A survey of UK medical schools' arrangements for early patient contact

Background: Many U.K. medical schools have patient contact in the first two years of the undergraduate course. Aim: To compare the purposes and organization of early patient contact in UK medical schools and to relate these arrangements to the schools' curricular objectives. Methods: A telephone survey of lead educators in UK medicals schools. Categories of contact were plotted against phases of the course to discern patterns of organisation. Results: The quantity of contact varies considerably (four to 65 days). There is a pattern, with learning objectives around the social context of health and illness preceding skills based work and integrated clinical knowledge for practice coming later. Schools fall into three categories: close adherence to the preclinical/clinical split, with limited early contact acting as an introduction to social aspects of health; provision of substantial patient contact to maximize the integration of knowledge and skills; and transitional, with limited clinical goals. General practice provides between one third and one half of early patient contact. Conclusions: Arrangements meet the objectives set by each school and reflect differing educational philosophies. Change is toward more early contact. There appears to be no national guidance which supports a minimum quantity of patient contact or specific educational purpose in the early years of U.K. basic medical training

Doctor-patient interaction in Finnish primary health care as perceived by first year medical students

BACKGROUND: In Finland, public health care is the responsibility of primary health care centres, which render a wide range of community level preventive, curative and rehabilitative medical care. Since 1990's, medical studies have involved early familiarization of medical students with general practice from the beginning of the studies, as this pre-clinical familiarisation helps medical students understand patients as human beings, recognise the importance of the doctor-patient relationship and identify practicing general practitioners (GPs) as role models for their professional development. Focused on doctor-patient relationship, we analysed the reports of 2002 first year medical students in the University of Kuopio. The students observed GPs' work during their 2-day visit to primary health care centres. METHODS: We analysed systematically the texts of 127 written reports of 2002, which represents 95.5% of the 133 first year pre-clinical medical students reports. The reports of 2003 (N = 118) and 2004 (N = 130) were used as reference material. RESULTS: Majority of the students reported GPs as positive role models. Some students reported GPs' poor attitudes, which they, however, regarded as a learning opportunity. Students generally observed a great variety of responsibilities in general practice, and expressed admiration for the skills and abilities required. They appreciated the GPs' interest in patients concerns. GPs' communication styles were found to vary considerably. Students reported some factors disturbing the consultation session, such as the GP staring at the computer screen and other team members entering the room. Working with marginalized groups, the chronically and terminally ill, and dying patients was seen as an area for development in the busy Finnish primary health care centres. CONCLUSION: During the analysis, we discovered that medical students' perceptions in this study are in line with the previous findings about the importance of role model (good or bad) in making good doctors. Therefore, medical students' pre-clinical primary health care centre visits may influence their attitudes towards primary health care work and the doctor-patient relationship. We welcome more European studies on the role of early pre-clinical general practice exposure on medical students' primary care specialty choice

Minimal residual disease prior to allogeneic hematopoietic cell transplantation in acute myeloid leukemia: a meta-analysis

Minimal residual disease prior to allogeneic hematopoietic cell transplantation has been associated with increased risk of relapse and death in patients with acute myeloid leukemia, but detection methodologies and results vary widely. We performed a systematic review and meta-analysis evaluating the prognostic role of minimal residual disease detected by polymerase chain reaction or multiparametric flow cytometry before transplant. We identified 19 articles published between January 2005 and June 2016 and extracted hazard ratios for leukemia-free survival, overall survival, and cumulative incidences of relapse and non-relapse mortality. Pre-transplant minimal residual disease was associated with worse leukemia-free survival (HR=2.76 [1.90-4.00]), overall survival (HR=2.36 [1.73-3.22]), and cumulative incidence of relapse (HR=3.65 [2.53-5.27]), but not non-relapse mortality (HR=1.12 [0.81-1.55]). These associations held regardless of detection method, conditioning intensity, and patient age. Adverse cytogenetics was not an independent risk factor for death or relapse. There was more heterogeneity among studies using flow cytometry-based than WT1 polymerase chain reaction-based detection (I(2)=75.1% vs. <0.1% for leukemia-free survival, 67.8% vs. <0.1% for overall survival, and 22.1% vs. <0.1% for cumulative incidence of relapse). These results demonstrate a strong relationship between pre-transplant minimal residual disease and post-transplant relapse and survival. Outcome heterogeneity among studies using flow-based methods may underscore site-specific methodological differences or differences in test performance and interpretation

