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BACKGROUND: A longstanding gap in the reproductive health field has been the availability of a screening instrument that can reliably predict a persons likelihood of becoming pregnant. The Desire to Avoid Pregnancy Scale is a new measure; understanding its sensitivity and specificity as a screening tool for pregnancy as well as its predictive ability and how this varies by socio-demographic factors is important to inform its implementation. METHODS: This analysis was conducted on a cohort of 994 non-pregnant participants recruited in October 2018 and followed up for one year. The cohort was recruited using social media as well as advertisements in a university, school, abortion clinic and outreach sexual health service. Almost 90% of eligible participants completed follow-up at 12 months; those lost to follow-up were not significantly different on key socio-demographic factors. We used baseline DAP score and a binary variable of whether participants experienced pregnancy during the study to assess the sensitivity, specificity, area under the ROC curve (AUROC) and positive and negative predictive values (PPV and NPV) of the DAP at a range of cut-points. We also examined how the predictive ability of the DAP varied according to socio-demographic factors and by the time frame considered (e.g., pregnancy within 3, 6, 9 and 12 months). RESULTS: At a cut-point of 2 on the 0-4 range of the DAP scale, the DAP had a sensitivity of 0.78, a specificity of 0.81 and an excellent AUROC of 0.87. In this sample the cumulative incidence of pregnancy was 16% (95%CI 13%, 18%) making the PPV 43% and the NPV 95% at this cut-point. The DAP score was the factor most strongly associated with pregnancy, even after age and number of children were taken into account. The association between baseline DAP score and pregnancy did not differ across time frames. CONCLUSIONS: This is the first study to assess the DAP scale as a screening tool and shows that its predictive ability is superior to the limited pre-existing pregnancy prediction tools. Based on our findings, the DAP could be used with a cut-point selected according to the purpose.

BackgroundA composite metric for the quality of glycemia from continuous glucose monitor (CGM) tracings could be useful for assisting with basic clinical interpretation of CGM data.MethodsWe assembled a data set of 14-day CGM tracings from 225 insulin-treated adults with diabetes. Using a balanced incomplete block design, 330 clinicians who were highly experienced with CGM analysis and interpretation ranked the CGM tracings from best to worst quality of glycemia. We used principal component analysis and multiple regressions to develop a model to predict the clinician ranking based on seven standard metrics in an Ambulatory Glucose Profile: very low-glucose and low-glucose hypoglycemia; very high-glucose and high-glucose hyperglycemia; time in range; mean glucose; and coefficient of variation.ResultsThe analysis showed that clinician rankings depend on two components, one related to hypoglycemia that gives more weight to very low-glucose than to low-glucose and the other related to hyperglycemia that likewise gives greater weight to very high-glucose than to high-glucose. These two components should be calculated and displayed separately, but they can also be combined into a single Glycemia Risk Index (GRI) that corresponds closely to the clinician rankings of the overall quality of glycemia (r = 0.95). The GRI can be displayed graphically on a GRI Grid with the hypoglycemia component on the horizontal axis and the hyperglycemia component on the vertical axis. Diagonal lines divide the graph into five zones (quintiles) corresponding to the best (0th to 20th percentile) to worst (81st to 100th percentile) overall quality of glycemia. The GRI Grid enables users to track sequential changes within an individual over time and compare groups of individuals.ConclusionThe GRI is a single-number summary of the quality of glycemia. Its hypoglycemia and hyperglycemia components provide actionable scores and a graphical display (the GRI Grid) that can be used by clinicians and researchers to determine the glycemic effects of prescribed and investigational treatments.

BackgroundAlthough unhealthy alcohol use is associated with increased morbidity and mortality among people with HIV (PWH), many are ambivalent about engaging in treatment and experience variable responses to treatment. We describe the rationale, aims, and study design for the Financial Incentives, Randomization, with Stepped Treatment (FIRST) Trial, a multi-site randomized controlled efficacy trial.MethodsPWH in care recruited from clinics across the United States who reported unhealthy alcohol use, had a phosphatidylethanol (PEth) >20 ng/mL, and were not engaged in formal alcohol treatment were randomized to integrated contingency management with stepped care versus treatment as usual. The intervention involved two steps; Step 1: Contingency management (n = 5 sessions) with potential rewards based on 1) short-term abstinence; 2) longer-term abstinence; and 3) completion of healthy activities to promote progress in addressing alcohol consumption or conditions potentially impacted by alcohol; Step 2: Addiction physician management (n = 6 sessions) plus motivational enhancement therapy (n = 4 sessions). Participants' treatment was stepped up at week 12 if they lacked evidence of longer-term abstinence. Primary outcome was abstinence at week 24. Secondary outcomes included alcohol consumption (assessed by TLFB and PEth) and the Veterans Aging Cohort Study (VACS) Index 2.0 scores; exploratory outcomes included progress in addressing medical conditions potentially impacted by alcohol. Protocol adaptations due to the COVID-19 pandemic are described.ConclusionsThe FIRST Trial is anticipated to yield insights on the feasibility and preliminary efficacy of integrated contingency management with stepped care to address unhealthy alcohol use among PWH.Clinicaltrialsgov identifier: NCT03089320.

BACKGROUND: Clinicians and women of reproductive age would benefit from a reliable way to identify who is likely to become pregnant in the next year, in order to direct health advice. The 14-item Desire to Avoid Pregnancy (DAP) scale is predictive of pregnancy; this paper compares it with other ways of assessing pregnancy preferences to shortlist options for clinical implementation. METHODS: A cohort of 994 UK women of reproductive age completed the DAP and other questions about pregnancy preferences, including the Attitude towards Potential Pregnancy Scale (APPS), at baseline and reported on pregnancies quarterly for a year. For each question, DAP item and combinations of DAP items, we examined the predictive ability, sensitivity, specificity, area under the receiver operating curve (AUROC), and positive and negative predictive values. RESULTS: The AUROCs and predictive ability of the APPS and DAP single items were weaker than the full DAP, though all except one had acceptable AUROCs (>0.7). The most predictive individual DAP item was It would be a good thing for me if I became pregnant in the next 3 months, where women who strongly agreed had a 66.7% chance of pregnancy within 12 months and the AUROC was acceptable (0.77). CONCLUSION: We recommend exploring the acceptability to women and healthcare professionals of asking a single DAP item (It would be a good thing for me if I became pregnant in the next 3 months), possibly in combination with additional DAP items. This will help to guide service provision to support reproductive preferences.

IntroductionUnhealthy alcohol use is associated with a range of adverse outcomes among people with HIV (PWH). Testing the efficacy and promoting the availability of effective interventions to address unhealthy alcohol use among PWH is thus a priority. Alcohol use outcomes in intervention studies are often measured by self-report alone, which can lead to spurious results due to information biases (eg, social desirability). Measuring alcohol outcomes objectively through biomarkers, such as phosphatidylethanol (PEth), in addition to self-report has potential to improve the validity of intervention studies. This protocol outlines the methods for a systematic review and individual participant data meta-analysis that will estimate the efficacy of interventions to reduce alcohol use as measured by a combined categorical self-report/PEth variable among PWH and compare these estimates to those generated when alcohol is measured by self-report or PEth alone.Methods and analysisWe will include randomised controlled trials that: (A) tested an alcohol intervention (behavioural and/or pharmacological), (B) enrolled participants 15 years or older with HIV; (C) included both PEth and self-report measurements, (D) completed data collection by 31 August 2023. We will contact principal investigators of eligible studies to inquire about their willingness to contribute data. The primary outcome variable will be a combined self-report/PEth alcohol categorical variable. Secondary outcomes will include PEth alone, self-report alone and HIV viral suppression. We will use a two-step meta-analysis and random effects modelling to estimate pooled treatment effects; I2 will be calculated to evaluate heterogeneity. Secondary and sensitivity analyses will explore treatment effects in adjusted models and within subgroups. Funnel plots will be used to explore publication bias.Ethics and disseminationThe study will be conducted with deidentified data from completed randomised controlled trials and will be considered exempt from additional ethical approval. Results will be disseminated through peer-reviewed publications and international scientific meetings.Prospero registration numberCRD42022373640.

