Mind-body (hypnotherapy) treatment of women with urgency urinary incontinence: changes in brain attentional networks.

BACKGROUND: Prior study of patients with urgency urinary incontinence by functional magnetic resonance imaging showed altered function in areas of the brain associated with interoception and salience and with attention. Our randomized controlled trial of hypnotherapy for urgency urinary incontinence demonstrated marked improvement in urgency urinary incontinence symptoms at 2 months. A subsample of these women with urgency urinary incontinence underwent functional magnetic resonance imaging before and after treatment. OBJECTIVE: This study aimed to determine if hypnotherapy treatment of urgency urinary incontinence compared with pharmacotherapy was associated with altered brain activation or resting connectivity on functional magnetic resonance imaging. STUDY DESIGN: A subsample of women participating in a randomized controlled trial comparing hypnotherapy vs pharmacotherapy for treatment of urgency urinary incontinence was evaluated with functional magnetic resonance imaging. Scans were obtained pretreatment and 8 to 12 weeks after treatment initiation. Brain activation during bladder filling and resting functional connectivity with an empty and partially filled bladder were assessed. Brain regions of interest were derived from those previously showing differences between healthy controls and participants with untreated urgency urinary incontinence in our prior work and included regions in the interoceptive and salience, ventral attentional, and dorsal attentional networks. RESULTS: After treatment, participants in both groups demonstrated marked improvement in incontinence episodes (P<.001). Bladder-filling task functional magnetic resonance imaging data from the combined groups (n=64, 30 hypnotherapy, 34 pharmacotherapy) demonstrated decreased activation of the left temporoparietal junction, a component of the ventral attentional network (P<.01) compared with baseline. Resting functional connectivity differed only with the bladder partially filled (n=54). Compared with pharmacotherapy, hypnotherapy participants manifested increased functional connectivity between the anterior cingulate cortex and the left dorsolateral prefrontal cortex, a component of the dorsal attentional network (P<.001). CONCLUSION: Successful treatment of urgency urinary incontinence with both pharmacotherapy and hypnotherapy was associated with decreased activation of the ventral (bottom-up) attentional network during bladder filling. This may be attributable to decreased afferent stimuli arising from the bladder in the pharmacotherapy group. In contrast, decreased ventral attentional network activation associated with hypnotherapy may be mediated by the counterbalancing effects of the dorsal (top-down) attentional network.

Self-regulation and emotional reactivity in infants with prenatal exposure to opioids and alcohol.

BACKGROUND: Infants with prenatal substance exposure are at increased risk for developmental problems, with self-regulatory challenges being some of the most pronounced. The current study aimed to investigate the extent to which prenatal substance exposure (alcohol, opioids) impacts infant self-regulation during a relational stressor and the association between self-regulation and infant affect. METHODS: Participants were 100 mother-child dyads recruited prenatally (Mean = 23.8 gestational weeks) and completed the Still Face Paradigm (SFP) when infants were 5 to 8 months of age (Mean = 6.9 months) as part of an ENRICH prospective birth cohort study. Based on prospective repeated assessment of maternal substance use in pregnancy, infants were grouped into: 1) Unexposed controls; 2) Alcohol-exposed; 3) Opioid-exposed due to maternal use of medications for opioid use disorder (MOUD) with or without other opioids; 4) MOUD and alcohol. Infant stress reactivity (negative affect) and self-regulation were assessed during the validated 5-episode SFP. Mixed effects linear models were used to analyze differences in the percent of self-regulation and percent of negative affect among the study groups across SFP episodes, as well as the group-by-self-regulation interaction with respect to infant negative affect. RESULTS: The MOUD+Alcohol group demonstrated significantly lower self-regulation at baseline compared to controls (p < 0.05). There was a significant group-by-self-regulation interaction (p = 0.028). Higher self-regulation was associated with lower negative affect across SFP episodes in the MOUD+Alcohol group (p = 0.025) but not other groups. CONCLUSION: Self-regulation skills are particularly important for emotional modulation in infants with prenatal polysubstance exposure, highlighting the development of these skills as a promising intervention target.

Hypnotherapy or medications: a randomized noninferiority trial in urgency urinary incontinent women.

BACKGROUND: Urgency urinary incontinence afflicts many adults, and most commonly affects women. Medications, a standard treatment, may be poorly tolerated, with poor adherence. This warrants investigation of alternative interventions. Mind-body therapies such as hypnotherapy may offer additional treatment options for individuals with urgency urinary incontinence. OBJECTIVE: To evaluate hypnotherapy's efficacy compared to medications in treating women with urgency urinary incontinence. MATERIALS AND METHODS: This investigator-masked, noninferiority trial compared hypnotherapy to medications at an academic center in the southwestern United States, and randomized women with non-neurogenic urgency urinary incontinence to weekly hypnotherapy sessions for 2 months (and continued self-hypnosis thereafter) or to medication and weekly counseling for 2 months (and medication alone thereafter). The primary outcome was the between-group comparison of percent change in urgency incontinence on a 3-day bladder diary at 2 months. Important secondary outcomes were between-group comparisons of percent change in urgency incontinence at 6 and 12 months. Outcomes were analyzed based on noninferiority margins of 5% for between group differences (P < 0.025) (that is, for between group difference in percentage change in urgency incontinence, if the lower bound of the 95% confidence interval was greater than -5%, noninferiority would be proved). RESULTS: A total of 152 women were randomized to treatment between April 2013 and October 2016. Of these women, 142 (70 hypnotherapy, 72 medications) had 3-day diary information at 2 months and were included in the primary outcome analysis. Secondary outcomes were analyzed for women with diary data at the 6-month and then 12-month time points (138 women [67 hypnotherapy, 71 medications] at 6 months, 140 women [69 hypnotherapy, 71 medications] at 12 months. There were no differences between groups' urgency incontinence episodes at baseline: median (quartile 1, quartile 3) for hypnotherapy was 8 (4, 14) and medication was 7 (4, 11) (P = .165). For the primary outcome, although both interventions showed improvement, hypnotherapy did not prove noninferior to medication at 2 months. Hypnotherapy's median percent improvement was 73.0% (95% confidence interval, 60.0-88˖9%), whereas medication's improvement was 88.6% (95% confidence interval, 78.6-100.0%). The median difference in percent change between groups was 0% (95% confidence interval, -16.7% to 0.0%); because the lower margin of the confidence interval did not meet the predetermined noninferiority margin of greater than -5%, hypnotherapy did not prove noninferior to medication. In contrast, hypnotherapy was noninferior to medication for the secondary outcomes at 6 months (hypnotherapy, 85.7% improvement, 95% confidence interval, 75.0-100%; medications, 83.3% improvement, 95% confidence interval, 64.7-100%; median difference in percent change between groups of 0%, 95% confidence interval, 0.0-6.7%) and 12 months (hypnotherapy, 85.7% improvement, 95% confidence interval, 66.7-94.4%; medications, 80% improvement, 95% confidence interval, 54.5-100%; median difference in percent change between groups of 0%, 95% confidence interval, -4.2% to -9.5%). CONCLUSION: Both hypnotherapy and medications were associated with substantially improved urgency urinary incontinence at all follow-up. The study did not prove the noninferiority of hypnotherapy compared to medications at 2 months, the study's primary outcome. Hypnotherapy proved noninferior to medications at longer-term follow-up of 6 and 12 months. Hypnotherapy is a promising, alternative treatment for women with UUI.

Prospective Randomized Controlled Trial on the Efficacy of Continuous Positive Airway Pressure and Adaptive Servo-Ventilation in the Treatment of Chronic Complex Insomnia.

BACKGROUND: Complex insomnia, the comorbidity of chronic insomnia and obstructive sleep apnea (OSA), is a common sleep disorder, but the OSA component, whether presenting overtly or covertly, often goes unsuspected and undiagnosed due to a low index of suspicion. Among complex insomniacs, preliminary evidence demonstrates standard CPAP decreases insomnia severity. However, CPAP causes expiratory pressure intolerance or iatrogenic central apneas that may diminish its use. An advanced PAP mode-adaptive servo-ventilation (ASV)-may alleviate CPAP side-effects and yield superior outcomes. METHODS: In a single-site protocol investigating covert complex insomnia (ClinicalTrials.gov identifier: NCT02365064), a low index of suspicion for this comorbidity was confirmed by exclusion of 455 of 660 eligible patients who presented during the study period with overt OSA signs and symptoms. Ultimately, stringent inclusion/exclusion criteria to test efficacy yielded 40 adult, covert complex insomnia patients [average Insomnia Severity Index (ISI) moderate-severe 19.30 (95% CI 18.42-20.17)] who reported no definitive OSA symptoms or risks and who failed behavioral or drug therapy for an average of one decade. All 40 were diagnosed with OSA and randomized (using block randomization) to a single-blind, prospective protocol, comparing CPAP (n = 21) and ASV (n = 19). Three successive PAP titrations fine-tuned pressure settings, facilitated greater PAP use, and collected objective sleep and breathing data. Patients received 14 weeks of treatment including intensive biweekly coaching and follow-up to foster regular PAP use in order to accurately measure efficaciousness. Primary outcomes measured insomnia severity and sleep quality. Secondary outcomes measured daytime impact: OSA-induced impairment, fatigue severity, insomnia impairment, and quality of life. Performance on these seven variables was assessed using repeated measures ANCOVA to account for the multiple biweekly time points. FINDINGS: At intake, OSA diagnosis and OSA as a cause for insomnia were denied by all 40 patients, yet PAP significantly decreased insomnia severity scores (p = 0.021 in the primary ANCOVA analysis). To quantify effect sizes, mean intake vs endpoint analysis was conducted with ASV yielding nearly twice the effects of CPAP [- 13.2 (10.7-15.7), Hedges' g = 2.50 vs - 9.3 (6.3-12.3), g = 1.39], and between mode effect size was in the medium-large range 0.65. Clinically, ASV led to remission (ISI < 8) in 68% of cases compared to 24% on CPAP [Fisher's exact p = 0.010]. Two sleep quality measures in the ANCOVA analysis again demonstrated superior significant effects for ASV compared to CPAP (both p < 0.03), and pre- and post-analysis demonstrated substantial effects for both scales [ASV (g = 1.42; g = 1.81) over CPAP (g = 1.04; g = 0.75)] with medium size effects between modes (0.54, 0.51). Measures of impairment, residual objective sleep breathing events, and normalized breathing periods consistently demonstrated larger beneficial effects for ASV over CPAP. INTERPRETATION: PAP therapy was highly efficacious in decreasing insomnia severity in chronic insomnia patients with previously undiagnosed co-morbid OSA. ASV proved superior to CPAP in this first efficacy trial to compare advanced to traditional PAP modes in complex insomnia. Future research must determine the following: pathophysiological mechanisms to explain how OSA causes chronic insomnia; general population prevalence of this comorbidity; and, cost-effectiveness of ASV therapy in complex insomnia. Last, efforts to raise awareness of complex insomnia are urgently needed as patients and providers appear to disregard both overt and covert signs and symptoms of OSA in the assessment of chronic insomnia.

Characterization of Cortisol Secretion Rate in Secondary Adrenal Insufficiency.

CONTEXT: In secondary adrenal insufficiency (SAI), chronic deficiency of adrenocorticotropin (ACTH) is believed to result in secondary changes in adrenocortical function, causing an altered dose-response relationship between ACTH concentration and cortisol secretion rate (CSR). OBJECTIVE: We sought to characterize maximal cortisol secretion rate (CSRmax) and free cortisol half-life in patients with SAI, compare results with those of age-matched healthy controls, and examine the influence of predictor variables on ACTH-stimulated cortisol concentrations. DESIGN: CSRmax was estimated from ACTH1-24 (250 µg)-stimulated cortisol time-concentration data. Estimates for CSRmax and free cortisol half-life were obtained for both dexamethasone (DEX) and placebo pretreatment conditions for all subjects. SETTING: Single academic medical center. PATIENTS: Patients with SAI (n = 10) compared with age-matched healthy controls (n = 21). INTERVENTIONS: The order of DEX vs placebo pretreatment was randomized and double-blind. Cortisol concentrations were obtained at baseline and at intervals for 120 minutes after ACTH1-24. MAIN OUTCOME MEASURES: CSRmax and free cortisol half-life were obtained by numerical modeling analysis. Predictors of stimulated cortisol concentrations were evaluated using a multivariate model. RESULTS: CSRmax was significantly (P < 0.001) reduced in patients with SAI compared with controls for both placebo (0.17 ± 0.09 vs 0.46 ± 0.14 nM/s) and DEX (0.18 ± 0.13 vs 0.43 ± 0.13 nM/s) conditions. Significant predictors of ACTH1-24-stimulated total cortisol concentrations included CSRmax, free cortisol half-life, and baseline total cortisol, corticosteroid-binding globulin, and albumin concentrations (all P < 0.05). CONCLUSIONS: Our finding of significantly decreased CSRmax confirms that SAI is associated with alterations in the CSR-ACTH dose-response curve. Decreased CSRmax contributes importantly to the laboratory diagnosis of SAI.

INSULIN TIMING: A PATIENT-CENTERED APPROACH TO IMPROVE CONTROL IN TYPE 1 DIABETES.

