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Associations between #gabapentinoids and #suicidal behaviour, unintentional overdoses, injuries, road traffic incidents, and violent crime: population based cohort study in Sweden

https://www.bmj.com/content/365/bmj.l2147

During the study period, 10 026 (5.2%) participants were treated for suicidal behaviour or died from suicide, 17 144 (8.9%) experienced an unintentional overdose, 12 070 (6.3%) had a road traffic incident or offence, 70 522 (36.7%) presented with head/body injuries, and 7984 (4.1%) were arrested for a violent crime. In within-individual analyses, gabapentinoid treatment was associated with increased hazards of suicidal behaviour and deaths from suicide (age adjusted hazard ratio 1.26, 95% confidence interval 1.20 to 1.32), unintentional overdoses (1.24, 1.19 to 1.28), head/body injuries (1.22, 1.19 to 1.25), and road traffic incidents and offences (1.13, 1.06 to 1.20). Associations with arrests for violent crime were less clear (1.04, 0.98 to 1.11). When the drugs were examined separately, pregabalin was associated with increased hazards of all outcomes, whereas gabapentin was associated with decreased or no statistically significant hazards. When stratifying on age, increased hazards of all outcomes were associated with participants aged 15 to 24 years.

Conclusions This study suggests that gabapentinoids are associated with an increased risk of suicidal behaviour, unintentional overdoses, head/body injuries, and road traffic incidents and offences. Pregabalin was associated with higher hazards of these outcomes than gabapentin.

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#Mental Illness Among Youth With Chronic #Physical Conditions

https://pediatrics.aappublications.org/content/early/2019/06/13/peds.2018-1819

Youth with chronic physical conditions (CPCs) may be at greater risk for developing chronic mental health conditions (MHCs), and limitations in the ability to engage in developmentally appropriate activities may contribute to the risk of MHCs among youth with CPCs.

The 2-year cumulative incidence of MHCs was 7.8% overall, 11.5% in youth with CPCs (14.7% of sample), and 7.1% in those without. The adjusted risk of incident MHCs was 51% greater (adjusted hazard ratio 1.51; 95% confidence interval 1.30–1.74) in youth with CPCs compared with those without. Activity limitations mediated 13.5% of this relationship (P < .001).

CONCLUSIONS: This nationally representative cohort study supports the hypotheses that youth with CPCs have increased risk for MHCs and that activity limitations may play a role in MHC development. Youth with CPCs may benefit from services to bolster their ability to participate in developmentally important activities and to detect and treat new onset MHC

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Dynamic Modulation of the Gut #Microbiota and Metabolome by #Bacteriophages in a Mouse Model

https://www.sciencedirect.com/science/article/pii/S193131281930246X?via%3Dihub

The human gut microbiome is comprised of densely colonizing microorganisms including bacteriophages, which are in dynamic interaction with each other and the mammalian host.

To address how bacteriophages impact bacterial communities in the gut, we investigated the dynamic effects of phages on a model microbiome. Gnotobiotic mice were colonized with defined human gut commensal bacteria and subjected to predation by cognate lytic phages.

We found that phage predation not only directly impacts susceptible bacteria but also leads to cascading effects on other bacterial species via interbacterial interactions. Metabolomic profiling revealed that shifts in the microbiome caused by phage predation have a direct consequence on the gut metabolome.

Our work provides insight into the ecological importance of phages as modulators of bacterial colonization, and it additionally suggests the potential impact of gut phages on the mammalian host with implications for their therapeutic use to precisely modulate the microbiome.

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Association of changes in red #meat consumption with total and cause specific #mortality among US women and men: two prospective cohort studies

https://www.bmj.com/content/365/bmj.l2110

Increases in red meat consumption over eight years were associated with a higher mortality risk in the subsequent eight years among women and men (both P for trend<0.05, P for heterogeneity=0.97). An increase in total red meat consumption of at least half a serving per day was associated with a 10% higher mortality risk (pooled hazard ratio 1.10, 95% confidence interval 1.04 to 1.17).

