Articles de revues : « Burcev en anderen »

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Yang, Shuang, et Wan Nur Tasnim Wan Hussin. « Research on Older Adults’ Willingness to Enroll in Health Care Services based on Andersen Behavioral Model ». Academic Journal of Management and Social Sciences 5, n^o 1 (14 novembre 2023) : 23–26. http://dx.doi.org/10.54097/ajmss.v5i1.13902.

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Ageing has increasingly become a severe social problem nowadays, resulting in burden for both whole society and each family unit. Jiangsu is a typical aging province in China with dramatically increasing aging population. This paper analyzed Andersen behavioral model theoretically and empirically, and made an overview about older adults’ healthcare services utilization behavior from three aspects, namely, predisposing characteristics, enabling resources, and need factors. This paper revealed that it is significant to apply Andersen behavioral model in older adults’ healthcare services utilization in Jiangsu to understand older adults’ healthcare enrollment behavior, and provide evidence for healthcare services providers and policy makers to better manage and allocate social resources to improve services quality thus relieve family pressure brought by aging society.

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Brown, Suzanne, David E. Biegel et Elizabeth M. Tracy. « Likelihood of Asking for Help in Caregivers of Women With Substance Use or Co-Occurring Substance Use and Mental Disorders ». Care Management Journals 12, n^o 3 (septembre 2011) : 94–100. http://dx.doi.org/10.1891/1521-0987.12.3.94.

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Family members are important to the well-being of their relatives with substance use disorders or co-occurring substance use and mental disorders. Many caregivers experience high levels of burden, negatively impacting their capacity to provide support to their ill family member. The Andersen health care utilization model (Andersen & Newman, 1973, 2005) was used to identify the impact of predisposing, enabling, and need factors hypothesized to predict caregivers’ likelihood of asking for help and support with their caregiving role. The sample include 82 women recruited from outpatient or inpatient substance abuse treatment centers and 82 family caregivers nominated by these women. Findings showed that almost half of caregivers were unlikely to ask for help. Multiple regression analysis found that two need variables were statistically significant predictors of caregivers’ likelihood to ask for help. Caregivers who had higher subject burden (worry) and caregivers who provided more assistance with daily living were more likely to ask for help. It is suggested that case managers assess the amount of worried family caregivers’ experience because their worries may provide the motivation to ask for help or to participate in help when it is offered to them.

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Rezazadeh, Saman, Jiqing Guo, Henry J. Duff, Raechel A. Ferrier et Brenda Gerull. « Reversible Dilated Cardiomyopathy Caused by a High Burden of Ventricular Arrhythmias in Andersen-Tawil Syndrome ». Canadian Journal of Cardiology 32, n^o 12 (décembre 2016) : 1576.e15–1576.e18. http://dx.doi.org/10.1016/j.cjca.2016.07.587.

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Lehmann, Karin. « Wirtschaftliche Führungskräfte der Bundesrepublik Deutschland (Sibylle Krause-Burger, Die andere Elite ; Dieter Balkhausen, Alfred Herrhausen) ». Jahrbuch für Wirtschaftsgeschichte / Economic History Yearbook 32, n^o 4 (1 octobre 1991) : 133–34. http://dx.doi.org/10.1515/jbwg-1991-320413.

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Bischof, Günter. « Heinrich Wildner Tagebücher 1938–1944 : “Heute geht es gegen die Juden, morgen kann es gegen die anderen gehen . . .” ed. by Gertrude Enderle-Burcel (review) ». Journal of Austrian Studies 57, n^o 2 (juin 2024) : 113–26. http://dx.doi.org/10.1353/oas.2024.a929391.

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Sun, Qian, Nan Lu, Nan Jiang et Vivian W. Q. Lou. « Intention to use respite services among informal care-givers of frail older adults in China : the role of care needs change ». Ageing and Society 41, n^o 1 (22 mai 2020) : 101–20. http://dx.doi.org/10.1017/s0144686x20000628.

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AbstractPopulation ageing in China calls for evidence-based solutions, especially in terms of fulfilling long-term care needs among frail older adults. Respite services are identified as effective resources for alleviating care-giver burden and promoting the wellbeing of both older adults and their family care-givers. However, respite care is often under-used in China. This research aimed to examine factors associated with intention to use respite services among informal care-givers in Shanghai, mainland China. This study was part of the Longitudinal Study on Family Caregivers for Frail Older Adults in Shanghai. Pairs of older adults and their care-givers (N = 583) who successfully completed the 2013 and 2016 waves were included in the data analysis. Two logistic regression models were conducted, one with time-invariant and one with time-variant factors. The model with time-variant factors had greater explanatory power than the original Andersen model with time-invariant factors influencing intention to use respite services among care-givers. Care-givers had higher odds of intending to use respite services if they had higher care-giving burden, were caring elderly people who experienced care-giver transitions, or were caring for elderly people with increased function of ambulation or decreased function of feeding. The findings imply that change in functional health was a significant determinant of intention to use respite care. Relevant policy and service implications will be discussed.

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Kilian, Jürgen. « Krieg auf Kosten anderer. Wehrmachtfinanzierung in Griechenland während des Zweiten Weltkriegs / War at the Expence of Others Financing the „Wehrmacht“ in Greece during the Second World War ». Südost-Forschungen 73, n^o 1 (8 août 2014) : 38–59. http://dx.doi.org/10.1515/sofo-2014-0104.

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Abstract After Greece had been conquered by the troops of the Axis Powers in spring 1941, they installed a rule of occupation existing until october 1944. The Government in Athens had to finance this occupation by making payments in advance and besides, making a forced credit available. This method led to an exorbitant overloading of the Greek economy and to a galloping inflation. The German Tax and Finance Ministry played an important, yet hardly noticed role as to the concrete implementation of the monetary exploitation. Almost unknown documents throw a light on the financing of the German Wehrmacht during WW II. Besides, the real burden on the Greek economy shall be estimated and connected with the general questions of war financing in the Third Reich.

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Wiedemann, Andreas, Vedat Dündar, Melanie Heese, Thomas Leufgens, Stefan Wirz, Robin Brauckmann et Hans-Jürgen Heppner. « Unerwünschte Arzneimittelwirkungen am Harntrakt – der Wittener Harntrakt-Nebenwirkungs-Score ». Aktuelle Urologie 52, n^o 05 (31 mai 2021) : 481–89. http://dx.doi.org/10.1055/a-1352-9370.

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ZusammenfassungObwohl der Harntrakt mit Restharnbildung, Harnverhaltung, Pollakisurie, Polyurie, Nykturie, Detrusorstimulation, Detrusorhemmung, Hämaturie, Dysurie und anderen Erscheinungen häufig den Schauplatz unerwünschter Arzneimittelwirkungen darstellt, fehlt es an einer Gesamtübersicht an Substanzen, die eine solche Harntraktnebenwirkung auslösen können und eine entsprechende Bewertung. Vorhandene Listen „potenziell inadäquater Medikation“ fokussieren entweder auf eine pharmakologische Gruppe von Nebenwirkungen („anticholinergic burden score“), eine Gruppe von Medikamenten bestimmter Indikation (LUTS-Forta) oder auf eine selektionierte Gruppe von Patienten (PRISKUS-Liste, beers-Liste).Mit dem folgenden interdisziplinären Projekt aus der Arbeitsgruppe Uro-Geriatrie der Universität Witten/Herdecke sollte diese Lücke geschlossen werden. Es erfolgte eine Identifikation von Substanzen, die eine Harntraktnebenwirkung lt. diverser Datenbanken prinzipiell auslösen können, eine Kategorisierung der hierzu vorhandenen Literatur (Kasuistik, Fallsammlung, RCT, Metaanalyse) und eine strukturierte Bewertung des Risikos durch 33 Experten. Das Ergebnis stellt eine Liste von 235 Substanzen dar, die zu verschiedenen Harntraktnebenwirkungen führen können. Diese Liste enthält einen die Nennung in Datenbanken bzw. deren Korrelat in der Literatur darstellenden „theroretischen“ Punktwert, einen die klinische Realität abbildenden „praktischen“ Punktwert, der die Expertenbewertung darstellt, und einen Summenscore – geordnet nach der Systematik der „Roten Liste“.Erstmals wäre damit sowohl bei der Neuverordnung einer Substanz vor dem Hintergrund bestehender patientenseitiger Risiken eine Einschätzung dieses Wirkstoffes im Hinblick auf Harntraktnebenwirkungen möglich; andersherum könnte die Durchsicht des Medikationsplanes bei Vorhandensein einer Harntraktfunktionsstörung die Frage klären, ob diese medikamentös (mit-) verursacht ist. Die Entwicklung des „Harntraktnebenwirkungs-Rechners“ als „App“ ist geplant.

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Snijders, Tjamke. « Burcht Pranger, God (1000–1300) en andere essays over literaire aspecten van het christendom [Middeleeuwse Studies en Bronnen 142]. Verloren, Hilversum 2013, 192 pp. ISBN 9789087043223. €25. » Church History and Religious Culture 94, n^o 1 (2014) : 90–91. http://dx.doi.org/10.1163/18712428-09401009.

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Du, Jinglin, Xue Yang, Mingsheng Chen et Zhonghua Wang. « Socioeconomic determinants of out-of-pocket pharmaceutical expenditure among middle-aged and elderly adults based on the China Health and Retirement Longitudinal Survey ». BMJ Open 9, n^o 7 (juillet 2019) : e024936. http://dx.doi.org/10.1136/bmjopen-2018-024936.

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ObjectiveOut-of-pocket pharmaceutical expenditure (OOPPE) is a considerable burden for middle-aged and elderly adults due to their high prevalence of diseases, insufficient income and absence of medical insurance in China. The objective of this study was to assess the determinants of OOPPE among Chinese middle-aged and elderly adults.MethodsThis is a cross-sectional study based on the China Health and Retirement Longitudinal Survey conducted in 2015. The Andersen behavioural health model was used to select the factors. Binary multivariable logistic and generalised linear regressions were both applied to examine the determinants of OOPPE.ResultsOf the respondents, 15.28%, 5.20% and 51.35% reported an OOPPE for outpatient services, inpatient services and self-medication, respectively. The OOPPE for outpatient services, inpatient services and self-medication was US$6.66, US$17.93 and US$15.32, respectively. Increased age significantly influenced the likelihood of OOPPE, and older people (aged >65 years) had lower OOPPE for outpatient services. Having health insurance significantly reduced the likelihood of OOPPE for outpatient and inpatient services but increased OOPPE for self-medication. In general, compared with the low-income group, higher income groups had a significantly lower likelihood of having an OOPPE, and when they did the amounts were less. Generally, middle-aged and elderly people with poor self-reported health status, limitation of daily activities, and critical or chronic diseases had a significantly higher likelihood of having an OOPPE and at a significantly higher amount.ConclusionPolicy-making efforts should focus on reducing self-medication OOPPE and alleviating its associated socioeconomic determinants to ease the economic burden of diseases among middle-aged and elderly adults in China.

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Younis, Arwa, Sanah Ali, Eileen Hsich, Ido Goldenberg, Scott McNitt, Bronislava Polonsky, Mehmet K. Aktas et al. « Arrhythmia and Survival Outcomes Among Black Patients and White Patients With a Primary Prevention Defibrillator ». Circulation 148, n^o 3 (18 juillet 2023) : 241–52. http://dx.doi.org/10.1161/circulationaha.123.065367.

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BACKGROUND: Black Americans have a higher risk of nonischemic cardiomyopathy (NICM) than White Americans. We aimed to evaluate differences in the risk of tachyarrhythmias among patients with an implantable cardioverter-defibrillator (ICD). METHODS: The study population comprised 3895 ICD recipients in the United States enrolled in primary prevention ICD trials. Outcome measures included ventricular tachyarrhythmia (VTA), atrial tachyarrhythmia (ATA), ICD therapies, VTA burden (using Andersen-Gill recurrent event analysis), death, and the predicted benefit of the ICD. All events were adjudicated blindly. Outcomes were compared between self-reported Black patients versus White patients with cardiomyopathy (ischemic and NICM). RESULTS: Black patients were more likely to be female (35% versus 22%) and younger (57±12 versus 62±12 years) with a higher frequency of comorbidities. In NICM, Black patients had a higher rate of first VTA, fast VTA, ATA, and appropriate and inappropriate ICD therapy (VTA ≥170 bpm, 32% versus 20%; VTA ≥200 bpm, 22% versus 14%; ATA, 25% versus 12%; appropriate therapy, 30% versus 20%; and inappropriate therapy, 25% versus 11%; P <0.001 for all). Multivariable analysis showed that Black patients with NICM experienced a higher risk of all types of arrhythmia or ICD therapy (VTA ≥170 bpm, hazard ratio [HR] 1.71; VTA ≥200 bpm, HR 1.58; ATA, HR 1.87; appropriate therapy, HR 1.62; inappropriate therapy, HR 1.86; P ≤0.01 for all), higher burden of tachyarrhythmias or therapies (VTA, HR 1.84; appropriate therapy, HR 1.84; P <0.001 for both), and a higher risk of death (HR 1.92; P =0.014). In contrast, in ischemic cardiomyopathy, the risk of all types of tachyarrhythmia, ICD therapy, or death was similar between Black patients and White patients. Both Black patients and White patients derived a significant and similar benefit from ICD implantation. CONCLUSIONS: Among patients with NICM with an ICD for primary prevention, Black patients compared with White patients had a high risk and burden of VTA, ATA, and ICD therapies with a lower survival rate. Nevertheless, the overall benefit of the ICD was maintained and was similar to that of White patients.

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Effiong, Ben Victor, et Oboma Lawrence Adhowhoarie. « Predictors of antenatal care services utilization by pregnant women in a selected Akwa Ibom state community, Nigeria ». American Journal of Social Sciences and Humanities 8, n^o 2 (11 mai 2023) : 173–86. http://dx.doi.org/10.55284/ajssh.v8i2.913.

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In Nigeria, the burden and incidence rate of maternal mortality significantly affects the achievement of the Sustainable Development Goal 3. The study was designed to investigate the factors and trends of Antenatal Care Services Utilization by Pregnant Women in Anua Community Akwa Ibom State, Nigeria. The assumptions of Andersen Behavioural Model of Health Services and Antonovsky Theory of Social Class were adopted to explain the use of antenatal care services. A combined survey was conducted to obtain primary data from 264 women between the ages of 15 and 49 selected as respondents through snowball and respondents driven sampling techniques; antenatal registers and documents at the Antenatal Care Unit of health facility were reviewed to obtain secondary data. Findings from the study showed an extended predictors of antenatal care services utilization rooted in the socio-cultural, economic, demographic and environmental configurations of the study area. Based on the findings, strengthening of health facility, the implementation of health intrventions and enforcement of policies such as free enrolment of all pregnancies and compulsory Antenatal Care Services Utilization in the study area were recommended. The recommendations have inplications to reduce the incidence rate of maternal mortality and improve child health outcomes in the study area.

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Nonoyama, Mika L., Douglas A. McKim, Jeremy Road, Denise Guerriere, Peter C. Coyte, Marina Wasilewski, Monica Avendano et al. « Healthcare utilisation and costs of home mechanical ventilation ». Thorax 73, n^o 7 (26 janvier 2018) : 644–51. http://dx.doi.org/10.1136/thoraxjnl-2017-211138.

