Nonresearch Settings Research Articles

A mathematical model and inference method for bacterial colonization in hospital units applied to active surveillance data for carbapenem-resistant enterobacteriaceae.

Widespread use of antibiotics has resulted in an increase in antimicrobial-resistant microorganisms. Although not all bacterial contact results in infection, patients can become asymptomatically colonized, increasing the risk of infection and pathogen transmission. Consequently, many institutions have begun active surveillance, but in non-research settings, the resulting data are often incomplete and may include non-random testing, making conventional epidemiological analysis problematic. We describe a mathematical model and inference method for in-hospital bacterial colonization and transmission of carbapenem-resistant Enterobacteriaceae that is tailored for analysis of active surveillance data with incomplete observations. The model and inference method make use of the full detailed state of the hospital unit, which takes into account the colonization status of each individual in the unit and not only the number of colonized patients at any given time. The inference method computes the exact likelihood of all possible histories consistent with partial observations (despite the exponential increase in possible states that can make likelihood calculation intractable for large hospital units), includes techniques to improve computational efficiency, is tested by computer simulation, and is applied to active surveillance data from a 13-bed rehabilitation unit in New York City. The inference method for exact likelihood calculation is applicable to other Markov models incorporating incomplete observations. The parameters that we identify are the patient–patient transmission rate, pre-existing colonization probability, and prior-to-new-patient transmission probability. Besides identifying the parameters, we predict the effects on the total prevalence (0.07 of the total colonized patient-days) of changing the parameters and estimate the increase in total prevalence attributable to patient–patient transmission (0.02) above the baseline pre-existing colonization (0.05). Simulations with a colonized versus uncolonized long-stay patient had 44% higher total prevalence, suggesting that the long-stay patient may have been a reservoir of transmission. High-priority interventions may include isolation of incoming colonized patients and repeated screening of long-stay patients.

Identification and Characterization of Peer Support for Cancer Prevention and Care: A Practice Review.

Research across the cancer care continuum indicates peer support can improve patient outcomes, yet little is known about how cancer peer support programs are implemented in practice. This study aimed to describe cancer peer support programs in “real world” (i.e., non-research) settings. A web search identified 100 programs in a wide variety of settings and locations; 48 published contact information on their website and were invited to participate in semi-structured interviews. Twenty-nine program leaders participated. From the interviews, we observed eight primary themes, which centered on challenges and responses regarding training and content of peer support services as well as program organization and support. Obstacles include inconsistent funding, reliance on volunteers, and physician concerns about peer supporters’ advice to patients, while increasing diversity, reach, and accessibility are future priorities. Peer support should be recognized and funded as a routine part of cancer care in order to expand its reach and address priorities such as increasing the diversity of supporters and those they help.Electronic supplementary materialThe online version of this article (10.1007/s13187-020-01861-8) contains supplementary material, which is available to authorized users.

Second tier non-invasive prenatal testing in a regional prenatal diagnosis service unit: a retrospective analysis and literature review.

The Hong Kong Hospital Authority has newly introduced a new Down's syndrome screening algorithm that offers free-of-charge non-invasive prenatal testing (NIPT) to women who screen as high risk. In preparation for this public-funded second tier NIPT service, the present study was conducted to retrospectively analyse women eligible for NIPT and to review the local literature. Our retrospective study included women screened as high risk for Down's syndrome (adjusted term risk ≥1:250) during the period of 1 January 2015 to 31 December 2016. We performed descriptive statistics and multivariable logistic regression to examine the factors associated with women's choice between NIPT and invasive testing. We also reviewed existing local literature about second tier NIPT. The study included 525 women who screened positive: 67% chose NIPT; 31% chose invasive diagnostic tests; and 2% declined further testing. Our literature review showed that in non-research (self-financed NIPT) settings, NIPT uptake rates have been increasing since 2011. Nulliparity, first trimester status, higher education, maternal employment, and conception by assisted reproductive technology are common factors associated with self-financed NIPT after positive screening. Among women choosing NIPT, the rates of abnormal results have typically been around 8% in studies performed in Hong Kong. Implementation of second tier NIPT in the public setting is believed to be able to improve quality of care. We expect that the public in Hong Kong will welcome the new policy.

