Trends and regional variation in vertebroplasty and kyphoplasty in Switzerland: a population-based small area analysis.

Regional variation in procedure use often reflects the uncertainty about the risks and benefit of procedures. In Switzerland, regional variation in vertebroplasty and balloon kyphoplasty rates was high, although the variation declined between 2013 and 2018. Substantial parts of the variation remained unexplained, and likely signal unequal access and differing physician opinion. PURPOSE: To assess trends and regional variation in percutaneous vertebroplasty (VP) and balloon kyphoplasty (BKP) use across Switzerland. METHODS: We conducted a population-based analysis using patient discharge data from all Swiss acute care hospitals for 2013-2018. We calculated age/sex-standardized mean procedure rates and measures of variation across VP/BKP-specific hospital areas (HSAs). We assessed the influence of potential determinants of variation using multilevel regression models with incremental adjustment for demographics, cultural/socioeconomic, health, and supply factors. RESULTS: We analyzed 7855 discharges with VP/BKP from 31 HSAs. The mean age/sex-standardized procedure rate increased from 16 to 20/100,000 persons from 2013 to 2018. While the variation in procedure rates across HSAs declined, the overall variation remained high (systematic component of variation from 56.8 to 6.9 from 2013 to 2018). Determinants explained 52% of the variation. CONCLUSIONS: VP/BKP procedure rates increased and regional variation across Switzerland declined but remained at a high level. A substantial part of the regional variation remained unexplained by potential determinants of variation.

Variation in global uptake of the Surgical Safety Checklist.

BACKGROUND: The Surgical Safety Checklist (SSC) is a patient safety tool shown to reduce mortality and to improve teamwork and adherence with perioperative safety practices. The results of the original pilot work were published 10 years ago. This study aimed to determine the contemporary prevalence and predictors of SSC use globally. METHODS: Pooled data from the GlobalSurg and Surgical Outcomes studies were analysed to describe SSC use in 2014-2016. The primary exposure was the Human Development Index (HDI) of the reporting country, and the primary outcome was reported SSC use. A generalized estimating equation, clustering by facility, was used to determine differences in SSC use by patient, facility and national characteristics. RESULTS: A total of 85 957 patients from 1464 facilities in 94 countries were included. On average, facilities used the SSC in 75·4 per cent of operations. Compared with very high HDI, SSC use was less in low HDI countries (odds ratio (OR) 0·08, 95 per cent c.i. 0·05 to 0·12). The SSC was used less in urgent compared with elective operations in low HDI countries (OR 0·68, 0·53 to 0·86), but used equally for urgent and elective operations in very high HDI countries (OR 0·96, 0·87 to 1·06). SSC use was lower for obstetrics and gynaecology versus abdominal surgery (OR 0·91, 0·85 to 0·98) and where the common or official language was not one of the WHO official languages (OR 0·30, 0·23 to 0·39). CONCLUSION: Worldwide, SSC use is generally high, but significant variability exists. Implementation and dissemination strategies must be developed to address this variability.

ANTECEDENTES: Se ha demostrado que la utilización de la lista de verificación de seguridad quirúrgica (Surgical Safety Checklist, SSC) reduce la mortalidad y mejora el trabajo en equipo, así como el cumplimiento de las prácticas de seguridad perioperatorias. Los resultados de un trabajo piloto original se publicaron hace 10 años. El objetivo de este estudio fue determinar la prevalencia actual y los predictores de uso de la SSC a nivel mundial. MÉTODOS: Se analizaron los datos agrupados de los estudios GlobalSurg y Surgical Outcomes para describir la utilización de la SSC entre 2014-2016. La principal variable de exposición fue el índice de desarrollo humano (Human Development Index, HDI) del país informante y la principal variable de resultado, la tasa de utilización de la SCC. Para determinar las diferencias en la utilización de la SSC por paciente, centro y características nacionales se utilizó una ecuación de estimación generalizada con conglomerados por centros. RESULTADOS: Se incluyeron 85.957 pacientes de 1.464 centros en 94 países. La tasa media de utilización de la SSC fue del 75,4% de las operaciones. Al compararlos con países de HDI muy alto, la utilización de la SCC fue menor en los países con HDI bajo (razón de oportunidades, odds ratio, OR 0,08, i.c. del 95% 0,05-0,12). En países con HDI bajo, la SSC se utilizó menos en operaciones urgentes en comparación con operaciones electivas (OR 0,68, i.c. del 95% 0,53- 0,86) a diferencia de los países con HDI elevado, en los que se utilizó por igual en ambas situaciones (OR 0,96, i.c. del 95% 0,87-1,06). La utilización de la SSC fue menor en operaciones de obstetricia y ginecología que en cirugía abdominal (OR 0,91, i.c. del 95% 0,85 a 0,98) y en aquellos países en los que el idioma habitual u oficial era diferente a los idiomas oficiales de la OMS (OR 0,30, i.c. del 95% 0,23 a 0,39). CONCLUSIÓN: A nivel mundial, el uso de SSC en general es alto, pero existe una variabilidad significativa. Se deben desarrollar estrategias de implementación y difusión para resolver esta variabilidad.

