Principles for being theoretical-Increasing the impact of research conducted in primary care.

Primary care is a unique research environment and is difficult to study well without disrupting the delivery of care. Recent developments in implementation and care delivery sciences have facilitated real world tests of interventions. However primary care research often misses a foundational component of quality - "being theoretical." Using cancer prevention and control as an example, this commentary advocates for the imperative of using theory to guide research and describes three principles for being theoretical. These principles, readily amenable to clinical settings, will produce studies that do more than answer "did it work?" and therefore increase the impact of primary care-based research across the cancer continuum.

Chemistry and hypoglycemic activity of N-[[(Dialkylamino)alkoxy]phenyl]benzamidines.

A series of N-[[(dialkylamino)alkoxyl]phenyl]benzamidines was synthesized and evaluated for hypoglycemic activity in the glucose-primed rat. Structure-activity relationship indicated that N'-phenyl-N-[4-[2(diisopropylamino)-ethoxy]phenyl]benzamidine dihydrobromide (7), N'-(4-chlorophenyl)-N-[4-[2-(diisopropylamino)ethoxy]phenyl]-benzamidine dihydrochloride (31), and N'-phenyl-N-[4-[(diisopropylamino)propoxy]phenyl]benzamidine dihydrobromide (11) are some of the more interesting compounds. A comparison of these hypoglycemic agents with classical standards (tolazamide, phenformin, and buformin) in several experimental models showed that the benzamidines seem to combine in one molecule some of the biological activities of the beta-cytotrophic sulfonylureas and some of the activities of the biguanides.

Chemistry and hypoglycemic activity of benzimidoylpyrazoles.

A series of benzimidoylpyrazoles was synthesized and evaluated as hypoglycemic agents. Methyl 1-(N-cyclohexylbenzimidoyl)-5-methyl-3-pyrazolecarboxylate (13) and methyl 1-[N-(4-methoxyphenyl)benzimidoyl]-5-methyl-3-pyrazolecarboxylate (33) are two of the more interesting compounds. A comparison of these benzimidoylpyrazoles with classical standards (tolazamide, phenformin, and buformin) in several experimental models show that these compounds seem to combine in one molecule some of the biological activities of the beta-cytotrophic sulfonylureas and some of the activities of the biguanides. A synthetic scheme for the preparation of the benzimidolypyrazoles and a preliminary structure-activity relationship are presented.

Preliminary observations of sildenafil treatment for erectile dysfunction in dialysis patients.

Erectile dysfunction is common in dialysis patients. We report our experience with sildenafil citrate in patients undergoing dialysis therapy. Male subjects attending the Outpatient Dialysis Unit at the University of Pennsylvania (Philadelphia, PA) who were prescribed sildenafil by their primary physician or nephrologist were asked to complete the International Index of Erectile Function before their first dose of sildenafil and after at least 4 weeks of therapy. Subjects' mean age was 50.3 +/- 14.63 (SD) years. Ninety-three percent of the subjects were black. Based on a global efficacy question, 66.7% of the subjects believed that treatment had improved their erections. Subjects reported no increase in the sexual desire domain despite experiencing a significant increase in erectile function, orgasmic function, and satisfaction with intercourse. Sildenafil was well tolerated in a selected group of patients who reported improved sexual function with no major adverse effects.

Dramatic recovery of renal function after 6 months of dialysis dependence following surgical correction of total renal artery occlusion in a solitary functioning kidney.

Revascularization of renal artery stenosis for the treatment of hypertension is an established procedure. In selected clinical scenarios, successful revascularization procedures may preserve or restore renal function. We present a 31-year-old man who underwent successful renal revascularization of a solitary functioning kidney after being dialysis dependent for approximately 190 days. He had dramatic improvement of renal function and has remained off dialysis since his surgery 18 months ago. He continues to have severe but controllable hypertension.

Is the volume of distribution of digoxin reduced in patients with renal dysfunction? Determining digoxin pharmacokinetics by fluorescence polarization immunoassay.

