Antibiotic treatment and factors influencing short and long term outcomes of acute exacerbations of chronic bronchitis.

BACKGROUND: The MOSAIC study compared moxifloxacin with three standard antibiotic regimens in patients with Anthonisen type 1 acute exacerbations of chronic bronchitis (AECB). Further exploratory analyses were performed to identify prognostic factors of short and long term clinical outcomes and their value for clinical research. METHODS: Outpatients aged > or =45 years were screened between AECB episodes, randomised to treatment upon presenting with an AECB, assessed 7-10 days after study treatment, and followed monthly until a new AECB or for up to 9 months. Logistic regression assessed the predictive factors for clinical cure (return to pre-AECB status) and clinical success (cure or improvement), and a stepwise Cox regression model time to a composite event (failure of study treatment, new AECB, or further antibiotic treatment for AECB). RESULTS: In multivariate analyses, clinical cure was positively influenced by treatment with moxifloxacin (odds ratio (OR) 1.49; 95% CI 1.08 to 2.04) while cardiopulmonary disease (OR 0.59; 95% CI 0.38 to 0.90), forced expiratory volume in 1 second (FEV1) <50% predicted (OR 0.48; 95% CI 0.35 to 0.67), and > or =4 AECBs in the previous year (OR 0.68; 95% CI 0.48 to 0.97) predicted a poorer outcome. For clinical success, treatment with moxifloxacin had a positive influence (OR 1.57; 95% CI 1.03 to 2.41) while cardiopulmonary disease (OR 0.41; 95% CI 0.25 to 0.68) and use of acute bronchodilators (OR 0.50; 95% CI 0.30 to 0.84) predicted a poorer outcome. The occurrence of the composite event was influenced by antibiotic treatment (hazard ratio (HR) 0.82; 95% CI 0.68 to 0.98), age > or =65 years (HR 1.22; 95% CI 1.01 to 1.47), FEV1<50% predicted (HR 1.27; 95% CI 1.05 to 1.53), > or =4 AECBs in previous year (HR 1.63; 95% CI 1.34 to 1.99), and acute bronchodilator use (HR 1.48; 95% CI 1.17 to 1.87). For the composite event the beneficial effect of moxifloxacin was primarily seen in patients aged > or =65 years. CONCLUSION: Despite selection of a homogeneous population of patients with chronic bronchitis, between group differences relating to antibiotic treatment could still be confounded by factors related to medical history, severity of disease, and use of concomitant medications. The design of future clinical trials should take these factors into account.

Effectiveness of oral moxifloxacin in standard first-line therapy in community-acquired pneumonia.

Based on recent guidelines for the management of community-acquired pneumonia, this study was designed to evaluate the effectiveness of a new fluoroquinolone compared with standard antimicrobial regimens, in conditions relating as closely as possible to the real world setting. In this study, 564 patients were randomised to either oral moxifloxacin (400 mg o.d.) or to standard oral therapy (amoxicillin 1 g t.i.d. or clarithromycin 500 mg b.i.d. alone or in combination) for up to 14 days using a double-blind procedure. The choice between the three standard regimens was made by the clinician prior to randomisation. Clinical response, quality of life, symptoms, healthcare resources and safety were assessed. In the per-protocol population, clinical success was reported for 201 of 215 (93.5%) and 217 of 231 (93.9%) in the moxifloxacin and standard groups, respectively, at 7-10 days post-therapy. At 28-35 days follow-up, continued clinical cure was observed in 183 of 192 (95.3%) moxifloxacin and 207 of 221 (93.7%) standard groups. Drug-related adverse events were reported in 55 of 274 (20%) moxifloxacin and 86 of 279 (31%) standard patients with diarrhoea >5%. Oral moxifloxacin monotherapy was as effective as, and better tolerated than, optimal antibiotic strategy represented either by mono- or combination therapy (amoxicillin and/or clarithromycin) in community-acquired pneumonia management.

Quality of life in acute exacerbation of chronic bronchitis: results from a German population study.

This study reports on data from a study conducted in the Federal Republic of Germany examining the quality of life (QoL) of patients with chronic bronchitis (CB) and its acute exacerbations (AECB). Data from 320 patients were collected at AECB and subsequently during a stable phase (non-AECB) utilizing the St George's Respiratory Questionnaire (SGRQ) and the Nottingham Health Profile (NHP). As expected, the QoL of CB patients was poor, even at non-AECB, with patients reporting lower scores than patients with other chronic conditions. Patients reported significantly poorer QoL at AECB than at non-AECB. After adjusting for the severity of the underlying condition, poorer QoL at AECB was significantly and independently associated with older age, unemployment, increasing BMI, increasing number of prior AECBs, and Anthonisen AECB grade. While younger subjects reported significantly greater deterioration in QoL at AECB, the factors most consistently and independently associated with relative QoL deterioration at AECB were the number of prior AECBs and exposure to air pollution at home. In conclusion, this study highlights the detrimental effect of CB, and in particular AECB, on QoL. The association between QoL and patient reports of previous AECB number and air pollution are consistent with reports from other studies.

Intravenous and oral antibiotics in respiratory tract infection: an international observational study of hospital practice.

BACKGROUND: Hospitalised patients with respiratory tract infections (RTI) frequently receive intravenous (i.v.) antibiotics followed by a short course of oral treatment. OBJECTIVES: To observe antibiotic use in hospitals in Germany, Spain, France, Italy and the UK and the reasons for choosing the i.v. route and switching to oral treatment. METHODS: Research pharmacists sought the opinions of physicians and senior nurses in the completion of a semi-structured questionnaire on the treatment of RTI with i.v. antibiotics. Questions focussed on antimicrobials of choice, reasons for choosing i.v., reasons for changing to oral administration, and duration of treatment. RESULTS: This study recruited 796 patients with RTI, usually pneumonia. Prescribing patterns varied widely between the five hospitals. Accepted clinical criteria were only commonly cited in Germany, Spain and the UK as reasons for choosing the i.v. route at the beginning of the study. These were more commonly cited at the time of switch, although other criteria such as improved condition, were other significant reasons. The mean duration of i.v. treatment ranged from 4 days in the UK to 10 days in Italy, where most patients received the full course of treatment by the i.v. route. Unlike the other hospitals studied, the few patients in Italy who were switched to another form of treatment were as likely to receive intramuscular as oral administration (13% and 11%, respectively). CONCLUSIONS: The practice of and reasons for prescribing i.v. antibiotics varied in the hospitals studied. Objective clinical criteria were inconsistently cited as reasons for administering i.v. antibiotics and in general these reasons were unrelated to those given for the switch from i.v. to oral administration. In order for guidelines for switching from i.v. to oral antimicrobials to be routinely employed, explicit physiological criteria need to be recorded in a routine fashion. Closer co-operation between pharmacists and physicians may help in developing and implementing guidelines at a local level.

The impact of metrifonate therapy on caregivers of patients with Alzheimer's disease: results from the MALT clinical trial. Metrifonate in Alzheimer's Disease Trial.

