Open-label Prospective Cohort Study Research Articles

Long-term echocardiography results in patients with ST-segment elevation myocardial infarction after pharmaco-invasive reperfusion therapy, depending on the choice of thrombolytic drug

Objectives: to analyze the results of echocardiography 1 year after STEMI in patients undergoing pharmaco-invasive reperfusion using various thrombolytic drugs.Materials and Methods: 240 patients with STEMI after pharmaco-invasive reperfusion were included in an open-label prospective cohort study. Depending on the thrombolytic agent used, the patients were divided into 4 groups: in the 1st (n = 73) — lysis was performed with alteplase; in the 2nd (n = 40) — tenecteplase; in the 3rd (n = 95) — forteplase; in the 4th (n = 32) — streptokinase. Depending on the fibrin-specificity of the thrombolytic, all patients were presented with 2 groups: the group of fibrin-specific thrombolytics (FST, n = 208) and the group of fibrin-nonspecific streptokinase (FNST, n = 32). Echocardiography was assessed 1 year after reperfusion.Results: after 1 year, there was a slight violation of the global LV systolic function, while the EF between the groups did not differ (p = 0.420). A higher EF was recorded in the FST group compared with FNST (49.8 ± 7.4 % versus 47.4 ± 6.8 %; p = 0.048). After 1 year, violations and local LV contractility persisted in each of the four groups (p = 0.161). At the same time, lower WMSI were recorded in the FST group compared to FNST (1.19 [1.06; 1.38] versus 1.25 [1.175; 1.5]; p = 0.029). In the FST group, significantly lower iEDV were recorded (p = 0.048), and iESV (p = 0.022) and LA size (p = 0.007) compared with FNST. In dynamics, 1 year after reperfusion in the FST group, there was a significant increase in EF by 5.5 % (p = 0.000) and a decrease in LV WMSI by 5 % (p = 0.000) compared with the FNST group.Conclusions: pharmaco-invasive treatment of STEMI with the use of thrombolytic drugs after 1 year of follow-up is characterized by comparable echocardiography parameters. After 1 year of follow-up, patients undergoing pharmaco-invasive treatment with fibrin-specific drugs had significantly higher EF, as well as lower WMSI, iEDV, iESV, and LA size compared to fibrin-nonspecific streptokinase.

Способ оценки эффективности лечения урогенитального туберкулеза

Methods for evaluating the efficiency of treatment which were developed for pulmonary tuberculosis (absence of bacterial transmission and closure of cavities) are not suitable for urogenital tuberculosis. To evaluate the use of scoring system for assessing the efficiency of treatment of urogenital tuberculosis. A pilot simple open-label prospective noncomparative cohort study was carried out, which included 15 patients with urogenital tuberculosis. All patients completed the urogenital tuberculosis score upon admission and after 1 month, along with standard clinical, laboratory and X-ray examinations. We developed this score to objectify evaluate the efficiency of antituberculosis therapy and it includes clinical and laboratory manifestations of urogenital tuberculosis. Eleven (73.3%) patients responded well to standard therapy, and 4 (26.7%) required therapy correction. Considering that the correction of therapy was carried out in a timely manner, the final result of the treatment was satisfactory. The efficiency of the proposed score has been demonstrated by clinical results. Using the urogenital tuberculosis score for assessing the results of treatment of urogenital tuberculosis allows timely correction of therapy according to objective criteria.

Effect of darifenacin on fecal incontinence in women with double incontinence.

To evaluate change in fecal incontinence symptom severity after 8weeks of darifenacin therapy in patients with double incontinence-urgency urinary incontinence (UUI) and fecal incontinence. Important secondary outcomes included fecal incontinence symptom distress and impact on quality of life, fecal incontinence episodes, global impression of improvement and overactive bladder symptom distress and impact. Prospective open-label cohort study of women presenting primarily with UUI, diagnosed with double incontinence and electing antimuscarinic therapy for UUI. Women ≥ 18years with moderate or greater bothersome UUI and fecal incontinence of liquid/solid stool with St. Marks (Vaizey) score ≥ 12 were included. Subjects were treated with darifenacin 15mg daily for 8weeks. The primary outcome was change in fecal incontinence symptom severity using the St. Marks (Vaizey) score after 8weeks. Sample size was based on the minimally important difference of the St. Marks, -5, and standard deviation, ± 8.5; 30 subjects provided 80% power and type I error of 0.05, including a 15% attrition rate. Thirty-two women were consented with mean baseline St. Marks (Vaizey) score of 18.0 ± 3.0. Mean age was 66.5 ± 10.3 years. Twenty-eight subjects (29/32, 87.5%) completed assessments. St. Marks (Vaizey) score significantly improved from 18.0 to 11.0 [mean difference - 7.0, 95% confidence interval (CI): -8.7, -5.3], and 19 subjects (19/32,67.9%) met the minimally important difference. Statistically significant improvements were also noted in fecal incontinence frequency, quality of life, and overactive bladder symptom bother and quality of life (all p< 0.01). Darifenacin can be considered a highly effective early intervention in women suffering from double incontinence. Bladder Antimuscarinic Medication and Accidental Bowel Leakage (BAMA), https://clinicaltrials.gov/ct2/show/NCT03543566 , NCT03543566.

