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The proteostasis network (PN) is a collection of protein folding and degradation pathways that spans cellular compartments and acts to preserve the integrity of the proteome. The differential expression of PN genes is a hallmark of many cancers, and the inhibition of protein quality control factors is an effective way to slow cancer cell growth. However, little is known about how the expression of PN genes differs between patients and how this impacts survival outcomes. To address this, we applied unbiased hierarchical clustering to gene expression data obtained from primary and metastatic cutaneous melanoma (CM) samples and found that two distinct groups of individuals emerge across each sample type. These patient groups are distinguished by the differential expression of genes encoding ATP-dependent and ATP-independent chaperones, and proteasomal subunits. Differences in PN gene expression were associated with increased levels of the transcription factors, MEF2A, SP4, ZFX, CREB1 and ATF2, as well as markedly different survival outcomes. However, surprisingly, similar PN alterations in primary and metastatic samples were associated with discordant survival outcomes in patients. Our findings reveal that the expression of PN genes demarcates CM patients and highlights several new proteostasis sub-networks that could be targeted for more effective suppression of CM within specific individuals., (© 2024. The Author(s).)

Introduction Social risks are associated with increased risk of COVID-19 transmission by limiting patients' ability to practice precautions and access care. Researchers need to understand the prevalence of patients' social risk factors during the pandemic and recognize how social risks may exacerbate COVID-19. Methods The authors conducted a national survey among Kaiser Permanente members between January and September 2020 and restricted analyses to those who responded to a set of COVID-19 items. The survey asked if they experienced social risks, knew of people with COVID-19, and if COVID-19 affected their emotional and mental health, and their preferred type of assistance. Results Social risks were reported by 62% of respondents, with 38% reporting having 2 or more social risks. Respondents most commonly reported financial strain (45%). One or more contact types with COVID-19 were reported by one-third of the respondents. Those with 2 or more COVID-19 contact types reported higher housing instability, financial strain, food insecurity, and social isolation than those with fewer contacts. Overall, 50% of respondents reported that COVID-19 negatively affected their emotional, mental health, and 19% noted that it affected their ability to maintain a job. Discussion People with any COVID-19 contacts reported more social risks compared to those who did not know anyone with COVID-19. This suggests that those with higher social risks during this time may have faced higher risk for COVID-19, or the converse may be true. Conclusion These findings highlight patients' social health during the pandemic and suggest that health systems develop interventions to assess social health and link patients to appropriate resources., Competing Interests: Conflicts of InterestNone declared

Background: Central nervous system (CNS) active medications have been consistently linked to falls in older people. However, few randomized trials have evaluated whether CNS-active medication reduction reduces falls and fall-related injuries. The objective of the Reducing CNS-active Medications to Prevent Falls and Injuries in Older Adults (STOP-FALLS) trial is to test the effectiveness of a health-system-embedded deprescribing intervention focused on CNS-active medications on the incidence of medically treated falls among community-dwelling older adults., Methods: We will conduct a pragmatic, cluster-randomized, parallel-group, controlled clinical trial within Kaiser Permanente Washington to test the effectiveness of a 12-month deprescribing intervention consisting of (1) an educational brochure and self-care handouts mailed to older adults prescribed one or more CNS-active medications (aged 60 + : opioids, benzodiazepines and Z-drugs; aged 65 + : skeletal muscle relaxants, tricyclic antidepressants, and antihistamines) and (2) decision support for their primary health care providers. Outcomes are examined over 18-26 months post-intervention. The primary outcome is first incident (post-baseline) medically treated fall as determined from health plan data. Our sample size calculations ensure at least 80% power to detect a 20% reduction in the rate of medically treated falls for participants receiving care within the intervention (n = 9) versus usual care clinics (n = 9) assuming 18 months of follow-up. Secondary outcomes include medication discontinuation or dose reduction of any target medications. Safety outcomes include serious adverse drug withdrawal events, unintentional overdose, and death. We will also examine medication signetur fields for attempts to decrease medications. We will report factors affecting implementation of the intervention., Discussion: The STOP-FALLS trial will provide new information about whether a health-system-embedded deprescribing intervention that targets older participants and their primary care providers reduces medically treated falls and CNS-active medication use. Insights into factors affecting implementation will inform future research and healthcare organizations that may be interested in replicating the intervention., Trial Registration: ClinicalTrial.gov NCT05689554. Registered on 18 January 2023, retrospectively registered., (© 2023. The Author(s).)

Background: Back pain prevalence and burden increase with age; approximately one-third of U.S. adults 65 years of age and older experience lower back pain (LBP). For chronic low back pain (cLBP), typically defined as lasting three months or longer, many treatments for younger adults may be inappropriate for older adults given their greater prevalence of comorbidities with attendant polypharmacy. While acupuncture has been demonstrated to be safe and effective for cLBP in adults overall, few studies of acupuncture have either included or focused on adults ≥65 years old., Methods: The BackInAction study is a pragmatic, multi-site, three-arm, parallel-groups randomized controlled trial designed to test the effectiveness of acupuncture needling for improving back pain-related disability among 807 older adults ≥65 years old with cLBP. Participants are randomized to standard acupuncture (SA; up to 15 treatment sessions across 12 weeks), enhanced acupuncture (EA; SA during first 12 weeks and up to 6 additional sessions across the following 12 weeks), and usual medical care (UMC) alone. Participants are followed for 12 months with study outcomes assessed monthly with the primary outcome timepoint at 6 months., Discussion: The BackInAction study offers an opportunity to further understand the effectiveness, dose-dependence, and safety of acupuncture in a Medicare population. Additionally, study results may encourage broader adoption of more effective, safer, and more satisfactory options to the continuing over-reliance on opioid- and invasive medical treatments for cLBP among older adults., Trial Registration: ClinicalTrials.gov Identifier: NCT04982315. Clinical trial registration date: July 29, 2021., Competing Interests: Declaration of Competing Interest The authors have no competing interests to disclose., (Copyright © 2023. Published by Elsevier Inc.)

Background: While many studies have assessed and measured patient attitudes toward deprescribing, less quantitative research has addressed the provider perspective. We thus sought to describe provider knowledge, beliefs, and self-efficacy to deprescribe, with a focus on opioids and sedative-hypnotics., Methods: An electronic anonymous survey was distributed to primary care providers at Kaiser Permanente Washington. Two reminder emails were sent. The survey included 10 questions on general deprescribing, and six questions each specific to opioid and sedative-hypnotic deprescribing. Knowledge questions used a multiple-choice response option format. Questions addressing beliefs and self-efficacy (i.e., confidence) used a 0-10 Likert scale. Scales were dichotomized at ≥7 to define agreement (belief questions) or confidence (self-efficacy questions). We calculated descriptive statistics to summarize the responses., Results: Of 370 eligible primary care providers, 95 (26%) completed the survey. For general deprescribing questions, a majority believed that lack of patient willingness, withdrawal symptoms and fear of symptom return, and time constraints impeded deprescribing. Approximately half chose the correct answers about opioid deprescribing, 21% were confident that they could alleviate patient concerns about opioid tapering, and 32% were confident managing chronic non-cancer pain without opioids. For sedative-hypnotics, 64%-87% of respondents correctly answered questions about risks and the relative effectiveness of alternatives, but only one-third correctly answered a question about sedative-hypnotic tapering. Roughly half were confident in their ability to successfully engage patients in sedative deprescribing conversations and select alternatives. Only 54% and 34% were confident in writing a tapering protocol for opioids and sedative-hypnotics, respectively., Conclusion: Results suggest that raising provider awareness of patient willingness to deprescribe, addressing knowledge gaps, and increasing self-efficacy for deprescribing are important targets for improving deprescribing. Support for writing tapering protocols and prescribing evidence-based drug and non-drug alternatives may be important to improve care., (© 2022 The American Geriatrics Society.)

