Molecular structure and polymorphism of a cyclohexanediol: trans-1,4-cyclohexanedimethanol

This study aims to investigate the molecular structure and polymorphism of trans-1,4-cyclohexanedimethanol, including the bi-axial/bi-equatorial equilibrium and the nature of the intermolecular H-bond networks in condensed phases created by the hydroxyl group torsions. The full conformational space of the single molecule was explored by MP2 calculations, showing that the optimized bi-equatorial conformers have similar stability and the bi-axial ones have much higher energies. The hydroxymethyl substituents have preference for gauche/anti or gauche+/gauche− conformations. Polymorphic forms were generated by crystallization from solutions and by cooling the melt, which were characterized by a combination of techniques: DSC, PLTM and XRD. Two polymorphs were isolated and their crystal structures were solved by direct methods based on single-crystal X-ray analysis. Both were found to contain two of the most stable conformers found in the computational calculations. The influence of H-bonding in the polymorphic structures was verified by analysis of the structural differences between the geometries present in the polymorphs determined by XRD and their single molecule counterparts resulting from the theoretical calculations. The bi-axial conformations are destabilized over the bi-equatorial ones in isolated and crystalline forms of trans-1,4-cyclohexanedimethanol

Co-crystals of diflunisal and isomeric pyridinecarboxamides – a thermodynamics and crystal engineering contribution

Diflunisal is an anti-inflammatory, non-steroidal drug, class II of the Biopharmaceutical Classification System, which has recently been the subject of renewed interest due to its potential for use in the oral therapy of familial amyloid polyneuropathy. In this study, a thermodynamics based approach is used to investigate binary mixtures (diflunisal + picolinamide and diflunisal + isonicotinamide) in order to identify solid forms that are potentially useful to improve the biopharmaceutical performance of this active pharmaceutical ingredient. Special emphasis is placed on the research of co-crystals and on the influence of structural changes in the pyridinecarboxamide co-former molecules for co-crystal formation with diflunisal. The thermodynamics based methodology described by ter Horst et al. in 2010 indicates that the formation of co-crystals is thermodynamically feasible for both systems. The binary solid–liquid phase diagrams were built and allowed unequivocal identification of the formation of co-crystals of diflunisal with each of the two isomers and also their stoichiometry of 1 : 1, (diflunisal : co-former) in the case of pyridine-2-carboxamide (picolinamide) and (2 : 1) for pyridine-4-carboxamide (isonicotinamide). Two binary eutectic mixtures, potentially relevant for pharmaceutical application, were also identified. Infrared spectroscopy allowed the identification of the acid⋯N-pyridine heterosynthon in the three co-crystals formed by diflunisal with the isomeric pyridinecarboxamides. However, the results clearly differentiated pyridine-2-carboxamide from pyridine-3-carboxamide and pyridine-4-carboxamide, that share similar crystalline arrangements, at least with respect to the supramolecular synthons

The impact of electronic versus paper-based data capture on data collection logistics and on missing scores in thyroid cancer patients.

The purpose of this study was to investigate the impact of the type of data capture on the time and help needed for collecting patient-reported outcomes as well as on the proportion of missing scores. In a multinational prospective study, thyroid cancer patients from 17 countries completed a validated questionnaire measuring quality of life. Electronic data capture was compared to the paper-based approach using multivariate logistic regression. A total of 437 patients were included, of whom 13% used electronic data capture. The relation between data capture and time needed was modified by the emotional functioning of the patients. Those with clinical impairments in that respect needed more time to complete the questionnaire when they used electronic data capture compared to paper and pencil (OR <sub>adj</sub> 24.0; p = 0.006). This was not the case when patients had sub-threshold emotional problems (OR <sub>adj</sub> 1.9; p = 0.48). The odds of having the researcher reading the questions out (instead of the patient doing this themselves) (OR <sub>adj</sub> 0.1; p = 0.01) and of needing any help (OR <sub>adj</sub> 0.1; p = 0.01) were lower when electronic data capture was used. The proportion of missing scores was equivalent in both groups (OR <sub>adj</sub> 0.4, p = 0.42). The advantages of electronic data capture, such as real-time assessment and fewer data entry errors, may come at the price of more time required for data collection when the patients have mental health problems. As this is not uncommon in thyroid cancer, researchers need to choose the type of data capture wisely for their particular research question

