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Update – CDC Recommendations for Managing and Reporting #Shigella Infections with Possible Reduced Susceptibility to #Ciprofloxacin
https://emergency.cdc.gov/han/han00411.asp
..If antibiotic treatment is necessary, monitor patients carefully.
If you identify or receive a report of a patient with Shigella infection and possible fluoroquinolone or #azithromycin treatment failure:
Consider consulting an infectious disease specialist to identify other treatment options, because some Shigella isolates with susceptible ciprofloxacin MICs may harbor one or more quinolone resistance mechanisms.
Contact your local health department to coordinate reporting treatment failure information. This information should be reported to CDC at EntericBacteria@cdc.gov.
Collect a stool specimen for culture, and work with your clinical microbiology laboratory to submit for additional antimicrobial susceptibility testing.
Request that your laboratory expedite submission of the Shigella isolate to your state public health laboratory. Your state laboratory should notify CDC at EntericBacteria@cdc.gov to coordinate additional laboratory testing and/or shipment of the isolate to CDC.
Update – CDC Recommendations for Managing and Reporting #Shigella Infections with Possible Reduced Susceptibility to #Ciprofloxacin
https://emergency.cdc.gov/han/han00411.asp
..If antibiotic treatment is necessary, monitor patients carefully.
If you identify or receive a report of a patient with Shigella infection and possible fluoroquinolone or #azithromycin treatment failure:
Consider consulting an infectious disease specialist to identify other treatment options, because some Shigella isolates with susceptible ciprofloxacin MICs may harbor one or more quinolone resistance mechanisms.
Contact your local health department to coordinate reporting treatment failure information. This information should be reported to CDC at EntericBacteria@cdc.gov.
Collect a stool specimen for culture, and work with your clinical microbiology laboratory to submit for additional antimicrobial susceptibility testing.
Request that your laboratory expedite submission of the Shigella isolate to your state public health laboratory. Your state laboratory should notify CDC at EntericBacteria@cdc.gov to coordinate additional laboratory testing and/or shipment of the isolate to CDC.
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The ##NAD+ Precursor #Nicotinamide Riboside Rescues Mitochondrial Defects and Neuronal Loss in iPSC and Fly Models of #Parkinson’s Disease
https://www.cell.com/cell-reports/fulltext/S2211-1247(18)30742-3
While mitochondrial dysfunction is emerging as key in Parkinson’s disease (PD), a central question remains whether mitochondria are actual disease drivers and whether boosting mitochondrial biogenesis and function ameliorates pathology. We address these questions using patient-derived induced pluripotent stem cells and Drosophila models of GBA-related PD (GBA-PD), the most common PD genetic risk. Patient neurons display stress responses, mitochondrial demise, and changes in NAD+ metabolism. NAD+ precursors have been proposed to ameliorate age-related metabolic decline and disease. We report that increasing NAD+ via the NAD+ precursor nicotinamide riboside (NR) significantly ameliorates mitochondrial function in patient neurons. Human neurons require nicotinamide phosphoribosyltransferase (NAMPT) to maintain the NAD+ pool and utilize NRK1 to synthesize NAD+ from NAD+ precursors. Remarkably, NR prevents the age-related dopaminergic neuronal loss and motor decline in fly models of GBA-PD. Our findings suggest NR as a viable clinical avenue for neuroprotection in PD and other neurodegenerative diseases.
The ##NAD+ Precursor #Nicotinamide Riboside Rescues Mitochondrial Defects and Neuronal Loss in iPSC and Fly Models of #Parkinson’s Disease
https://www.cell.com/cell-reports/fulltext/S2211-1247(18)30742-3
While mitochondrial dysfunction is emerging as key in Parkinson’s disease (PD), a central question remains whether mitochondria are actual disease drivers and whether boosting mitochondrial biogenesis and function ameliorates pathology. We address these questions using patient-derived induced pluripotent stem cells and Drosophila models of GBA-related PD (GBA-PD), the most common PD genetic risk. Patient neurons display stress responses, mitochondrial demise, and changes in NAD+ metabolism. NAD+ precursors have been proposed to ameliorate age-related metabolic decline and disease. We report that increasing NAD+ via the NAD+ precursor nicotinamide riboside (NR) significantly ameliorates mitochondrial function in patient neurons. Human neurons require nicotinamide phosphoribosyltransferase (NAMPT) to maintain the NAD+ pool and utilize NRK1 to synthesize NAD+ from NAD+ precursors. Remarkably, NR prevents the age-related dopaminergic neuronal loss and motor decline in fly models of GBA-PD. Our findings suggest NR as a viable clinical avenue for neuroprotection in PD and other neurodegenerative diseases.
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Association of Viral Suppression With Lower AIDS-Defining and Non–AIDS-Defining #Cancer Incidence in #HIV-Infected Veterans: A Prospective Cohort Study
http://annals.org/aim/article-abstract/2684480/association-viral-suppression-lower-aids-defining-non-aids-defining-cancer
Cancer incidence for HIV-positive versus uninfected persons was highest for unsuppressed persons (RR, 2.35 95% CI, 2.19 to 2.51), lower among persons with early suppression (RR, 1.99 CI, 1.87 to 2.12), and lowest among persons with long-term suppression (RR, 1.52 CI, 1.44 to 1.61). This trend was strongest for ADC (unsuppressed: RR, 22.73 CI, 19.01 to 27.19; early suppression: RR, 9.48 CI, 7.78 to 11.55; long-term suppression: RR, 2.22 CI, 1.69 to 2.93), much weaker for NADC caused by viruses (unsuppressed: RR, 3.82 CI, 3.24 to 4.49; early suppression: RR, 3.42 CI, 2.95 to 3.97; long-term suppression: RR, 3.17 CI, 2.78 to 3.62), and absent for NADC not caused by viruses
Antiretroviral therapy resulting in long-term viral suppression may contribute to cancer prevention, to a greater degree for ADC than for NADC. Patients with long-term viral suppression still had excess cancer risk.