Reducing surgical mortality in Scotland by use of the WHO Surgical Safety Checklist.

BACKGROUND: The WHO Surgical Safety Checklist has been implemented widely since its launch in 2008. It was introduced in Scotland as part of the Scottish Patient Safety Programme (SPSP) between 2008 and 2010, and is now integral to surgical practice. Its influence on outcomes, when analysed at a population level, remains unclear. METHODS: This was a population cohort study. All admissions to any acute hospital in Scotland between 2000 and 2014 were included. Standardized differences were used to estimate the balance of demographics over time, after which interrupted time-series (segmented regression) analyses were performed. Data were obtained from the Information Services Division, Scotland. RESULTS: There were 12 667 926 hospital admissions, of which 6 839 736 had a surgical procedure. Amongst the surgical cohort, the inpatient mortality rate in 2000 was 0·76 (95 per cent c.i. 0·68 to 0·84) per cent, and in 2014 it was 0·46 (0·42 to 0·50) per cent. The checklist was associated with a 36·6 (95 per cent c.i. -55·2 to -17·9) per cent relative reduction in mortality (P < 0·001). Mortality rates before implementation were decreasing by 0·003 (95 per cent c.i. -0·017 to +0·012) per cent per year; annual decreases of 0·069 (-0·092 to -0·046) per cent were seen during, and 0·019 (-0·038 to +0·001) per cent after, implementation. No such improvement trends were seen in the non-surgical cohort over this time frame. CONCLUSION: Since the implementation of the checklist, as part of an overall national safety strategy, there has been a reduction in perioperative mortality.

Quality of life after hepatic resection.

BACKGROUND: Long-term quality of life (QoL) after liver resection is becoming increasingly important, as improvements in operative methods and perioperative care have decreased morbidity and mortality rates. In this study, postoperative QoL after resection of benign or malignant liver tumours was evaluated. METHODS: In this single-centre study, QoL was evaluated prospectively using the European Organisation for Research and Treatment of Cancer QLQ-C30 and the liver-specific QLQ-LMC21 module before, and 1, 3, 6 and 12 months after open or laparoscopic liver surgery. RESULTS: Between June 2007 and January 2013, 188 patients (130 with malignant and 58 with benign tumours) requiring major liver resection were included. Global health status was no different between the two groups before and 1 month after liver resection. All patients showed an improvement in global health status at 3, 6 and 12 months after surgery. Patients with benign tumours had better global health status than those with malignant tumours at these time points (P < 0·001, P = 0·002 and P = 0·006 respectively). Patients with benign disease had better physical function scores (P = 0·011, P = 0·025 and P = 0·041) and lower fatigue scores (P = 0·001, P = 0·002 and P = 0·002) at 3, 6 and 12 months than those with malignant disease. CONCLUSION: This study confirmed overall good QoL in patients undergoing liver resection for benign or malignant tumours, which improved after surgery. Benign diseases were associated with better short- and long-term QoL scores.

Deconstructing knowledge brokering for commissioned rapid reviews: an observational study.

