Miracle-dz/UniFAR-FTUs huggingface dataset:
Spondylodiscitis: standards of current treatment

Abstract Background: Spinal infections are an important clinical problem that often require aggressive medical therapy, and sometimes even surgery. Known risk factors are advanced age, diabetes mellitus, rheumatoid arthritis, immunosuppression, alcoholism, long-term steroid use, concomitant infections, poly-trauma, malignant tumor, and previous surgery or invasive procedures (discography, chemonucleolysis, and surgical procedures involving or adjacent to the intervertebral disc space). The most common level of involvement is at the lumbar spine, followed by the thoracic, cervical and sacral levels: lesions at the thoracic spine tend to lead more frequently to neurological symptoms. Objective: The aim of the current paper is to describe current evidence-based standards of therapy in the management of SD by emphasizing pharmacological therapy and principles and indications for bracing and surgery. Methods: A PubMed and Google Scholar search using various forms and combinations of the key words: spondylodiscitis, spine, infection, therapy, surgery, radiology, treatment. Reference citations from publications identified in the literature search were reviewed. Publications highlighted in this article were extracted based on relevancy to established, putative, and emerging diagnostic and therapeutic standards, either conservative (antibiotic therapy and bracing) or surgical. Findings: To date, conservative therapy, based on targeted antibiotic therapy plus bracing, represents the mainstay in the management of SD. Proper diagnosis and tailored therapy can improve clinical results and decrease the chance of failure. Surgery should be an option only for patients with complications of this disease, namely deformity, neural compression and neurological compromise. Current standards in the setting of SD are continuously evolving, as can be seen in the recent advances in the field of radiological diagnostics, and the use of growth factors and cell-therapy strategies to promote infection eradication and bone healing after surgery.
How Do Self‐Assessment of Alexithymia and Sensitivity to Bodily Sensations Relate to Alcohol Consumption?

BACKGROUND Alexithymia describes an abnormality of emotional experience that is commonly expressed among individuals with addiction and alcohol abuse disorders. Alexithymic individuals are characterized by difficulties in identifying and describing their emotions. This impairment is linked to the development and maintenance of addiction. Moreover, an emergent theory suggests alexithymia is itself secondary to a failure of interoception (sensitivity to internal bodily signals, including physiological arousal states). METHODS This study tested for hypothesized contributory roles of alexithymia and dysfunctional interoception in the expression of social drinking. Alexithymia, subjective sensitivity to bodily sensations, and alcohol consumption scores were quantified using the Toronto Alexithymia Scale, the Body Perception Questionnaire, and the Alcohol Use Questionnaire, respectively, in a normative sample (N = 600). Regression and bootstrapping mediation analyses were used to test the hypothesis that alexithymia mediated the association between sensitivity to bodily sensations and alcohol consumption. RESULTS Alexithymia was positively correlated with sensitivity to bodily sensations and with alcohol consumption. Mediation analysis revealed that alexithymia, and more precisely, difficulty in identifying feelings, mediated the relationship between sensitivity to bodily sensations and alcohol consumption, such that the predictive effect of sensitivity to bodily sensations on alcohol intake became nonsignificant when controlling for alexithymia. CONCLUSIONS These results indicate that alexithymia is associated with subjective hypersensitivity to bodily sensations. Moreover, our findings support the theoretical proposal that alexithymia is an expression of impaired processing of bodily sensations including physiological arousal, which underpin the development of maladaptive coping strategies, including alcohol use disorders. Our observations extend a growing literature emphasizing the importance of interoception and alexithymia in addiction, which can inform the development of new therapeutic strategies.
Physiology of the Graafian follicle and ovulation

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Cardiac Pain, Sympathetic Afferents, and Life‐Threatening Arrhythmias

