Background Aspirin desensitization improves clinical outcomes in most patients with aspirin-exacerbated respiratory disease. Most protocols for desensitization are time-consuming. Objective Our ...objective was to use historical information about the course of aspirin desensitization to enhance the efficiency of the desensitization protocol. Methods Four hundred twenty subjects with suspected aspirin-exacerbated respiratory disease underwent oral aspirin challenges. Their clinical characteristics were analyzed in relation to features of reactions during aspirin challenges. Results Large (FEV1 decrease >30%) and moderate (FEV1 decrease 21% to 30%) bronchial reactions occurred in 9% and 20% of subjects, respectively. Multivariate analysis identified risk factors associated with these larger reactions, including lack of leukotriene modifier use, baseline FEV1 of less than 80% of predicted value, and previous asthma-related emergency department visits. Seventy-five percent of patients reacted to a provoking dose of either 45 or 60 mg. Only 3% of initial reactions occurred after 150- or 325-mg provoking doses, and none occurred after the 650-mg dose. Conclusions Most bronchial and naso-ocular reactions during oral aspirin challenges occurred within a narrow dosing range (45-100 mg). Only 1 of 26 patients without risk factors had a moderate reaction.
A definitive diagnosis of aspirin-exacerbated respiratory disease (AERD) requires a positive oral aspirin challenge (OAC), but predicting which patients will have positive challenges is often ...difficult.
To analyze information about historical aspirin- and nonsteroidal anti-inflammatory drug (NSAID)-associated respiratory reactions and clinical characteristics as potential markers to predict positive OACs.
A total of 243 patients underwent OACs. Data related to previous reactions and clinical characteristics of patients were correlated with the result of the OACs.
Without prior exposure to aspirin or NSAIDs, the chance of a positive OAC was 5 in 12 (42%) but was 198 in 231 (86%) for those with a history of aspirin- and NSAID-associated asthma attacks. Sex, atopy, number of sinus infections per year, and number of sinus surgical procedures were not associated with positive OACs. Patients with 2 or more prior aspirin- and NSAID-associated respiratory reactions had an 89% chance of having a positive OAC vs single reactors (80%; P = .04). Mild or moderate prior reactions were associated with 84% or 80% positive OACs, whereas 100% of the 45 patients with severe prior reactions had positive OACs (P = .007). Except for hospitalizations, treatment locations of prior reactions (home or emergency department) did not seem to make any difference. Logistic regression identified age, sense of smell, and multiple prior reactions as independent risk factors associated with positive OACs.
Age younger than 40 years, poor sense of smell, multiple prior respiratory reactions, and severe prior asthmatic reactions associated with aspirin and NSAIDs significantly increased the chances of a positive OAC.
Background/Aims: Lamivudine is effective in treatment-naive patients with chronic hepatitis B, but its role in interferon nonresponders has not been described. We assessed lamivudine treatment, with ...or without added interferon, in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B who had failed interferon therapy previously.
Methods: Patients were randomized to lamivudine (100 mg) or placebo for 52 weeks or to a 24-week regimen of lamivudine plus interferon. Primary treatment comparisons were at week 52, with a 16-week posttreatment follow-up period. Measurements included histology (primary endpoint), HBeAg response, normalization of alanine aminotransferase, reduction of hepatitis B virus (HBV) DNA, and safety.
Results: Among 238 patients, histologic response was significantly more common in patients treated with lamivudine (52 versus placebo 25%,
P=0.002) or the combination regimen (32%,
P=0.01). HBeAg loss was also more common with lamivudine (33 versus 13 versus 21%), as were virologic and alanine aminotransferase responses. Among 28 subjects with HBeAg loss/seroconversion, 71% had durable responses 16 weeks posttreatment.
Conclusions: Lamivudine for 52 weeks is as effective in interferon nonresponders as in previously reported treatment-naive patients; however, a combination of lamivudine for 24 weeks and interferon for 16 weeks was not effective in this population.
