Miracle-dz/UniFAR-FTUs huggingface dataset:
Systematic review of efficacy and safety of buprenorphine versus fentanyl or morphine in patients with chronic moderate to severe pain

Abstract Objective: To systematically assess efficacy and safety of buprenorphine patch versus fentanyl patch in patients with chronic moderate to severe pain. Methods: Fifteen databases were searched up to December 2010. Randomised and quasi-randomised trials assessing the efficacy in patients with chronic pain were included. Quantitative methods for data synthesis were used and two network meta-analyses were conducted. Results: Fourteen unique trials (17 publications) were included. No head-to-head randomised trials of buprenorphine patch compared with fentanyl patch were identified. Therefore, less robust evidence from indirect comparisons was used. Results from a network meta-analysis of non-enriched designs (eight trials), using trials versus placebo and trials versus morphine for indirect comparisons, indicated that transdermal fentanyl, in comparison with transdermal buprenorphine, showed significantly more nausea (odds ratio [OR] 4.66, 95% confidence interval (CI) 1.07 to 20.39), a significantly higher number of treatment discontinuations due to adverse events (OR 5.94, 95% CI 1.78 to 19.87), and non-significant differences on all other outcomes, including pain measures. In comparison with morphine, transdermal buprenorphine had a significantly higher decrease of pain intensity (MD [mean difference] −16.20, 95% CI −28.92 to −3.48) while morphine caused more cases of constipation (OR 7.50, 95% CI 1.45 to 38.85) and a significantly higher number of treatment discontinuations due to adverse events (OR 5.80, 95% CI 1.68 to 20.11). All other outcomes showed non-significant differences between transdermal buprenorphine and morphine. The results were similar when also including six trials using enriched designs with the exception of more cases of vomiting for fentanyl (OR 17.32, 95% CI 4.43 to 67.71) and morphine (OR 15.85, 95% CI 3.92 to 64.13) compared to buprenorphine. Conclusions: The findings indicate comparability of transdermal buprenorphine and transdermal fentanyl for pain measures with significantly fewer adverse events (nausea and treatment discontinuation due to adverse events) caused by transdermal buprenorphine.
Fixed-combination brimonidine–timolol versus latanoprost in glaucoma and ocular hypertension: a 12-week, randomized, comparison study

Abstract Objective: To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of fixed-combination brimonidine 0.2%–timolol 0.5% compared with latanoprost 0.005% in patients with glaucoma or ocular hypertension. Research design and methods: This was a prospective, randomized, multicenter, investigator-masked clinical trial. After washout of any previous IOP-lowering medications, patients with IOP of 24 mmHg or higher were randomized to twice-daily fixed-combination brimonidine 0.2%–timolol 0.5% (n = 73) or once-daily latanoprost 0.005% (n = 75, dosed in the evening, with vehicle control in the morning to maintain masking) for 12 weeks. IOP was measured at 8 a.m. (before dosing), 10 a.m., and 3 p.m. at baseline, week 6, and week 12. Clinical trial registration: The trial is registered with the identifier 00811564 at http://www.clinicaltrials. gov. Main outcome measures: The primary efficacy endpoint was diurnal IOP (averaged over 8 a.m., 10 a.m., and 3 p.m.) at week 12. Safety measures included biomicroscopy. Results: There was no statistically significant difference between the treatment groups in mean diurnal IOP at baseline (p = 0.118). At week 12, the mean (SD) diurnal IOP was 17.8 (2.9) mmHg with brimonidine–timolol and 17.9 (3.9) mmHg with latanoprost (p = 0.794). The percentage of patients achieving at least a 20% decrease from baseline diurnal IOP at week 12 was 87.7% in the brimonidine–timolol group and 77.3% in the latanoprost group (p = 0.131). Measured biomicroscopic changes from baseline to week 12 were infrequent in both groups. Conclusions: Fixed-combination brimonidine–timolol was as effective as latanoprost in reducing IOP in patients with glaucoma or ocular hypertension. Both treatments demonstrated favorable ocular tolerability. The duration of the study was 12 weeks, and additional studies will be needed to compare the efficacy and safety of fixed-combination brimonidine–timolol and latanoprost during long-term treatment.
A Randomized Clinical Trial Examining the Effect of Video‐Based Prevention of Alcohol and Marijuana Use Among Recent Sexual Assault Victims

