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Article ; Online: Formin tails act as a switch, inhibiting or enhancing processive actin elongation.

Bremer, Kathryn V / Wu, Carolyn / Patel, Aanand A / He, Kevin L / Grunfeld, Alex M / Chanfreau, Guillaume F / Quinlan, Margot E

The Journal of biological chemistry

2023 Volume 300, Issue 1, Page(s) 105557

Abstract: Formins are large, multidomain proteins that nucleate new actin filaments and accelerate elongation through a processive interaction with the barbed ends of filaments. Their actin assembly activity is generally attributed to their eponymous formin ... ...

Abstract	Formins are large, multidomain proteins that nucleate new actin filaments and accelerate elongation through a processive interaction with the barbed ends of filaments. Their actin assembly activity is generally attributed to their eponymous formin homology (FH) 1 and 2 domains; however, evidence is mounting that regions outside of the FH1FH2 stretch also tune actin assembly. Here, we explore the underlying contributions of the tail domain, which spans the sequence between the FH2 domain and the C terminus of formins. Tails vary in length from ∼0 to >200 residues and contain a number of recognizable motifs. The most common and well-studied motif is the ∼15-residue-long diaphanous autoregulatory domain. This domain mediates all or nothing regulation of actin assembly through an intramolecular interaction with the diaphanous inhibitory domain in the N-terminal half of the protein. Multiple reports demonstrate that the tail can enhance both nucleation and processivity. In this study, we provide a high-resolution view of the alternative splicing encompassing the tail in the formin homology domain (Fhod) family of formins during development. While four distinct tails are predicted, we found significant levels of only two of these. We characterized the biochemical effects of the different tails. Surprisingly, the two highly expressed Fhod-tails inhibit processive elongation and diminish nucleation, while a third supports activity. These findings demonstrate a new mechanism of modulating actin assembly by formins and support a model in which splice variants are specialized to build distinct actin structures during development.
MeSH term(s)	Actin Cytoskeleton/metabolism ; Actins/metabolism ; Drosophila melanogaster ; Drosophila Proteins/genetics ; Drosophila Proteins/metabolism ; Animals
Chemical Substances	Actins ; Drosophila Proteins
Language	English
Publishing date	2023-12-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1016/j.jbc.2023.105557
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Article ; Online: Association of Androgen Hormones, Sex Hormone-Binding Globulin, and the Menopausal Transition With Incident Diabetes Mellitus in Women With and Without HIV.

Abelman, Rebecca A / Schneider, Michael F / Cox, Christopher / Messerlian, Geralyn / Cohen, Mardge / Gustafson, Deborah / Plankey, Michael / Sharma, Anjali / Price, Jennifer / Grunfeld, Carl / Tien, Phyllis C

Journal of acquired immune deficiency syndromes (1999)

2024 Volume 95, Issue 5, Page(s) 486–493

Abstract: Background: HIV is associated with alterations in androgen hormone levels and sex hormone-binding globulin (SHBG) in women. Higher SHBG has been associated with a lower risk of diabetes in the general population, but the contribution of HIV, androgen ... ...

Abstract	Background: HIV is associated with alterations in androgen hormone levels and sex hormone-binding globulin (SHBG) in women. Higher SHBG has been associated with a lower risk of diabetes in the general population, but the contribution of HIV, androgen hormones, SHBG, and menopausal phase to diabetes is unclear. Methods: From April 2003 through February 2020, 896 women with HIV (WWH) and 343 women without HIV (WWOH) from the Women's Interagency HIV Study with morning total testosterone, dehydroepiandrosterone sulfate (DHEAS), and SHBG levels were followed to assess for incident diabetes. Parametric regression models were used with age as the time scale and relative times (RT) as the measure of association of hormone level and menopausal phase with incident diabetes. Analyses incorporated time-dependent androgen hormone, SHBG levels, and menopausal phase and were adjusted for race/ethnicity, enrollment year, smoking status, BMI, hepatitis C virus status, and HIV-related factors. Results: In total, 128 (14%) WWH and 47 (14%) WWOH developed diabetes. In WWH, a doubling of SHBG and DHEAS were associated with a 7% (RT = 1.07 [95% CI: 0.82 to 1.40] and 15% (RT = 1.15 [95% CI: 0.95 to 1.39]) longer time to diabetes, respectively; in WWOH, a doubling of SHBG and DHEAS were associated with 84% (RT = 1.84 [95% CI: 0.89 to 3.82]) and 41% (RT= 1.41 [95% CI: 0.82 to 2.44]) longer times to diabetes. Total testosterone was not associated. In WWH, later menopausal phase was associated with shorter times to diabetes. Conclusions: Despite alterations in androgen hormone and SHBG levels in HIV, regardless of HIV status, higher SHBG and DHEAS were associated with nonstatistically significant slower progression to diabetes. The menopausal transition may be a better hormonal indicator of diabetes risk in WWH.
MeSH term(s)	Humans ; Female ; Androgens ; Sex Hormone-Binding Globulin ; HIV Infections/complications ; HIV Infections/epidemiology ; Menopause ; Testosterone ; Diabetes Mellitus/epidemiology
Chemical Substances	Androgens ; Sex Hormone-Binding Globulin ; Testosterone (3XMK78S47O)
Language	English
Publishing date	2024-01-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	645053-2
ISSN	1944-7884 ; 1077-9450 ; 0897-5965 ; 0894-9255 ; 1525-4135
ISSN (online)	1944-7884 ; 1077-9450
ISSN	0897-5965 ; 0894-9255 ; 1525-4135
DOI	10.1097/QAI.0000000000003380
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Article: Burden of systemic lupus erythematosus in clinical practice: baseline data from the SLE Prospective Observational Cohort Study (SPOCS) by interferon gene signature.

Arnaud, Laurent / Furie, Richard / Morand, Eric F / Aringer, Martin / Peschken, Christine / Desta, Barnabas / Rapsomaniki, Eleni / Hedberg, Jonatan / Knagenhjelm, Jacob / Seo, Caroline / Grünfeld Eén, Tina / Sorrentino, Alessandro / Tummala, Raj / Stirnadel-Farrant, Heide A / Ding, Bo

Lupus science & medicine

2023 Volume 10, Issue 2

Abstract: Objective: The longitudinal Systemic Lupus Erythematosus Prospective Observational Cohort Study (SPOCS) aims to assess SLE disease course overall and according to type I interferon 4 gene signature (IFNGS). Here, we describe SPOCS patient ... ...

Abstract	Objective: The longitudinal Systemic Lupus Erythematosus Prospective Observational Cohort Study (SPOCS) aims to assess SLE disease course overall and according to type I interferon 4 gene signature (IFNGS). Here, we describe SPOCS patient characteristics by IFNGS and baseline disease activity. Methods: SPOCS (NCT03189875) is an international study of patients with SLE according to Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) criteria. Enrolled patients from 135 centres in 8 countries were followed biannually for ≤3 years from June 2017 to November 2022. Baseline demographics, disease characteristics, organ system involvement/damage and flares were analysed descriptively according to SLE Disease Activity Index-2000 score (SLEDAI-2K <10/≥10) and IFNGS status (high/low). Results: The study population (n=823) was 93.2% female, with mean (SD) age 45.3 (13.9) years and 11.1 (9.2) years since diagnosis; 52.4% had baseline SLICC/ACR Damage Index score ≥1. Patients with SLEDAI-2K scores ≥10 (241 of 584, 41.3%) vs <10 were younger (mean 42.8 (13.7) vs 46.6 (14.2) years; nominal p=0.001), had shorter SLE duration (10.4 (8.6) vs 12.4 (9.6) years; nominal p=0.012) and more severe flares (12.9% vs 5.3%; nominal p=0.001). IFNGS-high patients (522 of 739, 70.6%) were younger than IFNGS-low patients at first SLE manifestation (30.0 (12.7) vs 36.8 (14.6) years; nominal p<0.001). Proportions of IFNGS-high patients differed according to race (nominal p<0.001), with higher proportions among Asian (83.3%) and black (86.5%) versus white patients (63.5%). Greater proportions of IFNGS-high versus IFNGS-low patients had haematological (12.6% vs 4.1%), immunological (74.4% vs 45.6%) or dermal (69.7% vs 62.2%) involvement. Conclusions: We identified key characteristics of patients with high disease activity and/or elevated type I IFN signalling, populations with SLE with high unmet needs. Baseline SLEDAI-2K ≥10 was associated with shorter disease duration and more severe flares. IFNGS-high patients were younger at diagnosis and had distinct patterns of organ involvement, compared with IFNGS-low patients.
MeSH term(s)	Female ; Humans ; Male ; Middle Aged ; Disease Progression ; Interferon Type I ; Lupus Erythematosus, Systemic/drug therapy ; Lupus Erythematosus, Systemic/genetics ; Lupus Erythematosus, Systemic/complications ; Prospective Studies ; Time Factors ; United States ; Adult
Chemical Substances	Interferon Type I
Language	English
Publishing date	2023-12-20
Publishing country	England
Document type	Observational Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2779620-6
ISSN	2053-8790
ISSN	2053-8790
DOI	10.1136/lupus-2023-001032
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Article ; Online: Web-Based Asynchronous Tool to Facilitate Communication Between Primary Care Providers and Cancer Specialists: Pragmatic Randomized Controlled Trial.