The histological and clinical outcome of lamivudine 100
mg/day was assessed in 76 HBeAg-negative chronic hepatitis B patients previously randomised to a double-blind comparison study of lamivudine ...and placebo.
Paired liver biopsies were available before 1 year of randomised lamivudine treatment and after 2 years of further open-label treatment for 48 patients. Serum samples were analysed for hepatitis B markers and ALT levels (
n=74).
The histological activity index improved, remained unchanged and worsened in 64, 32 and 5%, respectively, for patients without YMDD-variant HBV compared to 15, 54 and 31% with the variant. None of the 42/48 patients without cirrhosis at baseline progressed to cirrhosis. Of 24/48 patients without bridging fibrosis at pre-treatment, 83% (20/24) did not progress to bridging fibrosis. Median HBV DNA remained below the lower limit of detection and ALT ≤1 times the ULN for patients without the variant whereas levels gradually increased to 11.3
Meq/ml (bDNA assay) and 2 times the upper limit of normal by month 24 for patients with variant.
The clinical benefit of lamivudine is greatest for patients without YMDD variants over 2 years of extended treatment. Additional therapies should be considered for patients with YMDD variants.
Background/Aims We aimed to evaluate nucleoside/nucleotide combination therapy in treatment-naïve HBeAg-positive patients with chronic hepatitis B (CHB). Methods One hundred and fifteen ...HBeAg-positive patients received lamivudine 100 mg daily plus placebo (monotherapy) or lamivudine 100 mg plus adefovir dipoxil 10 mg daily (combination therapy) for 104 weeks in a randomized double-blind study. Results Time-weighted average change in serum HBV DNA from baseline up to week 16 was −4.20 log10 copies/mL for both groups ( p = 0.936). At week 104, median serum HBV DNA change from baseline (log10 copies/mL) for monotherapy and combination therapy was −3.41 versus −5.22, respectively. HBV DNA breakthrough was detected in 44% of monotherapy and 19% of combination therapy patients. The M204V/I mutation was detected in 43% (15/35) and 15% (6/41) of each group, respectively. ALT normalization at week 100 and 104 was 34% (19/56) in the monotherapy group and 45% (23/51) in the combination therapy group ( p = 0.018). By week 104, HBeAg seroconversion occurred in 20% of monotherapy and 13% of combination therapy patients. Both regimens were well tolerated. Conclusions Lower rates of resistance to lamivudine, lower serum HBV DNA levels and higher rates of ALT normalization were seen in the combination therapy group after two years. However, serological outcomes were similar.
The Still Divided Academy Rothman, Stanley; Kelly-Woessner, April; Woessner, Matthew
Rowman & Littlefield Publishers, Inc,
2011, 2011-01-00, 2010-12-16, 20110101
eBook, Book
Drawing on data collected in a specially commissioned public opinion survey as well as other recent research on higher education, Rothman, Kelly-Woessner, and Woessner, create an incredibly readable ...presentation of both the similarities and differences between those running our universities and those attending them. The authors manage to remain impressively neutral; instead they give us a fuller perspective of the people on our college campuses.
