Long-term excess mortality associated with diabetes following acute myocardial infarction: a population-based cohort study.

BACKGROUND: The long-term excess risk of death associated with diabetes following acute myocardial infarction is unknown. We determined the excess risk of death associated with diabetes among patients with ST-elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) after adjustment for comorbidity, risk factors and cardiovascular treatments. METHODS: Nationwide population-based cohort (STEMI n=281 259 and NSTEMI n=422 661) using data from the UK acute myocardial infarction registry, MINAP, between 1 January 2003 and 30 June 2013. Age, sex, calendar year and country-specific mortality rates for the populace of England and Wales (n=56.9 million) were matched to cases of STEMI and NSTEMI. Flexible parametric survival models were used to calculate excess mortality rate ratios (EMRR) after multivariable adjustment. This study is registered at ClinicalTrials.gov (NCT02591576). RESULTS: Over 1.94 million person-years follow-up including 120 568 (17.1%) patients with diabetes, there were 187 875 (26.7%) deaths. Overall, unadjusted (all cause) mortality was higher among patients with than without diabetes (35.8% vs 25.3%). After adjustment for age, sex and year of acute myocardial infarction, diabetes was associated with a 72% and 67% excess risk of death following STEMI (EMRR 1.72, 95% CI 1.66 to 1.79) and NSTEMI (1.67, 1.63 to 1.71). Diabetes remained significantly associated with substantial excess mortality despite cumulative adjustment for comorbidity (EMRR 1.52, 95% CI 1.46 to 1.58 vs 1.45, 1.42 to 1.49), risk factors (1.50, 1.44 to 1.57 vs 1.33, 1.30 to 1.36) and cardiovascular treatments (1.56, 1.49 to 1.63 vs 1.39, 1.36 to 1.43). CONCLUSIONS: At index acute myocardial infarction, diabetes was common and associated with significant long-term excess mortality, over and above the effects of comorbidities, risk factors and cardiovascular treatments.

Determinants of excess mortality following unprotected left main stem percutaneous coronary intervention.

OBJECTIVE: For percutaneous coronary intervention (PCI) to the unprotected left main stem (UPLMS), there are limited long-term outcome data. We evaluated 5-year survival for UPLMS PCI cases taking into account background population mortality. METHODS: A population-based registry of 10 682 cases of chronic stable angina (CSA), non-ST-segment elevation acute coronary syndrome (NSTEACS), ST-segment elevation myocardial infarction with (STEMI+CS) and without cardiogenic shock (STEMI-CS) who received UPLMS PCI from 2005 to 2014 were matched by age, sex, year of procedure and country to death data for the UK populace of 56.6 million people. Relative survival and excess mortality were estimated. RESULTS: Over 26 105 person-years follow-up, crude 5-year relative survival was 93.8% for CSA, 73.1% for NSTEACS, 77.5% for STEMI-CS and 28.5% for STEMI+CS. The strongest predictor of excess mortality among CSA was renal failure (EMRR 6.73, 95% CI 4.06 to 11.15), and for NSTEACS and STEMI-CS was preprocedural ventilation (6.25, 5.05 to 7.75 and 6.92, 4.25 to 11.26, respectively). For STEMI+CS, the strongest predictor of excess mortality was preprocedural thrombolysis in myocardial infarction (TIMI) 0 flow (2.78, 1.87 to 4.13), whereas multivessel PCI was associated with improved survival (0.74, 0.61 to 0.90). CONCLUSIONS: Long-term survival following UPLMS PCI for CSA was high, approached that of the background populace and was significantly predicted by co-morbidity. For NSTEACS and STEMI-CS, the requirement for preprocedural ventilation was the strongest determinant of excess mortality. By contrast, among STEMI+CS, in whom survival was poor, the strongest determinant was preprocedural TIMI flow. Future cardiovascular cohort studies of long-term mortality should consider the impact of non-cardiovascular deaths.

Estimating the potential survival gains by eliminating socioeconomic and sex inequalities in stage at diagnosis of melanoma.

