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Pain Jan 2024This preregistered (CRD42021223379) systematic review and meta-analysis aimed to characterize the placebo and nocebo responses in placebo-controlled randomized clinical... (Meta-Analysis)
Meta-Analysis
This preregistered (CRD42021223379) systematic review and meta-analysis aimed to characterize the placebo and nocebo responses in placebo-controlled randomized clinical trials (RCTs) on painful diabetic neuropathy (PDN), updating the previous literature by a decade. Four databases were searched for PDN trials published in the past 20 years, testing oral medications, adopting a parallel-group design. Magnitude of placebo or nocebo responses, Cochrane risk of bias, heterogeneity, and moderators were evaluated. Searches identified 21 studies (2425 placebo-treated patients). The overall mean pooled placebo response was -1.54 change in the pain intensity from baseline [95% confidence interval (CI): -1.52, -1.56, I 2 = 72], with a moderate effect size (Cohen d = 0.72). The pooled placebo 50% response rate was 25% [95% CI: 22, 29, I 2 = 50%]. The overall percentage of patients with adverse events (AEs) in the placebo arms was 53.3% [95% CI: 50.9, 55.7], with 5.1% [95% CI: 4.2, 6] of patients dropping out due to AEs. The year of study initiation was the only significant moderator of placebo response (regression coefficient = -0.06, [95% CI: -0.10, -0.02, P = 0.007]). More recent RCTs tended to be longer, bigger, and to include older patients (N = 21, rs = 0.455, P = 0.038, rs = 0.600, P = 0.004, rs = 0.472, P = 0.031, respectively). Our findings confirm the magnitude of placebo and nocebo responses, identify the year of study initiation as the only significant moderator of placebo response, draw attention to contextual factors such as confidence in PDN treatments, patients' previous negative experiences, intervention duration, and information provided to patients before enrollment.
Topics: Humans; Nocebo Effect; Diabetic Neuropathies; Placebo Effect; Pain Measurement; Diabetes Mellitus
PubMed: 37530658
DOI: 10.1097/j.pain.0000000000003000 -
Annals of Allergy, Asthma & Immunology... Sep 2023Tezepelumab, a human monoclonal antibody, blocks thymic stromal lymphopoietin. In the phase 3 NAVIGATOR study, tezepelumab reduced exacerbations and improved lung... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Tezepelumab, a human monoclonal antibody, blocks thymic stromal lymphopoietin. In the phase 3 NAVIGATOR study, tezepelumab reduced exacerbations and improved lung function, asthma control, and health-related quality of life compared with placebo in patients with severe, uncontrolled asthma. However, little is known about the impact of tezepelumab on healthcare utilization (HCU) in these patients.
OBJECTIVE
To evaluate to what extent tezepelumab reduces patients' HCU.
METHODS
In NAVIGATOR, patients were randomized to receive subcutaneous tezepelumab 210 mg or placebo, every 4 weeks for 52 weeks. For this analysis, the main outcomes of interest were asthma-related HCU. A blinded, systematic analysis of the symptoms and HCU recorded in the investigator-reported narratives describing exacerbation-related hospitalizations was also conducted; the narratives included blinded ratings of event intensity, recorded as mild, moderate, or severe.
RESULTS
Recipients of tezepelumab (n = 528) required fewer asthma-related unscheduled specialist visits (tezepelumab, 285 events; placebo, 406 events), telephone calls with a healthcare provider (tezepelumab, 234; placebo, 599), ambulance transports (tezepelumab, 5; placebo, 22), emergency department visits (without subsequent hospitalization; tezepelumab, 16; placebo, 37), hospitalizations (tezepelumab, 14; placebo, 78), and intensive care days (tezepelumab, 0; placebo, 31) than did recipients of placebo (n = 531). Among patients with asthma exacerbation-related hospitalizations, 38% of those hospitalized and receiving tezepelumab (5/13) had an event rated as severe, compared with 82% of those hospitalized and receiving placebo (32/39).
CONCLUSION
Tezepelumab substantially reduced HCU across all outcomes measured compared with placebo, in addition to the severity of asthma exacerbations requiring hospitalization. Tezepelumab can reduce the overall burden of disease of severe, uncontrolled asthma.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov (https://clinicaltrials.gov/ct2/home), identifier: NCT03347279.