OBJECTIVE: The goal of insulin therapy in type 1 diabetes (T1D) is to reduce hemoglobin A1C (A1C) to ≤7.0% (53 mmol/mol) with minimal hypoglycemia. We investigated the possibility that "insulin timing" would improve A1C without incurring severe hypoglycemia in volunteers with T1D over a 6-month observation period. METHODS: Forty healthy adult volunteers with T1D were randomly assigned for 6 months to either a control group or an insulin timing group. The primary endpoint was the difference in A1C between the two groups. As a secondary endpoint, both groups were further divided to assess the importance of the baseline A1C in determining the response to timing. The insulin timing algorithm altered the time when the meal dose of insulin was injected or infused from 30 minutes before the meal to 15 minutes after the meal, depending upon the premeal blood glucose concentration. RESULTS: An improvement in mean A1C was observed in the timing group compared with no change in the control group, but this improvement did not reach statistical significance (P>.05). In contrast, when the two groups were analyzed according to baseline A1C, the timing volunteers with baseline A1C values in the upper half (separated by the A1C median of 7.45% [57.9 mmol/mol]) of the timing group had a more robust response to timing (decline in A1C) than the upper half of the control group (P<.05). CONCLUSION: Insulin timing is a patient-centered translational approach that is safe and effective in improving A1C in individuals with T1D with an elevated A1C. ABBREVIATIONS: A1C = hemoglobin A1C ANOVA = analysis of variance CGM = continuous glucose monitoring CSII = continuous subcutaneous insulin infusion MDI = multiple daily injection T1D = type 1 diabetes.

Methodology for a trial of brain-centered versus anticholinergic therapy in women with urgency urinary incontinence.

INTRODUCTION AND HYPOTHESIS: We describe the rationale and methodology for a study comparing mind-body treatment and pharmacotherapy in women with urgency urinary incontinence (UUI). To explore brain associations in UUI, a subset of patients will also undergo functional magnetic resonance imaging (fMRI). We hypothesize that hypnotherapy, a mind-body intervention, will be at least as effective as pharmacotherapy in treating UUI. We also hypothesize that fMRI findings will change following treatment, with changes potentially differing between groups. METHODS: We describe the development and design challenges of a study comparing the efficacy of hypnotherapy and conventional pharmacotherapy in the treatment of UUI. The study randomizes women to either of these treatments, and outcome measures include bladder diaries and validated questionnaires. Sample size estimates, based on a noninferiority test (alpha = 0.025, beta = 0.20), after considering dropout subjects and subjects lost to follow-up, indicated that approximately 150 woman would be required to test the hypothesis that hypnotherapy is not inferior to pharmacotherapy within a 5 % noninferiority margin. The study will also evaluate fMRI changes in a subset of participants before and after therapy. Challenges included designing a study with a mind-body therapy and a comparison treatment equally acceptable to participants, standardizing the interventions, and confronting the reality that trials are time-consuming for participants who have to make appropriate accommodations in their schedule. RESULTS: Study enrollment began in March 2013 and is ongoing. CONCLUSIONS: We describe the design of a randomized controlled trial comparing mind-body therapy and pharmacotherapy in the treatment of UUI and the challenges encountered in its implementation.

Vitamin D levels and perinatal depressive symptoms in women at risk: a secondary analysis of the mothers, omega-3, and mental health study.

BACKGROUND: Vitamin D insufficiency may be associated with depressive symptoms in non-pregnant adults. We performed this study to evaluate whether low maternal vitamin D levels are associated with depressive symptoms in pregnancy. METHODS: This study was a secondary analysis of a randomized trial designed to assess whether prenatal omega-3 fatty acid supplementation would prevent depressive symptoms. Pregnant women from Michigan who were at risk for depression based on Edinburgh Postnatal Depression Scale Score or history of depression were enrolled. Participants completed the Beck Depression Inventory (BDI) and Mini International Neuropsychiatric Interview at 12-20 weeks, 26-28 weeks, 34-36 weeks, and 6-8 weeks postpartum. Vitamin D levels were measured at 12-20 weeks (N = 117) and 34-36 weeks (N = 112). Complete datasets were available on 105 subjects. Using regression analyses, we evaluated the relationship between vitamin D levels with BDI scores as well as with MINI diagnoses of major depressive disorder and generalized anxiety disorder. Our primary outcome measure was the association of maternal vitamin D levels with BDI scores during early and late pregnancy and postpartum. RESULTS: We found that vitamin D levels at 12-20 weeks were inversely associated with BDI scores both at 12-20 and at 34-36 weeks' gestation (P < 0.05, both). For every one unit increase in vitamin D in early pregnancy, the average decrease in the mean BDI score was .14 units. Vitamin D levels were not associated with diagnoses of major depressive disorder or generalized anxiety disorder. CONCLUSIONS: In women at risk for depression, early pregnancy low vitamin D levels are associated with higher depressive symptom scores in early and late pregnancy. Future investigations should study whether vitamin D supplementation in early pregnancy may prevent perinatal depressive symptoms. TRIAL REGISTRATION: https://clinicaltrials.gov/ REGISTRATION NUMBER: NCT00711971.