BACKGROUND: Although inequalities in cancer survival are thought to reflect inequalities in stage at diagnosis, little evidence exists about the size of potential survival gains from eliminating inequalities in stage at diagnosis. METHODS: We used data on patients diagnosed with malignant melanoma in the East of England (2006-2010) to estimate the number of deaths that could be postponed by completely eliminating socioeconomic and sex differences in stage at diagnosis after fitting a flexible parametric excess mortality model. RESULTS: Stage was a strong predictor of survival. There were pronounced socioeconomic and sex inequalities in the proportion of patients diagnosed at stages III-IV (12 and 8% for least deprived men and women and 25 and 18% for most deprived men and women, respectively). For an annual cohort of 1025 incident cases in the East of England, eliminating sex and deprivation differences in stage at diagnosis would postpone approximately 24 deaths to beyond 5 years from diagnosis. Using appropriate weighting, the equivalent estimate for England would be around 215 deaths, representing 11% of all deaths observed within 5 years from diagnosis in this population. CONCLUSIONS: Reducing socioeconomic and sex inequalities in stage at diagnosis would result in substantial reductions in deaths within 5 years of a melanoma diagnosis.

The impact of eliminating age inequalities in stage at diagnosis on breast cancer survival for older women.

BACKGROUND: Older women with breast cancer have poorer relative survival outcomes, but whether achieving earlier stage at diagnosis would translate to substantial reductions in mortality is uncertain. METHODS: We analysed data on East of England women with breast cancer (2006-2010) aged 70+ years. We estimated survival for different stage-deprivation-age group strata using both the observed and a hypothetical stage distribution (assuming that all women aged 75+ years acquired the stage distribution of those aged 70-74 years). We subsequently estimated deaths that could be postponed beyond 5 years from diagnosis if women aged 75+ years had the hypothetical stage distribution. We projected findings to the English population using appropriate age and socioeconomic group weights. RESULTS: For a typically sized annual cohort in the East of England, 27 deaths in women with breast cancer aged 75+ years can be postponed within 5 years from diagnosis if their stage distribution matched that of the women aged 70-74 years (4.8% of all 566 deaths within 5 years post diagnosis in this population). Under assumptions, we estimate that the respective number for England would be 280 deaths (5.0% of all deaths within 5 years post diagnosis in this population). CONCLUSIONS: The findings support ongoing development of targeted campaigns aimed at encouraging prompt presentation in older women.

Understanding the impact of socioeconomic differences in breast cancer survival in England and Wales: avoidable deaths and potential gain in expectation of life.

BACKGROUND: Socioeconomic differences in cancer patient survival are known to exist for women diagnosed with breast cancer. Standard metrics tend not to place great emphasis on evaluating the actual impact of these differences. METHODS: We used two alternative, but related, methods of reporting the impact of socioeconomic differences for breast cancer patients in England and Wales. We calculated the average gain in life years for each patient should socioeconomic differences in relative survival be removed and show how this is related to the number of all-cause deaths that could be postponed by removing socioeconomic differences in cancer patient survival. RESULTS: Our results indicate that deprivation differences for women with breast cancer exist and result in women from more deprived areas losing a larger proportion of their life due to a diagnosis of cancer. We also estimate that on average 1.1 years could be gained for a 60 year old breast cancer patient in the most deprived group by improving their relative survival to match the least deprived group. However, our results also show that deprivation differences in general survival have a large impact on life expectancy; showing that over two-thirds of the gap in differential life expectancy is explained by differences in other-cause survival. CONCLUSION: Socioeconomic differences in relative survival have an impact on life expectancy for patients and result in higher early mortality for more deprived patients. However, differences in general survival across socioeconomic groups explain a larger proportion of the deprivation gap in life expectancy for breast cancer patients.

How much of the deprivation gap in cancer survival can be explained by variation in stage at diagnosis: an example from breast cancer in the East of England.

