Physician supply forecast: better than peering in a crystal ball?

<p>Abstract</p> <p>Background</p> <p>Anticipating physician supply to tackle future health challenges is a crucial but complex task for policy planners. A number of forecasting tools are available, but the methods, advantages and shortcomings of such tools are not straightforward and not always well appraised. Therefore this paper had two objectives: to present a typology of existing forecasting approaches and to analyse the methodology-related issues.</p> <p>Methods</p> <p>A literature review was carried out in electronic databases Medline-Ovid, Embase and ERIC. Concrete examples of planning experiences in various countries were analysed.</p> <p>Results</p> <p>Four main forecasting approaches were identified. The supply projection approach defines the necessary inflow to maintain or to reach in the future an arbitrary predefined level of service offer. The demand-based approach estimates the quantity of health care services used by the population in the future to project physician requirements. The needs-based approach involves defining and predicting health care deficits so that they can be addressed by an adequate workforce. Benchmarking health systems with similar populations and health profiles is the last approach. These different methods can be combined to perform a gap analysis. The methodological challenges of such projections are numerous: most often static models are used and their uncertainty is not assessed; valid and comprehensive data to feed into the models are often lacking; and a rapidly evolving environment affects the likelihood of projection scenarios. As a result, the internal and external validity of the projections included in our review appeared limited.</p> <p>Conclusion</p> <p>There is no single accepted approach to forecasting physician requirements. The value of projections lies in their utility in identifying the current and emerging trends to which policy-makers need to respond. A genuine gap analysis, an effective monitoring of key parameters and comprehensive workforce planning are key elements to improving the usefulness of physician supply projections.</p

Determining crystal structures through crowdsourcing and coursework

We show here that computer game players can build high-quality crystal structures. Introduction of a new feature into the computer game Foldit allows players to build and real-space refine structures into electron density maps. To assess the usefulness of this feature, we held a crystallographic model-building competition between trained crystallographers, undergraduate students, Foldit players and automatic model-building algorithms. After removal of disordered residues, a team of Foldit players achieved the most accurate structure. Analysing the target protein of the competition, YPL067C, uncovered a new family of histidine triad proteins apparently involved in the prevention of amyloid toxicity. From this study, we conclude that crystallographers can utilize crowdsourcing to interpret electron density information and to produce structure solutions of the highest quality

Treatment and outcome patterns in European patients with Waldenström’s macroglobulinaemia: a large, observational, retrospective chart review

Background: Treatment options for Waldenström&apos;s macroglobulinaemia are heterogeneous, and no well established treatment standards exist. Although guidelines from the Eighth International Workshop on Waldenstrom&apos;s Macroglobulinemia were published in 2016, inconsistent awareness and budget constraints have prevented their widespread implementation, and real-life treatment patterns might differ across health-care systems. We aimed to generate information about treatment and outcome patterns for patients with Waldenström&apos;s macroglobulinaemia outside of clinical trials. Methods: In this large, observational, retrospective chart review, academic and community physicians in ten European countries were invited to retrospectively complete electronic records for patients with symptomatic Waldenström&apos;s macroglobulinaemia who had begun treatment after Jan 1, 2000, and before Jan 1, 2014, and had available clinical and biological data. The primary endpoints were reasons for treatment initiation, treatment choices, progression-free survival, and overall survival. We assessed the variables that affected choice of front-line therapy, progression-free survival, and overall survival in multivariate analyses. Findings: Electronic records were reviewed for 454 eligible patients. The most frequent reasons for starting front-line treatment were anaemia (in 328 [72%] patients) and constitutional symptoms (in 264 [58%] patients). Choice of therapy varied between front-line, second-line, and third-line approaches; age; and type of institution. In the front-line setting, 193 (43%) of 454 patients received monotherapy, 164 (36%) received chemoimmunotherapy, and 95 (21%) received other combination regimens (data on front-line treatment were missing for one patient, and another patient received only steroids). After front-line treatment, median progression-free survival was 29 months (95% CI 25–31), median overall survival was not reached (not reached–not reached), and 10-year overall survival was 69% (62–74). In multivariate analyses, patients who were high risk according to the International Prognostic Scoring System for Waldenström Macroglobulinemia had significantly worse progression-free survival and overall survival than did those who were low risk. Additionally, progression-free survival was shortened in patients treated with monotherapy compared with those treated with chemoimmunotherapy or other combination therapies and in those treated at an academic institution compared with those treated in the community. Constitutional symptoms (excluding fatigue) were associated with worsened overall survival. Interpretation: This large observational dataset should inform and help set guidelines, and improve understanding of treatment practices and outcomes, for European patients with Waldenström&apos;s macroglobulinaemia. Funding: Pharmacyclics LLC (an AbbVie company). © 2018 Elsevier Lt

Ibrutinib for the treatment of Bing-Neel syndrome: A multicenter study

The treatment of patients with Bing-Neel syndrome (BNS) is not standardized. We included patients with Waldenström macroglobulinemia (WM) and a radiologic and/or cytologic diagnosis of BNS treated with ibrutinib monotherapy. Response assessment was based on criteria for BNS from the 8th International Workshop for WM. Survival from BNS diagnosis (BNS survival), survival from ibrutinib initiation to last follow-up or death (ibrutinib survival), and time from ibrutinib initiation to ibrutinib discontinuation for toxicity, progression, or death (event-free survival [EFS]) were estimated. Twenty-eight patients were included in our study. The median age at BNS diagnosis was 65 years. Ibrutinib was the first line of treatment for BNS in 39% of patients. Ibrutinib was administered orally at a dose of 560 and 420 mg once daily in 46% and 54% of patients, respectively; symptomatic and radiologic improvements were seen in 85% and 60% of patients within 3 months of therapy. At best response, 85% of patients had improvement or resolution of BNS symptoms, 83% had improvement or resolution of radiologic abnormalities, and 47% had cleared the disease in the cerebrospinal fluid. The 2-year EFS rate with ibrutinib was 80% (95% confidence interval [CI], 58%-91%), the 2-year ibrutinib survival rate was 81% (95% CI, 49%-94%), and the 5-year BNS survival rate was 86% (95% CI, 63%-95%). Ibrutinib therapy is effective in patients with BNS and should be considered as a treatment option in these patients.G.I. was awarded a Young Investigator Award at the 10th International Workshop for Waldenstrom Macroglobulinemia for this research. J.J.C. ¨ thanks the WMR Fund for support

Consensus treatment recommendations from the tenth International Workshop for Waldenström Macroglobulinaemia

Waldenström macroglobulinaemia is an indolent B-cell lymphoma with clearly defined criteria for diagnosis, initiation of therapy, and response, which was established by consensus panels at previous International Workshops for Waldenström Macroglobulinaemia (IWWM). The treatment options for Waldenström macroglobulinaemia continued to be researched after the publication of the eighth IWWM consensus recommendations in 2016, and at the tenth IWWM in New York, USA (October, 2018) an international consensus panel was formed to update treatment recommendations. Participants were selected as members of the consensus panel based on their expertise on Waldenström macroglobulinaemia. The initial live discussion took place during the tenth IWWM meeting and two separate teleconferences were held in June, 2019, and January, 2020, to refine recommendations. No external or financial support was received for the elaboration of these recommendations. According to these updated consensus recommendations, alkylating drugs (bendamustine, cyclophosphamide) and proteasome inhibitors (bortezomib, carfilzomib, ixazomib), both in combination with rituximab, as well as BTK inhibitors (ibrutinib), alone or in combination with rituximab, are preferred first-line therapy options for symptomatic patients with Waldenström macroglobulinaemia. In previously treated patients with Waldenström macroglobulinaemia who had an initial durable response, reuse of a previous regimen or another primary therapy regimen are acceptable options. Novel BTK inhibitors (acalabrutinib, zanubrutinib, tirabrutinib) and the BCL2 antagonist venetoclax appear safe and active, and represent emerging options for the treatment of Waldenström macroglobulinaemia. The choice of therapy should be guided by the patient&apos;s clinical profile, genomic features, and drug availability. © 2020 Elsevier Lt

Treatment and outcome patterns in European patients with Waldenström's macroglobulinaemia : a large, observational, retrospective chart review

Background: Treatment options for Waldenström's macroglobulinaemia are heterogeneous, and no well established treatment standards exist. Although guidelines from the Eighth International Workshop on Waldenstrom's Macroglobulinemia were published in 2016, inconsistent awareness and budget constraints have prevented their widespread implementation, and real-life treatment patterns might differ across health-care systems. We aimed to generate information about treatment and outcome patterns for patients with Waldenström's macroglobulinaemia outside of clinical trials. Methods: In this large, observational, retrospective chart review, academic and community physicians in ten European countries were invited to retrospectively complete electronic records for patients with symptomatic Waldenström's macroglobulinaemia who had begun treatment after Jan 1, 2000, and before Jan 1, 2014, and had available clinical and biological data. The primary endpoints were reasons for treatment initiation, treatment choices, progression-free survival, and overall survival. We assessed the variables that affected choice of front-line therapy, progression-free survival, and overall survival in multivariate analyses. Findings: Electronic records were reviewed for 454 eligible patients. The most frequent reasons for starting front-line treatment were anaemia (in 328 [72%] patients) and constitutional symptoms (in 264 [58%] patients). Choice of therapy varied between front-line, second-line, and third-line approaches; age; and type of institution. In the front-line setting, 193 (43%) of 454 patients received monotherapy, 164 (36%) received chemoimmunotherapy, and 95 (21%) received other combination regimens (data on front-line treatment were missing for one patient, and another patient received only steroids). After front-line treatment, median progression-free survival was 29 months (95% CI 25–31), median overall survival was not reached (not reached–not reached), and 10-year overall survival was 69% (62–74). In multivariate analyses, patients who were high risk according to the International Prognostic Scoring System for Waldenström Macroglobulinemia had significantly worse progression-free survival and overall survival than did those who were low risk. Additionally, progression-free survival was shortened in patients treated with monotherapy compared with those treated with chemoimmunotherapy or other combination therapies and in those treated at an academic institution compared with those treated in the community. Constitutional symptoms (excluding fatigue) were associated with worsened overall survival. Interpretation: This large observational dataset should inform and help set guidelines, and improve understanding of treatment practices and outcomes, for European patients with Waldenström's macroglobulinaemia. Funding: Pharmacyclics LLC (an AbbVie company)