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Objective To evaluate the dose trajectory of new opioid tapers and estimate the percentage of patients with sustained tapers at long-term follow-up. Design Retrospective cohort study. Setting Data from the OptumLabs Data Warehouse® which includes de-identified medical and pharmacy claims and enrollment records for commercial and Medicare Advantage enrollees, representing a diverse mixture of ages, ethnicities, and geographical regions across the United States. Subjects Patients prescribed stable, higher-dose opioids for ≥12 months from 2008 to 2018. Methods Tapering was defined as ≥15% relative reduction in average MME/day during any of six overlapping 60-day periods in the initial 7 months of follow-up after the period of stable baseline dosing. Average monthly dose was ascertained during consecutive 60-day periods up to 16 months of follow-up. Linear regression estimated the geometric mean relative dose by tapering status and follow-up duration. Poisson regression estimated the percentage of tapered patients with sustained dose reductions at follow-up and patient-level predictors of failing to sustain tapers. Results The sample included 113,618 patients with 203,920 periods of stable baseline dosing (mean follow-up = 13.7 months). Tapering was initiated during 37,170 follow-up periods (18.2%). After taper initiation, patients had a substantial initial mean dose reduction (geometric mean relative dose .73 [95% CI: .72–.74]) that was sustained through 16 months of follow-up; at which point, 69.8% (95% CI: 69.1%–70.4%) of patients who initiated tapers had a relative dose reduction ≥15%, and 14.2% (95% CI: 13.7%–14.7%) had discontinued opioids. Failure to sustain tapers was significantly less likely among patients with overdose events during follow-up (adjusted incidence rate ratio [aIRR]: .56 [95% CI: .48–.67]) and during more recent years (aIRR: .93 per year after 2008 [95% CI: .92–.94]). Conclusions In an insured and Medicare Advantage population, over two-thirds of patients who initiated opioid dose tapering sustained long-term dose reductions, and the likelihood of sustaining tapers increased substantially from 2008 to 2018.

Justice-involved youth are at a higher risk of negative outcomes from sexual activity and alcohol use relative to their non-justice involved peers. In the current study, we tested the extent to which variability in neurocognitive response (i.e., activation in the right superior parietal lobule; rSPL) during a risky decision-making task moderated the success of a sexual risk reduction intervention. In a cluster randomized trial blocked by gender, justice-involved adolescents (N = 269) first completed a risky decision-making task during a magnetic resonance imaging (MRI) session, then were assigned to an information-only control (GINFO) or sexual risk reduction intervention incorporating alcohol risk reduction content (GPI + GMET) and then re-contacted every three months for one year. Youth in the GPI + GMET intervention reported less sexual risk behavior 12 months after intervention than those in the control. Although neurocognitive activation was associated with sexual risk behavior, it did not moderate intervention outcomes. This risk-reduction intervention appears to work equally well across a range of neurocognitive responses.

Background: Physician denial of patient requests is associated with lower patient satisfaction. Our objective was to explore factors that influence physician request denial and patient satisfaction after request denial. Methods: Cross-sectional observational study of 1141 adult patients seen during 1319 outpatient visits with 56 primary care physicians. We measured patients9 postvisit self-report of requests and request fulfillment, visit satisfaction, sociodemographics, health status, symptom burden, life satisfaction, medical skepticism, and whether patients saw their usual physician and a faculty or resident physician. We used mixed-effects regression analyses to identify predictors of request denial and visit satisfaction among patients who had a request denied. Results: Patients made at least 1 request at 867 visits (65.7%) with at least 1 denied request reported at 182 visits (21.0%). Patients who saw their usual physician were less likely to report a request denial (adjusted Odds Ratio [aOR], 0.61; 95% CI, 0.42 to 0.88), and patients with the highest symptom burden (aOR, 2.21; 95% CI, 1.38 to 3.55) or greater medical skepticism (aOR, 1.35; 95% CI, 1.03 to 1.78) were more likely to report request denials. After request denials, patients seeing their usual physicians reported significantly greater visit satisfaction compared with not seeing their usual physician (adjusted percentile rank in visit satisfaction: 12.4%; 95% CI, 3.5% to 21.2%). Conclusions: Approximately one fifth of visits in primary care have a denied request. Having an office visit with one9s usual physician is associated with reduced likelihood of request denial and may mitigate the adverse impacts of request denial on patient visit satisfaction.

Importance Opioid-related mortality and national prescribing guidelines have led to tapering of doses among patients prescribed long-term opioid therapy for chronic pain. There is limited information about risks related to tapering, including overdose and mental health crisis. Objective To assess whether there are associations between opioid dose tapering and rates of overdose and mental health crisis among patients prescribed stable, long-term, higher-dose opioids. Design, Setting, and Participants Retrospective cohort study using deidentified medical and pharmacy claims and enrollment data from the OptumLabs Data Warehouse from 2008 to 2019. Adults in the US prescribed stable higher doses (mean ≥50 morphine milligram equivalents/d) of opioids for a 12-month baseline period with at least 2 months of follow-up were eligible for inclusion. Exposures Opioid tapering, defined as at least 15% relative reduction in mean daily dose during any of 6 overlapping 60-day windows within a 7-month follow-up period. Maximum monthly dose reduction velocity was computed during the same period. Main Outcomes and Measures Emergency or hospital encounters for (1) drug overdose or withdrawal and (2) mental health crisis (depression, anxiety, suicide attempt) during up to 12 months of follow-up. Discrete time negative binomial regression models estimated adjusted incidence rate ratios (aIRRs) of outcomes as a function of tapering (vs no tapering) and dose reduction velocity. Results The final cohort included 113 618 patients after 203 920 stable baseline periods. Among the patients who underwent dose tapering, 54.3% were women (vs 53.2% among those who did not undergo dose tapering), the mean age was 57.7 years (vs 58.3 years), and 38.8% were commercially insured (vs 41.9%). Posttapering patient periods were associated with an adjusted incidence rate of 9.3 overdose events per 100 person-years compared with 5.5 events per 100 person-years in nontapered periods (adjusted incidence rate difference, 3.8 per 100 person-years [95% CI, 3.0-4.6]; aIRR, 1.68 [95% CI, 1.53-1.85]). Tapering was associated with an adjusted incidence rate of 7.6 mental health crisis events per 100 person-years compared with 3.3 events per 100 person-years among nontapered periods (adjusted incidence rate difference, 4.3 per 100 person-years [95% CI, 3.2-5.3]; aIRR, 2.28 [95% CI, 1.96-2.65]). Increasing maximum monthly dose reduction velocity by 10% was associated with an aIRR of 1.09 for overdose (95% CI, 1.07-1.11) and of 1.18 for mental health crisis (95% CI, 1.14-1.21). Conclusions and Relevance Among patients prescribed stable, long-term, higher-dose opioid therapy, tapering events were significantly associated with increased risk of overdose and mental health crisis. Although these findings raise questions about potential harms of tapering, interpretation is limited by the observational study design.

