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Maternal opioid use poses a significant health concern not just to the expectant mother but also to the fetus. Notably, increasing numbers of children born suffering from neonatal opioid withdrawal syndrome (NOWS) further compounds the crisis. While epidemiological research has shown the heightened risk factors associated with NOWS, little research has investigated what molecular mechanisms underly the vulnerabilities these children carry throughout development and into later life. To understand the implications of in utero and post-natal opioid exposure on the developing brain, we sought to assess the response to one of the most common pediatric injuries: minor traumatic brain injury (mTBI). Using a rat model of in utero and post-natal oxycodone (IUO) exposure and a low force weight drop model of mTBI, we show that not only neonatal opioid exposure significantly affects neuroinflammation, brain metabolites, synaptic proteome, mitochondrial function, and altered behavior in juvenile rats, but also, in conjunction with mTBI these aberrations are further exacerbated. Specifically, we observed long term metabolic dysregulation, neuroinflammation, alterations in synaptic mitochondria, and impaired behavior were impacted severely by mTBI. Our research highlights the specific vulnerability caused by IUO exposure to a secondary stressor such as later life brain injury. In summary, we present a comprehensive study to highlight the damaging effects of prenatal opioid abuse in conjunction with mild brain injury on the developing brain., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Fragile X syndrome (FXS), the most prevalent heritable form of intellectual disability, is caused by the transcriptional silencing of the FMR1 gene. While neuronal contribution to FXS has been extensively studied in both animal and human-based models of FXS, the roles of astrocytes, a type of glial cells in the brain, are largely unknown. Here, we generated a human-based FXS model via differentiation of astrocytes from human-induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs) and characterized their development, function, and proteomic profiles. We identified shortened cell cycle, enhanced Ca 2+ signaling, impaired sterol biosynthesis, and pervasive alterations in the proteome of FXS astrocytes. Our work identified astrocytic impairments that could contribute to the pathogenesis of FXS and highlight astrocytes as a novel therapeutic target for FXS treatment., (© 2023 The Authors. GLIA published by Wiley Periodicals LLC.)

Oxygenic photogranules have received increasing interest due to their ability to treat wastewater without aeration and recover wastewater's chemical energy and solar energy. It has been reported that these photogranules can be produced under both hydrostatic and hydrodynamic conditions, and enrichment of filamentous cyanobacteria is required for this photogranulation to occur. Despite the critical role extracellular polymeric substances (EPS) play in granulation, EPS in photogranulation is yet virtually unknown. Here, we present the fate and dynamics of different fractions of EPS in sludge-based photogranulation under hydrostatic conditions. The study shows that during the transformation of activated sludge into a photogranular biomass, sludge's base-extractable proteins selectively degrade. Strong correlations between base-extracted proteins and the growth of chlorophyll a and chlorophyll a/ b ratio suggest that the bioavailability of this organic nitrogen is linked with selection and enrichment of filamentous cyanobacteria under hydrostatic conditions. The results of soluble and sonication-extractable EPS and microscopy also show that the growth of filamentous cyanobacteria required large amounts of polysaccharide-based EPS for their motility and maintenance. With findings on the progression of photogranulation, the fate and dynamics of EPS, and microscopy on microstructures associated with EPS, we discuss potential mechanisms of photogranulation occurring under hydrostatic conditions.

Microorganisms often respond to their environment by growing as densely packed communities in biofilms, flocs or granules. One major advantage of life in these aggregates is the retention of its community in an ecosystem despite flowing water. We describe here a novel type of granule dominated by filamentous and motile cyanobacteria of the order Oscillatoriales. These bacteria form a mat-like photoactive outer layer around an otherwise unconsolidated core. The spatial organization of the phototrophic layer resembles microbial mats growing on sediments but is spherical. We describe the production of these oxygenic photogranules under static batch conditions, as well as in turbulently mixed bioreactors. Photogranulation defies typically postulated requirements for granulation in biotechnology, i.e., the need for hydrodynamic shear and selective washout. Photogranulation as described here is a robust phenomenon with respect to inoculum characteristics and environmental parameters like carbon sources. A bioprocess using oxygenic photogranules is an attractive candidate for energy-positive wastewater treatment as it biologically couples CO 2 and O 2 fluxes. As a result, the external supply of oxygen may become obsolete and otherwise released CO 2 is fixed by photosynthesis for the production of an organic-rich biofeedstock as a renewable energy source.