OBJECTIVE: To assess the impact on burden reported by caregivers of patients with mild to moderate Alzheimer's disease (AD) who were treated with metrifonate during a randomized double blind clinical trial. DESIGN: Randomized clinical trial, with a 2-week screening period and a 26-week double blind, placebo controlled, treatment phase. Caregivers were assessed at baseline, at 12 weeks, and at end of trial. SETTING: Caregivers were interviewed at clinics as part of the assessment of the patients. PARTICIPANTS: Six hundred and three caregivers of AD patients who were enrolled in the MALT trial; 591 (98%) provided data suitable for analysis at baseline, and 546 (91%) provided data allowing for inclusion in the analysis of change scores. MEASUREMENTS: The Caregiver Burden Assessment consisted of the Screen for Caregiver Burden, including both subjective (SCB-subj) and objective (SCB-obj) scores; the cognitive subscale of Poulshock and Deimling (PD); an abridged version of the Relatives Stress Scale (aRSS); assessments of time spent in providing care, including the Caregiver Activity Time Scale (CATS); and demographic and background variables on both the patient and caregiver. RESULTS: Treatment of mild to moderate AD patients with metrifonate for a duration of 26 weeks significantly reduced the psychological burden of care to the caregivers, as measured by the SCB-subj, the PD, and the aRSS. There were no statistically significant differences on the measures assessing the time spent in caregiving, except for the caregiver's subjective impression of the change in time spent providing care during the trial. When comparing individual dose groups, most of the measures of burden showed the largest benefits in burden for the 60/80 mg group, followed by the 40/50 mg group, and then the placebo group. However, there was no statistically significant dose effect. CONCLUSIONS: This study provides the first evidence from a randomized clinical trial of any acetylcholinesterase inhibitor used in the treatment of AD demonstrating a positive impact on the patient's caregiver as well as benefits to the patient. These results were shown consistently across several measurement scales and were observed after six months of treatment. These findings reinforce the clinical significance of research that has shown that metrifonate has beneficial impacts on the cognitive, behavioral, and functional abilities of AD patients. Because caregiver burden is a leading factor in the decision for institutional care placement, the ability to favorably impact that burden through pharmacological treatment of the patient is important.

Health-related quality of life associated with lower urinary tract symptoms in four countries.

OBJECTIVES: To describe health-related quality of life (HRQL) associated with lower urinary tract symptoms (LUTS) assessed by validated questionnaires in four countries. METHODS: More than 6000 men, recruited by using community- or population-based sampling in four countries, completed questionnaires soliciting information about urinary symptom frequency, bother, degree of interference with daily activities, and other measures of HRQL. RESULTS: In all countries, disease-specific HRQL worsened with increasing age. Adjusting for age, most disease-specific HRQL measures were significantly worse with increasing symptom severity. The correlation between symptoms and HRQL was strongest in countries with higher prevalence of symptoms, such as Japan or the United States, and less pronounced in countries with lower prevalence (France, Scotland), possibly reflecting the lower variability in scores. CONCLUSIONS: HRQL measures are worse in older men, and increased urinary symptom severity is associated with worse disease-specific HRQL in all countries, despite potential cross-cultural differences in disease prevalence, medication use, perceptions, or willingness to report symptoms or worse HRQL. This cross-cultural consistency suggests that an assessment of symptom bother or interference with daily activities may be useful in patient evaluation.

The relationship between sexual life and urinary condition in the French community.

As part of a large, nationwide community-based study in France on health and urinary condition, involving 2011 men aged between 50 and 80 years, information was collected on sexual life factors (e.g., frequency of sexual desires and sexual relations, and the frequency of having difficulties with erection and ejaculation) in addition to an assessment of overall sexual life satisfaction. Data on sexual life were obtained by means of a self-administered questionnaire, while information on the frequency of urinary symptoms was obtained by a professional interviewer. The median number of sexual relations decreased with age from "once per week" in those aged 50-59 years to "less than once per week" in those aged 60-69 years to "never" in those aged over 70 years, while the percentage reporting difficulty with erection at least some of the time increased from 20 to 38% between 50-59 and 70-79 years, respectively. The number of sexual relations during the past month was by far the most important factor having an influence on overall sexual life satisfaction, with those men reporting relations less than once per week almost 10 times more likely to be dissatisfied. Severity of overall urinary symptoms (as well as many individual symptoms) was also inversely related to sexual life satisfaction, and the association persisted after taking account of the strong influence of age and the frequency of sexual relations. All other factors being equal (age, number of relations, comorbidities, and previous prostate surgery), the likelihood of men being dissatisfied with sexual life increased twofold in men with moderate symptoms and fourfold in those with severe symptoms. The results obtained in the current study should be considered preliminary, given the complexity of the relationship between these two factors and the lack of previously published evidence. They certainly call for further studies, which should include a detailed assessment of sexual function and a clinical assessment of the urinary condition.

International comparison of the community prevalence of symptoms of prostatism in four countries.

