| 1. |
- 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and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, ).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 Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients).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 The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis.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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| 2. |
- Dereke, J., et al.
(författare)
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Pregnancy-associated plasma protein-A2 levels are increased in early-pregnancy gestational diabetes : a novel biomarker for early risk estimation
- 2020
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Ingår i: Diabetic Medicine. - : Wiley. - 0742-3071 .- 1464-5491. ; 37:1, s. 131-137
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To determine whether pregnancy-associated plasma protein-A2 levels are increased in early pregnancies complicated by gestational diabetes and whether gestation age influences levels. The possible use of pregnancy-associated plasma protein-A2 as a pre-screening biomarker to reduce the need for performing oral glucose tolerance tests in pregnant women was also investigated. Methods: Pregnant women were diagnosed with gestational diabetes in early pregnancy after a 2-hour 75 g oral glucose tolerance test in the catchment area of Skåne University Hospital, Lund, Sweden during 2011–2015 (n = 99). Age- and BMI-matched pregnant women without diabetes were recruited at similar gestational ages from maternal healthcare centres in the same geographical area during 2014–2015 to act as controls (n = 100). Circulating pregnancy-associated plasma protein-A2 was analysed in participant serum using commercially available enzyme-linked immunosorbent assay kits. Results: Circulating pregnancy-associated plasma protein-A2 was increased in women diagnosed with gestational diabetes [13.5 (9.58–18.8) ng/ml] compared with controls [8.11 (5.74–11.3) ng/ml; P < 0.001]. Pregnancy-associated plasma protein-A2 was associated with gestational diabetes independent of age, BMI, C-peptide and adiponectin (P < 0.001). Pregnancy-associated plasma protein-A2 as a pre-screening biomarker to identify women at a decreased risk of gestational diabetes resulted in a negative predictive value of 99.7%, with a sensitivity of 96% and a specificity of 30% at a cut-off level of 6 ng/ml. Conclusions: This is the first study to show increased pregnancy-associated plasma protein-A2 levels in gestational diabetes. Pregnancy-associated plasma protein-A2 also shows promise as a pre-screening biomarker with the potential to reduce the need for performing oral glucose tolerance tests in early pregnancy. Future prospective cohort studies in a larger group of both high- and low-risk women are, however, needed to further confirm this observation.
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| 3. |
- Dereke, J., et al.
(författare)
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Structural and immunoendocrine remodeling in gut, pancreas and thymus in weaning rats fed powdered milk diets rich in Maillard reactants
- 2022
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Western diet is extending worldwide and suspected to be associated with various metabolic diseases. Many food products have skim milk powder added to it and, during processing, lactose reacts with milk proteins and Maillard reaction products (MRPs) are formed. Dietary MRPs are suggested risk factors for metabolic dysregulation, but the mechanisms behind are still enigmatic. Here we describe that weaning rats fed diets rich in MRPs are affected in both their immune and endocrine systems. Marked structural changes in pancreas, intestine and thymus are noted already after 1 week of exposure. The pancreatic islets become sparser, the intestinal mucosa is thinner, and thymus displays increased apoptosis and atrophy. Glucagon- like peptide-1 (GLP-1) seems to play a key role in that the number of GLP-1 expressing cells is up-regulated in endocrine pancreas but down-regulated in the intestinal mucosa. Further, intestinal GLP-1-immunoreactive cells are juxta positioned not only to nerve fibres and tuft cells, as previously described, but also to intraepithelial CD3 positive T cells, rendering them a strategic location in metabolic regulation. Our results suggest dietary MRPs to cause metabolic disorders, dysregulation of intestinal GLP-1- immunoreactive cells, arrest in pancreas development and thymus atrophy.
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| 4. |
- Petruzzo, P., et al.
(författare)
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VCA in the Era of the COVID-19 Pandemic
- 2022
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Ingår i: Transplantation. - : Ovid Technologies (Wolters Kluwer Health). - 0041-1337. ; 106:4, s. 690-692
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Tidskriftsartikel (refereegranskat)
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| 5. |
- Wendt, M, et al.
(författare)
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Long-Term Survival and Recurrence in Oropharyngeal Squamous Cell Carcinoma in Relation to Subsites, HPV, and p16-Status
- 2021
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:11
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Tidskriftsartikel (refereegranskat)abstract
- Long-term survival data in relation to sub-sites, human papillomavirus (HPV), and p16INK4a (p16) for patients with oropharyngeal squamous cell carcinoma (OPSCC) is still sparse. Furthermore, reports have indicated atypical and late recurrences for patients with HPV and p16 positive OPSCC. Therefore, we assessed long-term survival and recurrence in relation to oropharyngeal subsite and HPV/p16 status. A total of 529 patients with OPSCC, diagnosed in the period 2000–2010, with known HPVDNA and p16-status, were included. HPV/p16 status and sub-sites were correlated to disease-free and overall survival (DFS and OS respectively). The overexpression of p16 (p16+) is associated with significantly better long-term OS and DFS in tonsillar and base of tongue carcinomas (TSCC/BOTSCC), but not in patients with other OPSCC. Patients with HPVDNA+/p16+ TSCC/BOTSCC presented better OS and DFS compared to those with HPVDNA−/p16− tumors, while those with HPVDNA−/p16+ cancer had an intermediate survival. Late recurrences were rare, and significantly more frequent in patients with p16− tumors, while the prognosis after relapse was poor independent of HPVDNA+/−/p16+/− status. In conclusion, patients with p16+ OPSCC do not have more late recurrences than p16−, and a clear prognostic value of p16+ was only observed in TSCC/BOTSCC. Finally, the combination of HPVDNA and p16 provided superior prognostic information compared to p16 alone in TSCC/BOTSCC.
