Miracle-dz/UniFAR-FTUs huggingface dataset:
Pituitary-targeted medical therapy of Cushing's disease

Background: The goals of ideal medical therapy for Cushing's disease should be to target the aetiology of the disorder, as is the case for surgery, which is the current ‘gold standard’ treatment. However, no effective drug that directly and reliably targets the adrenocorticotropin-secreting pituitary adenoma has yet been found. Objective: To summarise pituitary-targeted medical treatment of Cushing's disease. Methods: Compounds with neuromodulatory properties and ligands of different nuclear hormone receptors involved in hypothalamo–pituitary regulation have been investigated. Results: The somatostatin analogue pasireotide and the dopamine agonist cabergoline, as well as their combination, show some therapeutic promise in the medical therapy of Cushing's disease. Other treatments such as retinoic acid analogues look promising and may be a possible option for further investigation. No other medical therapies seem to be reliably effective currently. Conclusion: Since a percentage of patients treated with surgery are not cured, or improve and subsequently relapse, there is an urgent need for effective medical therapies for this disorder. At present, only cabergoline and pasireotide are under active investigation.
Batf-dependent Th17 cells critically regulate IL-23 driven colitis-associated colon cancer

Objectives IBDs have an increased risk for development of colorectal cancer (CRC). Here, we aimed at the characterisation of the functional role of Th17-associated transcription factors in sporadic and colitis-associated colon cancer in vivo. Design We used mice deficient or transgenic for the activating protein 1 family member basic leucine zipper transcription factor ATF-like (Batf) to evaluate the role of Th17 cells during sporadic and inflammation-induced colon carcinogenesis. We also studied the expression of Batf and RORγt in patients with IBD and CRC. Results Batf but not retinoic acid-related orphan receptor γt(RORγt) expression was significantly increased together with interleukin (IL) 23 expression in UC but not in Crohn's disease (CD) tissue samples. In CRC also Batf but not RORγt expression was increased and its expression correlated with the IL-23 and IL-23 receptor (IL-23R) expression. Finally, Batf but not RORγt was coexpressed with IL-17a, IL-23R and IL-6 within CRC-infiltrating CD4+ T cells. Functional studies in mice revealed that Batf-dependent T cells are crucial regulators of sporadic and inflammation-induced CRC. Colitis-associated Batf−/− tumours lacked IL-17a+IL-23R+IL-6+CD4+ T cells, hence displaying characteristics reminiscent of human CRC-infiltrating CD4+ T cells. Strikingly, Batf−/− tumours contained low IL-23 but high IL-17a expression levels. Tumour formation and intratumoral IL-23 expression could be restored by administration of Hyper-IL-6 consisting of IL-6 and soluble IL-6 receptor. Conclusions Batf-dependent IL-23R+IL-6+CD4+ Th17 cells critically control IL-23 driven colitis-associated tumour formation and the progression of sporadic colon tumours. Batf-dependent IL-23R+ T cells represent a potential future therapeutic target limiting CRC progression.
ATG16L1 contributes to Crohn's disease susceptibility in Koreans: overmuch concern for ethnic difference?

The incidence of Crohn’s disease (CD) increases steadily in Asia, but is still quite low compared with Western countries.1 So far, over 140 susceptibility loci to CD have been identified in Caucasians through genome-wide association studies (GWASs) and meta-analyses.2 Recent GWASs in Korean and Japanese populations identified a few more susceptibility loci, but could not replicate many established CD loci.3 ,4 A Japanese large scale replication study consisting of 1311 cases and 6585 controls could replicate less than half of 71 CD susceptibility loci identified in Caucasians.5 Particularly, it aroused concern that such well-established loci as ATG16L1 and NOD2 have not been replicated. It was unclear whether the lack of association was due to limited statistical power, different linkage disequilibrium (LD) structure, …
A Prospective Evaluation of Shared Decision-making Regarding Analgesics Selection for Older Emergency Department Patients With Acute Musculoskeletal Pain.