Objective: To examine whether depression status before metabolic and bariatric surgery (MBS) influenced 5-year weight loss, diabetes, and safety/utilization outcomes in the PCORnet Bariatric Study., Summary of Background Data: Research on the impact of depression on MBS outcomes is inconsistent with few large, long-term studies., Methods: Data were extracted from 23 health systems on 36,871 patients who underwent sleeve gastrectomy (SG; n=16,158) or gastric bypass (RYGB; n=20,713) from 2005-2015. Patients with and without a depression diagnosis in the year before MBS were evaluated for % total weight loss (%TWL), diabetes outcomes, and postsurgical safety/utilization (reoperations, revisions, endoscopy, hospitalizations, mortality) at 1, 3, and 5 years after MBS., Results: 27.1% of SG and 33.0% of RYGB patients had preoperative depression, and they had more medical and psychiatric comorbidities than those without depression. At 5 years of follow-up, those with depression, versus those without depression, had slightly less %TWL after RYGB, but not after SG (between group difference = 0.42%TWL, P = 0.04). However, patients with depression had slightly larger HbA1c improvements after RYGB but not after SG (between group difference = - 0.19, P = 0.04). Baseline depression did not moderate diabetes remission or relapse, reoperations, revision, or mortality across operations; however, baseline depression did moderate the risk of endoscopy and repeat hospitalization across RYGB versus SG., Conclusions: Patients with depression undergoing RYGB and SG had similar weight loss, diabetes, and safety/utilization outcomes to those without depression. The effects of depression were clinically small compared to the choice of operation., Competing Interests: The other authors report no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Suicide risk prediction models can identify individuals for targeted intervention. Discussions of transparency, explainability, and transportability in machine learning presume complex prediction models with many variables outperform simpler models. We compared random forest, artificial neural network, and ensemble models with 1500 temporally defined predictors to logistic regression models. Data from 25,800,888 mental health visits made by 3,081,420 individuals in 7 health systems were used to train and evaluate suicidal behavior prediction models. Model performance was compared across several measures. All models performed well (area under the receiver operating curve [AUC]: 0.794-0.858). Ensemble models performed best, but improvements over a regression model with 100 predictors were minimal (AUC improvements: 0.006-0.020). Results are consistent across performance metrics and subgroups defined by race, ethnicity, and sex. Our results suggest simpler parametric models, which are easier to implement as part of routine clinical practice, perform comparably to more complex machine learning methods., (© 2023. The Author(s).)

Background: Health systems are increasingly attempting to intervene on social adversity as a strategy to improve health care outcomes. To inform health system efforts to screen for social adversity, we sought to explore the stability of social risk and interest in assistance over time and to evaluate whether the social risk was associated with subsequent healthcare utilization., Methods: We surveyed Kaiser Permanente members receiving subsidies from the healthcare exchange in Southern California to assess their social risk and desire for assistance using the Accountable Health Communities instrument. A subset of initial respondents was randomized to be re-surveyed at either three or six months later., Results: A total of 228 participants completed the survey at both time points. Social risks were moderate to strongly stable across three and six months (Kappa range = .59-.89); however, social adversity profiles that included participants' desire for assistance were more labile (3-month Kappa = .52; 95% CI = .41-.64 & 6-month Kappa = .48; 95% CI = .36-.6). Only housing-related social risks were associated with an increase in acute care (emergency, urgent care) six months after initial screening; no other associations between social risk and utilization were observed., Conclusions: This study suggests that screening for social risk may be appropriate at intervals of six months, or perhaps longer, but that assessing desire for assistance may need to occur more frequently. Housing risks were associated with increases in acute care. Health systems may need to engage in screening and referral to resources to improve overall care and ultimately patient total health., (© 2022. The Author(s).)

The age-related loss of protein homeostasis (proteostasis) is at the heart of numerous neurodegenerative diseases. Therefore, finding ways to preserve proteome integrity in aged cells may be a powerful way to promote long-term health. Here, we show that reducing the activity of a highly conserved mitochondrial outer membrane protein, MTCH-1/MTCH2, suppresses age-related proteostasis collapse in Caenorhabditis elegans without disrupting development, growth, or reproduction. Loss of MTCH-1 does not influence proteostasis capacity in aged tissues through previously described pathways but instead operates by reducing CED-4 levels. This results in the sequestration of HSP-90 by inactive CED-3, which in turn leads to an increase in HSF-1 activity, transcriptional remodeling of the proteostasis network, and maintenance of proteostasis capacity with age. Together, our findings reveal a role for programmed cell death factors in determining proteome health and suggest that inhibiting MTCH-1 activity in adulthood may safeguard the aging proteome and suppress age-related diseases., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Importance: Bariatric surgery is the most effective treatment for severe obesity; yet it is unclear whether the long-term safety and comparative effectiveness of these operations differ across racial and ethnic groups., Objective: To compare outcomes of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) across racial and ethnic groups in the National Patient-Centered Clinical Research Network (PCORnet) Bariatric Study., Design, Setting, and Participants: This was a retrospective, observational, comparative effectiveness cohort study that comprised 25 health care systems in the PCORnet Bariatric Study. Patients were adults and adolescents aged 12 to 79 years who underwent a primary (first nonrevisional) RYGB or SG operation between January 1, 2005, and September 30, 2015, at participating health systems. Patient race and ethnicity included Black, Hispanic, White, other, and unrecorded. Data were analyzed from July 1, 2021, to January 17, 2022., Exposure: RYGB or SG., Outcomes: Percentage total weight loss (%TWL); type 2 diabetes remission, relapse, and change in hemoglobin A1c (HbA1c) level; and postsurgical safety and utilization outcomes (operations, interventions, revisions/conversions, endoscopy, hospitalizations, mortality, 30-day major adverse events) at 1, 3, and 5 years after surgery., Results: A total of 36 871 patients (mean [SE] age, 45.0 [11.7] years; 29 746 female patients [81%]) were included in the weight analysis. Patients identified with the following race and ethnic categories: 6891 Black (19%), 8756 Hispanic (24%), 19 645 White (53%), 826 other (2%), and 783 unrecorded (2%). Weight loss and mean reductions in HbA1c level were larger for RYGB than SG in all years for Black, Hispanic, and White patients (difference in 5-year weight loss: Black, -7.6%; 95% CI, -8.0 to -7.1; P < .001; Hispanic, -6.2%; 95% CI, -6.6 to -5.9; P < .001; White, -5.9%; 95% CI, -6.3 to -5.7; P < .001; difference in change in year 5 HbA1c level: Black, -0.29; 95% CI, -0.51 to -0.08; P = .009; Hispanic, -0.45; 95% CI, -0.61 to -0.29; P < .001; and White, -0.25; 95% CI, -0.40 to -0.11; P = .001.) The magnitude of these differences was small among racial and ethnic groups (1%-3% of %TWL). Black and Hispanic patients had higher risk of hospitalization when they had RYGB compared with SG (hazard ratio [HR], 1.45; 95% CI, 1.17-1.79; P = .001 and 1.48; 95% CI, 1.22-1.79; P < .001, respectively). Hispanic patients had greater risk of all-cause mortality (HR, 2.41; 95% CI, 1.24-4.70; P = .01) and higher odds of a 30-day major adverse event (odds ratio, 1.92; 95% CI, 1.38-2.68; P < .001) for RYGB compared with SG. There was no interaction between race and ethnicity and operation type for diabetes remission and relapse., Conclusions and Relevance: Variability of the comparative effectiveness of operations for %TWL and HbA1c level across race and ethnicity was clinically small; however, differences in safety and utilization outcomes were clinically and statistically significant for Black and Hispanic patients who had RYGB compared with SG. These findings can inform shared decision-making regarding bariatric operation choice for different racial and ethnic groups of patients.