Socioeconomic differences in cancer patient survival exist in many countries and across cancer sites. In our article, we estimated the number of deaths in women with breast cancer that could be avoided within 5 years from diagnosis if it were possible to eliminate socioeconomic differences in stage at diagnosis. We analysed data on East of England women with breast cancer (2006-2010). We estimated survival for different stage-age-deprivation strata using both the observed and a hypothetical stage distribution (assuming all women acquired the stage distribution of the most affluent women). Data were analysed on 20,738 women with complete stage information (92%). Affluent women were less likely to be diagnosed in advanced stage. Relative survival decreased with increasing level of deprivation. Eliminating differences in stage at diagnosis could be expected to nearly eliminate differences in relative survival for women in deprivation groups 3 and 4, but would only approximately halve the difference in relative survival for women in the most deprived group (5). This means, for a typical cohort of women diagnosed in a calendar year with breast cancer, eliminating deprivation differences in stage at diagnosis would prevent ∼40 deaths in the East of England from occurring within 5 years from diagnosis. Using appropriate weighting we estimated the respective number of avoidable deaths for the whole of England to be ∼450. The findings suggest that policies aimed at reducing inequalities in stage at diagnosis between women with breast cancer are important to reduce inequalities in breast cancer survival.

A comprehensive assessment of the impact of errors in the cancer registration process on 1- and 5-year relative survival estimates.

BACKGROUND: When making international comparisons of cancer survival, it is essential reported differences are real effects and not an artefact of potential errors in cancer registration. METHODS: We use simulation methods to assess the impact of various cancer registration errors on commonly reported outcomes of cancer survival (1-, and 5-year relative survival estimates). We draw two samples of patients diagnosed with cancer from one population and introduce potential registration errors in one of the sample populations under various assumptions. We investigate the effect of errors individually as well as the composite effect when combined with other registration errors. RESULTS: The results indicate that high levels of cancer registration errors are necessary to make a noticeable effect on commonly reported metrics of cancer survival. Differences of up to 3 percentage units in the 5-year relative survival proportion are seen under plausible scenarios. CONCLUSION: This study is a comprehensive assessment of cancer registration errors and the consequent impact on commonly reported survival statistics. We show that under plausible scenarios, it is very unlikely that these biases are large enough to explain the variation in international comparisons of cancer survival. Registration errors will also impact on other metrics reported from registry data, such as incidence.

Should relative survival be used with lung cancer data?

BACKGROUND: Under certain assumptions, relative survival is a measure of net survival based on estimating the excess mortality in a study population when compared with the general population. Background mortality estimates are usually taken from national life tables that are broken down by age, sex and calendar year. A fundamental assumption of relative survival methods is that if a patient did not have the disease of interest then their probability of survival would be comparable to that of the general population. It is argued, as most lung cancer patients are smokers and therefore carry a higher risk of smoking-related mortalities, that they are not comparable to a population where the majority are likely to be non-smokers. METHODS: We use data from the Finnish Cancer Registry to assess the impact that the non-comparability assumption has on the estimates of relative survival through the use of a sensitivity analysis. RESULTS: Under realistic estimates of increased all-cause mortality for smokers compared with non-smokers, the bias in the estimates of relative survival caused by the non-comparability assumption is negligible. CONCLUSION: Although the assumption of comparability underlying the relative survival method may not be reasonable, it does not have a concerning impact on the estimates of relative survival, as most lung cancer patients die within the first 2 years following diagnosis. This should serve to reassure critics of the use of relative survival when applied to lung cancer data.

The relationship of psychiatric comorbidity to treatment outcomes in methadone maintained patients.

The authors examined the relationship of comorbid non-substance use psychiatric disorders to preadmission problem status and treatment outcomes in 278 methadone maintenance patients. Recent admissions were assigned DSM-III-R Axis I and II diagnoses according to structured diagnostic interviews. The Addiction Severity Index was administered at admission to assess past and current substance use and psychosocial problems and again 7 months later. Treatment retention and month 7 drug urinalysis results were also obtained. Across substance use and psychosocial domains, participants showed significant and comparable levels of improvement regardless of comorbidity. Comorbid participants received more concurrent psychiatric treatment which may have accounted for the lack of differential improvement among groups. Nevertheless, psychiatric comorbidity was associated with poorer psychosocial and medical status at admission and follow-up and participants with the combination of Axis I and II comorbidity had the most severe problems. Admission and month 7 substance use were, for the most part, not related to psychiatric comorbidity, although there was a trend indicating more treatment attrition for participants with personality disorders.

The effectiveness of two intensities of psychosocial treatment for cocaine dependence.

Structured treatments for cocaine dependence have been shown to be effective despite high attrition rates. What is unclear is what level of treatment intensity is needed to improve and sustain patient outcomes, especially among low SES urban residents. This study evaluated whether there were differences between two levels of treatment intensities for cocaine dependence in reducing substance use and improving health and social indicators. Ninety-four cocaine dependent predominantly African-American male veterans were randomly assigned to either a 12 h/week day hospital program (DH12) or a 6 h/week outpatient program (OP6) and were evaluated at baseline, during treatment and at 4 and 7 months post-treatment. Both treatments stressed abstinence, behavior change and prosocial adjustment and only differed in level of treatment intensity. During treatment measures included urine toxicologies, program attendance, treatment completion and aftercare attendance. Participants reported a 52% reduction in days of cocaine use and experienced significant improvements in employment and psychiatric functioning at seven months post-treatment. However, there was no significant difference between the DH12 and OP6 programs in terms of abstinence during treatment, treatment completion, treatment or aftercare attendance or any Addiction Severity Index (ASI)-related variable assessing level of functioning at 4 and 7 months. While future research with a larger community-based sample that includes female clients is necessary, the current findings demonstrate that a 6 h/week program is just as effective and thus has a significant cost savings compared to a 12 h/week treatment modality for cocaine dependence.

Generalizability of the clinical dimensions of the Addiction Severity Index to nonopioid-dependent patients.

Clinical dimensions (CDs) for the Addiction Severity Index recently have been established for application among opioid-dependent patients in methadone treatment (P. A. McDermott et al., 1996). This article examines the generalizability of the CDs to other substance-dependent patients. A sample of 2,027 adult nonopioid-dependent patients was identified; it comprised 581 primarily cocaine-dependent, 544 primarily alcohol-dependent, and 803 polydrug-dependent patients and 99 patients who were dependent on other varied drugs. Generality of dimensions was assessed through confirmatory components analysis, structural congruence, internal consistency, and variance partitioning in higher order factoring. The CDs were found generalizable overall and to specific nonopioid-dependent subgroups, and across patient gender and age, and to African American and White patients. Preliminary concurrent and predictive validity data supported the CD structure.

Baseline prediction of 7-month cocaine abstinence for cocaine dependence patients.

A broad range of baseline subject variables was evaluated to identify predictors of 7-month cocaine use for 160 lower socioeconomic cocaine dependent male veteran patients participating in either an intensive 1-month day hospital (DH; n=90) or a 1-month inpatient (INP; n=70) treatment program. The baseline measures included sociodemographic variables, the seven Addiction Severity Index composite scores, cocaine urine toxicology, craving, the SCL-90 total score, and lifetime psychiatric diagnoses. Since a proportion of subjects who reported no use at follow-up had positive urines, both liberal and conservative data estimation strategies were employed for subjects without urine toxicology data at follow-up who had reported no use (21% of subjects). Analyses were done separately for the DH and INP subjects. Under the conservative definition of cocaine abstinence/use, univariate correlations of predictor variables with 7-month cocaine use revealed no statistically significant relationships. Under the liberal definition of cocaine abstinence/use, only one variable, greater severity of alcohol problems at intake predicted cocaine abstinence at outcome. Because of the inability to predict treatment success, originally planned logistic regression analyses were not undertaken. The findings point to the difficulty of predicting long-term outcomes in cocaine dependent patients based on baseline information and to the importance of obtaining objective data on cocaine use.

Contrasts between admitters and deniers of drug use.

This study evaluated the agreement between self-reported drug use and urinalysis results in 232 men and 27 women opiate-dependent patients at 2, 7, and 24 months following admission to methadone maintenance treatment. Differences between deniers, those who stated that they had not used drugs, but whose urinalysis results were positive, and admitters of drug use on several psychosocial variables, Axis I and II pathology and degree of psychopathy were examined. Generally, more drug use was acknowledged by self-report than found in urinalyses. Evidence was limited that deniers were consistently different than admitters. Deniers had a significantly greater increase from initial psychopathy ratings made using interview only information to final psychopathy ratings made utilizing interview and collateral information.

Familial risk for alcoholism and self-reported psychopathology.

