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#Cognitive Impact of Cerebral Small #Vessel Disease Changes in Patients With Hypertension
https://www.ahajournals.org/doi/full/10.1161/HYPERTENSIONAHA.118.12090
Hypertension is one of the principal risk factors for cerebral small vessel disease progression and cognitive impairment.
Considering the progression of cerebral small vessel disease, the prevalence of incident infarcts was 6.1% and that of incident cerebral microbleeds was 5.5%; progression of periventricular WMH was 22% and that of deep WMH was 48%. Patients with marked progression of periventricular WMH showed a significant decrease in global cognition compared with patients without progression (adjusted mean [SE], −0.519 [0.176] versus 0.057 [0.044], respectively; P value=0.004) and a higher risk of incident mild cognitive impairment (OR, 6.184; 95% CI, 1.506–25.370; P value=0.011).
Therefore, our results indicate that hypertensive patients with progression of periventricular WMH have higher odds of cognitive impairment, even in the early stages of cognitive decline.
#Cognitive Impact of Cerebral Small #Vessel Disease Changes in Patients With Hypertension
https://www.ahajournals.org/doi/full/10.1161/HYPERTENSIONAHA.118.12090
Hypertension is one of the principal risk factors for cerebral small vessel disease progression and cognitive impairment.
Considering the progression of cerebral small vessel disease, the prevalence of incident infarcts was 6.1% and that of incident cerebral microbleeds was 5.5%; progression of periventricular WMH was 22% and that of deep WMH was 48%. Patients with marked progression of periventricular WMH showed a significant decrease in global cognition compared with patients without progression (adjusted mean [SE], −0.519 [0.176] versus 0.057 [0.044], respectively; P value=0.004) and a higher risk of incident mild cognitive impairment (OR, 6.184; 95% CI, 1.506–25.370; P value=0.011).
Therefore, our results indicate that hypertensive patients with progression of periventricular WMH have higher odds of cognitive impairment, even in the early stages of cognitive decline.
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#Blood–brain barrier breakdown is an early biomarker of human #cognitive dysfunction
https://www.nature.com/articles/s41591-018-0297-y
Abstract
Vascular contributions to cognitive impairment are increasingly recognized as shown by neuropathological neuroimaging and cerebrospinal fluid biomarker studies. Moreover, small vessel disease of the brain has been estimated to contribute to approximately 50% of all dementias worldwide, including those caused by Alzheimer’s disease (AD)..
Our data show that individuals with early cognitive dysfunction develop brain capillary damage and BBB breakdown in the hippocampus irrespective of Alzheimer’s Aβ and/or tau biomarker changes, suggesting that BBB breakdown is an early biomarker of human cognitive dysfunction independent of Aβ and tau.
#Blood–brain barrier breakdown is an early biomarker of human #cognitive dysfunction
https://www.nature.com/articles/s41591-018-0297-y
Abstract
Vascular contributions to cognitive impairment are increasingly recognized as shown by neuropathological neuroimaging and cerebrospinal fluid biomarker studies. Moreover, small vessel disease of the brain has been estimated to contribute to approximately 50% of all dementias worldwide, including those caused by Alzheimer’s disease (AD)..
Our data show that individuals with early cognitive dysfunction develop brain capillary damage and BBB breakdown in the hippocampus irrespective of Alzheimer’s Aβ and/or tau biomarker changes, suggesting that BBB breakdown is an early biomarker of human cognitive dysfunction independent of Aβ and tau.
Nature
Blood–brain barrier breakdown is an early biomarker of human cognitive dysfunction
Nature Medicine - Neuroimaging and cerebrospinal fluid analyses in humans reveal that loss of blood–brain barrier integrity and brain capillary pericyte damage are early biomarkers of...
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Accelerated Knee #Osteoarthritis is Characterized by Destabilizing #Meniscal Tears and Pre‐Radiographic Structural Disease Burden
https://onlinelibrary.wiley.com/doi/abs/10.1002/art.40826
At 1 year before the index visit, >75% of adults with AKOA had meniscal damage in ≥2 regions (vs typical KOA: OR=3.19, 95%CI=1.70 to 5.97). By the index visit, meniscal damage in >2 regions was ubiquitous in AKOA; including 42% with a destabilizing meniscal tear (typical KOA=14%). These changes corresponded to larger BMLs and greater cartilage loss.
Conclusion
AKOA is characterized by destabilizing meniscal tears in a knee compromised by meniscal damage in >2 regions, large BMLs, and cartilage loss
Accelerated Knee #Osteoarthritis is Characterized by Destabilizing #Meniscal Tears and Pre‐Radiographic Structural Disease Burden
https://onlinelibrary.wiley.com/doi/abs/10.1002/art.40826
At 1 year before the index visit, >75% of adults with AKOA had meniscal damage in ≥2 regions (vs typical KOA: OR=3.19, 95%CI=1.70 to 5.97). By the index visit, meniscal damage in >2 regions was ubiquitous in AKOA; including 42% with a destabilizing meniscal tear (typical KOA=14%). These changes corresponded to larger BMLs and greater cartilage loss.
Conclusion
AKOA is characterized by destabilizing meniscal tears in a knee compromised by meniscal damage in >2 regions, large BMLs, and cartilage loss
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Association of #Exercise Preconditioning With Immediate #Cardioprotection
https://jamanetwork.com/journals/jamacardiology/article-abstract/2664268
Preclinical evidence shows that 1 to 3 episodes of exercise per week will provide strong cardioprotection; gradual, modest cardiovascular risk factor modification or physiological artery remodeling cannot fully explain these benefits. This review highlights preclinical evidence that acute exercise-induced cardiac preconditioning has the ability to activate multiple pathways to confer immediate protection against ischemic events, reduce the severity of potentially lethal ischemic myocardiac injury, and act as a physiological first line of defense.
