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1.
Int J Gynecol Pathol ; 42(4): 353-363, 2023 Jul 01.
Article in English | MEDLINE | ID: mdl-36731023

ABSTRACT

Incorporation of molecular classification into clinicopathologic assessment of endometrial carcinoma (EC) improves risk stratification. Four EC molecular subtypes, as identified by The Cancer Genome Atlas, can be diagnosed through a validated algorithm Pro active M olecular R is k Classifier for E ndometrial Cancer (ProMisE) using p53 and mismatch repair (MMR) protein immunohistochemistry (IHC), and DNA polymerase epsilon ( POLE) mutational testing. Cost and access are major barriers to universal testing, particularly POLE analysis. We assessed a selective ProMisE algorithm (ProMisE-S): p53 and MMR IHC on all EC's with POLE testing restricted to those with abnormal MMR or p53 IHC (to identify POLEmut EC with secondary abnormalities in MMR and/or p53) and those with high-grade or non-endometrioid morphology, stage >IA or presence of lymphovascular space invasion (so as to avoid testing on the lowest risk tumors). We retrospectively compared the known ProMisE molecular classification to ProMisE-S in 912 EC. We defined a group of "very low-risk" EC (G1/G2, endometrioid, MMR-proficient, p53 wild-type, stage IA, no lymphovascular space invasion) in whom POLE testing will not impact on patient care; using ProMisE-S, POLE testing would not be required in 55% of biopsies and 38% of all EC's, after evaluation of the hysterectomy specimen, in a population-based cohort. "Very low-risk" endometrioid EC with unknown POLE status showed excellent clinical outcomes. Fifteen of 166 (9%) of all p53abn EC showed G1/G2 endometrioid morphology, supporting the potential value of universal p53 IHC. The addition of molecular testing changed the risk category in 89/896 (10%) EC's. In routine practice, POLE testing could be further restricted to only those patients in whom this would alter adjuvant therapy recommendations.


Subject(s)
Carcinoma, Endometrioid , Endometrial Neoplasms , Tumor Suppressor Protein p53 , Endometrial Neoplasms/genetics , Carcinoma, Endometrioid/genetics , Humans , Female , Mutation , Tumor Suppressor Protein p53/genetics , Retrospective Studies
2.
Ann Pharmacother ; 57(3): 341-347, 2023 03.
Article in English | MEDLINE | ID: mdl-35730211

ABSTRACT

OBJECTIVE: To review the pharmacokinetics, efficacy, and safety of recently approved calcipotriene and betamethasone dipropionate (C-BD) cream. DATA SOURCES: A literature review was conducted using MEDLINE (PubMed) and ClinicalTrials.gov from 2002 to mid-May 2022. STUDY SELECTION AND DATA EXTRACTION: Articles in English discussing the use of C-BD cream in the treatment of psoriasis were included. DATA SYNTHESIS: In 2 phase I trials, there was no phototoxic or photoallergic skin reaction at irradiated C-BD cream sites at baseline, 24 hours, 48 hours, and 72 hours postirradiation. In 2 phase III trials, after 8 weeks of treatment, more subjects treated with C-BD cream achieved Physician's Global Assessment treatment success (37.4%), compared to C-BD topical suspension (TS) (22.8%, P < 0.0001) and vehicle (3.7%, P < 0.0001). More subjects had greater mean percentage decline in Modified Psoriasis Area Severity Index (Trial 1: 52.9% and Trial 2: 64.6%), when compared to C-BD TS (Trial 1: 51.3%, P < 0.0001 and Trial 2: 56.4%, P < 0.0001) and vehicle (Trial 1: 22.9%, P < 0.0001 and Trial 2: 20.0%, P < 0.0001). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Psoriasis has a multifactorial pathogenesis and topical treatments are considered first line. Poor adherence is a major hurdle in management; the combination of 2 separate first-line drugs may address this by decreasing the complexity of treatment regimens. A cream formulation can be preferred, and C-BD is now Food and Drug Administration (FDA) approved as one. CONCLUSIONS: Newly FDA-approved C-BD cream with novel polyaphron dispersion (PAD) technology provides a safe efficacious combination therapy for mild-to-moderate psoriasis which may be preferred by some patients.


