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.

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Research
Dietary #fats and mortality among patients with type 2 #diabetes: analysis in two population based cohort studies

https://www.bmj.com/content/366/bmj.l4009

..After multivariate adjustment, intake of polyunsaturated fatty acids (PUFAs) was associated with a lower cardiovascular disease mortality, compared with total carbohydrates: hazard ratios comparing the highest with the lowest quarter were 0.76 (95% confidence interval 0.58 to 0.99; P for trend=0.03) for total PUFAs, 0.69 (0.52 to 0.90; P=0.007) for marine n-3 PUFAs, 1.13 (0.85 to 1.51) for α-linolenic acid, and 0.75 (0.56 to 1.01) for linoleic acid. Inverse associations with total mortality were also observed for intakes of total PUFAs, n-3 PUFAs, and linoleic acid, whereas monounsaturated fatty acids of animal, but not plant, origin were associated with a higher total mortality.

In models that examined the theoretical effects of substituting PUFAs for other fats, isocalorically replacing 2% of energy from saturated fatty acids with total PUFAs or linoleic acid was associated with 13% (hazard ratio 0.87, 0.77 to 0.99) or 15% (0.85, 0.73 to 0.99) lower cardiovascular disease mortality, respectively. A 2% replacement of energy from saturated fatty acids with total PUFAs was associated with 12% (hazard ratio 0.88, 0.83 to 0.94) lower total mortality.

Conclusions In patients with type 2 diabetes, higher intake of PUFAs, in comparison with carbohydrates or saturated fatty acids, is associated with lower total mortality and cardiovascular disease mortality. These findings highlight the important role of quality of dietary fat in the prevention of cardiovascular disease and total mortality among adults with type 2 diabetes.

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New concepts for body #shape-related #cardiovascular risk: role of fat distribution and adipose tissue function

https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehz411/5524772

While obesity is clearly associated with an increased risk for atherosclerotic cardiovascular disease (ASCVD), individuals with very low body weight are not characterized by reduced ASCVD events.2 Indeed, body weight and ASCVD show a U-shaped association.

The lower turning point of this U-curve for ASCVD or total mortality has increased over the years to a body mass index (BMI) of depicting an increase of risk not only for higher but similarly for lower body weight.

In addition, not everybody with obesity develops premature atherosclerosis and there is substantial variation in cardiovascular risk even in individuals with normal BMI.

Independently of other risk factors including smoking, LDL-cholesterol, hypertension, diabetes, and others, an unfavourable fat distribution characterized by increased central, abdominal, or trunk fat emerged as a stronger predictor for ASCVD and mortality than BMI or body fat mass.

In contrast, predominant fat accumulation in the lower body as measured by a higher leg to total body fat ratio is associated with a lower ASCVD risk. Collectively, there is epidemiological evidence that fat distribution determines cardiovascular morbidity and mortality more strongly than increased fat mass itself

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Cause‐Specific #Mortality in #Gout: Novel Findings of Elevated Risk of Non‐Cardiovascular Related Deaths

https://onlinelibrary.wiley.com/doi/abs/10.1002/art.41008

Persons with gout had higher prevalence of chronic kidney disease, metabolic and CV comorbidities. Gout was associated with 17% increased hazard of all‐cause mortality (HR 1.17, 95% confidence interval 1.14‐1.21) overall, and 23% (HR 1.23, 1.17‐1.30) in women and 15% (HR 1.15, 1.10‐1.19) in men. In terms of cause‐specific mortality, the strongest associations were seen for the relation of gout to risk of death due to renal disease (HR of 1.78, 1.34‐2.35), diseases of digestive system (HR 1.56, 1.34‐1.83), CV diseases (HR 1.27, 1.22‐1.33), infections (HR 1.20, 1.06‐1.35), dementia (HR 0.83, 0.72‐0.97).

Conclusions
Several non‐CV causes of mortality are increased in persons with gout, highlighting the need for improved management of comorbidities

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Sequential #LASER ART and CRISPR Treatments Eliminate #HIV-1 in a Subset of Infected Humanized Mice

https://www.nature.com/articles/s41467-019-10366-y

Elimination of HIV-1 requires clearance and removal of integrated proviral DNA from infected cells and tissues. Here, sequential long-acting slow-effective release antiviral therapy (LASER ART) and CRISPR-Cas9 demonstrate viral clearance in latent infectious reservoirs in HIV-1 infected humanized mice.

