Author Interviews, Depression, Gender Differences, NIH / 27.10.2014

Dr. Sunni Mumford PhD Earl Stadtman Investigator in the DESPR Epidemiology Branch Eunice Kennedy Shriver National Institute of Health and Human DevelopmentMedicalResearch.com Interview with: Dr. Sunni Mumford PhD Earl Stadtman Investigator in the DESPR Epidemiology Branch Eunice Kennedy Shriver National Institute of Health and Human Development Medical Research: What are the main findings of the study? Dr. Mumford: Depressive symptoms in healthy women who don’t have diagnosed clinical depression isn’t related to reproductive hormone levels, like estrogen, or impaired ovulation. Medical Research: What was most surprising about the results? Dr. Mumford: Earlier research indicates that changes in estrogen may be associated with depression, for instance during the menopausal transition. Our study identified significant associations between estrogen and depressive symptoms in models that didn’t account for confounding factors, but this relationship was completed eliminated when adjustments were made for common confounding factors like age, race, BMI, and also stress level in these premenopausal women. Another interesting finding was that a score describing mood-related menstrual symptoms indicated that such symptoms are highest in the premenstrual phase, but remain lower throughout the rest of women’s cycles. This tells us that altered mood symptoms are most frequent prior to menstruation. (more…)
Author Interviews, Depression, Heart Disease / 24.10.2014

MedicalResearch.com Interview with: Professor Pranas Serpytis Vilnius University Hospital Santariskiu Clinic Vilnius, Lithuania Medical Research: What are the main findings of the study? Professor Serpytis: The main findings of the study were that women are more likely to develop anxiety and depression after acute myocardial infarction. In our study depression was assessed by HADS scale: no depression (0-7 score), possible depression (8-10 score), definite depression (11+ score). The mean score of assessing depression were 6.87 (± 4.6) among men and 8.66 (± 3.7) among women (p <.05). Cardiovascular disease risk factors such as smoking increases patients anxiety levels, and low physical activity is associated with an increased risk to suffer from depression. Medical Research: What was most surprising about the results? Professor Serpytis: Most surprising about the results were that for women it is indeed more difficult to cope with the disease rather than for men. Women’s anxiety and depression rates are higher. Medical Research: What should clinicians and patients take away from your report? Professor Serpytis: Clinicians and patients should look after the possible symptoms and if needed refer the patients for psychologist or psychiatrist consultation in order get proper timely treatment. This could possibly improve the long-term treatment results. Medical Research: What recommendations do you have for future research as a result of this study? Professor Serpytis: Most definitely more research is needed in this field. Most importantly it is crucial to look for the impact of depression on the long-term effects on survival and general well-being. Citation: Women more likely to develop anxiety and depression after heart attack Acute Cardiovascular Care Association (ACCA) of the European Society of Cardiology (ESC) and takes place 18-20 October in Geneva, Switzerland.MedicalResearch.com Interview with: Professor Pranas Serpytis Vilnius University Hospital Santariskiu Clinic Vilnius, Lithuania Medical Research: What are the main findings of the study? Professor Serpytis: The main findings of the study were that women are more likely to develop anxiety and depression after acute myocardial infarction. In our study depression was assessed by HADS scale: no depression (0-7 score), possible depression (8-10 score), definite depression (11+ score). The mean score of assessing depression were 6.87 (± 4.6) among men and 8.66 (± 3.7) among women (p <.05). Cardiovascular disease risk factors such as smoking increases patients anxiety levels, and low physical activity is associated with an increased risk to suffer from depression. (more…)
Author Interviews, Depression, JAMA / 23.09.2014

A001_C001_03160QMedicalResearch.com Interview with: Dr. Philippe Courtet MD PhD Centre Hospitalier Régional Universitaire de Montpellier, Institut National de la Santé et de la Récherche Médicale , Université Montpellier, Montpellier, France Fondation Fondamental, Créteil, France Medical Research: What are the main findings of the study? Dr. Courtet: Depressed outpatients who are beginning the treatment with a SSRI at higher dose than recommended present an increased risk (x2) of worsening of suicidal ideation during the first 6 weeks of treatment. This is consistent with the study by Miller et al published in the same journal few weeks ago, reporting a double risk of suicide attempt in young subjects (<24 yrs) who are begun an SSRI at higher dose than recommended. Our results showed that the increased suicide risk with the high dose of SSRI is not restricted to youngsters and is independent of the severity of the depression. (more…)
Author Interviews, Depression, End of Life Care / 04.09.2014

