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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
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Once-Daily Single-Inhaler #Triple versus Dual Therapy in Patients with #COPD
https://www.nejm.org/doi/full/10.1056/NEJMoa1713901?query=featured_home
The rate of moderate or severe exacerbations in the triple-therapy group was 0.91 per year, as compared with 1.07 per year in the fluticasone furoate–vilanterol group (rate ratio with triple therapy, 0.85; 95% confidence interval CI, 0.80 to 0.90; 15% difference; P<0.001) and 1.21 per year in the umeclidinium–vilanterol group (rate ratio with triple therapy, 0.75; 95% CI, 0.70 to 0.81; 25% difference; P<0.001). The annual rate of severe exacerbations resulting in hospitalization in the triple-therapy group was 0.13, as compared with 0.19 in the umeclidinium–vilanterol group (rate ratio, 0.66; 95% CI, 0.56 to 0.78; 34% difference; P<0.001). There was a higher incidence of pneumonia in the inhaled-glucocorticoid groups than in the umeclidinium–vilanterol group, and the risk of clinician-diagnosed pneumonia was significantly higher with triple therapy than with umeclidinium–vilanterol, as assessed in a time-to-first-event analysis (hazard ratio, 1.53; 95% CI, 1.22 to 1.92; P<0.001).
CONCLUSIONS
Triple therapy with fluticasone furoate, umeclidinium, and vilanterol resulted in a lower rate of moderate or severe COPD exacerbations than fluticasone furoate–vilanterol or umeclidinium–vilanterol in this population. Triple therapy also resulted in a lower rate of hospitalization due to COPD than umeclidinium–vilanterol.
Once-Daily Single-Inhaler #Triple versus Dual Therapy in Patients with #COPD
https://www.nejm.org/doi/full/10.1056/NEJMoa1713901?query=featured_home
The rate of moderate or severe exacerbations in the triple-therapy group was 0.91 per year, as compared with 1.07 per year in the fluticasone furoate–vilanterol group (rate ratio with triple therapy, 0.85; 95% confidence interval CI, 0.80 to 0.90; 15% difference; P<0.001) and 1.21 per year in the umeclidinium–vilanterol group (rate ratio with triple therapy, 0.75; 95% CI, 0.70 to 0.81; 25% difference; P<0.001). The annual rate of severe exacerbations resulting in hospitalization in the triple-therapy group was 0.13, as compared with 0.19 in the umeclidinium–vilanterol group (rate ratio, 0.66; 95% CI, 0.56 to 0.78; 34% difference; P<0.001). There was a higher incidence of pneumonia in the inhaled-glucocorticoid groups than in the umeclidinium–vilanterol group, and the risk of clinician-diagnosed pneumonia was significantly higher with triple therapy than with umeclidinium–vilanterol, as assessed in a time-to-first-event analysis (hazard ratio, 1.53; 95% CI, 1.22 to 1.92; P<0.001).
CONCLUSIONS
Triple therapy with fluticasone furoate, umeclidinium, and vilanterol resulted in a lower rate of moderate or severe COPD exacerbations than fluticasone furoate–vilanterol or umeclidinium–vilanterol in this population. Triple therapy also resulted in a lower rate of hospitalization due to COPD than umeclidinium–vilanterol.
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Association of Efficacy of Resistance #Exercise Training With #Depressive Symptoms
Meta-analysis and Meta-regression Analysis of Randomized Clinical Trials
https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2680311?redirect=true
The number needed to treat was 4. Total volume of prescribed RET, participant health status, and strength improvements were not significantly associated with the antidepressant effect of RET. However, smaller reductions in depressive symptoms were derived from randomized clinical trials with blinded allocation and/or assessment.
Conclusions and Relevance Resistance exercise training significantly reduced depressive symptoms among adults regardless of health status, total prescribed volume of RET, or significant improvements in strength. Better-quality randomized clinical trials blinding both allocation and assessment and comparing RET with other empirically supported treatments for depressive symptoms are needed
Association of Efficacy of Resistance #Exercise Training With #Depressive Symptoms
Meta-analysis and Meta-regression Analysis of Randomized Clinical Trials
https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2680311?redirect=true
The number needed to treat was 4. Total volume of prescribed RET, participant health status, and strength improvements were not significantly associated with the antidepressant effect of RET. However, smaller reductions in depressive symptoms were derived from randomized clinical trials with blinded allocation and/or assessment.
