Effect of TELEmedicine for Inflammatory Bowel Disease on Patient Activation and Self-Efficacy.

INTRODUCTION: Limitations in inflammatory bowel disease (IBD) care necessitate greater patient activation and self-efficacy, measures associated with positive health outcomes. METHODS: We assessed change in patient activation and general self-efficacy from baseline to 12 months through our TELEmedicine for IBD trial, a multicenter, randomized controlled trial consisting of a web-based monitoring system that interacts with participants via text messaging. A total of 222 adults with IBD who had experienced an IBD flare within 2 years prior to the trial were randomized into either a control arm that received standard care (SC) or an intervention arm that completed self-testing through the TELE-IBD system every other week (EOW) or weekly (W). RESULTS: Changes in self-efficacy scores were not significantly different between control and experimental groups. Patient activation scores were significantly different between standard care and the TELE-IBD EOW group only (p = 0.03). CONCLUSIONS: Use of remote monitoring did not improve self-efficacy or patient activation compared to routine care.

Correction to: Effect of TELEmedicine for Inflammatory Bowel Disease on Patient Activation and Self-Efficacy.

This manuscript is a secondary analysis of a large multicenter randomized controlled trial. The primary study is Cross RK et al., A Randomized Controlled Trial of TELEmedicine for patients with Inflammatory Bowel Disease (TELE-IBD). Am J Gastroenterol, 2019 Mar.

A Randomized Controlled Trial of TELEmedicine for Patients with Inflammatory Bowel Disease (TELE-IBD).

INTRODUCTION: Telemedicine has shown promise in inflammatory bowel disease (IBD). The objective of this study was to compare disease activity and quality of life (QoL) in a 1-year randomized trial of IBD patients receiving telemedicine vs. standard care. METHODS: Patients with worsening symptoms in the prior 2 years were eligible for randomization to telemedicine (monitoring via texts EOW or weekly) or standard care. The primary outcomes were the differences in change in disease activity and QoL between the groups; change in healthcare utilization among groups was a secondary aim. RESULTS: 348 participants were enrolled (117 control group, 115 TELE-IBD EOW, and 116 TELE-IBD weekly). 259 (74.4%) completed the study. Age was 38.9 ± 12.3 years, 56.6% were women, 91.9% were Caucasian, 67.9% had Crohn's disease (CD) and 42.5% had active disease at baseline. In CD, all groups experienced a decrease in disease activity (control -5.2 ± 5.0 to 3.7 ± 3.6, TELE-IBD EOW 4.7 ± 4.1 to 4.2 ± 3.9, and TELE-IBD weekly 4.2 ± 4.2 to 3.2 ± 3.4, p < 0.0001 for each of the groups) In UC, only controls had a significant decrease in disease activity (control 2.9 ± 3.1 to 1.4 ± 1.4, p = 0.01, TELE-IBD EOW 2.7 ± 3.1 to 1.7 ± 1.9, p = 0.35, and TELE-IBD Weekly 2.5 ± 2.5 to 2.0 ± 1.8, p = 0.31). QoL increased in all groups; the increase was significant only in TELE-IBD EOW (control 168.1 ± 34.0 to 179.3 ± 28.2, p = 0.06, TELE-IBD EOW 172.3 ± 33.1 to 181.5 ± 28.2, p = 0.03, and TELE-IBD Weekly 172.3 ± 34.5 to 179.2 ± 32.8, p = 0.10). Unadjusted and adjusted changes in disease activity and QoL were not significantly different among groups. Healthcare utilization increased in all groups. TELE-IBD weekly were less likely to have IBD-related hospitalizations and more likely to have non-invasive diagnostic tests and electronic encounters compared to controls; both TELE-IBD groups had decreased non-IBD related hospitalizations and increased telephone calls compared to controls. DISCUSSION: Disease activity and QoL, although improved in all participants, were not improved further through use of the TELE-IBD system. TELE-IBD participants experienced a decrease in hospitalizations with an associated increase in non-invasive diagnostic tests, telephone calls and electronic encounters. Research is needed to determine if TELE-IBD can be improved through patient engagement and whether it can decrease healthcare utilization by replacing standard care.