Recently, the use of phototrophs for wastewater treatment has been revisited because of new approaches to separate them from effluent streams. One manifestation uses oxygenic photogranules (OPGs) which are dense, easily-settleable granular biofilms of cyanobacteria, which surrounding populations of heterotrophs, autotrophs, and microalgae. OPGs can remove COD and nitrogenous compounds without external aeration. To better grow and maintain biomass in the proposed wastewater process, this study seeks to understand the factors that contribute to successful granulation. Availability of initial inorganic nitrogen, particularly ammonium, was associated with successful cultivation of OPGs. In the first days of granulation, a decrease in ammonium coupled with an increase in a cyanobacterial-specific 16S rRNA gene, may suggest that ammonium was assimilated in cyanobacteria offering a competitive environment for growth. Though both successful and unsuccessful OPG formation demonstrated a shift from non-phototrophic bacterial dominated communities on day 0 to cyanobacterial dominated communities on day 42, the successful community had a greater relative abundance (46%) of OTUs associated with genera Oscillatoria and Geitlernema than the unsuccessful community (27%), supporting that filamentous cyanobacteria are essential for successful OPG formation. A greater concentration of chlorophyll b in the unsuccessful OPG formation suggested a greater abundance of algal species. This study offers indicators of granulation success, notably availability of inorganic nitrogen and chlorophyll a and b concentrations for monitoring the health and growth of biomass for a potential OPG process.

Background: Patients with advanced renal cell carcinoma in routine clinical practice can differ considerably from those in phase III studies., Patients and Methods: PREDICT (Patient characteristics in REnal cell carcinoma and Daily practICe Treatment with sorafenib) was a prospective, noninterventional study of open-label sorafenib for the treatment of advanced RCC conducted in 18 countries. Patient characteristics, therapy duration, tumor status, and tolerability were assessed at baseline and during routine follow-up., Results: Overall, 2599 patients were evaluable for safety and 2311 for efficacy. The diverse population included patients with brain metastases (5%), non-clear-cell histologies (17%), high Memorial Sloan-Kettering Cancer Center risk score (11%), poor Eastern Cooperative Oncology Group performance status (PS ≥ 2, 29%), and patients with no previous nephrectomy (16%) or no previous systemic therapy (37%). The median duration of sorafenib therapy was 7.3 months and was similar in clinically relevant subgroups (eg, patients with PS 2, brain metastases, or concomitant hypertension or diabetes [range, 6.7-7.0 months]). The median duration of therapy was shorter for patients with PS 3 or non-clear-cell histologies (4.6 and 4.8 months, respectively). The most common drug-related adverse events were hand-foot skin reaction (20%), diarrhea (17%), and rash (8%)., Conclusion: Sorafenib was generally well tolerated and provided clinical benefit in a large, diverse population of patients with advanced RCC treated in routine clinical practice., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

OBJECTIVES To compare two-year continuation rates and user satisfaction with the levonorgestrel releasing-intrauterine system (LNG-IUS) and the etonogestrel releasing-subdermal implant (ENG implant) in women in Europe. METHODS This prospective, non-interventional study was undertaken at 72 sites in France (n = 61), Great Britain (n = 2), Ireland (n = 3) and Slovakia (n = 6). Women opting to switch their method of contraception to the LNG-IUS or the ENG implant were followed-up over 24 months to document continuation and satisfaction with their chosen contraceptive method. Reasons for discontinuation were documented. RESULTS The data analysed were based on 363 women (LNG-IUS [n = 247] and ENG implant [n = 116]), aged 20 to 45 years, with at least one follow-up visit after contraceptive placement. The documented cumulative continuation rate was 82% in the LNG-IUS group and 67% in the ENG implant group at 24 months. The documented discontinuation rates were 13% and 17%, respectively. Bleeding problems were cited as reason for discontinuation in 4% and 11% of women in the LNG-IUS and ENG implant groups, respectively. CONCLUSIONS The LNG-IUS is associated with higher continuation rates and user satisfaction than the ENG implant in this study of women in Europe, though the groups were not similar in all respects. Bleeding problems with the ENG implant account for most of the reasons for discontinuing its use.

Objectives: To identify factors associated with late recovery (≥ 8 days from exacerbation start) in patients with acute exacerbations of chronic bronchitis/COPD (AECB/AECOPD)., Methods: An international, observational, non-interventional study in outpatients with AECB/AECOPD who received treatment for their exacerbation with the antibiotic moxifloxacin. Factors analyzed for late recovery included patient demographic characteristics, geographic region and disease severity. Additionally, logistic regression analysis was undertaken to identify factors associated with late recovery., Results: The analysis population was 40,435 patients aged ≥ 35 years, from Asia-Pacific, Europe, the Americas and Middle East/Africa. Most were male (63.1%), mean age 60.4 years and current or ex-smokers (60.6%) with history of ≥ 2 exacerbations in the previous year. Patients who underwent spirometry (n = 6408, 19.7%) had moderate airflow obstruction (mean FEV(1) 1.7 L). Both clinicians and patients reported that moxifloxacin provided clinical improvement in a mean of 3 days and recovery in 6 days. Clinical factors significantly associated with late recovery were: age ≥ 65 years, duration of chronic bronchitis >10 years, cardiac comorbidity, >3 exacerbations in the previous 12 months, current exacerbation type (Anthonisen I/II) and hospitalization in the last 12 months., Conclusions: In a large cohort of patients, all treated with the same antibiotic for an exacerbation of chronic bronchitis or COPD, the main factors associated with late recovery (≥ 8 days) were: older age, history of frequent exacerbations, current exacerbation type of Anthonisen I/II, history of prior hospitalizations and cardiac comorbid conditions., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

In Schwann cells, connexin 32 (Cx32) can oligomerize to form intracellular gap junction channels facilitating a shorter pathway for metabolite diffusion across the layers of the myelin sheath. The mechanisms of Cx32 intracellular channel regulation have not been clearly defined. However, Ca(2+), pH, and the phosphorylation state can regulate Cx32 gap junction channels, in addition to the direct interaction of protein partners with the carboxyl-terminal (CT) domain. In this study, we used different biophysical methods to determine the structure and characterize the interaction of the Cx32CT domain with the protein partners synapse-associated protein 97 (SAP97) and calmodulin (CaM). Our results revealed that the Cx32CT is an intrinsically disordered protein that becomes α-helical upon binding CaM. We identified the GUK domain as the minimal SAP97 region necessary for the Cx32CT interaction. The Cx32CT residues affected by the binding of CaM and the SAP97 GUK domain were determined as well as the dissociation constants for these interactions. We characterized three Cx32CT Charcot-Marie-Tooth disease mutants (R219H, R230C, and F235C) and identified that whereas they all formed functional channels, they all showed reduced binding affinity for SAP97 and CaM. Additionally, we report that in RT4-D6P2T rat schwannoma cells, Cx32 is differentially phosphorylated and exists in a complex with SAP97 and CaM. Our studies support the importance of protein-protein interactions in the regulation of Cx32 gap junction channels and myelin homeostasis.

Background: Iodine-based contrast agents such as iopromide play a central role in improving the diagnostic quality of imaging modalities using ionizing radiation., Purpose: To investigate the safety and diagnostic image quality of iopromide in the routine clinical setting., Material and Methods: This was an international, multicenter, prospective, single-arm, non-interventional study (NIS). The study was performed in out- and inpatients in 738 study centers in 21 countries in Europe and Asia. Iopromide was administered in a routine manner, in compliance with the local package insert. The use of premedication was at the discretion of the attending physician. Case report forms for 44,835 patients were analyzed (57.4% men). The median age of the patients was 55 years., Results: For the vast majority of patients (94.8%), the contrast quality was rated as 'good' (55.8%) or 'excellent' (39.0%). For 1265 (2.8%) patients, there were reports of adverse drug reactions (ADRs) excluding tolerance indicators (TIs) (i.e. injection site warmth, feeling hot, or injection site pain of mild intensity). At least one ADR including TIs was reported in 2415 (5.4%) patients. There were 11 (0.02%) patients with serious ADRs, and no drug-related deaths. Events of injection site warmth and/or feeling hot were reported by 3.5%, nausea and/or vomiting by 0.96%, and urticaria, erythema, and/or rash by 0.54% of patients. Patients at risk for an acute idiosyncratic reaction (i.e. patients with a history of bronchial asthma, allergies, and/or contrast media reaction) had a higher incidence of ADRs compared with the overall study population. At-risk patients who did not receive premedication reported distinctly more ADRs compared with those who received premedication (12.0% versus 5.9%)., Conclusion: Iopromide was shown to be a well-tolerated contrast agent whose usage resulted in high image quality. No unknown ADRs were observed. Premedication with antiallergy drugs should be considered in at-risk patients.