PurposeEmergency contraception (EC), the 'last chance' contraceptive method, has gained significance post-Roe, but most young people do not know their options.MethodsWe conducted an educational intervention on EC among 1,053 students aged 18-25 years. We assessed changes in knowledge of key aspects of EC using generalized estimating equations.ResultsAt baseline, virtually no one was aware of the intrauterine device for EC (4%), but postintervention, 89% correctly identified intrauterine devices as the most effective EC (adjusted odds ratio [aOR] = 116.6; 95% confidence interval [CI] 62.4, 217.8). Knowledge that levonorgestrel pills could be accessed without a prescription grew (60%-90%; aOR = 9.7, 95% CI 6.7-14.0), as did knowledge that pills work best when taken as soon as possible (75%-95%; aOR = 9.6, 95% CI 6.1-14.9). Multivariate results showed adolescent and young adult participants absorbed these key concepts across age, gender, and sexual orientation.DiscussionTimely interventions are needed to empower youth with knowledge of EC options.

ObjectivesTo estimate the effects on cervical mucus, ovarian activity and theoretical contraceptive protection of a 6-hour delay and of missing one norgestrel 0.075 mg progestogen-only pill.Study designIn a prospective, two-site, randomized, crossover study, healthy women aged 18 to 35 with BMI

Helping people with HIV (PWH) and without HIV (PWoH) understand the relationship between physical symptoms and alcohol use might help motivate them to decrease use. In surveys collected in the Veterans Aging Cohort Study from 2002 to 2018, PWH and PWoH were asked about 20 common symptoms and whether they thought any were caused by alcohol use. Analyses were restricted to current alcohol users (AUDIT-C > 0). We applied generalized estimating equations. The outcome was having any Symptoms Attributed to Alcohol use (SxAA). Primary independent variables were each of the 20 symptoms and HIV status. Compared to PWoH, PWH had increased odds of SxAA (OR 1.54; 95% CI 1.27, 1.88). Increased AUDIT-C score was also associated with SxAA (OR 1.32; 95% CI 1.28, 1.36), as were trouble remembering, anxiety, and weight loss/wasting. Evidence that specific symptoms are attributed to alcohol use may help motive people with and without HIV decrease their alcohol use.

ObjectiveTo evaluate the cervical mucus effects of a norgestrel 0.075 mg progestin-only contraceptive pill over a 28-day cycle.Study designWe recruited persons ages 18 to 35 with normal cycles at 2 US academic medical centers. Participants took norgestrel 0.075 mg daily for 28 days at the same time (within a 3 hour window) daily, recorded through a text-message based e-diary. We extracted cervical mucus using a standardized aspiration technique on the day of pill initiation and then at least every 3 to 4 days over the cycle. We monitored subjects for follicular activity with transvaginal ultrasound examination and blood sampling for ovarian hormones and gonadotropins at each visit. We assessed cervical mucus scoring using a 4-category/12-point modified Insler scale (score ≥9 [favoring fertility], 5-8 [intermediate], and ≤4 [unfavorable to fertility]). We stratified cervical mucus scores by serum estradiol levels and ovulatory status based on a modified Hoogland score.ResultsExcluding enrollment, we collected and evaluated 413 mucus samples from 51 participants. Participants had a median mucus score of 0 (Interquartile Range 0, 2); most had scores ≤4 (samples = 385, 93%) and none had a score ≥9 favoring fertility. Seventeen (33%) participants ovulated, of which 14 (82%) had unfavorable mucus scores (≤4) at the time of ovulation and 3 (18%) had intermediate scores (5-8).ConclusionsNorgestrel 0.075 mg daily prevents mucus changes that favor fertility, even during ovulatory cycles.ImplicationsDaily administration of norgestrel 0.075 mg over an initial 28-day cycle did not result in fertile cervical mucus. Although approximately one-third of users ovulated in this first cycle of pill use, contraceptive efficacy may be maintained by mucus effects.

ObjectiveTo explore the effect on ovarian activity and ovulation of 28 days of correct daily use of a progestogen-only pill containing norgestrel 0.075 mg.Study designWe performed a prospective, randomized, crossover study at 2 US sites, recruiting healthy women of reproductive age to use norgestrel 0.075 mg daily for three 28-day treatment cycles. We monitored ovarian activity every 3 to 4 days with reproductive hormone measurements and ovarian ultrasonography. Participants recorded pill use in daily diaries. An adjudication committee independent of the research sites assessed ovarian activity using a modified Hoogland score combining hormone concentrations and follicle diameter and appearance (quiescence 1-3, ovarian activity without ovulation 4-5, and ovulatory/postovulatory 6-7).ResultsWe report here the findings of the initial 28-day treatment cycle in which 51 of 52 recruited participants provided data sufficient for analysis. Two thirds of subjects had no evidence of ovulation (34/51, 66.6%); eight of these (15.7%) had quiescent ovaries (follicle 13 mm diameter) without ovulation. Seventeen participants ovulated, of whom 12 (23.5%) had a normal, and 5 (9.8%) an abnormal luteal phase. Persistent ovarian follicles were common among women who had ovarian activity without ovulation, 17 of 26 participants (65.4%) had a large follicle which persisted beyond 28 days.ConclusionDuring 28 days of exposure to a norgestrel 0.075 mg progestogen-only pill, most women had no evidence of ovulation.ImplicationsOvulation inhibition and follicle growth disturbance are important in the mechanism of action of a progestogen-only pill containing norgestrel 0.075 mg.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Small Cell Lung Cancer (SCLC) provide recommended management for patients with SCLC, including diagnosis, primary treatment, surveillance for relapse, and subsequent treatment. This selection for the journal focuses on metastatic (known as extensive-stage) SCLC, which is more common than limited-stage SCLC. Systemic therapy alone can palliate symptoms and prolong survival in most patients with extensive-stage disease. Smoking cessation counseling and intervention should be strongly promoted in patients with SCLC and other high-grade neuroendocrine carcinomas. The "Summary of the Guidelines Updates" section in the SCLC algorithm outlines the most recent revisions for the 2022 update, which are described in greater detail in this revised Discussion text.

Central aortic blood pressure could be helpful in the evaluation of patients with aortic stenosis (AS). The SphygmoCor XCEL device estimates central blood pressure (BP) measurement with its easy-to-use, operator-independent procedure. However, this device has not been properly validated against invasive measurement in patients with severe AS. We evaluated the relationship between cuff-brachial BP, transfer function-estimated and invasively measured central aortic pressure in patients with severe AS before and after transcatheter aortic valve replacement (TAVR). Agreement between techniques was analyzed and, according to the ARTERY Society recommendations, the minimum acceptable error was a mean difference ± SD ≤5 ± ≤8 mm Hg. A total of 94 patients with AS undergoing TAVR had simultaneous non-invasive and invasive measurements of central BP before and after the procedure. Before TAVR central systolic BP was in average slightly underestimated, though with wide variability, when using the default calibration of brachial-cuff SBP (mean difference ± SD, -3 ± 15 mm Hg), and after TAVR the degree of underestimation increased (mean difference ± SD, -9 ± 13 mm Hg). The agreement tended to improve for those patients with low aortic gradient stenosis compared to those with high gradient at baseline (mean difference ± SD, -2 ± 11 mm Hg vs. -4 ± 17, respectively, p = .3). The cuff-brachial systolic BP yielded numerically lower degree of agreement and weaker correlation with invasive measurements than SphygmoCor XCEL. In patients with severe AS the SphygmoCor XCEL cuff device, despite showing strong correlation, does not meet the ARTERY Society accuracy criteria for non-invasive measurement of central SBP.

The role of clinical researchers is vital to cancer progress. The teaching, research, and leadership roles that academic oncologists hold need to be accounted for and appropriately compensated. National metrics are currently inexistent, but are necessary to move the oncology research field forward. Clinical research and routine clinical care must be harmoniously integrated without competing. This article reviews the national landscape of clinical cancer research and proposes a call for action.

The use of antiretroviral therapy for people with HIV (PWH) has improved life expectancy. However, PWH now lose more life-years to tobacco use than to HIV infection. Unfortunately, PWH smoke at higher rates and have more difficulty maintaining abstinence than the general population, compounding their risk for chronic disease. In this Commentary, we describe a United States National Cancer Institute-led initiative to address the relative lack of research focused on developing, testing, and implementing smoking cessation interventions for PWH. This initiative supports seven clinical trials designed to systematically test and/or develop and test adaptations of evidence-based smoking cessation interventions for PWH (eg, combination of behavioral and pharmacological). We summarize each project, including setting/recruitment sites, inclusion/exclusion criteria, interventions being tested, and outcomes. This initiative provides critical opportunities for collaboration and data harmonization across projects. The knowledge gained will inform strategies to assist PWH to promote and maintain abstinence, and ensure that these efforts are adaptable and scalable, thereby addressing one of the major threats to the health of PWH. Reducing smoking behavior may be particularly important during the COVID-19 pandemic given that smokers who become infected with SARS-CoV-2 may be at risk for more severe disease.ImplicationsThis Commentary describes a National Cancer Institute-led initiative to advance the science and practice of treating tobacco use among PWH, which is now responsible for more life years lost than HIV. We describe the scope of the problem, the objectives of the initiative, and a summary of the seven funded studies. Harmonization of data across projects will provide information related to treatment mediators and moderators that was not previously possible. Stakeholders interested in tobacco cessation, including researchers, clinicians and public health officials, should be aware of this initiative and the evidence-base it will generate to advance tobacco treatment among this high-risk population.

Alcohol use increases non-adherence to antiretroviral therapy (ART) among persons living with HIV (PLWH). Dynamic longitudinal associations are understudied. Veterans Aging Cohort Study (VACS) data 2/1/2008-7/31/16 were used to fit linear regression models estimating changes in adherence (% days with ART medication fill) associated with changes in alcohol use based on annual clinically-ascertained AUDIT-C screening scores (range - 12 to + 12, 0 = no change) adjusting for demographics and initial adherence. Among 21,275 PLWH (67,330 observations), most reported no (48%) or low-level (39%) alcohol use initially, with no (55%) or small (39% ≤ 3 points) annual change. Mean initial adherence was 86% (SD 21%), mean annual change was - 3.1% (SD 21%). An inverted V-shaped association was observed: both increases and decreases in AUDIT-C were associated with greater adherence decreases relative to stable scores [p

Bronchoalveolar lavage (BAL) is a key clinical and research tool in lung transplantation (LTx). However, BAL collection and processing are not standardized across LTx centers. This International Society for Heart and Lung Transplantation-supported consensus document on BAL standardization aims to clarify definitions and propose common approaches to improve clinical and research practice standards. The following 9 areas are covered: (1) bronchoscopy procedure and BAL collection, (2) sample handling, (3) sample processing for microbiology, (4) cytology, (5) research, (6) microbiome, (7) sample inventory/tracking, (8) donor bronchoscopy, and (9) pediatric considerations. This consensus document aims to harmonize clinical and research practices for BAL collection and processing in LTx. The overarching goal is to enhance standardization and multicenter collaboration within the international LTx community and enable improvement and development of new BAL-based diagnostics.

Among young persons, ease of use, high efficacy, and high acceptability makes the etonogestrel contraceptive implant an important choice for this age group. Adolescent-friendly, patient-centered counseling considers the patient's cognitive development, the influence of friends and family, as well as their own preferences and values. Age-appropriate language, graphics, and models are useful to explain contraceptive options and relevant side effects. Effectiveness, reversibility, safety, noncontraceptive benefits, and side effects are important attributes and should be discussed when teens are choosing a contraceptive method. In this review we describe suggested best practices for counseling adolescents about the etonogestrel implant so they can make informed, prudent decisions about using this contraceptive method.

ObjectivesPeople with HIV (PWH) have a high burden of bacterial sexually transmitted infections (STIs). We examined the relationship of alcohol and drug use and partner pre-exposure prophylaxis (PrEP) use to STI prevalence in a cohort of PWH with a history of unhealthy alcohol use.MethodsWe analysed data from a primary care-based alcohol intervention study at Kaiser Permanente Northern California (KPNC). Participants were recruited between April 2013 and May 2015 and were followed for up to 24 months. We linked participant responses to questions from the 24 month follow-up interview, including alcohol and drug use and partner PrEP use, with STI test results (ie, syphilis, chlamydia, gonorrhoea) in the KPNC electronic health record. Prevalence ratios (PR) were estimated using Poisson models fitted with robust variance estimators to evaluate the association of substance use and partner use of PrEP with STIs.ResultsIn the analytic sample (n=465), the median age was 52 years (IQR 45-59); 67% were white; 95% were men who have sex with men. Thirty-two per cent of participants had HIV-positive partners only; 31% had HIV-negative partners with at least one on PrEP in the previous year and 37% had HIV-negative partners without any on PrEP. Twenty-three per cent reported alcohol and drug use prior to sex in the last 6 months. Eight per cent of participants had an STI. Partner PrEP use (adjusted PR (aPR) 2.99 (95% CI 1.11 to 8.08)) was independently associated with higher STI prevalence. Participants who reported use of alcohol (aPR 1.53 (0.61 to 3.83)), drugs (aPR 1.97 (0.71 to 5.51)) or both (aPR 1.93 (0.75 to 4.97)) prior to sex had a higher STI prevalence.ConclusionsThe higher prevalence of STIs among PWH with unhealthy alcohol use who have partners on PrEP suggests that this subgroup may be a high-yield focus for targeted outreach, STI screening and sexual health counselling.

AimsTo use electronic health record data from real-world clinical practice to assess demographics, clinical characteristics and disease burden of adults with type 1 diabetes (T1D) in the United States.Materials and methodsRetrospective observational study of adults with T1D for ≥24 months at their first visit with a T1D diagnosis code ("index date") between July 2014 and June 2016 in the Optum Humedica database. Demographic characteristics, acute complications (severe hypoglycaemia [SH], diabetic ketoacidosis [DKA]), microvascular complications, cardiovascular (CV) events and health care resource utilization during the 12 months before the index date ("baseline period") were compared between patients with optimal versus suboptimal glycaemic control (glycated haemoglobin [HbA1c] 30 000 adults with T1D showed that individuals with suboptimal versus optimal glycaemic control differed significantly in terms of health care coverage, comorbidities, diabetes-related complications, health care utilization and CV risk factors. However, suboptimal control was not associated with increased risk of CV outcomes.