The association of antidepressant treatment with COPD maintenance medication use and adherence in a comorbid Medicare population: A longitudinal cohort study.

The effect of treating comorbid depression to achieve optimal management of chronic obstructive pulmonary disease (COPD) has not yet empirically tested. We examined the association between antidepressant treatment and use of and adherence to COPD maintenance medications among patients with new-onset COPD and comorbid depression. METHODS: Using 2006-2012 Medicare data, this retrospective cohort study identified patients with newly diagnosed COPD and new-onset major depression. Two exposures-antidepressant use (versus non-use) and adherence measured by proportion of days covered (PDC) (PDC ≥0.8 versus <0.8)-were assessed quarterly. We used marginal structural models to estimate the effects of prior antidepressant use and adherence on subsequent COPD maintenance inhaler use and adherence outcomes, accounting for time-varying confounders. RESULTS: A total of 25 458 COPD-depression patients, 82% with antidepressant treatment, were followed for a median of 2.5 years. Nearly half (48%) used at least 1 COPD maintenance inhaler in any given quarter; among users, 3 in 5 (61%) had a PDC of <0.8. Compared to patients with no antidepressant treatment, those with antidepressant use were more likely to use (relative ratio [RR] = 1.15, 95% confidence interval [CI] = 1.12- 1.17) and adhere to (RR = 1.08, 95% = 1.03-1.14) their COPD maintenance inhalers. Patients who adhered to antidepressant treatment were more likely to use and adhere to COPD maintenance inhalers. CONCLUSION: Regularly treated depression may increase use of and adherence to necessary maintenance medications for COPD. Antidepressant treatment may be a key determinant to improving medication-taking behaviors among COPD patients comorbid with depression.

Reduced kynurenine pathway metabolism and cytokine expression in the prefrontal cortex of depressed individuals.

BACKGROUND: Neuroinflammatory processes are increasingly believed to participate in the pathophysiology of a number of major psychiatric diseases, including depression. Immune activation stimulates the conversion of the amino acid tryptophan to kynurenine, leading to the formation of neuroactive metabolites, such as quinolinic acid and kynurenic acid. These compounds affect glutamatergic neurotransmission, which plays a prominent role in depressive pathology. Increased tryptophan degradation along the kynurenine pathway (KP) has been proposed to contribute to disease etiology. METHODS: We used postmortem brain tissue from the ventrolateral prefrontal cortex (VLPFC) to assess tissue levels of tryptophan and KP metabolites, the expression of several KP enzymes and a series of cytokines as well as tissue pathology, including microglial activation. Tissue samples came from nonpsychiatric controls (n = 36) and individuals with depressive disorder not otherwise specified (DD-NOS, n = 45) who died of natural causes, homicide, accident, or suicide. RESULTS: We found a reduction in the enzymatic conversion of tryptophan to kynurenine, determined using the kynurenine:tryptophan ratio, and reduced messenger RNA expression of the enzymes indoleamine-2,3-dioxygenase 1 and 2 and tryptophan-2,3-dioxygenase in depressed individuals irrespective of the cause of death. These findings correlated with reductions in the expression of several cytokines, including interferon-γ and tumour necrosis factor-α. Notably, quinolinic acid levels were also lower in depressed individuals than controls. LIMITATIONS: Information on the use of antidepressants and other psychotropic medications was insufficient for statistical comparisons. CONCLUSION: Contrary to expectations, the present results indicate that depression, in the absence of medical illness or an overt inflammatory process, is associated with compromised, rather than increased, KP metabolism in the VLPFC.

New episodes of depression among Medicare beneficiaries with chronic obstructive pulmonary disease.

OBJECTIVES: Depression is a common comorbidity of chronic obstructive pulmonary disease (COPD) and is associated with increased exacerbations, healthcare utilization, and mortality. Among Medicare beneficiaries newly diagnosed with COPD, the objectives of this study were to (1) estimate the rate of new episodes of depression and (2) identify factors associated with depression. METHODS: We identified beneficiaries with a first diagnosis of COPD during 2006-2012 using a 5% random sample of Medicare administrative claims data by searching for ICD-9-CM codes 490, 491.x, 492.x, 494.x, or 496. We identified episodes of depression using ICD-9-CM codes 296.2x, 296.3x, and 311.xx. We calculated incidence rates and their 95% confidence intervals (95% CI) and used a discrete time analysis to identify factors associated with development of depression. RESULTS: Between 2006 and 2012, 125,348 beneficiaries meeting inclusion criteria were newly diagnosed with COPD. Twenty-three percent developed depression following COPD diagnosis. The annualized incidence rate of depression per 100 beneficiaries following COPD diagnosis was 9.4 (95% CI 9.3, 9.5). Rates were highest in the first 2 months following COPD diagnosis. COPD diagnosis was associated with increased risk of depression (risk ratio 1.76; 95% CI 1.73, 1.79) as were COPD-related hospitalizations (risk ratio 4.59; 95% CI 4.09, 5.15), a measure of COPD severity. CONCLUSIONS: Diagnosis of COPD increases the risk of depression. This study will aid in the allocation of resources to monitor and provide support for individuals with COPD at high risk of developing depression.

The Effect of Universal Glove and Gown Use on Adverse Events in Intensive Care Unit Patients.

BACKGROUND: No randomized trials have examined the effect of contact precautions or universal glove and gown use on adverse events. We assessed if wearing gloves and gowns during all patient contact in the intensive care unit (ICU) changes adverse event rates. METHODS: From January 2012 to October 2012, intervention ICUs of the 20-site Benefits of Universal Gloving and Gowning cluster randomized trial required that healthcare workers use gloves and gowns for all patient contact. We randomly sampled 1800 medical records of adult patients not colonized with antibiotic-resistant bacteria and reviewed them for adverse events using the Institute for Healthcare Improvement Global Trigger Tool. RESULTS: Four hundred forty-seven patients (24.8%) had 1 or more ICU adverse events. Adverse events were not associated with universal glove and gown use (incidence rate ratio [IRR], 0.81; 95% confidence interval [CI], .48-1.36). This did not change with adjustment for ICU type, severity of illness, academic hospital status, and ICU size, (IRR, 0.91; 95% CI, .59-1.42; P = .68). Rates of infectious adverse events also did not differ after adjusting for the same factors (IRR, 0.75; 95% CI, .47-1.21; P = .24). CONCLUSIONS: In ICUs where healthcare workers donned gloves and gowns for all patient contact, patients were no more likely to experience adverse events than in control ICUs. Concerns of adverse events resulting from universal glove and gown use were not supported. Similar considerations may be appropriate regarding use of contact precautions. CLINICAL TRIALS REGISTRATION: NCT0131821.

Stroke incidence following traumatic brain injury in older adults.

OBJECTIVE: Following traumatic brain injury (TBI), older adults are at an increased risk of hemorrhagic and thromboembolic events, but it is unclear whether the increased risk continues after hospital discharge. We estimated incidence rates of hemorrhagic and ischemic stroke following hospital discharge for TBI among adults 65 years or older and compared them with pre-TBI rates. PARTICIPANTS: A total of 16 936 Medicare beneficiaries 65 years or older with a diagnosis of TBI in any position on an inpatient claim between June 1, 2006, and December 31, 2009, who survived to hospital discharge. DESIGN: Retrospective analysis of a random 5% sample of Medicare claims data. MAIN MEASURES: Hemorrhagic stroke was defined as ICD-9 (International Classification of Diseases, Ninth Revision) codes 430.xx-432.xx. Ischemic stroke was defined as ICD-9 codes 433.xx-435.xx, 437.0x, and 437.1x. RESULTS: There was a 6-fold increase in the rate of hemorrhagic stroke following TBI compared with the pre-TBI period (adjusted rate ratio, 6.5; 95% confidence interval, 5.3-7.8), controlling for age and sex. A smaller increase in the rate of ischemic stroke was observed (adjusted rate ratio, 1.3; 95% CI, 1.2-1.4). CONCLUSION: Future studies should investigate causes of increased stroke risk post-TBI as well as effective treatment options to reduce stroke risk and improve outcomes post-TBI among older adults.

Transition of European Cooperative Acute Stroke Study III results to clinical practice: ninety-day outcomes in a US cohort.