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BackgroundIndividuals using home mechanical ventilation (HMV) frequently choose to live at home for quality of life, despite financial burden. Previous studies of healthcare utilisation and costs do not consider public and private expenditures, including caregiver time.ObjectivesTo determine public and private healthcare utilisation and costs for HMV users living at home in two Canadian provinces, and examine factors associated with higher costs.MethodsLongitudinal, prospective observational cost analysis study (April 2012 to August 2015) collecting data on public and private (out-of-pocket, third-party insurance, caregiving) costs every 2 weeks for 6 months using the Ambulatory and Home Care Record. Functional Independence Measure (FIM) was used at baseline and study completion. Regression models examined variables associated with total monthly costs selected a priori using Andersen and Newman’s framework for healthcare utilisation, relevant literature, and clinical expertise. Data are reported in 2015 Canadian dollars ($C1=US$0.78=₤0.51=€0.71).ResultsWe enrolled 134 HMV users; 95 with family caregivers. Overall median (IQR) monthly healthcare cost was $5275 ($2291–$10 181) with $2410 (58%) publicly funded; $1609 (39%) family caregiving; and $141 (3%) out-of-pocket (<1% third-party insurance). Median healthcare costs were $8733 ($5868–$15 274) for those invasively ventilated and $3925 ($1212–$7390) for non-invasive ventilation. Variables associated with highest monthly costs were amyotrophic lateral sclerosis (1.88, 95% CI 1.09 to 3.26, P<0.03) and lower FIM quintiles (higher dependency) (up to 6.98, 95% CI 3.88 to 12.55, P<0.0001) adjusting for age, sex, tracheostomy and ventilation duration.ConclusionsFor HMV users, most healthcare costs were publicly supported or associated with family caregiving. Highest costs were incurred by the most dependent users. Understanding healthcare costs for HMV users will inform policy decisions to optimise resource allocation, helping individuals live at home while minimising caregiver burden.

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Sriram, Shyamkumar, Arun Daniel Jayakumar, Pavan Kumar Gollapalli et Swetha Chadrasekar. « Demand-side barriers and economic burden in accessing Human Papillomavirus screening for cervical cancer prevention in rural India : Evidence from a cross-sectional study ». F1000Research 13 (13 juin 2024) : 630. http://dx.doi.org/10.12688/f1000research.150361.1.

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Introduction Cervical cancer is a significant global health concern, especially in low- and middle-income countries with limited access to preventive healthcare. India’s vast rural population amplifies the challenge, demanding immediate action. Despite advancements, cervical cancer remains prevalent among underserved rural communities, hindered by barriers to Human Papillomavirus (HPV) screening uptake, including socioeconomic and financial constraints. This study aims to evaluate the economic challenges encountered by rural women when accessing HPV screening. Methods A cross-sectional survey was conducted among 1502 women aged 30 to 45 in Pondicherry, India, utilizing the Andersen Model as a conceptual framework. Household questionnaires gathered data on HPV screening expenses, including patient travel costs, productivity loss, and companion costs. The analysis utilized regression models, to identify the factors impacting the economic challenges associated with accessing HPV screening. Results Employment status and higher education significantly increase total costs by 73.483 (p < 0.001) and 90.169 units (p < 0.001) respectively. Income level, though with a minimal coefficient (B = 0.000), shows a significant effect (p = 0.019) on total costs. Longer travel hours raise costs by 5.129 units (p < 0.001), while having a companion increases costs by 106.095 units (p = 0.004). Prolonged patient time at Primary Health Center (PHC) contributes to a 2.357-unit increase in costs (p < 0.001). Conclusions The study highlights the multifaceted economic challenges faced by rural populations accessing HPV screening for cervical cancer prevention in India. Notwithstanding diverse demographics and varying proximity to healthcare facilities, individuals encounter significant barriers such as travel time and associated costs. Addressing these challenges necessitates targeted interventions to reduce socioeconomic disparities and improve healthcare accessibility for vulnerable populations, thereby advancing cervical cancer prevention efforts and promoting health equity in rural communities.

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Bischoff, Werner, David Ornelles, Lauren Ivey et Bill Payne. « Assessing alternatives to HEPA air purification requirements to reduce viral pathogen transmission in healthcare HVAC systems ». Antimicrobial Stewardship & ; Healthcare Epidemiology 2, S1 (16 mai 2022) : s85. http://dx.doi.org/10.1017/ash.2022.217.

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Background: High-efficiency particulate air (HEPA) filters are currently recommended when using recirculated air to eliminate the risk of pathogen transmission such as SARS-CoV-2 from one patient care area to the next. We tested the efficacy of lower-grade air filters in eliminating airborne virus transmission. Methods: We conducted an experiment in 2 adjacent exam rooms in an unoccupied hospital emergency unit. The HVAC system contained a 15,000-cubic-feet-per-minute rooftop air handler. All outside air and exhaust dampers were closed during the trial (full air recirculation). We conducted experiments in 3 tests arms with varying grades of MERV filters (AAF Flanders, Louisville, KY): (1) control without filters, (2) MERV8+14 filters, and (3) MERV8+16 filters. We repeated 20-minute virus challenge runs 3 times per test arm. Live attenuated influenza vaccine (2 mL LAIV, FluMist Quadrivalent 2020/21, AstraZeneca, Wilmington, DE), was aerosolized into the HVAC system via a commercial nebulizer. Air was sampled using 3 six-stage Andersen air samplers placed in the center of the adjacent room. Environmental particle counts were collected using a particle counter (PEC-PCO-1, PCE Americas). Results: Concentrations of viral RNA were determined by qPCR, and viral concentrations (vg/mL) in each stage of each arm were compared directly. Pairwise comparisons of the virus and particle burdens across each stage of each test arm were made using a general linear model. LAIV was detected in the control arm at a virus burden of 2,277 vg/mL, indicating a >6.5 log reduction of the virus released in the HVAC system (8.8×109 total vg). In the second arm, the MERV8+MERV14 filters demonstrated in a 13-fold decrease in viral burden compared to the control arm (mean virus burden: 169 vg/mL, p Our study demonstrates that viral containing particles can be transported via a hospital HVAC system from one patient room to the next. Considering the decrease in detectable virus within the HVAC system, the combination of MERV8+MERV16 filters reduced the virus burden reaching an adjacent room to levels well below the human infectious dosages for influenza and other highly infective viruses. Conclusions: Our findings indicate that MERV8+MERV16 filters provide protection against virus transmission through HVAC systems and are a cost-conscious alternative to HEPA filters.Funding: NoneDisclosures: None

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Cornet, A., J. Andersen, F. Marchiori, A. Sturiene, A. Edwards, P. Mertz et L. Arnaud. « POS0571 ASSOCIATION BETWEEN DIAGNOSIS DELAY AND DISEASE ACTIVITY WITH BURDEN OF THE DISEASE IN 4150 EUROPEAN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS ». Annals of the Rheumatic Diseases 82, Suppl 1 (30 mai 2023) : 554.1–554. http://dx.doi.org/10.1136/annrheumdis-2023-eular.1250.

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BackgroundDespite significant improvements in diagnosis delay and treatment strategies, the burden of Systemic Lupus Erythematosus (SLE) remains high.ObjectivesThe objective of the study was to assess the association between diagnosis delay, disease activity and burden on daily life (BoDL) in a large sample of European patients with SLE.MethodsIn May 2020, Lupus Europe, the European umbrella patient association for SLE, conducted a multilingual anonymous online cross-sectional study to individuals with a self-reported physician’s diagnosis of SLE living in Europe. The BoDL score was computed using 1 to 5 Likert scales on 5 domains (mobility, anxiety/depression, self-care, daily activities and pain/discomfort) and the sum was transposed on a 0 (minimum Burden on daily life) to 100 (maximum BoDL) scale. Comparisons between independent groups were made using the Mann-Whitney test for continuous outcomes and the Chi-2 test (or Fisher’s exact test) for quantitative data.ResultsData of 4,150 SLE patients from 35 European countries were analysed.The mean (±SD) BoDL score in the study population was 37.8 (±18.7) with a modest downward trend of the BoDL based on age (from 33.4% to 42.1% from age less than 25 to age 65 - a loss of up to 9% points over up to 40 years).The diagnosis delay was reported to be <2 years in 1903 participants (47.5%), between 2 and <5 years in 1056 (26.3%) and ≥5 years or more in 1049 (26.2%). 142 did not answer.. Those with a diagnosis of SLE within 2 years of first symptoms had significantly lower mean Burden on daily life scores than those diagnosed after 5 years (33.6 versus 44.0, p<0.001). This trend is deemed robust as it was found across almost all European countries. These results highlight the importance of improving current diagnosis delay for SLE as a way to improve the burden of the disease on daily life.A total of 2980 (71.8%) patients felt that their “lupus has been under control over the last 3 months” while 1166 (28.1%) did not. 4 did not answer. The Burden on daily life score was significantly better in SLE patients feeling that their lupus had been under control during the past 3 months versus the others (34.0% versus 47.6%, p<0.001). Again, this trend was found across almost all European countries.ConclusionThis large patient survey reveals both the importance of prompt SLE diagnosis as well the relationship between disease activity and disease burden upon the daily life of European lupus patients. Further improvements should focus on reducing the diagnosis delay and identifying new therapeutic strategies for those with uncontrolled disease. Healthcare pathways, which may accelerate diagnosis and optimize therapeutic management, are necessary to improve patients’ outcomes in SLE.Reference[1]Cornet A, Andersen J, Myllys K, et al Living with systemic lupus erythematosus in 2020: a European patient survey Lupus Science & Medicine 2021;8:e000469. doi: 10.1136/lupus-2020-000469Acknowledgements:NIL.Disclosure of InterestsNone Declared.

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Zeng, Yanbing, Weiqian Xu et Xiaomeng Tao. « What factors are associated with utilisation of health services for the poor elderly ? Evidence from a nationally representative longitudinal survey in China ». BMJ Open 12, n^o 6 (juin 2022) : e059758. http://dx.doi.org/10.1136/bmjopen-2021-059758.

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ObjectivesTo investigate the status and factors of healthcare service utilisation among the poor elderly in China.MethodsWe selected the poor elderly from the China Health and Retirement Longitudinal Study (CHARLS) from 2011 to 2015. The main outcome measures include utilisation indicators for the probability and costs of outpatient/inpatient services. Based on modified Andersen behaviour model, a two-part model is designed to analyse the factors of the health service utilisation of the poor elderly.ResultsThe visit rate of outpatient services increased from 15.05% in 2011 to 21.26% in 2015, and the hospitalisation rate increased from 7.26% to 14.32%. The median cost of outpatient and inpatient services in 2015 for the poor elderly were 350 RMB and 10 000 RMB, respectively, and the out-of-pocket ratios were 85.2% and 53.3%, respectively. 78.44% of the people who actually needed healthcare did not use health services, and the main reason was financial difficulties (42.32%). The poor elderly who are higher educated, have children, live in central regions and have social security and a poor health status and who do not smoke or drink are more likely to use health services. The need factor plays a crucial role in determining health service utilisation.ConclusionsThe poor elderly tends to have a worse health status and a heavier medical burden but had a lower utilisation of health services. Predisposing, enabling, need and health behaviour variables should be considered to improve the health service utilisation and the health of the poor elderly.

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Levison, Julie H., Lourdes García-Fragoso, Ines E. García García, Paola Del Cueto, Leticia Gely, Maria F. Levis, Miguel Valencia-Prado et Dharma E. Cortés. « 1139. Adherence to Zika virus-related Pediatric Follow-up Care in Puerto Rico ». Open Forum Infectious Diseases 7, Supplement_1 (1 octobre 2020) : S598. http://dx.doi.org/10.1093/ofid/ofaa439.1325.

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Abstract Background Over three thousand children in Puerto Rico were potentially exposed to Zika virus infection during pregnancy during the 2016 Zika virus epidemic. This congenital exposure is an established risk factor for birth defects and neurodevelopmental abnormalities, which may appear after birth. Puerto Rico guidelines require consistent pediatric monitoring for early identification and intervention of children up to age five. Methods Our objective was to assess factors that influence caregiver adherence to Zika-related follow-up pediatric services in Puerto Rico. We conducted qualitative semi-structured focus groups and individual interviews with 57 individuals, including 35 caregivers (aged ≥18 years and a primary caregiver for a child with laboratory evidence of confirmed or possible Zika virus infection during pregnancy) and 22 healthcare providers or service coordinators. We explored participants’ views on barriers to Zika-related pediatric services and suggestions for improving appointment attendance. Interviews were recorded, transcribed, and translated. We developed and applied a coding scheme based on barriers and facilitators from the Andersen Model of Health Care Utilization and Katz Model for Adolescent Vaccine Adherence (a multi-step process influenced by adolescent and caregiver factors). Data were analyzed using thematic analysis. Results Three themes influencing adherence to Zika-related pediatric follow-up care were consistently reported throughout the interviews and focus groups discussions: (1) logistics of getting child to appointments based on clinic location, availability and costs associated with transportation, and physical requirements to transport child or multiple children; (2) complexity of requirements for follow-up appointments; and (3) caregiver burden including emotional, social, and time. Conclusion Barriers to Zika-related pediatric follow-up care in Puerto Rico are complex and multi-level. Core intervention targets should include caregiver burden, health system navigation, and coaching caregivers in communication with pediatric providers. Use of a caregiver-delivered manualized intervention led by community health workers seems appropriate to achieve these goals. Disclosures All Authors: No reported disclosures

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Siekmann, Helmut. « The Burden of an Ageing Society as a Public Debt : The Perspective of the German Constitutional Law and the Law of the European Union ». European Public Law 13, Issue 3 (1 septembre 2007) : 489–518. http://dx.doi.org/10.54648/euro2007028.

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This article is based on the assumption that the financial burden of an ageing society can be considered as an ‘implicit’ public debt. The future claims (‘prospective entitlements’) to unfunded public pension systems will result in severe financial strains for public finances because of the demographic developments in Germany and other industrialized nations. A closer analysis of the German (federal) constitution reveals that there are almost no provisions to handle the potential dangers from this foreseeable development. The rules on explicit public debt and the accounting requirements for the government are in this respect of little value. The law of the European Union, on the other hand, contains a somewhat better starting point as the EC Treaty requires the ‘sustainability’ of the fiscal policy. By this it offers at least a rudimentary guideline for a long term budget-policy regulation of the ‘implicit’ public debt. Stricter legal rules would, however, require an amendment of primary law of the European Union or at least a substantial redefinition of the existing definitions of the European system of Economic Accounts (ESA). One of the chief purposes of this article is to look for legal tools taking the expected financial burdens into proper account and make it more ‘visible’ for the budgetary process. It is not primarily designed to cut future pensions or to exclude ‘soft’ means from solving the underlying substantive problems. The comparative analysis of additional legal systems is left to further research. Dieser Artikel beruht auf der Annahme, dass die finanziellen Lasten einer alternden Gesellschaft als‘implizite’ Staatsschulden angesehen werden können. Anwartschaften auf Rentenzahlungen durch umlagenfinanzierte Alterssicherungssysteme können wegen des demographischen Wandels in Deutschland und anderen Industrienationen zu erheblichen Belastungen für die öffentlichen Finanzen führen. Eine genauere Prüfung der Vorgaben des Grundgesetzes für die Staatsfinanzen zeigt, dass es kaum Vorschriften gibt, welche sich mit den Gefahren aus der voraussehbaren Entwicklung befassen. Die Regeln über die Staatsverschuldung und die Rechnungslegung haben in dieser Hinsicht wenig Wert. Das Recht der Europäischen Union bietet dagegen etwas bessere Ansatzpunkte, da der EG-Vertrag die‘Nachhaltigkeit’ der Finanzpolitik verlangt. Dadurch bietet er zumindest eine rudimentäre Richtschnur für eine langfristige haushaltsmäßige Regelung der ‘impliziten’ öffentlichen Schulden. Striktere Rechtsregeln würden aber eine Änderung des primären Gemeinschaftsrechts oder zumindest eine substanzielle Umdeutung der Definitionen des Europäischen Systems der Europäischen Gesamtrechnung (ESVG) erfordern. Eines der Hauptziele dieser Untersuchung besteht darin, nach geeigneten juristischen Instrumenten zu suchen, welche die kommenden finanziellen Lasten hinreichend erfassen und im Rahmen des Finanzverfassungsrechts handhabbar machen. Sie ist nicht darauf ausgerichtet, Instrumente zur Kürzung künftiger Pensions- und Rentenzahlungen zu entwickeln oder ‘weichere’ Instrumente zur Lösung der zugrunde liegenden materiellen Probleme auszugrenzen. Die vergleichende Analyse weiterer Rechtsordnungen bleibt künftiger Forschung vorbehalten.