Establishing urban gardens on vacant land while considering international good practices: a legal case study from Portugal

There is a gap in most countries’ legal frameworks regarding their ability to connect vacant land and urban gardens. Hence, research is needed to understand how regulation on vacant land might be designed to promote a more sustainable purpose to it. Urban gardens are a type of urban agriculture that could be potentiated by such regulation. The aim of this paper is to show how that can be done through the Municipal Master Plans (MMP) legal and regulatory framework for the Portuguese case, by reviewing worldwide good practices on vacant land restorations for urban sustainable development. The paper comprises a literature review on good practices adopted in different countries regarding vacant lot restoration. The evaluation of good practices is built on the achievement of the three pillars of sustainability. Five Portuguese MMP were used, as empirical data, to support the design of a new legal and regulatory framework. The goal is to enhance the sustainable destination of vacant land by converting it into urban gardens. The analysis of these MMPs demonstrated that they disregard urban gardens as a tool to promote urban sustainability in spite of global trends to make urban territorial planning and management instruments greener. An additional outcome of this paper is to categorise different types of vacant land in the five municipalities under analysis according to their suitability for urban garden conversion. The design of the legal framework enhancing the conversion of vacant land into urban garden will contribute to the 2030 international agenda goals’ achievement. The proposal would create an innovative legal framework in the case of Portugal that could be replicated by other countries.info:eu-repo/semantics/acceptedVersio

Determination of the melting temperature, heat of fusion, and purity analysis of different samples of zidovudine (AZT) using DSC

The determination of chemical purity, melting range, and variation of enthalpy in the process of characterizing medicines is one of the principal requirements evaluated in quality control of the pharmaceutical industry. In this study, the method of purity determination using DSC was outlined, as well as the application of this technique for the evaluation of commercial samples of zidovudine (AZT) (raw material) supplied by different laboratories. To this end, samples from six different laboratories (A, B, C, D, E, and F) and the standard reference (R) from the United States Pharmacopeia (USP) were analyzed. The DSC curves were obtained in the temperature range of 25 to 200 ºC under the dynamic atmosphere of N2 (50 mL min-1), heating rate of β=2 ºC min-1, using an Al capsule containing approximately 2 mg of sample material. The results demonstrated that the standard reference presented a proportion of 99.83% whereas the AZT samples presented a variation ranging from 97.59 to 99.54%. In addition, the standard reference was found to present a temperature of onset of melting point of 122.80 °C. Regarding the samples of active agents provided by the different laboratories, a variation ranging from 118.70 to 122.87 °C was measured. In terms of ΔHm, the samples presented an average value of 31.12 kJ mol-1._________________________________________________________________________________________ RESUMO: A determinação da pureza química, a faixa de fusão e a variação de entalpia envolvida no processo de caracterização de fármacos é um dos principais requisitos avaliados no controle de qualidade em indústrias farmacêuticas. Neste trabalho é feita uma breve abordagem sobre o método de determinação de pureza utilizando DSC, assim como a aplicação desta técnica para avaliação de amostras comerciais de zidovudina (AZT) (matéria-prima) fornecida por diferentes laboratórios. Para tal, foram analisadas amostras de seis diferentes laboratórios (A,B,C,D,E e F) e a substância química de referência (R) da United States Pharmacopeia (USP). As curvas DSC foram obtidas na faixa de temperatura entre 25 a 200 ºC, sob atmosfera dinâmica de N2 (50 mL min-1), β=2 ºC min-1, utilizando cápsula de Al contendo aproximadamente 2 mg de amostra. De acordo com os resultados, pode-se observar que a substância química de referência apresentou teor igual a 99,83% e que as amostras de AZT apresentaram uma faixa de variação entre 97,59 e 99,54%. Pode-se verificar, ainda, que a substância química de referência apresentou uma temperatura onset de fusão igual a 122,80 °C. Para as amostras dos princípios ativos fornecidos pelos diferentes laboratórios, pode-se verificar uma faixa de variação entre 118,70 e 122,87 °C. No que se refere ao ΔHm, as amostras apresentaram valor médio de 31,12 kJ.mol-1

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic