Timothy L. McAuliffe

Patterns, correlates, and barriers to medication adherence among persons prescribed new treatments for HIV disease

New treatments for HIV can improve immune functioning and decrease mortality. However, lapses in adherence may render these complex regimens ineffective. Sixty-three men and 9 women on highly active antiretroviral therapy completed measures of medication adherence, psychological characteristics, and barriers to adherence. HIV viral load, a health outcome measure of virus amount present in blood, was also obtained. The sample was 36% African American and 56% Caucasian, with 35% reporting disability. Nearly one third of patients had missed medication doses in the past 5 days, and 18% had missed doses weekly over the past 3 months. Frequency of missed doses was strongly related to detectable HIV viral loads. Depression, side-effect severity, self-efficacy, and social support distinguished patients with good and poor adherence. Barriers also varied with adherence level. Implications for interventions promoting HIV treatment adherence are discussed.

Randomised, controlled, community-level HIV-prevention intervention for sexual-risk behaviour among homosexual men in US cities

BACKGROUND Community-level interventions may be helpful in population-focused HIV prevention. If members of populations at risk of HIV infection who are popular with other members can be engaged to advocate the benefits of behaviour change to peers, decreases in risk behaviour may be possible. We assessed a community-level intervention to lower the risk of HIV infection, focusing on men patronising gay bars in eight small US cities. METHODS We used a randomised community-level field design. Four cities received the intervention and four control cities did not. Participants were men from each city who went to gay bars. Men completed surveys about their sexual behaviour on entering the bars during 3-night periods at baseline and at 1-year follow-up. In the control cities, HIV educational materials were placed in the bars. In the intervention cities, we recruited popular homosexual men in the community and trained them to spread behaviour-change endorsements and recommendations to their peers through conversation. FINDINGS Population-level of risk behaviour decreased significantly in the intervention cities compared with the control cities at 1-year follow-up, after exclusion of surveys completed by transients and men with exclusive sexual partners in a city-level analysis, in the intervention cities we found a reduction in the mean frequency of unprotected anal intercourse during the previous 2 months (baseline 1.68 occasions; follow-up 0.59: p = 0.04) and an increase in the mean percentage of occasions of anal intercourse protected by condoms (baseline 44.7%; follow-up 66.8%, p = 0.02). Increased numbers of condoms taken from dispensers in intervention-city bars corroborated risk-behaviour self-reports. INTERPRETATION Popular and well-liked members of a community who systematically endorse and recommend risk-reduction behaviour can influence the sexual-risk practices of others in their social networks. Natural styles of communication, such as conversations, brought about population-level changes in risk behaviour.

Outcomes of a randomized community-level HIV prevention intervention for women living in 18 low-income housing developments

OBJECTIVES Women in impoverished inner-city neighborhoods are at high risk for contracting HIV. A randomized, multisite community-level HIV prevention trial was undertaken with women living in 18 low-income housing developments in 5 US cities. METHODS Baseline and 12-month follow-up population risk characteristics were assessed by surveying 690 women at both time points. In the 9 intervention condition housing developments, a community-level intervention was undertaken that included HIV risk reduction workshops and community HIV prevention events implemented by women who were popular opinion leaders among their peers. RESULTS The proportion of women in the intervention developments who had any unprotected intercourse in the past 2 months declined from 50% to 37.6%, and the percentage of womens acts of intercourse protected by condoms increased from 30.2% to 47.2%. Among women exposed to intervention activities, the mean frequency of unprotected acts of intercourse in the past 2 months tended to be lower at follow-up (mean = 4.0) than at baseline (mean = 6.0). These changes were corroborated by changes in other risk indicators. CONCLUSIONS Community-level interventions that involve and engage women in neighborhood-based HIV prevention activities can bring about reductions in high-risk sexual behaviors.

Generalizability of the surveillance, epidemiology, and end results registry population: Factors relevant to epidemiologic and health care research

To assess the generalizability of the population included in the Surveillance, Epidemiology, and End Results (SEER) tumor registries to the overall United States population, we compared the population of the 198 SEER counties to the population of the 2882 non-SEER counties regarding sociodemographic factors, physician availability, and availability of pertinent hospital resources. The population residing within the SEER areas is more affluent, has lower unemployment, and is substantially more urban than the remainder of the U.S. population (p < 0.001 for each). The SEER areas have fewer general and family practice physicians, but more total nonfederal physicians, general internists, and specialists relevant to cancer care. SEER areas have fewer Joint Commission on Accreditation of Hospitals accredited hospitals, hospital beds, and hospitals with CT scanners, but more hospitals with bone marrow transplantation. The differences between the SEER population and the remainder of the United States, especially SEERs higher socioeconomic status and more urban population, should be considered when generalizing from SEER to the entire country.

The relationship between insulin-like growth factor-I, adiposity, and aging.