MedicalResearch.com Interview with: Nenette M. Jessup MPH, CCRP Research Associate/Project Manager TASK II Indiana University School of Nursing Indianapolis, IN 46202 Medical Research: What are the main findings of the study? Dr. Jessup: Similar to others, we found that females and non-African American caregivers experienced more depressive symptoms and females perceived greater task difficulty. Because female caregivers comprise the largest group of caregivers in the United States, the consistency of this finding has implications for continued social policy efforts to improve their plight. However, our results also suggested an interaction effect between race and type of relationship, with African American spouses experiencing the most difficulty with tasks of caregiving. Inconsistencies in the existing literature about this finding signal the need for a greater understanding of group differences. Individualized interventions may also be of benefit for stroke caregivers. (more…)
Author Interviews, Depression, Journal Clinical Oncology, Metabolic Syndrome, Prostate Cancer / 14.07.2014

MedicalResearch.com with: Sandip M. Prasad MD Assistant Professor Medical University of South Carolina, Charleston, SCSandip M. Prasad MD Assistant Professor Medical University of South Carolina, Charleston, SC and Scott E. Eggener, MD Associate Professor of Surgery Co-Director, Prostate Cancer Program Director of Translational and Outcomes Research, Section of Urology University of Chicago Medical Center, Chicago, IL;Scott E. Eggener, MD Associate Professor of Surgery Co-Director, Prostate Cancer Program Director of Translational and Outcomes Research, Section of Urology University of Chicago Medical Center, Chicago, IL; Medical Research: What are the main findings of the study? Answer: Depressed men with a diagnosis of intermediate- or high-risk prostate cancer have worse overall outcomes than those without baseline depression and are less likely to undergo definitive therapy. The difference in overall survival between men with and without a depression diagnosis was independent of prostate cancer treatment type. (more…)
Author Interviews, Depression, Heart Disease / 19.06.2014

Dr. Amit J.Shah MD Assistant Research Professor Assistant Professor, Department of Epidemiology Emory, Rollins School of Public HealthMedicalResearch.com: Interview with Dr. Amit J.Shah MD Assistant Research Professor Assistant Professor, Department of Epidemiology Emory, Rollins School of Public Health MedicalResearch: What are the main findings of the study? Dr. Shah: We discovered that in a group of patients who were undergoing heart evaluation with coronary angiography, symptoms of depression predicted increased risk of coronary artery disease and death in women aged 55 years or less. This relationship was stronger in these women than older women, as well as in men aged 55 years or less. Over 1 in 4 women aged 55 years or less had moderate to severe depression, which was higher than any other group; these women had over twice the risk of having heart disease or dying over the next 3 years compared to those with none or mild depression. (more…)
Author Interviews, Depression, Heart Disease, NEJM, OBGYNE / 19.06.2014

Dr. Krista Huybrechts MD PhD Brigham & Women’s Hospital Department of Medicine Division of Pharmacoepidemiology & Pharmacoeconomics Boston, MA 02120MedicalResearch.com Interview Invitation Dr. Krista Huybrechts MD PhD Brigham & Women’s Hospital Department of Medicine Division of Pharmacoepidemiology & Pharmacoeconomics Boston, MA 02120 MedicalResearch: What are the main findings of the study? Dr. Huybrechts: In this cohort study including 949,504 pregnant women enrolled in Medicaid, we examined whether the use of selective serotonin reuptake inhibitors (SSRIs) and other antidepressants during the first trimester of pregnancy is associated with increased risks for congenital cardiac defects. In order to control for potential confounding by depression and associated factors, we restricted the cohort to women with a depression diagnosis and used propensity score adjustment to control for depression severity and other potential confounders. We found no substantial increased risk of cardiac malformations attributable to SSRIs. Relative risks for any cardiac defect were 1.25 (95%CI, 1.13-1.38) unadjusted, 1.12 (1.00-1.26) depression-restricted, and 1.06 (0.93-1.22) depression-restricted and fully-adjusted. We found no significant associations between the use of paroxetine and right ventricular outflow tract obstruction (1.07, 0.59-1.93), or the use of sertraline and ventricular septal defects (1.04, 0.76-1.41); two potential associations that had been of particular concern based on previous research findings. (more…)
Author Interviews, Depression, JAMA, Weight Research / 06.06.2014

