scholarly journals ML-10 Tirabrutinib, a second-generation BTK inhibitor in relapsed and refractory primary CNS lymphoma: A single institute study

2021 ◽  
Vol 3 (Supplement_6) ◽  
pp. vi23-vi23
Author(s):  
Kazuhiko Mishima ◽  
Shirahata Mitsuaki ◽  
Junichi Adachi ◽  
Tomonari Suzuki ◽  
Eita Uchida ◽  
...  
Keyword(s):  
Second Generation ◽  
Primary Cns Lymphoma ◽  
Progression Free Survival ◽  
Maculopapular Rash ◽  
Term Treatment ◽  
Cns Lymphoma ◽  
Long Term Treatment ◽  
Btk Inhibitor ◽  
One Year

Abstract BACKGROUND: The prognosis of relapsed and refractory (r/r) primary CNS lymphoma (PCNSL) is poor, and the development of new therapeutic agents is desirable. Comprehensive genetic analysis of PCNSL has shown that MYD88 and CD79B are frequently mutated and are oncogenic drivers, suggesting that Bruton’s tyrosine kinase (BTK), which is located downstream of MYD88 and CD79B, may be a reasonable therapeutic target. Tirabrutinib is a second-generation oral BTK inhibitor recently approved in Japan for the treatment of r/r PCNSL. In this study, we evaluated the efficacy and safety of tiraburtinib treatment of r/r PCNSL at Saitama Medical University. MATERIAL AND METHODS: Eighteen patients with r/r PCNSL to HD-MTX-based regimens were treated with 480 mg tiraburtinib daily under fasting conditions until disease progression. RESULTS: The median age was 63.5 years, and the median KPS was 70. Nine patients (50%) achieved a CR, 2 (11%) had a partial response, 3 (17%) had stable disease, and 4 (22%) had progressive disease. After a median follow-up of 17.3 months, the median progression-free survival was 7.9 months, and the median overall survival was 23.6 months. There were four cases of long-term treatment lasting more than one year. Grade 3 or higher adverse events were observed in 1 case of maculopapular rash, 1 case of cardiac failure, 1 case of neutropenia, and 1 case of lymphopenia. CONCLUSION: Tiraburtinib can be administered relatively safely to patients with relapsed or refractory PCNSL, and a certain degree of efficacy can be expected. Which patients can be treated with tiraburtinib over the long term, when can stop tirabrutinib treatment for patients with long-term CR, and the mechanism of tiraburtinib resistance needs to be determined.

Long-term treatment of acromegaly with the slow-release somatostatin analogue lanreotide

1994 ◽  
Vol 131 (1) ◽  
pp. 20-26 ◽  
Author(s):  
Josef Marek ◽  
Václav Hána ◽  
Michal Kršek ◽  
Vlasta Justová ◽  
France Catus ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Slow Release ◽  
Serum Levels ◽  
Term Treatment ◽  
Somatostatin Analogue ◽  
Tumour Mass ◽  
Long Term Treatment ◽  
Active Acromegaly ◽  
One Year

Marek J, Hána V. Kršek M. Justová V, Catus F, Thomas F. Long-term treatment of acromegaly with the slow-release somatostatin analogue lanreotide. Eur J Endocrinol 1994;131:20–6. ISSN 0804–4643 Thirteen patients with active acromegaly despite previous surgery were treated with 30 mg lanreotide im twice a month for 9 months. In 10 subjects the treatment continued to 19 months. GH serum levels of all patients decreased significantly from an initial value of 32.0 (29.4) μg/l [median (standard error of median)] to 10.0 (3.6) and 19.1 (5.7) after 3 and 9 months of treatment, respectively. In the 10 patients with the treatment longer than one year the decrease in GH was from 46.8 (29.4) μg/l to 12.5 (5.0) and 16.1 (5.3) after 13 and 19 months, respectively. IGF-I serum levels decreased significantly from 1193 (73)μg/l to 782 (99) and 621 (103) after 3 and 9 months, respectively, and were normalized in 3 patients. In the 10 patients treated for longer than one year, levels decreased significantly from 1318 (74)μg/l to 653 (170) and 742 (180) after 13 and 19 months, respectively. IGF BP-3 levels were reduced to the normal range in 6 patients and decreased from 8.7 (1.5)mg/l to 6.4 (0.8) and to 5.4 (1.0) after 3 and 9 months, respectively. In the patients with the 19 months treatment the decrease was from 9.3 (1.6) mg/l to 3.9 (0.9) and 4.8 (0.9) after 13 and 19 months, respectively. The IGF BP-3 to IFG I ratio increased in 7 patients. This elevation significantly correlated with the decrease in bioassayable somatomedin. Prolactin serum levels fell in all patients with increased prolactin secretion. Testosterone plasma levels increased in 4 out of 5 men without replacement therapy. Clinical improvement was observed in all patients. A reduction of tumour mass was observed in five patients and complete disappearance of the tumour in one subject. All patients complained of mild abdominal pain and softened stools for several days following the injections. However, these side effects never required interruption of treatment. Asymptomatic microlithiasis was seen in only one patient after 13 months, which led to treatment being suspended for a period of 3 months after which it was resumed. Fasting serum insulin and insulin area under the curve (AUC) after oral glucose tolerance test (OGTT) fell in all patients. Fasting blood glucose, fructosamine and glucose AUC after OGTT slightly increased during the treatment, but all blood glucose levels (fasting and during OGTT) remained within normal ranges. Lanreotide appears to be a safe and effective treatment in patients with active acromegaly unresolved by surgery. The long-acting formulation avoids the drawbacks associated with either repeated daily injections or continuous infusions of somatostatin analogues. Josef Marek, Third Department of Medicine, Charles University, U nemocnice 1, 128 21 Praha 2, The Czech Republic

scholarly journals Mitochondrial and Oxidative Impacts of Short and Long-term Administration of HAART on HIV Patients

2020 ◽  
Vol 15 (2) ◽  
pp. 110-124
Author(s):  
Joy E. Ikekpeazu ◽  
Oliver C. Orji ◽  
Ikenna K. Uchendu ◽  
Lawrence U.S. Ezeanyika
Keyword(s):  
Treatment Group ◽  
Term Treatment ◽  
Short Term ◽  
Short Term Treatment ◽  
Hiv Patients ◽  
Long Term Treatment ◽  
Term Administration ◽  
Short And Long Term ◽  
One Year

Background and Objective: There may be a possible link between the use of HAART and oxidative stress-related mitochondrial dysfunction in HIV patients. We evaluated the mitochondrial and oxidative impacts of short and long-term administration of HAART on HIV patients attending the Enugu State University Teaching (ESUT) Hospital, Enugu, Nigeria following short and long-term therapy. Methods: 96 patients categorized into four groups of 24 individuals were recruited for the study. Group 1 comprised of age-matched, apparently healthy, sero-negative individuals (the No HIV group); group 2 consisted of HIV sero-positive individuals who had not started any form of treatment (the Treatment naïve group). Individuals in group 3 were known HIV patients on HAART for less than one year (Short-term treatment group), while group 4 comprised of HIV patients on HAART for more than one year (Long-term treatment group). All patients were aged between 18 to 60 years and attended the HIV clinic at the time of the study. Determination of total antioxidant status (TAS in nmol/l), malondialdehyde (MDA in mmol/l), CD4+ count in cells/μl, and genomic studies were all done using standard operative procedures. Results: We found that the long-term treatment group had significantly raised the levels of MDA, as well as significantly diminished TAS compared to the Short-term treatment and No HIV groups (P<0.05). In addition, there was significantly elevated variation in the copy number of mitochondrial genes (mtDNA: D-loop, ATPase 8, TRNALEU uur) in the long-term treatment group. Interpretation and Conclusion: Long-term treatment with HAART increases oxidative stress and causes mitochondrial alterations in HIV patients.

Necessity of Intraventricular Chemotherapy with the Modified Bonn Protocol in Primary CNS Lymphoma (PCNSL) Patients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2452-2452
Author(s):  
Ingo G.H. Schmidt-Wolf ◽  
Hendrik Pels ◽  
Annika Juergens ◽  
Axel Glasmacher ◽  
Holger Schulz ◽  
...  
Keyword(s):  
Primary Cns Lymphoma ◽  
Progression Free Survival ◽  
Cns Lymphoma ◽  
High Dose ◽  
Free Survival ◽  
Intraventricular Chemotherapy ◽  
High Infection ◽  
Intraventricular Treatment