Petrovic, Bojana / Julian, Jim A / Liddy, Clare / Afkham, Amir / McGee, Sharon F / Morgan, Scott C / Segal, Roanne / Sussman, Jonathan / Pond, Gregory R / O'Brien, Mary Ann / Bender, Jacqueline L / Grunfeld, Eva

Journal of medical Internet research

2023 Volume 25, Page(s) e40725

Abstract: Background: Cancer poses a significant global health burden. With advances in screening and treatment, there are now a growing number of cancer survivors with complex needs, requiring the involvement of multiple health care providers. Previous studies ... ...

Abstract	Background: Cancer poses a significant global health burden. With advances in screening and treatment, there are now a growing number of cancer survivors with complex needs, requiring the involvement of multiple health care providers. Previous studies have identified problems related to communication and care coordination between primary care providers (PCPs) and cancer specialists. Objective: This study aimed to examine whether a web- and text-based asynchronous system (eOncoNote) could facilitate communication between PCPs and cancer specialists (oncologists and oncology nurses) to improve patient-reported continuity of care among patients receiving treatment or posttreatment survivorship care. Methods: In this pragmatic randomized controlled trial, a total of 173 patients were randomly assigned to either the intervention group (eOncoNote plus usual methods of communication between PCPs and cancer specialists) or a control group (usual communication only), including 104 (60.1%) patients in the survivorship phase (breast and colorectal cancer) and 69 (39.9%) patients in the treatment phase (breast and prostate cancer). The primary outcome was patient-reported team and cross-boundary continuity (Nijmegen Continuity Questionnaire). Secondary outcome measures included the Generalized Anxiety Disorder Screener (GAD-7), Patient Health Questionnaire on Major Depression, and Picker Patient Experience Questionnaire. Patients completed the questionnaires at baseline and at 2 points following randomization. Patients in the treatment phase completed follow-up questionnaires at 1 month and at either 4 months (patients with prostate cancer) or 6 months following randomization (patients with breast cancer). Patients in the survivorship phase completed follow-up questionnaires at 6 months and at 12 months following randomization. Results: The results did not show an intervention effect on the primary outcome of team and cross-boundary continuity of care or on the secondary outcomes of depression and patient experience with their health care. However, there was an intervention effect on anxiety. In the treatment phase, there was a statistically significant difference in the change score from baseline to the 1-month follow-up for GAD-7 (mean difference -2.3; P=.03). In the survivorship phase, there was a statistically significant difference in the change score for GAD-7 between baseline and the 6-month follow-up (mean difference -1.7; P=.03) and between baseline and the 12-month follow-up (mean difference -2.4; P=.004). Conclusions: PCPs' and cancer specialists' access to eOncoNote is not significantly associated with patient-reported continuity of care. However, PCPs' and cancer specialists' access to the eOncoNote intervention may be a factor in reducing patient anxiety. Trial registration: ClinicalTrials.gov NCT03333785; https://clinicaltrials.gov/ct2/show/NCT03333785.
MeSH term(s)	Male ; Humans ; Breast Neoplasms/therapy ; Continuity of Patient Care ; Prostatic Neoplasms ; Communication ; Internet
Language	English
Publishing date	2023-01-18
Publishing country	Canada
Document type	Randomized Controlled Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2028830-X
ISSN	1438-8871 ; 1438-8871
ISSN (online)	1438-8871
ISSN	1438-8871
DOI	10.2196/40725
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Article ; Online: Disruption or innovation? A qualitative descriptive study on the use of electronic patient-physician communication in patients with advanced cancer.