Topics: Humans; Anti-Asthmatic Agents; Quality of Life; Asthma; Patient Acceptance of Health Care; Double-Blind Method
PubMed: 37263380
DOI: 10.1016/j.anai.2023.05.028 -
Sleep Medicine Oct 2023To examine the effects of lemborexant (LEM) 5 mg (LEM5) or LEM 10 mg (LEM10) following extended placebo treatment. This post-hoc analysis used subject-reported sleep... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE/BACKGROUND
To examine the effects of lemborexant (LEM) 5 mg (LEM5) or LEM 10 mg (LEM10) following extended placebo treatment. This post-hoc analysis used subject-reported sleep outcomes data from a phase 3 trial.
PATIENTS/METHODS
The subjects in these post-hoc analyses were randomized to placebo for 6 months (Time Period [TP]1) in Study E2006-G000-303 (SUNRISE-2; NCT02952820). Following placebo exposure, subjects were re-randomized to LEM5 or LEM10 for another 6 months (TP2). Subject-reported sleep outcomes derived from sleep diaries included sleep onset latency (sSOL), wake after sleep onset (sWASO), sleep efficiency (sSE), and total sleep time (sTST). Magnitude and change rate in parameters were assessed for 7 days before/after initial randomization to placebo and 7 days before/after re-randomization to LEM (6 months later). Month 6 placebo non-responders were assessed for LEM response in TP2 using predetermined responder definitions. Safety was monitored throughout the study.
RESULTS
Overall, 321 subjects received placebo; 258 re-randomized subjects received LEM5 (n = 133) and LEM10 (n = 125). Subjective sleep outcomes improved during TP1 with approximately 62 subjects (∼20%) exhibiting a sustained placebo response. Upon re-randomization to LEM, all measures showed an additional incremental benefit, most prominently in sSOL and sTST. Among Month 6 placebo non-responders, 11%-15% subsequently responded to LEM as assessed at Month 12. The safety profile was similar between treatment periods and treatment groups.
CONCLUSIONS
These data suggest that even when insomnia symptoms have improved over time with placebo treatment, additional and sustained clinical gains in sleep outcomes are possible with active treatment using lemborexant.
Topics: Humans; Double-Blind Method; Pyridines; Sleep Initiation and Maintenance Disorders; Sleep; Treatment Outcome
PubMed: 37574610
DOI: 10.1016/j.sleep.2023.07.023 -
Current Oncology Reports May 2024This paper aims to address the latest findings in neuroendocrine tumor (NET) theranostics, focusing on new evidence and future directions of combined diagnosis with... (Review)
Review
PURPOSE OF REVIEW
This paper aims to address the latest findings in neuroendocrine tumor (NET) theranostics, focusing on new evidence and future directions of combined diagnosis with positron emission tomography (PET) and treatment with peptide receptor radionuclide therapy (PRRT).
RECENT FINDINGS
Following NETTER-1 trial, PRRT with [177Lu]Lu-DOTATATE was approved by FDA and EMA and is routinely employed in advanced G1 and G2 SST (somatostatin receptor)-expressing NET. Different approaches have been proposed so far to improve the PRRT therapeutic index, encompassing re-treatment protocols, combinations with other therapies and novel indications. Molecular imaging holds a potential added value in characterizing disease biology and heterogeneity using different radiopharmaceuticals (e.g., SST and FDG) and may provide predictive and prognostic parameters. Response assessment criteria are still an unmet need and new theranostic pairs showed preliminary encouraging results. PRRT for NET has become a paradigm of modern theranostics. PRRT holds a favorable toxicity profile, and it is associated with a prolonged time to progression, reduction of symptoms, and improved patients' quality of life. In light of further optimization, different new strategies have been investigated, along with the development of new radiopharmaceuticals.
Topics: Humans; Neuroendocrine Tumors; Radiopharmaceuticals; Octreotide; Positron-Emission Tomography; Receptors, Peptide; Theranostic Nanomedicine; Radioisotopes; Organometallic Compounds
PubMed: 38581469
DOI: 10.1007/s11912-024-01526-5 -
Balkan Medical Journal Sep 2023Anticoagulants are the mainstay of treatment for venous thromboembolism (VTE). Studies have shown conflicting results regarding statins ability to reduce the incidence... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Anticoagulants are the mainstay of treatment for venous thromboembolism (VTE). Studies have shown conflicting results regarding statins ability to reduce the incidence of VTE.