Aging is associated with both a relative accumulation of body fat and a reduction in growth hormone (GH) secretion. This study was devised to investigate the relationship between plasma insulin-like growth factor-I (IGF-I), an index of GH secretion, and anthropometric indices of body fat in normal subjects of various ages. Somatic and biochemical indices of nutrition were assessed in 107 subjects between the ages of 17 and 83 years who attended an outpatient clinic for general health supervision. Plasma IGF-I correlated negatively with age in both males (r = -.44, P = .001) and females (r = -.40, P = .005). In addition, plasma IGF-I correlated negatively with body mass index (BMI) (r = .35, P = .006), percentage of standard triceps skinfold (TSF) (r = -.26, P = .05), and percentage of standard weight (r = -.35, P = .006) in males, but not in females. Multiple regression analysis indicated that in males, BMI and percentage of standard weight correlated with plasma IGF-I independent of the effect of age. We conclude that adiposity and aging are independently associated with decreased plasma IGF-I concentrations. The negative correlations between indices of adiposity and IGF-I were observed only in males, whereas the age-associated decline in IGF-I was present in both males and females. We speculate that sex differences in the gonadal steroid milieu, combined with declining GH secretion in both sexes, may contribute to the age-associated development of obesity in males.

Comparison of 10% povidone-iodine and 0.5% chlorhexidine gluconate for the prevention of peripheral intravenous catheter colonization in neonates : a prospective trial

The purpose of the study was to compare the efficacy of 10% povidone-iodine with that of 0.5% chlorhexidine gluconate in 70% isopropyl alcohol for the prevention of peripheral intravenous catheter colonization in neonates. This was a multicenter, nonrandomized prospective study in a tertiary neonatal intensive care setting in which povidone-iodine and chlorhexidine gluconate were each used as antiseptic skin preparations over sequential 6-month periods. During the first 6 months of the study when povidone-iodine was in use 9.3% (38 of 408) of catheters were colonized. During the second 6 months of the study when chlorhexidine gluconate was in use, catheter colonization occurred in 4.7% (20 of 418, P = 0.01). Catheter-related bacteremia occurred during only 0.2% (2 of 826) of all catheterizations. Heavy skin colonization before catheter insertion (relative risk, 3.6; 95% confidence interval, 1.9, 7.0), catheterization > or = 72 hours (relative risk. 2.0; 95% confidence interval, 1.01, 3.8) and gestational age < or = 32 weeks (relative risk, 1.8; 95% confidence interval, 1.02, 3.3) increased colonization risk. Ampicillin infusion (relative risk, 0.4; 95% confidence interval, 0.2, 0.7) and 0.5% chlorhexidine gluconate cutaneous antisepsis (relative risk, 0.4; 95% confidence interval, 0.2, 0.8) were factors associated with decreased colonization risk. We conclude that 0.5% chlorhexidine gluconate in 70% isopropyl alcohol appears to be more efficacious than 10% povidone-iodine for the prevention of peripheral intravenous catheter colonization in neonates.

The role of neutrophils and platelets in a rabbit model of thromboembolic stroke.

Cerebral ischemia is accompanied by many of the cardinal features of acute inflammation such as neutrophil and platelet activation and accumulation. We sought to determine whether circulating neutrophils or platelets contribute to brain injury in a rabbit model of thromboembolic stroke that includes a fixed duration of superimposed systemic hypotension. We randomized 18 rabbits to receive either antineutrophil antiserum (n = 6), antiplatelet antiserum (n = 5), or nonimmune serum (n = 7). We assessed brain ischemia by measuring cerebral blood flow, intracranial pressure, and infarct size. Following the intracarotid administration of an autologous clot, cerebral blood flow in all groups fell to less than 5 ml/100 g/min during induced hypotension. After restoration of baseline blood pressure, mean cerebral blood flow in neutropenic animals recovered to 20-30 ml/100 g/min while that in control and thrombocytopenic rabbits remained at less than 10 ml/100 g/min. Intracranial pressure in control animals rose steadily to a final value of 241% of baseline, while a much smaller increase (148% of baseline) was noted in the thrombocytopenic group; no change from baseline was evident in the neutropenic group. Infarct size was significantly (p less than 0.05) reduced in the neutropenic group but not in the thrombocytopenic group. These results suggest that neutrophils may be important contributors to ischemia-induced brain injury whereas the role of platelets is more subtle.

A vancomycin-heparin lock solution for prevention of nosocomial bloodstream infection in critically ill neonates with peripherally inserted central venous catheters: a prospective, randomized trial.

