Change In Treatment Regimen Research Articles

C-reactive protein levels, the prognostic nutritional index, and the lactate dehydrogenase-to-lymphocyte ratio are important prognostic factors in primary central nervous system lymphoma: a single-center study of 223 patients

Primary central nervous system lymphoma (PCNSL) is a rare and highly aggressive type of extranodal non-Hodgkin lymphoma (NHL), and the prognosis is poor. Currently, the most used prognostic models are the Memorial Sloan-Kettering Cancer Center (MSKCC) and International Extranodal Lymphoma Study Group (IELSG) scores; however, their predictive effects are changing with increasing incidence and changing treatment regimens. A growing body of evidence has demonstrated that inflammatory and nutritional markers are factors that can determine tumor prognosis. Therefore, the aim of this study was to identify and validate novel prognostic factors for PCNSL. Clinical information was collected from 223 patients with PCNSL. Patients younger than 18 years of age were excluded. Progression-free survival (PFS) and overall survival (OS) were used as endpoints, and receiver operating characteristic (ROC) curve analyses were conducted to determine the cutoff values for the inflammatory indicators. Correlations between variables and PFS or OS were assessed using univariate and multivariate analyses, and positive indicators were selected for survival analysis. A prognostic nutritional index (PNI) < 49.38 was associated with worse PFS (p = 0.003), and outcomes significantly differed between patients with a PNI ≥ 49.38 and < 49.38 (p < 0.001). Age < 60 years (p < 0.001) and C-reactive protein (CRP) levels < 3.14 (p = 0.001) were associated with better OS. In elderly patients (≥ 60 years), a lactate dehydrogenase-to-lymphocyte ratio (LLR) < 95.69 (p = 0.021) was associated with better OS, and the outcome significantly differed between patients with an LLR ≥ 95.69 and LLR < 95.69 (p = 0.015). The PNI and CRP levels are prognostic factors for PCNSL, and CRP was the first time shown to be a prognosis factor of PCNSL. In elderly patients with PCNSL, the LLR can predict prognosis.

Plasma lipidomic profiling of thiopurine-induced leukopenia after NUDT15 genotype-guided dosing in Chinese IBD patients.

Thiopurines, azathiopurine (AZA) and mercaptopurine (6-MP) have been regularly used in the treatment of inflammatory bowel disease (IBD). Despite optimized dosage adjustment based on the NUDT15 genotypes, some patients still discontinue or change treatment regimens due to thiopurine-induced leukopenia. We proposed a prospective observational study of lipidomics to reveal the lipids perturbations associated with thiopurine-induced leukopenia. One hundred and twenty-seven IBD participants treated with thiopurine were enrolled, twenty-seven of which have developed thiopurine-induced leucopenia. Plasma lipid profiles were measured using Ultra-High-Performance Liquid Chromatography-Tandem Q-Exactive. Lipidomic alterations were validated with an independent validation cohort (leukopenia n = 26, non-leukopenia n = 74). Using univariate and multivariate analysis, there were 16 lipid species from four lipid classes, triglyceride (n = 11), sphingomyelin (n = 1), phosphatidylcholine (n = 1) and lactosylceramide (n = 3) identified. Based on machine learning feature reduction and variable screening strategies, the random forest algorithm established by six lipids showed an excellent performance to distinguish the leukopenia group from the normal group, with a model accuracy of 95.28% (discovery cohort), 79.00% (validation cohort) and an area under the receiver operating characteristic (ROC) curve (ROC-AUC) of 0.9989 (discovery cohort), 0.8098 (validation cohort). Our novel findings suggested that lipidomic provided unique insights into formulating individualized medication strategies for thiopurines in IBD patients.

Using tumor growth rate to inform treatment efficacy in pancreatic adenocarcinoma: From the metastatic to the neoadjuvant setting.