Introduction: The Real-Life Safety and Efficacy of vardenafil study is an international, open-label, prospective, noncomparative, noninterventional study in men with erectile dysfunction (ED)., Aim: To determine the safety and efficacy of vardenafil in a large international pool of men with ED (aged ≥ 18 years) and associated underlying conditions (N=73,946), in a real-life setting., Methods: Patients attended an initial physician visit and one to two follow-up visits. Data were acquired by physician interviews and patient diaries and recorded in case report forms (CRFs). Data were pooled from 47 countries in Europe, Asia-Pacific, Latin America, and the rest of the world (excluding the United States and Japan for methodological reasons). Results were stratified by baseline ED severity, body mass index (BMI), and the presence of hypertension, diabetes, lipid metabolism disorder, or cardiovascular disease (CVD)., Main Outcome Measures: CRFs and patient questionnaires containing questions on overall improvement of erection, satisfaction with efficacy, and desire to continue vardenafil use., Results: Many participants had hypertension (32.0%), diabetes (22.1%), lipid metabolism disorder (14.6%), or CVD (42.2%). High percentages of patients reported improvements in erectile function, irrespective of baseline ED severity (mild, 97.0%; moderate, 96.2%; severe, 85.5%), BMI (<25, 94.1%; ≥ 25 and <30, 94.6%; ≥ 30, 92.9%), or the presence of hypertension (93.6%), diabetes (92.6%), lipid metabolism disorder (94.7%), or CVD (93.3%). Over 90% of patients, including those with underlying conditions, reported being "satisfied" or "very satisfied" with vardenafil efficacy, and stated their intention to continue vardenafil use after the end of the study period. The incidence of adverse events was low, and 97.0% of patients were either "satisfied" or "very satisfied" with vardenafil tolerability., Conclusions: These data from a worldwide population of men with ED and associated underlying conditions show that vardenafil is effective and well-tolerated for the treatment of ED in a real-life setting, supporting its use as a first-line ED therapy., (© 2010 International Society for Sexual Medicine.)

Objective: The GIANT study collected information on patients with acute exacerbations of chronic bronchitis (AECB) and chronic obstructive pulmonary disease (COPD) and the effect of treatment with moxifloxacin., Methods: AECB history, concomitant diseases, moxifloxacin treatment, concomitant medication, clinical symptoms and adverse events were recorded. A questionnaire at the end of treatment recorded the impact on patients' daily lives., Results: Among 9225 patients from eight European countries, marked variation was seen in characteristics including age, smoking history and type of exacerbation. Spirometry use was more common among chest physicians (66.7%) than GPs (15.5%). Patients with Anthonisen type 1 and 2 exacerbations had more frequent exacerbations and these patients experienced a greater impact on daily activities compared with patients with type 3 episodes. Patient symptoms improved with moxifloxacin treatment after a mean (SD) of 3.4 (1.8) days, allowing return to normal daily activities after 5.4 (4.4) days and with full recovery taking 6.5 (3.1) days., Conclusions: Characteristics of patients with AECB and acute exacerbations of COPD differ among European countries. Spirometry is under-used, particularly in primary care and antibiotic treatment does not always follow current guidelines. Results confirm the efficacy of moxifloxacin in the treatment of AECB in real-life conditions.

