Miracle-dz/UniFAR-FTUs huggingface dataset:
Patient preferences for diabetes treatment attributes and drug classes

Abstract Objective: To identify which treatment attributes are most influential in determining patient preferences for diabetes treatments and explore patient preferences for diabetes drug classes. Research design and methods: US adults with type 1 or type 2 diabetes completed an online adaptive conjoint analysis survey. The survey examined 14 attributes, including efficacy, regimen, and risk of common side effects and rare but serious adverse events. Respondents selected between hypothetical treatments with different attributes. Sawtooth Software, ordinary least-squares regression, and hierarchical Bayes regression were used to calculate utilities (i.e. preference weights), importance ratings, and shares of preference across 13 diabetes drug classes or combination products. Results: A total of 167 adults (mean age 58 years; 55% female) with type 1 or type 2 diabetes completed the survey. Based on importance ratings, the most influential attributes driving preferences were regimen, risk of diarrhea, weight change, risk of hypoglycemia, and efficacy. Sodium–glucose co-transporter-2 inhibitors (SGLT-2is) were highly preferred in direct comparison to each of the other classes (range: 84.2–99.9%), with the exception of dipeptidyl peptidase-4 inhibitors (DPP-4is); DPP-4is (52.9%) were preferred over SGLT-2is (47.1%). Conclusions: Although preferences varied across participants, attributes with the greatest likelihood of affecting daily life and routine were generally more influential in determining patient preferences. DPP-4is and SGLT-2is were overwhelmingly preferred over other drug classes, primarily due to favorable regimen and side effect profiles. Understanding patient preferences can help optimize patient-centered treatment and may lead to improved patient satisfaction, adherence, and outcomes. Limitations: The primary limitations of this study are that a small sample size of type 1 diabetes patients were included, which may reduce the reliability of the preference estimates, and patients were recruited from a patient panel and may not be representative of patients with diabetes in the US.
Longer-term safety and tolerability of canagliflozin in patients with type 2 diabetes: a pooled analysis

Abstract Objective: To evaluate the longer-term safety of canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes mellitus (T2DM). Methods: The safety/tolerability of canagliflozin 100 and 300 mg were assessed using data pooled from seven placebo- and active-controlled studies of 52–104 weeks in duration that enrolled a broad range of patients with T2DM (N = 5598). Canagliflozin 100 and 300 mg as monotherapy or in combination with various background antihyperglycemic agents (AHAs) were compared with pooled non-canagliflozin treatments (i.e. placebo, sitagliptin, glimepiride). Safety was assessed based on adverse event (AE) reports, including the incidence of AEs related to the mechanism of SGLT2 inhibition. Results: Overall AE incidence was similar with canagliflozin 100 and 300 mg and non-canagliflozin (73.7%, 74.5%, and 73.7%). The incidence of AE-related discontinuations and serious AEs was low and balanced across groups. The incidence of male and female genital mycotic infections, urinary tract infections, and AEs related to osmotic diuresis or volume depletion was higher with canagliflozin versus non-canagliflozin; these AEs generally occurred early with decreased incidence over time and incidence was similar across baseline HbA1c subgroups. The incidence of fractures and diabetic ketoacidosis was low and similar across groups. Canagliflozin was associated with a low incidence of hypoglycemia when used with background AHAs that are not associated with hypoglycemia; the incidence was higher among patients on background AHAs associated with hypoglycemia (i.e. insulin, sulfonylurea, glinide). Limitations: Limitations of this analysis include its post hoc nature. While this analysis included a broad population of patients, including those with a history or risk of cardiovascular disease or chronic kidney disease, the longer-term safety in these patient populations was not specifically evaluated. Ongoing outcome studies will provide data on the long-term safety of canagliflozin in these populations. Conclusions: Longer-term exposure to canagliflozin as monotherapy or in combination with other agents was generally well tolerated in patients with T2DM. Trial registration: ClinicalTrials.gov identifiers: NCT01106625, NCT01081834, NCT01106677, NCT00968812, NCT01106651, NCT01106690, NCT01137812.
Adverse Drug Reaction Bulletin