Conclusions and Relevance Resistance exercise training significantly reduced depressive symptoms among adults regardless of health status, total prescribed volume of RET, or significant improvements in strength. Better-quality randomized clinical trials blinding both allocation and assessment and comparing RET with other empirically supported treatments for depressive symptoms are needed
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Effect of Coaching to Increase #Water Intake on Kidney Function Decline in Adults With Chronic #Kidney Disease
The CKD WIT Randomized Clinical Trial
https://jamanetwork.com/journals/jama/fullarticle/2680548
Of 631 randomized patients (mean age, 65.0 years; men, 63.4%; mean eGFR, 43 mL/min/1.73 m2; median urine albumin, 123 mg/d), 12 died (hydration group n = 5; control group n = 7). Among 590 survivors with 1-year follow-up measurements (95% of 619), the mean change in 24-hour urine volume was 0.6 L per day higher in the hydration group (95% CI, 0.5 to 0.7; P < .001). The mean change in eGFR was −2.2 mL/min/1.73 m2 in the hydration group and −1.9 mL/min/1.73 m2 in the control group (adjusted between-group difference, −0.3 mL/min/1.73 m2 95% CI, −1.8 to 1.2; P = .74). The mean between-group differences (hydration vs control) in secondary outcomes were as follows: plasma copeptin, −2.2 pmol/L (95% CI, −3.9 to −0.5; P = .01); creatinine clearance, 3.6 mL/min/1.73 m2 (95% CI, 0.8 to 6.4; P = .01); urine albumin, 7 mg per day (95% CI, −4 to 51; P = .11); and quality of health, 0.2 points (95% CI, −0.3 to 0.3; P = .22).
Conclusions and Relevance Among adults with chronic kidney disease, coaching to increase water intake compared with coaching to maintain the same water intake did not significantly slow the decline in kidney function after 1 year. However, the study may have been underpowered to detect a clinically important difference
Effect of Coaching to Increase #Water Intake on Kidney Function Decline in Adults With Chronic #Kidney Disease
The CKD WIT Randomized Clinical Trial
https://jamanetwork.com/journals/jama/fullarticle/2680548
Of 631 randomized patients (mean age, 65.0 years; men, 63.4%; mean eGFR, 43 mL/min/1.73 m2; median urine albumin, 123 mg/d), 12 died (hydration group n = 5; control group n = 7). Among 590 survivors with 1-year follow-up measurements (95% of 619), the mean change in 24-hour urine volume was 0.6 L per day higher in the hydration group (95% CI, 0.5 to 0.7; P < .001). The mean change in eGFR was −2.2 mL/min/1.73 m2 in the hydration group and −1.9 mL/min/1.73 m2 in the control group (adjusted between-group difference, −0.3 mL/min/1.73 m2 95% CI, −1.8 to 1.2; P = .74). The mean between-group differences (hydration vs control) in secondary outcomes were as follows: plasma copeptin, −2.2 pmol/L (95% CI, −3.9 to −0.5; P = .01); creatinine clearance, 3.6 mL/min/1.73 m2 (95% CI, 0.8 to 6.4; P = .01); urine albumin, 7 mg per day (95% CI, −4 to 51; P = .11); and quality of health, 0.2 points (95% CI, −0.3 to 0.3; P = .22).
Conclusions and Relevance Among adults with chronic kidney disease, coaching to increase water intake compared with coaching to maintain the same water intake did not significantly slow the decline in kidney function after 1 year. However, the study may have been underpowered to detect a clinically important difference
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#Vertebroplasty versus sham procedure for painful acute osteoporotic vertebral compression #fractures (VERTOS IV): randomised sham controlled clinical trial
https://www.bmj.com/content/361/bmj.k1551
The mean reduction in VAS score was statistically significant in the vertebroplasty and sham procedure groups at all follow-up points after the procedure compared with baseline. The mean difference in VAS scores between groups was 0.20 (95% confidence interval −0.53 to 0.94) at baseline, −0.43 (−1.17 to 0.31) at one day, −0.11 (−0.85 to 0.63) at one week, 0.41 (−0.33 to 1.15) at one month, 0.21 (−0.54 to 0.96) at three months, 0.39 (−0.37 to 1.15) at six months, and 0.45 (−0.37 to 1.24) at 12 months. These changes in VAS scores did not, however, differ statistically significantly between the groups during 12 months’ follow-up. The results for secondary outcomes were not statistically significant. Use of analgesics (non-opioids, weak opioids, strong opioids) decreased statistically significantly in both groups at all time points, with no statistically significant differences between groups. Two adverse events occurred in the vertebroplasty group: one respiratory insufficiency and one vasovagal reaction.
