Full Responders Research Articles

Personality traits and efficacy of anti-CGRP monoclonal antibodies in migraine prevention.

Anti-CGRP monoclonal antibodies (CGRPmAbs) enlarged migraine prevention options. They work targetedly, safely, and efficiently in many patients. Inexplicably, a proportion of patients show scarce improvement. To identify the possible role of personality traits, determined with the Personality Inventory for DSM5 (PID5), on the efficacy of CGRPmAbs on migraine. We evaluated 3 parameters: monthly headache days (MHD), monthly painkillers intake (MPI), and MIDAS. For each parameter, patients were classified as: (A) non-responders (reduction < 3 0% vs. baseline); (B) partial responders (30-49% reduction); (C) full responders (reduction > 50%). Ninety-seven patients treated with CGRP-mAbs were included (33 galcanezumab, 13 fremanezumab, 51 erenumab). Considering attack reduction (MHD), 53 (54.6%) were full responders, 13 (13.4%) partial responders, and 31 (32%) non-responders. Considering MPI, 61 (62.9%) were full responders, 11 (11.3%) partial responders, and 24 (24.7%) non-responders. Concerning MIDAS, 53 (53%) were full responders, 17 (17.5%) partial responders, and 21 (21.6%) were non-responders. All the 97 patients were tested with the PID5. In terms of MHDs, non-responders, in comparison with responders, showed a significant excess of disinhibition, especially in relation with the anhedonia and depressivity facets. Concerning MPI, non-responders showed increased depressivity and distractibility. MIDAS non-responders had significantly higher scores in the antagonism domain and submissiveness facet. Non-responders seem to have different personality traits in comparison to responders, with a higher tendency toward depressed mood and difficulty to feel pleasure previously found in migraineurs vs. non-migraineurs: the more strict certain traits are, the more difficult to treat the migraine could be.

Pain management and outcomes in cancer patients: comparison between oncological and palliative sets of care

&#x0D; Background: medical oncologists and palliative care physicians have different tasks even if they play a similar role when coping with pain of their patients. In spite of this converging goal, oncologists and palliative care therapists can not have the same approach and impact in managing pain. This study analyzes how pain is treated and which outcomes derive from in 1 461 cancer patients separately cared by oncologists or palliative care physicians.&#x0D; Methods: data derive from an observational, multicentre, prospective, longitudinal study carried out in 110 Italian hospitals. After inclusion, the data were recorded weekly for a 28 days period of follow-up.&#x0D; Results: 876 patients (60%) were cared by oncologists and 585 (40%) by palliative care physicians. The two professional categories tended to similarly manage the drugs of WHO analgesic ladder, while rescue and adjuvant therapies were more frequently used by palliative care physicians. Opioids daily dose increased from 68.3 to 92.5 mg/day (Effect size=0.282) among oncologists and from 70.8 to 107.8 mg/day (Effect size=0.402) among palliative care physicians. The switch of opioids was applied in 12.3% and in 19.1% (p=0.1634), respectively. Pain intensity decreased in both groups but more strongly in the palliative context. The full responders patients were 50% in oncology wards and 58.9% in palliative care (p=0.0588).&#x0D; Conclusions: this study indicates how much oncologists and palliative care physicians differ in managing cancer pain. The observational nature of this study reflects the natural and unaffected choice of the professionals. As intrinsic limit the study only describes their behaviors without a stringent comparative evaluation.&#x0D;

Left Ventricular Hemodynamics and Relationship With Myocardial Recovery and Optimization in Patients Supported on CF-LVAD Therapy

