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- Kravvariti, Evrydiki, et al.
(författare)
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Meta-analysis of placebo-arm dropouts in osteoporosis randomized-controlled trials and implications for nocebo-associated discontinuation of anti-osteoporotic drugs in clinical practice
- 2023
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Ingår i: Osteoporosis International. - : Springer. - 0937-941X .- 1433-2965. ; 34:3, s. 585-598
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Tidskriftsartikel (refereegranskat)abstract
- Summary: Dropout from placebo arms in randomized-controlled trials is a surrogate for nocebo responses, resulting from patients' negative expectations to treatment. Among 16,460 placebo-treated patients in oral anti-osteoporotic drug trials, nocebo dropouts were 8% on average, being higher in older patients. This implies that nocebo may contribute to the osteoporosis treatment gap in clinical practice.Purpose: Osteoporosis is a common disease requiring long-term treatment. Despite the availability of effective anti-osteoporotic drugs, adherence to treatment is low. Nocebo, a behavior mostly related to the negative expectations to a certain treatment, decreases adherence and negatively affects treatment outcomes and health-related care costs in chronic diseases. Since in double-blind placebo-controlled randomized trials any unfavorable outcome leading to discontinuation in placebo arms is considered as nocebo, we aimed to investigate the size of nocebo response in patients participating in osteoporosis trials.Methods: We searched MEDLINE, EMBASE, SCOPUS, and Cochrane databases for dropouts due to reported adverse events in the placebo arms (nocebo dropouts) in all double-blind trials investigating anti-osteoporotic drugs published between January 1993 and March 2022. Only data on bisphosphonates and selective estrogen receptor modulators (SERMs) were analyzed (Prospero registration number CRD42020212843).Results: Data from 44 trials were extracted. In 16,460 placebo-treated patients, the pooled nocebo-dropout was 8% both for bisphosphonates (average: 0.08; range 0.01-0.27; 95%CI 0.06-0.10) and SERMs (average: 0.08; range 0.03-0.15; 95%CI 0.05-0.13). Nocebo-dropouts were higher in bisphosphonate trials enrolling individuals >= 65 years (11%) (n = 18) compared to trials enrolling younger individuals (6%) (n = 18) (average: 0.11; 95%CI 0.08-0.13 vs. average: 0.06; 95%CI 0.05-0.08, respectively, p = 0.001). Participants' sex, dosing-intervals, publication year, or severity of osteoporosis had no impact on the nocebo-dropouts.Conclusion: Almost 1 in 10 osteoporosis patients receiving placebo in trials of bisphosphonates and SERMs experiences AEs leading to dropout, implying that nocebo contributes to treatment-discontinuation in clinical practice. Efforts to identify and minimize nocebo, especially in older patients, are warranted.
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| 2. |
- Pikilidou, Maria, et al.
(författare)
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Arterial Stiffness and Peripheral and Central Blood Pressure in Patients With Sickle Cell Disease.
- 2015
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Ingår i: The Journal of Clinical Hypertension. - : Wiley. - 1751-7176 .- 1524-6175. ; 17:9, s. 726-731
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Tidskriftsartikel (refereegranskat)abstract
- Blood pressure (BP) in patients with sickle cell disease (SCD) has been reported to be lower than in persons in the general population. Data on arterial stiffness, which is an important risk factor for the progression of BP, are inconclusive for this patient population. Forty-five adult patients with SCD and 40 controls matched for sex, age, and body mass index were studied. Brachial systolic BP (SBP) and diastolic BP (DBP) were significantly lower in the patient group (SBP 115.1±13.8 mm Hg vs 121.9±11.3 mm Hg and DBP 68.5±8.0 mm Hg vs 80.6±9.1 mm Hg, P<.05, respectively). Augmentation index (AIx), however, was significantly higher in SCD patients compared with healthy controls (24.9±9.6 for patients vs 12.4±10.8 for controls, P<.001), while carotid femoral pulse wave velocity was comparable between the two groups. The study shows that mechanisms other than arterial elasticity are involved in the low BP phenotype of patients with SCD.
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| 3. |
- Aktypis, Charalampos, et al.
(författare)
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Cardiovascular Toxicities Secondary to Biotherapy and Molecular Targeted Therapies in Neuroendocrine Neoplasms : A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials.
- 2021
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Ingår i: Cancers. - : MDPI. - 2072-6694. ; 13:9
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Forskningsöversikt (refereegranskat)abstract
- A broad spectrum of novel targeted therapies with prime antitumor activity and/or ample control of hormonal symptoms together with an overall acceptable safety profile have emerged for patients with metastatic neuroendocrine neoplasms (NENs). In this systematic review and quantitative meta-analysis, the PubMed, EMBASE, Cochrane Central Register of Controlled Trials and clinicaltrials.gov databases were searched to assess and compare the safety profile of NEN treatments with special focus on the cardiovascular adverse effects of biotherapy and molecular targeted therapies (MTTs). Quality/risk of bias were assessed using GRADE criteria. Placebo-controlled randomized clinical trials (RCTs) in patients with metastatic NENs, including medullary thyroid cancer (MTC) were included. A total of 3695 articles and 122 clinical trials registered in clinicaltrials.gov were screened. We included sixteen relevant RCTs comprising 3408 unique patients assigned to different treatments compared with placebo. All the included studies had a low risk of bias. We identified four drug therapies for NENs with eligible placebo-controlled RCTs: somatostatin analogs (SSAs), tryptophan hydroxylase (TPH) inhibitors, mTOR inhibitors and tyrosine kinase inhibitors (TKI). Grade 3 and 4 adverse effects (AE) were more often encountered in patients treated with mTOR inhibitors and TKI (odds ratio [OR]: 2.42, 95% CI: 1.87-3.12 and OR: 3.41, 95% CI: 1.46-7.96, respectively) as compared to SSAs (OR:0.77, 95% CI: 0.47-1.27) and TPH inhibitors (OR:0.77, 95% CI: 0.35-1.69). MTOR inhibitors had the highest risk for serious cardiac AE (OR:3.28, 95% CI: 1.66-6.48) followed by TKIs (OR:1.51, 95% CI: 0.59-3.83). Serious vascular AE were more often encountered in NEN patients treated with mTOR inhibitors (OR: 1.72, 95% CI: 0.64-4.64) and TKIs (OR:1.64, 95% CI: 0.35-7.78). Finally, patients on TKIs were at higher risk for new-onset or exacerbation of pre-existing hypertension (OR:3.31, 95% CI: 1.87-5.86). In conclusion, SSAs and TPH inhibitors appear to be safer as compared to mTOR inhibitors and TKIs with regards to their overall toxicity profile, and cardiovascular toxicities in particular. Special consideration should be given to a patient-tailored approach with anticipated toxicities of targeted NEN treatments together with assessment of cardiovascular comorbidities, assisting clinicians in treatment selection and early recognition/management of cardiovascular toxicities. This approach could improve patient compliance and preserve cardiovascular health and overall quality of life.
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