In a primary care population of 327 older adults (age 60+) with chronic osteoarthritis (OA) pain and insomnia, we examined the relationship between short-term improvement in sleep or pain and long-term sleep, pain, depression, and fatigue by secondary analyses of randomized controlled trial data. Study participants, regardless of trial arm, were classified as Sleep or Pain Improvers with ≥30% baseline to 2-month reduction on the Insomnia Severity Index or the Brief Pain Inventory, respectively, or Sleep or Pain Non-Improvers. After controlling for trial arm and potential confounders, both Sleep and Pain Improvers showed significant (p < .01) sustained improvements across 12 months compared to respective Non-Improvers for the Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index, Brief Pain Inventory-short form (total, Interference, and Severity subscales), Patient Health Questionnaire, and Flinders Fatigue Scale. The effect sizes (Cohen's f2) for the sustained benefits in both Sleep and Pain Improvers compared to their respective Non-Improvers for all variables were small (<0.15) with the exception of medium effect size for sustained reduction in insomnia symptoms for the Sleep Improvers. We conclude that short-term sleep improvements in pain populations with comorbid insomnia precede benefits not only for long-term improvement in sleep but also for reduced pain over the long-term, along with associated improvements in depression and fatigue. Short-term improvements in pain appear to have similar long-term sequelae. Successfully improving sleep in pain populations with comorbid insomnia may have the additional benefits of improving both short- and long-term pain, depression, and fatigue. Trial Registration: OsteoArthritis and Therapy for Sleep (OATS) NCT02946957: https://clinicaltrials.gov/ct2/show/NCT02946957., (© Sleep Research Society 2021. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Osteoarthritis-related insomnia is the most common form of comorbid insomnia among older Americans. A randomized clinical trial found that six sessions of telephone-delivered cognitive behavioral therapy for insomnia (CBT-I) improved sleep outcomes in this population. Using these data, we evaluated the incremental cost-effectiveness of CBT-I from a healthcare sector perspective., Methods: The study was based on 325 community-dwelling older adults with insomnia and osteoarthritis pain enrolled with Kaiser Permanente of Washington State. We measured quality-adjusted life years (QALYs) using the EuroQol 5-dimension scale. Arthritis-specific quality of life was measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Insomnia-specific quality of life was measured using the Insomnia Severity Index (ISI) and nights without clinical insomnia (i.e., "insomnia-free nights"). Total healthcare costs included intervention and healthcare utilization costs., Results: Over the 12 months after randomization, CBT-I improved ISI and WOMAC by -2.6 points (95% CI: -2.9 to -2.4) and -2.6 points (95% CI: -3.4 to -1.8), respectively. The ISI improvement translated into 89 additional insomnia-free nights (95% CI: 79 to 98) over the 12 months. CBT-I did not significantly reduce total healthcare costs (-$1072 [95% CI: -$1968 to $92]). Improvements in condition-specific measures were not reflected in QALYs gained (-0.01 [95% CI: -0.01 to 0.01]); at a willingness-to-pay of $150,000 per QALY, CBT-I resulted in a positive net monetary benefit of $369 with substantial uncertainty (95% CI: -$1737 to $2270)., Conclusion: CBT-I improved sleep and arthritis function without increasing costs. These findings support the consideration of telephone CBT-I for treating insomnia among older adults with comorbid OA. Our findings also suggest potential limitations of the general quality of life measures in assessing interventions designed to improve sleep and arthritis outcomes., (© 2021 The American Geriatrics Society.)

A number of regulatory factors are recruited to chromatin by specialized RNAs. Whether RNA has a more general role in regulating the interaction of proteins with chromatin has not been determined. We used proteomics methods to measure the global impact of nascent RNA on chromatin in embryonic stem cells. Surprisingly, we found that nascent RNA primarily antagonized the interaction of chromatin modifiers and transcriptional regulators with chromatin. Transcriptional inhibition and RNA degradation induced recruitment of a set of transcriptional regulators, chromatin modifiers, nucleosome remodelers, and regulators of higher-order structure. RNA directly bound to factors, including BAF, NuRD, EHMT1, and INO80 and inhibited their interaction with nucleosomes. The transcriptional elongation factor P-TEFb directly bound pre-mRNA, and its recruitment to chromatin upon Pol II inhibition was regulated by the 7SK ribonucleoprotein complex. We postulate that by antagonizing the interaction of regulatory proteins with chromatin, nascent RNA links transcriptional output with chromatin composition., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Importance: Scalable delivery models of cognitive behavioral therapy for insomnia (CBT-I), an effective treatment, are needed for widespread implementation, particularly in rural and underserved populations lacking ready access to insomnia treatment., Objective: To evaluate the effectiveness of telephone CBT-I vs education-only control (EOC) in older adults with moderate to severe osteoarthritis pain., Design, Setting, and Participants: This is a randomized clinical trial of 327 participants 60 years and older who were recruited statewide through Kaiser Permanente Washington from September 2016 to December 2018. Participants were double screened 3 weeks apart for moderate to severe insomnia and osteoarthritis (OA) pain symptoms. Blinded assessments were conducted at baseline, after 2 months posttreatment, and at 12-month follow-up., Interventions: Six 20- to 30-minute telephone sessions provided over 8 weeks. Participants submitted daily diaries and received group-specific educational materials. The CBT-I instruction included sleep restriction, stimulus control, sleep hygiene, cognitive restructuring, and homework. The EOC group received information about sleep and OA., Main Outcomes and Measures: The primary outcome was score on the Insomnia Severity Index (ISI) at 2 months posttreatment and 12-month follow-up. Secondary outcomes included pain (score on the Brief Pain Inventory-short form), depression (score on the 8-item Patient Health Questionnaire), and fatigue (score on the Flinders Fatigue Scale)., Results: Of the 327 participants, the mean (SD) age was 70.2 (6.8) years, and 244 (74.6%) were women. In the 282 participants with follow-up ISI data, the total 2-month posttreatment ISI scores decreased 8.1 points in the CBT-I group and 4.8 points in the EOC group, an adjusted mean between-group difference of -3.5 points (95% CI, -4.4 to -2.6 points; P < .001). Results were sustained at 12-month follow-up (adjusted mean difference, -3.0 points; 95% CI, -4.1 to -2.0 points; P < .001). At 12-month follow-up, 67 of 119 (56.3%) participants receiving CBT-I remained in remission (ISI score, ≤7) compared with 33 of 128 (25.8%) participants receiving EOC. Fatigue was also significantly reduced in the CBT-I group compared with the EOC group at 2 months posttreatment (mean between-group difference, -2.0 points; 95% CI, -3.1 to -0.9 points; P = <.001) and 12-month follow-up (mean between-group difference, -1.8 points; 95% CI, -3.1 to -0.6 points; P = .003). Posttreatment significant differences were observed for pain, but these differences were not sustained at 12-month follow-up., Conclusions and Relevance: In this randomized clinical trial, telephone CBT-I was effective in improving sleep, fatigue, and, to a lesser degree, pain among older adults with comorbid insomnia and OA pain in a large statewide health plan. Results support provision of telephone CBT-I as an accessible, individualized, effective, and scalable insomnia treatment., Trial Registration: Clinical Trials.gov Identifier: NCT02946957.

We use simulated data to examine the consequences of depletion of susceptibles for hazard ratio (HR) estimators based on a propensity score (PS). First, we show that the depletion of susceptibles attenuates marginal HRs toward the null by amounts that increase with the incidence of the outcome, the variance of susceptibility, and the impact of susceptibility on the outcome. If susceptibility is binary then the Bross bias multiplier, originally intended to quantify bias in a risk ratio from a binary confounder, also quantifies the ratio of the instantaneous marginal HR to the conditional HR as susceptibles are depleted differentially. Second, we show how HR estimates that are conditioned on a PS tend to be between the true conditional and marginal HRs, closer to the conditional HR if treatment status is strongly associated with susceptibility and closer to the marginal HR if treatment status is weakly associated with susceptibility. We show that associations of susceptibility with the PS matter to the marginal HR in the treated (ATT) though not to the marginal HR in the entire cohort (ATE). Third, we show how the PS can be updated periodically to reduce depletion-of-susceptibles bias in conditional estimators. Although marginal estimators can hit their ATE or ATT targets consistently without updating the PS, we show how their targets themselves can be misleading as they are attenuated toward the null. Finally, we discuss implications for the interpretation of HRs and their relevance to underlying scientific and clinical questions. See video Abstract: http://links.lww.com/EDE/B727.

Background: Research shows the profound impact of social factors on health, lead many healths systems to incorporate social risk screening. To help healthcare systems select among various screening tools we compared two tools, the Your Current Life Situation (YCLS) and the Accountable Health Communities (AHC) Screening tools, on key psychometric properties., Method: Kaiser Permanente Southern California subsidized exchange members ( n = 1008) were randomly invited to complete a survey containing either the YCLS or the AHC tool, as well as other measures related to care experience and health. Healthcare use was measured through the electronic health record. Agreement between the AHC and YCLS was assessed using adjusted kappas for six domains (food - worry, food - pay, insecure housing, housing quality, transportation, utilities). To assess predictive validity, items on the AHC and YCLS were compared to self-rated health and receipt of a flu shot., Results: Responders ( n = 450) and non-responders ( n = 558) significantly differed on sex, language, and depression ( P < 0.05) but not anxiety, race/ethnicity, or healthcare use. Agreement between the AHC and YCLS tools was substantial on all items (kappas > 0.60) except for housing quality (kappa 0.52). Four out of six screening questions on the AHC tool and four out of seven on the YCLS tool were associated with self-rated health ( P < 0.03). No social needs were associated with flu shot receipt except utilities on the AHC tool ( P = 0.028)., Conclusion: In this sample, the AHC and YCLS tools are similar in their ability to screen for social risks. Differences observed likely stem from the timeframe and wording of the questions, which can be used to guide selection in healthcare systems., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Journal of Family Medicine and Primary Care.)

Here, we describe the complete genome assemblies of seven Pseudomonas sp. isolates collected from a boreal forest soil on the University of Alaska Fairbanks campus. Using the VolTRAX v2 multiplex library preparation for Nanopore sequencing and Illumina reads for polishing, we assembled complete genome sequences for each of the isolates., (Copyright © 2020 Haan et al.)