Conclusions Percutaneous vertebroplasty did not result in statistically significantly greater pain relief than a sham procedure during 12 months’ follow-up among patients with acute osteoporotic vertebral compression fractures
#Vertebroplasty versus sham procedure for painful acute osteoporotic vertebral compression #fractures (VERTOS IV): randomised sham controlled clinical trial
https://www.bmj.com/content/361/bmj.k1551
The mean reduction in VAS score was statistically significant in the vertebroplasty and sham procedure groups at all follow-up points after the procedure compared with baseline. The mean difference in VAS scores between groups was 0.20 (95% confidence interval −0.53 to 0.94) at baseline, −0.43 (−1.17 to 0.31) at one day, −0.11 (−0.85 to 0.63) at one week, 0.41 (−0.33 to 1.15) at one month, 0.21 (−0.54 to 0.96) at three months, 0.39 (−0.37 to 1.15) at six months, and 0.45 (−0.37 to 1.24) at 12 months. These changes in VAS scores did not, however, differ statistically significantly between the groups during 12 months’ follow-up. The results for secondary outcomes were not statistically significant. Use of analgesics (non-opioids, weak opioids, strong opioids) decreased statistically significantly in both groups at all time points, with no statistically significant differences between groups. Two adverse events occurred in the vertebroplasty group: one respiratory insufficiency and one vasovagal reaction.
Conclusions Percutaneous vertebroplasty did not result in statistically significantly greater pain relief than a sham procedure during 12 months’ follow-up among patients with acute osteoporotic vertebral compression fractures
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Oral #Antibiotic Exposure and Kidney #Stone Disease
http://m.jasn.asnjournals.org/content/early/2018/05/09/ASN.2017111213
Exposure to any of five different antibiotic classes 3–12 months before index date was associated with nephrolithiasis. The adjusted odds ratio (95% confidence interval) was 2.33 (2.19 to 2.48) for sulfas, 1.88 (1.75 to 2.01) for cephalosporins, 1.67 (1.54 to 1.81) for fluoroquinolones, 1.70 (1.55 to 1.88) for nitrofurantoin/methenamine, and 1.27 (1.18 to 1.36) for broad-spectrum penicillins. In exploratory analyses, the magnitude of associations was greatest for exposure at younger ages (P<0.001) and 3–6 months before index date (P<0.001), with all but broad-spectrum penicillins remaining statistically significant 3–5 years from exposure.
Conclusions Oral antibiotics associated with increased odds of nephrolithiasis, with the greatest odds for recent exposure and exposure at younger age. These results have implications for disease pathogenesis and the rising incidence of nephrolithiasis, particularly among children
Oral #Antibiotic Exposure and Kidney #Stone Disease
http://m.jasn.asnjournals.org/content/early/2018/05/09/ASN.2017111213
Exposure to any of five different antibiotic classes 3–12 months before index date was associated with nephrolithiasis. The adjusted odds ratio (95% confidence interval) was 2.33 (2.19 to 2.48) for sulfas, 1.88 (1.75 to 2.01) for cephalosporins, 1.67 (1.54 to 1.81) for fluoroquinolones, 1.70 (1.55 to 1.88) for nitrofurantoin/methenamine, and 1.27 (1.18 to 1.36) for broad-spectrum penicillins. In exploratory analyses, the magnitude of associations was greatest for exposure at younger ages (P<0.001) and 3–6 months before index date (P<0.001), with all but broad-spectrum penicillins remaining statistically significant 3–5 years from exposure.
