Older populations in residential aged care facilities (RACFs) in many immigrant-receiving countries are now being increasingly culturally and linguistically diverse (CALD). CALD populations require tailored social and health services to support their needs and improve health outcomes. Falls among the elderly are common and can have significant health and psychosocial consequences. There is some evidence to suggest that country of birth may influence risk of falls among older people, but such evidence has been scarce. This study aimed to determine the association between place of birth and the incidence of falls in RACFs.Routinely collected incident data relating to 5,628 residents aged ≥ 65 years in 25 RACFs in Sydney, New South Wales, Australia were used. RACF residents were classified into two groups, Australia-born  and overseas-born . Overseas-born RACF residents were further categorised into two subgroups: overseas-English-speaking-country (N = 743) and overseas-non-English-speaking-country (N = 799). Outcomes measures were rate of all falls, injurious falls and falls requiring hospitalisation. Multilevel binary negative regression was used to examine the relationship between fall risk and place of birth.Incidence rates of all falls, injurious falls and falls requiring hospitalisation were 8.62, 3.72 and 1.07 incidents per 1,000 resident days, respectively, among the Australia-born RACF residents, but were higher at 11.02, 4.13 and 1.65, respectively, among the overseas-born RACF residents. Within those born overseas, fall rates were higher among the overseas-non-English-speaking-country-born residents  than those overseas-English-speaking-country-born . After controlling for confounders, the overseas-born RACF residents overall experienced a higher risk of all three types of falls  than the Australia-born RACF residents. Among the overseas-born RACF residents, males, respite residents and those overseas-non-English-speaking-country-born experienced higher rates of falls.Fall incidence in RACFs varies significantly by place of birth. With increasingly diverse RACF populations, fall intervention and prevention programs should consider cultural and linguistical backgrounds of RACF residents. Greater attention to understand the mechanisms for the differences by place of birth in risk profiles is warranted.The online version contains supplementary material available at 10.1186/s12877-023-03954-7. Falls and fall-related injuries among older populations are a prominent concern globally. Approximately 28–35% of people aged 65 and older in the community , 2 and mPrevious studies have identified a range of risk factors of falls, including older age, female gender, declined cognitive and physical functionality, use of psychotropic medication and fall history , 6, 11. Previous research has demonstrated that the prevalence and consequences of age-related conditions might prevail and pattern differently by country of birth and that such differences may persist despite moving to and residing in another country for many years , 18. FalWe conducted a retrospective longitudinal cohort study using routinely collected aged care data sourced from 25 RACFs of a large not-for-profit aged care provider in New South Wales, Australia. Routinely-collected data refer to information collected systematically and electronically by aged care providers for clinical and administration purposes on a day-to-day basis.  In this Our data contained information of 10,226 admissions from 6,727 residents. We excluded data of admissions in which age of participants was under 65 (N = 77), only interim care was used (N = 26), participants were discharged on the same date as admission (N = 198), participants’ date of entry was erroneously before the departure date (N = 1), or participations’ information of country of birth was missing . This yielded a final sample of 5,628 residents with 8,584 admissions, of which 4,729 were permanent admissions and 3,855 were respite admissions. The sample selection process is presented in Fig. We used resident profile data and incident reports. The profile dataset contained information of residents’ demographic characteristics , health conditions  and admission-related information . The incident data included all fall events occurring in facilities, including incident date, location  and consequences .We considered three fall outcome groups: all falls, injurious falls and falls requiring hospitalisation. All falls were defined as any fall in the incident dataset regardless of the fall consequences ; injurious falls were falls that caused any type of injury ; while falls requiring hospitalisation were those falls resulting in sequalae requiring hospital admission for further assessment and management.Two variables of the resident profile dataset, ‘whether Australia-born’ and ‘country of birth if born overseas’, were used to categorise participants as Australia-born or overseas-born. The overseas-born group was further divided into: residents born in an English- or non-English-speaking country based on whether English is listed as an official language in their country of birth . This isWe calculated fall incidence rates . Fall incidence rate for each RACF resident was based on their number of falls occurring during their length of stay. For RACF residents with more than one admission, falls occurring in all the admissions and the lengths of each stay were added up separately. We did not use two commonly used indicators of fall risk, whether an individual suffered a fall or not and the absolute number of falls that the individual experienced , 19, 28,We first described and compared the average incidence rate of the three types of falls for the Australia-born and the overseas-born RACF residents, and also for the two subgroups of the overseas-born RACF residents. We then conducted multilevel negative binomial regression to examine the association between fall and place of birth, controlling for age, gender, fall history and comorbidity status at time of admission , which have been previously been demonstrated as fall risk factors , 29–31. As shown in Table Figure Table Table Examination of fall risks by country of birth, gender, age and admission type Table  showed tPopulations are ageing and increasingly CALD in Australia and many other countries , 32. In This study demonstrates that immigrant status to Australia is associated with an increased fall risk among RACF residents. This finding is in contrast to previous Australian studies showing a lower fall risk for specific immigrant groups in the community-based setting , 15. HowResults also show that the greater vulnerability to falls for the overseas-born RACF residents is more prominent among those born in overseas non-English-speaking countries compared with those born in overseas English-speaking countries. This finding highlights the role of language barrier in health outcomes and wellbeing of the overseas-born RACF residents. Previous studies had demonstrated that low language proficiency is significantly associated with immigrants’ lower income, reduced employability and limited access to medical and health resources , which mThis study also demonstrated that the higher risk of falls of the overseas-born RACF residents was more significant among men. This is inconsistent with previous findings reporting a higher propensity of falls among women , 2, 5 buAnother interesting finding is that the overseas-born RACF residents’ higher risk of falls was more prominent among respite residents compared with permanent residents. This intriguing finding corresponds to previous studies demonstrating a higher risk of adverse events, such as hospitalisation, for older adults recently admitted to RACFs compared with those having stayed for a long period , 51. TheThis study has important policy implications for improved fall prevention and management in the RACF setting for those residents born overseas. In particular, male and respite residents are at increased risk of fall. The diverse cultural and linguistical backgrounds of residents should be considered when developing fall prevention and intervention programs. Providing culturally and linguistically appropriate care service support, such as employing bilingual and bicultural staff and reflecting cultural diversity in fall intervention strategies , is suggested. In Australia, 35% of aged care workforce were from a CALD background in 2020 and this proportion is increasing . HoweverWe conducted a retrospective longitudinal cohort study on fall and place of birth in the RACF setting based on routinely collected data from 25 Australian RACFs. The strengthens of this study lie in its large sample size  and its comprehensive measure of falls , which fortify the robustness of the results.This study has several limitations. First, the data used were sourced from one aged care service provider in Sydney, New South Wales, Australia and therefore may not be reflective of other RACF populations. Second, while the analysis in this study has considered a broad range of covariates, some variables, such as level of general health and frailty that are useful to explain our results, have not been included in the analysis given data unavailability. Additionally, factors at organisational or environmental level, such as the location of facility, the number of staff and the availability of registered nurse, that might also importantly affect falls were also not controlled given the same reason. Future studies are suggested to include such variables if data are available. Third, even though we had categorised the overseas-born RACF residents into two subgroups, there are still considerable cultural and linguistic variations within each group. We were unable to further explore the variations of fall risk by place of birth within each group or by language preference of residents due to a lack of data. It would be of interest for future studies to examine more nuanced differentials of fall risk among different immigrant groups  if data are available. Fourth, migrants’ health outcomes might differ by duration of residence , 41, whiThis study provides the first in-depth investigation into falls and place of birth in the RACF setting using a longitudinal cohort dataset in 25 RACFs Australia. Our analysis demonstrates that the overseas-born RACF residents experienced an overall higher fall risk than the Australia-born RACF residents, particularly among men, respite residents and those born in overseas non-English-speaking countries. The heightened fall risk associated with the overseas-born status highlights the importance of targeted fall prevention measures that are culturally and linguistically tailored for RACF residents.Below is the link to the electronic supplementary material.Supplementary Material 1: Table S1. Fall Risk of Overseas-born RACF Residents Compared with Australia-born RACF Residents, Male. Table S2. Fall Risk of Overseas-born RACF Residents Compared with Australia-born RACF Residents, Female. Table S3. Fall Risk of Overseas-born RACF Residents Compared with Australia-born RACF Residents, Age ≤ 85. Table S4. Fall Risk of Overseas-born RACF Residents Compared with Australia-born RACF Residents, Age > 85. Table S5. Fall Risk of Overseas-born RACF Residents Compared with Australia-born RACF Residents, Permanent Residents. Table S6. Fall Risk of Overseas-born RACF Residents Compared with Australia-born RACF Residents, Respite Residents.


