Miracle-dz/UniFAR-FTUs huggingface dataset:
Managing diabetic kidney disease

Introduction Diabetes mellitus (DM) is the leading cause of chronic kidney disease (CKD). This review covers the pillars of care essential for the management of diabetic kidney disease (DKD) including (1) early diagnosis, (2) improved glycaemic control, (3) treatment of hypertension, (4) identification and treatment of associated metabolic bone disease and (5) identification and effective management of dyslipidaemia and additional cardiovascular risk factors. Sources of data We searched PubMed for articles using search terms: diabetic nephropathy, diabetic kidney disease, diabetes and chronic kidney disease. We used clinical guidelines from NICE, the Association of British Clinical Diabetologists (ABCD), the Joint British Societies (JBS) and the Kidney Disease: Improving Global Outcomes (KDIGO) working group. Areas of agreement Multiple risk factor reduction targeting glycaemic control, blood pressure control, dyslipidaemia, smoking and management of obesity is important in preventing and in managing DKD. Areas of controversy Guidelines disagree on the individualized glycaemic targets for patients with diabetic kidney disease. Growing points The growing number of patients with DKD is causing increased pressure on limited primary care and specialized services. New ways of managing patients using novel technology solutions are required. Areas timely for development The use of novel anti-hyperglycaemic agents, particularly sodium glucose co-transporter 2 inhibitors and GLP-1 receptor agonists, has been associated with a reduction in cardiovascular disease and DKD.
The clinical and epidemiological profile of Lyme neuroborreliosis in Denmark 1985-1990. A prospective study of 187 patients with Borrelia burgdorferi specific intrathecal antibody production.

This prospective study reports the clinical and epidemiological features of 187 consecutive patients with neuroborreliosis recognized in Denmark over the 6-yr period, 1985-1990. Only patients with intrathecal Borrelia burgdorferi specific antibody synthesis were included. In 1990 regional incidences varied between 5.7 and 24.1 per million. Ninety-four percent of the patients had early (second stage) neuroborreliosis. The most common manifestation was a painful lymphocytic meningoradiculitis (Bannwarth's syndrome) either with paresis (61%) or as a radicular pain syndrome only (25%). Central nervous system (CNS) involvement in early neuroborreliosis was rare; 4% had signs of myelitis and only one patient had acute encephalitis. Children showed a different course of the disease. Six percent of the patients suffered a chronic course with a disease duration between 6 mths and 6 yrs either as chronic lymphocytic meningitis (1.6%) or as third stage chronic encephalomyelitis (4.3%). Meningeal signs were rare despite pronounced inflammatory cerebrospinal fluid (CSF) changes (median cell count 160/microliters; median protein concentration 1.13 g/l). High dose i.v. penicillin G was administered to 91% of the patients. Based on the clinical outcome and normalization of CSF no treatment failures were recognized. The final morbidity after a median follow-up of 33 mths was low; disabling sequelae were reported in nine patients, mainly those with previous CNS involvement. We conclude that neuroborreliosis is a common and characteristic neurological disorder. The diagnosis should be based on the demonstration of inflammatory CSF changes and B. burgdorferi specific intrathecal antibody production.
Use of the Over-The-Scope Clip for treatment of refractory upper gastrointestinal bleeding: a case series

The Over-The-Scope Clip (OTSC; Ovesco, Tübingen, Germany) is a novel endoscopic clipping device designed for tissue approximation. The device has been used in the closure of fistulas and perforations. We hereby report on a series of patients in whom OTSCs were used for endoscopic control of refractory or major upper gastrointestinal bleeding from lesions in the gastroduodenal tract between 1 July and 31 December 2012. Nine patients were included (median age 72.5 years, range 39 – 91) with bleeding gastric ulcers (n = 2), bleeding duodenal ulcers (n = 5), bleeding gastrointestinal stromal tumor in the stomach (n = 1), and bleeding from ulcerative carcinoma of the pancreas (n = 1). The median size of the ulcers was 2.5 cm (range 1 – 4). Six of the nine patients had undergone previous endoscopic hemostasis. Technical success was achieved in all patients and the clinical effectiveness was 77.8 %. The OTSC is a safe and effective method of endoscopic hemostasis for major bleeding from miscellaneous upper gastrointestinal causes and should be considered in patients with refractory bleeding after failure of conventional methods of endoscopic hemostasis.
Risk of recurrent gastric cancer after endoscopic resection with a positive lateral margin