Conclusions Oral antibiotics associated with increased odds of nephrolithiasis, with the greatest odds for recent exposure and exposure at younger age. These results have implications for disease pathogenesis and the rising incidence of nephrolithiasis, particularly among children
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Global statistics on #alcohol , #tobacco and illicit drug use: 2017 status report
https://onlinelibrary.wiley.com/doi/abs/10.1111/add.14234
European regions had the highest prevalence of heavy episodic alcohol use and daily tobacco use. The age‐standardised prevalence of alcohol dependence was 843.2 per 100,000 people; for cannabis, opioids, amphetamines and cocaine dependence it was 259.3, 220.4, 86.0 and 52.5 per 100,000 people, respectively. High‐Income North America region had among the highest rates of cannabis, opioid, and cocaine dependence. Attributable disability‐adjusted life‐years (DALYs) were highest for tobacco (170.9 million DALYs), followed by alcohol (85.0 million) and illicit drugs (27.8 million). Substance‐attributable mortality rates were highest for tobacco (110.7 deaths per 100,000 people), followed by alcohol and illicit drugs (33.0, and 6.9 deaths per 100,000 people, respectively). Attributable age‐standardised mortality rates and DALYs for alcohol and illicit drugs were highest in Eastern Europe; attributable age‐standardised tobacco mortality rates and DALYs were highest in Oceania.
Conclusions
In 2015 alcohol and tobacco use between them cost the human population more than a quarter of a billion disability‐adjusted life years, with illicit drugs costing a further tens of millions. Europeans proportionately suffered more but in absolute terms the mortality rate was greatest in low and middle income countries with large populations and where the quality of data was more limited. Better standardised and rigorous methods for data collection, collation and reporting are needed to assess more accurately the geographical and temporal trends in substance use and its disease burden
Global statistics on #alcohol , #tobacco and illicit drug use: 2017 status report
https://onlinelibrary.wiley.com/doi/abs/10.1111/add.14234
European regions had the highest prevalence of heavy episodic alcohol use and daily tobacco use. The age‐standardised prevalence of alcohol dependence was 843.2 per 100,000 people; for cannabis, opioids, amphetamines and cocaine dependence it was 259.3, 220.4, 86.0 and 52.5 per 100,000 people, respectively. High‐Income North America region had among the highest rates of cannabis, opioid, and cocaine dependence. Attributable disability‐adjusted life‐years (DALYs) were highest for tobacco (170.9 million DALYs), followed by alcohol (85.0 million) and illicit drugs (27.8 million). Substance‐attributable mortality rates were highest for tobacco (110.7 deaths per 100,000 people), followed by alcohol and illicit drugs (33.0, and 6.9 deaths per 100,000 people, respectively). Attributable age‐standardised mortality rates and DALYs for alcohol and illicit drugs were highest in Eastern Europe; attributable age‐standardised tobacco mortality rates and DALYs were highest in Oceania.
Conclusions
In 2015 alcohol and tobacco use between them cost the human population more than a quarter of a billion disability‐adjusted life years, with illicit drugs costing a further tens of millions. Europeans proportionately suffered more but in absolute terms the mortality rate was greatest in low and middle income countries with large populations and where the quality of data was more limited. Better standardised and rigorous methods for data collection, collation and reporting are needed to assess more accurately the geographical and temporal trends in substance use and its disease burden
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Risk of #stroke and transient ischaemic attack in patients with a diagnosis of resolved atrial #fibrillation: retrospective cohort studies
https://www.bmj.com/content/361/bmj.k1717
Adjusted incidence rate ratios for stroke or TIA in patients with resolved atrial fibrillation were 0.76 (95% confidence interval 0.67 to 0.85, P<0.001) versus controls with atrial fibrillation and 1.63 (1.46 to 1.83, P<0.001) versus controls without atrial fibrillation. Adjusted incidence rate ratios for mortality in patients with resolved atrial fibrillation were 0.60 (0.56 to 0.65, P<0.001) versus controls with atrial fibrillation and 1.13 (1.06 to 1.21, P<0.001) versus controls without atrial fibrillation. When patients with resolved atrial fibrillation and documented recurrent atrial fibrillation were excluded the adjusted incidence rate ratio for stroke or TIA was 1.45 (1.26 to 1.67, P<0.001) versus controls without atrial fibrillation.
