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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.

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#Sugary drink consumption and risk of #cancer: results from NutriNet-Santé prospective cohort

https://www.bmj.com/content/366/bmj.l2408

To assess the associations between the consumption of sugary drinks (such as sugar sweetened beverages and 100% fruit juices), artificially sweetened beverages, and the risk of cancer.

The consumption of sugary drinks was significantly associated with the risk of overall cancer (n=2193 cases, subdistribution hazard ratio for a 100mL/d increase 1.18, 95% confidence interval 1.10 to 1.27, P<0.0001) and breast cancer (693, 1.22, 1.07 to 1.39, P=0.004). The consumption of artificially sweetened beverages was not associated with the risk of cancer. In specific subanalyses, the consumption of 100% fruit juice was significantly associated with the risk of overall cancer (2193, 1.12, 1.03 to 1.23, P=0.007).


In this large prospective study, the consumption of sugary drinks was positively associated with the risk of overall cancer and breast cancer. 100% fruit juices were also positively associated with the risk of overall cancer. These results need replication in other large scale prospective studies. They suggest that sugary drinks, which are widely consumed in Western countries, might represent a modifiable risk factor for cancer prevention.

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Pandemic uropathogenic #fluoroquinolone-resistant #Escherichia coli have enhanced ability to persist in the gut and cause bacteriuria in healthy women

https://academic.oup.com/cid/advance-article-abstract/doi/10.1093/cid/ciz547/5528138

We report that fluoroquinolone resistant Escherichia coli are found in feces of 8.8% healthy adult women, with most bacteria belonging to pandemic multi-drug resistant ST131-H30R or ST1193 clonal groups.

Moreover, these highly uropathogenic clonal groups demonstrate an especially prolonged gut persistence and high rate of bacteriuria without documented UTI.

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Critical Role of the Interaction Gut #Microbiota – Sympathetic Nervous System in the Regulation of Blood #pressure

https://www.frontiersin.org/articles/10.3389/fphys.2019.00231/full

Association between gut dysbiosis and neurogenic diseases, such as hypertension, has been described. The aim of this study was to investigate whether changes in the gut microbiota alter gut-brain interactions inducing changes in blood pressure (BP).

..Increased levels of pro-inflammatory cytokines, tyrosine hydroxylase mRNA levels and NA content in the proximal colon, whereas reduced mRNA levels of gap junction proteins, were found in the S-S group as compared to the W-W group. These changes were inhibited by FMT from WKY to SHR. According to our correlation analyses, the abundance of Blautia and Odoribacter showed a negative correlation with high SBP.

In conclusion, in SHR gut microbiota is an important factor involved in BP control, at least in part, as consequence of its effect on neuroinflammation and the sympathetic nervous system activity.

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Association of Lifespan #Cognitive Reserve Indicator With #Dementia Risk in the Presence of Brain Pathologies

https://jamanetwork.com/journals/jamaneurology/fullarticle/2738336

Information on CR factors (education; early-life, midlife, and late-life cognitive activities; and social activities in late life) was obtained at baseline. Based on these factors, lifespan CR scores were captured using a latent variable from a structural equation model and was divided into tertiles (lowest, middle, and highest)

In autopsied participants, CR was not associated with most brain pathologies, and the association of CR with dementia remained significant after additional adjustment for brain pathologies (HR, 0.60; 95% CI, 0.42-0.86). The highest CR score tertile was associated with a reduction in dementia risk, even among participants with high Alzheimer disease pathology (HR, 0.57; 95% CI, 0.37-0.87) and any gross infarcts (HR, 0.34; 95% CI, 0.18-0.62).

Conclusions and Relevance High lifespan CR is associated with a reduction in dementia risk, even in the presence of high brain pathologies. Our findings highlight the importance of lifespan CR accumulation in dementia prevention.

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Benefit of Adding #Ezetimibe to #Statin Therapy on Cardiovascular Outcomes and Safety in Patients With Versus Without Diabetes Mellitus

https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.117.030950

...When stratified by the TIMI (Thrombolysis in Myocardial Infarction) Risk Score for Secondary Prevention, all patients with DM demonstrated benefit with E/S regardless of risk. In contrast, among patients without DM, those with a high risk score experienced a significant (18%) relative reduction in the composite of cardiovascular death, myocardial infarction, and ischemic stroke with E/S compared with placebo/simvastatin, whereas patients without DM at low or moderate risk demonstrated no benefit with the addition of ezetimibe to simvastatin (Pint =0.034).

Conclusions:

In IMPROVE-IT, the benefit of adding ezetimibe to statin was enhanced in patients with DM and in high-risk patients without DM.

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Benefits and Harms of Oral #Anticoagulant Therapy in Chronic #Kidney Disease: A Systematic Review and Meta-analysis

https://annals.org/aim/article-abstract/2738158/benefits-harms-oral-anticoagulant-therapy-chronic-kidney-disease-systematic-review

All but the 8 trials involving patients with ESKD excluded participants with creatinine clearance less than 20 mL/min or estimated glomerular filtration rate less than 15 mL/min/1.73 m2. In AF, compared with VKAs, NOACs reduced risks for stroke or systemic embolism (risk ratio RR, 0.79 95% CI, 0.66 to 0.93; high-certainty evidence) and hemorrhagic stroke (RR, 0.48 CI, 0.30 to 0.76; moderate-certainty evidence). Compared with VKAs, the effects of NOACs on recurrent VTE or VTE-related death were uncertain (RR, 0.72 CI, 0.44 to 1.17; low-certainty evidence). In all trials combined, NOACs seemingly reduced major bleeding risk compared with VKAs (RR, 0.75 CI, 0.56 to 1.01; low-certainty evidence).

Conclusion:
In early-stage CKD, NOACs had a benefit–risk profile superior to that of VKAs. For advanced CKD or ESKD, there was insufficient evidence to establish benefits or harms of VKAs or NOACs.