Importance: Bariatric surgery can lead to substantial improvements in type 2 diabetes (T2DM), but outcomes vary across procedures and populations. It is unclear which bariatric procedure has the most benefits for patients with T2DM., Objective: To evaluate associations of bariatric surgery with T2DM outcomes., Design, Setting, and Participants: This cohort study was conducted in 34 US health system sites in the National Patient-Centered Clinical Research Network Bariatric Study. Adult patients with T2DM who had bariatric surgery between January 1, 2005, and September 30, 2015, were included. Data analysis was conducted from April 2017 to August 2019., Interventions: Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG)., Main Outcome and Measures: Type 2 diabetes remission, T2DM relapse, percentage of total weight lost, and change in glycosylated hemoglobin (hemoglobin A1c)., Results: A total of 9710 patients were included (median [interquartile range] follow-up time, 2.7 [2.9] years; 7051 female patients [72.6%]; mean [SD] age, 49.8 [10.5] years; mean [SD] BMI, 49.0 [8.4]; 6040 white patients [72.2%]). Weight loss was significantly greater with RYGB than SG at 1 year (mean difference, 6.3 [95% CI, 5.8-6.7] percentage points) and 5 years (mean difference, 8.1 [95% CI, 6.6-9.6] percentage points). The T2DM remission rate was approximately 10% higher in patients who had RYGB (hazard ratio, 1.10 [95% CI, 1.04-1.16]) than those who had SG. Estimated adjusted cumulative T2DM remission rates for patients who had RYGB and SG were 59.2% (95% CI, 57.7%-60.7%) and 55.9% (95% CI, 53.9%-57.9%), respectively, at 1 year and 86.1% (95% CI, 84.7%-87.3%) and 83.5% (95% CI, 81.6%-85.1%) at 5 years postsurgery. Among 6141 patients who experienced T2DM remission, the subsequent T2DM relapse rate was lower for those who had RYGB than those who had SG (hazard ratio, 0.75 [95% CI, 0.67-0.84]). Estimated relapse rates for those who had RYGB and SG were 8.4% (95% CI, 7.4%-9.3%) and 11.0% (95% CI, 9.6%-12.4%) at 1 year and 33.1% (95% CI, 29.6%-36.5%) and 41.6% (95% CI, 36.8%-46.1%) at 5 years after surgery. At 5 years, compared with baseline, hemoglobin A1c was reduced 0.45 (95% CI, 0.27-0.63) percentage points more for patients who had RYGB vs patients who had SG., Conclusions and Relevance: In this large multicenter study, patients who had RYGB had greater weight loss, a slightly higher T2DM remission rate, less T2DM relapse, and better long-term glycemic control compared with those who had SG. These findings can help inform patient-centered surgical decision-making.

Saliva represents an ideal matrix for diagnostic biomarker development as it is readily available and requires no invasive collection procedures. However, salivary RNA is labile and rapidly degrades. Previous attempts to isolate RNA from saliva have yielded poor quality and low concentrations. Here we compare collection and processing methods and propose an approach for future studies. The effects of RNA stabilisers, storage temperatures, length of storage and fasting windows were investigated on pooled saliva samples from healthy volunteers. Isolated RNA was assessed for concentration and quality. Bacterial growth was investigated through RT-PCR using bacterial and human primers. Optimal conditions were implemented and quality controlled in a clinical setting. The addition of RNAlater increased mean RNA yield from 4912 ng/μl to 15,473 ng and RNA Integrity Number (RIN) from 4.5 to 7.0. No significant changes to RNA yield were observed for storage at room temperature beyond 1 day or at -80 °C. Bacterial growth did not occur in samples stored at ambient temperature for up to a week. There was a trend towards higher RNA concentration when saliva was collected after overnight fasting but no effect on RIN. In the clinic, RNA yields of 6307 ng and RINs of 3.9 were achieved, improving on previous reports. The method we describe here is a robust, clinically feasible saliva collection method using preservative that gives high concentrations and improved RINs compared to saliva collected without preservative., Competing Interests: The authors have declared that no competing interests exist.

Importance: Additional data comparing longer-term problems associated with various bariatric surgical procedures are needed for shared decision-making., Objective: To compare the risks of intervention, operation, endoscopy, hospitalization, and mortality up to 5 years after 2 bariatric surgical procedures., Design, Setting, and Participants: Adults who underwent Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) between January 1, 2005, and September 30, 2015, within the National Patient-Centered Clinical Research Network. Data from 33 560 adults at 10 centers within 4 clinical data research networks were included in this cohort study. Information was extracted from electronic health records using a common data model and linked to insurance claims and mortality indices. Analyses were conducted from January 2018 through October 2019., Exposures: Bariatric surgical procedures., Main Outcomes and Measures: The primary outcome was time until operation or intervention. Secondary outcomes included endoscopy, hospitalization, and mortality rates., Results: Of 33 560 adults, 18 056 (54%) underwent RYGB, and 15 504 (46%) underwent SG. The median (interquartile range) follow-up for operation or intervention was 3.4 (1.6-5.0) years for RYGB and 2.2 (0.9-3.6) years for SG. The overall mean (SD) patient age was 45.0 (11.5) years, and the overall mean (SD) patient body mass index was 49.1 (7.9). The cohort was composed predominantly of women (80%) and white individuals (66%), with 26% of Hispanic ethnicity. Operation or intervention was less likely for SG than for RYGB (hazard ratio, 0.72; 95% CI, 0.65-0.79; P < .001). The estimated, adjusted cumulative incidence rates of operation or intervention at 5 years were 8.94% (95% CI, 8.23%-9.65%) for SG and 12.27% (95% CI, 11.49%-13.05%) for RYGB. Hospitalization was less likely for SG than for RYGB (hazard ratio, 0.82; 95% CI, 0.78-0.87; P < .001), and the 5-year adjusted cumulative incidence rates were 32.79% (95% CI, 31.62%-33.94%) for SG and 38.33% (95% CI, 37.17%-39.46%) for RYGB. Endoscopy was less likely for SG than for RYGB (hazard ratio, 0.47; 95% CI, 0.43-0.52; P < .001), and the adjusted cumulative incidence rates at 5 years were 7.80% (95% CI, 7.15%-8.43%) for SG and 15.83% (95% CI, 14.94%-16.71%) for RYGB. There were no differences in all-cause mortality between SG and RYGB., Conclusions and Relevance: Interventions, operations, and hospitalizations were relatively common after bariatric surgical procedures and were more often associated with RYGB than SG., Trial Registration: ClinicalTrials.gov identifier: NCT02741674.

We consider the critical problem of pharmacosurveillance for adverse events once a drug or medical product is incorporated into routine clinical care. When making inference on comparative safety using large-scale electronic health records, we often encounter an extremely rare binary adverse outcome with a large number of potential confounders. In this context, it is challenging to offer flexible methods to adjust for high-dimensional confounders, whereas use of the propensity score (PS) can help address this challenge by providing both confounding control and dimension reduction. Among PS methods, regression adjustment using the PS as a covariate in an outcome model has been incompletely studied and potentially misused. Previous studies have suggested that simple linear adjustment may not provide sufficient control of confounding. Moreover, no formal representation of the statistical procedure and associated inference has been detailed. In this paper, we characterize a three-step procedure, which performs flexible regression adjustment of the estimated PS followed by standardization to estimate the causal effect in a select population. We also propose a simple variance estimation method for performing inference. Through a realistic simulation mimicking data from the Food and Drugs Administration's Sentinel Initiative comparing the effect of angiotensin-converting enzyme inhibitors and beta blockers on incidence of angioedema, we show that flexible regression on the PS resulted in less bias without loss of efficiency, and can outperform other methods when the PS model is correctly specified. In addition, the direct variance estimation method is a computationally fast and reliable approach for inference., (© 2019 John Wiley & Sons, Ltd.)

The OsteoArthritis and Therapy for Sleep (OATS) study is a population-based randomized controlled trial of cognitive behavioral therapy for insomnia (CBTI) with four innovative methodological aims. These are to: (1) Enroll representative participants across Washington state, including those from medically underserved communities; (2) Enroll persons with persistent insomnia and chronic osteoarthritis (OA) pain; (3) Test a scalable CBT-I intervention; and (4) Evaluate patient-reported outcomes (insomnia, pain severity, fatigue, depression) and cost-effectiveness over one year. This paper describes progress towards achieving these aims. The target population was persons age 60+ who had received OA care within the Kaiser Permanente Washington (KPW) health care system. We employed a two-phase screening via mail survey and telephone follow-up, with a 3-week interval between screens to exclude persons with spontaneous improvement in sleep or pain symptoms. Participants were randomized to a 6-session telephone-delivered CBT-I intervention or a 6-session telephone education only control condition (EOC). Blinded outcome assessments (completed online or on mailed paper forms) included primary and secondary sleep and pain outcome measures and quality of life measures. We obtained healthcare utilization from administrative claims data. Intent to treat analyses, including all participants randomized when they scheduled the first telephone session, will be conducted to compare CBT-I and EOC outcomes. The trial will be the largest experimental evaluation of telephone CBT-I to date, and the first to evaluate its cost-effectiveness. Trial registration: ClinicalTrials.gov identifier: NCT02946957., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: There has been a dramatic shift in use of bariatric procedures, but little is known about their long-term comparative effectiveness., Objective: To compare weight loss and safety among bariatric procedures., Design: Retrospective observational cohort study, January 2005 to September 2015. (ClinicalTrials.gov: NCT02741674)., Setting: 41 health systems in the National Patient-Centered Clinical Research Network., Participants: 65 093 patients aged 20 to 79 years with body mass index (BMI) of 35 kg/m2 or greater who had bariatric procedures., Intervention: 32 208 Roux-en-Y gastric bypass (RYGB), 29 693 sleeve gastrectomy (SG), and 3192 adjustable gastric banding (AGB) procedures., Measurements: Estimated percent total weight loss (TWL) at 1, 3, and 5 years; 30-day rates of major adverse events., Results: Total numbers of eligible patients with weight measures at 1, 3, and 5 years were 44 978 (84%), 20 783 (68%), and 7159 (69%), respectively. Thirty-day rates of major adverse events were 5.0% for RYGB, 2.6% for SG, and 2.9% for AGB. One-year mean TWLs were 31.2% (95% CI, 31.1% to 31.3%) for RYGB, 25.2% (CI, 25.1% to 25.4%) for SG, and 13.7% (CI, 13.3% to 14.0%) for AGB. At 1 year, RYGB patients lost 5.9 (CI, 5.8 to 6.1) percentage points more weight than SG patients and 17.7 (CI, 17.3 to 18.1) percentage points more than AGB patients, and SG patients lost 12.0 (CI, 11.6 to 12.5) percentage points more than AGB patients. Five-year mean TWLs were 25.5% (CI, 25.1% to 25.9%) for RYGB, 18.8% (CI, 18.0% to 19.6%) for SG, and 11.7% (CI, 10.2% to 13.1%) for AGB. Patients with diabetes, those with BMI less than 50 kg/m2, those aged 65 years or older, African American patients, and Hispanic patients lost less weight than patients without those characteristics., Limitation: Potential unobserved confounding due to nonrandomized design; electronic health record databases had missing outcome data., Conclusion: Adults lost more weight with RYGB than with SG or AGB at 1, 3, and 5 years; however, RYGB had the highest 30-day rate of major adverse events. Small subgroup differences in weight loss outcomes were observed., Primary Funding Source: Patient-Centered Outcomes Research Institute.

Purpose: Sharing of detailed individual-level data continues to pose challenges in multi-center studies. This issue can be addressed in part by using analytic methods that require only summary-level information to perform the desired multivariable-adjusted analysis. We examined the feasibility and empirical validity of 1) conducting multivariable-adjusted distributed linear regression and 2) combining distributed linear regression with propensity scores, in a large distributed data network., Patients and Methods: We compared percent total weight loss 1-year postsurgery between Roux-en-Y gastric bypass and sleeve gastrectomy procedure among 43,110 patients from 36 health systems in the National Patient-Centered Clinical Research Network. We adjusted for baseline demographic and clinical variables as individual covariates, deciles of propensity scores, or both, in three separate outcome regression models. We used distributed linear regression, a method that requires only summary-level information (specifically, sums of squares and cross products matrix) from sites, to fit the three ordinary least squares linear regression models. A comparison set of analyses that used pooled deidentified individual-level data from sites served as the reference., Results: Distributed linear regression produced results identical to those from the corresponding pooled individual-level data analysis for all variables in all three models. The maximum numerical difference in the parameter estimate or standard error for all the variables was 3×10 -11 across three models., Conclusion: Distributed linear regression analysis is a feasible and valid analytic method in multicenter studies for one-time continuous outcomes. Combining distributed regression with propensity scores via modeling offers more privacy protection and analytic flexibility., Competing Interests: Disclosure Dr Arterburn reports NIH funding outside the submitted work. Mr Moyneur reports StatLog was paid consulting fees to conduct study programming. All authors received funding from PCORI to support the submitted work. The authors report no other conflicts of interest in this work.

Background: Bariatric surgery has been used for treatment of severe obesity in adolescents but most studies have been small and limited in follow-up., Objectives: We hypothesized that electronic health record data could be used to compare effectiveness of bariatric procedures in adolescents., Setting: Data were obtained from clinical research networks using a common data model to extract data from each site., Methods: Adolescents who underwent a primary bariatric procedure from 2005 through 2015 were identified. The percent change in body mass index (BMI) at 1, 3, and 5 years was estimated using random effects linear regression for patients undergoing all operations. Propensity score adjusted estimates and 95% confidence intervals were estimated for procedures with >25 patients at each time period., Results: This cohort of 544 adolescents was predominantly female (79%) and White (66%), with mean (±standard deviation) age of 17.3 (±1.6) years and mean BMI of 49.8 (± 7.8) kg/m 2 . Procedures included Roux-en-Y gastric bypass (RYGB; n = 177), sleeve gastrectomy (SG; n = 306), and laparoscopic adjustable gastric banding (n = 61). For those undergoing RYGB, SG, and laparoscopic adjustable gastric banding, mean (95% confidence interval) BMI changes of -31% (-30% to -33%), -28% (-27% to -29%), and -10% (-8% to -12%), were estimated at 1 year. For RYGB and SG, BMI changes of -29% (-26% to -33%) and -25% (-22% to -28%) were estimated at 3 years., Conclusions: Adolescents undergoing SG and RYGB experienced greater declines in BMI at 1- and 3-year follow-up time points, while laparoscopic adjustable gastric banding was significantly less effective for BMI reduction., (Copyright © 2018 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Background: The STarT Back strategy for categorizing and treating patients with low back pain (LBP) improved patients' function while reducing costs in England., Objective: This trial evaluated the effect of implementing an adaptation of this approach in a US setting., Design: The Matching Appropriate Treatments to Consumer Healthcare needs (MATCH) trial was a pragmatic cluster randomized trial with a pre-intervention baseline period. Six primary care clinics were pair randomized, three to training in the STarT Back strategy and three to serve as controls., Participants: Adults receiving primary care for non-specific LBP were invited to provide data 2 weeks after their primary care visit and follow-up data 2 and 6 months (primary endpoint) later., Interventions: The STarT Back risk-stratification strategy matches treatments for LBP to physical and psychosocial obstacles to recovery using patient-reported data (the STarT Back Tool) to categorize patients' risk of persistent disabling pain. Primary care clinicians in the intervention clinics attended six didactic sessions to improve their understanding LBP management and received in-person training in the use of the tool that had been incorporated into the electronic health record (EHR). Physical therapists received 5 days of intensive training. Control clinics received no training., Main Measures: Primary outcomes were back-related physical function and pain severity. Intervention effects were estimated by comparing mean changes in patient outcomes after 2 and 6 months between intervention and control clinics. Differences in change scores by trial arm and time period were estimated using linear mixed effect models. Secondary outcomes included healthcare utilization., Key Results: Although clinicians used the tool for about half of their patients, they did not change the treatments they recommended. The intervention had no significant effect on patient outcomes or healthcare use., Conclusions: A resource-intensive intervention to support stratified care for LBP in a US healthcare setting had no effect on patient outcomes or healthcare use., Trial Registration: National Clinical Trial Number NCT02286141.