HIV-1 subgenomic DNA fragments, spanning the long terminal repeats and the Gag gene, are excised in vivo, resulting in elimination of integrated proviral DNA; virus is not detected in blood, lymphoid tissue, bone marrow and brain by nested and digital-droplet PCR as well as RNAscope tests. No CRISPR-Cas9 mediated off-target effects are detected.

...These data provide proof-of-concept that permanent viral elimination is possible.

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Association of Radioactive #Iodine Treatment With Cancer Mortality in Patients With #Hyperthyroidism

https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2737319

Radioactive iodine (RAI) has been used extensively to treat hyperthyroidism since the 1940s. Although widely considered a safe and effective therapy, RAI has been associated with elevated risks of total and site-specific cancer death among patients with hypothyroidism.

Mean total administered activity of sodium iodide I 131 was 375 MBq for patients with Graves disease and 653 MBq for patients with toxic nodular goiter. Mean organ or tissue dose estimates ranged from 20 to 99 mGy (colon or rectum, ovary, uterus, prostate, bladder, and brain/central nervous system), to 100 to 400 mGy (pancreas, kidney, liver, stomach, female breast, lung, oral mucosa, and marrow), to 1.6 Gy (esophagus), and to 130 Gy (thyroid gland)...


Conclusions and Relevance

In RAI-treated patients with hyperthyroidism, greater organ-absorbed doses appeared to be modestly positively associated with risk of death from solid cancer, including breast cancer. Additional studies are needed of the risks and advantages of all major treatment options available to patients with hyperthyroidism.

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Low-density #lipoprotein cholesterol and risk of intracerebral #hemorrhage
A prospective study

https://n.neurology.org/content/early/2019/07/02/WNL.0000000000007853

We identified 753 incident ICH cases during 9 years of follow-up. The ICH risk was similar among participants with LDL concentrations of 70 to 99 mg/dL and those with LDL-C concentrations ≥100 mg/dL.

In contrast, participants with LDL-C concentrations <70 mg/dL had a significantly higher risk of developing ICH than those with LDL-C concentrations of 70 to 99 mg/dL;

adjusted hazard ratios were 1.65 (95% confidence interval CI 1.32–2.05) for LDL-C concentrations of 50 to 69 mg/dL and 2.69 (95% CI 2.03–3.57) for LDL-C concentrations <50 mg/dL.

Conclusions

We observed a significant association between lower LDL-C and higher risk of ICH when LDL-C was <70 mg/dL, and the association became nonsignificant when LDL-C ≥70 mg/dL. These data can help determination of the ideal LDL range in patients who are at increased risk of both atherosclerotic disease and hemorrhagic stroke and guide planning of future lipid-lowering studies.

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Shining the light on #eating disorders, incidence, prognosis and profiling of patients in primary and secondary care: national data linkage study

https://www.cambridge.org/core/journals/the-british-journal-of-psychiatry/article/shining-the-light-on-eating-disorders-incidence-prognosis-and-profiling-of-patients-in-primary-and-secondary-care-national-data-linkage-study/A00E32E32B0FB324075CF2CF0973687F

Diagnosing eating disorders can be difficult and few people with the disorder receive specialist services despite the associated high morbidity and mortality.

The incidence peaked at 24 per 100 000 people in 2003/04. People with eating disorders showed higher levels of other mental disorders (odds ratio 4.32, 95% CI 4.01–4.66) and external causes of morbidity and mortality (odds ratio 2.92, 95% CI 2.44–3.50). They had greater prescription of central nervous system drugs (odds ratio 3.15, 95% CI 2.97–3.33), gastrointestinal drugs (odds ratio 2.61, 95% CI 2.45–2.79) and dietetic drugs (odds ratio 2.42, 95% CI 2.24–2.62) before diagnosis. These excess diagnoses and prescriptions remained 3 years after diagnosis. Mortality was raised compared with controls for some eating disorders, particularly in females with anorexia nervosa.

Conclusions
Incidence of diagnosed eating disorders is relatively low in the population but there is a major longer term burden in morbidity and mortality to the individual.

