Predictors of interest in taking pre-exposure prophylaxis among men who have sex with men who used a rapid HIV-testing site in Montreal (Actuel sur Rue).

OBJECTIVES: The effective use of pre-exposure prophylaxis (PrEP) as an HIV prevention strategy depends on its uptake by individuals at high risk of infection. Few Canadian data are available on interest in PrEP among men who have sex with men (MSM). This study aimed to identify predictors of interest in PrEP among MSM clients of a rapid HIV-testing site in Montreal's gay village (Actuel sur Rue). METHODS: Data were collected using a self-administered and a community agent-administered questionnaire. Among men reporting at least one male sexual partner and visiting the site between July 2012 and November 2013, we aimed to identify sociodemographic, sexual and temporal predictors of interest in taking effective PrEP with logistic regression analyses (univariate and multivariable). RESULTS: Over half (55%; n = 653) of the sample of 1179 MSM were interested in PrEP. Among the 14 variables considered in the univariate analyses, only (younger) age, (greater) number of sexual partners (in the past 3 months), being part of a serodiscordant couple (in the past 12 months), ever combining sex with drugs and temporal events were associated with interest in PrEP at P < 0.20 and were included in the multivariable analyses. In the multivariable model, only being part of a serodiscordant couple [adjusted odds ratio (aOR) 2.56; 95% confidence interval (CI) 1.44-4.58], having > 10 partners (aOR 1.73; 95% CI 1.17-2.55) and responding after the publication of Quebec's interim PrEP guidelines (aOR 1.82; 95% CI 1.22-2.71) proved significant. CONCLUSIONS: In this assessment of predictors of PrEP interest among Canadian MSM, partnering issues and the arrival of PrEP guidelines in Quebec (10 July 2013) were most closely linked to PrEP interest.

Anaesthetic effects of propofol polymeric micelle: a novel water soluble propofol formulation.

BACKGROUND: As a result of its very low water solubility, propofol is generally presented as a lipid-based formulation with well-characterized limitations. METHODS: Propofol (99.7%) was added directly to an aqueous solution of poly(N-vinyl-2-pyrrolidone)-block-poly(D,L-lactide)copolymers (PVP-PLA) block copolymers and stirred in order to obtain a clear solution. This formulation was filtered sterile and then lyophilized to its solid form Propofol-PM (propofol polymeric micelle) which reconstitutes to a propofol 1%w/v (10 mg ml(-1)) clear aqueous solution of 30-60 nm propofol-containing micelles. Population pharmacokinetic data from whole blood and plasma were obtained by administering reconstituted Propofol-PM formulations and a 1% oil in water formulation, Diprivan to male Sprague-Dawley rats (n = 40) at a dose of 10 mg kg(-1). Preliminary recovery data were obtained from a further small study. RESULTS: The pharmacokinetics were best described using a two-compartment mamillary population model, which incorporated sample matrix (blood or plasma) and propofol formulation (Diprivan) or Propofol-PM) as covariates. Sample matrix was applied to all structural model parameters as a dichotomous covariate. An influence of propofol formulation was observed for all parameters (excluding distributional clearance) but only when plasma was used for propofol quantification. In this preliminary pharmacodynamic study, there was no statistically significant difference in the timing of the recovery endpoints between the Propofol-PM formulation and Diprivan groups. CONCLUSIONS: Propofol-PM formulations produce anaesthesia in rats. Whole blood pharmacokinetics of Propofol-PM did not differ from those observed with Diprivan.

A two-decades (1975 to 1995) long experience in the incidence, in-hospital and long-term case-fatality rates of acute myocardial infarction: a community-wide perspective.