726 Background: The development of new treatments in oncology is a long, costly, and, too often, unsuccessful process. Methods for screening agents earlier in development and strategies for conducting smaller randomized controlled trials are needed. Methods: We used a mathematical model of tumor growth kinetics fit to serial radiographic tumor measurements or CA19-9 values to estimate rates of exponential tumor growth [g] and decay [d] during treatment for pancreatic ductal adenocarcinoma (PDAC). Results: We retrospectively collected and analyzed data from 2691 patients with stage III-IV PDAC who were enrolled in five clinical trials or were included in two large real-world data sets from Columbia University Irving Medical Center and Veterans Administration Medical Centers. Using log-rank comparison of Kaplan-Meier plots by quartile of g, we found that in patients with metastatic PDAC g correlates highly with overall (OS) and progression-free survival (PFS) (p&lt;0.001), with slower g associated with improved survival in this population. Pairwise comparisons showed significantly slower median g in the experimental arm versus control arm in the pivotal trials analyzed (p&lt;0.001). At the individual patient level, g was significantly faster for liver metastases as compared to primary pancreatic tumors and g consistently increased towards the end of therapy (often a threefold increase) suggesting development of chemoresistance. In addition to utility in the metastatic setting, a pilot analysis of data from a prospective study of patients treated with gemcitabine + docetaxel + capecitabine (GTX) in the neoadjuvant setting suggests that the emergence of a detectable g during neoadjuvant therapy may portend worse OS following surgery though sample size was small (n=45, median OS with detectable g 13.6 m v 33.1 without detectable g, p =0.35). Conclusions: We applied a tumor growth model to the data of over 2500 patients with PDAC and showed that g is inversely associated with survival in this population. Given the strong association between g and survival, g could be useful in clinical trials as an informative endpoint to expedite the assessment of novel therapies for the treatment of PDAC. Furthermore, g offers valuable patient-level data, including trends in resistance and variations in growth rate by metastatic disease site We plan to evaluate whether the emergence of g during neoadjuvant therapy should be considered a prompt to change treatment regimens.

Отдельные результаты пострегистрационного наблюдательного исследования по оценке клинической эффективности и переносимости терапии препаратами Бимикомби Антиглау ЭКО и Брим Антиглау ЭКО у пациентов с разными стадиями первичной открытоугольной глаукомы в реальной клинической практике (Brim Bimicombi Antiglau real World Ophthalmology, BRAWO)

Aim: to assess the clinical efficacy and tolerability of bimatoprost/timolol (Bimicombi Antiglau ECO) and brimonidine (Brim Antiglau ECO) in different stages of primary open-angle glaucoma (POAG) compared with prior therapy. Patients and Methods: data from 1036 patients were included in the final protocol of the multicenter combined scientific and clinical study. All patients were diagnosed with POAG or were glaucoma suspects (GS) with ocular hypertension (OHT). All patients underwent a complex eye examination. Treatment with the drugs studied should have lasted 2 to 4 months. Treatment choice resulted from the lack of efficacy, ineffectiveness, or intolerance of prior therapies. The control study was conducted once not less than a month after inclusion in the study. Results: POAG (any stage) was diagnosed in 982 patients (94.8%), and GS with OHT were 54 patients (5.2%). Changing treatment regimen (in a planned manner) prevented tachyphylaxis and tolerance to previously prescribed drugs, which was established by IOP measurements (a 20% reduction in IOP compared with prior data). If the regimen was changed for any reason (overall, 6 reasons were analyzed), three most common reasons were poor clinical efficacy (36.6%), discomfort (26.6%), and poor tolerability (23.9%). Prescription of preservative-free IOP-lowering medications (eye drops studied) for 1 month after the washout period significantly (by 19 times) reduced the number of these complaints. Preservative-free medications significantly increase the maximum satisfaction with prescribed treatment regimens (Likert score 4.61 of 5) and largely meet the expectations of doctors in terms of drug efficacy and tolerability (Likert score 4.67 of 5). Conclusion: preservative-free IOP-lowering medications (eye drops studied) are effective and well tolerated. KEYWORDS: glaucoma therapy, efficacy, tolerability, bimatoprost/timolol, brimonidine, primary open-angle glaucoma, real-world clinical practice, BRAWO. FOR CITATION: Kuroyedov A.V., Kosakovskaya M.V., Gapon'ko O.V., Gorodnichiy V.V., Lovpache D.N., Bulakh I.A. Selected results of a post- registration observational study on the clinical efficacy and tolerability of Bimicombi Antiglau ECO and Brim Antiglau ECO in different stages of primary open-angle glaucoma in real-world clinical practice (Brim Bimicombi Antiglau Real World Ophthalmology, BRAWO). Russian Journal of Clinical Ophthalmology. 2023;23(3):129–135 (in Russ.). DOI: 10.32364/2311-7729-2023-23-3-4.

Contemporary Imaging and Reporting Strategies for Head and Neck Cancer: MRI, FDG PET/MRI, NI-RADS, and Carcinoma of Unknown Primary-AJR Expert Panel Narrative Review.