Background and study aims: After noncurative endoscopic submucosal dissection (ESD) for differentiated-type early gastric cancer (EGC), close observation is often preferred when a cancer-positive lateral margin is the only noncurative factor. However, sometimes recurrence is found during the observation period. This study aimed to examine risk factors for recurrent cancer based on the long-term clinical outcomes after noncurative ESD in which the only noncurative factor was a cancer-positive lateral margin. Patients and methods: Among 3784 EGCs (3316 patients) treated by ESD between 1997 and 2010, 77 noncurative differentiated-type EGCs (75 patients) were retrospectively analyzed after meeting the following inclusion criteria: 1) the only noncurative factor was a cancer-positive lateral margin; 2) close observation was selected after the ESD; and 3) > 1 year follow-up after ESD. Results: Locally recurrent cancer was found in 10 lesions within a median follow-up period of 59.8 months; no metastasis or gastric cancer-related death occurred. The cumulative incidence of local recurrence 5 years after ESD was 11.9 %. All locally recurrent cancers were mucosal differentiated-type adenocarcinomas. Multivariate analysis indicated that a cancer-positive lateral margin length of ≥ 6 mm was significantly associated with local recurrence (hazard ratio 20.8; 95 % confidence interval 5.2 % – 82.9 %; P < 0.001). The cut-off value of 6 mm was determined by the receiver operating characteristic curve; the sensitivity and specificity for 5-year risk of developing local recurrence were 66.7 % and 95.6 %, respectively. Conclusions: A cancer-positive lateral margin length of ≥ 6 mm was an independent risk factor for local recurrence, and this may be a useful criterion for selecting high-risk cases for stricter management.
Integrative analysis of miRNA and mRNA paired expression profiling of primary fibroblast derived from diabetic foot ulcers reveals multiple impaired cellular functions

Diabetic foot ulcers (DFUs) are one of the major complications of diabetes. Its molecular pathology remains poorly understood, impeding the development of effective treatments. Although it has been established that multiple cell types, including fibroblasts, keratinocytes, macrophages, and endothelial cells, all contribute to inhibition of healing, less is known regarding contributions of individual cell type. Thus, we generated primary fibroblasts from nonhealing DFUs and evaluated their cellular and molecular properties in comparison to nondiabetic foot fibroblasts (NFFs). Specifically, we analyzed both micro‐RNA and mRNA expression profiles of primary DFU fibroblasts. Paired genomic analyses identified a total of 331 reciprocal miRNA–mRNA pairs including 21 miRNAs (FC > 2.0) along with 239 predicted target genes (FC > 1.5) that are significantly and differentially expressed. Of these, we focused on three miRNAs (miR‐21‐5p, miR‐34a‐5p, miR‐145‐5p) that were induced in DFU fibroblasts as most differentially regulated. The involvement of these microRNAs in wound healing was investigated by testing the expression of their downstream targets as well as by quantifying cellular behaviors in prospectively collected and generated cell lines from 15 patients (seven DFUF and eight NFF samples). We found large number of downstream targets of miR‐21‐5p, miR‐34a‐5p, miR‐145‐5p to be coordinately regulated in mRNA profiles, which was confirmed by quantitative real‐time PCR. Pathway analysis on paired miRNA–mRNA profiles predicted inhibition of cell movement and cell proliferation, as well as activation of cell differentiation and senescence in DFU fibroblasts, which was confirmed by cellular assays. We concluded that induction of miR‐21‐5p, miR‐34a‐5p, miR‐145‐5p in DFU dermal fibroblasts plays an important role in impairing multiple cellular functions, thus contributing to overall inhibition of healing in DFUs.
Endoscopic submucosal dissection for superficial rectal tumors: prospective evaluation in France

