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Lamictal (#lamotrigine ): Drug Safety Communication - Serious Immune System #Reaction
https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm605628.htm
The immune system reaction, called hemophagocytic lymphohistiocytosis (HLH), causes an uncontrolled response by the immune system. HLH typically presents as a persistent fever, usually greater than 101°F, and it can lead to severe problems with blood cells and organs throughout the body such as the liver, kidneys, and lungs
Advise patients to seek immediate medical attention if they experience symptoms of HLH during lamotrigine treatment. A diagnosis of HLH can be established if a patient has at least five of the following eight signs or symptoms:
fever and rash
enlarged spleen
cytopenias
elevated levels of triglycerides or low blood levels of fibrinogen
high levels of blood ferritin
hemophagocytosis identified through bone marrow, spleen, or lymph node biopsy
decreased or absent Natural Killer (NK) Cell activity
elevated blood levels of CD25 showing prolonged immune cell activation
Lamictal (#lamotrigine ): Drug Safety Communication - Serious Immune System #Reaction
https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm605628.htm
The immune system reaction, called hemophagocytic lymphohistiocytosis (HLH), causes an uncontrolled response by the immune system. HLH typically presents as a persistent fever, usually greater than 101°F, and it can lead to severe problems with blood cells and organs throughout the body such as the liver, kidneys, and lungs
Advise patients to seek immediate medical attention if they experience symptoms of HLH during lamotrigine treatment. A diagnosis of HLH can be established if a patient has at least five of the following eight signs or symptoms:
fever and rash
enlarged spleen
cytopenias
elevated levels of triglycerides or low blood levels of fibrinogen
high levels of blood ferritin
hemophagocytosis identified through bone marrow, spleen, or lymph node biopsy
decreased or absent Natural Killer (NK) Cell activity
elevated blood levels of CD25 showing prolonged immune cell activation
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Disorganized #Gyrification Network Properties During the Transition to #Psychosis
https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2678576
The 4 study groups comprised 161 participants with mean (SD) ages ranging from 24.0 (4.7) to 25.9 (5.7) years. Small-worldness was reduced in the ARMS-T and FEP groups and was associated with decreased integration and increased segregation in both groups (Hedges g range, 0.666-1.050). Using the connectome properties as features, a good classification performance was obtained (accuracy, 90.49%; balanced accuracy, 81.34%; positive predictive value, 84.47%; negative predictive value, 92.18%; sensitivity, 66.11%; specificity, 96.58%; and area under the curve, 88.30%).
Conclusions and Relevance These findings suggest that there is poor integration in the coordinated development of cortical folding in patients who develop psychosis. These results further suggest that gyrification-based connectomes might be a promising means to generate systems-based measures from anatomical data to improve individual prediction of a transition to psychosis in CHR individuals.
Disorganized #Gyrification Network Properties During the Transition to #Psychosis
https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2678576
The 4 study groups comprised 161 participants with mean (SD) ages ranging from 24.0 (4.7) to 25.9 (5.7) years. Small-worldness was reduced in the ARMS-T and FEP groups and was associated with decreased integration and increased segregation in both groups (Hedges g range, 0.666-1.050). Using the connectome properties as features, a good classification performance was obtained (accuracy, 90.49%; balanced accuracy, 81.34%; positive predictive value, 84.47%; negative predictive value, 92.18%; sensitivity, 66.11%; specificity, 96.58%; and area under the curve, 88.30%).
Conclusions and Relevance These findings suggest that there is poor integration in the coordinated development of cortical folding in patients who develop psychosis. These results further suggest that gyrification-based connectomes might be a promising means to generate systems-based measures from anatomical data to improve individual prediction of a transition to psychosis in CHR individuals.
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#Gut Microbiome Composition in Non-human Primates Consuming a Western or Mediterranean #Diet
https://www.frontiersin.org/articles/10.3389/fnut.2018.00028/full
Microbiome diversity in MD consumers was significantly higher by the Shannon diversity index compared to the WD consumers, with similar but non-significant trends noted for the diversity metrics of species richness (Chao 1), observed operational taxonomic units (OTUs) and phylogenetic diversity (PD) whole Tree. Compared to the MD, the WD group demonstrated a higher Firmicutes-Bacteroides ratio and a significantly higher abundance of families Clostridiacea and Lactobacillaceae. Further analyses reveal significantly higher abundance of genera Lactobacillus, Clostridium, Faecalibacterium, and Oscillospira and lower abundance of Ruminococcus and Coprococcus in MD consumers relative to WD consumers. OTUs belonging to several species also show significant differences between the two groups, with Lactobacillus species demonstrating a prominently higher abundance in the MD consumers. The data reveal several differences in the gut microbiome of primates consuming the two different diets and should be useful for further studies aimed at understanding the diet-microbiome-health interactions in primates
#Gut Microbiome Composition in Non-human Primates Consuming a Western or Mediterranean #Diet
https://www.frontiersin.org/articles/10.3389/fnut.2018.00028/full