STUDY OBJECTIVE: To determine digoxin pharmacokinetics in subjects with different degrees of renal function using fluorescence polarization immunoassay (FPIA), which is associated with less interference from digoxin-like immunoreactive substances (DLIS) than radioimmunoassay. SETTING: University hospital clinical research center. PARTICIPANTS: Eighteen subjects (mean age 44 yrs) with different degrees of renal function: group 1, creatinine clearance (Clcr) below 10 ml/minute; group 2, Clcr 10-50 ml/minute; and group 3, Clcr greater than 50 ml/minute (6 patients in each group). INTERVENTION: Over 5-7 days, 15 serum samples were collected after a single intravenous dose of digoxin 7 or 10 micrograms/kg actual body weight (WT) for serum concentration measurements by FPIA. Two-compartment pharmacokinetic parameters (zero-time intercept of the concentration-time curve of the initial distribution phase [A], zero-time intercept of the concentration-time curve of the terminal elimination phase [B], initial distribution phase constant [alpha], terminal elimination rate constant [beta], volume of distribution in the central compartment [Vc] and at steady state [Vss], total body clearance [Cl], mean residence time [MRT], area under the concentration-time curve [AUC]) were determined using a nonlinear least squares regression program. MEASUREMENTS AND MAIN RESULTS: No significant differences were found among groups for A, B, alpha, beta, beta-half-life Vc/WT, MRT, AUC, and Cl/WT. Significant differences were observed in Vss/WT (4.8 +/- 1.0, 6.6 +/- 0.5, 6.4 +/- 0.7 L/kg) between group 1 versus group 2 and group 1 versus group 3 (p < 0.01). Measured Clcr was correlated with Cl (r2 = 0.40, p < 0.01), Cl/WT (r2 = 0.29, p < 0.05), Vss (r2 = 0.35, p = 0.01), and Vss/WT (r2 = 0.24, p < 0.05). CONCLUSION: This study confirmed that Vss is smaller in patients with chronic renal failure (Clcr < 10 ml/min) than those without chronic renal failure. Therefore, previous recommendations that lower digoxin loading doses should be administered in patients with renal failure are applicable to digoxin serum concentration monitoring using FPIA.

Staff security and work pressure: contrasting patterns of stability and change across five dialysis units.

Differences among clinical care units in social dynamics and social organization are associated with differences in the clinical course of patients with a range of chronic illness. These differences are also associated with well-being of staff members. Recent attention has focused on understanding these differences among units with an eye towards correcting deficiencies and enhancing strengths of clinical care units. The current study sought to delineate the effect of social and organizational dynamics unique to each unit on staff perceptions of the security of their relationships with other staff and their perceived work pressure. The unit as a major source of differences among staff subjects was compared with the impact of ethnic identity, of work in the morning shift vs other shifts, and of professional role. Results confirmed that unit membership was, by far, the most important correlate of staff perceptions of the unit, particularly those concerning security of relationships with others and perceived work pressure. Moreover, the results suggested that unit differences in perceived security were due to differences among units in long standing turmoil within the unit or long standing problematic ties between the unit and the larger institution which controls it. However, perceived work pressure seems more transient and may reflect the challenge of shorter-term fluctuations in the demands of patient care.

Diabetic nephropathy.

Diabetic nephropathy is the most common cause of end-stage renal disease (ESRD) and accounts for 35% of the ESRD population in the United States. It results in considerable morbidity, mortality, and expense. The average cost of managing one diabetic patient with ESRD is approximately $50,000 a year. Over the last decade, several advances in the management of diabetic nephropathy have allowed physicians to intervene and retard the progression of renal failure in patients with diabetic nephropathy. Stalling the progression of renal failure allows patients to maintain a superior quality of life and saves society millions of dollars that can be allocated to other aspects of health care. The prevalence of diabetes mellitus continues to increase. With the continued advances in medical technology and care, persons with this disease will live longer, and the incidence of diabetic nephropathy will increase. Primary care physicians will have the most frequent contact with these patients and therefore will have the greatest potential to favorably affect their clinical course. This review focuses on the therapeutic interventions available to delay the progression of diabetic nephropathy. Clinicians should strive to secure euglycemia and obtain optimal blood pressure control in their patients. The unique renal-protective effects of angiotensin-converting enzyme inhibitors will be reviewed, as will the salutary effects of a low-protein diet, normalizing serum cholesterol, and the cessation of smoking. The optimal timing of dialysis access placement and the initiation of dialysis and transplantation will also be discussed.

