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.

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.

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.

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.

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.

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.

A systematic review of the relationship between weight status perceptions and weight loss attempts, strategies, behaviours and outcomes.

It is commonly assumed that a person identifying that they are 'overweight' is an important prerequisite to successful weight management. However, there has been no systematic evaluation of evidence supporting this proposition. The aim of the present research was to systematically review evidence on the relationship between perceived overweight and (i) weight loss attempts, (ii) weight control strategies (healthy and unhealthy), (iii) weight-related behaviours (physical activity and eating habits), (iv) disordered eating and (v) weight change. We synthesized evidence from 78 eligible studies and evaluated evidence linking perceived overweight with outcome variables separately according to the gender, age and objective weight status of study participants. Results indicated that perceived overweight was associated with an increased likelihood of attempting weight loss and with healthy and unhealthy weight control strategies in some participant groups. However, perceived overweight was not reliably associated with physical activity or healthy eating and was associated with greater disordered eating in some groups. Rather than being associated with improved weight management, there was consistent evidence that perceived overweight was predictive of increased weight gain over time. Individuals who perceive their weight status as overweight are more likely to report attempting weight loss but over time gain more weight.

Benefit of continuous treatment for responders with newly diagnosed multiple myeloma in the randomized FIRST trial.

The phase 3, randomized Frontline Investigation of Revlimid and Dexamethasone Versus Standard Thalidomide (FIRST) trial investigating lenalidomide plus low-dose dexamethasone until disease progression (Rd continuous) vs melphalan, prednisone and thalidomide for 12 cycles (MPT) and Rd for 18 cycles (Rd18) in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM) showed that Rd continuous prolonged progression-free survival and overall survival compared with MPT. A subanalysis of the FIRST trial was conducted to determine the benefits of Rd continuous in patients with NDMM based on depth of response. Patients randomized 1:1:1 to Rd continuous, Rd18 or MPT were divided into subgroups based on best response: complete response (CR; n=290), ⩾very good partial response (VGPR; n=679), ⩾partial response (PR; n=1 225) or ⩽stable disease (n=299). Over 13% of patients receiving Rd continuous who achieved ⩾VGPR as best response did so beyond 18 months of treatment. Rd continuous reduced the risk of progression or death by 67%, 51% and 35% vs MPT in patients with CR, ⩾VGPR and ⩾PR, respectively. Similarly, Rd continuous reduced the risk of progression or death by 61%, 54% and 38% vs Rd18 in patients with CR, ⩾VGPR and ⩾PR, respectively. In patients with CR, ⩾VGPR or ⩾PR, 4-year survival rates in the Rd continuous arm (81.1%, 73.1% or 64.6%, respectively) were higher vs MPT (70.8%, 59.8% or 57.2%, respectively) and similar vs Rd18 (76.5%, 67.7% and 62.5%, respectively). Rd continuous improved efficacy outcomes in all responding patients, including those with CR, compared with fixed duration treatment.

Focal irreversible electroporation for prostate cancer: functional outcomes and short-term oncological control.

BACKGROUND: Current data on the use of irreversible electroporation (IRE) in the treatment of prostate cancer (PCa) is limited. We aim to evaluate the safety, short-term functional and oncological outcomes of focal IRE in low-intermediate risk PCa. METHODS: Between February 2013 and May 2014, 32 consecutive men underwent IRE at a single centre. Patients with low-intermediate risk PCa who had not received previous PCa treatment were included for analysis. The tumour was ablated using 3-6 electrodes, ensuring a minimum 5-mm safety margin around the visible magnetic resonance imaging (MRI) lesion. Follow-up included recording Clavien complications, Expanded Prostate Cancer Index Composite (EPIC) questionnaires (baseline, 1.5, 3, 6 months), 6-month multi-parametric MRI (mp-MRI) and 7-month biopsy. Findings on mp-MRI and biopsy were sub-divided into infield, adjacent or outfield of the treatment zone. RESULTS: Twenty-five men were included for final analysis. Safety follow-up revealed one Clavien Grade 3 complication and five Grade 1 complications. Functional follow-up confirmed no significant change in American Urological Association urinary symptom score, sexual or bowel function. Infield, there were no suspicious findings on mp-MRI (n=24) or biopsy (n=21) in all patients. Adjacent to the treatment zone, five (21%) had suspicious findings on mp-MRI with four (19%) proving to be significant on biopsy. Outfield, there were two (8%) with suspicious findings on mp-MRI and one (5%) significant finding on biopsy. For the five patients with significant findings on follow-up biopsy, one is awaiting repeat IRE, one had radical prostatectomy and three remained on active surveillance. CONCLUSIONS: In selected patients with low-intermediate risk PCa, focal IRE appears to be safe with minimal morbidity. There were no infield recurrences and 76% of patients were histologically free of significant cancer at 8 months. Almost all recurrences were adjacent to the treatment zone, and this was addressed by widening the treatment margins.