Microbiome diversity in MD consumers was significantly higher by the Shannon diversity index compared to the WD consumers, with similar but non-significant trends noted for the diversity metrics of species richness (Chao 1), observed operational taxonomic units (OTUs) and phylogenetic diversity (PD) whole Tree. Compared to the MD, the WD group demonstrated a higher Firmicutes-Bacteroides ratio and a significantly higher abundance of families Clostridiacea and Lactobacillaceae. Further analyses reveal significantly higher abundance of genera Lactobacillus, Clostridium, Faecalibacterium, and Oscillospira and lower abundance of Ruminococcus and Coprococcus in MD consumers relative to WD consumers. OTUs belonging to several species also show significant differences between the two groups, with Lactobacillus species demonstrating a prominently higher abundance in the MD consumers. The data reveal several differences in the gut microbiome of primates consuming the two different diets and should be useful for further studies aimed at understanding the diet-microbiome-health interactions in primates
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Impact of Healthy #Lifestyle Factors on #Life Expectancies in the US Population
http://circ.ahajournals.org/content/early/2018/04/25/CIRCULATIONAHA.117.032047
we defined 5 low-risk lifestyle factors as never smoking, body mass index of 18.5 to 24.9 kg/m2, ≥30 min/d of moderate to vigorous physical activity, moderate alcohol intake, and a high diet quality score (upper 40%),
The population-attributable risk of nonadherence to 5 low-risk factors was 60.7% (95% CI, 53.6-66.7) for all-cause mortality, 51.7% (95% CI, 37.1-62.9) for cancer mortality, and 71.7% (95% CI, 58.1-81.0) for cardiovascular disease mortality. We estimated that the life expectancy at age 50 years was 29.0 years (95% CI, 28.3-29.8) for women and 25.5 years (95% CI, 24.7-26.2) for men who adopted zero low-risk lifestyle factors. In contrast, for those who adopted all 5 low-risk factors, we projected a life expectancy at age 50 years of 43.1 years (95% CI, 41.3-44.9) for women and 37.6 years (95% CI, 35.8-39.4) for men. The projected life expectancy at age 50 years was on average 14.0 years (95% CI, 11.8-16.2) longer among female Americans with 5 lowrisk factors compared with those with zero low-risk factors; for men, the difference was 12.2 years (95% CI, 10.1-14.2).
Conclusions—Adopting a healthy lifestyle could substantially reduce premature mortality and prolong life expectancy in US adults
Impact of Healthy #Lifestyle Factors on #Life Expectancies in the US Population
http://circ.ahajournals.org/content/early/2018/04/25/CIRCULATIONAHA.117.032047
we defined 5 low-risk lifestyle factors as never smoking, body mass index of 18.5 to 24.9 kg/m2, ≥30 min/d of moderate to vigorous physical activity, moderate alcohol intake, and a high diet quality score (upper 40%),
The population-attributable risk of nonadherence to 5 low-risk factors was 60.7% (95% CI, 53.6-66.7) for all-cause mortality, 51.7% (95% CI, 37.1-62.9) for cancer mortality, and 71.7% (95% CI, 58.1-81.0) for cardiovascular disease mortality. We estimated that the life expectancy at age 50 years was 29.0 years (95% CI, 28.3-29.8) for women and 25.5 years (95% CI, 24.7-26.2) for men who adopted zero low-risk lifestyle factors. In contrast, for those who adopted all 5 low-risk factors, we projected a life expectancy at age 50 years of 43.1 years (95% CI, 41.3-44.9) for women and 37.6 years (95% CI, 35.8-39.4) for men. The projected life expectancy at age 50 years was on average 14.0 years (95% CI, 11.8-16.2) longer among female Americans with 5 lowrisk factors compared with those with zero low-risk factors; for men, the difference was 12.2 years (95% CI, 10.1-14.2).
Conclusions—Adopting a healthy lifestyle could substantially reduce premature mortality and prolong life expectancy in US adults
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News release: 9 out of 10 people worldwide breathe #polluted #air
http://www.who.int/airpollution/en/
Air pollution levels remain at dangerously high levels in many parts of the world. New data reveals that 9 out of 10 people breathe air containing high levels of pollutants. like black carbon which penetrate deep into the lungs and cardiovascular system.
WHO estimates that around 7 million people die every year from exposure to fine particles in polluted air that lead to diseases such as stroke, heart disease, lung cancer, chronic obstructive pulmonary diseases and respiratory infections, including pneumonia
News release: 9 out of 10 people worldwide breathe #polluted #air
http://www.who.int/airpollution/en/
Air pollution levels remain at dangerously high levels in many parts of the world. New data reveals that 9 out of 10 people breathe air containing high levels of pollutants. like black carbon which penetrate deep into the lungs and cardiovascular system.
WHO estimates that around 7 million people die every year from exposure to fine particles in polluted air that lead to diseases such as stroke, heart disease, lung cancer, chronic obstructive pulmonary diseases and respiratory infections, including pneumonia
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Effects of #tobacco smoke and electronic cigarette vapor exposure on the oral and gut #microbiota in humans: a pilot study
https://peerj.com/articles/4693/
Tobacco smoking had a significant effect on the bacterial profiles in all sample types when compared to controls, and in feces and buccal swabs when compared to EC users. The most significant associations were found in the gut, with an increased relative abundance of Prevotella (P = 0.006) and decreased Bacteroides (P = 0.036) in tobacco smokers. The Shannon diversity was also significantly reduced (P = 0.009) in fecal samples collected from tobacco smokers compared to controls. No significant difference was found in the alpha diversity, beta-diversity or taxonomic relative abundances between EC users and controls.
