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Prevalence of #foot #pain across an international consortium of population based cohorts

https://onlinelibrary.wiley.com/doi/abs/10.1002/acr.23829

Despite the potential burden of foot pain, some of the most fundamental epidemiological questions surrounding the foot remain poorly explored. The prevalence of foot pain has proved difficult to compare across existing studies due to variations in case definitions.

Results
The precise definition of foot pain varied between the cohorts. The prevalence of foot pain ranged from 13 to 36% and was lowest within the cohort that used a case definition specific to pain, compared to the four remaining cohorts that included components of pain, aching or stiffness. Foot pain was generally more prevalent in women, the obese and generally increased with age, being much lower in younger participants (20‐44 years).

Conclusion
Foot pain is common and is associated with female sex, older age and obesity. The prevalence of foot pain is likely affected by the case definition used, therefore consideration must be given for future population studies to use consistent measures of data collection.

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Dietary #emulsifiers consumption alters #anxiety-like and social-related behaviors in mice in a sex-dependent manner

https://www.nature.com/articles/s41598-018-36890-3

Dietary emulsifiers carboxylmethylcellulose (CMC) and polysorbate 80 (P80) alter the composition of the intestinal microbiota and induce chronic low-grade inflammation, ultimately leading to metabolic dysregulations in mice. As both gut microbiota and intestinal health can influence social and anxiety-like behaviors, we investigated whether emulsifier consumption would detrimentally influence behavior

Importantly, emulsifier treatment altered anxiety-like behaviors in males and reduced social behavior in females. It also changed expression of neuropeptides implicated in the modulation of feeding as well as social and anxiety-related behaviors

This study reveals that these commonly used food additives may potentially negatively impact anxiety-related and social behaviors and may do so via different mechanisms in males and females

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#Direct-Acting Antiviral Therapy not Associated with Recurrence of #Hepatocellular Carcinoma in a Multicenter North American Cohort Study

https://www.gastrojournal.org/article/S0016-5085(19)30057-5/pdf

There is controversy over the effects of direct-acting antiviral (DAA) therapies for hepatitis C (HCV) infection on hepatocellular carcinoma (HCC) recurrence and tumor aggressiveness. We compared HCC recurrence patterns between DAA-treated and untreated HCV-infected patients who had achieved a complete response to HCC treatment in a North American cohort.

In DAA-treated and untreated patients, most recurrences were within the Milan criteria (74.2% vs 78.8%; P=.23). A larger proportion of DAA-treated than untreated patients received potentially curative HCC therapy for recurrent HCC (32.0% vs 24.6%) and achieved a complete or partial response (45.3% vs 41.0%) but neither achieved statistical significance.

Conclusion
In a large cohort of North American patients with complete response to HCC treatment, DAA therapy was not associated with increased overall or early HCC recurrence. HCC recurrence patterns, including treatment response, were similar in DAA-treated and untreated patients.

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The Imperative for #climate Action to Protect #Health

https://www.nejm.org/doi/full/10.1056/NEJMra1807873

The WHO predicts that 250,000 deaths yearly from 2030 to 2050 will be attributable to climate change. Reductions in greenhouse-gas emissions would be expected to have substantial health benefits — for example, reduced air pollution could lead to a lower risk of noncommunicable disease.

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Toxin Enzyme #Immunoassays Detect #Clostridioides difficile Infection with Greater Severity and Higher Recurrence Rates

https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciz009/5274659

Few data suggest Clostridioides difficile infections (CDI) detected by toxin enzyme immunoassays (EIA) are more severe and have worse outcomes than those detected by nucleic acid amplification tests (NAAT) only. We compared toxin-positive and NAAT-positive only CDI across geographically-diverse sites

Of 4878 cases, 2160 (44.3%) were toxin-positive and 2718 (55.7%) were NAAT-positive only. More toxin-positive than NAAT-positive only cases were aged ≥65 years (48.2% vs 38.0%; P<0.0001), had ≥3 unformed stool for ≥1 day (43.9% vs 36.6%; P<0.0001), and had white blood cells ≥15,000/µl (31.4% versus 21.4%; P<0.0001). In multivariable analysis, toxin-positivity was associated with recurrence (adjusted odds ratio [aOR]: 1.89, 95% CI: 1.61-2.23), but not with CDI-related complications (aOR: 0.91, 95% CI: 0.67-1.23) or 30-day mortality (aOR: 0.95; 95% CI: 0.73-1.24).