OBJECTIVES: The purpose of the present study is to describe changes over two decades (1975 to 1995) in the incidence, in-hospital and long-term case-fatality rates associated with acute myocardial infarction (AMI) from a multihospital community-wide perspective. BACKGROUND: Despite the magnitude of, and mortality associated with acute myocardial infarction (AMI), relatively limited population-based data are available to describe recent and temporal trends in the attack and case-fatality rates associated with AMI from a representative population-based perspective. METHODS: The community-based study included 5,270 residents of the Worcester, Massachusetts, metropolitan area hospitalized with confirmed initial AMI in all metropolitan Worcester, Massachusetts, hospitals (1990 census population = 437,000) in 10 one-year periods between 1975 and 1995. RESULTS: The age-adjusted incidence rates of initial AMI increased between 1975 (244 per 100,000) and 1981 (272 per 100,000), after which time these rates declined through 1995 (184 per 100,000). The crude and multivariable-adjusted in-hospital case-fatality rates exhibited a consistent decline between 1975/1978 (17.8%), 1986/1988 (17.0%) and 1993/1995 (11.7%). Although there were no statistically significant differences in the unadjusted long-term case-fatality rates of discharged hospital survivors over the periods under study, declines in the multivariable-adjusted risk of dying within the first year after hospital discharge were observed between the earliest and most recently discharged patients with AMI. CONCLUSIONS: The results of this population-based study of patients with validated initial AMI provide encouragement for efforts directed at the primary and secondary prevention of AMI given declining incidence and case-fatality rates.

Twenty-two year (1975 to 1997) trends in the incidence, in-hospital and long-term case fatality rates from initial Q-wave and non-Q-wave myocardial infarction: a multi-hospital, community-wide perspective.

OBJECTIVES: The goal of this study was to examine long-term trends in the incidence, in-hospital and long-term mortality patterns in patients with an initial non-Q-wave myocardial infarction (NQWMI) as compared with those with an initial Q-wave myocardial infarction (QWMI). BACKGROUND: Limited data are available describing trends in the incidence and mortality from an initial QWMI and NQWMI from a multi-hospital community-wide perspective. METHODS: Our study was an observational study of 5,832 metropolitan Worcester, Massachusetts residents (1990 census = 437,000) hospitalized with validated initial acute MI in all greater Worcester hospitals during 11 annual periods between 1975 and 1997. RESULTS: The incidence of QWMI progressively decreased between 1975/78 (incidence rate = 171/100,000 population) and 1997 (101/100,000 population). In contrast, the incidence of NQWMI progressively increased between 1975/78 (62/100,000 population) and 1997 (131/100,000 population). Hospital death rates were 19.5% for patients with QWMI and 12.5% for those with NQWMI. After controlling for various covariates, patients with QWMI remained at significantly increased risk for hospital mortality (adjusted odds ratio = 1.63; 95% confidence interval: 1.35, 1.97). While the hospital mortality of QWMI has progressively declined over time (1975/78 = 24%; 1997 = 14%), the in-hospital mortality for NQWMI has remained the same (1975/78 = 12%; 1997 = 12%). These trends remained after adjusting for potentially confounding prognostic factors. The multivariable adjusted two-year mortality after hospital discharge declined over time for patients with QWMI and NQWMI. CONCLUSIONS: Despite impressive declines in the incidence, in-hospital and long-term mortality associated with QWMI, NQWMI is increasing in frequency and has the same in-hospital mortality now as it did 22 years ago.

Twenty year trends (1975-1995) in the incidence, in-hospital and long-term death rates associated with heart failure complicating acute myocardial infarction: a community-wide perspective.

OBJECTIVES: To describe from a population-based perspective, recent and temporal (1975-1995) trends in the incidence, in-hospital and postdischarge case-fatality rates of heart failure (HF) complicating acute myocardial infarction (AMI). BACKGROUND: Extremely limited data are available describing the incidence and case-fatality rates associated with HF complicating AMI from a community-wide perspective. METHODS: The medical records of 6,798 residents of the Worcester, Massachusetts metropolitan area with validated MI and without previous HF hospitalized in 10 annual periods between 1975 and 1995 were reviewed. RESULTS: The proportion of AMI patients developing HF during hospitalization declined between 1975-1978 (38%) and 1993-1995 (33%) (p < 0.001). After controlling for potentially confounding factors, the risk of developing HF declined progressively, albeit modestly, over time. In-hospital case-fatality rates of patients with AMI complicated by HF declined by approximately 46% between 1975-1978 (33%) and 1993-1995 (18%) (p < 0.001). Improving trends in hospital survival were observed after adjusting for potentially confounding prognostic factors. The one-year post-discharge mortality rate for hospital survivors of HF did not change over the 20-year period under study, even after controlling for additional prognostic characteristics. CONCLUSIONS: The results of this community-wide study suggest encouraging declines in the incidence and hospital death rates associated with HF complicating AMI. Continued efforts need to be directed towards the prevention of HF given the magnitude of this clinical syndrome. Efforts of secondary prevention are needed to identify and improve the treatment of patients with symptomatic left ventricular dysfunction following AMI given the lack of improvement in the long-term prognosis of these patients.

