Endometriosis and Fertility: A Practical Guide

BackgroundEvidence based medicine (EBM) is considered an integral part of medical training, but integration of teaching various EBM steps in everyday clinical practice is uncommon. Currently EBM is predominantly taught through theoretical courses, workshops and e-learning. However, clinical teachers lack confidence in teaching EBM in workplace and are often unsure of the existing opportunities for teaching EBM in the clinical setting. There is a need for continuing professional development (CPD) courses that train clinical trainers to teach EBM through on-the-job training by demonstration of applied EBM real time in clinical practice. We developed such a course to encourage clinically relevant teaching of EBM in post-graduate education in various clinical environments.MethodsWe devised an e-learning course targeting trainers with EBM knowledge to impart educational methods needed to teach application of EBM teaching in commonly used clinical settings. The curriculum development group comprised experienced EBM teachers, clinical epidemiologists, clinicians and educationalists from institutions in seven European countries. The e-learning sessions were designed to allow participants (teachers) to undertake the course in the workplace during short breaks within clinical activities. An independent European steering committee provided input into the process.ResultsThe curriculum defined specific learning objectives for teaching EBM by exploiting educational opportunities in six different clinical settings. The e-modules incorporated video clips that demonstrate practical and effective methods of EBM teaching in everyday clinical practice. The course encouraged focussed teaching activities embedded within a trainer's personal learning plan and documentation in a CPD portfolio for reflection.ConclusionThis curriculum will help senior clinicians to identify and make the best use of available opportunities in everyday practice in clinical situations to teach various steps of EBM and demonstrate their applicability to clinical practice. Once fully implemented, the ultimate outcome of this pilot project will be a European qualification in teaching EBM, which will be used by doctors, hospitals, professional bodies responsible for postgraduate qualifications and continuing medical education.

Simple SummaryPrecision medicine has reached its current peak in non-small cell lung cancer (NSCLC), with a constantly growing number of predictive biomarkers and new targeted therapies that when applied, significantly affect and change outcomes. Hence, the matter in question is how we might optimally detect and implement them in the treatment of our patients in everyday clinical practice. The main problem in the diagnostic workup of NSCLC is the rather limited tumor sample used on many occasions in the classical diagnostic approach, which consists of a series of single-biomarker tests. Consequently, the introduction of comprehensive genomic profiling (CGP) in everyday diagnostic and clinical practice is one of the imperatives that could benefit everybody involved. Here, we present national data and our experiences with the application of comprehensive genomic profiling in NSCLC. The results have shown the utility and potential benefit of comprehensive genomic profiling, but also challenges involved in the implementation of precision oncology in clinical practice. So when possible, CGP should be used as an upfront backbone diagnostic and treatment-oriented work-up in patients with NSCLC.Non–small cell lung cancer (NSCLC) has become the best example of precision oncology’s impact on outcomes in everyday clinical practice, significantly changing the expectations of all stakeholders, including medical professionals, society, and most importantly, patients. Consequently, the implementation of the precision oncology concept in medical systems, in order to achieve optimal and proven curative effects in NSCLC, is imperative. In this study, we investigated the development, challenges, and results associated with the implementation of precision oncology in NSCLC on a national level in Croatia. We conducted a multicenter, retrospective, cross-sectional analysis on the total population of Croatian patients with metastatic lung cancer, on whose tumors specimen comprehensive genomic profiling (CGP) testing was performed during 2020 and 2021. A total of 48 patients were included in the study. CGP revealed clinically relevant genomic alterations (CRGA) in 37 patients (79%), with a median of 2 (IQR 1–3) CRGA per patient. From the panel of recommended tests, KRAS, MET, and EGFR were the most common alterations, detected in 16 (34%), 5 (11%), and 3 (6%) patients, respectively. CGP revealed additional targetable mutations in 29 (60%) patients who would not have been tested (and consequently, whose mutations would not have been detected) according to the existing everyday standard of practice in Croatia. The tumor mutational burden was reported as high (≥10 Muts/Mb) in 19 patients (40%). CGP analysis reported some kind of targeted therapy for 34 patients (72%). CGP revealed other potentially targetable mutations, and it also determined TMB to be high in a significant number of patients. In conclusion, when possible, CGP should be used as an upfront backbone diagnostic and treatment-oriented work-up in patients with NSCLC.

