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We report the discovery and confirmation of the planetary system TOI-1288. This late G dwarf harbours two planets: TOI-1288 b and TOI-1288 c. We combine TESS space-borne and ground-based transit photometry with HARPS-N and HIRES high-precision Doppler measurements, which we use to constrain the masses of both planets in the system and the radius of planet b. TOI-1288~b has a period of $2.699835^{+0.000004}_{-0.000003}$ d, a radius of $5.24 \pm 0.09$ R$_\oplus$, and a mass of $42 \pm 3$ M$_\oplus$, making this planet a hot transiting super-Neptune situated right in the Neptunian desert. This desert refers to a paucity of Neptune-sized planets on short period orbits. Our 2.4-year-long Doppler monitoring of TOI-1288 revealed the presence of a Saturn-mass planet on a moderately eccentric orbit ($0.13^{+0.07}_{-0.09}$) with a minimum mass of $84 \pm 7$ M$_\oplus$ and a period of $443^{+11}_{-13}$ d. The 5 sectors worth of TESS data do not cover our expected mid-transit time for TOI-1288 c, and we do not detect a transit for this planet in these sectors., 16 pages, 17 figures, under review MNRAS

The CHIME/FRB experiment has detected thousands of Fast Radio Bursts (FRBs) due to its sensitivity and wide field of view; however, its low angular resolution prevents it from localizing events to their host galaxies. Very Long Baseline Interferometry (VLBI), triggered by FRB detections from CHIME/FRB will solve the challenge of localization for non-repeating events. Using a refurbished 10-m radio dish at the Algonquin Radio Observatory located in Ontario Canada, we developed a testbed for a VLBI experiment with a theoretical ~, Accepted for publication by AJ

The Canadian Hydrogen Intensity Mapping Experiment (CHIME) has emerged as the prime telescope for detecting fast radio bursts (FRBs). CHIME/FRB Outriggers will be a dedicated very-long-baseline interferometry (VLBI) instrument consisting of outrigger telescopes at continental baselines working with CHIME and its specialized real-time transient-search backend (CHIME/FRB) to detect and localize FRBs with 50 mas precision. In this paper we present a minimally invasive clock stabilization system that effectively transfers the CHIME digital backend reference clock from its original GPS-disciplined ovenized crystal oscillator to a passive hydrogen maser. This enables us to combine the long-term stability and absolute time tagging of the GPS clock with the short and intermediate-term stability of the maser to reduce the clock timing errors between VLBI calibration observations. We validate the system with VLBI-style observations of Cygnus A over a 400 m baseline between CHIME and the CHIME Pathfinder, demonstrating agreement between sky-based and maser-based timing measurements at the 30 ps rms level on timescales ranging from one minute to up to nine days, and meeting the stability requirements for CHIME/FRB Outriggers. In addition, we present an alternate reference clock solution for outrigger stations which lack the infrastructure to support a passive hydrogen maser., 15 pages, 7 figures, submitted to AJ

Reducing nitrogen loading to water resources is a goal for resource managers in many regions experiencing water quality degradation. Onsite wastewater systems (OWS) are used for treating wa...

Objective: Several studies have demonstrated that cellular phone short message service (SMS) improve antiretroviral adherence for people living with HIV in Africa, although less data are available to support using SMS reminders to improve timeliness of antiretroviral therapy (ART) pharmacy pick up. This study tested the efficacy of SMS reminders on timeliness of ART pharmacy pickups at an urban clinic in Gaborone, Botswana. Design: A randomized-controlled trial evaluating the effect of SMS reminders on ART collection for patients with HIV on treatment. Methods: One hundred and eight treatment-experienced adult patients were enrolled and randomly assigned to a control group or an intervention group. Participants in the intervention group received SMS reminders that were sent in advance of monthly ART refills that needed to be collected. The primary outcome was 100% timeliness of pharmacy ART pickups. Secondary outcomes included frequency of physician visits, CD4 cell counts and viral loads. Results: Baseline characteristics in the intervention (n = 54) and control arms (n = 54) were similar. After six months, 85% of those receiving SMS reminders were 100% on time picking up monthly ART refills compared to 70% in the control group (p = 0.064). In secondary analysis, there were no significant changes in the CD4 counts and viral loads over the course of the study. Conclusions: Timeliness of ART pickup was not significantly improved by SMS reminders. Additionally, the intervention had no impact on immunologic or virologic outcomes in treatment-experienced patients.

To assess whether variation in serum human chorionic gonadotropin (hCG) measures, used to assess early gestation viability, are associated with differences in clinical presentation and patient factors.This retrospective cohort study included 285 women with first-trimester pain and bleeding and a pregnancy of unknown location for whom a normal intrauterine pregnancy was ultimately confirmed. Serial samples were collected at three U.S. sites and hCG changes were analyzed for differences by race, ethnicity, and clinical factors. A nonlinear, mixed-effects regression model was used assuming a random subject shift in the time axis.The hCG rise in symptomatic women with ongoing intrauterine pregnancy differs by patient factors and level at presentation. The 2-day minimum (first percentile) rise in hCG was faster when presenting hCG values were low and slower when presenting hCG value was high. African American women had a faster hCG rise (P.001) compared with non-African American women. Variation in hCG curves was associated with prior miscarriage (P=.014), presentation of bleeding (P.001), and pain (P=.002). For initial hCG values of less than 1,500, 1,500-3,000 and greater than 3,000 milli-international units/mL, the predicted 2-day minimal (first percentile) rise was 49%, 40%, and 33%, respectively.The rise of hCG levels in women with viable intrauterine pregnancies and symptoms of potential pregnancy failure varies significantly by initial value. Changes in hCG rise related to race should not affect clinical care. To limit interruption of a potential desired intrauterine pregnancy, a more conservative "cutoff" (slower rise) is needed when hCG values are high.ClinicalTrials.gov, https://clinicaltrials.gov, NCT00194168.

