Cortical Thickness Changes Associated with Photoparoxysmal Response

Photoparoxysmal response (PPR) is an EEG trait of spike and spike-wave discharges in response to photic stimulation that is closely linked to idiopathic generalized epilepsy (IGE). In our previous studies we showed that PPR is associated with functional alterations in the occipital and frontal cortices. The aim of the present study was to determine structural changes associated with PPR. For this purpose we analysed the cortical thickness as derived from T1 MRI images in PPR-positive-subjects (n = 12; 15.5 ± 8.6 years; 4 males), PPR-positive-IGE-patients (n = 12; 14.9 ± 2.7 years; 4 males) and compared these groups with a group of PPR-negative-healthy-controls (HC, n = 17; 15.3 ± 3.6 years; 6 males). Our results revealed an increase of cortical thickness in the occipital, frontal and parietal cortices bilaterally in PPR-positive-subjects in comparison to HC. Moreover PPR-positive-subjects presented a significant decrease of cortical thickness in the temporal cortex in the same group contrast. IGE patients exhibited lower cortical thickness in the temporal lobe bilaterally and in the right paracentral region in comparison to PPR-positive-subjects. Our study demonstrates structural changes in the occipital lobe, frontoparietal regions and temporal lobe, which also show functional changes associated with PPR. Patients with epilepsy present changes in the temporal lobe and supplementary motor area.     

Fungi predatory activity on embryonated <Emphasis Type="Italic">Toxocara canis</Emphasis> eggs inoculated in domestic chickens (<Emphasis Type="Italic">Gallus gallus domesticus</Emphasis>) and destruction of second stage larvae

The objective of this study was to evaluate the infectivity of Toxocara canis eggs after interacting with isolated nematophagous fungi of the species Duddingtonia flagrans (AC001) and Pochonia chlamydosporia (VC4), and test the predatory activity of the isolated AC001 on T. canis second stage larvae after 7 days of interaction. In assay A, 5000 embryonated T. canis eggs previously in contact with the AC001 and VC4 isolated for 10 days were inoculated into domestic chickens (Gallus gallus domesticus), and then these animals were necropsied to collect material (digested liver, intestine, muscles and lungs) at 3-, 7-, 14-, and 21-day intervals after inoculation. In assay A, the results demonstrated that the prior interaction of the eggs with isolated AC001 and VC4 decreases the amount of larvae found in the collected organs. Difference (p?<?0.01) was observed in the medium larvae counts recovered from liver, lung, intestine, and muscle of animals in the treated groups when compared to the animals in the control group. At the end of assay A, a percentage reduction of 87.1 % (AC001) and 84.5 % (VC4) respectively was recorded. In the result of assay B, the isolated AC001 showed differences (p?<?0.01) compared to the control group, with a reduction of 53.4 % in the recovery of L₂. Through these results, it is justified to mention that prior interaction of embryonated T. canis eggs with the tested fungal isolates were efficient in reducing the development and migration of this parasite, in addition to the first report of proven predatory activity on L₂.     

Computer-Aided Methodology for Syndromic Strabismus Diagnosis

Strabismus is a pathology that affects approximately 4 % of the population, causing aesthetic problems reversible at any age and irreversible sensory alterations that modify the vision mechanism. The Hirschberg test is one type of examination for detecting this pathology. Computer-aided detection/diagnosis is being used with relative success to aid health professionals. Nevertheless, the routine use of high-tech devices for aiding ophthalmological diagnosis and therapy is not a reality within the subspecialty of strabismus. Thus, this work presents a methodology to aid in diagnosis of syndromic strabismus through digital imaging. Two hundred images belonging to 40 patients previously diagnosed by an specialist were tested. The method was demonstrated to be 88 % accurate in esotropias identification (ET), 100 % for exotropias (XT), 80.33 % for hypertropias (HT), and 83.33 % for hypotropias (HoT). The overall average error was 5.6Δ and 3.83Δ for horizontal and vertical deviations, respectively, against the measures presented by the specialist.     