Association of Viral Suppression With Lower AIDS-Defining and Non–AIDS-Defining #Cancer Incidence in #HIV-Infected Veterans: A Prospective Cohort Study
http://annals.org/aim/article-abstract/2684480/association-viral-suppression-lower-aids-defining-non-aids-defining-cancer
Cancer incidence for HIV-positive versus uninfected persons was highest for unsuppressed persons (RR, 2.35 95% CI, 2.19 to 2.51), lower among persons with early suppression (RR, 1.99 CI, 1.87 to 2.12), and lowest among persons with long-term suppression (RR, 1.52 CI, 1.44 to 1.61). This trend was strongest for ADC (unsuppressed: RR, 22.73 CI, 19.01 to 27.19; early suppression: RR, 9.48 CI, 7.78 to 11.55; long-term suppression: RR, 2.22 CI, 1.69 to 2.93), much weaker for NADC caused by viruses (unsuppressed: RR, 3.82 CI, 3.24 to 4.49; early suppression: RR, 3.42 CI, 2.95 to 3.97; long-term suppression: RR, 3.17 CI, 2.78 to 3.62), and absent for NADC not caused by viruses
Antiretroviral therapy resulting in long-term viral suppression may contribute to cancer prevention, to a greater degree for ADC than for NADC. Patients with long-term viral suppression still had excess cancer risk.
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Outbreak of Hepatitis #A Virus (HAV) Infections among Persons Who Use #Drugs and Persons Experiencing #Homelessness
https://emergency.cdc.gov/han/han00412.asp
The Centers for Disease Control and Prevention (CDC) and state health departments are investigating hepatitis A outbreaks in multiple states among persons reporting drug use and/or homelessness and their contacts. This Health Alert Network (HAN) Advisory alerts public health departments, healthcare facilities, and programs providing services to affected populations about these outbreaks of hepatitis A infections and provides guidance to assist in identifying and preventing new infections.
Outbreak of Hepatitis #A Virus (HAV) Infections among Persons Who Use #Drugs and Persons Experiencing #Homelessness
https://emergency.cdc.gov/han/han00412.asp
The Centers for Disease Control and Prevention (CDC) and state health departments are investigating hepatitis A outbreaks in multiple states among persons reporting drug use and/or homelessness and their contacts. This Health Alert Network (HAN) Advisory alerts public health departments, healthcare facilities, and programs providing services to affected populations about these outbreaks of hepatitis A infections and provides guidance to assist in identifying and preventing new infections.
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#Screening for Cardiovascular Disease Risk With #Electrocardiography
US Preventive Services Task Force Recommendation Statement
https://jamanetwork.com/journals/jama/fullarticle/2684613
For asymptomatic adults at low risk of CVD events (individuals with a 10-year CVD event risk less than 10%), it is very unlikely that the information from resting or exercise ECG (beyond that obtained with conventional CVD risk factors) will result in a change in the patient’s risk category as assessed by the Framingham Risk Score or Pooled Cohort Equations that would lead to a change in treatment and ultimately improve health outcomes. Possible harms are associated with screening with resting or exercise ECG, specifically the potential adverse effects of subsequent invasive testing. For asymptomatic adults at intermediate or high risk of CVD events, there is insufficient evidence to determine the extent to which information from resting or exercise ECG adds to current CVD risk assessment models and whether information from the ECG results in a change in risk management and ultimately reduces CVD events. As with low-risk adults, possible harms are associated with screening with resting or exercise ECG in asymptomatic adults at intermediate or high risk of CVD events.
Conclusions and Recommendation The USPSTF recommends against screening with resting or exercise ECG to prevent CVD events in asymptomatic adults at low risk of CVD events. (D recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening with resting or exercise ECG to prevent CVD events in asymptomatic adults at intermediate or high risk
#Screening for Cardiovascular Disease Risk With #Electrocardiography
US Preventive Services Task Force Recommendation Statement
https://jamanetwork.com/journals/jama/fullarticle/2684613
For asymptomatic adults at low risk of CVD events (individuals with a 10-year CVD event risk less than 10%), it is very unlikely that the information from resting or exercise ECG (beyond that obtained with conventional CVD risk factors) will result in a change in the patient’s risk category as assessed by the Framingham Risk Score or Pooled Cohort Equations that would lead to a change in treatment and ultimately improve health outcomes. Possible harms are associated with screening with resting or exercise ECG, specifically the potential adverse effects of subsequent invasive testing. For asymptomatic adults at intermediate or high risk of CVD events, there is insufficient evidence to determine the extent to which information from resting or exercise ECG adds to current CVD risk assessment models and whether information from the ECG results in a change in risk management and ultimately reduces CVD events. As with low-risk adults, possible harms are associated with screening with resting or exercise ECG in asymptomatic adults at intermediate or high risk of CVD events.
Conclusions and Recommendation The USPSTF recommends against screening with resting or exercise ECG to prevent CVD events in asymptomatic adults at low risk of CVD events. (D recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening with resting or exercise ECG to prevent CVD events in asymptomatic adults at intermediate or high risk
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#Perimenstrual exacerbation of symptoms in borderline #personality disorder: evidence from multilevel models and the Carolina Premenstrual Assessment Scoring System
https://www.cambridge.org/core/journals/psychological-medicine/article/perimenstrual-exacerbation-of-symptoms-in-borderline-personality-disorder-evidence-from-multilevel-models-and-the-carolina-premenstrual-assessment-scoring-system/C3618015C8AFED6E6C1108A573869E3D
Most symptoms demonstrated midluteal worsening, a perimenstrual peak, and resolution of symptoms in the follicular or ovulatory phase. Post-hoc correlations with person-centered progesterone revealed negative correlations with most symptoms. Depressive symptoms showed an unexpected delayed pattern in which baseline levels of symptoms were observed in the ovulatory and midluteal phases, and exacerbations were observed during both the perimenstrual and follicular phases. The majority of participants met C-PASS criteria for clinically significant (⩾30%) symptom exacerbation. All participants met the emotional instability criterion of BPD, and no participant met DSM-5 criteria for premenstrual dysphoric disorder (PMDD).