BackgroundDespite interest in left ventricular (LV) recovery, there is an absence of data on the relationship between intrinsic LV hemodynamics and both reverse remodeling on a continuous flow LV assist device (CF-LVAD) therapy. We hypothesized that the markers of intrinsic LV function would be associated with remodeling, optimization, and outcomes. Methods and ResultsPatients with continuous flow LVADs between 2015 and 2019 who underwent combined left and right heart catheterization ramp protocol at a single institution were enrolled. Patients were stratified by response to continuous flow LV assist device therapy: full responders, partial responders, or nonresponders per the Utah–Inova criteria. Hemodynamic data, including LV hemodynamics of peak LV dP/dt and tau (τ) were obtained at each phase. The 1-year heart failure hospitalization-free survival was the primary end point. Among 61 patients included in the current study 38 (62%) were classified as nonresponders, 14 as partial responders (23%), and 9 as full responders (15%). The baseline LV dP/dt and τ varied by response status (P ≤ .02) and generally correlated with reverse remodeling on linear regression. Biventricular filling pressures varied with τ and there was an interaction effect of speed on the relationship between τ and pulmonary capillary wedge pressure (P = .04). Last, τ was a prognostic marker and associated with 1-year HF hospital-free survival (odds ratio 1.04, 95% confidence interval 1.00–1.07, P = .02 per millisecond increase). ConclusionsSignificant correlations between τ and LV dP/dt and reverse remodeling were noted, with τ serving as a prognostic marker. A higher LVAD speed was associated with a greater reliance on LVAD for unloading. Future work should focus on defining the optimal level of LVAD support in relation to LV recovery.

Comparison of the Institute for Credentialing Excellence Multi-Organization Survey of Certificants

Abstract Introduction/Objective The Institute for Credentialing Excellence (ICE) conducted a study to measure the value that credential holders place on certification, collecting survey data from a large sample of more than 12,000 credential holders representing six organizations (4 of which were healthcare). In May of 2019, ASCP BOC sent the survey to 47,384 individuals certified within the last 5 years. Of those who received the survey; 2,038 completed the 80 required questions. A comparison of survey data provided an overview of the top five differences in the full survey data (n=9,407) and the data from respondents credentialed by ASCP BOC (n = 2,038 or 22% of full survey respondents) and highlighted the primary reasons individuals pursue certification. Methods/Case Report This survey sought to define certificants’ attitudes toward and experiences with certification. Survey questions were grouped by four primary subject areas: The Value of Certification for Respondents’ Professions The Value of Certification for Employers The Value of Certification Outside the U.S. and Canada The Value of Certification for Certificants - Responses of themed queries of full survey data and BOC survey data were viewed side by side and averages, standard deviations and medians were calculated. The top 5 items indicating the highest difference from the full survey data results were highlighted. - Ranked primary motivational factors for the pursuit of certification were viewed side-by-side. Results (if a Case Study enter NA) Based on a side-by-side comparison of full survey data and BOC survey data, only minor differences were noted with the exception of the question pertaining to the perceived value of recertification. Both differences and items of agreement were highlighted. The top 10 reasons for seeking certification were the same amongst both the full survey and ASCP BOC survey respondents, with minor differences in priority order. Conclusion With the exception of the question regarding the value of recertification, discrepancies noted were minor. On most questions pertaining to the various benefits of certification, a majority of respondents gave a positive response about certification and its relationship to beneficial outcomes for their professions, employers, or themselves. It is clear that certificants place a high value on certification and believe that certification provides a number of valuable benefits.

Limitations of Current Rehabilitation Practices in Pediatric Oncology: Implications for Improving Comprehensive Clinical Care

ObjectiveTo identify the proportion of hospitals/clinics in the United States (US) that have a comprehensive pediatric oncology rehabilitation program and characterize current practices. DesignCross-sectional survey of rehabilitation providers in the US and internationally. SettingElectronic or telephone survey. ParticipantsRehabilitation or supportive care practitioners employed at a hospital, outpatient clinic, or medical university (N=231). InterventionsElectronic and telephone survey. The full electronic survey contained 39 questions, provided opportunities for open-ended responses, and covered 3 main categories specific to pediatric cancer rehabilitation: service delivery, rehabilitation program practices, and education/training. The short telephone survey included 4 questions from the full survey and was designed to answer the primary study objective. Main Outcome MeasuresProportion of hospitals/clinics with a comprehensive pediatric oncology rehabilitation program. ResultsThis cohort includes rehabilitation providers from 191 hospitals/clinics, 49 states within the US, and 5 countries outside of the US. Of hospitals/clinics represented from the full and short survey, 145 (76%) do not have an established pediatric oncology rehabilitation program. Nearly half of full survey respondents reported no knowledge of the prospective surveillance model, and 65% reported no education was provided to them regarding pediatric cancer rehabilitation. Qualitative survey responses fell into 3 major themes: variability in approach to rehabilitation service delivery, program gaps, and need for additional educational opportunities. ConclusionsThere is evidence of limited comprehensive rehabilitation programming for children with cancer as demonstrated by the lack of programs with coordinated interdisciplinary care, variability in long-term follow-up, and absence of education and training. Research is needed to support the development and implementation of comprehensive pediatric oncology rehabilitation programs.