Additional strategies are needed to prevent and treat tuberculosis (TB). Although vitamin D may have antimycobacterial effects, it is unknown whether low vitamin D status confers a risk for active TB in African children. This case-control study assessed serum 25-hydroxyvitamin D (25(OH)D) concentration in children with and without active TB in Gaborone, Botswana. A total of 80 children under 2 years old with and without active TB, seen at hospitals and clinics in the greater Gaborone area between September 2010 and November 2012, were enrolled. Of these, 39 cases did not differ from the 41 controls in median 25(OH)D levels (P = 0.84). The 25(OH)D was < 20 ng/mL in 8/39 (21%) cases and 7/41 (17%) controls (P = 0.69, χ(2)). Univariate analyses of subject clinical characteristics (other than 25(OH)D levels) showed that any degree of weight loss was associated with a diagnosis of TB (P = 0.047). Other clinical characteristics, including age (P = 0.08) or weight below third percentile (P = 0.58), showed no association with TB. There was no significant difference in vitamin D status between children under 2 years old with and without active TB. Lower vitamin D status did not appear to be a risk factor for TB in this small Gaborone cohort.

Background We examined the association between cognitive domains and research consent capacity in PD. Our hypothesis was that research consent capacity is best predicted by executive function. Methods A cohort of 90 PD patients and 30 healthy older adults were administered the MacArthur Competence Assessment Tool for Clinical Research, Dementia Rating Scale-2, and the MoCA. Experts classified patients as either “capable” or “not capable” of providing informed consent to participate in two clinical trials. Results MacArthur Competence Assessment Tool for Clinical Research Reasoning scores for both clinical trial types were most associated with executive functions and delayed recall. As scores on these domains improved, the odds of an expert rating of “capable of consent” increased. Conclusions These results extend our previous findings by demonstrating that memory and executive abilities appear closely associated with capacity when evaluated using either a structured interview or expert judgment of that interview. © 2016 International Parkinson and Movement Disorder Society

Background Subjective cognitive decline (SCD) is increasingly considered promising to detect preclinical Alzheimer's disease. How SCD is ascertained is critical for determining its potential utility in identifying at-risk individuals, yet SCD measures differ along several dimensions. Objective We aimed to examine the extent to which reports of SCD in healthy elderly may be influenced by the characteristics of the SCD measures. We investigated variations in rates of SCD endorsement across different measures, including an open-ended question. We also examined the association of responses across measures, and the degree to which specific SCD items were associated with objective memory performance. Methods 99 healthy elderly completed a series of questionnaires from which 10 items examining SCD for memory and other aspects of cognition were drawn. We applied Cochran's Q tests to assess differences in rates of SCD, correlation analyses to examine association of SCD responses, and regression models to determine the association between SCD items and delayed verbal memory. Results Rates of SCD varied as a function of the assessment format, ranging from 1 to 7% for memory and 5 to 20% for concentration. SCD was lower for memory versus non-memory domains. SCD items were associated both within and across domains. The most accurate predictor of memory was memory-related SCD in comparison to others the same age. Conclusion Characteristics of SCD items influence rates of endorsement. Querying SCD using an "age-anchored" question may provide the most accurate reflection of actual cognitive performance.

The goal of this study was to determine which cocaine dependent patients engaged in an intensive outpatient program (IOP) were most likely to benefit from extended continuing care (24 months). Participants (N=321) were randomized to: IOP treatment as usual (TAU), TAU plus Telephone Monitoring and Counseling (TMC), or TAU plus TMC plus incentives for session attendance (TMC+). Potential moderators examined were gender, stay in a controlled environment prior to IOP, number of prior drug treatments, and seven measures of progress toward IOP goals. Outcomes were: (1) abstinence from all drugs and heavy alcohol use, and (2) cocaine urine toxicology. Follow-ups were conducted at 3, 6, 9, 12, 18, and 24 months post-baseline. Results indicated that there were significant effects favoring TMC+ over TAU on the cocaine urine toxicology outcome for participants in a controlled environment prior to IOP and for those with no days of depression early in IOP. Trends were obtained favoring TMC over TAU for those in a controlled environment (cocaine urine toxicology outcome) or with high family/social problem severity (abstinence composite outcome), and TMC+ over TAU for those with high family/social problem severity or high self-efficacy (cocaine urine toxicology outcome). None of the other potential moderator effects examined reached the level of a trend. These results generally do not suggest that patients with greater problem severity or poorer performance early in treatment on the measures considered in this report will benefit to a greater degree from extended continuing care.