MedicalResearch.com Interview with: Aurélie Lasserre ,MD Center for psychiatric epidemiology and psychopathology Department of Psychiatry Lausanne University Hospital (CHUV) Site de Cery, Switzerland MedicalResearch: What are the main findings of this study? Dr. Lasserre: Several recent studies have shown that Major Depressive Disorder with atypical features (defined as having a depressive episode where mood reactivity is maintained and two of the following features: increase in appetite, hypersomnia (oversleeping), leaden paralysis (heavy limbs) and increased sensitivity to rejection) was associated with obesity, but the temporal sequence was not known, i.e. it was not clear whether atypical depression predisposes to obesity or the converse. Our study revealed that Major Depressive Disorder with atypical features does lead to an increase in body-mass index, obesity, waist circumference and fat mass over a period of 5 years. This result was not explained by socio-demographic characteristics, alcohol or tobacco consumption, physical activity, co-existing mental disorders or medication. Interestingly, we also observed that the weight gain in subjects with atypical features was not a temporary phenomenon but it persisted after the remission of the depressive episode and was not attributable to new episodes. (more…)
Author Interviews, Depression, Pediatrics, PLoS, Psychological Science / 29.03.2014

MedicalResearch.com Interview with: Dr. Prof. Natalia N. Kudryavtseva Head of Neurogenetics of Social Behavior Sector, Institute of Cytology and Genetics SD RAS, Novosibirsk, Russia MedicalResearch.com: What are the main findings of the study? Answer: Hostile environment and social instability stress can have a significant impact on adolescents, causing the development of anxiety and depression. (more…)
Author Interviews, Depression, Hearing Loss, JAMA / 12.03.2014

Dr. Chuan-Ming Li MD, PhD Statistician (Health/Medicine) Division of Scientific Programs The National Institute on Deafness and Other Communication DisordersMedicalResearch.com Interview with: Dr. Chuan-Ming Li MD, PhD Statistician (Health/Medicine) Division of Scientific Programs The National Institute on Deafness and Other Communication Disorders MedicalResearch.com: What are the main findings of the study? Dr. Chuan-Ming Li: We used data on adults 18 years or older from the National Health and Nutrition Examination Survey for the study and found that prevalence of moderate to severe depression was 4.9 percent for individuals who reported excellent hearing, 7.1 percent for those with good hearing and 11.4 percent for participants who reported having a little hearing trouble or greater hearing impairment (HI). Depression rates were higher in women than in men. The prevalence of depression increased as hearing impairment became worse, except among participants who were deaf. There was no association between self-reported HI and depression among people ages 70 years and older; however, an association between moderate HI measured by pure-tone threshold hearing exams and depression was found in women aged 70 years and older but not in men. (more…)
Author Interviews, Depression, Diabetes, Diabetes Care / 26.02.2014

Steven A. Safren, Ph.D., ABPP Professor of Psychology, Harvard Medical School Director, Behavioral Medicine, Department of Psychiatry Massachusetts General Hospital, Boston, MA 02114MedicalResearch.com Interview with: Steven A. Safren, Ph.D., ABPP Professor of Psychology, Harvard Medical School Director, Behavioral Medicine, Department of Psychiatry Massachusetts General Hospital, Boston, MA 02114 MedicalResearch.com: What are the main findings of the study? Dr. Safren:  The main findings of the study are that, in patients with uncontrolled type 2 diabetes and depression, a type of psychological treatment, cognitive behavioral therapy (CBT) that addressed both self-care and depression, resulted in improvements in both depressed mood, self-care, and glucose control.  This was a randomized controlled trial, and this cognitive-behavioral treatment worked better than lifestyle adherence and nutrition counseling alone; and the effects were sustained over 8 months. (more…)
Author Interviews, Depression, Diabetes, Diabetologia, Weight Research / 07.02.2014