The Effect of Free-Field Presentation and Processing Strategy on a Measure of Spectro-Temporal Processing by Cochlear-Implant Listeners.

The STRIPES (Spectro-Temporal Ripple for Investigating Processor EffectivenesS) test is a psychophysical test of spectro-temporal resolution developed for cochlear-implant (CI) listeners. Previously, the test has been strictly controlled to minimize the introduction of extraneous, nonspectro-temporal cues. Here, the effect of relaxing many of those controls was investigated to ascertain the generalizability of the STRIPES test. Preemphasis compensation was removed from the STRIPES stimuli, the test was presented over a loudspeaker at a level similar to conversational speech and above the automatic gain control threshold of the CI processor, and listeners were tested using the everyday setting of their clinical devices. There was no significant difference in STRIPES thresholds measured across conditions for the 10 CI listeners tested. One listener obtained higher (better) thresholds when listening with their clinical processor. An analysis of longitudinal results showed excellent test–retest reliability of STRIPES over multiple listening sessions with similar conditions. Overall, the results show that the STRIPES test is robust to extraneous cues, and that thresholds are reliable over time. It is sufficiently robust for use with different processing strategies, free-field presentation, and in nonresearch settings.

Practical peanut challenges for the clinician.

Background: There is an increasing incidence of peanut allergy in many Westernized countries. Unfortunately, current diagnostic tests that evaluate for sensitization can give false-positive results and may lead to overdiagnosis of peanut allergy. Due to this and to the fact that there are several therapies currently being investigated for the treatment of peanut allergy, it is imperative that practitioners who are caring for patients with food allergy be knowledgeable about and comfortable with performing oral challenges to peanut in nonresearch settings. Methods: Literature review and author experience. Results: This article focused on various aspects of a peanut challenge, including patient selection, contraindications, the location of the challenge, form of the peanut to be fed, the starting and goal doses for the challenge, and practical dosing schedules. It is meant to be a real-world overview for a practicing clinician. Conclusions: Clinicians should be able to perform open peanut challenges in properly selected patients.

Beyond the Constraints of an RCT: Naturalistic Treatment Outcomes for Anxiety-Related Disorders

Despite considerable data from randomized controlled trials supporting use of behavioral therapies for anxiety disorders and anxiety-related disorders, there is a relative scarcity of data demonstrating that such findings are generalizable to patients in nonresearch settings, and a lack of standardized repeated outcome measurement in such settings. Using one of the largest examinations of naturalistic outcomes of behavioral therapies in treatment-seeking patients (N = 489), we examined the clinical characteristics and treatment outcomes of patients seeking treatment for anxiety and anxiety-related disorders in the past 3 years. Patients seeking treatment at a clinic specializing in cognitive-behavioral therapy (CBT) completed self-report questionnaires via an electronic data capture system and diagnostic interview at baseline, and were reassessed at mid- and posttreatment. Patients with anxiety and related disorders were assessed for changes in symptom severity and secondary outcomes (impairment/functioning, quality of life, and depression) over the course of therapy. Patients showed clinically significant and statistically reliable improvement in anxiety symptom severity scores over treatment (p < .001), after controlling for number of sessions received. Patients also showed significant improvement in depression, quality of life, and functioning (p values ≤ .001). We also found significant improvement in disorder-specific symptoms, including obsessive-compulsive disorder, posttraumatic stress disorder, generalized anxiety disorder, and social anxiety disorder (p values ≤ .001). Importance of, and ways to facilitate, integration of more routine assessment of a broader range of symptoms via online assessment systems and methods to better determine the effectiveness of CBT in naturalistic clinics are discussed.

Considerations for Implementing Contingency Management in Substance Abuse Treatment Clinics: The Veterans Affairs Initiative as a Model.