CT, MRI, and FDG PET/CT play major roles in the diagnosis, staging, treatment planning, and surveillance of head and neck cancers. Nonetheless, an evolving understanding of head and neck cancer pathogenesis, advances in imaging techniques, changing treatment regimens, and a lack of standardized guidelines have led to areas of uncertainty in the imaging of head and neck cancer. This narrative review aims to address four issues in the contemporary imaging of head and neck cancer. The first issue relates to the standard and advanced sequences that should be included in MRI protocols for head and neck cancer imaging. The second issue relates to approaches to surveillance imaging after treatment of head and neck cancer, including the choice of imaging modality, the frequency of surveillance imaging, and the role of standardized reporting through the Neck Imaging Reporting and Data System. The third issue relates to the role of imaging in the setting of neck carcinoma of unknown primary. The fourth issue relates to the role of simultaneous PET/MRI in head and neck cancer evaluation. The authors of this review provide consensus opinions for each issue.

SITUATION OF DRUGS FOR TREATMENT INTESTINAL INFECTION

Objective: To survey the use of drugs to treat intestinal infection at Can Tho Children’s Hospital. Objects and methods: Cross-sectional retrospective descriptive study on 400 medical records of pediatric patients diagnosed with intestinal infection in Can Tho City Children’s Hospital in 2019. Result: There were 353 pediatric patients using rehydration and electrolytes measeurement, ORS with the highest frequency was 38.66%. The antibiotic with the highest frequency of use was the beta-lactam 3rd group. In which, Cefotaxim had the most use frequency. Single regimen of cefotaxim used the most with a frequency of 70.06%. Meanwhile, the antibiotic regimen cefotaxime combined with tobramycin was the highest in the combined regimen with 57.14%. Up to 70 cases changed the regimen due to ineffective results and 22 cases changed the regimen due to its effectiveness, reducing the amount of antibiotics. The first regimen with the highest frequency of change was the cefotaxim regimen with 33 cases. The 2nd regimens changed with the highest frequency were cefotaxim regimen and regimen of cefotaxim combined with tobramycin with 5 cases. The third change of regimen was mostly from combination antibiotic regimen to single regimen. Conclusion: Rehydration and electrolyte measures were mainly ORS. Antibiotics used mainly in the beta-lactam 3rd group, Cefotaxim had the highest frequency of use. Cefotaxim was used the most frequency in a single regimen. The antibiotic combined regimen between cefotaxime and tobramycin was the highest use in all combined regimens. Changing treatment regimen was mainly due to the ineffective effect.

Abstract PS14-06: Changes in management of breast cancer patients during first wave of COVID19, throughout the area of Kent, United Kingdom. An audit of ESMO guideline implementation

Abstract Background: The global COVID-19 pandemic has placed unprecedented burden on individual oncology patients, oncology departments, hospitals and national health systems. In order to protect individual patients from the risk of COVID-19 infection as well as improve capacity for COVID-19 patient management, a series of national and internationally agreed measures were proposed. During the first wave of infections the virulence and effect on cancer patients was not known. It is vitally important that the measures implemented to combat these risks are assessed and evaluated in order to learn best how to manage potential future waves of known and unknown viral infections.Methods: The international ESMO COVID-19 guidelines and national (NICE) guidelines were implemented across Kent, UK. All changes to treatment regimens were audited to assess what were the most frequent changes and in which patient groups could these be implemented. Data was subdivided for both early and advanced breast cancer as well as ER+, HER2+ or triple negative disease.Results: We collected full treatment history from 1,718 breast cancer patients currently receiving active oncology treatments. We were able to change treatment regimens due to COVID19 for 32.8% of patients. Of these 27.1% were early breast cancer patients compared with 43.7% were those with advanced metastatic disease. The most common changes for neoadjuvant changes were proceeding to surgery before completion of planned chemotherapy (10.2%), switch to 3 weekly Paclitaxel (10%) and chemotherapy break (8%). For adjuvant patients the most common changes included postponement of bisphosphonates (70.8%), chemotherapy break (13.5%), and curtailment to 6 months of adjuvant Trastuzumab (10.4%). For our palliative patients the most common changes included delay CDK4/6 inhibitor treatment (79.2%), postponement of bisphosphonates (24.8%), break in HER2 antibody (9.6%) and break in chemotherapy (8%).Conclusions: A large proportion of breast cancer oncology patients were deemed suitable to have a change in original planned treatment. We are fortunate to have comparatively large number of treatment options that can be customised on a patient basis to individual reduce risk of COVID-19. Further analysis is needed over time to compare the oncological outcomes of those in whom treatment was changes from the current gold standards of care. Citation Format: Simon N Rodney, Charlotte Abson, Russell Burcombe, Rema Jyothirmayi, Catherine Harper-Wynne. Changes in management of breast cancer patients during first wave of COVID19, throughout the area of Kent, United Kingdom. An audit of ESMO guideline implementation [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS14-06.

Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS): knowledge, perception, and attitude among pharmacists in Kelantan, Malaysia.

Introduction: Although pharmacists’ role in the care of human immunodeficiency virus (HIV)-infected and acquired immunodeficiency syndrome (AIDS) patients is well established, studies had reported pharmacists’ negative attitudes towards people living with HIV/AIDS (PLWHA), with negative impact on HIV management. This study aimed to explore pharmacists’ knowledge of HIV/AIDS, perception towards the changing of treatment regimens of HIV/AIDS, attitudes towards PLWHA, and to identify factors affecting the pharmacists’ attitudes towards PLWHA in the state of Kelantan, which reportedly have the third highest number of HIV/AIDS patients in Malaysia. Materials and method: A validated online 43-item questionnaire was distributed to 400 pharmacists in Kelantan. Multivariate logistic regression was performed to identify factors associated with pharmacists’ negative attitude towards PLWHA. Results: A total of 170 respondents (response rate 42%) completed the questionnaire. Respondents had knowledge on the potential causes of HIV infection [median(IQR) score=13.00(1); maximum score=14.00], and preventive measures of HIV/AIDS transmission [median(IQR) score=12.00(1); maximum score=12.00]. On decision in changing regimens, the respondents agreed on the need to change treatment regimen for HIV/AIDS when required [median(IQR) score=7.00(2); maximum score=8.00]. Up to 40.6% of respondents thought that the treatment regimen should not be switched based on cost. Two-thirds of the respondents had negative attitudes towards PLWHA (67.1%). Respondents who worked in community pharmacy reported positive attitudes towards PLWHA (Adj OR=0.125; 95%CI=0.025-0.623; p=0.011). Conclusion: Pharmacists in Kelantan had several misconceptions towards the causes of HIV/AIDS, preventive measures of HIV/AIDS transmission, and necessity in changing treatment regimen when required. Despite good disease related knowledge, most pharmacists had negative attitudes towards PLWHA, while pharmacists working in community settings presented more positive attitudes towards PLWHA.

Clarifying and Improving the Role of the Psychiatric Consultant

Clarifying and Improving the Role of the Psychiatric Consultant

Presentation of European Society of Oncology Pharmacy: the need in standartization of modern oncology / oncology pharmacy (QUAPOS)

Background. Ljubljana declaration (2006) states that the close cooperation between oncologists and oncopharmacologists is vitally important to provide an optimal medical care. Multiprofessional approach allows to increase the cost-effectiveness of treatment and to make it safer.&#x0D; Objective. To prove the importance of the multiprofessional approach and cooperation of various specialists in the oncology field.&#x0D; Materials and methods. Analysis of the literature data on this topic.&#x0D; Results and discussion. According to the questionnaires’ results, 59 % of the respondents want to receive information about drugs and their side effects from the pharmacist. It explains the importance of creation of European Society of Oncology Pharmacology (ESOP), which at the moment includes 63 countries. Key principles of ESOP are the compliance to the standards of treatment quality, continuous professional growth and multiprofessional collaboration. Tasks of ESOP include the increase of the compliance to the oral drugs for cancer treatment, the struggle with the lack of drugs in all the world and the providing safety for patients and healthcare workers, which works with cytotoxic drugs (CTD). According to the data of different authors, low adherence can be predicted by the depression and cognitive disorders, side effects of drugs, asymptomatic disease course, difficult and expensive treatment, unsatisfactory control of treatment, etc. Talking about lack of drugs, since 2000s their frequency has increased. Even the drugs, which are included in the List of the Essential Medicines, are not available in every country, that’s why doctors have to change treatment regimens, interchange drugs, decrease the doses and postpone treatment. Struggle to fight the environmental pollution by CTD is one more task of ESOP. Studies have revealed that the most polluted surfaces in hospitals include working surfaces, floors, counters, drug fridge doors. In general, such characteristics as patient-centricity, multidisciplinary and multiprofessional approach, general coordination of treatment process, defined responsibilities, strict treatment protocols, continuous education of medical stuff, and advanced information systems are the most important for high-quality medical care. ESOP also focuses on the increase of pharmacist’s influence, that’s why this organization provides specialized webinars, trainings and workshops in oncology pharmacy field.&#x0D; Conclusions. 1. High-quality of medical care in cancer needs a pharmacist involvement. 2. Key principles of the ESOP include the compliance to the standards of treatment quality, continuous professional growth and multiprofessional collaboration. 3. Tasks of ESOP include the increase of the compliance to the oral drugs for cancer treatment, the struggle with the lack of drugs in all the world and the providing safety for patients and healthcare workers.

IJU this issue

This issue deals with a wide range of clinical topics of urology, and contains one Guideline, 15 Original Articles, and three Urological Notes. The Clinical Practice Guidelines for Bladder Cancer were first published in 2009, and the first revision (2nd edition) was in 2015. Here, Matsumoto et al. (Ube, Japan) demonstrated a summary of the second revision in 2019 (3rd edition). There has been a major paradigm shift in the daily clinical practice of urology during the 4 years from the second edition to the present revision. Of note is the emergence of immune checkpoint inhibitors and the rapid dissemination of robot-assisted surgery. In this summary, clinical topics that contribute to the decision to change treatment regimens in response to such a large paradigm shift are selected and included as clinical questions. This issue also includes two interesting articles regarding bladder cancer. Weiner et al. (Chicago, USA) assessed the use of surgical resection of metastatic disease in a large national sample and its association with overall survival. They demonstrated that the use of metastasectomy for bladder cancer is low, although metastasectomy is associated with longer overall survival and in multiple subgroups. Of course, these results should be validated in future studies. As evidence supporting robot-assisted radical cystectomy with intracorporeal urinary diversion (iRARC) remained limited so far, Tan et al. (Singapore) compared the perioperative and oncological outcomes between iRARC versus open cystectomy (ORC) for bladder cancer in a contemporary Enhanced Recovery After Surgery cohort. They demonstrated that iRARC has perioperative benefits of lower estimated blood loss, with a trend toward faster bowel recovery and a shorter duration of opioid analgesia when compared with ORC. In addition, iRARC also achieved similar intermediate-term oncological and survival outcomes to ORC. Despite being the most common malignancy in men and the second leading cause of cancer-related deaths among men in the USA, the benefits of screening for prostate cancer remains more controversial than any other types of cancer screening. Leong et al. (Philadelphia, USA) examined the predictors of prostate-specific antigen (PSA) discussion with a physician and PSA testing in men aged ≥55 years. They demonstrated that significant inequalities in PSA testing and discussion exist among men in the USA, mainly driven by socioeconomic factors such as marital status, education, income, etc. Therefore, a better understanding of the socioeconomic factors influencing PSA testing/discussions can inform strategies to reduce existing gaps in care. Renal cell carcinoma is highly resistant to chemotherapy and radiation therapy, and surgical resection is the standard of care for early-stage disease. However, patients with advanced and metastatic disease have limited treatment options, and long-term survival for these patients is approximately 10%. Obeng et al. (Atlanta, USA) evaluated clear cell renal cell carcinoma-related gene mutations potentially associated with aggressive disease, sarcomatoid differentiation, or poor prognosis. Although there are pitfalls due to intratumoral heterogeneity and sampling bias, their results demonstrated that mutations in PBRM1 may be associated with metastasis and aggressive disease in clear cell renal cell carcinoma. Urolithiasis is one of the most frequently diagnosed urological diseases, and its prevalence is increasing throughout the world, including Japan. Hori et al. (Tokyo, Japan) developed a novel simple quantitative scoring system termed the T.O.HO. score consisting of three stone characteristics, (T)allness (1–5 points), (O)ccupied lesion (1–3 points), and (HO)unsfield units evaluation (1–3 points), for predicting stone-free status after a flexible ureteroscopy lithotripsy procedure by standardizing the complexity of ureteral stone characteristics. They reported that the T.O.HO. score is a useful tool for predicting stone-free status in patients who have undergone a flexible ureteroscopy lithotripsy procedure. None declared.

Lymphocyte recovery after fingolimod discontinuation in patients with MS.