Long-Term Treatment of Eosinophilic Esophagitis With Budesonide Oral Suspension

We evaluated treatment withdrawal, long-term outcomes, and safety of budesonide oral suspension (BOS) 2.0 mg twice daily in patients with eosinophilic esophagitis who completed a 12-week induction study. Induction full responders (≤6 eosinophils per high-power field [eos/hpf] and ≥30% reduction in the Dysphagia Symptom Questionnaire score) to BOS 2.0 mg twice daily (ORBIT1/SHP621-301/NCT02605837) were randomized to continue BOS (BOS-BOS) or withdraw to placebo (BOS-PBO) for 36 weeks (ORBIT2/SHP621-302/NCT02736409). Induction partial responders and nonresponders, and patients who received induction placebo, received BOS for 36 weeks. The primary end point was the proportion of BOS-BOS and BOS-PBO patients who relapsed (≥15 eos/hpf and ≥4 days of dysphagia [Dysphagia Symptom Questionnaire] over 2 weeks) by week 36. The key secondary end point was the proportion of induction partial responders and nonresponders who fully responded after 52 weeks of total BOS therapy. Other secondary end points included the proportion of induction full responders with histologic responses (≤1, ≤6, <15 eos/hpf) at week 12 of the extension study, and safety outcomes. The randomized withdrawal period enrolled 48 patients (BOS-BOS, n= 25; BOS-PBO, n= 23); 106 induction partial responders and nonresponders, and 65 induction placebo patients received BOS. More BOS-PBO than BOS-BOS patients relapsed over 36 weeks (43.5% vs 24.0%; P= .131) and had histologic responses at week 12 of therapy (P < .001). Overall, 13.2% of induction partial responders and nonresponders fully responded at week 36. BOS was well tolerated; therapy duration was not associated with new safety concerns. For induction full responders, continuing BOS numerically improved maintenance of efficacy vs withdrawal. A longer therapy duration did not raise safety concerns. (ClinicalTrials.gov: NCT02736409.).

Magnetic Resonance Imaging-Guided Laser Thermal Ventral Capsulotomy for Intractable Obsessive-Compulsive Disorder.

Obsessive-compulsive disorder (OCD) is a disabling condition characterized by intrusive thoughts and repetitive behaviors. A subset of individuals have severe, treatment-resistant illness and are nonresponsive to medication or behavioral therapies. Without response to conventional therapeutic options, surgical intervention becomes an appropriate consideration. To report clinical outcomes and the safety profile of bilateral ventral anterior capsulotomy for OCD using magnetic resonance (MR)-guided laser interstitial thermal therapy (LITT) in 10 patients followed for 6 to 24 mo. A total of 10 patients underwent LITT for severe OCD; 1 patient withdrew prior to follow-up. LITT is a minimally invasive ablative technique performed with precise targeting and use of thermography under MR guidance. Lesions of the ventral anterior limb of the internal capsule by other techniques have been shown to be efficacious in prior studies. A total of 7 of the 9 patients were considered full responders (77.8%; Yale-Brown Obsessive-Compulsive Scale change≥35%). Adverse effects included transient apathy/amotivation postsurgery (2 patients). One patient had a small tract hemorrhage where the laser fiber traversed the cerebral cortex as well as persistent insomnia postsurgery. One individual died after a drug overdose 7 mo postsurgery, which was judged unrelated to the surgery. LITT ventral capsulotomy was generally well tolerated, with promising evidence of effectiveness in the largest such series to date. Results were comparable to those after gamma knife ventral capsulotomy, as well as ventral anterior limb deep brain stimulation.