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| 6. |
- Kontogeorgos, Georgios, et al.
(författare)
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Hyperparathyroidism in men - morbidity and mortality during 21 years' follow-up
- 2020
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 80:1, s. 6-13
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Tidskriftsartikel (refereegranskat)abstract
- Hyperparathyroidism (HPT), including normocalcaemic, vitamin D sufficient (Serum (S)-25(OH)D >= 50 nmol/L) hyperparathyroidism (nHPT), has increasingly been diagnosed in the last few decades due to the more common use of the serum parathyroid hormone (S-PTH) assay. We investigated if men with HPT had higher morbidity and mortality than men without HPT during 21 years' follow-up. A random population sample of 750 men, all 50 years of age, was examined in 1993. Endpoints were retrieved 21 years later at 71 years of age. Albumin-corrected serum (S) calcium, S-25-hydroxyvitamin D and S-PTH were assessed along with data on cardiovascular risk factors and medication. Outcome data on fractures, stroke, myocardial infarction, cancer and death were retrieved in 2014; 21 years after primary assessment. The prevalence of HPT at 50 years of age was 9.3%; nHPT 2.8%, primary HPT 0.4%, secondary HPT 0.4%, and HPT with vitamin D insufficiency 6%. Fracture rate, myocardial infarction, stroke, cancer and death occurred similarly in men with or without HPT, as well as in men with nHPT as compared with men without calcium/PTH aberrations during 21 years' follow-up. S-PTH was evenly distributed in the univariable analyses for each outcome. Cox regression analyses showed no increase in serious morbidity or in mortality in men with HPT, irrespective of cause, compared with men with normal S-PTH over a 21-year period. None had HPT at a S-25(OH)D level of 100 nmol/L.
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| 7. |
- Kontogeorgos, Georgios, et al.
(författare)
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Low health-related quality of life in hypoparathyroidism and need for PTH analog
- 2022
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Ingår i: Endocrine Connections. - 2049-3614. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Hypoparathyroidism (HypoPT) is a rare endocrine disorder in which insufficient levels of parathyroid hormone (PTH) lead to low serum calcium (S-Ca) levels and muscular cramps. The aim was to study the health-related quality of life (HRQoL) and comorbidities in patients with HypoPT compared with the general population and to estimate the need of treatment with PTH analog. Design: Patients with HypoPT were identified and compared with a population sample. Short Form-36 (SF-36) and EuroQol-5 Dimensions Visual Analogue Scale questionnaires were used. All patients were followed up at the Sahlgrenska University Hospital outpatient clinic. Methods: From the medical records between 2007 and 2020, 203 patients with HypoPT were identified and compared with a population sample (n = 414) from the World Health Organization’s (WHO) MONICA project, Gothenburg, Sweden. Of the 203 patients who met the diagnostic criteria, 164 were alive and 65% answered the HRQoL questionnaires. Results: Patients with HypoPT, 80% postsurgical, and controls had similar age (60 years) and sex distribution (80% women). Patients had lower SF-36 summary component scores for physical (40.0 (interquartile range (IQR): 21) vs 51.2 (IQR: 14.6); P < 0.001) and mental (43.1 (IQR:17.4) vs 56.1(IQR:13.3); P < 0.001) well-being, irrespective of etiology or calcium levels. Individuals with HypoPT had more medications and lower renal function but not higher mortality than controls. Low HRQoL together with low calcium was present in 23% of individuals with HypoPT. Conclusion: HRQoL was markedly lower in patients with HypoPT than in controls and independent of S-Ca levels. Treatment with PTH analog could be considered at least among patients with both low HRQoL and low calcium levels. © 2022 The authors.
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| 8. |
- Kontogeorgos, Georgios, et al.
