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- Di Angelantonio, E., et al.
(författare)
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Association of Cardiometabolic Multimorbidity With Mortality
- 2015
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Ingår i: JAMA. - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 314:1, s. 52-60
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: The prevalence of cardiometabolic multimorbidity is increasing. OBJECTIVE: To estimate reductions in life expectancy associated with cardiometabolic multimorbidity. DESIGN, SETTING, AND PARTICIPANTS: Age- and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689,300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128,843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499,808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age-specific HRs for mortality to contemporary US age-specific death rates. EXPOSURES: A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI). MAIN OUTCOMES AND MEASURES: All-cause mortality and estimated reductions in life expectancy. RESULTS: In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95% CI, 2.0-2.2) in those with stroke, 2.0 (95% CI, 1.9-2.2) in those with MI, 3.7 (95% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy. CONCLUSIONS AND RELEVANCE: Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity.
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- Björling, G., et al.
(författare)
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Moderna antipsykotika ger färre biverkningar och lägre dödlighet: Men de är dyrare än äldre neuroleptika, visar studie från Västra Götaland
- 2012
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 109:29-31, s. 1350-1353
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Västra Götalandsregionen har drygt 1,5 miljoner invåna re. Patienter med diagnosen schizofreni (N = 4 593) under juli 2005 till och med decem ber 2009 har studerats. Läkemedelskostnaden var lägre för äldre neuroleptika än för nyare »atypiska« anti psykotika. Sjukhuskostna derna var lika för båda grup perna, medan öppenvårds kostnaderna var högre vid behandling med nya medel än med äldre. Totalkostnaden per patient varierade från 243 000 (äldre läkemedel) till 360 000 kro nor (nyare antipsykotika). Samsjukligheten tenderade att vara lägre för aripiprazol, men var lika för äldre och and ra nyare preparat. Sjukskrivningstiderna var lika oberoende av preparat. Dödligheten var 2,4 gånger högre hos schizofrenipatien ter än i totalbefolkningen, men den var inte signifikant lägre vid läkemedelsbehand ling än utan. Dock var den signifikant lägre vid behand ling med nyare antipsykotika än med äldre läkemedel.
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| 10. |
- Di Angelantonio, Emanuele, et al.
(författare)
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Association of Cardiometabolic Multimorbidity With Mortality : The Emerging Risk Factors Collaboration
- 2015
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Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 314:1, s. 52-60
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE The prevalence of cardiometabolic multimorbidity is increasing.OBJECTIVE To estimate reductions in life expectancy associated with cardiometabolic multimorbidity.DESIGN, SETTING, AND PARTICIPANTS Age-and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689 300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128 843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499 808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age-specific HRs for mortality to contemporary US age-specific death rates. EXPOSURES A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI).MAIN OUTCOMES AND MEASURES All-cause mortality and estimated reductions in life expectancy.RESULTS In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95% CI, 2.0-2.2) in those with stroke, 2.0 (95% CI, 1.9-2.2) in those with MI, 3.7 (95% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy.CONCLUSIONS AND RELEVANCE Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity.
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- Malmberg, K, et al.
(författare)
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Randomised trial of insuline-glucose infusion followed by subcutaneous insulin treatment in diabetic patients with acute myocardial infarction (DIGAMI-Study) Effects on mortality at 1 year
- 1995
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Ingår i: Journal of the American College of Cardiology. - : Elsevier Inc.. - 0735-1097 .- 1558-3597. ; 26:1, s. 57-65
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. We tested how insulin-glucose infusion followed by multidose insulin treatment in diabetic patients with acute myocardial infarction affected mortality during the subsequent 12 months of follow-up. Background. Despite significant improvements in acute coronary care, diabetic patients with acute myocardial infarction still have a high mortality rate. Methods. A total of 620 patients were studied : 306 randomized to treatment with insulin-glucose infusion followed by multidose subcutaneous insulin for ≥3 months and 314 to conventional therapy. Results. The two groups were well matched for baseline characteristics. Blood glucose decreased from 15.4 ± 4.1 to 9.6 ± 3.3 mmol/liter (mean ± SD) in the infusion group during the 1st 24 h, and from 15.7 ± 4.2 to 11.7 ± 4.1 among control patients (p < 0.0001). After 1 year 57 subjects (18.6%) in the infusion group and 82 (26.1%) in the control group had died (relative mortality reduction 29%, p = 0.027). The mortality reduction was particularly evident in patients who had a low cardiovascular risk profile and no previous insulin treatment (3-month mortality rate 6.5% in the infusion group vs. 13.5% in the control group [relative reduction 52%, p = 0.046] ; 1-year mortality rate 8.6% in the infusion group vs. 18.0% in the control group [relative reduction 52%, p = 0.020]). Conclusions. Insulin-glucose infusion followed by a multidose insulin regimen improved long-term prognosis in diabetic patients with acute myocardial infarction.