Dr Peter de Jonge Interdisciplinary Center for Psychopathology and Emotion Regulation, University Medical Center Groningen, University of Groningen, NetherlandsMedicalResearch.com Interview with: Dr Peter de Jonge Interdisciplinary Center for Psychopathology and Emotion Regulation, University Medical Center Groningen, University of Groningen, Netherlands MedicalResearch.com: What are the main findings of the study? Dr. de Jonge: The main findings were that depression and impulse control disorders, in particular binge eating and bulimia were associated with diabetes. (more…)
Author Interviews, Depression, JAMA, Johns Hopkins, Mental Health Research, Pain Research / 07.01.2014

Madhav Goyal MD, MPH Assistant Professor General Internal Medicine Johns Hopkins School of MedicineMedicalResearch.com Interview with: Madhav Goyal MD, MPH  Assistant Professor General Internal Medicine Johns Hopkins School of Medicine MedicalResearch.com: What are the main findings of the study? Dr. Goyal:
  • The evidence is moderately strong that there is a small but consistent benefit for mindfulness meditation programs to improve 3 symptoms: anxiety, depression, and pain.  We found low level evidence that mindfulness meditation helps with symptoms of stress and distress, as well as with the mental health dimension of quality of life.
  • For the symptoms of anxiety and depression for which we find moderate evidence of benefit, we need to keep in mind that most of the trials didn't study people with a clinical diagnosis of anxiety or depression (although a few did).  Most were studying diverse patient populations who may have had a low level of these symptoms, such as those with  breast cancer, fibromyalgia, organ transplant recipients, and caregivers of people with dementia.
  • We found about a 5-10% improvement in anxiety symptoms compared to placebo groups.  For depression, we found a roughly 10-20% improvement in depressive symptoms compared to the placebo groups. This is similar to the effects that other studies have found for the use of antidepressants in similar populations.
  • While we found that the evidence was moderately strong that mindfulness meditation programs may improve pain, there weren't as many trials evaluating chronic pain, and so we don't understand what kinds of pain this type of meditation may be most useful for.
(more…)
Author Interviews, Depression, Education, End of Life Care, JAMA, Stanford / 06.12.2013

J. Randall Curtis, MD, MPH Professor of Medicine Director, UW Palliative Care Center of Excellence Section Head, Pulmonary and Critical Care Medicine, Harborview Medical CenterA. Bruce Montgomery, M.D. – American Lung Association Endowed Chair in Pulmonary and Critical Care Medicine University of Washington, Seattle, WA 98104MedicalResearch.com Interview with: J. Randall Curtis, MD, MPH Professor of Medicine Director, UW Palliative Care Center of Excellence Section Head, Pulmonary and Critical Care Medicine, Harborview Medical CenterA. Bruce Montgomery, M.D. – American Lung Association Endowed Chair in Pulmonary and Critical Care Medicine, University of Washington, Seattle, WA 98104 MedicalResearch.com: What are the main findings of the study? Dr. Curtis: We examined the effect of a communication-skills intervention for internal medicine and nurse practitioner trainees on patient- and family-reported outcomes.  The study was funded by the National Institutes of Nursing Research of the National Institutes of Heatlh.  We conducted a randomized trial with 391 internal medicine and 81 nurse practitioner trainees at two universities.  Participants were randomized to either an 8-session simulation-based, communication-skills intervention or to usual education.  We collected outcome data from a large number of patients with life-limiting illness and their families, including 1866 patient ratings and 936 family ratings.  The primary outcome was patient-reported quality of communication and, overall, this outcome did not change with the intervention.  However, when we restricted our analyses to only patients who reported their own health status as poor, the intervention was associated with increased communication ratings. Much to our surprise, the intervention was associated with a small but significant increase in depression scores among post-intervention patients.  Overall, this study demonstrates that among internal medicine and nurse practitioner trainees, simulation-based communication training compared with usual education improved communication skills acquisition, but did not improve quality of communication about end-of-life care for all patients.  However, the intervention was associated with improved patient ratings of communication for the sickest patients. Furthermore, the intervention was associated with a small increase in patients’ depressive symptoms, and this appeared most marked among patients of the first-year residents. (more…)
Author Interviews, Depression, General Medicine, PLoS / 25.11.2013

