Alan Anschel

Bak and Bax Function To Limit Adenovirus Replication through Apoptosis Induction

ABSTRACT Adenovirus infection and expression of E1A induces both proliferation and apoptosis, the latter of which is blocked by the adenovirus Bcl-2 homologue E1B 19K. The mechanism of apoptosis induction and the role that it plays in productive infection are not known. Unlike apoptosis mediated by death receptors, infection with proapoptotic E1B 19K mutant viruses did not induce cleavage of Bid but nonetheless induced changes in Bak and Bax conformation, Bak-Bax interaction, caspase 9 and 3 activation, and apoptosis. In wild-type-adenovirus-infected cells, in which E1B 19K inhibits apoptosis, E1B 19K was bound to Bak, precluding Bak-Bax interaction and changes in Bax conformation. Infection with E1B 19K mutant viruses induced apoptosis in wild-type and Bax- or Bak-deficient baby mouse kidney cells but not in those deficient for both Bax and Bak. Furthermore, Bax and Bak deficiency dramatically increased E1A expression and virus replication. Thus, Bax- and Bak-mediated apoptosis severely limits adenoviral replication, demonstrating that Bax and Bak function as an antiviral response at the cellular level.

Burden of illness associated with painful diabetic peripheral neuropathy among adults seeking treatment in the US: Results from a retrospective chart review and cross-sectional survey

Background The purpose of this study was to characterize the burden of illness among adult subjects with painful diabetic peripheral neuropathy (pDPN) seeking treatment in the US. Methods This observational study recruited 112 subjects with pDPN during routine visits from general practitioner and specialist sites. Subjects completed a one-time questionnaire, which included demographics, symptom duration, health care resource use, out-of-pocket costs, employment status, and validated measures that assessed pain, functioning, sleep, anxiety and depression, health status, and productivity. Investigators completed a case report form based on a 6-month retrospective chart review to capture clinical information, pDPN-related treatments, and other pDPN-related health care resource use over the past 6 months. Annualized costs were extrapolated based on reported 6-month health care resource use. Results The mean age of the subjects was 61.1 years, 52.7% were female, and 17.9% were in paid employment. The most common comorbid conditions were sleep disturbance/insomnia (43.8%), depressive symptoms (41.1%), and anxiety (35.7%). The mean pain severity score was 5.2 (0–10 scale), and 79.5% reported moderate or severe pain. The mean pain interference with function score was 5.0 (0–10 scale) overall, with 2.0 among mild, 5.1 among moderate, and 7.0 among severe. The mean Medical Outcomes Study sleep problems index score was 48.5 (0–100 scale). The mean health state utility score was 0.61. Among subjects employed for pay, mean overall work impairment was 43.6%. Across all subjects, mean overall activity impairment was 52.3%. In total, 81.3% were prescribed at least one medication for their pDPN; 50.9% reported taking at least one nonprescription medication. Adjusted mean annualized total direct and indirect costs per subject were

Economic and humanistic burden of post-trauma and post-surgical neuropathic pain among adults in the United States

4841 and

Burden of spinal cord injury-related neuropathic pain in the United States: Retrospective chart review and cross-sectional survey

9730, respectively. Outcomes related to pain interference with function, sleep, health status, activity impairment, prescription medication use, and direct and indirect costs were significantly worse among subjects with more severe pain (P < 0.0020). Conclusion Subjects with pDPN exhibited high pain levels, which were associated with poor sleep, function, and productivity. Health care resource utilization in pDPN was prevalent and costs increased with greater pain severity. The burden of pDPN was greater among subjects with greater pain severity.

Pain severity and the economic burden of neuropathic pain in the United States: BEAT Neuropathic Pain Observational Study

Background Neuropathic pain (NeP) can be chronic, debilitating, and can interfere with sleep, functioning, and emotional well being. While there are multiple causes of NeP, few studies have examined the disease burden and treatment patterns associated with post-traumatic/post-surgical (PTPS) NeP. Objective To characterize pain, health status, function, health care resource utilization, lost productivity, and costs among subjects with PTPS NeP in the United States. Methods This observational study enrolled 100 PTPS NeP subjects recruited during routine visits from general practitioner and specialist sites. Subjects completed a one-time questionnaire with validated measures of pain severity and pain interference, health status, sleep, anxiety and depression, productivity, and study-specific items on demographics, employment status, and out-of-pocket expenses. Investigators completed a case report form based on a 6-month retrospective chart review, recording subjects’ clinical characteristics as well as current and previous medications/treatments for NeP. Subjects were stratified into mild, moderate, and severe pain groups. Results Subjects’ demographic characteristics were: mean age of 54.9 years, 53% female, and 22% employed for pay. Mean pain severity score was 5.6 (0–10 scale), with 48% and 35% classified as having moderate and severe pain, respectively. The mean number of comorbidities increased with greater pain severity (P = 0.0009). Patient-reported outcomes were worse among PTPS NeP subjects with more severe pain, including pain interference with function, health state utility, sleep, and depression (P < 0.0001). Eighty-two percent of subjects were prescribed two or more NeP medications. The total mean annualized adjusted direct and indirect costs per subject were

Health status, function, productivity, and costs among individuals with idiopathic painful peripheral neuropathy with small fiber involvement in the United States: results from a retrospective chart review and cross-sectional survey.

11,846 and

Burden of Chronic Low Back Pain with a Neuropathic Pain Component:Retrospective Chart Review and Cross-sectional Survey among AdultsSeeking Treatment in the United States

29,617, respectively. Across pain severity levels, differences in annualized adjusted direct and indirect costs were significant (P < 0.0001). Conclusion PTPS NeP subjects reported high pain scores, which were associated with poor health utility, sleep, mood, and function, as well as high health care resource utilization and costs. The quality of life impact and costs attributable to PTPS NeP suggest an unmet need for effective and comprehensive management.

Effects of Teriparatide and Vibration on Bone Mass and Bone Strength in People with Bone Loss and Spinal Cord Injury: A Randomized, Controlled Trial: TERIPARATIDE AND VIBRATION EFFECTS ON BONE MASS IN SCI

Study design:Cross-sectional, observational study.Objectives:Characterize demographic and clinical characteristics, health status, pain, function, productivity and economic burden in spinal cord injury-related neuropathic pain (SCI-NeP) subjects, by pain severity.Setting:United States.Methods:One hundred and three subjects diagnosed with SCI-NeP recruited during routine primary care or specialty physician office visits completed a questionnaire to assess patient-reported outcomes. Physicians completed a case report form on inclusion/exclusion criteria, subject clinical characteristics and health-care resource use (HRU) based on 6-month retrospective chart review.Results:Subjects’ mean age was 48.7, 69.9% were male and 48.5% were unable to walk. The most frequently reported comorbidities were sleep disturbance/insomnia (28.2%), depressive symptoms (25.2%) and anxiety (23.3%). Subjects’ mean pain severity score was 5.3 (0–10 scale), and 77.7% reported moderate or severe pain. On a 0–10 scale, subjects’ reported moderate pain interference with function: mean 5.4. Subjects’ health status, as measured by the EuroQol 5-dimensions health-state utility, was 0.49 (−0.11 to 1.00 scale). Pain interference with function and health status were significantly worse among subjects with more severe pain (P<0.0005). Among employed subjects (13.6%), overall work impairment was 38.0%. The proportion of subjects who were prescribed ⩾1 medication was 94.2%, and the mean number of physician office visits in past 6 months due to SCI-NeP was 2.2. Total annualized cost per subject was

Burden of Illness Associated with Peripheral and Central Neuropathic Pain among Adults Seeking Treatment in the United States: A Patient-Centered Evaluation

26 270 (direct:

NEUROPATHIC PAIN SECTION Original Research Articles Burden of Illness Associated with Peripheral and Central Neuropathic Pain among Adults Seeking Treatment in the United States: A Patient-Centered Evaluation

8636, indirect: