Independent Predictors Of Treatment Failure Research Articles

Community-Onset Methicillin-Resistant Staphylococcus aureus Skin and Soft-Tissue Infections: Impact of Antimicrobial Therapy on Outcome

Conflicting data exist on the role of antimicrobial therapy for the treatment of uncomplicated community-onset methicillin-resistant Staphylococcus aureus (MRSA) skin and soft-tissue infections (SSTIs). We performed a retrospective cohort study of 492 adult patients with 531 independent episodes of community-onset MRSA SSTIs, which consisted of abscesses, furuncles/carbuncles, and cellulitis, at 2 tertiary care medical centers. The purpose of the study was to determine the impact of active antimicrobial therapy (i.e., the use of an agent to which the organism is susceptible) and other potential risk factors on the outcome for patients with uncomplicated community-onset MRSA SSTIs. Treatment failure was the primary outcome of interest and was defined as worsening signs of infection associated with microbiological and/or therapeutic indicators of an unsuccessful outcome. Bivariate analyses and logistic regression analyses were preformed to determine predictors of treatment failure. An incision and drainage procedure was performed for the majority of patients. Treatment failure occurred in 45 (8%) of 531 episodes of community-onset MRSA SSTI. Therapy was successful for 296 (95%) of 312 patients who received an active antibiotic, compared with 190 (87%) of 219 of those who did not (P=.001 in bivariate analysis). Use of an inactive antimicrobial agent was an independent predictor of treatment failure on logistic regression analysis (adjusted odds ratio, 2.80; 95% confidence interval, 1.26-6.22; P=.01). Our findings suggest that certain patients with SSTIs that are likely caused by MRSA would benefit from treatment with an antimicrobial agent with activity against this organism.

Predictors of the failure of treatment with chloroquine plus chlorpheniramine, in children with acute, uncomplicated,Plasmodium falciparummalaria

Resistance to chloroquine in Plasmodium falciparum can be reversed, both in vitro and in vivo, by chlorpheniramine, a histamine H(1) receptor antagonist. This reversal raises the possibility of using chlorpheniramine to prolong the clinical usefulness of chloroquine in resource-poor communities. The factors that identify children at risk of treatment failure after being given chloroquine plus chlorpheniramine have now been evaluated in 281 children with uncomplicated, P. falciparum malaria. The children, who had taken part in six trials of antimalarial drugs between February 1996 and September 1999, in a hyper-endemic area of south-western Nigeria, were enrolled prospectively for the present study. Following treatment with chloroquine plus chlorpheniramine, 13 (5%) of the children failed treatment by day 7 or 14. In a multivariate analysis, an age of < or =3 years (adjusted odds ratio = 11.1; 95% confidence interval = 2.2-55.3; P = 0.003) and a parasitaemia that took >3 days to clear (adjusted odds ratio=7.9; 95% confidence interval = 1.3-49.4; P = 0.027) were found to be independent predictors of treatment failure. In addition, compared with the children who had a lower axillary temperature then, the children who had an axillary temperature of > or =38 degrees C 2 days after commencing treatment were significantly more likely to be treatment failures. In resource-poor communities using chloroquine plus chlorpheniramine, the easily identifiable predictors of treatment failure might be used to identify children requiring alternative antimalarial drugs.

Early HVPG measurement and TIPS for acute variceal hemorrhage: Is sooner really better?

Early HVPG measurement and TIPS for acute variceal hemorrhage: Is sooner really better?

PRINCIPAL ROLE OF DIHYDROPTEROATE SYNTHASE MUTATIONS IN MEDIATING RESISTANCE TO SULFADOXINE-PYRIMETHAMINE IN SINGLE-DRUG AND COMBINATION THERAPY OF UNCOMPLICATED MALARIA IN UGANDA

Antimalarial resistance to sulfadoxine-pyrimethamine (SP) is mediated by mutations in the dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) genes. However, the relative importance of different mutations is incompletely understood and has not been studied with combination therapy. Samples from 812 patients treated for uncomplicated malaria in Kampala, Uganda were tested for the presence of mutations commonly found in Africa. The dhps Glu-540 mutation was the strongest independent predictor of treatment failure. The dhfr Arg-59 mutation was only predictive of treatment failure in the presence of the dhps Glu-540 mutation. Comparing combination regimens with SP monotherapy, the addition of chloroquine to SP did not improve efficacy, the addition of artesunate lowered the risk of treatment failure only for infections with both the dhfr Arg-59 and dhps Glu-540 mutations, and the addition of amodiaquine lowered this risk for all dhfr/dhps mutation patterns. The dhps Glu-540 mutation played a principal role and the dhfr Arg-59 mutation a secondary role in mediating resistance to SP alone and in combination.

Who will benefit from pelvic floor muscle training for stress urinary incontinence?