Background: Patient requests for tests, treatments, or referrals occur frequently during primary care visits and pose challenges for clinicians to address, but little is known about patient characteristics that may predict requests. Objective: To identify patient characteristics associated with a higher rate of patient requests during primary care visits. Design, Setting, and Sample: Cross-sectional analyses of data from 1141 adult patients attending 1319 visits with 56 primary care physicians (including 45 resident and 11 faculty physicians) in an academic family medicine practice. Measurements: Postvisit patient surveys including measures of patient requests for tests, prescriptions, and referrals; sociodemographics; mental and physical health status; symptom bother or worry (3-item scale; range, 3 to 15; Cronbach9s α = 0.83); global life satisfaction; medical skepticism; and Five Factor Model personality traits. Results: Patients made 1 or more requests in 867 visits (65.7%). In multivariate analyses of the within-visit request count, the following patient variables were statistically significantly associated with a higher rate of requests: age in years (incidence rate ratio [IRR], 1.01 [95% CI, 1.00 to 1.01]), increased symptom bother or worry (IRR, 1.06 [95% CI, 1.03 to 1.08]), a more extroverted personality (IRR, 1.12 [95% CI, 1.03 to 1.08]), greater life satisfaction (IRR, 1.01 [95% CI, 1.00 to 1.02]), and any prior encounter with the visit physician (IRR, 1.17 [95% CI, 1.04 to 1.32]). Conclusions: Primary care physicians should expect a greater frequency of requests from older patients, patients with greater symptoms bother or worry, more extroverted patients, patients with greater global life satisfaction, and patients with whom they have had prior visits.

INTRODUCTION: There are no population-level estimates in the United States for achievement of blood pressure goals in patients with diabetes and hypertension by obesity weight class. AIM: We sought to examine the relationship between the extent of obesity and the achievement of guideline-recommended blood pressure goals and other quality of care metrics among patients with diabetes. METHODS: We conducted an observational population-based cohort study of electronic health data of three large health systems from 2010–2012 in rural, urban and suburban settings of 51,229 adults with diabetes. Outcomes were achievement of diabetes quality of care metrics: blood pressure, A1c, and LDL control, and A1c and LDL testing. Two blood pressure goals were examined given the recommendation for adults with diabetes of 130/80 mmHg from JNC7 and the recommendation of 140/90 mmHg from JNC8 in 2014. RESULTS: Patients in obesity classes I, II, and III with diagnosed hypertension were less likely to achieve blood pressure control at both the 140/90 mmHg and 130/80 mmHg control levels. The patients from obesity class III had the lowest likelihood of achieving control at the 130/80 mmHg goal, and control was markedly worse for the 130/80 mmHg threshold in all weight classes. There were minimal to no differences by weight class in LDL and A1c control and LDL and A1c testing. CONCLUSIONS: Although the cardiovascular risk for patients with obesity and diabetes is greater than for non-obese patients with diabetes, we found that patients with obesity are even further behind in achieving blood pressure control.

Importance A 2016 Centers for Disease Control and Prevention prescribing guideline cautioned against higher-dose long-term opioid therapy and recommended tapering daily opioid doses by approximately 10% per week if the risks outweigh the benefits. Warnings have since appeared regarding potential hazards of rapid opioid tapering. Objectives To characterize US trends in opioid dose tapering among patients prescribed long-term opioids from 2008 to 2017 and identify patient-level variables associated with tapering and a more rapid rate of tapering. Design, Setting, and Participants This retrospective cohort study used deidentified medical and pharmacy claims and enrollment records for 99 874 commercial insurance and Medicare Advantage enrollees, representing a diverse mixture of ages, races/ethnicities, and geographical regions across the United States. Adults with stable, higher-dosage (mean, ≥50 morphine milligram equivalents [MMEs]/d) opioid prescriptions for a 12-month baseline period and 2 or more months of follow-up from January 1, 2008, to December 31, 2017, were included in the study. Main Outcomes and Measures Tapering was defined as 15% or more relative reduction in mean daily MME during any of 6 overlapping 60-day windows within a 7-month follow-up period. The rate of tapering was computed as the maximum monthly percentage dose reduction. Results Among the 99 874 participants (53 358 [53.4%] women; mean [SD] age, 57.4 [11.8] years), from 2008 to 2015, the age- and sex-standardized percentage of patients tapering daily opioid doses increased from 12.7% to 16.2% (adjusted incidence rate ratio [aIRR] per year, 1.05 [95% CI, 1.05-1.06]) before increasing to 18.6% in 2016 and 23.1% in 2017 (aIRR in 2016-2017 vs 2008-2015, 1.16 [95% CI, 1.12-1.20]). Patient-level covariates associated with tapering included female sex (aIRR, 1.09 [95% CI, 1.07-1.11]) and higher baseline dose (aIRR for ≥300 MMEs/d vs 50-89 MMEs/d, 2.19 [95% CI, 2.12-2.27]). Among patients tapering daily opioid doses, the mean (SD) maximum dose reduction was 34.0% (27.4%) per month, and 26.5% of patients had a maximum tapering rate exceeding 40% per month (ie, faster than 10% per week). Higher maximum dose reduction rate was associated with age 18 to 34 years (vs older age groups), male sex, a high school education or less (vs more education), small town or rural residence (vs metropolitan, micropolitan, or unknown), a Charlson Comorbidity Index score of 3 or higher (vs 0) (adjusted difference, 1.9% [95% CI, 0.9%-2.9%]), lower baseline doses (50-89 MMEs vs 150-299 or ≥300 MMEs), and a recent drug overdose (adjusted difference, 10.2% [95% CI, 6.8%-13.6%]). Conclusions and Relevance Patients using long-term opioid therapy are increasingly undergoing dose tapering, particularly women and those prescribed higher doses; in addition, dose tapering has become more common since 2016. Many patients undergoing tapering reduce daily doses at a rapid maximum rate.

Young adults (aged 18 to 39years) have the lowest hypertension control rates compared with older adults. Shorter follow-up encounter intervals are associated with faster hypertension control rates in older adults; however, optimal intervals are unknown for young adults. The study objective was to evaluate the relationship between ambulatory blood pressure encounter intervals (average number of provider visits with blood pressures over time) and hypertension control rates among young adults with incident hypertension. A retrospective analysis was conducted of patients aged 18 to 39 years (n = 2990) with incident hypertension using Kaplan-Meier survival and Cox proportional hazards analyses over 24months. Shorter encounter intervals were associated with higher hypertension control: 6months (13%). Young adults with shorter encounter intervals also had lower medication initiation, supporting the effectiveness of lifestyle modifications. Sustainable interventions for timely young adult follow-up are essential to improve hypertension control in this hard-to-reach population.