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Hradová, Jana. « The Nature of Disease as a Pastoral Key. A Theological Reflection ». European Journal of Theology 28, n^o 2 (1 décembre 2020) : 154–60. http://dx.doi.org/10.5117/ejt2019.2.007.hrad.

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SummaryDo disease and suffering, in their deepest essence, represent blessings? Are they allowed or even intended by God? Are they, primarily, a test of faith and a cryptogram which needs to be decoded and responded to, or does their presence rather obscure the true nature of salvation? Specific ways of thinking about diseases, such as those of Smolík, MacNutt, Grün, Dufner and others, substantially influence the objectives and methods of pastoral work. In addition to some relevant biblical texts, this article deals with considerations of how the burden of suffering can be shared with other people, how the disappointed expectation of healing can be coped with, and how the goodness of God can be perceived in this context. The author gives the advice to enter the area of trust, because it is trust which primarily changes the very perception and experience of the reality, as it provides a new view of Christ, part of which is also healing by God’s grace. For this reason, the service of healing is a common part of life in the Christian community, not merely a memory of the practice in the Early Church or even an unexpected and completely surprising manifestation of the Spirit of God.ZusammenfassungStellen Krankheit und Leiden in ihrem tiefsten Wesen wirklich Segnungen dar? Sind sie von Gott zugelassen oder gar beabsichtigt? Verkörpern sie allem voran eine Glaubensprüfung und einen Geheimcode, der zu entschlüsseln und zu beantworten ist? Oder verdunkelt ihre Anwesenheit eher das, was Erlösung in ihrem eigentlichen Wesen ausmacht? Unterschiedliche Denkweisen über Krankheit, wie jene von Smolík, MacNutt, Grün, Dufner und anderen, beeinflussen ganz wesentlich die Ziele und Methoden pastoraler Arbeit. Der Artikel stellt einige relevante Bibeltexte zur Verfügung; zusätzlich denkt er darüber nach, wie die Last von Leiden mit anderen Menschen geteilt werden, wie man mit enttäuschten Heilungserwartungen umgehen und wie die Güte Gottes darin wahrgenommen werden kann. Die Autorin rät dazu, in den Raum des Vertrauens hineinzugehen, denn gerade Vertrauen verändert vor allem die Wahrnehmung und das Erleben von Realität, weil es eine neue Sicht auf Christus gewährt; und dazu gehört auch Heilung durch die Gnade Gottes. Aus diesem Grund ist der Heilungsdienst ein ganz normaler Teil im Leben der christlichen Gemeinde und eben nicht nur eine Erinnerung an die Praxis in der Urgemeinde oder gar eine unerwartete und völlig überraschende Manifestation des Geistes Gottes.RésuméLa maladie et la souffrance sont-elles par essence source de bénédiction ? Sont-elles permises, ou même voulues par Dieu ? Sont-elles principalement une mise à l’épreuve de la foi et un cryptogramme appelant un décodage et une réponse, ou bien leur présence obscurcit-elle la véritable nature du salut ? La manière particulière dont on considère les maladies a des incidences importantes sur les objectifs et les approches du ministère pastoral. Prêtant attention à certains textes bibliques pertinents, l’auteur considère comment le fardeau de la souffrance peut être porté avec d’autres personnes, comment on peut faire face à l’attente de guérison déçue, et comment la bonté de Dieu peut être perçue dans un tel contexte. Elle conseille d’adopter un état d’esprit confiant, car c’est la confiance qui change principalement la perception et l’expérience de la réalité, en conduisant à une nouvelle manière de voir Christ, qui, en partie, procure aussi une certaine guérison par la grâce divine. C’est pourquoi le ministère de guérison fait communément partie de la vie de la communauté chrétienne et ne se réduit pas au simple souvenir de la pratique de l’Église primitive, ou ne constitue pas une manifestation de l’Esprit de Dieu inattendue et totalement surprenante.

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S Masinde, Millicent, Joshua K Kayima, Wanyoike J Gichuhi, Eunice C Cheserem, Orora I Maranga et Samuel K Kabinga. « Infection with high-risk genotypes of human papillomavirus and cervical cytological findings among kidney transplant recipients in Kenya : a single centre experience ». African Health Sciences 22, n^o 2 (29 juillet 2022) : 88–96. http://dx.doi.org/10.4314/ahs.v22i2.11.

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Background: High-risk human papillomavirus (hrHPV) infection is linked with uterine cervix premalignant lesions and invasive carcinomaof the uterine cervix. Methods: Descriptive cross sectional study carried out among female kidney transplant (KTx) recipients in Kenyatta National Hospital, Nairobi-Kenya. We studied the risk factors for acquisition of hrHPV, examined cervical cytology and assayed for 14 hrHPV DNA using Cervista® HPV HR test and Cervista® MTA (Hologic®) automated platforms. Results: The 14-hrHPV genotypes assayed were 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68 and the prevalence rate was 31.25 % (10/32). Abnormal cervical cytology was noted in 4/32 (12.5%) and included low-grade squamous intraepithelial lesion (2/32), atypical squamous cells of undetermined significance (1/32) and atypical glandular cells (1/32). The average age was 41.9 years with mean age at first coitus being 20.4 years. Majority of the women 20(62.5%) were married while 8(25%) were single. About 18(56.3%) had only one sexual partner. About 20% of women were nulliparous and 4(12.5%) had a parity of five. Duration since transplantation ranged between 1-21 years. Conclusions: The burden of hrHPV and abnormal cervical cytology in our study seemed lower than that reported elsewhere andeven in general population. This study may form basis for further studies about HPV infections and carcinoma of the uterine cervixamong the kidney allograft recipients in our setting. Keywords: Cervical carcinoma; kidney transplant recipients; high risk Human Papillomavirus.

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Andersen, Stacy, et Patricia Heyn. « Alzheimer’s Disease Research and Outreach in the New Normal : Transitioning to the Virtual World ». Innovation in Aging 5, Supplement_1 (1 décembre 2021) : 135–36. http://dx.doi.org/10.1093/geroni/igab046.525.

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Abstract Following disruptions to research, clinical trials, and support for individuals with Alzheimer’s disease and related dementias (ADRD), 2020 taught us important lessons about the need for creativity, flexibility, and resourcefulness during an urgent and global public health crisis. The COVID-19 pandemic showed that we have knowledge and technology that can be rapidly implemented, adopted, and utilized by many sectors to allow the continued care and research of our older adult population with ADRD. Thus, this symposium will address virtual methods that are transforming ADRD research and support. First, Dr. Rhodus will discuss the implementation of online assessments in clinical trials at an Alzheimer’s Disease Research Center and the effects of sociodemographic disparities in online accessibility. Next, Dr. Bazzano will describe methods of remote collection of brain health data through tablets, smartphones, and wearables in the Bogalusa Heart Study. Then, Dr. Andersen will report on the transition from in-person to virtual assessments of cognitive and physical function in centenarian studies and address strategies for inclusivity of individuals with limited technology experience. Next, Dr. Fazio will introduce Project VITAL which aims to impact social isolation by increasing accessibility to virtual education and support for care community staff, family caregivers, and individuals with dementia. Finally, Dr. Penfold will report on the translation of a paper-based, face-to-face intervention for reducing caregiver burden into a self-directed online learning program. Overall, these presentations highlight successes and challenges in incorporating virtual-based methods to maintain engagement with participants, individuals with ADRD, and caregivers during the pandemic and beyond.

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Shrestha, Srijana, Amber Amspoker, Tracy L. Evans, Melinda Stanely, Jessica Freshour, Sheila Richey et Mark E. Kunik. « PREDICTORS OF MEDICAL, SOCIAL SERVICE, AND MENTAL HEALTH USE AMONG PEOPLE WITH DEMENTIA AND THEIR CAREGIVERS ». Innovation in Aging 3, Supplement_1 (novembre 2019) : S933—S934. http://dx.doi.org/10.1093/geroni/igz038.3396.

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Abstract People with Alzheimer’s disease use more medical services (Eaker et al., 2002) and are admitted to inpatient facilities at higher rates (Zhu et al., 2015) than normal controls. In addition, social services provide support for caregivers and are associated with positive outcomes for care-recipients and their caregivers (Neville, Beattle, Fielding, & MacAndrew, 2014). Despite high level of need, utilization of mental health services and social agencies for caregiver support remains low (Goodarzi, Mele, Roberts & Holroyd-Leduc, 2017; Weber, Pirraglia & Kunik, 2011). Following the Andersen and Newman model (1973), we examined whether predisposing factors (i.e., age of the caregiver and type of PWD-caregiver relationship), needs (i.e., memory impairment, disruptive behaviors, depression, anxiety, pain, functional impairment, caregiver burden, total number of prescribed medications), and enabling factors (i.e., PWD and caregiver income, quality of the PWD-caregiver relationship) differentially predicted the presence of medical, social, and mental health service use. A total of 228 dyads (PWD and the caregiver) were included. We examined each PWD and caregiver characteristic individually (univariate models) and then as a unique predictor of each of the three service use outcomes (multivariate models). A greater number of medications uniquely predicted higher medical service use, greater pain severity and PWD income were uniquely associated with higher social service use, and a greater number of medications and increased memory impairment predicted more mental health service use. These results show that distinct factors predict use of different types of service use among PWD and their caregivers.

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Torres, Juliana L., Silvia L. A. da Silva, Fabiane R. Ferreira, Liliane P. S. Mendes et Luciana A. Machado. « Chronic pain is associated with increased health care use among community-dwelling older adults in Brazil : the Pain in the Elderly (PAINEL) Study ». Family Practice 36, n^o 5 (5 décembre 2018) : 594–99. http://dx.doi.org/10.1093/fampra/cmy123.

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Abstract Background Chronic pain is known to increase health care use in high-income countries, but in Brazil, little is known. Objective To investigate the association between chronic pain and health care use among Brazilian older adults and explore the relationship between pain severity and health care use. Methods This cross-sectional study was derived from the population-based study Frailty in Brazilian Older People-FIBRA. Chronic pain, pain intensity and pain-related disability were assessed through additional telephone interviews. Health care use was measured by the number of doctor visits, hospitalization events and high health care use (highest quartile of the distribution for number of doctor visits) in the last 12 months. Associations were tested in regression analyses adjusted for predisposing, enabling and illness-level components from the Andersen Model. Results The 383 participants were predominantly female (71.0%), mean age was 75.6 (6.1 SD). The prevalence of chronic pain was 30.0%. Chronic pain was associated with number of doctor visits [unstandardized B coefficient 1.48; 95% confidence interval (CI) = 0.35–2.62] and high health care use [odds ratios (OR) = 2.27; 95% CI = 1.39–3.72]. Pain intensity was associated with high health care use in univariate (OR = 1.13; 95% CI = 1.06–1.20) but not multivariate analysis (OR = 1.12; 95% CI = 0.94–1.33). Pain-related disability was not associated with any outcome. Conclusion Chronic pain increased health care use among Brazilian older adults. Improving the quality of primary care management of individuals at greater risk of chronic pain should be a cornerstone of health policies directed towards reducing the personal and societal burden of ageing.

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Choi, Hyojin, Kristin Litzelman, Autumn Harnish et Maija Reblin. « RESOURCE UTILIZATION AMONG FAMILY CAREGIVERS : INDIVIDUAL AND NEIGHBORHOOD CHARACTERISTICS ». Innovation in Aging 6, Supplement_1 (1 novembre 2022) : 355. http://dx.doi.org/10.1093/geroni/igac059.1404.

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Abstract Resources in the community play a pivotal role in increasing well-being of both care recipients and caregivers and ensuring equitable access to needed resources is a crucial priority for policy and practice. Drawing on the Andersen Behavioral Model, this study explored the longitudinal relationship between individual and neighborhood factors and social resource utilization (i.e., paid caregivers, respite care, support group, training, financial help, or transportation) among family caregivers. Unpaid family caregivers for community-dwelling older adults were identified using data from the National Study of Caregiving and National Health and Aging Trends Study (Time 1: 2015, Time 2: 2017; n=616). Neighborhood characteristics were indicators of the Social Vulnerability Index and provider density at the census-tract level. Poisson regression was used to assess predictors of greater resource use (interpreted as incident rate ratios [IRR] with 95% confidence intervals [CI]). Nearly two-thirds of the sample reported using one or more services at each timepoint. Enabling factors were key predictors of resource use at Time 2, including income above 400% federal poverty level (IRR[CI]=1.53 [1.11,2.09]), better self-rated health (IRR[CI]=1.11 [1.01,1.22]), and resource use at Time 1 (IRR[CI]=1.64 [1.29,2.08]). Need-based predictors included greater frequency of personal care (IRR[CI]=1.13 [1.05,1.22] and longer care duration (IRR[CI]=0.99 [0.98,1.00]). Neighborhood factors were not associated with resource use in this analysis, nor were other need factors including caregiving burden. The findings highlight potential disparities in resource use by income, health status, or experience with systems navigation, with implications for policy and outreach.

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Knabe, Andreas, et Joachim Weimann. « Die Deutschlandrente : Wirksamkeit und Legitimität eines Nudges ». Vierteljahrshefte zur Wirtschaftsforschung 87, n^o 2 (1 avril 2018) : 33–46. http://dx.doi.org/10.3790/vjh.87.2.33.