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- Meijer, A., et al.
(författare)
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Adjusted prognostic association of depression following myocardial infarction with mortality and cardiovascular events: individual patient data meta-analysis
- 2013
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Ingår i: British Journal of Psychiatry. - : Royal College of Psychiatrists. - 0007-1250 .- 1472-1465. ; 203:2, s. 90-102
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Tidskriftsartikel (refereegranskat)abstract
- Background The association between depression after myocardial infarction and increased risk of mortality and cardiac morbidity may be due to cardiac disease severity. To combine original data from studies on the association between post-infarction depression and prognosis into one database, and to investigate to what extent such depression predicts prognosis independently of disease severity. An individual patient data meta-analysis of studies was conducted using multilevel, multivariable Cox regression analyses. Sixteen studies participated, creating a database of 10 175 post-infarction cases. Hazard ratios for post-infarction depression were 1.32 (95% CI 1.26-1.38, P<0.001) for all-cause mortality and 1.19 (95% CI 1.14-1.24, P<0.001) for cardiovascular events. Hazard ratios adjusted for disease severity were attenuated by 28% and 25% respectively. The association between depression following myocardial infarction and prognosis is attenuated after adjustment for cardiac disease severity. Still, depression remains independently associated with prognosis, with a 22% increased risk of all-cause mortality and a 13% increased risk of cardiovascular events per standard deviation in depression z-score.
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- Ronnberg, L, et al.
(författare)
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Mental impairment and utilization of community services: a study of the elderly in a parish of Stockholm
- 1996
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Ingår i: Scandinavian journal of social medicine. - : SAGE Publications. - 0300-8037. ; 24:3, s. 185-192
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Tidskriftsartikel (refereegranskat)abstract
- Before the implementation of the health care reform of 1992 (The Ädel Reform), a study of the frequency of mental impairment of people in different residential and care services was conducted in a parish of Stockholm. All residents, 65 years or older, registered with Primary Care Centres, Geriatric Hospitals and other institutions were assessed with respect to cognitive function according to the seven stage “Global Deterioration Scale” (GDS). The age-specific frequencies of mental impairment were similar to prevalences reported in earlier studies. The frequency of cognitive dysfunction of non-institutionalized and institutionalized elderly was 42% and 52%, respectively, and higher for women than for men. There was considerable variation in the prevalence of cognitive dysfunction among subjects in different types of accommodation. For the different stages of mental impairment the average age was about the same. With increasing need and demand for services, and limited resources, these variations in cognitive dysfunction have important implications for structuring appropriate support systems in a population with a rapidly rising proportion of elderly people.
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| 19. |
- Rosengren, Annika, 1951, et al.
(författare)
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Obesity and trends in cardiovascular risk factors over 40 years in Swedish men aged 50.