In order for balance therapy to be successful, the training must occur at the appropriate dosage. However, physical therapist (PT) visual evaluation, the current standard of care for intensity assessment, is not always effective during telerehabilitation. Alternative balance exercise intensity assessment methods have not previously been compared to expert PT evaluations. The aim of this study was therefore to assess the relationship between PT participant ratings of standing balance exercise intensity and balance participant self-ratings or quantitative posturographic measures.Ten balance participants with age or vestibular disorder-related balance concerns completed a total of 450 standing balance exercises  while wearing an inertial measurement unit on their lower back. They provided per-trial and per-exercise self-ratings of balance intensity on a scale from 1 (steady) to 5 . Eight PT participants reviewed video recordings and provided a total of 1,935 per-trial and 645 per-exercise balance intensity expert ratings.PT ratings were of good inter-rater reliability and significantly correlated with exercise difficulty, supporting the use of this intensity scale. Per-trial and per-exercise PT ratings were significantly correlated with both self-ratings (r = 0.77–0.79) and kinematic data (r = 0.35–0.74). However, the self-ratings were significantly lower than the PT ratings (difference of 0.314–0.385). Resulting predictions from self-ratings or kinematic data agreed with PT ratings approximately 43.0–52.4% of the time, and agreement was highest for ratings of a 5.These preliminary findings suggested that self-ratings best indicated two intensity levels  and sway kinematics were most reliable at intensity extremes. DosaTelerehabilitation has grown in popularity as a solution to both misdistribution of physical therapy services , 36 and While telerehabilitation may improve access to care, only 29% of PTs in a 2022 vestibular rehabilitation study expressed that telerehabilitation was as effective as in-person care ; 92% of In addition to telerehabilitation, home exercise programs may complement existing affordable physical therapy options available to patients, which have been limited in their duration. For example, until recently, public insurance for older adults in the United States  covered only approximately 14–16 outpatient physical therapy visits . In SingIn contexts where visual assessment of balance task intensity is difficult such as telerehabilitation and home-based training, PTs may time exercises, employ quantitative posturography, or ask for patient self-assessments . Timing Quantitative posturography, which is possible with inertial measurement units (IMUs) found in ubiquitous technology such as smart phones, can measure an individual's center of mass during standing balance and may therefore be indicative of task intensity –55. AlsuSelf-report measures of intensity are analogous to the Borg Rating of Perceived Exertion for aerobic exercise  or the OWhile quantitative posturography and self-assessment have both shown promise as methods for remote assessment of balance task intensity, few comparisons have been made to conventional visual assessment by expert PTs. This study therefore aimed to further assess the differences between PT expert assessments of balance intensity and self-assessments and kinematic measures.2.In this study on balance exercise intensity assessment, PT participant intensity ratings  were compared to balance participant intensity self-ratings  and kinematic measures.2.1.Two types of participants completed this study: balance participants with age or vestibular disorder-related balance concerns and PT participants. Balance participants completed standing balance exercises while wearing an IMU, and they provided self-ratings of balance intensity. PT participants reviewed video recordings of the balance participants and provided ratings of balance intensity. 450 balance exercise trials were completed by 10 adult balance participants. Six older adult balance participants  self-reported to be generally healthy with no muscular or neurological disorders, and four balance participants  self-reported vestibular dysfunction. In addition, 1,935 intensity ratings were provided by eight PT participants who specialized in the treatment of balance disorders (16 ± 10 years of experience). The number of participants and resulting quantity of data is consistent with a number of related previously published studies –66. The 2.2.Both PT and balance participants were provided a 5-point intensity rating scale .The per-exercise self-ratings were significantly correlated with the PT ratings . Additionally, the standard deviations of the difference in per-trial or per-exercise ratings were 0.920 and 0.961 , respectively. Self-ratings exhibited a smaller variance between trials of the same exercise than the PT ratings did .However, the per-trial and per-exercise self-ratings were lower than the PT ratings , p ≤ 0.001) and agreed with the PT ratings 43.0% and 52.4% of the time, respectively. As shown in The kinematic features were significantly correlated with PT ratings see . When us4.4.1.The per-trial and per-exercise PT ratings were of good inter-rater reliability, supporting that the study results may be replicable and that it would be possible for the alternative assessments to accurately predict PT ratings. Higher ratings were also associated with higher exercise difficulty along three out of four dimensions  when accHowever, it is important to note that while the descriptors for PT ratings 1, 2, and 3 referenced amount of sway, prior research has reported variable sway results for people with balance impairments  –90. Incr4.2.While the self-ratings were strongly correlated with the PT ratings, the self-ratings were an imperfect approximation of PT ratings. As has been described by the Dunning-Kruger effect and reported in other contexts –94, balaAs a result of these differences, predicted PT ratings based on self-ratings exhibited moderately low accuracy. The common confusion between ratings of a 4 or a 5 as well as between ratings of a 1 or a 2 and the overall ambiguity for ratings of a 3 might suggest that balance participants are better able to distinguish between two levels of balance intensity . The confusion between ratings of 1, 2, or 3 may also reflect the aforementioned scale limitation in which the PT's descriptors reference sway, which may indicate either good or poor balance. As a result of these issues, if using self-ratings to support intensity assessment during telehealth or other contexts in which traditional PT assessment might be difficult, self-ratings might be used to suggest higher or lower intensity but may not suggest more granular levels of intensity.4.3.The kinematics-predicted intensity ratings were also imperfect yet informative approximations of PT ratings, as reflected by strong correlations, but moderately low prediction accuracies. The correlations between kinematic features and per-trial PT ratings were higher in the ML direction than in either AP or Phi directions, suggesting that, on average, PT participants based their evaluation of balance intensity more heavily upon movement in the ML direction. Similar correlation values as well as higher correlations in the ML direction were also reported by Alsubaie et al. in two investigations of intensity self-ratings (R between 0.56 and 0.88) , 56. TheAgreement between kinematics-predicted intensity ratings and PT ratings was higher than for self-ratings, resulting in especially high rates of agreement for kinematics-predicted ratings of a 5. If using kinematics to support PT assessments during telehealth or other applications, kinematics may be more heavily considered during high-intensity exercises with ratings near a 5 or for low-intensity exercises with ratings of a 1 or 2.In this first and necessary study on the differences between alternative modes of balance intensity assessment, both self-ratings and sway kinematics were shown to have the potential to support PT assessment of balance exercise intensity when expert visual assessment is difficult or limited, with sway kinematics being more accurate than self-ratings. Intensity assessments might be used in conjunction with frameworks for exercise progression such as the one proposed by Klatt et al. so that balance training can be remotely assessed and progressed over time . HoweverLimitations of this study included the performance of a subset of balance exercises  and a subset of balance participants that would benefit from balance training . Future work could include the exploration of alternate scale descriptors without reference to amount of sway, evaluation of additional balance-related pathologies and balance exercises, evaluation of the effects of PT experience level, analysis of full-body kinematics, and the use of data science methodologies such as machine learning approaches to capture additional trends in the kinematic data.5.This study examined the relationship between PT intensity ratings, self-assessments, and kinematic measures. Both self-ratings and trunk kinematic features correlated significantly with PT ratings of intensity. Based on the findings from this study, self-ratings may better distinguish between two levels of intensity  than five levels of intensity. Furthermore, kinematics-predicted intensity ratings at either extreme  may be more reliable indicators of intensity than the other ratings in the evaluated scale. These findings suggest that self-assessments and kinematic measurements may support PT intensity assessments during contexts in which visual assessment is difficult .


Trans-femoral transcatheter aortic valve replacement (TF-TAVR) performed under conscious sedation (LACS) is not yet become routine practice in Taiwan. We aimed to compared the results between patients received general anesthesia (GA) versus LACS. Our cohort was divided into 3 groups: initial 48 patients received TF-TAVR under routine GA (GA group), subsequent 50 patients under routine LACS (LACS group 1), and recent 125 patients under LACS (LACS group 2). The baseline, procedural characteristics and all outcomes were prospectively collected and retrospectively compared. From Sep 2010 to July 2019, a total of 223 patients were included. The procedure time , contrast medium consumption , length of intensive care unit  and hospital stay  decreased significantly with LACS, combined with a trend of less hospital acquired pneumonia . 1-year survival rate were also different among 3 groups . In our single center experience, a “minimalist” approach of TF-TAVR procedure resulted in less medical resources usage, along with more favorable clinical outcomes. Previous registries reported the benefits of LACS with shorter procedure times, intensive care unit (ICU) and hospital stays, and lower 30-days mortality6. However, experiential heterogeneity would unavoidably confound the results because most centers started TAVR procedure with GA, and then switched to LACS with increasing experience. Otherwise, differences in clinical practice and patient characteristics may result in different results, and the benefit of LACS were not found in a recent randomized trial7. The economic effects of “minimalist” approach of TF-TAVR procedure were also unknown, and may be dependent on the local reimbursement system. Herein, we report our single center experience in Taiwan in streamlining TF-TAVR procedure from GA to LACS. We also divided the LACS population into 2 groups by time sequence to clarify the effect of experience and background heterogeneity on TAVR outcome.Since the introduction of transcatheter aortic valve replacement (TAVR), the procedures have been performed under general anesthesia (GA). With increasing operator experience, advancement of transcatheter valve systems, and economic considerations, streamlining transfemoral TAVR (TF-TAVR) procedure from GA to local anesthesia or conscious sedation (LACS) has been considered and advocated. The issues of GA included: potential discomfort and complications of tracheal intubation and mechanical ventilation, hemodynamic compromise induced by anesthetic agents and subsequent need for catecholamine use. These may be avoided by LACS, but aspiration may occur because of a non-protected airway. The absence of intra-procedural trans-esophageal echocardiography (TEE) under LACS may also lead to higher incidence of paravalvular leakage (PVL)245 consecutive patients with severe symptomatic aortic stenosis underwent TF-TAVR in National Taiwan University Hospital from September 2010 to June 2019. 223 patients were included in the final analysis, according to the flowchart depicted in Fig. All patients had signed informed consent, and the study was approved by the institutional review board of National Taiwan University Hospital. All methods were carried out in accordance with relevant guidelines and regulations.GA was performed with endotracheal intubation and mechanical ventilator support. Variable combination of intravenous anesthetic agents (sevofluorane or propofol), muscle relaxants (rocuronium or cisatracurium), and ultra-short-acting opioid (remifentanil). Proper anesthesia level was maintained to allow immediate extubation at the end of TF-TAVR procedure in the operating room. Assessment of peri-procedural TAVR results by TEE was performed in GA group in addition to the angiographic and hemodynamic evaluation.In LACS patients, local analgesics were applied by the operators. Conscious sedation was performed by an anesthesiologist with a continuous infusion of either midazolam, dexmedetomidine, or remifentanil. The medication was titrated to induce moderate sedation, during which patients respond purposefully to verbal commands, either alone or accompanied by light tactile stimulation. Post-TAVR assessment was based on angiographic and hemodynamic, and in some cases, transthoracic echocardiographic evaluation in LACS patients.10.Clinical follow-up was performed at discharge, 30 days, 6 and 12 months post TAVR. Definitions of procedure results were in accordance with the Valve Academic Research Consortium (VARC) consensusContinuous variables were presented as mean ± standard deviation (SD) or mean with interquartile range (IQR). ANOVA were used to compared 3 groups, and post hoc-analysis were performed between each 2 groups if ANOVA showed difference with an adjusted p value according to Bonferroni method. Categorical variables were presented as percentage and compared with either chi-square test or Fisher exact test. Cumulative rate of death was presented with Kaplan Meier method and assessed with log-rank test. Cox regression analysis were used to compared the 1-years survival of LACS1 vs. GA, and LACS2 vs. GA respectively, potential confounders  was also observed in LACS group 2. Higher incidence of hypertension , previous myocardial infarction  were seen in GA group. There was no difference in age and left ventricular systolic function among 3 groups.The baseline characteristics of 223 patients were summarized in Table 9. Procedure time , contrast medium consumption  were significantly reduced in LACS group 1 and 2. The percentage of more than moderate PVL post-TAVR was similar in GA, LACS group 1 and 2. The device success rate was higher in LACS group 2, as compared to that in GA group. .The procedural variables and results were presented in Table The in-hospital results and clinical outcomes were presented in Table 11. According to Transcatheter Valve Therapy Registry analyzing 120,080 TF-TAVR patients between January 2016 and March 2019 in the U.S., the use of LACS increased substantially from 33 to 64%, but 17% of the U.S. centers continued to use GA exclusively11. In Taiwan, TF-TAVR procedures performed under LACS were still less than 50%. Which anesthetic management is more favorable for TF-TAVR is now a subject of intense debate, leading to a considerable variation in clinical practice. Based on the results of this single center study, LACS is not only a feasible alternative to conventional GA for TF-TAVR, but also results in less resource usage, comparable with the observations in previous registries11  as compared to GA group, significantly less contrast medium consumption , shorter procedure time , ICU stay  and less in-hospital medical fee  were still observed in LACS group 1. Although the effect of improvement in technical skills can never be ruled out, the results could still be attributed to the “minimalist” approach: simplification of the anesthetic strategies and access pre-closure. The importance of reducing contrast medium usage is potentially lowering the risk of contrast-induced nephropathy, especially for the elderly with multiple comorbidities such as chronic kidney disease. The faster procedure sometimes represents the less complicated peri-procedural course. It will lead to less complicated post-procedural course, and may result in a significant reduction in health care expenses, which already suggested by a previous study14.Most centers started TAVR procedure with GA. But with increasing experience and familiarity with devices, operators tend to switch from GA to LACS16, or registry studies17 comparing of anesthetic managements. Peri-procedural infection is not part of the endpoints in Valve Academic Research Consortium (VARC), except for infective endocarditis after TAVR9. In the SOLVE-TAVI trial, infections requiring antibiotic treatment occurred in one-fifth of the patients, mainly attributable to pneumonia and urinary tract infection. The incidences of overall infections were reported similar between GA & LACS groups, but the risk of pneumonia was not mentioned specifically7. In our cohort, the incidence of hospital acquired pneumonia (HAP) in GA group was 2-times higher than that in LACS group 1 and 2, although not statistically significant due to sample size. Significantly lower HAP rate, however, was seen in LACS group 2 comparing to that in GA group, but this was probably confounded by the different risk profile of the patient populations.Tracheal intubation with mechanical ventilation, indwelling urinary tract catheters, hemodynamic instability, and prolonged hospitalization associated with GA may increase the risk of infection. Interestingly, TAVR peri-procedural infections were never reported in previous single center reports8. Stanger et al. reported a retrospective single center evaluation of 841 TAVR patients, and overall risk of upper GI bleeding following TAVR was found to be 2.0% (17/841)18. Patients on triple antithrombotic therapy are at highest risk for severe upper GI bleeding. Upper endoscopy evaluation or treatment was done in 12 patients, and the most common lesion was a distal esophageal or gastroesophageal junction ulceration with active bleeding. They postulated that the use of intraoperative TEE, which may cause local mechanical and thermal trauma, was the reason for these findings. The mechanism and impact of in-hospital GI bleeding following TAVR should be studied further in the future.Lower incidence of in-hospital gastro-intestinal (GI) bleeding was also found in the LACS groups in the present study, which was never reported in previous registries or randomized trial comparing GA versus LACS in TAVR. GI bleeding was included in major and minor bleeding complications in VARC definition, and was not counted independentlyThe present study has a number of limitations. Firstly, this is a single center study with a relatively small consecutive cohort. The 2 discussed anesthetic strategies were chosen arbitrarily over time without randomization, and also the baseline characteristics were different between each group which may bias the results. Thus the generalization of our finding was limited. Secondly, because of the chronological nature of the study, the results may be confounded by differences in procedure experience and patient risk profiles, as well as the simultaneous introduction of other technological advances in TAVR, such as newer generation of valve systems. Thirdly, the actual anesthetic agents and dosages applied in LACS or GA were not pre-specified or controlled, and their potential influence on the outcome was difficult to be examined by the present study.The present study provided the contemporary results of single center experience in Taiwan in streamlining TAVR procedure towards a “minimalist” approach. It demonstrated the feasibility and safety of TF-TAVR performed using exclusively LACS. The contrast volume, procedure time, ICU and hospital stays were all reduced significantly. There was also a trend of lower incidence of HAP and GI bleeding in patients receiving LACS. All these translated into less in-hospital medical cost without compromised efficacy and a very low 30-day and 1-year mortality. The results demonstrated that LACS is a viable alternative to a traditional GA for TF-TAVR, and should be considered by all institutions performing this procedure in Taiwan.