Epidemiology of mixed, stress, and urgency urinary incontinence in middle-aged/older women: the importance of incontinence history.

INTRODUCTION AND HYPOTHESIS: Urinary incontinence (UI) is common and the relationship among its subtypes complex. Our objective was to describe the natural history and predictors of the incontinence subtypes stress, urgency, and mixed, in middle-aged and older US women. We tested our hypothesis that UI subtype history predicted future occurrence, evaluating subtype incidence/remission over multiple time points in a stable cohort of women. METHODS: We analyzed longitudinal urinary incontinence data in 10,572 community-dwelling women aged ≥50 in the 2004-2010 Health and Retirement Study. Mixed, stress, and urgency incontinence prevalence (2004, 2006, 2008, 2010) and 2-year cumulative incidence and remissions (2004-2006, 2006-2008, 2008-2010) were estimated. Patient characteristics and incontinence subtype status 2004-2008 were entered into a multivariable, transition model to determine predictors for incontinence subtype occurrence in 2010. RESULTS: The prevalence of each subtype in this population (median age 63-66) was 2.6-8.9 %. Subtype incidence equaled 2.1-3.5 % and remissions for each varied between 22.3 and 48.7 %. Incontinence subtype incidence predictors included ethnicity/race, age, body mass index, and functional limitations. Compared with white women, black women had decreased odds of incident stress incontinence and Hispanic women had increased odds of stress incontinence remission. The age range 80-90 and severe obesity predicted incident mixed incontinence. Functional limitations predicted mixed and urgency incontinence. The strongest predictor of incontinence subtype was subtype history. The presence of the respective incontinence subtypes in 2004 and 2006 strongly predicted 2010 recurrence (odds ratio [OR] stress incontinence = 30.7, urgency OR = 47.4, mixed OR = 42.1). CONCLUSIONS: Although the number of remissions was high, a previous history of incontinence subtypes predicted recurrence. Incontinence status is dynamic, but tends to recur over the longer term.

Acetaminophen concentrations prior to 4 hours of ingestion: impact on diagnostic decision-making and treatment.

BACKGROUND: Consensus recommendations for acute acetaminophen exposure include plotting an acetaminophen concentration at ≥ 4 h post ingestion on the Rumack-Matthew nomogram to determine the need for acetylcysteine treatment. We studied the frequency of acetaminophen concentrations drawn within 4 h post ingestion and whether the Rumack-Matthew nomogram was properly used in making acetylcysteine treatment decisions. METHODS: This was a retrospective, observational case series at three regional poison centers of acute acetaminophen exposures between 1/1/13 and 12/31/13. Cases were analyzed for demographics, timing of acetaminophen concentrations, and application of the Rumack-Matthew nomogram in acetylcysteine initiation or termination. RESULTS: 1,123 cases of acute acetaminophen exposure were reviewed. Of 520 acute acetaminophen exposure cases presenting < 4 h post ingestion, 323 (62%) had a pre-4-hour acetaminophen concentration measured and 197 (38%) did not. Those with a known pre-4-hour acetaminophen concentration were less likely to have a 4-hour acetaminophen concentration (59% vs. 93%) or an acetaminophen concentration within 8 h (87% vs. 99%) and were more likely to be treated with acetylcysteine (29% vs. 17%) and less likely to be treated based on the Rumack-Matthew nomogram (72% vs. 97%). CONCLUSIONS: Patients with a known exposure time and presenting within 4 h of acetaminophen ingestion had a pre-4-hour acetaminophen concentration obtained 62% of the time. Pre-4-hour acetaminophen concentrations cannot be used to determine the need for acetylcysteine therapy and are associated with an increased likelihood of not obtaining optimally timed acetaminophen concentrations and acetylcysteine management not based on the proper application of the Rumack-Matthew nomogram. Current practice results in additional cost, unnecessary treatment, potential adverse medication effects, and the possibility of non-treatment of patients at risk of hepatotoxicity.

Reversible increase in maximal cortisol secretion rate in septic shock.