Objective: To compare the real-life treatment of acute exacerbations of chronic bronchitis (AECBs) using moxifloxacin tablets or one of the oral macrolides azithromycin, clarithromycin or roxithromycin in terms of symptom relief, time until improvement and cure, overall efficacy and tolerability., Methods: This prospective, non-interventional, multicentre study included out-patients with AECB whose last exacerbation was treated with a macrolide. The current AECB was treated either with moxifloxacin or with one of the macrolides azithromycin, clarithromycin or roxithromycin. Data were obtained on the patient's characteristics, disease and treatment history, the course of the current AECB including time to improvement and cure, and the final assessments of efficacy and tolerability. All adverse events were recorded in patients treated with moxifloxacin; for patients receiving macrolides, only drug-related adverse events were reported., Results: 464 physicians treated 904 patients with moxifloxacin and 846 patients with one of the macrolides. Age, sex and body mass index were well matched between the two treatment groups. However, more moxifloxacin than macrolide patients presented with a generally bad condition (62.8% vs 48.6%). About 42% of patients in both groups had had chronic bronchitis for 1-5 years, and about 27% for 5-10 years. The mean number of AECBs in the previous 12 months was 2.7 and 2.6, respectively. Moxifloxacin was administered to most patients for 5 (43.8%) or 7 days (42.4%). Patients in the macrolide group were treated in most cases with clarithromycin 500 mg for 4-7 days, roxithromycin 300 mg for 6-7 days or azithromycin 500 mg for 3 days. Physicians assessed overall efficacy and tolerability as 'very good' or 'good' in 96.1% and 98.1%, respectively, of moxifloxacin-treated patients and in 67.5% and 91.7%, respectively, of macrolide-treated patients. The mean duration until improvement and cure of AECB was 3.2 days (+/- SD 1.5) and 6.2 days (+/- 2.6) in moxifloxacin-treated patients compared with 4.5 days (+/- 1.8) and 7.5 days (+/- 3.0) in macrolide-treated patients (p < 0.0001)., Conclusion: The results of this study conducted under real-life treatment conditions in patients with AECBs who were previously treated with a macrolide showed faster symptom relief and higher recovery rates with moxifloxacin compared with macrolides. The two treatment groups had comparably good safety and tolerability profiles.

Objective: This study set out to obtain up-to-date information on the efficacy, safety and tolerability of ciprofloxacin as well as the time to improvement and recovery, and to explore data on drug utilisation in hospitalised patients with a special focus on intravenous therapy with ciprofloxacin. METHODS, DESIGN AND PATIENTS: Hospitalised patients with a broad spectrum of infections were included in this non-interventional multicentre study. In order to be included, the patients had to be treated with intravenous ciprofloxacin for a minimum of 2 days. Physicians were advised to pay attention to the contraindications mentioned in the summary of product characteristics. They documented demographic and anamnestic data, the type and severity of the infection, concomitant diseases and medications, the course of clinical and laboratory symptoms, and the treatment. In addition, they rated the overall efficacy of intravenous ciprofloxacin and recorded the time to improvement and recovery. All adverse events were reported., Results: 1012 hospitalised patients with mild to severe clinical infections were included. Their mean age was 61.5 years (SD 16.7), and 57.4% were males. Intravenous ciprofloxacin was given to 28.7% of patients exclusively and 69.6% started with intravenous ciprofloxacin and were switched later to oral treatment. The majority of patients presented with one defined source of infection (77.9%), mainly located in the respiratory tract (40.2%), the abdomen (21.4%), the urinary tract (14.9%) or the kidney (13.4%). Other infections involved the bones and joints (4.5%) or were classified as sepsis (8.0%); 39.6% of infections were classified as severe. Infection symptoms improved in 86.2% of the patients within 5 days. The overall improvement and recovery rates were 91.9% and 85.8%, respectively. Efficacy of ciprofloxacin was judged as 'very good' or 'good' in 86.5% of patients. Tolerability was judged as 'very good' or 'good' in 98.2% of patients. Adverse events occurred rarely and were reported in 2.17% of patients. Seventeen (1.68%) fulfilled the criteria of serious adverse events. In only 0.4% of patients was a relationship between the adverse event and ciprofloxacin treatment suspected., Conclusions: Intravenous ciprofloxacin is an effective and well tolerated antibacterial treatment in hospitalised patients experiencing a broad spectrum of mild to severe infections.