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Zusammenfassung: Der demografische Wandel wird die umlagefinanzierte gesetzliche Rentenversicherung in den kommenden Jahrzehnten stark belasten. Bisherige Rentenreformen zielten daher darauf ab, durch steuerliche Förderung die zusätzliche kapitalgedeckte Altersvorsorge zu stärken. Diese Möglichkeit wird aber bisher nur unzureichend in Anspruch genommen. Wir machen dafür vor allem zwei Ursachen verantwortlich. Zum einen ist gegenwärtig die private Altersvorsorge nach dem „Opt-In“-Prinzip organisiert. Nur derjenige sorgt zusätzlich vor, der sich aktiv dafür entscheidet. Zum anderen weisen viele private Rentenversicherungen hohe und vor allem intransparente Kosten auf. In der Folge halten sich viele Verbraucher bei der privaten Altersvorsorge zurück. Wir haben einen Vorschlag entwickelt, wie diese beiden Probleme gelöst werden können. Unser Modell der „Deutschlandrente“ sieht vor, bei der geförderten privaten Altersvorsorge vom „Opt-In“ zum „Opt-Out“ zu wechseln. Internationale Erfahrungen zeigen, dass ein solcher „Nudge“ zu einem deutlichen Anstieg der Ersparnisbildung führen kann. Um den Wettbewerb zu stärken, soll ein staatlich organisierter Rentenfonds eingeführt werden, der ein einfaches und kostengünstiges Vorsorgeprodukt anbietet und in fairem Wettbewerb zu privaten Anbietern steht. Die Kombination beider Maßnahmen kann die private Altersvorsorge effektiv und kostengünstig stärken. Summary: Demographic change is projected to impose a substantial burden on the public pay-as-you-go pension insurance in Germany in the next decades. Past pension reforms have thus aimed at encouraging additional private old-age provision in fully-funded pension insurances. A substantial share of the population, however, still has no or only insufficient private retirement savings. Two reasons are responsible. First, private pension provisions follow the „Opt-In“ principle. Only who actively decides to save will do so. Second, many private pension providers charge high and nontransparent fees. This keeps many consumers from saving more for their old age. We have developed a proposal that solves both problems. In our model “Deutschlandrente”, private old-age provision will be organized according to an opt-out- instead of „Opt-In“-principle. International experiences show that such a “nudge” would cause sizable increases in pension savings. To strengthen competition, a publicly organized pension fund will be introduced. This fund will offer a simple and inexpensive pension product and compete fairly with existing private providers. The combination of both measures can strengthen private old-age provision effectively and inexpensively.

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Guilatco, Angelo Jose, Marta Diaz-del-Castillo, Gabriel Alvares Borges, Neal I. Sannuli, Megan L. Ritting, Syed Mohammed Aalam, Nagarajan Kannan et al. « Abstract 2958 : Melphalan-treated multiple myeloma cells exhibit a senescent-like dormancy phenotype ». Cancer Research 84, n^o 6_Supplement (22 mars 2024) : 2958. http://dx.doi.org/10.1158/1538-7445.am2024-2958.

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Abstract Multiple myeloma (MM) is an incurable plasma cell (PC) cancer in which all patients are expected to relapse. Cytotoxic agents such as high-dose melphalan (HDM), which is used as a myeloablative agent prior to autologous stem cell transplant (ASCT) in MM, drive therapy-induced senescence (TIS) in non-cancerous tissues. We hypothesized that HDM similarly activates TIS pathways in surviving MM cells and this response may correlate with patient outcomes post-ASCT. To test this, we developed an in vitro model in which 5TGM1 mouse MM cells are cultured with 10uM melphalan (HDM) or vehicle (Veh) for 6 hours, followed by co-culture in normal media with primary mouse bone marrow stromal cells. Cultures were maintained for 10 days and imaged to quantify cumulative population doublings (CPDs). 5TGM1 were then isolated by FACS to measure telomere-associated DNA damage foci (TAFs), sensitivity to senolytic drugs, and senescence gene expression (RT-qPCR and scRNA-seq). To translate these studies, scRNA-seq was used to analyze CD138+ PCs from MM patient bone marrow post-ASCT. Additionally, longitudinal bone biopsies from MM patients at diagnosis and post-ASCT were stained for CD138+ PCs; PC burden was quantified using artificial intelligence assisted histology (HALO). HDM-5TGM1 exhibited stable growth arrest (decreased CPDs) and sustained DNA damage (increased TAFs) compared to Veh-5TGM1. HDM-5TGM1 were also significantly more sensitive to senolytic ablation (Dasatinib+Quercetin or Fisetin). HDM-5TGM1 showed increased senescence (Cdkn1a, Cdkn1c, Glb1), anti-apoptosis (Bcl2l1), and senescence associated secretory phenotype (Ccl5, Icam1, Mmp13) genes, as well as myeloid markers found to be increased in MM dormancy (Axl, Fcer1g, Mpeg1). Analysis by scRNA-seq revealed that HDM-5TGM1 were G0/G1 arrested, and gene set enrichment analysis (GSEA) confirmed upregulation of senescence pathways with downregulation of DNA replication and cell cycle pathways. Consistent with RT-qPCR results, these cells exhibited myeloid gene expression. Analysis of patient CD138+ PCs post-ASCT by scRNA-seq also revealed a myeloid-like cluster. Of interest, of the 491 genes upregulated in this cluster, 268 were also upregulated in HDM-5TGM1. CD138+ PCs could also be detected in patient bone biopsies post-ASCT, although PC burden was significantly reduced post-ASCT. Surprisingly, the percent reduction in PC burden post-ASCT was greater in relapsed (≤3 years) vs non-relapsed patients. Further, in relapsed patients, PC burden post-ASCT positively correlated with time in remission. Altogether, these findings demonstrate that HDM can induce senescence features and a myeloid-dormancy signature in surviving MM cells. This phenotype is associated with longer durable response, suggesting that activation of TIS may be a strategy to extend PFS. Further, senolytic therapy may be a novel approach to eliminate dormant MM cells and prevent relapse. Citation Format: Angelo Jose Guilatco, Marta Diaz-del-Castillo, Gabriel Alvares Borges, Neal I. Sannuli, Megan L. Ritting, Syed Mohammed Aalam, Nagarajan Kannan, Tamar Tchkonia, James L. Kirkland, Yi Lin, Taxiarchis Kourelis, Matthew T. Drake, Thomas Levin Andersen, Megan Weivoda. Melphalan-treated multiple myeloma cells exhibit a senescent-like dormancy phenotype [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2958.

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Henriksen, Tenna V., Christina Demuth, Amanda Frydendahl, Marijana Nesic, Mads H. Rasmussen, Thomas Reinert, Ole H. Larsen et al. « Abstract 2306 : Potential clinical utility of circulating tumor DNA detected by digital PCR in a nationwide Danish cohort of high-risk colorectal cancer patients ». Cancer Research 83, n^o 7_Supplement (4 avril 2023) : 2306. http://dx.doi.org/10.1158/1538-7445.am2023-2306.

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Abstract Introduction: Increasingly, circulating tumor DNA (ctDNA) is proposed as a tool for minimal residual disease (MRD) assessment, with the potential to guide postoperative treatment decisions. Low ctDNA levels immediately after surgery necessitate extremely sensitive detection methods. Additionally, for potential clinical implementation, detection methods should ideally feature short turnaround times (TATs) and low analysis costs. Compared to sequencing-based detection methods, digital PCR is low-cost, and features TATs of less than a day. Consequently, digital PCR is a good candidate for clinical implementation. Here, we present ctDNA detection results from a highly optimized, tumor-informed digital PCR strategy in a large cohort of stage II-III colorectal cancer (CRC) patients. Methods: Stage II-III CRC patients (n=864) treated with curative intent were recruited from Danish surgical centers from 2014 to 2021. Whole exome sequencing was conducted on matched tumor and buffy coat from all patients. After thorough clonality assessment, a mutational target was chosen for digital PCR analysis. Plasma samples (8mL) collected before and within 60 days after surgery, were investigated for ctDNA using digital PCR. Additionally, a subset of patients (n=229) had serial samples collected every three months analyzed for ctDNA. Results: Before surgery, ctDNA was detected in 569/828 (69%) analyzed blood samples. A minimum of 12 months of radiological follow-up was available for 598/864 patients at time of writing, enabling prognostic evaluation of ctDNA detection in these patients. Postoperative ctDNA detection was highly correlated to future recurrence (HR=9.6, 95%CI 6.3-15, P<0.001). The median time to recurrence was significantly shorter for postoperatively ctDNA positive patients (10 months, interquartile range (IQR) 3.8-12 months) compared to ctDNA negative patients (18 months, IQR 12-26 months, P<0.001), indicating a higher disease burden postoperatively in ctDNA positive patients. In a subset of patients with samples collected immediately after adjuvant treatment (n=95) and serially (n=186), ctDNA was also prognostic of recurrence (HR=6.4, CI95% 2.9-14, P<0.001; HR=27, 95%CI 14-52, P<0.001). A minimum of 12 months of follow-up is expected to be available for 700 patients before the AACR meeting 2023. Conclusion: These results from one of the largest ctDNA detection cohorts of stage II-III CRC patients demonstrate that our personalized digital PCR approach effectively detects MRD immediately after surgery. Additionally, our approach shows promise for serial ctDNA detection for recurrence surveillance applications. With digital PCR being a widespread and cost-effective method with low TATs, clinical implementation of ctDNA analysis may be more forthright using this method over cost-intensive sequencing-based methods. Citation Format: Tenna V. Henriksen, Christina Demuth, Amanda Frydendahl, Marijana Nesic, Mads H. Rasmussen, Thomas Reinert, Ole H. Larsen, Anders H. Madsen, Uffe S. Løve, Per V. Andersen, Ole Thorlacius-Ussing, Ismail Gögenur, Jakob Lykke, Allan G. Pedersen, Peter Bondeven, Nis H. Schlesinger, Lene H. Iversen, Kåre A. Gotschalck, Claus L. Andersen. Potential clinical utility of circulating tumor DNA detected by digital PCR in a nationwide Danish cohort of high-risk colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2306.

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Pérez Chacón, Gladymar, Parveen Fathima, Mark Jones, Rosanne Barnes, Peter C. Richmond, Heather F. Gidding, Hannah C. Moore et Thomas L. Snelling. « Pertussis immunisation in infancy and atopic outcomes : A protocol for a population-based cohort study using linked administrative data ». PLOS ONE 16, n^o 12 (7 décembre 2021) : e0260388. http://dx.doi.org/10.1371/journal.pone.0260388.

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Introduction The burden of IgE-mediated food allergy in Australian born children is reported to be among the highest globally. This illness shares risk factors and frequently coexists with asthma, one of the most common noncommunicable diseases of childhood. Findings from a case-control study suggest that compared to immunisation with acellular pertussis vaccine, early priming of infants with whole-cell pertussis vaccine may be associated with a lower risk of subsequent IgE-mediated food allergy. If whole-cell vaccination is protective of food allergy and other atopic diseases, especially if protective against childhood asthma, the population-level effects could justify its preferential recommendation. However, the potential beneficial effects of whole-cell pertussis vaccination for the prevention of atopic diseases at a population-scale are yet to be investigated. Methods and analysis Analyses of population-based record linkage data will be undertaken to compare the rates of admissions to hospital for asthma in children aged between 5 and 15 years old, who were born in Western Australia (WA) or New South Wales (NSW) between 1997 and 1999 (329,831) when pertussis immunisation in Australia transitioned from whole-cell to acellular only schedules. In the primary analysis we will estimate hazard ratios and 95% confidence intervals for the time-to-first-event (hospital admissions as above) using Cox proportional hazard models in recipients of a first dose of whole-cell versus acellular pertussis-containing vaccine before 112 days old (~4 months of age). Similarly, we will also fit time-to-recurrent events analyses using Andersen-Gill models, and robust variance estimates to account for potential within-child dependence. Hospitalisations for all-cause anaphylaxis, food anaphylaxis, venom, all-cause urticaria and atopic dermatitis will also be examined in children who received at least one dose of pertussis-containing vaccine by the time of the cohort entry, using analogous statistical methods. Presentations to the emergency departments will be assessed separately using the same statistical approach.

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Sonko, Ismaila, Min-Huey Chung, Wen-Hsuan Hou, Wei-Ti Chen et Pi-Chen Chang. « Predictors of HIV testing among youth aged 15–24 years in The Gambia ». PLOS ONE 17, n^o 2 (18 février 2022) : e0263720. http://dx.doi.org/10.1371/journal.pone.0263720.

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Background Worldwide, an estimated 38.0 million people lived with the human immunodeficiency virus in 2019, and 3.4 million young people aged 15~24 years were living with HIV. Sub-Saharan Africa carries a significant HIV burden with West and Central Africa most affected with HIV. Among the young people living with HIV in West and Central Africa, an estimated 810,000 were aged 15~24 years. This study aimed to assess predictors that influence the uptake of HIV testing among youth aged 15~24 years in The Gambia. Methods The 2013 Gambia Demographic and Health Survey data for youth aged 15~24 years was used. The Andersen behavioral model of health service use guided this study. A cross-sectional study design was used on 6194 subjects, among which 4730 were female. The analysis employed Chi-squared tests and hierarchical logistic regression. Results Less than one-quarter of the youth 1404 (22.6%) had ever been tested for HIV. Young people aged 20~24 years (adjusted odds ratio (aOR): 1.98), who were females (aOR: 1.13), married youth (aOR: 3.89), with a primary (aOR: 1.23), secondary or higher education (aOR: 1.46), and who were from the Jola/Karoninka ethnic group (aOR: 1.81), had higher odds of having been tested for HIV. Those with adequate HIV knowledge and those who were sexually active and had aged at first sex ≥15 years (aOR: 3.99) and those <15 years (aOR: 3.96) were more likely to have been tested for HIV compared to those who never had sex. Conclusion This study underscores the low level of model testing on HIV testing among youth (15~24 years) in The Gambia. Using Anderson’s Model of Health Service Utilization, the predisposing factors (socio-demographic and HIV knowledge) and the need-for-care factors (sexual risk behaviors) predict healthcare utilization services (HIV testing) in our study; however, only socio-demographic model explained most of the variance in HIV testing. The low effect of model testing could be related to the limited number of major variables selected for HIV knowledge and sexual risk behavior models. Thus, consideration for more variables is required for future studies.

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West, Ryan, John W. Thomas, Elaine Smith, Navneet Dhillon, Haritha Pabbathi, John Edward McKnight, Anita Johnson et Ricardo H. Alvarez. « Efficacy of screening and treatment of breast cancer patients reporting high level of distress. » Journal of Clinical Oncology 33, n^o 28_suppl (1 octobre 2015) : 101. http://dx.doi.org/10.1200/jco.2015.33.28_suppl.101.

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101 Background: Cancer patients (pts) are burdened by symptoms related to the disease itself or to the toxicities of treatment. The ASCO clinical oncology guideline adaptation recommends all health care providers routinely screen for the presence of emotional distress and specifically symptoms of anxiety from the point of diagnosis onward [Andersen BL, 2014].At Cancer Treatment Centers of America (CTCA) we perform screening assessments using a Symptom Inventory Tool (SIT) composed of 27 questions. Pts with moderate and severe levels of anxiety are evaluated by the Integrative Resource Assessment Program (IRAP) and subsequently referred to integrative oncology consultation. Methods: The SIT is an assessment tool that captures pts’ perceived symptom burden for real-time clinical intervention, taken at the point of no intervention (baseline) and every 21 days or greater. The SIT is comprised of 27 questions utilizing the M.D. Anderson Symptom Inventory tool (MDASI) and validated assessment instrument with 8 questions and a free text box added by CTCA. Symptoms were rated “at the worst” on an 11-point numeric scale ranging from 0 (“no present”) to 10 (“as bad as you can imagine”) in the previous 24 hours. Results: Between 9/1/2014 and 2/27/2015, 842 pts with multiple types of cancer were screened for distress and 435 (51.6%) scored 5 or greater, of which 212 completed a second screening assessment.58 breast cancer pts provided SIT distress scores at baseline and then again at least 23 days after the initial assessment. The average reduction in the distress scores for breast cancer patients was 2 (1st SIT mean = 6.2, 2ndSIT mean = 4.2) with 40 pts (69%) reporting a decrease, 7 pts (12%) having no change, and 11 pts (19%) reporting an increase in distress. The 4 interventions most frequently referred and completed by the pts were mind body therapy (100%), rehabilitation (66%), acupuncture (50%), and massage therapy (45%). Conclusions: Distress is a relevant symptom reported by cancer pts. This study demonstrates that early intervention in breast cancer pts using integrative oncology approaches will reduce the distress in 69% of cases.