Contingency management (CM) is an efficacious intervention for the treatment of substance use disorders that is widely applicable across a range of client populations and characteristics. Despite its strong evidence base, CM remains underutilized in real world practice. This article introduces CM for clinicians interested in adopting CM and briefly reviews this research evidence. In addition, CM protocols are described, with emphasis on the specific design considerations important to CM's efficacy. The recent Department of Veterans Affairs (VA) initiative, which represents the first successful large-scale implementation effort, is presented. It provides a model for the training and supervision components that may be critical to implementation with fidelity. Continued research in this area, as well as further demonstrations of successful dissemination and implementation, will be critical for improving the adoption of this intervention in clinical, nonresearch settings.

Making Health Research Matter: A Call to Increase Attention to External Validity.

Most of the clinical research conducted with the goal of improving health is not generalizable to nonresearch settings. In addition, scientists often fail to replicate each other's findings due, in part, to lack of attention to contextual factors accounting for their relative effectiveness or failure. To address these problems, we review the literature on assessment of external validity and summarize approaches to designing for generalizability. When investigators conduct systematic reviews, a critical need is often unmet: to evaluate the pragmatism and context of interventions, as well as their effectiveness. Researchers, editors, and grant reviewers can implement key changes in how they consider and report on external validity issues. For example, the recently published expanded CONSORT figure may aid scientists and potential program adopters in summarizing participation in and representativeness of a program across different settings, staff, and patients. Greater attention to external validity is needed to increase reporting transparency, improve program dissemination, and reduce failures to replicate research.

Multiple Myeloma Staging in Real World Clinical Practice Is Suboptimal: Absence of Beta-2-Microglobulin and Serum Lactase Dehydrogenase Testing Are Limiting Factors

Background: Staging systems, which help define prognosis and influence treatment decisions, for myeloma have evolved. The Durie-Salmon system (DS) was based largely on perceived myeloma cell tumor burden. In 2005, the International Staging System (ISS) was introduced and incorporated beta-2-microglobulin levels (a marker of tumor burden) and serum albumin (a marker of inflammatory cytokines). In 2015 the ISS was revised (R-ISS) to include high risk cytogenetics [17p-, t(4;14), t(14;16)} and serum lactase dehydrogenase (LDH) (correlating with tumor aggressiveness, extramedullary disease and proliferation rate). Although the ISS and R-ISS are relatively simple, they require additional laboratory studies outside of the diagnostic biopsy material and routine chemistry panel. The adequacy of staging using these newer systems in real world settings has not been reported, although only 69% of patients (pts) in the R-IPSS foundational study (Palumbo JCO 2015) had all of the elements available for complete staging.Methods: Cases were identified using the COTA Inc. database, which abstracts and organizes relevant demographic, diagnostic, treatment, and quality data from the electronic health records at all the clinical sites under business associate agreements. Trained COTA Inc. abstractors reviewed and confirmed the medical record-derived data. For the purposes of the present study, any laboratory or pathology report mentioning testing was counted as “tested,” regardless of method, vendor, or test completeness. The data were then merged with the study population using blinded identifiers for subsequent analysis. A limitation of this review is failure to document test results (or mention of test performance) in the electronic chart or physician notes, thus tests performed but not documented may not have been counted.Results: 857 pts diagnosed with MM between Jan 1, 2013 and Dec 31, 2016 were identified from 12 northeast USA centers (1 academic and 11 community based) treated by 81 hematologist-oncologists. At the time of MM presentation 831 pts (97%) had EHR documentation of immunoglobulin levels, hemoglobin, calcium concentration, renal function and number of bone lesions to permit Durie-Salmon staging. The ISS requires B2M and albumin; at the time of initial presentation 696 pts (81%) could be classified by the ISS but 161 pts (19%) had no documentation of B2M levels and thus could not be staged. The academic center was more likely to obtain B2M to permit complete ISS (84% academic obtained vs 72% community obtained; p<0.001). The R-ISS incorporates cytogenetic abnormalities and LDH. At the time of initial presentation, in addition to the pts without B2M, 353 pts (41%) had no documentation of LDH testing, 122 pts (14%) had no documentation of t(14;16) testing, 112 pts (13%) were without documentation of t(4;14) testing, and 91 pts (11%) were without documentation of del17 testing. The academic and community centers both failed to collect LDH equally (53% academic obtained vs 56% community; p=0.37; however notable that 18% of the academic patients were referred for transplant after initial staging in the community and may not have source documentation at the Cota center). Thus, only 350 pts (41%) could be classified by R-ISS. There was no difference in adequacy of obtaining R-ISS elements before (40%) and after (44%) publication of the R-ISS in late 2015 (p=0.22). The majority of the pts in the database were DS III at presentation. However DS did not correlate with ISS or R-ISS, thus demonstrating the need to perform the complete diagnostic/staging evaluation [Table1].Conclusions: In real world (non-research) settings staging of multiple myeloma using the ISS and R-ISS that require laboratories beyond diagnostic marrow based material (including cytogenetics) remains suboptimal and may reflect delayed incorporation of R-ISS (2015) into clinical use. Lack of obtaining B2M and LDH levels at initial presentation is the major deficiency.Table 1 Reclassification of DS staged pts by ISS and R-ISS DisclosuresBiran:Amgen: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Celgene: Consultancy, Honoraria, Speakers Bureau; BMS: Research Funding; Merck: Research Funding. Norden:Cota Inc: Employment. Siegel:Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau; Karyopharm: Consultancy, Honoraria; Novartis: Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Merck: Consultancy, Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau. Goldberg:COTA Inc.: Employment, Equity Ownership.

