresponding to low, and 3 to the high dose arms, corresponding to the drop-out rate of 50% and 27% in the respective arms. Interestingly, all discontinuations in the high dose group occurred within the first year of treatment (at weeks 16, 18 and 32), while the drop-outs in the low dose group (6 patients, 33%) discontinued the study after completion of their first year of treatment. Conclusions Efficacy and safety profile remain in line with expectations from other (pegylated) interferons. Overall response rate of >80% with cumulative CRs in 45-50%, accompanied by phlebotomy independence, normalization of hematological parameters and spleen size reduction in majority of patients have been observed. Significant and sustained JAK2 allelic burden decrease, starting from week 28 of treatment, was seen. No significant difference between the two mean dose levels regarding response rates or adverse events even during long-term treatment and observation could be observed. These finding are to be further verified in a larger prospective setting. Disclosures Gisslinger: Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau; AOP ORPHAN: Consultancy, Honoraria, Research Funding, Speakers Bureau; Geron: Consultancy; Sanofi Aventis: Consultancy; Janssen Cilag: Honoraria, Speakers Bureau. Buxhofer-Ausch:AOP Orphan: Research Funding. Thaler:AOP Orphan: Research Funding. Schlögl:AOP Orphan: Research Funding. Gastl:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; AOP Orphan: Research Funding. Ban:AOP Orphan: Research Funding. Egle:AOP Orphan: Research Funding. Melchardt:AOP Orphan: Research Funding. Burgstaller:AOP Orphan Pharmaceuticals: Honoraria, Research Funding; Novartis: Honoraria; Mundipharma: Honoraria; Celgene: Consultancy, Honoraria, Research Funding. Willenbacher:COMET Center ONCOTYROL: Research Funding; AOP Orphan: Research Funding. Kralovics:AOP Orphan: Research Funding; Qiagen: Membership on an entity's Board of Directors or advisory committees. Zörer:AOP Orphan: Employment. Ammann-Mwathi:AOP Orphan: Employment. Kadlecova:AOP Orphan: Consultancy. Zagrijtschuk:AOP Orphan: Employment. Klade:AOP Orphan: Employment. Greil:Pfizer: Honoraria, Research Funding; GSK: Research Funding; Boehringer-Ingelheim: Honoraria; AOP Orphan: Research Funding; Celgene: Consultancy; Janssen-Cilag: Honoraria; Genentech: Honoraria, Research Funding; Novartis: Honoraria; Astra-Zeneca: Honoraria; Amgen: Honoraria, Research Funding; Ratiopharm: Research Funding; Sanofi Aventis: Honoraria; Merck: Honoraria; Mundipharma: Honoraria, Research Funding; Eisai: Honoraria; Cephalon: Consultancy, Honoraria, Research Funding; Bristol-Myers-Squibb: Consultancy, Honoraria; Roche, Celgene: Honoraria, Research Funding.

scholarly journals Effect of high versus low dose of dexamethasone on clinical worsening in patients hospitalised with moderate or severe COVID-19 Pneumonia: an open-label, randomised clinical trial

2021 ◽  
pp. 2102518
Author(s):  
Manuel Taboada ◽  
Nuria Rodríguez ◽  
Pablo Manuel Varela ◽  
María Teresa Rodríguez ◽  
Romina Abelleira ◽  
...  
Keyword(s):  
Dose Group ◽  
Oxygen Therapy ◽  
Low Dose ◽  
Ordinal Scale ◽  
High Dose Group ◽  
High Dose ◽  
Open Label ◽  
Once Daily ◽  
Significant Difference ◽  
Clinical Worsening

