Summary Background On the basis of promising results that were reported in several phase 2 trials, we investigated whether the addition of the monoclonal antibody rituximab to first-line chemotherapy ...with fludarabine and cyclophosphamide would improve the outcome of patients with chronic lymphocytic leukaemia. Methods Treatment-naive, physically fit patients (aged 30–81 years) with CD20-positive chronic lymphocytic leukaemia were randomly assigned in a one-to-one ratio to receive six courses of intravenous fludarabine (25 mg/m2 per day) and cyclophosphamide (250 mg/m2 per day) for the first 3 days of each 28-day treatment course with or without rituximab (375 mg/m2 on day 0 of first course, and 500 mg/m2 on day 1 of second to sixth courses) in 190 centres in 11 countries. Investigators and patients were not masked to the computer-generated treatment assignment. The primary endpoint was progression-free survival (PFS). Analysis was by intention to treat. This study is registered with ClinicalTrials.gov , number NCT00281918. Findings 408 patients were assigned to fludarabine, cyclophosphamide, and rituximab (chemoimmunotherapy group) and 409 to fludarabine and cyclophosphamide (chemotherapy group); all patients were analysed. At 3 years after randomisation, 65% of patients in the chemoimmunotherapy group were free of progression compared with 45% in the chemotherapy group (hazard ratio 0·56 95% CI 0·46–0·69, p<0·0001); 87% were alive versus 83%, respectively (0·67 0·48–0·92; p=0·01). Chemoimmunotherapy was more frequently associated with grade 3 and 4 neutropenia (136 34% of 404 vs 83 21% of 396; p<0·0001) and leucocytopenia (97 24% vs 48 12%; p<0·0001). Other side-effects, including severe infections, were not increased. There were eight (2%) treatment-related deaths in the chemoimmunotherapy group compared with ten (3%) in the chemotherapy group. Interpretation Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab improves progression-free survival and overall survival in patients with chronic lymphocytic leukaemia. Moreover, the results suggest that the choice of a specific first-line treatment changes the natural course of chronic lymphocytic leukaemia. Funding F Hoffmann-La Roche.
The Coronavirus Disease 2019 (COVID-19) pandemic has exacerbated mental health challenges among physicians and non-physicians. However, it is unclear if the worsening mental health among physicians ...is due to specific occupational stressors, reflective of general societal stressors during the pandemic, or a combination. We evaluated the difference in mental health and addictions health service use between physicians and non-physicians, before and during the COVID-19 pandemic.
We conducted a population-based cohort study in Ontario, Canada between March 11, 2017 and August 11, 2021 using data collected from Ontario's universal health system. Physicians were identified using registrations with the College of Physicians and Surgeons of Ontario between 1990 and 2020. Participants included 41,814 physicians and 12,054,070 non-physicians. We compared the first 18 months of the COVID-19 pandemic (March 11, 2020 to August 11, 2021) to the period before COVID-19 pandemic (March 11, 2017 to February 11, 2020). The primary outcome was mental health and addiction outpatient visits overall and subdivided into virtual versus in-person, psychiatrists versus family medicine and general practice clinicians. We used generalized estimating equations for the analyses. Pre-pandemic, after adjustment for age and sex, physicians had higher rates of psychiatry visits (aIRR 3.91 95% CI 3.55 to 4.30) and lower rates of family medicine visits (aIRR 0.62 95% CI 0.58 to 0.66) compared to non-physicians. During the first 18 months of the COVID-19 pandemic, the rate of outpatient mental health and addiction (MHA) visits increased by 23.2% in physicians (888.4 pre versus 1,094.7 during per 1,000 person-years, aIRR 1.39 95% CI 1.28 to 1.51) and 9.8% in non-physicians (615.5 pre versus 675.9 during per 1,000 person-years, aIRR 1.12 95% CI 1.09 to 1.14). Outpatient MHA and virtual care visits increased more among physicians than non-physicians during the first 18 months of the pandemic. Limitations include residual confounding between physician and non-physicians and challenges differentiating whether observed increases in MHA visits during the pandemic are due to stressors or changes in health care access.
The first 18 months of the COVID-19 pandemic was associated with a larger increase in outpatient MHA visits in physicians than non-physicians. These findings suggest physicians may have had larger negative mental health during COVID-19 than the general population and highlight the need for increased access to mental health services and system level changes to promote physician wellness.