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呂美卿, 呂美卿, 劉翠瑤 IMei-Ching Liu et 洪啓峯 Tsui-Yao Liu. « 影響居家護理個案之照顧者對居家醫療整合照護使用意願之探討－以北部某區域醫院附設某居家護理所為例 ». 輔仁醫學期刊 21, n^o 2 (juin 2023) : 001–12. http://dx.doi.org/10.53106/181020932023062102001.

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目的：探討北部某區域醫院附設居家護理所之個案，影響參加居家醫療服務的相關因素。方法：橫斷性研究設計，使用Andersen所提出醫療利用性模式為架構，於2021年9至10月對居家護理個案主要決策之照顧者共91位進行結構式問卷，內容為：被照顧者及照顧者基本資料、居家醫療整合照護認知、照顧者知覺量表、照顧者負荷量表。統計方法為描述性統計、t檢定、Anova檢定、卡方檢定、皮爾森積差相關分析與多元邏輯斯迴歸分析。結果：不同的固定就醫場所與參加居家醫療呈統計上顯著差異。照顧者壓力生理負荷對壓力心理與社會負荷有高度正相關，壓力財務負荷對壓力生理、心理與社會負荷有中度正相關，壓力心理負荷與壓力社會負荷有高度正相關。影響居家醫療整合照護之預測因子為固定就醫場所。結論：本研究結果促使因素中個案有固定就醫場所，參加居家醫療整合照護服務達顯著相關。有無固定的就醫場所是消費者對組織易接近或熟悉的地方，常被用來預測醫療服務利用度的高低，有固定就醫地點、醫師，能有連續性及協調性的照護。  Objective: To investigate a case of a home care center attached to regional hos-pital in northern Taiwan, and to explore the relevant factors affecting participation in home medical integrated care. Methods: Using cross-sectional study design, a struc-tured questionnaire was administered to 91 caregivers who were the primary decision makers in home care cases from September 2021 to October 2021 using the model proposed by Andersen as a framework, with the following content: basic information about the care recipient and caregiver, home health integrated care perception, care-giver perception scale, caregiver burden scale. The statistical methods were descriptive statistics, t-test, ANOVA, chi-square, Pearson’s product correlation analysis, and multivariate logistic regression analysis. Results: Statistically significant differences were found between different fixed health care settings and participation in integrated home health care. Caregivers stress physiological load was highly positively correlated with stress psychological and social load, stress economic load was moderately positively correlated with stress physiological, psychological and social load, and stress psychological load was highly positively correlated with stress social load. The predictor of integrated home medical care is the fixed location. Conclusion: The re-sults of this study showed that there was a significant correlation between the pres-ence of a fixed medical site and the participation of home medical integrated care. The availability of a fixed health care site is a site that is familiar to consumers and is often used to predict the level of health care utilization. The presence of a regular home medical integrated care.

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Roderick, Justine, Scott Boiko, Courtney L. Andersen, Huiling Liang, Gregory Dowdell, Corinne Reimer, Lisa Drew, Danielle M. Townsley et Justin Cidado. « AZD4573 Effectively Induces Apoptosis in r/r MCL As a Monotherapy or in Combination with Acalabrutinib ». Blood 138, Supplement 1 (5 novembre 2021) : 2255. http://dx.doi.org/10.1182/blood-2021-151725.

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Abstract Mantle cell lymphoma (MCL) is an aggressive form of NHL where frequent relapse following standard therapies remains a serious concern, even for promising new treatments such as combinations of a BTK inhibitor with the selective Bcl2 inhibitor venetoclax. Previous studies have also shown that MCL cells develop resistance through tumor microenvironment interactions that increase levels of Mcl1, BclxL, and/or Bfl1. Given the ability of CDK9 inhibition to deplete Mcl1 and Bfl1 (Boiko et al 2021), we explored the potential of clinical-stage inhibitor AZD4573 to induce apoptosis in MCL cell lines and PDX models as a monotherapy or in combination with acalabrutinib. Currently, AZD4573 is being evaluated as a monotherapy in a first-in-human study for relapsed or refractory hematological malignancies (NCT03263637) as well as in combination with the BTK inhibitor, acalabrutinib, in patients with non-Hodgkin lymphoma (NHL) (NCT04630756). CDK9 is a serine/threonine kinase that mediates transcription elongation via phosphorylation of serine 2 of the RNA polymerase II carboxyl-terminal domain (pSer2-RNAP2). As previously shown, potent and selective inhibition of CDK9 by AZD4573 results in reduction of pSer2-RNAP2 levels leading to preferential depletion of labile proteins, including the Bcl2 family anti-apoptotic proteins Mcl1 and Bfl1 (as well as other known oncoproteins like Myc). This in turn drives rapid induction of apoptosis in a broad range of preclinical cancer models, particularly those derived from hematologic malignancies (Cidado et al 2020). Here, we used 7 MCL cell lines and 1 PDX organoid to assess the rapid apoptogenic potential of AZD4573 in vitro. Cleaved caspase-3 (CC3), a hallmark of apoptosis, was measured immediately following acute treatment (6h) using Caspase-Glo 3/7. Four models were sensitive to CDK9 inhibition (EC 50 < 100nM; max. CC3 > 50%) while 1 cell line exhibited intermediate sensitivity (EC 50 < 100nM; max. CC3 < 50%) and 3 others were resistant (EC 50 > 100nM; max. CC3 < 50%). Regardless of sensitivity, AZD4573 caused a dose- and time-dependent reduction of pSer2-RNAP2, Mcl1, and Myc, consistent with our prior reports. Most MCL cell lines are not responsive to BTK inhibition and, therefore, did not show combination benefit with AZD4573. We, therefore, chose to evaluate the in vivo activity of AZD4573 +/- acalabrutinib in 3 disseminated r/r MCL PDX models. In DFBL-44685, an acalabrutinib-unresponsive model harboring a CARD11 mutation, AZD4573 showed moderate activity, reducing MCL cells in all compartments analyzed (peripheral blood, bone marrow, and spleen) by >40% two weeks into treatment and increasing overall survival benefit (P<0.01). In an acalabrutinib-responsive MCL PDX, DFBL-96069, the combination of AZD4573 with acalabrutinib reduced tumor burden in all compartments analyzed by >80% and significantly increased survival over vehicle as well as monotherapy treatments (P<0.001). The third model, DFBL-98848, expresses high Bfl1. In this model, AZD4573 monotherapy reduced disease burden in all compartments analyzed by >50% and significantly increased survival over vehicle (P<0.001). Additionally, AZD4573 plus acalabrutinib further reduced disease burden and increased survival in this model compared to AZD4573 alone, although this did not reach statistical significance. Our findings show that targeting CDK9 with AZD4573 can effectively induce apoptosis in a range of MCL cell lines and PDX models, including acalabrutinib-sensitive and -insensitive models as well as those expressing high levels of Bfl1. In 3 r/r MCL PDX models, single agent AZD4573 significantly reduced the tumor burden in the peripheral blood, bone marrow, and spleen of the affected mice, resulting in increased survival. Combination of AZD4573 with acalabrutinib resulted in greater anti-tumor activity than either monotherapy. Altogether, these data suggest that AZD4573, alone or in combination with acalabrutinib, could be an effective therapy for patients with r/r MCL. Figure 1 Figure 1. Disclosures Boiko: AstraZeneca: Current Employment, Current equity holder in publicly-traded company. Andersen: AstraZeneca: Current Employment, Current equity holder in publicly-traded company. Liang: AstraZeneca: Current Employment, Current equity holder in publicly-traded company. Dowdell: AstraZeneca: Current Employment, Current equity holder in publicly-traded company. Reimer: AstraZeneca: Current Employment, Current equity holder in publicly-traded company. Drew: AstraZeneca: Current Employment, Current equity holder in publicly-traded company. Townsley: AstraZeneca: Current Employment, Current equity holder in publicly-traded company. Cidado: AstraZeneca: Current Employment, Current equity holder in publicly-traded company.

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Ladetto, Marco, Simone Ferrero, Daniela Drandi, Federica Cavallo, Luigia Monitillo, Paola Ghione, Sara Barbiero et al. « LONG-TERM RESULTS of the GIMEMA VTD Consolidation TRIAL In Autografted MULTIPLE Myeloma PATIENTS (VEL-03-096) : IMPACT of Minimal RESIDUAL DISEASE Detection by REAL Time Quantitative PCR On LATE Recurrences and Overall SURVIVAL ». Blood 118, n^o 21 (18 novembre 2011) : 827. http://dx.doi.org/10.1182/blood.v118.21.827.827.

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Abstract Abstract 827 Background and aims: We have recently shown that a consolidation therapy with bortezomib/thalidomide/dexamethasone (VTD) in multiple myeloma (MM) patients responding to autologous transplantation (ASCT) induces major tumor shrinking assessed by real time-quantitative (RQ)-PCR. Moreover we found that low levels of minimal residual disease (MRD) associated to a better progression-free survival (PFS) [GIMEMA VEL-03-096 trial, EudraCT Number 2004-000531-28: Ladetto et al, J Clin Oncol 2010]. We here present the updated results of this study at a median follow-up of 65 months. In the present analysis the following additional issues have been addressed: a) impact of MRD on PFS over time, with special interest to the role of MRD kinetics on outcome; b) impact of MRD on overall survival (OS). Patients and methods: Inclusion criteria and treatment schedule for this study have been already reported [Ladetto et al., J Clin Oncol 2010] and included: 1) a documented complete or very good partial remission following ASCT delivered as first line treatment; 2) no previous therapy with thalidomide or bortezomib; 3) presence of a molecular marker based on the immunoglobulin heavy chain rearrangement (IGH). MRD was assessed on bone marrow samples at diagnosis, study entry, after two VTD courses, at the end of treatment and then at six months intervals, up to clinical relapse. Patients underwent MRD detection using either qualitative nested PCR and RQ-PCR, employing IGH-derived patient specific primers as already described [Voena et al., Leukemia 1997; Ladetto et al., Biol Bone Marrow Transpl 2000]. For outcome analysis patients were grouped according to following definitions: a) MRD negativity on two consecutive samples by the most sensitive PCR method (nested PCR): full molecular remission (FMR); b) MRD negativity on two consecutive samples by RQ-PCR (less sensitive but currently better standardized, according to European Study Group on MRD detection guidelines [van der Vendel et al., Leukemia 2007]): standard molecular remission (SMR); c) post-treatment tumor load above the median by RQ-PCR: high tumor burden (HTB); d) post-treatment tumor load below the median by RQ-PCR: low tumor burden (LTB); e) recurrence of detectable MRD after FMR/SMR: molecular relapse (M-rel); f) increase of MRD levels of at least one log: active disease (AD). Results: Feasibility, toxicity and clinical outcome of the trial have been already reported [Ladetto et al., J Clin Oncol 2010]. Thirty-nine patients were enrolled and median clinical follow-up from start of first line treatment is 65 months. 270 of the planned samples for MRD monitoring (86%) were actually received by the centralized lab. So far 17 relapses and six deaths have been reported. Following VTD consolidation, 7/38 evaluable patients achieved FMR (18%) and 15/38 achieved SMR (39%). Three M-rel were observed, two of them followed by clinical relapse within six months. Achievement of SMR proved highly predictive for PFS (5-years (y) PFS 82% vs 44%, p=0.009, figure 1A), as well as the presence of HTB and AD (5-y PFS 35% vs 87%, p<0.001, figure 2). Interestingly, patients with LTB and no evidence of M-rel or AD had an excellent outcome with a 5-y PFS of 87%, (even considering that molecular follow-up was incomplete due to lack of samples in the two events observed in the low risk group, figure 2). Most notably, none of the patients achieving FMR or SMR has so far died and both SMR and AD proved to be significant predictors for OS (respectively, 5y-OS 100% vs 74%, p=0.012, figure 1B, and 5y-OS 86% vs 100%, p=0.037, data not shown). Conclusions: Our long-term results indicate that: 1) the achievement of SMR following VTD consolidation in MM patients is associated with a better outcome in terms of PFS and OS; 2) a dynamic increase in molecular tumor burden (AD), detectable by RQ-PCR, predicts late disease relapses several months before clinical recurrence. Taken together these results suggest the importance of developing tailored treatment for patients with high residual burden or showing increasing levels of MRD during follow-up, as already pursued for example in mantle cell lymphoma [Andersen et al., J Clin Oncol 2009]. Disclosures: Ladetto: Celgene: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Bayer: Honoraria; Mundipharma: Honoraria; Janssen-Cilag: Research Funding; Italfarmaco: Research Funding. Cavallo:celgene: Honoraria. Guglielmelli:celgene: Honoraria; Janssen-Cilag: Honoraria. Boccadoro:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Palumbo:Merck: Honoraria; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees; celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria.

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Andersen, Courtney L., Amanda L. Christie, Alan Rosen, Kim Maratea, Maureen Hattersley, Jon Travers, Justin Cidado et al. « Identification of Novel Combination Therapies Active in BCL2 Inhibitor-Resistant Patient-Derived AML Models ». Blood 134, Supplement_1 (13 novembre 2019) : 1273. http://dx.doi.org/10.1182/blood-2019-129475.

