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A Validated Clinical Risk Prediction Model for #Lung Cancer in #Smokers of All Ages and Exposure Types: A HUNT Study
https://www.sciencedirect.com/science/article/pii/S2352396418301142?via%3Dihub
Highlights
•
Applying this risk model in adults, screening 22% of ever-smokers would identify 81·85% of all lung cancers within 6 years.
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Two novel highly significant factors were identified, periodical daily cough, and hours of daily indoors exposure to smoke.
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The HUNT Lung Cancer Model is an accurate risk predictor useful in prospective screening studies for lung cancer.
Our final HUNT Lung Cancer Model included age, pack-years, smoking intensity, years since smoking cessation, body mass index, daily cough, and hours of daily indoors exposure to smoke. External validation showed a 0·879 concordance index (95% CI 0·866–0·891) with an area under the curve of 0·87 (95% CI 0·85–0·89) within 6 years. Only 22% of ever-smokers would need screening to identify 81·85% of all lung cancers within 6 years.
Our model of seven variables is simple, accurate, and useful for screening selection
A Validated Clinical Risk Prediction Model for #Lung Cancer in #Smokers of All Ages and Exposure Types: A HUNT Study
https://www.sciencedirect.com/science/article/pii/S2352396418301142?via%3Dihub
Highlights
•
Applying this risk model in adults, screening 22% of ever-smokers would identify 81·85% of all lung cancers within 6 years.
•
Two novel highly significant factors were identified, periodical daily cough, and hours of daily indoors exposure to smoke.
•
The HUNT Lung Cancer Model is an accurate risk predictor useful in prospective screening studies for lung cancer.
Our final HUNT Lung Cancer Model included age, pack-years, smoking intensity, years since smoking cessation, body mass index, daily cough, and hours of daily indoors exposure to smoke. External validation showed a 0·879 concordance index (95% CI 0·866–0·891) with an area under the curve of 0·87 (95% CI 0·85–0·89) within 6 years. Only 22% of ever-smokers would need screening to identify 81·85% of all lung cancers within 6 years.
Our model of seven variables is simple, accurate, and useful for screening selection
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Combined Analysis of #Asthma Safety Trials of Long-Acting #β2-Agonists
https://www.nejm.org/doi/full/10.1056/NEJMoa1716868
Among the 36,010 patients in the intention-to-treat study, there were three asthma-related intubations (two in the inhaled-glucocorticoid group and one in the combination-therapy group) and two asthma-related deaths (both in the combination-therapy group) in 4 patients. In the secondary analysis of serious asthma-related events (a composite of hospitalization, intubation, or death), 108 of 18,006 patients (0.60%) in the inhaled-glucocorticoid group and 119 of 18,004 patients (0.66%) in the combination-therapy group had at least one composite event (relative risk in the combination-therapy group, 1.09; 95% confidence interval CI, 0.83 to 1.43; P=0.55); 2100 patients in the inhaled-glucocorticoid group (11.7%) and 1768 in the combination-therapy group (9.8%) had at least one asthma exacerbation (relative risk, 0.83; 95% CI, 0.78 to 0.89; P<0.001).
CONCLUSIONS
Combination therapy with a LABA plus an inhaled glucocorticoid did not result in a significantly higher risk of serious asthma-related events than treatment with an inhaled glucocorticoid alone but resulted in significantly fewer asthma exacerbations
Combined Analysis of #Asthma Safety Trials of Long-Acting #β2-Agonists
https://www.nejm.org/doi/full/10.1056/NEJMoa1716868
Among the 36,010 patients in the intention-to-treat study, there were three asthma-related intubations (two in the inhaled-glucocorticoid group and one in the combination-therapy group) and two asthma-related deaths (both in the combination-therapy group) in 4 patients. In the secondary analysis of serious asthma-related events (a composite of hospitalization, intubation, or death), 108 of 18,006 patients (0.60%) in the inhaled-glucocorticoid group and 119 of 18,004 patients (0.66%) in the combination-therapy group had at least one composite event (relative risk in the combination-therapy group, 1.09; 95% confidence interval CI, 0.83 to 1.43; P=0.55); 2100 patients in the inhaled-glucocorticoid group (11.7%) and 1768 in the combination-therapy group (9.8%) had at least one asthma exacerbation (relative risk, 0.83; 95% CI, 0.78 to 0.89; P<0.001).
CONCLUSIONS
Combination therapy with a LABA plus an inhaled glucocorticoid did not result in a significantly higher risk of serious asthma-related events than treatment with an inhaled glucocorticoid alone but resulted in significantly fewer asthma exacerbations
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Risk of meticillin resistant #Staphylococcus aureus and #Clostridium difficile in patients with a documented #penicillin allergy: population based matched cohort study
https://www.bmj.com/content/361/bmj.k2400
The primary outcome was risk of incident MRSA and C difficile. Secondary outcomes were use of β lactam antibiotics and β lactam alternative antibiotics.
Results Among 64 141 adults with penicillin allergy and 237 258 matched comparators, 1365 developed MRSA (442 participants with penicillin allergy and 923 comparators) and 1688 developed C difficile (442 participants with penicillin allergy and 1246 comparators) during a mean 6.0 years of follow-up. Among patients with penicillin allergy the adjusted hazard ratio for MRSA was 1.69 (95% confidence interval 1.51 to 1.90) and for C difficile was 1.26 (1.12 to 1.40). The adjusted incidence rate ratios for antibiotic use among patients with penicillin allergy were 4.15 (95% confidence interval 4.12 to 4.17) for macrolides, 3.89 (3.66 to 4.12) for clindamycin, and 2.10 (2.08 to 2.13) for fluoroquinolones. Increased use of β lactam alternative antibiotics accounted for 55% of the increased risk of MRSA and 35% of the increased risk of C difficile.