BACKGROUND: Knowledge brokers are increasingly used by policy agencies, yet little is known about how they engage with policy-makers and facilitate discussions with them about their research needs. This study examines knowledge brokers' behaviour in one-off interactions with policy-makers commissioning rapid reviews. It describes how knowledge brokers engage with policy-makers, build trust and gain agreement about the review's parameters. METHODS: We observed and transcribed 15 structured knowledge brokering sessions and used line-by-line analysis to derive, test and refine a coding schedule. The final coding schedule was applied to all transcripts. We assigned 35 codes to three tasks identified in the data, namely eliciting information, exploring the policy context and negotiating the content of reviews. RESULTS: The knowledge brokers we observed were skilled facilitators who built trust by their open stance, neutrality, and knowledge of research and policy contexts. Trust engendered an interplay of expertise in which review questions and scope were clarified and contextual factors evaluated. Negotiation about the content of the review focused on understanding how it would contribute to the policy process, comparing options and assessing feasibility. Key functions of knowledge brokers included eliciting and clarifying information, linking the review questions to the context and purpose, moving fluidly between policy and research perspectives, and weighing up review options against policy objectives. Four knowledge brokering roles were identified, namely diagnostic, facilitative, deliberative and interpretative. CONCLUSIONS: This study identified ways in which knowledge brokers established rapport with policy-makers who commissioned reviews, enabled disclosure of essential information and explored contextual factors that affected the review's purpose and intended use. Knowledge brokers were competent in the discourse and conventions of both policy and research and were skilled in negotiating complex policy and political environments, assisting policy-makers to evaluate options and craft a review proposal that was targeted, responsive and feasible. Mutuality, respect and an interplay of expertise were integral to the knowledge brokering process. Future research might usefully examine whether other rapid review programmes using knowledge brokers have similar results as well as the transferability of the four knowledge brokering roles to other contexts and settings.

The Diagnostic Performance of Multiparametric Magnetic Resonance Imaging to Detect Significant Prostate Cancer.

PURPOSE: We assess the accuracy of multiparametric magnetic resonance imaging for significant prostate cancer detection before diagnostic biopsy in men with an abnormal prostate specific antigen/digital rectal examination. MATERIALS AND METHODS: A total of 388 men underwent multiparametric magnetic resonance imaging, including T2-weighted, diffusion weighted and dynamic contrast enhanced imaging before biopsy. Two radiologists used PI-RADS to allocate a score of 1 to 5 for suspicion of significant prostate cancer (Gleason 7 with more than 5% grade 4). PI-RADS 3 to 5 was considered positive. Transperineal template guided mapping biopsy of 18 regions (median 30 cores) was performed with additional manually directed cores from magnetic resonance imaging positive regions. The anatomical location, size and grade of individual cancer areas in the biopsy regions (18) as the primary outcome and in prostatectomy specimens (117) as the secondary outcome were correlated to the magnetic resonance imaging positive regions. RESULTS: Of the 388 men who were enrolled in the study 344 were analyzed. Multiparametric magnetic resonance imaging was positive in 77.0% of patients, 62.5% had prostate cancer and 41.6% had significant prostate cancer. The detection of significant prostate cancer by multiparametric magnetic resonance imaging had a sensitivity of 96%, specificity of 36%, negative predictive value of 92% and positive predictive value of 52%. Adding PI-RADS to the multivariate model, including prostate specific antigen, digital rectal examination, prostate volume and age, improved the AUC from 0.776 to 0.879 (p <0.001). Anatomical concordance analysis showed a low mismatch between the magnetic resonance imaging positive regions and biopsy positive regions (4 [2.9%]), and the significant prostate cancer area in the radical prostatectomy specimen (3 [3.3%]). CONCLUSIONS: In men with an abnormal prostate specific antigen/digital rectal examination, multiparametric magnetic resonance imaging detected significant prostate cancer with an excellent negative predictive value and moderate positive predictive value. The use of multiparametric magnetic resonance imaging to diagnose significant prostate cancer may result in a substantial number of unnecessary biopsies while missing a minimum of significant prostate cancers.

The impact of total body irradiation on the outcome of patients with follicular lymphoma treated with autologous stem-cell transplantation in the modern era: a retrospective study of the EBMT Lymphoma Working Party.