BackgroundPatient experience measures are widely used to compare performance at the individual physician level.ObjectiveTo assess the impact of unmeasured patient characteristics on visit-level patient experience measures and the sample sizes required to reliably measure patient experience at the primary care physician (PCP) level.DesignRepeated cross-sectional design.SettingAcademic family medicine practice in California.ParticipantsOne thousand one hundred forty-one adult patients attending 1319 visits with 56 PCPs (including 45 resident and 11 faculty physicians).MeasurementsPost-visit patient experience surveys including patient measures used for standard adjustment as recommend by the Consumer Assessment of Healthcare Providers and Systems (CAHPS) Consortium and additional patient characteristics used for expanded adjustment (including attitudes toward healthcare, global life satisfaction, patient personality, current symptom bother, and marital status).ResultsThe amount of variance in patient experience explained doubled with expanded adjustment for patient characteristics compared with standard adjustment (R2 = 20.0% vs. 9.6%, respectively). With expanded adjustment, the amount of variance attributable to the PCP dropped from 6.1% to 3.4% and the required sample size to achieve a reliability of 0.90 in the physician-level patient experience measure increased from 138 to 255 patients per physician. After ranking of the 56 PCPs by average patient experience, 8 were reclassified into or out of the top or bottom quartiles of average experience with expanded as compared to standard adjustment [14.3% (95% CI: 7.0-25.2%)].ConclusionsWidely used methods for measuring PCP-level patient experience may not account sufficiently for influential patient characteristics. If methods were adapted to account for these characteristics, patient sample sizes for reliable between-physician comparisons may be too large for most practices to obtain.

Objective To find clinically relevant combinations of chronic conditions among patients with diabetes and to examine their relationships with six diabetes quality metrics. Data Sources/Study Setting Twenty-nine thousand five hundred and sixty-two adult patients with diabetes seen at eight Midwestern U.S. health systems during 2010–2011. Study Design We retrospectively evaluated the relationship between six diabetes quality metrics and patients' combinations of chronic conditions. We analyzed 12 conditions that were concordant with diabetes care to define five mutually exclusive combinations of conditions (“classes”) based on condition co-occurrence. We used logistic regression to quantify the relationship between condition classes and quality metrics, adjusted for patient demographics and utilization. Data Collection We extracted electronic health record data using a standardized algorithm. Principal Findings We found the following condition classes: severe cardiac, cardiac, noncardiac vascular, risk factors, and no concordant comorbidities. Adjusted odds ratios and 95 percent confidence intervals for glycemic control were, respectively, 1.95 (1.7–2.2), 1.6 (1.4–1.9), 1.3 (1.2–1.5), and 1.3 (1.2–1.4) compared to the class with no comorbidities. Results showed similar patterns for other metrics. Conclusions Patients had distinct quality metric achievement by condition class, and those in less severe classes were less likely to achieve diabetes metrics.

Importance Prior studies suggesting clinician fulfillment or denial of requests affects patient satisfaction included limited adjustment for patient confounders. The studies also did not examine distinct request types, yet patient expectations and clinician fulfillment or denial might vary among request types. Objective To examine how patient satisfaction with the clinician is associated with clinician denial of distinct types of patient requests, adjusting for patient characteristics. Design, Setting, and Participants Cross-sectional observational study of 1319 outpatient visits to family physicians (n = 56) by 1141 adults at one Northern California academic health center. Main Outcomes and Measures We used 6 Consumer Assessment of Healthcare Providers and Systems Clinician and Group Adult Visit Survey items to measure patient satisfaction with the visit physician. Standardized items were averaged to form the satisfaction score (Cronbach α = 0.80), which was then percentile-transformed. Seven separate linear mixed-effects models examined the adjusted mean differences in patient satisfaction percentile associated with denial of each of the following requests (if present)—referral, pain medication, antibiotic, other new medication, laboratory test, radiology test, or other test—compared with fulfillment of the respective requests. The models adjusted for patient sociodemographics, weight, health status, personality, worry over health, prior visit with clinician, and the other 6 request categories and their dispositions. Results The mean (SD) age of the 1141 patients was 45.6 (16.1) years, and 902 (68.4%) were female. Among 1319 visits, 897 (68.0%) included at least 1 request; 1441 (85.2%) were fulfilled. Requests by category were referral, 294 (21.1%); pain medication, 271 (20.5%); antibiotic, 107 (8.1%); other new medication, 271 (20.5%); laboratory test, 448 (34.0%); radiology test, 153 (11.6%); and other tests, 147 (11.1%). Compared with fulfillment of the respective request type, clinician denials of requests for referral, pain medication, other new medication, and laboratory test were associated with worse satisfaction (adjusted mean percentile differences, −19.75 [95% CI, −30.75 to −8.74], −10.72 [95% CI, −19.66 to −1.78], −20.36 [95% CI, −29.54 to −11.18], and −9.19 [95% CI, −17.50 to −0.87]), respectively. Conclusions and Relevance Clinician denial of some types of requests was associated with worse patient satisfaction with the clinician, but not for others, when compared with fulfillment of the requests. In an era of patient satisfaction-driven compensation, the findings suggest the need to train clinicians to deal effectively with requests, potentially enhancing patient and clinician experiences.

Most patients with diabetes have comorbid chronic conditions that could support (concordant) or compete with (discordant) diabetes care. We sought to determine the impact of the number of concordant and discordant chronic conditions on diabetes care quality.Logistic regression analysis of electronic health record data from 7 health systems on 24,430 patients with diabetes aged 18-75 years. Diabetes testing and control quality care goals were the outcome variables. The number of diabetes-concordant and the number of diabetes-discordant conditions were the main explanatory variables. Analysis was adjusted for health care utilization, health system and patient demographics.A higher number of concordant conditions were associated with higher odds of achieving testing and control goals for all outcomes except blood pressure control. There was no to minimal positive association between the number of discordant conditions and outcomes, except for cholesterol testing which was less likely with 4+ discordant conditions.Having more concordant conditions makes diabetes care goal achievement more likely. The number of discordant conditions has a smaller, inconsistently significant impact on diabetes goal achievement. Interventions to improve diabetes care need to align with a patient's comorbidities, including the absence of comorbidities, especially concordant comorbidities.