Impact of the polymorphism in vitamin D receptor gene <Emphasis Type="Italic">BsmI</Emphasis> and the risk of systemic lupus erythematosus: an updated meta-analysis

The etiology of system lupus erythematosus (SLE) still remains unclear, and vitamin D is associated with immune response. Although a few studies are conducted to investigate the association between polymorphism in vitamin D receptor (VDR) genes and SLE risk, their results are conflicting. Following the guideline of PRISMA, we conducted a systematic search and meta-analysis of the BsmI polymorphism rs1544410 and the risk of SLE. The pooled odds ratios (OR) and its 95 % confidential interval (CI) were calculated by using Stata Version 10 with dominant and recessive model and allele analyses. Nine studies were included in our meta-analysis with a total of 1247 SLE cases and 1687 controls. No significant association was found in both models in the overall population. Only Bb?+?BB genotypes showed a significantly elevated SLE risk in Asian subgroup with an OR of 3.26 (95 % CI?=?1.30–8.17) while no significance was observed in Caucasian population. Notably, B allele significantly increased the SLE risk among Asian population with an OR of 2.29 (95 % CI?=?1.14–4.61). No positive findings were reported in Caucasian population and in the overall analysis. In Asian population, Bb?+?BB genotype and B allele can significantly increase the SLE risk.     

High adherence to all-oral directly acting antiviral HCV therapy among an inner-city patient population in a phase 2a study

Background

As treatment for chronic hepatitis C (HCV) virus has evolved to all-oral, interferon-free directly acting antiviral (DAA) therapy, the impact of these improvements on patient adherence has not been described.

Methods

Medication adherence was measured in 60 HCV, genotype-1, treatment-naïve participants enrolled in a phase 2a clinical trial at the National Institutes of Health and community clinics. Participants received either ledipasvir/sofosbuvir (LDV/SOF) (90 mg/400 mg) (one pill) daily for 12 weeks, LDV/SOF + GS-9451 (80 mg/day) (two pills) daily for 6 weeks, or LDV/SOF + GS-9669 (500 mg twice daily; three pills, two in the morning, one in the evening) for 6 weeks. Adherence was measured using medication event monitoring system (MEMS) caps, pill counts and patient report.

Results

Overall adherence to DAAs was high. Adherence declined over the course of the 12-week treatment (p = 0.04). While controlled psychiatric disease or symptoms of depression did not influence adherence, recent drug use was a risk factor for non-adherence to 12-week (p = 0.01), but not 6-week regimens. Adherence as measured by MEMS was lower than by patient report.

Conclusions

Adherence to short courses of DAA therapy with 1–3 pills a day was excellent in an urban population with multiple risk factors for non-adherence.

     

Treatment of DVT: how long is enough and how do you predict recurrence

Abstract Currently available anticoagulants are effective in reducing the recurrence rate of venous thromboembolism (VTE). However, anticoagulant treatment is associated with an increased risk for bleeding complications. Thus, anticoagulation has to be discontinued when benefit of treatment no longer clearly outweigh its risks. The duration of anticoagulant treatment is currently framed based on the estimated individual risk for recurrent VTE. The incidence of recurrent VTE can be estimated through a two-step decision algorithm. Firstly, the features of the patient (gender), of the initial event (proximal or distal deep vein thrombosis or pulmonary embolism), and the associated conditions (cancer, surgery, etc) provide essential information on the risk for recurrence after anticoagulant treatment discontinuation. Secondly, at time of anticoagulant treatment discontinuation, d-dimer levels and residual thrombosis have been indicated as predictors of recurrent VTE. Current evidence suggests that the risk of recurrence after stopping therapy is largely determined by whether the acute episode of VTE has been effectively treated and by the patient’s intrinsic risk of having a new episode of VTE. All patients with acute VTE should receive oral anticoagulant treatment for three months. At the end of this treatment period, physicians should decide for withdrawal or indefinite anticoagulation. Based on intrinsic patient’s risk for recurrent VTE and for bleeding complications and on patient preference, selected patients could be allocated to indefinite treatment with VKA with scheduled periodic re-assessment of the benefit from extending anticoagulation. Alternative strategies for secondary prevention of VTE to be used after conventional anticoagulation are currently under evaluation. Cancer patients should receive low molecular-weight heparin over warfarin in the long-term treatment of VTE. These patients should be considered for extended anticoagulation at least until resolution of underlying disease. Abbreviated abstract The risk for recurrent venous thromboembolism can be estimated through a two-step algorithm. Firstly, the features of the patient (gender), of the initial event (proximal or distal deep vein thrombosis or pulmonary embolism), and the associated conditions (cancer, surgery, etc) are essential to estimate the risk for recurrence after anticoagulant treatment discontinuation. Secondly, a correlation has been shown between d-dimer levels and residual thrombosis at time of anticoagulant treatment discontinuation and the risk of recurrence. Currently available anticoagulants are effective in reducing the incidence of recurrent venous thromboembolism, but they are associated with an increased risk for bleeding complications. All patients with acute venous thromboembolism should receive oral anticoagulant treatment for three months. At the end of this treatment period physicians should decide for definitive withdrawal or indefinite anticoagulation with scheduled periodic re-assessment of the benefit from extending anticoagulation.     