Discussion
From a microbial ecology perspective, the current pilot data demonstrate that the use of ECs may represent a safer alternative compared to tobacco smoking. However, validation in larger cohorts and greater understanding of the short and long-term impact of EC use on microbiota composition and function is warranted
Effects of #tobacco smoke and electronic cigarette vapor exposure on the oral and gut #microbiota in humans: a pilot study
https://peerj.com/articles/4693/
Tobacco smoking had a significant effect on the bacterial profiles in all sample types when compared to controls, and in feces and buccal swabs when compared to EC users. The most significant associations were found in the gut, with an increased relative abundance of Prevotella (P = 0.006) and decreased Bacteroides (P = 0.036) in tobacco smokers. The Shannon diversity was also significantly reduced (P = 0.009) in fecal samples collected from tobacco smokers compared to controls. No significant difference was found in the alpha diversity, beta-diversity or taxonomic relative abundances between EC users and controls.
Discussion
From a microbial ecology perspective, the current pilot data demonstrate that the use of ECs may represent a safer alternative compared to tobacco smoking. However, validation in larger cohorts and greater understanding of the short and long-term impact of EC use on microbiota composition and function is warranted
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Association of #Depression and #Anxiety Disorders With Autoimmune #Thyroiditis
A Systematic Review and Meta-analysis
https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2679767?utm_campaign=articlePDF&utm_medium=articlePDFlink&utm_source=articlePDF&utm_content=jamapsychiatry.2018.0190
Patients with AIT, Hashimoto thyroiditis, or subclinical or overt hypothyroidism had significantly higher scores on standardized depression instruments, with an odds ratio of 3.56 (95% CI, 2.14-5.94; I2 = 92.1%). For anxiety disorders, patients with AIT, Hashimoto thyroiditis, or subclinical or overt hypothyroidism had an odds ratio of 2.32 (95% CI, 1.40-3.85; I2 = 89.8%). Funnel plot asymmetry was detected for studies of depression. Study quality assessed with the Newcastle-Ottawa Scale for case-control studies (mean SD score: anxiety, 5.77 1.17; depression, 5.65 1.14; of a possible maximum score of 9) and proportion of females did not modulate the meta-analytic estimate, whereas mean age did.
Conclusions and Relevance This meta-analysis establishes the association between AIT and depression and anxiety disorders. Patients with AIT exhibit an increased chance of developing symptoms of depression and anxiety or of receiving a diagnosis of depression and anxiety disorders. This finding has important implications for patients and could lead to the choice of early treatment—and not only psychotherapeutic treatment—of the organic disorder.
Association of #Depression and #Anxiety Disorders With Autoimmune #Thyroiditis
A Systematic Review and Meta-analysis
https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2679767?utm_campaign=articlePDF&utm_medium=articlePDFlink&utm_source=articlePDF&utm_content=jamapsychiatry.2018.0190
Patients with AIT, Hashimoto thyroiditis, or subclinical or overt hypothyroidism had significantly higher scores on standardized depression instruments, with an odds ratio of 3.56 (95% CI, 2.14-5.94; I2 = 92.1%). For anxiety disorders, patients with AIT, Hashimoto thyroiditis, or subclinical or overt hypothyroidism had an odds ratio of 2.32 (95% CI, 1.40-3.85; I2 = 89.8%). Funnel plot asymmetry was detected for studies of depression. Study quality assessed with the Newcastle-Ottawa Scale for case-control studies (mean SD score: anxiety, 5.77 1.17; depression, 5.65 1.14; of a possible maximum score of 9) and proportion of females did not modulate the meta-analytic estimate, whereas mean age did.
Conclusions and Relevance This meta-analysis establishes the association between AIT and depression and anxiety disorders. Patients with AIT exhibit an increased chance of developing symptoms of depression and anxiety or of receiving a diagnosis of depression and anxiety disorders. This finding has important implications for patients and could lead to the choice of early treatment—and not only psychotherapeutic treatment—of the organic disorder.
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Support for midlife #anxiety diagnosis as an independent risk factor for #dementia: a systematic review
http://bmjopen.bmj.com/content/8/4/e019399
Searches yielded 3510 articles, of which 4 (0.02%) were eligible. The studies had a combined sample size of 29 819, and all studies found a positive association between clinically significant anxiety and future dementia. Due to the heterogeneity between studies, a meta-analysis was not conducted.
Conclusions Clinically significant anxiety in midlife was associated with an increased risk of dementia over an interval of at least 10 years. These findings indicate that anxiety may be a risk factor for late-life dementia, excluding anxiety that is related to prodromal cognitive decline. With increasing focus on identifying modifiable risk factors for dementia, more high-quality prospective studies are required to clarify whether clinical anxiety is a risk factor for dementia, separate from a prodromal symptom
Support for midlife #anxiety diagnosis as an independent risk factor for #dementia: a systematic review
http://bmjopen.bmj.com/content/8/4/e019399
Searches yielded 3510 articles, of which 4 (0.02%) were eligible. The studies had a combined sample size of 29 819, and all studies found a positive association between clinically significant anxiety and future dementia. Due to the heterogeneity between studies, a meta-analysis was not conducted.
