Potentiating the effects of radiotherapy in rectal cancer: the role of aspirin, statins and metformin as adjuncts to therapy.

BACKGROUND: Complete tumour response (pCR) to neo-adjuvant chemo-radiotherapy for rectal cancer is associated with a reduction in local recurrence and improved disease-free and overall survival, but is achieved in only 20-30% of patients. Drug repurposing for anti-cancer treatments is gaining momentum, but the potential of such drugs as adjuncts, to increase tumour response to chemo-radiotherapy in rectal cancer, is only just beginning to be recognised. METHODS: A systematic literature search was conducted and all studies investigating the use of drugs to enhance response to neo-adjuvant radiation in rectal cancer were included. 2137 studies were identified and following review 12 studies were extracted for full text review, 9 studies were included in the final analysis. RESULTS: The use of statins or aspirin during neo-adjuvant therapy was associated with a significantly higher rate of tumour downstaging. Statins were identified as a significant predictor of pCR and aspirin users had a greater 5-year progression-free survival and overall survival. Metformin use was associated with a significantly higher overall and disease-free survival, in a subset of diabetic patients. CONCLUSIONS: Aspirin, metformin and statins are associated with increased downstaging of rectal tumours and thus may have a role as adjuncts to neoadjuvant treatment, highlighting a clear need for prospective randomised controlled trials to determine their true impact on tumour response and overall survival.

Dipyridamole-induced headache and lower recurrence risk in secondary prevention of ischaemic stroke: a post hoc analysis.

BACKGROUND AND PURPOSE: Our objective was to investigate the association between recurrent stroke risk and headache induced by extended-release dipyridamole (ER-DP) when administered alone or with low-dose aspirin (ASA+ER-DP). METHODS: This was a post hoc analysis of prospectively collected data on recurrent stroke risk and headache as an adverse event or reason for treatment discontinuation from the PRoFESS (N = 20,332) and ESPS2 (N = 6602) trials. Hazard ratios (HRs) for recurrent stroke were calculated using the Cox model. RESULTS: In PRoFESS, the 2.5-year recurrent stroke risk in patients receiving ASA+ER-DP was 8.2% in those with headache within 7 days of starting treatment and 9.4% in those without [HR 0.85, 95% confidence interval (CI) 0.73-0.98; P = 0.03]. Recurrent stroke risk was 5.0% in patients who discontinued ASA+ER-DP due to headache by day 90 versus 9.2% in those who did not (HR 0.52, 95% CI 0.35-0.77; P = 0.001). No such difference was observed in clopidogrel-treated patients. In ESPS2, risk of recurrent stroke was 6.2% in patients who discontinued ASA+ER-DP due to headache by day 90 versus 9.8% in patients who did not (HR 0.62, 95% CI 0.31-1.27; P = 0.19) and 7.3% in patients who discontinued ER-DP due to headache by day 90 versus 13.2% in those who did not (HR 0.53, 95% CI 0.27-1.04; P = 0.06). CONCLUSIONS: Patients taking ASA+ER-DP in PRoFESS who developed headache had significantly reduced stroke recurrence risk versus those without headache. Similar (non-significant) findings for ASA+ER-DP and ER-DP in ESPS2 suggest that dipyridamole-induced headache may reflect better cerebrovascular function.

Comparison of polysomnographic and portable home monitoring assessments of obstructive sleep apnea in Saskatchewan women.

OBJECTIVES: To compare a commercially available, level III in-home diagnostic sleep test (Embletta, Embletta USA) and in-laboratory polysomnography (PSG) in women with suspected obstructive sleep apnea (OSA). METHODS: Consecutive women scheduled for routine PSG testing for evaluation of clinically suspected OSA and who met inclusion/exclusion criteria, were invited to participate. An in-home Embletta portable monitor test was performed one week before or after diagnostic PSG. RESULTS: Forty-seven of 96 women who met the inclusion/exclusion criteria agreed to participate. The mean (± SD) age of the patients was 52.0 ± 11.0 years, with a mean body mass index of 34.86 ± 9.04 kg/m2, and 66% (31 of 47) of patients were at high risk for OSA according to the Berlin score. Paired analysis of the overall population revealed no significant difference in mean apnea/hypopnea index (AHI) between the two diagnostic methods (P = 0.475). At an AHI of ≥ 5, the Embletta test was highly sensitive (90.6%) in determining abnormal versus normal OSA, with a positive predictive value of 82.7%. However, a higher Embletta AHI threshold of ≥ 10 may be more useful, with a higher level of agreement (kappa coefficient) with PSG testing and a positive predictive value of 92.3%. The in-home study was less useful at distinguishing severe from nonsevere OSA, yielding a sensitivity of 50%. CONCLUSIONS: In women believed to be at high-risk for OSA, Embletta in-home sleep testing is useful for the detection of sleep disordered breathing.