Objective:To identify predictors of improved asthma control under conditions of everyday practice in Switzerland.Research design and methods:A subgroup of 1380 patients with initially inadequately controlled asthma was defined from a cohort of 1893 asthmatic patients (mean age 45.3 ± 19.2 years) recruited by 281 office-based physicians who participated in a previously-conducted asthma control survey in Switzerland. Multiple regression techniques were used to identify predictors of improved asthma control, defined as an absolute decrease of 0.5 points or more in the Asthma Control Questionnaire between the baseline (V1) and follow-up visit (V2).Results:Asthma control between V1 and V2 improved in 85.7%. Add-on treatment with montelukast was reported in 82.9% of the patients. Patients with worse asthma control at V1 and patients with good self-reported adherence to therapy had significantly higher chances of improved asthma control (OR = 1.24 and 1.73, 95% CI 1.18–1.29 and 1.20–2.50, respectively). Compared to adding montelukast and continuing the same inhaled corticosteroid/fixed combination (ICS/FC) dose, the addition of montelukast to an increased ICS/FC dose yielded a 4 times higher chance of improved asthma control (OR = 3.84, 95% CI 1.58–9.29). Significantly, withholding montelukast halved the probability of achieving improved asthma control (OR = 0.51, 95% CI = 0.33–078). The probability of improved asthma control was almost 5 times lower among patients in whom FEV1 was measured compared to those in whom it was not (OR = 0.23, 95% CI = 0.09–0.55). Patients with severe persistent asthma also had a significantly lower probability of improved control (OR = 0.15, 95% CI = 0.07–0.32), as did older patients (OR = 0.98, 95% CI = 0.97–0.99). Subgroup analyses which excluded patients whose asthma may have been misdiagnosed and might in reality have been chronic obstructive pulmonary disease (COPD) showed comparable results.Conclusions:Under conditions of everyday clinical practice, the addition of montelukast to ICS/FC and good adherence to therapy increased the likelihood of achieving better asthma control at the follow-up visit, while older age and more severe asthma significantly decreased it.

e13100^ Background: The trifunctional antibody catumaxomab is approved in the EU for intraperitoneal (i.p.) treatment of malignant ascites in patients (pts) with EpCAM-positive carcinomas. Clinical data for catumaxomab are based on the pivotal trial and several phase I/II trials. So far, the routine use of catumaxomab in clinical practice has not been evaluated systematically. Therefore, a large prospective observational study was started in 2010. The study investigates the administration of catumaxomab in a total of 160 pts with malignant ascites under routine conditions in daily clinical practice. Here we show the results of the first pre-planned interim analysis. Methods: The analysis included 49 pts with malignant ascites due to EpCAM-positive carcinomas treated with i.p. catumaxomab under routine conditions in clinical practice. Participating centres were hospitals and practices of oncologists in Germany. Primary endpoint was puncture-free interval (PFI), secondary endpoints included safety and overall survival (OS). Results: At inclusion into the study pts already had undergone a median number of 9 ascites punctures. Malignant ascites had been diagnosed for the first time 3.3 months before (median). Patients suffered from typical ascites symptoms as follows: swelling (79.6%), pain (44.9%), dyspnea (26.5%), anorexia (26.5%), obstipation (12.2%). 49 pts were treated with catumaxomab, of whom 30 pts received all 4 infusions (61.2%). Median PFI was 108 days (d), the median OS was 102 d. Most frequent adverse events were fever, nausea and diarrhoe. Conclusions: This is the first systematic report on routine use of catumaxomab in clinical practice.. Although The study population mainly comprised patients with advanced tumor diseaset a clinical benefit after catumaxomab therapy could be demonstrated. The treatment showed an acceptable safety profile Theseresults are consistent with the data of the pivotal trial. The data will be evaluated in further analyses including larger patient numbers.

Editorial

Continuation Treatment With Antidepressants in Child and Adolescent Major Depression

Effectiveness and tolerability of Lymphomyosot N solution for injection in treating oedemas and swellings of thrombotic or inflammatory aetiology in general clinical practice

Severity of psoriasis appears to be multidimensional and its assessment in everyday clinical practice requires a complex holistic approach. To develop evidence-based recommendations to assess severity of plaque-type psoriasis in adult patients in everyday clinical practice. A scientific committee (10 members identified on the basis of their expertise in psoriasis) using Delphi methodology selected eight questions in three domains: severity, health-related quality of life (HR-QoL) and comorbidities. Three systematic literature reviews (one per domain) of all studies published between January 1980 and June 2009 were performed based on Pub-Med, Cochrane and Embase database. Selected articles were systematically reviewed and evidence appraised according to the Oxford Levels of Evidence. On June 2009, a group of 44 French dermatologists both hospital and office based participated in a meeting including three separate rounds of discussions, plenary sessions, and modified Delphi technique votes. Recommendations for clinical practice based on systematic review and clinical experience were formulated by the group. Subsequently, agreements among the participants regarding these recommendations as well as potential impact on clinical practice were evaluated. A total of 10 642 references were identified, of which 154 articles were analysed. Ten key recommendations on the assessment of psoriasis severity were formulated: three recommendations relating to severity assessment, three recommendations relating to HR-QoL (including the use of the Dermatology Life Quality Index [DLQI] in clinical practice) and four recommendations relating to comorbidities (including systematic screening for peripheral or axial inflammatory joint damage, regardless of psoriasis severity). Ten recommendations to assess the severity of plaque-type psoriasis in adult patients in daily practice were developed. The recommendations are based on systematic appraisal of available evidence. They were developed and supported by a panel of dermatologists, which enhances their validity and practical relevance.