Circulating monocyte-platelet aggregates are an early marker of acute myocardial infarction.

OBJECTIVES: We investigated whether elevated levels of circulating monocyte-platelet aggregates (MPA) can be used to identify patients with acute myocardial infarction (AMI). BACKGROUND: Commonly used blood markers of AMI reflect myocardial cell death, but do not reflect the earlier pathophysiologic processes of plaque rupture, platelet activation and resultant thrombus formation. Circulating MPA form after platelet activation. METHODS: In a single center between October 1998 and November 1999, we measured circulating MPA in a blinded fashion by whole blood flow cytometry in 211 consecutive patients who presented to the emergency department (ED) with chest pain and were admitted to rule out AMI. Acute myocardial infarction was diagnosed by a CK-MB fraction greater than three times control. RESULTS: Patients with AMI (n = 61), as compared with those without AMI (n = 150), had significantly higher numbers of circulating MPA (11.6 +/- 11.4 vs. 6.4 +/- 3.6, mean +/- SD, p < 0.0001). After controlling for age, the adjusted odds of developing AMI for patients in the 2nd, 3rd and 4th quartiles of MPA, in comparison with patients in the lowest quartile (odds ratio = 1.0), were 2.1 (95% confidence interval [CI]: 0.7, 6.8), 4.4 (95% CI: 1.5, 13.1) and 10.8 (95% CI: 3.6, 32.0), respectively. The number of circulating MPA in patients with AMI presenting within 4 h of symptom onset (14.4) was significantly greater than those presenting after 4 h (9.4) and after 8 h (7.0), (p < 0.001). Of the 61 patients with AMI, 35 (57%) had a normal creatine kinase isoenzyme ratio at the time of presentation to the ED, but had high levels of circulating MPA (13.3). CONCLUSIONS: Circulating MPA are an early marker of AMI.

Decade-long trends and factors associated with time to hospital presentation in patients with acute myocardial infarction: the Worcester Heart Attack study.

BACKGROUND: Duration of prehospital delay in patients with acute myocardial infarction (AMI) is receiving increasing attention given the time-dependent benefits associated with prompt use of coronary reperfusion strategies. OBJECTIVE: To examine trends (1986-1997) in time to hospital presentation and factors associated with prolonged delay in a community-wide study of patients with AMI. METHODS: Longitudinal study of 3837 residents of the Worcester, Mass, metropolitan area hospitalized with AMI in 7 one-year periods between 1986 and 1997 in whom information about prehospital delay was available. RESULTS: The mean, median, and distribution of delay times exhibited either inconsistent or no changes over time. In 1986, the mean and median prehospital delay times were 4.1 and 2.2 hours, respectively; these times were 4.3 and 2.0 hours, respectively, in patients hospitalized in 1997. Overall, with no significant differences noted over time, approximately 44% of patients with AMI presented to area-wide hospitals in less than 2 hours after the onset of acute coronary symptoms. Increasing age, history of angina or diabetes, onset of symptoms in the afternoon or evening, and hospitalization in the most recent study year (1997) were significantly associated with delays of more than 2 hours in seeking hospital care after controlling for a variety of factors that might affect delay. CONCLUSIONS: The results of this population-based study suggest that a large proportion of patients with AMI continue to exhibit prolonged delay. The characteristics of many of these individuals can be identified in advance for targeted educational efforts. Arch Intern Med. 2000;160:3217-3223.

Use of aspirin, beta-blockers, and lipid-lowering medications before recurrent acute myocardial infarction: missed opportunities for prevention?

BACKGROUND: For patients who have had a previous myocardial infarction (MI), the use of aspirin, beta-blockers, and lipid-lowering agents reduces the risk of recurrent MI and death. OBJECTIVE: To examine trends in and determinants of receipt of these 3 medications before hospitalization for recurrent acute MI (AMI). METHODS: The study population consisted of 1710 patients with a previous history of MI hospitalized with a validated recurrent AMI in all hospitals in Worcester, Mass, during 1986, 1988, 1990, 1991, 1993, and 1995. Logistic regression analyses were used to assess the effect of demographic, clinical, and temporal factors on the receipt of aspirin, beta-blockers, and lipid-lowering medications before hospital admission for recurrent AMI. RESULTS: More than 47% of patients in each study year were not receiving each medication before admission, although significant increases in use were noted over time for aspirin (from 13.5% to 52.6%), beta-blockers (from 33.2% to 44.4%), and lipid-lowering medications (from 0.8% to 11.7%). In multivariate analyses, advancing age was associated with not receiving aspirin (odds ratio [OR], 0.67; 95% confidence interval [CI], 0.51-0.89), lipid-lowering medications (OR, 0.14; 95% CI, 0.08-0.25), and beta-blockers (OR, 0.75; 95% CI, 0.57-1.00), although this effect was of borderline significance for beta-blockers. Being a woman was associated with not receiving aspirin (OR, 0.78; 95% CI, 0.62-0.98) but was positively associated with receiving lipid-lowering medications (OR, 1.59; 95% CI, 1.04-2.43). Coexisting medical conditions and concurrent use of other cardiovascular medications were also associated with receipt of each medication. CONCLUSION: Despite encouraging increases over time, the low absolute levels of receipt of medications shown to be efficacious in the long-term treatment of patients after an MI, and their variation by age and sex, suggest that substantial opportunities may exist to prevent recurrent AMIs through the increased use of aspirin, beta-blockers, and lipid-lowering medications.

Temporal trends (1986-1997) in cholesterol level assessment and management practices in patients with acute myocardial infarction: a population-based perspective.

BACKGROUND: Elevated serum cholesterol levels are associated with increased risk for acute myocardial infarction (AMI) and adverse patient outcomes. It is unclear what proportion of patients have their serum cholesterol levels measured during hospitalization for AMI and are given hypolipidemic therapy. OBJECTIVE: To examine decade-long trends in measurement of serum cholesterol levels during hospitalization for AMI and use of hypolipidemic therapy. METHODS: Observational study of 5204 residents of the Worcester, Mass, metropolitan area hospitalized with validated AMI in all greater Worcester hospitals in seven 1-year periods from 1986 through 1997. RESULTS: Increases in the measurement of serum cholesterol levels during hospitalization for AMI were observed between 1986 and 1991, followed by a progressive decrease; only 24% of patients with AMI in 1997 underwent cholesterol level testing. Younger age, male sex, and absence of a history of cardiovascular disease were associated with an increased likelihood measurement of serum cholesterol levels. Although the relative use of hypolipidemic therapy increased significantly over time (0.4% in 1986 vs 10.7% in 1997), the absolute rate of use remained low. In patients with elevated serum cholesterol levels (>/=6.2 mmol/L [>/=240 mg/dL]), 1.9% received hypolipidemic therapy in 1986 and 36.6% in 1997. CONCLUSIONS: These findings suggest recent declines in the assessment of total cholesterol levels in patients hospitalized with AMI. Although the use of hypolipidemic therapy during hospitalization for AMI has increased over time, considerable room for improvement remains.

Decade-long trends (1986 to 1997) in the medical treatment of patients with acute myocardial infarction: A community-wide perspective.