MO1027EFFICACY OF CALCINEURIN INHIBITORS IN CHILDREN WITH MONOGENIC STEROID-RESISTANT NEPHROTIC SYNDROME

Abstract Background and Aims Monogenic causes of steroid-resistant nephrotic syndrome (SRNS) have been reported for up to one-third of children depending on age of the disease onset. Immunosuppressive treatment of genetic SRNS with calcineurin inhibitors (CNIs) is still controversial. The aim of the study was to investigate the efficacy of CNIs with focus on inducing remission and long-term kidney function in children with monogenic SRNS. Method Retrospective analysis of efficacy CNIs in five children (2M/3F) with monogenic SRNS was performed. Kidney biopsy prior CNIs revealed FSGS (n=4) and MCD (n=1). The initial cyclosporine (CsA) dose was 5 mg/kg/24h to keep a target level of 80-150 ng/ml and tacrolimus (TAC) - 0.1 mg/kg/24h to achieve a target level of 5-10 ng/ml. CsA took all 5 patients with subsequent switching to TAC in 2 children due to cosmetic side effects. The median follow-up period was 165.0 (IQR: 59.0; 185.5) months. Next generation sequencing (NGS) was used for identification of pathogenic variants in all patients. Results The median age at onset of monogenic SRNS was 33.0 (IQR: 16.5; 63.0) months. 2/5 (40%) patients presented with acute SRNS, 1/5 (20%) child with infantile NS, 1/5 (20%) - with isolated nephrotic range proteinuria with hypoalbuminemia and 1/5 (20%) - with NS and extrarenal features of Nail-Patella syndrome. NGS identified previously described pathogenic variants in all 5 children, including NPHS2 homozygous c.28dup (p.Glu87Ter) (n=1), NPHS2 compound heterozygous c.868G&amp;gt;A (p.Val290Met) in combination with c.686G&amp;gt;A (p.Arg229Gln) (n=1), LMX1B heterozygous c.788T&amp;gt;G (p.Val263Gly) (n=1), LMX1B heterozygous c.737G&amp;gt;A (p.Arg246Gln) (n=1), and COL4A3 heterozygous c.2962G&amp;gt;A (p.Gly988Arg) variant (n=1). The median time from diagnosis to initiation of CNIs treatment was 72.0 (IQR: 33.0; 93.0) months. CNIs induced complete remission in 2/5 (40%) patients, presented with acute SRNS, including one girl with MCD due to NPHS2 compound heterozygous variants with mutation-dependent pathogenicity of one (p.R229Q) of them and one boy with FSGS due to COL4A3 heterozygous variant (n=1). Partial remission was induced by CNIs in 2/5 (40%) girls with FSGS due to LMX1B heterozygous variants with isolated SRNS (n=1) and Nail-Patella syndrome (n=1). The median duration of CNIs treatment to obtain complete or partial remission was 13.5 (IQR: 6.8; 15.8) months. Acute CNIs-associated nephrotoxicity had 2 patients with LMX1B variants. At the last follow up full and partial responders to CNIs treatment aged of 16.5 (IQR: 11.8; 17.5) years had CKD-1 (n=3) and CKD-2 (n=1). 1/5 (20%) boy with NPHS2-associated infantile NS was CNI resistant and developed CKD-5 at the age of 6.5 years with subsequent living related kidney transplantation. Conclusion We found that 4/5 (80%) children with monogenic SRNS demonstrated partial or full response to CNIs treatment with stable long-term kidney function. We assume that CNIs might improve podocyte function by stabilization of their cytoskeleton disrupted in patients with monogenic SRNS.

Dalfampridine improves slowed processing speed in multiple sclerosis patients with mild motor disability: post hoc analysis of a randomized controlled trial.