Conclusions
Females with BPD may be at elevated risk for perimenstrual worsening of emotional symptoms. Longitudinal studies with fine-grained hormonal measurement as well as hormonal experiments are needed to determine the pathophysiology of perimenstrual exacerbation in BPD
#Perimenstrual exacerbation of symptoms in borderline #personality disorder: evidence from multilevel models and the Carolina Premenstrual Assessment Scoring System
https://www.cambridge.org/core/journals/psychological-medicine/article/perimenstrual-exacerbation-of-symptoms-in-borderline-personality-disorder-evidence-from-multilevel-models-and-the-carolina-premenstrual-assessment-scoring-system/C3618015C8AFED6E6C1108A573869E3D
Most symptoms demonstrated midluteal worsening, a perimenstrual peak, and resolution of symptoms in the follicular or ovulatory phase. Post-hoc correlations with person-centered progesterone revealed negative correlations with most symptoms. Depressive symptoms showed an unexpected delayed pattern in which baseline levels of symptoms were observed in the ovulatory and midluteal phases, and exacerbations were observed during both the perimenstrual and follicular phases. The majority of participants met C-PASS criteria for clinically significant (⩾30%) symptom exacerbation. All participants met the emotional instability criterion of BPD, and no participant met DSM-5 criteria for premenstrual dysphoric disorder (PMDD).
Conclusions
Females with BPD may be at elevated risk for perimenstrual worsening of emotional symptoms. Longitudinal studies with fine-grained hormonal measurement as well as hormonal experiments are needed to determine the pathophysiology of perimenstrual exacerbation in BPD
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Association of Perioperative Red Blood Cell #Transfusions With Venous #Thromboembolism in a North American Registry
https://jamanetwork.com/journals/jamasurgery/fullarticle/2683886
..A significant dose-response effect was observed with increased odds of VTE as the number of intraoperative and/or postoperative RBC transfusion events increased (aOR, 2.1 95% CI, 2.0-2.3 for 1 event; 3.1 95% CI, 1.7-5.7 for 2 events; and 4.5 95% CI, 1.0-19.4 for ≥3 events vs no intraoperative or postoperative RBC transfusion; P < .001 for trend). In subgroup analyses, the association between any perioperative RBC transfusion and postoperative VTE remained statistically significant across all surgical subspecialties analyzed. The association between any perioperative RBC transfusion and the development of postoperative VTE also remained robust after 1:1 propensity score matching (47 142 matched pairs; matched OR, 1.9; 95% CI, 1.8-2.1).
Conclusions and Relevance The results of this study suggest that perioperative RBC transfusions may be significantly associated with the development of new or progressive postoperative VTE, independent of several putative confounders. These findings, if validated, should reinforce the importance of rigorous perioperative management of blood transfusion practices.
Association of Perioperative Red Blood Cell #Transfusions With Venous #Thromboembolism in a North American Registry
https://jamanetwork.com/journals/jamasurgery/fullarticle/2683886
..A significant dose-response effect was observed with increased odds of VTE as the number of intraoperative and/or postoperative RBC transfusion events increased (aOR, 2.1 95% CI, 2.0-2.3 for 1 event; 3.1 95% CI, 1.7-5.7 for 2 events; and 4.5 95% CI, 1.0-19.4 for ≥3 events vs no intraoperative or postoperative RBC transfusion; P < .001 for trend). In subgroup analyses, the association between any perioperative RBC transfusion and postoperative VTE remained statistically significant across all surgical subspecialties analyzed. The association between any perioperative RBC transfusion and the development of postoperative VTE also remained robust after 1:1 propensity score matching (47 142 matched pairs; matched OR, 1.9; 95% CI, 1.8-2.1).
Conclusions and Relevance The results of this study suggest that perioperative RBC transfusions may be significantly associated with the development of new or progressive postoperative VTE, independent of several putative confounders. These findings, if validated, should reinforce the importance of rigorous perioperative management of blood transfusion practices.
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Benefits and harms of #screening men for abdominal aortic #aneurysm in Sweden: a registry-based cohort study
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)31031-6/fulltext
AAA mortality in Swedish men has decreased from 36 to ten deaths per 100 000 men aged 65–74 years between the early 2000s and 2015. Mortality decreased at similar rates in all Swedish counties, irrespective of whether AAA screening was offered. After 6 years with screening, we found a non-significant reduction in AAA mortality associated with screening (adjusted odds ratio aOR 0·76, 95% CI 0·38–1·51), which means that two men (95% CI −3 to 7) avoid death from AAA for every 10 000 men offered screening. Screening was associated with increased odds of AAA diagnosis (aOR 1·52, 95% CI 1·16–1·99; p=0·002) and an increased risk of elective surgery (aOR 1·59, 95% CI 1·20–2·10; p=0·001), such that for every 10 000 men offered screening, 49 men (95% CI 25–73) were likely to be overdiagnosed, 19 of whom (95% CI 1–37) had avoidable surgery that increased their risk of mortality and morbidity.
Interpretation
AAA screening in Sweden did not contribute substantially to the large observed reductions in AAA mortality. The reductions were mostly caused by other factors, probably reduced smoking. The small benefit and substantially less favourable benefit-to-harm balance call the continued justification of the intervention into question
Benefits and harms of #screening men for abdominal aortic #aneurysm in Sweden: a registry-based cohort study
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)31031-6/fulltext
AAA mortality in Swedish men has decreased from 36 to ten deaths per 100 000 men aged 65–74 years between the early 2000s and 2015. Mortality decreased at similar rates in all Swedish counties, irrespective of whether AAA screening was offered. After 6 years with screening, we found a non-significant reduction in AAA mortality associated with screening (adjusted odds ratio aOR 0·76, 95% CI 0·38–1·51), which means that two men (95% CI −3 to 7) avoid death from AAA for every 10 000 men offered screening. Screening was associated with increased odds of AAA diagnosis (aOR 1·52, 95% CI 1·16–1·99; p=0·002) and an increased risk of elective surgery (aOR 1·59, 95% CI 1·20–2·10; p=0·001), such that for every 10 000 men offered screening, 49 men (95% CI 25–73) were likely to be overdiagnosed, 19 of whom (95% CI 1–37) had avoidable surgery that increased their risk of mortality and morbidity.