BackgroundLow dose dexamethasone demonstrated clinical improvement in patients with coronavirus disease 2019 (COVID-19) needing oxygen therapy; however, evidence on the efficacy of high dose of dexamethasone is limited.MethodsWe performed a randomised, open-label, controlled trial involving hospitalised patients with confirmed COVID-19 pneumonia needing oxygen therapy. Patients were randomly assigned in a 1:1 ratio to receive low dose dexamethasone (6 mg once daily for 10 days) or high dose dexamethasone (20 mg once daily for 5 days, followed by 10 mg once daily for additional 5 days). The primary outcome was clinical worsening within 11 days since randomisation. Secondary outcomes included 28-day mortality, time to recovery, and clinical status at day 5, 11, 14 and 28 on an ordinal scale ranging from 1 (discharged) to 7 (death).ResultsA total of 200 patients (mean (sd) age, 64 (14) years; 62% male) were enrolled. Thirty-two patients of 102 (31.4%) enrolled in the low dose group and 16 of 98 (16.3%) in the high dose group showed clinical worsening within 11 days since randomisation (rate ratio, 0.427; 95% CI, 0.216–0.842; p=0.014). The 28-day mortality was 5.9% in the low dose group and 6.1% in the high dose group (p=0.844). There was no significant difference in time to recovery, and in the 7-point ordinal scale at day 5, 11, 14 and 28.ConclusionsAmong hospitalised COVID-19 patients needing oxygen therapy, high dose of dexamethasone reduced clinical worsening within 11 days after randomisation as compared with low dose.

scholarly journals Long-term vitamin C supplementation has no markedly favourable effect on serum lipids in middle-aged Japanese subjects

2004 ◽  
Vol 91 (1) ◽  
pp. 81-90 ◽  
Author(s):  
Mi Kyung Kim ◽  
Satoshi Sasaki ◽  
Shizuka Sasazuki ◽  
Shunji Okubo ◽  
Masato Hayashi ◽  
...  
Keyword(s):  
Vitamin C ◽  
Dose Group ◽  
Low Dose ◽  
Favourable Effect ◽  
High Dose ◽  
Vitamin C Supplementation ◽  
The Mean ◽  
High Dose Vitamin ◽  
Β Carotene

Antioxidant vitamins have been reported to be associated with an improvement in blood lipid profiles, but results are not consistent. The present study was designed to determine whether long-term vitamin C supplementation could alter serum lipid concentrations in subjects who completed a 5-year population-based double-blind intervention trial. A total of 439 Japanese subjects with atrophic gastritis initially participated in the trial using vitamin C and β-carotene to prevent gastric cancer. Before and upon early termination of β-carotene supplementation, 134 subjects dropped out of the trial; finally, 161 subjects assigned to the high-dose group (500 mg vitamin C/d) and 144 subjects assigned to the low-dose group (50 mg vitamin C/d) were studied. No favourable effect of vitamin C supplementation on serum concentrations of total cholesterol, HDL- and LDL-cholesterol, and triacylglycerol was observed, although high-dose vitamin C supplementation increased serum vitamin C concentrations substantially. Among women, the mean change in serum triacylglycerol decreased (−0·12 mmol/l, 95 % CI −0·32, 0·09) in the high-dose group, but increased (+0·12 mmol/l, 95 % CI 0·03, 0·22) in the low-dose group. In addition, the mean change in serum triacylglycerol among women with hypertriacylglycerolaemia was statistically significant (−1·21, 95 % CI −2·38, −0·05) after high-dose vitamin C supplementation. The 5-year vitamin C supplementation had no markedly favourable effects on the serum lipid and lipoprotein profile. However, our present results do not preclude the possibility that vitamin C supplementation may decrease triacylglycerol concentrations among women with hypertriacylglycerolaemia.

scholarly journals Does Low Dose Steroids Confer Benefits in Sepsis and Septic Shock?

2017 ◽  
Vol 7 (1) ◽  
pp. 48-59
Author(s):  
Sarah Nehrina Nazim
Keyword(s):  
Septic Shock ◽  
Steroid Therapy ◽  
Low Dose ◽  
Pilot Trial ◽  
Teaching Hospitals ◽  
High Dose ◽  
Open Label ◽  
Optimal Dosing ◽  
Recent Recommendation ◽  
Sepsis And Septic Shock