The development an artificial intelligence algorithm for early sepsis diagnosis in the intensive care unit

BackgroundSevere sepsis and septic shock are still the leading causes of death in Intensive Care Units (ICUs), and timely diagnosis is crucial for treatment outcomes. The progression of electronic medical records (EMR) offers the possibility of storing a large quantity of clinical data that can facilitate the development of artificial intelligence (AI) in medicine. However, several difficulties, such as poor structure and heterogenicity of the raw EMR data, are encountered when introducing AI with ICU data. Labor-intensive work, including manual data entry, personal medical records sorting, and laboratory results interpretation may hinder the progress of AI. In this article, we introduce the developing of an AI algorithm designed for sepsis diagnosis using pre-selected features; and compare the performance of the AI algorithm with SOFA score based diagnostic method. Materials and methodsThis is a prospective open-label cohort study. A specialized EMR, named TED_ICU, was implemented for continuous data recording. One hundred six clinical features relevant to sepsis diagnosis were selected prospectively. A labeling work to allocate SEPSIS or NON_SEPSIS status for each ICU patient was performed by the in-charge intensivist according to SEPSIS-3 criteria, along with the automatic recording of selected features every day by TED_ICU. Afterward, we use de-identified data to develop the AI algorithm. Several machine learning methods were evaluated using 5-fold cross-validation, and XGBoost, a decision-tree based algorithm was adopted for our AI algorithm development due to best performance. ResultsThe study was conducted between August 2018 and December 2018 for the first stage of analysis. We collected 1588 instances, including 444 SEPSIS and 1144 NON-SEPSIS, from 434 patients. The 434 patients included 259 (59.6%) male patients and 175 female patients. The mean age was 67.6-year-old, and the mean APACHE II score was 13.8. The SEPSIS cohort had a higher SOFA score and increased use of organ support treatment. The AI algorithm was developed with a shuffle method using 80% of the instances for training and 20% for testing. The established AI algorithm achieved the following: accuracy = 82% ± 1%; sensitivity = 65% ± 5%; specificity = 88% ± 2%; precision = 67% ± 3%; and F1 = 0.66 ± 0.02. The area under the receiver operating characteristic curve (AUROC) was approximately 0.89. The SOFA score was used on the same 1588 instances for sepsis diagnosis, and the result was inferior to our AI algorithm (AUROC = 0.596). ConclusionUsing real-time data, collected by EMR, from the ICU daily practice, our AI algorithm established with pre-selected features and XGBoost can provide a timely diagnosis of sepsis with an accuracy greater than 80%. AI algorithm also outperforms the SOFA score in sepsis diagnosis and exhibits practicality as clinicians can deploy appropriate treatment earlier. The early and precise response of this AI algorithm will result in cost reduction, outcome improvement, and benefit for healthcare systems, medical staff, and patients as well.

Preliminary results of dulaglutide treatment in patients with non-alcoholic fatty liver disease (DEMOS study)

65 patients with nonalcoholic fatty liver disease (NAFLD) were included in open-label observative prospective cohort study. Mean age was 54.8 ± 10.5 y. o. All patients were treated with metformin before and during the study. All patients were treated by GLP-1 receptor agonist dulaglutide subcutaneously weekly 26 weeks. Patients of group with type 2 diabetes were treated with dulaglutide 0.75 mg weekly 2 weeks, than 1.5 weekly 24 weeks. Patients of group without diabetes were treated by dulaglutide 0.75 mg weekly 4 weeks, than 1.5 weekly 22 weeks. Both groups of patients were demonstrated significant reduce of body weight, BMI, waist circumference, glucose, HbA1c, insulin resistance indexes, transaminases and gamma-glutamyltranspeptidase activity. Fatty liver index and liver stiff ness also decreased after treatment. We can conclude that dulaglutide treatment in NAFLD patients decreases body wieight, improves glucose and lipid metabolism and decreases inflammatory activity of steatohepatitis.