OBJECTIVES Musculoskeletal pain is a common reason for emergency department (ED) visit by older adults. Outpatient pain management following ED visits in this population is challenging as a result of contraindications to, and side effects from, available therapies. Shared decision-making (SDM) between patients and emergency physicians may improve patient experiences and health outcomes. Among older ED patients with acute musculoskeletal pain, we sought to characterize their desire for involvement in the selection of outpatient analgesics. We also sought to assess the impact of SDM on change in pain at 1 week, patient satisfaction, and side effects. METHODS This was a prospective study of adults aged 60 years and older presenting to the ED with acute musculoskeletal pain. Participants' desire to contribute to outpatient analgesic selection was assessed by phone within 24 hours of ED discharge using the Control Preferences Scale and categorized as active, collaborative, or passive. The extent to which SDM occurred in the ED was also assessed within 24 hours of discharge using the 9-item Shared Decision Making Questionnaire, and scores were subsequently grouped into tertiles of low, middle, and high SDM. The primary outcome was change in pain severity between the ED visit and 1 week. Secondary outcomes included satisfaction regarding the decision about how to treat pain at home, satisfaction with the pain medication itself, and side effects. RESULTS Desire of participants (N = 94) to contribute to the decision regarding selection of outpatient analgesics varied: 16% active (i.e., make the final decision themselves), 37% collaborative (i.e., share decision with provider), and 47% passive (i.e., let the doctor make the final decision). The percentage of patients who desired an active role in the decision was higher for patients who were college educated versus those who were not college educated (28% vs. 11%; difference 17%, 95% confidence interval [CI] = 0% to 35%), received care from a nurse practitioner versus a resident or an attending physician (32% vs. 9%; difference 23%, 95% CI = 4% to 42%), or received care from a female versus a male provider (24% vs. 5%; difference 19%, 95% = CI 5% to 32%). After potential confounders were adjusted for, the mean decrease in pain severity from the ED visit to 1-week follow-up was not significantly different across tertiles of SDM (p = 0.06). Higher SDM scores were associated with greater satisfaction with the discharge pain medications (p = 0.006). SDM was not associated with the class of analgesic received. CONCLUSIONS In this sample of older adults with acute musculoskeletal pain, the reported desire of patients to contribute to decisions regarding analgesics varied based on both patient and provider characteristics. SDM was not significantly related to pain reduction in the first week or type of pain medication received, but was associated with greater patient satisfaction.
Urinary Squamous Epithelial Cells Do Not Accurately Predict Urine Culture Contamination, but May Predict Urinalysis Performance in Predicting Bacteriuria.

OBJECTIVES The presence of squamous epithelial cells (SECs) has been advocated to identify urinary contamination despite a paucity of evidence supporting this practice. We sought to determine the value of using quantitative SECs as a predictor of urinalysis contamination. METHODS Retrospective cross-sectional study of adults (≥18 years old) presenting to a tertiary academic medical center who had urinalysis with microscopy and urine culture performed. Patients with missing or implausible demographic data were excluded (2.5% of total sample). The primary analysis aimed to determine an SEC threshold that predicted urine culture contamination using receiver operating characteristics (ROC) curve analysis. The a priori secondary analysis explored how demographic variables (age, sex, body mass index) may modify the SEC test performance and whether SECs impacted traditional urinalysis indicators of bacteriuria. RESULTS A total of 19,328 records were included. ROC curve analysis demonstrated that SEC count was a poor predictor of urine culture contamination (area under the ROC curve = 0.680, 95% confidence interval [CI] = 0.671 to 0.689). In secondary analysis, the positive likelihood ratio (LR+) of predicting bacteriuria via urinalysis among noncontaminated specimens was 4.98 (95% CI = 4.59 to 5.40) in the absence of SECs, but the LR+ fell to 2.35 (95% CI = 2.17 to 2.54) for samples with more than 8 SECs/low-powered field (lpf). In an independent validation cohort, urinalysis samples with fewer than 8 SECs/lpf predicted bacteriuria better (sensitivity = 75%, specificity = 84%) than samples with more than 8 SECs/lpf (sensitivity = 86%, specificity = 70%; diagnostic odds ratio = 17.5 [14.9 to 20.7] vs. 8.7 [7.3 to 10.5]). CONCLUSIONS Squamous epithelial cells are a poor predictor of urine culture contamination, but may predict poor predictive performance of traditional urinalysis measures.
Potentially Avoidable Pediatric Interfacility Transfer Is a Costly Burden for Rural Families: A Cohort Study.