Fetal heart rate monitoring during nocturnal polysomnography.

STUDY OBJECTIVES: To evaluate the success rate of adding continuous electronic fetal heart rate monitoring (EFM) during full night polysomnography (PSG), in women with both gestational hypertension (GH) with uncomplicated singleton pregnancies. METHOD: As part of a larger study evaluating for the presence of sleep disordered breathing (SDB) in women with GH compared to women with uncomplicated pregnancies, continuous EFM was added to usual polysomnography. RESULTS: Forty-eight EFM studies (26 with GH and 22 with uncomplicated pregnancies) were evaluated. EFM studies were categorized by the percentage of time that interpretable tracings were obtained: < 25% of the time; 25-50% of the time; or > 50% of the time. We deemed > 50% of the time to be ideal, but under the test conditions 25-50% of the time to be acceptable. For women with GH, 71% of women had ideal or acceptable overnight EFM tracings compared to 82% for women with uncomplicated pregnancies. Of those women who were diagnosed with SDB, 77% had an acceptable or ideal EFM tracing. CONCLUSIONS: Adding EFM to conventional polysomnography is feasible and safe. It may prove an important adjunct as interest in sleep disorders of pregnancy continues to expand.

A survey of oysters (Crassostrea gigas) in New Zealand for Vibrio parahaemolyticus and Vibrio vulnificus.

A microbiological survey was conducted to determine the levels of total and pathogenic Vibrio parahaemolyticus (Vp) and Vibrio vulnificus (Vv) in Pacific oysters (Crassostrea gigas) collected from commercial growing areas in the North Island, New Zealand. The survey was intended to be geographically representative of commercial growing areas of Pacific oysters in New Zealand, while selecting the time frame most likely to coincide with the increased abundance of pathogenic vibrio species. Vp was detected in 94.8% of oyster samples examined (n=58) with a geometric mean concentration of 99.3 MPN/g, while Vv was detected in 17.2% of oyster samples examined with a geometric mean concentration of 7.4 MPN/g. The frequency of Vp positive samples was 1.7 fold greater than reported in a study conducted three decades ago in New Zealand. Potentially virulent (tdh positive) Vp was detected in two samples (3.4%, n=58) while no trh (another virulence marker) positive samples were detected. 16S rRNA genotype could be assigned only to 58.8% of Vv isolates (8:1:1 A:B:AB ratio, n=10). There was a good agreement [98.2% of Vp (n=280) and 94.4% of Vv (n=18) isolates] between molecular tests and cultivation based techniques used to identify Vibrio isolates and there was a significant (R(2)=0.95, P<0.001, n=18) linear relationship between the MPN estimates by real-time PCR and cultivation. There was no significant correlation between any of the environmental parameters tested and Vp or Vv concentrations.

Acceptance of interferon-gamma release assay by a high-risk urban cohort.

BACKGROUND: QuantiFERON ® -TB Gold (QFT-G), an interferon-gamma release assay, is approved for the diagnosis of latent tuberculosis infection (LTBI). It is unknown if patients at high risk for LTBI will more readily accept LTBI treatment based on tuberculosis skin testing (TST) or QFT-G. METHODS: Prospectively enrolled participants were interviewed, were read an informational paragraph on QFT-G, completed a questionnaire and were tested with QFT-G. RESULTS: A total of 230 consecutive participants with a history of hepatitis C virus infection and active or past illicit drug use were enrolled and underwent QFT-G testing: 77% had recent TST, 82% were human immuno- deficiency virus co-infected, 87% had a history of injection drug use, and 52% a history of homelessness. Of the 230 participants, 148 (64%) stated a preference for TST compared to QFT-G. The majority would take treatment based on either test (68%). A minority of patients (20%) stated a willingness to take LTBI treatment based on TST alone. Black race was associated with a willingness to take treatment based on TST (OR 2.72, 95%CI 1.05-7.10). CONCLUSIONS: Patients at high risk for LTBI were found to prefer TST to QFT-G. Most would accept treatment based on either test, and a subset stated unwillingness to take treatment based on QFT-G results. Outreach and education should accompany QFT-G roll-out in high-risk urban populations.