Background and study aims: Endoscopic submucosal dissection (ESD) provides a high en bloc resection rate for superficial colorectal tumors. The aims of this study were to assess the feasibility of ESD in France and to evaluate the complete resection rate at 1 year. Patients and methods: Patients with superficial rectal tumors ≥ 10 mm in size were prospectively included in the study at nine French expert centers between February 2010 and June 2012. The study was stopped temporarily because of a high complication rate. Study recruitment resumed following remedial action. Results: A total of 45 patients were included (mean age 67 years; 24 males). The immediate perforation rate was 18 % (n = 8), and salvage surgery was not required. Six patients (13 %) had late bleeding, which was treated endoscopically in five patients and surgically in one patient who had required blood transfusion. The mortality rate was zero. The en bloc resection rate was 64 % (29/45), and the curative R0 resection rate was 53 % (24/45). Three patients (7 %) had an invasive tumor (two sm1, one T2). At 1-year follow-up, endoscopic examinations showed complete resection in 38 /43 patients (88 %). At the end of the study, after the remedial action, the en bloc resection rate had increased from 52 % to 82 %, and the perforation rate had decreased significantly from 34 % to 0 %. Conclusions: The study reflects the initial prospective experience of ESD in France, and suggests that curative R0 resection rates should increase and complication rates should decrease with experience and corrective actions.
Use of implementation theory: a focus on PARIHS.

BACKGROUND Limited understanding and application of theory in implementation research contributes to variable effectiveness of implementation studies. Better understanding of direct experiences with theory could improve implementation research and the potency of interventions. AIMS This study was a conceptual exercise aimed at characterizing experiences with and applications of the Promoting Action on Research Implementation in Health Services (PARIHS) framework. METHODS This was a structured, qualitative study involving document reviews and interviews used to answer the following overarching questions about nine implementation research centers: Why and how was PARIHS used? What strengths and weaknesses were identified for PARIHS? FINDINGS PARIHS was being used for varied purposes, at varied levels, in varied ways, and to a varying extent within and across centers. Lack of implementation theory use in investigators' early years was common. Variability in the nature of theory use was attributable to characteristics of the centers, individual investigators, and features of PARIHS. Strengths and weaknesses of the PARIHS framework were identified. LINKING EVIDENCE TO ACTION The study provides information to researchers and theorists about the use of one well-known implementation framework. The information suggests areas for improvements in PARIHS as well as theory use in general, and should assist in the development of theory-based programs of research.
Heterozygous OPA1 mutations in Behr syndrome.

ARTICLE Sir, We read with interest the paper by Yu-Wai-Man et al. (2010) on patients with dominant optic atrophy-plus with OPA1 mutations, which follows on previous reports by the same group (Amati-Bonneau et al. , 2008; Hudson et al. , 2008), reporting the relatively high frequency (∼20%) and the large spectrum of extra-ocular neurological involvement in OPA1 disease. Here, we extend the clinical spectrum of OPA1 mutations to Behr syndrome, characterized by early-onset optic atrophy associated with pyramidal signs, ataxia and sometimes, posterior column sensory loss and mental retardation (Behr 1909; Thomas et al. , 1984). This clinical entity is probably a heterogeneous group of disorders, whose real causes are mostly unknown. In most cases, autosomal recessive inheritance has been suspected. A few patients with typical Behr syndrome and several with Costeff syndrome, a Behr syndrome-like disease associating optic atrophy with extrapyramidal signs, were shown to have type III 3-methylglutaconic aciduria (MGA type III), a recessive disease characterized …
Serotonin Transporter Gene Polymorphisms and Selective Serotonin Reuptake Inhibitor Tolerability: Review of Pharmacogenetic Evidence

Selective serotonin reuptake inhibitors (SSRIs) are first‐line pharmacotherapy for mood and anxiety disorders. The common mechanism of drugs in this class is antagonism of the serotonin transporter. Within the serotonin transporter gene SLC6A4, two polymorphic sites termed 5‐HTTLPR and STin2 are proposed to have functional consequences and thus have been attractive candidates for pharmacogenetic studies of SSRI efficacy and tolerability. This review summarizes approximately 15 years of study of these polymorphisms as they relate to SSRI tolerability phenotypes. Four online databases (PubMed, Cochrane CENTRAL, PsycINFO, and PharmGKB) were searched for articles on polymorphisms of SLC6A4 including 5‐HTTLPR and STin2 by using a systematic approach. Specific and general psychopharmacology terms, along with adverse effect and tolerability concepts, added to the search strategy. The Human Gene Mutation Database was checked for additional references. Forty studies met the inclusion criteria. While null and occasionally opposite associations are reported, the low expression 5‐HTTLPR S allele is generally associated with greater adverse drug reaction burden during SSRI therapy. The most convincing evidence is in studies of antidepressant‐induced mania and gastrointestinal adverse events. Studies of STin2 are sparse and have conflicting findings. In conclusion, the S allele of 5‐HTTLPR may be predictive of increased adverse event burden, and this effect appears specific to certain classes of adverse events. Limitations and challenges in interpreting this body of evidence include assay errors, dissimilar grouping of genotypes, the role of ethnicity in associations, and study methodological differences. The clinical utility of serotonin transporter genotypes is not yet delineated but will ultimately depend on genotypic effects on both tolerability and efficacy of SSRIs.
Thyroid dysfunction and reproductive health

