Ectopic Expression of Neurod1 Is Sufficient for Functional Recovery following a Sensory-Motor Cortical Stroke.

Stroke is the leading cause of adult disability worldwide. The majority of stroke survivors are left with devastating functional impairments for which few treatment options exist. Recently, a number of studies have used ectopic expression of transcription factors that direct neuronal cell fate with the intention of converting astrocytes to neurons in various models of brain injury and disease. While there have been reports that question whether astrocyte-to-neuron conversion occurs in vivo, here, we have asked if ectopic expression of the transcription factor Neurod1 is sufficient to promote improved functional outcomes when delivered in the subacute phase following endothelin-1-induced sensory-motor cortex stroke. We used an adeno-associated virus to deliver Neurod1 from the short GFAP promoter and demonstrated improved functional outcomes as early as 28 days post-stroke and persisting to at least 63 days post-stroke. Using Cre-based cell fate tracking, we showed that functional recovery correlated with the expression of neuronal markers in transduced cells by 28 days post-stroke. By 63 days post-stroke, the reporter-expressing cells comprised ~20% of all the neurons in the perilesional cortex and expressed markers of cortical neuron subtypes. Overall, our findings indicate that ectopic expression of Neurod1 in the stroke-injured brain is sufficient to enhance neural repair.

Mental illness and intensification of diabetes medications: an observational cohort study.

BACKGROUND: Mental health condition (MHC) comorbidity is associated with lower intensity care in multiple clinical scenarios. However, little is known about the effect of MHC upon clinicians' decisions about intensifying antiglycemic medications in diabetic patients with poor glycemic control. We examined whether delay in intensification of antiglycemic medications in response to an elevated Hemoglobin A1c (HbA1c) value is longer for patients with MHC than for those without MHC, and whether any such effect varies by specific MHC type. METHODS: In this observational study of diabetic Veterans Health Administration (VA) patients on oral antiglycemics with poor glycemic control (HbA1c ≥8) (N =52,526) identified from national VA databases, we applied Cox regression analysis to examine time to intensification of antiglycemics after an elevated HbA1c value in 2003-2004, by MHC status. RESULTS: Those with MHC were no less likely to receive intensification: adjusted Hazard Ratio [95% CI] 0.99 [0.96-1.03], 1.13 [1.04-1.23], and 1.12 [1.07-1.18] at 0-14, 15-30 and 31-180 days, respectively. However, patients with substance use disorders were less likely than those without substance use disorders to receive intensification in the first two weeks following a high HbA1c, adjusted Hazard Ratio 0.89 [0.81-0.97], controlling for sex, age, medical comorbidity, other specific MHCs, and index HbA1c value. CONCLUSIONS: For most MHCs, diabetic patients with MHC in the VA health care system do not appear to receive less aggressive antiglycemic management. However, the subgroup with substance use disorders does appear to have excess likelihood of non-intensification; interventions targeting this high risk subgroup merit attention.

Caring letters for suicide prevention: implementation of a multi-site randomized clinical trial in the U.S. military and Veteran Affairs healthcare systems.

Caring letters is a suicide prevention intervention that entails the sending of brief messages that espouse caring concern to patients following discharge from treatment. First tested more than four decades ago, this intervention is one of the only interventions shown in a randomized controlled trial to reduce suicide mortality rates. Due to elevated suicide risk among patients following psychiatric hospitalization and the steady increase in suicide rates among the U.S. military personnel, it is imperative to test interventions that may help prevent suicide among high-risk military personnel and veterans. This paper describes the design, methods, study protocol, and regulatory implementation processes for a multi-site randomized controlled trial that aims to evaluate the effectiveness of a caring emails intervention for suicide prevention in the military and VA healthcare systems. The primary outcome is suicide mortality rates to be determined 24 months post-discharge from index hospital stay. Healthcare re-utilization rates will also be evaluated and comprehensive data will be collected regarding suicide risk factors. Recommendations for navigating the military and VA research regulatory processes and implementing a multi-site clinical trial at military and VA hospitals are discussed.

Distress and pain during pelvic examinations: effect of sexual violence.

OBJECTIVE: To estimate the range and severity of distress and pain during pelvic examinations among female veterans with and without histories of sexual violence, and to examine whether posttraumatic stress disorder explains additional variance in examination-related distress and pain above that accounted for by exposure to sexual violence. METHODS: We employed a cross-sectional cohort design in which 67 selected female veterans completed self-administered questionnaires to assess history of sexual violence and experiences of distress and pain associated with the pelvic examination. A subsample of 49 completed an assessment for posttraumatic stress disorder approximately 2 weeks later. RESULTS: Distress associated with the pelvic examination was highest for women with prior sexual violence and posttraumatic stress disorder (median 5.49), next highest for women with sexual violence only (median 2.44), and lowest for women with neither (median 0), P=.015. Higher ratings of pain were also found among women with sexual violence (median 2.5) compared with those without (median 0), P=.04. However, posttraumatic stress disorder was not linked with increased pain from speculum insertion beyond that accounted for by sexual violence; limited power may have precluded detection of this effect. CONCLUSION: Distress and pain during pelvic examinations may indicate a history of previous sexual violence, particularly in those with posttraumatic stress disorder. Extra sensitivity to the special needs of this population is warranted and may contribute positively to the quality of patients' experiences. LEVEL OF EVIDENCE: II.

Impact of clinician gender on examination anxiety among female veterans with sexual trauma: a pilot study.

BACKGROUND: The sequelae of sexual trauma, including symptoms or diagnosis of posttraumatic stress disorder (PTSD), may impact women's anxiety and avoidance of preventive healthcare measures such as breast, pelvic, and rectal examinations. As sexual trauma is unfortunately a common occurrence among female patients, particularly veterans, understanding how it influences examination-related distress may improve provision of care to this population. We explored the impact of clinician gender and examination type (breast, pelvic, rectal, and dental) on anticipated examination-related anxiety among women veterans with a history of sexual trauma. METHODS: We present a cross-sectional pilot study that examines anticipated examination-related distress among 31 female veterans with a history of sexual trauma. Sexual trauma history was verified by chart review. Self-report instruments assessed patient demographics and patients' anticipated anxiety during breast, pelvic, rectal, and dental examinations (stratified by gender of clinician). The PTSD Checklist-Civilian Version (PCL-C) assessed symptom severity. RESULTS: The women reported significantly more anticipated anxiety during breast, pelvic, and rectal examinations, (p < 0.05) when clinician gender was male. Severity of PTSD symptoms was generally unrelated to anticipated examination-related anxiety. CONCLUSION: Anticipated anxiety was found to be a function of both examination type and clinician gender but not of PTSD symptom severity. These findings emphasize the importance of screening for sexual trauma and the careful consideration of female veterans' unique needs during sensitive medical procedures.

Predicting high-risk behaviors in veterans with posttraumatic stress disorder.

The present study sought to identify posttraumatic stress disorder (PTSD) patients at high risk for negative behavioral outcomes (violence, suicide attempts, and substance use). The Mississippi Scale for Combat-Related PTSD, the Beck Depression Inventory, and demographic and behavioral data from 409 male combat veterans who completed a VA residential rehabilitation program for PTSD were analyzed using signal detection methods (receiver operating characteristics). A validation sample (N = 221) was then used to test interactions identified in the signal detection analyses. The best predictors of behaviors at follow-up were those same behaviors shortly before intake, followed by depressive and PTSD symptoms. However, for each of the models other than that for hard drug use, cutoffs determined at the symptom level did not lend themselves to replication. Recent high-risk behaviors, rather than patients' history, appear to be more predictive of high-risk behaviors postdischarge.