Substance use disorders often have a chronic course, with afflicted individuals cycling through periods of abstinence, sporadic use, and heavy use (Hser, Longshore, & Anglin, 2007; McKay, 2009a; McLellan, Lewis, O’Brien, & Kleber, 2000). Wider use of effective continuing care has been recommended to increase rates of sustained recoveries and limit the severity and duration of relapse episodes that do occur (Dennis & Scott, 2007; Humphreys & Tucker, 2002; McKay, 2009a; Miller & Weisner, 2002). Continuing care interventions with longer durations and active efforts to deliver the intervention tend to show larger effects (McKay, 2009b; McKay et al., 2010; Scott & Dennis, 2009). Although effective, extended continuing care models for substance use disorders are labor intensive and add to the cost of treatment. It is therefore important to determine which patients are most likely to benefit from these interventions. One such group may be patients who are using drugs or alcohol immediately prior to intake, or who continue to use early in treatment. For example, prior studies shown that cocaine dependent patients who are using cocaine immediately prior to treatment have worse retention and drug use outcomes than those who have stopped using (Ahmadi et al., 2009; Alterman et al., 1997; Kampman et al., 2001). Similarly, patients who continue to use drugs or alcohol in the first few weeks of treatment are at higher risk for early dropout and poor outcomes (Higgins, Badger, & Budney, 2000; McKay et al., 1999, McKay et al., 2005; Plebani, Kampman, & Lynch, 2009; Preston et al., 1998). In a study by McKay et al. (1999), patients who continued to use cocaine or alcohol during a 4-week intensive outpatient treatment program had worse outcomes than those who remitted substance dependence during that period. However, providing coping-skills based relapse prevention continuing care to these patients produced better cocaine and alcohol use outcomes than standard care. Conversely, there were no continuing care effects in remitted patients. Alcohol use has also been reported to precipitate cocaine relapse in cocaine dependent individuals (McKay, Alterman, Rutherford, Cacciola, & McLellan, 1999). The goal of the present study was to determine whether substance use status immediately prior to intake and during the first few weeks of treatment could be used to identify patients who would most benefit from extended continuing care. Therefore, the study was designed to develop an adaptive model of treatment (McKay, 2009a; Murphy et al., 2007), in which patient progress is used to determine whether standard care needs to be augmented to achieve optimal outcomes. Participants were patients enrolled in publicly-funded intensive outpatient programs (IOPs); all were cocaine dependent and the majority were also alcohol dependent. Therefore, it was hypothesized that participants who were actively using cocaine or alcohol at intake or in the first few weeks of treatment would have worse substance use outcomes than those who had successfully achieved initial abstinence, but would benefit to a greater degree from extended continuing care. However, because patients with active use prior to or early in treatment are at greater risk to dropout, we also evaluated the impact of providing low-level incentives for continuing care session attendance. Incentivizing attendance has increased attendance rates in treatment for substance use disorders, although the magnitude of effects has been somewhat smaller than when abstinence is incentivized (Bride & Humble, 2008; Businelle et al., 2009; Lussier et al., 2006; Petry et al., 2006). A preliminary analysis of continuing care participation in the present study indicated that incentives dramatically increased the number of sessions attended in the first year of the follow-up (Van Horn, et al., 2011). The extended continuing care intervention in the study, Telephone Monitoring and Counseling, included a combination of telephone and in-person sessions. The intervention includes cognitive-behavioral therapy (CBT)-like elements, such as regular monitoring of current substance use and other risk and protective factors, identification of upcoming high-risk situations, and selection and rehearsal of coping strategies; and linkage to community supports (McKay et al., 2010). The telephone is well suited for the delivery of extended continuing care, because of added convenience for patients, reductions in barriers to attending clinic-based care, and greater flexibility in scheduling sessions (McKay, 2009b). Two prior studies have shown that this intervention produces better drug and alcohol use outcomes than standard care (McKay et al., 2005; McKay et al., 2010). In the present study, participants were cocaine dependent IOP patients (N=321) who were randomly assigned to standard care only (i.e., treatment as usual, or TAU), TAU and Telephone Monitoring and Counseling (TMC), or TAU and TMC plus incentives (TMC+), and followed for 24 months. Because many study participants were also dependent on alcohol and had a history of other drug use, the first outcome measure was abstinence from all drugs in a given follow-up period, as indicated by both urine toxicology tests and self-report, and no reported days of heavy alcohol use during the period. Cocaine urine toxicology was included as a second outcome, to provide a measure specific for cocaine use only. The following hypotheses were tested: TMC and TMC+ will produce better outcomes than TAU. Cocaine and alcohol use at intake or early in treatment will predict worse outcomes. Treatment effects favoring TMC and TMC+ over TAU will be larger in participants with cocaine or alcohol use at intake or early in treatment. Adding incentives for attendance to TMC will produce larger treatment effects.

Objective: To examine how cognitive impairment affects Parkinson disease (PD) patients9 research consent capacity. Methods: A cross-sectional study of 90 patients with PD, divided using Mattis Dementia Rating Scale–2 scores into 3 groups of 30 (normal, borderline, and impaired), and 30 neurologically normal older adults completed 2 capacity interviews (an early-phase randomized and controlled drug trial and a sham-controlled surgical implantation of genetic tissue) using the MacArthur Competence Assessment Tool for Clinical Research. Expert clinicians used the interviews to classify the patients as either capable or not capable of providing their own informed consent. These judgments were compared with performance on the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE). Results: Cognitively normal PD patients typically scored well on the capacity measures. In contrast, patients with impaired cognition were not capable of providing their own informed consent: 17% (5/30) on the drug trial and 3% (1/30) on the surgery trial were judged capable. Patients with borderline impairment showed adequate performance on measures of appreciation and reasoning, but impaired performance on understanding the drug trial compared with normal controls and normal PD patients, and on understanding the surgery trial compared with normal controls. Sixty-seven percent (20/30) on the drug trial and 57% (17/30) on the surgery trial were judged capable of consent. Receiver operating characteristic analyses showed that the MMSE and MoCA could detect the likelihood of impaired capacity, with the MoCA demonstrating greater sensitivity. Conclusions: PD patients with borderline cognitive impairment have impairments in their decisional capacity. The MoCA may be useful to identify the patients at risk of impaired capacity.

While 'personalized medicine' commonly refers to genetic markers or profiles associated with pharmacological treatment response, tailoring treatments to patient preferences and values is equally important.To describe and demonstrate a method to develop 'values markers,' or profiles based on the relative importance of attributes of depression treatment.Discrete choice analysis was used to assess individuals' relative preferences for features of depression treatment. Preference profiles were developed using latent profile analysis.Eighty-six adults participating in an internet-based discrete choice questionnaire.Participants were presented with two depression scenarios representing mild and severe depression. For each scenario, they were asked to compare 18 choice sets based on the type of medication side effect (nausea, dizziness, and sexual dysfunction) and severity (mild, moderate, and severe); and for counseling frequency (once per week or every other week) and provider setting (the office of a mental health professional, primary care doctor, or spiritual counselor).Three profiles were identified: profile 1 was associated with a preference for counseling and an avoidance of medication side effects; profile 2 with an avoidance of strong medication side effects and for receiving counseling in medical settings; and profile 3 with a preference for medication over counseling. When presented with a severe depression scenario, there was a higher prevalence for profile 1 and patients were more likely to prefer mental health over primary care and spiritual settings.Values markers may provide a foundation for personalized medicine, and reflect current initiatives emphasizing patient-centered care. Next steps should assess whether values markers are predictive of treatment initiation and adherence.

We sought to examine whether there are patterns of evolving depression symptoms among older primary care patients that are related to prognostic factors and long-term clinical outcomes.Primary care practices were randomly assigned to Usual Care or to an intervention consisting of a depression care manager offering algorithm-based depression care. In all, 599 adults 60 years and older meeting criteria for major depression or clinically significant minor depression were randomly selected. Longitudinal analysis via growth curve mixture modeling was carried out to classify patients according to the patterns of depression symptoms across 12 months. Depression diagnosis determined after a structured interview at 24 months was the long-term clinical outcome.Three patterns of change in depression symptoms over 12 months were identified: high persistent course (19.1% of the sample), high declining course (14.4% of the sample), and low declining course (66.5% of the sample). Being in the intervention condition was more likely to be associated with a course of high and declining depression symptoms than high and persistent depression symptoms (OR = 2.53, 95% CI [1.01, 6.37]). Patients with a course of high and persistent depression symptoms were much more likely to have a diagnosis of major depression at 24 months compared with patients with a course of low and declining depression symptoms (adjusted OR = 16.46, 95% CI [7.75, 34.95]).Identification of patients at particularly high risk of persistent depression symptoms and poor long-term clinical outcomes is important for the development and delivery of interventions.

One hundred twenty-four male Vietnam War veterans with chronic, severe posttraumatic stress disorder (PTSD) were randomly assigned to imagery rehearsal (n = 61) or a credible active comparison condition (n = 63) for the treatment of combat-related nightmares. There was pre-post change in overall sleep quality and PTSD symptoms for both groups, but not in nightmare frequency. Intent-to-treat analyses showed that veterans who received imagery rehearsal had not improved significantly more than veterans in the comparison condition for the primary outcomes (nightmare frequency and sleep quality), or for a number of secondary outcomes, including PTSD. Six sessions of imagery rehearsal delivered in group format did not produce substantive improvement in Vietnam War veterans with chronic, severe PTSD. Possible explanations for findings are discussed.

Background: Although antidepressants and counseling have been shown to be effective in treating patients with depression, non-treatment or under-treatment for depression is common, especially among the elderly and minorities. Previous work on patient preferences has focused on medication versus counseling, but less is known about the value that patients place on attributes of medication and counseling. Objective: To examine, using conjoint analysis, the relative importance of various attributes of depression treatment at the group level as well as to determine the range of individual-level relative preference weights for specific depression treatment attributes. In addition, to predict what modifications in treatment characteristics are associated with a change in the stated preferred alternative. Methods: A total of 86 adults who participated in an internet-based panel responded to an online discrete-choice task about depression treatment. Participants chose between medication and counseling based on choice sets presented first for a 'mild depression' scenario and then for a 'severe depression' scenario. Participants were given 18 choice sets that varied for medication based on type of side effect (nausea, dizziness, and sexual dysfunction) and severity of side effect (mild, moderate, and severe); and for counseling based on frequency of counseling sessions (once per week or every other week) and location of the sessions (mental health professional's office, primary-care doctor's office, or office of a spiritual counselor). Results: Treatment type (counseling vs medication) appeared to be more important in driving treatment choice than any specific attribute that was studied; specifically, counseling was preferred by most of the respondents. After treatment type, location and frequency of treatment were important considerations. Preferred attributes were similar in both the mild and severe depression scenarios. Side effect severity appeared to be most important in driving treatment choice compared with the other attributes studied. Individual-level relative preferences for treatment type revealed a distribution that was roughly bimodal; 27 participants had a strong preference for counseling and 14 had a strong preference for medication. Conclusions: Estimating individual-level preferences for treatment type allowed us to see the variability in preferences and determine which participants had a strong affinity for medication or counseling. We found that participants preferred counseling over medication, avoided options with severe side effects, and wanted to be seen in the primary-care doctor's office as opposed to other venues.

One of the pressing needs in the treatment of substance use disorders is the identification of adjunctive services or interventions that can be added to “treatment as usual” to improve outcomes. At this point, there is evidence that the provision of services to address psychiatric, family, employment, and housing problems can bring about improvements in these areas, and in some cases, in substance use outcomes (Friedmann, Hendrickson, Gerstein, & Zhang, 2004; McLellan et al., 1997, 1998; O'Farrell, Choquette, & Cutter, 1998). Continuing care, which serves to extend the duration of treatment, has also been shown to improve substance use outcomes (McKay, 2005). However, it can be difficult to deliver adjunctive interventions to patients in standard outpatient treatment due to the high drop out rates in these programs. For example, recent data from a national survey of addictions treatment programs indicated that the median length of stay in intensive outpatient programs was 46 days, with only 36% of admissions completing treatment (SAMHSA, 2008). One intervention that has shown considerable promise as a means to both increase retention and improve substance use outcomes is contingency management (CM), which provides incentives linked to performance. CM interventions, most notably in the form of voucher-based reinforcement therapy (VBRT) for abstinence, have demonstrated efficacy in the treatment of substance use disorders, as documented in several recent meta-analyses (Dutra, Stathopoulou, Basden, Leyro, Powers, & Otto, 2008; Lussier, Heil, Mongeon, Badger, & Higgines, 2006, Prendergast, Podus, Finney, Greenwell, & Roll, 2006). Notably, CM interventions have also proved effective in community settings (Petry, Alessi, Marx, Austin, & Tardif, 2005; Petry, Alessi, & Hanson, 2007). The majority of trials utilizing CM for drug abstinence have focused on initiating abstinence early in treatment. What has been much less frequently addressed is whether CM works as an adjunctive relapse prevention intervention in individuals who have achieved initial engagement in treatment and already sharply reduced or stopped using drugs. Another intervention that, at least theoretically, should promote better outcomes in initially stabilized patients with substance use disorders is relapse prevention, or RP (Marlatt & Gordon, 1985). Most RP interventions make use of techniques from cognitive-behavioral and social skills therapies to increase awareness of situations in which the individual has been particularly likely to use drugs (i.e., “high risk situations”) and improve coping responses for these situations through rehearsal and homework assignments (Annis & Davis, 1989; Carroll, 1998; Marlatt & Gordon, 1985). Improvements in these areas are thought to increase self-efficacy, which in term promotes further improvements in coping abilities. Although CBT-based interventions are widely seen as evidence-based (Carroll, 1996), recent research has suggested they are not more effective than other bona fide treatments for substance use disorders, whether delivered as a primary treatment or as a form of continuing care (Dutra et al., 2008; Irvin, Bowers, Dunn, & Wang, 1999; Longabaugh & Morgenstern, 1999; McKay et al., 1999; McKay, Lynch, Shepard, & Pettinati, 2005; Morgenstern & McKay, 2007; Rawson et al., 2006). Therefore, it is not clear that supplementing standard addiction treatment with RP for patients who have achieved initial engagement will in fact lead to better outcomes. There is also mixed evidence regarding possible additive effects for interventions that combine RP/CBT and CM over RP/CBT or CM alone. Epstein, Hawkins, Covi, Umbricht, and Preston (2003) reported that CM alone was more effective in decreasing cocaine use in methadone maintenance patients than CM+CBT during treatment, but additive effects favoring the CM+CBT condition over CM alone emerged at 12 months. Shoptaw et al. (2005) found that methamphetamine dependent participants had better drug use outcomes in CM+CBT than in CBT alone, but the combination condition was not more effective than CM alone. Finally, in studies with methadone maintenance and methamphetamine dependent patients, Rawson and colleagues found that while shorter term outcomes favored CM over CBT or control conditions, longer term outcomes in CBT conditions were not different from those in CM conditions. Moreover, there were no additive effects for CM+CBT over CM or CBT (Rawson et al., 2002; Rawson et al., 2006). It should be noted that all of these studies were done as abstinence-initiation projects, rather than as continuing care or relapse prevention projects. Another important consideration in the selection of adjunctive interventions to reduce relapse in stabilized patients is whether the effects of the intervention persist into the post-treatment period. There is some evidence that RP/CBT interventions can exhibit sleeper effects, where the positive effects of the intervention in relation to comparison conditions does not become apparent until after the interventions are over (Carroll et al., 1994; McKay et al., 1999; Rawson et al., 2002; Rawson et al., 2006), although this is not the case in all studies. Until recently, most studies of CM did not have post-treatment follow-ups. However, a number of newer studies have included post-treatment follow-ups, usually out to 12 months. The results have been mixed, with some studies showing evidence of sustained voucher effects (Alessi, Hanson, Wieners, & Petry, 2007; Epstein et al., 2003; Higgins, Wong, Badger, Ogden, & Dantona, 2000; Higgins et al., 2003; Higgins et al., 2006), and other studies showing no sustained effects (Milby et al., 2003; Petry et al., 2005; Petry et al., 2006; Rawson et al., 2002; Rawson et al., 2006; Shoptaw et al., 2005). This paper presents results from a program of research on the effectiveness of enhancements to improve continuing care in outpatient specialty care for drug and alcohol dependence. Participants were recruited from cocaine-dependent patients attending a publicly funded intensive outpatient program (IOP) in Philadelphia, who had successfully engaged in IOP for at least two weeks and met other study inclusion criteria. They also reported that they had been abstinent for an average of 44 consecutive days at entrance into the study, although abstinence was not a requirement for participation. The study featured a 2 × 2 design, which crossed contingency management (CM; yes/no) with relapse prevention (RP; yes/no). The CM protocol used in the study was modeled after the protocol developed by Silverman et al. (1996), which in turn was adapted from work by Higgins and colleagues (1993). Participants earned vouchers for cocaine-free urines on an escalating schedule over a 12 week period, with a total maximal value of $1,150 if all urines were cocaine-free. The vouchers could be redeemed for goods and services consistent with recovery. The cognitive-behavioral RP protocol (Annis & Davis, 1989) was delivered in up to 20 weekly individual sessions. Participants in the condition that provided both CM and RP were required to be attending their RP sessions for the first 12 weeks in order to be eligible to participate in the CM procedures during that time. The primary goal of the study was to determine whether providing CM, RP, or the combination of CM and RP to participants who had achieved initial engagement in intensive outpatient treatment would produce better cocaine use outcomes than treatment as usual (TAU) over an 18 month follow-up period. We predicted that significant main effects for CM and RP would be obtained, and the best outcomes would be found in the CM+RP condition. These predictions were tested through an examination of main and interaction effects in the 2 × 2 design and post hoc contrast analyses that compared the four treatment conditions.

Comparison of postal surveys of Friends in Britain Yearly Meeting in 1990 and 2003 showed modest differences for reported self-descriptions and beliefs. Quakers in 2003 appear to be less pacifist, somewhat less likely to describe God as ‘Spirit’, ‘Inward Light’, or ‘Love’ in absolute percentages, and less likely to describe Jesus as ‘containing that of God within as we all do’. Meeting for Worship was described less as ‘Seeking God’s will’, and more as ‘Listening’. The largest changes were an increase in reported levels of education and a 13-year increase in median age across the 13-year period. The change in sampling methodology between the two surveys did not appear substantially to affect the results.

Research that seeks to enroll noncompetent patients with Alzheimer's disease without presenting any potential benefit to participants is the source of substantial ethical controversy. The authors used hypothetical Alzheimer's disease studies that included either a blood draw or a blood draw and lumbar puncture to explore older persons' attitudes on this question.Face-to-face interviews were conducted with 538 persons age 65 and older. Questions explored participants' understanding of research concepts, their views on enrolling persons with Alzheimer's disease in research, and their preferences regarding having a proxy decision maker, granting advance consent, and granting their proxy leeway to override the participant's decision. Additional questions assessed altruism, trust, value for research, and perceptions of Alzheimer's disease.The majority (83%) were willing to grant advance consent to a blood draw study, and nearly half (48%) to a blood draw plus lumbar puncture study. Most (96%) were willing to identify a proxy for research decision making, and most were willing to grant their proxy leeway over their advance consent: 81% for the blood draw study and 70% for the blood draw plus lumbar puncture study. Combining the preferences for advance consent and leeway, the proportion who would permit being enrolled in the blood draw and lumbar puncture studies, respectively, were 92% and 75%. Multivariate models showed that willingness to be enrolled in research was most strongly associated with a favorable attitude toward biomedical research.Older adults generally support enrolling noncompetent persons with Alzheimer's disease into research that does not present a benefit to subjects. Willingness to grant their proxy leeway over advance consent and a favorable attitude about biomedical research substantially explain this willingness.

In the context of randomized intervention trials, we describe causal methods for analyzing how post-randomization factors constitute the process through which randomized baseline interventions act on outcomes. Traditionally, such mediation analyses have been undertaken with great caution, because they assume that the mediating factor is also randomly assigned to individuals in addition to the randomized baseline intervention (i.e., sequential ignorability). Because the mediating factors are typically not randomized, such analyses are unprotected from unmeasured confounders that may lead to biased inference. We review several causal approaches that attempt to reduce such bias without assuming that the mediating factor is randomized. However, these causal approaches require certain interaction assumptions that may be assessed if there is enough treatment heterogeneity with respect to the mediator. We describe available estimation procedures in the context of several examples from the literature and provide resources for software code.

OBJECTIVEThe major mechanism of fluoroquinolone (FQ) resistance in Pseudomonas aeruginosa (PSA) is modification of target proteins in DNA gyrase and topoisomerase IV, most commonly the gyrA and parC subunits. The objective of this study was to determine risk factors for PSA with and without gyrA or parC mutations.DESIGNCase-case-control studySETTINGTwo adult academic acute-care hospitalsPATIENTSCase 1 study participants had a PSA isolate on hospital day 3 or later with any gyrA or parC mutation; case 2 study participants had a PSA isolate on hospital day 3 or later without these mutations. Controls were a random sample of all inpatients with a stay of 3 days or more.METHODSEach case group was compared to the control group in separate multivariate models on the basis of demographics and inpatient antibiotic exposure, and risk factors were qualitatively compared.RESULTSOf 298 PSA isolates, 172 (57.7%) had at least 1 mutation. Exposure to vancomycin and other agents with extended Gram-positive activity was a risk factor for both cases (case 1 odds ratio [OR], 1.09; 95% confidence interval [CI], 1.04–1.13; OR, 1.14; 95% CI, 1.03–1.26; case 2 OR, 1.09; 95% CI, 1.03–1.14; OR, 1.13; 95% CI, 1.01–1.25, respectively).CONCLUSIONSExposure to agents with extended Gram-positive activity is a risk factor for isolation of PSA overall but not for gyrA/parC mutations. FQ exposure is not associated with isolation of PSA with mutations.Infect Control Hosp Epidemiol 2015;00(0): 1–7

Objective The aims of this study were to examine the daily affective experiences of patients with Parkinson disease (PD) and to determine their association with daily events and motor symptoms. Specifically, it was intended to test the hypothesis that PD, even in the absence of depression, is associated with anhedonia. Method Nondepressed male subjects with PD (N = 24) and a comparison group of healthy elderly males (N = 23) completed daily affect rating scales and, for the patients with PD, a supplemental self-assessment questionnaire of PD-related symptoms for 4 consecutive weeks. The effect of daily events and PD-related symptoms on daily affect was examined using linear and logistic mixed regression models. Results Overall, patients with PD reported significantly less positive and more negative affect than healthy peers over time. There were similar, and expected, associations between negative events and affect in both groups. Although patients with PD reported far fewer positive events than control subjects, they reported as great an improvement in affect in response to them. Regarding self-reported PD-related symptoms, only increasing severity of core motor symptoms was independently associated with worse affect. Conclusions Although the conclusions of this study are tempered by a comparison group that is not optimal, our results suggest that patients with PD do not demonstrate anhedonia in response to positive life events. The gross intergroup difference in daily events suggests the potential value of interventions that emphasize daily engagement in positive experiences to improve positive affective tone.

OBJECTIVES: To test for simvastatin-induced changes in affect and affective processes in elderly volunteers. DESIGN: Randomized, clinical trial. SETTING: The Geriatric Behavioral Psychopharmacology Laboratory at the University of Pennsylvania. PARTICIPANTS: Eighty older volunteers, average age 70, with high normal/mildly elevated serum cholesterol. INTERVENTION: Simvastatin up to 20 mg/d or placebo for 15 weeks. MEASUREMENTS: Daily diary records of positive and negative affects and of events and biweekly measures of depressive symptoms. Affect ratings were obtained using the Lawton positive and negative affect scales; independent raters coded the valences of events. RESULTS: Thirty-one of 39 subjects assigned to placebo and 33 of 41 receiving simvastatin completed the study. During biweekly assessments, four subjects on simvastatin and one on placebo experienced depressive symptoms, as manifest by Center for Epidemiological Studies Depression scale scores greater than 16 (exact P=.36). Diary data demonstrated significant effects on affective processes. For positive affect, there was a significant medication-by-time interaction that reflected decreases in positive affect in subjects receiving simvastatin, greatest in those patients whose final total cholesterol levels were below 148 mg/dL. For negative affect, there were significant medication-by-event, and medication-by-event-by-time interactions, reflecting a time-limited increase in the apparent effect of negative events. CONCLUSION: Simvastatin has statistically significant effects on affect and affective processes in elderly volunteers. The decrease in positive affect may be significant clinically and relevant to the quality of life of many patients.

Most US states have enacted or are considering legislation mandating hospitals to publicly report hospital-acquired infection (HAI) rates. We conducted a survey of infection control professionals and found that state-legislated public reporting of HAIs is not associated with perceived improvements in infection prevention program process measures or HAI rates.

Objective The authors sought to validate the diagnostic criteria for alcohol-related dementia. Methods The sample consisted of veterans consecutively admitted to a 240-bed VA Nursing Home Care Unit. Baseline and follow-up assessments included measures of cognition and functioning. The diagnosis and type of dementia was determined within 2 months of admission by a geropsychiatrist using patient interviews, chart review, and information from a structured collateral interview. Residents were followed for up to 2 years. Results Data were collected on 192 of the residents, of whom, 158 (82%) were diagnosed with some form of dementia. Alcohol-related dementia (ARD) was diagnosed in 16 residents (10.1%), probable Alzheimer dementia (AD), in 26 (16.5%); vascular dementia (VD), in 46 (29.1); and mixed or dementia of undetermined origin, in 70 (44.3%). Those with ARD were less cognitively impaired and were more often unmarried. Residents with ARD demonstrated a stabilization of both cognition and functional status, whereas those with AD and VD showed a general decline in both cognition and functional status. Conclusion These results serve to validate the diagnostic criteria for ARD and suggest that abstinence may be of clinical value in treating patients with dementia and alcohol dependence. Further research needs to be conducted to confirm the value of abstinence.