BACKGROUND AND PURPOSE: The European Cooperative Acute Stroke Study (ECASS) III showed benefit of intravenous tissue-type plasminogen activator for acute ischemic stroke 3 to 4.5 hours from onset in selected patients from Europe, with this extended treatment subsequently recommended by the American Stroke Association. We prospectively enrolled patients with acute ischemic stroke treated with intravenous tissue-type plasminogen activator, during the time this recommendation was being applied in clinical practice to determine safety and efficacy in a representative cohort from the United States. METHODS: Patients with acute ischemic stroke treated with intravenous tissue-type plasminogen activator were enrolled at 18 primary stroke centers throughout Maryland, including community hospitals and academic medical centers. Patients grouped by time to treatment (≤3 versus 3-4.5 hours) were compared for the presence of exclusion criteria from ECASS III that are not standard practice in the United States for ≤3 hours (age, >80 years; history of stroke and diabetes mellitus; oral anticoagulant treatment; and National Institutes of Health Stroke Scale, >25). Outcomes included good function at 90 days (modified Rankin Scale, 0-1 and 0-2), mortality, and symptomatic intracerebral hemorrhage. RESULTS: In the 3- to 4.5-hour treatment group, there were significantly fewer patients aged>80 years and no patients with the combination of stroke and diabetes mellitus. There were no statistically significant differences by time to treatment in symptomatic intracerebral hemorrhage, mortality, or functional outcome. CONCLUSIONS: For patients treated with intravenous tissue-type plasminogen activator 3 to 4.5 hours from onset in everyday practice in the United States, there is no evidence for increased risk or worse outcomes compared with standard treatment≤3 hours.

Prognostic factors for recent-onset interstitial cystitis/painful bladder syndrome.

UNLABELLED: Study Type - Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Interstitial cystitis/painful bladder syndrome (IC/PBS) comprises pain perceived to be from the bladder, urinary urgency and frequency, and nocturia. As diagnosed at present, it is primarily identified in adult women. It is a chronic disease yet its natural history has not been well studied. In a prospective study of 304 incident female IC/PBS cases followed for a median of 33 months after onset, women with baseline chronic fatigue syndrome had a worse prognosis for IC/PBS. Mild IC/PBS at baseline was the only variable that was directly associated with a good prognosis. OBJECTIVE: To identify baseline variables that predict the prognosis of interstitial cystitis/painful bladder syndrome (IC/PBS) in women seeking medical care for recent onset of this syndrome. SUBJECTS AND METHODS: In a prospective study of women with incident IC/PBS (≤12 months of symptoms), we contacted patients at intervals and asked standardized questions about IC/PBS symptoms in the previous week. Logistic regression analyses assessed baseline variables as predictors of mild vs more severe IC/PBS at the last follow-up. RESULTS: Median length of follow-up was 33 months after onset of IC/PBS; 304 (97%) patients had at least one follow-up assessment. Mild IC/PBS at baseline was the only variable that was directly associated with a mild IC/PBS endpoint. Conversely, a history of chronic fatigue syndrome (CFS) was inversely associated with a mild endpoint of IC/PBS (i.e. individuals with CFS had a worse prognosis for their IC/PBS symptoms). CONCLUSIONS: At a median of nearly 3 years after onset, baseline mild IC/PBS was directly associated with a milder disease severity. Baseline co-morbid CFS was associated with more severe disease. Whether CFS was uniquely associated or represented several co-morbid non-bladder syndromes (NBSs) could not be determined.

Comparative effectiveness of anti-TNF agents for Crohn's disease in a tertiary referral IBD practice.

