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Journal of the American Academy of... Jan 2022The heterogeneous course of moderate-to-severe atopic dermatitis necessitates treatment flexibility. (Randomized Controlled Trial)
Randomized Controlled Trial
Abrocitinib induction, randomized withdrawal, and retreatment in patients with moderate-to-severe atopic dermatitis: Results from the JAK1 Atopic Dermatitis Efficacy and Safety (JADE) REGIMEN phase 3 trial.
BACKGROUND
The heterogeneous course of moderate-to-severe atopic dermatitis necessitates treatment flexibility.
OBJECTIVE
We evaluated the maintenance of abrocitinib-induced response with continuous abrocitinib treatment, dose reduction or withdrawal, and response to treatment reintroduction following flare (JAK1 Atopic Dermatitis Efficacy and Safety [JADE] REGIMEN: National Clinical Trial 03627767).
METHODS
Patients with moderate-to-severe atopic dermatitis responding to open-label abrocitinib 200 mg monotherapy for 12 weeks were randomly assigned in a 1:1:1 ratio to blinded abrocitinib (200 or 100 mg) or placebo for 40 weeks. Patients experiencing flare received rescue treatment (abrocitinib 200 mg plus topical therapy).
RESULTS
Of 1233 patients, 798 responders to induction (64.7%) were randomly assigned. The flare probability during maintenance was 18.9%, 42.6%, and 80.9% with abrocitinib 200 mg, abrocitinib 100 mg, and placebo, respectively. Among patients with flare in the abrocitinib 200 mg, abrocitinib 100 mg, and placebo groups, 36.6%, 58.8%, and 81.6% regained investigator global assessment 0/1 response, respectively, and 55.0%, 74.5%, and 91.8% regained eczema area and severity index response, respectively, with rescue treatment. During maintenance, 63.2% and 54.0% of patients receiving abrocitinib 200 and 100 mg, respectively, experienced adverse events.
LIMITATIONS
The definition of protocol-defined flare was not established, limiting the generalizability of findings.
CONCLUSION
Induction treatment with abrocitinib was effective; most responders continuing abrocitinib did not flare. Rescue treatment with abrocitinib plus topical therapy effectively recaptured response.
Topics: Dermatitis, Atopic; Double-Blind Method; Humans; Janus Kinase 1; Pyrimidines; Retreatment; Severity of Illness Index; Sulfonamides; Treatment Outcome
PubMed: 34416294
DOI: 10.1016/j.jaad.2021.05.075 -
Journal of Physiotherapy 2012Does an exercise training program improve the quality of sleep in middle-aged and older adults with sleep problems? (Review)
Review
QUESTION
Does an exercise training program improve the quality of sleep in middle-aged and older adults with sleep problems?
DESIGN
Systematic review with meta-analysis of randomised trials.
PARTICIPANTS
Adults aged over 40 years with sleep problems.
INTERVENTION
A formal exercise training program consisting of either aerobic or resistance exercise.
OUTCOME MEASURES
Self-reported sleep quality or polysomnography.
RESULTS
Six trials were eligible for inclusion and provided data on 305 participants (241 female). Each of the studies examined an exercise training program that consisted of either moderate intensity aerobic exercise or high intensity resistance exercise. The duration of most of the training programs was between 10 and 16 weeks. All of the studies used the self-reported Pittsburgh Sleep Quality Index to assess sleep quality. Compared to the control group, the participants who were randomised to an exercise program had a better global Pittsburgh Sleep Quality Index score, with a standardised mean difference (SMD) of 0.47 (95% CI 0.08 to 0.86). The exercise group also had significantly reduced sleep latency (SMD 0.58, 95% CI 0.08 to 1.08), and medication use (SMD 0.44, 95% CI 0.14 to 0.74). However, the groups did not differ significantly in sleep duration, sleep efficiency, sleep disturbance, or daytime functioning.
CONCLUSION
Participation in an exercise training program has moderately positive effects on sleep quality in middle-aged and older adults. Physical exercise could be an alternative or complementary approach to existing therapies for sleep problems.
