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Abstract Objective: The authors evaluated the efficacy of the 2002 college-based National Alcohol Screening Day (NASD) by determining: (1) the demographic and clinical characteristics of the participants that were screened and (2) the degree to which those scoring at hazardous drinking levels received clinical intervention or were referred for further assessment or treatment. Participants: Of 45,368 participants, 23,334 were screened and 14,598 received some form of clinical intervention, defined as advice or referral. Methods: The authors conducted nonparametric and univariate analyses to test for statistical differences in demographics, clinical-characteristics, and interventions-as a function of-screening mode. Results: Nearly 34% of those screened in person had an AUDIT score of 8 or higher, indicating harmful or hazardous drinking. Of these, only 10% had ever undergone alcohol treatment. More than 58% of those screened online scored 8 or higher, and of this group, fewer than 6% had ever undergone alcohol treatment. Conclusions: These data suggest that the in-person event and the online interactive program associated with NASD are serving markedly different populations, particularly with regard to clinical indicators. (Contains 6 tables and 1 figure.)

National Alcohol Screening Day (NASD) is the nation's largest and most visible community-based intervention targeting alcohol misuse. Established in 1999 through a partnership between the National Institute on Alcohol Abuse [...]

In their final report presented last summer, the President's New Freedom Commission on Mental Health recommended six primary goals for transforming the nation's mental health care system. Included on this [...]

Background and Objectives: Rheumatoid arthritis (RA) is a chronic, debilitating disease affecting an estimated 1.5 million patients in the US. The condition is associated with a substantial health and economic burden. An economic model was developed to evaluate the cost-effectiveness of tofacitinib (a novel oral Janus kinase inhibitor) versus biologic therapies commonly prescribed in the US for the treatment of RA.Methods: A cost-utility model was developed whereby sequences of treatments were evaluated. Response to treatment was modeled by HAQ change, and informed by a network meta-analysis. Mortality, resource use and quality of life were captured in the model using published regression analyses based on HAQ score. Treatment discontinuation was linked to response to treatment and to adverse events. Patients were modeled as having had an inadequate response to methotrexate (MTX-IR), or to a first biologic therapy (TNFi-IR).Results: The tofacitinib strategy was associated with cost savings compared with alternative treatment sequences across all modeled scenarios (i.e. in both the MTX-IR and TNFi-IR scenarios), with lifetime cost savings per patient ranging from $65,205 to $93,959 (2015 costs). Cost savings arose due to improved functioning and the resulting savings in healthcare expenditure, and lower drug and administration costs. The tofacitinib strategies all resulted in an increase in quality-adjusted life years (QALYs), with additional QALYs per patient ranging from 0.01 to 0.22.Conclusions: Tofacitinib as a second-line therapy following methotrexate failure and as a third-line therapy following a biologic failure produces lower costs and improved quality of life compared with the current pathway of care. [ABSTRACT FROM AUTHOR]

Objectives. RA causes high disability levels and reduces health-related quality of life, triggering increased costs and risk of unemployment. Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. These post hoc analyses of phase 3 data aimed to assess monthly medical expenditure (MME) and risk of job loss for tofacitinib treatment vs placebo. Methods. Data analysed were from two randomized phase 3 studies of RA patients (n = 1115) with inadequate response to MTX or TNF inhibitors (TNFi) receiving tofacitinib 5 or 10 mg twice daily, adalimumab (one study only) or placebo, in combination with MTX. Short Form 36 version 2 Health Survey physical and mental component summary scores were translated into predicted MME via an algorithm and concurrent inability to work and job loss risks at 6, 12 and 24 months, using Medical Outcomes Study data. Results. MME reduction by month 3 was $100 greater for tofacitinib- than placebo-treated TNFi inadequate responders (P < 0.001); >20 and 6% reductions from baseline, respectively. By month 3 of tofacitinib treatment, the odds of inability to work decreased ≽16%, and risk of future job loss decreased ~20% (P < 0.001 vs placebo). MME reduction by month 3 was $70 greater for tofacitinib- than placebo-treated MTX inadequate responders (P < 0.001); ≽23 and 13% reductions from baseline, respectively. By month 3 of tofacitinib treatment, the odds of inability to work decreased ≽31% and risk of future job loss decreased ≽25% (P < 0.001 vs placebo). Conclusion. Tofacitinib treatment had a positive impact on estimated medical expenditure and risk of job loss for RA patients with inadequate response to MTX or TNFi. [ABSTRACT FROM AUTHOR]

Objective: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We compared patient-reported outcomes (PROs) in patients with RA treated with tofacitinib or placebo in combination with conventional disease-modifying antirheumatic drugs (DMARDs).Methods: In a 12-month, phase III randomized controlled trial (ORAL Sync), patients (n = 795) with active RA and previous inadequate response to therapy with ≥1 conventional or biologic DMARD were randomized 4:4:1:1 to tofacitinib 5 mg twice daily (BID), tofacitinib 10 mg BID, placebo advanced to 5 mg BID, or placebo to 10 mg BID, in combination with stable background DMARD therapy. PROs included patient global assessment of arthritis (PtGA), patient assessment of arthritis pain (Pain), physical function (Health Assessment Questionnaire disability index [HAQ DI]), health-related quality of life (Short Form 36 health survey [SF-36]), fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F]), and sleep (Medical Outcomes Study Sleep [MOS Sleep]).Results: At month 3, statistically significant improvements from baseline versus placebo were reported in PtGA, Pain, HAQ DI, all 8 SF-36 domains, FACIT-F, and MOS Sleep with tofacitinib 10 mg BID, and in PtGA, Pain, HAQ DI, 7 SF-36 domains, FACIT-F, and MOS Sleep with tofacitinib 5 mg BID. Improvements were sustained to month 12. Significantly more tofacitinib-treated patients reported improvements of greater than or equal to the minimum clinically important differences at month 3 versus placebo in all PROs, except the SF-36 role-emotional domain (significant for tofacitinib 10 mg BID).Conclusion: Patients with active RA treated with tofacitinib combined with background conventional DMARD therapy reported sustained, significant, and clinically meaningful improvements in PROs versus placebo. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and joint structural deterioration. Driven by recent expectations that patients in clinical trials randomized to placebo should be 'rescued' with active therapy within 6 months of starting treatment, the relative benefit of arresting joint damage with biologic agents beyond this period is unclear. With longer-term evidence of the rate of joint deterioration with minimal treatment, the efficacy of biologic agents and novel treatments might be projected beyond the placebo-controlled phase observed in clinical trials. The aim of this study was to estimate radiographic structural deterioration over time in patients with moderate-to-severe RA minimally treated with DMARDs.Methods: A literature review identified evidence of joint structural deterioration in patients with (DMARD-IR population) and without (non-DMARD-IR population) a history of inadequate response to DMARDs. Patients were minimally treated with one non-biologic DMARD or palliative care (non-DMARD-IR population only). Outcomes of interest were the (modified) Total Sharp Score (TSS) and subscales (Erosion Subscore [ES] and Joint Space Narrowing [JSN] Subscore), and Larsen score. Pooled joint-deterioration curves over time were obtained with meta-analysis models.Results: Mean change from baseline in TSS increased in the DMARD-IR population from 1.14 (95 % credible interval [CrI] 0.66, 1.67) to 9.84 (5.68, 14.46) at Weeks 12 and 104, respectively, and a non-linear increase of 1.56 (0.79, 2.34) and 5.13 (-1.35, 11.67) in the non-DMARD-IR population. At the same time points, mean changes (95 % CrI) were 0.51 (0.27, 0.83) and 4.43 (2.38, 7.21) for ES and 0.36 (0.09, 0.67) and 3.14 (0.80, 5.78) for JSN in the DMARD-IR population, whereas corresponding changes in the non-DMARD-IR population were 0.69 (0.31, 1.12) and 2.93 (0.92, 5.02), and 0.29 (0.17, 0.44) and 2.55 (1.45, 3.80), respectively. Larsen scores were only available for the non-DMARD-IR population, with mean changes (95 % CrI) of 0.08 (0.04, 0.11) and 0.65 (0.36, 0.96) at Weeks 12 and 104, respectively.Conclusion: Minimal treatment of RA with one non-biologic DMARD results in deterioration of joint structure in patients with or without a history of inadequate response to non-biologic DMARDs. [ABSTRACT FROM AUTHOR]

The article discusses a study that provided guidelines, tools, and required steps for successful implementation of patient-reported outcome measurement in rheumatoid arthritis (RA) clinical trials. Topics discussed include the core set of endpoints suggested for use in clinical studies of RA, a list of patient-centered domains received from qualitative studies of RA, and two related aspects of work limitations attributed to RA.

To estimate the minimally important difference (MID) for the Insomnia Severity Index (ISI) by examining the association of score differences of the ISI with health-related outcomes including health-related quality of life, productivity, and fatigue. Data came from a randomized, placebo-controlled clinical trial evaluating the long-term efficacy of eszopiclone for primary insomnia (N = 828). Logistic regression models were used to characterize the relationship between ISI change scores (from baseline to 6 months post-treatment) and outcomes/anchors from the SF-36 Health Survey, Work Limitations Questionnaire (WLQ), and Fatigue Severity Scale (FSS). Odds ratios were derived from the regression coefficients to calculate the probability of a given outcome being associated with different ISI change scores. Convergence between anchor- and distribution-based estimates was assessed. Higher ISI scores (indicating more severe insomnia) were significantly associated with higher probabilities of negative outcome in all models. Individuals with a 6-point score reduction in ISI scores (which corresponded to 1½ standard deviations) were 48% less likely to report 'feeling worn out' (SF-36) at 6 months, 46% less likely to be 'unable to think clearly' (WLQ), and 52% less likely to report 'feeling fatigued' (FSS). Similar results were found across a broad spectrum of all selected anchors. Based on results of the study, a 6-point reduction is recommended to represent a clinically meaningful improvement in individuals with primary insomnia. Research on generalizability of the recommended MID in this study to other patient populations and other type of treatment interventions is needed. [ABSTRACT FROM AUTHOR]

Background: The impact of alcohol abuse on worker productivity is considerable and appears to be increasing over time. Although early screening and intervention may help prevent or reduce the damaging health and productivity effects of problem drinking, barriers to behavioral change may render broad-based prevention efforts ineffectual. This study examined the correlates of two potential barriers to changes in drinking behavior – underestimation of drinking and lack of knowledge of helping resources – using data from web-based employee alcohol screenings. Methods: Anonymous screening data from 1185 employees of ten companies participating in the 2003 National Alcohol Screening Day were analyzed. The AUDIT, a 10-item screening instrument developed by the World Health Organization, was used to measure drinking behavior; employees' subjective assessments of their drinking were also obtained. Results: Over 53% of participants subjectively underestimated their drinking relative to their AUDIT results, and 58% of respondents did not know whether their medical insurance included benefits for alcohol treatment. Logistic regression analysis revealed that younger and male respondents tended to have the highest AUDIT scores and also (along with married respondents) were most likely to underestimate their drinking. Younger, unmarried respondents were least likely to be aware of their alcohol treatment insurance benefits. Conclusions: Current corporate efforts to curtail problem drinking among employees may not adequately address barriers to change. Targeting at-risk employee groups for alcohol screening and dissemination of information about health insurance benefits and treatment options is recommended, as is providing personalized feedback based on screening results to raise awareness of at-risk drinking and available helping resources. [ABSTRACT FROM AUTHOR]

Objective: To develop and validate the Premenstrual Symptoms Impact Survey (PMSIS), a brief web-based instrument for evaluating the impact of premenstrual symptoms on health-related quality of life (HRQOL). Methods: An item bank of 68 questions was administered to a nationally representative sample of 971 women using the web, aged 18–45, who experienced regular menstrual cycles in the past 3 months, were not currently pregnant or breastfeeding, and were not being treated or taking medications for depression-related disorders in the last 2 years. Item reduction was performed using forward stepwise linear regression of an overall symptom severity score onto item scores. Three standards were used to validate the instrument: (1) the American College of Obstetricians and Gynecologists retrospective diagnostic criteria for identifying participants “at risk” for clinically significant premenstrual syndrome (PMS), (2) the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders retrospective diagnostic criteria for identifying participants at risk for premenstrual dysphoric disorder (PMDD), and (3) the Medical Outcomes Study Short Form (SF-12) Health Survey. Results: Six items met entry criteria in the model. Approximately 6.0% of the participants were identified as being at risk for PMDD, and 17.3% were identified as being at risk for clinically significant PMS. PMSIS scale score differed significantly between participants who were and were not at risk for PMDD/clinically significant PMS. PMSIS scale score also differed significantly between participants having either high, average, or low HRQOL as defined by SF-12 physical and mental component summary scores. Conclusions: These results demonstrate that the PMSIS has excellent discriminative ability to detect differences in groups that are known to differ in terms of clinical criteria. The PMSIS can be used to educate consumers about the impact of their symptoms on QOL. [ABSTRACT FROM AUTHOR]

Objective: To propose the minimally important difference (MID) for the SF-36 Vitality (VT) scale by evaluating the association of score differences with clinical conditions and functional outcomes.Methods: Analyses were performed on data from the Medical Outcomes Study (n = 3445). The first analyses regressed VT scores (0-100 scale) on chronic conditions that cause fatigue in order to determine the impact of each condition on VT. The second set of analyses examined the relationship between baseline VT scores and other outcomes at baseline, 1-year, and 7-year follow-up.Results: VT scores were significantly reduced in patients with anemia [5 points (95% CI 2-9 points)], CHF [6 (3-9) points], and COPD [6 (3-9) points]. Decreases in VT score were significantly associated with increased odds of negative outcomes, including inability to work due to health at baseline [OR (5 points) = 1.27 (95% CI 1.24-1.31), OR (10 points) = 1.62 (1.54-1.71)], job loss at 1 year [OR (5) = 1.13 (1.08-1.19), OR (10) = 1.28 (1.17-1.41)], hospitalization at 1 year [OR (5) = 1.08 (1.05-1.11), OR (10) = 1.17 (1.10-1.23)], short-term mortality [0-18 months-Hazard Ratio (HR) (5) = 1.10-1.71, HR (10) = 1.21-2.39, depending on VT level] and long-term mortality [19+ months-HR (5) = 1.05-1.31, HR (10) = 1.10-1.54]. The mortality risk increase was largest at low VT levels.Conclusions: VT decrements of 5-10 points were seen for diseases known to cause fatigue. Further, differences of 5-10 points in the VT score were associated with significant increased risk of negative outcomes. We recommend an MID of 5 points for analyses of groups with VT scores below average. For follow-up of individual patients, we recommend a 10-point difference as important. [ABSTRACT FROM AUTHOR]

Rats were implanted bilaterally with cannulae into the dorsal hippocampus and trained in a Pavlovian fear-conditioning paradigm. Four groups of rats were infused intra-cranially with 1-(5′-isoquinolinesulfonyl)-2-methylpiperazine (H7-dihydrochloride), a potent inhibitor of both protein kinase C (PKC) and cAMP-dependent protein kinase (PKA), at different time intervals in order to examine their involvement in the acquisition and consolidation of contextual fear memory. We demonstrate a significant consolidation deficit of long-term contextual fear-conditioning memory that is maximal when PKA and PKC are inhibited at 90 min post-training. These results suggest the existence of a critical time window, during which these enzymes must be activated for the consolidation of long-term memories. [Copyright &y& Elsevier]

Argues that the hippocampus structure of the brain is involved most critically in learning and memory tasks in which discontiguous items must be associated, in terms of their temporal or spatial positioning, or both. Brief review of related literatures; Manner by which contextual information is represented in the hippocampus; Spatial learning performance of hippocampal-damaged animals; Components for context field development.

The article discusses a study that compared tofacitinib monotherapy with methotrexate monotherapy in patients with active moderate-to-severe rheumatoid arthritis who did not receive methotrexate previously. Eligible were patients at least 18 years old diagnosed with active rheumatoid arthritis in accordance with the revised criteria of the American College of Rheumatology. It suggests an association between tofacitinib monotherapy taken twice daily with reduced symptoms of rheumatoid arthritis.

Objectives: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Here we investigated the effects of tofacitinib on patient-reported outcomes (PRO) in patients with active RA., Methods: Two, 6-month, double-blind, placebo-controlled Phase 2b studies were performed. The combination study evaluated patients with inadequate response to methotrexate who received tofacitinib 1-15 mg twice daily (BID), 20 mg once daily or placebo, on background methotrexate. In the monotherapy study, patients with inadequate response to disease-modifying anti-rheumatic drugs received tofacitinib 1-15 mg BID, adalimumab 40 mg once every other week or placebo. PROs measured were: Patient's Assessment of Arthritis Pain (PAAP), Patient's Assessment of Disease Activity, HAQ-DI, FACIT-F and SF-36., Results: In the combination study (n=507), significant improvements (p<0.05) versus placebo were observed at Week 12 in PAAP (visual analogue scale) and HAQ-DI for all tofacitinib groups. In the monotherapy study (n=384), significant improvements in PAAP were observed at Week 12 for tofacitinib 5, 10 and 15 mg BID, and in HAQ-DI for tofacitinib 3, 5, 10 and 15 mg BID. Significant improvements versus placebo were seen at Week 2 in PAAP (both studies) and HAQ‑DI (monotherapy study) with tofacitinib, and were maintained throughout each study. In both studies, improvements in several domains of the SF-36 in the tofacitinib groups were observed at Weeks 12 and 24., Conclusions: In patients with active RA, tofacitinib, either in combination with methotrexate or as monotherapy, demonstrated rapid and sustained improvement in pain, physical functioning and health-related quality of life.

Objective: To link the Premenstrual Symptoms Impact Survey (PMSIS) scores to health-related quality of life (HRQOL) and sexual drive impact associated with premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD)., Study Design: Secondary data analysis was performed using the online survey study for PMSIS development. Women were sorted into 10 mutually exclusive score levels (N = 949). Their responses to the SF-12v2 Health Survey and the sexual drive question were dichotomized to indicate the presence of limitations/impairment. Chi-square analysis was conducted to compare the differences in percentages of women with limitations across 3 representative PMSIS score levels containing (1) women with no indication of PMS, (2) women at risk for PMS but not PMDD, and (3) women at risk for PMDD., Results: The higher the PMSIS score level (more severe impact), the greater the percentage of women reported functional limitations. Women either at risk for PMS or PMDD were significantly more likely to report limitations than women with no indication of PMS in all HRQOL areas except for 2 Physical Functioning items and 1 Mental Health item and the General Health item. Significantly more women with PMS (67.5%) and with PMDD (73.3%) reported sexual drive impact than in women with no PMS (45.7%)., Conclusion: The associations between PMSIS score levels and the premenstrual symptoms' impact on HRQOL and sexual functioning assist the interpretation of PMSIS scores and use of the tool in reproductive-age women.

Objective: Asthma is a multidimensional disease, characterized by changes in pulmonary function, transient and chronic symptoms, and effects on quality of life. In this study, we compared the psychometric properties and screening accuracy of three patient-based asthma control instruments including: the Asthma Control Test (ACT), a brief instrument developed to assess asthma control of patients in a clinical setting; the Asthma Control Questionnaire (ACQ), an instrument developed for use in clinical research; and the 'Rules of Two', a tool that has been used in both settings., Methods: Patients (N = 313) completed the ACT, ACQ, and Rules of Two during two asthma clinic visits 4-12 weeks apart. Office staff recorded pre- and post-bronchodilator FEV(1) measurements and asthma specialists provided a global rating of asthma control. Internal consistency reliability was computed and construct validity was evaluated using analysis of variance (ANOVA). Logistic regression and receiving operating characteristic (ROC) curve analysis was conducted to compare the screening accuracy of each measure in identifying patients with uncontrolled or moderate to severe asthma. The responsiveness of each measure to changes in asthma control and severity was tested using correlational and ANOVA methods., Results: Results show that the ACT and ACQ have comparable reliability, validity, screening accuracy, and responsiveness. The Rules of Two, however, did not meet some standards and therefore has weaker psychometric properties., Conclusion: The ACT and ACQ are comparable asthma control questionnaires. The choice of which questionnaire to use should be informed by considering several factors, such as the intended purpose and setting where the questionnaire will be used, as well as the content, practicality, availability of benchmark scores, and adaptability to multiple administration modes of each questionnaire. One potential limitation of the study is that the data were collected in a clinical setting with limited demographic information. Hence, additional studies are needed to evaluate the psychometric properties of each instrument across demographic and clinical subgroups of the general population.