We present an interactive tool compatible with existing software (Rhino/Grasshopper) to design ring structures with a paradoxic mobility, which are self‐collision‐free over the complete motion cycle. ...Our computational approach allows non‐expert users to create these invertible paradoxic loops with six rotational joints by providing several interactions that facilitate design exploration. In a first step, a rational cubic motion is shaped either by means of a four pose interpolation procedure or a motion evolution algorithm. By using the representation of spatial displacements in terms of dual‐quaternions, the associated motion polynomial of the resulting motion can be factored in several ways, each corresponding to a composition of three rotations. By combining two suitable factorizations, an arrangement of six rotary axes is achieved, which possesses a 1‐parametric mobility. In the next step, these axes are connected by links in a way that the resulting linkage is collision‐free over the complete motion cycle. Based on an algorithmic solution for this problem, collision‐free design spaces of the individual links are generated in a post‐processing step. The functionality of the developed design tool is demonstrated in the context of an architectural and artistic application studied in a master‐level studio course. Two results of the performed design experiments were fabricated by the use of computer‐controlled machines to achieve the necessary accuracy ensuring the mobility of the models.
Abstract
Background
The coronavirus pandemic necessitated the rapid transition to virtual care. At a 24-h walk-in mental health Crisis Response Centre (CRC) in Winnipeg, Canada we adapted crisis ...mental health assessments to be offered virtually while the crisis centre also remained open to in person visits. Little is known about the sustainability of virtual visits in the presence of comparable in person care, and which visits are more likely to be done virtually, particularly in the crisis setting.
Methods
An analysis of visits to the CRC from the first local lockdown on March 19, 2020 through the third local wave with heightened public health restrictions in June 2021. Analysis of Variance was used to compare the proportion of visits occurring virtually (telephone or videoconference) during the first wave of heightened public health restrictions (lockdown 1) and subsequent lockdowns as well as the in-between periods. A binary logistic regression examined visit, sociodemographic and clinical factors associated with receipt of a virtual visit compared to an in person visit over the first year of the pandemic.
Results
Out of 5,357 visits, 993 (18.5%) occurred virtually. There was a significant difference in proportion of virtual visits across the pandemic time periods (
F
(4, 62) = 8.56,
p
< .001). The proportion of visits occurring virtually was highest during lockdown 1 (mean 32.6% by week), with no differences between the other time periods. Receipt of a virtual visit was significantly associated with daytime weekday visits, age, non-male gender, living further away from the CRC, no prior year contact with the CRC, and visits that did not feature suicidal behaviour, substance use, psychosis or cognitive impairment.
Conclusions
A large proportion of virtual care occurring at the outset of the pandemic reflects public anxiety and care avoidance paired with health system rapid transformation. The use of virtual visits reduced over subsequent pandemic periods but was sustained at a meaningful level. Specific visit, sociodemographic and clinical characteristics are more likely to be present in visits occurring virtually compared to those in person. These results can help to inform the future planning and delivery of virtual crisis care.
The facultative intracellular pathogen Salmonella enterica resides in a special membrane compartment of the host cell and modifies its host to achieve intracellular survival and proliferation. The ...type III secretion system encoded by Salmonella pathogenicity island 2 (SPI2) has a central role in the interference of intracellular Salmonella with host cell functions. SPI2 function affects antimicrobial defense mechanisms of the host, intracellular transport processes, integrity and function of the cytoskeleton and host cell death. These modifications are mediated by translocation of a large number of effector proteins by the SPI2 system. In this review, we summarize recent work on the cellular phenotypes related to SPI2 function and contribution of SPI2 effector proteins to these manipulations. These studies reveal a complex set of pathogenic interferences between intracellular Salmonella and its host cells.
Background Studies have shown that staff who support adults with intellectual disabilities (ID) are exposed to challenging behaviour in their work including client aggression. Exposure to aggressive ...behaviour has been associated with staff stress and burnout. Study samples have been small however, and there has been very little data exploring this issue among North American staff.
Methods A cross‐sectional survey which included demographics, measures of frequency and severity (including perceived severity and a standardised severity score) of exposure to client aggression and the Maslach Burnout Inventory – Human Services Survey (MBI‐HSS) was completed by 926 community staff who support adults with ID in Ontario, Canada. Relationships between demographic variables and exposure to aggression were examined with descriptive statistics. Pearson correlations were used to analyse exposure variables and MBI‐HSS scores.
