louisbrulenaudet/clinical-trials huggingface dataset:
Clinical trial NCT01694316: Use of a Novel Neuroplasticity-based Neurobehavioral Intervention for PTSD
Official title: Use of a Novel Neuroplasticity-based Neurobehavioral Intervention for PTSD - A Nationwide, Online Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Anxiety
Depression
Keywords: Computerized neurobehavioral intervention
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2012-09-27
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The present study will explore the effectiveness of a computer based neurobehavioral intervention in alleviating symptoms and improving emotion regulation in individuals with PTSD. It will increase understanding of psychopathology at a neural-circuit level and aid development of new non-pharmacological treatment for PTSD. The study is managed by the Etkin Lab at Stanford University in California, but participants from the entire US are welcome to participate as the study is delivered online.


Eligibility criteria: Inclusion Criteria:

* current PTSD
* internet access

Exclusion Criteria:

* lifetime psychotic disorder,
* past-year substance dependence

Primary outcomes:
measure: WebNeuro Computerized Cognitive and Affective Assessment Battery
timeFrame: Baseline and 3-month
Secondary outcomes:
measure: Clinician-assessed PTSD symptoms
timeFrame: Baseline and 3-month
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University, Department of Psychiatry and Behavioral Sciences
state: California
Study officials:
References:
citation: Fonzo GA, Fine NB, Wright RN, Achituv M, Zaiko YV, Merin O, Shalev AY, Etkin A. Internet-delivered computerized cognitive & affective remediation training for the treatment of acute and chronic posttraumatic stress disorder: Two randomized clinical trials. J Psychiatr Res. 2019 Aug;115:82-89. doi: 10.1016/j.jpsychires.2019.05.007. Epub 2019 May 8.
Clinical trial NCT01145716: Exploration of Wrist Soft Tissue Injuries Associated With Wrist Fractures
Official title: Exploration of Acute TFCC-injuries in Association With Distal Radius Fractures
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Triangular Fibrocartilage Complex Injuries
Keywords: TFCC injuries
Distal radius fractures
Lead sponsor: Linkoeping University
Sponsor class: OTHER_GOV
First posted: 2010-06-17
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: The purpose of this study is to describe and stage lesions of the triangular fibrocartilage complex (TFCC) in association with distal radius fractures. 20 patients with dorsally dislocated AO type A fractures of the distal radius with sufficient displacement (based of cadaveric data) will be included. After stability testing and wrist arthroscopy. The TFCC is explored through a volar incision and injuries were documented and repaired from this approach.


Eligibility criteria: Inclusion Criteria:

* Age 18-65
* Distal radius fracture
* Displacement \> 20 degrees of dorsal angulation

Exclusion Criteria:

* Previous significant wrist injury
* Declines to participate
* Ulnar styloid fracture at base or proximal to it

Primary outcomes:
measure: Residual instability symptoms
timeFrame: Approx 2-6 months to include the patients that meet the inclusion criteria. They will be followed for 6 momths
Secondary outcomes:
measure: Adverse events
timeFrame: Three months
Other outcomes:
Locations:
city: Linkoeping
country: Sweden
facility: Dept of orthopedics
Study officials:
affiliation: Linkopeing University, Sweden
name: Lars E Adolfsson, Assoc prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lindau T, Hagberg L, Adlercreutz C, Jonsson K, Aspenberg P. Distal radioulnar instability is an independent worsening factor in distal radial fractures. Clin Orthop Relat Res. 2000 Jul;(376):229-35. doi: 10.1097/00003086-200007000-00031.
citation: Lindau T, Arner M, Hagberg L. Intraarticular lesions in distal fractures of the radius in young adults. A descriptive arthroscopic study in 50 patients. J Hand Surg Br. 1997 Oct;22(5):638-43. doi: 10.1016/s0266-7681(97)80364-6.
citation: Geissler WB, Fernandez DL, Lamey DM. Distal radioulnar joint injuries associated with fractures of the distal radius. Clin Orthop Relat Res. 1996 Jun;(327):135-46. doi: 10.1097/00003086-199606000-00018.
Clinical trial NCT06040216: Evolution of EIFL Following PPV
Official title: Long-term Follow-up Results of Ectopic Inner Foveal Retinal Layers Evolution Following Pars Plana Vitrectomy
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Epiretinal Membrane
Lead sponsor: Kocaeli University
Sponsor class: OTHER
First posted: 2023-09-15
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This retrospective study included 81 consecutive eyes with idiopathic epiretinal membrane that underwent vitrectomy surgery.