Investigation of the photochemistry of the poly{p-phenylenevinylene} precursor system: implications for nanolithography.

The photochemistry of poly{p-phenylene[1-(tetrahydrothiophen-1-io)ethylene chloride]} (PPTEC), a water soluble precursor of the semiconducting polymer, poly{p-phenylenevinylene} (PPV), has been studied both under atmospheric conditions and in environments devoid of oxygen. UV-visible spectroscopy and photoluminescence data has been used to provide a picture of the mechanistic pathways involved in UV irradiation of the PPTEC material. A new quantitative model for the effect of UV irradiation upon film morphology is presented, which leads to insights for the improved control of the characteristics of PPV nanostructures produced via near-field scanning optical lithography.

First Report of Phoma terrestris Causing Red Root Rot on Sweet Corn (Zea mays) in North Carolina.

Red root rot, caused by Phoma terrestris E. M. Hansen, caused premature senescence and yield reductions to fresh-market sweet corn in Hyde County, North Carolina in July 2006. Foliar symptoms developed over a period of 5 to 8 days approximately 1 to 2 weeks after anthesis and included desiccation of leaves and poor development of ears. By 3 weeks after pollination, when the sweet corn was harvested, crowns and the first aboveground internode of affected plants were rotted and reddish colored, but roots appeared normal. The root mass of affected plants tended to be greater than that of unaffected plants. Incidence of symptomatic plants was greater than 30% in some fields and was lower on crops planted and harvested early. Symptomatic and asymptomatic plants were adjacent in affected fields. Diseased plants were more common in fields of sweet corn that followed soybean (Glycine max) or a double-crop of onions (Allium cepa) than in fields that followed corn. Incidence of symptomatic plants also differed among adjacent plantings of different sweet corn hybrids. Hybrids '173A', '182A', '378a', and 'XTH1178' had a high incidence of symptomatic plants and '372A', '278A', '8101', and '8102' were less affected. Samples of symptomatic plants of the hybrid '182A' were examined at the North Carolina Plant Disease and Insect Clinic during August. Olivaceous black pycnidia with long setae around the ostioles were imbedded in the stalk near the first node aboveground. Numerous conidia (1.8 to 2.3 × 4.5 to 5.5 µm) were released in cirri from pycnidia. When cultured on potato dextrose agar (PDA), the fungus produced a red pigment and intercalary and terminal chlamydospores. Pathogenicity was demonstrated in the greenhouse by transplanting corn seedlings or direct-seeding corn into pots of soil infested with plates of PDA containing chlamydospores and hyphae. A suspension of chlamydospores and hyphae also was injected into the stems of plants 28 days after transplanting. Five replicates of the pathogenicity experiments were repeated twice with noninoculated controls. After 8 weeks, P. terrestris was recovered from the roots of all inoculated plants. Soil inoculation resulted in necrotic root tissue in approximately 25% of inoculated plants. Approximately 90% of inoculated plants had discolored crowns that resembled symptoms from field infected plants. Stem inoculations resulted in necrosis extending 2 to 5 cm from the point of injection and resulted in shoot death of 40% of inoculated plants that resulted in the development of an adventitious shoot. Red root rot was prevalent on field corn in the Delmarva Peninsula throughout the late 1980s and 1990s (1). To our knowledge, this is the first report of this disease causing damage to sweet corn in North Carolina. Foliar symptoms and discoloration of crowns of diseased sweet corn plants were similar to previously described symptoms of red root rot on field corn (2), however, roots of affected sweet corn plants were not substantially rotted and did not have a symptomatic reddish pink or dark carmine color, presumably because sweet corn is harvested prior to the development of root symptoms. References: (1) K. W. Campbell et al. Plant Dis. 75:1186, 1991. (2) D. G. White, ed. Compendium of Corn Diseases. The American Phytopathological Society, St Paul, MN, 1999.