To assess the feasibility of a remote care model for high-risk COVID-19 patients, identify risk factors for hospital admission, and propose modifications to the tested model.We conducted a multicenter observational study of 225 patients  treated at three primary care centers between October 2020 and February 2022. Patients were enrolled into a telemonitoring program if they had a mild-moderate course of COVID-19 confirmed by polymerase chain reaction testing and were classified as high-risk for COVID-19 deterioration. Patients measured their vital signs three times daily, consulted their primary care physician every other day, and were followed up for 14 days. At inclusion, data were collected with a semi-structured questionnaire, and blood was drawn for laboratory analysis. A multivariable Cox regression model was used to determine predictors of hospital admission.P = 0.015) and thrombocytopenia .The median age was 62 years (range 24-94). The hospital admission rate was 24.4%, and the mean time from inclusion to hospital admission was 2.7 ± 2.9 days. A total of 90.9% of patients were hospitalized within the first five days. A Cox regression model, adjusted for age, sex, and the presence of hypertension, revealed that the main predictors of hospital admission were type-2 diabetes (hazard ratio [HR] 2.38, 95% confidence interval [CI] 1.19-4.77, Telemonitoring of vital signs is a feasible method of remote care that helps identify patients requiring immediate hospital admission. For further scale-up, we suggest shortening call intervals in the first five days, when the risk of hospital admission is highest, and giving special attention to patients with type-2 diabetes and thrombocytopenia at inclusion. The global health care systems have been greatly affected by the COVID-19 pandemic, experiencing significant disruptions due to the rapid spread of the virus, its unpredictable nature, and the emergence of new virus variants , involving mainly suburban and rural populations. The study was approved by the Medical Ethics Committee of the Republic of Slovenia and complied with the Declaration of Helsinki.The study population included 225 patients who met the inclusion criteria and received a telemedicine package in the three primary care centers between October 2020 and February 2022.Inclusion criteria were (a) an infection with SARS-CoV-2 confirmed through polymerase chain reaction (PCR) testing, (b) a mild to moderate course of COVID-19, (c) a high-risk for deterioration as assessed by the patient’s primary care physician, and (d) the ability to independently measure vital signs or having a caregiver available to assist with the measurements.The high-risk criteria were (a) age ≥60 years, (b) the presence of chronic comorbidities such as cardiovascular disease, pulmonary disease, diabetes, oncologic disease, or other chronic conditions as determined by the primary care physician, and (c) exhibiting more severe symptoms of COVID-19 that could potentially lead to deterioration . Patients displaying clinical signs of pneumonia without hypoxemia were also classified as high-risk. These criteria were established based on initial reports identifying predictors of worse outcomes in COVID-19 patients .2), heart rate, and body temperature three times a day and document the readings in the measurement diary. The primary care physician provided guidance on the proper use of the pulse oximeter before its utilization.Enrolled patients were given a COVID-19 telemedicine package, which included a pulse oximeter , a measurement protocol, and a measurement diary. They were instructed to measure their oxygen saturation level .Finally, four multivariable Cox proportional hazards models were created to examine associations between variables while controlling for the selected confounders, namely sex, age, and body mass index. Age and body mass index were treated as continuous variables to maximize the amount of information obtained. The level of statistical significance was set at a The patients’ (N = 225) baseline clinical data are presented in The hospital admission rate was 24.4%. On average, patients were hospitalized within 2.7 ± 2.9 days from the inclusion, with the hospital admission period ranging from 0 to 11 days. The majority of hospital admissions (90.9%) occurred within the first five days, and the latest was observed on the 11th day from inclusion. Importantly, no patients were lost to follow-up during the study period.9/L at inclusion, type-2 diabetes, dyslipidemia, and chronic kidney disease (In the univariate Cox regression analysis, six factors were significantly associated with a higher hazard of hospital admission: age ≥60 years, arterial hypertension, platelet count <150 × 10 disease .9/L at inclusion was also independently predictive of 14-day hospital admission.In the multivariable Cox regression analysis , four moIn contrast to previous research focusing on non-monitored individuals, this study specifically investigated the risk factors within the monitored population, thereby providing valuable insights directly applicable to the remote care model employed.Previous studies have already established the efficacy and acceptability of telemonitoring systems in supporting COVID-19 patients in primary care and hospital settings ,15,18,25The study findings revealed that most patients sought help toward the end of the first week after experiencing COVID-19 symptoms, which coincided with the pulmonary phase of the disease . ConsequThe study identified type-2 diabetes and thrombocytopenia as significant risk factors for hospital admission within a 14-day period. These findings align with previous research that has recognized type-2 diabetes as an independent predictor of hospital admission in COVID-19 patients ,22,24. CBased on the study findings, recommendations were made to modify the remote care model. These recommendations include implementing daily follow-up calls for the first five days and gradually reducing the frequency to every other day from days 6 to 10, a step allowing close monitoring during the critical early phase and adjusting the monitoring frequency as the risk of hospital admission decreases. Delegating follow-up calls to nursing staff can help address the shortage of primary care physicians and ensure effective patient management. Additionally, expanding the high-risk criteria to incorporate laboratory parameters such as thrombocyte count would enhance the accurate identification of high-risk patients.The telemonitoring model used in this study is scalable and suitable for primary care and clinical settings. It offers advantages such as low startup costs and compatibility with existing clinical pathways ,16,17, w2 measurements. Furthermore, the reliability of reported temperatures was influenced by patients using their own thermometers at home. However, since temperature was not a critical factor for hospital admission, we considered this limitation when developing our model. Finally, while the study focused on high-risk populations, telemonitoring programs have demonstrated positive cost-effectiveness outcomes even in low-risk populations, a finding suggesting potential benefits for a broader range of COVID-19 patients (The study limitations include its non-randomized design and lack of a control group. Predictors of hospital admission were only analyzed at baseline, and further laboratory testing could provide additional insights. The exclusion of patients unable to use a pulse oximeter may have affected the results, although family members were encouraged to assist with SpOpatients ,34,35.In conclusion, the greatest challenge for primary care physicians during the COVID-19 pandemic was to identify patients at high risk of COVID-19 deterioration and subsequent hospital admission. The implementation of a telemonitoring protocol in primary care centers proved feasible and facilitated the continuous care of patients while remotely identifying those in need of immediate hospitalization. As the pandemic subsides, there is a compelling need to extend the application of this model to manage other acute respiratory diseases and exacerbations of chronic diseases such as asthma, chronic obstructive pulmonary disease, or heart failure. By adapting and transferring the telemonitoring protocol to these diverse health care scenarios, we can enhance patient management and improve outcomes in a wide range of health care settings.


The in-hospital mortality rate was significantly lower in PCI-treated patients . One-year mortality and 1-year re-hospitalization for AHF/AMI were less frequent in PCI-treated patients . The adjusted risks of the study endpoints were lower in PCI-treated patients: OR 0.37 (95% CI 0.36–0.39) for in-hospital mortality; HR 0.37 (95% CI 0.36–0.38) for 1-year mortality; HR 0.74 (95% CI 0.71–0.77) for 1-year re-hospitalization for AHF/AMI. Similar results were found in STEMI and NSTEMI patients considered separately. Conclusions. Our real-world data showed that in patients with AMI ≥ 75 years of age, PCI use is associated with lower in-hospital and 1-year mortality.Background. Older patients are less likely to receive percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) compared to younger patients. We investigated the prognostic impact of PCI in a large population of patients hospitalized with AMI in the period 2003–2018 by using the administrative Lombardy Health Database . Methods. We considered all patients aged ≥75 years hospitalized with AMI (either STEMI or NSTEMI) from 2003 to 2018 in Lombardy. Patients were grouped according to whether they were treated or not with PCI during the index hospitalization. The primary outcome was in-hospital mortality. The secondary endpoints were 1-year mortality and 1-year re-hospitalization for acute heart failure (AHF) or AMI. Results. 116,063 patients aged ≥75 years  were hospitalized with a primary diagnosis of AMI. Thirty-seven percent of them ( The cornerstone of treatment of acute myocardial infarction (AMI) is percutaneous coronary intervention (PCI), as a primary revascularization strategy in patients with ST-segment elevation myocardial infarction (STEMI) and as an urgent invasive approach in those with non-ST-elevation myocardial infarction (NSTEMI) ,2. In boIn this study, we analyzed administrative data from Lombardy, the most populous Italian region with more than 10 million inhabitants, to evaluate the prognostic impact of PCI in patients aged ≥75 years hospitalized with AMI. Moreover, we investigated whether the rate of PCI use in elderly AMI patients has increased over the last 15 years and whether this was associated with improvements in overall hospital mortality, 1-year mortality, and 1-year re-hospitalization for acute heart failure (AHF) or AMI.The present study used linkable administrative health databases of the Lombardy region in Italy, which include a population registry with demographic data on all residents and detailed information on hospital records and drug prescriptions. Data are available for about 10 million registered inhabitants of Lombardy from 2000 to 2019. Access to data is allowed within the agreement between the Centro Cardiologico Monzino, I.R.C.C.S., Milan, Italy, and the Regional Health Ministry of Lombardy. Healthcare in Italy is publicly funded for all residents, irrespective of social class or employment, and everyone is assigned a personal identification number kept in the National Civil Registration System. All registered residents are assisted by general practitioners and are covered by the National Health System (NHS) with a high level of completeness regarding drug prescriptions, diagnosis, and length of observation. The pharmacy prescription database contains the medication name, anatomic therapeutic chemical classification code (ATC), and date of dispensation