Abstract Background: Treatment of primary CNS lymphoma (PCNSL) with a combined systemic and intraventricular chemotherapy (Bonn protocol) has achieved an overall response rate (ORR) of 84% and long term complete remissions in a substantial fraction of patients younger than 60 years. Purpose: Due to a high infection rate of the Ommaya reservoir the question was addressed if intraventricular treatment is dispensable in this polychemotherapy protocol. Patients and Methods: Fifty patients with histologically confirmed PCNSL were enrolled onto a phase II-study evaluating chemotherapy without radiotherapy and without intraventricular treatment. A high-dose methotrexate (MTX) (cycles 1,2,4,5) and cytarabine (ara-C) (cycles 3,6) based systemic therapy (including dexamethasone, vinca-alkaloids, ifosfamide and cyclophosphamide) was administered. Results: In an ongoing trial thirty-five of 50 patients (18 pat. < 60 years, 17 pat. over 60 years) are yet assessable for response after a median follow up of nine months (range: 1 to 26 months). In 18 patients < 60 years, the ORR was 78%. However, median time to treatment failure (TTF) was eight months, and median progression free survival (PFS) only 7 months according to frequent early relapses. Conclusions: Early relapses are frequent in younger patients treated with the modified Bonn protocol without intraventricular treatment despite a high ORR. These preliminary results support the assumption that intraventricular treatment is essential to achieve sustained remissions after successful treatment of PCNSL.

Safety of dienogest in the long-term treatment of endometriosis: a one-year, open-label, follow-up study

2009 ◽  
Vol 92 (3) ◽  
pp. S107 ◽  
Author(s):  
C. Seitz ◽  
C. Gerlinger ◽  
T. Faustmann ◽  
T. Strowitzki
Keyword(s):  
Term Treatment ◽  
Open Label ◽  
Follow Up Study ◽  
Long Term Treatment ◽  
One Year

scholarly journals Continuous bubble streams for controlling marine biofouling on static artificial structures

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11323
Author(s):  
Grant A. Hopkins ◽  
Fletcher Gilbertson ◽  
Oli Floerl ◽  
Paula Casanovas ◽  
Matt Pine ◽  
...  
Keyword(s):  
Field Measurements ◽  
Field Trials ◽  
Term Treatment ◽  
Future Studies ◽  
Artificial Structures ◽  
Marine Biofouling ◽  
Long Term Treatment ◽  
One Year ◽  
Shear Stress Field

Biofouling accumulation is not proactively managed on most marine static artificial structures (SAS) due to the lack of effective options presently available. We describe a series of laboratory and field trials that examine the efficacy of continuous bubble streams in maintaining SAS free of macroscopic biofouling and demonstrate that this treatment approach is effective on surface types commonly used in the marine environment. At least two mechanisms were shown to be at play: the disruption of settlement created by the bubble stream, and the scouring of recently settled larvae through shear stress. Field trials conducted over a one-year period identified fouling on diffusers as a major issue to long-term treatment applications. Field measurements suggest that noise associated with surface mounted air blowers and sub-surface diffusers will be highly localised and of low environmental risk. Future studies should aim to develop and test systems at an operational scale.

scholarly journals Long-term effectiveness and prediction of treatment outcome in cognitive behavioral therapy and sertraline for late-life anxiety disorders

2009 ◽  
Vol 21 (6) ◽  
pp. 1148-1159 ◽  
Author(s):  
Josien Schuurmans ◽  
Hannie Comijs ◽  
Paul M. G. Emmelkamp ◽  
Ingrid J. C. Weijnen ◽  
Marcel van den Hout ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
Anxiety Disorders ◽  
Behavioral Therapy ◽  
Late Life ◽  
Term Treatment ◽  
Short Term ◽  
Long Term Treatment ◽  
One Year

ABSTRACTBackground: Although anxiety disorders are prevalent in older adults, randomized controlled trials of treatment effectiveness for late-life anxiety are scarce and have focused primarily on the effectiveness of psychotherapeutic interventions. However, recent findings suggest that in some cases, pharmacological treatment may be more beneficial for late-life anxiety disorders. As yet, there have been no systematic studies investigating prognostic factors for the outcome of cognitive behavioral therapy (CBT) and pharmacotherapy for late-life anxiety. The objective of the present study was to study long-term treatment outcomes and to explore differential predictors for both short-term and long-term treatment outcomes of sertraline and CBT for late-life anxiety disorders.Methods: Participants of a randomized controlled trial (RCT) comparing sertraline and CBT for the treatment of late-life anxiety were contacted one year after completing their treatment, so that predictors for both short-term and long-term treatment outcome could be established.Results: Sertraline showed a greater reduction of symptoms than CBT on anxiety (Hamilton Anxiety Rating Scale; HARS) and worry (Worry Domain Questionnaire) ratings at one-year follow-up. The strongest predictor for short-term CBT outcome was poor perceived health, explaining 40% of the variance in post-treatment residual gain scores on the HARS. The strongest predictor for long-term CBT outcome was neuroticism, explaining 20% of the variance in residual gain scores at one-year follow-up. Analyses revealed no significant predictors for treatment outcome in sertraline participants.Conclusions: Our study suggests that long-term use of sertraline might be more beneficial for late-life anxiety than a 15-week CBT program. Poor perceived health and neuroticism are predictive of less improvement after CBT in anxious older adults. Implications of these findings are discussed.