A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults.

BACKGROUND: The incidence and severity of herpes zoster and postherpetic neuralgia increase with age in association with a progressive decline in cell-mediated immunity to varicella-zoster virus (VZV). We tested the hypothesis that vaccination against VZV would decrease the incidence, severity, or both of herpes zoster and postherpetic neuralgia among older adults. METHODS: We enrolled 38,546 adults 60 years of age or older in a randomized, double-blind, placebo-controlled trial of an investigational live attenuated Oka/Merck VZV vaccine ("zoster vaccine"). Herpes zoster was diagnosed according to clinical and laboratory criteria. The pain and discomfort associated with herpes zoster were measured repeatedly for six months. The primary end point was the burden of illness due to herpes zoster, a measure affected by the incidence, severity, and duration of the associated pain and discomfort. The secondary end point was the incidence of postherpetic neuralgia. RESULTS: More than 95 percent of the subjects continued in the study to its completion, with a median of 3.12 years of surveillance for herpes zoster. A total of 957 confirmed cases of herpes zoster (315 among vaccine recipients and 642 among placebo recipients) and 107 cases of postherpetic neuralgia (27 among vaccine recipients and 80 among placebo recipients) were included in the efficacy analysis. The use of the zoster vaccine reduced the burden of illness due to herpes zoster by 61.1 percent (P<0.001), reduced the incidence of postherpetic neuralgia by 66.5 percent (P<0.001), and reduced the incidence of herpes zoster by 51.3 percent (P<0.001). Reactions at the injection site were more frequent among vaccine recipients but were generally mild. CONCLUSIONS: The zoster vaccine markedly reduced morbidity from herpes zoster and postherpetic neuralgia among older adults.

Severe pre-eclampsia remote from term: what to expect of expectant management.

OBJECTIVE: To describe the duration of expectant management and the indications for termination of expectant management of pregnancies complicated by severe pre-eclampsia remote from term. STUDY DESIGN: We identified pregnancies complicated by severe pre-eclampsia diagnosed between 24 weeks and 31 weeks 6 days at our institution in 1991-98. Pertinent clinical data were obtained from review of maternal and neonatal charts. Comparison of patients was based on the duration of time from admission to delivery: < 48 h (group 1), 48 h to 7 days (group 2), and > or = 7 days (group 3). RESULTS: A total of 142 women met all study criteria. Seventy-nine (55.6%) women were delivered within 48 h, 42 (29.6%) between 48 h and 7 days, and 21 (14.8%) at > or = 7 days from diagnosis. Of group 1 patients (< 48 h), 59 (74.7%) were delivered for maternal indications while 20 (25.3%) were delivered for fetal indications. Of group 2 patients (48 h to 7 days), 35 (83.3%) were delivered for maternal indications while seven (16.7%) were delivered for fetal indications. Of group 3 patients (> or = 7 days), 16 (76.2%) were delivered for maternal indications while five (23.8%) were delivered for fetal indications. There were no significant differences in the indications for delivery based on the duration from admission to delivery. CONCLUSIONS: Despite an aggressive approach towards expectant management of preterm pregnancies complicated by severe pre-eclampsia, most patients were delivered within 48 h for maternal indications.

The effect of intrapartum magnesium sulfate therapy on fetal cardiac troponin I levels at delivery.

OBJECTIVE: To determine whether intrapartum magnesium sulfate (MgSO4) therapy for seizure prophylaxis in pre-eclampsia-eclampsia is associated with biochemical evidence of subacute fetal myocardial damage at delivery. STUDY DESIGN: Troponin I, a cardiac-specific protein used to detect myocardial injury, was measured from the umbilical vein at delivery in term pregnancies complicated by pre-eclampsia and uncomplicated control pregnancies. Women with pre-eclampsia received intravenous MgSO4 as a 6-g load followed by 2 g/hour until delivery. Clinical characteristics and fetal troponin levels were compared between groups. RESULTS: There was no difference in troponin I concentrations between term patients with intrapartum MgSO4 therapy and controls who did not receive MgSO4 (median 0.86 ng/ml, range 0.72-1.10 vs. 0.89 ng/ml, range 0.68-1.50; p = 1.0). There was also no statistically significant difference in the number of patients with a troponin I level of > or = 1.0 ng/ml between groups (30.8% (4/13) vs. 15.4% (4/26); p = 0.4). CONCLUSIONS: Our findings suggest that, in term fetuses that are not growth impaired, exposure to intrapartum MgSO4 is not associated with subacute myocardial injury.