Three groups of young men varying in familial alcoholism risk (high density, high risk [HDHR]; low density, high risk [LDHR]; and low risk [LR]) were compared on the 11 clinical scales of the Personality Assessment Inventory. Significant group differences were found on 9 scales, with scores of the HDHR group exceeding those of the other 2 groups. No differences were found between the LDHR and LR groups. When the proportion with pathological scores per scale was examined, significant group differences were still revealed on 7 scales. The HDHR group exceeded the other 2 groups, but the LDHR group also exceeded the LR group on several scales. These findings support the need to more finely characterize familial alcoholism risk than is provided by the typical high-risk-low-risk dichotomy. Finally, statistically controlling for normal variations in response style reduced the number of group differences, although the same patterns persisted.

Generality of Psychopathy Checklist-Revised factors over prisoners and substance-dependent patients.

The Psychopathy Checklist-Revised (PCL-R; R. D. Hare, 1991) is an often-used device for assessment of adult antisociality. This research examined generalizability by replicating the 2-factor model for a sample of 326 male prisoners and assessing its congruence and relative reliability and specificity among 620 substance-dependent patients. Generality was assessed also across addiction subtypes (opioid, cocaine, and alcohol), age, gender, and ethnicity. The 2-factor model was found inappropriate for the substance-dependent samples, whereas a unidimensional model represented by the PCL-R total score was found generalizable across prison and substance-dependent samples.

Skin pH changes associated with iontophoresis.

STUDY DESIGN: Randomized controlled trial. The researcher measuring skin pH was blinded to group assignment. OBJECTIVES: To compare the skin surface pH changes associated with iontophoresis. The investigation was designed to address the question of whether significant skin pH changes occur under the cathode on the skin surface when performing iontophoresis and assessed the influence of different electrode-buffering systems intended to stabilize skin pH (surface). BACKGROUND: Whether buffers are needed to stabilize skin pH during iontophoresis has not been thoroughly addressed in the literature. The effectiveness of immobile resins versus simple phosphate buffers is also unclear. METHODS AND MEASURES: Sixty volunteer subjects were administered iontophoresis of normal saline using buffered or nonbuffered electrode systems. Each subject participated in 1 of the 12 doses by electrode conditions (i.e., 5 subjects per group). Surface skin pH was measured before and after iontophoresis with a flat-surface pH electrode in concert with an analog pH meter. The independent variables were electrode type (4 levels) and dosage (3 levels). The dependent variable was the change in skin surface pH. RESULTS: A significant change in skin pH was found only when the treatment dose was 80 mA/minute with a nonbuffered electrode (x = 3.14 +/- 1.09). CONCLUSIONS: The skin pH changes that occur during a properly delivered iontophoresis treatment at dosages of 20 and 40 mA/min were small and not significantly different with or without the addition of buffers. Those pH changes associated with 80 mA/min doses were significantly greater when no buffer was employed but were stabilized by each of the buffers used in the study (preloaded immobile resins or simple phosphates added at point of treatment).

Comparability of telephone and In-person structured clinical interview for DSM-III-R (SCID) diagnoses.

The SCID was administered twice, once by telephone and once in person (1 week later) to 41 college age men. For major depression (lifetime k =.64, current k =.66), results indicated good agreement. The lifetime occurrence estimate based on the telephone SCID diagnosis was lower than the in-person SCID estimate. Kappas for specific diagnoses were calculable for simple phobia (lifetime k =. 47, current k = .03) and social phobia (lifetime k =.29). Base rates were less than 10% for all individual diagnoses except lifetime major depression; therefore, the kappas may be unstable. For all diagnoses where there were any positive cases, percentages of negative agreement and specificity were high, whereas percentages of positive agreement and sensitivity were lower. Overall agreement was fair for specific lifetime diagnoses but poor for current diagnoses. These results suggest caution in assuming comparability of in-person and telephone SCID diagnoses. Circumstances under which a telephone SCID may be useful and ways to improve reliability are discussed.

Antisocial personality disorder and psychopathy in cocaine-dependent women.