Conclusions Clinically significant anxiety in midlife was associated with an increased risk of dementia over an interval of at least 10 years. These findings indicate that anxiety may be a risk factor for late-life dementia, excluding anxiety that is related to prodromal cognitive decline. With increasing focus on identifying modifiable risk factors for dementia, more high-quality prospective studies are required to clarify whether clinical anxiety is a risk factor for dementia, separate from a prodromal symptom
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Education plus #exercise versus corticosteroid injection use versus a wait and see approach on global outcome and pain from gluteal #tendinopathy: prospective, single blinded, randomised clinical trial
https://www.bmj.com/content/361/bmj.k1662
..EDX had better global improvement scores than CSI (19.9% (4.7% to 35.0%); 5.0 (2.9 to 21.1)). At eight weeks, reported pain on the numerical rating scale was mean score 1.5 (standard deviation 1.5) for EDX, 2.7 (2.4) for CSI, and 3.8 (2.0) for WS. EDX and CSI participants reported less pain than WS (mean difference −2.2 (95% confidence interval −2.89 to −1.54); −1.2 (−1.85 to −0.50); respectively), and EDX participants reported less pain than CSI (−1.04 (−1.72 to −0.37)). Success on the global rating of change was reported at 52 weeks by 51/65 EDX, 36/63 CSI, and 31/60 WS participants; EDX was better than CSI (20.4% (4.9% to 35.9%); 4.9 (2.8 to 20.6)) and WS (26.8% (11.3% to 42.3%); 3.7 (2.4 to 8.8)). Reported pain at 52 weeks was 2.1 (2.2) for EDX, 2.3 (1.9) for CSI, and 3.2 (2.6) for WS; EDX did not differ from CSI (−0.26 (−1.06 to 0.55)), but both treatments did better than WS (1.13 (−1.93 to −0.33); 0.87 (−1.68 to −0.07); respectively).
Conclusions For gluteal tendinopathy, education plus exercise and corticosteroid injection use resulted in higher rates of patient reported global improvement and lower pain intens
Education plus #exercise versus corticosteroid injection use versus a wait and see approach on global outcome and pain from gluteal #tendinopathy: prospective, single blinded, randomised clinical trial
https://www.bmj.com/content/361/bmj.k1662
..EDX had better global improvement scores than CSI (19.9% (4.7% to 35.0%); 5.0 (2.9 to 21.1)). At eight weeks, reported pain on the numerical rating scale was mean score 1.5 (standard deviation 1.5) for EDX, 2.7 (2.4) for CSI, and 3.8 (2.0) for WS. EDX and CSI participants reported less pain than WS (mean difference −2.2 (95% confidence interval −2.89 to −1.54); −1.2 (−1.85 to −0.50); respectively), and EDX participants reported less pain than CSI (−1.04 (−1.72 to −0.37)). Success on the global rating of change was reported at 52 weeks by 51/65 EDX, 36/63 CSI, and 31/60 WS participants; EDX was better than CSI (20.4% (4.9% to 35.9%); 4.9 (2.8 to 20.6)) and WS (26.8% (11.3% to 42.3%); 3.7 (2.4 to 8.8)). Reported pain at 52 weeks was 2.1 (2.2) for EDX, 2.3 (1.9) for CSI, and 3.2 (2.6) for WS; EDX did not differ from CSI (−0.26 (−1.06 to 0.55)), but both treatments did better than WS (1.13 (−1.93 to −0.33); 0.87 (−1.68 to −0.07); respectively).
Conclusions For gluteal tendinopathy, education plus exercise and corticosteroid injection use resulted in higher rates of patient reported global improvement and lower pain intens
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Inhibition of UGT8 suppresses basal-like breast cancer progression by attenuating sulfatide–αVβ5 axis
http://jem.rupress.org/content/early/2018/05/03/jem.20172048?PR=
Basal-like breast cancer (BLBC) is associated with a poor clinical outcome as a result of the few treatment options and poor therapeutic response. Here, we report that elevated expression of urine diphosphate–galactose ceramide galactosyltransferase (UGT8) specifically occurs in BLBC and predicts poor prognosis in breast cancer patients. UGT8 expression is transcriptionally up-regulated by Sox10, triggering the sulfatide biosynthetic pathway; increased sulfatide activates integrin αVβ5-mediated signaling that contributes to BLBC progression. UGT8 expression promotes, whereas UGT8 knockdown suppresses tumorigenicity and metastasis.
Importantly, we identify that zoledronic acid (ZA), a marketed drug for treating osteoporosis and bone metastasis, is a direct inhibitor of UGT8, which blocks the sulfatide biosynthetic pathway. Significantly, a clinically achievable dosage of ZA exhibits apparent inhibitory effect on migration, invasion, and lung metastasis of BLBC cells. Together, our study suggests that UGT8 is a potential prognostic indicator and druggable target of BLBC and that pharmacologic inhibition of UGT8 by ZA offers a promising opportunity for treating this challenging disease
Inhibition of UGT8 suppresses basal-like breast cancer progression by attenuating sulfatide–αVβ5 axis
http://jem.rupress.org/content/early/2018/05/03/jem.20172048?PR=
Basal-like breast cancer (BLBC) is associated with a poor clinical outcome as a result of the few treatment options and poor therapeutic response. Here, we report that elevated expression of urine diphosphate–galactose ceramide galactosyltransferase (UGT8) specifically occurs in BLBC and predicts poor prognosis in breast cancer patients. UGT8 expression is transcriptionally up-regulated by Sox10, triggering the sulfatide biosynthetic pathway; increased sulfatide activates integrin αVβ5-mediated signaling that contributes to BLBC progression. UGT8 expression promotes, whereas UGT8 knockdown suppresses tumorigenicity and metastasis.
