The primary objective was to investigate whether nonadherence to antiepileptic drugs (AEDs) is associated with increased mortality and the secondary objective to examine whether nonadherence ...increases the risk of serious clinical events, including emergency department (ED) visits, hospitalizations, motor vehicle accident (MVA) injuries, fractures, and head injuries.
A retrospective open-cohort design was employed using Medicaid claims data from Florida, Iowa, and New Jersey from January 1997 through June 2006. Patients aged > or =18 years with > or =1 diagnosis of epilepsy by a neurologist and > or =2 AED pharmacy dispensings were selected. Medication possession ratio (MPR) was used to evaluate AED adherence on a quarterly basis with MPR > or =0.80 considered adherent and <0.80 nonadherent. The association of nonadherence with mortality was assessed using a time-varying Cox regression model adjusting for demographic and clinical confounders. Incidence rates for serious clinical events were compared between adherent and nonadherent quarters using incidence rate ratios (IRRs) with 95% CIs calculated based on the Poisson distribution.
The 33,658 study patients contributed 388,564 AED-treated quarters (26% nonadherent). Nonadherence was associated with an over threefold increased risk of mortality compared to adherence (hazard ratio = 3.32, 95% CI = 3.11-3.54) after multivariate adjustments. Time periods of nonadherence were also associated with a significantly higher incidence of ED visits (IRR = 1.50, 95% CI = 1.49-1.52), hospital admissions (IRR = 1.86, 95% CI = 1.84-1.88), MVA injuries (IRR = 2.08, 95% CI = 1.81-2.39), and fractures (IRR = 1.21, 95% CI = 1.18-1.23) than periods of adherence.
These findings suggest that nonadherence to antiepileptic drugs can have serious or fatal consequences for patients with epilepsy.
Iflaviridae is a family of small non-enveloped viruses with monopartite, positive-stranded RNA genomes of approximately 9-11 kilobases. Viruses of all classified species infect arthropod hosts, with ...the majority infecting insects. Both beneficial and pest insects serve as hosts, and infections can be symptomless (Nilaparvatalugens honeydew virus 1) or cause developmental abnormalities (deformed wing virus), behavioural changes (sacbrood virus) and premature mortality (infectious flacherie virus). The host range has not been examined for most members. The most common route of infection for iflaviruses is the ingestion of virus-contaminated food sources. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the taxonomy of the Iflaviridae, which is available at www.ictv.global/report/iflaviridae.
Dicistroviridae is a family of small non-enveloped viruses with monopartite, linear, positive-sense RNA genomes of approximately 8-10 kb. Viruses of all classified species infect arthropod hosts, ...with some having devastating economic consequences, such as acute bee paralysis virus in domesticated honeybees and taura syndrome virus in shrimp farming. Conversely, the host specificity and other desirable traits exhibited by several members of this group make them potential natural enemies for intentional use against arthropod pests, such as triatoma virus against triatomine bugs that vector Chagas disease. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the taxonomy of the Dicistroviridae which is available at www.ictv.global/report/dicistroviridae.
Display omitted
Nonenveloped virus-like particles (VLPs) are self-assembled oligomeric structures composed of one or more proteins that originate from diverse viruses. Because these VLPs have similar ...antigenicity to the parental virus, they are successfully used as vaccines against cognate virus infection. Furthermore, after foreign antigenic sequences are inserted in their protein components (chimVLPs), some VLPs are also amenable to producing vaccines against pathogens other than the virus it originates from (these VLPs are named platform or epitope carrier). Designing chimVLP vaccines is challenging because the immunogenic response must be oriented against a given antigen without altering stimulant properties inherent to the VLP. An important step in this process is choosing the location of the sequence modifications because this must be performed without compromising the assembly and stability of the original VLP. Currently, many immunogenic data and computational tools can help guide the design of chimVLPs, thus reducing experimental costs and work. In this study, we analyze the structure of a novel VLP that originate from an insect virus and describe the putative regions of its three structural proteins amenable to insertion. For this purpose, we employed molecular dynamics (MD) simulations to assess chimVLP stability by comparing mutated and wild-type (WT) VLP protein trajectories. We applied this procedure to design a chimVLP that can serve as a prophylactic vaccine against the SARS-CoV-2 virus. The methodology described in this work is generally applicable for VLP-based vaccine development.
