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Context: Parkinson's disease and related disorders (PDRD) are fatal neurodegenerative disorders characterized by a fluctuating course that can complicate prognostication. The "surprise question" (SQ: "Would you be surprised if your patient died in the next year?") has been used to identify patients with limited prognosis but has not been assessed in PDRD., Objectives: To determine the validity of the SQ in predicting 12-month mortality in PDRD., Methods: Data was analyzed from 301 patients and 34 community-based neurologists who were participating in a clinical trial of outpatient palliative care for patients with PDRD. Clinicians answered the SQ for each patient at baseline. Descriptive statistics at baseline, chi-square tests of independence, 2 × 2 and 2 × 3 cross tables were used. Survival analysis compared SQ responses using Kaplan-Meier curves. Risk estimate analyses identified patient characteristics associated with clinicians' responses., Results: Mortality was 10.3% (N = 31) at 1 year. The sensitivity and specificity of the SQ was 80.7% and 58.9%, respectively with AUC = 0.70, positive predictive value of 18.4% and negative predictive value of 96.4%. Older age, atypical parkinsonism, and dementia were associated with responding "no" to the SQ., Conclusion: The SQ is sensitive to 12-month mortality in PDRD, with a high negative predictive value. The SQ may be useful for identifying patients less likely to die within a year and may be useful for identifying patients with palliative care needs outside of end-of-life care. This latter use may assist in mobilizing early and timely referral to specialist palliative care., (Copyright © 2023 American Academy of Hospice and Palliative Medicine. All rights reserved.)

The inadequate disposal and the difficulty in its removal from water treatment systems have made the endocrine disruptor bisphenol A (BPA) a significant hazard for humans and animals. The molecular-level mechanisms of BPA action are not known in detail, which calls for systematic investigations using cell membrane models. This paper shows that BPA affects Langmuir monolayers and giant unilamellar vesicles (GUVs) of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) used as membrane models, in a concentration-dependent manner and with effects that depend on BPA aggregation. BPA increases DPPC monolayer fluidity in surface pressure isotherms upon interacting with the headgroups through hydrogen bonding, according to polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS). In DPPC GUVs, BPA induced wrinkling and distortion in the spherical shape of the vesicles, but this was only observed for fresh solutions where it is not aggregated. BPA also decreased the viability of hamster ovary cells (CHO) in in vitro experiments. In contrast, aged, aggregated BPA solutions did not affect the GUVs and even increased CHO viability. These results may be rationalized in terms of size-dependent effects of BPA, which may be relevant for its endocrine-disrupting effects., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background and Aims: Risk stratification in acute myocardial infarction (AMI) is important for guiding clinical management. Current risk scores are mostly derived from clinical trials with stringent patient selection. We aimed to establish and evaluate a composite scoring system to improve short-term mortality classification after index episodes of AMI, independent of electrocardiography (ECG) pattern, in a large real-world cohort., Methods: Using electronic health records, patients admitted to our regional teaching hospital (derivation cohort, n = 1747) and an independent tertiary care center (validation cohort, n = 1276), with index acute myocardial infarction between January 2013 and December 2017, as confirmed by principal diagnosis and laboratory findings, were identified retrospectively., Results: Univariate logistic regression was used as the primary model to identify potential contributors to mortality. Stepwise forward likelihood ratio logistic regression revealed that neutrophil-to-lymphocyte ratio, peripheral vascular disease, age, and serum creatinine (NPAC) were significant for 90-day mortality (Hosmer- Lemeshow test, p = 0.21). Each component of the NPAC score was weighted by beta-coefficients in multivariate analysis. The C-statistic of the NPAC score was 0.75, which was higher than the conventional Charlson's score (C-statistic = 0.63). Judicious application of a deep learning model to our dataset improved the accuracy of classification with a C-statistic of 0.81., Conclusions: The NPAC score comprises four items from routine laboratory parameters to basic clinical information and can facilitate early identification of cases at risk of short-term mortality following index myocardial infarction. Deep learning model can serve as a gatekeeper to facilitate clinical decision-making., Competing Interests: Declaration of competing interest The authors declared they do not have anything to disclose regarding conflict of interest with respect to this manuscript., (Copyright © 2020. Published by Elsevier B.V.)