- 2009
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Ingår i: Journal of internal medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 266:3, s. 268-76
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To study trends over 40 years in cardiovascular risk factors in normal weight, overweight and obese men, all aged 50 when examined. Design. Cross-sectional studies of five successive cohorts of men aged 50. SETTING: City of Göteborg, Sweden. SUBJECTS: Random population samples of altogether 3251 urban Swedish men born in 1913, 1923, 1933, 1943 and 1953. MAIN OUTCOME MEASURES: Anthropometry, cardiovascular risk factors, rates of nonsmoking, normotension and serum cholesterol <5 mmol L(-1) over four decades. RESULTS: Over 40 years, there was a net increase in body mass index (BMI) from 24.8 (SD = 3.2) to 26.4 (3.7) kg m(-2) (P < 0.0001), with an increase in the prevalence of obesity (BMI >or= 30 kg m(-2)) from 6.0% in 1963 to 13.8% in 2003. Favourable trends with respect to smoking, blood pressure and serum cholesterol were observed similarly amongst normal weight, overweight and obese men. In 1963, 24% of obese men were normotensive compared to 45% in 2003, and 6% had serum cholesterol <5 mmol L(-1) compared to 34% in 2003. Compared with obese men in 1963, men who were obese in 2003 had an odds ratio (OR) of 3.39 being a nonsmoker [95% confidence interval (CI): 1.56 to 7.36], 2.67 of being normotensive (1.23 to 5.83) and having serum cholesterol <5 mmol L(-1) of 8.30 (2.37 to 29.0). However, optimal risk factor status - no smoking, normotension and total serum cholesterol <5 mmol L(-1)- was still present in less than one in six men in 2003, similar across BMI categories. CONCLUSIONS: Obese Swedish men who are now in their fifties have much lower levels of other risk factors compared with obese men 40 years ago. This could contribute to explain why coronary heart disease death rates still are falling despite increasing rates of obesity.
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- Sorbye, H, et al.
(författare)
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Predictive and prognostic factors for treatment and survival in 305 patients with advanced gastrointestinal neuroendocrine carcinoma (WHO G3) : the NORDIC NEC study
- 2013
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 24:1, s. 152-160
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Tidskriftsartikel (refereegranskat)abstract
- As studies on gastrointestinal neuroendocrine carcinoma (WHO G3) (GI-NEC) are limited, we reviewed clinical data to identify predictive and prognostic markers for advanced GI-NEC patients. Data from advanced GI-NEC patients diagnosed 2000-2009 were retrospectively registered at 12 Nordic hospitals. The median survival was 11 months in 252 patients given palliative chemotherapy and 1 month in 53 patients receiving best supportive care (BSC) only. The response rate to first-line chemotherapy was 31% and 33% had stable disease. Ki-67 < 55% was by receiver operating characteristic analysis the best cut-off value concerning correlation to the response rate. Patients with Ki-67 < 55% had a lower response rate (15% versus 42%, P < 0.001), but better survival than patients with Ki-67 >= 55% (14 versus10 months, P < 0.001). Platinum schedule did not affect the response rate or survival. The most important negative prognostic factors for survival were poor performance status (PS), primary colorectal tumors and elevated platelets or lactate dehydrogenase (LDH) levels. Advanced GI-NEC patients should be considered for chemotherapy treatment without delay.PS, colorectal primary and elevated platelets and LDH levels were prognostic factors for survival. Patients with Ki-67 < 55% were less responsive to platinum-based chemotherapy, but had a longer survival. Our data indicate that it may not be correct to consider all GI-NEC as one single disease entity.
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- Wilhelmsen, Lars, 1932, et al.
(författare)
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Factors associated with reaching 90 years of age : a study of men born in 1913 in Gothenburg, Sweden
- 2011
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 269:4, s. 441-451
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. Increasing numbers of people reach old age. We wanted to identify variables of importance for reaching 90 years old and determine how the predictive ability of these variables might change over time. Setting and subjects. All men in the city of Gothenburg born in 1913 on dates divisible by 3, which is on the 3rd, 6th, 9th etc., were included in the study. Thus, 973 men were invited, and 855 were examined in 1963 at age 50. Further examinations were made at age 54, 60 and 67. Anthropometric data, lifestyle and parental factors, blood pressure, lung function, X-ray of heart and lungs and maximum work performance were recorded. The area under the receiver operating characteristic curve was used to analyse the predictive capacity of a variable. Results. A total of 111 men (13%) reached 90 years of age, men who reached 90 years were more likely at age 50 to be nonsmokers, consume less coffee, have higher socio-economic status and have low serum cholesterol levels than those who did not reach this age; however, at age 50 or 62, parents' survival was of no prognostic importance. Variables of greatest importance at higher ages were low blood pressure and measures related to good cardiorespiratory function. In multivariable analysis, including all examinations, being a nonsmoker, consuming small amounts of coffee, having high housing costs at age 50, good maximum working capacity and low serum cholesterol were related to a better chance of survival to age 90. Conclusions. Low levels of cardiovascular risk factors, high socio-economic status and good functional capacity, irrespective of parents' survival, characterize men destined to reach the age of 90.