BACKGROUND: The three Food and Drug Administration (FDA)-approved anti-tumor necrosis factor drugs (anti-TNFs) for Crohn's disease (CD) have not been directly compared. AIM: To compare the efficacy of the three anti-TNFs for CD in clinical practice. METHODS: Retrospective review of patients initiated on anti-TNF between 2004 and 2008. Disease activity, quality of life, and remission rates were compared between groups over 1 year. RESULTS: Sixty patients with CD were initiated on anti-TNF from 2004 to 2008: 31 on infliximab (IFX) and 29 on adalimumab (ADA) or certolizumab pegol (CTZ). More patients in the ADA/CTZ scores group had prior exposure to anti-TNF (76 versus 10%, p < 0.01). Mean Harvey-Bradshaw Index (HBI) scores in the IFX group were lower than in the ADA/CTZ group at 12 months (2.72 ± 3.34 versus 5.63 ± 5.33, p = 0.03). At 12 months, more IFX patients were in remission compared with those on ADA/CTZ (88 versus 53%, p ≤ 0.01). Mean short inflammatory bowel disease questionnaire (SIBDQ) scores were not different between the IFX and ADA/CTZ groups at 12 months. Stratified analyses and logistic regression based on prior anti-TNF use did not show differences in remission rates at any time point post-baseline between groups. CONCLUSIONS: After adjustment for prior anti-TNF there was no difference in remission rates between the IFX and ADA/CTZ groups at any time point post-baseline. This suggests that differences between groups were accounted for by a higher rate of prior anti-TNF in the ADA/CTZ group. Our results should be reviewed with caution given the small sample size.

Pollen-specific immunoglobulin E positivity is associated with worsening of depression scores in bipolar disorder patients during high pollen season.

OBJECTIVE: An association between allergic disease and depression has been consistently reported, but whether the key mediating ingredients are predominantly biological, psychological, or mere artifacts remains unknown. In the current study, we examined a hypothesized relationship between allergen-specific immunoglobulin E (IgE) status and changes in allergy symptoms with worsening in depression scores. METHODS: In patients with recurrent mood disorders, we individually coupled sensitization to specific seasonal aeroallergens (as assessed by allergen-specific IgE) with temporal windows of exposure to aeroallergens (low versus high tree or ragweed pollen counts, measured according to the National Allergy Bureau guidelines). We compared Structured Interview Guide for the Hamilton Depression Rating Scale-Seasonal Affective Disorder Version (SIGH-SAD) depression score changes in 41 patients with mood disorders [25 with major depression and 16 with bipolar I disorder, diagnosed by Structured Clinical Interview for DSM (SCID)] seropositive for tree or ragweed pollen-specific IgE antibody versus 53 patients with mood disorders (30 with major depression and 23 with bipolar I disorder) seronegative for aeroallergen-specific IgE. RESULTS: Worsening in total depressive scores from low to high pollen exposure was greater in allergen-specific IgE-positive patients as compared to allergen-specific IgE antibody-negative patients (p = 0.01). When stratified by polarity, the association was significant only in patients with bipolar I disorder (p = 0.004). This relationship was resilient to adjustment for changes in allergy symptom scores. CONCLUSION: To our knowledge, this is the first report of coupling a molecular marker of vulnerability (allergen-specific IgE) with a specific environmental trigger (airborne allergens) leading to exacerbation of depression in patients with bipolar I disorder.

Improvement in depression scores after 1 hour of light therapy treatment in patients with seasonal affective disorder.

The purpose of this study was to investigate possible rapid effects of light therapy on depressed mood in patients with seasonal affective disorder. Participants received 1 hour of bright light therapy and 1 hour of placebo dim red light in a randomized order crossover design. Depressed mood was measured at baseline and after each hour of light treatment using two self-report depression scales (Profile of Mood States-Depression-Dejection [POMS-D] subscale and the Beck Depression Inventory II [BDI-II]). When light effects were grouped for the two sessions, there was significantly greater reduction in self-report depression scores by -1.3 (p = 0.02) on the BDI-II and -1.2 (p = 0.02) on the POMS-D. A significant but modest improvement was detected after a single active light session. This is the first study, to our knowledge, to document an immediate improvement with light treatment using a placebo-controlled design with a clinical sample of depressed individuals.

Staphylococcus aureus infections in US veterans, Maryland, USA, 1999-2008.