Importantly, we identify that zoledronic acid (ZA), a marketed drug for treating osteoporosis and bone metastasis, is a direct inhibitor of UGT8, which blocks the sulfatide biosynthetic pathway. Significantly, a clinically achievable dosage of ZA exhibits apparent inhibitory effect on migration, invasion, and lung metastasis of BLBC cells. Together, our study suggests that UGT8 is a potential prognostic indicator and druggable target of BLBC and that pharmacologic inhibition of UGT8 by ZA offers a promising opportunity for treating this challenging disease
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Efficacy of self-monitored blood #pressure, with or without telemonitoring, for titration of #antihypertensive medication (TASMINH4): an unmasked randomised controlled trial
https://www.sciencedirect.com/science/article/pii/S014067361830309X
1182 participants were randomly assigned to the self-monitoring group (n=395), the telemonitoring group (n=393), or the usual care group (n=394), of whom 1003 (85%) were included in the primary analysis. After 12 months, systolic blood pressure was lower in both intervention groups compared with usual care (self-monitoring, 137·0 SD 16·7 mm Hg and telemonitoring, 136·0 16·1 mm Hg vs usual care, 140·4 16·5; adjusted mean differences vs usual care: self-monitoring alone, −3·5 mm Hg 95% CI −5·8 to −1·2; telemonitoring, −4·7 mm Hg –7·0 to −2·4). No difference between the self-monitoring and telemonitoring groups was recorded (adjusted mean difference −1·2 mm Hg 95% CI −3·5 to 1·2). Results were similar in sensitivity analyses including multiple imputation. Adverse events were similar between all three groups.
Interpretation
Self-monitoring, with or without telemonitoring, when used by general practitioners to titrate antihypertensive medication in individuals with poorly controlled blood pressure, leads to significantly lower blood pressure than titration guided by clinic readings. With most general practitioners and many patients using self-monitoring, it could become the cornerstone of hypertension management in primary care.
Efficacy of self-monitored blood #pressure, with or without telemonitoring, for titration of #antihypertensive medication (TASMINH4): an unmasked randomised controlled trial
https://www.sciencedirect.com/science/article/pii/S014067361830309X
1182 participants were randomly assigned to the self-monitoring group (n=395), the telemonitoring group (n=393), or the usual care group (n=394), of whom 1003 (85%) were included in the primary analysis. After 12 months, systolic blood pressure was lower in both intervention groups compared with usual care (self-monitoring, 137·0 SD 16·7 mm Hg and telemonitoring, 136·0 16·1 mm Hg vs usual care, 140·4 16·5; adjusted mean differences vs usual care: self-monitoring alone, −3·5 mm Hg 95% CI −5·8 to −1·2; telemonitoring, −4·7 mm Hg –7·0 to −2·4). No difference between the self-monitoring and telemonitoring groups was recorded (adjusted mean difference −1·2 mm Hg 95% CI −3·5 to 1·2). Results were similar in sensitivity analyses including multiple imputation. Adverse events were similar between all three groups.
Interpretation
Self-monitoring, with or without telemonitoring, when used by general practitioners to titrate antihypertensive medication in individuals with poorly controlled blood pressure, leads to significantly lower blood pressure than titration guided by clinic readings. With most general practitioners and many patients using self-monitoring, it could become the cornerstone of hypertension management in primary care.
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High risk of #hepatocellular carcinoma and death in patients with immune-tolerant-phase chronic hepatitis #B
http://gut.bmj.com/content/67/5/945
The clinical outcomes of 413 untreated IT-phase patients with normal alanine aminotransferase (ALT) levels (females, <19 IU/mL; males, <30 IU/mL) were compared with those of 1497 immune-active (IA)-phase patients (ALT ≥80 IU/mL) treated with nucleos(t)ide analogues.
Results The IT group was significantly younger than the IA group (mean age, 38 vs 40 years at baseline, p=0.04). The 10-year estimated cumulative incidences of HCC (12.7% vs 6.1%; p=0.001) and death/transplantation (9.7% vs 3.4%; p<0.001) were significantly higher in the IT group than the IA group. In multivariable analyses, the IT group showed a significantly higher risk of HCC (HR 2.54; 95% CI 1.54 to 4.18) and death/transplantation (HR 3.38; 95% CI 1.85 to 6.16) than the IA group, which was consistently identified through inverse probability treatment weighting, propensity score-matched and competing risks analyses.
Conclusions Untreated IT-phase patients with CHB had higher risks of HCC and death/transplantation than treated IA-phase patients. Unnecessary deaths could be prevented through earlier antiviral intervention in select IT-phase patients
High risk of #hepatocellular carcinoma and death in patients with immune-tolerant-phase chronic hepatitis #B
http://gut.bmj.com/content/67/5/945
The clinical outcomes of 413 untreated IT-phase patients with normal alanine aminotransferase (ALT) levels (females, <19 IU/mL; males, <30 IU/mL) were compared with those of 1497 immune-active (IA)-phase patients (ALT ≥80 IU/mL) treated with nucleos(t)ide analogues.
Results The IT group was significantly younger than the IA group (mean age, 38 vs 40 years at baseline, p=0.04). The 10-year estimated cumulative incidences of HCC (12.7% vs 6.1%; p=0.001) and death/transplantation (9.7% vs 3.4%; p<0.001) were significantly higher in the IT group than the IA group. In multivariable analyses, the IT group showed a significantly higher risk of HCC (HR 2.54; 95% CI 1.54 to 4.18) and death/transplantation (HR 3.38; 95% CI 1.85 to 6.16) than the IA group, which was consistently identified through inverse probability treatment weighting, propensity score-matched and competing risks analyses.