Voruganti, Teja / Husain, Amna / Grunfeld, Eva / Webster, Fiona

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer

2018 Volume 26, Issue 8, Page(s) 2785–2792

Abstract: Purpose: In the advanced cancer context, care coordination is often inadequate, leading to suboptimal continuity of care. We evaluated an electronic web-based tool which assembles the patient, their caregivers, and their healthcare providers in a ... ...

Abstract	Purpose: In the advanced cancer context, care coordination is often inadequate, leading to suboptimal continuity of care. We evaluated an electronic web-based tool which assembles the patient, their caregivers, and their healthcare providers in a virtual space for team-based communication. We sought to understand participant perceptions on electronic communication in general and the added value of the new tool in particular. Methods: We conducted a qualitative descriptive study with participants (patients, caregivers, cancer physicians) who participated in a 3-month pilot trial evaluating the tool. Interviews were thematically analyzed and the perspectives from patients, caregivers, and cancer physicians were triangulated. Interviews from six patients, five of their caregivers, and seven cancer physicians conducted alongside monthly outcome assessments were analyzed. Results: We identified five themes relating participants' perspectives on electronic communication to their experience of care: (1) apparent gaps in care, (2) uncertainty in defining the circle of care, (3) relational aspects of communication, (4) incongruence between technology and social norms of patient-physician communication, and (5) appreciation but apprehension about the team-based communication tool for improving the experience of care. Conclusions: The potential of tools for electronic communication to bring together a team of healthcare providers with the patient and caregivers is significant but may pose new challenges to existing team structure and interpersonal dynamics. Patients and physicians were worried about the impact that electronic communication may have on the patient-physician relationship. Implementation approaches, which build on the relationship and integrate the team as a whole, could positively position electronic communication to enhance the team-based care.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Communication ; Female ; Humans ; Male ; Middle Aged ; Neoplasms/psychology ; Physician-Patient Relations/ethics ; Qualitative Research
Language	English
Publishing date	2018-03-04
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1134446-5
ISSN	1433-7339 ; 0941-4355
ISSN (online)	1433-7339
ISSN	0941-4355
DOI	10.1007/s00520-018-4103-7
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Article ; Online: Dépistage et prise en charge des anévrismes intracrâniens chez les patients atteints de polykystose rénale autosomique dominante.

Flahault, Adrien / Knebelmann, Bertrand / Nataf, François / Trystram, Denis / Grünfeld, Jean-Pierre / Joly, Dominique

Nephrologie & therapeutique

2017 Volume 13 Suppl 1, Page(s) S147–S153

Abstract: Autosomal dominant polycystic kidney disease is the most frequent hereditary kidney disease. Intracranial aneurysm prevalence in this population is four to five times higher than the prevalence in the general population. The most frequent complication of ...