Background: Subsequent to introduction in June 2010 in the United Kingdom and Spain of tetrahydrocannabinol (THC) : cannabidiol (CBD) oromucosal spray (Sativex®) for management of multiple sclerosis (MS) spasticity, and as part of a wider initiative to address British health authority requirements for post-marketing surveillance to identify possible short- and long-term risks associated with its use as a condition of marketing authorization, studies were undertaken to evaluate the safety of THC: CBDspray under clinical practice conditions. Methods: This prospective, observational, multicentre study reports on 205 patients with treatment-resistant MS spasticity who were prescribed THC: CBD spray as add-on therapy to existing antispasticity medications at 13 specialist MS centres across Spain. Safety evaluations were performed after 6 and 12 months’ exposure to THC: CBD spray. Results: Add-on THC: CBD spray was well tolerated during up to 12 months’ exposure. No new safety signals emerged and THC: CBD spray was not associated with any clinically-relevant occurrence of adverse events of special interest with cannabinoid-based medications such as falls requiring medical attention, psychiatric or psychotic symptoms, memory impairment, changes in driving ability, addiction or abuse. After 6 months’ and 12 months’ exposure, treating physicians considered that 139 patients (68% of original cohort) and 124 patients (60.5% of original cohort), respectively, were deriving sufficient anti-spasticity benefit from THC: CBD spray to warrant continued treatment. The mean dosage of THC: CBD spray (6.6 sprays/day) and carer requirements (~14.5 hours/day) remained stable throughout the study. Conclusions: THC: CBDspray as add-on therapy showed good tolerability and sustained anti-spasticity benefit in a relevant proportion (60.5%) of Spanish patients with MS-related spasticity treated for up to 12 months in everyday clinical practice.

Keeping clinicians in clinical research: the Clinical Research/Reproductive Scientist Training Program

Diagnosis and Treatment of Hyponatremia

In 1979 a study for drug surveillance in psychiatric patients (Arzneimitteluberwachung in der Psychiatrie, AMUP) was initiated by the Arbeitsgemeinschaft fur Neuropsychopharmakologie und Pharmakopsychiatrie, financed by the Federal Health Agency (Bundesgesundheitsamt) of the Federal Republic of Germany. The main aim of the study was to assess data on adverse drug reactions (ADRs) under conditions of everyday clinical practice. Data on type and frequency of ADRs for various psychotropic drugs are available from clinical trials, however in everyday clinical practice patients of all age groups, including the elderly, are treated; some patients have concomitant physical diseases, and frequently drug combinations are used, as polypharmacy is a common practice in psychiatry worldwide (Clark and Holden 1987; Grohmann et al. 1986; Schmidt et al. 1987; Swett 1979). As the need for additional information on the occurence of ADR under these treatment conditions had not previously been met by any large-scale drug surveillance study, the AMUP study was undertaken.

Drug regulatory agencies should ensure that the benefits of drugs outweigh their risks, but licensed medicines sometimes do not perform as expected in everyday clinical practice. Failure may relate to lower than anticipated efficacy or a higher than anticipated incidence or severity of adverse effects. Here we show that the problem of benefit-risk is to a considerable degree a problem of variability in drug response. We describe biological and behavioural sources of variability and how these contribute to the long-known efficacy-effectiveness gap. In this context, efficacy describes how a drug performs under conditions of clinical trials, whereas effectiveness describes how it performs under conditions of everyday clinical practice. We argue that a broad range of pre- and post-licensing technologies will need to be harnessed to bridge the efficacy-effectiveness gap. Successful approaches will not be limited to the current notion of pharmacogenomics-based personalized medicines, but will also entail the wider use of electronic health-care tools to improve drug prescribing and patient adherence.

Physiotherapists and clinicians require methods that can be used in everyday practice for measuring proprioception of the trunk in individuals with non-specific low back pain (NSLBP). Our objective was to conduct a systematic literature review of methods used for assessment of proprioception of the trunk in individuals with non-specific low back pain. Data were obtained from MEDLINE, CINAHL, Embase, PEDro and CENTRAL databases from their inception to December 2011. Reference lists of the selected reviews were hand searched for other potentially relevant studies. Randomized and nonrandomized controlled studies proprioception of the trunk in individuals with low back pain were selected. Thirty-six studies satisfied the selection criteria and were included in this review. Two reviewers independently selected the studies, conducted the quality assessment, and extracted data from each study. The Strobe scale was used to evaluate the scientific rigor of each selected study. This systematic review covered all the relevant literature, but none of the included studies offered a valid, reliable and feasible method to assess neuromotor capacity in everyday physiotherapy clinical practice.

Treating the individual: The need for a patient-focused approach to the management of renal cell carcinoma