Australia supports the concept that lesions in Australia have a better prognosis than those in Oxford because they are diagnosed at an earlier stage owing to greater public and professional awareness.4 At Queen's University, Belfast, we have now started a teaching programme to improve the recognition ofmelanomas by medical students. We plan to extend this into the postgraduate educational programme for general practitioners and other doctors. The public should also be made more aware of the possible dangers inherent in certain types of pigmented lesions and the curability of melanoma in its early stages. Unnecessary deaths can be prevented.
Differential effects of etomidate and its pyrrole analogue carboetomidate on the adrenocortical and cytokine responses to endotoxemia*

Objective:We developed a novel pyrrole analog of etomidate, (R)-ethyl 1-(1-phenylethyl)-1H-pyrrole-2-carboxylate (carboetomidate), which retains etomidate's desirable anesthetic and hemodynamic properties but lacks its potent inhibitory affect on adrenocorticotropic hormone-stimulated steroid synthesis. The objective of this study was to test the hypothesis that in contrast to etomidate, carboetomidate neither suppresses the adrenocortical response to endotoxemia nor enhances the accompanying production of proinflammatory cytokines. Design:Animal study. Setting:University research laboratory. Subjects:Male Sprague-Dawley rats. Interventions:For both single and multiple anesthetic dose studies, rats were injected with Escherichia coli lipopolysaccharide immediately followed by a hypnotic dose of etomidate, carboetomidate, or vehicle alone (dimethyl sulfoxide) as a control. For single-dose studies, no additional anesthetic (or vehicle) was administered. For multiple anesthetic dose studies, additional doses of anesthetic (or vehicle) were administered every 15 mins for a total of eight anesthetic (or vehicle) doses. Measurements and Main Results:Plasma adrenocorticotropic hormone, corticosterone, and cytokine concentrations were measured before lipopolysaccharide administration and intermittently throughout the 5-hr experiment. In single anesthetic dose studies, plasma adrenocorticotropic hormone and cytokine concentrations were not different at any time point among the etomidate, carboetomidate, and vehicle groups, whereas plasma corticosterone concentrations were briefly (60–120 mins) reduced in the etomidate group. In multiple anesthetic dose studies, plasma corticosterone concentrations were persistently lower and peak plasma interleukin-1&bgr; and interleukin-6 concentrations were higher in the etomidate group vs. the carboetomidate and control groups. Peak plasma interleukin-10 concentrations were similarly elevated in the etomidate and carboetomidate groups vs. the control group. Conclusions:Compared with etomidate, carboetomidate produces less suppression of adrenocortical function and smaller increases in proinflammatory cytokine production in an endotoxemia model of sepsis. These findings suggest that carboetomidate could be a useful alternative to etomidate for maintaining anesthesia for a prolonged period of time in patients with sepsis.
Atorvastatin decreases computed tomography and S100-assessed brain ischemia after subarachnoid aneurysmal hemorrhage: A comparative study*

Objective: Statins, which improve the bioavailability of endogenous nitric oxide and upregulate endothelial nitric oxide synthase, have been used to prevent cerebral vasospasm after aneurysmal subarachnoid hemorrhage. The objective of this study was to determine whether statin therapy diminished vasospasm-induced ischemia as assessed using daily measurements of serum S100B, a biomarker for cerebral ischemia, and computed tomography measurement of ischemic lesion volume. Design: Single-center study of cases and historical controls. Setting: Neurointensive care unit in a university hospital. Patients: Consecutive patients with aneurysmal subarachnoid hemorrhage treated with clipping or coiling within 96 hrs of symptom onset (n = 278) were included from April 2004 to October 2007. Intervention: Oral atorvastatin, 40 mg/day for 21 days, was used routinely starting on December 1, 2005, in 142 patients, who were compared with the 136 patients managed earlier. Measurements and Main Results: Ischemic lesion size was measured using computed tomography on the last available scan and serum S100B was assayed daily for 15 days after admission. Angiographic narrowing was semiquantitatively assessed in patients with vasospasm. In the overall population, cerebral vasospasm was significantly less common in the statin-treated group. Severity of vasospasm, as assessed on the most severe angiogram, was lowered with statin. Statins significantly reduced volume of ischemia in patients with vasospasm and an uncomplicated coiling procedure. S100B levels were significantly lower in statin-treated patients, and the decrease was greatest among high-grade patients (World Federation of Neurological Surgeons 3–5). No differences were found between statin-treated and untreated groups regarding rescue therapy intensity or 1-yr clinical outcomes. Conclusions: Atorvastatin reduces the incidence, the severity and the ischemic consequences of vasospasm as assessed on computed tomography. In high-grade World Federation of Neurological Surgeons patients, atorvastatin decreases serum levels of S100B, a biomarker of brain ischemia. Despite these positive effects on biomarkers, no improvement of outcome was seen in the overall population, although there was a tendency for a better clinical outcome in high-grade patients.
Prognostic effect of parotid area lymph node metastases after preliminary diagnosis of nasopharyngeal carcinoma: a propensity score matching study