Title translation	Screening and management of intracranial aneurisms in patients with autosomal dominant polycystic kidney disease.
Abstract	Autosomal dominant polycystic kidney disease is the most frequent hereditary kidney disease. Intracranial aneurysm prevalence in this population is four to five times higher than the prevalence in the general population. The most frequent complication of intracranial aneurysms is rupture with subarachnoidal hemorrhage, which is associated with a high morbidity and mortality. The only identified risk factor for unruptured intracranial aneurysm is a family history of intracranial aneurysm. However, most cases of aneurysm rupture occur without any family history of intracranial aneurysm. Magnetic resonance angiography without contrast medium injection facilitates screening, and progress have been made in preventive (endovascular or neurosurgical) treatment of intracranial aneurysm. Recommendations have recently been published concerning intracranial aneurysm screening, and suggest screening patients with autosomal dominant polycystic kidney disease and a family history of intracranial aneurysm, those who have an at-risk activity and those who request screening despite adequate information. Conflicting opinions exist, however, in the literature. Furthermore, a study of practice was conducted among French-speaking nephrologists in Europe and showed that approximately a third of the participants were in favor of systematic screening for intracranial aneurysm in all patients with autosomal dominant polycystic kidney disease. Beyond intracranial aneurysm prevalence, it is necessary to better define rupture rates in the autosomal dominant polycystic kidney disease population, with and without familial history of intracranial aneurysm. This would allow optimizing intracranial aneurysm screening practices in autosomal dominant polycystic kidney disease.
Language	French
Publishing date	2017-04
Publishing country	France
Document type	English Abstract ; Journal Article ; Review
ZDB-ID	2229575-6
ISSN	1872-9177 ; 1769-7255
ISSN (online)	1872-9177
ISSN	1769-7255
DOI	10.1016/j.nephro.2017.01.018
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Article ; Online: Implementation of a Web-Based Communication System for Primary Care Providers and Cancer Specialists.

Petrovic, Bojana / Bender, Jacqueline L / Liddy, Clare / Afkham, Amir / McGee, Sharon F / Morgan, Scott C / Segal, Roanne / O'Brien, Mary Ann / Julian, Jim A / Sussman, Jonathan / Urquhart, Robin / Fitch, Margaret / Schneider, Nancy D / Grunfeld, Eva

Current oncology (Toronto, Ont.)

2023 Volume 30, Issue 3, Page(s) 3537–3548

Abstract: Healthcare providers have reported challenges with coordinating care for patients with cancer. Digital technology tools have brought new possibilities for improving care coordination. A web- and text-based asynchronous system (eOncoNote) was implemented ... ...

Abstract	Healthcare providers have reported challenges with coordinating care for patients with cancer. Digital technology tools have brought new possibilities for improving care coordination. A web- and text-based asynchronous system (eOncoNote) was implemented in Ottawa, Canada for cancer specialists and primary care providers (PCPs). This study aimed to examine PCPs' experiences of implementing eOncoNote and how access to the system influenced communication between PCPs and cancer specialists. As part of a larger study, we collected and analyzed system usage data and administered an end-of-discussion survey to understand the perceived value of using eOncoNote. eOncoNote data were analyzed for 76 shared patients (33 patients receiving treatment and 43 patients in the survivorship phase). Thirty-nine percent of the PCPs responded to the cancer specialist's initial eOncoNote message and nearly all of those sent only one message. Forty-five percent of the PCPs completed the survey. Most PCPs reported no additional benefits of using eOncoNote and emphasized the need for electronic medical record (EMR) integration. Over half of the PCPs indicated that eOncoNote could be a helpful service if they had questions about a patient. Future research should examine opportunities for EMR integration and whether additional interventions could support communication between PCPs and cancer specialists.
MeSH term(s)	Female ; Humans ; Male ; Attitude of Health Personnel ; Breast Neoplasms ; Cancer Survivors ; Colorectal Neoplasms ; Digital Technology/methods ; Digital Technology/organization & administration ; Electronic Health Records/instrumentation ; Electronic Health Records/organization & administration ; Health Care Surveys ; Internet Access/statistics & numerical data ; Nurse Practitioners ; Nurses ; Oncologists/organization & administration ; Physicians, Primary Care/organization & administration ; Prostatic Neoplasms ; Random Allocation
Language	English
Publishing date	2023-03-21
Publishing country	Switzerland
Document type	Evaluation Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1236972-x
ISSN	1718-7729 ; 1198-0052
ISSN (online)	1718-7729
ISSN	1198-0052
DOI	10.3390/curroncol30030269
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Article ; Online: A longitudinal qualitative study of the experience of working following treatment for gynaecological cancer.