The persistence of steroid hormones disposed of in the environment may pose risks to the health of humans and wildlife, which brings the need of understanding their mode of action, believed to occur in cell membranes. In this study, we investigate the molecular-level interactions between the synthetic hormone 17 α-ethynylestradiol (EE2) and Langmuir monolayers that represent simplified cell membranes. In surface pressure isotherms, EE2 was found to expand the monolayers at low surface pressures of the positively charged dimethyldioctadecylammonium bromide (DODAB), zwitterionic 1,2-dipalmitoyl-sn-glycerol-3-phosphocholine (DPPC), negatively charged 1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol (DPPG), and partially anionized stearic acid (StAc). The largest effects were observed for the charged DODAB and DPPG. At the pressure (30mN.m -1 ) corresponding to the molecular packing of a cell membrane, EE2 caused the compressibility modulus to decrease, again with the largest changes occurring for DODAB and DPPG. The effects from EE2 on the packing of the lipid molecules at this high pressure depended essentially on the size of the headgroups, with EE2 contributing to the area per lipid for StAc and DODAB, whose headgroups are small. EE2 interacted with the headgroups of all lipids and StAc, also affecting the ordering of the tails for DODAB, DPPG and DPPC, according to in situ polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS). Based on the analysis with the two characterization methods, we propose a model for the EE2 positioning and molecular groups involved in the interaction, which should be relevant to unveil the endocrine disrupting action of EE2., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Most adolescent cannabis use occurs in social settings among peers. Solitary cannabis use during adolescence may represent an informative divergence from normative behavior with important implications for understanding risk for cannabis problems. This longitudinal study examined associations of adolescent solitary cannabis use with levels of cannabis use and problems in adolescence and in young adulthood., Methods: Cannabis using-adolescents aged 12-18 were recruited from clinical programs (n=354; 43.8% female; 83.3% Caucasian) and community sources (n=93; 52.7% female; 80.6% Caucasian). Participants reported on cannabis use patterns and diagnostic symptoms at baseline and multiple follow-ups into young adulthood., Results: Compared to social-only users, adolescent solitary cannabis users were more likely to be male and reported more frequent cannabis use and more DSM-IV cannabis use disorder (CUD) symptoms. Regression analyses showed that solitary cannabis use in adolescence predicted CUD symptom counts in young adulthood (age 25) after controlling for demographic variables and the frequency of adolescent cannabis use. However, solitary adolescent cannabis use was no longer predictive of age 25 CUD symptoms after additionally controlling for adolescent CUD symptoms., Conclusions: Solitary cannabis use is associated with greater cannabis use and problems during adolescence, but evidence is mixed that it predicts young adult cannabis problems., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Purpose: All residency programs must comply with the Accreditation Council for Graduate Medical Education (ACGME) work-hour guidelines, but compliance requires accurate interpretation of the rules. We previously surveyed the residents and program directors of general surgery residency programs and found significant discordance between what program directors and residents considered violations. Our current study expands our research to include family medicine and emergency medicine residents and program directors. This study aims to identify discrepancies of work-hour guideline interpretation within and between the specialties., Methods: We created 10 scenarios related to work-hour issues. The ACGME reviewed them and judged whether a violation occurred in each scenario. From these scenarios, an Internet-based survey was generated and distributed electronically to every family medicine and emergency medicine residency in the United States. (Surgery programs were previously surveyed from March 1 through May 21, 2007 with the same scenarios.) Responses were collected anonymously via our Internet-based survey database from March 1 through May 17, 2008. All respondents were asked to identify themselves as either a program director or a resident. After reading each scenario, participants were asked to answer either "yes," "no," or "maybe/not sure." The option of "maybe/not sure" was in place to discourage guessing; those responses were not included in our analysis. After the data were collected, we calculated the percent of respondents that answered "yes" or "no" for each of the 10 scenarios related to work-hour issues. The results from within specialties (program directors vs residents) and between specialties (general surgery, family medicine, emergency medicine) were compared., Results: There were a total of 883 respondents (334 general surgery, 374 family medicine, and 175 emergency medicine). Respondents identified themselves as program directors (97), assistant program directors (21), or residents (765). Statistically significant differences were identified in the responses of program directors and residents within and between specialties., Conclusions: Based on the scenarios we presented, there was a difference in interpretation between residents and program directors. There was even disagreement among program directors of different specialties on the interpretation of some of the scenarios. This finding reveals an ambiguity in the work-hour restrictions. We conclude that the ACGME-mandated work-hour guidelines are confusing and not universally understood. This problem is compounded by the cross-training with "off-service" residents from other specialties such as family medicine and emergency medicine. Hence, enforcement of the work-hour restrictions may be problematic, despite the best intentions and sincere effort of directors and residents to interpret the rules.