Background: Young adults (18-39 years old) have the lowest rates of hypertension control compared to middle-aged and older adults. Shorter follow-up encounter intervals have been associated with faster rates of hypertension control in middle-aged and older adults. However, the optimal follow-up interval is not defined in younger adults. The objective was to evaluate the relationship between ambulatory follow-up intervals, defined as the average number of provider-patient blood pressure encounters over time, and rates of hypertension control among young adults with incident hypertension. Methods: This was a retrospective analysis of 3,150 young adults receiving regular primary care in a large, Midwestern, academic group practice from 2008-2011. Patients were included upon meeting JNC7 clinical criteria for hypertension (≥140/90 mmHg) and followed for 24 months. Young adults with a previous hypertension diagnosis or prior antihypertensive medication were excluded. We calculated the average blood pressure encounter interval over 24 months and categorized the intervals using established categories of 6 month intervals. Summary statistics were constructed using frequencies and proportions for categorical data and median (25 th , 75 th percentile) for continuous variables. Univariate associations between continuous variables were assessed using two-sided t-test. The probability of achieving hypertension control ( Results: Among young adults with newly diagnosed hypertension (59% male, 83% White), those with the shortest average encounter interval (6 months (13%), pth -75 th percentile) by encounter intervals was: 2.8 (1.8-3.9), 7.1 (5.1-11.3), 10.5 (8.5-14.4), 16.4 (12.4-22.6), and 23.9 (22.5-24.1) months. Young adults with 2-3 month and 3-6 month encounter intervals had higher rates of antihypertensive medication initiation within 24 months, 28% (884/3150) and 27% (850/3150) respectively, compared to 21% (661/3150) with Conclusions: A shorter encounter interval (

Background Chronic alcohol abuse is related to numerous deleterious neurobiological consequences, including loss of gray matter, damage to white matter (WM), and impairment of cognitive and motor functions. Aerobic exercise has been demonstrated to slow cognitive decline and decrease the negative neural changes resulting from normal aging and from several diseases. It is possible that exercise may also prevent or repair alcohol-related neurological damage. This study tested the hypothesis that aerobic exercise protects WM in anterior and dorsal areas of the brain from damage related to heavy alcohol use. Methods Sixty individuals underwent a diffusion tensor imaging session and completed measures of alcohol consumption, loss of control over drinking, and aerobic exercise participation. Analyses examined the relationship of exercise, alcohol, and their interaction to fractional anisotropy (FA) in the superior longitudinal fasciculus (SLF), external capsule (EC), superior and anterior corona radiata, and fornix. The relationship of aerobic exercise and alcohol consumption to self-reported loss of control over drinking were also examined. Results A significant interaction was observed between alcohol consumption and aerobic exercise participation on FA in the SLF and EC. In the models examining loss of control over drinking, a significant interaction between aerobic exercise and alcohol consumption was observed, such that alcohol consumption was associated with loss of control more strongly for low exercisers than high exercisers. Conclusions These results indicate that the association between heavy alcohol consumption and WM damage in the EC and SLF and the association between alcohol consumption and loss of control over drinking are greater among individuals who do not exercise regularly. These results are consistent with the notion that exercise may protect WM integrity from alcohol-related damage.

In two studies, we examined nonsmokers' perceptions of smokers and consequences of the perceptions. In Study 1, smokers answered questions about their sense of self, dependence on smoking, and motivation to quit. Nonsmokers answered questions about their perceptions of these characteristics. Differences between smokers' self-descriptions and nonsmokers' perceptions were observed. Study 2 asked nonsmokers to judge two types of smokers for which the descriptions were based on Study 1 findings. Results showed that nonsmokers held a more negative attitude about and were less willing to engage in different close relationships with the smoker who was described in terms of nonsmokers' perceptions rather than smokers' reports. Attitude mediated the relationship between type of smoker and willingness to date a smoker.

Objective To explore how physician training in self-efficacy enhancing interviewing techniques (SEE IT) affects patient psychological health behavior change mediators (HBCMs). Methods We analyzed data from 131 patients visiting primary care physicians ≥4 months after the physicians participated in a randomized controlled trial. Experimental arm physicians (N = 27) received SEE IT training during three ≤20 min standardized patient instructor (SPI) visits. Control physicians (N = 23) viewed a diabetes medications video during one SPI visit. Physicians were blinded to patient participation. Outcomes were self-care self-efficacy, readiness, and health locus of control (Internal, Chance, Powerful Others), examined as a summary HBCM score (average of standardized means) and individually. Analyses adjusted for pre-visit values of the dependent variables. Results Patients visiting SEE IT-trained physicians had higher summary HBCM scores (+0.42, 95% CI 0.07–0.77; p = 0.021). They also had greater self-care readiness (AOR 3.04, 95% CI 1.02–9.03, p = 0.046) and less Chance health locus of control (−0.27 points, 95% CI −0.50–0.04, p = 0.023), with no significant differences in other HBCMs versus controls. Conclusion Improvement in psychological HBCMs occurred among patients visiting SEE IT-trained physicians, Practice implications If further research shows the observed HBCM effects improve health behaviors and outcomes, SEE IT training might be offered widely to physicians.

Individuals who exercise are at lower risk for breast cancer and have better post-diagnosis outcomes. The biological mechanisms behind this association are unclear, but DNA methylation has been suggested.We developed a composite measure of DNA methylation across 45 CpG sites on genes selected a priori. We examined the association of this measure to self-reported physical activity and objectively measured cardiovascular fitness in a sample of healthy nonsmoking adults (n = 64) in an exercise promotion intervention.Individuals who were more physically fit and who exercised more minutes per week had lower levels of DNA methylation. Those who increased their minutes of physical activity over 12 months experienced decreases in DNA methylation.DNA methylation may be a mechanism linking exercise and cancer incidence and could serve as a biomarker for behavioral intervention trials. Studies with larger samples, objectively measured exercise, and more cancer-related markers are needed.

Importance Adolescents in the juvenile justice system are at high risk for sexually transmitted infections (STIs). Concurrent use of alcohol and cannabis increase this risk. Objective To determine whether a theory-based sexual risk-reduction intervention that included alcohol- and cannabis-focused content resulted in greater reductions in STIs than an intervention that included alcohol-related content only and an intervention that did not include substance use content. Design, Setting, and Participants Cluster randomized clinical trial with 3 conditions. Between July 1, 2010, and December 10, 2014, adolescents living at a juvenile detention facility in the southwestern United States were tested and treated for STI before randomization and again 12 months after the intervention. Data analyses were conducted in July and August 2017. Eligibility criteria included (1) being aged 14 to 18 years, (2) able to speak English, (3) having a remaining detention term of less than 1 month, and (4) signing a release granting access to STI results if tested at intake. Six hundred ninety-three adolescents were assessed for eligibility. Of these, 460 completed baseline assessments and were randomized to 1 of 3 intervention conditions. Data analysis was by intent-to-treat. Interventions There were 3 intervention conditions: sexual risk reduction intervention (SRRI); SRRI plus alcohol content (SRRI + ETOH); and SRRI + ETOH plus cannabis content (SRRI + ETOH + THC). Interventions were conducted in same-sex groups by trained clinicians and included video presentations with discussion, group activities, and active feedback by participants, consistent with the principles of motivational enhancement therapy. Main Outcomes and Measures Although not the outcome on which the study was originally powered, the main outcome variable presented herein is STI incidence (Chlamydia trachomatisand/orNeisseria gonorrhoeae) 12 months after the intervention. Results Of the 460 participants randomized, mean (SD) age was 15.8 (1.1) years, 347 participants (75.4%) were male, and 57.0% were of Hispanic ethnicity. Among the participants, 143 were randomized to SSRI, 155 to SRRI + ETOH, and 162 to SRRI + ETOH + THC. Attrition at 12-month follow-up was 99 (21.5%) for the STI outcome variable. Participants in the SRRI + ETOH + THC intervention had lower incidence of STI at follow-up (3.9%) than those in either the SRRI (12.4%; odds ratio, 0.29; 95% CI, 0.10-0.84) or the SRRI + ETOH (10.2%; odds ratio, 0.36; 95% CI, 0.12-1.05) interventions. Conclusions and Relevance An intervention delivered in a motivational enhancement therapy format that includes theory-based sexual risk reduction combined with alcohol- and cannabis-focused elements is effective at reducing STI incidence among justice-involved adolescents. This 1-session manualized intervention can be delivered in the context of short-term detention and is easily disseminated to juvenile justice agencies. Trial Registration clinicaltrials.gov Identifier:NCT01170260