Grunfeld, E A / Cooper, A F

Psycho-oncology

2012 Volume 21, Issue 1, Page(s) 82–89

Abstract: Objective: There are an increasing number of gynaecological cancer survivors for whom returning to work is a realistic outcome. There is little research to date specifically examining the return to work experience of survivors of gynaecological cancers. ...

Abstract	Objective: There are an increasing number of gynaecological cancer survivors for whom returning to work is a realistic outcome. There is little research to date specifically examining the return to work experience of survivors of gynaecological cancers. The aim of this study was to explore gynaecological cancer survivors' experience of work over a 1-year period post-treatment. Methods: A total of 55 gynaecological cancer survivors completed a semi-structured interview following completion of their treatment and of these 36 also completed a follow-up interview 12 months later. In total, 91 interviews were recorded and transcribed verbatim. Framework analysis of the transcripts was undertaken. Results: Three super-ordinate themes were identified and these were labelled 'Meaning of work', 'Disclosure of cancer diagnosis' and 'Readjustment'. Overall, there were few changes in working patterns between the two interview points with the majority of women returning to the same role. Although a desire to make work-related changes was expressed at baseline, few women had initiated such changes 1-year post-treatment. Conclusions: Employees may experience difficulties due to residual symptoms, such as continuing fatigue, or as a result of unrealistic expectations about returning to full employment soon after treatment has completed. The results highlight the need for an intervention to support gynaecological cancer survivors to cope with long-term residual symptoms and manage expectations about returning to work.
MeSH term(s)	Adaptation, Psychological ; Adult ; Employment/psychology ; Female ; Follow-Up Studies ; Genital Neoplasms, Female/psychology ; Genital Neoplasms, Female/therapy ; Humans ; Interviews as Topic ; Longitudinal Studies ; Middle Aged ; Qualitative Research ; Socioeconomic Factors ; Survivors/psychology ; Treatment Outcome ; Truth Disclosure ; Work
Language	English
Publishing date	2012-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1118536-3
ISSN	1099-1611 ; 1057-9249
ISSN (online)	1099-1611
ISSN	1057-9249
DOI	10.1002/pon.1874
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Article ; Online: Patient and Healthcare Provider Perspectives on the Implementation of a Web-Based Clinical Communication System for Cancer: A Qualitative Study.

Petrovic, Bojana / O'Brien, Mary Ann / Liddy, Clare / Afkham, Amir / McGee, Sharon F / Morgan, Scott C / Segal, Roanne / Bender, Jacqueline L / Sussman, Jonathan / Urquhart, Robin / Fitch, Margaret / Schneider, Nancy D / Grunfeld, Eva

Current oncology (Toronto, Ont.)

2022 Volume 29, Issue 11, Page(s) 8401–8414

Abstract: Previous research has identified communication and care coordination problems for patients with cancer. Healthcare providers (HCPs) have reported communication issues due to the incompatibility of electronic medical records (EMR) software and not being ... ...

Abstract	Previous research has identified communication and care coordination problems for patients with cancer. Healthcare providers (HCPs) have reported communication issues due to the incompatibility of electronic medical records (EMR) software and not being consistently copied on patient reports. We evaluated an asynchronous web-based communication system ("eOncoNote") for primary care providers and cancer specialists to improve cancer care coordination. The objectives were to examine patients' perceptions of the role of eOncoNote in their healthcare, and HCPs' experiences of implementing eOncoNote. Qualitative interviews were conducted with patients with breast and prostate cancer, primary care providers, and cancer specialists. Eighteen patients and fourteen HCPs participated. Six themes were identified from the patient interviews focusing on HCP and patient roles related to care coordination and patient awareness of communication among their HCPs. Four themes were identified from HCP interviews related to the context of care coordination and experience with eOncoNote. Both patients and HCPs described the important role patients and caregivers play in care coordination. The results show that patients were often unaware of the communication between their HCPs and assumed they were communicating. HCPs encountered challenges incorporating eOncoNote into their workflow.
MeSH term(s)	Male ; Humans ; Health Personnel ; Qualitative Research ; Neoplasms ; Communication ; Internet
Language	English
Publishing date	2022-11-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1236972-x
ISSN	1718-7729 ; 1198-0052
ISSN (online)	1718-7729
ISSN	1198-0052
DOI	10.3390/curroncol29110662
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Article ; Online: Screening for intracranial aneurysms in autosomal dominant polycystic kidney disease is cost-effective.

