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Association Between Incident Exposure to #Benzodiazepines in Early Pregnancy and Risk of Spontaneous #Abortion

https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2733517

Among pregnancies ending with SA, 375 (1.4%) were among women exposed to benzodiazepines in early pregnancy compared with 788 (0.6%) of the 134 305 matched control pregnancies (crude OR, 2.39; 95% CI, 2.10-2.73). Adjusting for potential confounders, including maternal mood and anxiety disorders before pregnancy, and compared with nonuse, benzodiazepine exposure in early pregnancy was associated with an increased risk of SA (adjusted OR, 1.85; 95% CI, 1.61-2.12). The risk was similar among pregnancies exposed to short-acting (284 exposed cases; adjusted OR, 1.81; 95% CI, 1.55-2.12) and long-acting (98 exposed cases; adjusted OR, 1.73; 95% CI, 1.31-2.28) benzodiazepines during early pregnancy. All benzodiazepine agents were independently associated with an increased risk of SA (range of adjusted ORs, 1.13-3.43).

Conclusions and Relevance An increased risk of SA was observed among early pregnancies with incident exposure to short and long-acting benzodiazepines and all specific benzodiazepine agents during early pregnancy. Insomnia, anxiety, and mood disorders are prevalent during pregnancy; clinicians should carefully evaluate the risk/benefit ratio of prescribing benzodiazepines in early pregnancy since alternative nonpharmacologic treatments exist.

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#Fracture Risk After Roux-en-Y Gastric Bypass vs Adjustable #Gastric Banding Among Medicare Beneficiaries

https://jamanetwork.com/journals/jamasurgery/article-abstract/2733040

Roux-en-Y gastric bypass (RYGB) is associated with significant bone loss and may increase fracture risk, whereas substantial bone loss and increased fracture risk have not been reported after adjustable gastric banding (AGB). Previous studies have had little representation of patients aged 65 years or older, and it is currently unknown how age modifies fracture risk.

..Site-specific analyses demonstrated an increased fracture risk at the hip (HR, 2.81; 95% CI, 1.82-4.49), wrist (HR, 1.70; 95% CI, 1.33-2.14), and pelvis (HR, 1.48; 95% CI, 1.08-2.07) among RYGB recipients. No significant interactions of fracture risk with age, sex, diabetes status, or race were found. In particular, adults 65 years and older showed similar patterns of fracture risk to younger adults. Sensitivity analyses using propensity score matching showed similar results (nonvertebral fracture: HR 1.75; 95% CI, 1.22-2.52).

Conclusions and Relevance This study of a large, US population–based cohort including a substantial population of older adults found a 73% increased risk of nonvertebral fracture after RYGB compared with AGB, including increased risk of hip, wrist, and pelvis fractures. Fracture risk was consistently increased among RYGB patients vs AGB across different subgroups, and to a similar degree among older and younger adults. Increased fracture risk appears to be an important unintended consequence of RYGB.

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Ultra-#Processed Diets Cause Excess #Calorie Intake and Weight Gain: An Inpatient Randomized Controlled Trial of Ad Libitum Food Intake

https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30248-7

We investigated whether ultra-processed foods affect energy intake in 20 weight-stable adults, aged (mean ± SE) 31.2 ± 1.6 years and BMI = 27 ± 1.5 kg/m2. Subjects were admitted to the NIH Clinical Center and randomized to receive either ultra-processed or unprocessed diets for 2 weeks immediately followed by the alternate diet for 2 weeks. Meals were designed to be matched for presented calories, energy density, macronutrients, sugar, sodium, and fiber. Subjects were instructed to consume as much or as little as desired. Energy intake was greater during the ultra-processed diet (508 ± 106 kcal/day; p = 0.0001), with increased consumption of carbohydrate (280 ± 54 kcal/day; p < 0.0001) and fat (230 ± 53 kcal/day; p = 0.0004), but not protein (−2 ± 12 kcal/day; p = 0.85). Weight changes were highly correlated with energy intake (r = 0.8, p < 0.0001), with participants gaining 0.9 ± 0.3 kg (p = 0.009) during the ultra-processed diet and losing 0.9 ± 0.3 kg (p = 0.007) during the unprocessed diet.