For processed and unprocessed red meat consumption, an increase of at least half a serving per day was associated with a 13% higher mortality risk (1.13, 1.04 to 1.23) and a 9% higher mortality risk (1.09, 1.02 to 1.17), respectively. A decrease in consumption of processed or unprocessed red meat of at least half a serving per day was not associated with mortality risk. The association between increased red meat consumption and mortality risk was consistent across subgroups defined by age, physical activity, dietary quality, smoking status, or alcohol consumption.

Conclusion Increases in red meat consumption, especially processed meat, were associated with higher overall mortality rates.

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The “online brain”: how the #Internet may be changing our #cognition

https://onlinelibrary.wiley.com/doi/full/10.1002/wps.20617

Here we draw on recent psychological, psychiatric and neuroimaging findings to examine several key hypotheses on how the Internet may be changing our cognition. Specifically, we explore how unique features of the online world may be influencing: a) attentional capacities, as the constantly evolving stream of online information encourages our divided attention across multiple media sources, at the expense of sustained concentration; b) memory processes, as this vast and ubiquitous source of online information begins to shift the way we retrieve, store, and even value knowledge; and c) social cognition, as the ability for online social settings to resemble and evoke real‐world social processes creates a new interplay between the Internet and our social lives, including our self‐concepts and self‐esteem.

Overall, the available evidence indicates that the Internet can produce both acute and sustained alterations in each of these areas of cognition, which may be reflected in changes in the brain. However, an emerging priority for future research is to determine the effects of extensive online media usage on cognitive development in youth, and examine how this may differ from cognitive outcomes and brain impact of uses of Internet in the elderly.

We conclude by proposing how Internet research could be integrated into broader research settings to study how this unprecedented new facet of society can affect our cognition and the brain across the life course.

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Meta-Research: A comprehensive review of randomized clinical trials in three medical journals reveals 396 medical #reversals

https://elifesciences.org/articles/45183


The ability to identify medical reversals and other low-value medical practices is an essential prerequisite for efforts to reduce spending on such practices. Through an analysis of more than 3000 randomized controlled trials (RCTs) published in three leading medical journals (the Journal of the American Medical Association, the Lancet, and the New England Journal of Medicine), we have identified 396 medical reversals.

Most of the studies (92%) were conducted on populations in high-income countries, cardiovascular disease was the most common medical category (20%), and medication was the most common type of intervention (33%).

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#Systolic Blood Pressure and Outcomes in Patients With Heart #Failure With Reduced Ejection Fraction

http://www.onlinejacc.org/content/73/24/3054

National guidelines recommend that systolic blood pressure (SBP) in patients with heart failure with reduced ejection fraction (HFrEF) and hypertension be maintained below 130 mm Hg.

Thirty-day all-cause mortality occurred in 7% and 4% of matched patients with SBP <130 mm Hg versus ≥130 mm Hg, respectively (hazard ratio HR: 1.76; 95% confidence interval CI: 1.24 to 2.48; p = 0.001). HRs (95% CIs) for all-cause mortality, all-cause readmission, and HF readmission at 1 year, associated with SBP <130 mm Hg, were 1.32 (1.15 to 1.53; p < 0.001), 1.11 (1.01 to 1.23; p = 0.030), and 1.24 (1.09 to 1.42; p = 0.001), respectively. HRs (95% CIs) for 30-day and 1-year all-cause mortality associated with SBP 110 to 129 mm Hg (vs. ≥130 mm Hg) were 1.50 (1.03 to 2.19; p = 0.035), and 1.19 (1.02 to 1.39; p = 0.029), respectively.

Conclusions Among hospitalized older patients with HFrEF, SBP <130 mm Hg is associated with poor outcomes. This association persisted when the analyses were repeated after excluding patients with SBP <110 mm Hg. There is an urgent need for randomized controlled trials to evaluate optimal SBP reduction goals in patients with HFrEF.

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A machine learning approach to predicting #psychosis using semantic density and latent content analysis

https://www.nature.com/articles/s41537-019-0077-9

Subtle features in people’s everyday language may harbor the signs of future mental illness. Machine learning offers an approach for the rapid and accurate extraction of these signs. Here we investigate two potential linguistic indicators of psychosis in 40 participants of the North American Prodrome Longitudinal Study.

The results revealed that conversion to psychosis is signaled by low semantic density and talk about voices and sounds. When combined, these two variables were able to predict the conversion with 93% accuracy in the training and 90% accuracy in the holdout datasets.