OBJECTIVE: The goal of this study was to examine the lifetime prevalence of antisocial personality disorder according to five diagnostic systems and the prevalence of psychopathy in a study group of women. The relationship between antisocial personality disorder and psychopathy was also examined. Finally, differences in treatment admission variables based on the presence or absence of antisocial personality disorder and/or psychopathy were evaluated. METHOD: Antisocial personality disorder was diagnosed in 137 treatment-seeking, cocaine-dependent women according to the Feighner criteria, Research Diagnostic Criteria (RDC), and DSM-III, DSM-III-R, and DSM-IV criteria. Psychopathy was assessed by the Revised Psychopathy Checklist. RESULTS: Rates of antisocial personality disorder varied from 76% according to the Feighner criteria to 11% for the RDC. Nineteen percent (N = 26) of the women scored in the moderate to high range on the Revised Psychopathy Checklist. All of these women were diagnosed with antisocial personality disorder according to DSM-III and Feighner criteria, but only 15 of the 26 were diagnosed according to DSM-III-R, 12 according to DSM-IV, and six with the RDC. Moderate levels of psychopathy were associated with a history of illegal activity at treatment admission, whereas antisocial personality disorder was not. CONCLUSIONS: There was relatively little diagnostic agreement between classification systems. This study indicates that antisocial personality disorder and psychopathy are not synonymous terms for the same disorder. Findings support a need to redefine antisocial personality disorder diagnostic criteria to make them gender neutral by including behaviors associated specifically with antisociality in women.

The relationship of alcohol use to cocaine relapse in cocaine dependent patients in an aftercare study.

OBJECTIVE: To examine the relationship between alcohol use and cocaine relapse. METHOD: Ninety-eight cocaine-dependent male patients in aftercare were followed for 6 months following completion of an intensive outpatient rehabilitation program (IOP). Past and current alcohol dependence was assessed at entrance into aftercare, and drinking behavior prior to cocaine relapse and "near miss" episodes was assessed at 3- and 6-month follow-ups. Data on cocaine and alcohol use throughout the follow-up were also obtained. RESULTS: Patients who had never met criteria for alcohol dependence and those with current alcohol dependence had worse cocaine outcomes (cocaine use on 10% and 7% of the days in the follow-up, respectively) than those with past alcohol dependence (cocaine use on 3% of the days in the follow-up), although alcohol dependence status no longer predicted cocaine use outcomes when cocaine use in IOP was controlled. Alcohol use in 4 of the first 5 follow-up months significantly predicted cocaine relapse status in the next month after cocaine use in IOP and alcohol dependence diagnosis at baseline were controlled. Patients who experienced cocaine relapses were much more likely to report drinking before the onset of the episode than those who had "near misses," particularly on the day of the episode (40% vs. 6% at 3 months; 62% vs. 0% at 6 months). Alcohol did not appear to be a factor in the relapses of cocaine patients with no history of alcohol dependence, even though they did report drinking on 5% of the days in the follow-up. CONCLUSIONS: Relapse prevention efforts with cocaine abusers who have histories of alcohol dependence should include interventions designed to reduce drinking.

Personality pathology and drinking in young men at high and low familial risk for alcoholism.

OBJECTIVE: Three groups varying in familial alcoholism risk were compared with respect to amount of alcohol consumption, presence of personality pathology, and the relationship between personality pathology and alcohol consumption. METHOD: Research subjects were young adult men recruited from local colleges, a trade school and the community. The risk groups included (1) a group with a biological alcoholic father and significant additional familial alcoholism (n = 106); (2) subjects with an alcoholic father, but without significant additional familial alcoholism (n = 100); and (3) a group with no paternal alcoholism and at most only one second/third-degree alcoholic relative (n = 190). Absolute daily ounces of alcohol was determined using a standard quantity-frequency scale. Prevalence of DSM-III-R personality disorders (PDs) was evaluated using the Personality Disorder Questionnaire-Revised both with and without application of an impairment and distress scale. Familial risk determination was based on agreement between four separate self-report assessments. RESULTS: The first group consumed significantly more alcohol than the other two groups, which did not differ in alcohol consumption. The first group's subjects were more likely to meet criteria for virtually all of the PD diagnoses than were the other two groups. A greater proportion of the second group's subjects qualified for various PDs than did the third group's subjects. Personality pathology was consistently or usually associated with more drinking in the first and third groups, respectively, but associated with less consumption in the second group. CONCLUSIONS: Young men with high-density familial alcoholism are at greater risk for the development of alcoholism than those with alcoholic fathers and little additional familial alcoholism. Relationships between personality pathology and alcohol consumption, and possibly the development of alcoholism, differ for the three risk groups.