Results Nearly all staff reported being exposed to client aggression in the prior 6 months. Mean MBI‐HSS scores were comparable to previously published data in similar populations with the exception of a higher score in the personal accomplishment domain. All measures of exposure to aggression were significantly positively correlated with MBI‐HSS scores in the emotional exhaustion and depersonalisation dimensions of burnout.
Conclusions The prevalence of burnout in this North American sample is comparable to what has been reported in similar populations in other locations, although these staff may have a higher sense of accomplishment with regard to their work. Findings from this large sample support the evidence that exposure to client aggression affects staff emotional well‐being but is by no means the only important factor. Further study is needed to explore the differences and similarities reported here as well as other contributing factors which will guide the implementation of effective strategies to improve staff well‐being.
Revisions to the posttraumatic stress disorder (PTSD) diagnostic criteria in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM‐5; American Psychiatric Association, ...2013) clarify that secondary exposure can lead to the development of impairing symptoms requiring treatment. Historically known as secondary traumatic stress (STS), this reaction occurs through repeatedly hearing the details of traumatic events experienced by others. Professionals who work therapeutically with trauma victims may be at particular risk for this exposure. This meta‐analysis of 38 published studies examines 17 risk factors for STS among professionals indirectly exposed to trauma through their therapeutic work with trauma victims. Small significant effect sizes were found for trauma caseload volume (r = .16), caseload frequency (r = .12), caseload ratio (r = .19), and having a personal trauma history (r = .19). Small negative effect sizes were found for work support (r = −.17) and social support (r = −.26). Demographic variables appear to be less implicated although more work is needed that examines the role of gender in the context of particular personal traumas. Caseload frequency and personal trauma effect sizes were moderated by year of publication. Future work should examine the measurement of STS and associated impairment, understudied risk factors, and effective interventions.
Resumen
Revisiones de los criterios diagnósticos de la quinta edición del Manual Diagnóstico y Estadístico DSM 5 para el trastorno por estrés post traumático (TEPT) clarifican que la exposición secundaria puede conducir al desarrollo de síntomas de deterioro que requieren tratamiento. Históricamente conocida como estrés traumático secundario (ETS), esta reacción ocurre al escuchar repetidamente los detalles de un evento traumático experimentado por otras personas. Los profesionales que trabajan terapéuticamente con víctimas de trauma pueden estar particularmente en riesgo de esta exposición.
Este meta análisis de 38 estudios publicados examina 17 factores de riesgo para ETS entre profesionales indirectamente expuestos al trauma a través de su trabajo terapéutico con víctimas de trauma.
Se encontraron tamaños de efectos pequeños y significativos para: el volumen de casos de trauma asignados (r = .16), frecuencia de casos asignados (r = .12), proporción de casos atendidos (r = .19) y tener historia personal de trauma (r = .19). Tamaños de efecto pequeños y negativos fueron encontrados para el apoyo en el trabajo (r = −.17) y apoyo social (r = −.26). Las variables demográficas parecen estar menos implicadas aunque se necesitan más trabajos que examinen el rol del género en el contexto del trauma personal en particular. El tamaño de los efectos de la frecuencia de casos asignados y del trauma personal fue moderado por el año de la publicación. Futuros trabajos debieran examinar la medición del ETS y deterioro asociado, los factores de riesgo poco estudiados e intervenciones efectivas.
