Lauren Gee

Sexual transmission of HIV-1 among injection drug users in San Francisco, USA: risk-factor analysis

BACKGROUND Many new HIV-1 infections in the USA occur in injection drug users (IDUs). HIV-1seroconversion of IDUs is mainly associated with injection-related risk factors. Harm- reduction programmes concentrate on injection-risk behaviour. We aimed to establish whether injection or sexual risk factors, or both, were associated with HIV-1antibody seroconversion of street-recruited IDUs in San Francisco, from 1986 to 1998. METHODS IDUs were enrolled every 6 months from four community sites. We did a nested case-control study comparing 58 respondents who seroconverted between visits with 1134 controls who remained seronegative. Controls were matched with cases by sex and date. Adjusted odds ratios and 95% CI were calculated for men and women by use of conditional logistic regression. FINDINGS Men who had sex with men were 8.8 times as likely to seroconvert (95% CI 3.7-20.5) as heterosexual men. Women who reported having traded sex for money in the past year were 5.1 times as likely as others to seroconvert (95% CI 1.9-13.7). Women younger than 40 years were more likely to seroconvert than those 40 years or older (2.8 [1.05-7.6]), and women who reported having a steady sex-partner who injected drugs were less likely to seroconvert than other women (0.32 [0.11-0.92]). INTERPRETATION HIV-1 seroconversion of street-recruited IDUs in San Francisco is strongly associated with sexual behaviour. HIV-1risk might be reduced by incorporation of innovative sexual-risk-reduction strategies into harm-reduction programmes.

Housing Instability and Food Insecurity as Barriers to Health Care Among Low-Income Americans

BACKGROUND: Homelessness and hunger are associated with poor health outcomes. Housing instability and food insecurity describe less severe problems securing housing and food.OBJECTIVE: To determine the association between housing instability and food insecurity and access to ambulatory health care and rates of acute health care utilization.DESIGN: Secondary data analysis of the National Survey of American Families.PARTICIPANTS: 16,651 low-income adults.MEASUREMENT: Self-reported measures of past-year access: (1) not having a usual source of care, (2) postponing needed medical care, or (3) postponing medication; and past-year utilization: (1) not having an ambulatory care visit, (2) having emergency department (ED) visits, or (3) inpatient hospitalization.RESULTS: 23.6% of subjects had housing instability and 42.7% had food insecurity. In multivariate logistic regression models, housing instability was independently associated with not having a usual source of care (adjusted odds ratio [AOR] 1.31, 95% confidence interval [CI] 1.08 to 1.59), postponing needed medical care (AOR 1.84, 95% CI 1.46 to 2.31) and postponing medications (AOR 2.16, 95% CI 1.70 to 2.74), increased ED use (AOR: 1.43, 95% CI 1.20 to 1.70), and hospitalizations (AOR 1.30, 95% CI 1.01 to 1.67). Food insecurity was independently associated with postponing needed medical care (AOR 1.74, 95% CI 1.38 to 2.21) and postponing medications (AOR 2.15, 95% CI 1.62 to 2.85), increased ED use (AOR 1.39, 95% CI 1.17 to 1.66), and hospitalizations (AOR 1.42, 95% CI 1.09 to 1.85).CONCLUSIONS: Housing instability and food insecurity are associated with poor access to ambulatory care and high rates of acute care. These competing life demands may lead to delays in seeking care and predispose to acute care.

Serum MMP-9 and TIMP-1 levels are related to MRI activity in relapsing multiple sclerosis.