Over the last 40 years, the use of corticosteroids in sepsis and septic shock has evolved from the initial use of high-dose, short-duration steroid therapy in the 1980s, to the recent recommendation of using low-dose longerduration steroid therapy in refractory septic shock patients. A recent, prospective, open-label, randomized, controlled pilot trial of patients in four adult intensive care units in London-teaching hospitals showed that hydrocortisone decreased vasopressin requirements, reduced the duration and reduced the required dose, when used together in the treatment of septic shock, but it did not alter plasma vasopressin levels. The optimal dosing of hydrocortisone, about 300 mg/day, was agreed uniformly. As this dose also provides sufficient mineralocorticoid effects, the additional use of mineralocorticoid is not needed. Despite the fact that severely ill septic shock patients are given treatment, according to the current guidelines, the survival benefit is unproven. The benefits of steroids on less severely ill septic patients are still questionable. More research is highly recommended to successfully identify the benefits of steroids in septic shock.Birdem Med J 2017; 7(1): 48-59

scholarly journals Relacorilant, a Selective Glucocorticoid Receptor Modulator, Induces Clinical Improvements in Patients With Cushing Syndrome: Results From A Prospective, Open-Label Phase 2 Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Rosario Pivonello ◽  
Irina Bancos ◽  
Richard A. Feelders ◽  
Atil Y. Kargi ◽  
Janice M. Kerr ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Dose Group ◽  
Low Dose ◽  
Cushing Syndrome ◽  
High Dose ◽  
Phase 2 ◽  
Open Label ◽  
Drug Induced ◽  
Receptor Modulator ◽  
Open Label Phase

Introduction/PurposeRelacorilant is a selective glucocorticoid receptor modulator (SGRM) with no progesterone receptor activity. We evaluated the efficacy and safety of relacorilant in patients with endogenous Cushing syndrome (CS).Materials and MethodsA single-arm, open-label, phase 2, dose-finding study with 2 dose groups (NCT02804750, https://clinicaltrials.gov/ct2/show/NCT02804750) was conducted at 19 sites in the U.S. and Europe. Low-dose relacorilant (100-200 mg/d; n = 17) was administered for 12 weeks or high-dose relacorilant (250-400 mg/d; n = 18) for 16 weeks; doses were up-titrated by 50 mg every 4 weeks. Outcome measures included proportion of patients with clinically meaningful changes in hypertension and/or hyperglycemia from baseline to last observed visit. For patients with hypertension, clinical response was defined as a ≥5-mmHg decrease in mean systolic or diastolic blood pressure, measured by a standardized and validated 24-h ABPM. For patients with hyperglycemia, clinical response was defined ad-hoc as ≥0.5% decrease in HbA1c, normalization or ≥50-mg/dL decrease in 2-h plasma glucose value on oral glucose tolerance test, or decrease in daily insulin (≥25%) or sulfonylurea dose (≥50%).Results35 adults with CS and hypertension and/or hyperglycemia (impaired glucose tolerance or type 2 diabetes mellitus) were enrolled, of which 34 (24 women/10 men) received treatment and had postbaseline data. In the low-dose group, 5/12 patients (41.7%) with hypertension and 2/13 patients (15.4%) with hyperglycemia achieved response. In the high-dose group, 7/11 patients (63.6%) with hypertension and 6/12 patients (50%) with hyperglycemia achieved response. Common (≥20%) adverse events included back pain, headache, peripheral edema, nausea, pain at extremities, diarrhea, and dizziness. No drug-induced vaginal bleeding or hypokalemia occurred.ConclusionsThe SGRM relacorilant provided clinical benefit to patients with CS without undesirable antiprogesterone effects or drug-induced hypokalemia.

Intensive Initial Oral Anticoagulation and Shorter Heparin Treatment in Deep Vein Thrombosis

1984 ◽  
Vol 52 (03) ◽  
pp. 276-280 ◽  
Author(s):  
Sam Schulman ◽  
Dieter Lockner ◽  
Kurt Bergström ◽  
Margareta Blombäck
Keyword(s):  
Deep Vein Thrombosis ◽  
Oral Anticoagulation ◽  
Dose Group ◽  
Low Dose ◽  
Clinical Signs ◽  
Coagulation Factor ◽  
High Dose ◽  
Vein Thrombosis ◽  
Heparin Treatment ◽  
Deep Vein