AIMS
To perform a network meta-analysis to determine which lipid-lowering agent was more efficacious in and had more evidence regarding reducing the VTE risk.
STUDY DESIGN
Network meta-analysis of the randomized controlled trials (RCTs).
METHODS
RCTs that assessed the effectiveness and safety of statins or fibrates and compared them to a placebo or another statin were eligible for the study. The outcomes examined in the study were deep vein thrombosis, pulmonary embolism, and/or VTE. We conducted a comprehensive search of the Medline database from 1966 to February 2017, using specific search terms related to VTE and statins. Additionally, we screened, and cross-checked relevant systematic reviews and meta-analyses. We performed a network meta-analysis to compare the different lipid-lowering agents to each other and the placebo and their effectiveness.
RESULTS
Twenty-seven RCTs were included in the network meta-analysis (n = 137,940). Pairwise meta-analysis revealed a statistically significant lower incidence of VTE with statins than with placebos (0.79% vs 0.99%, respectively; risk ratios: 0.87, 0.77-0.98; = 0.022). Rosuvastatin had the most favorable effect in reducing VTE risk than the other statins, fenofibrate, and placebo. Fenofibrate was ranked the worst drug choice, because it increased risk of VTE when compared with the other statins. Rosuvastatin was the best choice for reducing the VTE risk when compared with the placebo (OR: 0.56, 0.42-0.75), atorvastatin (OR: 0.64, 0.44-0.95), pravastatin (OR: 0.50, 0.34-0.74), simvastatin (OR: 0.60, 0.42-0.86) and fenofibrate (OR: 0.37, 0.25-0.56). Compared with a placebo, rosuvastatin reduced the VTE risk by around 45% and fenofibrate increased the risk by 65%.
CONCLUSION
Rosuvastatin is significantly reduces the risk of VTE when compared with a placebo, other statin subtypes, and fibrate. Furthermore, fenofibrate increased the VTE risk when compared with a placebo and statins.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Venous Thromboembolism; Rosuvastatin Calcium; Fenofibrate; Network Meta-Analysis; Atorvastatin
PubMed: 37519020
DOI: 10.4274/balkanmedj.galenos.2023.2023-5-26 -
Biological Psychiatry Global Open... Oct 2023Psychosis is characterized by unusual percepts and beliefs in the form of hallucinations and delusions. Antipsychotic medication, the primary treatment for psychosis, is... (Review)
Review
Psychosis is characterized by unusual percepts and beliefs in the form of hallucinations and delusions. Antipsychotic medication, the primary treatment for psychosis, is often ineffective and accompanied by severe side effects, but research has not identified an effective alternative in several decades. One reason that clinical trials fail is that patients with psychosis tend to show a significant therapeutic response to inert control treatments, known as the placebo effect, which makes it difficult to distinguish drug effects from placebo effects. Conversely, in clinical practice, a strong placebo effect may be useful because it could enhance the overall treatment response. Identifying factors that predict large placebo effects could improve the future outlook of psychosis treatment. Biomarkers of the placebo effect have already been suggested in pain and depression, but not in psychosis. Quantifying markers of the placebo effect would have the potential to predict placebo effects in psychosis clinical trials. Furthermore, the placebo effect and psychosis may represent a shared neurocognitive mechanism in which prior beliefs are weighted against new sensory information to make inferences about reality. Examining this overlap could reveal new insights into the mechanisms underlying psychosis and indicate novel treatment targets. We provide a narrative review of the importance of the placebo effect in psychosis and propose a novel method to assess it.
