Mary Cheang

Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock

Objective:To determine the prevalence and impact on mortality of delays in initiation of effective antimicrobial therapy from initial onset of recurrent/persistent hypotension of septic shock. Design:A retrospective cohort study performed between July 1989 and June 2004. Setting:Fourteen intensive care units (four medical, four surgical, six mixed medical/surgical) and ten hospitals (four academic, six community) in Canada and the United States. Patients:Medical records of 2,731 adult patients with septic shock. Interventions:None. Measurements and Main Results:The main outcome measure was survival to hospital discharge. Among the 2,154 septic shock patients (78.9% total) who received effective antimicrobial therapy only after the onset of recurrent or persistent hypotension, a strong relationship between the delay in effective antimicrobial initiation and in-hospital mortality was noted (adjusted odds ratio 1.119 [per hour delay], 95% confidence interval 1.103–1.136, p < .0001). Administration of an antimicrobial effective for isolated or suspected pathogens within the first hour of documented hypotension was associated with a survival rate of 79.9%. Each hour of delay in antimicrobial administration over the ensuing 6 hrs was associated with an average decrease in survival of 7.6%. By the second hour after onset of persistent/recurrent hypotension, in-hospital mortality rate was significantly increased relative to receiving therapy within the first hour (odds ratio 1.67; 95% confidence interval, 1.12–2.48). In multivariate analysis (including Acute Physiology and Chronic Health Evaluation II score and therapeutic variables), time to initiation of effective antimicrobial therapy was the single strongest predictor of outcome. Median time to effective antimicrobial therapy was 6 hrs (25–75th percentile, 2.0–15.0 hrs). Conclusions:Effective antimicrobial administration within the first hour of documented hypotension was associated with increased survival to hospital discharge in adult patients with septic shock. Despite a progressive increase in mortality rate with increasing delays, only 50% of septic shock patients received effective antimicrobial therapy within 6 hrs of documented hypotension.

Female to male transmission of human immunodeficiency virus type 1: risk factors for seroconversion in men

To determine the frequency and risk factors for female to male sexual transmission of human immunodeficiency virus type 1 (HIV-1), a prospective study was carried out in 422 men who had acquired a sexually transmitted disease (STD) from a group of prostitutes with a prevalence of HIV-1 infection of 85%. The initial seroprevalence of HIV among the men was 12%. 24 of 293 (8.2%) initially seronegative men seroconverted to HIV-1. Newly acquired infection was independently associated with frequent prostitute contact (risk ratio 3.2, 95% confidence interval 1.2-8.1), with the acquisition of genital ulcer disease (risk ratio 4.7, 95% confidence interval 1.3-17.0), and with being uncircumcised (risk ratio 8.2, 95% confidence interval 3.0-23.0). 96% of documented seroconversions occurred in men with one or both of the latter two risk factors. In a subgroup of 73 seronegative men who reported a single prostitute sexual contact, the frequency of HIV-1 infection was 8.2% during 12 weeks of observation. No man without a genital ulcer seroconverted. A cumulative 43% of uncircumcised men who acquired an ulcer seroconverted to HIV-1 after a single sexual exposure. These data indicate an extremely high rate of female to male transmission of HIV-1 in the presence of STD and confirm a causal relation between lack of male circumcision, genital ulcer disease, and susceptibility to HIV-1 infection.

Human immunodeficiency virus infection among men with sexually transmitted diseases. Experience from a center in Africa

Heterosexual transmission of the human immunodeficiency virus (HIV) appears to occur readily in Africa but less commonly in North America and Europe. We conducted a case-control study among men attending a clinic for sexually transmitted diseases in Nairobi to determine the prevalence of HIV infection and the risk factors involved. HIV antibody was detected in 11.2 percent of 340 men who enrolled in the study. Reports of nonvaginal heterosexual intercourse and homosexuality were notably rare. Recent injections and blood transfusions were not associated with HIV infection. Travel and frequent contact with prostitutes were associated with HIV seropositivity. Men who were uncircumcised were more likely to have HIV infection (odds ratio, 2.7; P = 0.003), as were those who reported a history of genital ulcers (odds ratio, 7.2; P less than 0.001). A current diagnosis of genital ulcers was also associated with HIV seropositivity (odds ratio, 2.0; P = 0.028). Multivariate analysis revealed an independent association of genital ulcers with HIV infection in both circumcised and uncircumcised men. Uncircumcised men were more frequently infected with HIV, regardless of a history of genital ulcers. Our study finds that genital ulcers and an intact foreskin are associated with HIV infection in men with a sexually transmitted disease. Genital ulcers may increase mens susceptibility to HIV, or they may increase the infectivity of women infected with HIV. The intact foreskin may operate to increase the susceptibility to HIV.

A population-based case control study of potential risk factors for IBD.