Conclusion Patients with resolved atrial fibrillation remain at higher risk of stroke or TIA than patients without atrial fibrillation. The risk is increased even in those in whom recurrent atrial fibrillation is not documented. Guidelines should be updated to advocate continued use of anticoagulants in patients with resolved atrial fibrillation
Risk of #stroke and transient ischaemic attack in patients with a diagnosis of resolved atrial #fibrillation: retrospective cohort studies
https://www.bmj.com/content/361/bmj.k1717
Adjusted incidence rate ratios for stroke or TIA in patients with resolved atrial fibrillation were 0.76 (95% confidence interval 0.67 to 0.85, P<0.001) versus controls with atrial fibrillation and 1.63 (1.46 to 1.83, P<0.001) versus controls without atrial fibrillation. Adjusted incidence rate ratios for mortality in patients with resolved atrial fibrillation were 0.60 (0.56 to 0.65, P<0.001) versus controls with atrial fibrillation and 1.13 (1.06 to 1.21, P<0.001) versus controls without atrial fibrillation. When patients with resolved atrial fibrillation and documented recurrent atrial fibrillation were excluded the adjusted incidence rate ratio for stroke or TIA was 1.45 (1.26 to 1.67, P<0.001) versus controls without atrial fibrillation.
Conclusion Patients with resolved atrial fibrillation remain at higher risk of stroke or TIA than patients without atrial fibrillation. The risk is increased even in those in whom recurrent atrial fibrillation is not documented. Guidelines should be updated to advocate continued use of anticoagulants in patients with resolved atrial fibrillation
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#Cognitive Aging and Long-Term Maintenance of Attentional Improvements Following #Meditation Training
https://link.springer.com/article/10.1007/s41465-018-0068-1
we examined attentional performance on a sustained response inhibition task before, during, and after 3-months of full-time meditation. We now extend this prior investigation across additional follow-up assessments occurring up to 7 years after the conclusion of training. Performance improvements observed during periods of intensive practice were partially maintained several years later. Importantly, aging-related decrements in measures of response inhibition accuracy and reaction time variability were moderated by levels of continued meditation practice across the follow-up period. The present study is the first to offer evidence that intensive and continued meditation practice is associated with enduring improvements in sustained attention and response inhibition, with the potential to alter longitudinal trajectories of cognitive change across the lifespan.
#Cognitive Aging and Long-Term Maintenance of Attentional Improvements Following #Meditation Training
https://link.springer.com/article/10.1007/s41465-018-0068-1
we examined attentional performance on a sustained response inhibition task before, during, and after 3-months of full-time meditation. We now extend this prior investigation across additional follow-up assessments occurring up to 7 years after the conclusion of training. Performance improvements observed during periods of intensive practice were partially maintained several years later. Importantly, aging-related decrements in measures of response inhibition accuracy and reaction time variability were moderated by levels of continued meditation practice across the follow-up period. The present study is the first to offer evidence that intensive and continued meditation practice is associated with enduring improvements in sustained attention and response inhibition, with the potential to alter longitudinal trajectories of cognitive change across the lifespan.
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Is #psychosis a #multisystem disorder? A meta-review of central nervous system, immune, cardiometabolic, and endocrine alterations in first-episode psychosis and perspective on potential models
https://www.nature.com/articles/s41380-018-0058-9
For people with first episode psychosis compared with healthy controls, we observed alterations in immune parameters (summary effect size: g = 1.19), cardiometabolic parameters (g = 0.23); HPA parameters (g = 0.68); brain structure (g = 0.40); neurophysiology (g = 0.80); and neurochemistry (g = 0.43). Grouping non-CNS organ systems together provided an effect size for overall non-CNS alterations in patients compared with controls (g = 0.58), which was not significantly different from the overall CNS alterations effect size (g = 0.50). However, the summary effect size for immune alterations was significantly greater than that for brain structural (P < 0.001) and neurochemical alterations (P < 0.001), while the summary effect size for cardiometabolic alterations was significantly lower than neurochemical (P = 0.04), neurophysiological (P < 0.001), and brain structural alterations (P = 0.001). The summary effect size for HPA alterations was not significantly different from brain structural (P = 0.14), neurophysiological (P = 0.54), or neurochemical alterations (P = 0.22). These outcomes remained similar in antipsychotic naive sensitivity analyses.
We found some, but limited and inconsistent, evidence that non-CNS alterations were associated with CNS changes and symptoms in first episode psychosis. Our findings indicate that there are robust alterations in non-CNS systems in psychosis, and that these are broadly similar in magnitude to a range of CNS alterations.
We consider models that could account for these findings and discuss implications for future research and treatment
Is #psychosis a #multisystem disorder? A meta-review of central nervous system, immune, cardiometabolic, and endocrine alterations in first-episode psychosis and perspective on potential models
https://www.nature.com/articles/s41380-018-0058-9
For people with first episode psychosis compared with healthy controls, we observed alterations in immune parameters (summary effect size: g = 1.19), cardiometabolic parameters (g = 0.23); HPA parameters (g = 0.68); brain structure (g = 0.40); neurophysiology (g = 0.80); and neurochemistry (g = 0.43). Grouping non-CNS organ systems together provided an effect size for overall non-CNS alterations in patients compared with controls (g = 0.58), which was not significantly different from the overall CNS alterations effect size (g = 0.50). However, the summary effect size for immune alterations was significantly greater than that for brain structural (P < 0.001) and neurochemical alterations (P < 0.001), while the summary effect size for cardiometabolic alterations was significantly lower than neurochemical (P = 0.04), neurophysiological (P < 0.001), and brain structural alterations (P = 0.001). The summary effect size for HPA alterations was not significantly different from brain structural (P = 0.14), neurophysiological (P = 0.54), or neurochemical alterations (P = 0.22). These outcomes remained similar in antipsychotic naive sensitivity analyses.
We found some, but limited and inconsistent, evidence that non-CNS alterations were associated with CNS changes and symptoms in first episode psychosis. Our findings indicate that there are robust alterations in non-CNS systems in psychosis, and that these are broadly similar in magnitude to a range of CNS alterations.
We consider models that could account for these findings and discuss implications for future research and treatment
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Improving Prediction of #Dementia in Primary Care
http://www.annfammed.org/content/16/3/206
The Mini-Mental State Examination (MMSE) is one of the most widely used instruments to screen for cognitive deficits; however, this instrument alone is not sensitive enough to detect early symptoms of dementia. We aimed to investigate whether additionally using the Visual Association Test (VAT) improves the predictive value of the MMSE score for development of dementia
Patients having a decline of 2 points or more in total MMSE score over 2 years had an odds ratio of 3.55 (95% CI, 2.51–5.00) for developing dementia. Patients having the same decline in MMSE score plus an imperfect VAT score had an odds ratio of 9.55 (95% CI, 5.89–15.41) for developing dementia. A 1-point decline in MMSE score increased odds of dementia only when the VAT score was imperfect. Dementia risk for patients with a 2- or 3-point decrease in MMSE score and a perfect VAT score did not differ significantly from the average risk of the cohort as a whole.
CONCLUSIONS Administering the VAT in patients with a small decline on the MMSE over a 2-year period has substantial incremental value for identifying those at elevated risk for developing dementia. This simple test may help distinguish older adults who need further cognitive examination from those in whom a watchful waiting policy is justified
Improving Prediction of #Dementia in Primary Care
http://www.annfammed.org/content/16/3/206
The Mini-Mental State Examination (MMSE) is one of the most widely used instruments to screen for cognitive deficits; however, this instrument alone is not sensitive enough to detect early symptoms of dementia. We aimed to investigate whether additionally using the Visual Association Test (VAT) improves the predictive value of the MMSE score for development of dementia
Patients having a decline of 2 points or more in total MMSE score over 2 years had an odds ratio of 3.55 (95% CI, 2.51–5.00) for developing dementia. Patients having the same decline in MMSE score plus an imperfect VAT score had an odds ratio of 9.55 (95% CI, 5.89–15.41) for developing dementia. A 1-point decline in MMSE score increased odds of dementia only when the VAT score was imperfect. Dementia risk for patients with a 2- or 3-point decrease in MMSE score and a perfect VAT score did not differ significantly from the average risk of the cohort as a whole.