Interpretation
AAA screening in Sweden did not contribute substantially to the large observed reductions in AAA mortality. The reductions were mostly caused by other factors, probably reduced smoking. The small benefit and substantially less favourable benefit-to-harm balance call the continued justification of the intervention into question
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Circulating Vitamin #D and Colorectal #Cancer Risk: An International Pooling Project of 17 Cohorts
https://academic.oup.com/jnci/advance-article-abstract/doi/10.1093/jnci/djy087/5035027?redirectedFrom=fulltext
Compared with the lower range of sufficiency for bone health (50–<62.5 nmol/L), deficient 25(OH)D (<30 nmol/L) was associated with 31% higher colorectal cancer risk (RR = 1.31, 95% confidence interval CI = 1.05 to 1.62); 25(OH)D above sufficiency (75–<87.5 and 87.5–<100 nmol/L) was associated with 19% (RR = 0.81, 95% CI = 0.67 to 0.99) and 27% (RR = 0.73, 95% CI = 0.59 to 0.91) lower risk, respectively. At 25(OH)D of 100 nmol/L or greater, risk did not continue to decline and was not statistically significantly reduced (RR = 0.91, 95% CI = 0.67 to 1.24, 3.5% of control participants). Associations were minimally affected when adjusting for body mass index, physical activity, or other risk factors. For each 25 nmol/L increment in circulating 25(OH)D, colorectal cancer risk was 19% lower in women (RR = 0.81, 95% CI = 0.75 to 0.87) and 7% lower in men (RR = 0.93, 95% CI = 0.86 to 1.00) (two-sided Pheterogeneity by sex = .008). Associations were inverse in all subgroups, including colorectal subsite, geographic region, and season of blood collection.
Conclusions
Higher circulating 25(OH)D was related to a statistically significant, substantially lower colorectal cancer risk in women and non–statistically significant lower risk in men. Optimal 25(OH)D concentrations for colorectal cancer risk reduction, 75-100 nmol/L, appear higher than current IOM recommendations
Circulating Vitamin #D and Colorectal #Cancer Risk: An International Pooling Project of 17 Cohorts
https://academic.oup.com/jnci/advance-article-abstract/doi/10.1093/jnci/djy087/5035027?redirectedFrom=fulltext
Compared with the lower range of sufficiency for bone health (50–<62.5 nmol/L), deficient 25(OH)D (<30 nmol/L) was associated with 31% higher colorectal cancer risk (RR = 1.31, 95% confidence interval CI = 1.05 to 1.62); 25(OH)D above sufficiency (75–<87.5 and 87.5–<100 nmol/L) was associated with 19% (RR = 0.81, 95% CI = 0.67 to 0.99) and 27% (RR = 0.73, 95% CI = 0.59 to 0.91) lower risk, respectively. At 25(OH)D of 100 nmol/L or greater, risk did not continue to decline and was not statistically significantly reduced (RR = 0.91, 95% CI = 0.67 to 1.24, 3.5% of control participants). Associations were minimally affected when adjusting for body mass index, physical activity, or other risk factors. For each 25 nmol/L increment in circulating 25(OH)D, colorectal cancer risk was 19% lower in women (RR = 0.81, 95% CI = 0.75 to 0.87) and 7% lower in men (RR = 0.93, 95% CI = 0.86 to 1.00) (two-sided Pheterogeneity by sex = .008). Associations were inverse in all subgroups, including colorectal subsite, geographic region, and season of blood collection.
Conclusions
Higher circulating 25(OH)D was related to a statistically significant, substantially lower colorectal cancer risk in women and non–statistically significant lower risk in men. Optimal 25(OH)D concentrations for colorectal cancer risk reduction, 75-100 nmol/L, appear higher than current IOM recommendations
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Primary Prevention of #Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra-Virgin #Olive Oil or #Nuts
https://www.nejm.org/doi/10.1056/NEJMoa1800389
A primary end-point event occurred in 288 participants; there were 96 events in the group assigned to a Mediterranean diet with extra-virgin olive oil (3.8%), 83 in the group assigned to a Mediterranean diet with nuts (3.4%), and 109 in the control group (4.4%). In the intention-to-treat analysis including all the participants and adjusting for baseline characteristics and propensity scores, the hazard ratio was 0.69 (95% confidence interval CI, 0.53 to 0.91) for a Mediterranean diet with extra-virgin olive oil and 0.72 (95% CI, 0.54 to 0.95) for a Mediterranean diet with nuts, as compared with the control diet. Results were similar after the omission of 1588 participants whose study-group assignments were known or suspected to have departed from the protocol.
CONCLUSIONS
In this study involving persons at high cardiovascular risk, the incidence of major cardiovascular events was lower among those assigned to a Mediterranean diet supplemented with extra-virgin olive oil or nuts than among those assigned to a reduced-fat diet.
Primary Prevention of #Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra-Virgin #Olive Oil or #Nuts
https://www.nejm.org/doi/10.1056/NEJMoa1800389
A primary end-point event occurred in 288 participants; there were 96 events in the group assigned to a Mediterranean diet with extra-virgin olive oil (3.8%), 83 in the group assigned to a Mediterranean diet with nuts (3.4%), and 109 in the control group (4.4%). In the intention-to-treat analysis including all the participants and adjusting for baseline characteristics and propensity scores, the hazard ratio was 0.69 (95% confidence interval CI, 0.53 to 0.91) for a Mediterranean diet with extra-virgin olive oil and 0.72 (95% CI, 0.54 to 0.95) for a Mediterranean diet with nuts, as compared with the control diet. Results were similar after the omission of 1588 participants whose study-group assignments were known or suspected to have departed from the protocol.
CONCLUSIONS
In this study involving persons at high cardiovascular risk, the incidence of major cardiovascular events was lower among those assigned to a Mediterranean diet supplemented with extra-virgin olive oil or nuts than among those assigned to a reduced-fat diet.
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acceptability of 21 #antidepressant drugs for the acute treatment of adults with major #depressive disorder: a systematic review and network meta-analysis
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)32802-7/fulltext
In head-to-head studies, agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine, and vortioxetine were more effective than other antidepressants (range of ORs 1·19–1·96), whereas fluoxetine, fluvoxamine, reboxetine, and trazodone were the least efficacious drugs (0·51–0·84). For acceptability, agomelatine, citalopram, escitalopram, fluoxetine, sertraline, and vortioxetine were more tolerable than other antidepressants (range of ORs 0·43–0·77), whereas amitriptyline, clomipramine, duloxetine, fluvoxamine, reboxetine, trazodone, and venlafaxine had the highest dropout rates (1·30–2·32). 46 (9%) of 522 trials were rated as high risk of bias, 380 (73%) trials as moderate, and 96 (18%) as low; and the certainty of evidence was moderate to very low.