Subject(s)
Dermatologic Agents , Psoriasis , Humans , Dermatologic Agents/adverse effects , Drug Combinations , Psoriasis/drug therapy , Betamethasone/adverse effects , Treatment Outcome
3.
Ann Pharmacother ; 57(3): 333-340, 2023 03.
Article in English | MEDLINE | ID: mdl-35730479

ABSTRACT

OBJECTIVE: To review pharmacokinetics, efficacy, and safety of tralokinumab in treatment of atopic dermatitis (AD). DATA SOURCES: Literature review was conducted using MEDLINE (PubMed), EMBASE, and ClinicalTrials.gov for articles published between January 2010 and May 2022. STUDY SELECTION AND DATA EXTRACTION: Articles in English discussing tralokinumab in AD were included. DATA SYNTHESIS: In one phase 2 trial, more subjects treated with tralokinumab 150 and 300 mg achieved an Investigator's Global Assessment (IGA) of 0/1 with minimum ≥2 point IGA reduction (23%), versus placebo (11.8%, P = 0.10). During 2 phase 3 trials, more subjects treated with tralokinumab achieved IGA success (ECZTRA 1: 15.8% and ECZTRA 2: 22.2%), versus placebo (7.1% and 10.9%, respectively; P = 0.002 and P < 0.001). During one phase 3 trial, in conjunction with topical corticosteroids (TCS), more subjects treated with tralokinumab 300 mg achieved IGA success (ECZTRA 3: 38.9%), versus placebo (26.2%, P = 0.015). During another phase 3 trial in subjects with resistance or contraindication to oral cyclosporine, more subjects treated with tralokinumab 300 mg achieved an Eczema Area Severity Index 75 (64.2%), versus placebo (50.5%, P = 0.018). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Tralokinumab is efficacious for moderate-to-severe AD, as monotherapy, in conjunction with TCS, and resistance or contraindication to cyclosporine. Although IL-4 and IL-13 are both implicated in AD's pathogenesis, IL-13 is overexpressed, and head-to-head trials are needed to assess efficacy of tralokinumab, versus dupilumab. Compared with upadacitinib and abrocitinib, tralokinumab is not associated with black-box warnings. CONCLUSIONS: Tralokinumab is an efficacious and safe systemic treatment for moderate-to-severe AD.


Subject(s)
Dermatitis, Atopic , Dermatologic Agents , Humans , Dermatitis, Atopic/drug therapy , Dermatitis, Atopic/complications , Dermatitis, Atopic/pathology , Interleukin-13/therapeutic use , Treatment Outcome , Double-Blind Method , Severity of Illness Index , Glucocorticoids/therapeutic use , Cyclosporine/therapeutic use , Dermatologic Agents/therapeutic use , Immunoglobulin A/therapeutic use
4.
Int J Gynecol Cancer ; 33(5): 683-691, 2023 05 01.
Article in English | MEDLINE | ID: mdl-36963801

ABSTRACT

OBJECTIVE: The use of chemoradiation in patients with stage IVB cancer of the cervix was evaluated to determine if definitive treatment offers benefit. METHODS: A database of 546 patients with cancer of the cervix treated between January 2005 and May 2021 at a tertiary academic medical center was reviewed retrospectively to identify patients with stage IVB disease. Log rank test, regression analysis, and the Kaplan-Meier method were used to identify and compare variables and estimate progression free survival and overall survival. RESULTS: Thirty-three patients with stage IVB cervical cancer were identified. Median age was 53 years (range 28-78). Pathology subtypes were squamous cell (n=22, 67%), adenocarcinoma (n=8, 24%), and clear cell (n=3, 9%). Metastases were classified as lymphatic (n=14, 42%) or hematogenous (n=19, 58%). Following treatment to all sites with chemoradiotherapy and selected use of surgery (n=23), six patients (26%, lymphatic n=4, hematogenous n=2) remained disease free for a median duration of 4 years (range 3-17 years). Recurrences in the remaining patients were distant (n=13) or local (n=4). All patients in the chemotherapy group (n=10, 100%) progressed. Kaplan-Meier analysis showed that median progression free survival was longer for patients treated at all disease sites than for patients treated with chemotherapy alone (19 vs 11 months, p=0.01). However, this was not the case for overall survival (49 vs 33 months, p=0.15). Patients with metastases limited to lymph nodes also had longer median progression free survival (22 vs 11 months, p=0.04) but not overall survival (p=0.68). CONCLUSIONS: Patients with stage IVB cancer of the cervix may benefit from treatment to all sites of disease, if feasible and safe, as demonstrated by improved progression free survival.