Usefulness of Serum Free Thyroxine Concentration to Predict Ventricular Arrhythmia Risk in Euthyroid Patients With Structural Heart Disease

The aim of the present study was to determine whether free thyroxine (FT4) and calculated thyroid parameters predict the incidence of ventricular arrhythmias in euthyroid heart failure patients with implantable cardioverter-defibrillators (ICD). In this open-label prospective cohort study, 115 consecutive euthyroid patients (mean age 62.9 ± 1.3 years; 87% male; ischemic cardiomyopathy 63%) scheduled for primary prevention ICD implantation or exchange were enrolled. Serum concentrations of thyrotropin (thyroid-stimulating hormone) and FT4 were measured 1 day before device operation. Primary and secondary end points were defined as occurrence of appropriate ICD therapy (AIT) and cardiovascular death, respectively. During a mean follow-up of 1,191 ± 35 days, 24 patients (21%) experienced AIT, and cardiovascular death was observed in 10 patients (9%). Patients with AIT had higher FT4 concentrations compared with those without AIT (18.9 ± 0.48 vs 16.2 ± 0.22 pmol/L, p <0.001). FT4 was an independent predictor of AIT in an adjusted Cox regression (hazard ratio = 1.47, p <0.001). Kaplan-Meier analysis demonstrated that Jostel's thyroid-stimulating hormone index, reflecting the central component of the hypothalamus-pituitary-thyroid loop, and SPINA-GT as surrogate markers for thyroid's secretory capacity predicted AIT incidences. None of the indices predicted cardiovascular death. In conclusion, FT4 concentration predicts an increased incidence of ventricular arrhythmias in euthyroid patients receiving ICDs for primary prevention. Our data suggest that both impending primary hyperthyroidism and an increased thyroid homeostasis set point may increase the rate of AIT in this patient population.

Autologous nonmyeloablative hematopoietic stem cell transplantation for neuromyelitis optica.

To determine if autologous nonmyeloablative hematopoietic stem cell transplantation (HSCT) could be a salvage therapy for neuromyelitis optica spectrum disorder (NMOSD). Thirteen patients were enrolled in a prospective open-label cohort study (11 NMOSD aquaporin-4-immunoglobulin G [AQP4-IgG]-positive, 1 NMOSD without AQP4, and 1 NMOSD AQP4-IgG-positive with neuropsychiatric systemic lupus erythematosus [SLE]). Following stem cell mobilization with cyclophosphamide (2 g/m2) and filgrastim, patients were treated with cyclophosphamide (200 mg/kg) divided as 50 mg/kg IV on day -5 to day -2, rATG (thymoglobulin) given IV at 0.5 mg/kg on day -5, 1 mg/kg on day -4, and 1.5 mg/kg on days -3, -2, and -1 (total dose 6 mg/kg), and rituximab 500 mg IV on days -6 and +1. Unselected peripheral blood stem cells were infused on day 0. AQP4-IgG antibody status was determined by Clinical Laboratory Improvement Amendments-validated ELISA or flow cytometry assays. Cell-killing activity was measured using a flow cytometry-based complement assay. Median follow-up was 57 months. The patient with coexistent SLE died of complications of active lupus 10 months after HSCT. For the 12 patients with NMOSD without other active coexisting autoimmune diseases, 11 patients are more than 5 years post-transplant, and 80% are relapse-free off all immunosuppression (p < 0.001). At 1 and 5 years after HSCT, Expanded Disability Status Scale score improved from a baseline mean of 4.4 to 3.3 (p < 0.01) at 5 years. The Neurologic Rating Scale score improved after HSCT from a baseline mean of 69.5 to 85.7 at 5 years (p < 0.01). The Short Form-36 health survey for quality of life total score improved from mean 34.2 to 62.1 (p = 0.001) at 5 years. In the 11 patients whose baseline AQP4-IgG serostatus was positive, 9 patients became seronegative by the immunofluorescence or cell-binding assays available at the time; complement activating and cell-killing ability of patient serum was switched off in 6 of 7 patients with before and after HSCT testing. Two patients remained AQP4-IgG-seropositive (with persistent complement activating and cell-killing ability) and relapsed within 2 years of HSCT. No patient with seronegative conversion relapsed. Prolonged drug-free remission with AQP4-IgG seroconversion to negative following nonmyeloablative autologous HSCT warrants further investigation.