Interpretation
All antidepressants were more efficacious than placebo in adults with major depressive disorder. Smaller differences between active drugs were found when placebo-controlled trials were included in the analysis, whereas there was more variability in efficacy and acceptability in head-to-head trials. These results should serve evidence-based practice and inform patients, physicians, guideline developers, and policy makers on the relative merits of the different antidepressants.
acceptability of 21 #antidepressant drugs for the acute treatment of adults with major #depressive disorder: a systematic review and network meta-analysis
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)32802-7/fulltext
In head-to-head studies, agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine, and vortioxetine were more effective than other antidepressants (range of ORs 1·19–1·96), whereas fluoxetine, fluvoxamine, reboxetine, and trazodone were the least efficacious drugs (0·51–0·84). For acceptability, agomelatine, citalopram, escitalopram, fluoxetine, sertraline, and vortioxetine were more tolerable than other antidepressants (range of ORs 0·43–0·77), whereas amitriptyline, clomipramine, duloxetine, fluvoxamine, reboxetine, trazodone, and venlafaxine had the highest dropout rates (1·30–2·32). 46 (9%) of 522 trials were rated as high risk of bias, 380 (73%) trials as moderate, and 96 (18%) as low; and the certainty of evidence was moderate to very low.
Interpretation
All antidepressants were more efficacious than placebo in adults with major depressive disorder. Smaller differences between active drugs were found when placebo-controlled trials were included in the analysis, whereas there was more variability in efficacy and acceptability in head-to-head trials. These results should serve evidence-based practice and inform patients, physicians, guideline developers, and policy makers on the relative merits of the different antidepressants.
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#Influenza Virus Infectivity Is Retained in #Aerosols and Droplets Independent of Relative Humidity
https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiy221/5025997
Pandemic and seasonal influenza viruses can be transmitted through aerosols and droplets, in which viruses must remain stable and infectious across a wide range of environmental conditions. Using humidity-controlled chambers, we studied the impact of relative humidity on the stability of 2009 pandemic influenza A(H1N1) virus in suspended aerosols and stationary droplets. Contrary to the prevailing paradigm that humidity modulates the stability of respiratory viruses in aerosols, we found that viruses supplemented with material from the apical surface of differentiated primary human airway epithelial cells remained equally infectious for 1 hour at all relative humidities tested. This sustained infectivity was observed in both fine aerosols and stationary droplets. Our data suggest, for the first time, that influenza viruses remain highly stable and infectious in aerosols across a wide range of relative humidities. These results have significant implications for understanding the mechanisms of transmission of influenza and its seasonality.
#Influenza Virus Infectivity Is Retained in #Aerosols and Droplets Independent of Relative Humidity
https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiy221/5025997
Pandemic and seasonal influenza viruses can be transmitted through aerosols and droplets, in which viruses must remain stable and infectious across a wide range of environmental conditions. Using humidity-controlled chambers, we studied the impact of relative humidity on the stability of 2009 pandemic influenza A(H1N1) virus in suspended aerosols and stationary droplets. Contrary to the prevailing paradigm that humidity modulates the stability of respiratory viruses in aerosols, we found that viruses supplemented with material from the apical surface of differentiated primary human airway epithelial cells remained equally infectious for 1 hour at all relative humidities tested. This sustained infectivity was observed in both fine aerosols and stationary droplets. Our data suggest, for the first time, that influenza viruses remain highly stable and infectious in aerosols across a wide range of relative humidities. These results have significant implications for understanding the mechanisms of transmission of influenza and its seasonality.
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Position Paper for the Treatment of #Nightmare Disorder in Adults: An American Academy of #Sleep Medicine Position Paper
http://jcsm.aasm.org/ViewAbstract.aspx?pid=31290
The following therapies may be used for the treatment of PTSD-associated nightmares: cognitive behavioral therapy; cognitive behavioral therapy for insomnia; eye movement desensitization and reprocessing; exposure, relaxation, and rescripting therapy; the atypical antipsychotics olanzapine, risperidone and aripiprazole; clonidine; cyproheptadine; fluvoxamine; gabapentin; nabilone; phenelzine; prazosin; topiramate; trazodone; and tricyclic antidepressants.
The following therapies may be used for the treatment of nightmare disorder: cognitive behavioral therapy; exposure, relaxation, and rescripting therapy; hypnosis; lucid dreaming therapy; progressive deep muscle relaxation; sleep dynamic therapy; self-exposure therapy; systematic desensitization; testimony method; nitrazepam; prazosin; and triazolam.
The following are not recommended for the treatment of nightmare disorder: clonazepam and venlafaxine.
The ultimate judgment regarding propriety of any specific care must be made by the clinician, in light of the individual circumstances presented by the patient, accessible treatment options, and resources.
Position Paper for the Treatment of #Nightmare Disorder in Adults: An American Academy of #Sleep Medicine Position Paper
http://jcsm.aasm.org/ViewAbstract.aspx?pid=31290
The following therapies may be used for the treatment of PTSD-associated nightmares: cognitive behavioral therapy; cognitive behavioral therapy for insomnia; eye movement desensitization and reprocessing; exposure, relaxation, and rescripting therapy; the atypical antipsychotics olanzapine, risperidone and aripiprazole; clonidine; cyproheptadine; fluvoxamine; gabapentin; nabilone; phenelzine; prazosin; topiramate; trazodone; and tricyclic antidepressants.
The following therapies may be used for the treatment of nightmare disorder: cognitive behavioral therapy; exposure, relaxation, and rescripting therapy; hypnosis; lucid dreaming therapy; progressive deep muscle relaxation; sleep dynamic therapy; self-exposure therapy; systematic desensitization; testimony method; nitrazepam; prazosin; and triazolam.
The following are not recommended for the treatment of nightmare disorder: clonazepam and venlafaxine.
The ultimate judgment regarding propriety of any specific care must be made by the clinician, in light of the individual circumstances presented by the patient, accessible treatment options, and resources.