BACKGROUND This study examined whether a brief video intervention (Prevention of Post-Rape Stress [PPRS]) delivered in the emergency department to recent sexual assault (SA) victims reduced alcohol and marijuana use at 3 points over the course of a 6-month follow-up compared to treatment as usual (TAU) and an active control condition (Pleasant Imagery and Relaxation Instruction [PIRI]). Prior assault history, minority status, and pre-SA substance use also were examined as moderators of intervention efficacy. METHODS Women aged 15 and older (N = 154) who participated in a post-SA medical forensic examination were randomly assigned to watch the PPRS video (n = 54) or the PIRI video (n = 48) or receive TAU (n = 52) and completed at least 1 follow-up assessment targeted at 1.5 (T1), 3 (T2), or 6 (T3) months following the examination. RESULTS Regression analyses revealed that, relative to TAU, PPRS was associated with less frequent alcohol use at 6 months post-SA among women reporting pre-SA binge drinking and minority women. Relative to TAU, PPRS also was associated with fewer days of marijuana use at T1 among those who did not report pre-SA marijuana use and prior SA. Findings for pre-SA marijuana use were maintained at T3; however, findings for prior SA shifted such that PPRS was associated with fewer days of marijuana use at T3 for women with a prior SA. CONCLUSIONS PPRS may be effective at reducing substance use for some recent SA victims, including those with a prior SA history, a prior substance use history, and minority women.
Meta‐Analyses of Externalizing Disorders: Genetics or Prenatal Alcohol Exposure?

BACKGROUND Externalizing disorders are heritable precursors to alcohol dependence, common in children of alcoholics (COA), and in children with prenatal alcohol exposure (PAE). Pregnancies involving alcohol exposure sufficient to affect the fetus may involve women with genetic risk for alcohol dependence. We hypothesized that known PAE will increase the odds of having an externalizing disorder compared to COA. METHODS The odds ratios of 3 externalizing disorders (attention-deficit hyperactivity disorder [ADHD], conduct disorder [CD], and oppositional defiant disorder [ODD]) were obtained for 2 domains: (i) PAE and (ii) COA, by estimating the logged odds ratio (LOR) for each study. Permutation tests were implemented to compare LORs for PAE versus COA studies within each disorder, including PAE versus an alcohol dependent (AD) mother and PAE versus an AD father. RESULTS In PAE studies, the odds of ADHD and CD were elevated. Rates of all 3 disorders were elevated in COA studies. Permutation tests revealed that the mean LOR for ADHD was significantly higher in PAE studies compared to: COA (p = 0.01), AD mother (p < 0.05), and AD father (p = 0.03). No differences were found for ODD (p = 0.09) or CD (p = 0.21). CONCLUSIONS These results provide compelling evidence of an increased risk of ADHD in those with PAE beyond that due to parental alcohol dependence or a genetic liability, consistent with a unique etiology most likely due to direct alcohol exposure during prenatal development.
Revisiting the medication possession ratio threshold for adherence in lipid management

Abstract Objective: We sought to evaluate the relationship between different levels of medication possession ratio (MPR) attained and achievement of clinically meaningful reductions in lipid levels. Research design and methods: This was a retrospective cohort study of 4691 new statin users from the Department of Veteran Affairs (VA). Subjects were required to be eligible for VA medical and pharmacy services throughout the 1 year study period from index date and to have complete data for exposure, outcome, and adjustment variables. MPR was defined as number of days supplied with prescription medication divided by days of observation. Main outcome measures: Achieving 25% or greater reduction from baseline in lipid levels for three lipid outcomes: non-high-density lipoprotein (non-HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and total cholesterol (TC). Results: We observed a statistically significant trend of an increasing proportion of study subjects achieving a 25% reduction or more for all three lipid outcomes (p-values <0.001 for each of the three outcomes using the Cochran–Armitage trend test). Using multiple logistic regression, odds ratios (ORs) for each of the three outcomes were at a maximum for the 0.9–1.0 MPR category with ORs of 12.90 (95% confidence interval (CI), 9.60, 17.35) for the non-HDL cholesterol outcome; 11.29 (95% CI, 8.61, 14.80) for the LDL cholesterol outcome; and 9.11 (95% CI, 6.62, 12.53) for the TC outcome. Direct comparison of the 0.9–1.0 MPR category versus the 0.8–0.89 MPR category demonstrated an increase in odds of achieving 25% or more reduction for all three lipid outcomes. Conclusions: We conclude that significant improvements in outcomes are achieved with higher MPR thresholds than commonly targeted. The authors propose consideration of an MPR-adherence threshold of 0.9 MPR. Limitations include the possible modification of study findings in non-VA settings. MPR is a secondary adherence measure based on refill frequency.
Genome-wide association study identifies inversion in the CTRB1-CTRB2 locus to modify risk for alcoholic and non-alcoholic chronic pancreatitis