Conclusions Documented penicillin allergy was associated with an increased risk of MRSA and C difficile that was mediated by the increased use of β lactam alternative antibiotics. Systematically addressing penicillin allergies may be an important public health strategy to reduce the incidence of MRSA and C difficile among patients with a penicillin allergy label.
Risk of meticillin resistant #Staphylococcus aureus and #Clostridium difficile in patients with a documented #penicillin allergy: population based matched cohort study
https://www.bmj.com/content/361/bmj.k2400
The primary outcome was risk of incident MRSA and C difficile. Secondary outcomes were use of β lactam antibiotics and β lactam alternative antibiotics.
Results Among 64 141 adults with penicillin allergy and 237 258 matched comparators, 1365 developed MRSA (442 participants with penicillin allergy and 923 comparators) and 1688 developed C difficile (442 participants with penicillin allergy and 1246 comparators) during a mean 6.0 years of follow-up. Among patients with penicillin allergy the adjusted hazard ratio for MRSA was 1.69 (95% confidence interval 1.51 to 1.90) and for C difficile was 1.26 (1.12 to 1.40). The adjusted incidence rate ratios for antibiotic use among patients with penicillin allergy were 4.15 (95% confidence interval 4.12 to 4.17) for macrolides, 3.89 (3.66 to 4.12) for clindamycin, and 2.10 (2.08 to 2.13) for fluoroquinolones. Increased use of β lactam alternative antibiotics accounted for 55% of the increased risk of MRSA and 35% of the increased risk of C difficile.
Conclusions Documented penicillin allergy was associated with an increased risk of MRSA and C difficile that was mediated by the increased use of β lactam alternative antibiotics. Systematically addressing penicillin allergies may be an important public health strategy to reduce the incidence of MRSA and C difficile among patients with a penicillin allergy label.
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Systemic #isradipine treatment diminishes calcium-dependent mitochondrial oxidant stress
https://www.jci.org/articles/view/95898
The ability of the Cav1 channel inhibitor isradipine to slow the loss of substantia nigra pars compacta (SNc) dopaminergic (DA) neurons and the progression of #Parkinson’s disease (PD) is being tested in a phase 3 human clinical trial. But it is unclear whether and how chronic isradipine treatment will benefit SNc DA neurons in vivo. To pursue this question, isradipine was given systemically to mice at doses that achieved low nanomolar concentrations in plasma, near those achieved in patients. This treatment diminished cytosolic Ca2+ oscillations in SNc DA neurons without altering autonomous spiking or expression of Ca2+ channels, an effect mimicked by selectively knocking down expression of Cav1.3 channel subunits. Treatment also lowered mitochondrial oxidant stress, reduced a high basal rate of mitophagy, and normalized mitochondrial mass — demonstrating that Cav1 channels drive mitochondrial oxidant stress and turnover in vivo. Thus, chronic isradipine treatment remodeled SNc DA neurons in a way that should not only diminish their vulnerability to mitochondrial challenges, but to autophagic stress as well.
Systemic #isradipine treatment diminishes calcium-dependent mitochondrial oxidant stress
https://www.jci.org/articles/view/95898
The ability of the Cav1 channel inhibitor isradipine to slow the loss of substantia nigra pars compacta (SNc) dopaminergic (DA) neurons and the progression of #Parkinson’s disease (PD) is being tested in a phase 3 human clinical trial. But it is unclear whether and how chronic isradipine treatment will benefit SNc DA neurons in vivo. To pursue this question, isradipine was given systemically to mice at doses that achieved low nanomolar concentrations in plasma, near those achieved in patients. This treatment diminished cytosolic Ca2+ oscillations in SNc DA neurons without altering autonomous spiking or expression of Ca2+ channels, an effect mimicked by selectively knocking down expression of Cav1.3 channel subunits. Treatment also lowered mitochondrial oxidant stress, reduced a high basal rate of mitophagy, and normalized mitochondrial mass — demonstrating that Cav1 channels drive mitochondrial oxidant stress and turnover in vivo. Thus, chronic isradipine treatment remodeled SNc DA neurons in a way that should not only diminish their vulnerability to mitochondrial challenges, but to autophagic stress as well.
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Continuity of care with doctors—a matter of life and death? A systematic review of continuity of care and mortality
https://bmjopen.bmj.com/content/8/6/e021161
.. These studies came from nine countries with very different cultures and health systems. We found such heterogeneity of continuity and mortality measurement methods and time frames that it was not possible to combine the results of studies. However, 18 (81.8%) high-quality studies reported statistically significant reductions in mortality, with increased continuity of care. 16 of these were with all-cause mortality. Three others showed no association and one demonstrated mixed results. These significant protective effects occurred with both generalist and specialist doctors.
Conclusions This first systematic review reveals that increased continuity of care by doctors is associated with lower mortality rates. Although all the evidence is observational, patients across cultural boundaries appear to benefit from continuity of care with both generalist and specialist doctors. Many of these articles called for continuity to be given a higher priority in healthcare planning. Despite substantial, successive, technical advances in medicine, interpersonal factors remain important.
Continuity of care with doctors—a matter of life and death? A systematic review of continuity of care and mortality
https://bmjopen.bmj.com/content/8/6/e021161
.. These studies came from nine countries with very different cultures and health systems. We found such heterogeneity of continuity and mortality measurement methods and time frames that it was not possible to combine the results of studies. However, 18 (81.8%) high-quality studies reported statistically significant reductions in mortality, with increased continuity of care. 16 of these were with all-cause mortality. Three others showed no association and one demonstrated mixed results. These significant protective effects occurred with both generalist and specialist doctors.
Conclusions This first systematic review reveals that increased continuity of care by doctors is associated with lower mortality rates. Although all the evidence is observational, patients across cultural boundaries appear to benefit from continuity of care with both generalist and specialist doctors. Many of these articles called for continuity to be given a higher priority in healthcare planning. Despite substantial, successive, technical advances in medicine, interpersonal factors remain important.