We conducted an international comparison of the prevalence of urinary symptoms of prostatism in 4 countries, using a community-based random sampling of subjects, similar study procedures, and a single definition of cases that was based on a standardized symptom questionnaire. In Scotland 1,994 medically eligible men aged 40-79 years agreed to participate from 3 communities of the Forth Valley. In France, a nation-wide survey was conducted cross-sectionally in a representative sample of 2,011 French men aged 50-84 years. In the USA, the Olmsted County (OC) study recruited an age- and urban/rural-stratified random sample of 2,115 county residents drawn from medically eligible men aged 40-79 years. In Japan, 290 men aged 40-79 years from a fishing village participated in the study. Response rates were 55, 53, 55, and 43% in Scotland, France, OC and Japan, respectively. Urinary symptoms were assessed by the International Prostate Symptom Score (I-PSS), after metrologic validation in English and cross-cultural adaptation of the questionnaire. The prevalence of moderate to severe symptoms (I-PSS > 7) were 14, 18, 38, and 56% in France, Scotland, OC and Japan, respectively. This pattern was consistent within decades of age, and was found for most of the individual urinary symptoms. The proportion of men in Japan reporting very low I-PSS (0 or 1) was approximately 2, 4 and 8 times less frequent, than in OC, Scotland, and France, respectively. Differences in the prevalence of reported urinary symptoms might reflect between-country differences in the true prevalence of benign prostatic hyperplasia. However, cross-cultural differences in the perception and/or willingness to report urinary symptoms may play an important role in the observed differences. Further study will be required to elucidate the underlying causes of the observed differences.

Determinants of treatment-seeking behaviour for urinary symptoms in older men.

OBJECTIVE: To determine the factors associated with seeking treatment for urinary symptoms among older men in a European population. SUBJECTS AND METHODS: A community survey involving a representative nationwide sample of 2011 French men aged between 50 and 80 years was performed and information collected using an interviewer-administered questionnaire. RESULTS: Visiting a doctor for urinary symptoms was associated with the perceived bothersomeness of urinary symptoms, in addition to and independently of the level of symptom severity. It was also associated with higher socio-economic class. Many partners of men with urinary symptoms were unaware of their condition. CONCLUSIONS: This study emphasizes the importance of including the perception of bother associated with urinary symptoms in addition to urinary severity and provides information useful for inclusion in education programmes on urinary symptoms.

A brief male sexual function inventory for urology.

OBJECTIVES: To develop a brief questionnaire to measure male sexual function. METHODS: An initial set of questions was refined and reduced through cognitive testing and two serial validation studies. In each study, men were recruited from a sexual dysfunction clinic and a general medicine practice to complete the instrument. Test-retest reliabilities, internal consistencies, and construct validities were examined. RESULTS: The final instrument covers sexual drive (two items), erection (three items), ejaculation (two items), perceptions of problems in each area (three items), and overall satisfaction (one item). Psychometric performance was generally very satisfactory, although self-assessments of ejaculate volume are problematic. Translations have been developed and pilot tested in a number of languages. CONCLUSIONS: The Brief Sexual Function Inventory may be useful for measuring male sexual function in practice and research.

Impact of symptoms of prostatism on level of bother and quality of life of men in the French community.

The impact of symptoms of prostatism on level of bother and quality of life of French men was assessed nationwide, in a representative community sample of 2,011 subjects 50 to 84 years old. Bothersome level and quality of life associated with 12 urinary symptoms were assessed by face-to-face interviews, using a previously validated questionnaire for benign prostatic hyperplasia (BPH). The international prostate symptom score and the American Urological Association (AUA) bothersome index were also computed. Urgency was by far the most bothersome symptom in French men. Nocturia and wetting underclothes ranked second in subjects who did not undergo prostate surgery and among symptomatic patients, respectively. Overall, symptom frequency accounted for 72% of the variability of symptom bother but the form and strength of this correlation varied among symptoms from 0.18 to 0.43. Among the symptomatic subjects who had not yet undergone prostate surgery 11%, 10% and 79%, respectively, were dissatisfied, neutral and satisfied with the current urinary condition. Satisfaction with the urinary condition was positively linked to symptom frequency (p < 0.001) and symptom bother level (p < 0.001). Nocturia, dysuria, daytime repeat voiding, wetting clothes and urgency, when severely bothersome, were independent predictors of decreased satisfaction with the urinary condition (p = 0.01). Approximately half of the patients with severe BPH symptoms expressed serious worries and concerns with the urinary condition, and sizable levels of interference by the symptoms with daily activities, which are potentially affected by urinary troubles. The AUA bother index was the best determinant of subject level of worry about the urinary condition and of interference with daily life. This study supported the concomitant use of the international prostate symptom score and the AUA bother index in further research studies of BPH related impairments in quality of life.