BACKGROUND: The aim of this study was to investigate the impact of the high-dose regimen on the outcome of patients with follicular lymphoma (FL) having had autologous stem-cell transplantation (ASCT) in a recent time period. PATIENTS: Between 1995 and 2007, 2233 patients with FL had their first ASCT with either a total body irradiation (TBI)-containing regimen or carmustin, etoposide, cytarabine and melphalan (BEAM), of which 47% were autografted in first remission. RESULTS: After a median observation time of 73 months (interquartile range 30-107), 5- and 10-year non-relapse mortality (NRM) was similar (6% and 10% in both groups). No significant NRM differences became evident after multivariate adjustment for confounders. Secondary malignancies were observed in 9.7% and 7.9% of the patients after TBI and BEAM (P = 0.19), which were treatment-related myelodysplastic syndromes/acute myelogenous leukaemia (t-MDS/AML) in 3.4% and 2.8% (P = 0.57). The median time to t-MDS/AML was around 50 months in both groups. Because of a lower relapse incidence, TBI was associated with better event-free survival reaching statistical significance in the patients transplanted in first remission but not in those transplanted beyond first remission. CONCLUSIONS: In patients with FL who received TBI-based ASCT after 1995 increased NRM and t-MDS/AML risks did not emerge compared with BEAM while disease control was at least equivalent.

Bortezomib in multiple myeloma: systematic review and clinical considerations.

We conducted a systematic review to determine the appropriate use of bortezomib alone or in combination with other agents in patients with multiple myeloma (mm). We searched medline, embase, the Cochrane Library, conference proceedings, and the reference lists of included studies. We analyzed randomized controlled trials and systematic reviews if they involved adult mm patients treated with bortezomib and if they reported on survival, disease control, response, quality of life, or adverse effects. Twenty-six unique studies met the inclusion criteria. For patients with previously untreated mm and for candidates for transplantation, we found a statistically significant benefit in time to progression [hazard ratio (hr): 0.48, p < 0.001; and hr: 0.63, p = 0.006, respectively] and a better response with a bortezomib than with a non-bortezomib regimen (p < 0.001). Progression-free survival was longer with bortezomib and thalidomide than with thalidomide alone (p = 0.01). In non-candidates for transplantation, a significant benefit in overall survival was observed with a bortezomib regimen (hr compared with a non-bortezomib regimen: 0.61; p = 0.008), and in transplantation candidates receiving bortezomib, the response rate was improved after induction (p = 0.004) and after a first transplant (p = 0.016). In relapsed or refractory mm, overall survival (p = 0.03), time to progression (hr: 1.82; p = 0.000004), and progression-free survival (hr: 1.69; p = 0.000026) were significantly improved with bortezomib and pegylated liposomal doxorubicin (compared with bortezomib alone), and bortezomib monotherapy was better than dexamethasone alone (hr: 0.77; p = 0.027). Bortezomib combined with thalidomide and dexamethasone was better than either bortezomib monotherapy or thalidomide with dexamethasone (p < 0.001). In previously untreated or in relapsed or refractory mm patients, bortezomib-based therapy has improved disease control and, in some patients, overall survival.

A radiation hybrid transcript map of the mouse genome.

Expressed-sequence tag (EST) maps are an adjunct to sequence-based analytical methods of gene detection and localization for those species for which such data are available, and provide anchors for high-density homology and orthology mapping in species for which large-scale sequencing has yet to be done. Species for which radiation hybrid-based transcript maps have been established include human, rat, mouse, dog, cat and zebrafish. We have established a comprehensive first-generation-placement radiation hybrid map of the mouse consisting of 5,904 mapped markers (3,993 ESTs and 1,911 sequence-tagged sites (STSs)). The mapped ESTs, which often originate from small-EST clusters, are enriched for genes expressed during early mouse embryogenesis and are probably different from those localized in humans. We have confirmed by in situ hybridization that even singleton ESTs, which are usually not retained for mapping studies, may represent bona fide transcribed sequences. Our studies on mouse chromosomes 12 and 14 orthologous to human chromosome 14 show the power of our radiation hybrid map as a predictive tool for orthology mapping in humans.

A radiation hybrid map of mouse genes.