СОВРЕМЕННАЯ ЛУЧЕВАЯ ТЕРАПИЯ ЖЕЛУДКА

External beam radiation therapy (EBRT) is currently an important component of the treatment of gastric cancer (GC). In accordance with international and domestic recommendations, it can be used in the postoperative period, before the operation and as a sole option, with a curative and palliative purpose, usually in combination with chemotherapy. With the transition of RT to a new technological level, which involves the use of conformal, intensively modulated regimens, and image guidance the revision of indications for and doses of EBRT is required. The article discusses modern approaches to the determination of irradiated volumes in various clinical scenarios of current radiation therapy for GC and strategies aimed at reducing the dose in critical organs at risk and increasing the overall effectiveness of treatment.Дистанционная лучевая терапия (ЛТ) в настоящее время является важным компонентом лечения рака желудка (РЖ). В соответствии с международными и отечественными рекомендациями она может быть использована в послеоперационном периоде, перед операцией и самостоятельно, с лечебной и паллиативной целью, как правило, в сочетании с химиотерапией. В связи с переходом ЛТ на новый технологический уровень, предусматривающий использование конформных, интенсивно-модулированных режимов, требуется пересмотр показаний, доз и режимов дистанционного облучения. В статье рассмотрены современные подходы к определению облучаемых объемов при различных клинических сценариях современной ЛТ по поводу РЖ и обсуждены стратегии, направленные на снижение дозы в критических органах и повышение эффективности лечения

Влияние пандемии COVID-19 на показатели заболеваемости злокачественными опухолями, подлежащими скринингу в рамках диспансеризации (популяционное исследование)