Conclusions
Toxin-positive CDI is more severe, but there were no differences in adjusted CDI-related complication and mortality rates between toxin-positive and NAAT-positive only CDI that were detected by an algorithm that utilized an initial GDH screening test.

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#Cognitive Impact of Cerebral Small #Vessel Disease Changes in Patients With Hypertension

https://www.ahajournals.org/doi/full/10.1161/HYPERTENSIONAHA.118.12090

Hypertension is one of the principal risk factors for cerebral small vessel disease progression and cognitive impairment.

Considering the progression of cerebral small vessel disease, the prevalence of incident infarcts was 6.1% and that of incident cerebral microbleeds was 5.5%; progression of periventricular WMH was 22% and that of deep WMH was 48%. Patients with marked progression of periventricular WMH showed a significant decrease in global cognition compared with patients without progression (adjusted mean [SE], −0.519 [0.176] versus 0.057 [0.044], respectively; P value=0.004) and a higher risk of incident mild cognitive impairment (OR, 6.184; 95% CI, 1.506–25.370; P value=0.011).

Therefore, our results indicate that hypertensive patients with progression of periventricular WMH have higher odds of cognitive impairment, even in the early stages of cognitive decline.

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#Blood–brain barrier breakdown is an early biomarker of human #cognitive dysfunction

https://www.nature.com/articles/s41591-018-0297-y

Abstract
Vascular contributions to cognitive impairment are increasingly recognized as shown by neuropathological neuroimaging and cerebrospinal fluid biomarker studies. Moreover, small vessel disease of the brain has been estimated to contribute to approximately 50% of all dementias worldwide, including those caused by Alzheimer’s disease (AD)..

Our data show that individuals with early cognitive dysfunction develop brain capillary damage and BBB breakdown in the hippocampus irrespective of Alzheimer’s Aβ and/or tau biomarker changes, suggesting that BBB breakdown is an early biomarker of human cognitive dysfunction independent of Aβ and tau.

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Accelerated Knee #Osteoarthritis is Characterized by Destabilizing #Meniscal Tears and Pre‐Radiographic Structural Disease Burden

https://onlinelibrary.wiley.com/doi/abs/10.1002/art.40826

At 1 year before the index visit, >75% of adults with AKOA had meniscal damage in ≥2 regions (vs typical KOA: OR=3.19, 95%CI=1.70 to 5.97). By the index visit, meniscal damage in >2 regions was ubiquitous in AKOA; including 42% with a destabilizing meniscal tear (typical KOA=14%). These changes corresponded to larger BMLs and greater cartilage loss.

Conclusion
AKOA is characterized by destabilizing meniscal tears in a knee compromised by meniscal damage in >2 regions, large BMLs, and cartilage loss

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Association of #Exercise Preconditioning With Immediate #Cardioprotection

https://jamanetwork.com/journals/jamacardiology/article-abstract/2664268

Preclinical evidence shows that 1 to 3 episodes of exercise per week will provide strong cardioprotection; gradual, modest cardiovascular risk factor modification or physiological artery remodeling cannot fully explain these benefits. This review highlights preclinical evidence that acute exercise-induced cardiac preconditioning has the ability to activate multiple pathways to confer immediate protection against ischemic events, reduce the severity of potentially lethal ischemic myocardiac injury, and act as a physiological first line of defense.

Conclusions and Relevance Independent of the protective benefits of long-term exercise training on risk factors and adaptation of the cardiovascular system, cardiovascular preconditioning may contribute to the immediate cardioprotection of exercise. In practical terms, this means that 1 episode of exercise can create clinically relevant cardioprotection.