Benchmarks for Evaluating Life Review and Reminiscence Therapy in Alleviating Depression among Older Adults.

The efficacy of reminiscence and life review (LR) therapy in alleviating depression among older adults is well established. However, providers in nonresearch settings might implement these interventions inadequately, and such settings rarely can evaluate their outcomes using control groups. Alternatively, evaluators in such settings can calculate a within-group effect size and then compare it with average within-group effect size benchmarks derived from the randomized clinical trials (RCTs) supporting the intervention's effectiveness. This study developed these within-group effect size benchmarks. A search of RCTs from five systematic reviews and meta-analyses, and more recent RCTs published through 2016, yielded 25 studies that met inclusion criteria. Hedge's g for LR recipients and waitlist controls were .598 and -.20, respectively, and .568 and -.012 for reminiscence theory. These benchmarks offer an approach for evaluating the implementation of LR and reminiscence therapy when control groups are infeasible.

Applying machine learning to continuously monitored physiological data.

The use of machine learning (ML) in healthcare has enormous potential for improving disease detection, clinical decision support, and workflow efficiencies. In this commentary, we review published and potential applications for the use of ML for monitoring within the hospital environment. We present use cases as well as several questions regarding the application of ML to the analysis of the vast amount of complex data that clinicians must interpret in the realm of continuous physiological monitoring. ML, especially employed in bidirectional conjunction with electronic health record data, has the potential to extract much more useful information out of this currently under-analyzed data source from a population level. As a data driven entity, ML is dependent on copious, high quality input data so that error can be introduced by low quality data sources. At present, while ML is being studied in hybrid formulations along with static expert systems for monitoring applications, it is not yet actively incorporated in the formal artificial learning sense of an algorithm constantly learning and updating its rules without external intervention. Finally, innovations in monitoring, including those supported by ML, will pose regulatory and medico-legal challenges, as well as questions regarding precisely how to incorporate these features into clinical care and medical education. Rigorous evaluation of ML techniques compared to traditional methods or other AI methods will be required to validate the algorithms developed with consideration of database limitations and potential learning errors. Demonstration of value on processes and outcomes will be necessary to support the use of ML as a feature in monitoring system development: Future research is needed to evaluate all AI based programs before clinical implementation in non-research settings.

Rapid effectiveness of intravenous ketamine for ultraresistant depression in a clinical setting and evidence for baseline anhedonia and bipolarity as clinical predictors of effectiveness.