The results point to a larger project in which automated analyses of language are used to forecast a broad range of mental disorders well in advance of their emergence.

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The acceptability of addressing #alcohol consumption as a modifiable risk factor for #breast cancer: a mixed method study within breast screening services and symptomatic breast clinics

https://bmjopen.bmj.com/content/9/6/e027371

Potentially modifiable risk factors account for approximately 23% of breast cancers, with obesity and alcohol being the two greatest. Breast screening and symptomatic clinical attendances provide opportunities (‘teachable moments’) to link health promotion and breast cancer-prevention advice within established clinical pathways. This study explored knowledge and attitudes towards alcohol as a risk factor for breast cancer, and potential challenges inherent in incorporating advice about alcohol health risks into breast clinics and screening appointments.

Alcohol was identified as a breast cancer risk factor by 40/205 (19.5%) of attenders and 16/33 (48.5%) of staff. Overall 66.5% of attenders drank alcohol, and 56.6% could not estimate correctly the alcohol content of any of four commonly consumed alcoholic drinks. All women agreed that including a prevention-focussed intervention would not reduce the likelihood of their attendance at screening mammograms or breast clinics..

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Postdialysis #Hypokalemia and All-Cause #Mortality in Patients Undergoing Maintenance #Hemodialysis

https://cjasn.asnjournals.org/content/14/6/873

Almost half of patients on dialysis demonstrate a postdialysis serum potassium ≤3.5 mEq/L. We aimed to examine the relationship between postdialysis potassium levels and all-cause mortality.

Compared with postdialysis potassium of 3.0 to <3.5 mEq/L, the hazard ratios of postdialysis hypokalemia (<3.0 mEq/L) were 1.84 (95% confidence interval, 1.44 to 2.34) in the unadjusted model, 1.44 (95% confidence interval, 1.14 to 1.82) in the model without adjusting for predialysis serum potassium, and 1.10 (95% confidence interval, 0.84 to 1.44) in the model adjusted for predialysis serum potassium. The combination of pre- and postdialysis hypokalemia was associated with the highest mortality risk (hazard ratio, 1.72; 95% confidence interval, 1.35 to 2.19, reference; pre- and postdialysis nonhypokalemia).

Conclusions Postdialysis hypokalemia was associated with mortality, but this association was not independent of predialysis potassium.

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Safety and Efficacy of Antithrombotic Strategies in Patients With Atrial #Fibrillation Undergoing Percutaneous #Coronary Intervention

https://jamanetwork.com/journals/jamacardiology/article-abstract/2735647

The antithrombotic treatment of patients with atrial fibrillation (AF) and coronary artery disease, in particular with acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI), poses a significant treatment dilemma in clinical practice.

Compared with a regimen of vitamin K antagonist (VKA) plus dual antiplatelet therapy (DAPT; P2Y12 inhibitor plus aspirin), the odds ratios (ORs) for TIMI major bleeding were 0.58 (95% CI, 0.31-1.08) for VKA plus P2Y12 inhibitor, 0.49 (95% CI, 0.30-0.82) for non-VKA oral anticoagulant (NOAC) plus P2Y12 inhibitor, and 0.70 (95% CI, 0.38-1.23) for NOAC plus DAPT. Compared with VKA plus DAPT, the ORs for MACE were 0.96 (95% CI, 0.60-1.46) for VKA plus P2Y12 inhibitor, 1.02 (95% CI, 0.71-1.47) for NOAC plus P2Y12 inhibitor, and 0.94 (95% CI, 0.60-1.45) for NOAC plus DAPT.

Conclusions and Relevance A regimen of NOACs plus P2Y12 inhibitor was associated with less bleeding compared with VKAs plus DAPT. Strategies omitting aspirin caused less bleeding, including intracranial bleeding, without significant difference in MACE, compared with strategies including aspirin. Our results support the use of NOAC plus P2Y12 inhibitor as the preferred regimen post–percutaneous coronary intervention for these high-risk patients with AF. A regimen of VKA plus DAPT should generally be avoided.