SummaryIn order to investigate whether a more intensive initial oral anticoagulation still would be safe and effective, we performed a prospective randomized study in patients with deep vein thrombosis. They received either the conventional regimen of oral anticoagulation (“low-dose”) and heparin or a more intense oral anticoagulation (“high-dose”) with a shorter period of heparin treatment.In the first part of the study 129 patients were randomized. The “low-dose” group reached a stable therapeutic prothrombin complex (PT)-level after 4.3 and the “high-dose” group after 3.3 days. Heparin was discontinued after 6.0 and 5.0 days respectively. There was no difference in significant hemorrhage between the groups, and no clinical signs of progression of the thrombosis.In the second part of the study another 40 patients were randomized, followed with coagulation factor II, VII, IX and X and with repeated venograms. A stable therapeutic PT-level was achieved after 4.4 (“low-dose”) and 3.7 (“high-dose”) days, and heparin was discontinued after 5.4 and 4.4 days respectively. There were no clinical hemorrhages, the activity of the coagulation factors had dropped to the same level in both groups at the time when heparin was discontinued and no thromboembolic complications occurred.Our oral anticoagulation regimen with heparin treatment for an average of 4.4-5 days seems safe and reduces in-patient costs.

scholarly journals Newly Developed Recombinant Antithrombin Protects the Endothelial Glycocalyx in an Endotoxin-Induced Rat Model of Sepsis

2020 ◽  
Vol 22 (1) ◽  
pp. 176
Author(s):  
Toshiaki Iba ◽  
Jerrold H. Levy ◽  
Koichiro Aihara ◽  
Katsuhiko Kadota ◽  
Hiroshi Tanaka ◽  
...  
Keyword(s):  
Dose Group ◽  
Low Dose ◽  
Leukocyte Adhesion ◽  
Endothelial Glycocalyx ◽  
High Dose Group ◽  
Control Group ◽  
High Dose ◽  
Protective Effects ◽  
Circulating Levels

(1) Background: The endothelial glycocalyx is a primary target during the early phase of sepsis. We previously reported a newly developed recombinant non-fucosylated antithrombin has protective effects in vitro. We further evaluated the effects of this recombinant antithrombin on the glycocalyx damage in an animal model of sepsis. (2) Methods: Following endotoxin injection, in Wistar rats, circulating levels of hyaluronan, syndecan-1 and other biomarkers were evaluated in low-dose or high-dose recombinant antithrombin-treated animals and a control group (n = 7 per group). Leukocyte adhesion and blood flow were evaluated with intravital microscopy. The glycocalyx was also examined using side-stream dark-field imaging. (3) Results: The activation of coagulation was inhibited by recombinant antithrombin, leukocyte adhesion was significantly decreased, and flow was better maintained in the high-dose group (both p < 0.05). Circulating levels of syndecan-1 (p < 0.01, high-dose group) and hyaluronan (p < 0.05, low-dose group; p < 0.01, high-dose group) were significantly reduced by recombinant antithrombin treatment. Increases in lactate and decreases in albumin levels were significantly attenuated in the high-dose group (p < 0.05, respectively). The glycocalyx thickness was reduced over time in control animals, but the derangement was attenuated and microvascular perfusion was better maintained in the high-dose group recombinant antithrombin group (p < 0.05). (4) Conclusions: Recombinant antithrombin maintained vascular integrity and the microcirculation by preserving the glycocalyx in this sepsis model, effects that were more prominent with high-dose therapy.

High-dose statin therapy and the risk of haemorrhagic stroke in Asian patients with stable coronary artery disease: insights from the REAL-CAD study

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Takahashi ◽  
K Tsuchida ◽  
Y Sato ◽  
S Iimuro ◽  
K Kario ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Dose Group ◽  
Low Dose ◽  
Japanese Patients ◽  
Haemorrhagic Stroke ◽  
High Dose ◽  
The Real ◽  
Artery Disease ◽  
Stable Cad ◽  
Bleeding Score