We assessed the safety, efficacy and patient acceptability of vardenafil (Levitra, Bayer HealthCare, Leverkusen, Germany) under real-life conditions in patients with erectile dysfunction (ED) in a multinational post-marketing surveillance study. An initial and up to two follow-up visits were documented for 29 358 German ED patients receiving vardenafil. Patients were interviewed about overall treatment success, and individual sexual attempts were evaluated in a patient questionnaire. Overall erectile improvement was reported by 93.9% of physicians, and similar improvement rates were reported for both 10 mg and 20 mg vardenafil dosages. Most patients experienced improved erections after the first (73.6%) or second (88.5%) tablet. Sexual attempts were successful with respect to partner penetration in 94.9% of patients and with respect to maintenance of erection during intercourse in 87.7% of patients. Adverse drug reactions were very rare (1.3% of patients). Vardenafil was highly effective, reliable and well tolerated in ED patients treated under real-life conditions.

Objective: This study aimed to investigate the efficacy, safety and tolerability of sequential intravenous (IV)/oral therapy with moxifloxacin in pneumonia under general hospital treatment conditions., Patients and Methods: Patients with pneumonia were documented in this non-interventional multicentre study. The patients were treated with IV moxifloxacin or moxifloxacin sequential therapy (IV and oral) in hospitals throughout Germany. Exclusion criteria were limited to the contraindications mentioned in the summary of product characteristics. The participating hospital-based physicians documented the patients' demography, anamnesis, antibiotic pretreatment, concomitant diseases and medications. Moxifloxacin therapy and symptom status were recorded daily up to the ninth day and on the last day of treatment. The physicians assessed the efficacy and tolerability of IV moxifloxacin therapy and reported all adverse events observed within the treatment period., Results: The 1749 documented patients had a mean age of 66.2 (SD 15.5) years; 56.4% were males and 43.5% females. The majority (99.3%) were treated with moxifloxacin 400mg once daily. On average, moxifloxacin was given for 7.6 days (SD 3.2). In cases of sequential therapy (78.9% of patients), IV moxifloxacin was switched to oral moxifloxacin after a mean of 4.1 days (SD 1.8). Moxifloxacin produced a significant clinical improvement in 58.2% of patients by day 3 of therapy, in 84.2% by day 5 and in 89.4% by day 7. Recovery occurred in 27.0% of patients by day 5, in 54.0% by day 7 and in 87.0% by day 14. It took a mean of 3.4 days (SD 1.9) until improvement and 7.2 days (SD 3.0) until cure. Overall efficacy of IV moxifloxacin therapy was rated by the physicians as 'very good' or 'good' in 82.9% of patients. Tolerability was rated in 94.3% of patients as 'very good' or 'good'. Adverse events were recorded for 92 (5.3%) patients, but events were considered by the attending physician to be related to moxifloxacin therapy for only 45 patients (2.6%)., Conclusions: IV moxifloxacin shows high efficacy in the treatment of pneumonia under routine clinical treatment conditions. IV moxifloxacin relieves pneumonia-associated symptoms rapidly and allows an early switch to oral administration. Because of its high efficacy and very good safety and tolerability profile, moxifloxacin delivers excellent benefits as first-line therapy for pneumonia.

Objective: To assess the efficacy, safety and tolerability of oral moxifloxacin in outpatients with respiratory tract infections treated in general practices in Germany with the focus on community-acquired pneumonia (CAP). METHODS, DESIGN AND PATIENTS: This was an open-label, prospective, uncontrolled, post-marketing surveillance study undertaken between October 2001 and June 2002. Symptoms associated with pneumonia were documented at baseline and at follow-up visits. A general assessment was given and the number of days until improvement/cure were recorded by the attending physician at the end of therapy., Results: A total of 9036 patients were treated with moxifloxacin, of which 1467 had CAP. The recommended dosage of moxifloxacin (400mg once daily) was used in 97.8% of all CAP patients. Between the initial and final follow-up visits, symptoms of CAP were either improved or cured in 90-99% of patients. More than half of the patients showed improvement after 3 days (54.2%); 89.2% of patients were improved after 5 days. The mean time for patients to recover was 8.0 +/- 2.7 days, with 88.7% of patients recovered by day 10 of treatment. Physicians rated moxifloxacin therapy as 'very good' or 'good' in 96.6% of patients and virtually all favoured prescribing moxifloxacin again. Ten patients (0.7%) reported adverse events during moxifloxacin therapy, mostly gastrointestinal disturbances., Conclusions: Moxifloxacin is a very effective and safe treatment for patients with CAP and is highly accepted by physicians and patients because of rapid symptom improvement and good tolerability.