We're on holiday! No updates or just a few until 27th June! Stay tuned

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Natural History of Adrenal #Incidentalomas With and Without Mild Autonomous #Cortisol Excess: A Systematic Review and Meta-analysis

https://annals.org/aim/article-abstract/2736920/natural-history-adrenal-incidentalomas-without-mild-autonomous-cortisol-excess-systematic

Adrenal incidentalomas are mostly benign nonfunctioning adrenal tumors (NFATs) or adenomas causing mild autonomous cortisol excess (MACE), but their natural history is unclear.

Clinically significant tumor enlargement (≥10 mm) occurred in 2.5% of patients, and none developed adrenal cancer. Clinically overt hormone excess was unlikely to develop (<0.1%) in patients with NFAT or MACE. Only 4.3% of patients with NFAT developed MACE, and preexisting MACE was unlikely to resolve (<0.1%). Hypertension, obesity, dyslipidemia, and type 2 diabetes were highly prevalent (60.0%, 42.0%, 33.7%, and 18.1% of patients, respectively) and were more likely to develop and worsen in MACE than NFAT. New cardiovascular events were more prevalent in MACE (15.5%) than NFAT (6.4%). Mortality was 11.2% and was similar between NFAT and MACE.

During follow-up, NFAT and MACE do not show clinically relevant changes in size or hormonal function, but they may carry an increased risk for cardiometabolic comorbid conditions.

Effect of 1-Month Dual #Antiplatelet Therapy Followed by Clopidogrel vs 12-Month Dual Antiplatelet Therapy on Cardiovascular and Bleeding Events in Patients Receiving #pci

https://jamanetwork.com/journals/jama/article-abstract/2736563

Very short mandatory dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with a drug-eluting stent may be an attractive option.

One-month DAPT was both noninferior and superior to 12-month DAPT for the primary end point, occurring in 2.36% with 1-month DAPT and 3.70% with 12-month DAPT (absolute difference, −1.34% 95% CI, −2.57% to −0.11%; hazard ratio HR, 0.64 95% CI, 0.42-0.98), meeting criteria for noninferiority (P < .001) and for superiority (P = .04). The major secondary cardiovascular end point occurred in 1.96% with 1-month DAPT and 2.51% with 12-month DAPT (absolute difference, −0.55% 95% CI, −1.62% to 0.52%; HR, 0.79 95% CI, 0.49-1.29), meeting criteria for noninferiority (P = .005) but not for superiority (P = .34). The major secondary bleeding end point occurred in 0.41% with 1-month DAPT and 1.54% with 12-month DAPT (absolute difference, −1.13% 95% CI, −1.84% to −0.42%; HR, 0.26 95% CI, 0.11-0.64; P = .004 for superiority).

Conclusions and Relevance Among patients undergoing PCI, 1 month of DAPT followed by clopidogrel monotherapy, compared with 12 months of DAPT with aspirin and clopidogrel, resulted in a significantly lower rate of a composite of cardiovascular and bleeding events, meeting criteria for both noninferiority and superiority. These findings suggest that a shorter duration of DAPT may provide benefit, although given study limitations, additional research is needed in other populations

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Detection of Brain Activation in Unresponsive Patients with Acute #Brain #Injury

https://lnkd.in/dUB9c9F

Brain activation in response to spoken motor commands can be detected by electroencephalography (EEG) in clinically unresponsive patients.

A total of 16 of 104 unresponsive patients (15%) had brain activation detected by EEG at a median of 4 days after injury. The condition in 8 of these 16 patients (50%) and in 23 of 88 patients (26%) without brain activation improved such that they were able to follow commands before discharge. At 12 months, 7 of 16 patients (44%) with brain activation and 12 of 84 patients (14%) without brain activation had a GOS-E level of 4 or higher, denoting the ability to function independently for 8 hours (odds ratio, 4.6; 95% confidence interval, 1.2 to 17.1).

CONCLUSIONS
A dissociation between the absence of behavioral responses to motor commands and the evidence of brain activation in response to these commands in EEG recordings was found in 15% of patients in a consecutive series of patients with acute brain injury.