Brief summary: Various classification systems have been described for epiretinal membrane (ERM). One of them is a new OCT-based staging scheme based on displacement and reorganization of inner retinal layers called ectopic inner retinal layers (EIFL). We evaluated pre-and perioperative factors related to time for evolution of EIFL.


Eligibility criteria: Inclusion Criteria:

* Patients undergoing idiopathic epiretinal membrane surgery

Exclusion Criteria:

* Patients undergoing seconder epiretinal membrane surgery

Primary outcomes:
measure: Best corrected visual acuity
timeFrame: 1-month
Secondary outcomes:
Other outcomes:
Locations:
city: Kocaeli
country: Turkey
facility: Kocaeli University School of Medicine
state: None Selected
Study officials:
References:
Clinical trial NCT00576316: Symbicort Maintenance and Reliever Therapy - Experience in Real Life Setting in Malaysia
Official title: Symbicort Maintenance And Reliever Therapy - Experience in Real Life Setting in Malaysia - SMARTER Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Asthma
Keywords: Asthma
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2007-12-19
Enrollment: 201
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to evaluate the satisfaction level of patients using the Symbicort SMART approach for their asthma management.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of asthma for past 6 months and treated with inhaled glucocorticosteroids for at least 3 months.
* Patients who asthma is classified as uncontrolled or partially controlled as defined by GINA 2006 guidelines.

Exclusion Criteria:

* Patients already on Symbicort SMART treatment.
* Patients who has respiratory tract infection 30 days before study enrolment.

Primary outcomes:
measure: Change in Satisfaction With Asthma Treatment Questionnaire (SATQ) Scores From Baseline to the Mean of 3 Months and 6 Months After Patient Was Initially Treated With SMART
timeFrame: 6 months after each patient was initially treated with Symbicort SMART
Secondary outcomes:
measure: Changes in Asthma Control Questionnaire (ACQ-5) Score From Baseline to the Mean of 3 Months and 6 Months After Patient Was Initially Treated With SMART
timeFrame: 6 months after each patient was initially treated with Symbicort SMART
Other outcomes:
Locations:
city: Kuala Lumpur
country: Malaysia
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: Akhmal Yusof, MD
role: STUDY_DIRECTOR
affiliation: Kuala Lumpur Hospital
name: Aziah Ahmad Mahayiddin, MD
role: PRINCIPAL_INVESTIGATOR
References:
Clinical trial NCT02588716: Effects of Terlipressin on Blood Loss and Transfusion Requirements During Major Liver Resection.
Official title: Effects of Terlipressin on Blood Loss and Transfusion Requirements During Major Liver Resection.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatectomy, Surgical Blood Loss, Terlipressin
Keywords: Hepatectomy, Surgical Blood Loss, terlipressin
Lead sponsor: Assiut University
Sponsor class: OTHER
First posted: 2015-10-28
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: To evaluate the effects of Terlipressin infusion on blood loss \& transfusion requirements in cirrhotic patients undergoing major liver resections.


Eligibility criteria: Inclusion Criteria:

* All patients older than 18 years of age, American Society of Anesthesiology (ASA) classification class I and II and assigned for elective resection of 2 or more liver segments portal hypertension

Exclusion Criteria:

* Patients with Child-Turcotte-Pugh grade B or C, clinically significant portal hypertension (splenomegaly, thrombocytopenia with platelets \< 1011/L, esophageal varices grade 2 or more), Preoperative renal failure (GFR \< 50ml/min), heart failure, Bradyarrhythmia (heart rate \< 60/min), history of hemorrhagic stroke, Uncontrolled arterial hypertension (Blood pressure \>160/100mmHg), and Pregnancy