of drugs reimbursed by the NHS. The hospital database contains information on date of admission, discharge, death, primary diagnosis, and up to five co-existing clinical conditions and procedures performed. The diagnoses, uniformly coded according to the 9th International Code of Diseases (ICD-9-CM) and standardized for all Italian hospitals, are compiled by the hospital specialists directly in charge of the patients and validated by hospitals against detailed clinical-instrumental data as they determine reimbursement from the NHS. A unique identification code allows linkage of all databases. To ensure individual data protection, each identification code was automatically converted into an anonymous code before we received the dataset. In Italy, studies using retrospective anonymous data from administrative databases that do not involve direct access by investigators to identification data do not require Ethics Committee approval, notification, or patient informed consent.Patients with a hospitalization due to AMI (either STEMI or NSTEMI [ICD-9-CM codes 410.x]) from 1 January 2003 through 31 December 2018 were included in the analyses. Only hospitalizations in which an AMI-associated ICD-9 code was listed as a primary diagnosis were abstracted. When patients were transferred between hospitals, we evaluated the complete episode of care. Patients aged ≥75 years were grouped according to whether or not they underwent PCI during the index hospitalization. Patients undergoing urgent or elective coronary artery bypass grafting for the treatment of AMI were excluded from the study. Patients were then stratified into four groups according to the index hospitalization period: 2003–2006; 2007–2010; 2011–2014; and 2015–2018. Since medical data was recorded in the Lombardy registry in January 2000, past medical histories were available for all patients for at least 3 years before admission. Data collection was achieved by two trained reviewers.The primary endpoint of the study was in-hospital mortality. One-year all-cause mortality and 1-year re-hospitalization for AHF or AMI were considered secondary endpoints. Patients were followed up from the index admission date until death, migration, or the end of one-year follow-up.t-test. The differences between the patients stratified according to the four considered study periods were assessed by ANOVA and shown as a p for trend or Mantel-Haenszel χ2-test, as appropriate.Baseline characteristics were evaluated using descriptive statistics. Categorical variables were described using frequencies and percentages and compared using a Chi-square test; continuous variables were described using the mean and standard deviation (SD) and compared using a Student’s The association between in-hospital mortality and PCI was analyzed using a logistic model, and the results were reported as odds ratios (OR) and 95% confidence intervals (CI). The association between 1-year mortality and 1-year hospital readmission for AHF/AMI was investigated using either Cox regression or Cox regression to competing risk, as appropriate, and Kaplan-Meyer curves. The results were shown as the hazard ratio (HR) and 95% CI. The models were adjusted for all variables reported in the Table showing baseline characteristics of elderly patients treated or not treated with PCI and found to be significantly different between patients treated with and not treated with PCI. Medications taken before index hospitalization were considered for in-hospital mortality risk adjustment, while medications taken after hospital discharge were considered for 1-year endpoint risk adjustment.We also performed propensity score matching. The score was used to match the following two cohorts: older patients treated with and not treated with PCI. The two groups were matched in a 1:1 ratio using all variables included in the Table showing baseline characteristics of elderly patients treated or not treated with PCI.The preventable fraction of all endpoints associated with PCI was calculated as Pe × (1-OR [or HR]), where Pe is the prevalence of exposure and OR or HR is the risk for exposure relative to non-exposure.p-value less than 0.05 was required for statistical significance. All analyses were performed using SAS version 9.4 .All analyses were performed in the whole population, with STEMI and NSTEMI patients considered separately. A two-sided During the considered study period, 263,578 patients hospitalized with a primary diagnosis of AMI were identified. Of them, 116,063 (44%) patients were ≥75 years of age . The clinical characteristics of patients <75 years and ≥75 years are reported in p < 0.0001). Older AMI patients had significantly higher in-hospital  and 1-year  mortality, as well as a higher rate of 1-year hospitalization for AHF/AMI  than those <75 years of age.Patients ≥ 75 years were less likely to undergo PCI during index hospitalization as compared to younger ones  are shown in Patients treated with PCI were younger, more often STEMI patients, had fewer comorbidities, and experienced a less complicated in-hospital clinical course.The rates of the primary and secondary endpoints in the entire older population and in STEMI and NSTEMI patients considered separately were significantly lower in patients undergoing PCI as compared to those receiving medical therapy only .Similarly, PCI use was associated with a lower adjusted risk of all the considered endpoints .After propensity score matching, the study population included 79,222 older AMI patients . After matching, all variables were well balanced between the two groups. The risk of the primary and secondary endpoints was significantly lower in patients treated with PCI .The lower risk associated with PCI was maintained across the whole age spectrum in the entire AMI population , as wellThe Kaplan-Meyer curves for 1-year mortality and re-hospitalization for AHF/AMI in patients treated or not with PCI are shown in Among older patients not treated with PCI, 16,336 (22%) underwent diagnostic coronary angiography . Of themThe clinical characteristics of elderly patients stratified according to the four study periods are reported in This was true both for the overall older population and for STEMI and NSTEMI patients considered separately. In parallel with the progressive increase in PCI use over time, overall in-hospital and 1-year mortality, as well as 1-year re-hospitalization for AHF/AMI, significantly decreased from 2003 to 2018 .In the entire cohort of patients aged ≥75 years, the preventable fraction of in-hospital mortality associated with PCI  was 23% (26% in STEMI and 25% in NSTEMI patients). The preventable fractions of 1-year mortality and re-hospitalization for AHF/AMI associated with PCI were 26% (30% in STEMI and 25% in NSTEMI patients) and 12% (13% in STEMI and 10% in NSTEMI patients), respectively.Patients aged ≥ 75 years represent a large proportion of AMI hospitalizations, reaching 30% of those with STEMI and more than 40% of those with NSTEMI ,11,12. DIn our study, we found that patients aged ≥ 75 years represented about 40% of all patients hospitalized with AMI in Lombardy between 2003 and 2018, with an overall in-hospital mortality rate of 12%, a 4-fold higher rate than that of patients younger than 75 years. Notably, in our cohort, PCI was performed in only 37% of older adults, compared to 66% of younger patients. However, when older patients underwent PCI, regardless of AMI type (STEMI or NSTEMI), their in-hospital mortality was significantly lower than that of AMI patients not treated with PCI. In particular, the adjusted risk of in-hospital mortality was 60% lower in PCI-treated patients. The lower mortality risk associated with PCI was maintained across increasing age, even in the very old. A similar behavior was observed when 1-year mortality and 1-year re-hospitalization for AHF/AMI were considered, with 60% and 25% lower adjusted risks, respectively, in patients treated with PCI. Again, this was true for both STEMI and NSTEMI patients. Thus, our findings are in line with the increasing evidence on the clinical efficacy of PCI in elderly AMI patients in a large real-world setting and further support the current recommendations of the European Society of Cardiology guidelines for the management of AMI patients. Indeed, they state that advanced age should not be considered an element of exclusion from primary PCI in STEMI (1) and that the same interventional strategy should be applied to older patients as to younger patients with NSTEMI .To the best of our knowledge, ours is the largest study population focused on AMI patients older than 75 years, as almost all other studies included less than 3000–4000 patients ,19,20,22In the present study, we also evaluated whether PCI use changed over the considered time frame of 15 years and whether this was associated with a change in hospital and 1-year outcomes. Although the mortality risk difference associated with PCI in our cohort of older AMI patients remained unchanged over time, in-hospital mortality and 1-year outcomes progressively decreased across years. As PCI use increased from 22% during 2003–2006 to almost 50% during 2015–2018, it can be speculated that increased PCI use contributed, at least in part, to the gradual reduction in overall AMI mortality over the study period. Of note, this trend was also true when STEMI and NSTEMI patients were considered separately.Although there are several aspects that remain to be investigated in our study, including PCI-related complications, our data strongly support the European Society of Cardiology guidelines ,2 that aTherefore, future studies should not focus on defining an age limit beyond which PCI would not be indicated but, rather, on determining for which older patients PCI should be considered a futile treatment. Moreover, in this study, among patients not treated with PCI, those undergoing diagnostic coronary angiography experienced lower in-hospital and 1-year mortality than those not undergoing coronary angiography. This suggests that coronary angiography during AMI hospitalization, regardless of PCI use, is a useful prognostic stratification tool in older patients, allowing for the identification of the more appropriate therapeutic strategy .Administrative databases are a reliable tool to describe the outcomes of large cohorts representing the real clinical care setting since they collect data over time in a standardized fashion and, by the way, at a low cost. However, limitations that are typical of all the studies based on administrative datasets need to be acknowledged. Administrative data can suffer from systematic biases as their quality depends on the accuracy of coding. In particular, analyses relied on accurate coding of AMI and other conditions of interest, and biases may have resulted from underreporting or changes in diagnosis or coding patterns over time. Yet, it should be highlighted that the endpoints considered in the present study, in particular in-hospital and 1-year mortality, are less likely to be affected by coding errors. Second, some specific pieces of information on clinical variables or laboratory tests closely associated with AMI prognosis, in particular left ventricular ejection fraction, renal function, extent of coronary artery disease, completeness of myocardial revascularization, and late presentation in STEMI patients, were not available ,24. SimiIn conclusion, the present study based on large real-world data showed that in patients ≥ 75 years of age hospitalized with AMI, PCI use is associated with significantly lower in-hospital and 1-year mortality, as well as a reduction in 1-year re-hospitalization for AHF/AMI, compared to conservative treatment. The progressive increase in PCI use over the years may partially account for the improved outcome across years in older AMI patients.