Topics: Aged; Complementary Therapies; Exercise; Humans; Middle Aged; Resistance Training; Sleep; Sleep Initiation and Maintenance Disorders
PubMed: 22884182
DOI: 10.1016/S1836-9553(12)70106-6 -
Frontiers in Immunology 2021Although the majority of patients with acute myeloid leukemia (AML) treated with intensive chemotherapy achieve a complete remission (CR), many are destined to relapse... (Review)
Review
Although the majority of patients with acute myeloid leukemia (AML) treated with intensive chemotherapy achieve a complete remission (CR), many are destined to relapse if treated with intensive chemotherapy alone. Allogeneic stem cell transplant (allo-SCT) represents a pivotally important treatment strategy in fit adults with AML because of its augmented anti-leukemic activity consequent upon dose intensification and the genesis of a potent graft-versus-leukemia effect. Increased donor availability coupled with the advent of reduced intensity conditioning (RIC) regimens has dramatically increased transplant access and consequently allo-SCT is now a key component of the treatment algorithm in both patients with AML in first CR (CR1) and advanced disease. Although transplant related mortality has fallen steadily over recent decades there has been no real progress in reducing the risk of disease relapse which remains the major cause of transplant failure and represents a major area of unmet need. A number of therapeutic approaches with the potential to reduce disease relapse, including advances in induction chemotherapy, the development of novel conditioning regimens and the emergence of the concept of post-transplant maintenance, are currently under development. Furthermore, the use of genetics and measurable residual disease technology in disease assessment has improved the identification of patients who are likely to benefit from an allo-SCT which now represents an increasingly personalized therapy. Future progress in optimizing transplant outcome will be dependent on the successful delivery by the international transplant community of randomized prospective clinical trials which permit examination of current and future transplant therapies with the same degree of rigor as is routinely adopted for non-transplant therapies.
Topics: Acute Disease; Adult; Disease-Free Survival; Graft vs Leukemia Effect; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid; Remission Induction; Transplantation Conditioning; Transplantation, Homologous
PubMed: 34012445
DOI: 10.3389/fimmu.2021.659595 -
Gynecologic Oncology Aug 2022To assess safety and efficacy of niraparib + bevacizumab as a first-line maintenance therapy for patients with newly diagnosed advanced ovarian cancer.
OVARIO phase II trial of combination niraparib plus bevacizumab maintenance therapy in advanced ovarian cancer following first-line platinum-based chemotherapy with bevacizumab.
OBJECTIVE
To assess safety and efficacy of niraparib + bevacizumab as a first-line maintenance therapy for patients with newly diagnosed advanced ovarian cancer.
METHODS
This multicenter, phase II, single-arm, open-label study enrolled adult patients with stage IIIB to IV ovarian, fallopian tube, or primary peritoneal cancer (NCT03326193). Patients were required to have an attempt at debulking surgery and have a complete response, partial response, or no evidence of disease following first-line, platinum-based chemotherapy with ≥3 cycles of bevacizumab. The primary endpoint was the progression-free survival (PFS) rate at 18 months. Secondary endpoints included PFS, overall survival, and safety.
RESULTS
Among the 105 evaluable patients, the PFS rate at 18 months was 62% (95% CI 52-71%) in the overall population and 76% (95% CI 61-87) in the homologous recombination deficient (HRd), 47% (95% CI 31-64%) in the HR proficient (HRp), and 56% (95% CI 31-79%) in the HR not determined (HRnd) subgroups (December 24, 2020, cutoff). After a median follow-up time of 28.7 months (IQR, 23.9-32.5 months), median PFS was 19.6 months (95% CI 16.5-25.1) in the overall population (N = 105) and 28.3 months (95% CI 19.9-NE), 14.2 months (95% CI 8.6-16.8), and 12.1 months (95% CI 8.0-NE) in the HRd, HRp, and HRnd subgroups, respectively (June 16, 2021, cutoff). The most common any-grade treatment-related adverse events (related to niraparib and/or bevacizumab) were thrombocytopenia (74/105), fatigue (60/105), and anemia (55/105; December 24, 2020, cutoff).