Primary outcomes:
measure: blood loss
timeFrame: intraoperative period
Secondary outcomes:
measure: blood units transfused
timeFrame: intraoperative period
measure: lactate level
timeFrame: at start and end of resection
Other outcomes:
Locations:
city: Assiut
country: Egypt
facility: Assiut University hospital
state: Asyut Governorate
Study officials:
References:
citation: Abbas MS, Mohamed KS, Ibraheim OA, Taha AM, Ibraheem TM, Fadel BA, Elawamy A, Abbas AM. Effects of terlipressin infusion on blood loss and transfusion needs during liver resection: A randomised trial. Acta Anaesthesiol Scand. 2019 Jan;63(1):34-39. doi: 10.1111/aas.13226. Epub 2018 Aug 5.
Clinical trial NCT01408524: Control of Emergence Blood Pressure During Craniotomy for Tumor Surgery Between Labetolol and Diltiazem
Official title: A Comparative Study in the Control of Emergence Blood Pressure During Craniotomy for Tumor Surgery Between Labetolol (Avexa) and Diltiazem
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Hypertension
Craniotomy
Keywords: Hypertension
emergence
craniotomy
Hypertension during the emergence after craniotomy
Lead sponsor: Mahidol University
Sponsor class: OTHER
First posted: 2011-08-03
Enrollment: 184
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the effectiveness of the antihypertensive drugs in the control of emergence blood pressure after tumor resection craniotomy; compared between labetalol (Avexa) and diltiazem (Herbessor).

Also the investigators seek to determine the effective dose of the antihypertensive drugs and their side effects in Thai population.

Detailed description: The study was randomized equivalence trial

Eligibility criteria: Inclusion Criteria:

* patients who scheduled for craniotomy for tomor removal

Exclusion Criteria:

* allergic to labetalol or diltiazem
* Bradycardia \< 60 beat/min
* Second or third degree heart block
* Severe asthma or severe COPD
* Brain stem tumor

Primary outcomes:
measure: The number of the patients who have systolic blood pressure below 140 mmHg
timeFrame: 3 hours
Secondary outcomes:
measure: mean doses of the study drugs
timeFrame: 3hr
measure: the number of patients with Adverse Events as a Measure of Safety and Tolerability
timeFrame: 6 hour
Other outcomes:
Locations:
Study officials:
affiliation: Department of Anesthesiology, Siriraj Hospital, Mahidol University, Bangkok, Thailand
name: Busara - Sirivanasandha, MD
role: PRINCIPAL_INVESTIGATOR
References:
Clinical trial NCT03981224: The Value of Post-radiation Detectable Plasma EBV DNA in High-risk Nasopharyngeal Carcinoma Patients
Official title: Additional Blood Test Enhances Diagnostic Sensitivity of Relapse Detection and Predicts Survivals in High-risk Nasopharyngeal Carcinoma Patients With Post-radiation Detectable Plasma EBV DNA
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Nasopharyngeal Carcinoma
Keywords: Nasopharyngeal carcinoma
Radiotherapy
Epstein-Barr virus
Lead sponsor: Taichung Veterans General Hospital
Sponsor class: OTHER
First posted: 2019-06-10
Enrollment: 706
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: locally advanced NPC patients who finished curative RT with or without chemotherapy

Brief summary: An additional blood test at 2-3 months after RT is a valuable biomarker in predicting treatment outcome for NPC patients. Patients with persistently detectable EBV DNA during re-staging survey 2-3 months after RT should strengthen adjuvant therapy due to very high subsequent relapse rate and poor survivals.

Detailed description: One week post-radiation therapy (RT) blood test showing persistently detectable EBV DNA is a very poor prognostic factor for nasopharyngeal carcinoma (NPC) patients. We hypothesize that additional EBV DNA confirmation test could enhance diagnostic sensitivity of relapse detection and predict survivals.

We screened 706 newly diagnosed NPC patients who finished curative RT with or without chemotherapy from March 2001 to December 2012. Additional EBV DNA blood test was performed at re-staging survey 2-3 months after RT. The association between treatment outcome (tumor relapse and patients' survival) and this additional blood test along with various clinical parameters were analyzed.