Perceived and actual breast cancer risk: optimistic and pessimistic biases.

Perceived risk can influence health behaviors. Studies using various populations and breast cancer risk bias assessment methods have identified both risk over- and underestimation. Among 1803 women in primary care settings, 47 percent were at average epidemiologic risk (Gail calculated relative risk ±50 percent of age-adjusted population average) and 55 percent perceived themselves to be at average risk (compared to same-age others) but there were mismatches or 'biases': 31 percent underestimated personal risk; 26 percent overestimated. Multiple logistic regression revealed that smokers were more likely to overestimate risk. Overestimation decreased with more education. Mammography use did not independently predict perception bias but, among never-screened women aged over 40 years, those contemplating mammograms were most likely to overestimate risk; precontemplators were most likely to underestimate. Implications for research and intervention are discussed.

Opportunities for alcohol screening and counseling in primary care.

BACKGROUND: The physician can be an important part of a comprehensive strategy to assist persons with alcohol problems. This study was designed to contribute to the development of physician-initiated brief interventions for patients with alcohol problems by incorporating into an existing screening instrument questions that solicit information relevant to behavior change strategies. METHODS: Adult patients from 12 family practices in North Carolina (N = 2716) completed a self-administered questionnaire assessing alcohol consumption and other health-related behaviors. Alcohol problems were assessed using the four-item CAGE (Have you ever felt you should cut down on your drinking? Have people annoyed you by criticizing your drinking? Have you ever felt bad or guilty about your drinking? Have you ever had a drink first thing in the morning to steady your nerves, or to get rid of a hangover?). For this study, CAGE was adapted to address only the past 12 months. Patient interest in reducing the amount of alcohol consumed was measured using the Transtheoretical Model developed by Prochaska and colleagues. Patients were also asked about their motives for and barriers to reducing consumption. RESULTS: Five percent of all patients and 9% of patients who reported drinking alcohol gave positive responses on at least two CAGE items. Patients with three or four positive CAGE responses were 74% more likely to report an interest in reducing alcohol consumption than were those with one or two. Intrinsic reasons were the most important motives for reducing consumption. No pattern was found in barriers. CONCLUSIONS: We found that in the management of patients with alcohol-related problems, there are many clinical opportunities for patient counseling and referral in the family practice setting. Individually tailored brief interventions that take into consideration the patient's interest in, motives for, and barriers to reducing alcohol consumption are likely to be successful for the family practice physician.

The effects of computer-tailored smoking cessation messages in family practice settings.

BACKGROUND: Many conventional health education materials, such as pamphlets and booklets, are designed to reach as wide an audience as possible; they are therefore often lengthy and contain information irrelevant to many consumers. Computer technologies allow sophisticated tailoring of messages targeted to individual patients and free of irrelevant information. METHODS: In two studies in North Carolina (study 1, N = 51; study 2, N = 197), adult cigarette smokers were identified from a cohort of family practice patients. Cigarette consumption, interest in quitting smoking, perceived benefits and barriers to quitting, and other characteristics relevant to smoking cessation were collected. Based on this information, smoking cessation letters were tailored by computer to individuals. Smokers were randomly assigned to experimental (tailored health letters) or comparison groups (generic health letter in study 1, no health letter in study 2). Smoking status was assessed again at 4 months (study 1) or 6 months (study 2). RESULTS: Both studies found statistically significant positive effects of tailored health letters among moderate to light smokers. In study 1, 30.7% reported quitting after 6 months vs 7.1% in the control group (P < .05); in study 2, 19.1% vs 7.3% (P < .05). CONCLUSIONS: Results from both studies indicate positive effects of computer-tailored smoking messages among moderate to light smokers. These findings are consistent with the focus of our computer-tailored program on psychological and behavioral factors related to smoking cessation. Smoking cessation outcomes may be enhanced by combining tailored messages with nicotine replacement therapies to treat physical dependency. Methods of tailoring health messages and incorporating the results into family practice are described.