BACKGROUND: Although there are an increasing number and variety of medications available for the treatment of patients with acute myocardial infarction (AMI), few data are available describing recent, and changes over time in, use of different cardiac medications in patients with AMI from a more generalizable, community-wide perspective. Moreover, it is unclear whether the demographic and clinical profile of patients receiving these agents is similar or varies according to the type of agent prescribed. METHODS AND RESULTS: The purpose of this study was to examine recent patterns and changes over a decade-long period (1986 to 1997) in the use of cardiac medications during the acute hospitalization and at the time of hospital discharge in metropolitan Worcester, Mass, residents (1990 census estimate, 437,000) hospitalized with confirmed AMI. There was a marked increase in the use of angiotensin-converting enzyme inhibitors, aspirin, beta-blockers, lipid-lowering agents, and thrombolytic therapy between 1986 and 1997. The use of calcium antagonists, lidocaine, and other antiarrhythmic agents declined over this period. Similar trends were observed in the use of these agents in hospital survivors at the time of hospital discharge. Patient age, presence of comorbidities, and AMI-associated characteristics influenced the use of these therapies; sex differences in the use of several of these medications were also noted. CONCLUSIONS: The results of this population-based observational study provide insights into changing prescribing patterns in the hospital treatment of patients with AMI. Despite encouraging increases in the use of several of these agents, considerable opportunities for increased utilization remain.

Age-related trends in short- and long-term survival after acute myocardial infarction: a 20-year population-based perspective (1975-1995).

This study examines age-related differences and temporal trends in hospital and long-term survival after acute myocardial infarction (AMI) over a 2-decade-long (1975 to 1995) experience. A total of 8,070 patients with validated AMI hospitalized in all acute care hospitals in the Worcester, Massachusetts, metropolitan area (1990 census population 437,000) were studied over 10 one-year periods between 1975 and 1995. This population included 1,326 patients aged <55 years (16.4%), 1,768 patients aged 55 to 64 years (21.9%), 2,325 patients aged 65 to 74 years (28.8%), 1,880 patients aged 75 to 84 years (23.3%), and 771 patients aged > or = 85 years (9.6%). Compared with patients <55 years, patients 55 to 64 years were 2.2 times more likely to die during hospitalization for AMI, whereas patients 65 to 74, 75 to 84, and > or = 85 years were at 4.2, 7.8, and 10.2 times greater risk of dying, respectively. Similar age disparities in the risk of dying were seen when controlling for additional prognostic factors. Despite the adverse impact of increasing age on hospital survival after AMI, declining in-hospital death rates were seen in each of the age groups under study, with declining magnitude of these trends with advancing age. Among discharged hospital patients, increasing age was related to a significantly poorer long-term prognosis. Trends toward improving long-term prognosis were seen in patients discharged in the mid-1990s compared with those discharged in the mid- to late 1970s for patients aged <85 years. The present results demonstrate the marked impact of advancing age on survival after AMI. Despite the adverse impact of age on prognosis, encouraging trends in prognosis were observed in all age groups, although to a lesser extent in the oldest elderly patients. These findings emphasize the low death rates in middle-aged patients with AMI and the need for targeted secondary prevention efforts in elderly patients with AMI.

Ten-year trends in the incidence, treatment, and outcome of Q-wave myocardial infarction.