OBJECTIVE: Cortisol clearance is reduced in sepsis and may contribute to the development of impaired adrenocortical function that is thought to contribute to the pathophysiology of critical illness-related corticosteroid insufficiency. We sought to assess adrenocortical function using computer-assisted numerical modeling methodology to characterize and compare maximal cortisol secretion rate and free cortisol half-life in septic shock, sepsis, and healthy control subjects. DESIGN: Post hoc analysis of previously published total cortisol, free cortisol, corticosteroid-binding globulin, and albumin concentration data. SETTING: Single academic medical center. PATIENTS: Subjects included septic shock (n = 45), sepsis (n = 25), and healthy controls (n = 10). INTERVENTIONS: I.v. cosyntropin (250 µg). MEASUREMENTS AND MAIN RESULTS: Solutions for maximal cortisol secretion rate and free cortisol half-life were obtained by least squares solution of simultaneous, nonlinear differential equations that account for free cortisol appearance and elimination as well as reversible binding to corticosteroid-binding globulin and albumin. Maximal cortisol secretion rate was significantly greater in septic shock (0.83 nM/s [0.44, 1.58 nM/s] reported as median [lower quartile, upper quartile]) compared with sepsis (0.51 nM/s [0.36, 0.62 nM/s]; p = 0.007) and controls (0.49 nM/s [0.42, 0.62 nM/s]; p = 0.04). The variance of maximal cortisol secretion rate in septic shock was also greater than that of sepsis or control groups (F test, p < 0.001). Free cortisol half-life was significantly increased in septic shock (4.6 min [2.2, 6.3 min]) and sepsis (3.0 min [2.3, 4.8 min] when compared with controls (2.0 min [1.2, 2.6 min]) (both p < 0.004). CONCLUSIONS: Results obtained by numerical modeling are consistent with comparable measures obtained by the gold standard stable isotope dilution method. Septic shock is associated with generally not only higher levels but also greater variance of maximal cortisol secretion rate when compared with control and sepsis groups. Additional studies would be needed to determine whether assessment of cortisol kinetic parameters such as maximal cortisol secretion rate and free cortisol half-life is useful in the diagnosis or management of critical illness-related corticosteroid insufficiency.

Comparing Psychosocial Correlates of Condomless Anal Sex in HIV-Diagnosed and HIV-Nondiagnosed Men Who Have Sex with Men: A Series of Meta-Analyses of Studies from 1993-2013.

PURPOSE: Men who have sex with men (MSM) continue to be overrepresented in rates of incidence and prevalence of human immunodeficiency virus (HIV). Both HIV-diagnosed (HIV-D) and HIV-nondiagnosed (HIV-N) MSM report a variety of reasons for intentional and unintentional nonuse of condoms. Elucidating and comparing reasons for continued engagement in condomless anal sex specific to both HIV-D and HIV-N MSM likely is important to identifying effective prevention. METHODS: This study employed meta-analytic methods to evaluate and compare correlates to condomless anal sex in both HIV-D and HIV-N MSM from primary studies from 1993 to February 2013. RESULTS: Of the 19 individual correlates assessed within the subgroup of HIV-D MSM, variables that achieved significant effect were alcohol, mind-altering substance use, sexual-enhancement medication, intentional condom nonuse, self-efficacy, attitudes toward condom use, social support, gay identity, compulsivity, trading sex, and number of sex partners. Those that were statistically non-significant were intention to use a condom, perceived risk, perceived norms, perceived responsibility, HIV medical management, treatment optimism, mental health, and setting. Of the 12 correlates assessed within the subgroup of HIV-N MSM, variables that achieved significant effect were alcohol, mind-altering substance use, intentional condom nonuse, attitudes toward condom use, perceived risk, and setting. Those observed as statistically non-significant were perceived norms, social support, gay identity, mental health, trading sex, and number of sex partners. CONCLUSION: Study results have clinical implications that may guide future prevention research and practice by highlighting risk variables shared between HIV-N and HIV-D MSM, as well as variables observed to be unique to each group that may warrant more tailored intervention. Further investigation is recommended to elucidate the relationships among these variables such that optimal intervention can be determined.

Acrolein-exposed normal human lung fibroblasts in vitro: cellular senescence, enhanced telomere erosion, and degradation of Werner's syndrome protein.

BACKGROUND: Acrolein is a ubiquitous environmental hazard to human health. Acrolein has been reported to activate the DNA damage response and induce apoptosis. However, little is known about the effects of acrolein on cellular senescence. OBJECTIVES: We examined whether acrolein induces cellular senescence in cultured normal human lung fibroblasts (NHLF). METHODS: We cultured NHLF in the presence or absence of acrolein and determined the effects of acrolein on cell proliferative capacity, senescence-associated ß-galactosidase activity, the known senescence-inducing pathways (e.g., p53, p21), and telomere length. RESULTS: We found that acrolein induced cellular senescence by increasing both p53 and p21. The knockdown of p53 mediated by small interfering RNA (siRNA) attenuated acrolein-induced cellular senescence. Acrolein decreased Werner's syndrome protein (WRN), a member of the RecQ helicase family involved in DNA repair and telomere maintenance. Acrolein-induced down-regulation of WRN protein was rescued by p53 knockdown or proteasome inhibition. Finally, we found that acrolein accelerated p53-mediated telomere shortening. CONCLUSIONS: These results suggest that acrolein induces p53-mediated cellular senescence accompanied by enhanced telomere attrition and WRN protein down-regulation.