Effect of varying dialysate bicarbonate concentration on serum phosphate.

Hyperphosphatemia is practically a universal problem in patients with chronic renal failure. Conventional treatment of hyperphosphatemia in this situation is either only partially effective or may be associated with potentially serious adverse effects. The authors examined the effect of inducing a metabolic alkalosis on serum phosphate in chronic hemodialysis patients by increasing the concentration of bicarbonate in dialysate. Seven patients participated in the study. Each patient was on dialysis for 2 weeks with each of 2 dialysate regimens. Regimen A contained a bicarbonate concentration of 25 mEq/L and Regimen B a bicarbonate concentration of 40 mEq/L. Despite Regimen B resulting in a significant increase in predialysis and postdialysis serum bicarbonate concentration and arterial pH, no significant difference in serum phosphate was demonstrated after 2 weeks of therapy.

Systemic lupus erythematosus and the syndrome of inappropriate secretion of antidiuretic hormone.

The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) has been reported rarely in systemic lupus erythematosus (SLE) with central nervous system disease. Previous case reports linking SIADH with lupus have either not documented clearly that SLE was the sole cause of the problem, or have not demonstrated a correlation between indicators of lupus activity and the onset and resolution of antidiuretic hormone secretion. We describe a case in which SLE was the sole contributor to the initiation of SIADH and where other evidence of lupus activity correlated temporally with inappropriate antidiuretic hormone secretion.

Measurement of hemodialysis access recirculation: a two-needle method at the start of dialysis.

Conventional methods of measuring recirculation in hemodialysis access include a three site method performed during dialysis, and a two site technique conducted at the end of a hemodialysis treatment. This study describes a two site procedure performed at the beginning of a hemodialysis session. Blood samples are drawn from the arterial side of the hemodialysis access immediately prior to hemodialysis (AIPD), and from the same arterial line (A+5) and venous line (V+5) when maximal blood flows are reached 5 min after starting hemodialysis. Blood urea nitrogen (BUN) is measured in these samples, and the results entered into the formula AIPD - A+5/AIPD - V+5 X 100% to calculate the percent recirculation. Percent recirculation calculated by this method compared favorably with, and may hold several advantages over conventional techniques.

Hemodialysis vascular access morbidity.

Complications associated with hemodialysis vascular access represent one of the most important sources of morbidity among ESRD patients in the United States today. In this study, new data on the magnitude and growth of vascular access-related hospitalization in the United States is presented, demonstrating that the costs of this morbidity will soon exceed $1 billion per yr. This study also reviews published literature on the morbidity associated specifically with native arteriovenous fistulae, polytetrafluoroethylene bridge grafts, and permanent central venous catheters. Next, new information on the changing patterns of vascular access type in the United States is presented, demonstrating the continuing evolution of medical practice away from the use of arteriovenous fistulae in favor of more reliance on synthetic bridge grafts. Based on these data, a discussion is provided of the tradeoffs among the most commonly available modalities of vascular access today. Although radial arteriovenous fistulae continue to represent the optimal access modality, the appropriate roles for brachial arteriovenous fistulae, synthetic bridge grafts, and central venous catheters are less certain because of inadequate data on the long-term function of the first and the high rates of complications associated with the latter two. To reduce vascular access-related morbidity, strategies must be developed not only to prevent and detect appropriately early synthetic vascular access dysfunction, but to better identify the patients in a whom radial arteriovenous fistula is a viable clinical option.

Do cigarette smokers have unrealistic perceptions of their heart attack, cancer, and stroke risks?