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Acute myeloid leukemia (AML) is an aggressive, heterogeneous malignancy. AML patients whose disease relapses on chemotherapy or are unfit for aggressive induction regimens have limited therapeutic options. Many patients benefit from the combination of venetoclax (BCL2i) and a hypomethylating agent (HMA) but this regimen is rarely curative. The addition of novel agents could provide improved benefit for relapsed/refractory patients. To identify such regimens, we screened a panel of 10 AML cell lines with combinations of venetoclax and novel targeted agents. The agents used spanned multiple mechanisms of action (e.g. DNA damage response, kinase signaling, pro-apoptotic agents) and are all in early clinical development. Cells were treated for 72hrs and viability was assessed by CellTiter-Glo. In several of the cell lines that were insensitive or partially sensitive to venetoclax (OCI-AML3, KG1a, MonoMac6, THP1), combinations with inhibitors of MCL1 (AZD5991), AURKB (AZD2811), and BRD4 (AZD5153) showed synergistic activity (Loewe synergy score >5, growth inhibition > 180%) (Table 1). We next asked if these combinations were active in patient-derived xenograft (PDX) models of AML. We established an ex vivo co-culture assay using the HS-5 bone marrow stromal cell line. AML PDX cells were isolated from mouse spleens and plated in 96-well format in direct co-culture with HS-5 cells or in HS-5-derived conditioned media. Cells were treated with three doses of each monotherapy and three doses of fixed ratio combination. Replicate screens using cells from individual mice on different days confirmed data were reproducible (r2=0.687) across animals engrafted with the same PDX. Drug response was similar between conditioned media and direct co-culture assays (r2=0.81). Venetoclax sensitivity varied across PDX models ex vivo. Notably, 2/5 PDX models screened (DFAM-68555 and DFAM-10360) were insensitive to both venetoclax and the combination of venetoclax + 5-azacytidine (HMA) ex vivo. Both models were established from untreated/1L patients and harbor TP53 mutations. Combination treatments did not add additional benefit over venetoclax monotherapy in the DFAM-10360 model. However, in DFAM-68555, AZD5153, AZD5991, and AZD2811 showed improved activity over venetoclax alone (67%, 54%, and 67% vs. 26% decrease in viability for venetoclax alone, respectively). Since combination strategies will likely be most impactful in patients refractory to or relapsed after venetoclax, we chose this venetoclax insensitive model to prioritize in vivo. To confirm the translatability of these findings, we designed a pilot in vivo study using DFAM-68555. Mice were randomized to receive vehicle, venetoclax + HMA, or venetoclax + AZD5153 when peripheral blood disease reached ~5% (hCD45+hCD33+ cells by flow cytometry). After two weeks of dosing, animals were sacrificed to evaluate disease burden in bone marrow (sternum), spleen, and peripheral blood. The model remained insensitive to venetoclax + HMA in vivo. The combination of AZD5153 with venetoclax decreased disease burden in blood and spleen compared to vehicle (30% and 42% hCD45+CD33+ cells by flow cytometry vs 70% and 95%, respectively) with similar efficacy seen by immunohistochemistry in the bone. Finally, we screened these venetoclax combinations in additional aggressive AML PDX models which were resistant or only partially responsive to venetoclax in vivo. Addition of AZD2811NP and AZD5991 to venetoclax was more effective than venetoclax alone and venetoclax + HMA in the bone marrow. The most active combination varied from model to model. Efficacy screening in additional models is ongoing to further build ex vivo to in vivo translation and prioritize development of specific combinations. Also ongoing is genomic and transcriptomic profiling of these PDXs to identify potential predictive biomarkers of combination activity. In summary, we developed an ex vivo screening platform to test clinically actionable combinations for activity in clinically relevant models. Using this platform and subsequent in vivo efficacy, we identified venetoclax combinations across multiple mechanisms (pro-apoptotic, cell cycle regulation, transcriptional regulation, DNA damage response) with activity in venetoclax-insensitive models. These results suggest potential therapeutic options to explore clinically for AML patients. Disclosures Andersen: AstraZeneca: Employment. Christie:AstraZeneca: Employment. Rosen:Astrazeneca: Employment. Maratea:AstraZeneca: Employment. Hattersley:AstraZeneca: Employment. Travers:AstraZeneca: Employment. Cidado:AstraZeneca: Employment. Pulukuri:AstraZeneca: Employment. Saeh:AstraZeneca: Employment. Clark:AstraZeneca: Employment, Equity Ownership. Reimer:AstraZeneca: Employment. Mettetal:AstraZeneca: Employment.

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Kwok, Jaime Kirsten, Kevin Martell, Michael Sia, Bimal Bhindi, Tasnima Abedin, Shuang Lu et Harvey Charles Quon. « Local prostate radiotherapy in metastatic prostate cancer and symptomatic local events. » Journal of Clinical Oncology 39, n^o 6_suppl (20 février 2021) : 111. http://dx.doi.org/10.1200/jco.2021.39.6_suppl.111.

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111 Background: Local prostate radiotherapy (LPRT) is associated with improved overall survival in patients with low metastatic burden (MB) and is now standard of care. However, the role of LPRT in reducing symptomatic local events (SLE) in metastatic prostate cancer (MPC) remains unclear and requires long-term follow-up. The purpose of this study was two-fold: i) identify the risk factors associated with SLE, and ii) evaluate the association between LPRT and SLE in MPC. Methods: We conducted a retrospective, population-based cohort study of patients diagnosed with initial MPC between 2005 and 2016. Patients were identified through the Alberta Cancer Registry and patient, tumour, and treatment characteristics were collected by chart review. Data were linked to physician billing claims between 2004 and 2017 for diagnostic or therapeutic procedures potentially related to genitourinary (GU) and gastrointestinal (GI) SLE including percutaneous nephrostomy (PCN) and ureteric stent insertion (USI), cystoscopy, TURP, TURBT, colonoscopy and proctosigmoidoscopy. Both Andersen-Gill recurrent event and multivariable Cox regression time to first event analyses were conducted to evaluate the effect of LPRT on the occurrence of these procedures. Patients who underwent radical prostatectomy were excluded. LPRT was defined as 40 Gy or higher total dose to the prostate within one year of diagnosis. Patients with a SLE occurring after diagnosis but prior to LPRT were allocated to the control group. MB was defined as per STAMPEDE. Covariates for both models included MB, age at diagnosis, PSA at diagnosis, clinical T- and N-stage, and Gleason score (GS). Results: Of a total cohort of 1363 patients, 745 (54.7%) had high MB and 450 (33%) had low MB. Fifty-four (4%) received LPRT, of which 14.8% had high MB. Of those receiving LPRT, median PSA was 9.4, 79.6% had GS of 8-10, and 59.3% had T3-T4 disease. One or more SLE were observed in 43.5% and 37% of the control and LPRT groups, respectively. Among those with SLE, the median SLE frequency was 2 (interquartile range [IQR], 2-5) and 1 (IQR, 1-2.3) for the control and LPRT groups, respectively. On recurrent event analysis, LPRT was associated with lower risk of composite GU SLE (HR 0.34, 95% CI 0.17-0.67; p = 0.002), PCN and USI (HR 0.20, 95% CI 0.05-0.84; p = 0.027) and cystoscopy (HR 0.38, 95% CI 0.15-0.96; p = 0.041). Risk factors for GU SLE were T4 disease, GS of 8-10 and unknown GS. Risk factors for PCN and USI were T3, TX and N1 disease, GS of 8-10 and unknown GS. On time to first event analysis, there were no statistically significant differences for all outcomes between the control and LPRT groups. MB was not a risk factor for SLE in both analyses. Conclusions: LPRT was associated with lower risk for recurrent GU SLE, PCN and USI, and cystoscopy. The associated benefit in SLE reduction with LPRT warrants further study to determine if this effect is modified by MB and whether there may be a role for LPRT in patients with high MB.

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George, Goldy C., Clark R. Andersen, Xiaohui Tang, John A. Livingston, Michael E. Roth et Michelle A. Hildebrandt. « Abstract 1997 : Health-related quality of life at diagnosis in survivors of adolescent and young adult cancer ». Cancer Research 82, n^o 12_Supplement (15 juin 2022) : 1997. http://dx.doi.org/10.1158/1538-7445.am2022-1997.

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Abstract Purpose: Data are lacking on the distribution, factors associated with, and long-term impact of diminished health-related quality of life (HRQoL) at diagnosis in adolescent and young adult (AYA) cancer survivors (≥2 years post cancer diagnosis). Our goal was to fill this gap in knowledge. Methods: A cohort of AYA (15y - 39y) cancer patients treated at MD Anderson between 2000-2016 who had survived at least 2 y was identified from our Institutional Tumor Registry. HRQoL was assessed at diagnosis with the SF12v1 questionnaire. Demographic and behavioral risk factors, tumor type, and vital status were ascertained. Physical composite summary (PCS) and mental composite summary (MCS) scores were generated from SF12 responses following mean-based normalization; PCS or MCS < 50 indicated “poor” HRQoL. Statistical tests included ANOVA, quantile regression, and multivariable Cox proportional hazards. Results: 2,609 AYA cancer survivors (75% diagnosed between age of 26-39 y; 67% White, 18% Hispanic and 9% Black) were included. Breast cancer was the most frequent diagnosis (25%), followed by sarcoma (12%) and Hodgkin lymphoma (10%). Median follow-up for participants was 10.5 y. Overall mean PCS and MCS scores at diagnosis were 45.3 (SD: 11.4) and 47.0 (SD: 10.5), respectively. Female AYA cancer patients had significantly higher PCS, yet lower MCS compared to their male counterparts (both P<0.001). A positive association between age at diagnosis and PCS was observed (P<0.001), in contrast to the inverse association with MCS (P<0.001). Differences in PCS (P<0.001) and MCS (P=0.001) were also evident by tumor type. For example, women with breast cancer reported the most favorable PCS (51.5) at diagnosis, yet among the lowest MCS (46.1) of the nine tumor types analyzed. The Black AYA population had a larger burden of poor PCS at diagnosis with 61% of patients reporting scores <50 compared to 55% of Hispanic and 51% of non-Hispanic whites. Significant predictors of diminished PCS in AYA cancer survivors in the bottom 25% of PCS scores were younger age at diagnosis (P=0.003), male gender (P<0.001), diagnosis of a hematologic malignancy versus solid tumor (P<0.001), smoking (P=0.003) and not consuming any alcohol currently (P<0.001). Overall, low PCS (<50) at diagnosis (HR=1.57, P<0.001), and diagnosis of a solid tumor compared to a hematologic malignancy (HR=2.33, P<0.001) were associated with lower survival. Conclusions: In this large, diverse AYA cancer survivor cohort, physical and mental HRQoL at diagnosis were impacted by AYA’s age at diagnosis, gender, tumor type, and smoking status. Low PCS at diagnosis was an independent predictor of diminished survival among AYA cancer survivors ≥2y post diagnosis. Our findings suggest that patient-reported poor physical well-being at diagnosis is a biomarker of poor prognosis for AYA cancers. Further studies are needed to identify interventions to improve outcomes for this population. Citation Format: Goldy C. George, Clark R. Andersen, Xiaohui Tang, John A. Livingston, Michael E. Roth, Michelle A. Hildebrandt. Health-related quality of life at diagnosis in survivors of adolescent and young adult cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1997.

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Lowman, Geoffrey Marc, Dinesh Cyanam, Emily Norris, Michelle Toro, Coleen Nemes, Tanaya Puranik, Yan Zhu et al. « Abstract 232 : Fully automated comprehensive genomic profiling for detection of cancer variants, gene fusions, and complex oncology endpoints ». Cancer Research 83, n^o 7_Supplement (4 avril 2023) : 232. http://dx.doi.org/10.1158/1538-7445.am2023-232.

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Abstract Introduction: We present the comprehensive genomic profiling performance of the Ion Torrent Genexus system using the Oncomine Comprehensive Assay Plus (OCA Plus), a 500+ gene targeted AmpliSeq-based oncology research panel that evaluates DNA variants (including copy number alterations), RNA fusions, and key oncology research endpoints including tumor mutational burden (TMB), microsatellite instability (MSI), and homologous recombination repair deficiency (HRD) via characterization of genomic instability by the newly introduced Genomic Instability Metric (GIM). Methods: The Ion Torrent Genexus System provides comprehensive genomic profiling via automated sample-to-report workflow with next day results. The Genexus System supports oncology research panels such as OCA Plus, which is comprised of over 13,000 amplicons, and enables low input requirements of just 20ng of FFPE DNA and RNA. This study utilized cell lines, reference controls, and orthogonally tested FFPE research samples to evaluate detection of DNA variants, copy number alterations, RNA fusions, and key research endpoints, including MSI, TMB, and HRD. The OCA Plus panel was also evaluated for the ability to detect arm-level copy number changes in orthogonally validated FFPE samples. Results: Commercial reference controls and FFPE research samples were sequenced using OCA Plus on the Genexus System to an average depth of ≥24 million reads per sample, with four DNA and RNA samples supported per run. SNV and MNV calling performance was assessed using the AcroMetrix Oncology Hotspot Control which has 377 variants covered by OCA Plus and delivered SNV sensitivity and PPV >99% and MNV sensitivity of >99% and PPV >95%. MSI status was assessed using orthogonally tested FFPE samples from various tumor tissues (stomach, endometrial, colorectal) and returned status concordance of 99.4% with sensitivity and PPV >99%. The TMB endpoint was tested using commercial controls and FFPE samples with a correlation of r2 > 0.90 to orthogonal measurements. RNA Fusion reference controls showed 100% positive correlation. Copy number gain detection shows sensitivity of 99% and PPV >95%, while homologous copy loss gives 100% PPV and sensitivity of >90%. We also demonstrate high concordance to orthogonal methods in detection of HER2 amplifications, and the ability to detect arm-level copy number alterations such as 1p/19q co-deletions in IDH1 positive glioma samples. Conclusion: The Genexus System combines minimal touch points and a rapid turnaround time to enable comprehensive genomic profiling for research assays such as OCA Plus for detection of rare variants and low-level fusion transcripts. Further, by providing accurate characterization of key oncology research endpoints, the Genexus System can accelerate research in oncology. For research use only. Not for use in diagnostic procedures. Citation Format: Geoffrey Marc Lowman, Dinesh Cyanam, Emily Norris, Michelle Toro, Coleen Nemes, Tanaya Puranik, Yan Zhu, Alex Phan, Derek Wong, Portia Bernado, Anelia Kralcheva, Srinivas Nallandhighal, Loni Pickle, April Bigley, Mohit Gupta, Ying Jin, Sameh El-Difrawy, Amir Marcovitz, Fatima Zare, Charles Scafe, Yu-Ting Tseng, Jianjun Guo, Vinay Mittal, Scott Myrand, Santhoshi Bandla, Paul Williams, Eugene Ingerman, Elaine Wong-Ho, Seth Sadis, Mark Andersen, Rob Bennett. Fully automated comprehensive genomic profiling for detection of cancer variants, gene fusions, and complex oncology endpoints [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 232.

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Moore, Simon C., Mohammed Fasihul Alam, David Cohen, Kerenza Hood, Chao Huang, Simon Murphy, Rebecca Playle et al. « All-Wales Licensed Premises Intervention (AWLPI) : a randomised controlled trial of an intervention to reduce alcohol-related violence ». Public Health Research 3, n^o 10 (septembre 2015) : 1–152. http://dx.doi.org/10.3310/phr03100.

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BackgroundViolence in and around premises licensed for the on-site sale and consumption of alcohol continues to burden the NHS with assault-related injuries.Trial designA randomised controlled trial with licensed premises as the unit of allocation, with additional process and cost-effectiveness evaluations.MethodsPremises were eligible (n = 837) if they were licensed for on-site sale and consumption of alcohol, were within 1 of the 22 local authorities (LAs) in Wales and had previously experienced violence. Data were analysed using Andersen–Gill recurrent event models in an intention-to-treat analysis. An embedded process evaluation examined intervention implementation, reach, fidelity, dose and receipt. An economic evaluation compared costs of the intervention with benefits.InterventionPremises were randomised to receive a violence-reduction intervention, Safety Management in Licensed Environments (SMILE), which was delivered by an environmental health practitioner (EHP; the agent). SMILE consisted of an initial risk audit to identify known risks of violence, a follow-up audit scheduled to enforce change for premises in which serious risks had been identified, structured advice from EHPs on how risks could be addressed in premises and online materials that provided educational videos and related material.ObjectiveTo develop intervention materials that are acceptable and consistent with EHPs’ statutory remit; to determine the effectiveness of the SMILE intervention in reducing violence; to determine reach, fidelity, dose and receipt of the intervention; and to consider intervention cost-effectiveness.OutcomeDifference in police-recorded violence between intervention and control premises over a 455-day follow-up period.RandomisationA minimum sample size of 274 licensed premises per arm was required, rounded up to 300 and randomly selected from the eligible population. Licensed premises were randomly assigned by computer to intervention and control arms in a 1 : 1 ratio. Optimal allocation was used, stratified by LA. Premises opening hours, volume of previous violence and LA EHP capacity were used to balance the randomisation. Premises were dropped from the study if they were closed at the time of audit.ResultsSMILE was delivered with high levels of reach and fidelity but similar levels of dose to all premises, regardless of risk level. Intervention premises (n = 208) showed an increase in police-recorded violence compared with control premises (n = 245), although results are underpowered. An initial risk audit was less effective than normal practice (hazard ratio = 1.34, 95% confidence interval 1.20 to 1.51) and not cost-effective. Almost all eligible intervention premises (98.6%) received the initial risk audit; nearly 40% of intervention practices should have received follow-up visits but fewer than 10% received one. The intervention was acceptable to EHPs and to some premises staff, but less so for smaller independent premises.ConclusionsSMILE was associated with an increase in police-recorded violence in intervention premises, compared with control premises. A lack of follow-up enforcement visits suggests implementation failure for what was seen as a key mechanism of action. There are also concerns as to the robustness of police data for targeting and assessing outcome effectiveness, while intervention premises may have received greater attention from statutory agencies and, therefore, the identification of more violence than control premises. Although SMILE had high reach and was feasible and acceptable to EHPs, it was found to be ineffective and associated with increased levels of violence, compared with normal practice and it requires additional work to promote the implementation of follow-up enforcement visits. Future work will aim to better understand the role of intervention dose on outcomes and seek more objective measures of violence for use in similar trials.Trial registrationCurrent Controlled Trials ISRCTN78924818.FundingThis project was funded by the NIHR Public Health Research programme and will be published in full inPublic Health Research; Vol. 3, No. 10. See the NIHR Journals Library website for further project information.

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Matos, Jefferson David Melo de, Leonardo Jiro Nomura Nakano, André Guimarães Rodrigues, Alessandra Dossi Pinto, Mateus Favero Barra Grande, Guilherme da Rocha Scalzer Lopes et Valdir Cabral Andrade. « Orofacial clefts : treatment based on a multidisciplinary approach ». ARCHIVES OF HEALTH INVESTIGATION 9, n^o 5 (21 octobre 2020) : 468–73. http://dx.doi.org/10.21270/archi.v9i5.4804.

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Objective: The present study aims to expose through a literature review the cleft lip and/or cleft palate (CL/CP) and its treatment in a multidisciplinary approach. Methodology: This literature review was conducted by the leading health databases: Pubmed (https://www.ncbi.nlm.nih.gov/pubmed). The keywords for the textual search were: Cleft Lip; Cleft Palate; Dental Staff; Classification; Embryology. The inclusion criteria were: literature on the subject under study, literature of the last years, english language, laboratory and clinical studies and systematic review. Literature Review: Fissures can be defined by a space at the junction between two bones, usually where there would be a suture. Orofacial clefts are part of the congenital facial anomalies resulted from the non-junction of the embryonic facial processes. These changes occur due to an alteration in the migratory velocity of the neural crest cells, in charge of the phenomenon of fusion of the facial prominences between the 6th and 9thweek of embryonic life. Conclusion: The treatment of patients with orofacial clefts requires the approach of a multidisciplinary team that involves physicians in the area of plastic surgery, otorhinolaryngology, pediatrics, geneticists, dentists, prosthetics, nurses and speech pathologists, focusing on patient prevention, recovery and rehabilitation. However, further studies are needed for a better understanding of the subject and the steps that should be applied for each particular case.Descriptors: Cleft Lip; Cleft Palate; Dental Staff; Classification; Embryology.ReferencesShaw WC, Brattström V, Mølsted K, Prahl-Andersen B, Roberts CT, Semb G. The Eurocleft study: intercenter study of treatment outcome in patients with complete cleft lip and palate. Part 5: discussion and conclusions. Cleft Palate Craniofac J. 2005;42(1):93-8. Friede H, Lilja J. The Eurocleft Study: Intercenter study of treatment outcome in patients with complete cleft lip and palate. Cleft Palate Craniofac J. 2005;42(4):453-54.Rosenstein SW, Grasseschi M, Dado D. The Eurocleft Study: Intercenter study of treatment outcome in patients with complete cleft lip and palate. Cleft Palate Craniofac J. 2005;42(4):453.Semb G, Brattström V, Mølsted K, Prahl-Andersen B, Zuurbier P, Rumsey N, Shaw WC. The Eurocleft study: intercenter study of treatment outcome in patients with complete cleft lip and palate. Part 4: relationship among treatment outcome, patient/parent satisfaction, and the burden of care. Cleft Palate Craniofac J. 2005;42(1):83-92. Watkins SE, Meyer RE, Strauss RP, Aylsworth AS. Classification, epidemiology, and genetics of orofacial clefts. Clin Plast Surg. 2014;41(2):149-63. Coleman JR Jr, Sykes JM. The embryology, classification, epidemiology, and genetics of facial clefting. Facial Plast Surg Clin North Am. 2001;9(1):1-13.Pengelly RJ, Arias L, Martínez J, Upstill-Goddard R, Seaby EG, Gibson J, Ennis S, Collins A, Briceño I. Deleterious coding variants in multi-case families with non-syndromic cleft lip and/or palate phenotypes. Sci Rep. 2016;6:30457.Ren Y, Steegman R, Dieters A, Jansma J, Stamatakis H. Bone-anchored maxillary protraction in patients with unilateral complete cleft lip and palate and Class III malocclusion. Clin Oral Investig. 2019;23(5):2429-2441.Alberconi TF, Siqueira GLC, Sathler R, Kelly KA, Garib DG. Assessment of Orthodontic Burden of Care in Patients With Unilateral Complete Cleft Lip and Palate. Cleft Palate Craniofac J. 2018;55(1):74-78.Eriguchi M, Watanabe A, Suga K, Nakano Y, Sakamoto T, Sueishi K, Uchiyama T. Growth of Palate in Unilateral Cleft Lip and Palate Patients Undergoing Two-stage Palatoplasty and Orthodontic Treatment. Bull Tokyo Dent Coll. 2018;59(3):183-91.Smane L, Pilmane M. Evaluation of the presence of MMP-2, TIMP-2, BMP2/4, and TGFβ3 in the facial tissue of children with cleft lip and palate. Acta Med Litu. 2018;25(2):86-94. AlHayyan WA, Pani SC, AlJohar AJ, AlQatami FM. The Effects of Presurgical Nasoalveolar Molding on the Midface Symmetry of Children with Unilateral Cleft Lip and Palate: A Long-term Follow-up Study. Plast Reconstr Surg Glob Open. 2018;6(7):e1764. Thakur S, Singh A, Thakur NS, Diwana VK. Achievement in Nasal Symmetry after Cheiloplasty in Unilateral Cleft Lip and Palate Infants Treated with Presurgical Nasoalveolar Molding. Contemp Clin Dent. 2018;9(3):357-60. Turri de Castro Ribeiro T, Petri Feitosa MC, Almeida Penhavel R, Zanda RS, Janson G, Mazzottini R, Garib DG. Extreme maxillomandibular discrepancy in unilateral cleft lip and palate: Longitudinal follow-up in a patient with mandibular prognathism. Am J Orthod Dentofacial Orthop. 2018;154(2):294-304. Perillo L, Vitale M, d'Apuzzo F, Isola G, Nucera R, Matarese G. Interdisciplinary approach for a patient with unilateral cleft lip and palate. Am J Orthod Dentofacial Orthop. 2018;153(6):883-94. Hoffmannova E, Moslerová V, Dupej J, Borský J, Bejdová Š, Velemínská J. Three-dimensional development of the upper dental arch in unilateral cleft lip and palate patients after early neonatal cheiloplasty. Int J Pediatr Otorhinolaryngol. 2018;109:1-6. Tan ELY, Kuek MC, Wong HC, Ong SAK, Yow M. Secondary Dentition Characteristics in Children With Nonsyndromic Unilateral Cleft Lip and Palate: A Retrospective Study. Cleft Palate Craniofac J. 2018;55(4):582-89. Rodrigues R, Fernandes MH, Monteiro AB, Furfuro R, Sequeira T, Silva CC, Manso MC. SPINA classification of cleft lip and palate: A suggestion for a complement. Arch Pediatr. 2018;25(7):439-41. Ortiz-Posadas MR, Vega-Alvarado L, Maya-Behar J. A new approach to classify cleft lip and palate. Cleft Palate Craniofac J. 2001;38(6):545-50.Spina V, Psillakis JM, Lapa FS, Ferreira MC. Classificação das fissuras lábio-palatinas. Sugestão de modificação [Classification of cleft lip and cleft palate. Suggested changes]. Rev Hosp Clin Fac Med Sao Paulo. 1972;27(1):5-6. Allori AC, Mulliken JB, Meara JG, Shusterman S, Marcus JR. Classification of Cleft Lip/Palate: Then and Now. Cleft Palate Craniofac J. 2017;54(2):175-88. Spina V. A proposed modification for the classification of cleft lip and cleft palate. Cleft Palate J. 1973;10:251-2. Yun-Chia Ku M, Lo LJ, Chen MC, Wen-Ching Ko E. Predicting need for orthognathic surgery in early permanent dentition patients with unilateral cleft lip and palate using receiver operating characteristic analysis. Am J Orthod Dentofacial Orthop. 2018;153(3):405-14. Garib D, Yatabe M, de Souza Faco RA, Gregório L, Cevidanes L, de Clerck H. Bone-anchored maxillary protraction in a patient with complete cleft lip and palate: A case report. Am J Orthod Dentofacial Orthop. 2018;153(2):290-97. De Stefani A, Bruno G, Balasso P, Mazzoleni S, Baciliero U, Gracco A. Teeth agenesis evaluation in an Italian sample of complete unilateral and bilateral cleft lip and palate patients. Minerva Stomatol. 2018;67(4):156-64. Chang SY, Lonic D, Pai BC, Lo LJ. Primary Repair in Patients With Unilateral Complete Cleft of Lip and Primary Palate: Assessment of Outcomes. Ann Plast Surg. 2018;80(2S Suppl 1):S2-6.Vura N, Gaddipati R, Palla Y, Kumar P. An Intraoral Appliance to Retract the Protrusive Premaxilla in Bilateral Cleft Lip Patients Presenting Late for Primary Lip Repair. Cleft Palate Craniofac J. 2018;55(4):622-25.Massie JP, Bruckman K, Rifkin WJ, Runyan CM, Shetye PR, Grayson B, Flores RL. The Effect of Nasoalveolar Molding on Nasal Airway Anatomy: A 9-Year Follow-up of Patients With Unilateral Cleft Lip and Palate. Cleft Palate Craniofac J. 2018;55(4):596-601. Jabbari F, Wiklander L, Reiser E, Thor A, Hakelius M, Nowinski D. Secondary Alveolar Bone Grafting in Patients Born With Unilateral Cleft Lip and Palate: A 20-Year Follow-up. Cleft Palate Craniofac J. 2018;55(2):173-79.Jones CM, Roth B, Mercado AM, Russell KA, Daskalogiannakis J, Samson TD, Hathaway RR, Smith A, Mackay DR, Long RE Jr. The Americleft Project: Comparison of Ratings Using Two-Dimensional Versus Three-Dimensional Images for Evaluation of Nasolabial Appearance in Patients With Unilateral Cleft Lip and Palate. J Craniofac Surg. 2018;29(1):105-8. Gatti GL, Freda N, Giacomina A, Montemagni M, Sisti A. Cleft Lip and Palate Repair. J Craniofac Surg. 2017;28(8):1918-24.

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Knight, Robert. « Heinrich Wildner Tagebücher 1938–1944 ("Heute geht es gegen die Juden, morgen kann es gegen die anderen gehen…") ed. by Gertrude Enderle-Burcel, and : Das Tagebuch von Heinrich Wildner 1945 ("Ich bestelle Sie hiemit zur Leitung des Außenamtes,…") ed. by Roman Eccher et al., and : Das Tagebuch von Heinrich Wildner 1946 ("...freilich werden wir im neuen Jahr noch nicht frei werden...") ed. by Roman Eccher et al., and : Das Tagebuch von Heinrich Wildner 1947 ("Man ist noch immer nervös. Wir sind sehr scharf bewacht") ed. by Elisabeth Gmoser et al., and : Das Tagebuch von Heinrich Wildner 1948 ("Es regiert der Planet Pallawatsch") ed. by Ernst Aichinger et al., and : Das Tagebuch von Heinrich Wildner 1949 ("Wie soll das weiter gehen?") ed. by Josef Litschauer et al. (review) ». Austrian Studies 31, n^o 1 (2023) : 218–21. http://dx.doi.org/10.1353/aus.2023.a919435.

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Mungo, Chemtai. « Abstract NG13 : Feasibility of topical self-administered therapies to improve cervical precancer treatment outcomes among women living with HIV in low-and middle-income countries ». Cancer Research 83, n^o 7_Supplement (4 avril 2023) : NG13. http://dx.doi.org/10.1158/1538-7445.am2023-ng13.