This study determined whether adolescent-onset substance use disorders (SUDs) prospectively predicted early mortality. Among 870 adolescents, 21 young adulthood deaths were observed. Adolescent SUDs, as well as gender, ethnic group, hazardous substance use, and drug trafficking, predicted these deaths. Among African American males with SUDs, 23% died by age 25.

Type 2 diabetic patients who have not achieved adequate glucose control at the maximum tolerated doses of their oral therapies currently have no alternative other than insulin. A new approach has been developed, using the glucoregulatory properties of the intestinal incretin hormone glucagon-like peptide-1 (GLP-1). This has resulted in the development of a new therapeutic class, the incretin mimetics, of which exenatide is the first to have been approved. Exenatide can bind to the endogenous receptors of GLP-1 and mimic its glucoregulatory actions. It improves glycemic control by acting on the key organs involved in glucose homeostasis: it stimulates insulin secretion and suppresses glucagon secretion in a glucose-dependent way, slows gastric emptying and reduces food intake. It consequently produces significant reductions in fasting and postprandial hyperglycemia. Various clinical studies, both versus placebo and versus insulin, have shown a significant decrease in HbA1c levels (of about 1%), accompanied by weight loss, in patients treated with exenatide. Exenatide efficacy is sustained and all the studies have shown a comparable tolerance profile. The most frequently reported adverse effects were nausea and hypoglycemia when the patient received concomitant sulfonylurea therapy. The aim of this article is to summarize main clinical data on exenatide and to discuss its position in current therapeutic strategy.

Objective: DSM-IV alcohol dependence criteria of tolerance to alcohol and drinking more or longer than intended have relatively high prevalence among youth, and may be vulnerable to false positive symptom assignments that degrade diagnostic validity. We conducted a methodological study of DSM-IV symptom queries used to assess alcohol tolerance and impaired control over drinking to determine potential sources of measurement error., Method: Adolescents recruited from addictions treatment participated in either a focus group (n = 9) or an individual interview (n = 41) to provide data on their interpretation of selected items contained in a semi-structured diagnostic interview., Results: When alcohol tolerance is operationally defined as a change in quantity to obtain the same effect, large individual differences in the change in quantity that represents a high level of tolerance limit the utility of this operational definition as an indicator of dependence. The symptom "drinking more or longer than intended", includes the embedded assumption that a limit on use had been set. Teens, however, typically intended to become intoxicated, rather than to keep to a limit., Conclusions: Adolescents' understanding of symptom queries suggests how validity of DSM-IV alcohol symptoms and diagnoses can be improved through greater attention to developmental considerations affecting assessment.

Despite the critical importance of adolescent smoking, the assessment of nicotine dependence during this developmental period has been the subject of relatively little research. In this study, 301 adolescents (ages 12 through 18 years) reporting daily smoking were recruited for a project on alcohol use disorders (AUDs). The sample included 140 females and 161 males, 251 subjects from clinical and 50 from community sources, and 176 subjects with AUDs at the baseline assessment. Subjects were evaluated with the Nicotine Dependence Syndrome Scale (NDSS), the Fagerstrom Test for Nicotine Dependence (FTND) and a determination of average number of cigarettes per day (cigarettes/day). A varimax factor analysis of 27 NDSS items revealed four factors: (1) Drive/Tolerance (13 items; Cronbach alpha = 0.91); (2) Continuity (five items; Cronbach alpha = 0.67); (3) Priority (three items; Cronbach alpha = 0.64); (4) Stereotypy (five items; Cronbach alpha = 0.66). The NDSS total score, refined by the removal of four items, was also examined (23 items; Cronbach alpha = 0.90). Predicting cigarettes/day at follow-up, initial smoking rate was the best predictor, with the FTND and NDSS Total score showing significant and similar predictive validity. The NDSS Total showed incremental validity in the prediction of smoking progression in a model including demographic characteristics, initial smoking rate and FTND. The findings suggest that the NDSS has acceptable psychometric properties when applied to adolescents, complementing smoking rate and FTND in a multidimensional smoking assessment.

