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Defining CD4 T helper and T regulatory cell endotypes of progressive and remitting pulmonary sarcoidosis (BRITE): protocol for a US-based, multicentre, longitudinal observational bronchoscopy study

Por: Koth · L. L. · Harmacek · L. D. · White · E. K. · Arger · N. K. · Powers · L. · Werner · B. R. · Magallon · R. E. · Grewal · P. · Barkes · B. Q. · Li · L. · Gillespie · M. · Collins · S. E. · Cardenas · J. · Chen · E. S. · Maier · L. A. · Leach · S. M. · OConnor · B. P. · Hamzeh · N. Y.
Introduction

Sarcoidosis is a multiorgan granulomatous disorder thought to be triggered and influenced by gene–environment interactions. Sarcoidosis affects 45–300/100 000 individuals in the USA and has an increasing mortality rate. The greatest gap in knowledge about sarcoidosis pathobiology is a lack of understanding about the underlying immunological mechanisms driving progressive pulmonary disease. The objective of this study is to define the lung-specific and blood-specific longitudinal changes in the adaptive immune response and their relationship to progressive and non-progressive pulmonary outcomes in patients with recently diagnosed sarcoidosis.

Methods and analysis

The BRonchoscopy at Initial sarcoidosis diagnosis Targeting longitudinal Endpoints study is a US-based, NIH-sponsored longitudinal blood and bronchoscopy study. Enrolment will occur over four centres with a target sample size of 80 eligible participants within 18 months of tissue diagnosis. Participants will undergo six study visits over 18 months. In addition to serial measurement of lung function, symptom surveys and chest X-rays, participants will undergo collection of blood and two bronchoscopies with bronchoalveolar lavage separated by 6 months. Freshly processed samples will be stained and flow-sorted for isolation of CD4 +T helper (Th1, Th17.0 and Th17.1) and T regulatory cell immune populations, followed by next-generation RNA sequencing. We will construct bioinformatic tools using this gene expression to define sarcoidosis endotypes that associate with progressive and non-progressive pulmonary disease outcomes and validate the tools using an independent cohort.

Ethics and dissemination

The study protocol has been approved by the Institutional Review Boards at National Jewish Hospital (IRB# HS-3118), University of Iowa (IRB# 201801750), Johns Hopkins University (IRB# 00149513) and University of California, San Francisco (IRB# 17-23432). All participants will be required to provide written informed consent. Findings will be disseminated via journal publications, scientific conferences, patient advocacy group online content and social media platforms.

Distribution and specificity of high-sensitivity cardiac troponin T in older adults without acute cardiac conditions: cross-sectional results from the population-based AugUR study

Por: Dietl · A. · Zimmermann · M. E. · Brandl · C. · Wallner · S. · Burkhardt · R. · Maier · L. S. · Luchner · A. · Heid · I. M. · Stark · K. J.
Objective

European guidelines recommended a uniform upper reference limit of high-sensitivity cardiac troponin T (hsTnT) to rule out non-ST segment elevation myocardial infarction. Our study aimed to provide a hsTnT reference distribution and to assess the specificity of the 14 ng/L cut-off value in the mobile population ≥70 years of age.

Design

A cross-sectional analysis was performed in the German AugUR study (Altersbezogene Untersuchungen zur Gesundheit der University of Regensburg).

Setting

Study population was the mobile population aged 70+ years living in the city and county of Regensburg, Germany.

Participants

A random sample was derived from the local population registries of residence. Of the 5644 individuals invited, 1133 participated (response ratio=20.1%). All participants came to the study centre and were mentally and physically mobile to conduct the protocol (face-to-face interview, blood draw and standardised transthoracic echocardiography). None of the participants was in an acute state of myocardial infarction.

Results

Among the 1129 individuals with hsTnT measurements (overall median=10.0 ng/L

(25th, 75th percentile)=(7.0, 15.0 ng/L)), hsTnT was higher among the older individuals and higher among men (men 70–74 years median=9.6 ng/L (7.2, 13.1 ng/L); men 90–95 years median=21.2 ng/L (14.6, 26.0 ng/L); women 70–74 years median=6.3 ng/L (4.7, 8.7 ng/L); and women 90–95 years median=18.0 ng/L (11.0, 21.0 ng/L)). In participants with impaired kidney function (eGFRcrea2), hsTnT was elevated (median=13.6 ng/L (9.4, 20.6 ng/L)).

Specificity of recommended upper reference limit, 14 ng/L, is 68%. Most false positives were among men aged >79 years (specificity=34%). In a healthy subgroup (n=96, none of the following: overt heart disease, impaired renal function, blood pressure >160/100 mm Hg, left ventricular hypertrophy and diastolic/systolic dysfunction), specificity was 90%.

Conclusion

In the elderly population without acute myocardial infarction, hsTnT further increases with age showing different levels for men and women. The specificity of the 14 ng/L cut-off is considerably lower than 99%, even in healthy subjects.

Comparison of FORTA, PRISCUS and EU(7)-PIM lists on identifying potentially inappropriate medication and its impact on cognitive function in multimorbid elderly German people in primary care: a multicentre observational study

Por: Krüger · C. · Schäfer · I. · van den Bussche · H. · Bickel · H. · Dreischulte · T. · Fuchs · A. · König · H.-H. · Maier · W. · Mergenthal · K. · Riedel-Heller · S. G. · Schön · G. · Weyerer · S. · Wiese · B. · von Renteln-Kruse · W. · Langebrake · C. · Scherer · M.
Objectives

Our study aimed to assess the frequency of potentially inappropriate medication (PIM) use (according to three PIM lists) and to examine the association between PIM use and cognitive function among participants in the MultiCare cohort.

