Evaluation of the effect of cellular SMS reminders on consistency of antiretroviral therapy pharmacy pickups in HIV-infected adults in Botswana: a randomized controlled trial.

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.

Differences in Serum Human Chorionic Gonadotropin Rise in Early Pregnancy by Race and Value at Presentation.

OBJECTIVE: 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. METHOD: 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. RESULTS: 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. CONCLUSION: 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. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT00194168.

Vitamin D Status in Botswana Children Under 2 Years Old With and Without Active Tuberculosis.

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.

Research consent capacity varies with executive function and memory in Parkinson's disease.

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.

Identifying expectant parents at risk for psychological distress in response to a confirmed fetal abnormality.

The aim of the study was to determine the incidence of psychological distress among expectant women carrying fetuses with prenatal diagnosed abnormalities and their partners. A 2-year retrospective medical chart review was completed of 1032 expectant mothers carrying fetuses with a confirmed anomaly, and 788 expectant fathers, who completed the CFDT Mental Health Screening Tool. Furthermore, 19.3 % of women and 13.1 % of men reported significant post-traumatic stress symptoms, and 14 % of men and 23 % of women scored positive for a major depressive disorder. Higher risk was noted among expectant parents of younger age and minority racial/ethnic status, and women with post-college level education and current or prior use of antidepressant medications. Heightened distress was noted within fetal diagnostic subgroups including neck masses, sacrococcygeal teratomas, neurological defects, and miscellaneous diagnoses. Incorporating screening tools into prenatal practice can help clinicians better identify the potential risk for psychological distress among expectant parents within high-risk fetal settings.

Ascertaining Subjective Cognitive Decline: A Comparison of Approaches and Evidence for Using an Age-Anchored Reference Group.

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 relative contributions of disease label and disease prognosis to Alzheimer's stigma: A vignette-based experiment.

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.

Risk factors for gyrA and parC mutations in Pseudomonas aeruginosa.

OBJECTIVE: The 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. DESIGN: Case-case-control study SETTING: Two adult academic acute-care hospitals PATIENTS: Case 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. METHODS: Each 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. RESULTS: Of 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). CONCLUSIONS: Exposure 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.

Why are spousal caregivers more prevalent than nonspousal caregivers as study partners in AD dementia clinical trials?

OBJECTIVES: Most Alzheimer 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. RESULTS: A total of 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 [odds ratio (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. CONCLUSIONS: Spousal caregivers had both a higher willingness to participate and a more positive attitude toward research. Caregiver burden had no association with willingness to participate. The strongest predictor of willingness was research attitudes.

Who benefits from extended continuing care for cocaine dependence?

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.

An adaptive approach for identifying cocaine dependent patients who benefit from extended continuing care.

OBJECTIVE: Study tested whether cocaine dependent patients using cocaine or alcohol at intake or in the first few weeks of intensive outpatient treatment would benefit more from extended continuing care than patients abstinent during this period. The effect of incentives for continuing care attendance was also examined. METHOD: Participants (N = 321) were randomized to treatment as usual (TAU), TAU and telephone monitoring and counseling (TMC), or TAU and TMC plus incentives (TMC+). The primary outcomes were (a) abstinence from all drugs and heavy alcohol use and (b) cocaine urine toxicology. Follow-ups were at 3, 6, 9, 12, 18, and 24 months. RESULTS: Cocaine and alcohol use at intake or early in treatment predicted worse outcomes on both measures (ps ≤ .0002). Significant effects favoring TMC over TAU on the abstinence composite were obtained in participants who used cocaine (odds ratio [OR] = 1.95 [1.02, 3.73]) or alcohol (OR = 2.47 [1.28, 4.78]) at intake or early in treatment. A significant effect favoring TMC+ over TAU on cocaine urine toxicology was obtained in those using cocaine during that period (OR = 0.55 [0.31, 0.95]). Conversely, there were no treatment effects in participants abstinent at baseline and no overall treatment main effects. Incentives almost doubled the number of continuing care sessions received but did not further improve outcomes. CONCLUSION: An adaptive approach for cocaine dependence in which extended continuing care is provided only to patients who are using cocaine or alcohol at intake or early in treatment improves outcomes in this group while reducing burden and costs in lower risk patients.

Predicting the decline in human chorionic gonadotropin in a resolving pregnancy of unknown location.

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.

Cognitive impairment and PD patients' capacity to consent to research.

OBJECTIVE: To examine how cognitive impairment affects Parkinson disease (PD) patients' 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.

Public reporting of hospital-acquired infections is not associated with improved processes or outcomes.

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.

Towards personalizing treatment for depression : developing treatment values markers.

BACKGROUND: 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. OBJECTIVE: To describe and demonstrate a method to develop 'values markers,' or profiles based on the relative importance of attributes of depression treatment. STUDY DESIGN: Discrete choice analysis was used to assess individuals' relative preferences for features of depression treatment. Preference profiles were developed using latent profile analysis. PATIENTS OR OTHER PARTICIPANTS: Eighty-six adults participating in an internet-based discrete choice questionnaire. MAIN OUTCOME MEASURE: 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). RESULTS: 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. CONCLUSIONS: 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.

Prognostic factors, course, and outcome of depression among older primary care patients: the PROSPECT study.

OBJECTIVES: 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. METHOD: 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. RESULTS: 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]). CONCLUSION: 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.

Course of depression and mortality among older primary care patients.

CONTEXT: : Depression is a treatable illness that disproportionately places older adults at increased risk for mortality. OBJECTIVE: : We sought to examine whether there are patterns of course of depression severity among older primary care patients that are associated with increased risk for mortality. DESIGN AND SETTING: : Our study was a secondary analysis of data from a practice-based randomized controlled trial within 20 primary care practices located in greater New York City, Philadelphia, and Pittsburgh. PARTICIPANTS: : The study sample consisted of 599 adults aged 60 years and older recruited from primary care settings. Participants were identified though a two-stage, age-stratified (60-74 years; older than 75 years) depression screening of randomly sampled patients. Severity of depression was assessed using the 24-item Hamilton Depression Rating Scale (HDRS). MEASUREMENTS: : Longitudinal analysis via growth curve mixture modeling was carried out to classify patterns of course of depression severity across 12 months. Vital status at 5 years was ascertained via the National Death Index Plus. RESULTS: : Three patterns of change in course of depression severity over 12 months were identified: 1) persistent depressive symptoms, 2) high but declining depressive symptoms, 3) low and declining depressive symptoms. After a median follow-up of 52.0 months, 114 patients had died. Patients with persistent depressive symptoms were more likely to have died compared with patients with a course of high but declining depressive symptoms (adjusted hazard ratio 2.32, 95% confidence interval [1.15-4.69]). CONCLUSIONS: : Persistent depressive symptoms signaled increased risk of dying in older primary care patients, even after adjustment for potentially influential characteristics such as age, smoking status, and medical comorbidity.

Memory Awareness Influences Everyday Decision Making Capacity about Medication Management in Alzheimer's Disease.

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 elders F(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 AAD F(1,35) = 8.36, P = .007. Unawareness of memory loss should heighten clinicians' concern about everyday decision-making capacity in AD.

Measuring how people view biomedical research: Reliability and validity analysis of the Research Attitudes Questionnaire.

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.