499 – Improvement of Cognitive Function Following Effective Hepatitis C Viral Eradication: A Prospective Open Label Cohort Study

499 – Improvement of Cognitive Function Following Effective Hepatitis C Viral Eradication: A Prospective Open Label Cohort Study

The sustainable impact of an educational approach to improve the appropriateness of laboratory test orders in the ICU.

IntroductionFew studies described strategies to improve the use of diagnostic tests in intensive care units (ICU). No study assessed whether their impact was sustained or not. In this study, we assessed whether a multi-faceted intervention for more appropriate use of laboratory testing can decrease the number of tests, is sustainable, is not associated with additional morbidity and represents a potential cost saving.Material and methodsAn open-label prospective cohort study in two separated units of the same medical intensive care unit (ICU) including respectively 3315 and 2392 consecutive patients. After the observation period (2010), a reduction in ICU A of unnecessary diagnostics tests as part of a program including senior supervisory of juniors’ orders, encouragements for orders containment at each everyday round discussions (period 2; 2011). Period 3 (2012) consisted in the prolongation of the protocol as a routine care without supervision; Period 4 (2013) was a new period of observation without intervention. No modification was implemented in ICU B in periods 2–4.ResultsAfter the intervention, a decrease in the overall number of tests per ICU-patient-days (37.3±5.5 (baseline) to 15.2±3.2 (- 59%); p<0.0001) was observed. The total cost of the tests decreased from 239±41 to 104±28 euros per ICU-patient days; p<0.0001. The effect on laboratory test orders was sustainable in period 3 (-49%) and 4 (-30%). No significant secondary effect of the intervention was observed in period 2. In ICU B, there was no significant change in the overall laboratory test orders in between the periods.ConclusionsLaboratory test containment is effective, likely safe and sustainable provided that an educational program is repeatedly promoted, that it makes sense for the whole team, that senior and junior physicians are both committed in the program, and that encouragements for laboratory orders containment at each everyday round discussions.

Sex-differential effects of olanzapine vs. aripiprazole on glucose and lipid metabolism in first-episode schizophrenia

Abstract Objective To compare sex difference in metabolic effect of olanzapine versus aripiprazole on schizophrenia. Methods A twelve-week prospective open-label cohort study to compare four subgroups according to first-episode schizophrenia patients’ type of drug usage and sex: female aripiprazole (n = 11), male aripiprazole (n = 11), female olanzapine (n = 10), and male olanzapine (n = 11) for body mass index, fasting serum triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and fasting glucose. Results Aripiprazole may be associated with weight gain in female patients with low-baseline weight. Aripiprazole may have an adverse effect of weight and favorable effects of circulating glucose and lipid on female over male schizophrenia patients. The aripiprazole–induced changes in glucose and lipid may be independent of body fat storage, especially for female schizophrenia patients. Olanzapine may have adverse effects of weight, glucose and lipid profiles on female over male schizophrenic patients. Discussion Our findings fill the gap in knowledge and provide a sex-specific guidance to psychiatrist better tailoring treatment to individual sex-differential characteristics and a key clue to understand the sex-differential mechanism of antipsychotics-induced metabolic dysfunction.

Recombinant thrombomodulin for acute exacerbation in idiopathic interstitial pneumonias.

Acute exacerbation (AE) in idiopathic pulmonary fibrosis (IPF) or other idiopathic interstitial pneumonias (IIP) is a poor prognostic event despite conventional therapy with corticosteroids and/or immunosuppressants. We aimed to evaluate the efficacy and safety of recombinant human soluble thrombomodulin (rhTM) for AE-IIP. For this prospective single-arm open-label multicentre cohort study, we retrospectively registered 61 cases of AE-IIP treated with conventional therapy between 2011 and 2013 (control arm), and prospectively enrolled 39 cases of AE-IIP treated with conventional therapy and rhTM (380 U/kg/day for 6 days) between 2014 and 2016 (rhTM arm). To reduce potential confounding in treatment comparisons, an adjusted mortality analysis for 90-day survival was conducted with weighted Cox proportional hazards regression models using inverse probability of treatment weighting. Weights were derived from propensity scores estimated using a multivariable logistic regression analysis including potential confounders. The 90-day survival rates of AE-IIP patients treated with/without rhTM were 66.7% (26/39) and 47.5% (29/61), respectively. After adjusting for imbalances, rhTM therapy was significantly associated with reduced mortality (adjusted hazard ratio (HR): 0.453; 95% CI: 0.237-0.864; P = 0.0163). The frequencies of adverse events with/without rhTM were 17.9% (7/39) and 19.7% (12/61), which were similar in both arms (P = 1.0). Two bleeding-related adverse events occurred in the rhTM arm. Safety and efficacy were observed for rhTM treatment of AE-IIP. A future randomized controlled trial is required to draw final conclusions.