Summary
Background
Chronic constipation (CC) is a highly prevalent health problem, potentially associated with increased risk of colorectal cancer (CRCancer).
Aim
To investigate the association ...between CC, its severity, and CRCancer by estimating the relative risk of developing CRCancer and benign colorectal neoplasm (BCN) among severity‐stratified patients with and without CC.
Methods
Chronic constipation patients from a large retrospective US claims database were matched 1:3 with CC‐free controls by demographic characteristics. CRCancer and BCN prevalence were measured over 1 year. In pre‐index CRCancer‐ and BCN‐free patients, incidence rate ratios (IRRs) of new CRCancer and BCN were calculated. Multivariate regression models adjusted for comorbidities and family history. CC patients' disease severity was rated based on CC‐related resource use. IRRs for new CRCancer and BCN were estimated for CC severity groups and controls.
Results
Chronic constipation (N = 28 854) and CC‐free (N = 86 562) patients had mean age 61.9 years; 66.7% were female. One‐year CRCancer prevalence was 2.7% and 1.7%, and BCN prevalence was 24.8% and 11.9% for CC and CC‐free patients, respectively. Adjusted IRRs between CC and CC‐free patients were 1.59 95% confidence interval (CI): 1.43–1.78 and 2.60 95% CI: 1.51–2.70 for CRCancer and BCN, respectively. Patients with severe and very severe CC had significantly greater incidence of CRCancer and BCN. At ≥2 and ≥5 years of observation, CRCancer and BCN incidence remained consistently and significantly higher for CC patients.
Conclusions
Patients with chronic constipation are associated with significantly higher prevalence and incidence of colorectal cancer and benign colorectal neoplasm than matched chronic constipation‐free patients. These risks increase with the severity of chronic constipation.
Rockfalls strongly influence the evolution of steep rocky landscapes and represent a significant hazard in mountainous areas. Defining the most probable future rockfall source areas is of primary ...importance for both geomorphological investigations and hazard assessment. Thus, a need exists to understand which areas of a steep cliff are more likely to be affected by a rockfall. An important analytical gap exists between regional rockfall susceptibility studies and block-specific geomechanical calculations. Here we present methods for quantifying rockfall susceptibility at the cliff scale, which is suitable for sub-regional hazard assessment (hundreds to thousands of square meters). Our methods use three-dimensional point clouds acquired by terrestrial laser scanning to quantify the fracture patterns and compute failure mechanisms for planar, wedge, and toppling failures on vertical and overhanging rock walls. As a part of this work, we developed a rockfall susceptibility index for each type of failure mechanism according to the interaction between the discontinuities and the local cliff orientation. The susceptibility for slope parallel exfoliation-type failures, which are generally hard to identify, is partly captured by planar and toppling susceptibility indexes. We tested the methods for detecting the most susceptible rockfall source areas on two famously steep landscapes, Yosemite Valley (California, USA) and the Drus in the Mont-Blanc massif (France). Our rockfall susceptibility models show good correspondence with active rockfall sources. The methods offer new tools for investigating rockfall hazard and improving our understanding of rockfall processes.
Summary
Background Psoriasis is associated with poor health‐related quality of life, including sleep impairment.
Objective To assess the extent of sleep impairment, the effect of adalimumab on ...sleep and other patient‐reported outcomes, and correlations between changes in these outcomes and sleep quality in patients with psoriasis.
Methods Patients in the 16‐week, open‐label, Phase IIIb PROGRESS trial had chronic plaque psoriasis and suboptimal response to prior therapy (etanercept, methotrexate or narrowband ultraviolet B phototherapy). Adalimumab was self‐injected subcutaneously (80 mg at week 0, then 40 mg every other week from week 1). The focus for this analysis was the Medical Outcomes Study Sleep Scale. Other patient‐reported outcomes included the Dermatology Life Quality Index (DLQI), Psoriasis Area and Severity Index (PASI), Physician’s Global Assessment, a visual analogue scale for psoriasis/psoriatic arthritis (PsA) pain, and the Work Productivity and Activity Index Questionnaire‐Specific Health Problems.