A comprehensive gene-based map of a genome is a powerful tool for genetic studies and is especially useful for the positional cloning and positional candidate approaches. The availability of gene maps for multiple organisms provides the foundation for detailed conserved-orthology maps showing the correspondence between conserved genomic segments. These maps make it possible to use cross-species information in gene hunts and shed light on the evolutionary forces that shape the genome. Here we report a radiation hybrid map of mouse genes, a combined project of the Whitehead Institute/Massachusetts Institute of Technology Center for Genome Research, the Medical Research Council UK Mouse Genome Centre, and the National Center for Biotechnology Information. The map contains 11,109 genes, screened against the T31 RH panel and positioned relative to a reference map containing 2,280 mouse genetic markers. It includes 3,658 genes homologous to the human genome sequence and provides a framework for overlaying the human genome sequence to the mouse and for sequencing the mouse genome.

A YAC-based physical map of the mouse genome.

A physical map of the mouse genome is an essential tool for both positional cloning and genomic sequencing in this key model system for biomedical research. Indeed, the construction of a mouse physical map with markers spaced at an average interval of 300 kb is one of the stated goals of the Human Genome Project. Here we report the results of a project at the Whitehead Institute/MIT Center for Genome Research to construct such a physical map of the mouse. We built the map by screening sequenced-tagged sites (STSs) against a large-insert yeast artificial chromosome (YAC) library and then integrating the STS-content information with a dense genetic map. The integrated map shows the location of 9,787 loci, providing landmarks with an average spacing of approximately 300 kb and affording YAC coverage of approximately 92% of the mouse genome. We also report the results of a project at the MRC UK Mouse Genome Centre targeted at chromosome X. The project produced a YAC-based map containing 619 loci (with 121 loci in common with the Whitehead map and 498 additional loci), providing especially dense coverage of this sex chromosome. The YAC-based physical map directly facilitates positional cloning of mouse mutations by providing ready access to most of the genome. More generally, use of this map in addition to a newly constructed radiation hybrid (RH) map provides a comprehensive framework for mouse genomic studies.

Long-term survival after treatment for Hodgkin's disease (1973-2002): improved survival with successive 10-year cohorts.

BACKGROUND: The Nottinghamshire Lymphoma Registry contains the details of all the patients diagnosed with lymphoma (since 1 January 1973) within a defined geographical area with a population of 1.1 million. It was therefore possible to study the outcome of treatment for Hodgkin's disease for three 10-year cohorts (1973-1982, 1983-1992 and 1993-2002).The aims of the study were to compare survival time among the three patient cohorts, to identify prognostic factors and to estimate relative survival. METHODS: A total of 745 patients diagnosed between 1973 and 2002 were analysed for survival. Survivorship was estimated by the Kaplan-Meier method and parametric survival models. An accelerated failure-time regression was used for multivariate analysis. RESULTS: Overall, patients were observed for 9.8 (0.3-34.82) years (median(range)), on average. One, five and fifteen-year disease-specific survival was found to be 87% (85-90%), 77% (74-80%) and 70% (67-74%), respectively. For those for diagnosed between 1973 and 1982, the 15-year survival was found to be 57%; for 1983-1992, it was 74% and for 1993-2002, it was 83% (P<0.001). The difference remained significant after adjusting for prognostic factors. The actuarial risk of developing a second malignancy at 20 years was for the 1973-1982 cohort, 12.4%, and for the 1983-1992 cohort, 18.8%. CONCLUSION: Treatment advances and effective management of toxicities of treatment over time, have resulted in a significantly longer survival for patients with Hodgkin's disease diagnosed within a defined population.

Seasonal Phenology of Velvet Longhorned Beetle, Trichoferus campestris (Coleoptera: Cerambycidae) in Minnesota.

Knowledge of a species' phenology can assist with timing accurate surveys to detect presence and density in a novel environment. Trichoferus campestris (Faldermann) (Coleoptera: Cerambycidae) has been found in the United States since the 1990s, but its biology and behavior remain poorly understood. This study investigated the phenology of T. campestris in Minneapolis and St. Paul, Minnesota, USA, based on local temperature data. In the summers of 2019 and 2020, 30 and 40 pheromone-baited traps, respectively, were deployed in trees in suburban parks to monitor capture of local individuals. Traps were suspended from branches of mature trees selected at random, with nine genera of trees selected over both years. Early, peak, and late adult abundance were characterized, and the impact of tree genus in which each trap was hung was evaluated. Abundance was found to be unimodal both summers with a peak around 650 degree days (base 10°C) in early July. Significantly more adult T. campestris were caught in traps hung in trees of the genus Tilia than in trees of the genus Quercus. These findings are important first steps to improving monitoring of T. campestris presence and conducting risk assessments.

