Reliability of counting actinic keratoses before and after brief consensus discussion: the VA topical tretinoin chemoprevention (VATTC) trial.

OBJECTIVE: To assess the reliability of counts of actinic keratoses (AKs) and the effect of a brief joint discussion of discrepancies on that reliability. DESIGN AND INTERVENTION: Seven dermatologists independently counted AKs on the face and ears before and after a brief joint discussion of discrepancies. SETTING AND PATIENTS: A volunteer sample of 9 patients from the ongoing VA (Department of Veterans Affairs) Topical Tretinoin Chemoprevention (VATTC) Trial. All participating individuals are veterans and have had 2 or more keratinocyte carcinomas (basal or squamous cell carcinoma) in the 5 years before enrollment in the study. MAIN OUTCOME MEASURE: Standard deviation of estimates of the Poisson regression parameter for the dermatologists. RESULTS: Substantial variation was found among the dermatologists in their AK counts. The SD of the parameter estimates for the dermatologists decreased from 0.45 to 0.24 after the brief joint discussion, a 47% decrease (P =.076). The variation attributable to the dermatologists also decreased substantially (chi(2)(6) decrease, 94 to 12). CONCLUSIONS: Actinic keratoses are common, and there is a continuous spectrum of lesions that ranges from sun-damaged skin to squamous cell carcinoma in situ. Clinical distinguishing features may be difficult to delineate precisely. Counts of AK are commonly performed, but appear to be unreliable, even when performed by experienced dermatologists. Joint discussion of discrepancies may enhance the reliability of these counts, although substantial variation remains. Research that relied on these counts must be reevaluated in light of the marked variation among expert observers. Future studies should consider measures to assess and enhance reliability.

Dental endosseous implant assessments in a type 2 diabetic population: a prospective study.

Diabetes mellitus, a prevalent disorder worldwide, is associated with systemic adverse sequelae, such as wound healing alterations, which may affect osseointegration of dental implants. This prospective multicenter study assessed the success of 2-stage endosseous root-form implants (3 different implant systems) placed in the mandibular symphysis of 89 male type 2 diabetic subjects. The implants were uncovered approximately 4 months after placement, restored with an implant-supported, Hader bar clip-retained overdenture, and maintained at scheduled follow-up data collection examinations for 60 months after loading. Sixteen (9.0%) of the 178 implants failed. Life table methods calculated implant survival at approximately 88%, from prosthesis placement through the 60-month follow-up, and at approximately 90% from implant placement through the observation period. No implants failed between surgical placement and uncovering, 5 failed at uncovering, 7 failed after uncovering before prosthesis placement, and 4 failed after prosthesis placement. Fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) values were determined before implant placement (baseline) and approximately 4 months later at surgical uncovering (follow-up). The 5-year implant outcomes (successes versus failures) were analyzed against the following predictor variables: (1) baseline and follow-up FPG values, (2) baseline and follow-up HbA1c values, (3) subject age, (4) duration of diabetes (years), (5) baseline diabetic therapy, (6) smoking history, and (7) implant length. Regression analysis found only duration of diabetes (P < .025) and implant length (P < .001) to be statistically significant predictors of implant failure. There was no statistically significant difference in failure rates between the 3 different implant systems used. This study supports the use of dental implants in type 2 diabetic patients.

Prevention and Treatment of Hypertension Study (PATHS): effects of an alcohol treatment program on blood pressure.

OBJECTIVE: To determine whether blood pressure is reduced for at least 6 months with an intervention to lower alcohol intake in moderate to heavy drinkers with above optimal to slightly elevated diastolic blood pressure, and whether reduction of alcohol intake can be maintained for 2 years. DESIGN: A randomized controlled trial. METHODS: Six hundred forty-one outpatient veterans with an average intake of 3 or more alcoholic drinks per day in the 6 months before entry into the study and with diastolic blood pressure 80 to 99 mm Hg were randomly assigned to a cognitive-behavioral alcohol reduction intervention program or a control observation group for 15 to 24 months. The goal of the intervention was the lower of 2 or fewer drinks daily or a 50% reduction in intake. A subgroup with hypertension was defined as having a diastolic blood pressure of 90 to 99 mm Hg, or 80 to 99 mm Hg if recently taking medication for hypertension. RESULTS: Reduction in average weekly self-reported alcohol intake was significantly greater (P<.001) at every assessment from 3 to 24 months in the intervention group vs the control group: levels declined from 432 g/wk at baseline by 202 g/wk in the intervention group and from 445 g/wk by 78 g/wk in the control group in the first 6 months, with similar reductions after 24 months. The intervention group had a 1.2/0.7-mm Hg greater reduction in blood pressure than the control group (for each, P = .17 and P = .18) for the 6-month primary end point; for the hypertensive stratum the difference was 0.9/0.7 mm Hg (for each, P = .58 and P = .44). CONCLUSIONS: The 1.3 drinks per day average difference between changes in self-reported alcohol intake observed in this trial produced only small nonsignificant effects on blood pressure. The results from the Prevention and Treatment of Hypertension Study (PATHS) do not provide strong support for reducing alcohol consumption in nondependent moderate drinkers as a sole method for the prevention or treatment of hypertension.