Intravenous ketamine has been established as an efficacious and safe treatment, with transient effect, for treatment-resistant depression. However, the effectiveness of intravenous ketamine in non-research settings and with ultraresistant depression patients remains understudied. This study aims to measure the response and remission rates in ultraresistant depression patients in a clinical setting by means of a retrospective, open label, database study. Secondarily, the study will attempt to support previous findings of clinical predictors of effectiveness with intravenous ketamine treatment. Fifty patients with ultraresistant depression were treated between May 2015-December 2016, inclusive, in two community hospitals in Edmonton using six ketamine infusions of 0.5 mg/kg over 40 min over 2-3 weeks. Data were collected retrospectively from inpatient and outpatient charts. Statistical analysis to investigate clinical predictors of effectiveness included logistic regression analysis using a dependent variable of a 50% reduction in rating scale score at any point during treatment. At baseline, the average treatment resistance was severe, with a Maudsley Staging Method score of 12.1 out of 15, 90.0% were resistant to electroconvulsive therapy, and the average Beck Depression Inventory score was 34.2. The response rate was 44% and remission rate was 16%. As a single predictor, moderate or severe anhedonia at baseline predicted a 55% increased likelihood of response. As a combined predictor, this level of anhedonia at baseline with a diagnosis of bipolar depression predicted a 73% increase in likelihood of response. In a clinical setting, intravenous ketamine showed effectiveness in a complex, severely treatment-resistant, depressed population on multiple medication profiles concurrently. This study gave support to anhedonia and bipolar depression as clinical predictors of effectiveness.

O11.4. EDUCATION, EMPLOYMENT AND DISABILITY AMONG YOUNG PERSONS WITH EARLY PSYCHOSIS PARTICIPATING IN A COORDINATED SPECIALTY CARE PROGRAM

BackgroundComprehensive early treatment programs for individuals with early psychosis have demonstrated success internationally, spurring rapid expansion of the model in the United States. Between 2014–2016, U.S. federal funding to states to support Coordinated Specialty Care (CSC) for individuals with early psychosis increased to $50 million annually (Dixon, 2017). New York State (NYS) was an early adopter and has rapidly expanded CSC across the state. This study prospectively evaluated education and employment outcomes over time within NYS’s CSC program, OnTrackNY.MethodsEmployment and education trajectories were assessed for individuals with early psychosis who had at least one three-month follow-up assessment, from the program’s inception in October 2013, through September 2016 (N=325). Rates of Social Security Administration (SSA) disability enrollment were assessed for individuals enrolled from October 2013 to June 2017 (n=679).Education and employment status was estimated using longitudinal logistic models utilizing generalized estimating equations with an autoregressive covariance structure to account for within-subject correlations over time. To test how education/employment changed over time, pre-specified contrasts were tested from the longitudinal model for the mean change in sequential follow-up visits. A Kaplan-Meier estimator with discrete time to event and censoring at last observed follow-up month with no event was used to estimate the probability of any education/employment by one year after admission and to estimate the risk of disability by two years after admission.ResultsApproximately 40% of individuals with early psychosis were engaged in school or work upon enrollment in a CSC program; engagement increased to 80% after 6 months of care. The estimated probability of being employed or in school at some time during the year after admission was 87.9% (95% Confidence Interval (CI)= [82.9, 92.0]). Relative to women, men had significantly lower odds of education/employment. Relative to non-Hispanic whites, individuals who were Asian, Hispanic or Black had lower odds of education/ employment. Relative to individuals who had not yet completed high school, individuals whose highest educational attainment was High School (HS) or GED had lower odds of educational/employment.At admission, 2.5% (17/679) clients were receiving SSA disability benefits. The Kaplan-Meier estimates that 18.3% (95% CI= [13.9, 23.9]) of clients followed for two years obtained disability benefits. In bivariate cox regression analyses, individuals with lower (worse) occupational and social functioning scores have significantly greater risk of disability enrollment than individuals with higher scores (in multivariate analysis, only lower occupational functioning remains significant). Age, gender, race, ethnicity, and symptom scores were not significantly associated with disability enrollment.DiscussionThis study demonstrates that individuals with early psychosis who receive CSC in non-research community settings achieve significant improvements in education and employment. Gender, race/ethnicity, and baseline education predicted education and employment outcomes, while poorer functioning was associated with risk of SSA disability benefits. CSC teams should make particular efforts to support the work and school goals of individuals who may be more likely to struggle in achieving engagement in work and school.

