Miracle-dz/UniFAR-FTUs huggingface dataset:
Implications of the ACCORD Lipid study: perspective from the Residual Risk Reduction Initiative (R3i)

Abstract Most type 2 diabetes patients remain at high residual risk of cardiovascular events despite best treatment. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial aimed to address this challenge, by evaluating whether intensive control of glycaemia and high blood pressure, or as in ACCORD Lipid, extending lipid treatment with the combination of fenofibrate plus simvastatin, could impact this risk. ACCORD Lipid showed that treatment beyond low-density lipoprotein cholesterol was not appropriate for most type 2 diabetes patients. However, a subgroup analysis did suggest additional benefit in patients with atherogenic dyslipidaemia, the combination of high baseline triglycerides (≥204 mg/dL or 2.3 mmol/L) and low baseline plasma levels of high-density lipoprotein cholesterol (≤34 mg/dL or 0.88 mmol/L). This finding is concordant with subgroup analyses from other fibrate trials in patients with high triglycerides and low plasma levels of high-density lipoprotein cholesterol, and consistent with current guideline recommendations. This commentary from the Residual Risk Reduction Initiative (R3i), discusses the ACCORD Lipid study results and the next steps to establish the clinical relevance of these findings.
The active bacterial assemblages of the upper GI tract in individuals with and without Helicobacter infection

Objective Patients infected with Helicobacter pylori develop chronic gastritis with a subgroup progressing to further complications. The role of microbiota from the oral cavity swallowed with saliva and either transiting the stomach or persisting in the gastric mucosa is uncertain. It is also not known whether the bacterial community differs in luminal and mucosal niches. A key question is whether H. pylori influences the bacterial communities of gastroduodenal niches. Design Saliva, gastric and duodenal aspirates as well as gastric and duodenal biopsies were collected during oesophagogastroduodenoscopy from 24 patients (m:9, f:15, mean age 52.2±SD 14.5 years). RNA was extracted and the V1–V2 region of the retrotranscribed bacterial 16S rRNA amplified and sequenced on the Illumina MiSeq platform. Results Overall, 687 bacterial phylotypes that belonged to 95 genera and 11 phyla were observed. Each individual comprised a unique microbiota composition that was consistent across the different niches. However, the stomach fluid enriched for specific microbiota components. Helicobacter spp were shown to dominate the mucosa-associated community in the stomach, and to significantly influence duodenal and oral communities. Conclusions The detailed analysis of the active global bacterial communities from the five distinct sites of the upper GI tract allowed for the first time the differentiation between host effects and the influence of sampling region on the bacterial community. The influence of Helicobacter spp on the global community structures is striking.
The vestibulo‐collic reflex

Until now there has no been no simple, reliable clinical test that assesses the function of the otolith organs. However, recent work has suggested the occurrence of an easily identifiable electromyographic (EMG) waveform in isometrically contracting sternomastoid muscles in response to loud clicks. This is thought to represent an otolith evoked disynaptic reflex. Equipment routinely used for evoked response audiometry (ERA) has been adapted to investigate this response. A short latency (8 ms) positive-negative EMG waveform has been recorded in 31 of 32 normal subjects. The latency of the positive peak (P1) is 11.7 ms (SD = 0.89), and the negative peak (N1) is 20.5 ms (SD = 1.89). It is predominantly ipsilateral, although a contralateral response was present in 35.5%. The response has also been recorded in three patients with a severe unilateral sensorineural hearing loss and normal caloric responses, and in a patient undergoing cochlear implantation for profound bilateral sensorineural hearing loss. Further work is required to delineate the value of this technique in investigating vestibular lesions.
Serum uric acid and self-reported rheumatoid arthritis in a multiethnic adult female population

Abstract Objective: Studies suggest that serum uric acid (SUA) is significantly associated with cardiovascular disease (CVD) mortality among women and blacks. CVD rates are higher among patients with rheumatoid arthritis (RA) than the normal population. The objective of this study was to determine if there was an association between SUA levels and self-reported RA in a multiethnic female population in the United States. Methods: This cross-sectional study was conducted using data for 7374 women above 20 years of age in the Third National Health and Nutrition Examination Survey. Multiple and logistic regression methods were used to determine an association between SUA levels and self-reported RA. Results: Women self-reporting RA had significantly higher SUA levels (p < 0.0001) compared to women not self-reporting RA, also when adjusted for age and race (p < 0.0001). In a regression analysis, significant predictors of SUA levels were: self-reporting RA, race/ethnicity, being married, smoking, use of alcohol, high body mass index, high C-Reactive protein, elevated diastolic or systolic blood pressure, and increased glomerular filtration rate. Education and age were removed from the model. The model explained 24.0% of the variability seen in SUA levels (F = 208.62, p < 0.0001) in this multiethnic female population. When the analyses were repeated stratified by race, self-reporting RA was retained in the model as associated with SUA in white and Mexican American, but not in black women. Conclusion: Despite the limitations imposed by self-reporting of RA on self-administered questionnaires and in-person interviews, practitioners should be aware that women self-reporting RA are at risk of having high SUA levels as well as more traditional CVD risk factors. These women should be offered appropriate preventive interventions related to their increased risk for CVD events.
Development of a Microscopic Colitis Disease Activity Index: a prospective cohort study