ObjectivesTo evaluate if a simple method for characterizing vaginal bleeding patterns in etonogestrel contraceptive implant users can predict subsequent patterns and bleeding-related discontinuation over the first 2 years of use.Study designWe reanalyzed phase 3 study bleeding data for non-breastfeeding participants from the United States, Europe, Russia and Chile during the first 2 years of implant use to characterize and correlate bleeding patterns. We used 90-day reference periods with period 1.1 starting at Day 29 and ending at Day 118. We dichotomized bleeding patterns as "favorable" (amenorrhea, infrequent bleeding and normal frequency bleeding without prolonged bleeding) or "unfavorable' (prolonged and/or frequent bleeding) and tracked user groups based on these bleeding patterns in reference period 1.1 through Year 1 and from Year 1 through Year 2, respectively.ResultsWe evaluated data from 537 and 428 women with up to 1 and 2 years use, respectively. Of the 325 (60.5%) women with favorable bleeding in reference period 1.1, 275 (84.6%) reported favorable bleeding also in reference period 2, 197 (60.6%) reported favorable bleeding throughout Year 1, and favorable bleeding in 75-85% of reference periods in Year 2. Among 212 (39.5%) women with unfavorable bleeding in reference period 1.1, 118 (55.7%) continued with unfavorable bleeding in reference period 2, while about 40%-50% reported favorable patterns in RP 2, 3 and/or 4. Initial favorable bleeding resulted in lower discontinuation rates than initial unfavorable bleeding in years 1 (3.7% vs 12.7%, p≪.0001) and 2 (2.5% vs 16.5%, p≪.0001).ConclusionImplant users with favorable bleeding in the first reference period are likely to continue with favorable bleeding over the next 2 years. Initial bleeding patterns predict overall continuation rates in years 1 and 2. Implications Statement When evaluating vaginal bleeding in any 90-day reference period over 2 years of etonogestrel implant use, approximately 80% of women with favorable and 40% with unfavorable bleeding patterns will have favorable bleeding in the next reference periods. These findings can facilitate counseling regarding bleeding for women using the etonogestrel implant.

ObjectiveLung-MAP (SWOG S1400) is a master platform trial assessing targeted therapies in squamous NSCLC. The objective of study C (S1400C) was to evaluate the response rate to palbociclib, a cyclin-dependent kinase 4 and cyclin-dependent kinase 6 inhibitor, in patients with cell cycle gene abnormalities.MethodsPatients with squamous NSCLC, a performance status of 0 to 2, and normal organ function who had progressed after at least one prior platinum-based chemotherapy with cyclin-dependent kinase 4 gene (CDK4) or cyclin D1 gene (CCND1), cyclin D2 gene (CCND2), or cyclin D3 gene (CCND3) amplifications on tumor specimens were eligible. The study was originally designed as a phase II/III trial comparing palbociclib with docetaxel, but it was modified to a single-arm phase II trial with the primary end point of response when immunotherapy was approved. If two or fewer responses were seen in the first 20 patients, then the study would cease enrollment.ResultsA total of 88 patients (9% of patients screened) were assigned to S1400C, and 53 patients enrolled (including 17 to receive docetaxel). One patient who had been registered to receive docetaxel was re-registered to receive palbociclib after progression while taking docetaxel. The frequencies of cell cycle gene alterations in the eligible patients taking palbociclib (n = 32) were as follows: CCND1, 81% (n = 26); CCND2, 9% (n = 3); CCND3, 6% (n = 2); and CDK4, 3% (n = 1). In all, 32 eligible patients received palbociclib. There were two partial responses (response rate 6% [95% confidence interval (CI): 0%-15%]), both with CCND1 amplification. Twelve patients had stable disease (38% [95% CI: 21%-54%]). The median progression-free survival was 1.7 months (95% CI: 1.6-2.9 months) and the median overall survival was 7.1 months (95% CI: 4.2-12.5).ConclusionPalbociclib as monotherapy failed to demonstrate the prespecified criteria for advancement to phase III testing.

Aortic stenosis (AS) management is classically guided by symptoms and valvular metrics. However, the natural history of AS is dictated by coupling of the left ventricle, aortic valve, and vascular system. We investigated whether metrics of ventricular and vascular state add to the appreciation of AS state above valve gradient alone. Seventy patients with severe symptomatic AS were prospectively followed from baseline to 30 days after transcatheter aortic valve replacement (TAVR). Quality of life (QOL) was assessed using the Kansas City Cardiomyopathy Questionnaire. Left ventricular stroke work (SWLV) and vascular impedance spectrums were calculated noninvasively using in-house models based on central blood pressure waveforms, along with hemodynamic parameters from echocardiograms. Patients with higher preprocedural SWLV and lower vascular impedance were more likely to experience improved QOL after TAVR. Patients fell into two categories: those who did and those who did not exhibit increase in blood pressure after TAVR. In patients who developed hypertension (19%), vascular impedance increased and SWLV remained unchanged (impedance at zeroth harmonic: Z0, from 3964.4 to 4851.8 dyne·s/cm3, P = 0.039; characteristic impedance: Zc, from 376.2 to 603.2 dyne·s/cm3, P = 0.033). SWLV dropped only in patients who did not develop new hypertension after TAVR (from 1.58 to 1.26 J; P < 0.001). Reduction in valvular pressure gradient after TAVR did not predict change in SWLV (r = 0.213; P = 0.129). Reduction of SWLV after TAVR may be an important metric in management of AS, rather than relying solely on the elimination of transvalvular pressure gradients.

BackgroundAlcohol use influences HIV disease severity through multiple mechanisms. Whether HIV disease severity is sensitive to changes in alcohol use among people with HIV (PWH) is understudied.SettingNational Veterans Health Administration.MethodsPairs of AUDIT-C screens within 9-15 months (February 1, 2008-September 30, 2014) were identified among PWH from the Veterans Aging Cohort Study (VACS). Initial and follow-up VACS Index 2.0 pairs obtained 0-270 days after initial and follow-up AUDIT-Cs, respectively, determined change in VACS Index 2.0, a composite HIV severity measure. Change in VACS Index 2.0 was regressed on AUDIT-C change scores (-12 to +12) adjusted for demographics, initial VACS Index 2.0, and days between VACS Index measures.ResultsAmong 23,297 PWH (76,202 observations), most had no (51%) or low-level (38%) alcohol use initially. Most (54%) had no subsequent change; 21% increased and 24% decreased drinking. Initial VACS Index 2.0 scores ranged from 0 to 134, change scores ranged from -65 to +73, with average improvement of 0.76 points (SD 9.48). AUDIT-C change was associated with VACS Index 2.0 change (P < 0.001). Among those with stable alcohol use (AUDIT-C change ≤ │1│ point), VACS Index 2.0 improvements ranged 0.36-0.60 points. For those with maximum AUDIT-C increase (change from 0 to 12), VACS Index 2.0 worsened 3.74 points (95% CI: -4.71 to -2.78); for those with maximum AUDIT-C decrease (change from 12 to 0), VACS Index 2.0 changed minimally [-0.60 (95% CI: -1.43 to 0.23)].ConclusionsIn this national sample, improvement in HIV severity was generally greatest among those with stable alcohol use (primarily those with no use).