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Abstract Global trends of invasive cervical cancer (ICC) represent a dire global health inequity, with 85 percent of incident cases and 90 percent of deaths occurring in low- and middle-income countries (LMICs).1 ICC is the leading cause of cancer death among women living with HIV (WLWH) in sub-Saharan Africa, which accounts for 71% of the global burden of HIV infection, despite being home to only 12% of the global population.2 Compared to HIV-negative women, WLWH have increased incidence and persistence of human papillomavirus (HPV),3 have a shorter time from HPV infection to development of precancerous lesions,4 and have a six to eightfold increased risk of developing invasive cancer.5 In 2020, the World Health Organization (WHO) launched the 90/70/90 global strategy for cervical cancer elimination, which aims for 90% human papillomavirus (HPV) vaccination rate, 70% screening coverage, and 90% of precancerous lesions adequately treated by 2030. Current efforts towards this elimination agenda include scaling up HPV-based screening programs as well as improving access to precancer treatment using portable ablation and excisional devices in LMICs. However, among WLWH, current precancer treatment methods are limited by high rates of treatment failure. In a randomized trial of WLWH with cervical intraepithelial neoplasia grade 2/3 (CIN2/3), recurrence at 24 months was 30% in the ablation arm and 19% in the excision arm.6 These high rates of treatment failure, demonstrated in multiple studies, are driven by persistent HPV infection following treatment,7 and are highly consequential in LMICs settings follow-up mechanisms are weak. This highlights an urgent need for studies on feasible, innovative, yet accessible strategies to improve HPV clearance following precancer treatment for WLWH in LMICs. Use of self-administered topical therapies with anti-viral properties as adjunct treatment could be a feasible and highly scalable strategy to address this limitation. Several studies, have demonstrated the safety, and efficacy of 5-Flourouracil (5FU), a readily available topical drug as primary or adjuvant therapy for CIN2/3 among both HIV-positive and HIV-negative women in the U.S. In a Phase III multicenter trial of U.S WLWH with CIN2/3 randomized to self-administered intravaginal 5-Flourouracil (5FU) versus observation following standard treatment, participants in the 5FU arm had an 8% CIN2/3 recurrence rate at 18 month follow-up, compared to 31% in the observation arm (p=0.04).8 In another randomized trial of self-administered 5FU as primary treatment versus 6-month observation for CIN grade 2 (CIN2) among U.S women without HIV infection, 93% in the 5FU arm had disease regression, compared to 56% in the observation arm (p=0.01).9 In this study, 50% of participants in the 5FU arm cleared HPV at follow-up, compared to 22% in the observation arm (p<0.05). In both studies, 5-FU, used once every other week for 8 applications, was safe, with no grade 3 or 4 adverse events, and compliance and adherence to treatment was high. However, there are no studies evaluating whether self-administered therapies would be culturally acceptable to WLWH and their male partners in LMICs, or whether topical 5FU may be in this population. To fill this gap, with the support of the 2022 Victoria’s Secret Global Fund for Women’s Cancers Career Development award, in partnership with Pelotonia & the American Association for Cancer Research, using in-depth-interviews and focus group discussions, I am carrying out a mixed-methods qualitative study among WLWH with HPV and their male partners in Kenya and Malawi to investigate their perceptions towards using self-administered therapies for HPV and cervical precancer treatment, as well as perceived barriers and facilitators to uptake. Additionally, I will conduct a Phase I trial to evaluate the safety and adherence of self-administered intravaginal 5-FU following primary treatment among WLWH with CIN2/3 in Kenya. These studies will generate key preliminary data to support future randomized trials to investigate the efficacy of 5FU as adjuvant therapy to improve current precancer treatment strategies for WLWH in LMICs. References: 1. Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-249. doi:10.3322/caac.21660. 2. Joshi S, Sankaranarayanan R, Muwonge R, Kulkarni V, Somanathan T, Divate U. Screening of cervical neoplasia in HIV-infected women in India. Aids. 2013;27(4):607-615. doi:10.1097/QAD.0b013e32835b1041. 3. Smith JS, Sanusi B, Swarts A, et al. A randomized clinical trial comparing cervical dysplasia treatment with cryotherapy vs loop electrosurgical excision procedure in HIV-seropositive women from Johannesburg, South Africa. Am J Obstet Gynecol. 2017;217(2):183.e1-183.e11. doi:10.1016/j.ajog.2017.03.022. 4. Denslow SA, Rositch AF, Firnhaber C, Ting J, Smith JS. Incidence and progression of cervical lesions in women with HIV: a systematic global review. Int J STD AIDS. 2014;25(3):163-177. doi:10.1177/0956462413491735. 5. Dryden-Peterson S, Bvochora-Nsingo M, Suneja G, et al. HIV infection and survival among women with cervical cancer. J Clin Oncol. 2016;34(31):3749-3757. doi:10.1200/JCO.2016.67.9613. 6. Greene SA, De Vuyst H, John-Stewart GC, et al. Effect of Cryotherapy vs Loop Electrosurgical Excision Procedure on Cervical Disease Recurrence Among Women With HIV and High-Grade Cervical Lesions in Kenya: A Randomized Clinical Trial. JAMA. 2019;322(16):1570-1579. doi:10.1001/jama.2019.14969. 7. Chung MH, De Vuyst H, Greene SA, et al. Human Papillomavirus Persistence and Association With Recurrent Cervical Intraepithelial Neoplasia After Cryotherapy vs Loop Electrosurgical Excision Procedure Among HIV-Positive Women: A Secondary Analysis of a Randomized Clinical Trial. JAMA Oncol. Published online August 2021. doi:10.1001/jamaoncol.2021.2683. 8. Maiman M, Watts DH, Andersen J, Clax P, Merino M, Kendall MA. Vaginal 5-fluorouracil for high-grade cervical dysplasia in human immunodeficiency virus infection: A randomized trial. Obstet Gynecol. 1999;94(6):954-961. doi:10.1016/S0029-7844(99)00407-X. 9. Rahangdale L, Lippmann QK, Garcia K, Budwit D, Smith JS, Le L Van. Topical 5-flourourcil for treamtent of cervical intraepithelial Neoplasia 2 : a Randomized Controlled Trial. Am J Obstet Gynecol. 2014;2140():314.e1-314.e8. doi:10.1016/j.ajog.2013.12.042 Citation Format: Chemtai Mungo. Feasibility of topical self-administered therapies to improve cervical precancer treatment outcomes among women living with HIV in low-and middle-income countries. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr NG13.

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Ransom, Jacob L., Ka C. Wong, Jacqueline Kircher, Courtney Usry et Christopher Larson. « Bidirectional Ventricular Tachycardia in a Young Female : A Case of Andersen-Tawil Syndrome ». Military Medicine, 19 février 2021. http://dx.doi.org/10.1093/milmed/usab076.

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ABSTRACT Bidirectional ventricular tachycardia (VT) is a rare ventricular dysrhythmia with a limited differential diagnosis that includes digitalis toxicity, catecholaminergic polymorphic VT, aconite poisoning, and genetic channelopathy syndromes, specifically, Andersen–Tawil syndrome (ATS). We present a case of a young female with palpitations found to have bidirectional VT on cardiac event monitor and strong family history of cardiac dysrhythmias. Her physical examination findings included minor dysmorphic features of mandibular hypoplasia, hypertelorism, and clinodactyly. The patient was clinically diagnosed with ATS and started on a beta-blocker for control of ectopy. A second Holter review demonstrated markedly decreased burden of ventricular ectopy compared to the initial monitoring. She was referred for genetic testing, which revealed a KCNJ2 mutation. Bidirectional VT is an uncommon ventricular dysrhythmia that has a limited differential diagnosis, one of which is ATS—a rare genetic disorder that results from mutations in the KCNJ2 gene. The condition is frequently associated with developmental, skeletal, and cardiac abnormalities. Although there are no strong recommendations that exist for treatment of ventricular dysrhythmias associated with this genetic disorder, we demonstrate a case of clinical improvement in a patient with ATS by using the beta-blocker metoprolol succinate. Furthermore, we propose that ATS patients may not need exercise restrictions as overall ventricular ectopy burden decreased with exercise and there was no prolongation of the QT interval. This patient will continue to follow up in our clinic to reassess symptom burden and for continued monitoring for the development of any new features.

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Yang, Jing, Kun Li, Tingting Lv, Ying Xie, Fang Liu et Ping Zhang. « Case report : Mexiletine suppresses ventricular arrhythmias in Andersen-Tawil syndrome ». Frontiers in Cardiovascular Medicine 9 (25 août 2022). http://dx.doi.org/10.3389/fcvm.2022.992185.

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It is arduous to determine clinical solutions for Andersen-Tawil syndrome (ATS) in patients intolerant of β-blocker. Here, we present the case of a 7-year-old boy with periodic paralysis and dysmorphic features who experienced syncope four times during exercise. His ECG revealed enlarged U waves and QU-prolongation associated with ATS-specific U wave patterns, frequent PVCs, and non-sustained bidirectional or polymorphic ventricular tachycardia. The genetic test showed a de novo missense R218W mutation of KCNJ2. With the diagnosis of ATS and intolerance of β-blocker, the patient was prescribed oral medications of mexiletine 450 mg/day without severe adverse effects. The repeat ECG showed decreased PVC burden from 38 to 3% and absence of ventricular tachycardia. He remained symptom-free during over 2 years of outpatient follow-up. This case demonstrates a new anti-arrhythmic therapy with mexiletine for prevention of life-threatening cardiac events in patients with ATS who are intolerant of β-blocker treatment.

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« Globale Entwicklung der Healthy Life Expectancy (HALE) zwischen 1990 und 2017 ». Das Gesundheitswesen 81, n^o 08/09 (août 2019) : 579–80. http://dx.doi.org/10.1055/a-0955-0540.

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Weltweit ist aufgrund verbesserter Lebensbedingungen und einer hochwertigeren medizinischen Versorgung ein kontinuierlicher Anstieg der Lebenserwartung zu verzeichnen. Allerdings nimmt die gesunde Lebenserwartung („Healthy Life Expectancy“ [HALE]) nicht in gleichem Maß zu. Die „Global Burden of Diseases, Injuries, and Risk Factors Study“ (GBD) 2017 hat für 195 Länder über 28 Jahre hinweg unter anderem Muster und Trends zu der HALE analysiert.

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« Psychosozialer Stress durch Covid-19 – Pflegepersonal in Deutschland fühlte sich zu Beginn der Pandemie psychisch stark belastet ». Gesundheitsökonomie & ; Qualitätsmanagement 25, n^o 05 (octobre 2020) : 227–28. http://dx.doi.org/10.1055/a-1288-8789.

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Kramer V et al. Subjective burden and perspectives of German healthcare workers during the COVID-19 pandemic. Eur Arch Psychiatry Clin Neurosci. 2020 Aug 19. doi: 10.1007/s00406–020–01183–2 [Epub ahead of print] Beschäftigte im Gesundheitswesen, die Covid-19-Patienten und -Patientinnen pflegen und behandeln, waren zu Beginn der Pandemie gestresster und fühlten sich deutlich stärker belastet, als andere Beschäftigte, insbesondere in der Pflege. Dies ist das Ergebnis der deutschlandweit ersten Studie dazu. Insgesamt zeigten die Beschäftigten im deutschen Gesundheitswesen hohe Zustimmungsraten zu den von Krankenhäusern und Staat ergriffenen Maßnahmen.

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Younis, Arwa, Mehmet Aktas, Ilan Goldenberg, Scott McNitt, Bronislava Polonsky, Valentina Kutyifa, Spencer Z. ROSERO et al. « Abstract 17496 : The Effect of Statin on Ventricular Tachyarrhythmia Burden ». Circulation 142, Suppl_3 (17 novembre 2020). http://dx.doi.org/10.1161/circ.142.suppl_3.17496.

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Introduction: Statins may reduce risk for ventricular tachyarrhythmia (VTA) in patients with implantable cardioverter defibrillator (ICD). Ranolazine was shown to increase plasma concentrations of statin. Objective: To evaluate the effect of statin on recurrent VTA, and to explore the interaction with both Ranolizine and cardiomyopathy (CMP) origin. Methods: The Andersen-Gill extension of the Cox proportional hazards regression was used to assess the association between statin treatment and the risk for recurrent VTA among 1012 ICD patients enrolled in the Ranolazine Implantable Cardioverter-Defibrillator Trial (RAID). Interaction-term analysis with ranolazine and ischemic status were performed. Number of events was limited to a maximum of 10 VTA events per patient to avoid any patients having an undue influence on model estimates. Results: A total of 740 (73%) RAID patients were treated with statins. Multivariable analysis showed that statin use was associated with an overall 30% reduction in the risk for recurrent VTA (HR=0.70; p<0.001)(Figure). Interaction analysis showed that the benefit of statin use was seen only among patients with non-ischemic CMP (HR=0.53 [95%CI 0.41-0.69]; p<0.001), whereas there was no evidence of benefit among patients with ischemic CMP for recurrent VTA (HR=1.03 [95%CI 0.70-1.54] p=0.70), with an interaction p-value of <0.01 for the differential effect of statin use on recurrent VTA by CMP origin. The effect of statin was relatively consistent and did not differ significantly between the ranolazine and placebo arms (Figure). Statin use was not associated with increased adverse events, and ranolazine discontinuation was higher among those who were not treated with statins vs. those who received statin therapy (53% vs 42%, respectively; p<0.01). Conclusion: Our findings suggest that treatment with statin (regardless if with or without ranolazine) is highly effective in reducing VTA burden in non-ischemic ICD recipients.

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Kilian, Jürgen. « Krieg auf Kosten anderer. Wehrmachtfinanzierung in Griechenland während des Zweiten Weltkriegs / War at the Expence of Others Financing the „Wehrmacht“ in Greece during the Second World War ». Südost-Forschungen 73, n^o 1 (8 janvier 2014). http://dx.doi.org/10.1515/sofo-2016-0104.

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AbstractAfter Greece had been conquered by the troops of the Axis Powers in spring 1941, they installed a rule of occupation existing until october 1944. The Government in Athens had to finance this occupation by making payments in advance and besides, making a forced credit available. This method led to an exorbitant overloading of the Greek economy and to a galloping inflation.The German Tax and Finance Ministry played an important, yet hardly noticed role as to the concrete implementation of the monetary exploitation. Almost unknown documents throw a light on the financing of the German Wehrmacht during WW II. Besides, the real burden on the Greek economy shall be estimated and connected with the general questions of war financing in the Third Reich.

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Đoàn, Lan N., Yumie Takata, Karen Hooker, Carolyn Mendez-Luck et Veronica L. Irvin. « Trends in Cardiovascular Disease by Asian American, Native Hawaiian, and Pacific Islander Ethnicity, Medicare Health Outcomes Survey 2011-2015 ». Journals of Gerontology : Series A, 7 septembre 2021. http://dx.doi.org/10.1093/gerona/glab262.

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Abstract Background The burden of cardiovascular disease (CVD) is increasing in the aging population. However, little is known about CVD risk factors and outcomes for Asian American, Native Hawaiian, and Other Pacific Islander (NH/PI) older adults by disaggregated subgroups. Methods Data were from the Centers for Medicare & Medicaid Services 2011-2015 Health Outcomes Survey, which started collecting expanded racial/ethnic data in 2011. Guided by Andersen and Newman’s theoretical framework, multivariable logistic regression analyses were conducted to examine the prevalence and determinants of CVD risk factors (obesity, diabetes, smoking status, hypertension) and CVD conditions (coronary artery disease [CAD], congestive heart failure [CHF], myocardial infarction [MI], other heart conditions, stroke) for 12 Asian American and NH/PI subgroups and white adults. Results Among the 639,862 respondents, including 26,853 Asian American and 4,926 NH/PI adults, 13% reported CAD, 7% reported CHF, 10% reported MI, 22% reported other heart conditions, and 7% reported stroke. CVD risk factors varied by Asian American and NH/PI subgroup. The prevalence of overweight, obesity, diabetes and hypertension was higher among most Asian American and NH/PI subgroups than white adults. After adjustment, Native Hawaiians had significantly greater odds of reporting stroke than white adults. Conclusions More attention should focus on NH/PIs as a priority population based on the disproportionate burden of CVD risk factors compared to their white and Asian American counterparts. Future research should disaggregate racial/ethnic data to provide accurate depictions of CVD and investigate the development of CVD risk factors in Asian Americans and NH/PIs over the life course.

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Abdalla, Tasnim, Thomas Walwyn, Daniel White, Catherine S. Choong, Max Bulsara, David B. Preen et Jeneva L. Ohan. « Hospitalisations and Cost of Inpatient Care for Physical Diseases in Survivors of Childhood Cancer in Western Australia : a Longitudinal Matched Cohort Study. » Cancer Epidemiology, Biomarkers & ; Prevention, 6 juillet 2023. http://dx.doi.org/10.1158/1055-9965.epi-22-1313.

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Abstract Background. The long-term effects of childhood cancer are unclear in the Australian context. We examined hospitalisation trends for physical diseases and estimated the associated inpatient care costs in all 5-year childhood cancer survivors (CCS) diagnosed in Western Australia (WA) from 1982-2014. Methods. Hospitalisation records for 2,938 CCS and 24,792 comparisons were extracted from 1987- 2019 (median follow-up=12 years, min=1, max=32). The adjusted hazard ratio (aHR) of hospitalisation with 95% confidence intervals (CI) was estimated using the Andersen-Gill model for recurrent events. The cumulative burden of hospitalisations over time was assessed using the mean cumulative count method. The adjusted mean cost of hospitalisation was estimated using the generalised linear models. Results. We identified a higher risk of hospitalisation for all-cause (aHR=2.0, 95%CI= 1.8-2.2) physical disease in CCS than comparisons, with the highest risk for subsequent malignant neoplasms (aHR=15.0, 95%CI 11.3-19.8) and blood diseases (aHR=6.9, 95%CI 2.6-18.2). Characteristics associated with higher hospitalisation rates included female gender, diagnosis with bone tumours, cancer diagnosis age between 5-9 years, multiple childhood cancer diagnoses, multiple comorbidities, higher deprivation, increased remoteness, and Indigenous status. The difference in the mean total hospitalisation costs for any disease was significantly higher in survivors than comparisons (publicly funded $11,483 United States Dollar, p<0.05). Conclusions. The CCS population face a significantly higher risk of physical morbidity and higher cost of hospital-based care than the comparisons. Impact. Our study highlights the need for long-term follow-up healthcare services to prevent disease progression and mitigate the burden of physical morbidity on patients and hospital services.

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