Drug-resistant P.falciparum malaria is an increasing concern in sub-Saharan Africa (SSA), where previously effective monotherapy treatments were replaced by artemisinin combination therapies (ACT) ...because of resistance. ACTs typically have a good safety profile and high efficacy responses (>95%). Resistance to ACTs has been documented in Asia, but has not been observed in SSA. However, there are now signs artemisinin-resistance may be spreading to the African continent. An indication of artemisinin resistance is delayed parasite clearance time (PCT), defined as a slope half-life >5 hours (time to clear 50% of parasites). Artemisinin resistance may also cause ACT treatment failure (recrudescence). It is not clear though if delayed PCT or recrudescence is consistently explained by parasite factors such as resistance or host factors such as immunity. Exploring the determinants of both delayed PCT and recrudescence is the aim of this dissertation. Data from a large multi-center clinical trial conducted in 2006-7 when ACTs were first introduced in SSA were utilized for these analyses (n=1372). Candidate variables included: baseline parasitemia, sex, treatment, and surrogate factors for immunity (age, estimated endemicity, seasonality, previous malaria episodes, and geographic location). Logistic regression was used to assess significant factors associated with each outcome. In Aim 1, we found 24 cases with delayed PCT. Since the study occurred prior to the widespread introduction of ACTs in Africa, our data suggests that resistant parasite strains pre-existed the introduction of ACTs. Site (p<0.001) and baseline parasitemia (p<0.001) were significantly associated with delayed PCT. In Aim 2, slope half-life (p<0.001), treatment (p=0.004), seasonality (p=0.008), and endemicity (p=0.018) were significant factors in explaining recrudescence, with age (p=0.076) and sex (p=0.106) also having marginal contributions. In summary, our findings suggest that delayed PCT pre-dated the widespread use of artemisinin in Africa and that recrudescence may be related to environmental, host and parasite factors.
De juillet 1997 à juin 1998, 15 laboratoires de microbiologie, organisés en observatoire régional et répartis sur l'ensemble de l'Alsace, ont participé à un recrutement exhaustif des pneumocoques ...isolés en situation d'infection dans le but d'étudier leur sensibilité aux antibiotiques.
Les souches ont été isolées de prélèvements diagnostiques (prélèvements pulmonaires, hémocultures, liquides céphalorachidiens, prélèvements ORL).
L'observatoire a recruté 599 souches dont 32,9 % sont des pneumocoques de sensibilité diminuée à la pénicilline G (PSDP: concentrations minimales inhibitrices CMI > 0,06 mg/L). Parmi ces PSDP, dix souches présentent une résistance de haut niveau (CMI > 1 mg/L), trois sont résistantes à l'amoxicilline (CMI > 2 mg/L) et aucune au céfotaxime. La prévalence des PSDP est plus élevée chez l'enfant que chez l'adulte (45,3 % contre 28,2 %) et dans les pus d'oreille (59,4 %). Les PSDP sont fréquemment résistants à l'érythromycine (76,6 %), au cotrimoxazole (65,2 %) et à la fosfomycine (18,4 %). Les sérotypes 23, 14 et 9 sont les plus fréquents: 29,1 %, 26,1 % et 17,9 % des souches respectivement.
Cette enquête a permis de préciser, pour la première fois, l'impact exact de la résistance de
Streptococcus pneumoniae à la pénicilline G et aux antibiotiques dans la région Alsace. La prévalence des PSDP est l'une des plus faibles observées en France la même année avec une proportion très restreinte de souches résistantes à la pénicilline G et aux autres β-lactamines, γ compris dans les pus d'oreille de l'enfant.
From July 1997 to June 1998, 15 microbiological laboratories, set up as a regional survey unit in Alsace, collected
S. pneumoniae strains to assess their susceptibility to antibiotic agents,
The strains were isolated from various clinical samples (blood cultures, pulmonary samples, cerebrospinal fluid, otitis media).
599 strains were collected and the prevalence of Pneumococci with a Decreased Susceptibility to Penicillin G (PDSP) reached 32.9% (197 strains, MIC > 0.06 mg/L) but included a very small percentage of high level resistance strains to penicillin G (10 strains with MIC > 1 mg/L). Amoxicillin and cefotaxime remained active (3 and 0 resistant strains, respectively). The percentage of DPSP was much higher in the isolates of children (45.3%) than in those of adults (28.2%). The PDSP were rather resistant to erythromycin (76.6%), cotrimoxazole (65.2%), and fosfomycin (18.4%). Among PDSP, the most prevalent serotypes were 23, 14, and 9.
This epidemiological survey allowed to assess the local impact of pneumococcal resistance to antibiotics thanks to extensive collection and study.