Objective:To evaluate baseline characteristics predictive of improving information processing speed in multiple sclerosis (MS) and the relationship between cognitive and motor response to dalfampridine (DA) treatment.Methods:This is a post hoc analysis of a randomized, double-blind, placebo-controlled trial in patients with MS randomized to receive DA 10 mg or placebo twice daily for 12 consecutive weeks. Here, we include only data from 71 patients in the arm treated with DA. According to the median value of Symbol Digit Modalities Test (SDMT) response, patients were categorized as “full responders” (FR) or “partially responders” (PR).Results:There was higher possibility of being FR in the presence of a baseline lower Expanded Disability Status Scale [odds ratio (OR) 0.69; 95% confidence interval (CI) 0.5–0.97, p = 0.034], a higher Multiple Sclerosis Functional Composite value (OR 1.37; 95%CI 1.05–1.8, p = 0.022), a lower Timed 25-Foot Walk Test (OR 0.76; 95% CI 0.6–0.98, p = 0.033), and a lower 9-Hole Peg Test with dominant hand (OR 0.92; 95% CI 0.86–0.99, p = 0.029). FR group did not show any significant improvement of motor performance compared with PR group.Conclusion:The current analysis shows that in MS patients with cognitive deficit, the greatest improvement in SDMT provided by DA was observed in patients with milder motor impairment; cognitive and motor responses to treatments are not related.Trial registration:EU Clinical Trials Register; ID 2013-002558-64 (https://www.clinicaltrialsregister.eu/ctr-search/search?query=2013-002558-64)

Systematic review with meta-analysis: lubiprostone efficacy on the treatment of patients with constipation

Lubiprostone is a type 2 chloride channel activator that has been shown to be efficacious and safe in the treatment for chronic constipation. To systematically review randomized clinical trials (RCTs) assessing efficacy of lubiprostone for patients with chronic idiopathic constipation (CIC), irritable bowel syndrome with predominant constipation (IBS-C) and opioid-induced constipation (OIC). Searches were conducted in PubMed, LILACS, Cochrane Collaboration Database, and Centre for Reviews and Dissemination. Lubiprostone RCTs reporting outcomes of spontaneous bowel movements (SBM) and abdominal pain or discomfort were deemed eligible. Meta-analysis was performed calculating risk ratios and 95% confidence intervals, using the Mantel-Haenszel method and random effects model. Searches yielded 109 records representing 93 non-duplicate publications, and 11 RCTs (978 CIC, 1,366 IBS-C, 1,300 OIC, total = 3,644) met inclusion criteria. Qualitative synthesis showed that for CIC patients, lubiprostone is superior to placebo in terms of SBM outcomes. Meta-analysis for CIC was feasible for full responder and SBM within 24h rates, indicating superiority of lubiprostone over placebo. For IBS-C, lubiprostone was significantly superior for all SBM outcomes in follow-ups ranging from 1 week-3 months. In terms of abdominal pain, lubiprostone provided significantly better symptoms relief, particularly after 1 month of treatment. For OIC, lubiprostone was more effective than placebo for both SBM and discomfort measures. Our findings demonstrated that lubiprostone is superior to placebo in terms of SBM frequency for CIC, IBS-C and OIC. In terms of abdominal symptoms, the most pronounced effect was seen for abdominal pain in IBS-C patients.

Association of SLC1A1 gene polymorphism with obsessive compulsive disorder in a sample from southern India.

The glutamate transporter gene SLC1A1 has been shown to have an association with obsessive-compulsive disorder (OCD), and serotonin reuptake inhibitor (SRI) treatment response. One polymorphism (rs3056) in SLC1A1 has been associated with altered brain volumes in OCD. We investigated the association of this polymorphism with OCD and its relationship with various clinical parameters, including age of onset, disease severity, insight, factor analyzed symptom dimensions of OCD, and SRI treatment response. Three hundred seventy seven OCD patients (DSM-IV) aged between 18 to 60 years were recruited from a specialty OCD clinic. To study the association with SRI treatment response, we analyzed full responders (≥35% reduction in the Yale Brown Obsessive Compulsive Scale [YBOCS] and the Clinical Global Impression-Improvement [CGI-I] score of 1 or 2) to any SRI (n = 187) and nonresponders (<25% reduction in the YBOCS and the CGI-I score >4) to adequate trials of at least two SRIs for a duration of 12 weeks (n = 91). Healthy controls (n = 333) were recruited and evaluated using the Mini-International Neuropsychiatric Interview-Plus (MINI-Plus). All subjects were from southern India, and were genotyped for the SLC1A1 polymorphism (rs3056). Genotype frequencies did not deviate significantly from the Hardy-Weinberg equilibrium. Case-control association analysis revealed that the "GG" genotype was significantly more frequent in OCD cases than the controls (p = .04). No association was found with the age of onset, symptom severity, insight, and symptom dimensions. No significant association was found between genotype/allele frequencies with treatment response. To conclude, although there was a significant association between the SLC1A1 rs3056 polymorphism and OCD, there were no significant associations with other clinical parameters or treatment response. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Kepuasan kerja sebagai variabel mediasi pada pengaruh stres kerja terhadap niat keluar