ObjectiveOpioid use disorder (OUD) continues to be a leading cause of maternal death in the United States. The impact of OUD on pregnancy has dramatically grown in recent years, with OUD-related maternal deaths between 2007 and 2016 nearly doubling. However, the characteristics of pregnancy-associated-not-related (PANR) deaths from opioid overdose are not well understood. Specifically, the timing of OUD-related maternal deaths relative to the partum periods has not been fully described. In this study, we aimed to better characterize high-risk time periods for people with OUD, with the goal of elucidating factors that may contribute to opioid-related PANR deaths.MethodsIn this retrospective cohort study, we analyzed the Michigan Department of Health and Human Services Maternal Mortality Surveillance Program database from 2007 to 2015 to investigate the temporal trends in opioid-related PANR deaths.ResultsThere was an over fourfold increase in opioid-related PANR from 2007 to 2015 and a maternal mortality ratio of 23.0 per 100,000 births attributable to opioid-related PANR deaths. Ante- and postpartum opioid-related PANR deaths shared similar demographic distribution, were associated with polysubstance use, and had low rates of medication-assisted treatment (MAT). Most opioid-related PANR deaths occurred at a steady rate during the postpartum period. Only 3.6% of people who died in the postpartum period were uninsured, compared to 42.1% of people who died in the antepartum period.ConclusionThough ante and postpartum deaths share many characteristics, our study revealed key distinctions that can help better inform the care of pregnant patients with OUD. Opioid use disorder (OUD) continues to be a major concern in pregnancy and is increasingly seen during delivery hospitalization . People Understanding the characteristics and timing  of maternal death in cases of OUD may help inform health interventions and resource allocation to reduce maternal mortality . PreviouThe objectives of our study were to characterize high-risk time periods of opioid-related PANR deaths. Using the Michigan Department of Health and Human Services Maternal Mortality Surveillance Program database from 2007 to 2015, we compared the characteristics of opioid-related PANR deaths in antepartum and postpartum periods. By investigating the temporal trends of opioid-related PANR, we aim to further inform programs for the treatment and prevention of maternal mortality due to OUD.We conducted a retrospective cohort study of all PANR deaths using the Michigan Department of Health and Human Services Maternal Mortality Surveillance Program database from 2007-2015. This program was established to improve the quality of maternal death data in Michigan and to bring awareness to the importance of preventing death among women during or within one year of pregnancy. The state mandates reporting of all records associated with maternal death, and subsequently, a multidisciplinary team reviewed the process to determine causes of death and to make policy recommendations to prevent future deaths. This study was considered exempt from full review by the Institutional Review Board .We identified all PANR deaths within the database, which were defined as death occurring during pregnancy or within one year of the end of pregnancy, but not related to pregnancy. Inclusion criteria for the study are all PANR deaths in the state of Michigan from 2007 to 2015, deemed by the surveillance program to be related to OUD. The available records of each case of death, including prenatal and delivery records, birth certificates, death certificates, and police reports, were systematically reviewed. We collected information on the year of death, region of death, manner of death, patient demographics, delivery outcomes, comorbidities, and urine and post-mortem toxicology studies. Descriptive statistics were used to characterize baseline demographic data and temporal trends for opioid-related PANR deaths. Univariate analyses were performed to compare each variable characteristic of antepartum vs. postpartum opioid-related PANR deaths, with the Mann-Whitney U test for continuous variables and the Chi-squared test for categorical variables. A multivariable logistic regression model was built using maternal age, race/ethnicity, insurance status, and exposure to medication-assisted treatment (MAT) to determine which baseline characteristics were most correlated to opioid-related PANR deaths in the antepartum vs. postpartum period (postpartum period was used as the reference group). Differences in the timing of death between individuals with and without MAT was assessed by Kaplan-Meir curves and the log-rank test.From January 2007 to December 2015, 424 PANR deaths were identified in the state of Michigan. A total of 102/424 (24.1%) PANR deaths were related to OUD, of which 19/102 (19.6%) occurred during the antepartum period, and 83/102 (81.4%) occurred during the postpartum period. During the study period, the overall opioid-related PANR and non-opioid-related PANR mortality ratios were 9.7 and 30.8 deaths per 100,000 live births, respectively. There was a steady increase in opioid-related PANR deaths throughout the study years, with the maternal mortality ratio peaking at 23.0 per 100,000 live births in 2015  deaths were determined to be accidental deaths, 2/102 (2.0%) were suicides, and 23/102 (22.5%) were indeterminate. There was no difference in the distribution of manner of death between antepartum and postpartum deaths (p=0.514). An autopsy was performed in 100/102 (98.0%) of deaths, and toxicology was performed in 98/102 96.0%) of the cases. Benzodiazepine was found in 53/98 (54.0%) of autopsy toxicology studies, followed by cocaine in 23/98 (23.5%) studies. A comparison of non-opioid drugs detected from autopsy toxicology in antepartum opioid-related PANR deaths relative to postpartum opioid-related PANR deaths is shown in Figure .0% of thIn terms of geographic area, most opioid-related PANR deaths occurred in region 10, which includes the three most populous counties in Michigan. The proportion of opioid-related PANR deaths in region 10 was higher than the proportion of live births in this region . Our study showed a steady increase in opioid-related PANR deaths in the state of Michigan from 2007-2015, with an over four-fold increase over the study period. At the end of the study period, there was a maternal mortality ratio of 23.0 per 100,000 births attributable to opioid-related PANR deaths. This finding echoes previous studies that demonstrate increasing opioid-related PANR deaths in the United States over this time period . Ante- and postpartum opioid-related PANR deaths shared largely similar demographic distribution. We also see a low rate of MAT in both time frame of deaths, similar to previous reports ,6. This Most antepartum and postpartum opioid-related PANR deaths were associated with polysubstance use. These results reflect previous research, which suggests that most people with OUD use one or more additional substances. The most commonly found substance on toxicology was benzodiazepine, which dramatically increases overdose risk when combined with opiates Figure . Thus, tThe majority of opioid-related PANR deaths in this study occurred during the postpartum period, adding to an extensive body of literature that suggests that increased intervention for OUD is needed during this time period ,6,8. WhiAs opposed to in the postpartum period, 42.1% of antepartum opioid-related PANR deaths occurred in uninsured patients. The association between insurance status and antepartum death remained even after controlling for race/ethnicity, maternal age, and exposure to MAT. Furthermore, all the antepartum deaths occurred among people who did not have prenatal care. Although causation cannot be assumed, this relationship may indicate that obstetric-specific care could reduce opioid-related PANR deaths during ante- and postpartum periods. Unfortunately, previous studies have shown a low rate of postpartum care, even among people with pregnancy complications -16. WhilClassically, the opioid epidemic has mostly been attributed to White, middle-class, suburban, and rural communities ,18. WhilOur study is subject to several limitations. Because our data is limited to mortality data, we are unable to measure the impact of MAT in reducing opioid-associated PANR deaths. Additionally, despite the Michigan mandate to report OUD-related PANR deaths, it is possible that some healthcare encounters were not reported. Finally, repeating this study with a multi-state data set could illuminate additional trends by increasing sample size, especially in the antepartum period. In conclusion, ante- and postpartum opioid-related PANR deaths share demographic similarities, as well as associations with polysubstance use and low rates of MAT. However, key differences remain. Notably, a large proportion of antepartum opioid-related PANR deaths occur in uninsured patients. Additionally, the majority of opioid-related PANR happen at a steady rate during the postpartum period. These trends may help to tailor comprehensive programs for people with OUD during the pregnancy and postpartum periods globally.Our study supports the following: 1) access to initiate prenatal care is essential in the antepartum period, 2) along with improvement in access to insurance during the postpartum period, efforts to increase visits and healthcare interface needs to be performed, 3) MAT needs to be made accessible throughout pregnancy periods, and 4) while traditionally seen as majority White issue, equitable programs including campaign and effort in marginalized communities is of utmost importance.


Multiple prolonged symptoms are observed in patients who recover from acute coronavirus disease 2019 (COVID-19), defined as long COVID. Cough and sputum are presented by patients with long COVID during the acute and post-acute phases. This study aimed to identify specific risk factors for cough and sputum in patients with long COVID.Hospitalized patients with COVID-19 aged 18 years were enrolled in a multicenter cohort study at 26 medical institutions. Clinical data during hospitalization and patient-reported outcomes after discharge were collected from medical records, paper-based questionnaires, and smartphone apps.At the 3-, 6-, and 12-month follow-ups, there were no differences in the incidence rates of wet and dry coughs. In contrast, the proportion of patients presenting sputum without coughing increased over time compared to those with sputum and coughing. Univariate analyses of cough and sputum at all follow-up visits identified intermittent mandatory ventilation (IMV), smoking, and older age as risk factors for prolonged symptoms. At the 12-month follow-up, persistent cough and sputum were associated with the characteristics of severe COVID-19 based on imaging findings, renal and liver dysfunction, pulmonary thromboembolism, and higher serum levels of LDH, KL-6, and HbA1C. The Kaplan–Meier curves showed that the severity of acute COVID-19 infection was correlated with prolonged cough and sputum production. Multivariable logistic regression analysis showed that IMV ventilator management were independent risk factors for prolonged cough and sputum at 12 months.In a Japanese population with long COVID, prolonged cough and sputum production were closely associated with severe COVID-19. These findings emphasize that a preventive approach including appropriate vaccination and contact precaution and further development of therapeutic drugs for COVID-19 are highly recommended for patients with risk factors for severe infection to avoid persistent respiratory symptoms.The online version contains supplementary material available at 10.1186/s12931-023-02591-3. Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has spread worldwide since its outbreak in China in December 2019 . In mostCough is a protective response against the elimination of inhaled foreign substances and airway secretions . PatientWe conducted a longitudinal questionnaire survey on symptoms in COVID-19-infected patients over a 12-month period. We aimed to identify the specific risk factors for persistent cough and sputum in long COVID. This analysis focused on time-specific or temporal changes in these symptoms to provide a comprehensive evaluation.Previous studies have reported that female sex, respiratory illness comorbidities, and severity of COVID-19 infection are risk factors for post-COVID-19 cough . HoweverThe detailed protocol for this project has been reported previously . BrieflyThe severity of COVID-19 during hospitalization was classified according to the guidelines of the Ministry of Health, Labor, and Welfare in Japan  as follows: mild, peripheral oxygen saturation (SpO2) ≥ 96%, with no respiratory symptoms or coughing only, no shortness of breath; moderate I (patient does not suffer respiratory failure), 93% < SpO2 < 96%, with shortness of breath and pneumonia findings; moderate II (patient suffers respiratory failure), SpO2 ≤ 93% and oxygen administration is required; severe, requiring admission to the intensive care unit (ICU) or mechanical ventilation.Invitations to participate in the research were mailed to all inpatients within a certain period at each facility, and those who provided consent were asked to complete a questionnaire on paper or via a smartphone application at 3, 6, and 12 months after diagnosis.The following symptoms were identified after COVID-19 diagnosis: fever, cough, sputum, breathlessness (dyspnea), sore throat, taste impairment, smell impairment, abdominal pain, and diarrhea. Other symptoms that were not present among the 24 representative symptoms described above could be filled in with an optional comment on the questionnaire. During hospitalization, patients were asked about the presence of each symptom at 3, 6, and 12 months after diagnosis.Patients completed a paper-based questionnaire (paper patient-reported outcome [pPRO]) or a smartphone application-based questionnaire (electronic patient-reported outcome [ePRO]). Medical information covering 168 clinical survey items during medical treatment at each facility was collected over the Internet using an electronic data capture (EDC) system.Figure t-test and the chi-square test for group comparisons. Multivariable logistic regression was used to determine the independent predictors of persistent symptoms 12 months after recovery. Age and sex were entered into the multivariable logistic regression analysis, in addition to those that were significantly different in the univariate logistic regression analysis. All variables were included in the model. The log-rank test for trend and log-rank test were used to compare persistent symptoms according to COVID-19 severity. All analyses were performed with SPSS v.26 . A P value (two-tailed) of < 0.05 was considered statistically significant.Data are presented as mean and standard deviation (SD) or median (interquartile range (IQR)) for continuous variables and as number and percentage for categorical variables. We used the Student’s .The prevalence of cough and sputum decreased significantly from the acute phase to the 3-month follow-up, with only slight decreases at the 6- and 12-month follow-ups   and 12-month  follow-up time points.Patients who received ventilator management during hospitalization were defined as having severe acute COVID-19. Thus, we analyzed the relationship between prolonged cough and follow-up periods using classification of severity in acute COVID-19 infection: moderate II and severe COVID-19 patients who required oxygen therapy more frequently presented cough at the 12-month follow-up than non-severe patients who did not require oxygen therapy (Fig. This study was a longitudinal evaluation of cough and sputum production during the first 12 months after acute COVID-19 infection. To our knowledge, this is the first detailed report of sputum in patients with long-term COVID. Although the frequency of dry and productive cough was similar, the number of patients with sputum not accompanied by cough increased at 6 and 12 months after acute COVID-19 infection. This study identified the relationship between cough and sputum in long COVID and risk factors for severe infection. Among these, ventilator management was especially correlated with cough and sputum production during prolonged COVID. Furthermore, the severity of COVID-19 tended to be related to prolonged coughing and sputum formation during follow-up.In severe cases of COVID-19, pneumonia progression causes respiratory failure due to tissue damage . Airway In this study, cough was correlated with the severity and risk factors of severe COVID-19, especially at the 12-month follow-up. Cough is frequently observed as a respiratory symptom in both upper respiratory infections and pneumonia . Post-inSeveral previous reports have documented the prevalence of cough over time; Arnold et al. reported that 60–70% of patients complained of cough at admission, which decreased to approximately 10% at 12 weeks after admission due to COVID-19 infection . Carfi eIn this study, the prolonged symptoms of inpatients with acute COVID-19 infection were analyzed to evaluate long-term COVID, and the rate of patients with prolonged sputum was higher than that observed in previous studies that mainly relied on outpatient information . The higDry cough is common in viral pneumonia, suggesting that specific risk factors may be necessary for persistent sputum formation after viral pneumonia with regard to sputum . BronchiThis study had several limitations. First, not all enrolled patients answered all symptom questionnaires at the 3-, 6-, and 12-month follow-ups. Therefore, the overall population differed according to the analysis. Second, pulmonary function tests, or imaging studies, and the 6-minute walk test were not performed after acute COVID-19 infection. Therefore, the causal relationship after cough-, sputum-, and pneumonia-induced tissue damage remains unknown. Third, the degree of symptoms was not quantified, which may have rendered the evaluation of causal relationships inadequate.This study clarified the frequency and characteristics of coughing and sputum in long COVID. Importantly, both symptoms were highly associated with the severity and risk factors of severe COVID-19. Therefore, it is necessary to recognize that severe infections can cause sequelae of cough and sputum in clinical settings. In addition, these findings emphasize that a preventive approach including appropriate vaccination and contact precaution and further development of therapeutic drugs for COVID-19 should be highly recommended for patients with risk factors for severe infection. Long-term persistent cough and sputum are burdens on patients after recovery from acute COVID-19. Further investigations are needed to elucidate the underlying mechanisms and develop specific therapeutic drugs for these persistent symptoms in patients with long COVID.Below is the link to the electronic supplementary material.Supplementary Material 1


European Society for Blood and Marrow Transplantation (EBMT) hematologic response categories comprehensively assess complement inhibitor responses in patients with paroxysmal nocturnal hemoglobinuria (PNH). Using data from the 16-week randomized controlled period of the phase 3 PEGASUS trial (N = 80), we estimated the treatment cost per responder by the EBMT response category for pegcetacoplan and eculizumab in adults with PNH and a suboptimal response to eculizumab. Average drug costs per responder, number needed to treat, and incremental drug costs per responder were estimated using dosages administered during the trial (base case). A US payer perspective (2020 US dollars) was used. Scenario analyses were conducted for various costs, dosages, treatment durations, patient populations, and settings. In total, 30 of 41 (73%) who switched to pegcetacoplan and 2 of 39 (5%) patients who continued eculizumab had a good, major, or complete response (good-to-complete responders) at Week 16. Average weekly drug costs per good-to-complete responder were USD 15,923 with pegcetacoplan and USD 216,100 with eculizumab; average weekly drug costs per patient were USD 11,651 and USD 11,082, respectively. Average drug costs per good-to-complete responder with pegcetacoplan were similar across complement inhibitor-naïve populations and were consistently lower than with eculizumab. Switching from eculizumab to pegcetacoplan allowed more patients with a suboptimal response to attain a good-to-complete response at lower costs. These results apply to patients with a suboptimal response to prior eculizumab treatment only. Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, chronic disease that results in complement-mediated intravascular and extravascular hemolysis, leading to fatigue, hemolytic anemia, thrombosis, and peripheral blood cytopenias . PatientTreatment options have increased further, with three complement inhibitors approved in the United States for PNH treatment: eculizumab, ravulizumab (Ultomiris), and pegcetacoplan (Empaveli) . EculizuWith several PNH therapies available, clinicians and formulary decision-makers may need to weigh the costs and clinical outcomes of each therapy to quantify their relative value. Therapeutic decisions for patients with PNH may benefit from a careful economic evaluation because of the high expense of treating PNH with complement inhibitors, which approaches USD 500,000 per patient each year ,13.Without complement inhibitor therapy, patients with PNH experience pronounced symptoms of intravascular hemolysis as PNH red blood cells, which lack regulatory proteins needed to prevent attack by the terminal complement pathway, are destroyed intravascularly ,14. WhenThe C3 inhibitor pegcetacoplan is the first PNH treatment aimed at an upstream complement pathway target ,10,18. IThe 2021 FDA approval of pegcetacoplan for adults with PNH was primarily based on data from the PEGASUS trial (NCT03500549) . ResponsAlthough these end points were sufficient for short-term clinical trials, a composite of multiple outcomes could provide a comprehensive response assessment for use in clinical practice . To addrRisitano, who authored the original EBMT classification criteria , appliedLeveraging the analysis by Risitano and colleagues provides a unique opportunity to analyze the costs of switching from eculizumab to pegcetacoplan for patients with a limited response to eculizumab. The objective of the current analysis was to determine the average and incremental costs per responder for patients with PNH who had a prior incomplete response to eculizumab and switched to pegcetacoplan compared to those of patients who continued receiving eculizumab despite their incomplete responses. We undertook several scenario analyses, including costs-per-responder analyses of C5 inhibitor-naïve patients who received pegcetacoplan in other clinical trials and C5 inhibitor-naïve patients who received eculizumab in a real-world setting, to compare the findings to other populations.Costs per responder were assessed for pegcetacoplan and eculizumab using data from post hoc EBMT response categorization analyses of the PEGASUS ,22, PADDPEGASUS trial details have been published previously ,20. The During the 4-week run-in period, all patients received self-administered SC pegcetacoplan 1080 mg twice weekly while continuing their current IV eculizumab dosages to maintain sufficient complement inhibition while pegcetacoplan was introduced . After tcomplete response , major response , good response , partial response , minor response , and no response  . To. To26]. The following primary outcomes were calculated for pegcetacoplan and eculizumab: average drug costs per patient over 16 weeks, average drug costs per patient per week, average drug costs per responder , and percentage of total drug costs spent on patients with partial-to-no response or those with discontinued/missing status.The average drug costs by response category were calculated as mean drug costs per treated patient over 16 weeks divided by the percentage of patients with the stated EBMT response category. The incremental costs per incremental responder at 16 weeks for a given response level were calculated as follows: The number needed to treat (NNT) to achieve each level of response (compared with no treatment) was calculated at 16 weeks as the reciprocal of the percentage of patients with a given response for a given treatment.An initial scenario analysis was conducted, excluding administration costs, to compare the average costs per response from a pharmacy cost perspective. A second scenario was conducted using the label dosages for pegcetacoplan and eculizumab, without accounting for increased dosage, to provide a conservative estimate that does not account for real-world treatment variations.Calculation of the average drug costs per responder at Week 48 for patients with a suboptimal response to prior eculizumab treatment with the use of categorized response data for those treated with pegcetacoplan from both the randomized controlled period (Weeks 0–16) and the open-label period (Weeks 16–48) of the PEGASUS trial ,22 Supp.Calculation of the average drug costs per responder at Weeks 16 and 48 for C5 inhibitor-naïve patients  who initiated pegcetacoplan treatment with the use of nonrandomized, categorized response data from the phase 1b PADDOCK and the phase 2a PALOMINO trials  Supplem.Calculation of the average drug costs per responder at Week 26 for C5 inhibitor-naïve  patients initiating pegcetacoplan treatment with the use of nonrandomized, categorized response data from the phase 3 PRINCE trial  Supplem.Calculation of the average drug costs per responder at Months 6 and 12 with the use of categorized, real-world response data from C5 inhibitor-naïve patients initiating eculizumab treatment  Supplem.Additional scenario analyses were performed using all available data from recent PNH clinical trial response categorization studies (as of July 2022) ,22,23,24Baseline characteristics were generally balanced between the pegcetacoplan (N = 41) and eculizumab (N = 39) arms of PEGASUS . Over thTotal costs for patients with partial-to-no responses during 16 weeks of treatment were USD 2.0 million for pegcetacoplan and USD 6.5 million for eculizumab . In the Across all drug cost scenarios with and without administration costs and by dosage, the average costs per responder remained lower for pegcetacoplan than for eculizumab for good-to-complete responders and for partial-to-no responders over label and trial dosages and when excluding administration costs .The results of additional scenario analyses for patients with good-to-complete response and partial-to-no response in alternative PNH populations and with additional treatment durations using all available data from recent categorization studies of PNH response are shown in For C5 inhibitor-naïve patients treated with pegcetacoplan, the average drug costs per good-to-complete responder were lower in both the PADDOCK/PALOMINO trials and the PRINCE trial compared with the base case population from PEGASUS at all time points  21,22,2,222,23. For a real-world cohort of C5 inhibitor-naïve patients treated with eculizumab, the average drug costs per good-to-complete responder were lower  than that for the base case, eculizumab-treated population from PEGASUS ; at Weeks 16, 26, and 48 for C5 inhibitor-naïve patients initiating pegcetacoplan treatment in clinical trials; and at 6 months and 1 year for a real-world cohort of C5 inhibitor-naïve patients initiating eculizumab treatment. Average drug costs per good-to-complete response per week for pegcetacoplan were similar across all patient populations and treatment durations, except the base case, in which the average costs were higher. Higher costs in the base case population were expected because these patients had prior suboptimal responses to eculizumab.The scenario results for eculizumab based on real-world data show a higher rate of response to eculizumab than the rate of response observed in the PEGASUS trial data. These results were expected, as the real-world data are from C5 inhibitor-naïve patients initiating eculizumab treatment rather than from patients with a suboptimal response to eculizumab. Despite C5 inhibitor-naïve patients from a real-world cohort having a markedly higher eculizumab response rate and substantially lower drug costs per responder than patients from PEGASUS, the average drug costs per responder, percentage of total costs spent on patients with partial-to-no response, and NNT remained higher for eculizumab-treated patients than for any pegcetacoplan-treated population. The eculizumab response in the real-world data may be a best-case scenario for eculizumab, as the 30% to 61% of patients who discontinued eculizumab in the first 18 months of treatment were excluded ,33. ThesThis analysis has several limitations. First, it did not include the C5 inhibitor ravulizumab due to a lack of head-to-head data for all available complement inhibitor treatments. To our knowledge, there are no published analyses categorizing patients treated with ravulizumab based on EBMT hematologic response. Second, the populations studied were small because PNH is a rare disease, with an estimated 5000–6000 prevalent cases in the US . Third, The strengths of this analysis include the use of all available EBMT response categorization studies (as of July 2022) in the scenario analyses. These analyses showed similar average drug costs per response for pegcetacoplan across study populations with different treatment histories and baseline disease severities. Although the scenario analyses are based on uncontrolled  trial data for pegcetacoplan, the results suggest that our estimated average drug costs and average drug costs per response for pegcetacoplan are robust, at least for the first year of treatment. By using the EBMT consensus classifications to assess clinical response with a composite set of PNH-relevant measures, these results may inform payers of cost-efficient choices. Payers, physicians, and patients have become more interested in treatment costs and cost-effectiveness, particularly for chronic conditions such as PNH.This analysis of PEGASUS data showed that switching from eculizumab to pegcetacoplan is a cost-effective approach to improve responses in patients with PNH who have had a suboptimal response to eculizumab. Treatment of PNH with pegcetacoplan, a C3-targeted therapy, allowed more patients to have an EBMT-defined, good-to-complete response, and drug costs per patient achieving a good-to-complete response were substantially lower for those treated with pegcetacoplan. These results are applicable to patients with a suboptimal response to prior eculizumab treatment only. Scenario analysis results suggest avenues for future research.