The purpose of this study was to determine which patient characteristics are predictive of outcome before pelvic floor muscle training for stress urinary incontinence. This was an observational study at a single-center outdoor patient clinic in Brussels, Belgium, that comprised 447 women, aged 26 to 80 years (mean, 52.7 years), who had urinary stress incontinence. All the women received individual pelvic floor muscle training under the guidance of the same physiotherapist. Twenty-two patient characteristics were considered for outcome measurements. Forty-nine percent of the women considered their treatment to be successful; 51% of the women had experienced only some improvement, no change, or a worsening of their condition or had interrupted therapy. Three independent predictors of treatment failure were > or =2 leakages per day before treatment ( P < .0001), the chronic use of psychotropic medication ( P = .002), and a baseline positive stress test result at first cough ( P = .042). The odds were only 15% for an individual patient to be treated successfully when these 3 predictors were present. Pelvic floor muscle training is beneficial in one half of the patients who are treated in this manner. Two or more leakages per day at baseline and the chronic use of psychotropic medication significantly predicted therapy failure.

The clinical course of culture-negative peritonitis complicating peritoneal dialysis

Background: Culture-negative peritonitis is a serious complication in peritoneal dialysis patients. Methods: We studied all consecutive episodes of culture-negative peritonitis in our unit from 1995 to 2001. We identified 1,182 episodes of peritonitis recorded; 212 episodes in 149 patients had negative culture results. Results: The overall primary response rate was 67.5%, and the complete cure rate was 37.7%. In 95 episodes (44.8%), technical problems during the collection of dialysis effluent were suspected. There was a history of antibiotic therapy within 30 days before the onset in 56 episodes (26.4%). Recent antibiotic therapy was associated with a lower primary response rate (31 of 56 versus 113 of 156 episodes; P = 0.019) and lower complete cure rate (12 of 56 versus 68 of 156 episodes; P = 0.003). Furthermore, a history of peritonitis from 31 to 120 days before the onset also was associated with a lower complete cure rate (P = 0.001). Multivariate analysis showed that recent peritonitis was the only independent predictor of treatment failure (odds ratio, 2.87; 95% confidence interval, 1.56 to 5.29). Conclusion: Most of the culture-negative peritonitis could be explained by recent antibiotic therapy or technical problems during dialysate culture. Recent peritonitis and antibiotic therapy are associated with a poor treatment response. Early Tenckhoff catheter removal is recommended in this group of patients.

Comparison of outcomes of ureteroscopy for ureteral calculi located above and below the pelvic brim

Objectives. To compare the safety and efficacy of ureteroscopy performed for proximal and distal ureteral calculi in a contemporary cohort. Ureteroscopy has been used most often for distal ureteral calculi. However, advances in endoscopic equipment have facilitated access to the proximal urinary tract and have broadened the indications for ureteroscopy. Methods. One hundred ninety-one patients underwent rigid and/or flexible ureteroscopy for ureteral calculi at the University of Michigan between January 1, 1997 and September 30, 1999. Only 7 patients with either bilateral calculi or steinstrasse were excluded. The final cohort consisted of 184 patients who underwent ureteroscopy for distal stones (n = 103) or middle/upper ureteral stones (n = 81). Results. Bivariate analyses of pretreatment and perioperative characteristics were used to assess the sample population. The initial success rate for the distal and proximal ureteral calculi was 96% and 78%, respectively ( P = 0.0008). After a “second-look” procedure in 4 and 7 patients with distal and proximal calculi, respectively, the success rate improved to 99% and 88%, respectively ( P = 0.004). No differences were noted between groups regarding the intraoperative ( P = 0.51) or postoperative ( P = 0.85) complication rates. Multivariate logistic regression analysis confirmed that larger stone size (odds ratio 1.2, P = 0.0006) and proximal ureteral location (odds ratio 4.8, P = 0.01) are independent predictors of treatment failure. Conclusions. Ureteroscopic management of proximal and distal ureteral calculi is highly successful, and the difference in success rates has narrowed substantially. Currently, no greater risk is conferred to the patient for endoscopy of more proximal ureteral calculi.

Biological determinants of cancer progression in men with prostate cancer.

The recent increase in ability to diagnose prostatic adenocarcinoma has created a dilemma for treatment decisions. To determine whether prostate cancer progression is associated with a modified version of the Gleason grading system together with selected morphologic and clinical variables. Retrospective analysis of a cohort of patients with peripheral zone prostate cancers who underwent surgery between August 1983 and July 1992. University hospital. Radical prostatectomy specimens from 379 men treated only by surgical excision were prospectively studied for 8 morphologic variables using previously standardized techniques. Variables were percentage of each cancer occupied by Gleason grade 4/5 (% Gleason grade 4/5, the Stanford modified Gleason scale), cancer volume, vascular invasion, lymph node involvement, seminal vesicle invasion, capsular penetration, positive surgical margin, prostate weight, and preoperative prostate-specific antigen (PSA) level. Biochemical progression of prostate cancer as indicated by serum PSA level of 0.07 ng/mL and increasing. Cancer grade expressed as % Gleason grade 4/5 and cancer volume were highly predictive of disease progression. In a Cox proportional hazards model that included % Gleason grade 4/5, the traditional Gleason score was not an independent predictor of treatment failure. Positive lymph node findings and intraprostatic vascular invasion were the only other variables that remained significant at the .01 level. The % Gleason grade 4/5, cancer volume, positive lymph node findings, and intraprostatic vascular invasion were independently associated with prostate cancer progression, defined by an increasing PSA level. Techniques to accurately measure cancer volume and % Gleason grade 4/5 are needed to better predict which patient will experience cancer progression. The commonly accepted predictors of progression-capsular penetration and positive surgical margins-were not independently predictive of failure after radical prostatectomy.