Background: Breast cancer screening with magnetic resonance imaging (MRI) may be a useful adjunct to screening mammography in high-risk women, but MRI uptake may be increasing rapidly among low- and average-risk women for whom benefits are unestablished. Comparatively little is known about use of screening MRI in community practice., Objective: To assess relative utilization of MRI among women who do and do not meet professional society guidelines for supplemental screening, and describe utilization according to breast cancer risk indications., Design: Prospective cohort study conducted between 2007 and 2014., Participants: In five regional imaging registries participating in the Breast Cancer Surveillance Consortium (BCSC), 348,955 women received a screening mammogram, of whom 1499 underwent screening MRI., Main Measures: Lifetime breast cancer risk (< 20% or ≥ 20%) estimated by family history of two or more first-degree relatives, and Gail model risk estimates. Breast Imaging Reporting and Data System breast density and benign breast diseases also were assessed. Relative risks (RR) for undergoing screening MRI were estimated using Poisson regression., Key Results: Among women with < 20% lifetime risk, which does not meet professional guidelines for supplementary MRI screening, and no first-degree breast cancer family history, screening MRI utilization was elevated among those with extremely dense breasts [RR 2.2; 95% confidence interval (CI) 1.7-2.8] relative to those with scattered fibroglandular densities and among women with atypia (RR 7.4; 95% CI 3.9-14.3.) or lobular carcinoma in situ (RR 33.1; 95% CI 18.0-60.9) relative to women with non-proliferative disease. Approximately 82.9% (95% CI 80.8%-84.7%) of screening MRIs occurred among women who did not meet professional guidelines and 35.5% (95% CI 33.1-37.9%) among women considered at low-to-average breast cancer risk., Conclusion: Utilization of screening MRI in community settings is not consistent with current professional guidelines and the goal of delivery of high-value care.

Background and Objectives: Studies that use electronic health data typically identify heart failure (HF) events from hospitalizations with a principal diagnosis of HF. This approach may underestimate the total burden of HF among persons with CKD. We assessed the accuracy of algorithms for identifying validated HF events from hospitalizations and outpatient encounters, and we used this validation information to estimate the rate of HF events in a large CKD population., Design, Setting, Participants, & Measurements: We identified a cohort of 15,141 adults age 18-89 years with an eGFR<60 ml/min per 1.73 m 2 from 2008 to 2011. Potential HF events during follow-up were randomly sampled for validation with medical record review. Positive predictive values from the validation study were used to estimate the rate of validated HF events in the full cohort., Results: A total of 1864 participants had at least one health care encounter that qualified as a potential HF event during 2.7 years of mean follow-up. Among 313 potential events that were randomly sampled for validation, positive predictive values were 92% for hospitalizations with a principal diagnosis of HF, 32% for hospitalizations with a secondary diagnosis of HF, and 70% for qualifying outpatient HF encounters. Through use of this validation information in the full cohort, the rate of validated HF events estimated from the most comprehensive algorithm that included principal and secondary diagnosis hospitalizations and outpatient encounters was 35.2 events/1000 person-years (95% confidence interval, 33.1 to 37.4), compared with 9.5 events/1000 person-years (95% confidence interval, 8.7 to 10.5) from the algorithm that included only principal diagnosis hospitalizations. Outpatient encounters accounted for 20% of the total number of validated HF events., Conclusions: In studies that rely on electronic health data, algorithms that include hospitalizations with a secondary diagnosis of HF and outpatient HF encounters more fully capture the burden of HF, although validation of HF events may be necessary with this approach., (Copyright © 2016 by the American Society of Nephrology.)

Introduction: The large-scale assembly of electronic health care data combined with the use of sequential monitoring has made proactive postmarket drug- and vaccine-safety surveillance possible. Although sequential designs have been used extensively in randomized trials, less attention has been given to methods for applying them in observational electronic health care database settings., Existing Methods: We review current sequential-surveillance planning methods from randomized trials, and the Vaccine Safety Datalink (VSD) and Mini-Sentinel Pilot projects-two national observational electronic health care database safety monitoring programs., Future Surveillance Planning: Based on this examination, we suggest three steps for future surveillance planning in health care databases: (1) prespecify the sequential design and analysis plan, using available feasibility data to reduce assumptions and minimize later changes to initial plans; (2) assess existing drug or vaccine uptake, to determine if there is adequate information to proceed with surveillance, before conducting more resource-intensive planning; and (3) statistically evaluate and clearly communicate the sequential design with all those designing and interpreting the safety-surveillance results prior to implementation. Plans should also be flexible enough to accommodate dynamic and often unpredictable changes to the database information made by the health plans for administrative purposes., Conclusions: This paper is intended to encourage dialogue about establishing a more systematic, scalable, and transparent sequential design-planning process for medical-product safety-surveillance systems utilizing observational electronic health care databases. Creating such a framework could yield improvements over existing practices, such as designs with increased power to assess serious adverse events.

Background: Despite numerous options for treating back pain and the increasing healthcare resources devoted to this problem, the prevalence and impact of back pain-related disability has not improved. It is now recognized that psychosocial factors, as well as physical factors, are important predictors of poor outcomes for back pain. A promising new approach that matches treatments to the physical and psychosocial obstacles to recovery, the STarT Back risk stratification approach, improved patients' physical function while reducing costs of care in the United Kingdom (UK). This trial evaluates implementation of this strategy in a United States (US) healthcare setting., Methods: Six large primary care clinics in an integrated healthcare system in Washington State were block-randomized, three to receive an intensive quality improvement intervention for back pain and three to serve as controls for secular trends. The intervention included 6 one-hour training sessions for physicians, 5 days of training for physical therapists, individualized and group coaching of clinicians, and integration of the STarT Back tool into the electronic health record. This prognostic tool uses 9 questions to categorize patients at low, medium or high risk of persistent disabling pain with recommendations about evidence-based treatment options appropriate for each subgroup. Patients at least 18 years of age, receiving primary care for non-specific low back pain, were invited to provide data 1-3 weeks after their primary care visit and follow-up data 2 months and 6 months (primary endpoint) later. The primary outcomes are back-related physical function and pain severity. Using an intention to treat approach, intervention effects on patient outcomes will be estimated by comparing mean changes at the 2 and 6 month follow-up between the pre- and post-implementation periods. The inclusion of control clinics permits adjustment for secular trends. Differences in change scores by intervention group and time period will be estimated using linear mixed models with random effects. Secondary outcomes include healthcare utilization and adherence to clinical guidelines., Discussion: This trial will provide the first randomized trial evidence of the clinical effectiveness of implementing risk stratification with matched treatment options for low back pain in a United States health care delivery system., Trial Registration: NCT02286141. Registered November 5, 2014.

Objectives: To examine the relationships among implementing decision aids (DAs) for benign prostatic hyperplasia (BPH) and prostate cancer (PRCA), and treatment rates and costs., Study Design: A pre-post observational evaluation of a quality improvement initiative in a healthcare system in Washington state., Methods: Men with BPH seen in urology clinics and all men diagnosed with localized PRCA were identified for an intervention period, in which urologists were instructed to order a DA for every patient with those conditions, and a historical control period. Outcomes were 6-month rates of surgery for BPH, any active treatment (hormone therapy, radiation, or surgery) for PRCA, and total healthcare costs. Results During the intervention, DAs were delivered to 22% of men with recent BPH drug treatment, 24% of men with untreated BPH, and 56% of men with PRCA. DA implementation was associated with a 32% lower rate of surgery among men with treated BPH (rate ratio [RR], 0.68; 95% CI, 0.49-0.94) and a nonsignificant 22% lower rate of surgery among men with previously untreated BPH (RR, 0.78; 95% CI, 0.50-1.22). For PRCA, DA implementation was associated with a 27% lower rate of active treatment (RR, 0.73; 95% CI, 0.57-0.93). We found no significant associations between DA implementation and costs of care for either condition., Conclusions: Implementing patient DAs was associated with lower rates of elective surgery for previously treated BPH and active treatment for localized PRCA; however, implementation of these DAs was not associated with lower costs of care.

Background: Cardiotoxicity is a known complication of certain breast cancer therapies, but rates come from clinical trials with design features that limit external validity. The ability to accurately identify cardiotoxicity from administrative data would enhance safety information., Objective: To characterize the performance of clinical coding algorithms for identification of cardiac dysfunction in a cancer population., Research Design: We sampled 400 charts among 6460 women diagnosed with incident breast cancer, tumor size ≥ 2 cm or node positivity, treated within 8 US health care systems between 1999 and 2007. We abstracted medical records for clinical diagnoses of heart failure (HF) and cardiomyopathy (CM) or evidence of reduced left ventricular ejection fraction. We then assessed the performance of 3 different International Classification of Diseases, 9th Edition (ICD-9)-based algorithms., Results: The HF/CM coding algorithm designed a priori to balance performance characteristics provided a sensitivity of 62% (95% confidence interval, 40%-80%), specificity of 99% (range, 97% to 99%), positive predictive value (PPV) of 69% (range, 45% to 85%), and negative predictive value (NPV) of 98% (range, 96% to 99%). When applied only to incident HF/CM (ICD-9 codes and gold standard diagnosis both occurring after breast cancer diagnosis) in patients exposed to anthracycline and/or trastuzumab therapy, the PPV was 42% (range, 14% to 76%)., Conclusions: Claims-based algorithms have moderate sensitivity and high specificity for identifying HF/CM among patients with invasive breast cancer. As the prevalence of HF/CM among the breast cancer population is low, ICD-9 codes have high NPV but only moderate PPV. These findings suggest a significant degree of misclassification due to HF/CM overcoding versus incomplete clinical documentation of HF/CM in the medical record.