We propose a method for estimating the marginal causal log-odds ratio for binary outcomes under treatment non-compliance in placebo-randomized trials. This estimation method is a marginal alternative to the causal logistic approach by Nagelkerke et al. (2000) that conditions on partially unknown compliance (that is, adherence to treatment) status, and also differs from previous approaches that estimate risk differences or ratios in subgroups defined by compliance status. The marginal causal method proposed in this paper is based on an extension of Robins' G-estimation approach for fitting linear or log-linear structural nested models to a logistic model. Comparing the marginal and conditional causal log-odds ratio estimates provides a way of assessing the magnitude of unmeasured confounding of the treatment effect due to treatment non-adherence. More specifically, we show through simulations that under weak confounding, the conditional and marginal procedures yield similar estimates, whereas under stronger confounding, they behave differently in terms of bias and confidence interval coverage. The parametric structures that represent such confounding are not identifiable. Hence, the proof of consistency of causal estimators and corresponding simulations are based on two different models that fully identify the causal effects being estimated. These models differ in the way that compliance is related to potential outcomes, and thus differ in the way that the causal effect is identified. The simulations also show that the proposed marginal causal estimation approach performs well in terms of bias under the different levels of confounding due to non-adherence and under different causal logistic models. We also provide results from the analyses of two data sets further showing how a comparison of the marginal and conditional estimators can help evaluate the magnitude of confounding due to non-adherence.

Background The classification of Alzheimer's disease is undergoing a significant transformation. Researchers have created the category of “preclinical Alzheimer's,” characterized by biomarker pathology rather than observable symptoms. Diagnosis and treatment at this stage could allow preventing Alzheimer's cognitive decline. While many commentators have worried that persons given a preclinical Alzheimer's label will be subject to stigma, little research exists to inform whether the stigma attached to the label of clinical Alzheimer's will extend to a preclinical disorder that has the label of “Alzheimer's” but lacks the symptoms or expected prognosis of the clinical form. Research questions The present study sought to correct this gap by examining the foundations of stigma directed at Alzheimer's. It asked: do people form stigmatizing reactions to the label “Alzheimer's disease” itself or to the condition's observable impairments? How does the condition's prognosis modify these reactions? Methods Data were collected through a web-based experiment with N = 789 adult members of the U.S. general population (median age = 49, interquartile range, 32–60, range = 18–90). Participants were randomized through a 3 × 3 design to read one of 9 vignettes depicting signs and symptoms of mild stage dementia that varied the disease label (“Alzheimer's” vs. “traumatic brain injury” vs. no label) and prognosis (improve vs. static vs. worsen symptoms). Four stigma outcomes were assessed: discrimination, negative cognitive attributions, negative emotions, and social distance. Results The study found that the Alzheimer's disease label was generally not associated with more stigmatizing reactions. In contrast, expecting the symptoms to get worse, regardless of which disease label those symptoms received, resulted in higher levels of perceived structural discrimination, higher pity, and greater social distance. Conclusion These findings suggest that stigma surrounding pre-clinical Alzheimer's categories will depend highly on the expected prognosis attached to the label. They also highlight the need for models of Alzheimer's-directed stigma that incorporate attributions about the condition's mutability.

NIH Public Access Author Manuscript Alzheimer Dis Assoc Disord. Author manuscript; available in PMC 2016 January 01. NIH-PA Author Manuscript Published in final edited form as: Alzheimer Dis Assoc Disord. 2015 ; 29(1): 70–74. doi:10.1097/WAD.0000000000000047. Why are spousal caregivers more prevalent than nonspousal caregivers as study partners in AD dementia clinical trials? Mark S. Cary, PhD a , Jonathan D. Rubright, PhD b , Joshua D. Grill, PhD c , and Jason Karlawish, MD d,* a Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania b American Institute of Certified Public Accountants. Ewing, New Jersey c Mary S. Easton Center for Alzheimer’s Disease Research, Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles CA d Departments NIH-PA Author Manuscript of Medicine and Medical Ethics and Health Policy, Center for Clinical Epidemiology and Biostatistics, Alzheimer’s Disease Center, Leonard Davis Institute of Health Economics, University of Pennsylvania Abstract Objectives—Most Alzheimer’s disease (AD) caregivers are not spouses and yet most AD dementia trials enroll spousal study partners. This study examines the association between caregiver relationship to the patient and willingness to enroll in an AD clinical trial and how caregiver burden and research attitudes modify willingness. Design—Interviews with 103 AD caregivers who met criteria for ability to serve as a study partner. NIH-PA Author Manuscript Results—54% of caregivers were spouses or domestic partners and the remaining were adult children. Willingness to enroll a patient in a clinical trial was associated with being a spouse (OR = 2.53, p = 0.01), increasing age (OR = 1.39, p = 0.01), and increasing scores on the Research Attitudes Questionnaire (OR = 1.39, p < 0.001). No measures of caregiver burden or patient health were significant predictors of willingness. In multivariate models both research attitudes (OR = 1.37, p < 0.001) and being a spouse, as opposed to an adult child, (OR = 2.06, p = 0.048) were independently associated with willingness to participate. Corresponding Author: Jason Karlawish, MD, University of Pennsylvania, 3615 Chestnut Street Philadelphia, PA 19104, Jason.karlawish@uphs.upenn.edu, Phone: 215-615-0975 Fax: 215-573-8784. Conflicts of Interest For the remaining authors none were declared. Author Contributions. Author Contributions are as follows: Mark S. Cary was responsible for drafting/revising the manuscript, study concept and design, and statistical analysis. Jonathan D. Rubright was responsible for drafting/revising the manuscript, study concept and design, and statistical analysis. Joshua D. Grill was responsible for drafting/revising the manuscript, study concept and design, and statistical analysis. Jason Karlawish was responsible for drafting/revising the manuscript, study concept and design, statistical analysis, study supervision and coordination, and obtaining funding. The opinions expressed in this article are those of the authors and do not necessarily reflect the views of the American Institute of Certified Public Accountants

The central thesis of evolutionary psychology is that ‘the mind is a system of organs of computation, designed by natural selection to solve the kinds of problems our ancestors faced in their foraging way of life’. Little time has elapsed for our minds to adapt to the new conditions. Thus, our ‘mental organs’ are designed for Stone Age problems. This article discusses these implications for modern advertising and concludes that advertising that appeals to both the civilised needs and the underlying ‘Stone Age’ motivations should be more effective.

We report two girls, ages 9 and 17 years, with a clinical diagnosis of neurofibromatosis 1 (NF-1) who presented with ill-defined, blanchable, erythematous patches on the dorsal feet and ankles. We hypothesized that these patches were a rare cutaneous finding in NF-1 that exist on a clinical and histopathologic spectrum with previously described NF-1 vascular lesions including blue-red macules and skin ulceration due to NF-1 vasculopathy. We suggest that these lesions be called neurovascular stains (NVSs) to unify their clinical and histopathologic features.