This research is motivated by the high turnover among Y and Z generation caused by the level of. work stress caused by workload and unclear work procedures. This study aimed to determine job satisfaction as a mediator of the relationship between work stress and turnover intention. This study used quantitative methods with full sampling and respondents as many as 65 employees. The data analysis technique was performed using SEM test with WarpPLS 7.0 software. Based on the test, results showed that work stress has a significant effect on turnover intention and job satisfaction is evident to be intervening variable.

Endothelial Cells Derived From Patients With Diabetic Macular Edema Recapitulate Clinical Evaluations of Anti-VEGF Responsiveness Through the Neuronal Pentraxin 2 Pathway.

Diabetic macular edema (DME) remains a leading cause of vision loss worldwide. DME is commonly treated with intravitreal injections of vascular endothelial growth factor (VEGF)-neutralizing antibodies. VEGF inhibitors (anti-VEGFs) are effective, but not all patients fully respond to them. Given the potential side effects, inconvenience, and high cost of anti-VEGFs, identifying who may not respond appropriately to them and why is essential. Herein we determine first the response to anti-VEGFs, using spectral-domain optical coherence tomography scans obtained from a cohort of patients with DME throughout the 1st year of treatment. We found that fluid fully cleared at some time during the 1st year in 28% of eyes ("full responders"); fluid cleared only partly in 66% ("partial responders"); and fluid remained unchanged in 6% ("nonresponders"). To understand this differential response, we generated induced pluripotent stem cells (iPSCs) from full responders and nonresponders, from subjects with diabetes but no DME, and from age-matched volunteers without diabetes. We differentiated these iPSCs into endothelial cells (iPSC-ECs). Monolayers of iPSC-ECs derived from patients with diabetes showed a marked and prolonged increase in permeability upon exposure to VEGF; the response was significantly exaggerated in iPSC-ECs from nonresponders. Moreover, phosphorylation of key cellular proteins in response to VEGF, including VEGFR2, and gene expression profiles, such as that of neuronal pentraxin 2, differed between full responders and nonresponders. In this study, iPSCs were used in order to predict patients' responses to anti-VEGFs and to identify key mechanisms that underpin the differential outcomes observed in the clinic. This approach identified NPTX2 as playing a significant role in patient-linked responses and as having potential as a new therapeutic target for DME.

Calcineurin inhibitors in nephrotic syndrome secondary to podocyte gene mutations: a systematic review.

Calcineurin inhibitor (CNI) use in genetic steroid-resistant nephrotic syndrome (SRNS) is controversial as response rate is reported to be lower than non-genetic disease and no plausible mechanism of action is known. We reviewed PubMed for publications on CNI use in hereditary SRNS to determine (1) CNI response rate; (2) impact of response on renal outcome; and (3) clinical and molecular predictors of response. Variant pathogenicity was assessed according to American College of Medical Genetics criteria and patients were assigned to 1 of 4 categories based on estimated genotype contribution to phenotype. Cases with non-existing phenotype-to-genotype contribution were excluded. Subgroup analysis was performed for the possible and confirmed genetic cases. Data of 178 genetic SRNS cases from 22 studies were analyzed; 35% responded (fully or partially) to CNI with minimal change being the commonest biopsy pattern among responders. Full responders had superior kidney survival compared with partial and non-responders (log-rank test χ2 = 10.7; P < 0.01). WT1 variant carriers were most likely to respond to CNI compared with any other mutation [OR 4.7 (2.0-11.3); P < 0.01]. These findings support the current recommendation for using CNI as first-line treatment for children with SRNS whilst genetic analyses are pending. This would allow assessment of treatment response even in cases later established as genetic ensuring that benefits on kidney function are balanced with treatment toxicity.

Interpatient heterogeneity in hepatic microvascular blood flow during vascular inflow occlusion (Pringle manoeuvre).