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| 26. |
- Ahlqvist, Josefin, et al.
(författare)
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Crystal structure of DNA polymerase I from Thermus phage G20c
- 2022
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Ingår i: Acta crystallographica. Section D, Structural biology. - 2059-7983. ; 78:Pt 11, s. 1384-1398
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Tidskriftsartikel (refereegranskat)abstract
- This study describes the structure of DNA polymerase I from Thermus phage G20c, termed PolI_G20c. This is the first structure of a DNA polymerase originating from a group of related thermophilic bacteriophages infecting Thermus thermophilus, including phages G20c, TSP4, P74-26, P23-45 and phiFA and the novel phage Tth15-6. Sequence and structural analysis of PolI_G20c revealed a 3'-5' exonuclease domain and a DNA polymerase domain, and activity screening confirmed that both domains were functional. No functional 5'-3' exonuclease domain was present. Structural analysis also revealed a novel specific structure motif, here termed SβαR, that was not previously identified in any polymerase belonging to the DNA polymerases I (or the DNA polymerase A family). The SβαR motif did not show any homology to the sequences or structures of known DNA polymerases. The exception was the sequence conservation of the residues in this motif in putative DNA polymerases encoded in the genomes of a group of thermophilic phages related to Thermus phage G20c. The structure of PolI_G20c was determined with the aid of another structure that was determined in parallel and was used as a model for molecular replacement. This other structure was of a 3'-5' exonuclease termed ExnV1. The cloned and expressed gene encoding ExnV1 was isolated from a thermophilic virus metagenome that was collected from several hot springs in Iceland. The structure of ExnV1, which contains the novel SβαR motif, was first determined to 2.19 Å resolution. With these data at hand, the structure of PolI_G20c was determined to 2.97 Å resolution. The structures of PolI_G20c and ExnV1 are most similar to those of the Klenow fragment of DNA polymerase I (PDB entry 2kzz) from Escherichia coli, DNA polymerase I from Geobacillus stearothermophilus (PDB entry 1knc) and Taq polymerase (PDB entry 1bgx) from Thermus aquaticus.
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- Dillon, Joseph S., et al.
(författare)
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Time to Sustained Improvement in Bowel Movement Frequency with Telotristat Ethyl : Analyses of Phase III Studies in Carcinoid Syndrome
- 2021
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Ingår i: Journal of Gastrointestinal Cancer. - : Springer Science and Business Media LLC. - 1941-6628 .- 1941-6636. ; 52:1, s. 212-221
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundTelotristat ethyl is approved to treat carcinoid syndrome diarrhea in combination with somatostatin analogs. In TELESTAR and TELECAST phase III studies, patients with carcinoid syndrome received telotristat ethyl 250 or 500 mg 3 times per day (tid) or placebo tid in addition to somatostatin analogs. The aim of this prespecified analysis was to examine the time to reductions in bowel movements (BMs) in the TELESTAR and TELECAST studies using survival analysis methods.MethodsFirst occurrence of sustained response was defined as the time to the first day of 2 consecutive weeks with a mean BM frequency improvement of ≥ 30% from baseline during the 12-week double-blind treatment periods. Time to first ≥ 30% worsening in BM frequency was also measured. Treatments were compared with the log-rank test; Cox regression models provided point and confidence interval estimates of the hazard ratios for each trial.ResultsIn TELESTAR and TELECAST, majority of patients (69%) on telotristat ethyl experienced a sustained ≥ 30% improvement in BM frequency. The median time to sustained reduction of at least 30% in BM frequency was significantly faster (fewer days to onset) for telotristat ethyl compared with placebo in both TELESTAR (250 mg, HR = 2.3 [95% CI, 1.3–4.1, P = 0.004]; 500 mg, HR = 2.2 [95% CI, 1.2–3.9, P = 0.009]) and TELECAST (250 mg, HR = 3.9 [95% CI, 1.6–11.1, P = 0.003]; 500 mg, HR = 4.2 [95% CI, 1.7–11.7, P = 0.002]). In TELECAST, 42% of patients on placebo experienced sustained worsening in BM frequency compared with 20% on telotristat ethyl; no significant difference was observed in TELESTAR.ConclusionThe time of onset of sustained BM frequency improvement mean and range are important when considering use of telotristat ethyl in patients with carcinoid syndrome diarrhea. Telotristat ethyl may also reduce sustained worsening in BM frequency.