Trends in Staphylococcus aureus infections are not well described. To calculate incidence in overall S. aureus infection and invasive and noninvasive infections according to methicillin susceptibility and location, we conducted a 10-year population-based retrospective cohort study (1999-2008) using patient-level data in the Veterans Affairs Maryland Health Care System. We found 3,674 S. aureus infections: 2,816 (77%) were noninvasive; 2,256 (61%) were methicillin-resistant S. aureus (MRSA); 2,517 (69%) were community onset, and 1,157 (31%) were hospital onset. Sixty-one percent of noninvasive infections were skin and soft tissue infections; 1,112 (65%) of these were MRSA. Ten-year averaged incidence per 100,000 veterans was 749 (± 132 SD, range 549-954) overall, 178 (± 41 SD, range 114-259) invasive, and 571 (± 152 SD, range 364-801) noninvasive S. aureus infections. Incidence of all S. aureus infections significantly increased (p<0.001), driven by noninvasive, MRSA, and community-onset infections (p<0.001); incidence of invasive S. aureus infection significantly decreased (p<0.001).

Sun exposure, vitamin D intake and progression to disability among veterans with progressive multiple sclerosis.

BACKGROUND: Early life events have been suggested to influence multiple sclerosis (MS) susceptibility, and to potentially modulate its clinical course. We assessed vitamin D-related exposures from childhood to disease onset and their associations with MS progression. METHODS: Among veterans in the Multiple Sclerosis Surveillance Registry, 219 reported having the progressive form and met the inclusion criteria. Participants reported their past sun exposure, vitamin D-related intake and age at disability milestones using the Patient-Determined Disease Steps (PDDS). The Cox proportional hazards model was used to examine the association between vitamin D-related exposures and time (years) to disability. RESULTS: Low average sun exposure in the fall/winter before disease onset was associated with an increased risk of progressing to a PDDS score of 8 (hazard ratio, HR: 2.13, 95% confidence interval, CI: 1.20-3.78), whereas use of cod liver oil during childhood and adolescence was associated with a reduced risk (HR: 0.44, 95% CI: 0.20-0.96). CONCLUSIONS: These results suggest that exposure to vitamin D before MS onset might slow disease-related neurodegeneration and thus delay progression to disability among patients with the progressive subtype.

Sun exposure, vitamin D and age at disease onset in relapsing multiple sclerosis.

BACKGROUND: Current evidence suggests that sun exposure and vitamin D intake, during childhood and adolescence, are associated with a reduced risk of multiple sclerosis (MS). However, the role of these environmental agents in the timing of disease symptom onset remains to be investigated. METHODS: Using a cross-sectional study design, we recruited participants from the Veterans Health Administration-Multiple Sclerosis Surveillance Registry. Self-reported histories of residential locations, sun exposure and intake of vitamin D were used to estimate vitamin-D-related exposures. Multivariable linear regression analysis was used to examine the associations between these variables and age at MS onset. RESULTS: Among veterans with relapsing MS who resided in low-to-medium solar radiation areas (n = 540), low sun exposure in the fall/winter during the ages of 6-15 years was significantly associated with earlier symptom onset by 2.1 years (p = 0.02). Intake of cod liver oil during the same age period was associated with later onset of MS symptoms by 4 years (p = 0.02). CONCLUSIONS: The current study provides evidence for an association between vitamin-D-related exposures during childhood and early adolescence and the timing of MS symptom onset, and supports vitamin D as a potential modulator of the clinical course of this disease.

Toxoplasma gondii seropositivity and suicide rates in women.

Toxoplasma gondii (T. gondii) is an intracellular protozoan parasite that infects roughly a third of the world population. In an immunocompetent host, infection is generally chronic and asymptomatic, as the immune system keeps T. gondii confined to cysts and the intracellular space within the muscle and brain. Seropositivity has been linked to schizophrenia, car accidents, changes in personality, and more recently, suicidal attempts. Very recently, seroprevalence for 20 European countries was found to be associated with increased suicide rates. Although suicide rates were age-standardized, given that T. gondii seroprevalence increases with age and that the blood samples were drawn in women, we now retested in women only the association between suicide and T. gondii seropositivity, stratified by age. Simple correlations between ranked T. gondii seropositivity and suicide rate identified statistically significant relationships in women 60 years or older (p < 0.05); adjusting for GDP, the statistical significance expanded to include women 45 years and older. The strongest association was in the 60- to 74-year-old group where, after adjustment for GDP, the relationship (p = 0.007) resisted Bonferroni adjustment for multiple comparisons. In conclusion, the results suggest that a positive relationship between rates of infection with T. gondii and suicide is apparent in women of postmenopausal age. Prospective studies are necessary to further confirm this association predictively and to explore mechanisms mediating this relationship.