Safety of botulinum toxin for dysphagia in oculopharyngeal muscular dystrophy.

INTRODUCTION: Despite multiple studies reporting marked benefit of botulinum toxin (BTX) for treatment of cricopharyngeal dysphagia, little is known about its safety for this indication. We examined the safety of cricopharyngeal BTX for dysphagia in oculopharyngeal muscular dystrophy (OPMD). METHODS: We reviewed records of patients with OPMD who received cricopharyngeal BTX. RESULTS: Twenty-four patients underwent 66 procedures. Overall adverse event frequency was 44%. The most common adverse events were dysphonia (24%) and worsened dysphagia (14%). Logistic regression demonstrated that dose was a significant predictor of worsened dysphagia (P = 0.036) and of the composite event of dysphonia or worsened dysphagia (P = 0.009). There was a nonsignificant trend for dose as a predictor of dysphonia (P = 0.073). 59% of procedures were associated with symptomatic improvement. CONCLUSIONS: While BTX appears to be beneficial for treatment of dysphagia in OPMD, caution is warranted when injecting the cricopharyngeus muscle due to dose-related risk of dysphonia or worsened dysphagia.

The Mothers, Omega-3, and Mental Health Study: a double-blind, randomized controlled trial.

OBJECTIVES: Maternal deficiency of the omega-3 fatty acid, docosahexaenoic acid (DHA), has been associated with perinatal depression, but there is evidence that supplementation with eicosapentaenoic acid (EPA) may be more effective than DHA in treating depressive symptoms. This trial tested the relative effects of EPA- and DHA-rich fish oils on prevention of depressive symptoms among pregnant women at an increased risk of depression. STUDY DESIGN: We enrolled 126 pregnant women at risk for depression (Edinburgh Postnatal Depression Scale score 9-19 or a history of depression) in early pregnancy and randomly assigned them to receive EPA-rich fish oil (1060 mg EPA plus 274 mg DHA), DHA-rich fish oil (900 mg DHA plus 180 mg EPA), or soy oil placebo. Subjects completed the Beck Depression Inventory (BDI) and Mini-International Neuropsychiatric Interview at enrollment, 26-28 weeks, 34-36 weeks, and at 6-8 weeks' postpartum. Serum fatty acids were analyzed at entry and at 34-36 weeks' gestation. RESULTS: One hundred eighteen women completed the trial. There were no differences between groups in BDI scores or other depression endpoints at any of the 3 time points after supplementation. The EPA- and DHA-rich fish oil groups exhibited significantly increased postsupplementation concentrations of serum EPA and serum DHA respectively. Serum DHA- concentrations at 34-36 weeks were inversely related to BDI scores in late pregnancy. CONCLUSION: EPA-rich fish oil and DHA-rich fish oil supplementation did not prevent depressive symptoms during pregnancy or postpartum.

Promotion rates for assistant and associate professors in obstetrics and gynecology.

OBJECTIVE: To estimate promotion rates of physician faculty members in obstetrics and gynecology during the past 30 years METHODS: Data were collected annually by the Association of American Medical Colleges from every school between 1980 and 2009 for first-time assistant and associate professors to determine whether and when they were promoted. Data for full-time physician faculty were aggregated by decade (1980-1989, 1990-1999, 2000-2009). Faculty were included if they remained in academia for 10 years after beginning in rank. Data were analyzed by constructing estimated promotion curves and extracting 6-year and 10-year promotion rates. RESULTS: The 10-year promotion rates (adjusted for attrition) declined significantly for assistant professors from 35% in 1980-1989 to 32% in 1990-1999 to 26% in 2000-2009 (P<.001), and for associate professors from 37% to 32% to 26%, respectively (P<.005). These declines most likely resulted from changes in faculty composition. The most recent 15 years saw a steady increase in the proportion of entry-level faculty who were women (now 2:1) and primarily on the nontenure track. The increasing number of faculty in general obstetrics and gynecology had lower promotion probabilities than those in the subspecialties (odds ratio 0.16; P<.001). Female faculty on the nontenure track had lower promotion rates than males on the nontenure track, males on the tenure track, and females on the tenure track (odds ratio 0.8 or less; P<.01). CONCLUSION: A decline in promotion rates during the past 30 years may be attributable to changes in faculty composition. LEVEL OF EVIDENCE: II.