ObjectiveTo investigate the dynamics of immune cells recovery after treatment discontinuation of fingolimod in real-life clinical practice, we analyzed the course of lymphocyte reconstitution and its potential influencing factors in patients with multiple sclerosis (MS).MethodsWe analyzed leukocyte, lymphocyte, and granulocyte counts of 58 patients at 3, 6, and 12 months after fingolimod cessation and the following parameters as potential risk factors for a prolonged lymphopenia up to 12 months: age; sex; Expanded Disability Status Scale, and disease duration at the time of fingolimod start; type and number of previous immunomodulatory treatments; fingolimod treatment duration; lymphocyte count at baseline before fingolimod, at fingolimod stop, and at the time of therapy switch; time interval between fingolimod cessation and new treatment initiation; type of the follow-up immunomodulatory treatment; and corticosteroid administration after fingolimod cessation.ResultsAll patients showed a drop of the lymphocyte count under fingolimod with no relevant leukopenia or neutropenia. One year after discontinuation, still 22% of the patients were lymphopenic and 54% of them did not reach 80% of the baseline lymphocyte value. Low lymphocyte counts before fingolimod start, under fingolimod, and at therapy switch, successive treatment with rituximab, and pretreatment with mitoxantrone were significantly associated with a prolonged immune cell recovery.ConclusionsProlonged lymphopenia after fingolimod cessation exists in a subgroup of patients with MS and should be considered in clinical practice, particularly when changing treatment regimens.

Clinical outcomes in hemophilia A patients undergoing tailoring of prophylaxis based on population-based pharmacokinetic dosing

IntroductionStandard prophylaxis dosing based on bodyweight may result in over- or under-dosing due to interpatient variability. Adopting individual pharmacokinetic (PK) based tailoring may improve adherence to treatment guideline, and consequently clinical outcomes. Here we report clinical observations performed across the adoption of individual PK based tailoring in a single center in Japan. MethodsAn individual PK study on sparse samples was modeled on myPKFiT or WAPPS-Hemo, depending on concentrate, and used to optimize treatment regimens. Adherence to prophylaxis and bleeding rate were calculated from patient diaries. Radiological joint scores were used to assess arthropathy, and SPSS to perform all the analyses. ResultsThirty-nine patients underwent PK profiling, and 20 required and accepted a modification of their treatment (8 increases in dose, 5 reductions in frequency, 5 switches to extended half-life (EHL)). Adherence to prophylaxis remained the same in those increasing the dose, whilst increased in all the other groups. Annualized bleeding rate (ABR) and annualized joint bleeding rate (AjBR) decreased in all the groups but reached statistical significance only in those switched to EHL and showed a larger reduction in those patients without baseline arthropathy. Longer time spent above a 1% or 5% threshold was associated with a decrease in the ABR/AjBR. ConclusionsOur study results suggest that PopPK based tailoring supported changing treatment regimen in nearly half of the patients, and may have contributed to an improvement in the adherence and a reduction in the ABR/AjBR.

WGS-based surveillance of third-generation cephalosporin-resistant Escherichia coli from bloodstream infections in Denmark.

To evaluate a genome-based surveillance of all Danish third-generation cephalosporin-resistant Escherichia coli (3GC-R Ec ) from bloodstream infections between 2014 and 2015, focusing on horizontally transferable resistance mechanisms. A collection of 552 3GC-R Ec isolates were whole-genome sequenced and characterized by using the batch uploader from the Center for Genomic Epidemiology (CGE) and automatically analysed using the CGE tools according to resistance profile, MLST, serotype and fimH subtype. Additionally, the phylogenetic relationship of the isolates was analysed by SNP analysis. The majority of the 552 isolates were ESBL producers (89%), with bla CTX-M-15 being the most prevalent (50%) gene, followed by bla CTX-M-14 (14%), bla CTX-M-27 (11%) and bla CTX-M-101 (5%). ST131 was detected in 50% of the E. coli isolates, with the remaining isolates belonging to 73 other STs, including globally disseminated STs (e.g. ST10, ST38, ST58, ST69 and ST410). Five of the bloodstream isolates were carbapenemase producers, carrying bla OXA-181 (3) and bla OXA-48 (2). Phylogenetic analysis revealed 15 possible national outbreaks during the 2 year period, one caused by a novel ST131/ bla CTX-M-101 clone, here observed for the first time in Denmark. Additionally, the analysis revealed three individual cases with possible persistence of closely related clones collected more than 13 months apart. Continuous WGS-based national surveillance of 3GC-R Ec , in combination with more detailed epidemiological information, can improve the ability to follow the population dynamics of 3GC-R Ec , thus allowing for the detection of potential outbreaks and the effects of changing treatment regimens in the future.