Labor induction for the preterm severe pre-eclamptic patient: is it worth the effort?

OBJECTIVE: The purpose of this study was to examine the success rate of labor induction in patients with severe pre-eclampsia delivered at < or = 34 weeks' gestation; to identify factors associated with its success; and to evaluate neonatal outcomes based on induction success or failure. METHODS: We identified pregnancies complicated by severe pre-eclampsia delivered at < or = 34 weeks' at our institution from 1991 to 1998. Women who underwent labor induction and had successful vaginal delivery were compared to those who underwent labor induction, but required Cesarean delivery. Multiple logistic regression analyses were performed to assess factors associated with successful induction and neonatal outcome. RESULTS: Over the 7-year study period, there were 215 patients meeting the criteria. Sixty-four (29.8%) did not undergo a labor attempt; 69 of 151 (46%) women who underwent labor induction achieved vaginal delivery. Labor induction was successful in 0%, 6.6%, 35.3% and 68.5% of cases at 24-26, 27-28, 29-31 and 32-34 weeks' gestation, respectively. By logistic regression the only factor positively associated with successful induction was gestational age at delivery (p = 0.001), while induction for non-reassuring fetal testing was inversely associated (p = 0.02). Induction attempt, failed induction and delivery mode were not associated with increased neonatal morbidity. CONCLUSIONS: In women with severe pre-eclampsia remote from term, attempted labor induction did not appear to increase neonatal morbidity, but was rarely successful at < 28 weeks.

Methacholine challenge: test-shortening procedures.

STUDY OBJECTIVES: Validation of test-shortening procedures for the 2-min tidal breathing methacholine challenge method. DESIGN: Retrospective chart review. SETTING: Tertiary-care university clinical pulmonary function laboratory. PATIENTS: One thousand subjects aged 10 to 85 years (mean +/- SD, 44.5 +/- 16.0 years), 44.5% male, referred for methacholine challenge. INTERVENTION: Two-minute tidal breathing methacholine challenge was performed, with both physician and technician access to published test-shortening procedures. MEASUREMENTS AND RESULTS: There were 315 positive test results (provocative concentration of methacholine causing a 20% fall in FEV(1) [PC(20)] < or = 8 mg/mL) and 685 negative test results. The subjects with positive test results were less likely to be male (39.1 vs 47.5%; p < 0.02) and had lower FEV(1) (91.8 +/- 14.9% predicted vs 97.2 +/- 13.9% predicted; p < 0.001). The average starting PC(20) was between 0.5 mg/mL and 1.0 mg/mL; the most common PC(20) was 1 mg/mL (67%). There were 431 skipped concentrations in 380 subjects. The mean number of methacholine inhalations was 3.7 +/- 1.1 (3.9 +/- 0.1 for negative test results vs 3.3 +/- 1.2 for positive test results; p < 0.001). Eighteen subjects had a > or = 20% FEV(1) fall on the first inhalation, and 11 subjects had a > or = 20% FEV(1) fall after a skipped concentration. In only one case (0.1%) an FEV(1) fall > or = 40% on the first concentration was reported, compared with no cases after a skipped concentration and seven cases with a > or = 40% FEV(1) fall after a routine doubling dose step-up. CONCLUSIONS: The 2-min tidal breathing methacholine test in clinical practice can be safely shortened to an average of less than four inhalations using starting concentrations based on FEV(1), asthma medication, and clinical features, and by occasionally omitting concentrations.

Safer sex decision-making among men with haemophilia and HIV and their female partners.

An exploratory qualitative study of adult heterosexual men with haemophilia and HIV and women who were their sexual partners was conducted as formative research to better understand cognitive factors involved in behavioural intentions and practices which comprise HIV risk-reduction for sexual transmission. The study sought to generate hypotheses, uncover themes, and develop a broad perspective on possible determinants of behaviours related to HIV transmission risk reduction. Qualitative analysis of these data served as a basis for developing a subsequent quantitative, hypothesis-testing survey and an intervention. Face-to-face interviews were conducted with 23 single men and 28 married men with haemophilia and HIV infection, and 28 married women partners selected through stratified, purposeful sampling. The interviews identified beliefs, attitudes, and values underlying decisions regarding target behaviours related to preventing sexual transmission of HIV, including (1) using condoms consistently during vaginal intercourse and (2) talking to partners about risk reduction. The interviews elicited information about perceived advantages and disadvantages of performing each of the targeted behaviours, and factors that facilitate or prevent performing them. Qualitative analysis of coded responses yielded important themes regarding how choices are made about sexual activity and safer sex. Most notably, communication between partners (1) plays a direct, key role in facilitating condom use and (2) forms the basis for maintaining emotional intimacy in these relationships. The link between condom use and communicating about safer sex was viewed as pivotal in achieving HIV prevention for individuals in serodiscordant couples. Recommendations for risk reduction intervention development are discussed.

High prevalence of the very rare Wilson disease gene mutation Leu708Pro in the Island of Gran Canaria (Canary Islands, Spain): a genetic and clinical study.

The molecular basis of Wilson disease (WD), an autosomal recessive disorder, is the presence of mutations in the ATP7B gene, a copper transporting ATPase. Hospital records indicated a higher prevalence of WD (1 in 2,600) in some counties in the northeastern region of the island of Gran Canaria (Canary Islands, Spain) that was around 10-fold higher than that described for European populations (1 in 30,000). The ATP7B gene was analyzed for mutations in 24 affected subjects, revealing a high prevalence of the rare Leu708Pro mutation present in 12 homozygous and 7 heterozygous individuals. In these patients, who constitute one of the largest described cohorts of WD homozygotes, we found a variable clinical presentation of the disease, although the biochemical picture was homogenous and characteristic, thereby confirming that the Leu708Pro change is indeed a mutation associated with WD. Haplotype analysis of subjects homozygous for the Leu708Pro mutation showed a conserved shared region smaller than 1 centimorgan (cM), and the region of linkage disequilibrium between the Leu708Pro mutation and neighboring microsatellite markers extended approximately 4.6 cM. When comparing the amount of linkage disequilibrium versus genetic distance from the disease mutation, it was estimated that a common ancestral Leu708Pro chromosome may have been introduced in Gran Canaria over 56 generations ago, dating it back to pre-Hispanic times. The prevalence, and the tight geographical distribution of the Leu708Pro chromosome suggests that the Canary Islands can be considered a genetic isolate for linkage disequilibrium studies.

Evaluation and technical assistance for successful HIV program delivery.

Agencies that provide HIV prevention programs (including agencies using science-based interventions) need to conduct evaluation to facilitate the transfer of effective interventions, provide ongoing assistance to intervention providers, document services provided, demonstrate effectiveness, and improve programs. The Centers for Disease Control and Prevention (CDC) assists health departments, community-based organizations, and other CDC grantees with evaluation by providing direct, customized technical assistance and written guidance. Together, these activities assist grantees in conducting evaluations that provide the information that grantees need as their programs develop.

Routine pulse oximetry during methacholine challenges is unnecessary for safety.