Association of maternal interaction with emotional regulation in 4- and 9-month infants during the Still Face Paradigm.

This study used the Still Face Paradigm to investigate the relationship of maternal interaction on infants' emotion regulation responses. Seventy infant-mother dyads were seen at 4 months and 25 of these same dyads were re-evaluated at 9 months. Maternal interactions were coded for attention seeking and contingent responding. Emotional regulation was described by infant stress reaction and overall positive affect. Results indicated that at both 4 and 9 months mothers who used more contingent responding interactions had infants who showed more positive affect. In contrast, mothers who used more attention seeking play had infants who showed less positive affect after the Still Face Paradigm. Patterns of stress reaction were reversed, as mothers who used more attention seeking play had infants with less negative affect. Implications for intervention and emotional regulation patterns over time are discussed.

Prematurity affects cortical maturation in early childhood.

Cortical development in the first years of age for children with very low birth weight is not well characterized. We obtained high-resolution structural magnetic resonance images from children aged 18-22 months (16 very low birth weight/7 term) and 3-4 years (12 very low birth weight/8 term). Cortical surface area and thickness of the brain were assessed using the FreeSurfer data analysis program, and manually inspected for accuracy. For children with very low birth weight, a negative correlation was evident between birth weight and cortical thickness at 18-22 months (P = 0.04), and a positive correlation with cortical surface area at 3-4 years (P = 0.02). Between groups, children with very low birth weight demonstrated a consistent trend for thicker cortices and reduced surface area, compared with control term children (18-22 month surface area, P = 0.08; thickness, P = 0.11; 3-4 year surface area, P = 0.73; thickness, P = 0.14). The normal processes of cortical thinning and surface area expansion in the first several years of age may be delayed by premature delivery, a potentially more prominent effect with greater degrees of prematurity.

Retention of entry-level faculty members in obstetrics and gynecology.

OBJECTIVE: The purpose of this study was to examine retention rates of entry-level physician faculty members in obstetrics and gynecology. STUDY DESIGN: Ongoing data were collected by the Association of American Medical Colleges between 1981 and 2009 for full-time, entry-level assistant professors to determine whether they remained at their original departments, switched to another school, or left academia. Retention curves and 5- and 10-year retention rates at their original department and for academia were determined. RESULTS: The number of entry-level faculty members per year increased significantly for women and those faculty members in general obstetrics and gynecology. Retention rates at the original departments improved for all disciplines in recent years (2000-09), regardless of sex. Among those faculty members who left their original department, faculty members in general obstetrics/gynecology were more likely than subspecialists to leave academia. CONCLUSION: Growth in the number of entry-level physician faculty members was accompanied by higher retention rates at their original departments only in recent years.

A system-based intervention to improve colorectal cancer screening uptake.

OBJECTIVE: To determine whether mailing guaiac-based fecal occult blood tests (gFOBTs) directly to patients who are due for colorectal cancer screening would achieve higher screening uptake than using visit-based screening. STUDY DESIGN: Comparative effectiveness analysis. METHODS: We used an electronic medical record to identify 7053 New Mexico Veterans Affairs Health Care System patients aged 50 to 80 years who were due for screening in 2008. We invited 3869 randomly selected patients to participate in a randomized controlled trial comparing adherence with different fecal blood tests; 202 intervention patients were assigned to receive mailed gFOBTs. We identified the following 3 control groups who could receive only visit-based colorectal cancer screening: 3184 individuals who were not invited for the randomized controlled trial (control group 1), 2525 individuals who did not respond to invitations to participate in the randomized controlled trial (control group 2), and 255 individuals who could not be contacted (control group 3). We measured gFOBT screening within 3 months after enrollment in the intervention group, as well as gFOBT or colonoscopy screening within 6 months of identification as a control subject. We compared screening across groups using multivariate logistic regression analysis to adjust for sex, race/ethnicity, clinic site, previous gFOBT, and comorbidities. RESULTS: Colorectal screening occurred less often in each of the control groups (in 18.6% of control group 1, in 14.3% of control group 2, and in 18.8% of control group 3) than among patients mailed a gFOBT (48.5%). Adjusted odds ratios for screening among the control groups were all less than in the intervention group (adjusted odds ratios, 0.25, 0.19, and 0.23, respectively; all, P <.001). CONCLUSION: Using an electronic medical record to identify screening-eligible patients and mailing them gFOBT cards achieved higher colorectal screening uptake than performing visit-based screening.