Subcutaneous Absorption Contributes to Observed Interindividual Variability in Adalimumab Serum Concentrations in Crohn's Disease: A Prospective Multicentre Study.

Therapeutic drug monitoring is used to optimise adalimumab therapy in patients with Crohn's disease [CD]. However, the interindividual variability in drug absorption and the quantitative effect on drug clearance of anti-adalimumab antibodies [AAA], measured with a drug-resistant assay, are unclear. We aimed to characterise adalimumab population pharmacokinetics [PopPK] and identify determinants of interindividual variability in patients with CD. In a prospective multicentre open-label cohort study in 28 patients with CD starting adalimumab therapy peak, intermediate, and trough serum samples were analysed for adalimumab and AAA concentrations using a drug resistant assay. Adalimumab concentration-time data were analysed by non-linear mixed effects modelling and were adequately described by a PopPK model with first-order absorption and one-compartment disposition with linear elimination. Clinical remission at Week 12 [W12] was defined as a Harvey-Bradshaw index ≤4. The absorption rate, volume of distribution, and clearance estimates of a typical patient were respectively 0.343 /day, 7.8 L, and 0.330 L/day. A 4-fold difference in the range of adalimumab concentrations was observed 7 days after the first dose and found to be inversely correlated with baseline lean body weight [LBW], soluble tumour necrosis factor [s-TNF], and s-TNF receptor-1 whereas positive AAA and higher LBW were found to be important predictors of accelerated clearance. An adalimumab concentration at W12 of >7.3 µg/mL was significantly associated with achieving clinical remission at W12. Variability in subcutaneous drug absorption is an important contributor to the observed interindividual variability in adalimumab concentrations, in addition to drug clearance [ClinicalTrials.gov NCT02450513].

Bemiparin as a Prophylaxis After an Unexplained Stillbirth: Open-Label Interventional Prospective Study.

Stillbirth is a devastating event to the parents, relatives, friends, and families. The role of anticoagulants in the prevention of unexplained stillbirths is uncertain. An open-label interventional prospective cohort study was conducted on 144 women with a history of unexplained stillbirths. The intervention group had a high umbilical artery resistance index (RI) and received bemiparin. The nonintervention group had a normal RI and did not receive any intervention. We measured the adjusted odds ratio (OR) and 95% confidence interval (CI) of the main outcome for these variables using logistic regression analysis. Fresh stillbirth and early neonatal death rates were lower (P = .005, OR = 11.949 and 95% CI = 2.099-68.014) and newborn weight was higher (P = .015, OR = 0.048, 95% CI = 0.004-0.549) in the group that received bemiparin. Bemiparin is effective in decreasing the rate of stillbirth in women with a history of previous unexplained stillbirths.

Choosing Between Daily and Event-Driven Pre-exposure Prophylaxis: Results of a Belgian PrEP Demonstration Project.

Daily pre-exposure prophylaxis and event-driven pre-exposure prophylaxis (PrEP) are efficacious in reducing HIV transmission among men who have sex with men (MSM). We analyzed baseline data from a PrEP demonstration project "Be-PrEP-ared" in Antwerp, Belgium, to understand preferences for daily PrEP or event-driven PrEP among MSM at high risk of HIV and factors influencing their initial choice. Cross-sectional data from an open-label prospective cohort study, using mixed methods. Participants who preregistered online were screened for eligibility and tested for sexually transmitted infections (STIs). Eligible participants chose between daily PrEP and event-driven PrEP and reported on behavioral data through an electronic questionnaire. In-depth interviews were conducted with a selected subsample. Bivariate associations were examined between preferred PrEP regimens and sociodemographic factors, sexual behavior, and STIs at screening. In total, 200 participants were enrolled between October 2015 and December 2016. Self-reported levels of sexual risk-taking before enrollment were high. STI screening revealed that 39.5% had at least 1 bacterial STI. At baseline, 76.5% of participants preferred daily PrEP and 23.5% event-driven PrEP. Feeling able to anticipate HIV risk was the most frequent reason for preferring event-driven PrEP. Regimen choice was associated with sexual risk-taking behavior in the past 3 months. Almost all participants (95.7%) considered it likely that they would change their dosing regimen the following year. Event-driven PrEP was preferred by 23.5% of the participants, which better suits their preventive needs. Event-driven PrEP should be included in PrEP provision as a valuable alternative to daily PrEP for MSM at high risk of HIV.

