Increased oxidative stress in obesity and diabetes is associated with morbidity and mortality ris... more Increased oxidative stress in obesity and diabetes is associated with morbidity and mortality risks. Levels of oxidative damage to DNA and RNA can be estimated through measurement of 8-oxo-7,8-dihydro-2´-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo) in urine. Both markers have been associated with type 2 diabetes, where especially 8-oxoGuo is prognostic for mortality risk. We hypothesized that Roux-en-Y gastric bypass (RYGB) surgery that has considerable effects on bodyweight, hyperglycemia and mortality, might be working through mechanisms that reduce oxidative stress, thereby reducing levels of the urinary markers. We used liquid chromatography coupled with tandem mass spectrometry to analyze the content of 8-oxodG and 8-oxoGuo in urinary samples from 356 obese patients treated with the RYGB-procedure. Mean age (SD) was 44.2 (9.6) years, BMI was 42.1 (5.6) kg/m2. Ninety-six (27%) of the patients had type 2 diabetes. Excretion levels of each marker before and a...
Unacknowledged inconsistencies in the reporting of clinical trials undermine the validity of the ... more Unacknowledged inconsistencies in the reporting of clinical trials undermine the validity of the results of the trials. Little is known about inconsistency in the reporting of academic clinical drug trials. Therefore, we investigated the prevalence of consistency between protocols and published reports of academic clinical drug trials. A comparison was made between study protocols and their corresponding published reports. We assessed the overall consistency, which was defined as the absence of discrepancy regarding study type (categorized as either exploratory or confirmatory), primary objective, primary endpoint, and - for confirmatory trials only - hypothesis and sample size calculation. We used logistic regression, χ(2), and Fisher's exact test. A total of 282 applications of academic clinical drug trials were submitted to the Danish Health and Medicines Authority in 1999, 2001, and 2003, 95 of which fulfilled the eligibility criteria and had at least one corresponding publi...
Unacknowledged inconsistencies in the reporting of clinical trials undermine the validity of the ... more Unacknowledged inconsistencies in the reporting of clinical trials undermine the validity of the results of the trials. Little is known about inconsistency in the reporting of academic clinical drug trials. Therefore, we investigated the prevalence of consistency between protocols and published reports of academic clinical drug trials. A comparison was made between study protocols and their corresponding published reports. We assessed the overall consistency, which was defined as the absence of discrepancy regarding study type (categorized as either exploratory or confirmatory), primary objective, primary endpoint, and - for confirmatory trials only - hypothesis and sample size calculation. We used logistic regression, χ(2), and Fisher's exact test. A total of 282 applications of academic clinical drug trials were submitted to the Danish Health and Medicines Authority in 1999, 2001, and 2003, 95 of which fulfilled the eligibility criteria and had at least one corresponding publi...
Scandinavian journal of clinical and laboratory investigation, Jan 15, 2016
Oxidative stress to DNA from smoking was investigated in one randomized smoking cessation study a... more Oxidative stress to DNA from smoking was investigated in one randomized smoking cessation study and in 36 cohort studies from excretion of urinary 8-oxo-7-hydrodeoxyguanosine (8-oxodG). Meta-analysis of the 36 cohort studies showed smoking associated with a 15.7% (95% CL 11.0:20.3, p < 0.0001) increased oxidative stress to DNA, in agreement with the reduction of oxidative stress to DNA found in the smoking cessation study. Meta-analysis of the 22 studies that used chromatography methodology on 1709 persons showed a significant 29.3% increase in smokers (95% CL 17.3;41.3), but meta-analysis of 14 studies on 3668 persons using ELISA methodology showed a non-significant effect of 8.7% [95% CL -1.2;18.6]. Tobacco smoke induces oxidative damage to DNA; however, this is not detected with ELISA methodology. Currently, the use of existing ELISA methodology to measure urinary excretion of 8-oxo-7-hydrodeoxyguanosine cannot be recommended.
