Retinal light sensitivity as outcome measure in recessive Stargardt disease

Background/aimsTo evaluate the applicability of mesopic light sensitivity measurements obtained by fundus-controlled perimetry (FCP, also termed ‘microperimetry’) as clinical trial endpoint in Stargardt disease (STGD1).MethodsIn this retrospective, monocentre cohort study, 271 eyes of 136 patients (age, 37.1 years) with STGD1 and 87 eyes of 54 healthy controls (age, 41.0 years) underwent mesopic FCP, using a pattern of 50 stimuli (achromatic, 400–800 nm) centred on the fovea. The concurrent validity of mesopic FCP testing using the MAIA device (CenterVue, Italy), the retest variability and its determinants, and the progression of sensitivity loss over time were investigated using mixed-model analyses. The main outcomes were the average pointwise sensitivity loss in dependence of patients’ demographic, functional and imaging characteristics, the intrasession 95% coefficient of repeatability, and the pointwise sensitivity loss over time.ResultsPointwise sensitivity loss was on average (estimate (95% CI)) 13.88 dB (12.55 to 15.21) along the horizontal meridian and was significantly associated with the electrophysiological subgroup, presence/absence of foveal sparing, best-corrected visual acuity and disease duration. The 95% coefficient of repeatability was 12.15 dB (10.78 to 13.38) and varied in dependence of the underlying mean sensitivity and local sensitivity slope. The global progression rate for the sensitivity loss was 0.45 dB/year (0.13 to 0.78) and was higher for the central and inner ETDRS subfields compared with more peripheral regions.ConclusionsMesopic light sensitivity measured by FCP is reliable and susceptible for functional changes. It constitutes a potential clinical outcome for both natural history studies as well as future interventional studies in patients with STGD1.

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Multidisciplinary Evaluation of Pacifier Removal on Oro-Dentofacial Structures: A Controlled Clinical Trial

Frontiers in Pediatrics ◽

10.3389/fped.2021.703695 ◽

2021 ◽

Vol 9 ◽

Author(s):

Kelly Guedes de Oliveira Scudine ◽

Camila Nobre de Freitas ◽

Kizzy Silva Germano Nascimento de Moraes ◽

Silvana Bommarito ◽

Rosana de Fátima Possobon ◽

...

Keyword(s):

Clinical Trial ◽

Mixed Model ◽

Control Group ◽

Controlled Clinical Trial ◽

Functional Changes ◽

Mixed Model Anova ◽

And Function ◽

Clinical Trials Registry ◽

Facial Anthropometry ◽

Over Time

It is well recognized that pacifier habit leads to occlusal and orofacial functional changes in children. However, the effects of the interruption of prolonged pacifier habit on the development of the dento-facial complex has not yet been fully characterized. Thus, the aim of this study was to investigate the influence of pacifier removal on aspects of oro-dentofacial morphology and function in preschool children. For that, a pacifier group (n = 28) and a control group (n = 32) of 4-year-old children with and without pacifier habit, respectively, were followed up by a group of dentists and speech therapists at baseline, 6 and 12 months after habit removal. Bite force and lip pressure were assessed using digital systems, and the evaluation of breathing and speech functions was performed using validated protocols, together with the measurements of dental casts and facial anthropometry. The Two-way mixed model ANOVA was used in data analysis. After 12 months, a decrease in malocclusion frequency was observed in pacifier group. Additionally, a change over time was observed in facial, intermolar and palate depth measurements, as well in bite and lip forces and speech function scores, increasing in both groups (p < 0.01). The upper and lower intercanine widths and breathing scores differed between groups at baseline and changed over time reducing the differences. The presence of speech distortions was more frequent in the pacifier group at baseline and decreased over time (p < 0.05). The interruption of pacifier habit improved the maxillary and mandibular intercanine widths, as well as the breathing and speech functions, overcoming the oro-dentofacial changes found.Trial Registration: This clinical trial was registered in the Brazilian Clinical Trials Registry (ReBEC; http://www.ensaiosclinicos.gov.br/), protocol no. RBR-728MJ2.