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Association of #Aspirin Use for Primary Prevention With #Cardiovascular Events and Bleeding Events

https://jamanetwork.com/journals/jama/article-abstract/2721178

The role for aspirin in cardiovascular primary prevention remains controversial, with potential benefits limited by an increased bleeding risk

Aspirin use was associated with significant reductions in the composite cardiovascular outcome compared with no aspirin (57.1 per 10 000 participant-years with aspirin and 61.4 per 10 000 participant-years with no aspirin) (hazard ratio [HR], 0.89 [95% credible interval, 0.84-0.95]; absolute risk reduction, 0.38% [95% CI, 0.20%-0.55%]; number needed to treat, 265). Aspirin use was associated with an increased risk of major bleeding events compared with no aspirin (23.1 per 10 000 participant-years with aspirin and 16.4 per 10 000 participant-years with no aspirin) (HR, 1.43 [95% credible interval, 1.30-1.56]; absolute risk increase, 0.47% [95% CI, 0.34%-0.62%]; number needed to harm, 210).

Conclusions and Relevance The use of aspirin in individuals without cardiovascular disease was associated with a lower risk of cardiovascular events and an increased risk of major bleeding. This information may inform discussions with patients about aspirin for primary prevention of cardiovascular events and bleeding.

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How effective are trained #dogs at alerting their owners to changes in blood #glycaemic levels?: Variations in performance of glycaemia alert dogs

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0210092

Dogs varied in their performance, with median sensitivity to out-of-range episodes at 70% (25th percentile = 50, 75th percentile = 95). To hypoglycaemic episodes the median sensitivity was 83% (66–94%) while to hyperglyaemic episodes it was 67% (17–91%). The median positive predictive value (PPV) was 81% (68–94%), i.e. on average 81% of alerts occurred when glucose levels were out of target range. For four dogs, PPV was 100%. Individual characteristics of the dog, the partnership and the household were significantly associated with performance (e.g., whether the dog was previously a pet, when it was trained, whether its partner was an adult or child).

Conclusions
The large sample shows that the individual performance of dogs is variable, but overall their sensitivity and specificity to OOR episodes are better than previous studies suggest. Results show that optimal performance of glycaemic alert dogs depends not only on good initial and ongoing training, but also careful selection of dogs for the conditions in which they will be working

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Three week versus six week #immobilisation for stable Weber B type ankle #fractures: randomised, multicentre, non-inferiority clinical trial

https://www.bmj.com/content/364/bmj.k5432

212 of 247 randomised participants (86%) completed the study. At 52 weeks, the mean OMAS was 87.6 (SD 18.3) in the six week cast group, 91.7 (SD 12.9) in the three week cast group, and 89.8 (SD 18.4) in the three week orthosis group. The between group difference at 52 weeks for the three week cast versus six week cast was 3.6 points (95% confidence interval −1.9 to 9.1, P=0.20), and for the three week orthosis versus six week cast was 1.7 points (−4.0 to 7.3, P=0.56). In both comparisons, the confidence intervals did not include the predefined inferiority margin of −8.8 points. The only statistically significant between group differences observed in the secondary outcomes and harms in the two primary comparisons were slight improvement in ankle plantar flexion and incidence of deep vein thrombosis, both in the three week orthosis group versus six week cast group.

Conclusion Immobilisation for three weeks with a cast or orthosis was non-inferior to conventional cast immobilisation for six weeks in the treatment of an isolated stable Weber B type fracture.

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Outpatient Parenteral #Antibiotic Treatment (OPAT) for Infective #Endocarditis: a Prospective Cohort Study From the GAMES Cohort

https://academic.oup.com/cid/advance-article-abstract/doi/10.1093/cid/ciz030/5289192

Outpatient parenteral antibiotic treatment (OPAT) has proven efficacious and safe for treating infective endocarditis (IE). However, the 2001 IDSA criteria for OPAT in IE are very restrictive. We aimed to compare the outcomes of OPAT with those of hospital-based antibiotic treatment (HBAT).

The most frequent causal microorganisms were viridans group streptococci (18.6%), Staphylococcus aureus (15.6%), and coagulase-negative staphylococci (14.5%). The median length of antibiotic treatment was 42 days (IQR 32–54), and 44% of patients underwent cardiac surgery. One-year mortality was 8% (42% for HBAT; P<0.001), 1.4% of patients relapsed, and 10.9% were readmitted during the first three months after discharge (no significant differences compared with HBAT). Charlson score (OR 1.21, 95%CI 1.04–1.42; P=0.01) and cardiac surgery (OR 0.24, 95%CI 0.09–0.63; P=0.04) were associated with one-year mortality, whereas aortic valve involvement (OR 0.47, 95%CI 0.22–0.98; P=0.007) was the only predictor of readmission at one year. Failing to fulfill IDSA criteria was not a risk factor for mortality or readmission.