Coercion and HIV self-testing in Chinese men who have sex with men: implementation data from a cross-sectional survey

BackgroundThe wide range of interventions to promote HIV testing might inadvertently contribute to coerced testing. There has been concern about coerced HIV self-testing in non-research settings where there is minimal supervision. The aim of this study was to examine the prevalence and correlates of coerced HIV testing among men who have sex with men (MSM) in China. MethodsIn July 2016, we recruited MSM from eight cities through BlueD, a gay social network mobile application. Data on sociodemographics, HIV self-testing, HIV facility testing, test coercion, condomless sex in the past 3 months, and transactional sex were collected. Coerced testing was defined as someone (partner, friend, employer, or others) forcing the participant to take an HIV test. Multivariable logistic regression was used to examine correlates of coerced testing among MSM who had ever received HIV testing. Findings1312 men were included, most of whom were young (mean age 26·9 years [SD 6·3]). 1002 (76%) men were identified as gay, and 685 (52%) men had used HIV self-testing. 64 (15%) men reported coerced testing, and 39 of these men were forced to have a self-test. Adjusting for age, education, income, and residence, men who reported coerced testing were more likely to have ever self-tested for HIV (adjusted odds ratio 4·25; 95% CI 2·23–8·09). Coerced testing was more common among men who had sex with casual partners in exchange for gifts or money (3·34; 1·90–5·86) than among men who did not report transactional sex. Coerced testing was also more common among MSM who reported condomless anal sex in the preceding 3 months (2·38; 1·43–3·98) than among men who did not report condomless anal sex. InterpretationHIV test coercion is uncommon among MSM in China, but is more likely in men who used HIV self-tests. As HIV self-testing is scaled up worldwide, research and enhanced post-test surveillance are needed. FundingNational Institute of Allergy and Infectious Diseases (1R01AI114310-01) and the Australian National Health Medical Research Council (APP1104781). The funders had no role in the design of the study, the collection, analysis, and interpretation of data, or in the writing of the Abstract.

A capability framework to develop leadership for evidence-informed therapies in publicly-funded mental health services

PurposeIt is difficult to replicate evidence-informed models of psychosocial and assertive care interventions in non-research settings, and means to determine workforce capability for psychosocial therapies have not been readily available. The purpose of this paper is to describe and provide a rationale for the Therapy Capability Framework (TCF) which aims to enhance access to, and quality of, evidence-informed practice for consumers of mental health services (MHSs) by strengthening workforce capabilities and leadership for psychosocial therapies.Design/methodology/approachGuided by literature regarding the inadequacies and inconsistencies of evidence-informed practice provided by publicly-funded MHSs, this descriptive paper details the TCF and its application to enhance leadership and provision of evidence-informed psychosocial therapies within multi-disciplinary teams.FindingsThe TCF affords both individual and strategic workforce development opportunities. Applying the TCF as a service-wide workforce strategy may assist publicly-funded mental health leaders, and other speciality health services, establish a culture that values leadership, efficiency, and evidence-informed practice.Originality/valueThis paper introduces the TCF as an innovation to assist publicly-funded mental health leaders to transform standard case management roles to provide more evidence-informed psychosocial therapies. This may have clinical and cost-effective outcomes for public MHSs, the consumers, carers, and family members.

Muscle Protein Turnover and the Molecular Regulation of Muscle Mass during Hypoxia.