Objective Alcohol-related pancreatitis is associated with a disproportionately large number of hospitalisations among GI disorders. Despite its clinical importance, genetic susceptibility to alcoholic chronic pancreatitis (CP) is poorly characterised. To identify risk genes for alcoholic CP and to evaluate their relevance in non-alcoholic CP, we performed a genome-wide association study and functional characterisation of a new pancreatitis locus. Design 1959 European alcoholic CP patients and population-based controls from the KORA, LIFE and INCIPE studies (n=4708) as well as chronic alcoholics from the GESGA consortium (n=1332) were screened with Illumina technology. For replication, three European cohorts comprising 1650 patients with non-alcoholic CP and 6695 controls originating from the same countries were used. Results We replicated previously reported risk loci CLDN2-MORC4, CTRC, PRSS1-PRSS2 and SPINK1 in alcoholic CP patients. We identified CTRB1-CTRB2 (chymotrypsin B1 and B2) as a new risk locus with lead single-nucleotide polymorphism (SNP) rs8055167 (OR 1.35, 95% CI 1.23 to 1.6). We found that a 16.6 kb inversion in the CTRB1-CTRB2 locus was in linkage disequilibrium with the CP-associated SNPs and was best tagged by rs8048956. The association was replicated in three independent European non-alcoholic CP cohorts of 1650 patients and 6695 controls (OR 1.62, 95% CI 1.42 to 1.86). The inversion changes the expression ratio of the CTRB1 and CTRB2 isoforms and thereby affects protective trypsinogen degradation and ultimately pancreatitis risk. Conclusion An inversion in the CTRB1-CTRB2 locus modifies risk for alcoholic and non-alcoholic CP indicating that common pathomechanisms are involved in these inflammatory disorders.
Rediscovering catatonia: the biography of a treatable syndrome

Catatonia, a disorder of movement and mood, was described and named in 1874. Other observers quickly made the same recognition. By the turn of the century, however, catatonia was incorporated as a type within a conjured syndrome of schizophrenia. There, catatonia has lain in the psychiatric classification for more than a century.
Real-time differentiation of adenomatous and hyperplastic diminutive colorectal polyps during analysis of unaltered videos of standard colonoscopy using a deep learning model

Background In general, academic but not community endoscopists have demonstrated adequate endoscopic differentiation accuracy to make the ‘resect and discard’ paradigm for diminutive colorectal polyps workable. Computer analysis of video could potentially eliminate the obstacle of interobserver variability in endoscopic polyp interpretation and enable widespread acceptance of ‘resect and discard’. Study design and methods We developed an artificial intelligence (AI) model for real-time assessment of endoscopic video images of colorectal polyps. A deep convolutional neural network model was used. Only narrow band imaging video frames were used, split equally between relevant multiclasses. Unaltered videos from routine exams not specifically designed or adapted for AI classification were used to train and validate the model. The model was tested on a separate series of 125 videos of consecutively encountered diminutive polyps that were proven to be adenomas or hyperplastic polyps. Results The AI model works with a confidence mechanism and did not generate sufficient confidence to predict the histology of 19 polyps in the test set, representing 15% of the polyps. For the remaining 106 diminutive polyps, the accuracy of the model was 94% (95% CI 86% to 97%), the sensitivity for identification of adenomas was 98% (95% CI 92% to 100%), specificity was 83% (95% CI 67% to 93%), negative predictive value 97% and positive predictive value 90%. Conclusions An AI model trained on endoscopic video can differentiate diminutive adenomas from hyperplastic polyps with high accuracy. Additional study of this programme in a live patient clinical trial setting to address resect and discard is planned.
Five Nurses' Experiences of Hospice Care in a Long-Term Perspective