OBJECTIVES Interhospital transfer is a common strategy to provide high-quality regionalized care in rural emergency departments (EDs), but several reports have highlighted problems with selection of children for transfer. The purpose of this study is to characterize the burden of potentially avoidable transfer (PAT) and to estimate the medical and family-oriented costs associated with PAT. METHODS This study was a cohort study of all children treated in Iowa EDs between 2004 and 2013. PAT was defined as a child who was transferred and then either discharged from the receiving ED or admitted for ≤ 1 day, without having any separately billed procedures performed. Costs of care were estimated from 1) medical costs, 2) ambulance transfer, and 3) family costs (travel and lodging). RESULTS Over 10 years, 2,117,317 children were included (1% transferred to another hospital). Only 63% were transferred to a designated children's hospital, and PATs were identified in 39% of all transfers. PAT was associated with $909 in additional cost. The conditions most strongly associated with PAT were seizure (additional cost $1,138), fracture ($814), isolated traumatic brain injury without extra-axial bleeding ($1,455), respiratory infection ($556), and wheezing ($804). Few of these charges are attributable to nonmedical family costs ($21). CONCLUSIONS Potentially avoidable pediatric interhospital transfer is common and is responsible for significant healthcare-related costs. Future work should focus on improving selection of children who benefit from interhospital transfer for high-yield conditions, to reduce the costly and distressing burden that PAT places on rural patients and their families.
Near-infrared Spectroscopy Monitoring During Cardiac Arrest: A Systematic Review and Meta-analysis.

BACKGROUND Tissue oximetry using near-infrared spectroscopy (NIRS) is a noninvasive monitor of cerebral oxygenation. This new technology has been used during cardiac arrest (CA) because of its ability to give measures in low-blood-flow situations. The aim of this study was to assess the evidence regarding the association between the types of NIRS measurements (mean, initial, and highest values) and resuscitation outcomes (return of spontaneous circulation [ROSC], survival to discharge, and good neurologic outcome) in patients undergoing cardiopulmonary resuscitation. METHODS This review was registered (Prospero CRD42015017380) and is reported as per the PRISMA guidelines. Medline, Embase, and CENTRAL were searched. All studies, except case reports and case series of fewer than five patients, reporting on adults that had NIRS monitoring during CA were eligible for inclusion. Two reviewers assessed the quality of the included articles and extracted the data. The outcome effect was standardized using standardized mean difference (SMD). RESULTS Twenty nonrandomized observational studies (15 articles and five conference abstracts) were included in this review, for a total of 2,436 patients. We found a stronger association between ROSC and mean NIRS values (SMD = 1.33; 95% confidence interval [CI] = 0.92 to 1.74) than between ROSC and initial NIRS measurements (SMD = 0.51; 95% CI = 0.23 to 0.78). There was too much heterogeneity among the highest NIRS measurements group to perform meta-analysis. Only two of the 75 patients who experienced ROSC had a mean NIRS saturation under 30%. Patients who survived to discharge and who had good neurologic outcome displayed superior combined initial and mean NIRS values than their counterparts (SMD = 1.63; 95% CI = 1.34 to 1.92; and SMD = 2.12; 95% CI = 1.14 to 3.10). CONCLUSIONS Patients with good resuscitation outcomes have significantly higher NIRS saturations during resuscitation than their counterparts. The types of NIRS measurements during resuscitation influenced the association between ROSC and NIRS saturation. Prolonged failure to obtain a NIRS saturation higher than 30% may be included in a multimodal approach to the decision of terminating resuscitation efforts (Class IIb, Level of Evidence C-Limited Data).
Double-blind Randomized Controlled Trial of Intranasal Dexmedetomidine Versus Intranasal Midazolam as Anxiolysis Prior to Pediatric Laceration Repair in the Emergency Department.