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.

Cost-effectiveness of lenalidomide plus dexamethasone vs. bortezomib plus melphalan and prednisone in transplant-ineligible U.S. patients with newly-diagnosed multiple myeloma.

OBJECTIVE: To conduct a cost-effectiveness assessment of lenalidomide plus dexamethasone (Rd) vs bortezomib plus melphalan and prednisone (VMP) as initial treatment for transplant-ineligible patients with newly-diagnosed multiple myeloma (MM), from a U.S. payer perspective. METHODS: A partitioned survival model was developed to estimate expected life-years (LYs), quality-adjusted LYs (QALYs), direct costs and incremental costs per QALY and LY gained associated with use of Rd vs VMP over a patient's lifetime. Information on the efficacy and safety of Rd and VMP was based on data from multinational phase III clinical trials and a network meta-analysis. Pre-progression direct costs included the costs of Rd and VMP, treatment of adverse events (including prophylaxis) and routine care and monitoring associated with MM. Post-progression direct costs included costs of subsequent treatment(s) and routine care and monitoring for progressive disease, all obtained from published literature and estimated from a U.S. payer perspective. Utilities were obtained from the aforementioned trials. Costs and outcomes were discounted at 3% annually. RESULTS: Relative to VMP, use of Rd was expected to result in an additional 2.22 LYs and 1.47 QALYs (discounted). Patients initiated with Rd were expected to incur an additional $78,977 in mean lifetime direct costs (discounted) vs those initiated with VMP. The incremental costs per QALY and per LY gained with Rd vs VMP were $53,826 and $35,552, respectively. In sensitivity analyses, results were found to be most sensitive to differences in survival associated with Rd vs VMP, the cost of lenalidomide and the discount rate applied to effectiveness outcomes. CONCLUSIONS: Rd was expected to result in greater LYs and QALYs compared with VMP, with similar overall costs per LY for each regimen. Results of this analysis indicated that Rd may be a cost-effective alternative to VMP as initial treatment for transplant-ineligible patients with MM, with an incremental cost-effectiveness ratio well within the levels for recent advancements in oncology.

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.

Bortezomib in multiple myeloma: a practice guideline.

AIMS: Bortezomib (Velcade™, PS-341), a first-in-class proteasome inhibitor, has been extensively studied either alone or in combination with other agents for the treatment of multiple myeloma. We created a provincial guideline for the use of bortezomib, in newly diagnosed individuals (both eligible and ineligible for transplant) and in individuals with relapsed or refractory multiple myeloma. MATERIALS AND METHODS: A systematic review was conducted searching MEDLINE, EMBASE, the Cochrane Library and relevant meeting abstracts. Outcomes of interest were survival, disease control, response rate, response duration, quality of life and adverse effects. Members of the Cancer Care Ontario Hematology Disease Site Group (CCO HDSG), comprising physicians with content expertise, epidemiologists and consumers, developed a guideline through a systematic process that involved assessment of the best available evidence, consensus interpretation of the evidence and a validation process involving practitioners across the province. RESULTS: The CCO HDSG recommends the use of bortezomib-based combinations in previously untreated patients with multiple myeloma who are candidates for autologous stem cell transplantation and in individuals who are ineligible for autologous stem cell transplantation. The group further recommends the use of bortezomib, alone or in combination, for patients with relapsed/refractory disease. The evidence did not establish a subgroup of patients with myeloma that should be uniquely targeted for therapy with bortezomib. Qualifying statements by the HDSG address alternative dosing options, the management of cytopenias and the prevention of toxicities, including herpes zoster reactivation. CONCLUSIONS: Bortezomib alone or in combination with other agents can be recommended for both previously untreated or relapsed/refractory patients with multiple myeloma. Guidelines for monitoring and reducing toxicity are provided.