Subject(s)
Adenocarcinoma , Uterine Cervical Neoplasms , Female , Humans , Adult , Middle Aged , Aged , Uterine Cervical Neoplasms/pathology , Retrospective Studies , Neoplasm Staging , Adenocarcinoma/pathology , Lymph Nodes/pathology
5.
Int J Gynecol Cancer ; 33(7): 1023-1043, 2023 07 03.
Article in English | MEDLINE | ID: mdl-37369376

ABSTRACT

BACKGROUND: As part of its mission to improve the quality of care for women with gynecological cancers across Europe, the European Society of Gynaecological Oncology (ESGO) first published in 2017 evidence-based guidelines for the management of patients with vulvar cancer. OBJECTIVE: To update the ESGO guidelines based on the new evidence addressing the management of vulvar cancer and to cover new topics in order to provide comprehensive guidelines on all relevant issues of diagnosis and treatment of vulvar cancer. METHODS: The ESGO Council nominated an international development group comprised of practicing clinicians who provide care to vulvar cancer patients and have demonstrated leadership through their expertize in clinical care and research, national and international engagement and profile as well as dedication to the topics addressed to serve on the expert panel (18 experts across Europe). To ensure that the statements were evidence-based, new data identified from a systematic search were reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the international development group. Prior to publication, the guidelines were reviewed by 206 international practitioners in cancer care delivery and patient representatives. RESULTS: The updated guidelines cover comprehensively diagnosis and referral, staging, pathology, pre-operative investigations, surgical management (local treatment, groin treatment, sentinel lymph node procedure, reconstructive surgery), (chemo)radiotherapy, systemic treatment, treatment of recurrent disease (vulvar, inguinal, pelvic, and distant recurrences), and follow-up. Management algorithms are also defined.


Subject(s)
Gynecology , Plastic Surgery Procedures , Vulvar Neoplasms , Female , Humans , Europe , Gynecology/methods , Vulvar Neoplasms/diagnosis , Vulvar Neoplasms/therapy , Vulvar Neoplasms/pathology
6.
Rev Cardiovasc Med ; 23(12): 412, 2022 Dec.
Article in English | MEDLINE | ID: mdl-39076659

ABSTRACT

Background: Recent studies have shown that epicardial adipose tissue (EAT) is an independent atrial fibrillation (AF) prognostic marker and has influence on the myocardial function. In computed tomography (CT), EAT volume (EATv) and density (EATd) are parameters that are often used to quantify EAT. While increased EATv has been found to correlate with the prevalence and the recurrence of AF after ablation therapy, higher EATd correlates with inflammation due to arrest of lipid maturation and with high risk of plaque presence and plaque progression. Automation of the quantification task diminishes the variability in readings introduced by different observers in manual quantification and results in high reproducibility of studies and less time-consuming analysis. Our objective is to develop a fully automated quantification of EATv and EATd using a deep learning (DL) framework. Methods: We proposed a framework that consists of image classification and segmentation DL models and performs the task of selecting images with EAT from all the CT images acquired for a patient, and the task of segmenting the EAT from the output images of the preceding task. EATv and EATd are estimated using the segmentation masks to define the region of interest. For our experiments, a 300-patient dataset was divided into two subsets, each consisting of 150 patients: Dataset 1 (41,979 CT slices) for training the DL models, and Dataset 2 (36,428 CT slices) for evaluating the quantification of EATv and EATd. Results: The classification model achieved accuracies of 98% for precision, recall and F 1 scores, and the segmentation model achieved accuracies in terms of mean ( ± std.) and median dice similarity coefficient scores of 0.844 ( ± 0.19) and 0.84, respectively. Using the evaluation set (Dataset 2), our approach resulted in a Pearson correlation coefficient of 0.971 ( R 2 = 0.943) between the label and predicted EATv, and the correlation coefficient of 0.972 ( R 2 = 0.945) between the label and predicted EATd. Conclusions: We proposed a framework that provides a fast and robust strategy for accurate EAT segmentation, and volume (EATv) and attenuation (EATd) quantification tasks. The framework will be useful to clinicians and other practitioners for carrying out reproducible EAT quantification at patient level or for large cohorts and high-throughput projects.

