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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. |
- Tsoli, Marina, et al.
(författare)
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Pancreatic metastases in patients with neuroendocrine neoplasms : A multi-centre cohort study
- 2023
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Ingår i: Journal of neuroendocrinology. - : Blackwell Publishing. - 0953-8194 .- 1365-2826. ; 35:4
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Tidskriftsartikel (refereegranskat)abstract
- Pancreatic metastases (PMs) from neuroendocrine neoplasms (NENs) are rare but the increased sensitivity of new diagnostic tools such as 68 Ga-DOTATATE PET/CT has resulted in their increased recognition at initial diagnosis or follow-up. A retrospective analysis of the data of patients from six tertiary referral centres was performed in order to identify the characteristics and the prognostic significance of PMs in patients with NENs. We used a control group of 69 age-, sex- and primary tumour - matched NEN patients from the same cohort with stage IV disease but no PMs. Overall survival (OS) was assessed using the Kaplan-Meier method log-rank analysis was used to assess the impact of various clinical and histopathological variables in OS. We identified 25 patients (11 females) with PMs with a median age at diagnosis of 60 years. The small intestine was the most common primary (80%) with a prevalence of 4.2% PMs (21/506). Fourteen patients presented with synchronous PMs whereas 11 developed metachronous PMs after a median time of 28 months (range: 7-168 months). Grading was available in 24 patients; 16 patients had G1 tumours, four G2, two atypical lung carcinoid, one typical and one atypical thymic carcinoid. Most patients had other concomitant metastases (12 hepatic, 4 lung and 6 bone) while five patients exhibited peritoneal carcinomatosis. Median OS in the PMs group was not reached compared with 212 months in the control group (95% CI: 26-398). The univariate analysis identified no prognostic factors statistically significantly associated with the OS. In conclusion, PMs are encountered with a low prevalence among NEN patients mostly developing in patients with advanced metastatic disease. The presence of PMs does not seem to be associated with a negative prognostic impact in OS.
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| 3. |
- Wedin, Maria, 1977-, et al.
(författare)
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Rare metastases diagnosed on 68Ga-DOTATOC-PET/CT in small intestinal and pancreatic NETs
- 2023
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Ingår i: Journal of neuroendocrinology. - : John Wiley & Sons. - 0953-8194 .- 1365-2826. ; 35:Suppl. 1, s. 116-116
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Neuroendocrine metastases to the orbita, heart, breast, bone, Virchow's lymph node, and pancreas are rarely encountered in small intestinal (SI-NETs) and pancreatic NETs (P-NETs).Aim(s): We aimed to assessthe prevalence of rare metastatic locations in patients with well-differentiated SI-NETs and P-NETs, who had undergone 68Ga-DOTATOC-PET/CT at diagnosis and/or follow-up.Materials and methods: In this retrospective analysis of 753 SI-NET patients and 418 P-NET patients treated at two tertiary referral centers, rare metastases were evident in 26.5% (310/1171) of the patient cohort.Results: Among patients with rare metastases (n=310), 45 % were women and median age at metastases diagnosis was 70 years (43-90). Median Ki-67 was 7% (1-70); 106 were G1 tumors, 142 G2, 11 G3 and 51 of unknown grade. Rare metastatic sites were present in bone 18 % (215/1171), Virchow's lymph node 6 % (75/1171) and 4 % (42/1171) in the lung/pleura. Metastases to the pancreas, breast, heart and orbita were only encountered in SI-NET primaries with a frequency of 5 % (41/753), 2 % (17/753), 2 % (14/753) and 2 % (12/753) respectively. Concomitant liver metastases were present in 86 %. Uncommon metastases were more frequent in SI-NET as compared with P-NET primaries, 255/753 [34%] vs. 55/418 [13%], p ˂0.00001. Bone metastases were present in 23 % (175/753) of SI-NET and 10 % (40/418) of p-NET primaries.Conclusion: In conclusion, rare metastases are more frequent in SI-NET than p-NETs. The variety and pattern of rare metastases seems different between SI-NETs and P-NET primaries, as orbita, heart, breast and Virchow's lymph node deposits were only encountered in SI-NETs patients; and bone metastases were approximately twice more often inthis group.
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