CONCLUSIONS Administering the VAT in patients with a small decline on the MMSE over a 2-year period has substantial incremental value for identifying those at elevated risk for developing dementia. This simple test may help distinguish older adults who need further cognitive examination from those in whom a watchful waiting policy is justified
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Disruption of neonatal #cardiomyocyte physiology following exposure to #bisphenol-a
https://www.nature.com/articles/s41598-018-25719-8
..A range of doses were tested to mimic environmental exposure (10−9–10−8M), maximum clinical exposure (10−5M), and supraphysiological exposure levels (10−4M). Acute BPA exposure altered cardiomyocyte functionality, resulting in a slowed spontaneous beating rate and increased beat rate variability. BPA exposure also impaired intracellular calcium handling, resulting in diminished calcium transient amplitudes, prolonged calcium transient upstroke and duration time. Alterations in calcium handling also increased the propensity for alternans and skipped beats. Notably, the effect of BPA-treatment on calcium handling was partially reversible.
Our data suggest that acute BPA exposure could precipitate secondary adverse effects on contractile performance and/or electrical alternans, both of which are dependent on intracellular calcium homeostasis.
Disruption of neonatal #cardiomyocyte physiology following exposure to #bisphenol-a
https://www.nature.com/articles/s41598-018-25719-8
..A range of doses were tested to mimic environmental exposure (10−9–10−8M), maximum clinical exposure (10−5M), and supraphysiological exposure levels (10−4M). Acute BPA exposure altered cardiomyocyte functionality, resulting in a slowed spontaneous beating rate and increased beat rate variability. BPA exposure also impaired intracellular calcium handling, resulting in diminished calcium transient amplitudes, prolonged calcium transient upstroke and duration time. Alterations in calcium handling also increased the propensity for alternans and skipped beats. Notably, the effect of BPA-treatment on calcium handling was partially reversible.
Our data suggest that acute BPA exposure could precipitate secondary adverse effects on contractile performance and/or electrical alternans, both of which are dependent on intracellular calcium homeostasis.
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Deprescribing #benzodiazepine receptor agonists
http://www.cfp.ca/content/64/5/339
We recommend that deprescribing (tapering slowly) of BZRAs be offered to elderly adults (≥ 65 years) who take BZRAs, regardless of duration of use, and suggest that deprescribing (tapering slowly) be offered to adults aged 18 to 64 who have used BZRAs for more than 4 weeks. These recommendations apply to patients who use BZRAs to treat insomnia on its own (primary insomnia) or comorbid insomnia where potential underlying comorbidities are effectively managed. This guideline does not apply to those with other sleep disorders or untreated anxiety, depression, or other physical or mental health conditions that might be causing or aggravating insomnia.
Conclusion Benzodiazepine receptor agonists are associated with harms, and therapeutic effects might be short term. Tapering BZRAs improves cessation rates compared with usual care without serious harms. Patients might be more amenable to deprescribing conversations if they understand the rationale (potential for harm), are involved in developing the tapering plan, and are offered behavioural advice. This guideline provides recommendations for making decisions about when and how to reduce and stop BZRAs. Recommendations are meant to assist with, not dictate, decision making in conjunction with patients.
Deprescribing #benzodiazepine receptor agonists
http://www.cfp.ca/content/64/5/339
We recommend that deprescribing (tapering slowly) of BZRAs be offered to elderly adults (≥ 65 years) who take BZRAs, regardless of duration of use, and suggest that deprescribing (tapering slowly) be offered to adults aged 18 to 64 who have used BZRAs for more than 4 weeks. These recommendations apply to patients who use BZRAs to treat insomnia on its own (primary insomnia) or comorbid insomnia where potential underlying comorbidities are effectively managed. This guideline does not apply to those with other sleep disorders or untreated anxiety, depression, or other physical or mental health conditions that might be causing or aggravating insomnia.
Conclusion Benzodiazepine receptor agonists are associated with harms, and therapeutic effects might be short term. Tapering BZRAs improves cessation rates compared with usual care without serious harms. Patients might be more amenable to deprescribing conversations if they understand the rationale (potential for harm), are involved in developing the tapering plan, and are offered behavioural advice. This guideline provides recommendations for making decisions about when and how to reduce and stop BZRAs. Recommendations are meant to assist with, not dictate, decision making in conjunction with patients.