| 1. |
- Shepherd, L., et al.
(författare)
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Infection-related and -unrelated malignancies, HIV and the aging population
- 2016
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Ingår i: HIV Medicine. - : Wiley. - 1464-2662 .- 1468-1293. ; 17:8, s. 590-600
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: HIV-positive people have increased risk of infection-related malignancies (IRMs) and infection-unrelated malignancies (IURMs). The aim of the study was to determine the impact of aging on future IRM and IURM incidence. Methods: People enrolled in EuroSIDA and followed from the latest of the first visit or 1 January 2001 until the last visit or death were included in the study. Poisson regression was used to investigate the impact of aging on the incidence of IRMs and IURMs, adjusting for demographic, clinical and laboratory confounders. Linear exponential smoothing models forecasted future incidence. Results: A total of 15 648 people contributed 95 033 person-years of follow-up, of whom 610 developed 643 malignancies [IRMs: 388 (60%); IURMs: 255 (40%)]. After adjustment, a higher IRM incidence was associated with a lower CD4 count [adjusted incidence rate ratio (aIRR) CD4 count < 200 cells/μL: 3.77; 95% confidence interval (CI) 2.59, 5.51; compared with ≥ 500 cells/μL], independent of age, while a CD4 count < 200 cells/μL was associated with IURMs in people aged < 50 years only (aIRR: 2.51; 95% CI 1.40–4.54). Smoking was associated with IURMs (aIRR: 1.75; 95% CI 1.23, 2.49) compared with never smokers in people aged ≥ 50 years only, and not with IRMs. The incidences of both IURMs and IRMs increased with older age. It was projected that the incidence of IRMs would decrease by 29% over a 5-year period from 3.1 (95% CI 1.5–5.9) per 1000 person-years in 2011, whereas the IURM incidence would increase by 44% from 4.1 (95% CI 2.2–7.2) per 1000 person-years over the same period. Conclusions: Demographic and HIV-related risk factors for IURMs (aging and smoking) and IRMs (immunodeficiency and ongoing viral replication) differ markedly and the contribution from IURMs relative to IRMs will continue to increase as a result of aging of the HIV-infected population, high smoking and lung cancer prevalence and a low prevalence of untreated HIV infection. These findings suggest the need for targeted preventive measures and evaluation of the cost−benefit of screening for IURMs in HIV-infected populations.
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| 2. |
- Axfors, Cathrine, et al.
(författare)
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Association between convalescent plasma treatment and mortality in COVID-19 : a collaborative systematic review and meta-analysis of randomized clinical trials
- 2021
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Ingår i: BMC Infectious Diseases. - : BioMed Central (BMC). - 1471-2334. ; 21:1
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Forskningsöversikt (refereegranskat)abstract
- Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, ). Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I-2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.
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| 3. |
- Lundgren, Jens D, et al.
(författare)
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Long-Term Benefits from Early Antiretroviral Therapy Initiation in HIV Infection.
- 2023
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Ingår i: NEJM evidence. - : Massachusetts Medical Society. - 2766-5526. ; 2:3
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Tidskriftsartikel (refereegranskat)abstract
- For people with HIV and CD4+ counts >500 cells/mm3, early initiation of antiretroviral therapy (ART) reduces serious AIDS and serious non-AIDS (SNA) risk compared with deferral of treatment until CD4+ counts are <350 cells/mm3. Whether excess risk of AIDS and SNA persists once ART is initiated for those who defer treatment is uncertain.The Strategic Timing of AntiRetroviral Treatment (START) trial, as previously reported, randomly assigned 4684 ART-naive HIV-positive adults with CD4+ counts .500 cells/mm3 to immediate treatment initiation after random assignment (n = 2325) or deferred treatment (n= 2359). In 2015, a 57% lower risk of the primary end point (AIDS, SNA, or death) for the immediate group was reported, and the deferred group was offered ART. This article reports the follow-up that continued to December 31, 2021. Cox proportional-hazards models were used to compare hazard ratios for the primary end point from randomization through December 31, 2015, versus January 1, 2016, through December 31, 2021.Through December 31, 2015, approximately 7 months after the cutoff date from the previous report, the median CD4+ count was 648 and 460 cells/mm3 in the immediate and deferred groups, respectively, at treatment initiation. The percentage of follow-up time spent taking ART was 95% and 36% for the immediate and deferred groups, respectively, and the time-averaged CD4+ difference was 199 cells/mm3. After January 1, 2016, the percentage of follow-up time on treatment was 97.2% and 94.1% for the immediate and deferred groups, respectively, and the CD4+ count difference was 155 cells/mm3. After January 1, 2016, a total of 89 immediate and 113 deferred group participants experienced a primary end point (hazard ratio of 0.79 [95% confidence interval, 0.60 to 1.04] versus hazard ratio of 0.47 [95% confidence interval, 0.34 to 0.65; P<0.001]) before 2016 (P=0.02 for hazard ratio difference).Among adults with CD4+ counts >500 cells/mm3, excess risk of AIDS and SNA associated with delaying treatment initiation was diminished after ART initiation, but persistent excess risk remained. (Funded by the National Institute of Allergy and Infectious Diseases and others.).
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| 4. |
- Brieghel, Christian, et al.
(författare)
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Identifying patients with chronic lymphocytic leukemia without need of treatment : End of endless watch and wait?