BackgroundPre-exposure prophylaxis (PrEP) for HIV is effective, yet many providers continue to lack knowledge and comfort in providing this intervention. It remains unclear whether internal medicine (IM) residents receive appropriate training in PrEP care and if this affects their future practices.ObjectiveWe sought to evaluate the relationship between current IM residents' prior PrEP training and knowledge, comfort, and practice regarding the provision of PrEP.Design and participantsWe created an online survey to assess IM residents' knowledge, attitudes, and behaviors related to PrEP. The survey was distributed among five IM programs across the USA.Key resultsWe had a 35% response rate. Of 229 respondents, 96% (n = 220) had heard of PrEP but only 25% (n = 51) had received prior training and 11% (n = 24) had prescribed PrEP. Compared with those without, those with prior training reported good to excellent knowledge scores regarding PrEP (80% versus 33%, p

Background: Adjunct therapy can help patients with type 1 diabetes achieve glycemic goals while potentially mitigating some of the side effects of insulin. In this study, we used a patient survey to identify the unmet needs in type 1 diabetes therapy, patient views of treatment benefit-risk trade-offs, and patient preferences for the use of an adjunct therapy. Methods: A quantitative survey was sent to 2084 adults with type 1 diabetes in November 2017. "Jobs-to-be-done" and conjoint analyses were performed on survey responses to identify unmet needs and the importance of treatment-associated benefits and risks to patients. A 5-point Likert scale measured the importance and satisfaction with patients' current therapy, and with gaps relating to unmet needs. In the conjoint analysis, patients were asked to choose between "packages" of attributes of two doses of adjunct therapy (200 and 400 mg) and placebo, based on established benefits and side effects. Results: A total of 1313 patients (63%) responded. The greatest unmet needs identified were simplifying treatment, lowering/maintaining glycated hemoglobin (HbA1c), reducing mental effort, and increasing time in range (TIR). Conjoint analysis showed that reductions in body weight and TIR had the highest attribute importance (25% and 18%, respectively). The majority (93%) of patients had a preference for the adjunct therapy (either dose) over placebo. Conclusions: This survey highlights the importance of measures beyond HbA1c, such as treatment simplification and TIR, and patient preference for adjunct therapies that help address unmet needs in type 1 diabetes treatment.

BackgroundPeople living with HIV (PLWH) commonly report marijuana use for chronic pain, although there is limited empirical evidence to support its use. There is hope that marijuana may reduce prescription opioid use. Our objective was to investigate whether marijuana use among PLWH who have chronic pain is associated with changes in pain severity and prescribed opioid use (prescribed opioid initiation and discontinuation).MethodsParticipants completed self-report measures of chronic pain and marijuana use at an index visit and were followed up for 1 year in the Center for AIDS Research Network of Integrated Clinical Systems (CNICS). Self-reported marijuana use was the exposure variable. Outcome variables were changes in pain and initiation or discontinuation of opioids during the study period. The relationship between exposure and outcomes was assessed using generalized linear models for pain and multivariable binary logistic regression models for opioid initiation/discontinuation.ResultsOf 433 PLWH and chronic pain, 28% reported marijuana use in the past 3 months. Median pain severity at the index visit was 6.3/10 (interquartile range 4.7-8.0). Neither increases nor decreases in marijuana use were associated with changes in pain severity, and marijuana use was not associated with either lower odds of opioid initiation or higher odds of opioid discontinuation.ConclusionsWe did not find evidence that marijuana use in PLWH is associated with improved pain outcomes or reduced opioid prescribing. This suggests that caution is warranted when counseling PLWH about potential benefits of recreational or medical marijuana.

BackgroundFor people living with HIV (PLWH), alcohol use is harmful and may be influenced by unique challenges faced by PLWH living in rural areas. We describe patterns of alcohol use across rurality among PLWH.MethodsVeterans Aging Cohort Study electronic health record data were used to identify patients with HIV (ICD-9 codes for HIV or AIDS) who completed AUDIT-C alcohol screening between February 1, 2008, and September 30, 2014. Regression models estimated and compared 4 alcohol use outcomes (any use [AUDIT-C > 0] and alcohol use disorder [AUD; ICD-9 codes for abuse or dependence] diagnoses among all PLWH, and AUDIT-C risk categories: lower- [1-3 men/1-2 women], moderate- [4-5 men/3-5 women], higher- 6-7]), and severe-risk [8-12], and heavy episodic drinking (HED; ≥1 past-year occasion) among PLWH reporting use) across rurality (urban, large rural, small rural) and census-defined region.FindingsAmong 32,699 PLWH (29,540 urban, 1,301 large rural, and 1,828 small rural), both any alcohol use and AUD were highest in urban areas, although this varied across region. Predicted prevalence of any alcohol use was 54.1% (53.5%-54.7%) in urban, 49.6% (46.9%-52.3%) in large rural, and 50.6% (48.3%-52.9%) in small rural areas (P < .01). Predicted prevalence of AUD was 14.4% (14.0%-14.8%) in urban, 11.8% (10.0%-13.5%) in large rural, and 12.3% (10.8%-13.8%) in small rural areas (P < .01). Approximately 12% and 25% had higher- or severe-risk drinking and HED, respectively, but neither differed across rurality.ConclusionThough some variation across rurality and region was observed, alcohol-related interventions are needed for PLWH across all geographic locations.

Many patients with type 1 diabetes (T1D) struggle to achieve glycaemic control and experience significant fluctuations in glucose concentrations, despite insulin treatment. Sodium-glucose co-transporter (SGLT)-2 inhibitors and dual SGLT-1/2 inhibitors increase glucose elimination via the kidneys and reduce hyperglycaemia via insulin-independent mechanisms. This review examines available efficacy and safety data for these agents under investigation as adjunctive therapy for T1D. Across randomized trials of up to 52 weeks, SGLT-2 inhibitors or SGLT-1/2 inhibitors as an adjunct to insulin demonstrated significant reductions in glycated haemoglobin, glucose exposure, and measures of glycaemic variability, as well as increased time in the target glycaemic range, compared with placebo. Non-glycaemic benefits included reductions in body weight and insulin doses, as well as improvements in some cardiovascular risk factors and treatment satisfaction. SGLT-2 inhibitors and SGLT-1/2 inhibitors were associated with similar rates of hypoglycaemia but a higher incidence of genitourinary infections, compared with placebo. Diabetic ketoacidosis occurred more often with SGLT-2 inhibitors and SGLT-1/2 inhibitors vs placebo, although the incidence was generally low. Risk mitigation strategies in light of clinical trial data are also discussed. Positive data from randomized controlled trials of the SGLT-2 inhibitor dapagliflozin have led to the approval of dapagliflozin as an adjunct to insulin in adults with T1D having body mass index ≥27 kg/m2 in whom insulin does not provide adequate glycaemic control in Europe and to approval as an adjunct to insulin for adults with T1D in Japan.

We evaluated associations between levels of alcohol use and HIV care continuum components using national Veterans Aging Cohort Study data for all patients with HIV and AUDIT-C screening (2/1/2008-9/30/2014). Poisson regression models evaluated associations between alcohol use levels (non-drinking, low-, medium-, high-, and very high-level drinking) and: (1) engagement with care (documented CD4 cells/µl or viral load copies/ml labs), (2) ART treatment (≥ 1 prescription), and (3) viral suppression (HIV RNA

ObjectivesTo investigate whether gender is associated with three recommended stages of the HIV care continuum and whether gender modifies known associations between level of alcohol use and HIV care among US veterans.DesignRetrospective cohort.MethodsVeterans Aging Cohort Study data were used to identify Veterans Health Administration (VA) patients with HIV and AUDIT-C alcohol screening from 1 February 2008 to 30 September 2014. Modified Poisson regression models estimated the relative risk and predicted prevalences of engagement in HIV care (documented CD4 cells/μl or viral load copies/ml lab values), ART treatment (at least one prescription), and viral suppression (HIV RNA

BackgroundChronic pain occurs in up to 85% of persons living with HIV and is commonly treated with long-term opioid therapy (LTOT). We investigated the impact of chronic pain and LTOT on HIV outcomes.MethodsThis was prospective cohort study conducted between July 2015 and July 2016 in 5 HIV primary care clinics. Chronic pain was defined as ≥moderate pain for ≥3 months on the Brief Chronic Pain Questionnaire. Chronic pain and LTOT were assessed at an index visit. Suboptimal retention, defined as at least one "no-show" to primary care, and virologic failure were measured over the subsequent year. Multivariable logistic regression models were built for each outcome adjusting for site.ResultsAmong 2334 participants, 25% had chronic pain, 27% had suboptimal retention, 12% had virologic failure, and 19% were prescribed LTOT. Among individuals not on LTOT, chronic pain was associated with increased odds of suboptimal retention [adjusted odds ratio (aOR) 1.46, 95% confidence interval (CI): 1.10 to 1.93, P = 0.009] and virologic failure (aOR 1.97, 95% CI: 1.39 to 2.80, P < 0.001). Among individuals with chronic pain, there was no association between LTOT and retention, but LTOT was associated with lower rates of virologic failure (aOR 0.56, 95% CI: 0.33 to 0.96, P = 0.03).ConclusionsChronic pain in participants not on LTOT was associated with virologic failure. This reinforces the need to identify effective chronic pain treatments for persons living with HIV and investigate their impact on HIV outcomes. The apparent protective association between LTOT and virologic failure in those with pain merits further exploration.