Parotid area lymph node (PLN) metastasis in nasopharyngeal carcinoma (NPC) is rare, and its prognosis remains largely unknown. Our study aimed to investigate the prognostic value and staging categories of PLN metastasis in patients with NPC and treated with intensity‐modulated radiation therapy (IMRT), to provide a reference for clinical treatment for NPC with PLN metastasis. Records for 1616 untreated NPC patients without distant metastasis was retrospectively reviewed. All patients underwent magnetic resonance imaging (MRI) examination prior to treatment and then received IMRT as their primary treatment. Forty‐five NPC patients (2.8%) showed initial PLN metastasis on follow‐up MRI. PLN metastasis was significantly associated with the N classification and clinical stage. Univariate analysis showed that PLN metastasis had an unfavorable influence on overall survival (OS), progression‐free survival (PFS), distant metastasis‐free survival (DMFS), and regional relapse‐free survival (RRFS) in NPC patients. Using propensity score matching (PSM) to calibrate selection bias and confounding bias, it was observed that PLN metastasis remained an adverse prognostic factor for OS, PFS, DMFS, and RRFS. Furthermore, the 5‐year DMFS and RRFS curves for PLN metastasis were significantly separated from that for N2 disease but crossed that for N3 disease. Therefore, PLN metastasis was found to be an adverse prognostic factor for NPC and to be associated with the same DMFS as N3 disease. Therefore, more aggressive therapeutic strategies consistent with those for N3 disease are recommended for NPC with PLN metastasis to reduce distant metastasis.
Durability of response to dapagliflozin: a review of long-term efficacy and safety

Abstract Background: Due to the chronic nature of type 2 diabetes (T2D), it is essential for an anti-diabetic drug to have durable efficacy and a good long-term safety profile. Dapagliflozin is a member of a unique class of anti-diabetic drugs that inhibit the sodium-glucose cotransporter 2 (SGLT-2) in the renal tubules and have an insulin-independent mechanism of action. In short-term studies (≤ 24 weeks), dapagliflozin reduced glycated hemoglobin (A1c), weight, and systolic blood pressure, and had a good safety profile. Methods: This review summarizes the findings of long-term studies that evaluated the efficacy and safety of dapagliflozin. Results: These findings indicate that dapagliflozin is effective as monotherapy and in combination with other anti-hyperglycemic agents, including insulin and oral anti-diabetic therapies, in improving glycemic control and reducing blood pressure and weight for up to 4 years. The findings were fairly consistent across various patient populations with T2D, including those with cardiovascular disease (CVD) and mild renal impairment. Extended use of dapagliflozin was not associated with an increase in safety signals over time. Frequently observed adverse events (AEs) were consistent with the drug’s mechanism of action and were generally mild in intensity. No substantial impact of dapagliflozin on renal function was observed, and findings show that the drug is safe in T2D patients with CVD or mild renal impairment, as well as elderly patients. Conclusions: The findings across the studies support the use of dapagliflozin for the long-term treatment of T2D across a broad spectrum of patients.
Population Growth and Economic Development in Low Income Countries

has itself been the 'most immediate beneficiary of nationalism's victory in terms of political power and social prestige, if not also in terms of material betterment' (p. 46). He views it to be their task to fuse themselves with the masses, and to bridge the gap between the city and the countryside. The West, in his opinion, cannot any longer exercise a decisive influence, yet it can playa significant role 'by aiding wisely, honorably, and generously' (p. 52). Other contributions are by an economist, a scientist, a sociologist and the President of the University of Rochester, who from their respective angles plead for a new approach to the non-Western world and a better understanding of the non-Western world by the Americans. 4 April 1959 VISHAL SINGH
Uric acid and incident chronic kidney disease in dyslipidemic individuals