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| 30. |
- Dumanski, Jan P., et al.
(författare)
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A MUTYH germline mutation is associated with small intestinal neuroendocrine tumors
- 2017
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Ingår i: Endocrine-Related Cancer. - 1351-0088 .- 1479-6821. ; 24:8, s. 427-443
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Tidskriftsartikel (refereegranskat)abstract
- The genetics behind predisposition to small intestinal neuroendocrine tumors (SI-NETs) is largely unknown, but there is growing awareness of a familial form of the disease. We aimed to identify germline mutations involved in the carcinogenesis of SI-NETs. The strategy included next-generation sequencing of exome- and/or whole-genome of blood DNA, and in selected cases, tumor DNA, from 24 patients from 15 families with the history of SI-NETs. We identified seven candidate mutations in six genes that were further studied using 215 sporadic SI-NET patients. The result was compared with the frequency of the candidate mutations in three control cohorts with a total of 35,688 subjects. A heterozygous variant causing an amino acid substitution p.(Gly396Asp) in the MutY DNA glycosylase gene (MUTYH) was significantly enriched in SI-NET patients (minor allele frequencies 0.013 and 0.003 for patients and controls respectively) and resulted in odds ratio of 5.09 (95% confidence interval 1.56-14.74; P value = 0.0038). We also found a statistically significant difference in age at diagnosis between familial and sporadic SI-NETs. MUTYH is involved in the protection of DNA from mutations caused by oxidative stress. The inactivation of this gene leads to specific increase of G:C- > T:A transversions in DNA sequence and has been shown to cause various cancers in humans and experimental animals. Our results suggest that p.(Gly396Asp) in MUTYH, and potentially other mutations in additional members of the same DNA excision-repair pathway (such as the OGG1 gene) might be involved in driving the tumorigenesis leading to familial and sporadic SI-NETs.
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| 35. |
- 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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| 36. |
- Koppram, Rakesh, 1986, et al.