Magnetic resonance imaging using ultrasmall superparamagnetic particles of iron oxide for abdominal aortic aneurysm: a risk prediction study

Background Abdominal aortic aneurysm (AAA) rupture is a common cause of sudden death. Pre-emptive elective surgical repair can prevent aneurysm rupture and be life-saving. Ultrasmall superparamagnetic particles of iron oxide (USPIO) detect cellular inflammation using magnetic resonance imaging (MRI) in patients with AAAs. For this reason, USPIO-enhanced MRI represents a promising new technique that could improve risk prediction and better guide surgical intervention. Objectives To assess whether or not USPIO-enhanced MRI can predict aneurysm growth rates and clinical outcomes in patients with AAAs. Design A prospective multicentre open-label observational cohort study. Setting Three secondary and tertiary care hospitals in Scotland. Participants Patients (n = 342) aged &gt; 40 years with a maximum anteroposterior AAA diameter of ≥ 40 mm confirmed by abdominal ultrasonography, and under ultrasonographic surveillance as part of routine clinical care. Interventions USPIO-enhanced MRI of AAA. Main outcome measures The primary end point was the composite of aneurysm rupture or repair. Secondary outcomes included rate of aneurysm growth, all-cause mortality and aneurysm-related mortality. Results Participants (85% male, aged 73.1 ± 7.2 years) had a baseline aneurysm diameter of 49.6 ± 7.7 mm, and USPIO enhancement was identified in 146 participants (42.7%), absent in 191 participants (55.8%) and indeterminate in 5 participants (1.5%). During follow-up (1005 ± 280 days), there were 17 AAA ruptures (5.0%), 126 AAA repairs (36.8%) and 48 deaths (14.0%). Compared with those without uptake, patients with USPIO enhancement have increased rates of aneurysm expansion (3.1 ± 2.5 vs. 2.5 ± 2.4 mm/year; p = 0.0424), although this was not independent of current smoking habits (p = 0.1993). The primary end point (aneurysm rupture or repair) occurred more frequently in participants with USPIO enhancement [69/146 (47.3%) vs. 68/191 (35.6%), difference 11.7%, 95% confidence interval 1.1% to 22.2%; p = 0.0308]: this was similar for each component of rupture (6.8% vs. 3.7%; p = 0.1857) or repair (41.8% vs. 32.5%; p = 0.0782). USPIO enhancement was associated with reduced event-free survival for aneurysm rupture or repair (p = 0.0275). Baseline AAA diameter (p &lt; 0.0001) and current smoking habits (p = 0.0446) also predicted the primary outcome, and the addition of USPIO enhancement to the multivariate model did not improve event prediction (c-statistic 0.7935 to 0.7936). Conclusions USPIO-enhanced MRI is a novel approach to the identification of aortic wall cellular inflammation in patients with AAAs, and predicts the rate of aneurysm growth and clinical outcome. USPIO-enhanced MRI does not provide independent prediction of aneurysm expansion or clinical outcomes in a model incorporating known clinical risk factors. Larger trials are now needed to explore the prediction of emergent aneurysm events to establish the added benefit of USPIO-enhanced MRI. Comparative outcome studies should determine whether or not using other imaging biomarkers that track alternative disease processes have better predictive capability than USPIO-enhanced MRI. Trial registration Current Controlled Trials ISRCTN76413758. Funding This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research partnership.

Switching antipsychotic treatment to aripiprazole in psychotic patients with neuroleptic-induced tardive dyskinesia: a 24-week follow-up study.