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CAABL-AF (California Study of #Ablation for Atrial #Fibrillation)
Mortality and Stroke, 2005 to 2013
http://circep.ahajournals.org/content/11/6/e005739
Ablation for atrial fibrillation (AF) is superior to medical therapy for rhythm control. We compared stroke and mortality among patients undergoing ablation for AF to matched controls in a large multiethnic population
There were 4169 ablation cases and 4169 weighted-matched controls; 39% percent of the ablation group was >65 years, 72% men, 84% white; mean follow-up was up to 3.6±0.9 years. In adjusted models, ablation was associated with significantly lower mortality (per patient-years) 0.9% versus 1.9%, hazard ratio=0.59 (P<0.0001; confidence interval: 0.45–0.77); ischemic stroke (>30 days post-ablation ≤5 years), 0.37% versus 0.59%, hazard ratio=0.68 (P=0.04; confidence interval: 0.47–0.97); hemorrhagic stroke 0.11% versus 0.35%, hazard ratio=0.36 (P=0.001; confidence interval: 0.20–0.64) compared with controls.
Conclusions: In this large population-based study of hospitalized patients with nonvalvular AF, ablation was associated with lower mortality, ischemic stroke, and hemorrhagic stroke compared with controls
CAABL-AF (California Study of #Ablation for Atrial #Fibrillation)
Mortality and Stroke, 2005 to 2013
http://circep.ahajournals.org/content/11/6/e005739
Ablation for atrial fibrillation (AF) is superior to medical therapy for rhythm control. We compared stroke and mortality among patients undergoing ablation for AF to matched controls in a large multiethnic population
There were 4169 ablation cases and 4169 weighted-matched controls; 39% percent of the ablation group was >65 years, 72% men, 84% white; mean follow-up was up to 3.6±0.9 years. In adjusted models, ablation was associated with significantly lower mortality (per patient-years) 0.9% versus 1.9%, hazard ratio=0.59 (P<0.0001; confidence interval: 0.45–0.77); ischemic stroke (>30 days post-ablation ≤5 years), 0.37% versus 0.59%, hazard ratio=0.68 (P=0.04; confidence interval: 0.47–0.97); hemorrhagic stroke 0.11% versus 0.35%, hazard ratio=0.36 (P=0.001; confidence interval: 0.20–0.64) compared with controls.
Conclusions: In this large population-based study of hospitalized patients with nonvalvular AF, ablation was associated with lower mortality, ischemic stroke, and hemorrhagic stroke compared with controls
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#Marijuana Use, Respiratory Symptoms, and #Pulmonary Function: A Systematic Review and Meta-analysis
http://annals.org/aim/article-abstract/2686986/marijuana-use-respiratory-symptoms-pulmonary-function-systematic-review-meta-analysis
Twenty-two studies were included. A pooled analysis of 2 prospective studies showed that marijuana use was associated with an increased risk for cough (risk ratio RR, 2.04 95% CI, 1.02 to 4.06) and sputum production (RR, 3.84 CI, 1.62 to 9.07). Pooled analysis of cross-sectional studies (1 low and 3 moderate risk of bias) showed that marijuana use was associated with cough (RR, 4.37 CI, 1.71 to 11.19), sputum production (RR, 3.40 CI, 1.99 to 5.79), wheezing (RR, 2.83 CI, 1.89 to 4.23), and dyspnea (RR, 1.56 CI, 1.33 to 1.83). Data on pulmonary function and obstructive lung disease were insufficient
Low-strength evidence suggests that smoking marijuana is associated with cough, sputum production, and wheezing. Evidence on the association between marijuana use and obstructive lung disease and pulmonary function is insufficient
#Marijuana Use, Respiratory Symptoms, and #Pulmonary Function: A Systematic Review and Meta-analysis
http://annals.org/aim/article-abstract/2686986/marijuana-use-respiratory-symptoms-pulmonary-function-systematic-review-meta-analysis
Twenty-two studies were included. A pooled analysis of 2 prospective studies showed that marijuana use was associated with an increased risk for cough (risk ratio RR, 2.04 95% CI, 1.02 to 4.06) and sputum production (RR, 3.84 CI, 1.62 to 9.07). Pooled analysis of cross-sectional studies (1 low and 3 moderate risk of bias) showed that marijuana use was associated with cough (RR, 4.37 CI, 1.71 to 11.19), sputum production (RR, 3.40 CI, 1.99 to 5.79), wheezing (RR, 2.83 CI, 1.89 to 4.23), and dyspnea (RR, 1.56 CI, 1.33 to 1.83). Data on pulmonary function and obstructive lung disease were insufficient
Low-strength evidence suggests that smoking marijuana is associated with cough, sputum production, and wheezing. Evidence on the association between marijuana use and obstructive lung disease and pulmonary function is insufficient
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#Anticonvulsants in the treatment of low #back pain and lumbar radicular pain: a systematic review and meta-analysis
http://www.cmaj.ca/content/190/26/E786
Nine trials compared topiramate, gabapentin or pregabalin to placebo in 859 unique participants. Fourteen of 15 comparisons found anticonvulsants were not effective to reduce pain or disability in low back pain or lumbar radicular pain; for example, there was high-quality evidence of no effect of gabapentinoids versus placebo on chronic low back pain in the short term (pooled mean difference MD −0.0, 95% confidence interval CI −0.8 to 0.7) or for lumbar radicular pain in the immediate term (pooled MD −0.1, 95% CI −0.7 to 0.5). The lack of efficacy is accompanied by increased risk of adverse events from use of gabapentinoids, for which the level of evidence is high.