7.
J Nucl Cardiol ; 29(2): 440-446, 2022 04.
Article in English | MEDLINE | ID: mdl-32918247

ABSTRACT

AIM: The purpose of this study was to determine the inter- and intra-observer variability in 99mtechnetium-pyrophosphate (99mTc-PYP) scan interpretation for diagnosis of transthyretin cardiac amyloidosis (ATTR). METHODS AND RESULTS: Our study cohort comprised 100 consecutive subjects referred for 99mTc-PYP imaging based on clinical suspicion of ATTR cardiac amyloidosis. Myocardial 99mTc-PYP uptake was assessed by both visual (comparison of myocardial to rib uptake) and semi-quantitative (heart-to-contralateral lung uptake ratio, H:CL) methods. Twenty scans were analyzed twice, at least 48 hours apart, by each of two independent observers. Patients with visual scores of ≥ 2 on planar imaging as well as myocardial uptake on SPECT/CT were classified as ATTR positive. Diagnosis of ATTR by visual 99mTc-PYP grade was perfectly reproducible [concordance: positive and negative scans 100% (53/53 and 47/47, respectively). Both inter- and intra-observer correlations for H:CL ratio (r2 = 0.90, 0.99 (Observer 1) and 0.98 (Observer 2), respectively) and repeatability values on Bland-Altman plots were excellent. The coefficient of variation (%) for Observers 1 and 2 was 3.21 (2.14 to 4.29) and 7.49 (4.95 to 10.09), respectively. In addition, there was 100% concordance in positive and negative scan interpretation by visual grading between novice CV imagers (< 3 years' experience) and an experienced CV imager (10 years' experience). CONCLUSIONS: This study showed excellent inter-observer reproducibility and intra-observer repeatability of 99mTc-PYP visual scan interpretation and H:CL ratio for diagnosis of cardiac ATTR amyloidosis. Cardiac ATTR amyloidosis can be diagnosed reliably using 99mTc-PYP SPECT/CT by novice and experienced CV imagers.


Subject(s)
Amyloidosis , Cardiomyopathies , Diphosphates , Humans , Prealbumin , Radiopharmaceuticals , Reproducibility of Results , Technetium Tc 99m Pyrophosphate
8.
Int J Gynecol Cancer ; 32(1): 9-14, 2022 01.
Article in English | MEDLINE | ID: mdl-34795019

ABSTRACT

During the COVID-19 pandemic, pressures on clinical services required adaptation to how care was prioritised and delivered for women with gynecological cancer. This document discusses potential 'salvage' measures when treatment has deviated from the usual standard of care. The British Gynaecological Cancer Society convened a multidisciplinary working group to develop recommendations for the onward management and follow-up of women with gynecological cancer who have been impacted by a change in treatment during the pandemic. These recommendations are presented for each tumor type and for healthcare systems, and the impact on gynecological services are discussed. It will be important that patient concerns about the impact of COVID-19 on their cancer pathway are acknowledged and addressed for their ongoing care.


Subject(s)
COVID-19/epidemiology , Genital Neoplasms, Female/epidemiology , Genital Neoplasms, Female/therapy , Female , Gynecology , Humans , Pandemics , SARS-CoV-2/isolation & purification , United Kingdom/epidemiology
9.
Prev Med ; 147: 106460, 2021 06.
Article in English | MEDLINE | ID: mdl-33609616

ABSTRACT

Vulnerable populations such as the uninsured, unemployed, and unhoused face significant morbidity and mortality from influenza but are less likely to receive the annual vaccine and have limited access to medical care. We describe an interprofessional, student-run vaccine outreach program (VOP) in Davidson County, Tennessee that lowers barriers to vaccination through free vaccination events in nontraditional community locations. We provide this framework as a model to expand novel, seasonal, or outbreak-oriented vaccine outreach to resource-poor populations. Demographic data were collected from the patients who received an influenza vaccine between 2015 and 2019 through an optional survey to determine whether these events were reaching unhoused, uninsured, and/or unemployed individuals. Of 1,803 patients, 1,733 (96.1%) completed at least one field of the demographic form. Overall, 481 (27.8%) were individuals without homes or living in temporary housing and 673 (38.8%) were unemployed. Most patients, 1,109 (64.0%), did not have health insurance at any point during the prior two years. With the addition of a nurse practitioner student to VOP leadership, the 2018-2019 VOP reached the most unhoused or temporarily-housed (228, 32.3%), unemployed (313, 18.5%), and disabled (60, 8.5%) patients. The VOP can be adapted to meet community needs, funding, and volunteer interest. The VOP model may be applicable to a SARS-CoV-2 vaccine, especially since the economic impact of COVID-19 has increased unemployment rates and housing instability. Healthcare students serve as an eager, underutilized resource who can be leveraged to disseminate vaccines to individuals with limited access to care.