Results Patients with psoriasis had impaired sleep at baseline. The degree of sleep impairment was significantly associated with the extent of work productivity for all sleep measures and, for some sleep measures, was associated with DLQI impairment, clinical severity measured by PASI, the presence of PsA, and depression. Adalimumab treatment significantly improved sleep quality by 15% from baseline, as well as DLQI score, pain and work productivity. The improvement in sleep was partially explained (R2 = 0·16, P < 0·001) by improvements in the objectively measured psoriasis signs in PASI.
Conclusions Adalimumab treatment improved sleep outcomes and other patient‐reported outcomes including health‐related quality of life, work productivity, daily activity and disease‐related pain.
•VLPs from Triatoma virus are used as adjuvants for the development of vaccines in the context of Chagas disease.•TrV-VLPs have the ability to preferentially induce IgG2b and IgG3 antibodies in ...murine model.•TrV-VLPs as an adjuvant can polarize the induction of the immune response together recombinant chimeric antigens from Trypanosoma cruzi.
The infection caused by the protozoan Trypanosoma cruzi affects humans and is called as Chagas disease. Currently, the main measures available to reduce the incidence of this disease are drug treatment and vector control. Traditionally, the development of vaccines occurs mainly through the use of antigenic candidates of the etiologic agent in the form of a vaccine preparation. Virus-like particles (VLPs) are structures analogous to viral capsids composed essentially of structural proteins and are widely used in vaccination protocols because of their immunostimulatory properties. In this context, the objective of this study was to use strategies in a murine immunization model to characterize the immunostimulatory capacity of VLPs from Triatoma virus (TrV-VLPs), analysed in the presence or absence of the aluminium vaccine adjuvant. In parallel, to characterize the immunogenic behaviour of four T. cruzi chimeric recombinant proteins (mix-IBMP) associated with TrV-VLPs or aluminium vaccine adjuvant.
We immunized BALB/c mice once or twice, depending on the strategy, and collected serum samples at 15, 30 and 45 days after the immunization. Subsequently, serum samples from animals immunized with TrV-VLPs were used to determine total IgG, IgG1, IgG2a, IgG2b and IgG3 anti-TrV-VLPs by enzyme-linked immunosorbent assay (ELISA).
Data obtained demonstrate the ability of TrV-VLPs to preferably induce IgG2b and IgG3 type antibodies in the absence of aluminium adjuvant. In fact, the use of aluminium did not interfere with the total IgG profile of anti-TrV-VLPs. Interestingly, mix-IBMP had a better profile of total IgG, IgG1 and IgG3 subclasses when mixed with TrV-VLPs.
In conclusion, these results suggest the potential of TrV-VLPs as a vaccine adjuvant and the use of T. cruzi chimeric antigens as a rational strategy for the development of vaccines against the experimental model of Chagas disease.
Background Psoriasis is frequently associated with comorbidities.
Objective To estimate the incremental economic burden associated with comorbidities in patients with psoriasis, accounting for ...psoriasis severity.
Methods Patients continuously enrolled ≥ 6 months after a randomly selected psoriasis diagnosis date were selected from the Ingenix Impact National Managed Care Database (1999–2004). Comorbidities identified during the 6‐month study included: psoriatic arthritis, cardiovascular disease, depression, diabetes, hyperlipidemia, hypertension, obesity, cerebrovascular diseases and peripheral vascular disease. Resource utilization and costs during the 6‐month follow‐up period were compared for patients with ≥ 1 comorbidity vs. those without and for patients with a specific comorbidity vs. those without. Adjusted incidence rate ratios (IRRs) and odds ratios (ORs) were estimated for resource utilization using negative binomial and logistic regression models, respectively. Adjusted incremental costs associated with comorbidities were reported using general linear models with log‐link and gamma distributions or two‐part models. Models controlled for age, sex and psoriasis severity.
Results A total of 114 512 patients were included; 51% had ≥ 1 comorbidity. Hyperlipidemia (27%) and hypertension (25%) were most prevalent. Patients with comorbidities were more likely to experience urgent care OR (95% confidence interval (CI)) = 1.58 (1.51–1.65) than patients without comorbidities. They also had significantly greater hospitalization rates IRR (95% CI) = 2.27 (2.13–2.42) and outpatient visits IRR (95% CI) = 1.53 (1.52–1.55). Compared with patients who did not have comorbidities, patients with comorbidities incurred $2184 (P < 0.001) greater total costs.
Conclusion Comorbidities present a significant economic burden in patients with psoriasis.
PDF