CONCLUSION
Niraparib + bevacizumab first-line maintenance therapy displayed promising PFS results. Safety was consistent with the known safety profiles of niraparib and bevacizumab as monotherapy.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Female; Humans; Indazoles; Maintenance Chemotherapy; Ovarian Neoplasms; Piperidines; Platinum
PubMed: 35690498
DOI: 10.1016/j.ygyno.2022.05.020 -
Journal of the American Academy of... Mar 2019
Topics: Adrenal Cortex Hormones; Alopecia; Anti-Bacterial Agents; Dermatologic Agents; Drug Therapy, Combination; Evidence-Based Medicine; Folliculitis; Humans; Maintenance Chemotherapy; Recurrence; Remission Induction
PubMed: 30092322
DOI: 10.1016/j.jaad.2018.07.050 -
International Journal of Yoga Therapy Jan 2021Extended sleep onset latency (SOL), or "sleep onset insomnia," can decrease total sleep time, increasing risk for many health conditions, including heart disease,... (Randomized Controlled Trial)
Randomized Controlled Trial
Extended sleep onset latency (SOL), or "sleep onset insomnia," can decrease total sleep time, increasing risk for many health conditions, including heart disease, stroke, and all-cause mortality. Sleep disorders persist in the United States despite current behavioral/pharmaceutical remedies, with 10% to 15% of the population suffering from insomnia. Mind-body therapies offer additional solutions, as meditation has been correlated with decreased SOL. More research on use of mind-body practices for insomnia is needed. This study investigates the guided meditation practice of Yoga Nidra (yogic sleep) as a promising intervention for sleep disorders because of its purported ability to induce mental, physical, and emotional relaxation. In this pilot study, we address the feasibility of Yoga Nidra for insomnia, appropriateness of our selected measurement systems, and effect of Yoga Nidra on brainwaves, sleep onset, and the autonomic nervous system. Our study sample includes 22 adults, ages 18-45, with insomnia. The design includes two clinic visits (V1, lying quietly for 90 min; V2, randomization to 90-min lying quietly vs. 30-min Yoga Nidra plus 60-min lying quietly), taking place 1 to 14 days apart. Outcomes measured during/after Yoga Nidra (vs. control) include sleep onset, electroencephalography (EEG) power, heart rate variability (HRV), and respiratory rate. Self-reported mood and anxiety will be measured before/after each visit. Resulting physiological, psychological, and feasibility data will be used to inform future clinical studies of Yoga Nidra for sleep and relaxation.
Topics: Adolescent; Adult; Humans; Meditation; Middle Aged; Pilot Projects; Sleep; Sleep Initiation and Maintenance Disorders; Yoga; Young Adult
PubMed: 33175980
DOI: 10.17761/2021-D-20-00004 -
JAMA Oncology Mar 2020In metastatic colorectal cancer, induction combination chemotherapy with a targeted agent is considered the mainstay of treatment. Multiple randomized clinical trials... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
In metastatic colorectal cancer, induction combination chemotherapy with a targeted agent is considered the mainstay of treatment. Multiple randomized clinical trials have examined different strategies of continuing cytotoxic therapy until progression compared with a period of either observation or the use of various maintenance agents. However, those randomized clinical trials have shown inconsistent efficacy results that make it challenging to draw any conclusion on which strategy is preferred. Therefore, a network meta-analysis is helpful to compare different agents across randomized clinical trials.
OBJECTIVE
To evaluate the comparative effectiveness of different treatment strategies for patients with metastatic colorectal cancer.
EVIDENCE REVIEW
MEDLINE, Embase, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials were searched for randomized clinical trials evaluating different strategies for patients with previously untreated metastatic colorectal cancer. Trials of interest included those including patients with metastatic colorectal cancer who were treated with an initial period of cytotoxic chemotherapy (with or without a biologic) and then switched to one of the following strategies: observation; maintenance with bevacizumab (Bev), fluoropyrimidine (FP), or both (FP + Bev); or continuing the induction regimen until progression. Outcomes of interest included overall survival (OS) and progression-free survival (PFS). The overall effect was pooled using the DerSimonian and Laird random-effects model. Network meta-analysis was conducted using a random-effects consistency model to pool evidence from direct and indirect comparisons. Agents were ranked using surface under the cumulative ranking (SUCRA) probabilities. Higher SUCRA scores correspond to greater efficacy. Initial analysis was performed on December 18, 2018. An updated search was performed in April 2019, and no additional studies were added.
FINDINGS
Twelve trials at low risk of bias (5540 patients; age range, 23-85 years; 64.4 % male) were included. Network meta-analysis showed no benefit of continuing full cytotoxic chemotherapy until progression vs observation in terms of PFS (hazard ratio, 0.71; 95% CI, 0.46-1.09) and OS (hazard ratio, 0.95; 95% CI, 0.85-1.07). Compared with observation, maintenance therapy showed a PFS benefit (hazard ratio, 0.58; 95% CI, 0.43-0.77) but not an OS benefit (hazard ratio, 0.91; 95% CI, 0.83-1.01). All maintenance strategies (FP, FP + Bev, and Bev) showed significant improvement in PFS vs observation. On SUCRA analysis, maintenance treatment (FP or FP + Bev) had the highest likelihood of achieving improved PFS (67.1% for FP, 99.8% for FP + Bev, and 36.5% for Bev) and OS (81.3% for FP, 73.2% for FP + Bev, and 32.6% for Bev).
