Further Clarification of Pain Management Complexity in Radiotherapy: Insights from Modern Statistical Approaches

Background: The primary objective of this study was to assess the adequacy of analgesic care in radiotherapy (RT) patients, with a secondary objective to identify predictive variables associated with pain management adequacy using a modern statistical approach, integrating the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm and the Classification and Regression Tree (CART) analysis. Methods: This observational, multicenter cohort study involved 1387 patients reporting pain or taking analgesic drugs from 13 RT departments in Italy. The Pain Management Index (PMI) served as the measure for pain control adequacy, with a PMI score < 0 indicating suboptimal management. Patient demographics, clinical status, and treatment-related factors were examined to discern the predictors of pain management adequacy. Results: Among the analyzed cohort, 46.1% reported inadequately managed pain. Non-cancer pain origin, breast cancer diagnosis, higher ECOG Performance Status scores, younger patient age, early assessment phase, and curative treatment intent emerged as significant determinants of negative PMI from the LASSO analysis. Notably, pain management was observed to improve as RT progressed, with a greater discrepancy between cancer (33.2% with PMI < 0) and non-cancer pain (73.1% with PMI < 0). Breast cancer patients under 70 years of age with non-cancer pain had the highest rate of negative PMI at 86.5%, highlighting a potential deficiency in managing benign pain in younger patients. Conclusions: The study underscores the dynamic nature of pain management during RT, suggesting improvements over the treatment course yet revealing specific challenges in non-cancer pain management, particularly among younger breast cancer patients. The use of advanced statistical techniques for analysis stresses the importance of a multifaceted approach to pain management, one that incorporates both cancer and non-cancer pain considerations to ensure a holistic and improved quality of oncological care

Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

: The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135-15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359-5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138-5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184-5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598-9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090-6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286-5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p < 0.001; 95% CI 1.912-7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p = 0.018; 95% CI 0.138-0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143-0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990)

Temozolomide and Radiotherapy versus Radiotherapy Alone in High Grade Gliomas: A Very Long Term Comparative Study and Literature Review

Temozolomide (TMZ) is the first line drug in the care of high grade gliomas. The combined treatment of TMZ plus radiotherapy is more effective in the care of brain gliomas then radiotherapy alone. Aim of this report is a survival comparison, on a long time (>10 years) span, of glioma patients treated with radiotherapy alone and with radiotherapy + TMZ. Materials and Methods. In this report we retrospectively reviewed the outcome of 128 consecutive pts with diagnosis of high grade gliomas referred to our institutions from April 1994 to November 2001. The first 64 pts were treated with RT alone and the other 64 with a combination of RT and adjuvant or concomitant TMZ. Results. Grade 3 (G3) haematological toxicity was recorded in 6 (9%) of 64 pts treated with RT and TMZ. No G4 haematological toxicity was observed. Age, histology, and administration of TMZ were statistically significant prognostic factors associated with 2 years overall survival (OS). PFS was for GBM 9 months, for AA 11. Conclusions. The combination of RT and TMZ improves long term survival in glioma patients. Our results confirm the superiority of the combination on a long time basis

Adequacy of Pain Treatment in Radiotherapy Departments: Results of a Multicenter Study on 2104 Patients (Arise)

Aim: The frequent inadequacy of pain management in cancer patients is well known. Moreover, the quality of analgesic treatment in patients treated with radiotherapy (RT) has only been rarely assessed. In order to study the latter topic, we conducted a multicenter, observational and prospective study based on the Pain Management Index (PMI) in RT Italian departments. Methods: We collected data on age, gender, tumor site and stage, performance status, treatment aim, and pain (type: CP—cancer pain, NCP—non-cancer pain, MP—mixed pain; intensity: NRS: Numeric Rating Scale). Furthermore, we analyzed the impact on PMI on these parameters, and we defined a pain score with values from 0 (NRS: 0, no pain) to 3 (NRS: 7–10: intense pain) and an analgesic score from 0 (pain medication not taken) to 3 (strong opioids). By subtracting the pain score from the analgesic score, we obtained the PMI value, considering cases with values < 0 as inadequate analgesic prescriptions. The Ethics Committees of the participating centers approved the study (ARISE-1 study). Results: Two thousand one hundred four non-selected outpatients with cancer and aged 18 years or older were enrolled in 13 RT departments. RT had curative and palliative intent in 62.4% and 37.6% patients, respectively. Tumor stage was non-metastatic in 57.3% and metastatic in 42.7% of subjects, respectively. Pain affected 1417 patients (CP: 49.5%, NCP: 32.0%; MP: 18.5%). PMI was < 0 in 45.0% of patients with pain. At multivariable analysis, inadequate pain management was significantly correlated with curative RT aim, ECOG performance status = 1 (versus both ECOG-PS3 and ECOG- PS4), breast cancer, non-cancer pain, and Central and South Italy RT Departments (versus Northern Italy).Conclusions: Pain management was less adequate in patients with more favorable clinical condition and stage. Educational and organizational strategies are needed in RT departments to reduce the non-negligible percentage of patients with inadequate analgesic therapy

Starlikeness of Libera transformation (II) (Applications of Complex Function Theory to Differential Equations)

The GEOTRACES Intermediate Data Product 2017 (IDP2017) is the second publicly available data product of the international GEOTRACES programme, and contains data measured and quality controlled before the end of 2016. The IDP2017 includes data from the Atlantic, Pacific, Arctic, Southern and Indian oceans, with about twice the data volume of the previous IDP2014. For the first time, the IDP2017 contains data for a large suite of biogeochemical parameters as well as aerosol and rain data characterising atmospheric trace element and isotope (TEI) sources. The TEI data in the IDP2017 are quality controlled by careful assessment of intercalibration results and multi-laboratory data comparisons at crossover stations. The IDP2017 consists of two parts: (1) a compilation of digital data for more than 450 TEIs as well as standard hydrographic parameters, and (2) the eGEOTRACES Electronic Atlas providing an on-line atlas that includes more than 590 section plots and 130 animated 3D scenes. The digital data are provided in several formats, including ASCII, Excel spreadsheet, netCDF, and Ocean Data View collection. Users can download the full data packages or make their own custom selections with a new on-line data extraction service. In addition to the actual data values, the IDP2017 also contains data quality flags and 1-σ data error values where available. Quality flags and error values are useful for data filtering and for statistical analysis. Metadata about data originators, analytical methods and original publications related to the data are linked in an easily accessible way. The eGEOTRACES Electronic Atlas is the visual representation of the IDP2017 as section plots and rotating 3D scenes. The basin-wide 3D scenes combine data from many cruises and provide quick overviews of large-scale tracer distributions. These 3D scenes provide geographical and bathymetric context that is crucial for the interpretation and assessment of tracer plumes near ocean margins or along ridges. The IDP2017 is the result of a truly international effort involving 326 researchers from 25 countries. This publication provides the critical reference for unpublished data, as well as for studies that make use of a large cross-section of data from the IDP2017. This article is part of a special issue entitled: Conway GEOTRACES - edited by Tim M. Conway, Tristan Horner, Yves Plancherel, and Aridane G. González

Pancreatic surgery outcomes: multicentre prospective snapshot study in 67 countries

Background: Pancreatic surgery remains associated with high morbidity rates. Although postoperative mortality appears to have improved with specialization, the outcomes reported in the literature reflect the activity of highly specialized centres. The aim of this study was to evaluate the outcomes following pancreatic surgery worldwide.Methods: This was an international, prospective, multicentre, cross-sectional snapshot study of consecutive patients undergoing pancreatic operations worldwide in a 3-month interval in 2021. The primary outcome was postoperative mortality within 90 days of surgery. Multivariable logistic regression was used to explore relationships with Human Development Index (HDI) and other parameters.Results: A total of 4223 patients from 67 countries were analysed. A complication of any severity was detected in 68.7 percent of patients (2901 of 4223). Major complication rates (Clavien-Dindo grade at least IIIa) were 24, 18, and 27 percent, and mortality rates were 10, 5, and 5 per cent in low-to-middle-, high-, and very high-HDI countries respectively. The 90-day postoperative mortality rate was 5.4 per cent (229 of 4223) overall, but was significantly higher in the low-to-middle-HDI group (adjusted OR 2.88, 95 per cent c.i. 1.80 to 4.48). The overall failure-to-rescue rate was 21 percent; however, it was 41 per cent in low-to-middle-compared with 19 per cent in very high-HDI countries.Conclusion: Excess mortality in low-to-middle-HDI countries could be attributable to failure to rescue of patients from severe complications. The authors call for a collaborative response from international and regional associations of pancreatic surgeons to address management related to death from postoperative complications to tackle the global disparities in the outcomes of pancreatic surgery (NCT04652271; ISRCTN95140761)

The GEOTRACES Intermediate Data Product 2017

Unidad de excelencia María de Maeztu MdM-2015-0552The GEOTRACES Intermediate Data Product 2017 (IDP2017) is the second publicly available data product of the international GEOTRACES programme, and contains data measured and quality controlled before the end of 2016. The IDP2017 includes data from the Atlantic, Pacific, Arctic, Southern and Indian oceans, with about twice the data volume of the previous IDP2014. For the first time, the IDP2017 contains data for a large suite of biogeochemical parameters as well as aerosol and rain data characterising atmospheric trace element and isotope (TEI) sources. The TEI data in the IDP2017 are quality controlled by careful assessment of intercalibration results and multi-laboratory data comparisons at crossover stations. The IDP2017 consists of two parts: (1) a compilation of digital data for more than 450 TEIs as well as standard hydrographic parameters, and (2) the eGEOTRACES Electronic Atlas providing an on-line atlas that includes more than 590 section plots and 130 animated 3D scenes. The digital data are provided in several formats, including ASCII, Excel spreadsheet, netCDF, and Ocean Data View collection. Users can download the full data packages or make their own custom selections with a new on-line data extraction service. In addition to the actual data values, the IDP2017 also contains data quality flags and 1-σ data error values where available. Quality flags and error values are useful for data filtering and for statistical analysis. Metadata about data originators, analytical methods and original publications related to the data are linked in an easily accessible way. The eGEOTRACES Electronic Atlas is the visual representation of the IDP2017 as section plots and rotating 3D scenes. The basin-wide 3D scenes combine data from many cruises and provide quick overviews of large-scale tracer distributions. These 3D scenes provide geographical and bathymetric context that is crucial for the interpretation and assessment of tracer plumes near ocean margins or along ridges. The IDP2017 is the result of a truly international effort involving 326 researchers from 25 countries. This publication provides the critical reference for unpublished data, as well as for studies that make use of a large cross-section of data from the IDP2017. This article is part of a special issue entitled: Conway GEOTRACES - edited by Tim M. Conway, Tristan Horner, Yves Plancherel, and Aridane G. González