Co-morbidity of lifetime psychiatric disorder among male alcoholic patients.

The lifetime co-morbidity of major psychiatric disorders among male alcoholics was examined with the structured Psychiatric Diagnostic Interview (PDI), which was administered to 928 patients undergoing alcoholism treatment at six Veterans Administration Medical Centers. Thirty-eight percent were positive for alcoholism only; 62% fulfilled inclusive lifetime diagnostic criteria for at least one other additional psychiatric syndrome. Thirty percent satisfied criteria for one additional syndrome; 16% for two additional syndromes; 12% for three; and 4% for four or more disorders in addition to alcoholism. Depression and antisocial personality were the most frequently identified co-occurring syndromes (36% and 24%, respectively) followed by drug abuse and mania (17% each). The additional psychiatric syndromes in this sample were clearly not randomly distributed; instead, certain disorders tended to cluster together such as: drug abuse and antisocial personality; mania and depression; depression and anxiety disorder; and schizophrenia and affective disorder. Implications for classification and treatment are discussed.

Prevention and Treatment of Hypertension Study (PATHS). Rationale and design.

Alcohol consumption has been recognized as an important correlate of blood pressure in many epidemiologic studies, but few interventional studies have been conducted to examine the effect of a reduction in alcohol intake on blood pressure. Because these studies have usually included few subjects and been of short duration, the National Heart, Lung, and Blood Institute (NHLBI), the National Institute on Alcohol Abuse and Alcoholism (NIAAA), and the Veterans Affairs (VA) Cooperative Studies Program have initiated a randomized, controlled, multicenter trial to determine whether blood pressure and left ventricular mass are lowered over 6 months of alcohol moderation in non-dependent moderate to heavy drinkers (three or more drinks per day average but not alcohol dependent) with above-average normal (80 to 89 mm Hg) and mildly hypertensive (90 to 99 mm Hg) levels of diastolic blood pressure, and whether a reduction in alcohol intake can be maintained for 2 years. Eligible veterans are randomized to either an alcohol reduction intervention or a control observation group at seven clinical sites. The projected sample size is 580 participants. Alcohol intake is assessed by self-report using a retrospective diary (Chronological Drinking Record) and by various biochemical markers, including apolipoproteins, HDL cholesterol (and subfractions), and carbohydrate deficient transferrin, analyzed at a central laboratory. The alcohol intervention technique is a cognitive-behavioral program, the intensive phase of which consists of six counseling sessions over 3 months. Echocardiograms are obtained at baseline and 6 months after randomization. This trial has important implications for both the prevention and treatment of hypertension.

Implants for type II diabetic patients: interim report. VA Implants in Diabetes Study Group.

One hundred seventy-eight implants from three systems were placed in 89 type II diabetic patients at 13 Department of Veterans Affairs medical centers. Four failures (2.2 percent) were found at uncovering. The failure rate increased to 7.3 percent at the end of 1 year (nine additional failures). Study patients will be monitored for an additional 4 years. Initial results suggest that type II diabetic patients can be considered for dental implant therapy.

A comparison of familial and nonfamilial male alcoholic patients without a coexisting psychiatric disorder.

Both family history of alcoholism and the presence of additional psychiatric disorder in male alcoholic patients are associated with an earlier onset of problem drinking, greater alcoholism severity and poorer clinical outcomes. To assess the relative contribution of family history alone, a sample of 212 male alcoholics not positive for any other psychiatric disorder was selected and divided into those with a family history of alcoholism (FH+) or no family history of alcoholism (FH-) among first degree relatives. Although FH+ alcoholics reported a younger age of onset of problem drinking and greater severity of some alcohol-related sequelae, the differences were not as extensive or pronounced as those found in a previous study of a sample of psychiatrically heterogeneous patients (Penick et al., 1987). A bi-dimensional typology of alcoholism incorporating both additional psychiatric diagnoses and a positive family history of alcoholism is suggested.