Limiting consumption of ultra-processed foods may be an effective strategy for obesity prevention and treatment.

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Daily #aspirin use associated with reduced risk for fibrosis progression in patients with nonalcoholic fatty #liver disease

https://www.cghjournal.org/article/S1542-3565(19)30493-8/fulltext

Compared with non-regular use, daily aspirin use was associated with significantly lower odds of NASH (adjusted odds ratio, 0.68; 95% CI, 0.37–0.89) and fibrosis (adjusted odds ratio, 0.54; 95% CI, 0.31–0.82). Among individuals with baseline F0–F2 fibrosis (n=317), 86 developed advanced fibrosis over 3692 person-years. Daily aspirin users had significantly lower risk for developing incident advanced fibrosis vs non-regular users (adjusted hazard ratio aHR, 0.63; 95% CI. 0.43–0.85). This relationship appeared to be duration dependent (adjusted P trend=.026), with the greatest benefit found with at least 4 years or more of aspirin use (aHR, 0.50; 95% CI, 0.35–0.73). Conversely, use of nonaspirin NSAIDs was not associated with risk for advanced fibrosis (aHR, 0.93; 95% CI, 0.81–1.05).

Conclusions
In a prospective study of patients with biopsy-proven NAFLD, daily aspirin use was associated with less severe histologic features of NAFLD and NASH, and lower risk for progression to advanced fibrosis with time.

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Association of Age With Short-term and Long-term #Mortality Among Patients Discharged From #Intensive Care Units in France

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2733169?resultClick=3

An aging population is increasing the need for intensive care unit (ICU) beds. The benefit of ICU admission for elderly patients remains a subject of debate; however, long-term outcomes across all adult age strata are unknown.

rge mortality rates, respectively, were 30.5% and 44.9% in patients 80 years and older compared with 16.5% and 22.5% in those younger than 80 years. Total 3-year mortality was 61.4% among patients 80 years and older vs 35.1% in those younger than 80. After age and sex standardization, excess mortality was highest among young patients during their first year after hospital discharge and persisted into the second and third years. In contrast, the mortality risk was close to the general population risk among elderly patients (≥80 years). Age and reason for hospitalization were strongly associated with long-term mortality (9-, 13-, and 20-fold increase in the risk of death 3 years after ICU discharge in patients aged 80-84, 85-89, and ≥90 years, respectively, compared with patients aged <35 years), while organ support use during ICU showed a weaker association (all organ support had 1.3-fold or lower increase in the risk of death).

Conclusions and Relevance Results of this study suggest that aging was associated with an increased risk of mortality in the 3 years after hospital discharge that included an ICU admission, with a sharp increase in those 80 years and older. However, compared with the general population matched by age and sex, excess long-term mortality was high in young surviving patients but not in elderly patients.

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Association of High Intakes of Vitamins #B6 and #B12 From Food and Supplements With Risk of Hip #Fracture Among Postmenopausal Women in the Nurses’ Health Study

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2733176

..Median (interquartile range) cumulative average intakes of total vitamins B6 and B12 were 3.6 (4.8) mg/d and 12.1 (11.7) μg/d, respectively. Both vitamin B6 (RR, 1.29; 95% CI, 1.04-1.59 for an intake of ≥35 vs <2 mg/d; P = .06 for linear trend) and vitamin B12 (RR, 1.25; 95% CI, 0.98-1.58 for an intake of ≥30 vs <5 μg/d; P = .02 for linear trend) were associated with increased fracture risk. Risk was highest in women with a combined high intake of both vitamins (B6 ≥35 mg/d and B12 ≥20 μg/d), exhibiting an almost 50% increased risk of hip fracture (RR, 1.47; 95% CI, 1.15-1.89) compared with women with a low intake of both vitamins (B6 <2 mg/d and B12 <10 μg/d).

Conclusions and Relevance In this cohort study, a combined high intake of vitamins B6 and B12 was associated with an increased risk of hip fracture. The intakes were far higher than the recommended dietary allowances. These findings add to previous studies suggesting that vitamin supplements should be used cautiously because adverse effects can occur.