Effects of electronic psychiatric consultations on primary care provider perceptions of mental health care: Survey results from a randomized evaluation

BackgroundPrimary care is the main point-of-entry for identifying and treating mental health problems. This research examines the effect of a new model of supporting primary care providers (PCPs) treating mental health disorders, the electronic consultation (eConsults), a standard process for communication between PCPs and psychiatrists through an electronic health records system. MethodsA cluster-randomized evaluation of the psychiatric eConsults model, as implemented in a large integrated delivery system. Web survey data before and after the implementation of psychiatric eConsults were collected on PCPs’ perceptions of their capability and skill to deliver mental health services, and analyzed with linear regression models. ResultsAt baseline PCPs had mixed assessments of perceived support for delivering mental health services and of the availability of specialist consultations, but had relatively high perceived self-efficacy and skill for identifying, diagnosing and treating depression. PCPs in the Treatment group had statistically significant 18%, 13%, and 16% improvements in perceived support for diagnosing mental health problems, making treatment decisions, and changing treatment regimens, respectively; and 24% improved perceived ease of access to consultations for mental health, compared to the Control group. Evidence of effects on self-efficacy and perceived skill around depression was more limited. ConclusionsThe psychiatric eConsults model improved PCPs’ perceptions of support for delivering mental health care and perceptions of access to specialist consultations. ImplicationsElectronic consultations may be a promising approach to support the delivery of mental health services in primary care settings. Level of evidencePre- and post-intervention web surveys from a cluster-randomized trial.

Switching from pro re nata to treat-and-extend regimen improves visual acuity in patients with neovascular age-related macular degeneration.

To evaluate the visual outcome after transitioning from a pro re nata (PRN) intravitreal injection regimen to a treat-and-extend (TAE) regimen for patients with neovascular age-related macular degeneration (AMD). A retrospective review of patients who were switched from a PRN regimen with intravitreal injections of bevacizumab, ranibizumab or aflibercept to a TAE regimen. The best corrected visual acuity (BCVA), central retinal thickness (CRT) and type of medication used at baseline, at the time of changing treatment regimen and at the end of the study were analysed. Twenty-one eyes of 21 patients met the inclusion criteria. Prior to the switch, the patients received a mean of 13.8 injections (median, 10; range, 3-39 injections) with the PRN regimen for 44months (range, 3-100months), which improved the visual acuity in five patients (24%). After a mean of 6.1 injections (median, 5; range, 3-14 injections) with the TAE regimen over 8months (range, 2-16months), the visual acuity improved in 12 patients (57%). The improvement in visual acuity during treatment with the TAE regimen was statistically significant (p=0.005). The proportion of patients with a visual acuity of 0.2 or better was significantly higher after treatment with the TAE regimen than after treatment with the PRN regimen (p=0.048). No significant differences in CRT were found between the two treatment regimens. Even after prolonged treatment and a high number of intravitreal injections, switching AMD patients from a PRN regimen to a strict TAE regimen significantly improves visual acuity.

New Direct Acting Antiviral Agents for the Treatment of Hepatitis C: 2016 and Beyond.

Hepatitis C is one of the commonest public health problems with 130 million people infected worldwide and the burden is increasing. Previously, Interferon along with Ribavirin was the mainstay of treatment but it was associated with toxic side effects. An all-oral regimen with higher rates of sustained viral response (SVR), minimal side effects and no restriction for liver fibrosis staging, was long awaited. Several all-oral interferon-free direct acting antiviral agents (DAAs) have now been approved by FDAfor different genotypes of HCV. These include Sofosbuvir, Ledipasvir, Daclatasvir, Simeprevir, Dasabuvir, Ombitasvir, Paritaprevir and Ritonavir. These agents are also available in different combinations commercially under various trade names. Anumber of studies have proved their efficacy and the AASLD and EASLguidelines recommend several options for each genotype in different categories including treatment naïve, relapsers, failure, compensated and decompensated cirrhosis. The purpose of this article is to review the persistently changing treatment regimens for hepatitis C and to simplify the dynamicity of the subject and selection of appropriate regimen for these patients.

Use of ultrasound in treatment decisions for patients with rheumatoid arthritis: an observational study in Italy.