Conclusions
OPAT provided excellent results despite the use of broader criteria than those recommended by IDSA; OPAT criteria should therefore be expanded.

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Association between use of #azathioprine and risk of acute #pancreatitis in children with inflammatory bowel disease: a Swedish–Danish nationwide cohort study

https://www.thelancet.com/journals/lanchi/article/PIIS2352-4642(18)30401-2/fulltext

Studies have shown an association between use of azathioprine and increased risk of acute pancreatitis in adult inflammatory bowel disease. However, whether an association exists among paediatric patients is not known.

Within the first 90 days following initiation of azathioprine, 40 acute pancreatitis events occurred (incidence rate 49·1 events per 1000 person-years) compared with six events in the no-use group (8·4 events per 1000 person-years). Azathioprine use was associated with an increased risk of acute pancreatitis (incidence rate ratio 5·82 [95% CI 2·47–13·72]; absolute difference 1·0 [95% CI 0·3–2·6] events per 100 patients) during the 90-day risk period.

Interpretation
Use of azathioprine was associated with an increased risk of acute pancreatitis in children with inflammatory bowel disease during the first 90 days following treatment initiation, suggesting the need for regular and rigorous monitoring. The risk of acute pancreatitis needs to be considered when deciding on optimal treatment strategies

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#Benzodiazepines or related drugs and risk of #pneumonia: A systematic review and meta‐analysis

https://onlinelibrary.wiley.com/doi/full/10.1002/gps.5048

Benzodiazepines and benzodiazepine‐related drugs (BZRDs) are used to treat various psychiatric diseases. However, there are concerns that BZRDs increase the risk of pneumonia.

After pooling the estimates, the odds for developing pneumonia were 1.25‐fold higher (odd ratio, OR = 1.25; 95% confidence interval (CI), 1.09‐1.44) in BZRD users compared with individuals who had not taken BZRD. On the basis of exposure window, we found an increased risk of pneumonia among current (OR = 1.4; 95%CI, 1.22‐1.6) and recent (OR = 1.38; 95%CI, 1.06‐1.8) users, but not with the past users (OR = 1.11; 95%CI, 0.96‐1.27).

Conclusion
Current or recent exposure to BZRD is associated with an increased pneumonia risk. Clinicians need to weight the benefit‐risk balance of BZRD use, especially those with other risk factors for pneumonia.

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#Ejaculation Frequency and Risk of #Prostate Cancer: Updated Results with an Additional Decade of Follow-up

https://www.europeanurology.com/article/S0302-2838(16)00377-8/abstract/abstract_52392463?mobileUi=0

Evidence suggests that ejaculation frequency may be inversely related to the risk of prostate cancer (PCa), a disease for which few modifiable risk factors have been identified.

Ejaculation frequency at age 40–49 yr was positively associated with age-standardized body mass index, physical activity, divorce, history of sexually transmitted infections, and consumption of total calories and alcohol. Prostate-specific antigen (PSA) test utilization by 2008, number of PSA tests, and frequency of prostate biopsy were similar across frequency categories. In multivariable analyses, the hazard ratio for PCa incidence for ≥21 compared to 4–7 ejaculations per month was 0.81 for frequency at age 20–29 yr and 0.78 for frequency at age 40–49 yr. Associations were driven by low-risk disease, were similar when restricted to a PSA-screened cohort, and were unlikely to be explained by competing causes of death.

Conclusions
These findings provide additional evidence of a beneficial role of more frequent ejaculation throughout adult life in the etiology of PCa, particularly for low-risk disease.