This study examined whether perceived risks of heart attack, cancer, and stroke were higher among smokers than nonsmokers; whether smokers were more likely to underestimate these risks; and the demographic correlates of unrealistic risk estimation among smokers. Two thousand seven hundred eight-five patients from 12 North Carolina family practices completed a questionnaire including a health risk appraisal and questions concerning smoking behavior and perceived risks of heart attack, cancer, and stroke. While most smokers accurately perceived their health risks to be greater than nonsmokers', smokers were also more likely to underestimate their risks. This optimistic distortion of risk was associated with age, gender, and education levels. Smokers may not yet understand the magnitude of health risks posed by smoking. These data suggest the need for renewed attention to perceptions of the health risks of smoking. As long as smokers underestimate their risks, they underestimate the imperative to quit.

Behavioral and biochemical indices of compliance in hemodialysis patients.

Noncompliance has been implicated in modifying morbidity and mortality in end stage renal disease patients; however, the data are conflicting, and measurement of compliance has been difficult. Traditional measurements of compliance include serum potassium (K) and phosphorus (P) concentrations, and interdialytic fluctuations in weight gain (IWG). This study correlated three indices: 1) Adequacy of dialysis (Kt/V); 2) protein ingestion (PCR); and 3) the percentage of time dialyzed compared with the total dialysis time prescribed (% Time) with the traditional measurements of compliance. Correlations were calculated among pre- and post-BUN (blood urea nitrogen), Kt/V, K and P, PCR, IWG, and % Time. As expected, BUN levels correlated with Kt/V, K, P, PCR, IWG, and % Time. Protein ingestion correlated with K and IWG, but not with % Time. Adequacy of dialysis correlated with P levels, but not with PCR, WG, or % Time. Phosphorus correlated with pre- and post-BUN, Kt/V, and % Time, but not with K. Potassium, P, and IWG did not correlate internally. The authors conclude that standard biochemical measures of compliance reflect different compliance behaviors (dietary selection and restriction, restriction of fluid and salt intake, and adherence to medication regimens). Percent time may be a powerful, independent measure of patient compliance with the dialysis regimen.

A controlled clinical trial of angiotensin-converting enzyme inhibition in type I diabetic nephropathy: study design and patient characteristics. The Collaborative Study Group.

A placebo-controlled, double-blind clinical trial has been initiated to determine whether angiotensin-converting enzyme inhibitor (ACEI) therapy with captopril (25 mg three times daily) slows the progressive loss of renal function in patients with type 1 diabetes mellitus. Entry criteria include; (1) ages 18 to 50 yr; (2) onset of insulin-dependent diabetes before the age of 30 yr, insulin dependent for at least 7 yr; (3) 24-h urine protein excretion > 500 mg, plus: (a) diabetic retinopathy or (b) if no retinopathy, a renal biopsy diagnosis of diabetic nephropathy; (4) serum creatinine (SCr) < 2.5 mg/dL; (5) informed consent. Patients follow strict medical management protocols. Systemic blood pressure is controlled to predefined goals (< 140-90 mm Hg). The primary outcome of the Study is a doubling of the patients' entry SCr to at least 2 mg/dL confirmed by a > 50% decrease in GFR by radioactive iothalamate clearance technique. Baseline characteristics of the cohort at entry into the Study are (mean +/- SD): male/female, 52%/48%; age, 35 +/- 8 yr; duration of diabetes, 21 +/- 7 yr; duration of proteinuria, 2.8 +/- 3.3 yr; duration of retinopathy, 4.5 +/- 4.1 yr; 50% of cohort presented with hypertension, duration, 4 +/- 4.7 yr; blood pressure, 139/86 +/- 19/12; SCr, 1.35 +/- 0.44 mg/dL; GFR 78 +/- 32 mL/min; BUN, 24 +/- 11 mg/dL; proteinuria, 3.1 +/- 3.3 g/day; cholesterol, 236 +/- 50 mg/dL; total glycosylated hemoglobin, 11.1 +/- 2.1%.(ABSTRACT TRUNCATED AT 250 WORDS)