Subject(s)
Community-Institutional Relations , Delivery of Health Care/methods , Influenza Vaccines/administration & dosage , Influenza, Human/prevention & control , Students/statistics & numerical data , Vaccination/methods , COVID-19 , COVID-19 Vaccines , Female , Humans , Male , SARS-CoV-2 , Tennessee , Workforce
10.
Int J Gynecol Cancer ; 31(1): 12-39, 2021 01.
Article in English | MEDLINE | ID: mdl-33397713

ABSTRACT

A European consensus conference on endometrial carcinoma was held in 2014 to produce multi-disciplinary evidence-based guidelines on selected questions. Given the large body of literature on the management of endometrial carcinoma published since 2014, the European Society of Gynaecological Oncology (ESGO), the European SocieTy for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) jointly decided to update these evidence-based guidelines and to cover new topics in order to improve the quality of care for women with endometrial carcinoma across Europe and worldwide.


Subject(s)
Endometrial Neoplasms/diagnosis , Endometrial Neoplasms/therapy , Genital Neoplasms, Female/diagnosis , Genital Neoplasms, Female/therapy , Medical Oncology/standards , Endometrial Neoplasms/pathology , Europe , Female , Humans , Preoperative Care , Risk Factors
11.
Int J Hyperthermia ; 38(1): 623-632, 2021.
Article in English | MEDLINE | ID: mdl-33882792

ABSTRACT

OBJECTIVE: To document longitudinal symptom, quality-of-life and imaging response in patients with recurrent gynecological tumors treated with magnetic resonance guided high intensity focused ultrasound (MRgHIFU), and compare changes in patients with intra- versus extra-pelvic lesions. METHODS: Eleven symptomatic patients with painful recurrent gynecological tumors were treated with MRgHIFU (Profound Sonalleve) in a prospective single center study (NCT02714621). Pain scores, analgesic intake and quality-of-life metrics, whole tumor volume, and perfused tumor volume from Gadolinium-enhanced T1W imaging documented before and up to 90 days after treatment were compared between patients with intra- and extra-pelvic tumors. RESULTS: Two of five patients with intra-pelvic and three of six patients with extra-pelvic tumors were classified as responders (>2 point reduction in NRS pain score without analgesia increase or a > 25% reduction in analgesic use). Cohort reductions in worst pain scores were not significant for either group. Emotional functioning for the whole cohort improved, although physical functioning did not. Ablative thermal temperatures were achieved in three patients with extra-pelvic tumors, but in none whose tumors were intra-pelvic. Pain response did not correlate with thermal dose. Tumor volume increased by 18% immediately post-treatment in the extra-pelvic but not in the intra-pelvic group. Ratio of perfused to whole lesion volume decreased by >20% by day 30 in extra-pelvic, but not intra-pelvic tumors although at day 30 both extra-pelvic and intra-pelvic tumors increased in volume. CONCLUSION: MRgHIFU treatments can be delivered safely to patients with recurrent gynecological tumors. Extra-pelvic tumors responded better than intra-pelvic tumors and showed immediate swelling and reduction in perfused volume by day 30.


Subject(s)
Genital Neoplasms, Female , High-Intensity Focused Ultrasound Ablation , Feasibility Studies , Female , Genital Neoplasms, Female/diagnostic imaging , Humans , Magnetic Resonance Imaging , Prospective Studies , Quality of Life
12.
Support Care Cancer ; 28(10): 4881-4889, 2020 Oct.
Article in English | MEDLINE | ID: mdl-31997018

ABSTRACT

BACKGROUND AND AIM: Long-term changes in gastrointestinal function impacting quality of life after treatment for cancer are common. Peer reviewed guidance to investigate and manage GI dysfunction following cancer treatment has been published. This study reviewed gastrointestinal symptoms of women previously treated for gynaecological cancer and considered whether suggested algorithms could be amended to optimise management for this cohort. METHODS: Demographic and clinical data recorded for patients attending a specialist consequences of cancer treatment gastroenterology service prospectively are reported using median and range. The Wilcoxon signed rank test analysed changes in symptoms between initial assessment to discharge from the service. RESULTS: Between April 2013 and March 2016, 220 women, with a median age of 57 years (range 24-83 years), treated for gynaecological cancer (cervical (50%)), endometrial (28%), ovarian (15%), vaginal or vulval (7%) attended. Twelve gastrointestinal symptoms were statistically significantly reduced by time of discharge from the specialist gastroenterology clinic including bowel frequency ≥ 4/day (88%), type 6 or 7 stool consistency (36%), urgency (31%) and incontinence (21%). General quality of life improved from a median score of 4 at first assessment to a median of 6 at discharge (p < 0.001). A median of four (range, 1-9) diagnoses were made. CONCLUSION: Women with gastrointestinal symptoms after cancer treatment benefit from a systematic management approach. After excluding disease recurrence, a proposed investigational algorithm and the oncology team includes FBC, U&Es, LFTs, thyroid function test, vitamin B12, vitamin D, a hydrogen methane breath test and a SeHCAT scan. If rectal bleeding is present, iron studies, flexible sigmoidoscopy or colonoscopy should be performed. Patients with normal investigations or symptoms not responding to treatment require gastroenterology input.