- 2022
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Ingår i: European Journal of Haematology. - : John Wiley & Sons. - 0902-4441 .- 1600-0609. ; 108:5, s. 369-378
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Early-stage chronic lymphocytic leukemia (CLL) challenges specialized management and follow-up.Methods We developed and validated a prognostic index to identify newly diagnosed patients without need of treatment (CLL-WONT) by a training/validation approach using data on 4708 patients. Composite scores derived from weighted hazards by multivariable analysis defined CLL-WONT risk groups.Results Age (>65 years: 1 point), Binet stage (B: 2 points), lactate dehydrogenase (LDH) (>205 U/L: 1 point), absolute lymphocyte count (15-30 x 10(9)/L: 1 point; >30 x 10(9)/L; 2 points), beta 2-microglobulin (>4 mg/L: 1 point), IGHV mutation status (unmutated: 1 point), and 11q or 17p deletion (1 point) were independently associated with shorter time to first treatment (TTFT). Low-risk patients demonstrated 5-year TTFT of 2% by internal validation, but 7-19% by external validation. Including all patients with complete scores, the 5-year TTFT was 10% for the 756 (39%) CLL-WONT low-risk patients, and the 704 (37%) patients who were both CLL-WONT and CLL-IPI low risk demonstrated even lower 5-year TTFT (8%).Conclusion We have adopted the CLL-WONT at an institution covering 1 800 000 individuals to allow patients with both low-risk CLL-WONT and CLL-IPI to be managed by primary healthcare providers, thereby prioritizing specialized hematology services for patients in dire need.
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| 5. |
- Ng, Nawi, 1974, et al.
(författare)
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Sustainable Behavior Change for Health Supported by Person-Tailored, Adaptive, Risk-Aware Digital Coaching in a Social Context: Study Protocol for the STAR-C Research Programme
- 2021
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Ingår i: Frontiers in Public Health. - : Frontiers Media SA. - 2296-2565. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The Vasterbotten Intervention Programme (VIP) in the Region Vasterbotten Sweden is one of the very few cardiovascular disease (CVD) prevention programmes globally that is integrated into routine primary health care. The VIP has been shown as a cost-effective intervention to significantly reduce CVD mortality. However, little is known about the effectiveness of a digital solution to tailor risk communication strategies for supporting behavioral change. STAR-C aims to develop and evaluate a technical platform for personalized digital coaching that will support behavioral change aimed at preventing CVD. Methods: STAR-C employs a mixed-methods design in seven multidisciplinary projects, which runs in two phases during 2019-2024: (i) a formative intervention design and development phase, and (ii) an intervention implementation and evaluation phase. In the 1st phase, STAR-C will model the trajectories of health behaviors and their impact on CVDs (Project 1), evaluate the role of the social environment and social networks on behavioral change (Project 2) and assess whether and how social media facilitates the spread of health information beyond targeted individuals and stimulates public engagement in health promotion (Project 3). The findings will be utilized in carrying out the iterative, user-centered design, and development of a person-tailored digital coaching platform (Project 4). In the 2nd phase, STAR-C will evaluate the implementation of the coaching programme and its effectiveness for promoting behavioral change and the spreading of health information across social networks and via social media (Project 5). The cost-effectiveness (Project 6) and ethical issues (Project 7) related to the coaching programme intervention will be evaluated. Discussion: The STAR-C research programme will address the knowledge and practice research gaps in the use of information technologies in health promotion and non-communicable disease (NCD) prevention programmes in order to narrow the health inequality gaps. Ethics: STAR-C has received approval from the Swedish Ethical Review Authority (Dnr. 2019-02924;2020-02985). Dissemination: The collaboration between Umea University and Region Vasterbotten will ensure the feasibility of STAR-C in the service delivery context. Results will be communicated with decision-makers at different levels of society, stakeholders from other regions and healthcare professional organizations, and through NGOs, local and social media platforms.
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| 6. |
- Zetterberg, Eva, et al.
(författare)
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Platelet count kinetics following Interruption of antiretroviral treatment: Results from the SMART study.
- 2013
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Ingår i: AIDS. - 1473-5571. ; 27:1, s. 59-68
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To investigate the mechanisms of platelet kinetics in the SMART study that demonstrated excess mortality with CD4 guided episodic antiretroviral therapy (ART) (drug conservation [DC]) compared to continuous treatment (viral suppression [VS]). Follow up analyses of stored plasma samples demonstrated increased activation of both inflammatory and coagulation pathways after stopping ART. DESIGN: SMART patients from sites that determined platelets routinely. METHODS: Platelet counts were retrospectively collected from 2206 patients from visits at study entry, and during follow-up. D-dimer levels were measured at study entry, month 1, and 2. RESULTS:: Platelet levels decreased in the DC group following randomization, but remained stable in the VS group [median (IQR) decline from study entry to month 4: -24,000/μL(-54,000-4,000) vs. 3000 (-22,000-24,000), respectively, p < 0.0001)] and the rate of developing thrombocytopenia (<100,000/μL) was significantly higher in the DC versus the VS arm (unadjusted DC/VS HR (95%CI) = 1.8 (1.2-2.7)). The decline in platelet count among DC participants on fully suppressive ART correlated with the rise in D-dimer from baseline to either month 1 or 2 (r = -0.41; p = 0.02). Among DC participants who resumed ART 74% recovered to their study entry platelet levels. CONCLUSION: Interrupting ART increases the risk of thrombocytopenia, but re-initiation of ART typically reverses it. Factors contributing to declines in platelets after interrupting ART may include activation of coagulation pathways or HIV-1 replication itself. The contribution of platelets in HIV-related pro-coagulant activity requires further study.
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