The benefits of coronary reperfusion and antiplatelet therapy for patients with Q-wave acute myocardial infarction (Q-AMI) are well established in the context of randomized, controlled trials. The use and recent impact of these and other therapies on the broader, community-wide population of patients with Q-AMI is less well established. Residents of the Worcester, Massachusetts, metropolitan area (1990 census population 437,000) hospitalized with confirmed Q-AMI in all metropolitan Worcester, Massachusetts, hospitals in 4 1-year periods between 1986 and 1997 comprised the sample of interest. We examined the rates of occurrence, use of reperfusion strategies, and hospital mortality in a cohort of 711 patients with Q-AMI treated early in the reperfusion era (1986 and 1988) in comparison to 669 patients with Q-AMI treated a decade later (1995 and 1997). The percentage of Q-AMI among all hospitalized patients with AMI decreased over the decade of reperfusion therapy: 52% in 1986 and 1988 versus 35% in 1995 and 1997 (p < 0.001). Use of reperfusion therapy for patients with Q-AMI increased from 22% to 57%, with a marked increase in the use of primary angioplasty over time (1% vs 16%). The profile of patients receiving reperfusion therapy also changed significantly over the study period. Marked increases in use of antiplatelet therapy, beta blockers, angiotensin-converting enzyme inhibitors, and decreased use of calcium channel blockers, were observed over time. The crude in-hospital case fatality rate declined from 19% (1986 and 1988) to 14% (1995 and 1997) in patients with Q-AMI. Results of a multivariable regression analysis showed lack of reperfusion therapy, older age, anterior wall AMI, and cardiogenic shock to be independent predictors of in-hospital mortality in patients with Q-AMI. Thus, the percentage of all AMI's presenting as Q-AMI, and hospital mortality after Q-AMI, has decreased significantly in the past 10 years. The decrease in mortality occurs in the setting of broader use of reperfusion and adjunctive therapy (including primary angioplasty).

Outcomes and early revascularization for patients > or = 65 years of age with cardiogenic shock.

Hospital survival of patients with acute myocardial infarction (AMI) complicated by cardiogenic shock has improved during recent years. It is unclear whether this mortality benefit also applies to elderly patients with cardiogenic shock. Elderly residents (age > or = 65 years) of the Worcester, Massachusetts metropolitan area (1990 census population = 437,000) hospitalized with confirmed AMI and cardiogenic shock in all metropolitan Worcester, Massachusetts hospitals between 1986 and 1997 constituted the sample of interest. We examined the use of coronary reperfusion strategies, adjunctive therapy, and hospital mortality in a cohort of 166 cardiogenic patients treated early in the reperfusion era (1986 to 1991) compared with 144 patients with AMI treated approximately 1 decade later (1993 to 1997). There was a significant increase in the use of an early revascularization strategy over time (2% vs 16%, p <0.001). Marked increases in use of antiplatelet therapy, beta blockers, and angiotensin-converting enzyme inhibitors were also observed over the decade-long experience. In-hospital case fatality declined significantly over time, from 80% (1986 to 1991) to 69% (1993 to 1997) in elderly patients who developed cardiogenic shock (p = 0.03). After adjusting for differences in potentially confounding prognostic characteristics between patients hospitalized in the 2 study periods, an even more pronounced reduction in hospital mortality (42%) was observed for the most recently hospitalized cohort. The most powerful predictor of in-hospital survival was use of an early revascularization approach to treatment. Thus, hospital mortality has declined for patients > or = 65 years of age with AMI complicated by cardiogenic shock, and this decline has occurred in the setting of broader use of early revascularization and adjunctive medical therapy for this high-risk population.

Poly(N-vinylpyrrolidone)-block-poly(D,L-lactide) as a new polymeric solubilizer for hydrophobic anticancer drugs: in vitro and in vivo evaluation.

The majority of novel anticancer drugs developed to date are intended for parenteral administration. Paradoxically, most of these drugs are water-insoluble, delaying their clinical development. A common approach to confering water solubility to drugs is to use amphiphilic, solubilizing agents, such as polyethoxylated castor oil (e.g., Cremophor EL, CrmEL). However, these vehicles are themselves associated with a number of pharmacokinetic and pharmaceutical concerns. The present work is aimed at evaluating a novel polymeric solubilizer for anticancer drugs, i.e., poly(N-vinylpyrrolidone)-block-poly(D,L-lactide) (PVP-b-PDLLA). This copolymer self-assembles in water to yield polymeric micelles (PM) that efficiently solubilize anticancer drugs, such as paclitaxel (PTX), docetaxel (DCTX), teniposide (TEN) and etoposide (ETO). A PM-PTX formulation was evaluated, both, in vitro on three different cancer cell lines and in vivo for its safety, pharmacokinetics, biodistribution and antitumor activity. In vitro, cytotoxicity studies revealed that the drug-loaded PM formulation was equipotent to the commercial PTX formulation (Taxol). In the absence of drug, PVP-b-PDLLA with 37% DLLA content was less cytotoxic than CrmEL. In vivo, acute toxicity was assessed in mice after a single injection of escalating dose levels of formulated PTX. PM-PTX was well tolerated and the maximum tolerated dose (MTD) was not reached even at 100 mg/kg, whereas the MTD of Taxol was established at 20 mg/kg. At 60 mg/kg, PM-PTX demonstrated greater in vivo antitumor activity than Taxol injected at its MTD. Finally, it was shown in mice and rabbits that the areas under the plasma concentration-time curves were inversely related to PM drug loading.