Abstract Background: Elevated uric acid (UA) is a recognized risk factor for chronic kidney disease (CKD). This study aimed to investigate whether this association exists in dyslipidemic patients receiving multifactorial treatment. Methods: An observational study conducted in Greece including 1,269 dyslipidemic individuals followed-up in a lipid clinic for ≥3 years. Estimated glomerular filtration rate (eGFR) was calculated by CKD-EPI equation and CKD was defined as ≤60 mL/min/1.73 m2. The correlation was assessed between UA levels and the CKD risk after adjusting for potential confounding factors, after defining the following UA quartiles: Q1: < 4, Q2: 4–5, Q3: 5–6, and Q4: > 6 mg/dL. Results: After excluding patients with baseline eGFR <60 mL/min/1.73 m2, gout and those taking UA-lowering drugs, 1,095 individuals were eligible; of those, 91% and 69% were treated with statins and anti-hypertensive drugs, respectively. During their follow-up (6 years; IQR = 4–10), 11.9% of the subjects developed CKD, whereas the median annual eGFR decline was 0.69 mL/min/1.73 m2 (IQR = 0.45–2.33). Multivariate analysis showed that baseline UA levels (HR = 1.26; 95% CI = 1.09–1.45, p = .001), female gender (HR = 1.74; 95% CI = 1.14–2.65, p = .01), age (HR = 1.10; 95% CI = 1.07–1.12, p < .001), diabetes (HR = 1.67; 95% CI = 1.05–2.65, p = .03), cardiovascular disease (HR = 1.62; 95% CI = 1.02–2.58, p = .04), decreased baseline renal function (eGFR <90 mL/min/1.73 m2) (HR = 2.38; 95% CI = 1.14–4.81, p = .02), and low-density lipoprotein cholesterol reduction (HR = 0.995; 95% CI = 0.991–0.998, p = .01) were associated with incident CKD. Additionally, patients with UA ≥6 mg/dL exhibited a higher risk of incident CKD compared with those in the lowest UA quartile (HR = 2.01; 95% CI = 1.11–3.65, p = .02). Conclusion: Higher UA levels are correlated with a higher risk of incident CKD in dyslipidemic individuals taking multifactorial treatment.
PAI‐1, a target gene of miR‐143, regulates invasion and metastasis by upregulating MMP‐13 expression of human osteosarcoma

Despite recent improvements in the therapy for osteosarcoma, 30–40% of osteosarcoma patients die of this disease, mainly due to its lung metastasis. We have previously reported that intravenous injection of miR‐143 significantly suppresses lung metastasis of human osteosarcoma cells (143B) in a mouse model. In this study, we examined the biological role and mechanism of miR‐143 in the metastasis of human osteosarcoma cells. We identified plasminogen activator inhibitor‐1 (PAI‐1) as a direct target gene of miR‐143. To determine the role of PAI‐1 in human osteosarcoma cells, siRNA was transfected into 143B cells for knockdown of PAI‐1 expression. An in vitro study showed that downregulation of PAI‐1 suppressed cell invasion activity, but not proliferation. Moreover, injection of PAI‐1 siRNA into a primary lesion in the osteosarcoma mouse model inhibited lung metastasis compared to control siRNA‐injected mice, without influencing the proliferative activity of the tumor cells. Subsequent examination using 143B cells revealed that knockdown of PAI‐1 expression resulted in downregulation of the expression and secretion of matrix metalloproteinase‐13 (MMP‐13), which is also a target gene of miR‐143 and a proteolytic enzyme that regulates tumor‐induced osteolysis. Immunohistochemical analysis using clinical samples showed that higher miR‐143 expressing cases showed poor expression of PAI‐1 in the primary tumor cells. All such cases belonged to the lung metastasis‐negative group. Moreover, the frequency of lung metastasis‐positive cases was significantly higher in PAI‐1 and MMP‐13 double‐positive cases than in PAI‐1 or MMP‐13 single‐positive or double‐negative cases (P < 0.05). These results indicated that PAI‐1, a target gene of miR‐143, regulates invasion and lung metastasis via enhancement of MMP‐13 expression and secretion in human osteosarcoma cells, suggesting that these molecules could be potential therapeutic target genes for preventing lung metastasis in osteosarcoma patients.
Foundation hospitals: we've been here before

Here are some headlines. “Health reforms ‘no cure for cash crises’. ” “A private hospital by any other name…” “Unsafe hands when the heart's not in it. ” Here's an editorial entitled “Doctor, they're in trouble” and which starts, “Imagine the fuss if an untested and untried drug appeared on the market. ” Here's another: “When the NHS market crashes”—it begins, “Doctors must be uncertain whether to laugh or cry. ” These headlines are the main reason that foundation hospitals are doomed. The headlines are from news-papers in 1989-90, at the time of the Conservatives' reforms. They could be recycled. Politicians show no signs of learning the most important lesson: stop fiddling about. The difference now, 13 years on, is that those working in the NHS have already seen the failure of numerous other attempts to reform its structure—18 since 1980, according to Kieran Walshe, reader in public management and director of research at Manchester Centre for Healthcare …
Cost-effectiveness of using an extensively hydrolyzed casein formula containing Lactobacillus rhamnosus GG in managing infants with cow’s milk allergy in the US

Abstract Objective: To estimate the cost-effectiveness of using an extensively hydrolyzed casein formula containing the probiotic Lactobacillus rhamnosus GG (eHCF + LGG; Nutramigen LGG) compared with an eHCF alone and an amino acid formula (AAF) in treating cow’s milk allergy (CMA) in the US, from the perspective of third-party insurers and from parents. Methods: A decision model was used to estimate the probability of cow’s milk allergic infants developing tolerance to cow’s milk by 18 months. The model also estimated the cost to insurers and parents (US dollars at 2016 prices) of managing infants over 18 months after starting one of the formulae, as well as the relative cost-effectiveness of each of the formulae. Results: The probability of developing tolerance to cow’s milk was higher among infants who were fed eHCF + LGG compared with those fed an eHCF alone or an AAF. Infants who are initially fed with eHCF + LGG are expected to utilize fewer healthcare resources than those fed with one of the other formulae. Hence, the estimated total healthcare cost incurred by third-party insurers and parents of initially feeding infants with eHCF + LGG was less than that of feeding infants with an eHCF alone or an AAF. Conclusion: Initial management of newly-diagnosed cow's milk allergic infants with eHCF + LGG was found to afford a cost-effective strategy to both third-party insurers and parents when compared to an eHCF alone or an AAF.
Coupling elastic solids with smoothed particle hydrodynamics fluids

We propose a method for handling elastic solids in smoothed particle hydrodynamics fluids. Our approach samples triangulated surfaces of solids using boundary particles. To prevent fluid particle tunneling in case of large expansions, additional boundary particles are adaptively generated to prevent gaps and undesired leakage. Furthermore, as an object compresses, particles are adaptively removed to avoid unnecessary computations. We demonstrate that our approach produces plausible interactions of smoothed particle hydrodynamics fluids with both slowly and rapidly deforming solids. Copyright © 2013 John Wiley & Sons, Ltd.
Estrogen therapy after menopause: role in normal cognition and Alzheimer's disease

Preclinical biological studies in vitro and in vivo as well as epidemiological surveys in humans strongly support the importance of adequate estrogen support for cognitive function in the older female and identify the cognitive and biological consequences of estrogen loss. Nonetheless, therapeutic intervention studies have not shown definitively that estrogen administration is salutary for brain function after menopause, and in fact some studies (e.g., the Women’s Health Initiative) have actually shown either no improvement or increased risk of cognitive impairment or dementia. Significant progress has been made in understanding the molecular and cellular consequences of estrogen loss and treatment. What has been lacking has been a linkage between these advances in estrogen neurobiology and known mechanisms of age- and disease-related cognitive impairment in humans. This paper briefly reviews advances in the known effects of estrogen on the aging brain and recent evidence regarding the nature of some of t.