OBJECTIVE The objective of this study was to compare anxiolysis with intranasal dexmedetomidine, an alpha-2 agonist, versus intranasal midazolam for pediatric laceration repairs. METHODS We performed a double-blind, randomized controlled trial of 40 patients 1-5 years with lacerations requiring suture repair in an academic pediatric emergency department (ED). Patients were randomized to receive either intranasal dexmedetomidine or intranasal midazolam. Our primary outcome measure was the anxiety score at the time of patient positioning for the laceration repair. We chose this time point to isolate the anxiolysis from the medications prior to intervention. Patient encounters were videotaped and scored for anxiety at multiple time points using the modified Yale Preoperative Anxiety Scale. The scale is 23.3-100 with higher scores indicating higher anxiety. We also evaluated these scores as a secondary outcome by dichotomizing them into anxious versus not anxious with a previously validated score cutoff. RESULTS Of the 40 patients enrolled, 20 in the dexmedetomidine group and 18 in the midazolam group completed the study and were included in the analysis. The median age was 3.3 years (range = 1.0-5.4 years). The median baseline anxiety score was 48.3. The anxiety score at position for procedure for patients receiving dexmedetomidine was 9.2 points lower than those receiving midazolam (median difference = 9.2, 95% confidence interval = 5 to 13.3; median score for dexmedetomidine = 23.3, median score for midazolam = 36.3). The proportion of patients who were classified as not anxious at the position for procedure was significantly higher in the dexmedetomidine group (70%) versus the midazolam group (11%). The number needed to treat with dexmedetomidine instead of midazolam to obtain the result of a not anxious patient at this time point was 1.7 patients. There were also significantly more patients who were classified as not anxious at the time of wound washout in the dexmedetomidine group compared to the midazolam group (35% vs. 6%). Dexmedetomidine and midazolam performed similarly with respect to all other measures including anxiety at other time points, parental perceived anxiety, parent and proceduralist satisfaction, procedural success, complications, and time in the ED. There were no serious adverse events seen in either group. CONCLUSIONS Intranasal dexmedetomidine is an alternative anxiolytic medication to intranasal midazolam for pediatric laceration repairs, performing similarly in our study, except that patients who received dexmedetomidine had less anxiety at the time of positioning for procedure.
Clinical manifestations in primary ciliary dyskinesia: systematic review and meta-analysis

Few original studies have described the prevalence and severity of clinical symptoms of primary ciliary dyskinesia (PCD). This systematic review and meta-analysis aimed to identify all published studies on clinical manifestations of PCD patients, and to describe their prevalence and severity stratified by age and sex. We searched PubMed, Embase and Scopus for studies describing clinical symptoms of ≥10 patients with PCD. We performed meta-analyses and meta-regression to explain heterogeneity. We included 52 studies describing a total of 1970 patients (range 10–168 per study). We found a prevalence of 5% for congenital heart disease. For the rest of reported characteristics, we found considerable heterogeneity (I2 range 68–93.8%) when calculating the weighted mean prevalence. Even after taking into account the explanatory factors, the largest part of the between-studies variance in symptom prevalence remained unexplained for all symptoms. Sensitivity analysis including only studies with test-proven diagnosis showed similar results in prevalence and heterogeneity. Large differences in study design, selection of study populations and definition of symptoms could explain the heterogeneity in symptom prevalence. To better characterise the disease, we need larger, multicentre, multidisciplinary, prospective studies that include all age groups, use uniform diagnostics and report on all symptoms. Review of the clinical manifestations of PCD found between-study variation; large prospective studies needed http://ow.ly/Y5GC300Sw73
Challenges Enrolling Children Into Traumatic Brain Injury Trials: An Observational Study