BackgroundAmong groups of persons living with HIV (PLWH), high-risk drinking trajectories are associated with HIV severity. Whether changes in individuals' alcohol use are associated with changes in HIV severity over the same period is unknown.MethodsVeterans Aging Cohort Study (VACS) data from VA's EHR (2/1/2008-9/30/2016) identified AUDIT-C screens for all PLWH. Pairs of AUDIT-C screens within 9-15 months were included if CD4 and/or viral load (VL) was measured within 9 months after baseline and follow-up AUDIT-Cs. Linear regression assessed change in HIV severity (CD4 and logVL) associated with AUDIT-C change adjusted for confounders. Mean changes in HIV severity were estimated for each AUDIT-C change value. For all measures of change, positive values indicate improvements (lower drinking and improved HIV severity).ResultsAmong PLWH, 21,999 and 22,143 were eligible for CD4 and VL analyses, respectively. Most had non- or low-level drinking and stable consumption over time (mean AUDIT-C change = .08, SD = 1.91). HIV severity improved over time [mean CD4 change = 20.5 (SD 180.8); mean logVL change = 0.12 (SD 0.71)]. AUDIT-C changes were associated non-linearly with changes in CD4 (p = 0.03) and logVL (p

BackgroundUnhealthy alcohol use may be particularly detrimental among individuals living with HIV and/or hepatitis C virus (HCV), and is often under-reported. Direct biomarkers of alcohol exposure may facilitate improved detection of alcohol use.MethodsWe evaluated the association of alcohol exposure determined by both self-report [Alcohol Use Disorders Identification Test-Consumption (AUDIT-C)] and a direct biomarker [phosphatidylethanol (PEth)], with mortality among HIV-infected and HIV-uninfected in the Veterans Aging Cohort Study-Biomarker Cohort. We considered PEth

Large for-profit nursing home chains in the United States have generally reported low nurse staffing levels. This historical case study examined a class action litigation case regarding staffing levels, resident rights, and quality outcomes in 12 Arkansas nursing homes owned by a large for-profit chain. The questions were as follows: (1) How did the residents' care needs compare with actual nurse staffing levels? (2) How did the staffing levels compare with federal and state nurse staffing requirements and professional staffing standards? (3) Did the facilities comply with state and federal residents' rights and quality of care requirements? The findings showed staffing levels marginally above state minimum standards, staffing shortages that violated state standards, staffing levels not adjusted for resident acuity, and shortages that resulted in omitted care. Staffing levels were lower than needed according to nursing directors, lower than average facilities in the state, and lower than professional standards. The findings showed many resident grievances regarding basic care and residents' rights, clinical measures of poor quality, and state deficiencies. A large settlement was agreed on to compensate the residents. The case shows that chain's management, as well as the regulatory system, failed to ensure adequate staffing levels that took into account regulatory requirements and professional standards and resulted in violations of residents' rights, health, safety, and well-being.

BACKGROUND: In 2012 U.S. diabetes costs were estimated to be $245 billion, with $176 billion related to direct diabetes treatment and associated complications. Although a few studies have reported positive glycemic and economic benefits for diabetes patients treated under primary care physician (PCP)-pharmacist collaborative practice models, no studies have evaluated the cost-effectiveness of an endocrinologist-pharmacist collaborative practice model treating complex diabetes patients versus usual PCP care for similar patients. OBJECTIVE: To estimate the cost-effectiveness and cost benefit of a collaborative endocrinologist-pharmacist Diabetes Intense Medical Management (DIMM) Tune-Up clinic for complex diabetes patients versus usual PCP care from 3 perspectives (clinic, health system, payer) and time frames. METHODS: Data from a retrospective cohort study of adult patients with type 2 diabetes mellitus (T2DM) and glycosylated hemoglobin A1c (A1c) ≥ 8% who were referred to the DIMM clinic at the Veterans Affairs San Diego Health System were used for cost analyses against a comparator group of PCP patients meeting the same criteria. The DIMM clinic took more time with patients, compared with usual PCP visits. It provided personalized care in three 60-minute visits over 6 months, combining medication therapy management with patient-specific diabetes education, to achieve A1c treatment goals before discharge back to the PCP. Data for DIMM versus PCP patients were used to evaluate cost-effectiveness and cost benefit. Analyses included incremental cost-effectiveness ratios (ICERs) at 6 months, 3-year estimated total medical costs avoided and return on investment (ROI), absolute risk reduction of complications, resultant medical costs, and quality-adjusted life-years (QALYs) over 10 years. RESULTS: Base case ICER results indicated that from the clinic perspective, the DIMM clinic costs $21 per additional percentage point of A1c improvement and $115-$164 per additional patient at target A1c goal level compared with the PCP group. From the health system perspective, medical cost avoidance due to improved A1c was $8,793 per DIMM patient versus $3,506 per PCP patient (P = 0.009), resulting in an ROI of $9.01 per dollar spent. From the payer perspective, DIMM patients had estimated lower total medical costs, a greater number of QALYs gained, and appreciable risk reductions for diabetes-related complications over 2-, 5- and 10-year time frames, indicating that the DIMM clinic was dominant. Sensitivity analyses indicated results were robust, and overall conclusions did not change appreciably when key parameters (including DIMM clinic effectiveness and cost) were varied within plausible ranges. CONCLUSIONS: The DIMM clinic endocrinologist-pharmacist collaborative practice model, in which the pharmacist spent more time providing personalized care, improved glycemic control at a minimal cost per additional A1c benefit gained and produced greater cost avoidance, appreciable ROI, reduction in long-term complication risk, and lower cost for a greater gain in QALYs. Overall, the DIMM clinic represents an advanced pharmacy practice model with proven clinical and economic benefits from multiple perspectives for patients with T2DM and high medication and comorbidity complexity. DISCLOSURES: No outside funding supported this study. The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Preliminary versions of the study data were presented in abstract form at the American Pharmacists Association Annual Meeting & Exposition; March 27, 2015; San Diego, California, and the Academy of Managed Care Pharmacy Annual Meeting; April 21, 2016; San Francisco, California. Study concept and design were contributed by Hirsch, Bounthavong, and Edelman, along with Morello and Morreale. Arjmand, Ourth, Ha, Cadiz, and Zimmerman collected the data. Data interpretation was performed by Ha, Morreale, and Morello, along with Cadiz, Ourth, and Hirsch. The manuscript was written primarily by Hirsch and Zimmerman, along with Arjamand, Ourth, and Morello, and was revised by Hirsch and Cadiz, along with Bounthavong, Ha, Morreale, and Morello.

The clinical benefits of real time continuous glucose monitoring (rtCGM) use have been well demonstrated in both CSII- and MDI-treated individuals in large clinical trials. However, recommendations for patient use of rtCGM in everyday life situations are lacking. This article provides guidance to clinicians and patients with type 1 diabetes (T1D) in effective use of rtCGM data, including glucose rate of change (ROC) arrows, for insulin dosing adjustments and other treatment decisions. The recommendations presented here are based on our own clinical experiences as endocrinologists, our personal experiences living with T1D using rtCGM, and findings from a recent survey of T1D patients who have successfully used rtCGM in their self-management. It is important that both clinicians and people with diabetes understand the utility and limitations of rtCGM. Maintaining a collaborative clinician-user relationship remains an important factor in safe, successful rtCGM use.