OBJECTIVE To 1) compare monthly serum levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of MMP-type 1 (TIMP-1) in patients with relapsing-remitting MS (RRMS) versus healthy controls and 2) determine the relationship among monthly serum levels of MMP-9 and TIMP-1 and MRI activity. BACKGROUND Activated T-cells and macrophages secrete MMPs that may facilitate their migration across vascular subendothelial basement membranes into the CNS. The serum concentration of MMP-9 is reported to be higher in patients with RRMS than healthy controls. METHODS Monthly evaluations including gadolinium-enhanced (Gd+) brain MRI and measures of serum MMP-9 and TIMP-1 were performed for up to 15 months in 24 patients with RRMS and for up to 4 months in 10 controls. RESULTS Serum MMP-9 but not TIMP-1 levels are elevated in RRMS patients compared to healthy controls (p = 0.025, p = 0.61). In a univariate analysis, high MMP-9 and low TIMP-1 levels precede appearance of new Gd+ lesions (respectively; odds ratio = 3.3, p = 0.008; odds ratio = 2.2, p = 0.086). In a multivariate analysis, in comparison to months when MMP-9 is low and TIMP-1 high, MRI scans obtained the month following high MMP-9 and low TIMP-1 serum concentrations are more likely to report new Gd+ lesions (p = 0.0006, odds ratio = 21.5). CONCLUSION An increase in the activity of matrix metalloproteinase-9 (MMP-9) relative to tissue inhibitor of MMP-type 1 (TIMP-1) may be related to formation of new MS lesions, suggesting that serum levels of MMP-9 and TIMP-1 may be surrogate markers of disease activity in relapsing-remitting MS.

A serial study of new MS lesions and the white matter from which they arise

Objective: To compare MS normal-appearing white matter (NAWM) where new gadolinium-enhancing (Gd+) lesions do and do not arise. Methods: A total of 22 relapsing-remitting MS patients and 11 healthy control subjects completed as many as 12 monthly brain MRI sessions. Quantitative measures of gadolinium enhancement (GDR), water proton density (PDN), water proton T2 relaxation time constants (T2), magnetization transfer ratio (MTR), and T1-weighted signal intensity (T1N) were followed serially in healthy control and MS NAWM. Results: A total of 129 new Gd+ lesions were identified in 11 patients. PDN, T2, MTR, and T1N were diffusely abnormal in MS NAWM. NAWM regions in which new Gd+ lesions arose have increased GDR, PDN, and T2, and reduced MTR and T1N compared with contralateral homologous NAWM regions in which no new Gd+ lesions arose. Differences between these NAWM regions preceded lesion appearance for at least several months. After lesions became visible, GDR returned to baseline within 2 months, and PDN and MTR had larger residual abnormalities than T2 or T1N. Conclusions: Quantitative MRI measures are diffusely abnormal in MS NAWM. These measures are, on average, more abnormal in NAWM regions in which new Gd+ lesions arise. After the appearance of Gd+ lesions, measures of PDN and MTR may provide more appealing markers of relatively irreversible tissue damage than measures of T2 and T1N.

The Effect of Syringe Exchange Use on High-Risk Injection Drug Users: A Cohort Study

Objective:To determine whether syringe exchange program use is associated with cessation of syringe sharing among high-risk injection drug users. Design and methods:Between 1992 and 1996, street-recruited injection drug users were interviewed and received HIV testing and counseling semi-annually, as part of a dynamic cohort study. We examined a cohort of 340 high-risk injection drug users for whom two observations, 6-months apart, were available and who reported syringe sharing at the first interview. Multivariate logistic regression analysis was performed to determine the relationship between syringe exchange program use and cessation of syringe sharing, while controlling for confounding factors. Results:At follow-up interview, 60% (204 of 340) reported quitting syringe sharing. High-risk injection drug users who began using the syringe exchange program were more likely to quit sharing syringes [adjusted odds ratio (AOR), 2.68; 95% confidence interval (CI), 1.35–5.33], as were those who continued using the syringe exchange program (AOR,1.98; 95% CI, 1.05–3.75) in comparison with non-syringe exchange program users, while controlling for confounding factors. Conclusions:The initiation and continuation of syringe exchange program use among high-risk injection drug users is independently associated with cessation of syringe sharing. Syringe exchange program use can be an important component in reducing the spread of blood-borne infectious diseases among high-risk injection drug users.