Objective Microscopic colitis (MC) is a common cause of chronic diarrhoea, often with additional symptoms. No validated instruments exist to assess disease activity in MC, making it difficult to compare efficacy of treatments between clinical trials. We aimed to identify clinical features that independently predicted disease severity and create a Microscopic Colitis Disease Activity Index (MCDAI). Design Patients with MC were prospectively administered a survey assessing their GI symptoms and the IBD Questionnaire (IBDQ). A single investigator also scored a physician global assessment (PGA) of disease severity on a 10-point scale. Multiple linear regression identified which symptoms best predicted the PGA. These symptoms were then combined in a weighted formula to create the MCDAI. The relationship between MCDAI and the IBDQ was investigated. Results Of the 175 patients enrolled, 13 (7.4%) did not complete the survey. The remaining 162 had a median age of 66 years (range, 57–73) and 74% were female. Several clinical features were independently associated with PGA (number of unformed stools daily, presence of nocturnal stools, abdominal pain, weight loss, faecal urgency and faecal incontinence). These parameters were combined to create the MCDAI, which strongly predicted the PGA (R2=0.80). A 1-unit decrease in disease activity (ΔMCDAI) was associated with a 9-unit increase in quality of life (ΔIBDQ). Conclusions The MCDAI strongly predicted the PGA and correlated with a validated measure of quality of life. Several symptoms in addition to diarrhoea are associated with disease severity in MC.
Treatment Interference in Critically Ill Patients: An Update on Unplanned Extubation

This study was undertaken to update the state of knowledge of the problem of treatment interference, which is the self-removal or disruption of technologic devices, with special focus on self-extubation of endotracheal tubes and to examine clinical interventions and recommendations to prevent treatment interference. A combined computerized and hand search of the nursingandmedical literature (MEDLINE,June1996toJune2001;CINAHL,June1996toJune 2001) was conducted using the following terms: treatment interference, device disruption, self-extubation, accidental extubation, unplanned extubation. Thirteen published research studies, one research abstract, and two quality improvement reports specific to unplanned extubation were reviewed along with the associated literature on preventive strategies in the intensive care unit (ICU). The reported incidence of unplanned extubation (UE) and physical restraintuseatthetimeofUEhavenotchangedappreciablyinrecentyears.Primaryriskfactors for UE are restlessness/agitation, confusion, previous treatment interference, medical ICU, decreased level of consciousness, and oral (versus nasotracheal) intubation. The influence of nursing presence and workload remains equivocal and may vary with the mechanism of UE (accidentalvsself-extubation). Reintubationriskismostcloselyassociatedwiththemechanism of UE (accidental) and extent of ventilatory support (full). Patients who experience UE are more likely to require longer duration of mechanical ventilation and longer ICU stays. Physical restraints carry inherent physiologic and psychologic dangers. Sedation, although potentially effective in decreasing the incidence of UE, risks prolongation of mechanical ventilation and paradoxical agitation. The next step in research and practice improvement is to focus staff education and work redesign on agitation-sedation assessment and treatment with an emphasis on nonrestraint strategies in the prevention of treatment interference.
Prevalence and documentation of malnutrition in hospitals: A case study in a large private hospital setting

Objectives: To determine the prevalence of malnutrition and whether the malnourished participants were being identified and documented as malnourished. To evaluate the impact of poor documentation on financial reimbursement to the hospital. Subjects: Three hundred and twenty-four inpatients from a total of 690 randomly selected patients consented to participate in the study. Design and setting: Subjective Global Assessment (SGA) was used to assess the nutritional status of inpatients. There were 1906 patients were admitted over a three-month period. Of these, 1860 were eligible and 690 were randomly selected from computer generated ward lists. The referral rate for nutrition intervention of malnourished participants was determined by viewing the patient medical records retrospectively. The Australian National Diagnostic Related Group (AN-DRG) of the malnourished subjects, not documented in the medical record as malnourished, were redetermined with the addition of the malnutrition code. The potential shortfall in financial reimbursement to the hospital was calculated by subtracting the average costing based on original AN-DRGs from the average costing based on the revised AN-DRGs. Main outcome measures: Prevalence of malnutrition, levels of malnourished patients identified and documented, revenue losses under case payment system. Statistical analyses: Logistic regression analyses were used to evaluate group differences in sex across SGA categories and to investigate predictors of referral versus non referral. Analysis of variance was used to evaluate group differences in age across SGA categories. Results: One hundred and twenty-seven (42.3%) of the 324 subjects were malnourished. Only one of 137 malnourished patients was documented as malnourished in the medical records and only 21 (15.3%) were referred for nutrition intervention. The inclusion of the malnutrition code to the AN-DRG of the identified malnourished patients highlighted a shortfall of $125 311 in reimbursements to the hospital. Conclusions: The degree of malnutrition in this hospital is similar to that found internationally. Malnourished patients are not being identified using the current referral method. Failure to flag malnourished patients requiring nutrition intervention potentially impacts on length of stay, hospital costs and patient outcomes and ultimately results in a shortfall for case payment funded institutions.
Dietary emulsifiers directly alter human microbiota composition and gene expression ex vivo potentiating intestinal inflammation