Maladaptive epithelial repair from chronic injury is a common feature in fibrotic diseases, which in turn activates a pathogenic fibroblast response that produces excessive matrix deposition. Dysregulated microRNAs (miRs) can regulate expression of multiple genes and fundamentally alter cellular phenotypes during fibrosis. Although several miRs have been shown to be associated with lung fibrosis, the mechanisms by which miRs modulate epithelial behavior in lung fibrosis are lacking. Here, we identified miR-323a-3p to be downregulated in the epithelium of lungs with bronchiolitis obliterans syndrome (BOS) after lung transplantation, idiopathic pulmonary fibrosis (IPF), and murine bleomycin-induced fibrosis. Antagomirs for miR-323a-3p augment, and mimics suppress, murine lung fibrosis after bleomycin injury, indicating that this miR may govern profibrotic signals. We demonstrate that miR-323a-3p attenuates TGF-α and TGF-β signaling by directly targeting key adaptors in these important fibrogenic pathways. Moreover, miR-323a-3p lowers caspase-3 expression, thereby limiting programmed cell death from inducers of apoptosis and ER stress. Finally, we find that epithelial expression of miR-323a-3p modulates inhibitory crosstalk with fibroblasts. These studies demonstrate that miR-323a-3p has a central role in lung fibrosis that spans across murine and human disease, and downregulated expression by the lung epithelium releases inhibition of various profibrotic pathways to promote fibroproliferation.

BackgroundAs the retirement rate of senior nursing faculty increases, the need to implement new models for providing mentorship to early career academics will become key to developing and maintaining an experienced faculty.PurposeThis evaluation of a peer mentorship program for predoctoral and postdoctoral gerontological nurses examined its efficacy, utility, and potential for improvement.MethodsA web-based survey was developed, implemented, and completed by 22 mentees and 17 mentors (71% and 61% response rates, respectively) as part of the evaluation.DiscussionThe peer mentorship program was found to be valuable by both mentors (64.7%) and mentees (72.7%) in helping mentees further develop their careers and networks and providing mentors with supported mentorship experience.ConclusionThe peer mentorship program could serve as a model for other professional organizations, academic institutions, and consortiums to enhance and extend the formal vertical mentorship provided to early academic career individuals.

BackgroundHereditary angioedema (HAE) due to C1 inhibitor deficiency manifests as recurrent swelling attacks that can be disabling and sometimes fatal. Long-term prophylaxis with twice-weekly intravenous injections of plasma-derived C1-inhibitor (pdC1-INH) has been established as an effective treatment. Subcutaneous (SC) administration of pdC1-INH has not been studied in patients with HAE.MethodsThis open-label, dose-ranging, crossover study (COMPACT Phase II) was conducted in 18 patients with type I or II HAE who received two of twice-weekly 1500, 3000, or 6000 IU SC doses of highly concentrated volume-reduced CSL830 for 4 weeks each. The mean trough plasma levels of C1-INH functional activity, C1-INH and C4 antigen levels during Week 4, and overall safety and tolerability were evaluated. The primary outcome was model-derived steady-state trough C1-INH functional activity.ResultsAfter SC CSL830 administration, a dose-dependent increase in trough functional C1-INH activity was observed. C1-INH and C4 levels both increased. The two highest dose groups (3000 and 6000 IU) achieved constant C1-INH activity levels above 40% values, a threshold that was assumed to provide clinical protection against angioedema attacks. Compared with intravenous injection, pdC1-INH SC injection with CSL830 showed a lower peak-to-trough ratio and more consistent exposures. All doses were well tolerated. Mild-to-moderate local site reactions were noted with pain and swelling being the most common adverse event.ConclusionsSubcutaneous volume-reduced CSL830 was well tolerated and led to a dose-dependent increase in physiologically relevant functional C1-INH plasma levels. A clinical outcome study of SC CSL830 in patients with HAE warrants further investigation.

This paper applies theoretical frameworks from organizational sociology and sociolegal studies to examine factors associated with educators' conceptions of students' rights to due process in disciplinary actions. We analyze a unique representative data set of 402 teachers and 200 administrators in U.S. high schools to investigate how educators understand the rights to due process articulated in the Supreme Court case of Goss v. Lopez (1975). We then examine whether individual characteristics and participation in organizational processes are associated with educators' understandings of students' due process rights. Findings suggest that educators' understandings of students' entitlements to due process vary with educators' level of education, experience of school-related legal threats, and participation in district or diocese in-service training programs on students' rights. Results point to organizational climate as a key factor in shaping educators' rights conceptions and the role of law in American schools.

OBJECTIVES:Community viral load (CVL) estimates vary based on analytic methods. We extended the CVL concept and used data from the Veterans Health Administration (VA) to determine trends in the health care system viral load (HSVL) and its sensitivity to varying definitions of the clinical population and assumptions regarding missing data. METHODS:We included HIV-infected patients in the Veterans Aging Cohort Study, 2000-2010, with at least one documented CD4 count, HIV-1 RNA or antiretroviral prescription (n = 37 318). We created 6-month intervals including patients with at least one visit in the past 2 years. We assessed temporal trends in clinical population size, patient clinical status and mean HSVL and explored the impact of varying definitions of the clinical population and assumptions about missing viral load. RESULTS:The clinical population size varied by definition, increasing from 16 000-19 000 patients in 2000 to 23 000-26 000 in 2010. The proportion of patients with suppressed HIV-1 RNA increased over time. Over 20% of patients had no viral load measured in a given interval or the past 2 years. Among patients with a current HIV-1 RNA, mean HSVL decreased from 97 800 HIV-1 RNA copies/mL in 2000 to 2000 copies/mL in 2010. When current HIV-1 RNA data were unavailable and the HSVL was recalculated using the last available HIV-1 RNA, HSVL decreased from 322 300 to 9900 copies/mL. HSVL was underestimated when using only current data in each interval. CONCLUSIONS:The CVL concept can be applied to a health care system, providing a measure of health care quality. Like CVL, HSVL estimates depend on definitions of the clinical population and assumptions about missing data.

OBJECTIVES:Community viral load (CVL) estimates vary based on analytic methods. We extended the CVL concept and used data from the Veterans Health Administration (VA) to determine trends in the health care system viral load (HSVL) and its sensitivity to varying definitions of the clinical population and assumptions regarding missing data. METHODS:We included HIV-infected patients in the Veterans Aging Cohort Study, 2000-2010, with at least one documented CD4 count, HIV-1 RNA or antiretroviral prescription (n = 37 318). We created 6-month intervals including patients with at least one visit in the past 2 years. We assessed temporal trends in clinical population size, patient clinical status and mean HSVL and explored the impact of varying definitions of the clinical population and assumptions about missing viral load. RESULTS:The clinical population size varied by definition, increasing from 16 000-19 000 patients in 2000 to 23 000-26 000 in 2010. The proportion of patients with suppressed HIV-1 RNA increased over time. Over 20% of patients had no viral load measured in a given interval or the past 2 years. Among patients with a current HIV-1 RNA, mean HSVL decreased from 97 800 HIV-1 RNA copies/mL in 2000 to 2000 copies/mL in 2010. When current HIV-1 RNA data were unavailable and the HSVL was recalculated using the last available HIV-1 RNA, HSVL decreased from 322 300 to 9900 copies/mL. HSVL was underestimated when using only current data in each interval. CONCLUSIONS:The CVL concept can be applied to a health care system, providing a measure of health care quality. Like CVL, HSVL estimates depend on definitions of the clinical population and assumptions about missing data.