Subtyping male alcoholics by family history of alcohol abuse and co-occurring psychiatric disorder: a bi-dimensional model.

Six studies of 568 alcoholics in treatment are summarized to illustrate the interactive effects of familial alcoholism, other forms of family psychopathology and the lifetime prevalence of additional psychiatric disorder on the onset and course of male alcoholism. A family history of alcoholism as well as additional co-occurring psychiatric syndromes were associated with (1) earlier onsets of problem drinking, (2) a more virulent course and (3) greater heterogeneity of psychopathology among first degree relatives. A bi-dimensional method of classifying male alcoholics is proposed which combines a family history of abusive drinking and the presence or absence of co-morbid psychiatric disorders. Implications for the clinical researcher and practitioner are briefly discussed.

V.A. Cooperative Study of antiplatelet agents in diabetic patients after amputation for gangrene: unobserved, sudden, and unexpected deaths.

We report on unobserved, sudden, and unexpected deaths that occurred in a randomized multicenter trial. The long-term effects of aspirin plus dipyridamole on major vascular outcome variables were studied in 231 non insulin-dependent diabetic men with either a recent amputation for gangrene or active gangrene. Depending upon the definition of sudden death used, there were 14, 22, or 17 deaths in the drug group versus 6, 6, or 3 deaths in the placebo group (p = 0.04, 0.001, or 0.001, respectively). Total deaths from atherosclerotic vascular disease or deaths from all causes did not differ in the two treatment groups. Since this finding of a secondary end point is found only after multiple analyses of the data, it must be interpreted with caution. However, it is suggested that further studies on effects of antiplatelet agents on sudden deaths should be performed.

Primary and secondary depression in alcoholic men: an important distinction?

The primary-secondary depression distinction was investigated in male alcoholic patients from five Veterans Administration Medical Centers. The Psychiatric Diagnostic Interview, a DSM-III-compatible, criterion-referenced, structured interview, was administered to 565 patients admitted to the Alcoholism and Drug Treatment Units. Seventy-eight patients (13.8%) who exhibited only alcoholism and depression were divided into three subgroups based on the temporal onset of depression relative to the onset of alcoholism. Although few statistical differences were found, observed trends suggested more impairment in alcoholic patients with primary depression than in those with concurrent or secondary depression. The findings indicate that the primary-secondary depression distinction may have important clinical relevance and should be made whenever possible.

A comparative study of familial alcoholism.

In a large multicenter study of 568 male alcoholics, structured interviews were used to compare the clinical characteristics of patients with a positive (65%) or negative (35%) family history of abusive drinking among first degree relatives. Alcoholics with a positive family history were found to have: an earlier onset of alcoholism, greater alcoholic severity, more medical and legal problems, a broader range of treatments, an increased lifetime prevalence of additional psychiatric disorders and a greater diversity of psychiatric disturbance among biological relatives. The degree of psychiatric heterogeneity in the patients roughly corresponded to the degree of psychiatric heterogeneity in their families. Assortative mating was proposed as a possible mechanism to account for clinical differences between the familial and nonfamilial alcoholic.

The "constant intake rate" assumption in interim recruitment goal methodology for multicenter clinical trials.

A primary concern of any multihospital clinical trial is the recruitment of a predetermined number of patients during a prespecified interval of time. In several recent papers a Poisson based model was used to estimate the time needed to recruit a predetermined number of patients and the probabilities of recruiting specified fractions of the sample during subintervals. The Poisson model requires the assumption that patients be recruited at a constant rate over the entire length of the interval. In this paper we test the adequacy of this model and assumption using patient intake data from nine multihospital VA clinical trials and propose an alternative Bayesian model.

Veterans Administration Cooperative Study on antiplatelet agents in diabetic patients after amputation for gangrene: II. Effects of aspirin and dipyridamole on atherosclerotic vascular disease rates.

We report the results of a randomized multicenter clinical trial on the effects of aspirin plus dipyridamole versus placebo on major vascular end points in 231 non-insulin-dependent diabetic men with either a recent amputation for gangrene or active gangrene. Primary end points were death from atherosclerotic vascular disease plus amputation of the opposite extremity for gangrene. There were 24 atherosclerotic deaths in the drug treatment group (21.8%) and 23 in the placebo group (19.0%). There were 22 patients in the drug treatment group (20.0%) and 29 patients in the placebo group (24.0%) with opposite-side amputations. Survival curve analyses revealed little difference between these groups for major vascular end points, total mortality, all amputations, or myocardial infarctions. The most noteworthy group difference was observed for cerebrovascular end points (strokes and transient ischemic attacks), with an incidence of 8.2% (9 patients) in the drug treatment group and 19.0% (23 patients) in the placebo group. We conclude from this study that antiplatelet agents have no effect on the primary vascular end points, vascular deaths and/or amputation of the opposite extremity, in this population. Similarly, no effects were seen on secondary vascular end points, except for a suggestion of protection versus strokes and transient ischemic attacks. However, this finding must be interpreted with caution, since it is a secondary end point and was found only after multiple analyses of the data.