Cardiac Pain, Sympathetic Afferents, and Life‐Threatening Arrhythmias. Myocardial ischemia activates receptors of sympathetic and vagal afferent fibers. Although both afferent pathways are excited, this article primarily focuses on the sympathetic pathways. Increased sympathetic afferent activity to cells of the spinal cord can lead to cardiac pain and reflex sympathetic hyperactivity that can be quite arrhythmogenic. Complicating factors that affect the relationship arises from activation of vagal afferent fibers. Sympathetic afferent fibers in the ventricle appear to be composed of mechanosensitive and chemosensitive receptors. Sympathetic afferent fibers excite cells of origin of the spinothalamic tract, the classical pain pathway that transmits information about noxious somatic and visceral episodes to areas of the brain involved with pain perception. Activation of selected brainstem nuclei, the vagus, and the dorsal columns can suppress afferent information from the heart that excites spinothalamic tract cells. Excitation of sympathetic afferent fibers initiates a series of cardiovascular reflexes, some of which may affect cardiac electrical stability significantly. Increased arrhythmogenesis can be reduced when C8‐T5 dorsal roots are transected. Stimulation of cardiac nerves that involve the left stellate ganglion can produce life‐threatening arrhythmias, particularly if combined with myocardial ischemia or infarction. Through reflex mechanisms, activation of sympathetic afferent fibers can suppress activity of vagal efferent fibers. If prevention of cardiac pain through reduced firing or inhibition of cells in the spinothalamic tract reduces afferent sympathetic activity that occurs during acute myocardial ischemia, it would be logical to surmise that another significant benefit would follow, namely reduced risk for malignant arrhythmias.
Utilization of duloxetine and celecoxib in osteoarthritis patients

Abstract Objectives: To describe utilization patterns of duloxetine and celecoxib and subsequent opioid use among patients with osteoarthritis. Research design and methods: Pharmacy and medical claims from SDI Health were analyzed for adult osteoarthritis patients (ICD-9-CM: 715.xx) who initiated duloxetine or celecoxib between 11/30/2010 and 4/30/2011. Initiation was defined as no pill coverage in the prior 90 days. Included patients had continuous enrollment for 6 months before and after the initiation and did not use opioid for 90 days before initiation. Propensity score matching was used to select patients with similar demographic and clinical characteristics for duloxetine and celecoxib cohorts. Compliance to index medication was assessed via medication possession ratio (MPR), proportion of days covered (PDC), and proportion discontinued (no access for 60 days). Initiating dose and opioid use after the index date was assessed. A Cox proportional hazard model was estimated to compare time to first opioid use. Results: A total of 1360 patients initiated duloxetine and 1408 patients initiated celecoxib. After matching, 784 patients were selected for the duloxetine (mean age: 66, female: 78%) and celecoxib (mean age: 66; female: 76%) cohorts, respectively. Of the duloxetine cohort 92.5% started on ≤60 mg/day, the recommended dose, and 72.8% of the celecoxib cohort started on ≤200 mg/day. The duloxetine cohort had higher MPR and PDC and a lower proportion of discontinuation than the celecoxib cohort (MPR: 0.81 vs. 0.70; PDC: 0.51 vs. 0.35; discontinuation: 57% vs. 78%; all p < 0.001). A lower proportion of the duloxetine cohort used opioids after the index date (48.6% vs. 68.5%, p < 0.001), and they started on opioids later than the celecoxib cohort (25th percentile: 69.5 vs. 32 days; median: >183 days vs. 117 days, p < 0.001). After controlling for baseline characteristics, the duloxetine cohort initiated opioids later than the celecoxib cohort (hazard ratio: 0.66, 95% confidence interval: 0.58–0.76). Conclusion: Osteoarthritis patients initiating duloxetine had better compliance and a lower likelihood of opioid utilization than those initiating celecoxib. Study limitations included lack of information on reasons for medication initiation and discontinuation, severity of disease symptoms, and use of over-the-counter medications.
Impact of adding prophylactic probiotics to a bundle of standard preventative measures for Clostridium difficile infections: enhanced and sustained decrease in the incidence and severity of infection at a community hospital