INTERPRETATION: There is moderate- to high-quality evidence that anticonvulsants are ineffective for treatment of low back pain or lumbar radicular pain. There is high-quality evidence that gabapentinoids have a higher risk for adverse events
#Anticonvulsants in the treatment of low #back pain and lumbar radicular pain: a systematic review and meta-analysis
http://www.cmaj.ca/content/190/26/E786
Nine trials compared topiramate, gabapentin or pregabalin to placebo in 859 unique participants. Fourteen of 15 comparisons found anticonvulsants were not effective to reduce pain or disability in low back pain or lumbar radicular pain; for example, there was high-quality evidence of no effect of gabapentinoids versus placebo on chronic low back pain in the short term (pooled mean difference MD −0.0, 95% confidence interval CI −0.8 to 0.7) or for lumbar radicular pain in the immediate term (pooled MD −0.1, 95% CI −0.7 to 0.5). The lack of efficacy is accompanied by increased risk of adverse events from use of gabapentinoids, for which the level of evidence is high.
INTERPRETATION: There is moderate- to high-quality evidence that anticonvulsants are ineffective for treatment of low back pain or lumbar radicular pain. There is high-quality evidence that gabapentinoids have a higher risk for adverse events
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Is local #platelet-rich plasma injection clinically superior to hyaluronic acid for treatment of knee #osteoarthritis? A systematic review of randomized controlled trials
https://arthritis-research.biomedcentral.com/articles/10.1186/s13075-018-1621-0
Seven articles reporting 908 patients and 908 knees were analyzed, including 44% men and 56% women with a mean age of 59.8 years. All studies met the minimal clinically important difference criteria and showed statistically significant improvements in clinical outcomes, including pain, physical function, and stiffness, with PRP treatment. All except two studies showed significant differences between PRP and HA regarding clinical outcomes of pain and function.
Conclusions
PRP intra-articular injection of the knee may be an effective alternative treatment for knee OA, especially in patients with mild knee OA. Although some studies suggested that the effect of PRP was no better than HA, we found that it was no worse. A large, multicenter, randomized trial is needed to further assess the efficacy of PRP treatment for patients with knee OA.
Is local #platelet-rich plasma injection clinically superior to hyaluronic acid for treatment of knee #osteoarthritis? A systematic review of randomized controlled trials
https://arthritis-research.biomedcentral.com/articles/10.1186/s13075-018-1621-0
Seven articles reporting 908 patients and 908 knees were analyzed, including 44% men and 56% women with a mean age of 59.8 years. All studies met the minimal clinically important difference criteria and showed statistically significant improvements in clinical outcomes, including pain, physical function, and stiffness, with PRP treatment. All except two studies showed significant differences between PRP and HA regarding clinical outcomes of pain and function.
Conclusions
PRP intra-articular injection of the knee may be an effective alternative treatment for knee OA, especially in patients with mild knee OA. Although some studies suggested that the effect of PRP was no better than HA, we found that it was no worse. A large, multicenter, randomized trial is needed to further assess the efficacy of PRP treatment for patients with knee OA.
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Organic #solvents and #MS susceptibility
Interaction with MS risk HLA genes
http://n.neurology.org/content/early/2018/07/03/WNL.0000000000005906
Overall, exposure to organic solvents increased the risk of MS (odds ratio 1.5, 95% confidence interval 1.2–1.8, p = 0.0004). Among both ever and never smokers, an interaction between organic solvents, carriage of HLA-DRB115, and absence of HLA-A02 was observed with regard to MS risk, similar to the previously reported gene-environment interaction involving the same MS risk HLA genes and smoke exposure.
Conclusion The mechanism linking both smoking and exposure to organic solvents to MS risk may involve lung inflammation with a proinflammatory profile. Their interaction with MS risk HLA genes argues for an action of these environmental factors on adaptive immunity, perhaps through activation of autoaggressive cells resident in the lungs subsequently attacking the CNS.
Organic #solvents and #MS susceptibility
Interaction with MS risk HLA genes
http://n.neurology.org/content/early/2018/07/03/WNL.0000000000005906
Overall, exposure to organic solvents increased the risk of MS (odds ratio 1.5, 95% confidence interval 1.2–1.8, p = 0.0004). Among both ever and never smokers, an interaction between organic solvents, carriage of HLA-DRB115, and absence of HLA-A02 was observed with regard to MS risk, similar to the previously reported gene-environment interaction involving the same MS risk HLA genes and smoke exposure.
Conclusion The mechanism linking both smoking and exposure to organic solvents to MS risk may involve lung inflammation with a proinflammatory profile. Their interaction with MS risk HLA genes argues for an action of these environmental factors on adaptive immunity, perhaps through activation of autoaggressive cells resident in the lungs subsequently attacking the CNS.
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Association of Midlife Cardiorespiratory #Fitness With Incident #Depression and #Cardiovascular Death After Depression in Later Life
https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2686049
... After 117 218 person-years of Medicare follow-up, 2701 depression diagnoses, 610 deaths due to CVD without prior depression, and 231 deaths due to CVD after depression were observed. A high level of fitness in midlife was associated with a 16% lower risk of depression (hazard ratio HR, 0.84; 95% CI, 0.74-0.95) compared with a low level of fitness. A high fitness level was also associated with a 61% lower risk of death due to CVD without depression (HR, 0.39; 95% CI, 0.31-0.48) compared with a low level of fitness. After a diagnosis of depression, a high fitness level was associated with a 56% lower risk of death due to CVD (HR, 0.44; 95% CI, 0.31-0.64) compared with a low fitness level.
Conclusions and Relevance Midlife fitness is associated with a lower risk of later-life depression, CVD mortality, and CVD mortality after incident later-life depression. These findings suggest the importance of midlife fitness in primary prevention of depression and subsequent CVD mortality in older age and should encourage physicians to consider fitness and physical activity in promoting healthy aging.