Age and sex differences in presentation of symptoms among patients with acute coronary disease: the REACT Trial. Rapid Early Action for Coronary Treatment.

BACKGROUND: There are few data on possible age and sex differences in presentation of symptoms for patients with acute coronary disease. OBJECTIVE: To investigate demographic differences in presentation of symptoms at the time of hospital presentation for acute myocardial infarction (AMI) and unstable angina. METHODS: The medical records of patients who presented with chest pain and who also had diagnoses of AMI (n = 889) or unstable angina (n = 893) on discharge from 43 hospitals were reviewed as part of data collection activities of the Rapid Early Action for Coronary Treatment trial based in 10 pair-matched communities throughout the USA. RESULTS: Dyspnea (49%), arm pain (46%), sweating (35%), and nausea (33%) were commonly reported by men and women of all ages in addition to the presenting complaint of chest pain. After we had controlled for various characteristics through regression modeling, older persons with AMI were significantly less likely than were younger persons to complain of arm pain and sweating, and men were significantly less likely to report vomiting than were women. Among persons with unstable angina, arm pain and sweating were reported significantly less often by elderly patients. Nausea and back, neck, and jaw pain were more common complaints of women. CONCLUSIONS: Results of this study suggest that there are differences between symptoms at presentation of men and women, and those in various age groups, hospitalized with acute coronary disease. Clinicians should be aware of these differences when diagnosing and managing patients suspected to have coronary heart disease.

Quantification of GR90291 in human blood by high resolution gas chromatography-mass selective detection (HRGC-MSD).

A specific and sensitive high resolution gas chromatography-mass spectrometry method for the determination of GR90291 in human blood is described. The extraction of GR90291 from blood required a polar organic solvent mixture. The crude extract was further purified by successive liquid-liquid partitioning prior to esterification with an HCl-n-butanol solution. This derivative was analysed using a deuterium-labelled internal standard by selected ion monitoring mass spectrometry. The calibration curve ranged from 1 to 100 ng ml-1. The method is reliable for the determination of GR90291 pharmacokinetics in human subjects.

Analysis of enloplatin by liquid chromatography and of platinum by atomic absorption spectrometry in various biological fluids.

Analytical methods were developed and validated for the determination of enloplatin (an anticancer agent) in plasma by reversed-phase LC and for platinum (an elemental component of enloplatin) in plasma, plasma ultrafiltrate (PUF) and whole blood by flameless atomic absorption spectrometry (FAAS). The LC procedure involved protein precipitation with dilute perchloric acid. The supernatant was mixed with sodium phosphate buffer and injected into the LC system. A C18 or a cyano column was used, depending on sample matrix, with UV detection at 230 nm. The LC method was linear from 0.50 to 50.0 micrograms ml-1. Inter-day and intra-day precision (RSD%) and accuracy (relative error%) were < +/- 14%. The FAAS procedure utilized a graphite furnace, a hollow cathode platinum (Pt) lamp, and Zeeman background correction. An aliquot of plasma, PUF, or whole blood was mixed with a solution of Triton X-100 and Antifoam-B and injected into the FAAS system. The FAAS method showed goodness of fit from 0.05 to 10.0 micrograms Pt/ml. Inter-day and intra-day precision and accuracy were < +/- 15%. The methods were developed to support pharmacokinetic studies in humans, dogs and rats.