(författare)
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Simultaneous saccharification and co-fermentation for bioethanol production using corncobs at lab, PDU and demo scales
- 2013
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Ingår i: Biotechnology for Biofuels. - : Springer Science and Business Media LLC. - 1754-6834 .- 1754-6834. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundWhile simultaneous saccharification and co-fermentation (SSCF) is considered to be a promising process for bioconversion of lignocellulosic materials to ethanol, there are still relatively little demo-plant data and operating experiences reported in the literature. In the current work, we designed a SSCF process and scaled up from lab to demo scale reaching 4% (w/v) ethanol using xylose rich corncobs.ResultsSeven different recombinant xylose utilizing Saccharomyces cerevisiae strains were evaluated for their fermentation performance in hydrolysates of steam pretreated corncobs. Two strains, RHD-15 and KE6-12 with highest ethanol yield and lowest xylitol yield, respectively were further screened in SSCF using the whole slurry from pretreatment. Similar ethanol yields were reached with both strains, however, KE6-12 was chosen as the preferred strain since it produced 26% lower xylitol from consumed xylose compared to RHD-15. Model SSCF experiments with glucose or hydrolysate feed in combination with prefermentation resulted in 79% of xylose consumption and more than 75% of the theoretical ethanol yield on available glucose and xylose in lab and PDU scales. The results suggest that for an efficient xylose conversion to ethanol controlled release of glucose from enzymatic hydrolysis and low levels of glucose concentration must be maintained throughout the SSCF. Fed-batch SSCF in PDU with addition of enzymes at three different time points facilitated controlled release of glucose and hence co-consumption of glucose and xylose was observed yielding 76% of the theoretical ethanol yield on available glucose and xylose at 7.9% water insoluble solids (WIS). With a fed-batch SSCF in combination with prefermentation and a feed of substrate and enzymes 47 and 40 g l-1 of ethanol corresponding to 68% and 58% of the theoretical ethanol yield on available glucose and xylose were produced at 10.5% WIS in PDU and demo scale, respectively. The strain KE6-12 was able to completely consume xylose within 76 h during the fermentation of hydrolysate in a 10 m3 demo scale bioreactor.ConclusionsThe potential of SSCF is improved in combination with prefermentation and a feed of substrate and enzymes. It was possible to successfully reproduce the fed-batch SSCF at demo scale producing 4% (w/v) ethanol which is the minimum economical requirement for efficient lignocellulosic bioethanol production process.
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| 37. |
- Koppram, Rakesh, 1986, et al.
(författare)
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Simultaneous saccharification and co-fermentation for bioethanol production using corncobs at lab, PDU and demo scales
- 2015
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Ingår i: Fuel production from non-food biomass: Corn stover. - : Apple Academic Press. - 9781498728430 - 9781771881234 ; , s. 155-179
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- The global CO2 emissions in 2010 from fossil energy use grew at the fastest rate since 1969. The year 2010 also witnessed that the global oil production did not match the rapid growth in consumption [1]. These recent data further intensify worldwide concerns about greenhouse gas emissions and energy security for a sustained economic development. For a reduced dependence on oil from fossil reserves, use of biofuels such as bioethanol from abundantly available lignocellulosic biomass is of great interest nowadays because they will count towards meeting the mandate of 10% binding target for biofuels from renewable sources in the transport for all European member states by 2020 [2]. Along with this interest comes increased interest in commercializing ethanol production technology from inexpensive lignocellulosic feedstocks which includes wood biomass, agricultural and forestry residues, biodegradable fraction of industrial and municipal wastes. Irrespective of type, the basic structural composition of lignocellulosic biomass consists of cellulose, hemicellulose and lignin. The cellulose and hemicellulose that form the polysaccharide fraction are embedded in a recalcitrant and inaccessible arrangement [3] and therefore requires a pretreatment step to disrupt the structure and make it accessible for subsequent steps. Since lignocellulosic materials are very complex, not one pretreatment method can apply for all the materials. Several methods that are classified in to physical, physico-chemical, chemical and biological pretreatment have been investigated and an elaborate review on each of these methods has been presented by Taherzadeh and Karimi [4]. One of the most commonly used pretreatment methods is steam explosion, with the addition of H2SO4 or SO2, which removes most of the hemicellulose, followed by enzymatic hydrolysis to convert cellulose to glucose [5,6].
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| 38. |
- Kulke, Matthew H., et al.