Design

MultiCare is conducted as a longitudinal, multicentre, observational cohort study.

Setting

The MultiCare study is located in eight different study centres in Germany.

Participants

3189 patients (59.3% female).

Primary and secondary outcome measures

The study had a cross-sectional design using baseline data from the German MultiCare study. Prescribed and over-the-counter drugs were classified using FORTA (Fit fOR The Aged), PRISCUS (Latin for ‘time-honoured’) and EU(7)-PIM lists. A mixed-effect multivariate linear regression was performed to calculate the association between PIM use patients’ cognitive function (measured with (LDST)).

Results

Patients (3189) used 2152 FORTA PIM (mean 0.9±1.03 per patient), 936 PRISCUS PIM (0.3±0.58) and 4311 EU(7)-PIM (1.4±1.29). The most common FORTA PIM was phenprocoumon (13.8%); the most prevalent PRISCUS PIM was amitriptyline (2.8%); the most common EU(7)-PIM was omeprazole (14.0%). The lists rate PIM differently, with an overall overlap of 6.6%. Increasing use of PIM is significantly associated with reduced cognitive function that was detected with a correlation coefficient of –0.60 for FORTA PIM (p=0.002), –0.72 for PRISCUS PIM (p=0.025) and –0.44 for EU(7)-PIM (p=0.005).

Conclusion

We identified PIM using FORTA, PRISCUS and EU(7)-PIM lists differently and found that PIM use is associated with cognitive impairment according to LDST, whereby the FORTA list best explained cognitive decline for the German population. These findings are consistent with a negative impact of PIM use on multimorbid elderly patient outcomes.

Trial registration number

ISRCTN89818205.

Impact of prehabilitation on objectively measured physical activity levels in elective surgery patients: a systematic review

Por: Wagnild · J. M. · Akowuah · E. · Maier · R. H. · Hancock · H. C. · Kasim · A.
Objective

To systematically review the impact of prehabilitation on objectively measured physical activity (PA) levels in elective surgery patients.

Data sources

Articles published in Web of Science Core Collections, PubMed, Embase (Ovid), CINAHL (EBSCOHost), PsycInfo (EBSCOHost) and CENTRAL through August 2020.

Study selection

Studies that met the following criteria: (1) written in English, (2) quantitatively described the effect(s) of a PA intervention among elective surgery patients prior to surgery and (3) used and reported objective measures of PA in the study.

Data extraction and synthesis

Participant characteristics, intervention details, PA measurement, and clinical and health-related outcomes were extracted. Risk of bias was assessed following the revised Cochrane risk of bias tool. Meta-analysis was not possible due to heterogeneity, therefore narrative synthesis was used.

Results

6533 unique articles were identified in the search; 21 articles (based on 15 trials) were included in the review. There was little evidence to suggest that prehabilitation is associated with increases in objectively measured PA, but this may be due to insufficient statistical power as most (n=8) trials included in the review were small feasibility/pilot studies. Where studies tested associations between objectively measured PA during the intervention period and health-related outcomes, significant beneficial associations were reported. Limitations in the evidence base precluded any assessment via meta-regression of the association between objectively measured PA and clinical or health-related outcomes.

Conclusions

Additional large-scale studies are needed, with clear and consistent reporting of objective measures including accelerometry variables and outcome variables, to improve our understanding of the impact of changes in PA prior to surgery on surgical and health-related outcomes.

PROSPERO registration number

CRD42019151475.

Giving midwives a voice – Qualitative perspectives of an ‘empowering decision‐making workshop’

Abstract

Aim/objective

To establish midwives’ perceptions of the value of workshops designed to empower their decision-making and leadership skills using validated midwifery clinical reasoning frameworks and appreciative inquiry methods.

Background

The medical lens of childbirth can disempower women and midwives. Midwives often face challenges navigating their role as autonomous practitioners and advocates for shared decision-making, particularly when there is tension between women's wishes, governance frameworks and organisational requirements. This can lead to ‘Midwifery Abdication’ and/or the midwifery voice being silenced.

Design/Methods

Appreciative inquiry, involving qualitative analysis of 31 midwives’ personal reflections during ‘Empowering Midwives’ Decision-Making’ workshops. Standards for reporting qualitative research (SRQR criteria) guided the preparation of this manuscript.

Results

Decision-making tools and ‘appreciative’ strategies can strengthen leadership attributes, enhance feelings of empowerment and deepen understanding. Reflecting on ‘Midwifery Abdication’ was perceived as confronting. Workshop activities offered understanding the reasons why ‘Midwifery Abdication’ may or may not occur. One overarching, key theme was identified: ‘Finding my midwifery voice’. This theme encompassed three sub-themes: ‘I am not alone’, ‘Using leadership to promote collaboration to effect change’ and ‘An onward journey of enlightenment and empowerment’.

Conclusion

Midwives need to find their voice and develop skills in both clinical reasoning and transformative reflection. Workshops, using Appreciative Inquiry approaches, that focused on reflection, clinical decision-making and ‘Midwifery Abdication’, facilitate this and may create feelings of reunification in midwives and rejuvenate inherent passion for the profession.

Relevance to clinical practice

Sharing feelings around providing care in the often-contested space that is advocating for women using midwifery philosophy may provide relief from moral distress and a sense of shared identity desperately sought after by midwives struggling to navigate the increasingly complex terrain of maternity care. Findings encourage the need for further discussions around strengthening midwifery leadership which may be achievable using Appreciative Inquiry frameworks and approaches.

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