Background The vast majority of patients with diabetes have multiple chronic conditions, increasing complexity of care; however, clinical practice guidelines, interventions, and public reporting metrics do not adequately address the interaction of these multiple conditions. To advance the understanding of diabetes clinical care in the context of multiple chronic conditions, we must understand how care overlaps, or doesn’t, between diabetes and its co-occurring conditions. This study aimed to determine which chronic conditions are concordant (share care goals with diabetes) and discordant (do not share care goals) with diabetes care, according to primary care provider expert opinion. Methods Using the Delphi technique, we administered an iterative, two-round survey to 16 practicing primary care providers in an academic practice in the Midwestern USA. The expert panel determined which specific diabetes care goals were also care goals for other chronic conditions (concordant) and which were not (discordant). Our diabetes care goals were those commonly used in quality reporting, and the conditions were 62 ambulatory-relevant condition categories. Results Sixteen experts participated and all completed both rounds. Consensus was reached on the first round for 94% of the items. After the second round, 12 conditions were concordant with diabetes care and 50 were discordant. Of the concordant conditions, 6 overlapped in care for 4 of 5 diabetes care goals and 6 overlapped for 3 of 5 diabetes care goals. Thirty-one discordant conditions did not overlap with any of the diabetes care goals, and 19 overlapped with only 1 or 2 goals. Conclusions This study significantly adds to the number of conditions for which we have information on concordance and discordance for diabetes care. The results can be used for future studies to assess the impact of concordant and discordant conditions on diabetes care, and may prove useful in developing multimorbidity guidelines and interventions. Electronic supplementary material The online version of this article (doi:10.1186/s12875-015-0253-6) contains supplementary material, which is available to authorized users.

BackgroundEarly hypertension control reduces the risk of cardiovascular complications among patients with diabetes mellitus. There is a need to improve hypertension management among patients with diabetes mellitus.ObjectiveWe aimed to evaluate rates and associations of hypertension diagnosis and treatment among patients with diabetes mellitus and incident hypertension.DesignThis was a 4-year retrospective analysis of electronic health records.ParticipantsAdults ≥ 18 years old (n = 771) with diabetes mellitus, who met criteria for incident hypertension and received primary care at a large, Midwestern academic group practice from 2008 to 2011 were includedMain measuresCut-points of 130/80 and 140/90 mmHg were used to identify incident cases of hypertension. Kaplan-Meier analysis estimated the probability of receiving: 1) an initial hypertension diagnosis and 2) antihypertensive medication at specific time points. Cox proportional-hazard frailty models (HR; 95 % CI) were fit to identify associations of time to hypertension diagnosis and treatment.Key resultsAmong patients with diabetes mellitus who met clinical criteria for hypertension, 41 % received a diagnosis and 37 % received medication using the 130/80 mmHg cut-point. At the 140/90 mmHg cut-point, 52 % received a diagnosis and 49 % received medication. Atrial fibrillation (HR 2.18; 1.21-4.67) was associated with faster diagnosis rates; peripheral vascular disease (HR 0.18; 0.04-0.74) and fewer primary care visits (HR 0.93; 0.88-0.98) were associated with slower diagnosis rates. Atrial fibrillation (HR 3.07; 1.39-6.74) and ischemic heart disease/congestive heart failure (HR 2.16; 1.24-3.76) were associated with faster treatment rates; peripheral vascular disease (HR 0.16; 0.04-0.64) and fewer visits (HR 0.93; 0.88-0.98) predicted slower medication initiation. Diagnosis and treatment of incident hypertension were similar using cut-points of 130/80 and 140/90 mmHg.ConclusionsAmong patients with diabetes mellitus, even using a cut-point of 140/90 mmHg, approximately 50 % remained undiagnosed and untreated for hypertension. Future interventions should target patients with multiple comorbidities to improve hypertension and diabetes clinical care.

Objective Multimorbidity affects 26 million persons with diabetes, and care for comorbid chronic conditions may impact diabetes care quality. The aim of this study was to determine which chronic conditions were related to lack of achievement or achievement of diabetes care quality goals to determine potential targets for future interventions. Research design and methods This is an exploratory retrospective analysis of electronic health record data for 23 430 adults, aged 18–75, with diabetes who were seen at seven Midwestern US health systems. The main outcome measures were achievement of six diabetes quality metrics in the reporting year, 2011 (glycated haemoglobin (HbA1c) control and testing, low-density lipoprotein control and testing, blood pressure control, kidney testing). Explanatory variables were 62 chronic condition indicators. Analyses were adjusted for baseline patient sociodemographic and healthcare utilization factors. Results The 62 chronic conditions varied in their relationships to diabetes care goal achievement for specific care goals. Congestive heart failure was related to lack of achievement of cholesterol management goals. Obesity was related to lack of HbA1c and BP control. Mental health conditions were related to both lack of achievement and achievement of different care goals. Three conditions were related to lack of cholesterol testing, including congestive heart failure and substance-use disorders. Of 17 conditions related to achieving control goals, 16 were related to achieving HbA1c control. One-half of the comorbid conditions did not predict diabetes care quality. Conclusions Future interventions could target patients at risk for not achieving diabetes care for specific care goals based on their individual comorbidities.

A in deep review of neurotransmitter regulation of gH release in the sheep, an important experimental model for the study of hypophiseal portal blood.

The current study examined the relationships among marijuana dependence, a theoretical model of condom use intentions, and subsequent condom use behavior in justice-involved adolescents. Participants completed baseline measures of prior sexual and substance use behavior. Of the original 720 participants, 649 (90.13 %) completed follow-up measures 6 months later. There were high levels of marijuana use (58.7 % met criteria for dependence) and risky sexual behavior among participants. Baseline model constructs were associated with condom use intentions, and intentions were a significant predictor of condom use at follow-up. Marijuana dependence did not significantly influence the relationships between model constructs, nor did it moderate the relationship of model constructs with subsequent condom use. Findings suggest that the theoretical model of condom use intentions is equally valid regardless of marijuana dependence status, suggesting that interventions to reduce sexual risk behavior among both marijuana dependent and non-dependent justice-involved adolescents can be appropriately based on the model.