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Factors associated with professional identity formation within psychiatry residency training: A longitudinal study

Perspectives on Medical Education ◽

10.1007/s40037-021-00673-w ◽

2021 ◽

Author(s):

Qian Hui Chew ◽

Yvonne Steinert ◽

Kang Sim

Keyword(s):

Professional Identity ◽

Identity Formation ◽

Psychiatry Residency ◽

Mixed Model ◽

Linear Mixed Model ◽

Developmental Stages ◽

Rate Of Change ◽

Psychiatry Residents ◽

Factors Associated ◽

Over Time

Abstract Introduction Conceptual frameworks for professional identity (PI) formation highlight the importance of developmental stages and socialization as the learner progresses from legitimate peripheral to full participation. Based on extant literature and clinical impressions, the authors aimed to explore factors associated with PI formation in psychiatry residents over time, and hypothesized that time in training, seniority status, and duration of exposure to psychiatry prior to residency would be associated with PI formation. Methods Eighty out of 96 psychiatry residents (response rate, 83.3%) from the National Psychiatry Residency Program in Singapore participated and rated their PI development using the Professional Self Identity Questionnaire (PSIQ) across four timepoints from January 2016–December 2019. The residents were classified as junior (first 3 years) or senior residents (years 4–5). Linear mixed model analyses were conducted, with time in training, seniority status (junior versus senior residents), duration of psychiatry postings prior to residency, and their interaction as associated factors with PI over time. Results Time in training, seniority, and duration of psychiatry postings before residency (all p < 0.01) were significantly associated with higher PSIQ scores at baseline. Over time, although all residents had increases in PSIQ scores, this rate of change did not differ significantly between junior and senior residents. Discussion Exposure to psychiatry postings before residency, time in learning, and seniority are factors which influence PI development in residents. This has implications for psychiatry residency selection and training, adequate clinical exposure during training rotations, and continual support for new and senior residents to foster PI formation over time.

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Improvement in prefrontal thalamic connectivity during the early course of the illness in recent-onset psychosis: a 12-month longitudinal follow-up resting-state fMRI study

Psychological Medicine ◽

10.1017/s0033291720004808 ◽

2020 ◽

pp. 1-9

Author(s):

Daniel Bergé ◽

Tyler A. Lesh ◽

Jason Smucny ◽

Cameron S. Carter

Keyword(s):

Resting State ◽

Resting State Fmri ◽

Functional Changes ◽

Recent Onset ◽

Fmri Study ◽

Clinical Meaning ◽

Mixed Pattern ◽

The Right ◽

Over Time

Abstract Background Previous research in resting-state functional magnetic resonance imaging (rs-fMRI) has shown a mixed pattern of disrupted thalamocortical connectivity in psychosis. The clinical meaning of these findings and their stability over time remains unclear. We aimed to study thalamocortical connectivity longitudinally over a 1-year period in participants with recent-onset psychosis. Methods To this purpose, 129 individuals with recent-onset psychosis and 87 controls were clinically evaluated and scanned using rs-fMRI. Among them, 43 patients and 40 controls were re-scanned and re-evaluated 12 months later. Functional connectivity between the thalamus and the rest of the brain was calculated using a seed to voxel approach, and then compared between groups and correlated with clinical features cross-sectionally and longitudinally. Results At baseline, participants with recent-onset psychosis showed increased connectivity (compared to controls) between the thalamus and somatosensory and temporal regions (k = 653, T = 5.712), as well as decreased connectivity between the thalamus and left cerebellum and right prefrontal cortex (PFC; k = 201, T = −4.700). Longitudinal analyses revealed increased connectivity over time in recent-onset psychosis (relative to controls) in the right middle frontal gyrus. Conclusions Our results support the concept of abnormal thalamic connectivity as a core feature in psychosis. In agreement with a non-degenerative model of illness in which functional changes occur early in development and do not deteriorate over time, no evidence of progressive deterioration of connectivity during early psychosis was observed. Indeed, regionally increased connectivity between thalamus and PFC was observed.

