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Background/aimsTuberculosis remains one of the leading causes of death from an infectious disease globally. Both choices of outcome definitions and approaches to handling events happening post-randomisation can change the treatment effect being estimated, but these are often inconsistently described, thus inhibiting clear interpretation and comparison across trials.MethodsStarting from the ICH E9(R1) addendum's definition of an estimand, we use our experience of conducting large Phase III tuberculosis treatment trials and our understanding of the estimand framework to identify the key decisions regarding how different event types are handled in the primary outcome definition, and the important points that should be considered in making such decisions. A key issue is the handling of intercurrent (i.e. post-randomisation) events (ICEs) which affect interpretation of or preclude measurement of the intended final outcome. We consider common ICEs including treatment changes and treatment extension, poor adherence to randomised treatment, re-infection with a new strain of tuberculosis which is different from the original infection, and death. We use two completed tuberculosis trials (REMoxTB and STREAM Stage 1) as illustrative examples. These trials tested non-inferiority of new tuberculosis treatment regimens versus a control regimen. The primary outcome was a binary composite endpoint, 'favourable' or 'unfavourable', which was constructed from several components.ResultsWe propose the following improvements in handling the above-mentioned ICEs and loss to follow-up (a post-randomisation event that is not in itself an ICE). First, changes to allocated regimens should not necessarily be viewed as an unfavourable outcome; from the patient perspective, the potential harms associated with a change in the regimen should instead be directly quantified. Second, handling poor adherence to randomised treatment using a per-protocol analysis does not necessarily target a clear estimand; instead, it would be desirable to develop ways to estimate the treatment effects more relevant to programmatic settings. Third, re-infection with a new strain of tuberculosis could be handled with different strategies, depending on whether the outcome of interest is the ability to attain culture negativity from infection with any strain of tuberculosis, or specifically the presenting strain of tuberculosis. Fourth, where possible, death could be separated into tuberculosis-related and non-tuberculosis-related and handled using appropriate strategies. Finally, although some losses to follow-up would result in early treatment discontinuation, patients lost to follow-up before the end of the trial should not always be classified as having an unfavourable outcome. Instead, loss to follow-up should be separated from not completing the treatment, which is an ICE and may be considered as an unfavourable outcome.ConclusionThe estimand framework clarifies many issues in tuberculosis trials but also challenges trialists to justify and improve their outcome definitions. Future trialists should consider all the above points in defining their outcomes.

Salpe Malkon,1 Björn Wettermark,1 Thomas Kahan,2 Pia Bastholm-Rahmner,3 Jan Hasselström,4 Miriam Qvarnström1 1Department of Pharmacy, Uppsala University, Uppsala, Sweden; 2Karolinska Institutet, Department of Clinical Sciences, Danderyd Hospital, Division of Cardiovascular Medicine, Stockholm, Sweden; 3Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; 4Department of Neurobiology and Care Sciences and Society, Karolinska Institutet, Stockholm, SwedenCorrespondence: Miriam Qvarnström, Department of Pharmacy, Faculty of Pharmacy, Uppsala University, Box 580, Uppsala, 751 23, Sweden, Email miriam.qvarnstrom@farmaci.uu.sePurpose: Few studies explored what patients initiated on blood pressure medication in primary care think about their disease and their medications. The aim of this study was to gain an understanding of hypertensive patients’ views on and experiences of hypertension and the use of antihypertensive medications.Methods: A qualitative study based on open-ended questions from a survey on medication adherence, which captured treated hypertensive patients’ perspective on their condition and treatment. Data were collected for 219 patients on antihypertensive medication, ≥ 30 years old, who consulted 25 primary health care centers in Stockholm, Sweden, during 2016. Thematic analysis with both inductive and deductive approach was applied.Results: We identified 21 codes from the data and grouped them under the World Health Organization’s five dimensions of adherence: condition-, therapy-, health care team and system-, patient-, and socioeconomic-related factors. The analyses revealed that many patients with hypertension have limited knowledge of their disease, are afraid of drug side effects and experience various issues in primary health care that may negatively impact adherence, including short doctor appointments, prescribing without communication and room for improvement in individualization of therapy and a person-centered approach.Conclusion: Many patients with hypertension have limited understanding of their hypertension and fear of adverse events from their antihypertensive medications. There is also room for improvement in how the patients are managed in primary health care. Interventions should focus on these issues to promote a better blood pressure target achievement.Plain Language Summary: Few studies have explored what patients initiated on blood pressure medication in primary care think about their disease and their medications.In this study, we analyzed free comments collected from 219 patients responding to a survey on medication adherence. Those who responded used antihypertensive medication, were ≥ 30 years old, and consulted primary health care centers in Stockholm, Sweden.The analyses revealed that many patients with hypertension have limited knowledge of their disease, are afraid of drug side effects and experience various issues in primary health care that may negatively impact adherence, including short doctor appointments, prescribing without communication and room for improvement in individualization of therapy and a person-centered approach.Interventions to promote a better blood pressure treatment would likely benefit from targeting these problems raised by patients.Keywords: hypertension, antihypertensive treatment, medication adherence, patient perspectives, primary health care, qualitative studies