Report Form for Aggressive Episodes: Preliminary Report

1996 ◽  
Vol 83 (3_suppl) ◽  
pp. 1139-1152 ◽  
Author(s):  
Stål Bjørkly
Keyword(s):  
Preliminary Report ◽  
Rating Scale ◽  
Term Treatment ◽  
Clinical Use ◽  
Long Term Treatment ◽  
Case Vignettes ◽  
Secure Unit ◽  
One Year ◽  
Very High

This paper gives a description of the development and initial empirical testing of the Report Form for Aggressive Episodes, a behavioural rating scale used to measure displayed aggressive behaviour and the situational determinant(s) according to a list of 30 potential precipitants to aggression. Findings from a one-year study in a special secure unit for the long-term treatment of dangerous patients show very high rates of underreporting of aggressive episodes in ward journals and patient files compared to this scale. Illustrations of the clinical use of the scale are provided by scoring examples and two case vignettes.

Long-Term Treatment of Angina Pectoris with Carteolol: A New Beta-Adrenergic Receptor Blocking Agent

1986 ◽  
Vol 14 (4) ◽  
pp. 167-174 ◽  
Author(s):  
Robert R Luther ◽  
Harriet N Glassman ◽  
David C Jordan ◽  
Michael J Klepper ◽  
Keyword(s):  
Heart Rate ◽  
Angina Pectoris ◽  
Treatment Phase ◽  
Blocking Agent ◽  
Term Treatment ◽  
Double Product ◽  
Long Term Treatment ◽  
Exercise Induced ◽  
One Year

Seventy-two patients entered the treatment phase of an open, long-term, dose-ranging trial of carteolol in stable, exercise-induced angina pectoris. Patients were to be treated with progressive doses of carteolol (2.5, 5, 10, 20, 40, and 60 mg), given as a single daily oral dose. Thirty of the patients (42%) completed one year of treatment with carteolol as the sole antianginal therapy. The most frequent final carteolol doses were 20 mg and 40 mg once daily. Statistically significant improvements from baseline in exercise tolerance as reflected in time to onset of angina, time to the endpoint of exercise and time to the onset of 1 mm S-T segment change on ECG were observed in carteolol-treated patients. Exercise-induced increases in heart rate and double-product were significantly suppressed, compared to baseline, throughout the study. Resting heart rate and double-product were modestly decreased. Carteolol was shown to be effective and safe when administered on a long-term basis to patients with angina pectoris.

scholarly journals Long-Term Disease Control by Pomalidomide-/Dexamethasone-Based Therapy in a Patient with Advanced Multiple Myeloma: A Case Report and Review of the Literature

2015 ◽  
Vol 8 (1) ◽  
pp. 189-195 ◽  
Author(s):  
Sophia Danhof ◽  
Martin Schreder ◽  
Susanne Strifler ◽  
Hermann Einsele ◽  
Stefan Knop
Keyword(s):  
Multiple Myeloma ◽  
Case Report ◽  
Proteasome Inhibitors ◽  
Progression Free Survival ◽  
Infectious Complications ◽  
Term Treatment ◽  
Novel Agents ◽  
Virus Reactivation ◽  
Long Term Treatment

Background: Therapy for multiple myeloma (MM) has substantially improved in the era of immunomodulatory drugs and bortezomib. However, the prognosis of patients with progressive disease despite treatment with these ‘novel agents' remains poor. Recently, pomalidomide was approved in this setting, but a median progression-free survival of <4 months still leaves room for improvement. Pomalidomide-based combination therapies are currently under investigation, but data on long-term treatment are lacking. Case Report: We present the case of a 68-year-old woman with refractory MM who received pomalidomide in combination with various drugs including anthracyclines, alkylators and proteasome inhibitors. Initially, major hematological toxicities and infectious complications including a hepatitis B virus reactivation were encountered. With careful dose adjustments and selection of combination partners, pomalidomide treatment was maintained for over 4 years and led to a sustained partial remission. In particular, the well-tolerated regimen of bortezomib, cyclophosphamide and dexamethasone together with pomalidomide was administered for >30 cycles. Conclusion: This case illustrates the value of an individualized approach to myeloma care given an increasing availability of ‘novel agents'. Tailored treatment using these drugs as a backbone is essential to achieve long-lasting responses and minimize side effects.

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