Objective The intestinal microbiota plays a central role in the development of many chronic inflammatory diseases including IBD and metabolic syndrome. Administration of substances that alter microbiota composition, including the synthetic dietary emulsifiers polysorbate 80 (P80) and carboxymethylcellulose (CMC), can promote such inflammatory disorders. However, that inflammation itself impacts microbiota composition has obfuscated defining the extent to which these compounds or other substances act directly upon the microbiota versus acting on host parameters that promote inflammation, which subsequently reshapes the microbiota. Design We examined the direct impact of CMC and P80 on the microbiota using the mucosal simulator of the human intestinal microbial ecosystem (M-SHIME) model that maintains a complex stable human microbiota in the absence of a live host. Results This approach revealed that both P80 and CMC acted directly upon human microbiota to increase its proinflammatory potential, as revealed by increased levels of bioactive flagellin. The CMC-induced increase in flagellin was rapid (1 day) and driven by altered microbiota gene expression. In contrast, the P80-induced flagellin increase occurred more slowly and was closely associated with altered species composition. Transfer of both emulsifier-treated M-SHIME microbiotas to germ-free recipient mice recapitulated many of the host and microbial alterations observed in mice directly treated with emulsifiers. Conclusions These results demonstrate a novel paradigm of deconstructing host–microbiota interactions and indicate that the microbiota can be directly impacted by these commonly used food additives, in a manner that subsequently drives intestinal inflammation.
Alcohol-Induced Developmental Origins of Adult-Onset Diseases.

Fetal alcohol exposure may impair growth, development, and function of multiple organ systems and is encompassed by the term fetal alcohol spectrum disorders (FASD). Research has so far focused on the mechanisms, prevention, and diagnosis of FASD, while the risk for adult-onset chronic diseases in individuals exposed to alcohol in utero is not well explored. David Barker's hypothesis on Developmental Origins of Health and Disease (DOHaD) suggests that insults to the milieu of the developing fetus program it for adult development of chronic diseases. In the 25 years since the introduction of this hypothesis, epidemiological and animal model studies have made significant advancements in identifying in utero developmental origins of chronic adult-onset diseases affecting cardiovascular, endocrine, musculoskeletal, and psychobehavioral systems. Teratogen exposure is an established programming agent for adult diseases, and recent studies suggest that prenatal alcohol exposure correlates with adult onset of neurobehavioral deficits, cardiovascular disease, endocrine dysfunction, and nutrient homeostasis instability, warranting additional investigation of alcohol-induced DOHaD, as well as patient follow-up well into adulthood for affected individuals. In utero epigenetic alterations during critical periods of methylation are a key potential mechanism for programming and susceptibility of adult-onset chronic diseases, with imprinted genes affecting metabolism being critical targets. Additional studies in epidemiology, phenotypic characterization in response to timing, dose, and duration of exposure, as well as elucidation of mechanisms underlying FASD-DOHaD inter relation, are thus needed to clinically define chronic disease associated with prenatal alcohol exposure. These studies are critical to establish interventional strategies that decrease incidence of these adult-onset diseases and promote healthier aging among individuals affected with FASD.
Chromoendoscopy versus narrow band imaging in UC: a prospective randomised controlled trial