Subject(s)
Gastrointestinal Diseases/etiology , Gastrointestinal Diseases/therapy , Genital Neoplasms, Female/therapy , Adult , Aged , Aged, 80 and over , Algorithms , Cohort Studies , Combined Modality Therapy , Female , Humans , Middle Aged , Quality of Life , Young Adult
14.
Med Teach ; 41(5): 505-509, 2019 05.
Article in English | MEDLINE | ID: mdl-29378455

ABSTRACT

Medical students employ various study strategies to master large amounts of information during their medical education. Digital flashcards are an interactive, self-directed study stool that may improve knowledge retention by combining the principles of active recall and spaced-repetition. They may be studied during and beyond undergraduate medical education. However, making flashcards can be an onerous task. In this article, we describe twelve tips on how to establish and maintain a collaborative digital flashcard project based on the undergraduate medical curriculum.


Subject(s)
Cooperative Behavior , Education, Medical, Undergraduate/methods , Humans , Interpersonal Relations , Learning , Software , Students, Medical
15.
Epilepsia ; 59(12): 2305-2317, 2018 12.
Article in English | MEDLINE | ID: mdl-30374948

ABSTRACT

OBJECTIVE: The European Union-funded E-PILEPSY project was launched to develop guidelines and recommendations for epilepsy surgery. In this systematic review, we aimed to assess the diagnostic accuracy of functional magnetic resonance imaging (fMRI), Wada test, magnetoencephalography (MEG), and functional transcranial Doppler sonography (fTCD) for memory and language decline after surgery. METHODS: The literature search was conducted using PubMed, Embase, and CENTRAL. The diagnostic accuracy was expressed in terms of sensitivity and specificity for postoperative language or memory decline, as determined by pre- and postoperative neuropsychological assessments. If two or more estimates of sensitivity or specificity were extracted from a study, two meta-analyses were conducted, using the maximum ("best case") and the minimum ("worst case") of the extracted estimates, respectively. RESULTS: Twenty-eight papers were eligible for data extraction and further analysis. All tests for heterogeneity were highly significant, indicating large between-study variability (P < 0.001). For memory outcomes, meta-analyses were conducted for Wada tests (n = 17) using both memory and language laterality quotients. In the best case, meta-analyses yielded a sensitivity estimate of 0.79 (95% confidence interval [CI] = 0.67-0.92) and a specificity estimate of 0.65 (95% CI = 0.47-0.83). For the worst case, meta-analyses yielded a sensitivity estimate of 0.65 (95% CI = 0.48-0.82) and a specificity estimate of 0.46 (95% CI = 0.28-0.65). The overall quality of evidence, which was assessed using Grading of Recommendations Assessment, Development, and Evaluation methodology, was rated as very low. Meta-analyses concerning diagnostic accuracy of fMRI, fTCD, and MEG were not feasible due to small numbers of studies (fMRI, n = 4; fTCD, n = 1; MEG, n = 0). This also applied to studies concerning language outcomes (Wada test, n = 6; fMRI, n = 2; fTCD, n = 1; MEG, n = 0). SIGNIFICANCE: Meta-analyses could only be conducted in a few subgroups for the Wada test with low-quality evidence. Thus, more evidence from high-quality studies and improved data reporting are required. Moreover, the large between-study heterogeneity underlines the necessity for more homogeneous and thus comparable studies in future research.