PurposeThe Hartford Gerontological Nursing Leaders (HGNL) formerly known as the Building Academic Geriatric Nursing Capacity Initiative (BAGNC), in conjunction with the National Hartford Centers of Gerontological Nursing Excellence (NHCGNE), developed and executed a peer mentoring program beginning in 2011 to enhance both (a) the experience of newly selected scholars and fellows to the NHCGNE and (b) the ongoing professional development of HGNL members. The purpose of this article is to describe key strategies used to develop and execute the peer mentoring program and to present formative program evaluation.DesignThe program was launched in January 2011 with seven peer mentor and mentee matches. In June 2012, the peer mentoring committee solicited feedback on the development of the peer mentoring program and changes were made for the subsequent cohorts.FindingsAn additional 12 matches were made in the following 2 years (2012 and 2013), for a total of 31 matches to date. We have learned several key lessons from our three cohorts regarding how to structure, implement, and carefully evaluate a peer mentoring program.ConclusionsInformal evaluation of our peer mentoring program noted several challenges for both peer mentors and mentees. Having knowledge of and addressing those challenges may increase the overall quality and effectiveness of peer mentoring programs and, in turn, benefit academic nursing by strengthening the faculty workforce.Clinical relevanceFindings from development and implementation of a peer mentoring program for gerontological faculty could lead to new and adaptable programs in a variety of clinical and education settings.

Non-small cell lung cancer constitutes 85% to 90% of lung cancer and is the most common cause of cancer death. Over the past 50 years, substantial progress has been made in all aspects of lung cancer including screening, diagnostic evaluation, surgery, radiation therapy, and chemotherapy. This review focuses on the advances in systemic therapy during this half century.

ObjectiveHistologic subtyping has been advocated to select chemotherapy for patients with advanced-stage non-small-cell lung cancer (NSCLC). To determine whether histologic subtype was associated with efficacy for the commonly used antimicrotubule (AMT) agents, paclitaxel, docetaxel, and vinorelbine plus a platinum compound, we examined the Southwest Oncology Group (SWOG) lung cancer database.MethodsData from 4 randomized trials (S9308, S9509, S9806, and S0003) administering an AMT agent plus platinum in patients receiving first-line treatment for advanced-stage NSCLC were analyzed. Overall survival (OS) and progression-free survival (PFS) comparisons were performed using Cox proportional hazard regression, adjusting for sex. Median survival times were estimated by Kaplan-Meier.ResultsOf 1146 patients included in this analysis, 640 had adenocarcinoma (56%), 220 had squamous cell carcinoma (19%), 121 had large cell carcinoma (11%), and 165 had NSCLC not otherwise specified (NOS) (14%). Median OS times by histologic subtypes were 8.5, 8.4, 8.2, and 9.6 months, respectively, and median PFS times were 4.2, 4.3, 4.3, and 4.6 months, respectively. No difference in OS or PFS was observed by histologic subtype and, specifically, between nonsquamous and squamous histologies.ConclusionsThis pooled analysis from 4 SWOG trials using an AMT-platinum regimen did not show a difference in survival outcomes by histologic subtype. Because the majority of patients with advanced NSCLC continue to receive chemotherapy, defining molecular-based predictive markers of responsiveness is warranted.

Cystic fibrosis (CF) is associated with abnormal lipid metabolism. We have recently shown variations in plasma levels of several phosphatidylcholine (PC) and lysophopshatidylcholine (LPC) species related to disease severity in CF patients. Here our goal was to search for blood plasma lipid signatures characteristic of CF patients bearing the same mutation (F508del) and different phenotypes, and to study their correlation with forced expiratory volume in 1 s (FEV1) and Pseudomonas aeruginosa chronic infection, evaluated at the time of testing (t = 0) and three years later (t = 3). Samples from 44 F508del homozygotes were subjected to a lipidomic approach based on LC-ESI-MS. Twelve free fatty acids were positively correlated with FEV1 at t = 0 (n = 29). Four of them (C20:3n-9, C20:5n-3, C22:5n-3, and C22:6n-3) were also positively correlated with FEV1 three years later, along with PC(32:2) and PC(36:4) (n = 31). Oleoylethanolamide (OEA) was negatively correlated with FEV1 progression (n = 17). Chronically infected patients at t = 0 showed lower PC(32:2), PC(38:5), and C18:3n-3 and higher cholesterol, cholesterol esters, and triacylglycerols (TAG). Chronically infected patients at t = 3 showed significantly lower levels of LPC(18:0). These results suggest a potential prognostic value for some lipid signatures in, to our knowledge, the first longitudinal study aimed at identifying lipid biomarkers for CF.

Lipid analysis has been a crucial source of information in cystic fibrosis (CF). New methodologies for qualitative and quantitative lipidomics allow evaluation of a large number of samples, of special interest in patient screening for diagnostic and prognostic biological markers, as well as in cell physiology. In this chapter, two new complementary approaches are described: matrix-assisted laser desorption coupled to time of flight (MALDI-TOF-ClinProTools™) and liquid chromatography coupled to ion trap mass spectrometry (LC-MS( n )). MALDI-TOF-ClinProTools™ offers a large unbiased screening for the discovery of potential lipid alterations in diseased patients. LC-MS( n ) represents a state-of-the-art lipidomic tool for the identification and quantification of such alterations. The combination of both may open new perspectives in the quest for lipids participating in CF pathogenesis, therapy targets, and biomarkers.

The aim of this study was to search for lipid signatures in blood plasma from cystic fibrosis (CF) patients using a novel MALDI-TOF-ClinProTools strategy, initially developed for protein analysis, and thin layer chromatography coupled to MALDI-TOF (TLC-MALDI). Samples from 33 CF patients and 18 healthy children were subjected to organic extraction and column chromatography separation of lipid classes. Extracts were analyzed by MALDI-TOF, ion signatures were compared by the ClinProTools software and by parallel statistical analyses. Relevant peaks were identified by LC-MSn. The ensemble of analyses provided 11 and 4 peaks differentially displayed in CF vs healthy and in mild vs severe patients respectively. Ten ions were significantly decreased in all patients, corresponding to 4 lysophosphatidylcholine (18:0, 18:2, 20:3, and 20:5) and 6 phosphatidylcholine (36:5, O-38:0, 38:4, 38:5, 38:6, and P-40:1) species. One sphingolipid, SM(d18:0), was significantly increased in all patients. Four PC forms (36:3, 36:5, 38:5, and 38:6) were consistently downregulated in severe vs mild patients. These observations were confirmed by TLC-MALDI. These results suggest that plasma phospholipid signatures may be able to discriminate mild and severe forms of CF, and show for the first time MALDI-TOF-ClinProTools as a suitable methodology for the search of lipid markers in CF.

This study was conducted to determine whether early initiation of combined hormonal contraception under direct clinical observation following successful medical abortion increases continuation rates with the method compared to traditional "Sunday start."Women enrolled in a multicenter medical abortion trial with mifepristone and misoprostol who requested combined hormonal contraception (pill, ring or patch) following medical abortion were recruited. Women were randomized to initiate the method under supervision either at the 1-week medical abortion follow-up visit ("observed start") or at the first Sunday following this visit ("Sunday start"). Primary outcome was continuation of the chosen method at 6 weeks.Of the 1128 women in the primary trial, 261 subjects enrolled in this substudy and 36/261 (13.8%) were lost to follow-up. There was no significant difference in method continuation at 6 weeks [observed start 108/114 (94.7%), Sunday start 101/111 (91.0%, p=.27].Short-term continuation rates among those choosing hormonal contraception following medical abortion are high and are not significantly improved by initiating the method at the time of the first follow-up visit.