Conclusions Untreated IT-phase patients with CHB had higher risks of HCC and death/transplantation than treated IA-phase patients. Unnecessary deaths could be prevented through earlier antiviral intervention in select IT-phase patients
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#Rest-related consolidation protects the fine detail of new #memories
https://www.nature.com/articles/s41598-018-25313-y#Abs1
However, recent research has shown that awake quiescence, too, can support consolidation: people remember more new memories if they quietly rest after encoding than if they engage in a task. It is not yet known how exactly this rest-related consolidation benefits new memories, and whether it affects the fine detail of new memories. Using a sensitive picture recognition task, we show that awake quiescence aids the fine detail of new memories. Young adults were significantly better at discriminating recently encoded target pictures from similar lure pictures when the initial encoding of target pictures had been followed immediately by 10 minutes of awake quiescence than an unrelated perceptual task. This novel finding indicates that, in addition to influencing how much we remember, our behavioural state during wakeful consolidation determines, at least in part, the level of fine detail of our new memories. Thus, our results suggest that rest-related consolidation protects the fine detail of new memories, allowing us to retain detailed memories
#Rest-related consolidation protects the fine detail of new #memories
https://www.nature.com/articles/s41598-018-25313-y#Abs1
However, recent research has shown that awake quiescence, too, can support consolidation: people remember more new memories if they quietly rest after encoding than if they engage in a task. It is not yet known how exactly this rest-related consolidation benefits new memories, and whether it affects the fine detail of new memories. Using a sensitive picture recognition task, we show that awake quiescence aids the fine detail of new memories. Young adults were significantly better at discriminating recently encoded target pictures from similar lure pictures when the initial encoding of target pictures had been followed immediately by 10 minutes of awake quiescence than an unrelated perceptual task. This novel finding indicates that, in addition to influencing how much we remember, our behavioural state during wakeful consolidation determines, at least in part, the level of fine detail of our new memories. Thus, our results suggest that rest-related consolidation protects the fine detail of new memories, allowing us to retain detailed memories
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Management of Type 1 #Diabetes With a Very Low–Carbohydrate #Diet
http://pediatrics.aappublications.org/content/early/2018/05/03/peds.2017-3349
Of 316 respondents, 131 (42%) were parents of children with T1DM, and 57% were of female sex. Suggestive evidence of T1DM (based on a 3-tier scoring system in which researchers took into consideration age and weight at diagnosis, pancreatic autoimmunity, insulin requirement, and clinical presentation) was obtained for 273 (86%) respondents. The mean age at diagnosis was 16 ± 14 years, the duration of diabetes was 11 ± 13 years, and the time following a VLCD was 2.2 ± 3.9 years. Participants had a mean daily carbohydrate intake of 36 ± 15 g. Reported mean HbA1c was 5.67% ± 0.66%. Only 7 (2%) respondents reported diabetes-related hospitalizations in the past year, including 4 (1%) for ketoacidosis and 2 (1%) for hypoglycemia.
CONCLUSIONS: Exceptional glycemic control of T1DM with low rates of adverse events was reported by a community of children and adults who consume a VLCD. The generalizability of these findings requires further studies, including high-quality randomized controlled trials.
Management of Type 1 #Diabetes With a Very Low–Carbohydrate #Diet
http://pediatrics.aappublications.org/content/early/2018/05/03/peds.2017-3349
Of 316 respondents, 131 (42%) were parents of children with T1DM, and 57% were of female sex. Suggestive evidence of T1DM (based on a 3-tier scoring system in which researchers took into consideration age and weight at diagnosis, pancreatic autoimmunity, insulin requirement, and clinical presentation) was obtained for 273 (86%) respondents. The mean age at diagnosis was 16 ± 14 years, the duration of diabetes was 11 ± 13 years, and the time following a VLCD was 2.2 ± 3.9 years. Participants had a mean daily carbohydrate intake of 36 ± 15 g. Reported mean HbA1c was 5.67% ± 0.66%. Only 7 (2%) respondents reported diabetes-related hospitalizations in the past year, including 4 (1%) for ketoacidosis and 2 (1%) for hypoglycemia.
CONCLUSIONS: Exceptional glycemic control of T1DM with low rates of adverse events was reported by a community of children and adults who consume a VLCD. The generalizability of these findings requires further studies, including high-quality randomized controlled trials.
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Acute Effect of #Alcohol Intake on Cardiovascular Autonomic Regulation During the First Hours of #Sleep in a Large Real-World Sample of Finnish Employees: Observational Study
http://mental.jmir.org/2018/1/e23/
Alcohol intake was dose-dependently associated with increased sympathetic regulation, decreased parasympathetic regulation, and insufficient recovery. In addition to moderate and high alcohol doses, the intraindividual effects of alcohol intake on the ANS regulation were observed also with low alcohol intake (all P<.001). For example, HRV-derived physiological recovery state decreased on average by 9.3, 24.0, and 39.2 percentage units with low, moderate, and high alcohol intake, respectively. The effects of alcohol in suppressing recovery were similar for both genders and for physically active and sedentary subjects but stronger among young than older subjects and for participants with lower baseline sleep HR than with higher baseline sleep HR.
Conclusions: Alcohol intake disturbs cardiovascular relaxation during sleep in a dose-dependent manner in both genders. Regular PA or young age do not protect from these effects of alcohol. In health promotion, wearable HR monitoring and HRV-based analysis of recovery might be used to demonstrate the effects of alcohol on sleep on an individual level.