Background Patients with long-standing UC have an increased risk for the development of colonic neoplastic lesions. Chromoendoscopy (CE) has been proven to enhance neoplasia detection while the role of virtual chromoendoscopy (VC) is still to be defined. Objective To compare the performance of CE to VC for the detection of neoplastic lesions in patients with long-standing UC. Design A multicentre prospective randomised controlled trial. 131 patients with long-standing UC were randomised between CE with methylene blue 0.1% (n=66) or VC with narrow band imaging (NBI) (n=65). Biopsies were taken from visible lesions and surrounding mucosa. No random biopsies were performed. The primary outcome was the difference in total number of neoplastic lesions detected in each group. Results There was no significant difference between NBI and CE for neoplasia detection. Mean number of neoplastic lesions per colonoscopy was 0.47 for CE and 0.32 for NBI (p=0.992). The neoplasia detection rate was not different between CE (21.2%) and NBI (21.5%) (OR 1.02 (95% CI 0.44 to 2.35, p=0.964). Biopsies from the surrounding mucosa yielded no diagnosis or dysplasia. The per lesion neoplasia detection was 17.4% for CE and 16.3% for NBI (OR 1.09 (95% CI 0.59 to 1.99, p=0.793). The total procedural time was on average 7 min shorter in the NBI group. Conclusion CE and NBI do not differ significantly for detection of colitis-associated neoplasia. Given the longer withdrawal time for CE and easier applicability, NBI may possibly replace classical CE. Trial registration number NCT01882205; Results.
Proof-of-Concept Study to Assess the Nociceptin Receptor Antagonist LY2940094 as a New Treatment for Alcohol Dependence.

BACKGROUND This was a proof-of-concept study to evaluate the efficacy of LY2940094, a nociceptin/orphanin FQ peptide receptor antagonist, in reducing alcohol consumption in actively alcohol-drinking patients with alcohol dependence. METHODS Eighty-eight patients, 21 to 66 years of age, diagnosed with alcohol dependence, reporting 3 to 6 heavy drinking days per week, were randomized (1:1) to 8 weeks of treatment with once-daily oral placebo (N = 44) or 40 mg/d of LY2940094 (N = 44). The primary efficacy analysis was the change from baseline in number of drinks per day (NDD) utilizing mixed-model repeated measures comparing LY2940094 and placebo in Month 2 of the 8-week double-blind treatment period. The probability that the difference relative to placebo in NDD was ≤0 at endpoint was calculated, and a probability ≥80% was considered to be evidence that LY2940094 was associated with the reduction in NDD. RESULTS After 8 weeks of treatment, reduction in mean NDD did not differ between LY2940094 versus placebo (-1.4 vs. -1.5, respectively, 44% probability of greater reduction relative to placebo), but there was a greater reduction in the mean percentage of heavy drinking days in a month with LY2940094 versus placebo (-24.5 vs. -15.7%, respectively, 93% probability of a greater reduction relative to placebo), and an increase in the mean percentage of abstinent days in a month compared to placebo (9.1 vs. 1.9%, respectively, 91% probability of a greater increase relative to placebo). Patients who were treated with LY2940094 showed decreased plasma levels of gamma-glutamyl transferase with probabilities ≥98% for greater reduction compared with placebo at Weeks 1, 4, 6, and 8. Treatment-emergent adverse events in ≥5% of patients treated with LY2940094 included insomnia, vomiting, and anxiety. There were no serious adverse events or significant changes in laboratory assessments or vital signs with LY2940094. CONCLUSIONS Although not reducing the NDD, LY2940094, compared to placebo, did reduce heavy drinking days and increased abstinence days in patients with alcohol dependence.
Safety and efficacy of maintenance infliximab therapy for moderate-to-severe Crohn’s disease in children: REACH open-label extension

Abstract Objective: Assess long-term effects of maintenance infliximab therapy in children with moderately-to-severely active Crohn’s disease. Research design and methods: One hundred twelve patients with a Pediatric Crohn’s Disease Activity Index (PCDAI) score >30 received infliximab 5 mg/kg at weeks 0, 2, and 6 in the REACH study. Patients considered responders at week 10 were randomized to infliximab 5 mg/kg every 8 (q8w) or 12 (q12w) weeks. Patients who completed treatment through week 46, and who the investigator believed would benefit from continued treatment, could enter the open-label extension (OLE) and receive up to three additional years of infliximab. No hypothesis testing was performed. Clinical trial registration: www.clinicaltrials. gov, identifier: NCT0020767. Results: Sixty children entered the OLE: 33, 12, and 15 patients were receiving infliximab 5 mg/kg q8w, 5 mg/kg q12w, and 10 mg/kg q8w, respectively, at extension entry. Patients receiving infliximab for up to 3 years during the OLE maintained clinical benefit, with approximately 80% of patients consistently having no to mild disease activity per the physician’s global assessment and very good to fair health in the past 2 weeks per the patient and parent/guardian global assessments. Patients with ≥1-year delay in bone age at baseline trended toward improvement in height during the OLE. Respiratory system disorders, most commonly upper respiratory infections, were the most prevalent adverse events reported; six (10%) patients had serious infections. Conclusions: Among children with moderately-to-severely active Crohn’s disease who received infliximab for 46 weeks in REACH and then for up to 3 additional years in the REACH OLE, infliximab was effective in maintaining clinical benefit and was generally well-tolerated.