In this study, five nurses' experiences of regularly having to face the incurable illness and death of dying patients were explored. Qualitative interviews were conducted on two occasions, with an interval of 11 years. An interpretive method was used to discern the nurses' thoughts, feelings, and attitudes over the years toward death and dying. The main finding was that working in hospice care and facing the dying and death of many patients had an impact on daily work and private life. Narrations from the first occasion were conceptualized as the theme "death as an agent of change. " Eleven years later, the presence of death took a less dominant place in the nurses' lives and the theme became "death as a companion in life. " In the long term, nurses emphasized that their professional and personal growth was fostered by their relationship with the dying patients.
Efficacy of gemcitabine-based chemotherapy in metastatic breast cancer: a meta-analysis of randomized controlled trials

Abstract Objectives: To compare the effects of gemcitabine-based chemotherapy and gemcitabine-free regimens, a meta-analysis of all relevant randomized controlled trials was performed to investigate the improvement in overall response rate (ORR), time to progression (TTP), and overall survival (OS). A subgroup of gemcitabine-based doublet compared with single agent was also analyzed. Methods: The PubMed and Embase databases were searched for relevant publications reporting randomized controlled trials comparing gemcitabine-based chemotherapy and gemcitabine-free regimens between January 1990 and December 2012. Hazard ratios (HRs) with their 95% confidence intervals (CIs), or data for calculating HRs with 95% CI were derived. Results: Nine trials with a total of 2651 patients were included in this meta-analysis. Compared with gemcitabine-free chemotherapy, gemcitabine-based therapy demonstrated no improvement in terms of ORR (HR 1.09, 95% CI 0.73–1.62; P = 0.67), TTP (HR 0.91, 95% CI 0.72–1.15; P = 0.44) and OS (HR 1.05, 95% CI 0.88–1.25; P = 0.60). In a subgroup including patients who received adjuvant chemotherapy containing anthracyclines or taxanes, sub-analysis assessment revealed that gemcitabine-based doublets were superior to monotherapy in ORR (HR 1.64, 95% CI 1.26–2.12; P = 0.0002) and TTP (HR 0.71, 95% CI 0.62–0.81; P < 0.00001), but no benefit was observed for OS (HR 0.90, 95% CI 0.79–1.03; P = 0.14). The rates of grade 3 and 4 anemia (HR 2.02, 95% CI 1.35–3.02; P = 0.006), neutropenia (HR 2.33, 95% CI 1.37–3.63; P = 0.01), and thrombocytopenia (HR 8.31, 95% CI 5.00–13.82; P < 0.0001) were significantly higher in the gemcitabine-based arm. Conclusions: The present study suggests that gemcitabine-based chemotherapy was as effective as gemcitabine-free chemotherapy in patients with metastatic breast cancer with increased hematological toxicity. Subgroup analysis indicated that adding gemcitabine to monotherapy might be more effective.
Band-pass ΣΔ architectures with single and two parallel paths

The design strategies for band-pass SigmaDelta modulators are discussed. This paper studies two different approaches: the use of resonators and the synthesis of the noise transfer function (NTF) starting from a closer function. The use of a MASH configuration to obtain multiple zeros or splitting the complex zeros of the NTF is also discussed. The sensitivity to components mismatch of the proposed solutions is studied to identify advantages and limits of various presented architectures. Results show that mismatch errors in the fraction of percent range do not degrade the SNR significantly.
Pericardial, intra‐abdominal, and subcutaneous adipose tissue in patients with major depressive disorder

Major depressive disorder (MDD) is associated with an increased risk for developing coronary artery disease (CAD). Recently, pericardial adipose tissue, a metabolically active visceral fat depot surrounding the heart, has been implicated in the pathogenesis of CAD. Therefore, we investigated pericardial adipose tissue volumes in patients with MDD and compared them to healthy comparison subjects.
Obsessive–compulsive symptoms in at‐risk mental states for psychosis: associations with clinical impairment and cognitive function

Obsessive–compulsive symptoms (OCS) constitute a major comorbidity in schizophrenia. Prevalence estimations of OCS for patients with at‐risk mental states (ARMS) for psychosis vary largely. It is unclear how ARMS patients with or without comorbid OCS differ regarding general psychosocial functioning, psychotic and affective symptoms and neurocognitive abilities.
DNA methylation defines regional identity of human intestinal epithelial organoids and undergoes dynamic changes during development