Thyroid disease is a common condition in the reproductive medicine setting due to the complex interplay between the hypothalamo‐pituitary axis and the thyoid gland. Abnormalities in thyroid function, including hyperthyroidism and hypothyroidism, can have an adverse effect on reproductive health and result in reduced rates of conception, increased early pregnancy loss, and adverse pregnancy and neonatal outcomes. There is increasing evidence for the role of autoantibodies in subfertility and early pregnancy loss, even in euthyroid women. Evidence suggests that treating thyroid disorders and keeping thyroid‐stimulating hormone levels at the lower end of normal in euthyroid women may improve conception rates in subfertile women and reduce early pregnancy loss.
Considerations for Optimal Blood Pressure Goals in the Elderly Population: A Review of Emergent Evidence

Recent hypertension clinical trials and national guideline updates have created a debate on the most appropriate treatment goals in elderly patients with hypertension. In 2014, recommendations by the Eighth Joint National Committee allowed a more lenient goal for patients 60 years and older compared with previous guidelines. Since then, several large clinical trials and meta‐analyses have added more information regarding strict versus lenient treatment goals. Most recently, the American College of Cardiology and American Heart Association Task Force published their highly anticipated hypertension guideline developed in conjunction with nine additional interdisciplinary organizations. This review discusses the culmination of emerging data to provide more insight into the treatment of hypertension in the elderly. A literature search was conducted using PubMed, the Cumulative Index of Nursing and Allied Health, the Cochrane database, and by hand‐searching references from relevant articles. The following key terms were used: hypertension, blood pressure, systolic, and elderly. Available literature suggests that it is reasonable to target an office systolic blood pressure of less than 130 mm Hg in elderly patients with hypertension. An individualized approach is reasonable for those who are institutionalized, with high comorbidity burden, or have a short life expectancy. A diastolic blood pressure of less than 60 mm Hg should be avoided due to the potential for an increase in cardiovascular risk. The method of blood pressure measurement is extremely important to consider when determining the blood pressure goal, and proper procedures for accurate blood pressure measurement must be followed. Other factors important to consider may include the patient's comorbidities, frailty, as well as the patient's potential for adverse drug reactions.
Child sexual abuse among Asian communities: Developing materials to raise awareness in Bradford

This article starts from a recognition that child sexual abuse is perpetrated in all communities, but appears to be under-reported to varying degrees in different communities. It acknowledges that children who have been sexually abused will usually benefit from services designed to assist them in moving on from this experience and to provide future protection from perpetrators. It notes, in particular, the apparent disproportionately low take-up of relevant services by members of Asian communities in Britain. It places this in the context of reported responses to child sexual abuse in Pakistan, India and Bangladesh and explores the likely impact of factors arising from cultural norms in relation to family structure and role relationships. It reports on work begun within Asian communities in Bradford to increase awareness of and appropriate responses to child sexual abuse which hopefully address issues which are of relevance elsewhere. In particular, it discusses responses to a preliminary questionnaire, discussions with community groups, a consultation event held in April 2003, and a multilingual information booklet produced as a result. It urges respectful dialogue with women, men, children and young people in Asian communities as being essential to progress regarding appropriate responses to child sexual abuse.
Single-subject oscillatory gamma responses in tinnitus