OBJECTIVES In preparation for a clinical trial of therapeutic agents for children with moderate-to-severe blunt traumatic brain injuries (TBIs) in emergency departments (EDs), we conducted this feasibility study to (1) determine the number and clinical characteristics of eligible children, (2) determine the timing of patient and guardian arrival to the ED, and (3) describe the heterogeneity of TBIs on computed tomography (CT) scans. METHODS We conducted a prospective observational study at 16 EDs of children ≤ 18 years of age presenting with blunt head trauma and Glasgow Coma Scale scores of 3-12. We documented the number of potentially eligible patients, timing of patient and guardian arrival, patient demographics and clinical characteristics, severity of injuries, and cranial CT findings. RESULTS We enrolled 295 eligible children at the 16 sites over 6 consecutive months. Cardiac arrest and nonsurvivable injuries were the most common characteristics that would exclude patients from a future trial. Most children arrived within 2 hours of injury, but most guardians did not arrive until 2-3 hours after the injury. There was a substantial range in types of TBIs, with subdural hemorrhages being the most common. CONCLUSION Enrolling children with moderate-to-severe TBI into time-sensitive clinical trials will require large numbers of sites and meticulous preparation and coordination and will prove challenging to obtain informed consent given the timing of patient and guardian arrival. The Federal Exception from Informed Consent for Emergency Research will be an important consideration for enrolling these children.
Audit of the use of psychotropic medication for challenging behaviour in a community learning disability service

AIMS AND METHOD The aims of the study were to identify patients in a community learning disability service receiving psychotropic medication for challenging behaviour, to examine prescribing practice and to compare this against local consensus standards. Local consensus standards were agreed by the consultants and the notes were reviewed by the author. RESULTS A total of 102 patients were identified as receiving psychotropic medication for challenging behaviour (26.7% of notes examined). The most common additional diagnoses were autism (29%) and epilepsy (28%). The average duration of treatment was 5.3 years, and multiple drugs were used in 34% of these patients. Antipsychotics were the most commonly used drugs (96% of patients). There was rarely a detailed description of the challenging behaviour. There was little regular monitoring of side-effects or warning about potential side-effects when the medication was started. CLINICAL IMPLICATIONS Challenging behaviour is a common cause of multiple prescribing in learning disability patients, and is often long-term in the absence of a strong evidence base. Other specialties use medication to control disturbed behaviour, particularly in people with dementia or personality disorder, so this audit may also be of interest to old age, adult and forensic psychiatrists.
Management of continuous positive airway pressure treatment compliance using telemonitoring in obstructive sleep apnoea

Continuous positive airway pressure (CPAP) is an effective treatment for obstructive sleep apnoea (OSA), but treatment compliance is often unsatisfactory. This study investigated the efficacy and cost-effectiveness of telemonitoring for improving CPAP compliance. 100 newly diagnosed OSA patients requiring CPAP (apnoea–hypopnoea index >15 events·h−1) were randomised to standard management or a telemonitoring programme that collected daily information about compliance, air leaks and residual respiratory events, and initiated patient contact to resolve issues. Clinical/anthropometric variables, daytime sleepiness and quality of life were recorded at baseline and after 3 months. Patient satisfaction, additional visits/calls, side-effects and total costs were assessed. There were no significant differences between the standard and telemedicine groups in terms of CPAP compliance (4.9±2.2 versus 5.1±2.1 h·night−1), symptoms, clinical variables, quality of life and unwanted effects. Telemedicine was less expensive than standard management (EUR123.65 versus EUR170.97; p=0.022) and was cost-effective (incremental cost-effectiveness ratio EUR17 358.65 per quality-adjusted life-year gained). Overall patient satisfaction was high, but significantly more patients rated satisfaction as high/very high in the standard management versus telemedicine group (96% versus 74%; p=0.034). Telemonitoring did not improve CPAP treatment compliance and was associated with lower patient satisfaction. However, it was more cost-effective than traditional follow-up. Telemonitoring did not improve CPAP compliance, showed lower patient satisfaction, but proved to be cost-effective http://ow.ly/UvHX306AC0V