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Decline of ovarian function in patients with rheumatoid arthritis: serum anti-Müllerian hormone levels in a longitudinal cohort

RMD Open ◽

10.1136/rmdopen-2020-001307 ◽

2020 ◽

Vol 6 (3) ◽

pp. e001307

Author(s):

Jenny Brouwer ◽

Radboud J E M Dolhain ◽

Johanna M W Hazes ◽

Nicole S Erler ◽

Jenny A Visser ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Mixed Model ◽

Linear Mixed Model ◽

Ovarian Function ◽

Reproductive Function ◽

Related Factors ◽

Original Cohort ◽

Primordial Follicles ◽

Age At Menopause ◽

Over Time

ObjectiveRheumatoid arthritis (RA) often affects women in their fertile age, and is known to compromise female fertility. Serum anti-Müllerian hormone (AMH) levels are a proxy for the total number of primordial follicles, and a reliable predictor of the age at menopause. Our objective was to study the longitudinal intra-individual decline of serum AMH levels in female RA patients.MethodsFemale RA patients from a nationwide prospective cohort (2002–2008) were re-assessed in 2015–2016. Serum AMH levels were measured using the picoAMH assay and compared with healthy controls. A linear mixed model (LMM) was built to assess the effect of RA-related clinical factors on the decline of AMH levels.ResultsA group of 128 women were re-assessed at an age of 42.6±4.4 years, with a median disease duration of 15.8 (IQR 12.7–21.5) years. The time between first and last AMH assessments was 10.7±1.8 (range 6.4–13.7) years. Participants represented a more fertile selection of the original cohort. At follow-up, 39% of patients had AMH levels below the 10th percentile of controls (95% CI 31% to 48%), compared with 16% (95% CI 9.3% to 22%) at baseline. The LMM showed a significant decline of AMH with increasing age, but no significant effect of RA-related factors on AMH.ConclusionAMH levels in RA patients showed a more pronounced decline over time than expected, supporting the idea that in chronic inflammatory conditions, reproductive function is compromised, resulting in a faster decline of ovarian function over time and probably an earlier age at menopause.

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Mood and Global Symptom Changes among Psychotherapy Clients with Depressive Personality

Depression Research and Treatment ◽

10.1155/2012/208435 ◽

2012 ◽

Vol 2012 ◽

pp. 1-12

Author(s):

Rachel E. Maddux ◽

Lars-Gunnar Lundh

Keyword(s):

Repeated Measures ◽

Mixed Model ◽

Psychological Symptoms ◽

Self Report ◽

Treatment Results ◽

Repeated Measures Analysis ◽

Depressive Personality ◽

Symptom Changes ◽

Psychotherapy Clients ◽

Over Time

The present study assessed the rate of depressive personality (DP), as measured by the self-report instrument depressive personality disorder inventory (DPDI), among 159 clients entering psychotherapy at an outpatient university clinic. The presenting clinical profile was evaluated for those with and without DP, including levels of depressed mood, other psychological symptoms, and global severity of psychopathology. Clients were followed naturalistically over the course of therapy, up to 40 weeks, and reassessed on these variables again after treatment. Results indicated that 44 percent of the sample qualified for DP prior to treatment, and these individuals had a comparatively more severe and complex presenting disposition than those without DP. Mixed-model repeated-measures analysis of variance was used to examine between-groups changes on mood and global severity over time, with those with DP demonstrating larger reductions on both outcome variables, although still showing more symptoms after treatment, than those without DP. Only eleven percent of the sample continued to endorse DP following treatment. These findings suggest that in routine clinical situations, psychotherapy may benefit individuals with DP.

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Using Redox Potential as a Feasible Marker for Banked Blood Quality and the State of Oxidative Stress in Stored Red Blood Cells

10.21203/rs.3.rs-104378/v1 ◽

2020 ◽

Author(s):

Rodney C Daniels ◽

Hyesun Jun ◽

Robertson D Davenport ◽

Maryanne M Collinson ◽

Kevin R Ward

Keyword(s):