Flahault, Adrien / Trystram, Denis / Nataf, François / Fouchard, Marie / Knebelmann, Bertrand / Grünfeld, Jean-Pierre / Joly, Dominique

Kidney international

2017 Volume 93, Issue 3, Page(s) 716–726

Abstract: Intracranial aneurysm rupture is a dramatic complication of autosomal dominant polycystic kidney disease (ADPKD). It remains uncertain whether screening should be widespread or only target patients with risk factors (personal or familial history of ... ...

Abstract	Intracranial aneurysm rupture is a dramatic complication of autosomal dominant polycystic kidney disease (ADPKD). It remains uncertain whether screening should be widespread or only target patients with risk factors (personal or familial history of intracranial aneurysm), with an at-risk profession, or those who request screening. We evaluated this in a single-center cohort of 495 consecutive patients with ADPKD submitted to targeted intracranial aneurysm screening. Cerebral magnetic resonance angiography was proposed to 110 patients with a familial history of intracranial aneurysm (group 1), whereas it was not our intention to propose it to 385 patients without familial risk (group 2). Magnetic resonance angiography results, intracranial aneurysm prophylactic repair, rupture events, and cost-effectiveness of intracranial aneurysm screening strategies were retrospectively analyzed. During a median follow up of 5.9 years, five non-fatal intracranial aneurysm ruptures occurred (incidence rate 2.0 (0.87-4.6)/1000 patients-year). In group 1, 90% of patients were screened and an intracranial aneurysm was detected in 14, treated preventively in five, and ruptured in one patient despite surveillance. In group 2, 21% of patients were screened and an intracranial aneurysm was detected in five, and treated preventively in one. Intracranial aneurysm rupture occurred in four patients in group 2. Systematic screening was deemed cost-effective and provides a gain of 0.68 quality-adjusted life years compared to targeted screening. Thus, the intracranial aneurysm rupture rate is high in ADPKD despite targeted screening, and involves mostly patients without familial risk factors. Hence, cost-utility analysis suggests that intracranial aneurysm screening could be proposed to all ADPKD patients.
MeSH term(s)	Adult ; Aneurysm, Ruptured/diagnostic imaging ; Aneurysm, Ruptured/economics ; Aneurysm, Ruptured/etiology ; Aneurysm, Ruptured/therapy ; Cerebral Angiography/economics ; Cerebral Angiography/methods ; Clinical Decision-Making ; Cost-Benefit Analysis ; Female ; Health Care Costs ; Humans ; Intracranial Aneurysm/diagnostic imaging ; Intracranial Aneurysm/economics ; Intracranial Aneurysm/etiology ; Intracranial Aneurysm/therapy ; Magnetic Resonance Angiography/economics ; Male ; Mass Screening/economics ; Mass Screening/methods ; Middle Aged ; Patient Selection ; Polycystic Kidney, Autosomal Dominant/complications ; Polycystic Kidney, Autosomal Dominant/diagnosis ; Polycystic Kidney, Autosomal Dominant/economics ; Predictive Value of Tests ; Prognosis ; Program Evaluation ; Quality-Adjusted Life Years ; Reproducibility of Results ; Retrospective Studies ; Risk Factors ; Time Factors
Language	English
Publishing date	2017-10-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	120573-0
ISSN	1523-1755 ; 0085-2538
ISSN (online)	1523-1755
ISSN	0085-2538
DOI	10.1016/j.kint.2017.08.016
Database	MEDical Literature Analysis and Retrieval System OnLINE

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