Predictors and Prevention of Nonfatal Overdose Among Street-Recruited Injection Heroin Users in the San Francisco Bay Area, 1998–1999

OBJECTIVES This study sought to determine prevalence of and risk factors for nonfatal recent overdose among street-recruited injection heroin users. METHODS From August 1998 through July 1999, 1427 heroin injectors were recruited from 6 inner-city neighborhoods in the San Francisco Bay Area, Calif, and interviewed. Factors hypothesized to be associated with recent overdose were analyzed with logistic regression. RESULTS Of the 1427 participants, 684 (48%) had had an overdose, 466 (33%) had experienced 2 or more overdose events, and 182 (13%) had had a recent overdose. In multiple logistic regression, being younger (adjusted odds ratio [OR] for each year of increasing age = 0.95; 95% confidence interval [CI] = 0.94, 0.97), having been arrested 3 or more times in the past year (adjusted OR = 2.50; 95% CI = 1.61, 3.87), drinking 4 or more alcoholic drinks per day (adjusted OR = 2.05; 95% CI = 1.37, 3.05), and having participated in methadone detoxification during the past year (adjusted OR = 1.47; 95% CI = 1.03, 2.09) were independently associated with recent overdose. Being homeless; identifying as gay, lesbian, bisexual, or transgender; having spent 5 or more years in prison or jail; and having engaged in sex work also were associated with recent overdose. CONCLUSIONS Targeted interventions that decrease risk for overdose are urgently needed.

Naloxone Distribution and Cardiopulmonary Resuscitation Training for Injection Drug Users to Prevent Heroin Overdose Death: A Pilot Intervention Study

Fatal heroin overdose has become a leading cause of death among injection drug users (IDUs). Several recent feasibility studies have concluded that naloxone distribution programs for heroin injectors should be implemented to decrease heroin overdose deaths, but there have been no prospective trials of such programs in North America. This pilot study was undertaken to investigate the safety and feasibility of training injection drug using partners to perform cardiopulmonary resuscitation (CPR) and administer naloxone in the event of heroin overdose. During May and June 2001, 24 IDUs (12 pairs of injection partners) were recruited from street settings in San Francisco. Participants took part in 8-hour training in heroin overdose prevention, CPR, and the use of naloxone. Following the intervention, participants were prospectively followed for 6 months to determine the number and outcomes of witnessed heroin overdoses, outcomes of participant interventions, and changes in participants’ knowledge of overdose and drug use behavior. Study participants witnessed 20 heroin overdose events during 6 months follow-up. They performed CPR in 16 (80%) events, administered naloxone in 15 (75%) and did one or the other in 19 (95%). All overdose victims survived. Knowledge about heroin overdose management increased, whereas heroin use decreased. IDUs can be trained to respond to heroin overdose emergencies by performing CPR and administering naloxone. Future research is needed to evaluate the effectiveness of this peer intervention to prevent fatal heroin overdose.

Herpetic Eye Disease Study: A Controlled Trial of Topical Corticosteroids for Herpes Simplex Stromal Keratitis

PURPOSE To evaluate the efficacy of topical corticosteroids in treating herpes simplex stromal keratitis. METHODS The authors performed a randomized, double-masked, placebo-controlled, multicenter clinical trial of 106 patients with active herpes simplex stromal keratitis who had not received any corticosteroids for at least 10 days before study enrollment. Patients were assigned to the placebo group (n = 49) or the steroid group (topical prednisolone phosphate; n = 57); both regimens were tapered over 10 weeks. Both groups received topical trifluridine. Visual acuity assessment and slit-lamp biomicroscopy were performed weekly for 10 weeks, every other week for an additional 6 weeks or until removal from the trial, and at 6 months after randomization. RESULTS The time to treatment failure (defined by specific criteria as persistent or progressive stromal keratouveitis or an adverse event) was significantly longer in the steroid group compared with the placebo group. Compared with placebo, corticosteroid therapy reduced the risk of persistent or progressive stromal keratouveitis by 68%. The time from randomization to resolution of stromal keratitis and uveitis was significantly shorter in the steroid group compared with the placebo group even though both groups included patients who were removed from the study and treated with topical corticosteroids according to best medical judgment. Nineteen (33%) of the steroid-treated patients and 11 (22%) of the placebo-treated patients completed the 10 weeks of protocol therapy and had stable, noninflamed corneas after 16 weeks. At 6 months after randomization, no clinically or statistically significant differences in visual outcome or recurrent herpetic eye disease were identified between the steroid and placebo groups. CONCLUSIONS The topical corticosteroid regimen used in this study was significantly better than placebo in reducing persistence or progression of stromal inflammation and in shortening the duration of herpes simplex stromal keratitis. Postponing steroids during careful observation for a few weeks delayed resolution of stromal keratitis but had no detrimental effect as assessed by visual outcome at 6 months.