Conclusions and Relevance Independent of the protective benefits of long-term exercise training on risk factors and adaptation of the cardiovascular system, cardiovascular preconditioning may contribute to the immediate cardioprotection of exercise. In practical terms, this means that 1 episode of exercise can create clinically relevant cardioprotection.
Association of #Exercise Preconditioning With Immediate #Cardioprotection
https://jamanetwork.com/journals/jamacardiology/article-abstract/2664268
Preclinical evidence shows that 1 to 3 episodes of exercise per week will provide strong cardioprotection; gradual, modest cardiovascular risk factor modification or physiological artery remodeling cannot fully explain these benefits. This review highlights preclinical evidence that acute exercise-induced cardiac preconditioning has the ability to activate multiple pathways to confer immediate protection against ischemic events, reduce the severity of potentially lethal ischemic myocardiac injury, and act as a physiological first line of defense.
Conclusions and Relevance Independent of the protective benefits of long-term exercise training on risk factors and adaptation of the cardiovascular system, cardiovascular preconditioning may contribute to the immediate cardioprotection of exercise. In practical terms, this means that 1 episode of exercise can create clinically relevant cardioprotection.
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Association of #Aspirin Use for Primary Prevention With #Cardiovascular Events and Bleeding Events
https://jamanetwork.com/journals/jama/article-abstract/2721178
The role for aspirin in cardiovascular primary prevention remains controversial, with potential benefits limited by an increased bleeding risk
Aspirin use was associated with significant reductions in the composite cardiovascular outcome compared with no aspirin (57.1 per 10 000 participant-years with aspirin and 61.4 per 10 000 participant-years with no aspirin) (hazard ratio [HR], 0.89 [95% credible interval, 0.84-0.95]; absolute risk reduction, 0.38% [95% CI, 0.20%-0.55%]; number needed to treat, 265). Aspirin use was associated with an increased risk of major bleeding events compared with no aspirin (23.1 per 10 000 participant-years with aspirin and 16.4 per 10 000 participant-years with no aspirin) (HR, 1.43 [95% credible interval, 1.30-1.56]; absolute risk increase, 0.47% [95% CI, 0.34%-0.62%]; number needed to harm, 210).
Conclusions and Relevance The use of aspirin in individuals without cardiovascular disease was associated with a lower risk of cardiovascular events and an increased risk of major bleeding. This information may inform discussions with patients about aspirin for primary prevention of cardiovascular events and bleeding.
Association of #Aspirin Use for Primary Prevention With #Cardiovascular Events and Bleeding Events
https://jamanetwork.com/journals/jama/article-abstract/2721178
The role for aspirin in cardiovascular primary prevention remains controversial, with potential benefits limited by an increased bleeding risk
Aspirin use was associated with significant reductions in the composite cardiovascular outcome compared with no aspirin (57.1 per 10 000 participant-years with aspirin and 61.4 per 10 000 participant-years with no aspirin) (hazard ratio [HR], 0.89 [95% credible interval, 0.84-0.95]; absolute risk reduction, 0.38% [95% CI, 0.20%-0.55%]; number needed to treat, 265). Aspirin use was associated with an increased risk of major bleeding events compared with no aspirin (23.1 per 10 000 participant-years with aspirin and 16.4 per 10 000 participant-years with no aspirin) (HR, 1.43 [95% credible interval, 1.30-1.56]; absolute risk increase, 0.47% [95% CI, 0.34%-0.62%]; number needed to harm, 210).
Conclusions and Relevance The use of aspirin in individuals without cardiovascular disease was associated with a lower risk of cardiovascular events and an increased risk of major bleeding. This information may inform discussions with patients about aspirin for primary prevention of cardiovascular events and bleeding.
Jamanetwork
Association of Aspirin Use for Primary Prevention of CVD With Cardiovascular Events and Bleeding
This meta-analysis estimates the association between use of aspirin for primary prevention of cardiovascular disease and the rate of cardiovascular mortality, nonfatal myocardial infarction, nonfatal stroke, and bleeding.
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How effective are trained #dogs at alerting their owners to changes in blood #glycaemic levels?: Variations in performance of glycaemia alert dogs
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0210092
Dogs varied in their performance, with median sensitivity to out-of-range episodes at 70% (25th percentile = 50, 75th percentile = 95). To hypoglycaemic episodes the median sensitivity was 83% (66–94%) while to hyperglyaemic episodes it was 67% (17–91%). The median positive predictive value (PPV) was 81% (68–94%), i.e. on average 81% of alerts occurred when glucose levels were out of target range. For four dogs, PPV was 100%. Individual characteristics of the dog, the partnership and the household were significantly associated with performance (e.g., whether the dog was previously a pet, when it was trained, whether its partner was an adult or child).
Conclusions
The large sample shows that the individual performance of dogs is variable, but overall their sensitivity and specificity to OOR episodes are better than previous studies suggest. Results show that optimal performance of glycaemic alert dogs depends not only on good initial and ongoing training, but also careful selection of dogs for the conditions in which they will be working
How effective are trained #dogs at alerting their owners to changes in blood #glycaemic levels?: Variations in performance of glycaemia alert dogs
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0210092
Dogs varied in their performance, with median sensitivity to out-of-range episodes at 70% (25th percentile = 50, 75th percentile = 95). To hypoglycaemic episodes the median sensitivity was 83% (66–94%) while to hyperglyaemic episodes it was 67% (17–91%). The median positive predictive value (PPV) was 81% (68–94%), i.e. on average 81% of alerts occurred when glucose levels were out of target range. For four dogs, PPV was 100%. Individual characteristics of the dog, the partnership and the household were significantly associated with performance (e.g., whether the dog was previously a pet, when it was trained, whether its partner was an adult or child).
Conclusions
The large sample shows that the individual performance of dogs is variable, but overall their sensitivity and specificity to OOR episodes are better than previous studies suggest. Results show that optimal performance of glycaemic alert dogs depends not only on good initial and ongoing training, but also careful selection of dogs for the conditions in which they will be working
journals.plos.org
How effective are trained dogs at alerting their owners to changes in blood glycaemic levels?: Variations in performance of glycaemia…
Aims Domestic dogs are trained to a wide variety of roles including an increasing number of medical assistance tasks. Glycaemia alert dogs are reported to greatly improve the quality of life of owners living with Type 1 diabetes. Research into their value…
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Three week versus six week #immobilisation for stable Weber B type ankle #fractures: randomised, multicentre, non-inferiority clinical trial
https://www.bmj.com/content/364/bmj.k5432
212 of 247 randomised participants (86%) completed the study. At 52 weeks, the mean OMAS was 87.6 (SD 18.3) in the six week cast group, 91.7 (SD 12.9) in the three week cast group, and 89.8 (SD 18.4) in the three week orthosis group. The between group difference at 52 weeks for the three week cast versus six week cast was 3.6 points (95% confidence interval −1.9 to 9.1, P=0.20), and for the three week orthosis versus six week cast was 1.7 points (−4.0 to 7.3, P=0.56). In both comparisons, the confidence intervals did not include the predefined inferiority margin of −8.8 points. The only statistically significant between group differences observed in the secondary outcomes and harms in the two primary comparisons were slight improvement in ankle plantar flexion and incidence of deep vein thrombosis, both in the three week orthosis group versus six week cast group.
Conclusion Immobilisation for three weeks with a cast or orthosis was non-inferior to conventional cast immobilisation for six weeks in the treatment of an isolated stable Weber B type fracture.
Three week versus six week #immobilisation for stable Weber B type ankle #fractures: randomised, multicentre, non-inferiority clinical trial
https://www.bmj.com/content/364/bmj.k5432
212 of 247 randomised participants (86%) completed the study. At 52 weeks, the mean OMAS was 87.6 (SD 18.3) in the six week cast group, 91.7 (SD 12.9) in the three week cast group, and 89.8 (SD 18.4) in the three week orthosis group. The between group difference at 52 weeks for the three week cast versus six week cast was 3.6 points (95% confidence interval −1.9 to 9.1, P=0.20), and for the three week orthosis versus six week cast was 1.7 points (−4.0 to 7.3, P=0.56). In both comparisons, the confidence intervals did not include the predefined inferiority margin of −8.8 points. The only statistically significant between group differences observed in the secondary outcomes and harms in the two primary comparisons were slight improvement in ankle plantar flexion and incidence of deep vein thrombosis, both in the three week orthosis group versus six week cast group.
Conclusion Immobilisation for three weeks with a cast or orthosis was non-inferior to conventional cast immobilisation for six weeks in the treatment of an isolated stable Weber B type fracture.
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Outpatient Parenteral #Antibiotic Treatment (OPAT) for Infective #Endocarditis: a Prospective Cohort Study From the GAMES Cohort
https://academic.oup.com/cid/advance-article-abstract/doi/10.1093/cid/ciz030/5289192
Outpatient parenteral antibiotic treatment (OPAT) has proven efficacious and safe for treating infective endocarditis (IE). However, the 2001 IDSA criteria for OPAT in IE are very restrictive. We aimed to compare the outcomes of OPAT with those of hospital-based antibiotic treatment (HBAT).
The most frequent causal microorganisms were viridans group streptococci (18.6%), Staphylococcus aureus (15.6%), and coagulase-negative staphylococci (14.5%). The median length of antibiotic treatment was 42 days (IQR 32–54), and 44% of patients underwent cardiac surgery. One-year mortality was 8% (42% for HBAT; P<0.001), 1.4% of patients relapsed, and 10.9% were readmitted during the first three months after discharge (no significant differences compared with HBAT). Charlson score (OR 1.21, 95%CI 1.04–1.42; P=0.01) and cardiac surgery (OR 0.24, 95%CI 0.09–0.63; P=0.04) were associated with one-year mortality, whereas aortic valve involvement (OR 0.47, 95%CI 0.22–0.98; P=0.007) was the only predictor of readmission at one year. Failing to fulfill IDSA criteria was not a risk factor for mortality or readmission.
Conclusions
OPAT provided excellent results despite the use of broader criteria than those recommended by IDSA; OPAT criteria should therefore be expanded.
Outpatient Parenteral #Antibiotic Treatment (OPAT) for Infective #Endocarditis: a Prospective Cohort Study From the GAMES Cohort
https://academic.oup.com/cid/advance-article-abstract/doi/10.1093/cid/ciz030/5289192
Outpatient parenteral antibiotic treatment (OPAT) has proven efficacious and safe for treating infective endocarditis (IE). However, the 2001 IDSA criteria for OPAT in IE are very restrictive. We aimed to compare the outcomes of OPAT with those of hospital-based antibiotic treatment (HBAT).
The most frequent causal microorganisms were viridans group streptococci (18.6%), Staphylococcus aureus (15.6%), and coagulase-negative staphylococci (14.5%). The median length of antibiotic treatment was 42 days (IQR 32–54), and 44% of patients underwent cardiac surgery. One-year mortality was 8% (42% for HBAT; P<0.001), 1.4% of patients relapsed, and 10.9% were readmitted during the first three months after discharge (no significant differences compared with HBAT). Charlson score (OR 1.21, 95%CI 1.04–1.42; P=0.01) and cardiac surgery (OR 0.24, 95%CI 0.09–0.63; P=0.04) were associated with one-year mortality, whereas aortic valve involvement (OR 0.47, 95%CI 0.22–0.98; P=0.007) was the only predictor of readmission at one year. Failing to fulfill IDSA criteria was not a risk factor for mortality or readmission.