Alize J. Ferrari University of Queensland School of Population Health Herston, Queensland, AustraliaMedicalResearch.com Interview with: Alize J. Ferrari University of Queensland School of Population Health Herston, Queensland, Australia MedicalResearch.com: What are the main findings of the study? Answer: In our paper recently published in PloS Medicine, we report findings from the Global Burden of Disease Study 2010 for depression. We found that depression (defined as major depressive disorder and dysthymia) accounted fr 8% of the non fatal burden in 2010, making it the second leading cause of disability worldwide. Burden due to depression increased by 35% between 1990 and 2010, although this increase was entirely driven by population growth and ageing. Burden occurred across the entire lifespan, was higher in females compared to males, and there were differences between world regions.When depression was considered a risk factor for other health outcomes it explained 46% of the burden allocated to suicide and 3% of the burden allocated ischemic heart disease. (more…)
Author Interviews, Depression, JAMA / 07.11.2013

Richard L. Kravitz, MD, MSPH Professor and Co-vice Chair (Research) Interim Director, UC Center Sacramento Co-Editor in Chief, Journal of General Internal MedicineMedicalResearch.com Interview with: Richard L. Kravitz, MD, MSPH Professor and Co-vice Chair (Research) Interim Director, UC Center Sacramento Co-Editor in Chief, Journal of General Internal Medicine MedicalResearch.com: What is the background for your study? Dr. Kravitz: Depression in the United States is both undertreated and overtreated.  As the de facto mental health care system for many, primary care is at the nexus of this problem.  Up to 30% of patients with major depression in primary care go undiagnosed.  At the same time, partly as a result of marketing, lots of patients who don’t need meds are started on antidepressants.   So we were interested in finding ways to get more truly depressed patients into treatment without overtreating patients who don’t need it. (more…)
Author Interviews, Depression, Exercise - Fitness / 30.08.2013

Jannique van Uffelen, PhD, MSc (epidemiology), MSc (human movement sciences), BHealth Senior Research Fellow Active Ageing INSTITUTE OF SPORT, EXERCISE & ACTIVE LIVING (ISEAL) VICTORIA UNIVERSITYMedicalResearch.com Interview with: Jannique van Uffelen, PhD, MSc (epidemiology), MSc (human movement sciences), BHealth Senior Research Fellow Active Ageing INSTITUTE OF SPORT, EXERCISE & ACTIVE LIVING (ISEAL) VICTORIA UNIVERSITY MedicalResearch.com: What are the main findings of the study? Answer: We examined the link between sitting-time and physical activity with current and future depressive symptoms in 8,950 mid aged women, who participated in the Australian Longitudinal Study on Women’s Health. Both high sitting-time and low physical activity levels were associated with higher risk of current depressive symptoms, and in combination, the risk further increased. Compared with women sitting ≤4 hours/day and meeting the physical activity recommendations of at least 150 minutes of moderate intensity activity per week, women who sat >7 hrs/day and who did no physical activity were three times as likely to have depressive symptoms. However, only lack of physical activity was associated with increased risk of future depressive symptoms, irrespective of sitting-time. Women who did no physical activity were 26% more likely to have future depressive symptoms than women meeting physical activity recommendations. (more…)
Blood Pressure - Hypertension, Depression / 27.08.2013

MedicalResearch.com Interview with: Marcos A Sanchez-Gonzalez, M.D., Ph.D., EPC Postdoctoral Associate Department of Biomedical Sciences College of Medicine The Florida State University 1115 W Call Street BMS 2300-24 & The Family Institute Behavioral Cardiology Laboratory Longmire 301 Tallahassee, FL 32306 MedicalResearch.com:  What are the main findings of the study? Answer: The findings of our study were the following: (1) The low frequency component of systolic blood pressure variability (LFSBP;  a marker of sympathovagal tone) was a stronger predictor of depressive symptoms than conventional measures of cardiovascular functioning such as laboratory measurement of blood pressure and heart rate variability as well as home based ambulatory blood pressure monitoring (2) Depressive symptoms were associated with a blunted LFSBP response to sympathetic stimulation via cold pressor test; and (3) Participants with acute depression (a score of ≥16 using the CES-D scale) had higher LFSBP than those with normal depressive symptom scores.  These findings suggest that depressive symptoms evoke alterations in vascular sympathetic activity, and more importantly, this alteration is occurs early in the progression of the disease.  This is fascinating owing to the fact that we have documented a common pathway of disease between depression and cardiovascular diseases. (more…)
Author Interviews, BMJ, Depression / 27.08.2013