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Single-Sample Confirmatory #Testing for Undiagnosed #Diabetes: A Prospective Cohort Study
http://annals.org/aim/article-abstract/2684927/prognostic-implications-single-sample-confirmatory-testing-undiagnosed-diabetes-prospective-cohort
Among 12 268 participants without diagnosed diabetes, 978 had elevated levels of fasting glucose or HbA1c at baseline (1990 to 1992). Among these, 39% had both (confirmed undiagnosed diabetes), whereas 61% had only 1 elevated measure (unconfirmed undiagnosed diabetes). The confirmatory definition had moderate sensitivity (54.9%) but high specificity (98.1%) for identification of diabetes cases diagnosed during the first 5 years of follow-up, with specificity increasing to 99.6% by 15 years. The 15-year positive predictive value was 88.7% compared with 71.1% for unconfirmed cases. Confirmed undiagnosed diabetes was significantly associated with cardiovascular and kidney disease and mortality, with stronger associations than unconfirmed diabetes.
A single-sample confirmatory definition of diabetes had a high positive predictive value for subsequent diagnosis and was strongly associated with clinical end points. Our results support the clinical utility of using a combination of elevated fasting glucose and HbA1c levels from a single blood sample to identify undiagnosed diabetes in the population.
Single-Sample Confirmatory #Testing for Undiagnosed #Diabetes: A Prospective Cohort Study
http://annals.org/aim/article-abstract/2684927/prognostic-implications-single-sample-confirmatory-testing-undiagnosed-diabetes-prospective-cohort
Among 12 268 participants without diagnosed diabetes, 978 had elevated levels of fasting glucose or HbA1c at baseline (1990 to 1992). Among these, 39% had both (confirmed undiagnosed diabetes), whereas 61% had only 1 elevated measure (unconfirmed undiagnosed diabetes). The confirmatory definition had moderate sensitivity (54.9%) but high specificity (98.1%) for identification of diabetes cases diagnosed during the first 5 years of follow-up, with specificity increasing to 99.6% by 15 years. The 15-year positive predictive value was 88.7% compared with 71.1% for unconfirmed cases. Confirmed undiagnosed diabetes was significantly associated with cardiovascular and kidney disease and mortality, with stronger associations than unconfirmed diabetes.
A single-sample confirmatory definition of diabetes had a high positive predictive value for subsequent diagnosis and was strongly associated with clinical end points. Our results support the clinical utility of using a combination of elevated fasting glucose and HbA1c levels from a single blood sample to identify undiagnosed diabetes in the population.
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Effect of #Tamsulosin on Passage of Symptomatic Ureteral #Stones
A Randomized Clinical Trial
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2684477
The mean age of 512 participants randomized to tamsulosin or placebo was 40.6 years (range, 18-74 years), 139 (27.1%) were female, and 110 (22.8%) were nonwhite. The mean (SD) diameter of the urinary stones was 3.8 (1.4) mm. Four hundred ninety-seven patients were evaluated for the primary outcome. Stone passage rates were 50% in the tamsulosin group and 47% in the placebo group (relative risk, 1.05; 95.8% CI, 0.87-1.27; P = .60), a nonsignificant difference. None of the secondary outcomes were significantly different. All analyses were performed according to the intention-to-treat principle, although patients lost to follow-up before stone passage were excluded from the analysis of final outcome.
Conclusions and Relevance Tamsulosin did not significantly increase the stone passage rate compared with placebo. Our findings do not support the use of tamsulosin for symptomatic urinary stones smaller than 9 mm. Guidelines for medical expulsive therapy for urinary stones may need to be revised.
Effect of #Tamsulosin on Passage of Symptomatic Ureteral #Stones
A Randomized Clinical Trial
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2684477
The mean age of 512 participants randomized to tamsulosin or placebo was 40.6 years (range, 18-74 years), 139 (27.1%) were female, and 110 (22.8%) were nonwhite. The mean (SD) diameter of the urinary stones was 3.8 (1.4) mm. Four hundred ninety-seven patients were evaluated for the primary outcome. Stone passage rates were 50% in the tamsulosin group and 47% in the placebo group (relative risk, 1.05; 95.8% CI, 0.87-1.27; P = .60), a nonsignificant difference. None of the secondary outcomes were significantly different. All analyses were performed according to the intention-to-treat principle, although patients lost to follow-up before stone passage were excluded from the analysis of final outcome.
Conclusions and Relevance Tamsulosin did not significantly increase the stone passage rate compared with placebo. Our findings do not support the use of tamsulosin for symptomatic urinary stones smaller than 9 mm. Guidelines for medical expulsive therapy for urinary stones may need to be revised.
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#Emergency Department Discharge of Pulmonary #Embolus Patients
https://onlinelibrary.wiley.com/doi/abs/10.1111/acem.13451
Of 114 randomized subjects, 51 were early discharge and 63 were SOC. Of 112 (98.2%) receiving at least one dose of study drug, 99 (86.8%) completed the study. Initial hospital LOS was 4.8 hours versus 33.6 hours, with a mean difference of –28.8 hours (95% confidence interval CI = –42.55 to –15.12 hours) for early discharge versus SOC, respectively. At 90 days, mean total hospital days (for any reason) were less for early discharge than SOC, 19.2 hours versus 43.2 hours, with a mean difference of 26.4 hours (95% CI = –46.97 to –3.34 hours). At 90 days, there were no bleeding events, recurrent VTE, or deaths. The composite safety endpoint was similar in both groups, with a difference in proportions of 0.005 (95% CI = –0.18 to 0.19). Total costs were $1,496 for early discharge and $4,234 for SOC, with a median difference of $2,496 (95% CI = –$2,999 to –$2,151).
Conclusions
Low‐risk ED PE patients receiving early discharge on rivaroxaban have similar outcomes to SOC, but fewer total hospital days and lower costs over 30 days
#Emergency Department Discharge of Pulmonary #Embolus Patients
https://onlinelibrary.wiley.com/doi/abs/10.1111/acem.13451
Of 114 randomized subjects, 51 were early discharge and 63 were SOC. Of 112 (98.2%) receiving at least one dose of study drug, 99 (86.8%) completed the study. Initial hospital LOS was 4.8 hours versus 33.6 hours, with a mean difference of –28.8 hours (95% confidence interval CI = –42.55 to –15.12 hours) for early discharge versus SOC, respectively. At 90 days, mean total hospital days (for any reason) were less for early discharge than SOC, 19.2 hours versus 43.2 hours, with a mean difference of 26.4 hours (95% CI = –46.97 to –3.34 hours). At 90 days, there were no bleeding events, recurrent VTE, or deaths. The composite safety endpoint was similar in both groups, with a difference in proportions of 0.005 (95% CI = –0.18 to 0.19). Total costs were $1,496 for early discharge and $4,234 for SOC, with a median difference of $2,496 (95% CI = –$2,999 to –$2,151).