Conclusions
OPAT provided excellent results despite the use of broader criteria than those recommended by IDSA; OPAT criteria should therefore be expanded.
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Association between use of #azathioprine and risk of acute #pancreatitis in children with inflammatory bowel disease: a Swedish–Danish nationwide cohort study
https://www.thelancet.com/journals/lanchi/article/PIIS2352-4642(18)30401-2/fulltext
Studies have shown an association between use of azathioprine and increased risk of acute pancreatitis in adult inflammatory bowel disease. However, whether an association exists among paediatric patients is not known.
Within the first 90 days following initiation of azathioprine, 40 acute pancreatitis events occurred (incidence rate 49·1 events per 1000 person-years) compared with six events in the no-use group (8·4 events per 1000 person-years). Azathioprine use was associated with an increased risk of acute pancreatitis (incidence rate ratio 5·82 [95% CI 2·47–13·72]; absolute difference 1·0 [95% CI 0·3–2·6] events per 100 patients) during the 90-day risk period.
Interpretation
Use of azathioprine was associated with an increased risk of acute pancreatitis in children with inflammatory bowel disease during the first 90 days following treatment initiation, suggesting the need for regular and rigorous monitoring. The risk of acute pancreatitis needs to be considered when deciding on optimal treatment strategies
Association between use of #azathioprine and risk of acute #pancreatitis in children with inflammatory bowel disease: a Swedish–Danish nationwide cohort study
https://www.thelancet.com/journals/lanchi/article/PIIS2352-4642(18)30401-2/fulltext
Studies have shown an association between use of azathioprine and increased risk of acute pancreatitis in adult inflammatory bowel disease. However, whether an association exists among paediatric patients is not known.
Within the first 90 days following initiation of azathioprine, 40 acute pancreatitis events occurred (incidence rate 49·1 events per 1000 person-years) compared with six events in the no-use group (8·4 events per 1000 person-years). Azathioprine use was associated with an increased risk of acute pancreatitis (incidence rate ratio 5·82 [95% CI 2·47–13·72]; absolute difference 1·0 [95% CI 0·3–2·6] events per 100 patients) during the 90-day risk period.
Interpretation
Use of azathioprine was associated with an increased risk of acute pancreatitis in children with inflammatory bowel disease during the first 90 days following treatment initiation, suggesting the need for regular and rigorous monitoring. The risk of acute pancreatitis needs to be considered when deciding on optimal treatment strategies
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#Benzodiazepines or related drugs and risk of #pneumonia: A systematic review and meta‐analysis
https://onlinelibrary.wiley.com/doi/full/10.1002/gps.5048
Benzodiazepines and benzodiazepine‐related drugs (BZRDs) are used to treat various psychiatric diseases. However, there are concerns that BZRDs increase the risk of pneumonia.
After pooling the estimates, the odds for developing pneumonia were 1.25‐fold higher (odd ratio, OR = 1.25; 95% confidence interval (CI), 1.09‐1.44) in BZRD users compared with individuals who had not taken BZRD. On the basis of exposure window, we found an increased risk of pneumonia among current (OR = 1.4; 95%CI, 1.22‐1.6) and recent (OR = 1.38; 95%CI, 1.06‐1.8) users, but not with the past users (OR = 1.11; 95%CI, 0.96‐1.27).
Conclusion
Current or recent exposure to BZRD is associated with an increased pneumonia risk. Clinicians need to weight the benefit‐risk balance of BZRD use, especially those with other risk factors for pneumonia.
#Benzodiazepines or related drugs and risk of #pneumonia: A systematic review and meta‐analysis
https://onlinelibrary.wiley.com/doi/full/10.1002/gps.5048
Benzodiazepines and benzodiazepine‐related drugs (BZRDs) are used to treat various psychiatric diseases. However, there are concerns that BZRDs increase the risk of pneumonia.
After pooling the estimates, the odds for developing pneumonia were 1.25‐fold higher (odd ratio, OR = 1.25; 95% confidence interval (CI), 1.09‐1.44) in BZRD users compared with individuals who had not taken BZRD. On the basis of exposure window, we found an increased risk of pneumonia among current (OR = 1.4; 95%CI, 1.22‐1.6) and recent (OR = 1.38; 95%CI, 1.06‐1.8) users, but not with the past users (OR = 1.11; 95%CI, 0.96‐1.27).
Conclusion
Current or recent exposure to BZRD is associated with an increased pneumonia risk. Clinicians need to weight the benefit‐risk balance of BZRD use, especially those with other risk factors for pneumonia.
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#Ejaculation Frequency and Risk of #Prostate Cancer: Updated Results with an Additional Decade of Follow-up
https://www.europeanurology.com/article/S0302-2838(16)00377-8/abstract/abstract_52392463?mobileUi=0
Evidence suggests that ejaculation frequency may be inversely related to the risk of prostate cancer (PCa), a disease for which few modifiable risk factors have been identified.
Ejaculation frequency at age 40–49 yr was positively associated with age-standardized body mass index, physical activity, divorce, history of sexually transmitted infections, and consumption of total calories and alcohol. Prostate-specific antigen (PSA) test utilization by 2008, number of PSA tests, and frequency of prostate biopsy were similar across frequency categories. In multivariable analyses, the hazard ratio for PCa incidence for ≥21 compared to 4–7 ejaculations per month was 0.81 for frequency at age 20–29 yr and 0.78 for frequency at age 40–49 yr. Associations were driven by low-risk disease, were similar when restricted to a PSA-screened cohort, and were unlikely to be explained by competing causes of death.
Conclusions
These findings provide additional evidence of a beneficial role of more frequent ejaculation throughout adult life in the etiology of PCa, particularly for low-risk disease.