Enhancing compliance not a prerequisite for effective eradication of Helicobacter pylori: the HelP study

OBJECTIVE: The aim of this study was to compare cure rates of Helicobacter pylori ( H. pylori) infection, compliance, and side effects in patients given 10 days of omeprazole 20 mg b.d., amoxycillin 500 mg t.d.s., and metronidazole 400 mg t.d.s. (OAM) or 10 days OAM plus compliance enhancing measures. METHODS: A total of 119 H. pylori-positive patients were prospectively randomized to receive either 10 days OAM or 10 days OAM plus compliance enhancing measures (medication in a dose dispensing unit, medication chart, an information sheet about H. pylori treatment, and phone call 2 days after starting therapy). H. pylori eradication was assessed by 13C-UBT at least 4 wk after cessation of therapy, compliance by phone interview on the last day of therapy and returned pill count, and side effects by phone interview and returned side effects form. RESULTS: In 113 patients attending 13C-UBT H. pylori was eradicated in 51 of 57 patients (89.5%) after 10 days OAM and in 48 of 56 (85.7%) after 10 days OAM plus compliance enhancing measures ( p = 0.54). In both groups 97% of medications were taken. Side effects were common (82% of patients). Both side effects ( p = 0.001) and ulcer versus nonulcer at endoscopy ( p = 0.016) were independent predictors of treatment failure; side effects also predicted noncompliance ( p = 0.02). CONCLUSIONS: Ten days of OAM was effective for H. pylori eradication in our clinical population. Patient compliance was excellent and attempts to increase compliance had no impact on outcome or compliance. Side effects were very common and were significantly associated with treatment failure and decreased compliance.

Epidemiology and Clinical Consequences of Drug-Resistant Tuberculosis in a Guatemalan Hospital

To determine the epidemiology and clinical consequences of drug-resistant TB in Guatemala. A prospective study conducted for 12 months. A thoracic referral hospital in western Guatemala. Three hundred and seventy-six patients with confirmed TB. Of 376 confirmed cases, 335 (89%) were culture-positive. Tests of drug sensitivities to four first-line antituberculous drugs were performed in 172 (51%) of the culture-positive cases. Fifty-one patients (30%) were resistant to at least one antimicrobial agent, and 26 (15%) were resistant to at least two drugs. In a multivariate model of clinically available patient characteristics, only cavitary disease (odds ratio=2.1; 95% confidence interval, 1.1-6.6) and a history of taking anti-TB medication for >2 weeks (OR=3.0; 95% CI, 1.5-10.3) were independent predictors of resistance to two or more anti-TB agents. Resistance to two or more anti-TB drugs was the single independent predictor of treatment failure (OR=6.4; 95% CI, 2.3-17.8). Twenty-four of 172 patients (14%) who denied having received prior anti-TB therapy were infected with resistant organisms, suggesting ongoing transmission of drug-resistant strains. Although 84% (69 of 82 cases) of patients with fully susceptible organisms and 89% (17 of 19 cases) with singly resistant organisms were cured, only 45% of patients (10 of 22 cases) infected with organisms resistant to two or more agents were successfully treated. At this sentinel site for complicated TB, a substantial subset of cases who are infected with drug-resistant bacteria cannot be easily identified or treated.

Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome: a multivariate analysis of factors predicting the response to plasma exchange.

The aim of this study was to investigate pretreatment prognostic factors that could be useful in predicting the response to plasma exchange in thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS). Thirty-two patients with TTP/HUS, treated with plasma exchange at our institution from 1980 to 1994, were studied. The main clinical and laboratory data at the beginning of plasma exchanges were analyzed by the Cox stepwise logistic regression, applied to either treatment failure or death. Seventeen (53%) patients attained a complete remission and 22 (69%) survived (five in advanced renal failure and long-term hemodialysis). Longer delay in initiating plasma exchanges, presence of stupor or coma, and higher creatinine levels at the beginning of plasma exchanges were independent predictors of treatment failure. Stupor or coma at the beginning of plasma exchanges was the only predictor of mortality from unremitted TTP/HUS. Hemoglobin levels, platelet count, and LDH activity, traditionally envisaged as markers of disease activity, neither correlated with previous duration of TTP/HUS nor had any prognostic value. Early diagnosis of TTP/HUS and prompt initiation of intensive plasma exchange emerged from this study as the most effective interventions for improving the prognosis of TTP/HUS patients.