BACKGROUND:We aimed to pursue potential etiological clues to Crohns disease (CD) and ulcerative colitis (UC) through a population-based case control survey study.METHODS:Cases with CD (n = 364) and UC (n = 217), ages 18–50 yr were drawn from the population-based University of Manitoba IBD Research Registry. Potential control subjects were drawn from the population-based Manitoba Health Registry by age, gender, and geographic residence matching to the cases (n = 433). Subjects were administered a multiitem questionnaire.RESULTS:By univariate analysis, some of the variables predictive of CD included lower likelihood of living on a farm, of having drunk unpasteurized milk or having eaten pork, and UC patients were less likely to have drunk unpasteurized milk and to have eaten pork. On multivariate analysis, variables significantly associated with CD were being Jewish (OR = 4.32, 95% CI 1.10–16.9), having a first degree relative with IBD (OR = 3.07, 95% CI 1.73–5.46), ever having smoked (OR = 1.54, 95% CI, 1.06–2.25), living longer with a smoker (OR = 1.03, 95% CI, 1.01–1.04). Being a first generation Canadian (OR = 0.33, 95% CI, 0.17–0.62), having pet cats before age 5 (OR = 0.66, 95% CI, 0.46–0.96) and having larger families (OR = 0.87, 95% CI, 0.79–0.96) were protective against CD. For UC being Jewish (OR = 7.46, 95% CI, 2.33–23.89), having a relative with IBD (OR = 2.23, 95% CI, 1.27–3.9), and ever smoking (OR = 1.62, 95% CI, 1.14–2.32) were predictive.CONCLUSION:This study reinforced the increased risk associated with family history, being Jewish, and smoking history, however, a number of significant associations with CD and UC on univariate and multivariate analysis may support the “hygiene hypothesis” and warrant further exploration in prospective studies.

A prospective population-based study of triggers of symptomatic flares in IBD.

OBJECTIVES:We aimed to determine whether any of the nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics, infections, and stress trigger symptomatic flares of inflammatory bowel diseases (IBDs).METHODS:Participants drawn from a population-based IBD research registry were surveyed every 3 months for 1 year. They simultaneously tracked the use of NSAIDs, antibiotics, infections, major life events, mood, and perceived stress. Social networks, childhood socioeconomic status, and smoking were assessed at baseline. Disease flare was identified using the Manitoba Inflammatory Bowel Disease Index, a validated disease activity index. Across any two consecutive survey periods, participants were categorized as having a flare (inactive/active), having no flare (inactive/inactive), or remaining active (active/active). Potential triggers were evaluated for the first 3-month period to determine predictive rather than concurrent relationships. Data from only one pair of 3-month periods from an individual were analyzed.RESULTS:A total of 704 participants completed the baseline survey; 552 (78.3%) returned all 5 surveys. In all, 174 participants who had a flare were compared with 209 who had no flare. Perceived stress, negative affect (mood), and major life events were the only trigger variables significantly associated with flares. There were no differences between those who flared and those who did not, in the use of NSAIDs, antibiotics, or in the presence of infections. Multivariate logistic regression analyses indicated that only high-perceived stress (adjusted odds ratio=2.40 (1.35, 4.26)) was associated with an increased risk of flare.CONCLUSIONS:This study adds to the growing evidence that psychological factors contribute to IBD symptom flares. There was no support for differential rates of use of NSAIDS, antibiotics, or for the occurrence of (non-enteric) infections related to IBD flares.

How Long Should Catheter-Acquired Urinary Tract Infection in Women Be Treated?: A Randomized Controlled Study

OBJECTIVE To determine the optimal management of catheter-acquired bacteriuria after short-term catheter use in women. PATIENTS Asymptomatic patients (119) with catheter-acquired bacteriuria were randomly assigned to receive no therapy, a single dose (320-1600 mg) of therapy with trimethoprim-sulfamethoxazole, or 10 days (160-800 mg twice daily) of therapy. Thirty-two patients with lower tract symptoms alone received a single dose or 10 days of therapy, and 10 patients with upper tract symptoms or signs received 10 days of therapy. MAIN RESULTS The mean and median durations of catheter use were 6 and 4 days, respectively. Bacteriuria resolved within 14 days without therapy in 15 of 42 (36%; 95% CI, 21% to 51%) asymptomatic patients. Seven of the remaining patients developed symptoms. Single-dose therapy resolved infection in 30 of 37 patients (81%; CI, 68% to 94%); 10 days of therapy resolved infection in 26 of 33 (79%; CI, 65% to 93%). For patients with lower tract symptoms alone, resolution rates with single-dose therapy or 10 days of therapy were similar (11 of 14 [79%] and 13 of 16 [81%], respectively). Ten days of therapy resolved infection in 6 of 9 (67%) patients with upper tract symptoms. Infection was resolved more often in women who were less than or equal to 65 years than in older women (62 of 70 [89%] versus 24 of 39 [62%]; P less than 0.001). Bacteriuria resolved spontaneously more frequently in younger (14 of 19 [74%] compared with 1 of 23 older women [4%]; P less than 0.001). Single-dose therapy resolved infection in 31 of 33 (94%) patients who were less than or equal to 65 years. CONCLUSIONS Asymptomatic bacteriuria after short-term catheter use frequently becomes symptomatic and should be treated. For asymptomatic patients and patients with lower tract symptoms alone, single-dose therapy was as effective as 10 days of therapy; it was very effective in women who were less than or equal to 65 years. Bacteriuria resolved spontaneously within 14 days after catheter removal more commonly in women who were less than or equal to 65 years and both types of therapy were less effective in older women.