(författare)
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Teriparatide treatment in severe osteoporosis - a controlled 10-year follow-up study
- 2022
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Ingår i: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Teriparatide was the first anabolic agent recommended for the treatment of osteoporosis. Long-term real-world, controlled studies are not available. The purpose was to evaluate the long-term effects of treatment with teriparatide on fractures and Health Related Quality of Life in subjects with established osteoporosis in comparison with placebo treated patients with osteoporosis and the general population. Methods A 10-year follow-up was performed after a prospective, open-labelled study with teriparatide 20 mu g given subcutaneously daily for a mean of 18 months (range 14-24 months) in 40 women, mean age 69 years, with osteoporosis and vertebral compression. Placebo treated women, n = 25, mean age 60 years, from a randomized, double-blind, placebo-controlled growth hormone trial with daily subcutaneous injections for 18 months, with osteoporosis were used as controls. Dual energy x-ray absorptiometry and questionnaires were performed at start, after 18 months, after 36 months and after 10 years. Women, n = 233, of similar age from a random population sample, also served as controls and were followed in parallel. All fractures were X-ray verified. Results Fractures decreased from 100 to 35% in the teriparatide treated patients (p < 0.0001) to similar levels as in the population sample, 25 to 28% at start and after 10 years, respectively. Bone mineral density increased on teriparatide but returned to levels at treatment start after 10 years. Health Related Quality of Life was lower in the teriparatide group than in the population (p < 0.001) before and, after treatment and at 10 years. Conclusions Anabolic hormonal treatment with teriparatide reduced fracture prevalence to similar levels as in the general population at 10 years' follow-up. Health Related Quality of Life was low in osteoporosis and unaffected by bone specific treatment.
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| 9. |
- Lindqvist, Pelle G., et al.
(författare)
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Women with fair phenotypes seem to confer a survival advantage in a low UV milieu. A nested matched case control study
- 2020
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Sun exposure in combination with skin pigmentation is the main determinant for vitamin D status. Human skin color seems to be adapted and optimized for regional sun ultraviolet (UV) intensity. However, we do not know if fair, UV-sensitive skin is a survival advantage in regions with low UV radiation. Methods A population-based nested case-control study of 29,518 Caucasian women, ages 25 to 64 years from Southern Sweden who responded to a questionnaire regarding risk-factors for malignant melanoma in 1990 and followed for 25 years. For each fair woman, defined as having red hair or freckles (n = 11,993), a control was randomly selected from all non-fair women from within the cohort of similar age, smoking habits, education, marital status, income, and comorbidity, i.e., 11,993 pairs. The main outcome was the difference in allcause mortality between fair and non-fair women in a low UV milieu, defined as living in Sweden and having low-to-moderate sun exposure habits. Secondary outcomes were mortality by sun exposure, and among those non-overweight. Results In a low UV milieu, fair women were at a significantly lower all-cause mortality risk as compared to non-fair women (log rank test p = 0.04) with an 8% lower all-cause mortality rate (hazard ratio [HR] = 0.92, 95% CI 0.84-1.0), including a 59% greater risk of dying from skin cancer among fair women (HR 1.59, 95% CI 1.26-2.0). Thus, it seem that the beneficial health effect from low skin coloration outweigh the risk of skin cancer at high latitudes. Conclusion In a region with low UV milieu, evolution seems to improve all-cause survival by selecting a fair skin phenotype, i.e., comprising fair women with a survival advantage.
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| 10. |
- Lindqvist, PG, et al.
(författare)
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Low sun exposure habits is associated with a dose-dependent increased risk of hypertension: a report from the large MISS cohort
- 2021
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Ingår i: Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology. - : Springer Science and Business Media LLC. - 1474-9092. ; 20:2, s. 285-292
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Tidskriftsartikel (refereegranskat)abstract
- In prospective observational cohort studies, increasing sun exposure habits have been associated with reduced risk of cardiovascular mortality. Our aim was to assess possible observational mechanisms for this phenomenon. A written questionnaire was answered by 23,593 women in the year 2000 regarding risk factors for melanoma, including factors of possible interest for hypertension, such as detailed sun exposure habits, hypertension, marital status, education, smoking, alcohol consumption, BMI, exercise, and chronic high stress. Hypertension was measured by the proxy “use of hypertension medication” 2005–2007, and high stress by “need of anti-depressive medication”. Sun exposure habits was assessed by the number of `yes’ to the following questions; Do you sunbath during summer?, During winter vacation?, Do you travel south to sunbath?, Or do you use sun bed? Women answering ‘yes’ on one or two questions had moderate and those answering ‘yes’ on three or four as having greatest sun exposure. The main outcome was the risk of hypertension by sun exposure habits adjusted for confounding. As compared to those women with the greatest sun exposure, women with low and moderate sun exposure were at 41% and 15% higher odds of hypertension (OR 1.41, 95% CI 1.3‒1.6, p < 0.001 and OR 1.15, 95% CI 1.1‒1.2, p < 0.001), respectively. There was a strong age-related increased risk of hypertension. Other risk factors for hypertension were lack of exercise (OR 1.36), a non-fair phenotype (OR 1.08), chronic high stress level (OR 1.8), and lack of university education (OR 1.3). We conclude that in our observational design sun exposure was associated with a dose-dependent reduced risk of hypertension, which might partly explain the fewer deaths of cardiovascular disease with increasing sun exposure.
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