Abstract Background: In 2003, hospitals in Quebec, Canada experienced an increase of NAP1/027 Clostridium difficile infections following antibiotic administration (CDIAA). At Pierre-Le Gardeur Hospital (PLGH), the incidence increased from 10 to over 25 cases per 1000 patient admissions. Methods: We report a quasi-experimental, prospective cohort study evaluating the effect on CDIAA of a probiotic added to existing C. difficile infection (CDI) standard preventative measures (SPM) in 31,832 hospitalized patients receiving antibiotics. Phase I (1580) measured the impact of SPM alone. In Phase II, 50 to 60 × 109 cfu daily dose of oral Lactobacillus acidophilus CL1285 and L. casei LBC80R probiotic formula (Bio-K+) was administered to all patients receiving antibiotics. Phase III included the same intervention after a move to a new hospital facility. Phases II and III included 4968 patients. During Phase IV, 25,284 patients were submitted to the same regimen but outcome data were compared to those of similar hospitals in Quebec. Results: At the end of Phase III, CDIAA had decreased from more than 18 cases per 1000 patient admissions in Phase I to less than 5 cases. Reductions of CDI cases (73%) (p < 0.001) and severe CDI cases (76.4%) (p < 0.001) were observed. CDI recurrence rate was reduced by 39% (p < 0.001). During the following 6 years, the CDI rate averaged 2.71 cases per 10,000 patient-days at PLGH compared to 8.50 cases per 10,000 patient-days in equivalent hospitals located in Quebec. Study limitation: This study is not a randomized clinical trial; it is an open prospective study and should be treated as such. Also, following Phase II, PLGH moved into a new facility and this could have contributed to lower CDI. Conclusions: Specific probiotic product added to SPM and antibiotic stewardship activities resulted in a further reduction in CDI rates and was shown to be safe.
Improved harmonic analysis of RC-active phase shift oscillators

This paper describes an improved method for calculating the harmonic distortion content of active-RC phase shift oscillators. The proposed method introduces the truncated harmonic transfer function (THTF) which is related to the two-sinusoidal-input describing function (TSIDF) of non-linear control theory. This allows accurate calculation of the distortion terms in oscillator systems containing higher signal levels and therefore higher levels of nonlinearity than is possible with conventional methods. Although the method is quite general in its application, in this paper it is demonstrated using examples employing the Wien RC-bandpass oscillator with a quadratic nonlinearity.
Comparative effectiveness of fingolimod versus interferons or glatiramer acetate for relapse rates in multiple sclerosis: a retrospective US claims database analysis

Abstract Objective: Disease-modifying therapies, such as fingolimod, interferon (IFN) and glatiramer acetate (GA), have differing effects on relapse rates in patients with multiple sclerosis (MS), but little is known about the real-world differences in relapse rates with these treatments. This retrospective study assessed relapse rates in patients with active MS initiating fingolimod, IFN or GA therapy in a real-world setting. Methods: Using administrative claims data from the US PharMetrics Plus database, we identified previously treated and untreated patients with MS who initiated fingolimod, IFN or GA treatment between 1 October 2010 and 31 March 2011 and had experienced a relapse in the previous year. A claims-based algorithm was used to identify relapses over the persistence period in patients with 540 days of post-index continuous enrolment. A logistic regression model assessed the probability of having at least one relapse and a generalized linear model estimated differences in annualized relapse rates (ARRs). Results: The study enrolled 525 patients (fingolimod, n = 128; combined IFN/GA cohort, n = 397) of the 31,041 initially identified. Similar findings for fingolimod and IFN/GA were observed for the unadjusted proportion of patients experiencing relapses (31.3% vs. 34.0%, respectively; p = 0.5653) and ARRs (0.50 vs. 0.55, respectively) while persistent to treatment. After adjusting for baseline differences, fingolimod was associated with a 52% reduction in the probability of having a relapse (odds ratio, 0.48; 95% confidence interval [CI], 0.28–0.84; p = 0.0097) and a 50% reduction in ARR (rate ratio, 0.50; 95% CI, 0.34–0.75; p = 0.0006) compared with IFN/GA. Limitations: Identification of relapses is based on the claims in the database rather than on a clinical assessment. Conclusions: In a real-world setting, fingolimod was shown to be associated with significantly lower relapse rates than IFN/GA in patients with MS who had a history of relapses.
Proceedings from the 9th Annual Meeting of International Society for Medical Publication Professionals Roundtable Session: key insights