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Controlled Trial of #Budesonide– #Formoterol as Needed for Mild #Asthma

https://www.nejm.org/doi/full/10.1056/NEJMoa1901963

In double-blind, placebo-controlled trials, budesonide–formoterol used on an as-needed basis resulted in a lower risk of severe exacerbation of asthma than as-needed use of a short-acting β2-agonist (SABA); the risk was similar to that of budesonide maintenance therapy plus as-needed SABA..

..The number of severe exacerbations was lower in the budesonide–formoterol group than in both the albuterol group (9 vs. 23; relative risk, 0.40; 95% CI, 0.18 to 0.86) and the budesonide maintenance group (9 vs. 21; relative risk, 0.44; 95% CI, 0.20 to 0.96). The mean (±SD) dose of inhaled budesonide was 107±109 μg per day in the budesonide–formoterol group and 222±113 μg per day in the budesonide maintenance group. The incidence and type of adverse events reported were consistent with those in previous trials and with reports in clinical use.

CONCLUSIONS
In an open-label trial involving adults with mild asthma, budesonide–formoterol used as needed was superior to albuterol used as needed for the prevention of asthma exacerbations.

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Association Between #Statin Use and Risk of #dementia After a Concussion

https://jamanetwork.com/journals/jamaneurology/article-abstract/2733673

Concussions are an acute injury that may lead to chronic disability, while statin use might improve neurologic recovery.

This study identified 28 815 patients diagnosed as having a concussion (median age, 76 years; 61.3% female), of whom 7058 (24.5%) received a statin, and 21 757 (75.5%) did not receive a statin. A total of 4727 patients subsequently developed dementia over a mean follow-up of 3.9 years, equal to an incidence of 1 case per 6 patients. Patients who received a statin had a 13% reduced risk of dementia compared with patients who did not receive a statin (relative risk, 0.87; 95% CI, 0.81-0.93; P < .001). The decreased risk of dementia associated with statin use applied to diverse patient groups, remained independent of other cardiovascular medication use, intensified over time, was distinct from the risk of subsequent depression, and was not observed in patients after an ankle sprain.

Conclusions and Relevance In this study, older adults had a substantial long-term risk of dementia after a concussion, which was associated with a modest reduction among patients receiving a statin.

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Risks and clinical predictors of #cirrhosis and #hepatocellular #carcinoma diagnoses in adults with diagnosed NAFLD: real-world study of 18 million patients in four European cohorts

https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-019-1321-x

Non-alcoholic fatty liver disease (NAFLD) is a common condition that progresses in some patients to steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC)..

Coded NAFLD/NASH patients were more likely to have diabetes, hypertension and obesity than matched controls. HR for cirrhosis in patients compared to controls was 4.73 (95% CI 2.43–9.19) and for HCC, 3.51 (95% CI 1.72–7.16). HR for either outcome was higher in patients with NASH and those with high-risk Fib-4 scores. The strongest independent predictor of a diagnosis of HCC or cirrhosis was baseline diagnosis of diabetes.

Conclusions
Real-world population data show that recorded diagnosis of NAFLD/NASH increases risk of life-threatening liver outcomes. Diabetes is an independent predictor of advanced liver disease diagnosis, emphasising the need to identify specific groups of patients at highest risk.

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Identifying Changepoints in #Biomarkers During the Preclinical Phase of #Alzheimer’s Disease

https://www.frontiersin.org/articles/10.3389/fnagi.2019.00074/full

A single measure, CSF t-tau, had an early changepoint (34 years prior to symptom onset). A group of measures, including the remaining CSF measures (CSF Abeta and phosphorylated tau) and all cognitive tests had changepoints 10–15 years prior to symptom onset. A second group is formed by medial temporal lobe shape composite measures, with a 6-year time difference between the right and left side (respectively nine and 3 years prior to symptom onset).

Conclusion: These findings highlight the long period of time prior to symptom onset during which AD pathology is accumulating in the brain. There are several significant findings, including the early changes in cognition and the laterality of the MRI findings. Additional work is needed to clarify their significance.

