Risk Indicators of Sarcoidosis Evolution-Unified Protocol (RISE-UP): protocol for a multi-centre, longitudinal, observational study to identify clinical features that are predictive of sarcoidosis progression

Introduction
Sarcoidosis is a pulmonary and systemic granulomatous disease with a wide range of potential outcomes, from spontaneous resolution to end-stage organ damage and death. Currently, clinicians have no easy-to-use risk stratification tools for important clinical outcomes in sarcoidosis, such as progressive lung disease. This study will address two clinical practice needs: (1) development of a risk calculator that provides an estimate of the likelihood of pulmonary progression in sarcoidosis patients during the follow-up period and (2) determine the optimal interval for serial clinical monitoring (eg, 6, 12, 18 months) using these risk prediction tools.

Methods and analysis
The Risk Indicators of Sarcoidosis Evolution-Unified Protocol study is a National Institutes of Health-sponsored, longitudinal observational study of adults with pulmonary sarcoidosis who will be enrolled at five US tertiary care centres. Participants will be evaluated at approximately 6-month intervals for up to 60 months with collection of lung function, blood samples and clinical data. The target sample size is 557 and the primary objective is to determine which clinical features measured during a routine clinic visit carry the most prognostic information for predicting clinical progression of pulmonary sarcoidosis over the follow-up period. The primary outcome measure will be quantified by a clinically meaningful change in forced vital capacity, forced expiratory volume in 1 s or diffusing capacity of the lung for carbon monoxide. The secondary objective is to determine if blood biomarkers measured during a routine clinic visit can improve the risk assessment modelling for progression of pulmonary sarcoidosis over the follow-up period.

Ethics and dissemination
The study protocol has been approved by the Institutional Review Boards at each centre and the reliance Institutional Review Board overseeing the study (WCG, Protocol #20222400). Participants will provide informed consent prior to enrolment. Results will be disseminated via publication in a relevant peer-reviewed journal.

Trial registration number
NCT05567133.

Leggi
Aprile 2023

Loss to 5-year follow-up in the population-based Telemark Study: risk factors and potential for bias

Objectives
This study aimed to characterise participants lost to follow-up and identify possible factors associated with non-participation in a prospective population-based study of respiratory health in Norway. We also aimed to analyse the impact of potentially biased risk estimates associated with a high proportion of non-responders.

Design
Prospective 5-year follow-up study.

Setting
Randomly selected inhabitants from the general population of Telemark County in south-eastern Norway were invited to fill in a postal questionnaire in 2013. Responders in 2013 were followed-up in 2018.

Participants
16 099 participants aged 16–50 years completed the baseline study. 7958 responded at the 5-year follow-up, while 7723 did not.

Main outcome measures
2 test was performed to compare demographic and respiratory health-related characteristics between those who participated in 2018 and those who were lost to follow-up. Adjusted multivariable logistic regression models were used to assess the relationship between loss to follow-up, background variables, respiratory symptoms, occupational exposure and interactions, and to analyse whether loss to follow-up leads to biased risk estimates.

Results
7723 (49%) participants were lost to follow-up. Loss to follow-up was significantly higher for male participants, those in the youngest age group (16–30 years), those in lowest education level category and among current smokers (all p

Leggi
Marzo 2023

Women and health professionals perspectives on a conditional cash transfer programme to improve pregnancy follow-up: a qualitative analysis of the NAITRE randomised controlled study

Objectives
Women of low socioeconomic status have been described as having suboptimal prenatal care, which in turn has been associated with poor pregnancy outcomes. Many types of conditional cash transfer (CCT) programmes have been developed, including programmes to improve prenatal care or smoking cessation during pregnancy, and their effects demonstrated. However, ethical critiques have included paternalism and lack of informed choice. Our objective was to determine if women and healthcare professionals (HPs) shared these concerns.

Design
Prospective qualitative research.