Abstract Introduction During the 9th Annual Meeting of the International Society for Medical Publication Professionals (ISMPP, April 29–May 1, 2013 in Baltimore, MD), ∼650 participants attended two of 13 available roundtable sessions. Participants included medical publication professionals from industry, communication agencies, and journals. Discussion topics Roundtable participants discussed how to best interpret and implement various guidances, such as Good Publication Practices 2 (GPP2), the International Committee of Medical Journal Editors (ICMJE) guidelines, and the Physician Payment Sunshine Act. The impact of and compliance with Corporate Integrity agreements (CIAs) on medical publication planning practices was debated. Roundtable participants also discussed ways of advancing both advocacy for the medical publication professional field and internal and external collaborations. The development of review manuscripts, publications from regions newly emerging in publication planning, medical devices publications, and real-world experience publications were discussed. Participants also considered the benefits and uncertainties of new technologies in medical publications such as multimedia and social media. Summary This is the first ever article to be published following the well-attended ISMPP roundtable sessions. The objective of this manuscript is to summarize key learnings that will aid continued discussions about challenges and opportunities facing medical publication professionals.
Naftopidil for the treatment of benign prostate hyperplasia: a systematic review

Abstract Objectives: The aim of the study was to systematically review the effects of the adrenoreceptor A1D antagonist naftopidil in the management of lower urinary tract symptoms (LUTS). Methods: A structured and comprehensive MEDLINE search was conducted for original articles, reviews, and metanalyses assessing the clinical pharmacology as well as the safety of naftopidil in the treatment of LUTS secondary to BPH. English-language publications dating from 1950 to 2013 were considered. Results: In the considered timeframe, 14 randomized clinical trials (RCT) were reported. Overall, the outcome measures assessed in the various reports included in the present review were changes from baseline in: International Prostate Symptom Score (IPSS), quality of life (QoL) score, maximum urinary flow rate (Qmax), residual volume (PVR), and adverse effects. Although additional well designed, worldwide, placebo-controlled and randomized studies are necessary to confirm the long-term outcomes of naftopidil pharmacotherapy, current data suggest that naftopidil administration in BPH patients provides comparable improvements in total IPSS, QoL, and urinary symptoms from baseline relative to 0.2 mg/d tamsulosin and 8 mg/d silodosin. However, improvements in Qmax are generally less with naftopidil than with tamsulosin. Reported adverse effects related to naftopidil administration are negligible and usually mild. Conclusion: It remains unknown whether the data reported on naftopidil in the Japanese population are applicable in symptomatic BPH patients from western countries given that: (1) no English-language clinical trials have compared naftopidil to placebo in Western countries; (2) all clinical trials available were carried out in Japan; (3) in the comparative studies with tamsulosin, the dose of this drug was lower than the recommended dose in Western countries; (4) no data from long-term clinical trials evaluating drug safety beyond 18 weeks.
Association between regular molecular monitoring and tyrosine kinase inhibitor therapy adherence in chronic myelogenous leukemia in the chronic phase

Abstract Objective: Adherence with oral tyrosine kinase inhibitor (TKI) therapy over prolonged timeframes is required for successful outcomes among patients with chronic phase chronic myelogenous leukemia (CP-CML). Since quantitative polymerase chain reaction (qPCR) monitoring may identify early suboptimal responses, and thereby permit detection of non-adherence to therapy, we sought to assess the association between frequency of molecular monitoring and medication adherence. Research design and methods: This is a retrospective cohort study design of diagnosed CP-CML obtained from two large US administrative claims databases. Patients were grouped into cohorts based on the number of qPCR tests they had. Adherence was assessed both by medication possession ratio (MPR) and proportion of days covered (PDC) and was compared between qPCR cohorts. A sensitivity analysis was performed by adjusting for the number of oncology outpatient visits not due to routine molecular monitoring. Results: Over the 12 month study period, 1205 CML patients met the selection criteria; 41.0% had no qPCR tests, 31.9% had 1–2 tests, and 27.1% had 3–4 tests; 88.9% of patients were initiated on imatinib. Patients in the 3–4 qPCR tests cohort had an average MPR that was 10.22 (p < 0.001) and 9.54 (p < 0.001) percentage points higher compared to patients in the 0 tests cohort and the 1–2 tests cohort. When using PDC as a measure of adherence, similar results were obtained. The results of the sensitivity analysis were consistent with core analysis findings, excluding number of physician visits as a potential driver of adherence. Limitations: These findings demonstrate an association, not causation, between molecular monitoring frequency and adherence. Conclusions: Frequent molecular monitoring (3–4 times per year as recommended in current guidelines) is associated with greater TKI treatment adherence for patients diagnosed with CML. Since TKI adherence >80% has been associated with better clinical outcomes, this study underscores the importance of molecular monitoring.
A randomised trial of the effect of omega-3 polyunsaturated fatty acid supplements on the human intestinal microbiota