(författare)
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Telotristat Ethyl, a Tryptophan Hydroxylase Inhibitor for the Treatment of Carcinoid Syndrome
- 2017
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Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 35:1, s. 14-23
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Preliminary studies suggested that telotristat ethyl, a tryptophan hydroxylase inhibitor, reduces bowel movement (BM) frequency in patients with carcinoid syndrome. This placebo-controlled phase III study evaluated telotristat ethyl in this setting. Patients and Methods Patients (N = 135) experiencing four or more BMs per day despite stable-dose somatostatin analog therapy received (1: 1: 1) placebo, telotristat ethyl 250 mg, or telotristat ethyl 500 mg three times per day orally during a 12-week double-blind treatment period. The primary end point was change from baseline in BM frequency. In an open-label extension, 115 patients subsequently received telotristat ethyl 500 mg. Results Estimated differences in BM frequency per day versus placebo averaged over 12 weeks were -0.81 for telotristat ethyl 250 mg (P < .001) and -0.69 for telotristat ethyl 500 mg (P,.001). At week 12, mean BM frequency reductions per day for placebo, telotristat ethyl 250 mg, and telotristat ethyl 500 mg were -0.9, -1.7, and -2.1, respectively. Responses, predefined as a BM frequency reduction >= 30% from baseline for >= 50% of the double-blind treatment period, were observed in 20%, 44%, and 42% of patients given placebo, telotristat ethyl 250 mg, and telotristat ethyl 500 mg, respectively. Both telotristat ethyl dosages significantly reduced mean urinary 5-hydroxyindole acetic acid versus placebo at week 12 (P < .001). Mild nausea and asymptomatic increases in gamma-glutamyl transferase were observed in some patients receiving telotristat ethyl. Follow-up of patients during the open-label extension revealed no new safety signals and suggested sustained BM responses to treatment. Conclusion Among patients with carcinoid syndrome not adequately controlled by somatostatin analogs, treatment with telotristat ethyl was generally safe and well tolerated and resulted in significant reductions in BM frequency and urinary 5-hydroxyindole acetic acid.
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| 40. |
- Parodis, Ioannis, 1981-, et al.
(författare)
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EULAR recommendations for the non-pharmacological management of systemic lupus erythematosus and systemic sclerosis
- 2024
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Ingår i: Annals of the Rheumatic Diseases. - : HighWire Press. - 0003-4967 .- 1468-2060. ; 83, s. 720-729
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To develop evidence-based recommendations for the non-pharmacological management of systemic lupus erythematosus (SLE) and systemic sclerosis (SSc).METHODS: A task force comprising 7 rheumatologists, 15 other healthcare professionals and 3 patients was established. Following a systematic literature review performed to inform the recommendations, statements were formulated, discussed during online meetings and graded based on risk of bias assessment, level of evidence (LoE) and strength of recommendation (SoR; scale A-D, A comprising consistent LoE 1 studies, D comprising LoE 4 or inconsistent studies), following the European Alliance of Associations for Rheumatology standard operating procedure. Level of agreement (LoA; scale 0-10, 0 denoting complete disagreement, 10 denoting complete agreement) was determined for each statement through online voting.RESULTS: Four overarching principles and 12 recommendations were developed. These concerned common and disease-specific aspects of non-pharmacological management. SoR ranged from A to D. The mean LoA with the overarching principles and recommendations ranged from 8.4 to 9.7. Briefly, non-pharmacological management of SLE and SSc should be tailored, person-centred and participatory. It is not intended to preclude but rather complement pharmacotherapy. Patients should be offered education and support for physical exercise, smoking cessation and avoidance of cold exposure. Photoprotection and psychosocial interventions are important for SLE patients, while mouth and hand exercises are important in SSc.CONCLUSIONS: The recommendations will guide healthcare professionals and patients towards a holistic and personalised management of SLE and SSc. Research and educational agendas were developed to address needs towards a higher evidence level, enhancement of clinician-patient communication and improved outcomes.
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| 41. |
- Rusek, Linnéa, et al.
(författare)
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Lifetime risk of stroke in the general male population
- 2020
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Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 142:1, s. 30-36
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Most previous studies of incidence rates of stroke are from register studies, while data from prospective cohort studies are limited. The aim of the present study was to describe hazard rates, prevalence and cumulative proportion free from stroke during a lifelong follow-up of a representative sample of middle-aged men sampled from the general population. Methods A population-based sample of 855 men, all born in 1913, was investigated at 50 years of age and followed up with repeated medical examinations at age 54, 60, 67, 75 and 80. Data from hospital records and the Cause of Death Register were collected, and all stroke events during 48 years of follow-up were registered. Medical records were scrutinized in order to confirm and validate the stroke diagnoses. Results One man was excluded because of stroke prior to baseline, while 176 of the remaining 854 men (20.7%) suffered a first-ever stroke during follow-up. The total 5-year stroke risk (hazard rate) increased with age, from 3.54 (95% CI: 0-7.55) per 1000 persons at risk at age 50 years, to 119.05 (95% CI: 45.39-192.70) at age 90 years. The stroke prevalence peaked at age 80 and older, with about 120 cases per 1000 years of observation. The survival rate (cumulative proportion free from stroke) at age 98 was 50.0%. Conclusion One out of five men in this population sample suffered a stroke of any type during follow-up from 50 to 98 years of age and the cumulative incidence was close to 50%.