Setting
We included economically disadvantaged women, as defined by health insurance data, who participated in the French NAITRE randomised trial assessing a CCT programme during prenatal follow-up to improve pregnancy outcomes. The HP worked in some maternities participating in this trial.

Participants
26 women, 14 who received CCT and 12 who did not, mostly unemployed (20/26), and – 7 HPs.

Interventions
We conducted a multicentre cross-sectional qualitative study among women and HPs who participated in the NAITRE Study to assess their views on CCT. The women were interviewed after childbirth.

Results
Women did not perceive CCT negatively. They did not mention feeling stigmatised. They described CCT as a significant source of aid for women with limited financial resources. HP described the CCT in less positive terms, for example, expressing concern about discussing cash transfer at their first medical consultation with women. Though they emphasised ethical concerns about the basis of the trial, they recognised the importance of evaluating CCT.

Conclusions
In France, a high-income country where prenatal follow-up is free, HPs were concerned that the CCT programme would change their relationship with patients and wondered if it was the best use of funding. However, women who received a cash incentive said they did not feel stigmatised and indicated that these payments helped them prepare for their baby’s birth.

Trial registration number
NCT02402855

Leggi
Marzo 2023

Extended Follow-up of Microbiome Therapeutic SER-109 for Recurrent Clostridioides difficile Infection—Reply

In Reply Dr Hamilton and colleagues question why taper/pulse regimens of vancomycin were not used in the ECOSPOR III trial for patients with recurrent C difficile infection. Vancomycin has excellent bactericidal activity against C difficile bacteria with no detectable toxin concentrations by day 4, but has no activity against C difficile spores, which germinate in a disrupted microbiome, leading to C difficile infection. The rationale for taper/pulse regimens is to allow microbiome diversification with decreasing antibiotic exposure.

Leggi
Marzo 2023

Extended Follow-up of Microbiome Therapeutic SER-109 for Recurrent Clostridioides difficile Infection

To the Editor The ECOSPOR III trial compared an investigational microbiome therapy (SER-109) with placebo for the treatment of recurrent Clostridioides difficile infection, with results on recurrence through 24 weeks published recently in JAMA. Although it is encouraging to see a new agent for treatment of recurrent C difficile infection, we have some questions about this study. First, the inclusion criteria mandated more than 3 episodes of C difficile infection within the last year, the most recent of which could be treated with a maximum of 10 to 21 days of therapy with either vancomycin or fidaxomicin. Yet the 2017 and 2021 Infectious Diseases Society of America (IDSA) guidelines suggested that when vancomycin is used to treat such patients, it should be tapered and/or pulsed or followed with additional therapy (eg, rifaximin). Therefore, for the 73% of participants who received vancomycin, the length of therapy may have been inappropriately short, which may have contributed to the 47.3% treatment failure and recurrence rate observed.

Leggi
Marzo 2023

Thirty-year follow-up of the NICHD Study of Early Child Care and Youth Development (SECCYD): the challenges and triumphs of conducting in-person research at a distance

Purpose
The purpose of the current study, The National Institute of Child Health and Human Development (NICHD) Study of Health in Early and Adult Life (SHINE), was to build on the landmark Study of Early Child Care and Youth Development (SECCYD), a longitudinal birth cohort initiated in 1991, by conducting a health-focused follow-up of the now adult participants. This effort has produced an invaluable resource for the pursuit of life course research examining links between early life risk and resilience factors and adulthood health and disease risk.

Participants
Of the 927 NICHD SECCYD participants available for recruitment in the current study, 705 (76.1%) participated in the study. Participants were between 26 and 31 years and living in diverse geographic locations throughout the USA.