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Association of Initiation of Maintenance #Dialysis with #functional Status and Caregiver Burden

https://cjasn.asnjournals.org/content/early/2019/06/26/CJN.13131118

Little is known about the functional course after initiating dialysis in elderly patients with ESKD

At the start of dialysis, 79% were care dependent in functional status. After 6 months, 40% experienced a decline in functional status, 34% remained stable, 18% improved, and 8% died. The prevalence of high caregiver burden increased from 23%–38% (P=0.004). In the multivariable analysis age (odds ratio, 1.05; 95% confidence interval, 1.00 to 1.10 per year older at baseline) and a high Groningen Frailty Indicator compared with low score (odds ratio, 1.97; 95% confidence interval, 1.05 to 3.68) were associated with functional decline/death.

Conclusions In patients aged ≥65 years, functional decline within the first 6 months after initiating dialysis is highly prevalent. The risk is higher in older and frail patients. Loss in functional status was mainly driven by decline in instrumental activities of daily life. Moreover, initiation of dialysis is accompanied by an increase in caregiver burden.

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Development and validation of a ceramide- and #phospholipid-based cardiovascular risk estimation score for #coronary artery disease patients

https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehz387/5519585

Distinct ceramide lipids have been shown to predict the risk for cardiovascular disease (CVD) events, especially cardiovascular death. As phospholipids have also been linked with CVD risk, we investigated whether the combination of ceramides with phosphatidylcholines (PCs) would be synergistic in the prediction of CVD events in patients with atherosclerotic coronary heart disease in three independent cohort studies

This score was highly significant in predicting CVD mortality multiadjusted hazard ratios (HRs; 95% confidence interval) per standard deviation were 1.44 (1.28–1.63) in WECAC, 1.47 (1.34–1.61) in the LIPID trial, and 1.69 (1.31–2.17) in KAROLA. In addition, a combination of the risk score with high-sensitivity troponin T increased the HRs to 1.63 (1.44–1.85) and 2.04 (1.57–2.64) in WECAC and KAROLA cohorts, respectively. The C-statistics in WECAC for the risk score combined with sex and age was 0.76 for CVD death. The ceramide-phospholipid risk score showed comparable and synergistic predictive performance with previously published CVD risk models for secondary prevention.

Conclusion
A simple ceramide- and phospholipid-based risk score can efficiently predict residual CVD event risk in patients with coronary artery disease.

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#Caffeine exposure induces #browning features in adipose tissue in vitro and in vivo

https://www.nature.com/articles/s41598-019-45540-1

Brown adipose tissue (BAT) is able to rapidly generate heat and metabolise macronutrients, such as glucose and lipids, through activation of mitochondrial uncoupling protein 1 (UCP1).

Diet can modulate UCP1 function but the capacity of individual nutrients to promote the abundance and activity of UCP1 is not well established. Caffeine consumption has been associated with loss of body weight and increased energy expenditure, but whether it can activate UCP1 is unknown

In vivo, drinking coffee (but not water) stimulated the temperature of the supraclavicular region, which co-locates to the main region of BAT in adult humans, and is indicative of thermogenesis.

Taken together, these results demonstrate that caffeine can promote BAT function at thermoneutrality and may have the potential to be used therapeutically in adult humans

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Association of #Carpal Tunnel Syndrome With #Amyloidosis, Heart #Failure, and Adverse Cardiovascular Outcomes

http://www.onlinejacc.org/content/74/1/15

Recent studies have suggested that transthyretin amyloidosis (ATTR) is a more common cause of heart failure (HF) than previously appreciated, and novel treatments for amyloidosis are emerging. About one-half of patients with ATTR cardiac amyloidosis have a history of carpal tunnel syndrome (CTS).

As expected, CTS was associated with a future diagnosis of amyloidosis (hazard ratio: 12.12 95% confidence interval: 4.37 to 33.60). CTS was associated with a higher incidence of HF, and this held true in the adjusted analysis yielding a hazard ratio of 1.54 (95% confidence interval: 1.45 to 1.64). No significant interaction with sex was found (p = 0.5). Risk of other adverse outcomes was also associated with CTS (p < 0.0001 for atrial fibrillation, atrioventricular heart block, and pacemaker implantation).

Conclusions Patients who undergo surgical treatment for CTS are associated with a higher risk of amyloidosis and HF relative to matched control subjects from the general population. Other cardiovascular outcomes were also increased with CTS.