Use of consumer wearables to monitor and predict pain in patients with sickle cell disease.

Background: In sickle cell disease (SCD), unpredictable episodes of acute severe pain, known as vaso-occlusive crises (VOC), disrupt school, work activities and family life and ultimately lead to multiple hospitalizations. The ability to predict VOCs would allow a timely and adequate intervention. The first step towards this ultimate goal is to use patient-friendly and accessible technology to collect relevant data that helps infer a patient's pain experience during VOC. This study aims to: (1) determine the feasibility of remotely monitoring with a consumer wearable during hospitalization for VOC and up to 30 days after discharge, and (2) evaluate the accuracy of pain prediction using machine learning models based on physiological parameters measured by a consumer wearable. Methods: Patients with SCD (≥18 years) who were admitted for a vaso-occlusive crisis were enrolled at a single academic center. Participants were instructed to report daily pain scores (0-10) in a mobile app (Nanbar) and to continuously wear an Apple Watch up to 30 days after discharge. Data included heart rate (in rest, average and variability) and step count. Demographics, SCD genotype, and details of hospitalization including pain scores reported to nurses, were extracted from electronic medical records. Physiological data from the wearable were associated with pain scores to fit 3 different machine learning classification models. The performance of the machine learning models was evaluated using: accuracy, F1, root-mean-square error and area under the receiver-operating curve. Results: Between April and June 2022, 19 patients (74% HbSS genotype) were included in this study and followed for a median time of 28 days [IQR 22-34], yielding a dataset of 2,395 pain data points. Ten participants were enrolled while hospitalized for VOC. The metrics of the best performing model, the random forest model, were micro-averaged accuracy of 92%, micro-averaged F1-score of 0.63, root-mean-square error of 1.1, and area under the receiving operating characteristic curve of 0.9. Conclusion: Our random forest model accurately predicts high pain scores during admission for VOC and after discharge. The Apple Watch was a feasible method to collect physiologic data and provided accuracy in prediction of pain scores.

Predicting Pain in People With Sickle Cell Disease in the Day Hospital Using the Commercial Wearable Apple Watch: Feasibility Study.

BACKGROUND: Sickle cell disease (SCD) is a genetic red blood cell disorder associated with severe complications including chronic anemia, stroke, and vaso-occlusive crises (VOCs). VOCs are unpredictable, difficult to treat, and the leading cause of hospitalization. Recent efforts have focused on the use of mobile health technology to develop algorithms to predict pain in people with sickle cell disease. Combining the data collection abilities of a consumer wearable, such as the Apple Watch, and machine learning techniques may help us better understand the pain experience and find trends to predict pain from VOCs. OBJECTIVE: The aim of this study is to (1) determine the feasibility of using the Apple Watch to predict the pain scores in people with sickle cell disease admitted to the Duke University SCD Day Hospital, referred to as the Day Hospital, and (2) build and evaluate machine learning algorithms to predict the pain scores of VOCs with the Apple Watch. METHODS: Following approval of the institutional review board, patients with sickle cell disease, older than 18 years, and admitted to Day Hospital for a VOC between July 2021 and September 2021 were approached to participate in the study. Participants were provided with an Apple Watch Series 3, which is to be worn for the duration of their visit. Data collected from the Apple Watch included heart rate, heart rate variability (calculated), and calories. Pain scores and vital signs were collected from the electronic medical record. Data were analyzed using 3 different machine learning models: multinomial logistic regression, gradient boosting, and random forest, and 2 null models, to assess the accuracy of pain scores. The evaluation metrics considered were accuracy (F1-score), area under the receiving operating characteristic curve, and root-mean-square error (RMSE). RESULTS: We enrolled 20 patients with sickle cell disease, all of whom identified as Black or African American and consisted of 12 (60%) females and 8 (40%) males. There were 14 individuals diagnosed with hemoglobin type SS (70%). The median age of the population was 35.5 (IQR 30-41) years. The median time each individual spent wearing the Apple Watch was 2 hours and 17 minutes and a total of 15,683 data points were collected across the population. All models outperformed the null models, and the best-performing model was the random forest model, which was able to predict the pain scores with an accuracy of 84.5%, and a RMSE of 0.84. CONCLUSIONS: The strong performance of the model in all metrics validates feasibility and the ability to use data collected from a noninvasive device, the Apple Watch, to predict the pain scores during VOCs. It is a novel and feasible approach and presents a low-cost method that could benefit clinicians and individuals with sickle cell disease in the treatment of VOCs.