Background. During the COVID-19 pandemic, annual adult check-ups have been postponed, resulting in cancer screening disruption.The aim of the study was to evaluate changes in the incidence and stage distribution of malignancies included in the screening program during the COVID-19 pandemic using the Arkhangelsk Regional Cancer Registry (ARRC).Material and Methods. We assessed the changes of the incidence rates and stage distribution for the colon, rectum, lung, breast, cervix, uterine body, ovary, prostate and kidney cancers over the periods 2018–19 and 2020–21. Results. A total of 12354 cases with 9 cancers were selected: 6680 for the period 2018–19 and 5674 (-15.1 %) for the period 2020-21. The most significant decrease in crude and age-standardized incidence rates was registered in patients with lung (-18.0–18.1 %), rectum (-25.1–25.9 %) and cervix (-33.6–36.9 %) cancers, p&lt;0.001. The decrease was not signifcant in patients with breast, uterine body, and kidney cancers. The proportion of patients with stage I decreased in lung cancer (-20.0 %, from 14.8 % to 11.8 %), rectum (-20.2 %, from 20.9 % to 16.7 %), and uterine cervix (-37.1 %, from 53.2 % to 33.5 %). In prostate and kidney cancers, the proportion of patients with stage I increased by 30 % (from 19.5 % to 25.4 %) and 17.6 % (from 45.9 % to 54.0 %), respectively. A signifcant reduction in the proportion of early stages during the COVID-19 pandemic was observed in lung and cervical cancer. Conclusion Postponed health checkups due to COVID-19 pandemic disruptions have led to substantial reductions in new cancers being diagnosed, mainly for cervical, lung, colon and rectal cancers. No signifcant changes were observed for other cancers. Further analysis of mortality and survival of cancer patients is required. Key words: health checkup, cancer screening, COVID-19 pandemic, cancer incidence, stage distribution&gt;˂0.001. The decrease was not significant in patients with breast, uterine body, and kidney cancers. The proportion of patients with stage I decreased in lung cancer (-20.0 %, from 14.8 % to 11.8 %), rectum (-20.2 %, from 20.9 % to 16.7 %), and uterine cervix (-37.1 %, from 53.2 % to 33.5 %). In prostate and kidney cancers, the proportion of patients with stage I increased by 30 % (from 19.5 % to 25.4 %) and 17.6 % (from 45.9 % to 54.0 %), respectively. A significant reduction in the proportion of early stages during the COVID-19 pandemic was observed in lung and cervical cancer.Conclusion. Postponed health checkups due to COVID-19 pandemic disruptions have led to substantial reductions in new cancers being diagnosed, mainly for cervical, lung, colon and rectal cancers. No significant changes were observed for other cancers. Further analysis of mortality and survival of cancer patients is required. Актуальность. В период пандемии COVID-19 была приостановлена диспансеризация отдельных групп взрослого населения (ДОГВН), что могло привести к ухудшению скрининга ряда злокачественных новообразований (ЗНО).Цель исследования ‒ оценить изменения заболеваемости и стадийной структуры ЗНО, включенных в программу скрининга в рамках ДОГВН, во время пандемии COVID-19 по данным Архангельского областного канцер-регистра (АОКР).Материал и методы. Оценивали динамику показателей заболеваемости и распределения по стадии при индексных ЗНО (иЗНО) ободочной, прямой кишки, легкого, молочной железы, шейки, тела матки, яичников, предстательной железы и почки в периоды 2018–19 гг. и 2020–21 гг.Результаты. Всего отобрано 12354 случая заболевания при девяти иЗНО: в 2018–19 гг. выявлено 6680, в 2020–21 гг. – 5674 (-15,1 %). Наиболее выраженное снижение «грубых» и стандартизованных по возрасту показателей заболеваемости зарегистрировано при раке легкого (-18,0–18,1 %), прямой кишки (-25,1–25,9 %) и шейки матки (-33,6–36,9 %), различия статистически значимы (р&lt;0,001). Снижение было статистически незначимым при раке молочной железы, тела матки, почки. Доля больных I стадии уменьшалась при раке легкого (на 20,0 %, с 14,8 до 11,8 %), прямой кишки (на 20,2 %, с 20,9 до 16,7 %), шейки матки (на 37,1 %, с 53,2 до 33,5 %). При раке предстательной железы и почки зарегистрировано увеличение доли I стадии на 30 % (с 19,5 до 25,4 %) и 17,6 % (с 45,9 до 54,0 %) соответственно. В возрастных группах скрининга в рамках ДОГВН значимое снижение доли ранних стадий в период пандемии COVID-19 наблюдали при раке легкого и шейки матки. Заключение. Ограничение ДОГВН в период пандемии привело к уменьшению числа выявленных иЗНО в основном за счет ранних стадий при раке шейки матки, легкого, ободочной и прямой кишки. При других иЗНО эти изменения были не столь явными. В дальнейшем требуется анализ смертности и выживаемости больных иЗНО. Ключевые слова: диспансеризация взрослого населения, скрининг рака, индексные злокачественные новообразования, пандемия COVID-19, заболеваемость, распределение по стадии.&gt;˂ 0,001). Снижение было статистически незначимым при раке молочной железы, тела матки, почки. Доля больных I стадии уменьшалась при раке легкого (на 20,0 %, с 14,8 до 11,8 %), прямой кишки (на 20,2 %, с 20,9 до 16,7 %), шейки матки (на 37,1 %, с 53,2 до 33,5 %). При раке предстательной железы и почки зарегистрировано увеличение доли I стадии на 30 % (с 19,5 до 25,4 %) и 17,6 % (с 45,9 до 54,0 %) соответственно. В возрастных группах скрининга в рамках ДОГВН значимое снижение доли ранних стадий в период пандемии COVID-19 наблюдали при раке легкого и шейки матки.Заключение. Ограничение ДОГВН в период пандемии привело к уменьшению числа выявленных иЗНО в основном за счет ранних стадий при раке шейки матки, легкого, ободочной и прямой кишки. При других иЗНО эти изменения были не столь явными. В дальнейшем требуется анализ смертности и выживаемости больных иЗНО.

A destabilized bacterial luciferase for dynamic gene expression studies

Fusions of genetic regulatory elements with reporter genes have long been used as tools for monitoring gene expression and have become a major component in synthetic gene circuit implementation. A major limitation of many of these systems is the relatively long half-life of the reporter protein(s), which prevents monitoring both the initiation and the termination of transcription in real-time. Furthermore, when used as components in synthetic gene circuits, the long time constants associated with reporter protein decay may significantly degrade circuit performance. In this study, short half-life variants of LuxA and LuxB from Photorhabdus luminescens were constructed in Escherichia coli by inclusion of an 11-amino acid carboxy-terminal tag that is recognized by endogenous tail-specific proteases. Results indicated that the addition of the C-terminal tag affected the functional half-life of the holoenzyme when the tag was added to luxA or to both luxA and luxB, but modification of luxB alone did not have a significant effect. In addition, it was also found that alteration of the terminal three amino acid residues of the carboxy-terminal tag fused to LuxA generated variants with half-lives of intermediate length in a manner similar to that reported for GFP. This report is the first instance of the C-terminal tagging approach for the regulation of protein half-life to be applied to an enzyme or monomer of a multi-subunit enzyme complex and will extend the utility of the bacterial luciferase reporter genes for the monitoring of dynamic changes in gene expression

Эпидемиологические факторы прогноза выживаемости больных раком тела матки: популяционный анализ

Cancer of the corpus uteri (CCU) is one of the most common gynecological malignancies in high- and middleincome countries. The objective of the study was to evaluate the factors predicting survival in CCU patients over the period 2000-2021 using the data of population-based cancer registry of the Arkhangelsk region. Material and Methods. Cancer-specific survival (CSS) of patients with CCU for the period 2000-21 was evaluated using life tables and Kaplan-Mayer methods with a log-rank test. The Cox proportional hazards regression model was used to assess the effect of prognostic factors on survival time. Results. A total of 3272 cases were selected for the analysis. The 5-year survival rates improved from 70.6 % in 2000-04 to 75.6 % in 2015-19. In stage I, II, III, and IV CUN, the 5-year survival rates were 90.8 % (95 % CI 89.3-92.0 %), 71.1 (95 % CI 66.3-75.4 %), 46.7 (95 % CI 41.4-51.8 %), and 3.9 (95 % CI 1.5-7.5 %), respectively; p&lt;0.001. In the multivariate regression model, for stage II, III, and IV CCU, the hazard ratios for death from cancer were respectively 2.69 (2.14-3.39), 5.73 (4.66-7.03), and 20.26 (16.13-25.44) compared to stage I. The risk of death from CCU was 2.0-2.7 times higher in patients with aggressive histological subtypes and sarcomas compared to that in patients with endometrioid adenocarcinoma; 2.0-2.8 times higher in patients older than 60 years compared to younger patients, and 1.3 times higher in rural patients compared to urban patients (p&lt;0.05). There was no increase in the risk of death from CCU over the period of COVID-19 pandemic. Conclusion. In this population-based study, we have found that the survival of patients with CCU is significantly affected by age and place of residence, which may indicate a limited access of some patients to effective treatment and requires further analysis. No increased risk of death from CCU during the COVID-19 pandemic was found.Актуальность. Злокачественные новообразования тела матки (ЗНО ТМ) лидируют среди гинекологических опухолей в России и мире. Цель исследования - оценить факторы прогноза выживаемости при ЗНО ТМ в период с 2000 по 2021 г. по данным популяционного канцер-регистра Архангельской области (АОКР). Материал и методы. Опухолеспецифическую выживаемость (ОСВ) больных ЗНО ТМ, зарегистрированных в АОКР за период 2000-21 гг., оценивали актуарным методом и методом Каплана-Майера с лог-ранговым критерием. Прогностическое значение популяционных факторов определяли с помощью регрессии Кокса; включение в модель прогностических факторов осуществляли форсированным способом. Результаты. Для анализа отобрано 3272 случая. Показатели 5-летней выживаемости улучшались с 70,6 % в 2000-04 гг. до 75,6 % в 2015-19 гг. При I, II, III, IV стадиях ЗНО ТМ 5-летняя выживаемость составила 90,8 (95 % ДИ 89,3-92,0 %), 71,1 (95 % ДИ 66,3-75,4 %), 46,7 (95 % ДИ 41,4-51,8 %), 3,9 % (95 % ДИ 1,5-7,5 %), p&lt;0,001. В множественной регрессионной модели при II, III, IV стадиях отношение рисков смерти по сравнению с I стадией составило 2,69 (2,14-3,39), 5,73 (4,66-7,03), 20,26 (16,13-25,44) соответственно. Риск смерти от ЗНО ТМ в 2,0-2,7 раза был выше при агрессивных гистологических подтипах и саркомах по сравнению с эндометриоидной аденокарциномой, в 2-2,8 раза выше у больных старше 60 лет по сравнению с более молодыми пациентками, у больных, проживающих в сельской местности, - в 1,3 раза выше по сравнению с больными из городов (р&lt;0,05). Заключение. Установлено, что на выживаемость пациенток с ЗНО ТМ, помимо клинических факторов, значимо влияют возраст и место проживания, что может свидетельствовать об ограниченном доступе части больных к эффективному лечению и требует дальнейшего изучения. Риск смерти от ЗНО ТМ в период пандемии COVID-19 не повышался