: Effects of environmental hypoxia on fat-free mass are well studied. Negative energy balance, increased nitrogen excretion, and fat-free mass loss are commonly observed in lowlanders sojourning at high altitude. Reductions in fat-free mass can be minimized if energy consumption matches energy expenditure. However, in nonresearch settings, achieving energy balance during high-altitude sojourns is unlikely, and myofibrillar protein mass is usually lost, but the mechanisms accounting for the loss of muscle mass are not clear. At sea level, negative energy balance reduces basal and blunts postprandial muscle protein synthesis, with no relevant change in muscle protein breakdown. Downregulations in muscle protein synthesis and loss of fat-free mass during energy deficit at sea level are largely overcome by consuming at least twice the recommended dietary allowance for protein. Hypoxia may increase or not affect resting muscle protein synthesis, blunt postexercise muscle protein synthesis, and markedly increase proteolysis independent of energy status. Hypoxia-induced mTORC1 dysregulation and an upregulation in calpain- and ubiquitin proteasome-mediated proteolysis may drive catabolism in lowlanders sojourning at high altitude. However, the combined effects of energy deficit, exercise, and dietary protein manipulations on the regulation of muscle protein turnover have never been studied at high altitude. This article reviews the available literature related to the effects of high altitude on fat-free mass, highlighting contemporary studies that assessed the influence of altitude exposure (or hypoxia) on muscle protein turnover and intramuscular regulation of muscle mass. Knowledge gaps are addressed, and studies to identify effective and feasible countermeasures to hypoxia-induced muscle loss are discussed.

External Validity of the New York University Caregiver Intervention: Key Caregiver Outcomes Across Multiple Demonstration Projects.

Purpose of the Study: The Administration on Aging funded six New York University Caregiver Intervention (NYUCI) demonstration projects, a counseling/support intervention targeting dementia caregivers and families. Three sites (Georgia, Utah, Wisconsin) pooled data to inform external validity in nonresearch settings. This study (a) assesses collective changes over time, and (b) compares outcomes across sites on caregiver burden, depressive symptoms, satisfaction with social support, family conflict, and quality of life. Design and Methods: Data included baseline/preintervention (N = 294) and follow-up visits (approximately 4, 8, 12 months). Results: Linear mixed models showed that social support satisfaction increased (p < .05) and family conflict decreased (p < .05; Cohen's d = 0.49 and 0.35, respectively). Marginally significant findings emerged for quality of life increases (p = .05) and burden decreases (p < .10). Depressive symptoms remained stable. Slopes did not differ much by site. Implications: NYUCI demonstrated external validity in nonresearch settings across diverse caregiver samples.

Is the use of minimally invasive fusion technologies associated with improved outcomes after elective interbody lumbar fusion? Analysis of a nationwide prospective patient-reported outcomes registry

Background ContextOver the last decade, clinical investigators and biomedical industry groups have used significant resources to develop advanced technologies that enable less invasive spine fusions. These minimally invasive surgery (MIS) technologies often require increased expenditures by hospitals and payers. Although several small single center studies have suggested MIS technologies decrease surgical morbidity and reduce hospital stay, evidence documenting benefit from a patient perspective remains limited. Furthermore, MIS outcomes have yet to be evaluated from the perspective of multiple practice types representing the broad spectrum of US spine surgery. PurposeThis study aimed to examine a population of patients who underwent one- or two-level interbody lumbar fusion diagnosed with lumbar stenosis or Grade 1 spondylolisthesis in an observational, prospective national registry for the purposes of determining how MIS and traditional open technologies affect postsurgical and patient-reported outcomes (PROs). Study Design/SettingThis study used observational analysis of prospectively collected data. Patient SampleThe sample consisted of cases from the National Neurosurgery Quality and Outcomes Database (N2QOD). Outcome MeasuresNumeric rating scale for back and leg pain, Oswestry Disability Index, EuroQol-5D, return to work, and perioperative morbidity were the outcome measures. MethodsThe N2QOD is a prospective PROs registry enrolling patients undergoing elective spine surgery from 60 hospitals in 27 US states via representative sampling. We analyzed the N2QOD aggregate dataset (2010–2014) to identify one- and two-level lumbar interbody fusion procedures performed for lumbar stenosis or Grade 1 spondylolisthesis with 12 months' follow-up where surgical instrumentation and implant types were clearly identified. Perioperative and 1-year outcomes were compared between cases performed with MIS enabling technologies versus traditional open technologies before and after propensity matching. ResultsThere were 467 (24%) patients who underwent elective interbody lumbar fusion using MIS enabling technologies whereas 1,480 (76%) underwent the procedure using traditional open technologies. The MIS patients were slightly healthier (American Society of Anesthesiologists grade), had private insurance more frequently, and underwent two-level fusion less frequently. Unmatched, the MIS cohort was associated with reduced blood loss, a 0.7-day reduction in mean length of hospital stay, and 5% reduced need for post-discharge inpatient rehabilitation, but equivalent 90-day safety measures. After propensity matching, the MIS cohort remained associated with reduced blood loss and a shorter length of stay for one-level fusion (p<.05) but had equivalent length of stay for two-level fusion. Outcomes in all other 90-day safety measures were similar. In both unadjusted and propensity-matched comparison, MIS versus open technologies were associated with equivalent return to work, patient-reported pain, physical disability, and quality of life at 3 and 12 months' follow-up. ConclusionsIn a representative sampling registry of elective interbody lumbar spine fusion procedures spanning 27 US states, nearly a quarter of procedures performed from 2010 to 2014 used minimally invasive enabling technologies. Regardless of approach, interbody lumbar fusion was associated with significant and sustained improvements in all measured health domains. When used in everyday care by a wide spectrum of spine surgeons in non-research settings, the use of MIS technologies was associated with reduced intraoperative blood loss but only a half-day reduction in mean length of hospital stay for one-level fusions. Minimally invasive surgery was not associated with any improved perioperative safety measures or 12-month outcomes. Although MIS enabling technologies may increase some in-hospital care efficiencies, MIS clinical outcomes are similar to open surgery for patients undergoing one- and two-level interbody lumbar fusions.