Vascular inflow occlusion (VIO) during liver resections (Pringle manoeuvre) can be applied to reduce blood loss, however may at the same time, give rise to ischemia-reperfusion injury (IRI). The aim of this study was to assess the characteristics of hepatic microvascular perfusion during VIO in patients undergoing major liver resection. Assessment of hepatic microcirculation was performed using a handheld vital microscope (HVM) at the beginning of surgery, end of VIO (20 minutes) and during reperfusion after the termination of VIO. The microcirculatory parameters assessed were: functional capillary density (FCD), microvascular flow index (MFI) and sinusoidal diameter (SinD). A total of 15 patients underwent VIO; 8 patients showed hepatic microvascular perfusion despite VIO (partial responders) and 7 patients showed complete cessation of hepatic microvascular perfusion (full responders). Functional microvascular parameters and blood flow levels were significantly higher in the partial responders when compared to the full responders during VIO (FCD: 0.84±0.88 vs. 0.00±0.00 mm/mm2, P<0.03, respectively, and MFI: 0.69-0.22 vs. 0.00±0.00, P<0.01, respectively). An interpatient heterogeneous response in hepatic microvascular blood flow was observed upon VIO. This may explain why clinical strategies to protect the liver against IRI lacked consistency.

The hepatic microcirculation of a full responder to VIO

The hepatic microcirculation of a full responder to VIO

The prognostic value of voiding chart data in therapy-resistant enuresis

The case history is the primary tool when investigating the enuretic child. To further determine whether nocturnal polyuria or detrusor overactivity is present, a full voiding chart, is the method of choice. However, there is no robust evidence that daytime voiding chart data actually do predict nocturnal detrusor function. The aim of this study was to assess the predictive value of anamnestic data and the voiding chart in the treatment of children with therapy-resistant enuresis. The patients all suffered from enuresis resistant to first-line therapy. None of the children had daytime incontinence. In accordance with international recommendations, the children were first treated with anticholinergics. If the therapeutic effect was not satisfactory dosage was adjusted and desmopressin was added. If sufficient treatment effect was not achieved, antidepressant therapy was tried next, combined with desmopressin if needed. Since this was an evaluation of clinical practice, not a randomized trial, treatment success was graded according to family satisfaction, not the actual frequency of wet nights. Thus, only children who reported that they were completely dry were regarded as full responders and those who stated that there was a substantial and useful reduction of wet nights were labeled intermediate responders. In total, 154 patients were included. Few and inconsistent differences were found between the groups responding or not responding to the various treatment regimens, and this was true both for anamnestic and voiding chart data (see Table). The only statistically significant findings were that responders to antidepressant therapy were older (p=0.013) than non-responders, and patients who benefited from addition of desmopressin had a higher micturition frequency than those who did not (p=0.027). The children who needed desmopressin as part of combination treatment to become dry did not have significantly higher nocturnal urine production than those who had no such benefit (p=0.619). Neither the presence of urgency nor a history of previous daytime incontinence was significantly more common in children responding to anticholinergics (p=0.375 and 0.072, respectively). No clear and consistent differences in either anamnestic factors or voiding chart data were found between the patients responding or not responding to the various treatment regimens. Not even urgency could predict anticholinergic efficacy. Somewhat surprisingly, no association between nocturnal polyuria and desmopressin benefit was found. In this study no prognostic value was found in anamnestic or voiding chart data in children with therapy resistant enuresis.

Decision-Making by Patients With Methamphetamine Use Disorder Receiving Contingency Management Treatment: Magnitude and Frequency Effects.