The clinical relevance of oliguria in the critically ill patient : Analysis of a large observational database

Funding Information: Marc Leone reports receiving consulting fees from Amomed and Aguettant; lecture fees from MSD, Pfizer, Octapharma, 3 M, Aspen, Orion; travel support from LFB; and grant support from PHRC IR and his institution. JLV is the Editor-in-Chief of Critical Care. The other authors declare that they have no relevant financial interests. Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Urine output is widely used as one of the criteria for the diagnosis and staging of acute renal failure, but few studies have specifically assessed the role of oliguria as a marker of acute renal failure or outcomes in general intensive care unit (ICU) patients. Using a large multinational database, we therefore evaluated the occurrence of oliguria (defined as a urine output 16 years) patients in the ICON audit who had a urine output measurement on the day of admission were included. To investigate the association between oliguria and mortality, we used a multilevel analysis. Results: Of the 8292 patients included, 2050 (24.7%) were oliguric during the first 24 h of admission. Patients with oliguria on admission who had at least one additional 24-h urine output recorded during their ICU stay (n = 1349) were divided into three groups: transient - oliguria resolved within 48 h after the admission day (n = 390 [28.9%]), prolonged - oliguria resolved > 48 h after the admission day (n = 141 [10.5%]), and permanent - oliguria persisting for the whole ICU stay or again present at the end of the ICU stay (n = 818 [60.6%]). ICU and hospital mortality rates were higher in patients with oliguria than in those without, except for patients with transient oliguria who had significantly lower mortality rates than non-oliguric patients. In multilevel analysis, the need for RRT was associated with a significantly higher risk of death (OR = 1.51 [95% CI 1.19-1.91], p = 0.001), but the presence of oliguria on admission was not (OR = 1.14 [95% CI 0.97-1.34], p = 0.103). Conclusions: Oliguria is common in ICU patients and may have a relatively benign nature if only transient. The duration of oliguria and need for RRT are associated with worse outcome.publishersversionPeer reviewe

Temporal changes in the epidemiology, management, and outcome from acute respiratory distress syndrome in European intensive care units: a comparison of two large cohorts

Background: Mortality rates for patients with ARDS remain high. We assessed temporal changes in the epidemiology and management of ARDS patients requiring invasive mechanical ventilation in European ICUs. We also investigated the association between ventilatory settings and outcome in these patients. Methods: This was a post hoc analysis of two cohorts of adult ICU patients admitted between May 1–15, 2002 (SOAP study, n = 3147), and May 8–18, 2012 (ICON audit, n = 4601 admitted to ICUs in the same 24 countries as the SOAP study). ARDS was defined retrospectively using the Berlin definitions. Values of tidal volume, PEEP, plateau pressure, and FiO2 corresponding to the most abnormal value of arterial PO2 were recorded prospectively every 24&nbsp;h. In both studies, patients were followed for outcome until death, hospital discharge or for 60&nbsp;days. Results: The frequency of ARDS requiring mechanical ventilation during the ICU stay was similar in SOAP and ICON (327[10.4%] vs. 494[10.7%], p = 0.793). The diagnosis of ARDS was established at a median of 3 (IQ: 1–7) days after admission in SOAP and 2 (1–6) days in ICON. Within 24&nbsp;h of diagnosis, ARDS was mild in 244 (29.7%), moderate in 388 (47.3%), and severe in 189 (23.0%) patients. In patients with ARDS, tidal volumes were lower in the later (ICON) than in the earlier (SOAP) cohort. Plateau and driving pressures were also lower in ICON than in SOAP. ICU (134[41.1%] vs 179[36.9%]) and hospital (151[46.2%] vs 212[44.4%]) mortality rates in patients with ARDS were similar in SOAP and ICON. High plateau pressure (&gt; 29 cmH2O) and driving pressure (&gt; 14 cmH2O) on the first day of mechanical ventilation but not tidal volume (&gt; 8&nbsp;ml/kg predicted body weight [PBW]) were independently associated with a higher risk of in-hospital death. Conclusion: The frequency of and outcome from ARDS remained relatively stable between 2002 and 2012. Plateau pressure &gt; 29 cmH2O and driving pressure &gt; 14 cmH2O on the first day of mechanical ventilation but not tidal volume &gt; 8&nbsp;ml/kg PBW were independently associated with a higher risk of death. These data highlight the continued burden of ARDS and provide hypothesis-generating data for the design of future studies