Objective.Critically ill neonates are at high risk for vascular catheter–related bloodstream infection (CRBSI), most often caused by coagulase-negative staphylococci. Most CRBSIs with long-term devices derive from intraluminal contaminants. The objective of this study was to ascertain the safety and the efficacy of a vancomycin-heparin lock solution for prevention of CRBSI. Methods.A prospective, randomized double-blind trial was conducted during 2000–2001 at a community hospital level III NICU. Very low birth weight and other critically ill neonates with a newly placed peripherally inserted central venous catheter were randomized to have the catheter locked 2 or 3 times daily for 20 or 60 minutes with heparinized normal saline (n = 43) or heparinized saline that contained vancomycin 25 μg/mL (n = 42). The origin of each nosocomial bloodstream infection (BSI) was studied by culturing skin, catheter hubs, and implanted catheter segments and blood cultures, demonstrating concordance by restriction-fragment DNA subtyping. Surveillance axillary and rectal cultures were performed to detect colonization by vancomycin-resistant organisms. The main outcome measures were (1) CRBSIs and (2) colonization or infection by vancomycin-resistant Gram-positive bacteria. Results.Two (5%) of 42 infants in the vancomycin-lock group developed a CRBSI as compared with 13 (30%) of 43 in the control group (2.3 vs 17.8 per 1000 catheter days; relative risk: 0.13; 95% confidence interval: 0.01–0.57). No vancomycin-resistant enterococci or staphylococci were recovered from any cultures. Vancomycin could not be detected in the blood of infants who did not receive systemic vancomycin therapy. Twenty-six neonates (8 vancomycin-lock group, 18 control group) had at the end of a catheter-lock period asymptomatic hypoglycemia that resolved promptly when glucose-containing intravenous fluids were restarted. Conclusions.Prophylactic use of a vancomycin-heparin lock solution markedly reduced the incidence of CRBSI in high-risk neonates with long-term central catheters and did not promote vancomycin resistance but was associated with asymptomatic hypoglycemia. The use of an anti-infective lock solution for prevention of CRBSI with long-term intravascular devices has achieved proof of principle and warrants selective application in clinical practice.

A Three-day Course of Dexamethasone Therapy to Prevent Chronic Lung Disease in Ventilated Neonates: A Randomized Trial

Background. Although several trials of early dexamethasone therapy have been completed to determine if such therapy would reduce mortality and chronic lung disease (CLD) in infants with respiratory distress, optimal duration and side effects of such therapy remain unknown. Purpose. The purpose of this study was: 1) to determine if a 3-day course of early dexamethasone therapy would reduce CLD and increase survival without CLD in neonates who received surfactant therapy for respiratory distress syndrome and 2) to determine adverse effects associated with such therapy. Design. This was a prospective multicenter randomized trial comparing a 3-day course of dexamethasone therapy beginning at 24 to 48 hours of life to placebo therapy. Two hundred forty-one neonates (dexamethasone n = 118, placebon = 123), who weighed between 500 g and 1500 g, received surfactant therapy, and were at significant risk for CLD or death using a model to predict CLD or death at 24 hours of life, were enrolled in the trial. Infants randomized to receive early dexamethasone were given 6 doses of dexamethasone at 12-hour intervals beginning at 24 to 48 hours of life. The primary outcomes compared were survival without CLD and CLD. CLD was defined by the need for supplemental oxygen at the gestational age of 36 weeks. Complication rates and adverse effects of study drug therapy were also compared. Results. Neonates randomized to early dexamethasone treatment were more likely to survive without CLD (RR: 1.3; 95% CI: 1.03, 1.7) and were less likely to develop CLD (RR: 0.6; CI: 0.3, 0.98). Mortality rates were not significantly different. Subsequent dexamethasone therapy use was less in early dexamethasone-treated neonates (RR: 0.8; CI: 0.7, 0.96). Very early (≤7 days of life) intestinal perforations were more common among dexamethasone-treated neonates (8% vs 1%). Conclusion. We conclude that an early 3-day course of dexamethasone therapy increases survival without CLD, reduces CLD, and reduces late dexamethasone therapy in high-risk, low birth weight infants who receive surfactant therapy for respiratory distress syndrome. Potential benefits of early dexamethasone therapy at the dosing schedule used in this trial need to be weighed against the risk for early intestinal perforation.

Prevention of HIV and sexually transmitted diseases in high risk social networks of young Roma (Gypsy) men in Bulgaria: randomised controlled trial

Objective To determine the effects of a behavioural intervention for prevention of HIV and sexually transmitted diseases that identified, trained, and engaged leaders of Roma (Gypsy) mens social networks to counsel their own network members. Design A two arm randomised controlled trial. Setting A disadvantaged, impoverished Roma settlement in Bulgaria. Participants 286 Roma men from 52 social networks recruited in the community. Intervention At baseline all participants were assessed for HIV risk behaviour, tested and treated for sexually transmitted diseases, counselled in risk reduction, and randomised to intervention or control groups. Network leaders learnt how to counsel their social network members on risk prevention. Networks were followed up three and 12 months after the intervention to determine evidence of risk reduction. Main outcome measure Occurrence of unprotected intercourse during the three months before each assessment. Results Reported prevalence of unprotected intercourse in the intervention group fell more than in control group (from 81% and 80%, respectively, at baseline to 65% and 75% at three months and 71% and 86% at 12 months). Changes were more pronounced among men with casual partners. Effects remained strong at long term follow-up, consistent with changes in risk reduction norms in the social network. Other measures of risk reduction corroborated the interventions effects. Conclusions Endorsement and advice on HIV prevention from the leader of a social network produces well maintained change in the reported sexual practices in members of that network. This model has particular relevance for health interventions in populations such as Roma who may be distrustful of outsiders. Trial registration Clinical Trials NCT00310973.