Oxidative Stress ◽

Redox Potential ◽

Red Blood Cells ◽

Healthy Volunteers ◽

Blood Cells ◽

Storage Time ◽

Cell Function ◽

Venous Blood ◽

Functional Changes ◽

Over Time

Abstract Background Stored Red Blood Cells (RBCs) may undergo oxidative stress over time, with functional changes affecting critical tasks such as oxygen delivery. Central to these changes are oxidation-reduction (redox) reactions and the redox potential (RP) that must be maintained for proper cell function. RP imbalance can lead to oxidative stress that may contribute to storage lesions and transfusion-related morbidities. Direct measures of RP may allow for evaluation of erythrocyte quality and enable corrections of RP prior to transfusion. Methods Multiple random RBC segments were tested, ranging in age from 5 to 40 days at 5 day intervals. RP was recorded by measuring open circuit potential of RBCs using novel nanoporous gold electrodes with Ag/AgCl reference. RP measures were also performed on peripheral venous blood samples from 10 healthy volunteers. RP measures were compared between groups of aged RBCs, and with volunteer blood. Results Stored RBCs show time-dependent increases in RP. There were significant differences in Day 5 RP compared to all other groups (p≤0.005), Day 10-15 vs ages ≥ Day 20 (p≤0.025), Day 20-25 vs Day 40 (p=0.039), and all groups compared to healthy volunteers. RP became more positive over time suggesting ongoing oxidation as RBCs age. However, storage time alone does not predict the ultimate RP value measured from a given unit.Conclusions There are significant differences in RP between freshly stored RBCs and all others, with RP becoming more positive over time. However, storage time alone does not predict RP, indicating RP screening may be important independent of storage time and may serve as a marker of RBC quality and state of oxidative stress. RP measurements may also provide a target by which to restore RP balance in aged pRBCs, improving their clinical effectiveness while reducing associated morbidities.

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Fibrinolysis after an Elective Caesarean Section without Postpartum Hemorrhage: Pilot Study for Reference Values from the Simultaneous Thrombin and Plasmin Generation Assays

Austin Hematology ◽

10.26420/austinhematol.2021.1035 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Ducloy-Bouthors A S ◽

◽

Lassalle F ◽

Gilliot S ◽

Kyheng M ◽

...

Keyword(s):

Blood Loss ◽

Postpartum Hemorrhage ◽

Mixed Model ◽

Elective Caesarean Section ◽

Individual Variability ◽

Elective Cesarean Section ◽

Time Interval ◽

Simultaneous Generation ◽

D Dimer ◽

Over Time

ntroduction: Postpartum Hemorrhage (PPH)-induced coagulopathy should be better explored. An innovative Simultaneous Generation of Thrombin and Plasmin Assay (SGTPA) was developed. Objective: To establish postpartum SGTPA references. Methods: Blood samples collected immediately after delivery (T0) and then 30, 60, 120 and 360 minutes later. Thrombin Generation (TG) and Plasmin Generation (PG) changes over time analyzed in 51 women after elective cesarean section without PPH and compared with Non-Pregnant (NP) women. The SGTPA variables’ correlations with fibrinogen levels, D-dimer levels and physiological blood loss were assessed in a mixed model. Results: 37 women were included. TG and PG were higher in the postpartum group than in the NP group. TG increased early and then remained stable (baseline TG Area Under the Curve (AUC) [95% Confidence Interval (CI)] = 41037 [36850-43537] nM.min). The fibrinogen level varied over time, along with TG (p<0.001). Plasmin generation increased from 30 to 120 minutes (AUC [95% CI]: 2104 [1437; 2613] nM.min), along with a change in the D-dimer level (p=0.018). The time to the plasmin peak and the time interval between the TG and PG peaks showed the greatest inter-individual variability at T0 and were associated with physiological volumes of blood loss during cesarean delivery. Conclusion: Reference SGTPA postpartum range was established. The SGTPA appears to be valuable for measuring TG and PG. TG and coagulation activation increased immediately after delivery, whereas PG and fibrinolysis increased later.

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The Multiple Sclerosis Severity Score: fluctuations and prognostic ability in a longitudinal cohort of patients with MS

Multiple Sclerosis Journal - Experimental Translational and Clinical ◽

10.1177/2055217319837254 ◽

2019 ◽

Vol 5 (1) ◽

pp. 205521731983725 ◽

Cited By ~ 2

Author(s):

RH Gross ◽

SH Sillau ◽

AE Miller ◽

C Farrell ◽

SC Krieger

Keyword(s):