Marijuana and alcohol use are associated with increased sexual risk behavior among justice-involved youth. A multi-behavior intervention may reduce all three risk behaviors. The purpose of this study is to examine the relationships among multiple risk behaviors and the Theory of Planned Behavior (TPB) constructs guiding the development of the Motivating Adolescents to Reduce Sexual risk (MARS) intervention. We describe the MARS study design to inform the process through which a multi-behavior intervention trial can be implemented and evaluated. Participants completed questionnaires prior to randomization to one of three interventions. Relationships were found between TPB constructs and risk behavior. A single latent variable was inadequate to capture all three risk behaviors. Interventions to reduce sexual risk behavior can include content related to the role of substance use in influencing sexual risk behavior with only minimal modifications to the curriculum, and preliminary data suggest a common theory can apply across risk behaviors.

Juvenile justice involved youth are at great risk for negative outcomes of risky sexual behavior including HIV/AIDS. Given the strong connection between alcohol use and risky sex in this population, it is important to consider alcohol use in interventions designed to decrease risky sexual behavior.This paper provides support for an integrative translational model that incorporates psychosocial, neurobiological, and genetic factors to better predict alcohol-related sexual risk behavior. Specifically, we present the design, methods, and baseline data from a complex randomized control trial, Project SHARP (Sexual Health and Adolescent Risk Prevention) in order to illustrate how this broad array of factors can best predict alcohol-related sexual risk behavior. Participants were justice-involved adolescents (n=284) who completed an fMRI and self-report assessments prior to randomization to either a sexual risk plus alcohol risk reduction group intervention or to an information-only contact control group intervention. Structural equation modeling was utilized and findings supported the hypothesized relationships in the translational model. Preliminary data suggest that interventions among justice-involved adolescents targeting alcohol-related sexual risk behavior may be more effective if a biopsychosocial approach is considered.

Using ecological momentary assessment (EMA), we sought to determine whether differences in reporting would exist for smokers who self-monitored their smoking-related negative thoughts five times daily in comparison to a non-EMA control group. One hundred and seventeen smokers were randomly assigned to two conditions. Eighty-eight smokers carried personal digital assistants (PDAs) for two weeks and monitored negative thoughts each day and 29 smokers did not self-monitor their negative thoughts. All smokers completed pretest and posttest assessments reporting their perceived risk and worry associated with smoking consequences. The data revealed evidence of self-monitoring effects, as smokers in the EMA condition reported less worry after two weeks of self-monitoring compared to smokers in the control condition. The two conditions did not differ in their reports of perceived risk of smoking consequences. These data suggest that EMA procedures asking respondents to self-monitor their thoughts about smoking may influence feelings about their smoking behavior.

Background:Maximal oxygen uptake (VO2max), an assessment of cardiorespiratory fitness, is regularly used as the primary outcome in exercise interventions. Many criteria have been suggested for validating such tests—most commonly, a plateau in oxygen consumption. The current study investigated the proportion of inactive individuals who reached a plateau in oxygen uptake and who achieved a valid test as assessed by secondary criteria (RERmax ≥ 1.1; RPEmax ≥ 18; age predicted HRmax ±10bpm), and the correlates of a successful plateau or achievement of secondary criteria during a VO2max session.Methods:Participants (n = 240) were inactive individuals who completed VO2max assessments using an incremental treadmill test. We explored physical, behavioral, and motivational factors as predictors of meeting criteria for meeting a valid test.Results:Approximately 59% of the sample achieved plateau using absolute (increase of VO2 of 150ml O2 or less) and 37% achieved plateau using relative (increase of VO2 of 1.5ml/kg O2 or less) criteria. Being male, having a higher BMI, a greater waist-to-hip ratio, and increased self-efficacy were associated with lower odds of achieving an absolute plateau, whereas none of these factors predicted odds of achieving relative plateau.Conclusion:Findings raise questions about the validity of commonly used criteria with less active populations.

SummaryStress-induced stimulation of corticotropic function involves the activation of hypothalamic corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP), which can be measured by improved methods of neuroendocrine investigation. The antiserotoninergic tricyclic antidepressant, tianeptine, reduces the corticotropic response to stress, as shown by a reduction in hypothalamo-hypophyseal portal CRH and AVP levels.

Multiple studies suggest an association of marijuana use with increased rates of sexual risk behavior and sexually transmitted diseases (STDs). Most studies have focused on global associations of marijuana use with sexual risk outcomes and few have examined relevant cognitive variables. Adolescents in the juvenile justice system are at elevated risk for HIV/STDs and preliminary evidence suggests that marijuana is a potentially important cofactor for sexual risk behavior in this population. This study evaluated global, situational and event-level associations of marijuana use and sex-related marijuana expectancies with sexual risk outcomes in a large, racially diverse sample of adjudicated youth (n = 656, 66% male, mean age = 16.7 years). Cross-sectional and prospective analyses identified associations of marijuana use and dependence symptoms with sexual risk outcomes, including lower frequency of condom use and higher STD incidence. Stronger sex-related marijuana expectancies predicted greater intentions for and frequency of marijuana use in sexual situations. In event-level analyses that controlled for alcohol, marijuana use predicted a significantly decreased likelihood of condom use; this association was moderated by sex-related marijuana expectancies. Mediation analyses suggested that behavioral intentions partly accounted for the prospective association of expectancies with marijuana use before sex. These results provide further evidence that marijuana use is a potentially important cofactor for HIV/STD transmission in high-risk adolescents and suggest that cognitive factors could be important for characterizing this association.

Objective. Many women worry about the possibility of developing breast cancer, but there is conflicting evidence concerning whether cancer worry acts as a facilitator or inhibitor of breast cancer screening. Method. We conducted a meta-analysis of 12 prospective studies that measured worry about breast cancer at baseline and subsequent breast self-examination (BSE) or mammography utilization among 3342 high-risk and general population women. Results. The data consistently show that breast cancer worry has a small but reliable ( r = 0.12) association with breast cancer screening behavior, such that greater worry predicts a greater likelihood of screening. We also found that the means for breast cancer worry were consistently in the lower third of the scales, despite differences in measurement approaches, sample utilization, or the date that the study was conducted. Conclusion. The meta-analysis supports the contention that breast cancer worry may motivate screening behavior, and that high levels of breast cancer worry are uncommon.