[Adaptation and validation in the French language of the International Score of Symptoms of Benign Prostatic Hypertrophy]. / Adaptation et validation en langue française du score international des symptômes de l'hypertrophie bénigne de la prostate.

The International Prostate Symptom Score, which was proposed during the First Consultation on Benign Prostatic Hyperplasia in June 1991, was culturally adapted and linguistically validated in French. In a first step, the English version, adapted from the questionnaire developed by the American Urological Association, was translated into French. In a second step, the French version was submitted to a multidisciplinary group who made linguistic improvements. In a third step, the refined version was tested in 30 persons and amended. Finally, the questionnaire was submitted to a linguistic validation study in a representative sample of 100 men aged 65 to 80. The use of this index will allow standardized measurements of urinary symptoms status in patients with benign prostatic hyperplasia.

Results of an epidemiological survey using a modified American Urological Association symptom index for benign prostatic hyperplasia in France.

The prevalence of urinary symptoms associated with benign prostatic hyperplasia was studied in a community-based, nationwide, representative sample of 2,011 French men 50 to 80 years old. Symptoms were assessed by the American Urological Association symptom index. After exclusion of patients with prostate cancer, 6.9% of the subjects reported having undergone prostate surgery. Among the surgery-free subjects, nocturia and repeat voiding within 2 hours were the most prevalent symptoms. Based on the American Urological Association symptom index, 18.8% of the men were considered free of urinary symptoms, and 67%, 13% and 1.2%, respectively, ranked between 1 and 7, 8 and 19, and 20 or more. The proportion of men scoring greater than 7 approximately doubled with each decade of age. Our estimation indicated that in 1992 approximately 1.14 million French men had moderate to severe urinary symptoms that were likely to be associated with benign prostatic hyperplasia. Previous studies had yielded higher prevalence estimates, probably due to differences in sampling design and diagnostic criteria.

[Evidences for genetic transmission of pulse arterial pressure]. / Evidences pour une transmission génétique de la pulsatilité artérielle.

Systolic (PS), diastolic (PD), and pulse (PULS) arterial blood pressure were examined in 151 French-West-Indies families. After adjustment for sex, age, Na/K urinary ratio, alcohol consumption, use of anti-hypertensive drug, the distributions of PS and PD were correctly fitted by two commingled normal distributions, one of them including 5% of the highest values of blood pressure which have to be compared to the high prevalence of hypertension in this population (10 to 20%). By performing segregation analyses under Lalouel et al.'s unified model we do not support any genetic transmission for PS and PD. On the contrary, large evidence for genetic transmission of PULS was found, involving one locus, two equally frequent alleles. However dominance cannot be correctly inferred. Accordingly, PULS appears to be of larger interest than PS and PD to study the genetic regulation of the arterial blood pressure.

Genealogical and genetical African admixture estimations, blood pressure and hypertension in a Caribbean community.

This study examines the relationships between blood pressure, prevalence of hypertension, and the degree of black African admixture in the population of the Caribbean Island of La Désirade which is homogeneous with respect to the environmental factors and for which the socioeconomical stratification does not match racial origin. The degree of admixture was estimated by using both genealogical information and genetic markers. Blood pressure was repeatedly measured using an automatic sphygmomanometer. After adjustment for age, sex, ponderal index, Na/K urinary ratio, and clinical alcoholism, blood pressure and prevalence of hypertension were found to be significantly higher for the individuals having the largest proportion of genes of black origin. Identical results were obtained when either genetic markers or genealogical information were used as an individual--estimator of admixture.