Pinnatifidenyne-Derived Ethynyl Oxirane Acetogenins from Laurencia viridis.

Red algae of Laurencia continue to provide wide structural diversity and complexity of halogenated C15 acetogenin medium-ring ethers. Here, we described the isolation of three new C15 acetogenins (3-5), and one truncated derivative (6) from Laurencia viridis collected on the Canary Islands. These compounds are interesting variations on the pinnatifidenyne structure that included the first examples of ethynyl oxirane derivatives (3-4). The structures were elucidated by extensive study of NMR (Nuclear Magnetic Resonance) data, J-based configuration analysis and DFT (Density Functional Theory) calculations. Their antiproliferative activity against six human solid tumor cell lines was evaluated.

Phosphopantetheinyl transferase CfwA/NpgA is required for Aspergillus nidulans secondary metabolism and asexual development.

Polyketide synthases (PKSs) and/or nonribosomal peptide synthetases (NRPSs) are central components of secondary metabolism in bacteria, plants, and fungi. In filamentous fungi, diverse PKSs and NRPSs participate in the biosynthesis of secondary metabolites such as pigments, antibiotics, siderophores, and mycotoxins. However, many secondary metabolites as well as the enzymes involved in their production are yet to be discovered. Both PKSs and NRPSs require activation by enzyme members of the 4'-phosphopantetheinyl transferase (PPTase) family. Here, we report the isolation and characterization of Aspergillus nidulans strains carrying conditional (cfwA2) and null (DeltacfwA) mutant alleles of the cfwA gene, encoding an essential PPTase. We identify the polyketides shamixanthone, emericellin, and dehydroaustinol as well as the sterols ergosterol, peroxiergosterol, and cerevisterol in extracts from A. nidulans large-scale cultures. The PPTase CfwA/NpgA was required for the production of these polyketide compounds but dispensable for ergosterol and cerevisterol and for fatty acid biosynthesis. The asexual sporulation defects of cfwA, DeltafluG, and DeltatmpA mutants were not rescued by the cfwA-dependent compounds identified here. However, a cfwA2 mutation enhanced the sporulation defects of both DeltatmpA and DeltafluG single mutants, suggesting that unidentified CfwA-dependent PKSs and/or NRPSs are involved in the production of hitherto-unknown compounds required for sporulation. Our results expand the number of known and predicted secondary metabolites requiring CfwA/NpgA for their biosynthesis and, together with the phylogenetic analysis of fungal PPTases, suggest that a single PPTase is responsible for the activation of all PKSs and NRPSs in A. nidulans.

Compliment del tractament tuberculostàtic entre la població visitada a l’Hospital del Mar de Barcelona. 10 anys de control / Cumplimiento del tratamiento tuberculostático entre la población atendida en el Hospital del Mar de Barcelona. 10 años de seguimiento / Compliance with tuberculostatic therapy among patients seen at Hospital del Mar in Barcelona. Ten-year follow up