Association Between Parental Medical Claims for #Opioid Prescriptions and Risk of #Suicide Attempt by Their Children

https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2733148

Of the children with parents who did not use opioids, 212 (0.14%) attempted suicide; of the children with parents who did use opioids, 678 (0.37%) attempted suicide. Parental use of opioids was associated with a doubling of the risk of a suicide attempt by their offspring (odds ratio OR, 1.99; 95% CI, 1.71-2.33). The association remained significant after adjusting for child age and sex (OR, 1.85; 95% CI, 1.58-2.17), addition of child and parental depression and diagnoses of substance use disorder (OR, 1.46; 95% CI, 1.24-1.72), and addition of parental history of suicide attempt (OR, 1.45; 95% CI, 1.23-1.71). Geographical variation in opioid use did not change the association (OR, 2.00; 95% CI, 1.71-2.34).

Conclusions and Relevance Children of parents who use prescription opioids are at increased risk for suicide attempts, which could be a contributing factor to the time trend in adolescent suicidality. The care of families with a parent who uses opioids should include mental health screening of their children.

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Sex Differences in the Relationship Between #Inflammation and Reward Sensitivity: A Randomized Controlled Trial of #Endotoxin

https://www.sciencedirect.com/science/article/pii/S2451902219300795?via%3Dihub

There are robust sex differences in the prevalence of depression. Inflammation and anhedonia may play a role in understanding these sex differences. Indeed, sex differences in inflammation-induced neural responses to reward may provide insight into the sex gaps in depression, but no study has examined this question.

As such, the current study examined whether there were sex differences in reward-related neural activity (i.e., ventral striatum VS activity) in response to an experimental inflammatory challenge.

Results
Results demonstrated that endotoxin (vs. placebo) led to reduced VS activity in anticipation of reward and that there were sex differences in this effect. Specifically, in female participants, endotoxin (vs. placebo) led to decreased VS activity in anticipation of reward, but this effect was not present in male participants. In addition, within the endotoxin condition, decreases in VS activity in anticipation of reward were related to increases in inflammation for female but not male participants.

Conclusions
These findings may have implications for understanding how inflammation may contribute to sex differences in rates of depression

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Effects of #antiplatelet therapy after stroke due to intracerebral #haemorrhage (RESTART): a randomised, open-label trial

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)30840-2/fulltext

Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear

Participants were followed for a median of 2·0 years (IQR 1·0– 3·0; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 95% CI 0·25–1·03; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 0·39–1·30; p=0·27), and 39 15% participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 14% allocated to avoid antiplatelet therapy (1·02 0·65–1·60; p=0·92).
Interpretation
These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention.

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#Vision impairment and subjective #cognitive decline- related functional limitations

https://www.cdc.gov/mmwr/volumes/68/wr/mm6820a2.htm?s_cid=mm6820a2_w

Vision impairment often co-occurs with cognitive decline, which can be associated with functional limitations. The association between vision impairment and functional limitations related to subjective (self-reported) cognitive decline (SCD) has not been well characterized.

Analysis of 2015–2017 Behavioral Risk Factor Surveillance System data determined that, after adjusting for age and other demographic and smoking characteristics, 18% of adults who reported vision impairment also reported SCD-related functional limitations, compared with only 4% of those without vision impairment.

What are the implications for public health practice?

Prevention or correction of vision impairment might be important in in reducing functional limitations related to cognitive decline in adults aged ≥45 years.

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#Neurocognitive development in perinatally #HIV-infected adolescents on long-term treatment compared to healthy matched controls: a longitudinal study

https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciz386/5492020

Cross-sectional analysis of the NOVICE cohort showed significant cognitive impairment in combination antiretroviral therapy (cART)-treated perinatally HIV-infected adolescents (PHIV+) compared to age-, sex-, ethnicity- and socioeconomic status (SES)-matched HIV-negative controls (HIV-).

Processing speed, working memory, learning ability and visual-motor function trajectories were not statistically different between groups. Univariately, those who had started cART at older age deviated more in executive functioning (-0.13 z-score, 95%CI -0.24 to -0.02, p=0.043). The prevalence of cognitive impairment by MNC was similar in both groups at both time-points.

Conclusions
cART-treated PHIV+ adolescents appear to have similar global cognitive development compared to healthy peers. Executive functioning trajectory appears to deviate, potentially explained by earlier brain damage.