BACKGROUND: Methacholine-induced bronchoconstriction is associated with significant hypoxemia, which can be assessed noninvasively by transcutaneous oxygen tension and pulse oximetry. OBJECTIVES: To assess the value of the monitoring of finger pulse oximetry during routine methacholine challenges in a clinical pulmonary function laboratory with regard to both safety and the possibility that a significant fall in oxygen saturation as measured by pulse oximetry (SpO(2)) might be a useful surrogate for determining the response to methacholine. METHODS: Two hundred consecutive patients undergoing diagnostic methacholine challenges in the pulmonary function laboratory of a tertiary-care, university-based referral hospital were studied. Methacholine challenges were performed by the standardized 2-min tidal breathing technique, and the DeltaFEV(1) was calculated from the lowest postsaline solution inhalation to the lowest postmethacholine inhalation value. SpO(2) was measured immediately prior to each spirogram, and the DeltaSpO(2) was measured from the lowest postsaline solution inhalation value to the lowest postmethacholine inhalation value. We examined the data for safety (ie, any SpO(2) value < 90). Based on previous reports, we used a DeltaSpO(2) of > or = 3 as significant and looked at the sensitivity, specificity, and positive and negative predictive values for DeltaSpO(2) > or = 3 vis-à-vis a fall in FEV(1) of > or = 15%. RESULTS: There were 119 nonresponders (DeltaFEV(1), < 15%) and 81 responders. The baseline FEV(1) percent predicted was slightly but significantly lower in the responders (responders [+/- SD], 91.6 +/- 15%; nonresponders, 96.4 +/- 14%; p < 0.05). DeltaSpO(2) was 3.1 +/- 1.6 in the responders and 1.6 +/- 1.8 in the nonresponders (p < 0. 001). There was a single recording in one patient of SpO(2) < 90 (88). A DeltaSpO(2) > or = 3 had a sensitivity of 68%, a specificity of 73%, a positive predictive value of 63%, and negative predictive value of 77% for a fall in FEV(1) > or = 15%. CONCLUSIONS: Pulse oximetry is not routinely useful for safety monitoring during methacholine challenge. DeltaSpO(2) is not helpful in predicting a positive spirometric response to methacholine. However, the negative predictive value is adequate to allow the DeltaSpO(2) to be used as an adjunct in assessing a negative result of a methacholine test in patients who have difficulty performing spirometry.

Differences between women and men in adverse events and CD4+ responses to nucleoside analogue therapy for HIV infection. The Aids Clinical Trials Group 175 Team.

OBJECTIVE: To prospectively examine differences in baseline characteristics and study outcomes between HIV-infected women and men during a clinical trial of nucleoside analogue therapy. METHODS: ACTG 175 randomized HIV-infected patients with CD4+ counts between 200 and 500 cells/mm3 to one of four nucleoside analogue regimens: zidovudine (ZDV), didanosine (ddI), ZDV + ddI, or ZDV + zalcitabine (ddC). Differences in time to first dose modification, voluntary withdrawal, development of toxicity and symptomatology, and AIDS progression were compared by gender. RESULTS: The study included 438 women and 2029 men. Baseline values of HIV RNA plasma concentrations were significantly lower for women (0.3 log10) than men in a subset of patients in whom assays were taken and this difference persisted after adjustment for CD4+ count. Women reported reducing dosage and discontinue ddI-containing regimens more frequently than men did; adjustment for weight did not completely explain this difference. Women were at lower risk than men for progression to a study endpoint (19% of women versus 24% of men; p <.0001). Among those antiretroviral-naive study subjects receiving ZDV, men were four times more likely to progress to a study endpoint than women. CONCLUSIONS: Differences in pretreatment characteristics and on study experiences were demonstrated between women and men enrolled in this clinical trial. The suggestion of a gender difference in response to ZDV monotherapy by antiretroviral-naive study subjects and the lower baseline values for HIV RNA in women compared with those in men provides evidence for gender differences in the relationship between virus replication, CD4+ decline, and responses to nucleoside analogue therapy.

CDC HIV prevention indicators: monitoring and evaluating HIV prevention in the USA.

OBJECTIVE: This study selected and field tested indicators to track changes in HIV prevention effectiveness in the USA. METHODS: During 1996-1999, the Centers for Disease Control and Prevention held two 2 day expert consultations with more than 80 national, state and local experts. A consensus-driven, evidence-based approach was used to select 70 indicators, which had to be derived from existing data, available in more than 25 states, and meaningful to state health officials in monitoring HIV. A literature review was performed for each indicator to determine general relevance, validity, and reliability. Two field tests in five US sites determined accessibility, feasibility, and usefulness. RESULTS: The final 37 core indicators represent four categories: biological, behavioral, services, and socio-political. Specific indicators reflect the epidemic and associated risk factors for men who have sex with men, injection drug users, heterosexuals at high risk, and childbearing women. CONCLUSIONS: Despite limitations, the indicators sparked the regular, proactive integration and review of monitoring data, facilitating a more effective use of data in HIV prevention community planning.