Objective Omega-3 polyunsaturated fatty acids (PUFAs) have anticolorectal cancer (CRC) activity. The intestinal microbiota has been implicated in colorectal carcinogenesis. Dietary omega-3 PUFAs alter the mouse intestinal microbiome compatible with antineoplastic activity. Therefore, we investigated the effect of omega-3 PUFA supplements on the faecal microbiome in middle-aged, healthy volunteers (n=22). Design A randomised, open-label, cross-over trial of 8 weeks’ treatment with 4 g mixed eicosapentaenoic acid/docosahexaenoic acid in two formulations (soft-gel capsules and Smartfish drinks), separated by a 12-week ‘washout’ period. Faecal samples were collected at five time-points for microbiome analysis by 16S ribosomal RNA PCR and Illumina MiSeq sequencing. Red blood cell (RBC) fatty acid analysis was performed by liquid chromatography tandem mass spectrometry. Results Both omega-3 PUFA formulations induced similar changes in RBC fatty acid content, except that drinks were associated with a larger, and more prolonged, decrease in omega-6 PUFA arachidonic acid than the capsule intervention (p=0.02). There were no significant changes in α or β diversity, or phyla composition, associated with omega-3 PUFA supplementation. However, a reversible increased abundance of several genera, including Bifidobacterium, Roseburia and Lactobacillus was observed with one or both omega-3 PUFA interventions. Microbiome changes did not correlate with RBC omega-3 PUFA incorporation or development of omega-3 PUFA-induced diarrhoea. There were no treatment order effects. Conclusion Omega-3 PUFA supplementation induces a reversible increase in several short-chain fatty acid-producing bacteria, independently of the method of administration. There is no simple relationship between the intestinal microbiome and systemic omega-3 PUFA exposure. Trial registration number ISRCTN18662143.
Management of patients on antithrombotic agents undergoing emergency and elective endoscopy: joint Asian Pacific Association of Gastroenterology (APAGE) and Asian Pacific Society for Digestive Endoscopy (APSDE) practice guidelines

This Guideline is a joint official statement of the Asian Pacific Association of Gastroenterology (APAGE) and the Asian Pacific Society for Digestive Endoscopy (APSDE). It was developed in response to the increasing use of antithrombotic agents (antiplatelet agents and anticoagulants) in patients undergoing gastrointestinal (GI) endoscopy in Asia. After reviewing current practice guidelines in Europe and the USA, the joint committee identified unmet needs, noticed inconsistencies, raised doubts about certain recommendations and recognised significant discrepancies in clinical practice between different regions. We developed this joint official statement based on a systematic review of the literature, critical appraisal of existing guidelines and expert consensus using a two-stage modified Delphi process. This joint APAGE-APSDE Practice Guideline is intended to be an educational tool that assists clinicians in improving care for patients on antithrombotics who require emergency or elective GI endoscopy in the Asian Pacific region.
Bicaudate index in computerized tomography of Huntington disease and cerebral atrophy

Ventricular sizes on computerized tomographic (CT) scans were compared in seven patients with Huntington disease, 20 patients with cerebral atrophy, and 20 normal controls. The bicaudate index—the ratio of the width of both lateral ventricles at the level of the heads of the caudate nuclei to the distance between the outer tables of the skull at the same level—significantly discriminated among the three groups. The bicaudate indices were: Huntington disease 0.209 ± 0.007, cerebral atrophy 0.121 ± 0.006, and controls 0.092 ± 0.003.