Subject(s)
Epilepsy/surgery , Language Disorders/etiology , Language Tests , Magnetic Resonance Imaging/methods , Magnetoencephalography/methods , Memory Disorders/etiology , Postoperative Complications/psychology , Ultrasonography, Doppler, Transcranial/methods , Amobarbital , Humans , Sensitivity and Specificity
16.
Curr Opin Oncol ; 29(5): 343-350, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28697002

ABSTRACT

PURPOSE OF REVIEW: Re-irradiation historically has been associated with unacceptable toxicity and limited benefit. Recent advances in radiotherapy can change the treatment paradigm to provide new salvage treatments for recurrences of cervical and endometrial cancer. RECENT FINDINGS: Image-guided brachytherapy is an effective method for salvaging central pelvic recurrence, although it has resulted in 20-25% severe late toxicity. Pelvic sidewall disease is not accessible to brachytherapy, so a combined modality approach with radical surgery and intraoperative radiotherapy is an alternative approach. Stereotactic body radiotherapy (SBRT) now provides the option of radical re-irradiation with local control rates of 50-80% and a low incidence of severe late complications. SUMMARY: Initial outcomes using SBRT and image-guided brachytherapy for re-irradiation of gynaecological cancer are encouraging. There has been good local control and acceptable toxicity. Further, large-scale studies are required to define optimal target doses and OAR limits.


Subject(s)
Endometrial Neoplasms/radiotherapy , Uterine Cervical Neoplasms/radiotherapy , Brachytherapy/methods , Endometrial Neoplasms/diagnostic imaging , Female , Humans , Radiosurgery/methods , Radiotherapy Planning, Computer-Assisted , Uterine Cervical Neoplasms/diagnostic imaging
17.
Epilepsia ; 58(11): 1939-1945, 2017 11.
Article in English | MEDLINE | ID: mdl-28960284

ABSTRACT

OBJECTIVE: Studies using relative measures, such as standardized mortality ratios, have shown that patients with epilepsy have an increased mortality. Reports on more direct and absolute measure such as life expectancy are sparse. We report potential years lost and how life expectancy has changed over 40 years in a cohort of patients with newly diagnosed epilepsy. METHODS: We analyzed life expectancy in a cohort of adult patients diagnosed with definite epilepsy between 1970 and 2010. Those with brain tumor as cause of epilepsy were excluded. By retrospective probabilistic record linkage, living or death status was derived from the national death registry. We estimated life expectancy by a Weibull regression model using gender, age at diagnosis, epilepsy etiology, and year of diagnosis as covariates at time of epilepsy diagnosis, and 5, 10, 15, and 20 years after diagnosis. Results were compared to the general population, and 95% confidence intervals are given. RESULTS: There were 249 deaths (105 women, age at death 19.0-104.0 years) in 1,112 patients (11,978.4 person-years, 474 women, 638 men). A substantial decrease in life expectancy was observed for only a few subgroups, strongly depending on epilepsy etiology and time of diagnosis: time of life lost was highest in patients with symptomatic epilepsy diagnosed between 1970 and 1980; the impact declined with increasing time from diagnosis. Over half of the analyzed subgroups did not differ significantly from the general population. This effect was reversed in the later decades, and life expectancy was prolonged in some subgroups, reaching a maximum in those with newly diagnosed idiopathic and cryptogenic epilepsy between 2001 and 2010. SIGNIFICANCE: Life expectancy is reduced in symptomatic epilepsies. However, in other subgroups, a prolonged life expectancy was found, which has not been reported previously. Reasons may be manifold and call for further study.


Subject(s)
Epilepsy/diagnosis , Epilepsy/mortality , Life Expectancy/trends , Adult , Aged , Aged, 80 and over , Cohort Studies , Female , Follow-Up Studies , Humans , Male , Middle Aged , Young Adult
18.
Int J Gynecol Cancer ; 27(7): 1550-1559, 2017 09.
Article in English | MEDLINE | ID: mdl-28590950

ABSTRACT

BACKGROUND AND AIM: Worldwide, 1,470,900 women are diagnosed yearly with a gynecological malignancy (21,000 in the UK). Some patients treated with pelvic radiotherapy develop chronic changes in their bowel function. This systematic review summarizes current research on the impact of cancer treatment on the gut and vaginal microbiome in women with a gynecological malignancy. METHODS: The Preferred reporting Items for Systematic Reviews and Meta-analyses guidelines for systematic reviews were used to ensure transparent and complete reporting. Quantitative studies exploring the gut or vaginal microbiome in this patient cohort were included. Animal studies were excluded. There were no language restrictions. RESULTS: No studies examined the possible effects of surgery or chemotherapy for gynecological cancers on the gut or vaginal microbiome.Three prospective cohort studies were identified using sequencing of changes in the gut microbiome reporting on a total of 23 women treated for gynecological cancer. All studies included patients treated with radiotherapy with a dosage ranging from 43.0 to 54.0 Gy. Two studies assessed gastrointestinal toxicity formally; 8 women (57%) developed grade 2 or 3 diarrhea during radiotherapy. The outcomes suggest a correlation between changes in the intestinal microbiome and receiving radiotherapy and showed a decrease in abundance and diversity of the intestinal bacterial species. Before radiotherapy, those who developed diarrhea had an increased abundance of Bacteroides, Dialister, and Veillonella (P < 0.01), and a decreased abundance of Clostridium XI and XVIII, Faecalibacterium, Oscillibacter, Parabacteroides, Prevotella, and unclassified bacteria (P < 0.05). CONCLUSION: The limited evidence to date implies that larger studies including both the vaginal and gut microbiome in women treated for a gynecological malignancy are warranted to explore the impact of cancer treatments on the microbiome and its relation to developing long-term gastrointestinal toxicity. This may lead to new avenues to stratify those at risk and explore personalized treatment options and prevention of gastrointestinal consequences of cancer treatments.