Association of Midlife Cardiorespiratory #Fitness With Incident #Depression and #Cardiovascular Death After Depression in Later Life
https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2686049
... After 117 218 person-years of Medicare follow-up, 2701 depression diagnoses, 610 deaths due to CVD without prior depression, and 231 deaths due to CVD after depression were observed. A high level of fitness in midlife was associated with a 16% lower risk of depression (hazard ratio HR, 0.84; 95% CI, 0.74-0.95) compared with a low level of fitness. A high fitness level was also associated with a 61% lower risk of death due to CVD without depression (HR, 0.39; 95% CI, 0.31-0.48) compared with a low level of fitness. After a diagnosis of depression, a high fitness level was associated with a 56% lower risk of death due to CVD (HR, 0.44; 95% CI, 0.31-0.64) compared with a low fitness level.
Conclusions and Relevance Midlife fitness is associated with a lower risk of later-life depression, CVD mortality, and CVD mortality after incident later-life depression. These findings suggest the importance of midlife fitness in primary prevention of depression and subsequent CVD mortality in older age and should encourage physicians to consider fitness and physical activity in promoting healthy aging.
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Changes in the serum metabolite profile correlate with decreased brain #grey matter volume in moderate-to-heavy-#drinking young adults
https://www.sciencedirect.com/science/article/pii/S0741832917309849
Alterations in amino acid and energy metabolism were observed in the moderate-to-heavy drinking young adults when compared to the controls. After correction for multiple testing, the group of moderate-to-heavy drinking young adults had increased serum concentrations of 1-methylhistamine (p = 0.001, d = 0.82) when compared to the controls. Furthermore, concentrations of 1-methylhistamine (r = -0.48, p = 0.004) and creatine (r = -0.52, p = 0.001) were negatively correlated with the brain grey matter volumes in the females. Overall, our results show association between moderate-to-heavy use of alcohol and altered metabolite profile in young adults as well as suggest that some of these changes could be associated with the reduced brain grey matter volume.
Changes in the serum metabolite profile correlate with decreased brain #grey matter volume in moderate-to-heavy-#drinking young adults
https://www.sciencedirect.com/science/article/pii/S0741832917309849
Alterations in amino acid and energy metabolism were observed in the moderate-to-heavy drinking young adults when compared to the controls. After correction for multiple testing, the group of moderate-to-heavy drinking young adults had increased serum concentrations of 1-methylhistamine (p = 0.001, d = 0.82) when compared to the controls. Furthermore, concentrations of 1-methylhistamine (r = -0.48, p = 0.004) and creatine (r = -0.52, p = 0.001) were negatively correlated with the brain grey matter volumes in the females. Overall, our results show association between moderate-to-heavy use of alcohol and altered metabolite profile in young adults as well as suggest that some of these changes could be associated with the reduced brain grey matter volume.
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Risks and benefits of direct oral #anticoagulants versus #warfarin in a real world setting: cohort study in primary care
https://www.bmj.com/content/362/bmj.k2505
In patients with atrial fibrillation, compared with warfarin, apixaban was associated with a decreased risk of major bleeding (adjusted hazard ratio 0.66, 95% confidence interval 0.54 to 0.79) and intracranial bleeding (0.40, 0.25 to 0.64); dabigatran was associated with a decreased risk of intracranial bleeding (0.45, 0.26 to 0.77). An increased risk of all cause mortality was observed in patients taking rivaroxaban (1.19, 1.09 to 1.29) or on lower doses of apixaban (1.27, 1.12 to 1.45). In patients without atrial fibrillation, compared with warfarin, apixaban was associated with a decreased risk of major bleeding (0.60, 0.46 to 0.79), any gastrointestinal bleeding (0.55, 0.37 to 0.83), and upper gastrointestinal bleeding (0.55, 0.36 to 0.83); rivaroxaban was associated with a decreased risk of intracranial bleeding (0.54, 0.35 to 0.82). Increased risk of all cause mortality was observed in patients taking rivaroxaban (1.51, 1.38 to 1.66) and those on lower doses of apixaban (1.34, 1.13 to 1.58).
Conclusions Overall, apixaban was found to be the safest drug, with reduced risks of major, intracranial, and gastrointestinal bleeding compared with warfarin. Rivaroxaban and low dose apixaban were, however, associated with increased risks of all cause mortality compared with warfarin
Risks and benefits of direct oral #anticoagulants versus #warfarin in a real world setting: cohort study in primary care
https://www.bmj.com/content/362/bmj.k2505
In patients with atrial fibrillation, compared with warfarin, apixaban was associated with a decreased risk of major bleeding (adjusted hazard ratio 0.66, 95% confidence interval 0.54 to 0.79) and intracranial bleeding (0.40, 0.25 to 0.64); dabigatran was associated with a decreased risk of intracranial bleeding (0.45, 0.26 to 0.77). An increased risk of all cause mortality was observed in patients taking rivaroxaban (1.19, 1.09 to 1.29) or on lower doses of apixaban (1.27, 1.12 to 1.45). In patients without atrial fibrillation, compared with warfarin, apixaban was associated with a decreased risk of major bleeding (0.60, 0.46 to 0.79), any gastrointestinal bleeding (0.55, 0.37 to 0.83), and upper gastrointestinal bleeding (0.55, 0.36 to 0.83); rivaroxaban was associated with a decreased risk of intracranial bleeding (0.54, 0.35 to 0.82). Increased risk of all cause mortality was observed in patients taking rivaroxaban (1.51, 1.38 to 1.66) and those on lower doses of apixaban (1.34, 1.13 to 1.58).