MedicalResearch.com Interview with: David A Richards, PhD Professor of Mental Health Services Research and NIHR Senior Investigator University of Exeter Medical School Sir Henry Wellcome Building University of Exeter Washington Singer Building The Queen’s Drive Exeter EX4 4QQ United Kingdom MedicalResearch.com: What are the main findings of the study? Answer: We found that collaborative care improves depression immediately after treatment compared to usual care, has effects that persist to 12 month follow-up and is preferred bypatients over usual care. This difference in effect equated to a standardized effect size of 0.26 (95% CI 0.07 to 0.46). More participants receiving collaborative care than those receiving usual care met criteria for recovery (odds ratio 1.67 (95% confidence interval 1.22 to 2.29); number needed to treat=8.4) and response (1.77 (1.22 to 2.58); 7.8 at 4 months. At 12 months follow up more participants in collaborative care than those in usual care met criteria for recovery (odds ratio 1.88 (95% confidence interval 1.28 to 2.75); number needed to treat=6.5) and response (1.73 (1.22 to 2.44); 7.3. Collaborative care is as effective in the UK healthcare system—an example of an integrated health system with a well developed primary care sector—as in the US. (more…)
Author Interviews, Brain Injury, Depression, Mental Health Research, UT Southwestern / 04.06.2013

MedicalResearch.com eInterview with: John Hart, M.D. Medical Science Director at the Center for BrainHealth Jane and Bud Smith Distinguished Chair Cecil Green Distinguished Chair The University of Texas at DallasJohn Hart, M.D. Medical Science Director at the Center for BrainHealth Jane and Bud Smith Distinguished Chair Cecil Green Distinguished Chair The University of Texas at Dallas MedicalResearch.com: What are the main findings of the study? Dr. Hart: Football players often sustain numerous concussive and subconcussive impacts—head impacts that do not elicit neurologic symptoms that may lead to white matter damage. We evaluated a population of retired NFL players in order to study the relationship between white matter integrity and the manifestation of depressive symptoms. We identified, for the first time, a correlation between depression and white matter abnormalities in former players with a remote history of concussion using diffusion tensor imaging (DTI). Our data demonstrated a significant association between white matter integrity, as measured by DTI Fractional Anisotropy (FA), and the presence as well as severity of depressive symptoms in retired NFL athletes with a history of concussive or subconcussive impacts. We also found that dysfunction of the anterior aspect of the corpus callosum (forceps minor) and its projections to the frontal lobe can identify those with depression with 100% sensitivity and 95% specificity. (more…)
Author Interviews, Breast Cancer, Cancer Research, Depression, Mental Health Research / 28.03.2013

MedicalResearch.com Interview with Mylin A. Torres, M.D. Assistant Professor Department of Radiation Oncology Emory University School of Medicine Atlanta, GA 30322 MedicalResearch.com: What are the main findings of the study?  Dr. Torres: Radiation treatment for breast cancer is not associated with increased depressive symptoms, but of disease and treatment-related factors, prior chemotherapy treatment is a significant predictor of depression before and after radiation treatment.  Prior chemotherapy treatment was associated with inflammatory mediators, including nuclear factor-kappa B DNA binding, soluble tumor necrosis factor-alpha receptor 2, and interleukin-6, which predicted for depressive symptoms after radiation on univariate analysis. (more…)
Alzheimer's - Dementia, Depression, Mental Health Research / 22.03.2013

Laura B. Zahodne, PhD Postdoctoral fellow in the cognitive neuroscience division in the Department of Neurology and the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain Columbia University Medical Center.MedicalResearch.com Interview with: Laura B. Zahodne, PhD Postdoctoral fellow in the cognitive neuroscience division in the Department of Neurology and the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain Columbia University Medical Center. MedicalResearch.com: What are the main findings of the study? Dr. Zahodne: Having more depressive symptoms early on in Alzheimer’s disease was associated with more rapid declines in the ability to handle tasks of everyday living, and this relationship was independent of cognitive decline. MedicalResearch.com: Were any of the findings unexpected? Dr. Zahodne: Previous studies have shown that depressive symptoms are associated with more difficulties with thinking and daily activities. This study additionally shows that depressive symptoms herald not only more rapid declines in thinking, but also daily functioning, over time. (more…)