Subject(s)
Gastrointestinal Microbiome , Genital Neoplasms, Female/microbiology , Genital Neoplasms, Female/therapy , Vagina/microbiology , Cohort Studies , Female , Gastrointestinal Microbiome/drug effects , Gastrointestinal Microbiome/radiation effects , Humans , Prospective Studies
19.
Health Expect ; 20(4): 734-741, 2017 08.
Article in English | MEDLINE | ID: mdl-28078763

ABSTRACT

BACKGROUND: Discharge communication is an important aspect of high-quality emergency care. This study addresses the gap in knowledge on how to describe discharge communication in a paediatric emergency department (ED). OBJECTIVE: The objective of this feasibility study was to develop and test a coding scheme to characterize discharge communication between health-care providers (HCPs) and caregivers who visit the ED with their children. DESIGN: The Pediatric Emergency Discharge Interaction Coding Scheme (PEDICS) and coding manual were developed following a review of the literature and an iterative refinement process involving HCP observations, inter-rater assessments and team consensus. SETTING AND PARTICIPANTS: The coding scheme was pilot-tested through observations of HCPs across a range of shifts in one urban paediatric ED. MAIN VARIABLES STUDIED: Overall, 329 patient observations were carried out across 50 observational shifts. Inter-rater reliability was evaluated in 16% of the observations. The final version of the PEDICS contained 41 communication elements. RESULTS: Kappa scores were greater than .60 for the majority of communication elements. The most frequently observed communication elements were under the Introduction node and the least frequently observed were under the Social Concerns node. HCPs initiated the majority of the communication. CONCLUSION: Pediatric Emergency Discharge Interaction Coding Scheme addresses an important gap in the discharge communication literature. The tool is useful for mapping patterns of discharge communication between HCPs and caregivers. Results from our pilot test identified deficits in specific areas of discharge communication that could impact adherence to discharge instructions. The PEDICS would benefit from further testing with a different sample of HCPs.


Subject(s)
Aftercare/methods , Clinical Coding/statistics & numerical data , Emergency Service, Hospital/statistics & numerical data , Patient Discharge , Pediatrics , Adolescent , Caregivers/education , Child , Child, Preschool , Communication , Feasibility Studies , Female , Health Personnel , Humans , Infant , Infant, Newborn , Male , Reproducibility of Results
20.
Curr Opin Oncol ; 27(5): 405-11, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26222643

ABSTRACT

PURPOSE OF REVIEW: With increasing numbers of cancer survivors, management of the consequences of treatment is a major clinical problem. This article discusses recent advances in preventing and managing radiotherapy-related toxicity. RECENT FINDINGS: Often underreported in clinical studies, radiation toxicity should be assessed with validated assessment tools to assess impact on quality of life. Prevention strategies targeting reactive oxygen species and proinflammatory cytokines show promise. Bowel toxicity is the most common late effect, and algorithm-led investigation and management can significantly improve outcomes. Oral and intravesical therapies are options for bladder toxicity if conservative measures fail. SUMMARY: With better understanding of the mechanisms of acute and chronic radiation-induced changes, more effective treatments are now possible. Following pelvic radiotherapy, patients should be proactively assessed for early intervention by a specialist multidisciplinary team.


Subject(s)
Genital Neoplasms, Female/radiotherapy , Pelvic Neoplasms/radiotherapy , Radiation Injuries/prevention & control , Dose-Response Relationship, Radiation , Female , Genital Neoplasms, Female/pathology , Humans , Pelvic Neoplasms/pathology , Practice Guidelines as Topic , Quality of Life , Radiation Injuries/pathology , Radiotherapy Dosage , Treatment Outcome
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