Conclusions Overall, apixaban was found to be the safest drug, with reduced risks of major, intracranial, and gastrointestinal bleeding compared with warfarin. Rivaroxaban and low dose apixaban were, however, associated with increased risks of all cause mortality compared with warfarin
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Periconception glycaemic control in women with type 1 #diabetes and risk of major birth #defects: population based cohort study in Sweden
https://www.bmj.com/content/362/bmj.k2638
..Compared with 18 cases of major non-cardiac defects per 1000 infants of mothers without diabetes, the rates among infants of mothers with type 1 diabetes were 22 per 1000 for a glycated haemoglobin level of <6.5% (adjusted risk ratio 1.18, 0.68 to 2.07), 19 per 1000 for 6.5% to <7.8% (1.01, 0.66 to 1.54), 17 per 1000 for 7.8% to <9.1% (0.89, 0.46 to 1.69), and 32 per 1000 for ≥9.1% (1.68, 0.85 to 3.33).
Conclusion Among liveborn infants of mothers with type 1 diabetes, increasingly worse glycaemic control in the three months before or after estimated conception was associated with a progressively increased risk of major cardiac defects. Even with glycated haemoglobin within target levels recommended by guidelines (<6.5%), the risk of major cardiac defects was increased more than twofold. The risk of major non-cardiac defects was not statistically significantly increased at any of the four glycated haemoglobin levels examined; the study had limited statistical power for this outcome and was based on live births only.
Periconception glycaemic control in women with type 1 #diabetes and risk of major birth #defects: population based cohort study in Sweden
https://www.bmj.com/content/362/bmj.k2638
..Compared with 18 cases of major non-cardiac defects per 1000 infants of mothers without diabetes, the rates among infants of mothers with type 1 diabetes were 22 per 1000 for a glycated haemoglobin level of <6.5% (adjusted risk ratio 1.18, 0.68 to 2.07), 19 per 1000 for 6.5% to <7.8% (1.01, 0.66 to 1.54), 17 per 1000 for 7.8% to <9.1% (0.89, 0.46 to 1.69), and 32 per 1000 for ≥9.1% (1.68, 0.85 to 3.33).
Conclusion Among liveborn infants of mothers with type 1 diabetes, increasingly worse glycaemic control in the three months before or after estimated conception was associated with a progressively increased risk of major cardiac defects. Even with glycated haemoglobin within target levels recommended by guidelines (<6.5%), the risk of major cardiac defects was increased more than twofold. The risk of major non-cardiac defects was not statistically significantly increased at any of the four glycated haemoglobin levels examined; the study had limited statistical power for this outcome and was based on live births only.
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Second-generation #antipsychotic drugs and short-term #mortality: a systematic review and meta-analysis of placebo-controlled randomised controlled trials
https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(18)30177-9/fulltext
We found no evidence of a difference between antipsychotic drugs and placebo in mortality by any cause (OR 1·19; 95% CI 0·93–1·53), from natural causes (1·29; 0·85–1·94), from suicide (1·15; 0·47–2·81), and from other non-natural causes (1·55; 0·66–3·63). Most subgroup and meta-regression analyses did not indicate any important effect moderators. The exceptions were increased mortality in patients with dementia (OR 1·56; 95% CI 1·10–2·21), in elderly patients (1·38; 1·01–1·89), in aripiprazole-treated patients (2·20; 1·00–4·86), and in studies with a higher proportion of women (regression coefficient 0·025; 95% credible interval 0·010–0·040). However, the effects in elderly patients, aripiprazole-treated patients, and women were mainly based on the included dementia trials. For patients with schizophrenia there was no evidence of an increased mortality risk (OR 0·69; 95% CI 0·35–1·35).
Interpretation
Overall, and for the main indication of schizophrenia, there is no evidence from randomised trials that antipsychotic drugs increase mortality. However, vulnerable populations (particularly patients with dementia) might be at increased risk. This meta-analysis could only address acute treatment effects leading to death in the short-term, and not long-term effects of antipsychotic drugs on mortality.
Second-generation #antipsychotic drugs and short-term #mortality: a systematic review and meta-analysis of placebo-controlled randomised controlled trials
https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(18)30177-9/fulltext
We found no evidence of a difference between antipsychotic drugs and placebo in mortality by any cause (OR 1·19; 95% CI 0·93–1·53), from natural causes (1·29; 0·85–1·94), from suicide (1·15; 0·47–2·81), and from other non-natural causes (1·55; 0·66–3·63). Most subgroup and meta-regression analyses did not indicate any important effect moderators. The exceptions were increased mortality in patients with dementia (OR 1·56; 95% CI 1·10–2·21), in elderly patients (1·38; 1·01–1·89), in aripiprazole-treated patients (2·20; 1·00–4·86), and in studies with a higher proportion of women (regression coefficient 0·025; 95% credible interval 0·010–0·040). However, the effects in elderly patients, aripiprazole-treated patients, and women were mainly based on the included dementia trials. For patients with schizophrenia there was no evidence of an increased mortality risk (OR 0·69; 95% CI 0·35–1·35).
Interpretation
Overall, and for the main indication of schizophrenia, there is no evidence from randomised trials that antipsychotic drugs increase mortality. However, vulnerable populations (particularly patients with dementia) might be at increased risk. This meta-analysis could only address acute treatment effects leading to death in the short-term, and not long-term effects of antipsychotic drugs on mortality.
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The 2016 global and national burden of #diabetes mellitus attributable to PM2·5 air #pollution
https://www.thelancet.com/journals/lanpla/article/PIIS2542-5196(18)30140-2/fulltext
..In adjusted models, a 10 μg/m3 increase in PM2·5 was associated with increased risk of diabetes (HR 1·15, 95% CI 1·08–1·22). PM2·5 was associated with increased risk of death as the positive outcome control (HR 1·08, 95% CI 1·03–1·13), but not with lower limb fracture as the negative outcome control (1·00, 0·91–1·09). An IQR increase (0·045 μg/m3) in ambient air sodium concentration as the negative exposure control exhibited no significant association with the risk of diabetes (HR 1·00, 95% CI 0·99–1·00). An integrated exposure response function showed that the risk of diabetes increased substantially above 2·4 μg/m3, and then exhibited a more moderate increase at concentrations above 10 μg/m3. Globally, ambient PM2·5 contributed to about 3·2 million (95% uncertainty interval UI 2·2–3·8) incident cases of diabetes, about 8·2 million (95% UI 5·8–11·0) DALYs caused by diabetes, and 206 105 (95% UI 153 408–259 119) deaths from diabetes attributable to PM2·5 exposure. The burden varied substantially among geographies and was more heavily skewed towards low-income and lower-to-middle-income countries.