Antibody to Chlamydial hsp60 Predicts an Increased Risk for Chlamydial Pelvic Inflammatory Disease

To determine whether serum antibody to Chlamydia trachomatis antigens alters the risk of C. trachomatis pelvic inflammatory disease (PID), 280 female sex workers were prospectively evaluated over a 33-month period for incident C. trachomatis and Neisseria gonorrhoeae cervical infection and for clinical PID. At enrollment, women were tested for antibody to C. trachomatis elementary bodies by an indirect microimmunofluorescence assay and to recombinant chlamydial hsp60 (Chsp60) by an ELISA format. At each follow-up visit, women were tested for cervical chlamydial and gonococcal infection and were identified as having clinical PID if they complained of lower abdominal pain and were found to have uterine and adnexal tenderness on pelvic examination. The data demonstrate that antibody to Chsp60 predicts a 2- to 3-fold increased risk for C. trachomatis PID.

Defining the predictors of the placebo response in irritable bowel syndrome

BACKGROUND AND AIMS We sought to determine the components of irritable bowel syndrome (IBS) clinical trials that correlate with higher levels of placebo response. METHODS We performed a systematic review of placebo-controlled trials in patients with IBS to assess which variables correlate with a higher placebo response. Placebo responses for global symptom improvement and for decreased abdominal pain were assessed. Univariate and multiple linear regression analyses were conducted. RESULTS Higher rates of global improvement correlated with frequency of administration of study intervention ( r = .31, P = .03), duration of the study ( r = .28, P = .04), and overall treatment effect of the active agent being studied ( r = .33, P = .02). Higher rates of decreased abdominal pain correlated with the frequency of intervention ( r = .39, P = .02) and overall treatment effect ( r = .40, P = .01), whereas lower placebo response rates correlated with year of the study ( r = -.36, P = .03), median age ( r = -.38, P = .04), and duration of study run-in period ( r = -.33, P = .04). On multivariate analysis, global improvement in the placebo group was associated significantly with intervention frequency ( P = .0079), overall treatment response ( P = .0031), and parallel study design ( P = .0044). Decreased abdominal pain was associated significantly with frequency of intervention ( P = .0061) and overall treatment response ( P = .0128). CONCLUSIONS In IBS studies, higher placebo response rates correlated with frequency of the intervention and with overall treatment effect of the active agent being studied. In designing IBS trials, it may be possible to minimize placebo response by less frequent dosing. In treating patients with IBS, it may be possible to harness the placebo response and maximize therapeutic response rates by more frequent dosing.

EPIDEMIOLOGY OF OPHTHALMIA NEONATORUM IN KENYA

In a Nairobi hospital where ocular prophylaxis against ophthalmia neonatorum has been discontinued, 1,019 women were screened for Neisseria gonorrhoeae and Chlamydia trachomatis during labour and 7 and 28 days postpartum. The prevalence of gonococcal infection was 7% and that of chlamydial was 29%. 52.4% of gonococcal isolates produced penicillinase. The incidence of ophthalmia neonatorum was 23.2 per 100 live births, and incidences of gonococcal and chlamydial ophthalmia were 3.6 and 8.1 per 100 live births, respectively. Of 181 cases of neonatal conjunctivitis, 31% were caused by C trachomatis, 12% by N gonorrhoeae, and 3% by both. In 67 babies exposed to maternal gonococcal infection and 201 exposed to maternal chlamydial infection, rates of transmission to the eye were 42% and 31%, respectively, and to the throat were 7% and 2%. Gonococcal transmission rate was higher in mothers with concomitant chlamydial infection (68%; p = 0.01). Postpartum endometritis was associated with ophthalmia neonatorum (p less than 0.001). Ocular prophylaxis at birth for gonococcal ophthalmia should be reintroduced.

Status epilepticus in children

We have prospectively reviewed the data on 52 children who presented with status epilepticus. Thirty-four (65%) of the 52 had not had seizures before. Children who were previously abnormal were more likely to present with partial status epilepticus or to have seizures greater than 60 minutes than those who were previously normal. The median age (24 months) of those who presented with status epilepticus was the same as that of children with seizures of shorter duration. The causes were equally distributed among the idiopathic, acute encephalopathic and chronic encephalopathic groups. Three children died and 13 (28%) were left with neurological sequelae. The outcome was favorable for those in the idiopathic category.