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Association of #Frailty and Postoperative Complications With Unplanned Readmissions After Elective Outpatient #Surgery

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2734068

length of stay (LOS)

.. In multivariate analysis, frailty doubled the risk of unplanned readmission (LOS = 0: adjusted relative risk RR, 2.1; 95% CI, 2.0-2.3; LOS ≥ 1: adjusted RR, 1.8; 95% CI, 1.6-2.1). Complications occurred in 3.1% of the entire cohort, and frailty was associated with increased risk of complications (unadjusted RR, 2.6; 95% CI, 2.4-2.8). Mediation analysis confirmed that complications are a significant mediator in the association between frailty and readmissions; however, it also indicated that the association of frailty with readmission was only partially mediated by complications (LOS = 0, 22.8%; LOS ≥ 1, 29.3%).

Conclusions and Relevance These findings suggest that frailty is a significant risk factor for unplanned readmission after elective outpatient surgery both independently and when partially mediated through increased complications. Screening for frailty might inform the development of interventions to decrease unplanned readmissions, including those for outpatient procedures.

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#Plastic leachates impair growth and oxygen production in Prochlorococcus, the ocean’s most abundant #photosynthetic bacteria

https://www.nature.com/articles/s42003-019-0410-x

Plastic pollution is a global threat to marine ecosystems. Plastic litter can leach a variety of substances into marine environments; however, virtually nothing is known regarding how this affects photosynthetic bacteria at the base of the marine food web.

..We show leachate exposure strongly impairs Prochlorococcus in vitro growth and photosynthetic capacity and results in genome-wide transcriptional changes. The strains showed distinct differences in the extent and timing of their response to each leachate.

Consequently, plastic leachate exposure could influence marine Prochlorococcus community composition and potentially the broader composition and productivity of ocean phytoplankton communities

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Low plasma #adropin concentrations increase risks of #weight gain and metabolic dysregulation in response to a high-sugar diet in male nonhuman primates

http://m.jbc.org/content/early/2019/04/15/jbc.RA119.007528

Mouse studies linking adropin, a peptide hormone encoded by the energy homeostasis associated (ENHO) gene, to biological clocks and to glucose and lipid metabolism suggest a potential therapeutic target for managing diseases of metabolism. However, adropin’s roles in human metabolism are unclear.

ENHO expression is abundant in brain, including ventromedial and lateral hypothalamic nuclei regulating appetite and autonomic function. Lower ENHO expression is present in liver, lung, kidney, ileum, and some endocrine glands. Hepatic ENHO expression associates with genes involved in glucose and lipid metabolism.

During consumption of a high sugar (fructose) diet which induced 10% weight gain, animals with low adropin had larger increases of plasma leptin and more severe hyperglycemia. Declining adropin concentrations were correlated with increases of plasma APOC3 and triglycerides.

In summary, peripheral ENHO expression associates with pathways related to epigenetic and neural pathways, and carbohydrate and lipid metabolism, suggesting co-regulation in nonhuman primates. Low circulating adropin predicts increased weight gain and metabolic dysregulation during consumption of a high-sugar diet.

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Blood #Pressure-Lowering by the Antioxidant #Resveratrol is Counterintuitively Mediated by Oxidation of cGMP-Dependent Protein Kinase

https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.118.037398

The polyphenolic rings of resveratrol enable it to react with and detoxify otherwise injurious oxidants. Whilst the protective actions of resveratrol are commonly ascribed to its antioxidant activity, here we show that this is a misconception

Oxidation of the phenolic rings of resveratrol paradoxically leads to oxidative modification of proteins, explained by formation of a reactive quinone that oxidises the thiolate side chain of cysteine residues - events that were enhanced in cells under oxidative stress. Consistent with these observations and its ability to induce vasodilation, resveratrol induced oxidative activation of PKG1α and lowered blood pressure in hypertensive wild-type mice, but not C42S PKG1α knock-in mice that are resistant to disulfide activation.

Conclusions: Resveratrol mediates lowering of blood pressure by paradoxically inducing protein oxidation, especially during times of oxidative stress, a mechanism that may be a common feature of 'antioxidant' molecules.