Purpose: Content analysis of school websites may reveal the degree to which schools value physical education (PE) and physical activity (PA). We used the approach to quantify Maryland's private school websites' PE/PA content and associations with school characteristics. Method: The analytic sample (n = 387) was examined for mention of PE-/PA-related content (e.g., curriculum, dosage, intramurals). Associations between content and school characteristics (e.g., grade levels offered, religious orientation) were examined using Pearson's chi-squared test. Results: PE (∼75% of school websites) was mentioned most frequently, and PA images and PE curriculum (∼30% each) were mentioned least frequently. Elementary and Catholic school websites were proportionately less and more likely, respectively, to mention various PE/PA content. Discussion/Conclusion: Representation of PE/PA content among Maryland's private schools surpassed that found in previous studies. Nonetheless, relative omission of some content may allude to PE/PA being less valued compared with other academic subjects. Follow-up with stakeholders may help elucidate factors that influence content gatekeeping. [ABSTRACT FROM AUTHOR]

Islam supports participation in regular physical activity for health. However, various contextual factors related to the school setting, and traditional physical education curriculum and instruction may hinder full student engagement. The article's purposes are to: (1) provide an update on and implications of research conducted with US Muslim youth on school and out-of-school physical activity; and (2) provide practical suggestions for how physical educators can create an education setting that optimizes their Muslim students' engagement.

Key Clinical Message A unique ER/PR‐positive mucinous adenocarcinoma of breast but CK7/CK20 negativity. A rare finding of Lymphoplasmacytic Infiltration is noted. Successful treatment included modified radical mastectomy and tamoxifen‐based therapy, leads to remission. Abstract Mucinous carcinoma, which is characterized by the presence of abundant extracellular mucin, is a rare and distinctive subtype of invasive breast cancer. This subtype accounts for less than 5% of all invasive breast cancers, with pure mucinous carcinoma representing only around 2%. It is most commonly found in older patients, typically in the sixth to early eighth decade of life. We present the case of a 55‐year‐old female with a 15‐year history of a painless, gradually enlarging palpable lump on her left breast. Upon examination, a 5 × 5 cm lump with well‐defined margins and a hard consistency was found in the lower outer quadrant of the left breast. Histopathological examination confirmed a diagnosis of Mucinous Adenocarcinoma of the Left Breast. The patient underwent modified radical mastectomy and received adjuvant endocrine therapy with tamoxifen due to hormone receptor‐positive status. Mucinous carcinoma of the breast is a unique entity with specific histological features including the presence of extracellular mucin pools. Immunohistochemical staining is crucial for determining hormone receptor status, which can guide treatment decisions. Although surgical intervention is the primary approach, the extent of surgery may vary, ranging from lumpectomy to mastectomy. Adjuvant therapies such as chemotherapy and radiotherapy may also be considered based on individual cases. This case underscores the importance of a multidisciplinary approach in managing rare subtypes of breast cancer, such as mucinous carcinoma. Accurate diagnosis, appropriate surgical intervention, adjuvant therapy, and long‐term follow‐up are critical components of treatment.

Background Public reporting of performance data has become a common tool in evaluation of healthcare providers. The rating may be misleading if the association between the measured variables and the outcome is weak.Methods and results Nationwide, register-based, cohort study. All Swedish patients hospitalised with an acute coronary syndrome during the time periods 2006–2010 and 2015–2017 were included in the study. Possible associations between cardiovascular morbidity and mortality for these patients and ranking scores for each hospital in a Swedish healthcare quality register for acute coronary syndromes were analysed. We found no association between the ranking score and mortality, and no or weak associations between the ranking score and readmissions.Conclusions Lack of associations between quality measurements and patient outcomes warrants improvement in ranking scores. Cautious use of the ranking results is necessary in comparisons between healthcare providers.