Comparison of anomalous experiences after ingesting psilocybin mushrooms in research and non-research settings

Comparison of anomalous experiences after ingesting psilocybin mushrooms in research and non-research settings

Getting pregnant in HIV clinical trials: women’s choice and safety needs. The experience from the ANRS12169-2LADY and ANRS12286-MOBIDIP trials

Introduction: Pregnancy is an exclusion criteria in most clinical trials involving antiretroviral therapy (ART) and modern contraception methods are systematically proposed to women of childbearing age. Nevertheless pregnancies are often observed. Reproductive choices during clinical trials should be understood to adapt interventions to the level of risk for mother and baby safety. Our goal was to describe the reproductive behavior and pregnancy outcomes among HIV-infected women on second-line antiretroviral treatment enrolled in two clinical trials and to compare them with those of HIV-positive women in non-research settings.Methods: The number and outcomes of pregnancies were recorded among 281 non menopausal women enrolled in the ANRS 12169-2LADY and ANRS 12286-MOBIDIP clinical trials in Cameroon, Senegal and Burkina Faso. All participants had agreed to use a least one contraceptive method (barrier or non-barrier) which was provided for free during the study. Data were collected through revision of pregnancy notification forms and by data extraction from the study database, regularly updated and checked during the study.Results: Sixty-six women had 84 pregnancies between January 2010 and July 2015 resulting in a pregnancy rate of 8.0 per 100 women-years (WY) (95% CI 6.5–9.9) which is similar to the ones observed in cohort studies in Sub-Saharan Africa (varying from 2.5 to 9.4 pregnancies per 100 WY). Among 60 live births, 10 (16.6%) were born prematurely and 9 (15%) had a low birth weight. Sixteen miscarriages/stillbirths occurred (19.5%). This percentage is comparable to the one expected in the seronegative population which is reassuring for HIV-positive women considering pregnancy on ART. Only one minor birth defect was diagnosed. In univariate and multivariate analysis, miscarriages/stillbirths were not associated either with age, nadir of CD4 count, duration of ART, CD4 count, or viral load at the beginning of pregnancy.Conclusion: HIV-positive women participating in clinical trials conducted in Sub-Saharan Africa tend to get pregnant as often as seropositive women who received medical care in non-research settings. It is therefore essential to adopt a pragmatic approach by re-evaluating the relevance of the criteria for exclusion of pregnant women according to the risk associated with exposure and to seek more effective and innovating contraceptive strategies when using potentially teratogenic molecules.