VA cooperative study on antiplatelet agents in diabetic patients after amputation for gangrene. IV. Issues in design, interpretation, and analysis.

This paper review some of the issues faced by the investigators involved in a VA Cooperative Study on Antiplatelet Agents in Diabetic Patients after Amputation for Gangrene. The study was a negative one, and some of the reasons for this are considered. In addition, suggestive results in two subgroups, cerebrovascular disease and unexpected, sudden, or unobserved deaths, were found. The implications and interpretation of these findings are discussed.

V.A. Cooperative Study on antiplatelet agents in diabetic patients after amputation for gangrene: III. Definitions and review of design and baseline characteristics.

This report summarizes the major design features, methods, and baseline characteristics of patients enrolled in a Veterans Administration Cooperative Study. In eleven V.A. centers, 231 male diabetic patients who had either a recent amputation for gangrene (N = 207) or active gangrene (N = 24) were randomly assigned to a group which received aspirin (325 mg t.i.d.) plus dipyridamole (75 mg t.i.d.) (N = 110) or two placeboes t.i.d. (N = 121). Major end point were vascular death and amputation of the opposite extremity for gangrene. Forty-one percent of the 563 patients screened were enrolled during a 39 month period. Enrollment errors were found in 8.7%. Historically, the two groups were well matched regarding the following variables: age, duration of diabetes, insulin therapy, previous oral agent therapy, hypertension, myocardial infarction, congestive heart failure, renal disease, sensory neuropathy, and smoking. The drug therapy group had an increased frequency of a history of cerebrovascular disease (19% vs 7%, p = 0.01). The groups were well matched regarding amputation site, obesity, extent of lower extremity vascular disease, retinopathy, and neuropathy upon examination. Their baseline fasting values of glucose, cholesterol, triglycerides, and creatinine were also comparable. We conclude that this study should provide definitive data on the efficacy of these antiplatelet agents in preventing further vascular disease in this patient group. It should also provide new prospective data on the natural history of vascular disease, and the association of vascular risk factors with subsequent vascular events in this patient population.

V.A. Cooperative Study on antiplatelet agents in diabetic patients after amputation for gangrene: I. Design, methods, and baseline characteristics.

This report describes the experimental design, methods, and baseline characteristics of patients enrolled in a Veterans Administration Cooperative Study on the effect of aspirin (325 mg t.i.d.) and dipyridamole (75 mg t.i.d.) (110 patients), or placebo (121 patients) on major vascular outcome variables in noninsulin-dependent diabetic patients with either a recent amputation for gangrene (n = 207) or active gangrene (n = 24). It also describes the baseline characteristics of the patients. A total of 231 patients of 563 screened (41%) were enrolled at 11 participating V.A. Medical Centers during a 39 month period. The median age at entry was 60 years, the median duration of diabetes was 10 years, and weight was 110% of desirable. All patients were men. Sixty-eight percent were treated with insulin and 32% with diet alone. Only 42% were smokers at entry, 40% had retinopathy, 61% sensory neuropathy, 42% hypertension, and 29% had a history of myocardial infarction, angina, and/or congestive heart failure. Thirteen percent had a history of cerebrovascular disease. Despite randomization, the treatment group had an increased frequency of a history of cerebrovascular disease (p = 0.01), diagnosed as stroke (p = 0.03), a finding suggesting that the treatment group was at a slightly increased risk for vascular disease upon enrollment in the study. Other baseline variables did not differ significantly between the two groups. This study should provide definitive data on the efficacy of these doses of antiplatelet agents in preventing further vascular disease in diabetic men with gangrene or recent amputation for gangrene, using death due to vascular disease and subsequent amputation of the opposite extremity for gangrene as major outcome variables. It should also give useful information on the effect of antiplatelet therapy on vascular outcome variables such as same side amputations, myocardial infarction, stroke, transient ischemic attack, retinopathy, and renal failure. Finally, the study should provide useful data on the natural history and significance of risk factors in this patient population.