Jaika Grossman formó parte de las juventudes judías que resistieron la política de persecución del nazismo. Militante de la organización sionista-socialista “Hashomer Hatzair”, integró la resistencia clandestina en el gueto de Bialystock. A posteriori, como sobreviviente y emigrada al Estado de Israel, fue una de las referentes del partido de izquierda MAPAM. En su derrotero político, Jaika Grossman visitó Argentina en tres oportunidades: 1963, 1967 y 1985. En estas ocasiones haría uso de la experiencia de resistencia contra el nazismo para interpelar a diversos actores públicos y étnico-comunitarios. El presente trabajo se propone relevar cuáles fueron los modos en los que la memoria de la resistencia judía durante el Holocausto circuló en el país en contextos específicos: los de la radicalización política y la recuperación democrática. Esta aproximación, a su vez, tendrá en cuenta las implicancias y sentidos cambiantes de la recepción del conflicto árabe-israelí en la agenda política local.

IntroductionAortic stiffness plays a critical role in the evolution of cardiovascular diseases, but the assessment requires specialized equipment. Photoplethysmography (PPG) and single-lead electrocardiogram (ECG) are readily available in healthcare and wearable devices. We studied whether a brief PPG registration, alone or in combination with single-lead ECG, could be used to reliably estimate aortic stiffness.MethodsA proof-of-concept study with simultaneous high-resolution index finger recordings of infrared PPG, single-lead ECG, and finger blood pressure (Finapres) was performed in 33 participants [median age 44 (range 21–66) years, 19 men] and repeated within 2 weeks. Carotid–femoral pulse wave velocity (cfPWV; two-site tonometry with SphygmoCor) was used as a reference. A brachial single-cuff oscillometric device assessed aortic pulse wave velocity (aoPWV; Arteriograph) for further comparisons. We extracted 136 established PPG waveform features and engineered 13 new with improved coupling to the finger blood pressure curve. Height-normalized pulse arrival time (NPAT) was derived using ECG. Machine learning methods were used to develop prediction models.ResultsThe best PPG-based models predicted cfPWV and aoPWV well (root-mean-square errors of 0.70 and 0.52 m/s, respectively), with minor improvements by adding NPAT. Repeatability and agreement were on par with the reference equipment. A new PPG feature, an amplitude ratio from the early phase of the waveform, was most important in modelling, showing strong correlations with cfPWV and aoPWV (r = −0.81 and −0.75, respectively, both P

French Musical Life: Local Dynamics in the Century to World War II, by Katharine Ellis. AMS Studies in Music. New York: Oxford University Press, 2022. xv, 417 pp. In her [...]

Background and Objectives: One of the members of the neurotrophin (NT) family is the brain-derived neurotrophic factor (BDNF). In addition to its role in the nerve system, it has been found to play a role in lung health and diseases. Materials and Methods: The serum concentrations of BDNF were assessed in 57 patients with COPD and in 19 control individuals and the possible associations of BDNF with the spirometric indexes and disease stages were explored. Results: We did not find a significant difference between the serum concentrations of BDNF of patients and controls (p = 0.521). A significant negative correlation of the serum BDNF levels with the age of the patients (Rho = −0.279, p = 0.036) was observed. In addition, a borderline negative correlation with the age of disease onset (Rho= −0.244, p = 0.063) was also found. When analyzing these correlations in different genders, we found stronger statistical significance in male patients (Rho = −0.398, p = 0.009; and Rho = −0.419, p = 0.006), while no such significance was found in females (p = 0.574 and p = 0.342). The analyses of the possible relations of serum BDNF concentration with the spirometric parameters in the whole group of patients did not reveal any significance (p = 0.231 for FEV1%pr. and p = 0.271 for FEV1/FVC%). However, when the patients were dichotomized on the basis of smoking habits, we obtained a strong positive correlation between BDNF and FEV1%pr. (Rho = 0.501, p = 0.048) in non-smokers, but strong negative correlations with FEV1%pr. (Rho = −0.468, p = 0.003) and with FEV1/FVC% (Rho = −0.331, p = 0.040) in ex/current smokers. Non-smokers with moderate disease (GOLD II) had higher BDNF serum concentrations than patients with GOLD stage III/IV (p = 0.031). In ex/current smokers, there was an opposite association (p = 0.045). Conclusions: The results of our study suggest that the expression and secretion of BDNF are changed in COPD, but its effects and functions may differ according to the smoking history of the patients.