#Ejaculation Frequency and Risk of #Prostate Cancer: Updated Results with an Additional Decade of Follow-up
https://www.europeanurology.com/article/S0302-2838(16)00377-8/abstract/abstract_52392463?mobileUi=0
Evidence suggests that ejaculation frequency may be inversely related to the risk of prostate cancer (PCa), a disease for which few modifiable risk factors have been identified.
Ejaculation frequency at age 40–49 yr was positively associated with age-standardized body mass index, physical activity, divorce, history of sexually transmitted infections, and consumption of total calories and alcohol. Prostate-specific antigen (PSA) test utilization by 2008, number of PSA tests, and frequency of prostate biopsy were similar across frequency categories. In multivariable analyses, the hazard ratio for PCa incidence for ≥21 compared to 4–7 ejaculations per month was 0.81 for frequency at age 20–29 yr and 0.78 for frequency at age 40–49 yr. Associations were driven by low-risk disease, were similar when restricted to a PSA-screened cohort, and were unlikely to be explained by competing causes of death.
Conclusions
These findings provide additional evidence of a beneficial role of more frequent ejaculation throughout adult life in the etiology of PCa, particularly for low-risk disease.
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#Porphyromonas gingivalis in #Alzheimer’s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors
http://advances.sciencemag.org/content/5/1/eaau3333
Porphyromonas gingivalis, the keystone pathogen in chronic periodontitis, was identified in the brain of Alzheimer’s disease patients. Toxic proteases from the bacterium called gingipains were also identified in the brain of Alzheimer’s patients, and levels correlated with tau and ubiquitin pathology. Oral P. gingivalis infection in mice resulted in brain colonization and increased production of Aβ1–42, a component of amyloid plaques
#Porphyromonas gingivalis in #Alzheimer’s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors
http://advances.sciencemag.org/content/5/1/eaau3333
Porphyromonas gingivalis, the keystone pathogen in chronic periodontitis, was identified in the brain of Alzheimer’s disease patients. Toxic proteases from the bacterium called gingipains were also identified in the brain of Alzheimer’s patients, and levels correlated with tau and ubiquitin pathology. Oral P. gingivalis infection in mice resulted in brain colonization and increased production of Aβ1–42, a component of amyloid plaques
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Skeletal #Muscles Do Not Undergo Apoptosis During Either #Atrophy or Programmed Cell Death-Revisiting the Myonuclear Domain Hypothesis
https://www.frontiersin.org/articles/10.3389/fphys.2018.01887/full
Muscle memory discovery ends 'use it or lose it' dogma
Skeletal muscles are the largest cells in the body and are one of the few syncytial ones. There is a longstanding belief that a given nucleus controls a defined volume of cytoplasm, so when a muscle grows (hypertrophy) or shrinks (atrophy), the number of myonuclei change accordingly. This phenomenon is known as the “myonuclear domain hypothesis.”
Recently, two independent models, one from rodents and the other from insects, have demonstrated that nuclei are not lost from skeletal muscle fibers when they undergo either atrophy or programmed cell death. These and other data argue against the current interpretation of the myonuclear domain hypothesis and suggest that once a nucleus has been acquired by a muscle fiber it persists.
Skeletal #Muscles Do Not Undergo Apoptosis During Either #Atrophy or Programmed Cell Death-Revisiting the Myonuclear Domain Hypothesis
https://www.frontiersin.org/articles/10.3389/fphys.2018.01887/full
Muscle memory discovery ends 'use it or lose it' dogma
Skeletal muscles are the largest cells in the body and are one of the few syncytial ones. There is a longstanding belief that a given nucleus controls a defined volume of cytoplasm, so when a muscle grows (hypertrophy) or shrinks (atrophy), the number of myonuclei change accordingly. This phenomenon is known as the “myonuclear domain hypothesis.”
Recently, two independent models, one from rodents and the other from insects, have demonstrated that nuclei are not lost from skeletal muscle fibers when they undergo either atrophy or programmed cell death. These and other data argue against the current interpretation of the myonuclear domain hypothesis and suggest that once a nucleus has been acquired by a muscle fiber it persists.
Frontiers
Frontiers | Skeletal Muscles Do Not Undergo Apoptosis During Either Atrophy or Programmed Cell Death-Revisiting the Myonuclear…
Skeletal muscles are the largest cells in the body and are one of the few syncytial ones. There is a longstanding belief that a given nucleus controls a defi...
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Injuries Associated With #Standing Electric #Scooter Use
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2722574
Twenty-seven patients were younger than 18 years (10.8%). Ten riders (4.4%) were documented as having worn a helmet, and 12 patients (4.8%) had either a blood alcohol level greater than 0.05% or were perceived to be intoxicated by a physician. Frequent injuries included fractures (79 [31.7%]), head injury (100 [40.2%]), and contusions, sprains, and lacerations without fracture or head injury (69 [27.7%]). The majority of patients (234 [94.0%]) were discharged home from the emergency department; of the 15 admitted patients, 2 had severe injuries and were admitted to the intensive care unit. Among 193 observed electric scooter riders in the local community in September 2018, 182 (94.3%) were not wearing a helmet.
Conclusions and Relevance Injuries associated with standing electric scooter use are a new phenomenon and vary in severity. In this study, helmet use was low and a significant subset of injuries occurred in patients younger than 18 years, the minimum age permitted by private scooter company regulations. These findings may inform public policy regarding standing electric scooter use.
Injuries Associated With #Standing Electric #Scooter Use
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2722574
Twenty-seven patients were younger than 18 years (10.8%). Ten riders (4.4%) were documented as having worn a helmet, and 12 patients (4.8%) had either a blood alcohol level greater than 0.05% or were perceived to be intoxicated by a physician. Frequent injuries included fractures (79 [31.7%]), head injury (100 [40.2%]), and contusions, sprains, and lacerations without fracture or head injury (69 [27.7%]). The majority of patients (234 [94.0%]) were discharged home from the emergency department; of the 15 admitted patients, 2 had severe injuries and were admitted to the intensive care unit. Among 193 observed electric scooter riders in the local community in September 2018, 182 (94.3%) were not wearing a helmet.