Aripiprazole is a second-generation antipsychotics, acting as a partial dopamine D2 receptor agonist. Previous studies on aripiprazole for tardive dyskinesia (TD) treatment were limited and inconclusive. This study was aimed to examine the effectiveness of aripiprazole in psychotic patients with a pre-existing TD. This was an open-label 24-week prospective cohort study conducted in a public mental hospital in Northern Taiwan from January 2009 to February 2010. Psychotic patients were cross-titrated of prior antipsychotics with aripiprazole, and the severity of TD was assessed at baseline and at weeks 2, 4, 8, 12, 16, 20, and 24. The primary study outcome was the change of TD severity, assessed by Abnormal Involuntary Movement Scale (AIMS) total score. Responder was defined as the reduction of AIMS total scores of no less than 50% from baseline to the study endpoint (24 weeks). Thirty psychotic patients with neuroleptic-induced TD were recruited. The AIMS total scores significantly decreased from baseline to the study endpoint (-7.17±5.55). The significant decrease of AIMS total scores started at week 2 (P<0.0001), and the change remained significant throughout the entire study period (P<0.0001). A greater severity of TD (adjusted odds ratio: 1.35, 95% confidence interval: 1.04-1.76, P=0.03) or a lower severity of parkinsonism (adjusted odds ratio: 0.78, 95% confidence interval: 0.61-0.99, P=0.04) at baseline was significantly associated with treatment responders. Our findings implicated that aripiprazole can be a promising treatment for clinicians considering drug switch in psychotic patients with TD. Further large randomized, controlled trials are warranted to confirm our findings.

Predictors of response to occipital nerve stimulation in refractory chronic headache.

Background Occipital nerve stimulation is a promising treatment for refractory chronic headache disorders, but is invasive and costly. Identifying predictors of response would be useful in selecting patients. We present the results of an open-label prospective cohort study of 100 patients (35 chronic migraine, 33 chronic cluster headache, 20 short-lasting unilateral neuralgiform headache attacks and 12 hemicrania continua) undergoing occipital nerve stimulation, using a multivariate binary regression analysis to identify predictors of response. Results Response rate of the cohort was 48%. Multivariate analysis showed short lasting unilateral neuralgiform headache attacks (OR 6.71; 95% CI 1.49-30.05; p = 0.013) and prior response to greater occipital nerve block (OR 4.22; 95% CI 1.35-13.21; p = 0.013) were associated with increased likelihood of response. Presence of occipital pain (OR 0.27; 95% CI 0.09-0.76; p = 0.014) and the presence of severe anxiety and/or depression (as measured on hospital anxiety and depression score) at time of implantation (OR 0.32; 95% CI 0.11-0.91; p = 0.032) were associated with reduced likelihood of response. Conclusion Possible clinical predictors of response to occipital nerve stimulation for refractory chronic headaches have been identified. Our data shows that those with short-lasting unilateral neuralgiform headache attacks respond better than those with chronic migraine, and that a prior response to greater occipital nerve block is associated with positive outcomes. This study suggests that the presence of occipital pain and severe mood disorder at time of implant are both associated with poor outcomes to occipital nerve stimulation.

Aortic Wall Inflammation Predicts Abdominal Aortic Aneurysm Expansion, Rupture, and Need for Surgical Repair.

Ultrasmall superparamagnetic particles of iron oxide (USPIO) detect cellular inflammation on magnetic resonance imaging (MRI). In patients with abdominal aortic aneurysm, we assessed whether USPIO-enhanced MRI can predict aneurysm growth rates and clinical outcomes. In a prospective multicenter open-label cohort study, 342 patients with abdominal aortic aneurysm (diameter ≥40 mm) were classified by the presence of USPIO enhancement and were monitored with serial ultrasound and clinical follow-up for ≥2 years. The primary end point was the composite of aneurysm rupture or repair. Participants (85% male, 73.1±7.2 years) had a baseline aneurysm diameter of 49.6±7.7 mm, and USPIO enhancement was identified in 146 (42.7%) participants, absent in 191 (55.8%), and indeterminant in 5 (1.5%). During follow-up (1005±280 days), 17 (5.0%) abdominal aortic aneurysm ruptures, 126 (36.8%) abdominal aortic aneurysm repairs, and 48 (14.0%) deaths occurred. Compared with those without uptake, patients with USPIO enhancement have increased rates of aneurysm expansion (3.1±2.5 versus 2.5±2.4 mm/year, P=0.0424), although this was not independent of current smoking habit (P=0.1993). Patients with USPIO enhancement had higher rates of aneurysm rupture or repair (47.3% versus 35.6%; 95% confidence intervals, 1.1-22.2; P=0.0308). This finding was similar for each component of rupture (6.8% versus 3.7%, P=0.1857) or repair (41.8% versus 32.5%, P=0.0782). USPIO enhancement was associated with reduced event-free survival for aneurysm rupture or repair (P=0.0275), all-cause mortality (P=0.0635), and aneurysm-related mortality (P=0.0590). Baseline abdominal aortic aneurysm diameter (P<0.0001) and current smoking habit (P=0.0446) also predicted the primary outcome, and the addition of USPIO enhancement to the multivariate model did not improve event prediction (c-statistic, 0.7935-0.7936). USPIO-enhanced MRI is a novel approach to the identification of aortic wall cellular inflammation in patients with abdominal aortic aneurysms and predicts the rate of aneurysm growth and clinical outcome. However, it does not provide independent prediction of aneurysm expansion or clinical outcomes in a model incorporating known clinical risk factors. URL: http://www.isrctn.com. Unique identifier: ISRCTN76413758.