Conventional surgical treatment of anastomotic false abdominal aortic aneurysms (AFAA) is technically difficult. Morbidity-mortality rates are higher than those for surgery of infrarenal abdominal aortic aneurysm (AAA). Endovascular management without laparotomy or aortic clamping represents an attractive alternative. The purpose of this study was to determine the immediate and middle-term outcome of endovascular management of AFAA. Between 1998 and 2001, 10 patients were treated for AFAA by placement of an endograft. The initial procedure was aortobifemoral bypass for occlusive artery disease in eight cases and resection and grafting for AAA in two cases. Mean age was 70 years. Seven patients were classified ASA 3 or 4. Three patients presented cardiac insufficiency with left ventricular ejection fraction

The effects of rapid changes of circulating cortisol levels on ACTH secretion and on corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) concentrations into hypophysial portal blood were studied in six adult rams. Pharmacological adrenalectomy was obtained by 3 h metyrapone infusion (100 mg·kg−1·h−1). Blockade of cortisol synthesis induced a tenfold increase of plasma ACTH levels accompanied by a moderate increase of CRF secretion (150% vs preinjection levels) and a large increment of AVP secretion (535% vs preinjection levels). ACTH levels remained high during the 3 h following the end of metyrapone infusion. During the same period, CRF secretion was still elevated (231% vs preinjection levels), while AVP secretion was further stimulated (2,151% vs preinjection levels). Subsequent hydrocortisone infusion (66 μg·kg−1·h−1) for 2 h induced a rapid decrease of both ACTH and AVP secretion, while CRF levels in hypophysial portal blood still remained elevated. These data suggest that changes in ACTH secretion induced by acute modifications of the negative glucocorticoid feedback are, in addition to the well documented direct effect of cortisol on the corticotropes, mainly mediated by variations of hypothalamic AVP secretion.

BIM 23014 is a somatostatin analog displaying an increased biological half life due to resistance to enzymatic degradation. This peptide inhibits GH release directly at the level of pituitary somatotrophs. In addition, an action of BIM 23014 at the level of the hypothalamus is possible since somatostatinergic fibers and receptors have been identified on GH-RH neurons. To evaluate the effect of BIM 23014 on GH-RH secretion, hypophysial portal blood (HPB) was continuously collected in conscious sheep. Twelve rams (40–45 kg, 9-month-old) with chronically implanted perihypophysical cannulae were i.v. injected with BIM 23014 (1 mg) or saline. HPB and jugular blood were collected for 3–5 hours before and after the injection for the determinations of GH-RH and GH concentrations respectively. The acute injection of BIM 23014 induced a rapid decrease of plasma GH within the first two hours. Simultaneously, GH-RH in HPB decreased significantly. After reaching a nadir, GH concentrations increased to values greater than baseline. A similar rebound in GH-RH levels in HPB was also observed. These data indicate that BIM 23014 acts at the level of GH-RH hypothalamic neurons, in addition to its well-know effect on the pituitary gland.

The physiological role of endogenous circulating GHreleasing hormone (GHRH) and somatostatin (SRIH) on spontaneous pulsatile and neostigmine-induced secretion of GH was investigated in adult rams actively immunized against each neuropeptide. All animals developed antibodies at concentrations sufficient for immunoneutralization of GHRH and SRIH levels in hypophysial portal blood. In the anti GHRH group, plasma GH levels were very low; the amplitude of GH pulses was strikingly reduced, although their number was unchanged. No stimulation of GH release was observed after neostigmine administration. The reduction of GH secretion was associated with a decreased body weight and a significant reduction in plasma IGF-I concentration. In the antiSRIH group, no changes in basal and pulsatile GH secretion or the GH response to neostigmine were observed as compared to controls. Body weight was not significantly altered and plasma IGF-I levels were reduced in these animals. These results suggest that in sheep, circulating SRIH (in the systemic and hypophysial portal vasculature) does not play a significant role in pulsatile and neostigmine-induced secretion of GH. The mechanisms of its influence on body weight and production of IGF-I remain to be determined. Journal of Endocrinology (1995) 144, 83–90

The action of serotonin on growth hormone (GH) secretion is controversial because of interspecies differences and lack of specificity of serotoninergic drugs. Serotonin (5-HT) appears to inhibit GH release in the sheep and in man. We have investigated the site of action of tianeptine, a 5-HT uptake enhancer, in sheep since it is possible to collect hypophysial portal blood for the simultaneous determination of growth hormone-releasing hormone (GHRH) and somatostatin in this species under conscious, unstressed conditions. Tianeptine injection (10 mg/kg i.v.) resulted in a significant, immediate and short-lasting (30 min) increase in peripheral GH (+750%; P < 0.01) and hypophysial portal GHRH (+180%; P < 0.01). No change in the secretion of somatostatin was recorded during the same time. These data suggest that serotoninergic inputs are inhibitory to GH secretion. Tianeptine acts centrally to stimulate GH secretion in the sheep and its effect is mediated through changes in GHRH but not somatostatin release into hypophysial portal blood.

GH secretion is stimulated by the administration of an alpha 2-adrenergic agonist, clonidine, in several species, including man. This action is probably mediated at the level of the hypothalamus, where the drug may act through inhibition of somatostatin (SRIH) and/or stimulation of GH-releasing hormone (GHRH) release. We have investigated the mode and site of action of clonidine in sheep, because it is possible to collect hypophysial portal blood for the simultaneous determination of GHRH and SRIH in this species under conscious unstressed conditions. Clonidine injection (0.3 mg, iv) resulted in a significant, immediate, and short-lasting (30-min) increase in peripheral GH (14.4 +/- 3.1 vs. 4.8 +/- 1.1 ng/ml; P < 0.01) and portal GHRH (2.7 +/- 0.5 vs. 1.0 +/- 0.2 pg/min; P < 0.01) levels. No change in SRIH secretion was recorded during the same period. Next, we tested the effect of clonidine in sheep actively immunized against GHRH or SRIH. The alpha 2-adrenergic agonist did not affect GH secretion in the anti-GHRH group, whereas immunization against SRIH did not modify the GH response. Finally, we observed that clonidine did not influence GH release from cultured ovine pituitary cells. These data suggest that clonidine acts centrally to stimulate hypophysial GH secretion in the sheep and that this effect is mediated through changes in GHRH, but not SRIH, release into hypophysial portal blood.

The effects of acute stress on growth hormone (GH) secretion and the mechanisms involved in its changes have been investigated in sheep. An acute isolation-restraint stress induced a rapid and significant increase in jugular GH levels in 12 out of 14 rams. GH-releasing hormone (GHRH) and somatostatin secretion during the same stress were studied in 5 animals prepared for hypophysial portal blood collection. A 3.5-fold increase in portal GHRH levels was observed concomitantly with a slight elevation in portal somatostatin. Portal corticotropin-releasing hormone (CRH) and jugular cortisol plasma levels increased during the same stress. Our data suggest that an isolation-restraint stress stimulates GH secretion in the sheep and that GHRH may be responsible for GH response.

The mechanisms involved in the genesis of pulsatile GH secretion are not well understood. Recently, methods for hypophyseal portal blood collection in conscious sheep became available. Using this method, GHRH and SRIH secretion into hypophyseal portal blood (HPB) and GH release from the pituitary gland were simultaneous assessed and the relationship between GHRH and SRIH changes in HPB and GH in peripheral blood was investigated. In 23 rams (9-11 month old, 35-45 kg bw), 126 hours of HPB were analysed. Fifty-four spontaneous GH peaks were detected. The majority of GH peaks (48.1%) was associated with an increased portal GHRH and a fall in somatostatin concentrations. A simultaneous increase in GHRH and somatostatin levels was observed in 18.5% of GH peaks while 12.9% of peaks occurred with a fall in SRIH and no modification in GHRH concentrations. Finally, 5/54 (9.3%) GH peaks occurred without any modification in portal GHRH and SRIH release. Our data indicate that the GHRH/SRIH interplay is complex. The occurrence of spontaneous GH peaks may be due not only to a coordinate increase in GHRH and reduction in SRIH release similar to male rat, but also to other patterns of GHRH/SRIH secretion.