Adolescents with alcohol use disorders (AUDs) often have major depressive disorder (MDD). While physical abuse and sexual abuse (PS Abuse) have been observed to be common in adolescents with AUDs, the influence of PS Abuse on comorbid MDD and AUD has not been determined. The effect of pre-existing PS Abuse on the young adulthood outcomes of adolescents with AUDs has also not been adequately explored. This study examined the relationships among PS Abuse, MDD, and AUD in adolescence, as well as related young adult outcomes. Adolescents (mean age: 16.4 years; range: 14-18 years) were recruited from clinical and community sources and classified into four groups: (1) AUD+PS Abuse (n=154), (2) AUD only (n=255), (3) PS Abuse only (n=74), and (4) Controls (n=268). Subjects were longitudinally assessed through young adulthood (age 19 years or older). Measures included interview assessments of DSM-IV AUD and MDD, classified as "primary" or "secondary", and questionnaire measures of alcohol consumption and depression. Primary MDD preceded AUD whereas secondary MDD had a later onset than AUD. PS Abuse accelerated the onsets of primary MDD, secondary MDD and AUD. While affected adolescents had typically improved in both alcohol consumption and depression at the young adult assessment, the majority of those with adolescent AUD had AUDs in young adulthood, and MDD remained common in those with a history of PS Abuse. These results indicate that MDD among adolescents with AUD may be partly attributable to PS Abuse.

Objective: Summary prevalence data are critical to determining the utility of DSM-IV criteria for alcohol use disorders among adolescents. This study examined cross-study consistency in the relative prevalence of DSM-IV alcohol symptoms, the ratio of alcohol abuse to dependence diagnoses, the prevalence of the physiological dependence subtype, and the proportion of subthreshold cases of dependence., Method: DSM-IV alcohol diagnosis and symptom prevalence data were obtained from five community and four clinical adolescent samples., Results: There was a moderate level of cross-study agreement on the relative prevalence of alcohol symptoms (mean Spearman p = 0.47). The most common symptoms were dependence criteria: tolerance and drinking more or longer than intended. A relatively high degree of variability in the ratio of abuse to dependence diagnoses and the proportion with physiological dependence was observed. All samples included a significant proportion of subthreshold cases of dependence: up to 12% in community and up to 34% in clinical samples., Conclusions: Alcohol dependence symptoms of tolerance and drinking more or longer than intended have relatively high prevalence among adolescents. These high prevalence symptoms affect the ratio of abuse to dependence diagnoses in some studies, the prevalence of the physiological dependence subtype, and the proportion of subthreshold cases of dependence.

Diagnostic interviews for substance use disorders tend to have high reliability among adults. We examined the inter-rater reliability of the substance use disorders section of the Structured Clinical Interview for the DSM, using 46 male and 25 female adolescent drinkers recruited from community and treatment sources. Inter-rater reliability was high for individual DSM-IV alcohol symptoms (kappa=0.84-1.0) and diagnoses (kappa=0.94), and for other substance use disorder diagnoses (kappa=0.82-1.0).

Little is known about risky sexual activity among adolescents with alcohol use disorders. This study of 371 adolescent drinkers found that those with alcohol disorders were more likely than other drinkers to be sexually active, to have greater numbers of partners, and to initiate sexual activity at slightly younger ages. Independent of alcohol group, females were more likely than males to have unprotected sexual encounters.

Investigations of adults with a psychoactive substance use disorder (PSUD) or antisocial behavior have reported diminished secretion of the adrenal "stress" hormone, cortisol. Consequently, we determined whether prepubertal sons of PSUD fathers, at high risk for later PSUD, differed from controls on salivary cortisol concentrations before, and after, an anticipated stressor. The roles of problematic behavioral disposition and state anxiety in the cortisol responses were also examined. A significant risk-group x time interaction for salivary cortisol concentrations was found, with high-risk boys secreting less salivary cortisol than controls when anticipating the task. High-risk boys also had significantly higher scores for aggressive delinquency and impulsivity that wholly accounted for the risk-group x time effect on salivary cortisol. Thus, cortisol hyporesponsivity was associated with the dysregulated behaviors prevalent among high-risk boys. The results suggest that cortisol hyporesponsivity could be a "marker" for later antisociality and PSUD.

Heightened activity level has been implicated in the liability for substance abuse, but no prior research has directly examined motor activity in a sample of prepubertal boys at high-risk for substance abuse. The magnitude of behavioral activity of 10-12 year-old sons of substance abusing fathers (SA +) (n = 42) and controls (SA -) (n = 60) was assessed using a microprocessor-based activity monitor during tasks that demanded significant concentration, effort, and constraint on motor activity, and when no such demands were present. Psychiatric status, measures of temperament traits, and measures of internalizing and externalizing behaviors were also obtained on the boys. Although the groups did not differ during the lower demand task, SA + boys showed significantly greater motor activity than SA - boys during the tasks that required concerted effort, attention, and behavioral suppression. Multiple regression analysis indicated that under the low-demand condition, the presence of an anxiety disorder in the boy was the only significant predictor of activity level. However, under the conditions that demanded effort, concerted attention and behavioral suppression, SA + group membership, and having low rhythmicity (as a temperament trait) predicted heightened activity. Statistically controlling for rhythmicity, the SA + boys were estimated to have about 24% higher activity than control boys. The results suggest that heightened motor activity may be associated with susceptibility to substance abuse.

We performed a double-blind placebo-controlled study of the effects of extradural administration of methadone 5 mg or saline, followed by bupivacaine, in 42 women in early labour. Motor block and pain scores were significantly less in the methadone group. The requirement for bupivacaine also was reduced by methadone, but this was not statistically significant. There were no troublesome side effects attributable to methadone.

This study examined the association between malpractice, measured by perception and experience scores, and practice activities of orthodontists. Data from 184 Florida orthodontists were obtained in the form of continuous/ordinal responses to survey questions in five areas: demographic, work load, personality, perception of the malpractice environment, and practice activities (malpractice experience, record taking, disclosure, and rapport). Mutually exclusive recency categories were selected on the basis of when an activity was last performed. Descriptive statistics and plots of the data were examined. A malpractice experience score for each respondent was determined by means of factor analysis procedures on the activity question responses. The association between perception/experience scores and responses to activity, demographic, work load, and personality questions were examined with the use of stepwise multiple regression procedures. The results indicated that practice activities, in the areas of record taking and doctor-patient rapport, were moderately associated with both experience scores (R2 = 0.47, p = 0.08) and perception scores (R2 = 0.29, p less than 0.06). Perception of the malpractice environment was associated with practice activities of orthodontists but to a lesser extent than active experiences in that environment were.

We evaluated the accuracy of a new device for continuous noninvasive measurement of cutaneous PCO2. The Hewlett-Packard capnometer (model 47210/HA) works by means of an infrared transducer applied to the forearm over an area of skin that has been stripped of the stratum corneum. Capnometer transcutaneous carbon dioxide pressure (CPCO2) was compared with arterial carbon dioxide pressure (PaCO2) during 60 simultaneously obtained measurements in 13 hemodynamically stable patients. Each patient was studied for 1 1/2 to 5 hours, and a wide range of PaCO2 values (21 to 82 mm Hg) was represented. The data show a clinically significant relationship whereby PaCO2 = CPCO2 - 4.13, with a SE of +/- 2.19 mm Hg. Clinical usefulness of noninvasive cutaneous CO2 monitoring can be foreseen in patients whose ventilatory support is being tapered, in those with respiratory depression caused by various neuromuscular disorders, and in patients with chronic obstructive pulmonary disease and acute respiratory failure. Our results indicate that continuous transcutaneous CPCO2 measurements are safe and accurate and strongly suggest that they can be of clinical usefulness in a select group of hemodynamically stable patients.