Online academic courses provide students with flexible learning opportunities by allowing them to make choices regarding diverse aspects of their learning process; hence, such courses support personalized learning. This study aimed to analyze the ways students make use of flexibility in online academic courses based on learning time, place, and access to learning resources, as well as to investigate how this relates to differences in course achievement. The study examined 587 students in four online courses. Educational data mining (EDM) methodology was used to trace students' behavior in the courses and to compute 34 variables, which describe their use of flexibility. The results show that students developed different patterns of learning time, place, and access to content, which indicates that flexibility was used substantially. Students' achievements were significantly related to patterns of learning time and access to learning resources. Understanding the different patterns of flexibility usage may support the design of personalized learning and increase collaboration among students with similar characteristics.

Purpose: Studies tracking changes in physical education (PE) policy adherence after an intervention are scarce. In California, successful litigation against 37 school districts for not providing adequate PE time compelled district schools' teachers to post PE schedules online or on-site for 3 years. We performed a follow-up study 4 years after the expiration of lawsuit settlement stipulations to determine the level of adherence in the absence of external accountability. Methods: We reexamined the websites of all 37 school districts, 106 schools' websites that posted time information in spring 2018 (Time 1), and a proportionate 20% random sample of schools' websites (n = 150) that posted no information at Time 1. We used descriptive statistics and paired t tests to detect differences between Times 1 and 2. Discussion/Conclusion: District websites mostly maintained postings of PE time documents and information, while the proportion of Time 1 posting school websites with such content dropped by 58%–67%. At the school level, compliance to policy mandates was positively, but not permanently impacted by a lawsuit intervention. [ABSTRACT FROM AUTHOR]

The purpose of this study was to prove the effect of regular physical activity in helping to increase the physical fitness level of elementary school students during the coronavirus disease 2019 (COVID-19) pandemic. Materials and methods. This research is true experimental with the randomized pretest-posttest control group design. A total of 48 students from the Kabuh District Public Elementary School, Jombang Regency, East Java, Indonesia, aged 10–11 years participated in the study. The students were divided into two groups, namely the control group (G1; n = 21) and the experimental group (G2; n = 27). Measurement of physical fitness level using a) body mass index (BMI); (b) sit-and-reach test; (c) lie down for 30 seconds; (d) pull-up modification; and (e) the 20-meter multistage shuttle run test was performed before and after treatment. The data analysis technique used the Statistical Package for Social Sciences (SPSS) software version 21. Results. The results showed that there was a significant difference in the average level of physical fitness between the pretest and posttest in the experimental group (G2) (p ≤ 0.001), while the control group (G1) did not show a significant difference (p ≥ 0.05). Conclusions. Based on the results of the study it was concluded that providing regular physical activity had a positive impact on increasing the level of physical fitness in elementary school students during the COVID-19 pandemic.

Abstract Background Clinical trials aim to draw conclusions about the effects of treatments, but a trial can address many different potential questions. For example, does the treatment work well for patients who take it as prescribed? Or does it work regardless of whether patients take it exactly as prescribed? Since different questions can lead to different conclusions on treatment benefit, it is important to clearly understand what treatment effect a trial aims to investigate—this is called the ‘estimand’. Using estimands helps to ensure trials are designed and analysed to answer the questions of interest to different stakeholders, including patients and public. However, there is uncertainty about whether patients and public would like to be involved in defining estimands and how to do so. Public partners are patients and/or members of the public who are part of, or advise, the research team. We aimed to (i) co-develop a tool with public partners that helps explain what an estimand is and (ii) explore public partner’s perspectives on the importance of discussing estimands during trial design. Methods An online consultation meeting was held with 5 public partners of mixed age, gender and ethnicities, from various regions of the UK. Public partner opinions were collected and a practical tool describing estimands, drafted before the meeting by the research team, was developed. Afterwards, the tool was refined, and additional feedback sought via email. Results Public partners want to be involved in estimand discussions. They found an introductory tool, to be presented and described to them by a researcher, helpful for starting a discussion about estimands in a trial design context. They recommended storytelling, analogies and visual aids within the tool. Four topics related to public partners’ involvement in defining estimands were identified: (i) the importance of addressing questions that are relevant to patients and public in trials, (ii) involving public partners early on, (iii) a need for education and communication for all stakeholders and (iv) public partners and researchers working together. Conclusions We co-developed a tool for researchers and public partners to use to facilitate the involvement of public partners in estimand discussions.