Fonament. L’èxit terapèutic tuberculostàtic es fonamenta en el correcte compliment. Objectiu. Valorar el compliment del tractament tuberculostàtic. Mètode. 109 infants. Metodologia: 1) verbalització, preguntes directes i indirectes; 2) comprovació colorimè- trica de presència de rifampicina i isoniazida a orina. Resultats. Malaltia tuberculosa: 36 casos (3 perduts); 27 fan totes visites. Compliment a totes visites 23 (71.8%); irregular 4. Taxa de compliment 81.25%. Infecció tuberculosa: 45 casos (2 perduts); 30 fan totes visites. Compliment correcte 24 (55.8%); irregular 13. Taxa de compliment 77.08%. Quimioprofilaxi primària: 28 casos. Compliment correcte 15; irregular 8. Conclusions. 1) El compliment terapèutic és fonamental per minvar malaltia. El millor mètode és el tractament directament observat, no sempre factible. 2) Les taxes de compliment (81.25 i 77.08%) són acceptables, però millorables. 3) La metodologia per a la valoració no és idònia, però és innòcua, fàcil, pràctica i de baix cost; 4) És imprescindible que el pediatre mentalitzi i eduqui en la importància de la malaltia i el compliment terapèutic. 5) Mantenir el mateix equip metge-infermeria pot afavorir adherències. 6) En tractaments curts és més fàcil el compliment (AU)

Fundamento. El éxito terapéutico tuberculostático se basa en el correcto cumplimiento. Objetivo. Valorar el cumplimiento de los tratamientos tuberculostáticos. Métodos. 109 niños. Metodología: 1) verbalización, preguntas directas e indirectas; 2) comprobación colorimétrica de la presència de rifampicina e isoniazida en orina. Resultados. Enfermedad tuberculosa: 36 casos (3 perdidos); 27 asisten a todas las visitas. Cumplimiento terapéutico en todas 23 (71.8%), irregular 4. Tasa de cumplimiento 81.25%. Infección tuberculosa: 45 (2 perdidos); 30 asisten a todas las visitas. Cumplimiento correcto 24 (55.8%); irregular 13. Tasa de cumplimiento 77.8%. Quimioprofilaxis primaria: 28. Cumplimiento correcto 15; irregular 8. Conclusiones. 1) El cumplimiento terapéutico es fundamental para la reducción de la tuberculosis. El mejor método es el tratamiento directamente observado, no siempre factible. 2) Las tasas de cumplimiento (81.25 y 77.8%) son aceptables pero mejorables. 3) La metodología para la valoración no es idónea, pero es inócua, fácil y de bajo costo. 4) Es imprescindible que el pediatra mentalice y eduque en la importancia de la enfermedad y el cumplimiento terapéutico. 5) Mantener el mismo equipo médico-enfermeria favorece la adherencia. 6) Con tratamientos cortos el cumplimiento es más fácil (AU)

Background. The success of tuberculostatic therapy correlates directly with compliance. Objective. To evaluate the compliance with tuberculostatic treatment among a group of children seen at a single institution. Method. 109 children receiving different tuberculostatic regimens were evaluated for compliance. The methods used included: 1) disclosure in response to direct and indirect questions; 2) colorimetric test for the presence of rifampin and isoniazid in urine. Results. Among the 36 cases of pulmonary tuberculosis, 3 patients were lost to follow-up and 27 patients have complied with all the follow-up visits. Of those, good therapeutic compliance was documented in 23 patients (71.8%), and it was estimated to be irregular in 4 patients. Thus, the overall compliance rate for patients with pulmonary tuberculosis was 81.25%. Among the 45 cases of latent tuberculosis infection, 2 patients were lot to follow-up, and 30 patients complied with all the follow-up visits. Of those, therapeutic compliance was good in 24 patients (55.8%), and it was irregular in 13 patients. Thus, the overall compliance rate for patients with latent tuberculosis infection was 77.8%. Among the 28 patients receiving primary chemoprophylaxis, therapeutic compliance wasgood in 15 patients, and irregular in 8 patients. Conclusions. 1) A good therapeutic compliance is very important to decrease the prevalence of tuberculois. The best method to improve compliance is direct supervision, which is not always feasible. 2) The compliance rates in our population (81.25% and 77.8%) are satisfactory, but could be improved. 3) The methodology used in our study is not optimal, but it is harmless, cheap and easy to perform. 4) It is essential that the primary pediatrician educates the patients on the severity of the disease and the importance of a good therapeutic compliance. 5) A stable health-care team facilitates the therapeutic compliance. 6) Short regimens are associated with better compliance (AU)