Scandinavian journal of clinical and laboratory investigation, Jan 15, 2016
Oxidative stress to DNA from smoking was investigated in one randomized smoking cessation study a... more Oxidative stress to DNA from smoking was investigated in one randomized smoking cessation study and in 36 cohort studies from excretion of urinary 8-oxo-7-hydrodeoxyguanosine (8-oxodG). Meta-analysis of the 36 cohort studies showed smoking associated with a 15.7% (95% CL 11.0:20.3, p < 0.0001) increased oxidative stress to DNA, in agreement with the reduction of oxidative stress to DNA found in the smoking cessation study. Meta-analysis of the 22 studies that used chromatography methodology on 1709 persons showed a significant 29.3% increase in smokers (95% CL 17.3;41.3), but meta-analysis of 14 studies on 3668 persons using ELISA methodology showed a non-significant effect of 8.7% [95% CL -1.2;18.6]. Tobacco smoke induces oxidative damage to DNA; however, this is not detected with ELISA methodology. Currently, the use of existing ELISA methodology to measure urinary excretion of 8-oxo-7-hydrodeoxyguanosine cannot be recommended.
Undisclosed use of illicit drugs and prescription controlled substances is frequent in some setti... more Undisclosed use of illicit drugs and prescription controlled substances is frequent in some settings. The aim of the present study was to estimate the reliability of self-reported use of amphetamine, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, and opiates among acutely hospitalized medical patients. Patients admitted to an acute medical department were interviewed about their drug use. Patients provided blood and urine samples for drug analysis. Results of a toxicology screen were compared to self-reported drug use. Toxicology screens positive for drugs not reported during the interview were only considered truly positive after verification by a substance specific analysis. Five hundred patients were included. The median age was 72 years and 298 (60%) were female. In total, 103 patients (21%) reported use of opiates and 65 patients (13%) used benzodiazepines. Only 8 patients reported use of illicit drugs (cannabinoids, 2%). Toxicology analyses were performed in a randomly selected sub-sample of 100 patients. Among 27 patients (27%), the analyses indicated use of one or more drugs, mainly benzodiazepines (15 patients), morphine (12 patients) or cannabinoids (5 patients). Another 6 patients had screenings unexpectedly positive for opiates, but the verification analysis indicated use of codeine-containing drugs. The overall sensitivity of self-reports in detecting drug use was 66%. The negative predictive value of a patient not reporting use of a drug was over 90% for all 7 drug-types screened. Among 100 randomly selected mainly elderly medical patients, undeclared use of illicit drugs was rare. However, some patients underreported use of benzodiazepines and cannabinoids.
Undisclosed use of illicit drugs and prescription controlled substances is frequent in some setti... more Undisclosed use of illicit drugs and prescription controlled substances is frequent in some settings. The aim of the present study was to estimate the reliability of self-reported use of amphetamine, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, and opiates among acutely hospitalized medical patients. Patients admitted to an acute medical department were interviewed about their drug use. Patients provided blood and urine samples for drug analysis. Results of a toxicology screen were compared to self-reported drug use. Toxicology screens positive for drugs not reported during the interview were only considered truly positive after verification by a substance specific analysis. Five hundred patients were included. The median age was 72 years and 298 (60%) were female. In total, 103 patients (21%) reported use of opiates and 65 patients (13%) used benzodiazepines. Only 8 patients reported use of illicit drugs (cannabinoids, 2%). Toxicology analyses were performed in a randomly selected sub-sample of 100 patients. Among 27 patients (27%), the analyses indicated use of one or more drugs, mainly benzodiazepines (15 patients), morphine (12 patients) or cannabinoids (5 patients). Another 6 patients had screenings unexpectedly positive for opiates, but the verification analysis indicated use of codeine-containing drugs. The overall sensitivity of self-reports in detecting drug use was 66%. The negative predictive value of a patient not reporting use of a drug was over 90% for all 7 drug-types screened. Among 100 randomly selected mainly elderly medical patients, undeclared use of illicit drugs was rare. However, some patients underreported use of benzodiazepines and cannabinoids.
Misoprostol can be used in the prevention of gastric ulcer in treatment with diclofenac and is us... more Misoprostol can be used in the prevention of gastric ulcer in treatment with diclofenac and is used in rheumatic diseases. Since misoprostol causes contractions of the uterus, it can also be used to induce abortions when administrated vaginally. The aim of the study was to investigate if early pregnancy exposure to oral diclofenac/misoprostol was associated with miscarriage. We conducted a nationwide cohort study identifying all registered pregnancies in Denmark from 1997 to 2011. All births were identified using the Medical Birth Registry, and all records of induced abortion and miscarriage were from the National Hospital Register. Data on drug use were from the National Prescription Register. Cox proportional hazard regression models were used to calculate the hazard of miscarriage in women exposed to diclofenac/misoprostol in early pregnancy. We identified 1,338,824 pregnancies (970,491 births, 142,147 miscarriages, 226,145 induced abortions). One hundred sixty-six were exposed to diclofenac/misoprostol in the early pregnancy of which 28.3 % (47) ended up in a miscarriage compared to 10.6 % among unexposed. The adjusted hazard ratio of having a miscarriage after exposure to diclofenac/misoprostol in the first trimester was 3.6 (CI 95 % 2.6-4.9). We found an increased risk of miscarriage after exposure to diclofenac/misoprostol during the early pregnancy. Women in the fertile age should not be treated with the combination of diclofenac/misoprostol if other options were available.
Misoprostol can be used in the prevention of gastric ulcer in treatment with diclofenac and is us... more Misoprostol can be used in the prevention of gastric ulcer in treatment with diclofenac and is used in rheumatic diseases. Since misoprostol causes contractions of the uterus, it can also be used to induce abortions when administrated vaginally. The aim of the study was to investigate if early pregnancy exposure to oral diclofenac/misoprostol was associated with miscarriage. We conducted a nationwide cohort study identifying all registered pregnancies in Denmark from 1997 to 2011. All births were identified using the Medical Birth Registry, and all records of induced abortion and miscarriage were from the National Hospital Register. Data on drug use were from the National Prescription Register. Cox proportional hazard regression models were used to calculate the hazard of miscarriage in women exposed to diclofenac/misoprostol in early pregnancy. We identified 1,338,824 pregnancies (970,491 births, 142,147 miscarriages, 226,145 induced abortions). One hundred sixty-six were exposed to diclofenac/misoprostol in the early pregnancy of which 28.3 % (47) ended up in a miscarriage compared to 10.6 % among unexposed. The adjusted hazard ratio of having a miscarriage after exposure to diclofenac/misoprostol in the first trimester was 3.6 (CI 95 % 2.6-4.9). We found an increased risk of miscarriage after exposure to diclofenac/misoprostol during the early pregnancy. Women in the fertile age should not be treated with the combination of diclofenac/misoprostol if other options were available.
Increased oxidative stress in obesity and diabetes is associated with morbidity and mortality ris... more Increased oxidative stress in obesity and diabetes is associated with morbidity and mortality risks. Levels of oxidative damage to DNA and RNA can be estimated through measurement of 8-oxo-7,8-dihydro-2´-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo) in urine. Both markers have been associated with type 2 diabetes, where especially 8-oxoGuo is prognostic for mortality risk. We hypothesized that Roux-en-Y gastric bypass (RYGB) surgery that has considerable effects on bodyweight, hyperglycemia and mortality, might be working through mechanisms that reduce oxidative stress, thereby reducing levels of the urinary markers. We used liquid chromatography coupled with tandem mass spectrometry to analyze the content of 8-oxodG and 8-oxoGuo in urinary samples from 356 obese patients treated with the RYGB-procedure. Mean age (SD) was 44.2 (9.6) years, BMI was 42.1 (5.6) kg/m2. Ninety-six (27%) of the patients had type 2 diabetes. Excretion levels of each marker before and a...
Unacknowledged inconsistencies in the reporting of clinical trials undermine the validity of the ... more Unacknowledged inconsistencies in the reporting of clinical trials undermine the validity of the results of the trials. Little is known about inconsistency in the reporting of academic clinical drug trials. Therefore, we investigated the prevalence of consistency between protocols and published reports of academic clinical drug trials. A comparison was made between study protocols and their corresponding published reports. We assessed the overall consistency, which was defined as the absence of discrepancy regarding study type (categorized as either exploratory or confirmatory), primary objective, primary endpoint, and - for confirmatory trials only - hypothesis and sample size calculation. We used logistic regression, χ(2), and Fisher's exact test. A total of 282 applications of academic clinical drug trials were submitted to the Danish Health and Medicines Authority in 1999, 2001, and 2003, 95 of which fulfilled the eligibility criteria and had at least one corresponding publi...
Unacknowledged inconsistencies in the reporting of clinical trials undermine the validity of the ... more Unacknowledged inconsistencies in the reporting of clinical trials undermine the validity of the results of the trials. Little is known about inconsistency in the reporting of academic clinical drug trials. Therefore, we investigated the prevalence of consistency between protocols and published reports of academic clinical drug trials. A comparison was made between study protocols and their corresponding published reports. We assessed the overall consistency, which was defined as the absence of discrepancy regarding study type (categorized as either exploratory or confirmatory), primary objective, primary endpoint, and - for confirmatory trials only - hypothesis and sample size calculation. We used logistic regression, χ(2), and Fisher's exact test. A total of 282 applications of academic clinical drug trials were submitted to the Danish Health and Medicines Authority in 1999, 2001, and 2003, 95 of which fulfilled the eligibility criteria and had at least one corresponding publi...
Scandinavian journal of clinical and laboratory investigation, Jan 15, 2016
Oxidative stress to DNA from smoking was investigated in one randomized smoking cessation study a... more Oxidative stress to DNA from smoking was investigated in one randomized smoking cessation study and in 36 cohort studies from excretion of urinary 8-oxo-7-hydrodeoxyguanosine (8-oxodG). Meta-analysis of the 36 cohort studies showed smoking associated with a 15.7% (95% CL 11.0:20.3, p < 0.0001) increased oxidative stress to DNA, in agreement with the reduction of oxidative stress to DNA found in the smoking cessation study. Meta-analysis of the 22 studies that used chromatography methodology on 1709 persons showed a significant 29.3% increase in smokers (95% CL 17.3;41.3), but meta-analysis of 14 studies on 3668 persons using ELISA methodology showed a non-significant effect of 8.7% [95% CL -1.2;18.6]. Tobacco smoke induces oxidative damage to DNA; however, this is not detected with ELISA methodology. Currently, the use of existing ELISA methodology to measure urinary excretion of 8-oxo-7-hydrodeoxyguanosine cannot be recommended.
Scandinavian journal of clinical and laboratory investigation, Jan 15, 2016
Oxidative stress to DNA from smoking was investigated in one randomized smoking cessation study a... more Oxidative stress to DNA from smoking was investigated in one randomized smoking cessation study and in 36 cohort studies from excretion of urinary 8-oxo-7-hydrodeoxyguanosine (8-oxodG). Meta-analysis of the 36 cohort studies showed smoking associated with a 15.7% (95% CL 11.0:20.3, p < 0.0001) increased oxidative stress to DNA, in agreement with the reduction of oxidative stress to DNA found in the smoking cessation study. Meta-analysis of the 22 studies that used chromatography methodology on 1709 persons showed a significant 29.3% increase in smokers (95% CL 17.3;41.3), but meta-analysis of 14 studies on 3668 persons using ELISA methodology showed a non-significant effect of 8.7% [95% CL -1.2;18.6]. Tobacco smoke induces oxidative damage to DNA; however, this is not detected with ELISA methodology. Currently, the use of existing ELISA methodology to measure urinary excretion of 8-oxo-7-hydrodeoxyguanosine cannot be recommended.
Undisclosed use of illicit drugs and prescription controlled substances is frequent in some setti... more Undisclosed use of illicit drugs and prescription controlled substances is frequent in some settings. The aim of the present study was to estimate the reliability of self-reported use of amphetamine, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, and opiates among acutely hospitalized medical patients. Patients admitted to an acute medical department were interviewed about their drug use. Patients provided blood and urine samples for drug analysis. Results of a toxicology screen were compared to self-reported drug use. Toxicology screens positive for drugs not reported during the interview were only considered truly positive after verification by a substance specific analysis. Five hundred patients were included. The median age was 72 years and 298 (60%) were female. In total, 103 patients (21%) reported use of opiates and 65 patients (13%) used benzodiazepines. Only 8 patients reported use of illicit drugs (cannabinoids, 2%). Toxicology analyses were performed in a randomly selected sub-sample of 100 patients. Among 27 patients (27%), the analyses indicated use of one or more drugs, mainly benzodiazepines (15 patients), morphine (12 patients) or cannabinoids (5 patients). Another 6 patients had screenings unexpectedly positive for opiates, but the verification analysis indicated use of codeine-containing drugs. The overall sensitivity of self-reports in detecting drug use was 66%. The negative predictive value of a patient not reporting use of a drug was over 90% for all 7 drug-types screened. Among 100 randomly selected mainly elderly medical patients, undeclared use of illicit drugs was rare. However, some patients underreported use of benzodiazepines and cannabinoids.