Background: Clinical trials demonstrated that women treated for breast cancer with anthracycline or trastuzumab are at increased risk for heart failure and/or cardiomyopathy (HF/CM), but the generalizability of these findings is unknown. We estimated real-world adjuvant anthracycline and trastuzumab use and their associations with incident HF/CM., Methods: We conducted a population-based, retrospective cohort study of 12,500 women diagnosed with incident, invasive breast cancer from January 1, 1999 through December 31, 2007, at eight integrated Cancer Research Network health systems. Using administrative procedure and pharmacy codes, we identified anthracycline, trastuzumab, and other chemotherapy use. We identified incident HF/CM following chemotherapy initiation and assessed risk of HF/CM with time-varying chemotherapy exposures vs no chemotherapy. Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) with adjustment for age at diagnosis, stage, Cancer Research Network site, year of diagnosis, radiation therapy, and comorbidities., Results: Among 12 500 women (mean age = 60 years, range = 22-99 years), 29.6% received anthracycline alone, 0.9% received trastuzumab alone, 3.5% received anthracycline plus trastuzumab, 19.5% received other chemotherapy, and 46.5% received no chemotherapy. Anthracycline and trastuzumab recipients were younger, with fewer comorbidities than recipients of other chemotherapy or none. Compared with no chemotherapy, the risk of HF/CM was higher in patients treated with anthracycline alone (adjusted HR = 1.40, 95% CI = 1.11 to 1.76), although the increased risk was similar to other chemotherapy (adjusted HR = 1.49, 95% CI = 1.25 to 1.77); the risk was highly increased in patients treated with trastuzumab alone (adjusted HR = 4.12, 95% CI = 2.30 to 7.42) or anthracycline plus trastuzumab (adjusted HR = 7.19, 95% CI = 5.00 to 10.35)., Conclusions: Anthracycline and trastuzumab were primarily used in younger, healthier women and associated with increased HF/CM risk compared with no chemotherapy. This population-based observational study complements findings from clinical trials on cancer treatment safety.

Decision aids are evidence-based sources of health information that can help patients make informed treatment decisions. However, little is known about how decision aids affect health care use when they are implemented outside of randomized controlled clinical trials. We conducted an observational study to examine the associations between introducing decision aids for hip and knee osteoarthritis and rates of joint replacement surgery and costs in a large health system in Washington State. Consistent with prior randomized trials, our introduction of decision aids was associated with 26 percent fewer hip replacement surgeries, 38 percent fewer knee replacements, and 12-21 percent lower costs over six months. These findings support the concept that patient decision aids for some health conditions, for which treatment decisions are highly sensitive to both patients' and physicians' preferences, may reduce rates of elective surgery and lower costs.

It is controversial whether starting combination antiretroviral therapy (cART) during primary HIV infection (PHI) is beneficial. Subjects in this observational cohort began cART <30 days (group 1: acute treatment, n = 40), 31-180 days (group 2: early treatment, n = 82) or >180 days (group 3: delayed treatment, n = 35) after HIV infection, and were compared with 27 historical and 60 contemporary controls. Time to HIV-related diagnoses did not differ for group 1 (adjusted hazard ratio [aHR] 1.44, P = 0.3) or group 2 (aHR 1.17, P = 0.5) compared with contemporary controls, but it was delayed for both treated groups (aHR 0.38 for group 1, P = 0.01; and aHR 0.28 for group 2, P < 0.0001) compared with historical controls. Although rates of HIV-related diagnoses were similar in acutely treated subjects and contemporary controls, results were confounded by associations between higher CD4 counts, lower HIV RNA levels and delayed disease progression as reasons for deferring treatment. Randomized trials are needed to address benefits of cART during PHI.

Background/aims: We investigated the psychometric properties of a German translation of the 12-item Autonomy over Tobacco Scale (AUTOS) among 1,195 eighth-grade students., Methods: Data for this study were collected as part of the fourth wave of data collection of the Smokefree Class Competition intervention in the Saxony-Anhalt region of Germany. Students from the control arm of the Smokefree Class Competition study who indicated that they had ever smoked 'at least a few puffs' on a cigarette were classified as ever-smokers. They self-completed questionnaires distributed by teachers., Results: AUTOS scores ranged from 0 to 36 with a distribution highly skewed toward lower-response categories. Inter-item correlations ranged from 0.65 to 0.89 (mean = 0.79, SD = 0.06). Composite reliability for the AUTOS was high (Ω = 0.96) and 3 lower-order factors were also reliable (withdrawal: 0.89, psychological dependence: 0.91, cue-induced cravings: 0.87). Concurrent validity was supported by strong relationships between the AUTOS and both lifetime cigarette consumption and current smoking frequency. Youths were 18 times more likely to be current smokers (95% CI = 11.9-27.2, p < 0.001) if they endorsed any AUTOS item., Conclusion: The German AUTOS is reliable and valid, and the results are consistent with the English AUTOS for use with adolescents., (Copyright © 2011 S. Karger AG, Basel.)

Background: Identifying persons with recent human immunodeficiency virus (HIV) antibody seroconversion is useful for treatment, research, and prevention, but the sensitivity and specificity of tests for this purpose are uncertain., Methods: We used longitudinal specimens panels from 155 persons identified prior to HIV seroconversion to assess antibody-based methods for classifying persons as within 30, 60, or 90 days of seroconversion, including 2 incidence assays, a less-sensitive (LS) enzyme immunoassay (EIA), and the BED assay., Results: Sensitivity and specificity, respectively, for identifying persons within 30 days of seroconversion were: 34%-57% and 98%-100% for 2 standard EIAs (employing a signal-to-cutoff ≤4.0; ≥1.0 defines HIV positive), 84% and 73% for the LS-EIA (≤0.2 cutoff), 88% and 72% for the BED (≤0.2 cutoff), and 43%-58% and 98% (≤3 bands) for 2 Western blot (WB) assays. By area under the receiver operator curves, the best test for identifying persons within 30 days of seroconversion was the number of bands on the Bio-Rad WB (0.90); within 60 days, the LS-EIA and BED (both 0.85); and for persons within 90 days the BED (0.86)., Conclusions: Standard EIAs, Western blots, and HIV incidence assays provide useful information for identifying persons 30 to 90 days after seroconversion.

Background: Few studies have evaluated the effectiveness of massage for chronic low back pain., Objective: To compare the effectiveness of 2 types of massage and usual care for chronic back pain., Design: Parallel-group randomized, controlled trial. Randomization was computer-generated, with centralized allocation concealment. Participants were blinded to massage type but not to assignment to massage versus usual care. Massage therapists were unblinded. The study personnel who assessed outcomes were blinded to treatment assignment. (ClinicalTrials.gov registration number: NCT00371384), Setting: An integrated health care delivery system in the Seattle area., Patients: 401 persons 20 to 65 years of age with nonspecific chronic low back pain., Intervention: Structural massage (n = 132), relaxation massage (n = 136), or usual care (n = 133)., Measurements: Roland Disability Questionnaire (RDQ) and symptom bothersomeness scores at 10 weeks (primary outcome) and at 26 and 52 weeks (secondary outcomes). Mean group differences of at least 2 points on the RDQ and at least 1.5 points on the symptom bothersomeness scale were considered clinically meaningful., Results: The massage groups had similar functional outcomes at 10 weeks. The adjusted mean RDQ score was 2.9 points (95% CI, 1.8 to 4.0 points) lower in the relaxation group and 2.5 points (CI, 1.4 to 3.5 points) lower in the structural massage group than in the usual care group, and adjusted mean symptom bothersomeness scores were 1.7 points (CI, 1.2 to 2.2 points) lower with relaxation massage and 1.4 points (CI, 0.8 to 1.9 points) lower with structural massage. The beneficial effects of relaxation massage on function (but not on symptom reduction) persisted at 52 weeks but were small., Limitation: Participants were not blinded to treatment., Conclusion: Massage therapy may be effective for treatment of chronic back pain, with benefits lasting at least 6 months. No clinically meaningful difference between relaxation and structural massage was observed in terms of relieving disability or symptoms., Primary Funding Source: National Center for Complementary and Alternative Medicine.