Conclusions
Low‐risk ED PE patients receiving early discharge on rivaroxaban have similar outcomes to SOC, but fewer total hospital days and lower costs over 30 days
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#Sleep duration and #mortality – Does weekend sleep matter?
https://onlinelibrary.wiley.com/doi/10.1111/jsr.12712
... Among individuals <65 years old, short sleep (≤5 hr) during weekends at baseline was associated with a 52% higher mortality rate (hazard ratios 1.52; 95% confidence intervals 1.15–2.02) compared with the reference group (7 hr), while no association was observed for long (≥9 hr) weekend sleep. When, instead, different combinations of weekday and weekend sleep durations were analysed, we observed a detrimental association with consistently sleeping ≤5 hr (hazard ratios 1.65; 95% confidence intervals 1.22–2.23) or ≥8 hr (hazard ratios 1.25; 95% confidence intervals 1.05–1.50), compared with consistently sleeping 6–7 hr per day (reference). The mortality rate among participants with short sleep during weekdays, but long sleep during weekends, did not differ from the rate of the reference group. Among individuals ≥65 years old, no association between weekend sleep or weekday/weekend sleep durations and mortality was observed. In conclusion, short, but not long, weekend sleep was associated with an increased mortality in subjects <65 years. In the same age group, short sleep (or long sleep) on both weekdays and weekend showed increased mortality. Possibly, long weekend sleep may compensate for short weekday sleep.
#Sleep duration and #mortality – Does weekend sleep matter?
https://onlinelibrary.wiley.com/doi/10.1111/jsr.12712
... Among individuals <65 years old, short sleep (≤5 hr) during weekends at baseline was associated with a 52% higher mortality rate (hazard ratios 1.52; 95% confidence intervals 1.15–2.02) compared with the reference group (7 hr), while no association was observed for long (≥9 hr) weekend sleep. When, instead, different combinations of weekday and weekend sleep durations were analysed, we observed a detrimental association with consistently sleeping ≤5 hr (hazard ratios 1.65; 95% confidence intervals 1.22–2.23) or ≥8 hr (hazard ratios 1.25; 95% confidence intervals 1.05–1.50), compared with consistently sleeping 6–7 hr per day (reference). The mortality rate among participants with short sleep during weekdays, but long sleep during weekends, did not differ from the rate of the reference group. Among individuals ≥65 years old, no association between weekend sleep or weekday/weekend sleep durations and mortality was observed. In conclusion, short, but not long, weekend sleep was associated with an increased mortality in subjects <65 years. In the same age group, short sleep (or long sleep) on both weekdays and weekend showed increased mortality. Possibly, long weekend sleep may compensate for short weekday sleep.
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Longitudinal analysis of #impulse control disorders in #Parkinson disease
http://n.neurology.org/content/early/2018/06/20/WNL.0000000000005816
Among 411 patients (40.6% women, mean age 62.3 years, average follow-up 3.3 years, SD 1.7 years), 356 (86.6%) took a DA at least once since disease onset. In 306 patients without ICDs at baseline, the 5-year cumulative incidence of ICDs was 46.1% (95% confidence interval CI 37.4–55.7, DA ever users 51.5% 95% CI 41.8–62.1, DA never users 12.4% 95% CI 4.8–30.0). ICD prevalence increased from 19.7% at baseline to 32.8% after 5 years. ICDs were associated with ever DA use (prevalence ratio 4.23, 95% CI 1.78–10.09). Lifetime average daily dose and duration of treatment were independently associated with ICDs with significant dose-effect relationships. Similar analyses for levodopa were not in favor of a strong association. ICDs progressively resolved after DA discontinuation.
Conclusion In this longitudinal study of patients with PD characterized by a high prevalence of DA treatment, the 5-year cumulative incidence of ICDs was ≈46%. ICDs were strongly associated with DA use with a dose-effect relationship; both increasing duration and dose were associated with ICDs. ICDs progressively resolved after DA discontinuation.
Longitudinal analysis of #impulse control disorders in #Parkinson disease
http://n.neurology.org/content/early/2018/06/20/WNL.0000000000005816
Among 411 patients (40.6% women, mean age 62.3 years, average follow-up 3.3 years, SD 1.7 years), 356 (86.6%) took a DA at least once since disease onset. In 306 patients without ICDs at baseline, the 5-year cumulative incidence of ICDs was 46.1% (95% confidence interval CI 37.4–55.7, DA ever users 51.5% 95% CI 41.8–62.1, DA never users 12.4% 95% CI 4.8–30.0). ICD prevalence increased from 19.7% at baseline to 32.8% after 5 years. ICDs were associated with ever DA use (prevalence ratio 4.23, 95% CI 1.78–10.09). Lifetime average daily dose and duration of treatment were independently associated with ICDs with significant dose-effect relationships. Similar analyses for levodopa were not in favor of a strong association. ICDs progressively resolved after DA discontinuation.
Conclusion In this longitudinal study of patients with PD characterized by a high prevalence of DA treatment, the 5-year cumulative incidence of ICDs was ≈46%. ICDs were strongly associated with DA use with a dose-effect relationship; both increasing duration and dose were associated with ICDs. ICDs progressively resolved after DA discontinuation.