Interpretation
The global toll of diabetes attributable to PM2·5 air pollution is significant. Reduction in exposure will yield substantial health benefits.
The 2016 global and national burden of #diabetes mellitus attributable to PM2·5 air #pollution
https://www.thelancet.com/journals/lanpla/article/PIIS2542-5196(18)30140-2/fulltext
..In adjusted models, a 10 μg/m3 increase in PM2·5 was associated with increased risk of diabetes (HR 1·15, 95% CI 1·08–1·22). PM2·5 was associated with increased risk of death as the positive outcome control (HR 1·08, 95% CI 1·03–1·13), but not with lower limb fracture as the negative outcome control (1·00, 0·91–1·09). An IQR increase (0·045 μg/m3) in ambient air sodium concentration as the negative exposure control exhibited no significant association with the risk of diabetes (HR 1·00, 95% CI 0·99–1·00). An integrated exposure response function showed that the risk of diabetes increased substantially above 2·4 μg/m3, and then exhibited a more moderate increase at concentrations above 10 μg/m3. Globally, ambient PM2·5 contributed to about 3·2 million (95% uncertainty interval UI 2·2–3·8) incident cases of diabetes, about 8·2 million (95% UI 5·8–11·0) DALYs caused by diabetes, and 206 105 (95% UI 153 408–259 119) deaths from diabetes attributable to PM2·5 exposure. The burden varied substantially among geographies and was more heavily skewed towards low-income and lower-to-middle-income countries.
Interpretation
The global toll of diabetes attributable to PM2·5 air pollution is significant. Reduction in exposure will yield substantial health benefits.
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Adverse effect of long work #hours on incident #diabetes in 7065 Ontario workers followed for 12 years
https://drc.bmj.com/content/6/1/e000496
Long work hours did not increase the risk of developing diabetes among men. However, among women, those usually working 45 hours or more per week had a significantly higher risk of diabetes than women working between 35 and 40 hours per week (HR: 1.63 (95% CI 1.04 to 2.57)). The effect was slightly attenuated when adjusted for the potentially mediating factors which are smoking, leisure time physical activity, alcohol consumption and body mass index.
Conclusion Working 45 hours or more per week was associated with an increased incidence of diabetes among women, but not men. Identifying modifiable risk factors such as long work hours is of major importance to improve prevention strategies and orient policy making.
Adverse effect of long work #hours on incident #diabetes in 7065 Ontario workers followed for 12 years
https://drc.bmj.com/content/6/1/e000496
Long work hours did not increase the risk of developing diabetes among men. However, among women, those usually working 45 hours or more per week had a significantly higher risk of diabetes than women working between 35 and 40 hours per week (HR: 1.63 (95% CI 1.04 to 2.57)). The effect was slightly attenuated when adjusted for the potentially mediating factors which are smoking, leisure time physical activity, alcohol consumption and body mass index.
Conclusion Working 45 hours or more per week was associated with an increased incidence of diabetes among women, but not men. Identifying modifiable risk factors such as long work hours is of major importance to improve prevention strategies and orient policy making.
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Effect of #cannabis use in people with chronic non-cancer #pain prescribed opioids: findings from a 4-year prospective cohort study
https://www.thelancet.com/journals/lanpub/article/PIIS2468-2667(18)30110-5/fulltext?code=lancet-site
At 4-year follow-up, compared with people with no cannabis use, we found that participants who used cannabis had a greater pain severity score (risk ratio 1·14, 95% CI 1·01–1·29, for less frequent cannabis use; and 1·17, 1·03–1·32, for daily or near-daily cannabis use), greater pain interference score (1·21, 1·09–1·35; and 1·14, 1·03–1·26), lower pain self-efficacy scores (0·97, 0·96–1·00; and 0·98, 0·96–1·00), and greater generalised anxiety disorder severity scores (1·07, 1·03–1·12; and 1·10, 1·06–1·15). We found no evidence of a temporal relationship between cannabis use and pain severity or pain interference, and no evidence that cannabis use reduced prescribed opioid use or increased rates of opioid discontinuation.
Interpretation
Cannabis use was common in people with chronic non-cancer pain who had been prescribed opioids, but we found no evidence that cannabis use improved patient outcomes. People who used cannabis had greater pain and lower self-efficacy in managing pain, and there was no evidence that cannabis use reduced pain severity or interference or exerted an opioid-sparing effect. As cannabis use for medicinal purposes increases globally, it is important that large well designed clinical trials, which include people with complex comorbidities, are conducted to determine the efficacy of cannabis for chronic non-cancer pain
Effect of #cannabis use in people with chronic non-cancer #pain prescribed opioids: findings from a 4-year prospective cohort study
https://www.thelancet.com/journals/lanpub/article/PIIS2468-2667(18)30110-5/fulltext?code=lancet-site
At 4-year follow-up, compared with people with no cannabis use, we found that participants who used cannabis had a greater pain severity score (risk ratio 1·14, 95% CI 1·01–1·29, for less frequent cannabis use; and 1·17, 1·03–1·32, for daily or near-daily cannabis use), greater pain interference score (1·21, 1·09–1·35; and 1·14, 1·03–1·26), lower pain self-efficacy scores (0·97, 0·96–1·00; and 0·98, 0·96–1·00), and greater generalised anxiety disorder severity scores (1·07, 1·03–1·12; and 1·10, 1·06–1·15). We found no evidence of a temporal relationship between cannabis use and pain severity or pain interference, and no evidence that cannabis use reduced prescribed opioid use or increased rates of opioid discontinuation.