This study used magnetoencephalography to record oscillatory activity in a group of 17 patients with chronic tinnitus. Two methods, residual inhibition and residual excitation, were used to bring about transient changes in spontaneous tinnitus intensity in order to measure dynamic tinnitus correlates in individual patients. In residual inhibition, a positive correlation was seen between tinnitus intensity and both delta/theta (6/14 patients) and gamma band (8/14 patients) oscillations in auditory cortex, suggesting an increased thalamocortical input and cortical gamma response, respectively, associated with higher tinnitus states. Conversely, 4/4 patients exhibiting residual excitation demonstrated an inverse correlation between perceived tinnitus intensity and auditory cortex gamma oscillations (with no delta/theta changes) that cannot be explained by existing models. Significant oscillatory power changes were also identified in a variety of cortical regions, most commonly midline lobar regions in the default mode network, cerebellum, insula and anterior temporal lobe. These were highly variable across patients in terms of areas and frequency bands involved, and in direction of power change. We suggest a model based on a local circuit function of cortical gamma-band oscillations as a process of mutual inhibition that might suppress abnormal cortical activity in tinnitus. The work implicates auditory cortex gamma-band oscillations as a fundamental intrinsic mechanism for attenuating phantom auditory perception.
Bioequivalence Study of Two Imatinib Formulations after Single-dose Administration in Healthy Korean Male Volunteers

Abstract Objective: Imatinib mesylate is effective for chronic myeloid leukaemia and gastrointestinal tumours. We aimed to evaluate the pharmacokinetics of a 200-mg imatinib tablet compared to 2×100-mg imatinib tablets in order to meet the regulatory requirements for marketing in Korea. Methods: An open-label, randomized, single-dose, 2-period, 2-treatment cross-over study was conducted in 28 healthy Korean male volunteers. Subjects were administered a 200-mg imatinib tablet and 2×100-mg imatinib tablets under a fasting state according to a randomly assigned order with a 2-week wash-out period. Serial blood samples were collected up to 72 h post-dose. The pharmacokinetic parameters were calculated using non-compartmental methods. Results: A total of 28 subjects were enrolled and 23 subjects completed the study. There were no serious adverse events during the study. 23 mild to moderate adverse events were reported (11 events with 200-mg imatinib vs. 12 events with 2×100-mg imatinib) and subjects recovered without sequelae. The Cmax value was 922.8±318.8 μg/L at 3.15 h for 200-mg imatinib tablet, and 986.3±266.0 μg/L at 2.91 h for the 2×100-mg imatinib tablet. The AUClast of 200-mg and 2×100-mg tablets were 13 084.3±39.1 and 14 131.7±3 826.2 h · μg/L, respectively. The geometric mean ratios (90% confidence intervals) for Cmax and AUClast were 0.9121 (0.8188, 1.0161) and 0.9558 (0.8685, 1.0519), respectively. Conclusion: A newly developed 200-mg imatinib tablet was bioequivalent to 2×100-mg imatinib tablets in healthy Korean subjects. A single-dose of either of the 2 formulations was generally well tolerated.
Schedule for personality assessment from notes and documents (SPAN-DOC): Preliminary validation, links to the ICD-11 classification of personality disorder, and use in eating disorders.

BACKGROUND The underlying core of personality is insufficiently assessed by any single instrument. This has led to the development of instruments adapted for written records in the assessment of personality disorder. AIMS To test the construct validity and inter-rater reliability of a new personality assessment method. METHOD This study (four parts) assessed the construct validity of the Schedule for Personality Assessment from Notes and Documents (SPAN-DOC), a dimensional assessment from clinical records. We examined inter-rater reliability using case vignettes (Part 1) and convergent validity in three ways: by comparison with NEO Five-Factor Inventory in 130 Korean patients (Part 2), with agreed ICD-11 personality severity levels in two populations (Part 3) and determining its use in assessing the personality status in 90 British patients with eating disorders (Part 4). RESULTS Internal consistency (alpha = .90) and inter-rater reliability (intraclass correlation coefficient ≥ .88) were satisfactory. Each factor in the five-factor model of personality was correlated with conceptually valid SPAN-DOC variables. The SPAN-DOC domain traits in those with eating disorders were categorized into 3 clusters: self-aggrandisement, emotionally unstable, and anxious/dependent. CONCLUSIONS This study provides preliminary support for the usefulness of SPAN-DOC in the assessment of personality disorder. Copyright © 2016 John Wiley & Sons, Ltd.