Acute Effect of #Alcohol Intake on Cardiovascular Autonomic Regulation During the First Hours of #Sleep in a Large Real-World Sample of Finnish Employees: Observational Study
http://mental.jmir.org/2018/1/e23/
Alcohol intake was dose-dependently associated with increased sympathetic regulation, decreased parasympathetic regulation, and insufficient recovery. In addition to moderate and high alcohol doses, the intraindividual effects of alcohol intake on the ANS regulation were observed also with low alcohol intake (all P<.001). For example, HRV-derived physiological recovery state decreased on average by 9.3, 24.0, and 39.2 percentage units with low, moderate, and high alcohol intake, respectively. The effects of alcohol in suppressing recovery were similar for both genders and for physically active and sedentary subjects but stronger among young than older subjects and for participants with lower baseline sleep HR than with higher baseline sleep HR.
Conclusions: Alcohol intake disturbs cardiovascular relaxation during sleep in a dose-dependent manner in both genders. Regular PA or young age do not protect from these effects of alcohol. In health promotion, wearable HR monitoring and HRV-based analysis of recovery might be used to demonstrate the effects of alcohol on sleep on an individual level.
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Association of Mild Traumatic #Brain Injury With and Without Loss of Consciousness With #Dementia in US Military Veterans
https://jamanetwork.com/journals/jamaneurology/fullarticle/2679879
The study included 178 779 patients diagnosed with a TBI in the Veterans Health Administration health care system and 178 779 patients in a propensity-matched comparison group. Veterans had a mean (SD) age of nearly 49.5 (18.2) years at baseline; 33 250 (9.3%) were women, and 259 136 (72.5%) were non-Hispanic white individuals. Differences between veterans with and without TBI were small. A total of 4698 veterans (2.6%) without TBI developed dementia compared with 10 835 (6.1%) of those with TBI. After adjustment for demographics and medical and psychiatric comobidities, adjusted hazard ratios for dementia were 2.36 (95% CI, 2.10-2.66) for mild TBI without LOC, 2.51 (95% CI, 2.29-2.76) for mild TBI with LOC, 3.19 (95% CI, 3.05-3.33) for mild TBI with LOC status unknown, and 3.77 (95% CI, 3.63-3.91) for moderate to severe TBI.
Conclusions and Relevance In this cohort study of more than 350 000 veterans, even mild TBI without LOC was associated with more than a 2-fold increase in the risk of dementia diagnosis. Studies of strategies to determine mechanisms, prevention, and treatment of TBI-related dementia in veterans are urgently needed
Association of Mild Traumatic #Brain Injury With and Without Loss of Consciousness With #Dementia in US Military Veterans
https://jamanetwork.com/journals/jamaneurology/fullarticle/2679879
The study included 178 779 patients diagnosed with a TBI in the Veterans Health Administration health care system and 178 779 patients in a propensity-matched comparison group. Veterans had a mean (SD) age of nearly 49.5 (18.2) years at baseline; 33 250 (9.3%) were women, and 259 136 (72.5%) were non-Hispanic white individuals. Differences between veterans with and without TBI were small. A total of 4698 veterans (2.6%) without TBI developed dementia compared with 10 835 (6.1%) of those with TBI. After adjustment for demographics and medical and psychiatric comobidities, adjusted hazard ratios for dementia were 2.36 (95% CI, 2.10-2.66) for mild TBI without LOC, 2.51 (95% CI, 2.29-2.76) for mild TBI with LOC, 3.19 (95% CI, 3.05-3.33) for mild TBI with LOC status unknown, and 3.77 (95% CI, 3.63-3.91) for moderate to severe TBI.
Conclusions and Relevance In this cohort study of more than 350 000 veterans, even mild TBI without LOC was associated with more than a 2-fold increase in the risk of dementia diagnosis. Studies of strategies to determine mechanisms, prevention, and treatment of TBI-related dementia in veterans are urgently needed
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The Intensive Care Unit (ICU) course and outcome in Acute-on-chronic #liver #failure are comparable to other populations
https://www.journal-of-hepatology.eu/article/S0168-8278(18)32043-9/fulltext?mobileUi=0
The outcome of ACLF, when compared to septic or medical ICU patients, matched for baseline parameters of illness severity, was similar regarding length of ICU stay, development of new infections, organ failure and septic shock. ICU, hospital and 90-day mortality were similar between the groups. C-reactive protein and platelet levels were lower in ACLF throughout the first week. Cytokines on day 1 including IL-10, IL-1β, IL-6, and IL-8 were similarly elevated in ACLF and septic ICU patients. TNF-α levels were however higher in ACLF.
Conclusion
ACLF patients admitted to the ICU showed comparable clinical and ICU outcomes compared to ICU patients without chronic liver disease with similar baseline severity of illness characteristics. This suggests that ICU admission criteria should not be different in ACLF compared to other populations.
The Intensive Care Unit (ICU) course and outcome in Acute-on-chronic #liver #failure are comparable to other populations
https://www.journal-of-hepatology.eu/article/S0168-8278(18)32043-9/fulltext?mobileUi=0
The outcome of ACLF, when compared to septic or medical ICU patients, matched for baseline parameters of illness severity, was similar regarding length of ICU stay, development of new infections, organ failure and septic shock. ICU, hospital and 90-day mortality were similar between the groups. C-reactive protein and platelet levels were lower in ACLF throughout the first week. Cytokines on day 1 including IL-10, IL-1β, IL-6, and IL-8 were similarly elevated in ACLF and septic ICU patients. TNF-α levels were however higher in ACLF.