We conducted a retrospective cohort study assessing the association between diabetes mellitus (DM) and immune recovery in HIV-infected adults. Immune reconstitution after initiating antiretroviral therapy was more rapid in DM patients (120.4 cells/year) compared to non-DM patients (94.2 cells/year, p < 0.023). Metformin use was associated with improved CD4 recovery (p = 0.034).

Objectives To characterize the curve derived from serial human chorionic gonadotropin (hCG) values in women with spontaneous resolution of pregnancy of unknown location and to assess factors that modify the decline. Methods Data from three sites were extracted from a clinical database of women with a symptomatic pregnancy of unknown location that required follow-up with serial hCG levels. A nonlinear mixed-effects regression model was used to generate hCG elimination curves. Results Four hundred forty-three women presenting with a pregnancy of unknown location that resolved without intervention were studied between September 2007 and May 2009. Women older than 35 years had a slower hCG decline (P=.001) and those with pain had a steeper decline (P=.006), but these changes did not alter the curve in a clinically meaningful way. The decline in hCG is faster for those with a higher level at presentation. The average decline of hCG in women with spontaneous resolution is slower than previously reported. However, the minimal decline in hCG for women with spontaneous resolution of a pregnancy of unknown location ranged from 35% to 50% at 2 days of follow-up and from 66% to 87% at 7 days, which is more rapid than previously reported. Conclusion In a diverse population, using updated statistical methods, it was observed that the minimal decline in hCG for women with spontaneous resolution is more rapid than previously reported. A decline slower than these thresholds may indicate the presence of retained trophoblastic tissue or ectopic pregnancy. Level of evidence III.

Background. There is little in the literature on HIV and diabetes mellitus (DM) in sub-Saharan Africa. Objective. To assess the characteristics of HIV and DM in patients on antiretroviral therapy (ART) in Botswana. Methods. A retrospective case-control study was conducted at 4 sites. Each HIV-infected patient with DM ( n =48) was matched with 2 HIV-infected controls ( n =108) by age (±2 years) and sex. Primary analysis was conditional logistic regression to estimate univariate odds and 95% confidence intervals (CIs) for each characteristic. Results. There was no significant association between co-morbid diseases, tuberculosis, hypertension or cancer and risk of diabetes. DM patients were more likely to have higher pre-ART weight (odds ratio (OR) 1.09; 95% CI 1.04 - 1.14). HIV-infected adults >70 kg were significantly more likely to have DM (OR 12.30; 95% CI 1.40 - 107.98). Participants on efavirenz (OR 4.58; 95% CI 1.44 - 14.57) or protease inhibitor therapy (OR 20.7; 95% CI 1.79 - 240.02) were more likely to have DM. Neither mean pre-ART CD4 cell count (OR 1.0; 95% CI 0.99 - 1.01) nor pre-ART viral load >100 000 copies/ml (OR 0.71; 95% CI 0.21 - 2.43) were associated with a significant risk of diabetes. Conclusions. These findings suggest a complex interrelation among traditional host factors and treatment-related metabolic changes in the pathogenesis of DM inpatients receiving ART. Notably, pre-ART weight, particularly if >70 kg, is associated with the diagnosis of diabetes in HIV-infected patients in Botswana.

Author(s): Bender, M; Jaski, BE; Glaser, D; Thomas, V; Cary, DS; Smith, SC | Abstract: Introduction It is unclear whether inpatient heart failure (HF) performance measures reduce post-discharge adverse events. This exploratory study examined the association between systematic adherence to a set of performance measures and outcomes. Measures included all four Joint Commission (JC) HF core measures and AHA recommended beta blockade prescription on discharge. Methods A retrospective review of a 3-hospital system was performed for all patients discharged with a primary diagnosis of HF in 2008-2009. Patients were included if they met eligibility criteria for one or more measures (n=1270). ‘Perfect care’ was defined as compliance with all eligible measures. Subsequent all-cause 30-day readmission and 1-year mortality was determined via electronic records and social security national database. Results ‘Perfect care’ significantly reduced 30-day readmissions (19.2% vs. 24.9%, p=.045; OR=.72, 95% CI 0.52-0.99). ‘Perfect care’ did not influence 1-year mortality. Conclusions Adherence to this set of composite performance measures positively influenced short-term patient outcomes. Benefit of adherence was found despite the longer LOS and higher severity of illness on index admission for patients receiving ‘perfect care’. The data support the clinical value of a systematic approach towards HF care on patient care quality. ‘Perfect care’ did not influence long term outcomes, which may be because inpatient processes do not extend to long term outpatient medical management.

With increasing numbers of studies on research ethics and a need to improve the recruitment of research subjects, the ability to measure attitudes toward biomedical research has become important. The Research Attitudes Questionnaire is a significant predictor of the public's attitudes toward and willingness to participate in research, yet limited data are available on its psychometric properties. This study establishes the scale's internal consistency and dimensionality using a large Internet-based sample from the United States. One item was removed due to a poor item-total correlation, and three additional items were removed which formed a reverse-wording measurement artifact factor. With improved internal consistency and dimensionality, the seven-item version has the advantages of shorter administration time and improved psychometric properties.

Memory awareness in early Alzheimer’s disease (AD) influences capacity to provide informed consent for a memory treatment. This study investigated the extent to which aspects of memory awareness influence everyday decision-making capacity about medication management in AD. 42 participants with mild AD and 50 healthy elders underwent clinical ratings of memory awareness, metamemory testing, and an interview of everyday decision-making capacity regarding medication management. 45% of AD subjects were classified as aware (AAD) and 55% as unaware (UAD) based on clinical ratings and supported by metamemory testing (P=.015). Capacity was impaired in each of the AD groups as compared to the healthy eldersF(2, 67)=17.63, UAD,P<.01; AAD,P=.01). Within the AD group, capacity correlated selectively with awareness as measured with clinical ratings (r=−.41,P=.007) but not objective metamemory testing (r=−.10,P=.60). Appreciation scores were lower in UAD as compared with AADF(1, 35)=8.36,P=.007. Unawareness of memory loss should heighten clinicians’ concern about everyday decision-making capacity in AD.