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#Porphyromonas gingivalis in #Alzheimer’s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors

http://advances.sciencemag.org/content/5/1/eaau3333

Porphyromonas gingivalis, the keystone pathogen in chronic periodontitis, was identified in the brain of Alzheimer’s disease patients. Toxic proteases from the bacterium called gingipains were also identified in the brain of Alzheimer’s patients, and levels correlated with tau and ubiquitin pathology. Oral P. gingivalis infection in mice resulted in brain colonization and increased production of Aβ1–42, a component of amyloid plaques

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Skeletal #Muscles Do Not Undergo Apoptosis During Either #Atrophy or Programmed Cell Death-Revisiting the Myonuclear Domain Hypothesis

https://www.frontiersin.org/articles/10.3389/fphys.2018.01887/full

Muscle memory discovery ends 'use it or lose it' dogma

Skeletal muscles are the largest cells in the body and are one of the few syncytial ones. There is a longstanding belief that a given nucleus controls a defined volume of cytoplasm, so when a muscle grows (hypertrophy) or shrinks (atrophy), the number of myonuclei change accordingly. This phenomenon is known as the “myonuclear domain hypothesis.”

Recently, two independent models, one from rodents and the other from insects, have demonstrated that nuclei are not lost from skeletal muscle fibers when they undergo either atrophy or programmed cell death. These and other data argue against the current interpretation of the myonuclear domain hypothesis and suggest that once a nucleus has been acquired by a muscle fiber it persists.

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Injuries Associated With #Standing Electric #Scooter Use

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2722574

Twenty-seven patients were younger than 18 years (10.8%). Ten riders (4.4%) were documented as having worn a helmet, and 12 patients (4.8%) had either a blood alcohol level greater than 0.05% or were perceived to be intoxicated by a physician. Frequent injuries included fractures (79 [31.7%]), head injury (100 [40.2%]), and contusions, sprains, and lacerations without fracture or head injury (69 [27.7%]). The majority of patients (234 [94.0%]) were discharged home from the emergency department; of the 15 admitted patients, 2 had severe injuries and were admitted to the intensive care unit. Among 193 observed electric scooter riders in the local community in September 2018, 182 (94.3%) were not wearing a helmet.

Conclusions and Relevance Injuries associated with standing electric scooter use are a new phenomenon and vary in severity. In this study, helmet use was low and a significant subset of injuries occurred in patients younger than 18 years, the minimum age permitted by private scooter company regulations. These findings may inform public policy regarding standing electric scooter use.

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Human #Papillomavirus #Vaccination Before 13 and 15 Years of Age: Analysis of National Immunization Survey Teen Data

https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiy682/5265326

Human papillomavirus (HPV) vaccination is suboptimally used in the United States. Vaccination before the 13th birthday is recommended by the Advisory Committee on Immunization Practices and vaccination before the 15th birthday requires only 2 doses. We estimated the proportion of adolescents up to date for HPV vaccine using provider-verified vaccination data from the 2016 National Immunization Survey-Teen.

Only 16% of US adolescents completed HPV vaccination before turning 13, and 35% completed HPV vaccination before turning 15. With sexual activity initiation increasing throughout adolescence and higher immunogenicity for younger vaccinees, vaccination before the 13th birthday can provide better protection against HPV-related cancers.

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Effect of Intensive vs Standard Blood #Pressure Control on Probable #Dementia

https://jamanetwork.com/journals/jama/fullarticle/2723256

Participants were randomized to a systolic blood pressure goal of either less than 120 mm Hg (intensive treatment group; n = 4678) or less than 140 mm Hg (standard treatment group; n = 4683).

The median intervention period was 3.34 years. During a total median follow-up of 5.11 years, adjudicated probable dementia occurred in 149 participants in the intensive treatment group vs 176 in the standard treatment group (7.2 vs 8.6 cases per 1000 person-years; hazard ratio HR, 0.83; 95% CI, 0.67-1.04). Intensive BP control significantly reduced the risk of mild cognitive impairment (14.6 vs 18.3 cases per 1000 person-years; HR, 0.81; 95% CI, 0.69-0.95) and the combined rate of mild cognitive impairment or probable dementia (20.2 vs 24.1 cases per 1000 person-years; HR, 0.85; 95% CI, 0.74-0.97).

Conclusions and Relevance Among ambulatory adults with hypertension, treating to a systolic blood pressure goal of less than 120 mm Hg compared with a goal of less than 140 mm Hg did not result in a significant reduction in the risk of probable dementia. Because of early study termination and fewer than expected cases of dementia, the study may have been underpowered for this end point.