Conclusion
ACLF patients admitted to the ICU showed comparable clinical and ICU outcomes compared to ICU patients without chronic liver disease with similar baseline severity of illness characteristics. This suggests that ICU admission criteria should not be different in ACLF compared to other populations.
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Quantitative Analysis of the Benefits and Risk of #Thyroid #Nodule Evaluation in Patients ≥70 Years Old
https://www.liebertpub.com/doi/10.1089/thy.2017.0655
A total of 1129 patients ≥70 years old with 2527 nodules ≥1 cm were evaluated. FNA was safe in all, and cytology proved benign in 67.3% of patients. However, FNA led to surgery in 208 patients, of whom 93 (44.7%) had benign histopathology. Among all patients who underwent FNA, only 17 (1.5%) SRTC were identified, all of which were preoperatively identifiable by imaging and/or cytology. These SRTC were responsible for all (n = 10; 0.9%) thyroid cancer deaths. Among all other patients (n = 1112), 160 deaths (14.4%) were confirmed during a median follow-up of four years. None of these were thyroid cancer related. Survival analysis for these 1112 patients demonstrated that a separate non-thyroidal malignancy or coronary artery disease at the time of nodule evaluation was associated with increased mortality compared to those without these diagnoses (hazard ratio = 2.32 confidence interval 1.66–3.26; p < 0.01), confirming these are important variables to identify prior to thyroid nodule evaluation.
Conclusions: For patients ≥70 years old, US and FNA are safe and prove helpful in identifying SRTC and benign cytology. However, the surgical management of patients ≥70 years old presenting without high-risk findings should be tempered, especially when comorbid illness is identified
Quantitative Analysis of the Benefits and Risk of #Thyroid #Nodule Evaluation in Patients ≥70 Years Old
https://www.liebertpub.com/doi/10.1089/thy.2017.0655
A total of 1129 patients ≥70 years old with 2527 nodules ≥1 cm were evaluated. FNA was safe in all, and cytology proved benign in 67.3% of patients. However, FNA led to surgery in 208 patients, of whom 93 (44.7%) had benign histopathology. Among all patients who underwent FNA, only 17 (1.5%) SRTC were identified, all of which were preoperatively identifiable by imaging and/or cytology. These SRTC were responsible for all (n = 10; 0.9%) thyroid cancer deaths. Among all other patients (n = 1112), 160 deaths (14.4%) were confirmed during a median follow-up of four years. None of these were thyroid cancer related. Survival analysis for these 1112 patients demonstrated that a separate non-thyroidal malignancy or coronary artery disease at the time of nodule evaluation was associated with increased mortality compared to those without these diagnoses (hazard ratio = 2.32 confidence interval 1.66–3.26; p < 0.01), confirming these are important variables to identify prior to thyroid nodule evaluation.
Conclusions: For patients ≥70 years old, US and FNA are safe and prove helpful in identifying SRTC and benign cytology. However, the surgical management of patients ≥70 years old presenting without high-risk findings should be tempered, especially when comorbid illness is identified
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B-Type Natriuretic Peptide Levels and #Mortality in Patients With and Without Heart Failure
http://www.onlinejacc.org/content/71/19/2079?sso=1&sso_redirect_count=1&access_token=
#BNP levels were lower in patients without HF (median 89 pg/ml; interquartile range: 34 to 238 pg/ml) compared with those with HF (median 388 pg/ml; interquartile range: 150 to 940 pg/ml) (p < 0.0001). Over 90,898 person-years of follow-up, 5,903 patients without HF (31%) and 6,181 patients with HF (53%) died. In multivariate models including demographic and clinical characteristics, BNP and age were the strongest predictors of death in both patients with and those without HF. In acute care settings and even among outpatients with modestly elevated BNP, the risk for death according to BNP was similar between patients with and those without HF. For instance, a BNP level of 400 pg/ml was associated with a 3-year risk for death of 21% (95% confidence interval: 20% to 23%) and 19% (95% confidence interval: 17% to 20%) in patients with and those without HF, respectively.
Conclusions Among patients without HF, plasma BNP level is a stronger predictor of death than traditional risk factors. The risk for death associated with any given BNP level is similar between patients with and those without HF, particularly in the acute care setting
B-Type Natriuretic Peptide Levels and #Mortality in Patients With and Without Heart Failure
http://www.onlinejacc.org/content/71/19/2079?sso=1&sso_redirect_count=1&access_token=
#BNP levels were lower in patients without HF (median 89 pg/ml; interquartile range: 34 to 238 pg/ml) compared with those with HF (median 388 pg/ml; interquartile range: 150 to 940 pg/ml) (p < 0.0001). Over 90,898 person-years of follow-up, 5,903 patients without HF (31%) and 6,181 patients with HF (53%) died. In multivariate models including demographic and clinical characteristics, BNP and age were the strongest predictors of death in both patients with and those without HF. In acute care settings and even among outpatients with modestly elevated BNP, the risk for death according to BNP was similar between patients with and those without HF. For instance, a BNP level of 400 pg/ml was associated with a 3-year risk for death of 21% (95% confidence interval: 20% to 23%) and 19% (95% confidence interval: 17% to 20%) in patients with and those without HF, respectively.
Conclusions Among patients without HF, plasma BNP level is a stronger predictor of death than traditional risk factors. The risk for death associated with any given BNP level is similar between patients with and those without HF, particularly in the acute care setting