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#Electronic Cigarette Use and Myocardial #Infarction Among Adults in the US Population Assessment of Tobacco and Health

https://www.ahajournals.org/doi/10.1161/JAHA.119.012317

Every‐day (adjusted odds ratio, 2.25, 95% CI: 1.23–4.11) and some‐day (1.99, 95% CI: 1.11–3.58) e‐cigarette use were independently associated with increased odds of having had an MI with a significant dose‐response (P<0.0005). Odds ratio for daily dual use of both products was 6.64 compared with a never cigarette smoker who never used e‐cigarettes. Having had a myocardial infarction at Wave 1 did not predict e‐cigarette use at Wave 2 (P>0.62), suggesting that reverse causality cannot explain the cross‐sectional association between e‐cigarette use and MI observed at Wave 1.

Conclusions

Some‐day and every‐day e‐cigarette use are associated with increased risk of having had a myocardial infarction, adjusted for combustible cigarette smoking. Effect of e‐cigarettes are similar as conventional cigarette and dual use of e‐cigarettes and conventional cigarettes at the same time is risker than using either product alone.

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#Neuropsychiatric Sequelae in Adolescents With Acute Synthetic #Cannabinoid Toxicity

https://pediatrics.aappublications.org/content/early/2019/07/04/peds.2018-2690

Adolescents presenting to the ED with SC-only exposure (n = 107) had higher odds of coma and/or central nervous system depression (odds ratio OR 3.42; 95% confidence interval CI 1.51–7.75) and seizures (OR 3.89; 95% CI 1.39–10.94) than those with cannabis-only exposure (n = 86). SC-only drug exposure was associated with lower odds of agitation than cannabis-only exposure (OR 0.18; 95% CI 0.10–0.34). In contrast, the group with SC-polydrug exposures (n = 38) had higher odds of agitation (OR 3.11; 95% CI 1.56–7.44) and seizures (OR 4.8; 95% CI 1.80–12.74) than the cannabis-polydrug exposures group (n = 117).

CONCLUSIONS: In this multisite cohort of US adolescents assessed in the ED, SC exposure was associated with higher odds of neuropsychiatric morbidity than cannabis exposure providing a distinct neurospychiatric profile of acute SC toxicity in adolescents.

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A four‐group #urine risk classifier for predicting outcomes in patients with #prostate cancer

https://onlinelibrary.wiley.com/doi/10.1111/bju.14811

To develop a risk classifier using urine‐derived extracellular vesicle (EV)‐RNA capable of providing diagnostic information on disease status prior to biopsy, and prognostic information for men on active surveillance (AS).

PUR‐4 status predicted the presence of clinically significant intermediate‐ or high‐risk disease (area under the curve = 0.77, 95% confidence interval CI 0.70–0.84). Application of PUR provided a net benefit over current clinical practice. In an AS sub‐cohort (n = 87), groups defined by PUR status and proportion of PUR‐4 had a significant association with time to progression (interquartile range hazard ratio HR 2.86, 95% CI 1.83–4.47; P < 0.001). PUR‐4, when used continuously, dichotomized patient groups with differential progression rates of 10% and 60% 5 years after urine collection (HR 8.23, 95% CI 3.26–20.81; P < 0.001).

Conclusion
Urine‐derived EV‐RNA can provide diagnostic information on aggressive prostate cancer prior to biopsy, and prognostic information for men on AS. PUR represents a new and versatile biomarker that could result in substantial alterations to current treatment of patients with prostate cancer.

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Excess #Antibiotic Treatment Duration and Adverse Events in Patients Hospitalized With #Pneumonia: A Multihospital Cohort Study

https://annals.org/aim/article-abstract/2737823/excess-antibiotic-treatment-duration-adverse-events-patients-hospitalized-pneumonia-multihospital

..Excess days were calculated by subtracting each patient's shortest effective (expected) treatment duration (based on time to clinical stability, pathogen, and pneumonia classification community-acquired vs. health care–associated) from the actual duration.

..Excess treatment was not associated with lower rates of any adverse outcomes, including death, readmission, emergency department visit, or Clostridioides difficile infection. Each excess day of treatment was associated with a 5% increase in the odds of antibiotic-associated adverse events reported by patients after discharge.

Conclusion:
Patients hospitalized with pneumonia often receive excess antibiotic therapy. Excess antibiotic treatment was associated with patient-reported adverse events. Future interventions should focus on whether reducing excess treatment and improving documentation at discharge improves outcomes.

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A Nationwide Flash-Mob Study for Suspected Acute #Coronary Syndrome

http://www.annfammed.org/content/17/4/296.abstract

Our primary objective was to evaluate the Marburg Heart Score (MHS), a clinical decision rule, or to develop an adapted clinical decision rule for family physicians (FPs) to safely rule out acute coronary syndrome (ACS) in patients referred to secondary care for suspected ACS..