Impact of an Evidence-Based Medicine Curriculum on Resident Use of Electronic Resources: A Randomized Controlled Study

Background  Evidence-based medicine (EBM) is widely taught in residency, but evidence for effectiveness of EBM teaching on changing residents’ behavior is limited. Objective  To investigate the impact of an EBM curriculum on residents’ use of evidence-based resources in a simulated clinical experience. Design/Participants  Fifty medicine residents randomized to an EBM teaching or control group. Measurements  A validated test of EBM knowledge (Fresno test) was administered before and after intervention. Post intervention, residents twice completed a Web-based, multiple-choice instrument (15 items) comprised of clinical vignettes, first without then with access to electronic resources. Use of electronic resources was tracked using ProxyPlus software. Within group pre–post differences and between group post-test differences were examined. Results  There was more improvement in EBM knowledge (100-point scale) for the intervention group compared to the control group (mean score increase 22 vs. 12, p = 0.012). In the simulated clinical experience, the most commonly accessed resources were Ovid (71% of residents accessed) and InfoPOEMs (62%) for the EBM group and UptoDate (67%) and MDConsult (58%) for the control group. Residents in the EBM group were more likely to use evidence-based resources than the control group. Performance on clinical vignettes was similar between the groups both at baseline (p = 0.19) and with access to information resources (p = 0.89). Conclusions  EBM teaching improved EBM knowledge and increased use of evidence-based resources by residents, but did not improve performance on Web-based clinical vignettes. Future studies will need to examine impact of EBM teaching on clinical outcomes.     

Reducing risk of stroke in patients with acute coronary syndrome: is screening for asymptomatic carotid disease useful?

Stroke is a rare but severe event after acute coronary syndrome. Relations between both arterial territories are still discussed but prevalence of asymptomatic carotid stenosis potentially implicated in the mechanism of stroke is under-investigated. This study aimed to determine the prevalence of asymptomatic carotid stenosis in that population and review the value of screening in a view to potential surgical correction or other preventive therapies. Systematic carotid Doppler ultrasound screening was implemented on 152 consecutive patients admitted to the intensive care unit due to acute coronary syndrome. Fifty-two percent of patients had at least one carotid artery stenosis determined using the NASCET method. Forty-three percent had at least one carotid stenosis <30%, 6% had mild (30–60%) stenosis, and 2.6% had high-grade (>60%) stenosis. Existence of carotid stenosis was associated with age, diabetes mellitus, hypertension, and with the extent of the coronary atherosclerosis (left main artery stenosis). In multivariate analysis, age and diabetes were independently associated with existence of a carotid stenosis. When ultrasound screening was restricted to patients identified by multivariate analysis, the prevalence of carotid stenosis potentially requiring surgical treatment rose to 4.6%. The frequency of asymptomatic carotid atherosclerosis was high in this population but lesions were mild. While the small number of high-grade lesions indicates that systematic screening is not to be recommended, screening of patients aged >65 years or with diabetes, or both, with a view to surgery may be envisaged, since the role of mild stenosis in the occurrence of stroke remains debatable.     

Carcinoma of the distal and middle bile duct: surgical results,prognostic factors,and long-term follow-up

Background/Purpose

Carcinoma of the distal bile duct is associated with poor prognosis. Surgical resection remains the only potentially curative treatment. We conducted a retrospective study to identify prognostic factors determining longterm survival.

Methods

From 1990 to 2006, 95 patients with distal and/or middle bile duct carcinoma had resections. Fifty-four patients underwent pylorus-preserving pancreaticoduodenectomy (57%) and 41 patients underwent standard Kausch-Whipple pancreaticoduodenectomy (43%). Nine patients underwent pancreaticoduodenectomy including portal vein resection (9%).

Results

Overall 1-, 3-, and 5-year survival rates were 60%, 36%, and 29%, respectively. Five-year survival after R0 resection was 34%, and after R1 resection it was 0%. Four patients died during their hospital stay (4%). Multivariate analysis showed negative resection margins (P = 0.040), lymphatic vessel invasion (P = 0.036), and portal vein infiltration (P = 0.027) as strong predictors for survival, whereas the location of the tumor (distal bile duct vs middle bile duct) and lymph node status were not identified as independent prognostic factors.

Conclusions

Five-year survival depends strongly on negative resection margins, independent of nodal status. Portal vein resections in patients with portal vein involvement fail to ameliorate long-term survival. Primary tumor site — middle bile duct or distal bile duct — did not determine prognosis.