Lack of Association of C-Reactive Protein and Coronary Calcium by Electron Beam Computed Tomography in Postmenopausal Women: Implications for Coronary Artery Disease Screening

OBJECTIVES We sought to test the hypothesis that C-reactive protein, a marker of inflammation, would correlate positively with coronary calcium, a marker of atherosclerosis, in postmenopausal women. BACKGROUND High sensitivity testing for C-reactive protein (hsCRP) has recently been shown in large population studies to predict cardiac events in asymptomatic postmenopausal women. Coronary calcification determined by electron beam computerized tomography (EBCT) has also been suggested to be predictive of cardiac events in women. METHODS We performed hsCRP testing and determined calcium scores by EBCT in 172 asymptomatic postmenopausal women (mean age: 64.5 +/- 7.9 years) at risk for cardiac disease. Risk factors were determined by history, physical, electrocardiogram, exercise testing, and lipoprotein profiles. RESULTS Calcium scores ranged from 0 to 2,618. For analysis, calcium scores were divided into three groups; none (0 to 10), minimal (>10 to 50), and significant (>50). Overall, there was no significant positive relationship between hsCRP level and calcium score. Specifically, the hsCRP levels (mg/dl) were 0.24 +/- 0.43, 0.33 +/- 0.47 and 0.17 +/- 0.32 (medians 0.11, 0.15, and 0.06) for women with none, minimal, and significant coronary calcification, respectively. In subgroup analysis, a similar lack of positive association was observed after stratification by smoking status and by hormone replacement therapy use, two factors known to increase hsCRP. CONCLUSIONS In contrast to our a priori hypothesis, we found no evidence of a positive association between hsCRP and calcium score by EBCT. These data thus raise the possibility that hsCRP and EBCT calcium score reflect different pathologic processes, an issue with implications for coronary artery disease screening.

Herpetic Eye Disease Study: A Controlled Trial of Oral Acyclovir for Herpes Simplex Stromal Keratitis

PURPOSE To evaluate the efficacy of oral acyclovir in treating stromal keratitis caused by herpes simplex virus (HSV) in patients receiving concomitant topical corticosteroids and trifluridine. METHODS The authors performed a randomized, double-masked, placebo-controlled, multicenter trial in 104 patients with HSV stromal keratitis without accompanying HSV epithelial keratitis. Sample size was chosen so that a 5%, one-tailed test would have an 80% chance of detecting a doubling of the median time to treatment failure. Patients were randomized to receive a 10-week course of either oral acyclovir (400 mg 5 times daily, n = 51) or placebo (n = 53). All patients also received a standard regimen of topical prednisolone phosphate and trifluridine. Ophthalmologic examinations were performed weekly during the 10-week treatment period, every 2 weeks for an additional 6 weeks, and at 6 months after entry into the trial. RESULTS The median time to treatment failure (defined as worsening or no improvement of stromal keratitis or an adverse event) was 84 days (95% confidence interval, 69-93 days) for the acyclovir group and 62 days (95% confidence interval, 57-90 days) for the placebo group. By 16 weeks, 38 patients (75%) in the acyclovir group and 39 patients (74%) in the placebo group had failed treatment. Also by that time, the keratitis had resolved with trial medications, and there was no subsequent worsening in nine patients (18%) in the acyclovir group and ten (19%) in the placebo group. None of these results were significantly different between the two groups. However, visual acuity improved over 6 months in significantly more patients in the acyclovir group than in the placebo group. CONCLUSION There was no statistically or clinically significant beneficial effect of oral acyclovir in treating HSV stromal keratitis in patients receiving concomitant topical corticosteroids and trifluridine with regard to time to treatment failure, proportion of patients who failed treatment, proportion of patients whose keratitis resolved, time to resolution, or 6-month best-corrected visual acuity. Visual acuity improved over 6 months in more patients in the acyclovir group than in the placebo group.