Objective: Bariatric surgery is considered the only therapeutic alternative for morbid obesity and its comorbidities. High risks factors are usually linked with this kind of surgery. In order to reduce it, we consider that losing at least 10% of overweight in Morbid Obese (MO) and a minimum of 20% in Super- Obese patients (SO) before surgery, may reduce the morbidity of the procedure. The aim of our study is to demonstrate the effectiveness and tolerance of a balanced energy formula diet at the preoperative stage, comparing it against a low calorie regular diet., Method: We studied 120 patients divided into two groups of 60 each, group A was treated 20 days prior to bariatric surgery with a balanced energy formula diet, based on 200 Kcal every 6 hours for 12 days and group B was treated with a low calorie regular diet with no carbs or fat. The last eight days prior to surgery both groups took only clear liquids. We studied the evolution of weight loss, the BMI, as well as behavior of co-morbidities as systolic blood pressure, diastolic blood pressure, glucose controls and tolerance at the protocol., Results: The study shows that patients undergoing a balanced energy formula diet improved their comorbidities statistically significant in terms of decrease in weight and BMI loss, blood pressure and glucose, compared to the group that was treated before surgery with a low calorie regular diet. Nevertheless both groups improving the weight loss and co-morbidities with better surgical results and facilities., Conclusion: A correct preparation of the Morbid Obese patients prior of surgery can reduce the operative risks improving the results. Our study show that the preoperative treatment with a balanced energy formula diet as were included in our protocol in patients undergoing bariatric surgery improves statistical better their overall conditions, lowers cardiovascular risk and metabolic diseases that the patients with regular diet alone.

Background: Back pain, one of the most prevalent conditions afflicting American adults, is the leading reason for using complementary and alternative medicine (CAM) therapies. Yoga is an increasingly popular "mind-body" CAM therapy often used for relieving back pain and several small studies have found yoga effective for this condition. This study will assess whether yoga is effective for treating chronic low back pain compared with self care and exercise and will explore the mechanisms responsible for any observed benefits., Methods/design: A total of 210 participants with low back pain lasting at least 3 months will be recruited from primary care clinics of a large healthcare system based in Seattle. They will be randomized in a 2:2:1 ratio to receive 12 weekly yoga classes, 12 weekly conventional therapeutic exercise classes of comparable physical exertion, or a self-care book. Interviewers masked to participants' treatment group will assess outcomes at baseline and 6, 12 and 26 weeks after randomization. Primary outcomes will be back-related dysfunction and symptom bothersomeness. In addition, data will be collected on physical measurements (e.g., flexion) at baseline and 12 weeks and saliva samples will be obtained at baseline, 6 and 12 weeks. Information will be collected on specific physical, psychological, and physiological factors to allow exploration of possible mechanisms of action through which yoga could relieve back pain and dysfunction. The effectiveness of yoga will be assessed using analysis of covariance (using general estimating equations - GEE) within an intention-to-treat context. If yoga is found effective, further analyses will explore whether yoga's benefits are attributable to physical, psychological and/or physiological factors., Conclusions: This study will provide the clearest evidence to date about the value of yoga as a therapeutic option for treating chronic back pain, and if the results are positive, will help focus future, more in-depth, research on the most promising potential mechanisms of action identified by this study.

Objective, Participants, and Methods: In this study, the authors explored the psychometric properties of the Hooked on Nicotine Checklist (HONC) among 300 college students who were current smokers. The HONC is a 10-item survey instrument designed to measure diminished autonomy over smoking, a key aspect of dependence. Autonomy is diminished when symptoms present a barrier to cessation., Results: Internal consistency was high (alpha = .89), as was concurrent validity. Students who began smoking earlier and heavier smokers reported more symptoms than did those who started later and smoked less. After controlling for smoking frequency, the HONC was predictive of the likelihood of a failed cessation attempt, with each additional symptom doubling that likelihood., Conclusions: College health professionals could use the HONC to help new smokers recognize their symptoms of diminished autonomy. The HONC may serve as a recruiting tool for cessation programs, which could benefit such early-phase smokers.

Objective: To describe short term patterns of smoking acquisition exhibited by adolescent smokers., Design: Interview records from the prospective development and assessment of nicotine dependence in youth study were examined retrospectively. Interviews were conducted three times per year over 30 months., Subjects: 164 students in grades 7-9 (ages 12-15 years, 86 girls, 78 boys) who had used cigarettes at least twice., Main Outcome Measures: A continuous timeline of smoking activity, beginning with the subject's first use of tobacco and continuing through follow up, was translated into six patterns--abstinent, sporadic, occasional, daily, escalating, and intermittent. Outcome measures were the proportion of subjects starting/ending in each pattern, and the number of transitions per subject between patterns., Results: There was a general but discontinuous progression from infrequent to more frequent use, with many interspersed periods of not smoking. Escalation to daily smoking was common after the development of dependence symptoms, but was rare among those who did not have symptoms. After the appearance of symptoms, both transitions to heavier daily smoking and attempts at cessation increased., Conclusions: Movement to heavier, more frequent smoking is generally unidirectional, although many youths attempt to quit one or more times. The appearance of any symptom of dependence altered the subsequent pattern of smoking behaviour. Future investigators might consider using more frequent data points and a continuous timeline to track smoking behaviour.

Concentrations of preformed vitamin A and five individual carotenoids (alpha-carotene, beta-carotene, cryptoxanthin, lutein and lycopene) were determined in liver, kidney and lung tissue from 20 autopsies of subjects ranging in age from 4 mo to 86 y. Total carotenoid concentrations in liver tissue were always greater than in kidney or lung tissue within the same patient. Total carotenoid concentration in adult subjects was 2.5-77.1 nmol/g tissue (mean 21.0 nmol/g tissue) in liver tissue (n = 14), 0.2-12.7 nmol/g tissue (mean 3.1 nmol/g tissue) in kidney tissue (n = 13) and 0.1-8.4 nmol/g tissue (mean 1.9 nmol/g tissue) in lung tissue (n = 13). Carotenoid content in tissue samples from two infants was low, ranging from 0 to 1.0 nmol/g tissue. beta-Carotene and lycopene were almost always the predominant carotenoids found in liver, kidney and lung tissue. beta-Carotene was positively correlated (P less than 0.05) with alpha-carotene, lycopene and total carotenoids in all of the tissues examined. In addition, beta-carotene and total carotenoids from liver tissue were positively correlated with the same carotenoids in both kidney and lung tissue within each patient. Total vitamin A (free plus esterified) concentration was 8.7-1102.2 nmol/g tissue in liver (n = 17), 3.5-343.9 nmol/g tissue in kidney (n = 14) and 0.7-404.6 nmol/g tissue in lung (n = 14). Vitamin A concentrations were significantly correlated with both beta-carotene and total provitamin A carotenoid concentrations in liver tissue, but not in kidney or lung tissue.

A patient who experienced exacerbation of a previously diagnosed condition of lymphomatoid papulosis during infertility treatment with danazol is reported. The condition worsened over the first month of treatment with medication and resolved completely upon discontinuation of the medication.

Two surveys assessing attitudes toward and beliefs about suicide were conducted with undergraduates. There were 473 participants in Survey I and 692 participants in Survey II. Sex differences were found in participants' receptivity to suicidal individuals, beliefs about the behavior of suicidal peers, attitudes concerning the worth of suicidal people, incidence of adolescent suicide, and morality of suicide. There was no sex difference in participants' own frequency or seriousness of suicide ideation or suicide attempts. Results are discussed in terms of hypotheses concerning traditional socialization of males and females, resulting in sex-role differentiation that may influence attitudes toward and beliefs about suicide.

The abundance of N(15) relative to N(14) is significantly altered during experiments in vitro in which nitrate and nitrite are microbiologically reduced to nitrogen gas. In all studies to date, N(14)O(3)-and N(14)O(2)-species have been preferentially reduced. This selectivity has a complex dependence on conditions in the medium. The results are not only relevant to natural variations in N(15) relative to N(14) but should be seriously considered during N(15) tracer studies in soils.

One of the problems in treating all types of long term patients both young and old is the physical handling involved. Therapists are often faced with the major task of getting heavy patients who have been in bed for a long time or have significant muscle weakness or paralysis, on to their feet again. Additional difficulties relate to the fact that there is often a loss of postural reflex adjustment, in that: (1) Elderly patients forget how to stand after not having done so for a long time, and treating a frightened, heavy, elderly man who will not straighten his legs as he is lifted upright can put a strain on a therapist, which may well result in injury. (2) All patients who have been lying for a length of time need to be brought to the upright position progressively, to allow their circulation to adjust to the changes in gravitational pull, and an easily progressed change of angle whilst lying fully supported is desirable., (Copyright © 1966 Australian Physiotherapy Association. Published by . All rights reserved.)