Objective Human intestinal epithelial organoids (IEOs) are increasingly being recognised as a highly promising translational research tool. However, our understanding of their epigenetic molecular characteristics and behaviour in culture remains limited. Design We performed genome-wide DNA methylation and transcriptomic profiling of human IEOs derived from paediatric/adult and fetal small and large bowel as well as matching purified human gut epithelium. Furthermore, organoids were subjected to in vitro differentiation and genome editing using CRISPR/Cas9 technology. Results We discovered stable epigenetic signatures which define regional differences in gut epithelial function, including induction of segment-specific genes during cellular differentiation. Established DNA methylation profiles were independent of cellular environment since organoids retained their regional DNA methylation over prolonged culture periods. In contrast to paediatric and adult organoids, fetal gut-derived organoids showed distinct dynamic changes of DNA methylation and gene expression in culture, indicative of an in vitro maturation. By applying CRISPR/Cas9 genome editing to fetal organoids, we demonstrate that this process is partly regulated by TET1, an enzyme involved in the DNA demethylation process. Lastly, generating IEOs from a child diagnosed with gastric heterotopia revealed persistent and distinct disease-associated DNA methylation differences, highlighting the use of organoids as disease-specific research models. Conclusions Our study demonstrates striking similarities of epigenetic signatures in mucosa-derived IEOs with matching primary epithelium. Moreover, these results suggest that intestinal stem cell-intrinsic DNA methylation patterns establish and maintain regional gut specification and are involved in early epithelial development and disease.
Incorporating Pharmacogenomics into Practice

The goal for this issue of the Journal of Pharmacy Practice is to provide an overview of pharmacogenomics and highlight research done in select therapeutic areas such as oncology, psychiatry, cardiology, and HIV, although pharmacogenomics is taking center stage in other therapeutic areas as well. At the root of all pharmacogenomic investigations is pharmacy, which is why it is so important for pharmacists to gain an understanding of this field and clinical applications of this science, particularly as it relates to their practice and their patients. Pharmacists are experts in pharmacokinetics and pharmacodynamics, and they therefore represent ideal health care professionals for incorporating pharmacogenomics into therapeutic drug monitoring. We are currently in a critical period of time in which pharmacists need to become engaged in the decision-making process regarding how best to implement pharmacogenomics into clinical practice. As part of this chapter, we will outline the role of the Human Genome Project and the Food and Drug Administration, both of which are instrumental to the advancement of pharmacogenomics. Lastly, we will be summarizing some of the barriers we still face regarding clinical applicability of this science and the potential role of genetic counselors in the incorporation of this science into clinical practice.
Efficacy and safety of telmisartan, a selective AT1 receptor antagonist, compared with enalapril in elderly patients with primary hypertension

ObjectiveTo assess the antihypertensive efficacy and safety of the novel AT1 receptor antagonist, telmisartan, compared with that of enalapril in elderly patients with mild to moderate hypertension.DesignA 26–week, multicenter, double-blind, parallel-group, dosage titration study.MethodsA total of 2
Association of alpha2a and beta2 adrenoceptor expression with clinical outcome in breast cancer

Abstract Background: Alpha2-adrenoceptor (α2 AR) antagonists inhibit the growth of breast cancer cells. The action of beta2-adrenoceptors (β2 AR) on cell proliferation is still controversial. In this study, we investigated the association of α2a and β2 AR expression with tumor-relevant biological markers and clinical outcome. Methods: The expression of α2a and β2 AR was examined in paraffin-embedded samples of 220 operable breast tumors by immunohistochemistry. Associations between AR expression and tumor-relevant biomarkers were evaluated using the chi-square or Fisher’s exact tests. Univariate analysis was modeled using Kaplan–Meier plots and multivariate analysis was modeled using the Cox test and adjusted for age, tumor size, lymph node status, and ER, PR and Her-2 status. Results: The α2a AR expression was associated with Her-2 status (P = 0.048) and a marginal significance was observed between α2a AR expression and ER (P = 0.061). In hormone receptor positive breast cancer patients, strong β2 AR expression correlated with better disease free survival (DFS) than weak expression (P = 0.031) and β2 AR (HR = 0.31, P = 0.039) and lymph node status (HR = 2.85, P = 0.031) were independent predictors of DFS on multivariate analysis. Conclusion: In hormone receptor positive breast cancer patients, strong β2 AR expression is correlated with better DFS than weak β2 AR expression and an interaction may exist between β2 AR and hormone receptor pathways. Some limitations of this study were the relatively small sample size and the intrinsic nature of retrospective study per se. Findings of the study are for hypothesis only and need to be confirmed in large prospective studies.