[Profile of aged traffic victims on the road to Sherbrooke (Quebec)]. / Profil de victimes âgées de la route à Sherbrooke (Québec).

This article draws a portrait of the victims, 65 years of age and over, of road accidents in a mid-size Quebec town. By examining four variables--age, sex, condition of the victims and the type of road users--we measured the magnitude and severity of road accident injuries in senior citizens, and identified those road users most at risk. Results indicate that, in the city of Sherbrooke as elsewhere in Quebec, road accident injuries are increasing slowly but constantly in this age group. Analysis of the severity of injuries and of the category of road users, shows that senior citizens have a high degree of vulnerability and are over-represented in statistics dealing with pedestrians who are victims of accidents. We discuss these results and their impact on public health.

HIV-risk practices among homeless and low-income housed mothers.

BACKGROUND: Knowledge of human immunodeficiency virus (HIV) and its risk behaviors have not been systematically studied in homeless mothers. The identification of the factors associated with HIV-risk practices will guide interventions for low-income housed and homeless women. METHODS: We interviewed 220 homeless and 216 low-income housed mothers living in Worcester, Massachusetts, to gather information on demographic, psychosocial , and HIV-risk practice characteristics. We used standardized instruments and questions drawn from national surveys. The primary study outcome was high HIV-risk behavior. RESULTS: Although homeless mothers were more likely than low-income housed mothers to report first sexual contact at an early age, multiple partners during the last 6 months, and a history of intravenous drug use, homelessness was not associated with high HIV-risk practices. Both homeless and low-income housed mothers demonstrated misconceptions about HIV transmission through casual contact. Among high-risk women, approximately 75% perceived themselves as having low or no risk for contracting HIV. A history of childhood victimization, adult partner violence, or both placed women at a significantly increased likelihood of high HIV-risk practices. African American race, knowledge about HIV, and self-perception of risk were also significantly associated with high-risk practices. CONCLUSIONS: Homeless mothers are a subgroup of poor women at high risk for HIV and should be targeted for preventive interventions. In addition, there are potentially modifiable factors associated with HIV-risk practices in both low-income housed and homeless mothers that should be directly addressed.

Population pharmacokinetics of terfenadine.

PURPOSE: After oral administration of terfenadine, plasma concentrations of the parent drug are usually below the limits of quantitation of conventional analytical methods because of extensive first-pass metabolism. Data are usually reported on the carboxylic acid metabolite (M1) but there are no published reports of pharmacokinetic parameters for terfenadine itself. The present study was undertaken to evaluate the population pharmacokinetics of terfenadine. METHODS: Data from 132 healthy male subjects who participated in several different studies were included in this analysis. After an overnight fast, each subject received a single 120 mg oral dose of terfenadine; blood samples were collected for 72 hours. Terfenadine plasma concentrations were measured using HPLC with mass spectrometry detection and M1 plasma concentrations were measured using HPLC with fluorescence detection. A 2-compartment model was fitted to the terfenadine data using NONMEM; terfenadine and M1 data were also analyzed by noncompartmental methods. RESULTS: Population mean Ka was 2.80 hr-1, Tlag was 0.33 hr, Cl/F was 4.42 x 10(3) 1/hr, Vc/F was 89.8 x 10(3) 1. Q/F was 1.85 x 10(3) 1/hr and Vp/F was 29.1 x 10(3) 1. Intersubject CV ranged from 66 to 244% and the residual intrasubject CV was 21%. Based on noncompartmental methods, mean terfenadine Cmax was 1.54 ng/ml, Tmax was 1.3 hr, t1/2 lambda Z was 15.1 hr, Cl/F was 5.48 x 10(3) 1/hr and V lambda Z/F was 119.2 x 10(3) 1. M1 concentrations exceeded terfenadine concentrations by more than 100 fold and showed less intersubject variability. CONCLUSIONS: Terfenadine disposition was characterized by a 2-compartment model with large intersubject variability, consistent with its significant first-pass effect.