PubMed: 37881581
DOI: 10.1016/j.bpsgos.2023.02.008 -
Molecular Diagnosis & Therapy May 2024Theranostics with radioligands (radiotheranostics) has played a pivotal role in oncology. Radiotheranostics explores the molecular targets expressed on tumor cells to... (Review)
Review
Theranostics with radioligands (radiotheranostics) has played a pivotal role in oncology. Radiotheranostics explores the molecular targets expressed on tumor cells to target them for imaging and therapy. In this way, radiotheranostics entails non-invasive demonstration of the in vivo expression of a molecular target of interest through imaging followed by the administration of therapeutic radioligand targeting the tumor-expressed molecular target. Therefore, radiotheranostics ensures that only patients with a high likelihood of response are treated with a particular radiotheranostic agent, ensuring the delivery of personalized care to cancer patients. Within the last decades, a couple of radiotheranostics agents, including Lutetium-177 DOTATATE (Lu-DOTATATE) and Lutetium-177 prostate-specific membrane antigen (Lu-PSMA), were shown to prolong the survival of cancer patients compared to the current standard of care leading to the regulatory approval of these agents for routine use in oncology care. This recent string of successful approvals has broadened the interest in the development of different radiotheranostic agents and their investigation for clinical translation. In this work, we present an updated appraisal of the literature, reviewing the recent advances in the use of established radiotheranostic agents such as radioiodine for differentiated thyroid carcinoma and Iodine-131-labeled meta-iodobenzylguanidine therapy of tumors of the sympathoadrenal axis as well as the recently approved Lu-DOTATATE and Lu-PSMA for differentiated neuroendocrine tumors and advanced prostate cancer, respectively. We also discuss the radiotheranostic agents that have been comprehensively characterized in preclinical studies and have shown some clinical evidence supporting their safety and efficacy, especially those targeting fibroblast activation protein (FAP) and chemokine receptor 4 (CXCR4) and those still being investigated in preclinical studies such as those targeting poly (ADP-ribose) polymerase (PARP) and epidermal growth factor receptor 2.
Topics: Humans; Radiopharmaceuticals; Neoplasms; Theranostic Nanomedicine; Precision Medicine; Radioisotopes; Lutetium; Animals; Medical Oncology; Ligands
PubMed: 38555542
DOI: 10.1007/s40291-024-00702-4 -
Journal of Integrative Medicine Sep 2023The placebo response of sham acupuncture in patients with primary dysmenorrhea is a substantial factor associated with analgesia. However, the magnitude of the placebo... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The placebo response of sham acupuncture in patients with primary dysmenorrhea is a substantial factor associated with analgesia. However, the magnitude of the placebo response is unclear.
OBJECTIVE
This meta-analysis assessed the effects of sham acupuncture in patients with primary dysmenorrhea and the factors contributing to these effects.
SEARCH STRATEGY
PubMed, Embase, Web of Science, and Cochrane CENTRAL databases were searched from inception up to August 20, 2022.
INCLUSION CRITERIA
Randomized controlled trials (RCTs) using sham acupuncture as a control for female patients of reproductive age with primary dysmenorrhea were included.
DATA EXTRACTION AND ANALYSIS
Pain intensity, retrospective symptom scale, and health-related quality of life were outcome measures used in these trials. Placebo response was defined as the change in the outcome of interest from baseline to endpoint. We used standardized mean difference (SMD) to estimate the effect size of the placebo response.
RESULTS
Thirteen RCTs were included. The pooled placebo response size for pain intensity was the largest (SMD = -0.99; 95% confidence interval [CI], -1.31 to -0.68), followed by the retrospective symptom scale (Total frequency rating score: SMD = -0.20; 95% CI, -0.80 to -0.39. Average severity score: SMD = -0.35; 95% CI, -0.90 to -0.20) and physical component of SF-36 (SMD = 0.27; 95% CI, -0.17 to 0.72). Studies using blunt-tip needles, single-center trials, studies with a low risk of bias, studies in which patients had a longer disease course, studies in which clinicians had < 5 years of experience, and trials conducted outside Asia were more likely to have a lower placebo response.
CONCLUSION
Strong placebo response and some relative factors were found in patients with primary dysmenorrhea. PROSPERO registration number: CRD42022304215. Please cite this article as: Sun CY, Xiong ZY, Sun CY, Ma PH, Liu XY, Sun CY, Xin ZY, Liu BY, Liu CZ, Yan SY. Placebo response of sham acupuncture in patients with primary dysmenorrhea: A meta-analysis. J Integr Med. 2023; 21(5): 455-463.