抽象
Traditional and Simplified Chinese s by AsianSTSS
標題: 與創傷受害者進行治療工作的繼發性創傷壓力風險因素元分析
撮要: 《精神疾病診斷與統計手冊》第五版(DSM‐5)中，對創傷後壓力症(PTSD) 診斷準則的修正，澄清繼發性暴露能引致功能損傷症狀，需要治療。這種反應長久以來被稱為繼發性創傷壓力(STS)，透過重複聽見他人所經歷的創傷性事件細節而發生。與創傷受害者進行治療工作的專業人士，有可能在這種暴露下有特殊風險。這項元分析透過38份已出版的研究，檢視專業人士在對創傷受害者進行治療工作時，間接暴露於創傷的17個STS風險因素。在創傷工作容量(r = .16)、工作量頻次(r = .12)、工作量比例(r = .19)及擁有個人創傷壓史(r = .19)方面，均有小型顯著的效應量。 職場支持(r = −.17)及社會支持(r = −.26)方面均有小型的負效應量。雖然人口統計變量顯示受較少牽連，但仍需進一步研究以檢視性別在特殊的個人創傷語境中擔當的角色。工作量頻次及個人創傷的效應量受出版年份而有所調度。未來的研究應檢視STS及其相關功能損傷的測量方法、缺乏研究的風險因素及有效的干預方法。
标题: 与创伤受害者进行治疗工作的继发性创伤压力风险因素元分析
撮要: 《精神疾病诊断与统计手册》第五版(DSM‐5)中，对创伤后压力症(PTSD) 诊断准则的修正，澄清继发性暴露能引致功能损伤症状，需要治疗。这种反应长久以来被称为继发性创伤压力(STS)，透过重复听见他人所经历的创伤性事件细节而发生。与创伤受害者进行治疗工作的专业人士，有可能在这种暴露下有特殊风险。这项元分析透过38份已出版的研究，检视专业人士在对创伤受害者进行治疗工作时，间接暴露于创伤的17个STS风险因素。在创伤工作容量(r = .16)、工作量频次(r = .12)、工作量比例(r = .19)及拥有个人创伤压史(r = .19)方面，均有小型显著的效应量。 职场支持(r = −.17)及社会支持(r = −.26)方面均有小型的负效应量。虽然人口统计变量显示受较少牵连，但仍需进一步研究以检视性别在特殊的个人创伤语境中担当的角色。工作量频次及个人创伤的效应量受出版年份而有所调度。未来的研究应检视STS及其相关功能损伤的测量方法、缺乏研究的风险因素及有效的干预方法。
ObjectivesThe aim of this study was to investigate physician benzodiazepine (BZD) self-use pre-COVID-19 pandemic and to examine changes in BZD self-use during the first year of the ...pandemic.DesignPopulation-based retrospective cohort study using linked routinely collected administrative health data comparing the first year of the pandemic to the period before the pandemic.SettingProvince of Ontario, Canada between March 2016 and March 2021.ParticipantsInterventionOnset of the COVID-19 pandemic in March 2020.Outcomes measuresThe primary outcome measure was the receipt of one or more prescriptions for BZD, which was captured via the Narcotics Monitoring System.ResultsIn a cohort of 30 798 physicians (mean age 42, 47.8% women), we found that during the year before the pandemic, 4.4% of physicians had 1 or more BZD prescriptions. Older physicians (6.8% aged 50+ years), female physicians (5.1%) and physicians with a prior mental health (MH) diagnosis (12.4%) were more likely than younger (3.7% aged <50 years), male physicians (3.8%) and physicians without a prior MH diagnosis (2.9%) to have received 1 or more BZD prescriptions. The first year of the COVID-19 pandemic was associated with a 10.5% decrease (adjusted OR (aOR) 0.85, 95% CI: 0.80 to 0.91) in the number of physicians with 1 or more BZD prescriptions compared with the year before the pandemic. Female physicians were less likely to reduce BZD self-use (aORfemale=0.90, 95% CI: 0.83 to 0.98) compared with male physicians (aORmale=0.79, 95% CI: 0.72 to 0.87, pinteraction=0.046 during the pandemic. Physicians presenting with an incident MH visit had higher odds of filling a BZD prescription during COVID-19 compared with the prior year.ConclusionsPhysicians’ BZD prescriptions decreased during the first year of the COVID-19 pandemic in Ontario, Canada. These findings suggest that previously reported increases in mental distress and MH visits among physicians during the pandemic did not lead to greater self-use of BZDs.
Objective To assess the experience of virtual care among both patients and physicians across a range of clinical scenarios during the COVID-19 pandemic. Methods A web-based survey was disseminated to ...patients and physicians through a variety of media and healthcare communications from May 2020 to July 2021. Demographic details and attitudes across a range of virtual care domains were collected. Quantitative responses were analyzed descriptively. Open-text responses were gathered to contrast when a virtual visit was superior or inferior to an in-person one, and a thematic content analysis was used. Results There were 197 patients and 93 physician respondents, representing a range of demographic and practice characteristics. Patients noted several benefits of virtual care and felt it should continue to be available. Physicians felt they could do a lot of their care virtually. Common themes related to the superiority of virtual care were for “quick” visits, reviewing test results, chronic disease monitoring, and medication needs. Virtual care was less ideal when a physical exam was needed, and was not perceived as a good fit for an individual's cultural, language, or emotional needs. Certain conditions were identified as both ideal and non-ideal for the virtual format (e.g. mental healthcare). Discussion Certain situations are more amenable to virtual care with personal preferences among both patients and physicians. Future priorities should ensure that virtual care is effective across the range of clinical situations in which it may be used and that both virtual and in-person options are equally available to those who want them.
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