Findings to date
In descriptive analyses, the sample exhibited risk on health status indicators, especially related to obesity, hypertension and diabetes. Of particular concern, the prevalence of hypertension (29.4%) and diabetes (25.8%) exceeded national estimates in similar-age individuals. Health behaviour indicators generally tracked with the parameters of poor health status, showing a pattern of poor diet, low activity and disrupted sleep. The juxtaposition of the sample’s relatively young age (mean=28.6 years) and high educational status (55.6% college educated or greater) with its poor health status is noteworthy, suggesting a dissociation between health and factors that are typically health protective. This is consistent with observed population health trends, which show a worsening of cardiometabolic health status in younger generations of Americans.

Future plans
The current study, SHINE, lays the groundwork for future analyses in which the uniquely robust measures collected as a part of the original NICHD SECCYD will be leveraged to pinpoint specific early life risk and resilience factors as well as the correlates and potential mechanisms accounting for variability in health and disease risk indicators in young adulthood.

Leggi
Marzo 2023

School readiness of children at high risk of cerebral palsy randomised to early neuroprotection and neurorehabilitation: protocol for a follow-up study of participants from four randomised clinical trials

Introduction
School readiness includes cognitive, socio-emotional, language and physical growth and development domains which share strong associations with life-course opportunities. Children with cerebral palsy (CP) are at increased risk of poor school readiness compared with their typically developing peers. Recently, earlier diagnosis of CP has allowed interventions to commence sooner, harnessing neuroplasticity. First, we hypothesise that early referral to intervention for children at-risk of CP will lead to improved school readiness at 4–6 years relative to placebo or care as usual. Second, we hypothesise that receipt of early diagnosis and early intervention will lead to cost-savings in the form of reduced healthcare utilisation.

Methods and analysis
Infants identified as at-risk of CP ≤6 months corrected age (n=425) recruited to four randomised trials of neuroprotectants (n=1), early neurorehabilitation (n=2) or early parenting support (n=1) will be re-recruited to one overarching follow-up study at age 4–6 years 3 months. A comprehensive battery of standardised assessments and questionnaires will be administered to assess all domains of school readiness and associated risk factors. Participants will be compared with a historical control group of children (n=245) who were diagnosed with CP in their second year of life. Mixed-effects regression models will be used to compare school readiness outcomes between those referred for early intervention versus placebo/care-as-usual. We will also compare health-resource use associated with early diagnosis and intervention versus later diagnosis and intervention.

Ethics and dissemination
The Children’s Health Queensland Hospital and Health Service, The University of Queensland, University of Sydney, Monash University and Curtin University Human Research Ethics Committees have approved this study. Informed consent will be sought from the parent or legal guardian of every child invited to participate. Results will be disseminated in peer-reviewed journals, scientific conferences and professional organisations, and to people with lived experience of CP and their families.

Trial registration number
ACTRN12621001253897.

Leggi
Febbraio 2023

Risk Prediction of New Intracranial Aneurysms at Follow-Up Screening in People With a Positive Family History

Stroke, Ahead of Print. Background:In first-degree relatives of patients with aneurysmal subarachnoid hemorrhage (aSAH), the risk of an intracranial aneurysm can be predicted at initial screening but not at follow-up screening. We aimed to develop a model for predicting the probability of a new intracranial aneurysm after initial screening in people with a positive family history of aSAH.Methods:In a prospective study, we obtained data from follow-up screening for aneurysms of 499 subjects with ≥2 affected first-degree relatives. Screening took place at the University Medical Center Utrecht, the Netherlands, and the University Hospital of Nantes, France. We studied associations between potential predictors and the presence of aneurysms using Cox regression analysis and the predictive performance at 5, 10, and 15 years after initial screening using C statistics and calibration plots, while correcting for overfitting.Results:In 5050 person-years of follow-up, intracranial aneurysms were found in 52 subjects. The risk of aneurysm at 5 years was 2% to 12%, at 10 years, 4% to 28%, and at 15 years, 7% to 40%. Predictors were female sex, history of intracranial aneurysms/aneurysmal subarachnoid hemorrhage, and older age. The sex, previous history of intracranial aneurysm/aSAH, older age score had a C statistic of 0.70 (95% CI, 0.61–0.78) at 5 years, 0.71 (95% CI, 0.64–0.78) at 10 years, and 0.70 (95% CI, 0.63–0.76) at 15 years and showed good calibration.Conclusions:The sex, previous history of intracranial aneurysm/aSAH, older age score provides risk estimates for finding new intracranial aneurysms at 5, 10, and 15 years after initial screening, based on 3 easily retrievable predictors; this can help to define a personalized screening strategy after initial screening in people with a positive family history for aSAH.