The acute effect of a new GH-releasing peptide, hexarelin (1 mg, iv), on GH secretion and the mechanisms involved in its changes were investigated in conscious sheep. Peripheral GH levels and GH-releasing hormone (GHRH) and somatostatin concentrations in hypophysial portal blood were measured in six rams. An increase in jugular GH levels was observed 15 min after hexarelin injection (9.1 +/- 1.8 vs. 3.9 +/- 0.8 ng/ml; P < 0.05). This was associated with a stimulation of GHRH release into hypophysial portal blood (145.4 +/- 19.9 vs. 59.2 +/- 10.8 pg/ml; P < 0.01) without a change in somatostatin secretion. Our data indicate that GH-releasing peptide-induced GH stimulation in the sheep involves an activation of GHRH neurons in addition to the previously demonstrated direct effect on the pituitary cells.

GH secretion is stimulated by the administration of cholinesterase inhibitors (such as pyridostigmine and neostigmine) in several species, including man. On the basis of indirect experiments, it has been postulated that this action is mediated by a decrease in hypothalamic somatostatin release. We have investigated the effect of neostigmine in sheep, since it is possible to collect hypophysial portal blood for GH-releasing hormone (GHRH) and somatostatin determination in this species under a conscious unstressed state. First, after i.v. injection of neostigmine (1 mg), a significant increase in plasma GH levels and an unequivocal potentiation of the GH response to GHRH were observed. Then, we observed that i.v. injection of neostigmine (1 mg) induced an immediate, short-lasting (30 min), and marked increase in GHRH (126.1 +/- 17 vs. 14.5 +/- 2.1 pg/ml; P < 0.01) levels in hypophysial portal blood of rams chronically implanted with perihypophysial cannulae. No change in somatostatin secretion was recorded during the same period. These data suggest that the stimulating effect of cholinergic drugs on GH secretion is mediated by stimulation of GHRH release. A direct effect of neostigmine at the level of pituitary gland is possible and may explain the potentiation of GHRH-induced GH release.

ACTH and cortisol diurnal variations and responses to two types of stress (insulin-induced hypoglycemia and isolation-restraint stress) and to an acute injection of CRF were determined in intact as well as in actively antiarginine vasopressin (AVP)-immunized rams. All immunized sheep developed antibodies to AVP, displayed diabetes insipidus, and looked healthy in spite of their lower gain weight. Basal secretion and diurnal variations of ACTH and cortisol were unaltered in the group of anti-AVP-immunized animals. In contrast, ACTH and cortisol responses to both types of stress and CRF injection were significantly reduced compared to those in controls. These results suggest that endogenous AVP plays a physiological role in the corticotropic response to stress. However, endogenous AVP does not appear to affect basal secretion and diurnal variations of ACTH and cortisol.

ACTH and cortisol diurnal variations and responses to two types of stress (insulin-induced hypoglycemia and isolation-restraint stress) or to an acute injection of lysine-vasopressin were studied in intact and anti-corticotropin-releasing factor (CRF) actively immunized rams. Immunization was obtained by the injection of synthetic ovine CRF coupled to BSA with carbodiimide. All animals developed antibodies anti-CRF and displayed an alteration of their general condition and a body weight reduction. The mean basal ACTH and cortisol secretion as well as the number and mean amplitude of diurnal pulses of these hormones was significantly reduced in the group of anti-CRF immunized rams. However, the reduction in all three parameters was much more pronounced for cortisol than for ACTH. No ACTH and cortisol response to insulin-induced hypoglycemia and isolation-restraint stress was observed. The stimulating action of lysine-vasopressin on ACTH release was significantly reduced as compared to controls. These results indicate that CRF is a major physiological component of the ovine hypothalamo-hypophysial-adrenal axis and participates in the events that regulate ACTH and cortisol diurnal variations and response to stress.

Background Arterial allografts (AAs) have been recently reconsidered in the treatment of critical limb ischaemia when vein material is absent, because of the disappointing results with artificial grafts. The aim of this study was to report the results observed in three centres where AAs were used for infrainguinal reconstruction in critical limb ischaemia. Methods Between 1991 and 1997, 165 AA bypasses were performed in 148 patients (90 men) with a mean age of 70 (range 20–93) years. Indications for operation were rest pain in 54 patients and tissue loss in 111. Mean resting ankle pressure was 53 mmHg in 96 non-diabetic patients and mean transcutaneous partial pressure of oxygen was 10 mmHg in 52 diabetic patients. AAs were obtained from cadaveric donors. The distal anastomosis was to the below-knee popliteal artery in 34 cases, to a tibial artery in 114 and to a pedal artery in 17. Results At 30 days, the mortality rate was 3 per cent, primary patency 83 per cent, secondary patency 90 per cent and limb salvage rate 98 per cent. During follow-up (mean 31 months) 65 grafts failed primarily. Causes of primary failure were thought to be progression of the distal disease in 15 cases, myointimal hyperplasia in 16, graft degradation in ten (four dilatations, three stenoses, two ruptures and one dissection), other causes in eight and not known in 16. Primary and secondary patency rates at 3 years were 35(s.e. 9) per cent and 42(s.e. 10) per cent. The limb salvage rate at 3 years was 76(s.e. 8) per cent. Conclusion AAs lead to a good foot salvage rate but poor patency rates. The results are similar to those obtained with polytetrafluoroethylene grafts.

Objective to show how differences in anatomical and physiological risk factors can affect the outcome of endovascular repair of AAA by describing the experience of two centres with different selection policies. Methods one hundred and thirty-five patients (group I) were treated at Queen's Medical Centre (Nottingham, U.K.) using 101 in-house made and 34 manufactured stent-grafts. Median diameter, length and angulation of the proximal aneurysm neck were 26 mm, 27 mm, 40°, respectively. Seventy-six patients had ischaemic heart disease, 47 had left ventricular failure, median forced expiratory volume in one second (FEV1) was 83%, median creatinine was 100 μmol/l and median age was 72 years. Fifty patients (group II) were treated at Timone Hospital (Marseilles, France) using seven in-house made and 43 manufactured stent-grafts. Median diameter, length and angulation of the proximal aneurysm neck were 25 mm, 34 mm, 33°, respectively. Thirteen patients had ischaemic heart disease, two had left ventricular failure, median forced expiratory volume in one second was 101%, median creatinine was 108 μmol/l and mean age was 72 years. Results anatomical characteristics of the proximal neck were significantly worse in group I (p=0.02 for the three variables). Cardiac comorbidities were more frequent and mean FEV1 was lower in group I (p