Conclusions and Relevance Injuries associated with standing electric scooter use are a new phenomenon and vary in severity. In this study, helmet use was low and a significant subset of injuries occurred in patients younger than 18 years, the minimum age permitted by private scooter company regulations. These findings may inform public policy regarding standing electric scooter use.
Jamanetwork
Injuries Associated With Standing Electric Scooter Use
This study of a case series investigates injuries associated with standing electric scooter use, characteristics and outcomes of injured patients, and common use practices of scooters in a US city.
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Human #Papillomavirus #Vaccination Before 13 and 15 Years of Age: Analysis of National Immunization Survey Teen Data
https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiy682/5265326
Human papillomavirus (HPV) vaccination is suboptimally used in the United States. Vaccination before the 13th birthday is recommended by the Advisory Committee on Immunization Practices and vaccination before the 15th birthday requires only 2 doses. We estimated the proportion of adolescents up to date for HPV vaccine using provider-verified vaccination data from the 2016 National Immunization Survey-Teen.
Only 16% of US adolescents completed HPV vaccination before turning 13, and 35% completed HPV vaccination before turning 15. With sexual activity initiation increasing throughout adolescence and higher immunogenicity for younger vaccinees, vaccination before the 13th birthday can provide better protection against HPV-related cancers.
Human #Papillomavirus #Vaccination Before 13 and 15 Years of Age: Analysis of National Immunization Survey Teen Data
https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiy682/5265326
Human papillomavirus (HPV) vaccination is suboptimally used in the United States. Vaccination before the 13th birthday is recommended by the Advisory Committee on Immunization Practices and vaccination before the 15th birthday requires only 2 doses. We estimated the proportion of adolescents up to date for HPV vaccine using provider-verified vaccination data from the 2016 National Immunization Survey-Teen.
Only 16% of US adolescents completed HPV vaccination before turning 13, and 35% completed HPV vaccination before turning 15. With sexual activity initiation increasing throughout adolescence and higher immunogenicity for younger vaccinees, vaccination before the 13th birthday can provide better protection against HPV-related cancers.
OUP Academic
Human Papillomavirus Vaccination Before 13 and 15 Years of Age: Analysis of National Immunization Survey Teen Data
Timely human papillomavirus vaccination, before 13 years of age as recommended, is low in the United States. While nearly 50% of US adolescents are up to date f
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Effect of Intensive vs Standard Blood #Pressure Control on Probable #Dementia
https://jamanetwork.com/journals/jama/fullarticle/2723256
Participants were randomized to a systolic blood pressure goal of either less than 120 mm Hg (intensive treatment group; n = 4678) or less than 140 mm Hg (standard treatment group; n = 4683).
The median intervention period was 3.34 years. During a total median follow-up of 5.11 years, adjudicated probable dementia occurred in 149 participants in the intensive treatment group vs 176 in the standard treatment group (7.2 vs 8.6 cases per 1000 person-years; hazard ratio HR, 0.83; 95% CI, 0.67-1.04). Intensive BP control significantly reduced the risk of mild cognitive impairment (14.6 vs 18.3 cases per 1000 person-years; HR, 0.81; 95% CI, 0.69-0.95) and the combined rate of mild cognitive impairment or probable dementia (20.2 vs 24.1 cases per 1000 person-years; HR, 0.85; 95% CI, 0.74-0.97).
Conclusions and Relevance Among ambulatory adults with hypertension, treating to a systolic blood pressure goal of less than 120 mm Hg compared with a goal of less than 140 mm Hg did not result in a significant reduction in the risk of probable dementia. Because of early study termination and fewer than expected cases of dementia, the study may have been underpowered for this end point.
Effect of Intensive vs Standard Blood #Pressure Control on Probable #Dementia
https://jamanetwork.com/journals/jama/fullarticle/2723256
Participants were randomized to a systolic blood pressure goal of either less than 120 mm Hg (intensive treatment group; n = 4678) or less than 140 mm Hg (standard treatment group; n = 4683).
The median intervention period was 3.34 years. During a total median follow-up of 5.11 years, adjudicated probable dementia occurred in 149 participants in the intensive treatment group vs 176 in the standard treatment group (7.2 vs 8.6 cases per 1000 person-years; hazard ratio HR, 0.83; 95% CI, 0.67-1.04). Intensive BP control significantly reduced the risk of mild cognitive impairment (14.6 vs 18.3 cases per 1000 person-years; HR, 0.81; 95% CI, 0.69-0.95) and the combined rate of mild cognitive impairment or probable dementia (20.2 vs 24.1 cases per 1000 person-years; HR, 0.85; 95% CI, 0.74-0.97).
Conclusions and Relevance Among ambulatory adults with hypertension, treating to a systolic blood pressure goal of less than 120 mm Hg compared with a goal of less than 140 mm Hg did not result in a significant reduction in the risk of probable dementia. Because of early study termination and fewer than expected cases of dementia, the study may have been underpowered for this end point.
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External Validation of the #MEESSI Acute Heart #Failure Risk Score: A Cohort Study
https://annals.org/aim/article-abstract/2723394/external-validation-meessi-acute-heart-failure-risk-score-cohort-study
The MEESSI-AHF (Multiple Estimation of risk based on the Emergency department Spanish Score In patients with AHF) score was developed to predict 30-day mortality in patients presenting with acute heart failure (AHF) to emergency departments (EDs) in Spain.
The score predicted 30-day mortality with excellent discrimination (c-statistic, 0.80). Assessment of cumulative mortality showed a steep gradient in 30-day mortality over 6 predefined risk groups (0 patients in the lowest-risk group vs. 35 28.5% in the highest-risk group). Risk was overestimated in the high-risk groups, resulting in a Hosmer–Lemeshow P value of 0.022. However, after adjustment of the intercept, the model showed good concordance between predicted risks and observed outcomes (P = 0.23). Findings were confirmed in sensitivity analyses that used multiple imputation for missing values in the overall cohort of 1572 patients.
External validation of the MEESSI-AHF risk score showed excellent discrimination. Recalibration may be needed when the score is introduced to new populations.
External Validation of the #MEESSI Acute Heart #Failure Risk Score: A Cohort Study
https://annals.org/aim/article-abstract/2723394/external-validation-meessi-acute-heart-failure-risk-score-cohort-study
The MEESSI-AHF (Multiple Estimation of risk based on the Emergency department Spanish Score In patients with AHF) score was developed to predict 30-day mortality in patients presenting with acute heart failure (AHF) to emergency departments (EDs) in Spain.
The score predicted 30-day mortality with excellent discrimination (c-statistic, 0.80). Assessment of cumulative mortality showed a steep gradient in 30-day mortality over 6 predefined risk groups (0 patients in the lowest-risk group vs. 35 28.5% in the highest-risk group). Risk was overestimated in the high-risk groups, resulting in a Hosmer–Lemeshow P value of 0.022. However, after adjustment of the intercept, the model showed good concordance between predicted risks and observed outcomes (P = 0.23). Findings were confirmed in sensitivity analyses that used multiple imputation for missing values in the overall cohort of 1572 patients.
External validation of the MEESSI-AHF risk score showed excellent discrimination. Recalibration may be needed when the score is introduced to new populations.
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#β-Blocker Therapy and Risk of Chronic Obstructive #Pulmonary Disease – A Danish Nationwide Study of 1·3 Million Individuals
https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(19)30004-5/fulltext
Highlights
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Users of β-blockers had an overall 19·7% lower risk of COPD hospitalization compared to users of any other antihypertensive drug during follow-up.
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Users of β-blockers had an overall 44% lower risk of death from COPD compared to users of any other antihypertensive drug.
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Results from this study advocates changes in the present hesitation of treatment with β-blockers in patients at risk of or with concomitant COPD.
#β-Blocker Therapy and Risk of Chronic Obstructive #Pulmonary Disease – A Danish Nationwide Study of 1·3 Million Individuals
https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(19)30004-5/fulltext
Highlights
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Users of β-blockers had an overall 19·7% lower risk of COPD hospitalization compared to users of any other antihypertensive drug during follow-up.
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Users of β-blockers had an overall 44% lower risk of death from COPD compared to users of any other antihypertensive drug.
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Results from this study advocates changes in the present hesitation of treatment with β-blockers in patients at risk of or with concomitant COPD.
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Clinical Features of Non-obese, Apparently Healthy Japanese Men with Reduced #Adipose Tissue #Insulin Sensitivity
https://academic.oup.com/jcem/advance-article-abstract/doi/10.1210/jc.2018-02190/5298594?redirectedFrom=fulltext
Adipose tissue insulin resistance is observed in obese subjects and is considered an early metabolic defect preceding insulin resistance in muscle and liver. While Asians readily develop metabolic disease without obesity, the clinical features of non-obese, apparently healthy Asians with reduced adipose tissue insulin sensitivity (ATIS) have not been elucidated.
Based on the median ATIS value, subjects were divided into low- and high-FFA suppression groups. The low-FFA suppression group had moderate fat accumulation in abdominal subcutaneous adipose tissue and liver. Compared with the high-FFA group, they also had a lower fitness level, decreased insulin clearance, impaired insulin sensitivity in muscle, moderately elevated triglycerides, and lowered high-density lipoprotein cholesterol levels. All these factors were significantly correlated with ATIS. Hepatic insulin sensitivity was comparable between the two groups.
Conclusions
In non-obese, apparently healthy Japanese men, reduced ATIS was associated with moderate fat accumulation in subcutaneous fat and liver, lower insulin clearance, muscle insulin resistance, and moderate lipidemia. These data suggest that reduced ATIS may occur early in the development of metabolic syndrome, even in non-obese, apparently healthy men.
Clinical Features of Non-obese, Apparently Healthy Japanese Men with Reduced #Adipose Tissue #Insulin Sensitivity
https://academic.oup.com/jcem/advance-article-abstract/doi/10.1210/jc.2018-02190/5298594?redirectedFrom=fulltext
Adipose tissue insulin resistance is observed in obese subjects and is considered an early metabolic defect preceding insulin resistance in muscle and liver. While Asians readily develop metabolic disease without obesity, the clinical features of non-obese, apparently healthy Asians with reduced adipose tissue insulin sensitivity (ATIS) have not been elucidated.
Based on the median ATIS value, subjects were divided into low- and high-FFA suppression groups. The low-FFA suppression group had moderate fat accumulation in abdominal subcutaneous adipose tissue and liver. Compared with the high-FFA group, they also had a lower fitness level, decreased insulin clearance, impaired insulin sensitivity in muscle, moderately elevated triglycerides, and lowered high-density lipoprotein cholesterol levels. All these factors were significantly correlated with ATIS. Hepatic insulin sensitivity was comparable between the two groups.
Conclusions
In non-obese, apparently healthy Japanese men, reduced ATIS was associated with moderate fat accumulation in subcutaneous fat and liver, lower insulin clearance, muscle insulin resistance, and moderate lipidemia. These data suggest that reduced ATIS may occur early in the development of metabolic syndrome, even in non-obese, apparently healthy men.