In rheumatoid arthritis (RA), treatment response is generally assessed using standard clinical disease activity measures. However, ultrasound has become increasingly popular among rheumatologists to monitor disease activity and response. The purpose of this analysis of ECOgraphic evaluation for STaging ARthritis (ECOSTAR) study data was to determine how ultrasound affects clinicians' decisions about changing treatment in RA. ECOSTAR was an observational, cohort study conducted between March 2010 and December 2012 at nine clinical centers in Italy in RA patients being considered for treatment change. After clinical evaluation of each patient, patients underwent diagnostic ultrasound (US) investigations and each patient was given a total echography score using a combination of scores for joint effusion, synovial hypertrophy, and power Doppler. The US results were provided to the clinicians and the influence of US on the clinicians' treatment choices were recorded. Ninety-five patients screened for study inclusion had confirmed RA (mean age 53.9years; mean disease duration 8.9years). Therapy changes were made by clinicians according to the hand and wrist joint US scores: score 0 appeared to have no influence on clinicians' decision to modify treatment, scores >0-3 were associated with a numerically higher estimated probability of not changing therapy than changing therapy, and scores >3 had a greater influence on the clinician to modify therapy and an increased probability of the clinician changing therapy versus not changing therapy. Ultrasonography scores appear to influence treatment decisions in patients with RA, with clinicians appearing less likely to alter treatment regimens in patients with low ultrasound scores and more likely to change treatment regimens when higher scores are obtained. Further research is warranted.

Single-Molecule Sequencing Reveals Complex Genome Variation of Hepatitis B Virus during 15 Years of Chronic Infection following Liver Transplantation.

Chronic hepatitis B (CHB) is prevalent worldwide. The infectious agent, hepatitis B virus (HBV), replicates via an RNA intermediate and is error prone, leading to the rapid generation of closely related but not identical viral variants, including those that can escape host immune responses and antiviral treatments. The complexity of CHB can be further enhanced by the presence of HBV variants with large deletions in the genome generated via splicing (spHBV variants). Although spHBV variants are incapable of autonomous replication, their replication is rescued by wild-type HBV. spHBV variants have been shown to enhance wild-type virus replication, and their prevalence increases with liver disease progression. Single-molecule deep sequencing was performed on whole HBV genomes extracted from samples, including the liver explant, longitudinally collected from a subject with CHB over a 15-year period after liver transplantation. By employing novel bioinformatics methods, this analysis showed that the dynamics of the viral population across a period of changing treatment regimens was complex. The spHBV variants detected in the liver explant remained present posttransplantation, and a highly diverse novel spHBV population as well as variants with multiple deletions in the pre-S genes emerged. The identification of novel mutations outside the HBV reverse transcriptase gene that co-occurred with known drug resistance-associated mutations highlights the relevance of using full-genome deep sequencing and supports the hypothesis that drug resistance involves interactions across the full length of the HBV genome. Single-molecule sequencing allowed the characterization, in unprecedented detail, of the evolution of HBV populations and offered unique insights into the dynamics of defective and spHBV variants following liver transplantation and complex treatment regimens. This analysis also showed the rapid adaptation of HBV populations to treatment regimens with evolving drug resistance phenotypes and evidence of purifying selection across the whole genome. Finally, the new open-source bioinformatics tools with the capacity to easily identify potential spliced variants from deep sequencing data are freely available.

Inhaled antibiotics for the treatment of chronic Pseudomonas aeruginosa infection in cystic fibrosis patients: challenges to treatment adherence and strategies to improve outcomes.

BackgroundInhaled antibiotics (ABs) are recommended for use in the therapy of chronic Pseudomonas aeruginosa infection in patients with cystic fibrosis (CF). The aim of this systematic literature review was to identify level of adherence to inhaled ABs and to determine predictors and consequences of nonadherence in CF.MethodsA systematic literature search of English-language articles was conducted in April 2015 using Medline and Embase. No publication date limit was applied. The literature screening was conducted by two independent reviewers. All of the included studies were assessed for quality.ResultsThe search yielded 193 publications, of which ten met the inclusion criteria and underwent data extraction. Seven studies focused on inhaled tobramycin, one on inhaled colistimethate, one on inhaled levofloxacin, and one on inhaled aztreonam lysine. Medication adherence to inhaled ABs was analyzed by pharmacy refill history, daily phone diary, parent and child self-reports, vials counting, or electronic monitoring. In randomized controlled trials (n=3), proportion of adherent patients (>75%–80% of required doses taken) ranged from 86% to 97%; in prospective cohort studies (n=3), adherence rates ranged between 36% and 92%, and in retrospective studies (n=4) it ranged between 60% and 70%. The adherence to inhaled ABs in CF was found to be associated with the complexity of treatment, time of drug administration, age of patients, treatment burden (adverse events, taste), and patient satisfaction.ConclusionThe high diversity of adherence data was because of the different study designs (randomized controlled trials vs real-world studies) and the lack of a commonly accepted consensus on the definition of adherence in the reviewed articles. Routine adherence monitoring during CF care, discussing the possible reasons of suboptimal adherence with the patient, and changing treatment regimens on the basis of patient burden can individualize CF therapy for patients and may improve the level of adherence.