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| 42. |
- Shilova, Anastasiia, et al.
(författare)
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Current status and future opportunities for serial crystallography at MAX IV Laboratory
- 2020
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Ingår i: Journal of Synchrotron Radiation. - Chichester : Wiley-Blackwell. - 0909-0495 .- 1600-5775. ; 27, s. 1095-1102
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Tidskriftsartikel (refereegranskat)abstract
- Over the last decade, serial crystallography, a method to collect complete diffraction datasets from a large number of microcrystals delivered and exposed to an X-ray beam in random orientations at room temperature, has been successfully implemented at X-ray free-electron lasers and synchrotron radiation facility beamlines. This development relies on a growing variety of sample presentation methods, including different fixed target supports, injection methods using gas-dynamic virtual-nozzle injectors and high-viscosity extrusion injectors, and acoustic levitation of droplets, each with unique requirements. In comparison with X-ray free-electron lasers, increased beam time availability makes synchrotron facilities very attractive to perform serial synchrotron X-ray crystallography (SSX) experiments. Within this work, the possibilities to perform SSX at BioMAX, the first macromolecular crystallography beamline at studies from the SSX user program: an implementation of a high-viscosity extrusion injector to perform room temperature serial crystallography at BioMAX using two solid supports - silicon nitride membranes (Silson, UK) and XtalTool (Jena Bioscience, Germany). Future perspectives for the dedicated serial crystallography beamline MicroMAX at MAX IV Laboratory, which will provide parallel and intense micrometre-sized X-ray beams, are discussed.
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| 49. |
- Weickert, Martin O., et al.
(författare)
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Changes in Weight Associated With Telotristat Ethyl in the Treatment of Carcinoid Syndrome
- 2018
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Ingår i: Clinical Therapeutics. - : ELSEVIER. - 0149-2918 .- 1879-114X. ; 40:6, s. 952-962
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: In the placebo-controlled Phase III TELE-STAR (Telotristat Etiprate for Somatostatin Analogue Not Adequately Controlled Carcinoid Syndrome) trial, the oral tryptophan hydroxylase inhibitor telotristat ethyl significantly reduced bowel movement (BM) frequency during a 12-week, double-blind treatment period in 135 patients with metastatic neuroendocrine tumors with carcinoid syndrome and >= 4 BMs per day. Patients (mean [SD] age, 63.5 [8.9] years; mean [SD] body mass index, 24.9 [4.9] kg/m(2)) received placebo, telotristat ethyl 250 mg, or telotristat ethyl 500 mg 3 times per day (TID) in addition to somatostatin analogue therapy. Weight loss is associated with uncontrolled carcinoid syndrome and may be associated with reduced survival.Methods: Assessment of the occurrence of weight change >= 3% at week 12 was prespecified in the statistical analysis plan.Findings: In 120 patients with weight data available, weight gain >= 3% was observed in 2 of 39 patients (5.1%) taking placebo [1.1), 7 of 41 (17.1%) taking telotristat ethyl 250 mg TID, and 13 of 40 (32.5%) taking telotristat ethyl 500 mg TID (P = 0.0017) at week 12. Weight loss >= 3% was observed in 5 of 39 patients (12.8%) taking placebo TID, 4 of 41 (9.8%) taking telotristat ethyl 250 mg TID, and 6 of 40 (15.0%) taking telotristat ethyl 500 mg TID (P = 0.77). Biochemical and metabolic parameters of serum albumin and cholesterol significantly increased (P = 0.02 and P = 0.001, respectively) in patients gaining weight and decreased in patients who lost weight, suggesting an improvement in overall nutritional status.
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