Objective: To assess the efficacy, safety and tolerability of moxifloxacin, an 8-methoxy fluoroquinolone, in patients with respiratory tract infections (RTIs) treated in general practice in Germany. Different RTIs were analysed separately, and this paper focuses on patients with acute sinusitis. METHODS, DESIGN AND PATIENTS: This was an open-label, prospective, uncontrolled, post-marketing surveillance study undertaken between October 2001 and June 2002. Symptoms of sinusitis (fever, cough, nasal obstruction, nasal secretion and headache) were assessed at baseline and at follow-up visits, and classified as 'absent', 'mild' or 'severe' by the attending physician., Results: Altogether 9036 patients were treated with moxifloxacin, of whom 2405 adult men and women had sinusitis. Sinusitis symptoms were improved or cured in at least 92% of patients. Moxifloxacin produced significant improvements after only 3 days (71.6% of patients); 96.2% of patients were improved after 5 days. Most patients (89.5%) had recovered by day 8 and 97.3% by day 10. Physicians rated moxifloxacin therapy as 'good' or 'very good' in 96.6% of patients and almost all favoured prescribing moxifloxacin in the future. Very few adverse events were reported with moxifloxacin (<0.4%), and were mostly gastrointestinal disturbances., Conclusions: Moxifloxacin is a very effective and safe treatment for patients with acute sinusitis in general practice and is highly regarded by both physicians and patients because of rapid symptom improvement and good tolerability.

Objective: To monitor the efficacy and safety of moxifloxacin in respiratory tract infections (RTIs) focussing on acute exacerbations of chronic bronchitis (AECB)., Methods: Patients with RTIs could be enrolled in this open-label, prospective, non-controlled post-marketing surveillance study from October 2001 until June 2002 unless moxifloxacin was contraindicated. At the initial visit, data were recorded on patient demographics, diagnosis and clinical symptoms. Two follow-up examinations could be performed to determine cure or improvement based on clinical symptoms, and to record adverse events. Clinical symptoms including fever, cough and purulent sputum were assessed individually. Efficacy, tolerability and patient acceptance were assessed globally at the final visit., Results: Of 9036 enrolled patients, 4328 had AECB, most of whom were treated with moxifloxacin at a daily dose of 400mg. Mean +/- SD time to clinical improvement was 3.4 +/- 1.5 days, and mean +/- SD time to clinical cure was 6.6 +/- 2.4 days. Cure rates were 39.4% at day 5 and 94.3% at day 10. By day 6, the proportion of patients with severe cough decreased from 85.4% at the initial visit to 6.9%, and those with severe dyspnoea from 22.5% to 1.2%. Purulent sputum was absent within 4 days in the majority of cases. Physicians rated efficacy, tolerability and patient acceptance as 'very good' or 'good' in approximately 95% of patients. There were 59 adverse events in 44 (1.0%) patients, most frequently gastrointestinal and nervous system disorders., Conclusions: This study further confirms that AECB patients treated with moxifloxacin benefit from more rapid symptom relief and that this therapy option is well accepted in general practice.

Objective and Design: This post-marketing surveillance study collected data on the efficacy and tolerability of acarbose in patients with insulin-treated type 2 diabetes mellitus and, in particular, on its effect on postprandial blood glucose under normal daily practice conditions., Patients and Methods: A total of 1142 patients were included in this observational study in which the treating physicians had sole responsibility for determining acarbose doses and other therapeutic measures. Efficacy parameters consisted of fasting and postprandial blood glucose and glycosylated haemoglobin (HbA(1c)). Additionally, cholesterol, triglycerides and weight were analysed. All patient data had to be recorded by the attending physician on a case report form. Patients were asked to self-monitor blood glucose daily after breakfast (1h) and to keep a diary., Results: Mean HbA(1c) improved by 0.9%, fasting blood glucose by 32.4 mg/dL, and postprandial hyperglycaemia by 49.7 mg/dL during the observation period compared with baseline. Comparable results were obtained in combination with conventional, functional or intensive insulin therapy. Mean weight was reduced by 0.7kg. The incidence of acarbose-related side effects was low (6.9%) and consisted mostly of gastrointestinal complaints. The majority of patients assessed acarbose treatment positively., Conclusion: The addition of acarbose to different insulin regimens provided an efficacious and safe treatment for better glycaemic and weight control.