OUP Academic
Clinical Features of Nonobese, Apparently Healthy, Japanese Men With Reduced Adipose Tissue Insulin Sensitivity
Even in nonobese, apparently healthy, Japanese men, reduced adipose tissue insulin sensitivity was associated with clinical features of metabolic syndrome.
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Effect of #breakfast on #weight and energy intake: systematic review and meta-analysis of randomised controlled trials
https://www.bmj.com/content/364/bmj.l42
Meta-analysis of the results found a small difference in weight favouring participants who skipped breakfast (mean difference 0.44 kg, 95% confidence interval 0.07 to 0.82), but there was some inconsistency across trial results (I2=43%). Participants assigned to breakfast had a higher total daily energy intake than those assigned to skip breakfast (mean difference 259.79 kcal/day, 78.87 to 440.71; 1 kcal=4.18 kJ), despite substantial inconsistency across trial results (I2=80%). All of the included trials were at high or unclear risk of bias in at least one domain and had only short term follow-ups (mean period seven weeks for weight, two weeks for energy intake). As the quality of the included studies was mostly low, the findings should be interpreted with caution.
Conclusion This study suggests that the addition of breakfast might not be a good strategy for weight loss, regardless of established breakfast habit. Caution is needed when recommending breakfast for weight loss in adults, as it could have the opposite effect. Further randomised controlled trials of high quality are needed to examine the role of breakfast eating in the approach to weight management
The author of an accompanying opinion piece — a regular breakfast eater — concludes, "No harm can be done in trying out your own personal experiments in skipping breakfast."
Effect of #breakfast on #weight and energy intake: systematic review and meta-analysis of randomised controlled trials
https://www.bmj.com/content/364/bmj.l42
Meta-analysis of the results found a small difference in weight favouring participants who skipped breakfast (mean difference 0.44 kg, 95% confidence interval 0.07 to 0.82), but there was some inconsistency across trial results (I2=43%). Participants assigned to breakfast had a higher total daily energy intake than those assigned to skip breakfast (mean difference 259.79 kcal/day, 78.87 to 440.71; 1 kcal=4.18 kJ), despite substantial inconsistency across trial results (I2=80%). All of the included trials were at high or unclear risk of bias in at least one domain and had only short term follow-ups (mean period seven weeks for weight, two weeks for energy intake). As the quality of the included studies was mostly low, the findings should be interpreted with caution.
Conclusion This study suggests that the addition of breakfast might not be a good strategy for weight loss, regardless of established breakfast habit. Caution is needed when recommending breakfast for weight loss in adults, as it could have the opposite effect. Further randomised controlled trials of high quality are needed to examine the role of breakfast eating in the approach to weight management
The author of an accompanying opinion piece — a regular breakfast eater — concludes, "No harm can be done in trying out your own personal experiments in skipping breakfast."
The BMJ
Effect of breakfast on weight and energy intake: systematic review and meta-analysis of randomised controlled trials
Objective To examine the effect of regular breakfast consumption on weight change and energy intake in people living in high income countries.
Design Systematic review and meta-analysis.
Data sources PubMed, Ovid Medline, and CINAHL were searched for randomised…
Design Systematic review and meta-analysis.
Data sources PubMed, Ovid Medline, and CINAHL were searched for randomised…
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Cost‐effectiveness of combination disease‐modifying antirheumatics vs. tumour necrosis factor inhibitors in active #rheumatoid arthritis: TACIT trial
https://onlinelibrary.wiley.com/doi/abs/10.1002/acr.23830
205 participants were recruited, 104 in the #cDMARDs arm, 101 in the TNFis arm. cDMARD arm participants with poor response at 6 months were offered TNFis; 46 (44%) switched. Relevant cost and outcome data were available for 93% of participants at 6 month follow‐up and 91‐92% at 12 month follow‐up. The cDMARDs arm had significantly lower total costs from all perspectives (6 month H&SC adjusted mean difference ‐£3615 (95% confidence interval ‐£4104 to ‐£3182); 12 month H&SC adjusted mean difference ‐£1930 (95% confidence interval ‐£2599 to ‐£1301)). The HAQ showed benefit to the cDMARDs arm at 12 months (‐0.16; 95% CI‐0.32 to ‐0.01); other outcomes/follow‐ups showed no differences.
Conclusion
Starting treatment with cDMARDs, rather than TNFis, achieves similar outcomes at significantly lower costs. Patients with active rheumatoid arthritis and meeting NICE criteria for expensive biologics can cost‐effectively be treated with combinations of intensive synthetic disease modifying drugs.
Cost‐effectiveness of combination disease‐modifying antirheumatics vs. tumour necrosis factor inhibitors in active #rheumatoid arthritis: TACIT trial
https://onlinelibrary.wiley.com/doi/abs/10.1002/acr.23830
205 participants were recruited, 104 in the #cDMARDs arm, 101 in the TNFis arm. cDMARD arm participants with poor response at 6 months were offered TNFis; 46 (44%) switched. Relevant cost and outcome data were available for 93% of participants at 6 month follow‐up and 91‐92% at 12 month follow‐up. The cDMARDs arm had significantly lower total costs from all perspectives (6 month H&SC adjusted mean difference ‐£3615 (95% confidence interval ‐£4104 to ‐£3182); 12 month H&SC adjusted mean difference ‐£1930 (95% confidence interval ‐£2599 to ‐£1301)). The HAQ showed benefit to the cDMARDs arm at 12 months (‐0.16; 95% CI‐0.32 to ‐0.01); other outcomes/follow‐ups showed no differences.
Conclusion
Starting treatment with cDMARDs, rather than TNFis, achieves similar outcomes at significantly lower costs. Patients with active rheumatoid arthritis and meeting NICE criteria for expensive biologics can cost‐effectively be treated with combinations of intensive synthetic disease modifying drugs.