CONCLUSIONS AND RELEVANCE
For patients with metastatic colorectal cancer, there is no benefit to continuing the full induction regimen until progression, without a period of either observation or maintenance treatment. A maintenance strategy with a fluoropyrimidine, with or without the addition of bevacizumab, is preferred. However, given the lack of a clear OS benefit, shared decision-making should include observation as an acceptable alternative.
Topics: Colorectal Neoplasms; Humans; Maintenance Chemotherapy; Network Meta-Analysis; Randomized Controlled Trials as Topic
PubMed: 31855256
DOI: 10.1001/jamaoncol.2019.4489 -
International Journal of Molecular... Apr 2019Telomerase, an enzyme responsible for the synthesis of telomeres, is activated in many cancer cells and is involved in the maintenance of telomeres. The activity of... (Review)
Review
Telomerase, an enzyme responsible for the synthesis of telomeres, is activated in many cancer cells and is involved in the maintenance of telomeres. The activity of telomerase allows cancer cells to replicate and proliferate in an uncontrolled manner, to infiltrate tissue, and to metastasize to distant organs. Studies to date have examined the mechanisms involved in the survival of cancer cells as targets for cancer therapeutics. These efforts led to the development of telomerase inhibitors as anticancer drugs, drugs targeting telomere DNA, viral vectors carrying a promoter for human telomerase reverse transcriptase (hTERT) genome, and immunotherapy targeting hTERT. Among these novel therapeutics, this review focuses on immunotherapy targeting hTERT and discusses the current evidence and future perspectives.
Topics: Animals; Antigens, Neoplasm; Antineoplastic Agents; Cancer Vaccines; Cell- and Tissue-Based Therapy; Dendritic Cells; Genetic Therapy; Humans; Immunotherapy; Molecular Targeted Therapy; Neoplasms; Telomerase; Vaccines, DNA
PubMed: 31013796
DOI: 10.3390/ijms20081823 -
Blood Reviews Sep 2021Relapse in acute myeloid leukemia (AML) is common, especially in older patients, and there is currently no standard of care maintenance therapy for those who achieve... (Review)
Review
Relapse in acute myeloid leukemia (AML) is common, especially in older patients, and there is currently no standard of care maintenance therapy for those who achieve complete remission. Finding effective, tolerable maintenance therapy to prolong remission has been a goal for decades, but early clinical trials testing a variety of agents demonstrated disappointing results with no overall survival benefit. CC-486, an oral hypomethylating agent, was recently approved in the United States for maintenance treatment in patients with AML in first remission following chemotherapy. A number of ongoing studies are assessing various therapeutics in the maintenance setting, including other hypomethylating agents, targeted small-molecule inhibitors, monoclonal antibodies, and immunomodulators. New strategies are needed to identify patients most likely to benefit from maintenance therapy, including those for whom a preemptive approach reliant on monitoring of measurable residual disease would be advantageous.
Topics: Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Azacitidine; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Maintenance Chemotherapy; Remission Induction; Survival Analysis
PubMed: 33832807
DOI: 10.1016/j.blre.2021.100829 -
Annals of Oncology : Official Journal... Oct 2010Multiple myeloma (MM) is the second most common hematological malignancy, with an incidence of 6/100,000 in Europe. Interactions between myeloma cells and the... (Review)
Review
Multiple myeloma (MM) is the second most common hematological malignancy, with an incidence of 6/100,000 in Europe. Interactions between myeloma cells and the microenvironment are essential for MM cell survival. Better knowledge of disease biology has led to the introduction of novel agents for the management of myeloma patients. Patients with asymptomatic MM may remain stable for a long time without any therapy, and treatment is needed only in symptomatic disease. Patients who are eligible for high-dose therapy and autologous stem cell transplantation (ASCT) are usually treated with bortezomib- or immunomodulatory drug (IMiD)-based regimens as induction therapy pre-ASCT. In elderly patients, the combination of melphalan and prednisone with either thalidomide (MPT) or bortezomib (MPV) is considered as the standard of care in this setting. Novel agent-based therapies are used for the management of relapsed/refractory disease. However, previous therapies, age, comorbidities and drug safety have to be taken into consideration before deciding the appropriate therapy for patients with relapsed/refractory myeloma. Patients with renal impairment or with extended bone disease may be treated with bortezomib-based regimens, while patients with pre-existing peripheral neuropathy may be treated with lenalidomide-based combinations. Maintenance therapy with thalidomide can be administered post-ASCT; however, caution is needed due to thalidomide toxicity.
Topics: Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Genomic Instability; Hematopoietic Stem Cell Transplantation; Humans; Multiple Myeloma; Thalidomide; Transplantation, Autologous
PubMed: 20943607
DOI: 10.1093/annonc/mdq370