..A final diagnosis was obtained for 243 patients (94.2%), of whom 45 (18.5%) received a diagnosis of ACS. Sex, sex-adjusted age, and ischemic changes on electrocardiography were significantly associated with ACS. The sensitivity of the MHS (cut-off ≤2) was 75.0%, specificity was 44.0%, positive predictive value was 24.3%, and negative predictive value was 88.0%. For the FP assessment (cut-off ≤5), these test characteristics were 86.7%, 41.4%, 25.2%, and 93.2%, respectively.

CONCLUSIONS For patients referred to emergency care, ACS could not be safely ruled out using the MHS or FP clinical assessment. The flash-mob study design may be a feasible alternative research method to investigate relatively simple, clinically relevant research questions in family medicine on a large scale and over a relatively short time frame.

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Comorbidities in #Osteoarthritis: A systematic review and meta‐analysis of observational studies

https://onlinelibrary.wiley.com/doi/abs/10.1002/acr.24008

Pooled prevalence of any comorbidity was 67% (95%CI: 57%‐74%) in people with OA versus 56% (95%CI: 44%‐68%) in people without OA. The pooled PR for any comorbidity was 1.21 (95%CI: 1.02‐1.45). The PR increased from 0.73 (95%CI: 0.43‐1.25) for one comorbidity, to 1.58 (95%CI: 1.03‐2.42) for two, and 1.94 (95%CI 1.45‐ 2.59) for three or more comorbidities. The key comorbidities associated with OA were stroke (PR 2.61; 95%CI: 2.13‐3.21), peptic ulcer (PR 2.36; 95%CI: 1.71‐3.27) and metabolic syndrome (PR 1.94; 95%CI 1.21‐3.12).

Conclusions
People with OA are more likely to have other chronic conditions. The association is dose‐dependent in terms of the number of comorbidities, suggesting multimorbidities. Further studies on the causality of this association and clinical implications are needed.

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Effectiveness of a #treadmill-based aerobic exercise intervention on pain, daily functioning, and quality of life in women with primary #dysmenorrhea: A randomized controlled trial

https://www.contemporaryclinicaltrials.com/article/S1551-7144(19)30050-3/fulltext?mobileUi=0

Objective
To evaluate the effectiveness of a treadmill-based aerobic exercise intervention on pain and associated symptoms of primary dysmenorrhea..

After the 4-week training, compared to the control group exercise significantly improved primary outcomes pain quality (mean difference (MD) -1.9, 95% CI 3.8 to −0.04, p < .05), and intensity (MD -4.7, 95% CI -9.3 to −0.09, p < .05), but not present pain. Significant effects were also reported for pain interference (MD -1.7, 95% CI -3.4 to −0.02, p < .05) at 4 weeks; the other outcomes did not significantly differ between groups at this time. During the follow-up period of 7-months, the effect on pain improved to 22 mm (95% CI 18 to 25). Significant benefits of exercise were maintained up to 7-months for present pain, QoL and daily functioning.

Conclusion
Exercise has significant effects on primary dysmenorrhea-related pain, QoL and function.

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#C-Reactive Protein Testing to Guide Antibiotic Prescribing for #COPD Exacerbations

https://www.nejm.org/doi/full/10.1056/NEJMoa1803185

Point-of-care testing of C-reactive protein (CRP) may be a way to reduce unnecessary use of antibiotics without harming patients who have acute exacerbations of chronic obstructive pulmonary disease (COPD).

A lower percentage of patients in the CRP-guided group than in the usual-care group received an antibiotic prescription at the initial consultation (47.7% vs. 69.7%, for a difference of 22.0 percentage points; adjusted odds ratio, 0.31; 95% CI, 0.21 to 0.45) and during the first 4 weeks of follow-up (59.1% vs. 79.7%, for a difference of 20.6 percentage points; adjusted odds ratio, 0.30; 95% CI, 0.20 to 0.46). Two patients in the usual-care group died within 4 weeks after randomization from causes considered by the investigators to be unrelated to trial participation.

CONCLUSIONS
CRP-guided prescribing of antibiotics for exacerbations of COPD in primary care clinics resulted in a lower percentage of patients who reported antibiotic use and who received antibiotic prescriptions from clinicians, with no evidence of harm.