Interpretation
Cannabis use was common in people with chronic non-cancer pain who had been prescribed opioids, but we found no evidence that cannabis use improved patient outcomes. People who used cannabis had greater pain and lower self-efficacy in managing pain, and there was no evidence that cannabis use reduced pain severity or interference or exerted an opioid-sparing effect. As cannabis use for medicinal purposes increases globally, it is important that large well designed clinical trials, which include people with complex comorbidities, are conducted to determine the efficacy of cannabis for chronic non-cancer pain
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Does #Caffeine Consumption Increase the Risk of New-Onset Atrial #Fibrillation?
https://www.karger.com/Article/Abstract/489843
No significant difference was found in AF incidence when the subjects consuming less than 2 cups of coffee per day were compared to subjects with higher consumption, 1.068 (0.937–1.216). The risk of AF was higher among subjects consuming less than 2 cups of coffee daily when compared to higher daily consumption subjects. A lower incidence of AF was found among people consuming more than 436 mg daily.
Conclusion: The incidence of AF is not increased by coffee consumption. In fact, we found a lower incidence of AF when caffeine consumption exceeded 436 mg/day. Therefore, based on available evidence there is no association between caffeine intake and AF risk.
Does #Caffeine Consumption Increase the Risk of New-Onset Atrial #Fibrillation?
https://www.karger.com/Article/Abstract/489843
No significant difference was found in AF incidence when the subjects consuming less than 2 cups of coffee per day were compared to subjects with higher consumption, 1.068 (0.937–1.216). The risk of AF was higher among subjects consuming less than 2 cups of coffee daily when compared to higher daily consumption subjects. A lower incidence of AF was found among people consuming more than 436 mg daily.
Conclusion: The incidence of AF is not increased by coffee consumption. In fact, we found a lower incidence of AF when caffeine consumption exceeded 436 mg/day. Therefore, based on available evidence there is no association between caffeine intake and AF risk.
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Cross-sex #Hormones and Acute #Cardiovascular Events in Transgender Persons: A Cohort Study
http://annals.org/aim/article-abstract/2687653/cross-sex-hormones-acute-cardiovascular-events-transgender-persons-cohort-study
Transfeminine participants had a higher incidence of VTE, with 2- and 8-year risk differences of 4.1 (95% CI, 1.6 to 6.7) and 16.7 (CI, 6.4 to 27.5) per 1000 persons relative to cisgender men and 3.4 (CI, 1.1 to 5.6) and 13.7 (CI, 4.1 to 22.7) relative to cisgender women. The overall analyses for ischemic stroke and myocardial infarction demonstrated similar incidence across groups. More pronounced differences for VTE and ischemic stroke were observed among transfeminine participants who initiated hormone therapy during follow-up. The evidence was insufficient to allow conclusions regarding risk among transmasculine participants.
Conclusion:
The patterns of increases in VTE and ischemic stroke rates among transfeminine persons are not consistent with those observed in cisgender women. These results may indicate the need for long-term vigilance in identifying vascular side effects of cross-sex estrogen.
Cross-sex #Hormones and Acute #Cardiovascular Events in Transgender Persons: A Cohort Study
http://annals.org/aim/article-abstract/2687653/cross-sex-hormones-acute-cardiovascular-events-transgender-persons-cohort-study
Transfeminine participants had a higher incidence of VTE, with 2- and 8-year risk differences of 4.1 (95% CI, 1.6 to 6.7) and 16.7 (CI, 6.4 to 27.5) per 1000 persons relative to cisgender men and 3.4 (CI, 1.1 to 5.6) and 13.7 (CI, 4.1 to 22.7) relative to cisgender women. The overall analyses for ischemic stroke and myocardial infarction demonstrated similar incidence across groups. More pronounced differences for VTE and ischemic stroke were observed among transfeminine participants who initiated hormone therapy during follow-up. The evidence was insufficient to allow conclusions regarding risk among transmasculine participants.
Conclusion:
The patterns of increases in VTE and ischemic stroke rates among transfeminine persons are not consistent with those observed in cisgender women. These results may indicate the need for long-term vigilance in identifying vascular side effects of cross-sex estrogen.
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Physicians’ Views of Self-#Monitoring of Blood Glucose in Patients With Type 2 #Diabetes Not on Insulin
http://www.annfammed.org/content/16/4/349.abstract
This qualitative study examines to what extent and why physicans still prescribe self-monitoring of blood glucose (SMBG) in patients with non–insulin-treated type 2 diabetes (NITT2D) when the evidence shows it increases cost without improving hemoglobin A1c (HbA1c), general well being, or health-related quality of life. Semistructured phone interviews with 17 primary care physicians indicated that the majority continue to recommend routine self-monitoring of blood glucose due to a compelling belief in its ability to promote the lifestyle changes needed for glycemic control. Targeting physician beliefs about the effectiveness of self-monitoring of blood glucose, and designing robust interventions accordingly, may help reduce this practice.
Physicians’ Views of Self-#Monitoring of Blood Glucose in Patients With Type 2 #Diabetes Not on Insulin
http://www.annfammed.org/content/16/4/349.abstract
This qualitative study examines to what extent and why physicans still prescribe self-monitoring of blood glucose (SMBG) in patients with non–insulin-treated type 2 diabetes (NITT2D) when the evidence shows it increases cost without improving hemoglobin A1c (HbA1c), general well being, or health-related quality of life. Semistructured phone interviews with 17 primary care physicians indicated that the majority continue to recommend routine self-monitoring of blood glucose due to a compelling belief in its ability to promote the lifestyle changes needed for glycemic control. Targeting physician beliefs about the effectiveness of self-monitoring of blood glucose, and designing robust interventions accordingly, may help reduce this practice.