Undisclosed use of illicit drugs and prescription controlled substances is frequent in some setti... more Undisclosed use of illicit drugs and prescription controlled substances is frequent in some settings. The aim of the present study was to estimate the reliability of self-reported use of amphetamine, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, and opiates among acutely hospitalized medical patients. Patients admitted to an acute medical department were interviewed about their drug use. Patients provided blood and urine samples for drug analysis. Results of a toxicology screen were compared to self-reported drug use. Toxicology screens positive for drugs not reported during the interview were only considered truly positive after verification by a substance specific analysis. Five hundred patients were included. The median age was 72 years and 298 (60%) were female. In total, 103 patients (21%) reported use of opiates and 65 patients (13%) used benzodiazepines. Only 8 patients reported use of illicit drugs (cannabinoids, 2%). Toxicology analyses were performed in a randomly selected sub-sample of 100 patients. Among 27 patients (27%), the analyses indicated use of one or more drugs, mainly benzodiazepines (15 patients), morphine (12 patients) or cannabinoids (5 patients). Another 6 patients had screenings unexpectedly positive for opiates, but the verification analysis indicated use of codeine-containing drugs. The overall sensitivity of self-reports in detecting drug use was 66%. The negative predictive value of a patient not reporting use of a drug was over 90% for all 7 drug-types screened. Among 100 randomly selected mainly elderly medical patients, undeclared use of illicit drugs was rare. However, some patients underreported use of benzodiazepines and cannabinoids.
Misoprostol can be used in the prevention of gastric ulcer in treatment with diclofenac and is us... more Misoprostol can be used in the prevention of gastric ulcer in treatment with diclofenac and is used in rheumatic diseases. Since misoprostol causes contractions of the uterus, it can also be used to induce abortions when administrated vaginally. The aim of the study was to investigate if early pregnancy exposure to oral diclofenac/misoprostol was associated with miscarriage. We conducted a nationwide cohort study identifying all registered pregnancies in Denmark from 1997 to 2011. All births were identified using the Medical Birth Registry, and all records of induced abortion and miscarriage were from the National Hospital Register. Data on drug use were from the National Prescription Register. Cox proportional hazard regression models were used to calculate the hazard of miscarriage in women exposed to diclofenac/misoprostol in early pregnancy. We identified 1,338,824 pregnancies (970,491 births, 142,147 miscarriages, 226,145 induced abortions). One hundred sixty-six were exposed to diclofenac/misoprostol in the early pregnancy of which 28.3 % (47) ended up in a miscarriage compared to 10.6 % among unexposed. The adjusted hazard ratio of having a miscarriage after exposure to diclofenac/misoprostol in the first trimester was 3.6 (CI 95 % 2.6-4.9). We found an increased risk of miscarriage after exposure to diclofenac/misoprostol during the early pregnancy. Women in the fertile age should not be treated with the combination of diclofenac/misoprostol if other options were available.
Misoprostol can be used in the prevention of gastric ulcer in treatment with diclofenac and is us... more Misoprostol can be used in the prevention of gastric ulcer in treatment with diclofenac and is used in rheumatic diseases. Since misoprostol causes contractions of the uterus, it can also be used to induce abortions when administrated vaginally. The aim of the study was to investigate if early pregnancy exposure to oral diclofenac/misoprostol was associated with miscarriage. We conducted a nationwide cohort study identifying all registered pregnancies in Denmark from 1997 to 2011. All births were identified using the Medical Birth Registry, and all records of induced abortion and miscarriage were from the National Hospital Register. Data on drug use were from the National Prescription Register. Cox proportional hazard regression models were used to calculate the hazard of miscarriage in women exposed to diclofenac/misoprostol in early pregnancy. We identified 1,338,824 pregnancies (970,491 births, 142,147 miscarriages, 226,145 induced abortions). One hundred sixty-six were exposed to diclofenac/misoprostol in the early pregnancy of which 28.3 % (47) ended up in a miscarriage compared to 10.6 % among unexposed. The adjusted hazard ratio of having a miscarriage after exposure to diclofenac/misoprostol in the first trimester was 3.6 (CI 95 % 2.6-4.9). We found an increased risk of miscarriage after exposure to diclofenac/misoprostol during the early pregnancy. Women in the fertile age should not be treated with the combination of diclofenac/misoprostol if other options were available.
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