Leggi
Febbraio 2023

Assessing the impact of COVID-19 pandemic on the health of residents and the healthcare system in Alberta, Canada: an observational study–The Alberta POST-COVID Follow-up Study

Introduction
Very little is known about how the COVID-19 pandemic has affected the health of residents and the healthcare system in Alberta, Canada. The purpose of this study is to establish an observational study to characterise the health of residents in Alberta, Canada, over time, covering a population that tested negative or positive for COVID-19 during the pandemic. The primary outcome is to characterise ‘long COVID-19’ and the health status of residents during the COVID-19 pandemic. Secondary outcomes include the estimation of the risk of and risk factors associated with adverse health outcomes and healthcare utilisation and burdens.

Methods and analysis
This is a population-level provincial observational study which will follow-up with Alberta residents who underwent testing for COVID-19 and completed surveys adapted from the ISARIC COVID-19 long-term follow-up survey. The survey data will be linked with medical records. Statistical analyses will be carried out to characterise ‘long COVID-19’ and the health status of residents during the pandemic. The outcomes of this study will inform strategies for primary care and rehabilitation services to prevent chronic consequences; contribute to healthcare management, interventional studies, rehabilitation and health management to reduce overall morbidity and improve long-term outcomes of COVID-19 and the COVID-19 pandemic and potentially guide a self-evaluation of a remote monitoring system to manage individuals’ health.

Ethics and dissemination
This study was reviewed and approved by the University of Alberta ethics committee (Study ID: Pro00112053 & Pro00113039) on 13 August 2021 and adheres to the Alberta Health Services research information management policy. Study results will be used to manage clinical care, published in peer-reviewed journals and presented at local, national and international conferences.

Protocol version
6 June 2022

EuroQol ID
161 015.

Leggi
Febbraio 2023

Opticare protocol: a randomised control trial to evaluate the impact of a mobile antenatal care clinic in isolated rural areas on prenatal follow-up

Introduction
Rural residence appears to be a factor of vulnerability among pregnant women with poor clinical antenatal care. Our principal objective is to assess the impact of an infrastructure for a mobile antenatal care clinic on the completion of antenatal care for women identified as geographically vulnerable in a perinatal network.

Methods and analysis
Controlled cluster-randomised study in two parallel arms comparing an intervention group with an open-label control group. This study will concern the population of pregnant women who must live in one of the municipalities covered by the perinatal network and considered to be an area of geographic vulnerability. The cluster randomisation will take place according to the municipality of residence. The intervention will be the implementation of pregnancy monitoring by a mobile antenatal care clinic. The completion of antenatal care between the intervention and control groups will be a binary criterion: 1 will be attributed to each antenatal care that includes all visits and supplementary examinations. Sample size has been estimated to be 330 at least with an 80% participation rate.
The univariate analyses will compare the follow-up rates (with Fisher’s exact test), and all individual characteristics collected (Fisher’s exact test, Student’s t-test) between the two groups. The multivariate analysis will use a mixed linear model analysis and consider the cluster effect as random; the initial model will include known confounders from the literature, confounders identified in univariate analyses, and the clinically relevant prognostic factors. All of these factors will be taken into account in the model as a fixed effect.

Ethics and dissemination
The Patient Protection Committee North-West II approved this study on 4 February 2021 (IRB 2020-A02247-32). The results will be the subject of scientific communications and publications.

Trial registration number
NCT04823104.

Leggi
Febbraio 2023