Multiple Sclerosis ◽

Severity Score ◽

Mixed Model ◽

Linear Models ◽

Longitudinal Cohort ◽

Kaplan Meier ◽

The Individual ◽

Survival Plot ◽

The Impact ◽

Over Time

Background The Multiple Sclerosis Severity Score (MSSS), combining the Expanded Disability Status Scale (EDSS) and disease duration, attempts to stratify multiple sclerosis (MS) patients based on their rate of progression. Its prognostic ability in the individual patient remains unproven. Objectives To assess the stability of MSSS within individual persons with MS in a longitudinal cohort, to evaluate whether certain factors influence MSSS variability, and to explore the ability of MSSS to predict future ambulatory function. Methods A single-center retrospective review was performed of patients following a single provider for at least 8 years. Mixed model regression modeled MSSS over time. A Kaplan–Meier survival plot was fitted, using change of baseline MSSS by at least one decile as the event. Cox modeling assessed the influence of baseline clinical and demographic factors on the hazard of changing MSSS by at least one decile. Linear models evaluated the impact of baseline EDSS, baseline MSSS, and other factors on the Timed 25-Foot Walk (T25FW). Results Out of 122 patients, 68 (55.7%) deviated from baseline MSSS by at least one decile. Final T25FW had slightly weaker correlation to baseline MSSS than to baseline EDSS, which was moderately strongly correlated with future log T25FW. Conclusion Individual MSSS scores often vary over time. Clinicians should exercise caution when using MSSS to prognosticate.

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Impacts of rTMS on Refractory Depression and Comorbid PTSD Symptoms at a Military Treatment Facility

Military Medicine ◽

10.1093/milmed/usaa148 ◽

2020 ◽

Vol 185 (9-10) ◽

pp. e1420-e1427

Author(s):

Sean Wilkes ◽

Celia Ona ◽

Michael Yang ◽

Pingyang Liu ◽

Amber Benton ◽

...

Keyword(s):

Repeated Measures ◽

Mixed Model ◽

Repetitive Transcranial Magnetic Stimulation ◽

Active Duty ◽

Ptsd Symptoms ◽

Refractory Depression ◽

Antidepressant Medications ◽

Treatment Of Depression ◽

Changes Over Time ◽

Over Time

Abstract Introduction Repetitive transcranial magnetic stimulation (rTMS) as a treatment for depression has been studied for over two decades. Repetitive TMS was approved by the Food and Drug Administration in 2008 for the treatment of depression after at least one failed trial of an antidepressant medication of adequate dose and duration. This study evaluated whether rTMS treatments may be associated with measurable improvements in depression and post-traumatic stress disorder (PTSD) symptoms for treated military beneficiaries in Hawaii suffering from depression. It also examined the number of failed medication trials that patients underwent before rTMS treatment. Materials and Methods A retrospective chart review of 77 rTMS patients who received and completed treatment between January 1, 2010 and October 31, 2016 was performed. Under a typical treatment regimen, patients receive rTMS for 6 weeks as well as weekly psychiatric assessments, which included completion of Beck’s Depression Inventory (BDI) and PTSD Checklist (PCL). A mixed model repeated measures analysis was done assuming an autoregressive order one covariance structure to evaluate changes over time. Adjusted analyses were done to assess whether changes over time differed by age, prior diagnosis of PTSD, active duty status, and gender. Results The majority of patients were from the army (74%) and 56% were on active duty. Just over half (53%) were male. Most patients (52%) had completed trials of three or more different antidepressant medications before initiation of treatment with rTMS. The mean number of antidepressant trials was 2.7. BDI and PCL scores were significantly lower at end of treatment on average compared to the pretreatment baseline scores. Mean differences for BDI and PCL were significant with P < 0.001 15, 30, and 45 days after TMS treatment was initiated. Overall, 44% of patients experienced a reduction ≥10 points on BDI, and 38% experienced a reduction ≥10 points on PCL. Additionally, scores fell similarly regardless of whether or not patients had a comorbid diagnosis of PTSD. Conclusions Our research suggests that rTMS treatments may produce a reduction in symptoms of both depression and PTSD in patients with refractory depression and comorbid PTSD. It may be a useful alternative to antidepressants in the treatment of depression in the military population, including those with comorbid PTSD. Broader implementation of this treatment modality may prove beneficial for the purposes of military readiness, given current policies and restrictions on service members who are initiated on antidepressant medications.

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