Uterine and fetal blood flow indexes and fetal growth assessment after chronic estrogen suppression in the second half of baboon pregnancy.

Although estrogen regulates important aspects of maternal cardiovascular physiology, the role of estrogen on uteroplacental and fetal blood flow is incompletely understood. This study tested the hypothesis that chronically suppressing endogenous estrogen production during the second half of baboon pregnancy alters uterine and fetal blood flow dynamics assessed by ultrasonography. Pregnant baboons were untreated or treated daily with the aromatase inhibitor letrozole or letrozole plus estradiol on days 100-160 of gestation (term = 184 days). Blood flow dynamics were determined by Doppler ultrasonography on day 60 and longitudinally between days 110 and 160 of gestation. Letrozole decreased maternal serum estradiol and estrone concentrations by 95% (P < 0.001). Fetal growth biometrical parameters increased (P < 0.001) between days 110 and 160 of gestation and were similar in untreated and letrozole-treated animals. Uterine, umbilical, and fetal middle cerebral artery pulsatility index and resistance index declined (P < 0.01) by 30-50% and uterine artery volume flow increased sixfold (P < 0.001) between days 60 and 160, but values were similar in untreated, letrozole-treated, and letrozole plus estradiol-treated baboons. Thus uterine and fetal artery blood flow indexes, uterine artery volume flow, and fetal growth were maintained at normal levels despite chronic estrogen suppression in the second half of baboon pregnancy. This suggests that elevated levels of endogenous estrogen are not required to maintain low impedance blood flow within the uteroplacental vascular bed during the second half of nonhuman primate pregnancy.

A prospective early history of incident interstitial cystitis/painful bladder syndrome.

PURPOSE: The longitudinal history of interstitial cystitis/painful bladder syndrome has been studied infrequently. In a national sample of incident cases we assessed changes in symptoms during the first several years of interstitial cystitis/painful bladder syndrome. MATERIALS AND METHODS: We recruited 312 women with a history of interstitial cystitis/painful bladder syndrome symptoms of 12 months or less and interviewed them by telephone at baseline, and 6, 12, 18, 24, 36 and 48 months later. We queried symptoms in the last week and interval medication use. Individual and composite symptom categories were constructed. RESULTS: The median history of symptoms at study enrollment was 9 months. Median followup was 33 months after onset. The 57 study withdrawals (18%) were not substantively different than those remaining in followup. Many cases of severe and moderate interstitial cystitis/painful bladder syndrome at enrollment improved with time. As followup progressed, increasing proportions reported improvement while decreasing proportions reported symptom worsening. Of the women 27 (9%) reported at least temporary symptom remission. CONCLUSIONS: Of 304 women with incident interstitial cystitis/painful bladder syndrome 35% reported improvement from baseline in symptoms at last followup a median of 33 months after onset. However, the disappearance of all symptoms at any followup was uncommon.

Time of birth, residential solar radiation and age at onset of multiple sclerosis.

UNLABELLED: BACKGROUNDS/AIM: Gestational and early life events have been suggested to contribute to multiple sclerosis (MS) susceptibility. We assessed the effects of time and place of birth on the age at onset of MS symptoms. METHODS: We selected a national cohort of 967 veterans from the Multiple Sclerosis Surveillance Registry for whom month and season (time) of birth, and birthplace (city and state) were available. Multiple linear regression analyses were used to examine the association between time of birth, birthplace latitude and solar radiation, and the age at onset of MS symptoms among the study sample. RESULTS: Patients with a relapsing form of the disease (R-MS), who were born in winter and whose birthplace was in low solar radiation areas, had disease symptom onset on average 2.8 years earlier than those born in seasons other than winter and in medium- and high-solar radiation areas (p = 0.02). CONCLUSIONS: These results suggest that exposure early in life to geographical and seasonal factors, possibly related to the protective effect of sunlight, and thus vitamin D, is associated with a delay in MS symptom onset. Other larger studies are required to examine the period-specific (from conception to adulthood) environmental factors that are associated with MS susceptibility.