An international phase II trial of single-agent lenalidomide for relapsed or refractory aggressive B-cell non-Hodgkin's lymphoma.

BACKGROUND: Lenalidomide is an immunomodulatory agent with antitumor activity in B-cell malignancies. This phase II trial aimed to demonstrate the safety and efficacy of lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), follicular grade 3 lymphoma (FL-III), or transformed lymphoma (TL). METHODS: Patients received oral lenalidomide 25 mg on days 1-21 every 28 days as tolerated or until progression. The primary end point was overall response rate (ORR). RESULTS: Two hundred and seventeen patients enrolled and received lenalidomide. The ORR was 35% (77/217), with 13% (29/217) complete remission (CR), 22% (48/217) partial remission, and 21% (45/217) with stable disease. The ORR for DLBCL was 28% (30/108), 42% (24/57) for MCL, 42% (8/19) for FL-III, and 45% (15/33) for TL. Median progression-free survival for all 217 patients was 3.7 months [95% confidence interval (CI) 2.7-5.1]. For 77 responders, the median response duration lasted 10.6 months (95% CI 7.0-NR). Median response duration was not reached in 29 patients who achieved a CR and in responding patients with FL-III or MCL. The most common adverse event was myelosuppression with grade 4 neutropenia and thrombocytopenia in 17% and 6%, respectively. CONCLUSION: Lenalidomide is well tolerated and produces durable responses in patients with relapsed or refractory aggressive non-Hodgkin's lymphoma.

CSACI guidelines for the ethical, evidence-based and patient-oriented clinical practice of oral immunotherapy in IgE-mediated food allergy.

BACKGROUND: Oral immunotherapy (OIT) is an emerging approach to the treatment of patients with IgE-mediated food allergy and is in the process of transitioning to clinical practice. OBJECTIVE: To develop patient-oriented clinical practice guidelines on oral immunotherapy based on evidence and ethical imperatives for the provision of safe and efficient food allergy management. MATERIALS AND METHODS: Recommendations were developed using a reflective patient-centered multicriteria approach including 22 criteria organized in five dimensions (clinical, populational, economic, organizational and sociopolitical). Data was obtained from: (1) a review of scientific and ethic literature; (2) consultations of allergists, other healthcare professionals (pediatricians, family physicians, nurses, registered dieticians, psychologists, peer supporters), patients and caregivers; and patient associations through structured consultative panels, interviews and on-line questionnaire; and (3) organizational and economic data from the milieu of care. All data was synthesized by criteria in a multicriteria deliberative guide that served as a platform for structured discussion and development of recommendations for each dimension, based on evidence, ethical imperatives and other considerations. RESULTS: The deliberative grid included 162 articles from the literature and media reviews and data from consultations involving 85 individuals. Thirty-eight (38) recommendations were made for the practice of oral immunotherapy for the treatment of IgE mediated food allergy, based on evidence and a diversity of ethical imperatives. All recommendations were aimed at fostering a context conducive to achieving objectives identified by patients and caregivers with food allergy. Notably, specific recommendations were developed to promote a culture of shared responsibility between patients and healthcare system, equity in access, patient empowerment, shared decision making and personalization of OIT protocols to reflect patients' needs. It also provides recommendations to optimize organization of care to generate capacity to meet demand according to patient choice, e.g. OIT or avoidance. These recommendations were made acknowledging the necessity of ensuring sustainability of the clinical offer in light of various economic considerations. CONCLUSIONS: This innovative CPG methodology was guided by patients' perspectives, clinical evidence as well as ethical and other rationales. This allowed for the creation of a broad set of recommendations that chart optimal clinical practice and define the conditions required to bring about changes to food allergy care that will be sustainable, equitable and conducive to the well-being of all patients in need.