Abstract Background/Introduction The REAL-CAD study identified that aggressive lipid lowering with high-dose statin reduced cardiovascular events also in Japanese patients with coronary artery disease (CAD). However, data from the SPARCL trial found that the benefits of high-dose atorvastatin treatment were partially offset by an increase in haemorrhagic stroke (HS). Although meta-analysis showed statin does not increase HS in Western countries, the evidence about the relation between statin and HS in Asian countries is still conflicting. In addition, the CREDO-Kyoto score is one of the prediction scorings for bleeding after coronary revascularization and might be a useful tool for the prediction of HS in this cohort. Recognizing the risk of HS and predicting of HS in the Asian cohort is clinically important. Purpose This study examined the factors associated with HS using the REAL-CAD cohort. Furthermore, we evaluated the performance of the CREDO-Kyoto bleeding risk score to predict HS in this cohort. We also performed the corresponding analysis of ischaemic stroke for reference purposes. Methods We sub-analysed the REAL-CAD study, prospective, multicentre, randomized, open-label, blinded endpoint study, in which 13,054 Japanese patients with stable CAD were randomized to high-dose (4 mg/day) or low-dose (1 mg/day) pitavastatin. Associations for stroke were determined using competing risk models: the Fine and Gray subdistribution hazards model accounting for the competing risk of death in models of haemorrhagic and ischaemic stroke in REAL-CAD trial. Patients were categorized to low (score 0), moderate (score 1–2), and high (score&gt;3) according to CREDO-Kyoto bleeding score for predicting of HS. Results The HS events in high-dose group tended to be higher than low-dose group (4mg vs. 1mg: 43 (0.7%) vs. 30 (0.5%)). The associated factors of HS on univariate analysis were non-prior myocardial (hazard ratio (HR): 0.62, 95% CI: 0.39–0.99) and non-prior cerebral (HR: 0.25, 95% CI: 0.09–0.70) infarction, atrial fibrillation (HR: 2.4, 95% CI: 1.2–4.7), prior HS (HR: 4.2, 95% CI: 1.5–11.8), anaemia (HR: 2.4, 95% CI: 1.4–4.1), and non-statins use before run-in period (HR: 0.52, 95% CI: 0.28–0.99). High-dose pitavastatin was not a correlate with HS. The multivariate analysis revealed anaemia might have a relation with HS (HR: 4.3, 95% CI: 0.90–20.6). The number of HS was the highest in the high CREDO-Kyoto bleeding score group (Figure 1, HR: 2.4, 95% CI: 1.3–4.6), whereas there was no significant difference in the number of HS between the moderate- and low-risk groups (HR: 1.4, 95% CI: 0.84–2.3). Conclusions High-dose pitavastatin was not associated with the incidence of HS in this large Japanese cohort with stable CAD. High CREDO-Kyoto bleeding score was associated with HS as compared with low or moderate scores, even each of the variables consisting of CREDO-Kyoto score was not associated with HS. Figure 1 Funding Acknowledgement Type of funding source: None

scholarly journals The Effect of Long-Term Low-Dose Atropine on Refractive Progression in Myopic Australian School Children

2021 ◽  
Vol 10 (7) ◽  
pp. 1444
Author(s):  
William Myles ◽  
Catherine Dunlop ◽  
Sally A. McFadden
Keyword(s):  
Low Dose ◽  
High Dose ◽  
Eye Drops ◽  
Myopia Progression ◽  
At Risk Children ◽  
Slow Group ◽  
Blue Eyes ◽  
Global Population ◽  
Axial Growth

Myopia will affect half the global population by 2050 and is a leading cause of vision impairment. High-dose atropine slows myopia progression but with undesirable side-effects. Low-dose atropine is an alternative. We report the effects of 0.01% or 0.005% atropine eye drops on myopia progression in 13 Australian children aged between 2 and 18 years and observed for 2 years without and up to 5 years (mean 2.8 years) with treatment. Prior to treatment, myopia progression was either ‘slow’ (more positive than −0.5D/year; mean −0.19D/year) or ‘fast’ (more negative than −0.5D/year; mean −1.01D/year). Atropine reduced myopic progression rates (slow: −0.07D/year, fast: −0.25D/year, combined: before: −0.74, during: −0.18D/year, p = 0.03). Rebound occurred in 3/4 eyes that ceased atropine. Atropine halved axial growth in the ‘Slow’ group relative to an age-matched model of untreated myopes (0.098 vs. 0.196mm/year, p < 0.001) but was double that in emmetropes (0.051mm/year, p < 0.01). Atropine did not slow axial growth in ‘fast’ progressors compared to the age-matched untreated myope model (0.265 vs. 0.245mm/year, p = 0.754, Power = 0.8). Adverse effects (69% of patients) included dilated pupils (6/13) more common in children with blue eyes (5/7, p = 0.04). Low-dose atropine could not remove initial myopia offsets suggesting treatment should commence in at-risk children as young as possible.

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