Thalidomide induces clinical remission and mucosal healing in adults with active Crohn's disease: a prospective open-label study.

Background:Thalidomide is effective in inducing and maintaining clinical remission in children and adolescents with refractory Crohn’s disease (CD). However, little is known about the efficacy and safety of thalidomide for adult patients with CD.Methods:We conducted a prospective open-label cohort study between January 2013 and April 2015. A total of 47 adult patients with active CD who were dependent/resistant or intolerant to corticosteroids and/or immunomodulators or biologics received 50–100 mg of thalidomide daily. Primary outcome was clinical remission evaluated at week 8. Endoscopic assessment was performed at week 24 and defined as endoscopic response (decrease in Crohn’s Disease Endoscopic Index of Severity [CDEIS] score > 5 points from baseline CDEIS of 6 or more), complete endoscopic remission (CDEIS score < 3), and mucosal healing (MH) (no ulceration).Results:A total of 47 adults with active CD were enrolled. The clinical remission rate was 14.9% and 23.4% at week 4 and week 8, but increased to 46.8% at week 12 and 53.2% at week 24 out of all the 47 patients included (intention-to-treat analysis). Altogether 32 patients consented and underwent ileocolonoscopy at week 24. The rate of endoscopic response and complete endoscopic remission were 68.4% and 43.8%. MH (no ulceration) was achieved in 28.1% of patients. Adverse events occurred in 27/47 (57.4%) patients but necessitated therapy discontinuation in only 5/47 (10.6%) of patients.Conclusions:Low-dose thalidomide was effective and tolerated for inducing and maintaining clinical remission in adult patients with active CD, but the optimal time frame for thalidomide to induce clinical remission may be longer than previously appreciated and is probably optimal at 12 weeks. MH could reasonably be achievable with thalidomide.

Pre-Exposure Prophylaxis (PrEP) as an Additional Tool for HIV Prevention Among Men Who Have Sex With Men in Belgium: The Be-PrEP-ared Study Protocol.

BackgroundPre-exposure prophylaxis (PrEP) is a promising and effective tool to prevent HIV. With the approval of Truvada as daily PrEP by the European Commission in August 2016, individual European Member states prepare themselves for PrEP implementation following the examples of France and Norway. However, context-specific data to guide optimal implementation is currently lacking.ObjectiveWith this demonstration project we evaluate whether daily and event-driven PrEP, provided within a comprehensive prevention package, is a feasible and acceptable additional prevention tool for men who have sex with men (MSM) at high risk of acquiring HIV in Belgium. The study’s primary objective is to document the uptake, acceptability, and adherence to both daily and event-driven PrEP, while several secondary objectives have been formulated including impact of PrEP use on sexual behavior.MethodsThe Be-PrEP-ared study is a phase 3, single-site, open-label prospective cohort study with a large social science component embedded in the trial. A total of 200 participants choose between daily or event-driven PrEP use and may switch, discontinue, or restart their regimen at the 3-monthly visits for a duration of 18 months. Data are collected on several platforms: an electronic case report form, a Web-based tool where participants register their sexual behavior and pill use, a more detailed electronic self-administered questionnaire completed during study visits on a tablet computer, and in-depth interviews among a selected sample of participants. To answer the primary objective, the recruitment rate, (un)safe sex behavior during the last 6 months, percentage of reported intention to use PrEP in the future, retention rates in different regimens, and attitudes towards PrEP use will be analyzed. Adherence will be monitored using self-reported adherence, pill count, tenofovir drug levels in blood samples, and the perceived skills to adhere.ResultsAll participants are currently enrolled, and the last study visit is planned to take place around Q3 2018.ConclusionsAs PrEP is not yet available in Belgium for use, this study will provide insights into how to optimally implement PrEP within the current health care provision and will shape national and European guidelines with regard to the place of PrEP in HIV prevention strategies.ClinicalTrialEU Clinical Trial 2015-000054-37; https://www.clinicaltrialsregister.eu/ctr-search/trial/2015-000054-37/BE (Archived by WebCite at http://www.webcitation.org/6nacjSdmM).