BackgroundIndividuals with substance use disorders exhibit maladaptive decision-making on the Iowa Gambling Task (IGT), which involves selecting from card decks differing in the magnitudes of rewards, and the frequency and magnitude of losses. We investigated whether baseline IGT performance could predict responses to contingency management (CM) by treatment-seeking individuals with methamphetamine use disorder (MA Use Disorder) in Cape Town, South Africa.MethodsTwenty-nine individuals with MA Use Disorder underwent an 8-week, escalating reinforcement, voucher-based CM treatment in a study on the suitability of CM therapy for the South African context. Along with 20 healthy control participants, they performed a computerized version of the IGT before starting CM treatment. Seventeen participants maintained abstinence from methamphetamine throughout the trial (full responders), and 12 had an incomplete response (partial responders). Performance on the IGT was scored for magnitude effect (selection of large immediate rewards with high long-term loss) and for frequency effect (preference for frequent rewards and avoidance of frequent losses). Group differences were investigated using linear mixed-effect modeling.ResultsPartial responders made more selections from decks providing large, immediate rewards and long-term losses than healthy controls [p = 0.038, g = -0.77 (-1.09: -0.44)]. Full responders showed a greater, nonsignificant preference for frequent rewards and aversion to frequent losses than partial responders [p = 0.054, g = -0.63 (-0.95: -0.29)].ConclusionsA predilection for choices based on the size and immediacy of reward may reflect a cognitive strategy that works against CM. Pretesting with a decision-making task, such as the IGT, may help in matching cognitive therapies to clients with MA Use Disorder.

A Randomized Controlled Study of a Psychoeducation Group Intervention for Patients With Borderline Personality Disorder

The objective of this study was to assess the impact of a 6-session psychoeducational group (PEG) intervention for borderline personality disorder (BPD) in an underserved community-based outpatient setting. The study was conducted between July 2015 and January 2017. Of 96 outpatients who met DSM-IV criteria for BPD, the first 48 received the experimental treatment, whereas the next 48 were assigned to a wait list. All received non-intensive treatment as usual. The primary outcome measure, the Zanarini Rating Scale for DSM-IV Borderline Personality Disorder (ZAN-BPD), was administered at baseline, at the end of treatment, and 2 months after the end of treatment. The PEG intervention was associated with a significant improvement on all sectors of BPD (P < .001). Improvements were greater for the PEG on all sectors except impulsivity. Benefits remained stable during 2-month follow-up. The PEG intervention had a large effect size (Cohen d = -1.16), whereas the wait list effect size was small (Cohen d = -0.18). The between-arms effect size was 0.80 after treatment and 0.90 at follow-up. With full response defined as a decrease of ≥ 50% from baseline in ZAN-BPD total score, 22 patients (46%) in the psychoeducation group and 3 (6%) in the wait list group were considered full responders. This study shows that a PEG intervention can be an effective treatment for patients with BPD. The overall cost benefits of group interventions and the the applicability of a PEG intervention to underserved patients demonstrate its potential to address significant public health needs.

Effects of La Crosse virus infection on the host-seeking behavior and levels of two neurotransmitters in Aedes triseriatus

BackgroundLa Crosse virus (LACV) infection has been shown to manipulate the blood-feeding behaviors of its main vector, Aedes triseriatus. Here, we investigated the effects of virus infection on serotonin and dopamine and their potential roles in host-seeking. In mosquitoes, serotonin depletion has been shown to interfere with blood-feeding but not host-seeking. Dopamine depletion does not affect either blood-feeding or host-seeking; elevations of dopamine, however, has been shown to inhibit host-seeking. The purpose of this study was to determine the effects of LACV infection on the host-seeking behavior of and neurotransmitter levels in Ae. triseriatus.MethodsHost-seeking behavior was evaluated using a uni-port olfactometer and a membrane feeder assay. Levels of serotonin and dopamine in infected and control mosquito heads were measured using HPLC-ED.ResultsInfection with LACV significantly inhibited the activation and attraction of Ae. triseriatus females to a host. A higher proportion of uninfected Ae. triseriatus females were activated by the presence of a host compared to infected mosquitoes and more uninfected mosquitoes were full responders (95.7%) compared to infected ones (91.1%). However, infection with LACV did not significantly affect the landing, probing, or blood-feeding rates of female mosquitoes. LACV-infected mosquitoes had lower serotonin levels than controls (104.5 vs 138.3 pg/head) while the dopamine levels were not affected by infection status (282.3 vs 237 pg/head).ConclusionsOur work suggests that virus-induced reduction of serotonin is related to previously reported blood-feeding alterations in LACV-infected mosquitoes and could lead to enhanced transmission and increased vectorial capacity. In addition, some aspects of host-seeking were inhibited by virus infection.