Eligibility criteria: Inclusion Criteria:

* histologically-proven nasopharyngeal carcinoma without distant metastasis (M0) at initial presentation
* NPC patients who finished curative RT with or without chemotherapy

Exclusion Criteria:

* initial present M1 disease
* Secondary primary cancer diagnosed within 5 years
* performance status (WHO scale) less than 2

Primary outcomes:
measure: relapse-free survival (RFS)
timeFrame: 5 years
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: 5 years
Other outcomes:
measure: locoregional failure-free survival (LRFFS)
timeFrame: 5 years
measure: distant metastasis failure-free survival (DMFFS)
timeFrame: 5 years
Locations:
Study officials:
affiliation: Taichung Veterans General Hospital
name: Jin-Ching Lin, M.D.,PhD
role: PRINCIPAL_INVESTIGATOR
References:
Clinical trial NCT03808324: Heart Failure After Heart Transplantation Due to Chronic Rejection
Official title: Allograft Vasculopathy and Unexplained Graft Dysfunction During Long-term Follow-up After Heart Transplantation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Cardiac Allograft Vasculopathy
Chronic Rejection of Cardiac Transplant
Graft Dysfunction
Lead sponsor: Sahlgrenska University Hospital
Sponsor class: OTHER
First posted: 2019-01-17
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: This study will investigate the prevalence of allograft vasculopathy and unexplained graft dysfunction during long-term follow-up after heart transplantation. Risk factors as well diagnostic approaches will be investigated.

Detailed description: During long-term follow-up heart transplant recipients are at risk of developing different complications that are likely to affect quality of life and survival. The most common cause of death during the later stages after heart transplantation is cardiac allograft vasculopathy, followed by unexplained graft dysfunction. In this study, advanced imaging techniques will be used to describe the frequency of these two complications, examine possible risk factors and study consequences on functional capacity and quality of life. Further, the investigators will investigate whether it is feasible to screen for these conditions with non-invasive imaging methods. By studying patients that have performed cardiac transplantation between 10 and 20 years ago, the investigators expect to have a significant proportion of patients with these pathological conditions. Methods that will be used include cardiac magnetic resonance imaging, coronary flow velocity reserve assessment, right heart catheterization and coronary imaging with angiography and optical coherence tomography.

Eligibility criteria: Inclusion Criteria:

* Heart transplant performed more than 10 years and less than 21 years ago
* Scheduled yearly post-transplant control
* Signed informed consent

Exclusion Criteria:

* Estimated GFR \< 30 mL/min/1,73m2
* Radiographic contrast allergy
* Severe asthma or COLD with FEV1 \< 50%
* Second or third degree AV block
* Pregnancy
* In the Investigator's opinion, the patient has a clinically significant disease that could be adversely affected by study participation

Primary outcomes:
measure: Degree of stenosis in coronary arteries
timeFrame: 4 hours
measure: Restrictive allograft hemodynamics
timeFrame: 2 hours
measure: Functional assessment of the microvasculature
timeFrame: 2 hours
measure: Degree of myocardial fibrosis
timeFrame: 4 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Gothenburg
country: Sweden
facility: Sahlgrenska University Hospital
Study officials:
References:
Clinical trial NCT02760524: Desensitizing Distressing Recollections in Cancer Patients
Official title: Desensitizing Distressing Recollections in Cancer Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cancer
Lead sponsor: Thomas Jefferson University
Sponsor class: OTHER
First posted: 2016-05-03
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The major goal of this study is to determine whether Neuro-Emotional Technique is a viable treatment option for decreasing distress in cancer patients. The potential advantages of NET are: 1) it is designed specifically to address distressing stimuli and unresolved emotional memories; 2) it is a brief, time-limited intervention; and 3) its multi-modal design may appeal to and benefit a broader range of patients than a single mode intervention


Eligibility criteria: Inclusion Criteria:

* Age ≥18 years of age
* Distressing cancer-related recollection that has persisted for at least six months
* Distressing cancer-related recollection that causes physiological reactivity (i.e., increased heart rate and/or increased skin conductance level - SCL), as described in section 4.2.3.
* Received a cancer diagnosis at least 6 months prior to being contacted for participation in this study

Exclusion Criteria:

* Any current Major Mental Disorder, as assessed by Structured Clinical Interview for DSM IV Axis I Disorders (SCID - Clinical Version, First et al, 1997)
* History of Post-traumatic Stress Disorder
* Current active mood primary disorder prior to the cancer diagnosis (as per PI or designate)
* History or current diagnosis of substance or alcohol abuse or dependence (as per PI or designate)
* Use of psychotropic medications within the past month or current use of medications that would interfere with autonomic nervous system measures (benzodiazepines, barbiturates, major tranquilizers).
* Use of some psychotropic medications are allowed such as SSRIs and certain sleep aids, but dosages must be stable from six weeks prior to enrollment and throughout study period
* Any psychological or musculoskeletal problems that would interfere with psychophysiological assessments and treatment
* Currently receiving chemotherapy or radiation
* Are in the terminal stages of illness

Primary outcomes:
measure: Post traumatic Cognitions Inventory
timeFrame: baseline/ 4 weeks/6 months follow up
measure: State Trait Anxiety Inventory
timeFrame: baseline/4 weeks/6 months follow up
measure: Brief Symptom Inventory
timeFrame: baseline/4 weeks/6 month follow up
Secondary outcomes:
measure: Autonomal response to distressing recollections
timeFrame: baseline/4 weeks follow up
measure: Genomic testing
timeFrame: baseline/ 4 weeks follow up
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
Study officials:
affiliation: Thomas Jefferson University
name: Daniel A Monti, MD
role: PRINCIPAL_INVESTIGATOR
References:
Clinical trial NCT02050724: ThoHSpEkt Thoracoscopic Ectomy of Radioactively Marked Pulmonary Nodules With Free-hand SPECT
Official title: Thorakoskopische Handheld-SPECT Gesteuerte Ektomie Von Radioaktiv-markierten Pulmonalen Rundherden. Proof of Feasibility of Thoracoscopic Ectomy of Radioactively Marked Pulmonary Nodules With the Help of Free-hand SPECT.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Solitary Pulmonary Nodule
Bronchial Neoplasms
Keywords: Solitary Pulmonary Nodule
Thoracoscopy
Thoracic Surgery
Video-Assisted
Radioactive Tracers
Radioguided surgery
Handheld-SPECT
Lead sponsor: Cantonal Hospital of St. Gallen
Sponsor class: OTHER
First posted: 2014-01-31
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: Title ThoHSpEkt

Study Design Pilot Study concerning the technical operative methods and a phase II study concerning the radiopharmaceutical (therapeutic-explorative study with an approved drug in a new indication)

Location Kantonsspital St.Gallen

Aim Proof of feasibility of thoracoscopic ectomy of radioactively marked pulmonary nodules with the help of free-hand SPECT.

Background In the Cantonal Hospital of St.Gallen an average of 30 - 40 patients will be operated with thoracoscopic ectomy for a pulmonary nodule. When localisation of the nodule is not possible a switch to minithoracotomy is performed.

Study intervention Marking of pulmonary nodules with radioactivity. Free-hand SPECT guided surgery

Risks Risks of bronchoscopic or CT-intervention Radiation risk (minimal)

Rational for patient number 10 patients for each group are enough to prove the feasibility, to manage difficulties and to record complications

Duration approximately 24 months.


Eligibility criteria: Inclusion Criteria:

* age over 18 years
* Planed thoracoscopic surgery of a pulmonary nodule
* Informed consent

Exclusion Criteria:

* mental incapacity
* contraindications for this treatment
* pregnancy

Primary outcomes:
measure: Successful thoracoscopic ectomies
timeFrame: 1 week
Secondary outcomes:
measure: CT labelling
timeFrame: 1 day
measure: CT Labelling complications
timeFrame: 1 day
measure: Successful labeling using electro-magnetically navigated bronchoscopy
timeFrame: 1 day
measure: Complications after labeling using electro-magnetically navigated bronchoscopy
timeFrame: 1 day
Other outcomes:
Locations:
city: St. Gallen
country: Switzerland
facility: Cantonal Hospital St.Gallen
Study officials:
affiliation: Cantonal Hospital St. Gallen
name: Joachim Müller, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Muller J, Putora PM, Schneider T, Zeisel C, Brutsche M, Baty F, Markus A, Kick J. Handheld single photon emission computed tomography (handheld SPECT) navigated video-assisted thoracoscopic surgery of computer tomography-guided radioactively marked pulmonary lesions. Interact Cardiovasc Thorac Surg. 2016 Sep;23(3):345-50. doi: 10.1093/icvts/ivw136. Epub 2016 May 20.