Topics: Female; Humans; Dysmenorrhea; Acupuncture Therapy; Pain Management; Needles; Placebo Effect
PubMed: 37620224
DOI: 10.1016/j.joim.2023.08.005 -
Canadian Journal of Psychiatry. Revue... Jul 2023Obsessive-compulsive disorder (OCD) is a major mental health condition with a lifetime prevalence rate of 1.3% among adults. While placebo effects are well described for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Obsessive-compulsive disorder (OCD) is a major mental health condition with a lifetime prevalence rate of 1.3% among adults. While placebo effects are well described for conditions such as depressive and anxiety disorders, they have not been systematically characterized in OCD.
OBJECTIVES
We aimed to determine the impact of placebos in improving different symptom domains in patients with OCD.
METHODS
We systematically searched PubMed, EMBASE, Scopus, Web of Science, Ovid, the Cochrane Library, and Google Scholar databases/search engine from inception to January 2021 for randomized controlled trials of treatments for OCD with a placebo arm. A modified Cohen's effect size (ES) was calculated using change in baseline to endpoint scores for different measurement scales within placebo arms to estimate placebo effects and to investigate their correlates by random-effects model meta-analyses.
RESULTS
Forty-nine clinical trials (placebo group = 1993), reporting 80 OCD specific (153 measures in general) were included in the analysis. Overall placebo ES (95% confidence interval [CI]) was 0.32 (0.22-0.41) on OCD symptoms, with substantial heterogeneity (I-square = 96.1%). Among secondary outcomes, general scales, ES: 0.27 (95%CI: 0.14-0.41), demonstrated higher ES than anxiety and depression scales, ES: 0.14 (95%CI: -0.4 to 0.32) and 0.05 (95%CI: -0.05 to 0.14), respectively. Clinician-rated scales, ES: 0.27(95%CI: 0.20-0.34), had a higher ES than self-reported scales, ES: 0.07 (95%CI: -0.08 to 0.22). More recent publication year, larger placebo group sample size, shorter follow-up duration, and younger age of participants were all associated with larger placebo ES. Egger's test reflected possible small-study effect publication bias ( = 0.029).
CONCLUSION
Placebo effects are modest in OCD trials and are larger in clinician ratings, for younger patients, and early in the treatment course. These findings underscore the need for clinicians and scientists to be mindful of placebo effects when formulating treatments or research trials for OCD.
SYSTEMATIC REVIEW REGISTRATION NUMBER
PROSPERO CRD42019125979.
Topics: Adult; Humans; Placebo Effect; Obsessive-Compulsive Disorder; Anxiety Disorders
PubMed: 35876317
DOI: 10.1177/07067437221115029 -
International Journal of Molecular... Nov 2023Tumors are a major public health issue of concern to humans, seriously threatening the safety of people's lives and property. With the increasing demand for early and... (Review)
Review
Tumors are a major public health issue of concern to humans, seriously threatening the safety of people's lives and property. With the increasing demand for early and accurate diagnosis and efficient treatment of tumors, noninvasive optical imaging (including fluorescence imaging and photoacoustic imaging) and tumor synergistic therapies (phototherapy synergistic with chemotherapy, phototherapy synergistic with immunotherapy, etc.) have received increasing attention. In particular, light in the near-infrared second region (NIR-II) has triggered great research interest due to its penetration depth, minimal tissue autofluorescence, and reduced tissue absorption and scattering. Nanomaterials with many advantages, such as high brightness, great photostability, tunable photophysical properties, and excellent biosafety offer unlimited possibilities and are being investigated for NIR-II tumor imaging-guided synergistic oncotherapy. In recent years, many researchers have tried various approaches to investigate nanomaterials, including gold nanomaterials, two-dimensional materials, metal sulfide oxides, polymers, carbon nanomaterials, NIR-II dyes, and other nanomaterials for tumor diagnostic and therapeutic integrated nanoplatform construction. In this paper, the application of multifunctional nanomaterials in tumor NIR-II imaging and collaborative therapy in the past three years is briefly reviewed, and the current research status is summarized and prospected, with a view to contributing to future tumor therapy.
Topics: Humans; Phototherapy; Polymers; Nanostructures; Neoplasms; Optical Imaging; Nanoparticles; Theranostic Nanomedicine
PubMed: 38069279
DOI: 10.3390/ijms242316949