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Multiscale Analysis of Independent #Alzheimer’s Cohorts Finds Disruption of Molecular, Genetic, and Clinical Networks by Human #Herpesvirus
https://www.cell.com/neuron/fulltext/S0896-6273(18)30421-5
Investigators have long suspected that pathogenic microbes might contribute to the onset and progression of Alzheimer’s disease (AD) although definitive evidence has not been presented Whether such findings represent a causal contribution, or reflect opportunistic passengers of neurodegeneration, is also difficult to resolve. We constructed multiscale networks of the late-onset AD-associated virome, integrating genomic, transcriptomic, proteomic, and histopathological data across four brain regions from human post-mortem tissue. We observed increased human herpesvirus 6A (HHV-6A) and human herpesvirus 7 (HHV-7) from subjects with AD compared with controls. These results were replicated in two additional, independent and geographically dispersed cohorts. We observed regulatory relationships linking viral abundance and modulators of APP metabolism, including induction of APBB2, APPBP2, BIN1, BACE1, CLU, PICALM, and PSEN1 by HHV-6A. This study elucidates networks linking molecular, clinical, and neuropathological features with viral activity and is consistent with viral activity constituting a general feature of AD
Multiscale Analysis of Independent #Alzheimer’s Cohorts Finds Disruption of Molecular, Genetic, and Clinical Networks by Human #Herpesvirus
https://www.cell.com/neuron/fulltext/S0896-6273(18)30421-5
Investigators have long suspected that pathogenic microbes might contribute to the onset and progression of Alzheimer’s disease (AD) although definitive evidence has not been presented Whether such findings represent a causal contribution, or reflect opportunistic passengers of neurodegeneration, is also difficult to resolve. We constructed multiscale networks of the late-onset AD-associated virome, integrating genomic, transcriptomic, proteomic, and histopathological data across four brain regions from human post-mortem tissue. We observed increased human herpesvirus 6A (HHV-6A) and human herpesvirus 7 (HHV-7) from subjects with AD compared with controls. These results were replicated in two additional, independent and geographically dispersed cohorts. We observed regulatory relationships linking viral abundance and modulators of APP metabolism, including induction of APBB2, APPBP2, BIN1, BACE1, CLU, PICALM, and PSEN1 by HHV-6A. This study elucidates networks linking molecular, clinical, and neuropathological features with viral activity and is consistent with viral activity constituting a general feature of AD
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Bioimpedance and New‐Onset Heart Failure: A Longitudinal Study of >500 000 Individuals From the General Population
http://jaha.ahajournals.org/content/7/13/e008970
... Mean reticulocyte volume appeared as one novel factor and leg bioimpedance another, the latter appearing as the most important new marker. Leg bioimpedance was lower in those who developed heart failure during an up to 9.8‐year follow‐up. When adjusting for known heart failure risk factors, leg bioimpedance was inversely related to heart failure (hazard ratio [95% confidence interval], 0.60 [0.48–0.73] and 0.75 [0.59–0.94], in age‐ and sex‐adjusted and fully adjusted models, respectively, comparing the upper versus lower quartile). A model including leg bioimpedance, age, sex, and self‐reported history of myocardial infarction showed good discrimination for future heart failure hospitalization (Concordance index [C‐index]=0.82) and good calibration.
Conclusions Leg bioimpedance is inversely associated with heart failure incidence in the general population. A simple model of exclusively noninvasive measures, combining leg bioimpedance with history of myocardial infarction, age, and sex provides accurate predictive capacity
Bioimpedance and New‐Onset Heart Failure: A Longitudinal Study of >500 000 Individuals From the General Population
http://jaha.ahajournals.org/content/7/13/e008970
... Mean reticulocyte volume appeared as one novel factor and leg bioimpedance another, the latter appearing as the most important new marker. Leg bioimpedance was lower in those who developed heart failure during an up to 9.8‐year follow‐up. When adjusting for known heart failure risk factors, leg bioimpedance was inversely related to heart failure (hazard ratio [95% confidence interval], 0.60 [0.48–0.73] and 0.75 [0.59–0.94], in age‐ and sex‐adjusted and fully adjusted models, respectively, comparing the upper versus lower quartile). A model including leg bioimpedance, age, sex, and self‐reported history of myocardial infarction showed good discrimination for future heart failure hospitalization (Concordance index [C‐index]=0.82) and good calibration.
Conclusions Leg bioimpedance is inversely associated with heart failure incidence in the general population. A simple model of exclusively noninvasive measures, combining leg bioimpedance with history of myocardial infarction, age, and sex provides accurate predictive capacity
Journal of the American Heart Association
Bioimpedance and New‐Onset Heart Failure: A Longitudinal Study of >500 000 Individuals From the General Population
Background Heart failure constitutes a high burden on patients and society, but although lifetime risk is high, it is difficult to predict without costly or invasive testing. We aimed to establish new risk factors of heart failure, which potentially could…
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CDKN1B/p27 is localized in #mitochondria and improves respiration-dependent processes in the cardiovascular system—New mode of action for #caffeine
http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.2004408
...In addition, mitochondrial p27 protects cardiomyocytes against apoptosis. Moreover, mitochondrial p27 is necessary and sufficient for cardiac myofibroblast differentiation. In addition, p27 deficiency and aging decrease respiration in heart mitochondria. Caffeine does not increase respiration in p27-deficient animals, whereas aged mice display improvement after 10 days of caffeine in drinking water. Moreover, caffeine induces transcriptome changes in a p27-dependent manner, affecting mostly genes relevant for mitochondrial processes. Caffeine also reduces infarct size after myocardial infarction in prediabetic mice and increases mitochondrial p27. Our data characterize mitochondrial p27 as a common denominator that improves mitochondria-dependent processes and define an increase in mitochondrial p27 as a new mode of action of caffeine
CDKN1B/p27 is localized in #mitochondria and improves respiration-dependent processes in the cardiovascular system—New mode of action for #caffeine
http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.2004408
...In addition, mitochondrial p27 protects cardiomyocytes against apoptosis. Moreover, mitochondrial p27 is necessary and sufficient for cardiac myofibroblast differentiation. In addition, p27 deficiency and aging decrease respiration in heart mitochondria. Caffeine does not increase respiration in p27-deficient animals, whereas aged mice display improvement after 10 days of caffeine in drinking water. Moreover, caffeine induces transcriptome changes in a p27-dependent manner, affecting mostly genes relevant for mitochondrial processes. Caffeine also reduces infarct size after myocardial infarction in prediabetic mice and increases mitochondrial p27. Our data characterize mitochondrial p27 as a common denominator that improves mitochondria-dependent processes and define an increase in mitochondrial p27 as a new mode of action of caffeine