Efficacy and safety of tigecycline versus levofloxacin for community-acquired pneumonia.

Abstract Background: Tigecycline, an expanded broad-spectrum glycylcycline, exhibits in vitro activity against many common pathogens associated with community-acqui red pneumonia (CAP), as well as penetration into lung tissues that suggests effectiveness in ho spitalized CAP patients. The aim of the present study was to compare the efficacy and safety of intravenous (IV) tigecycline with IV levofloxacin in hospitalized adults with CAP. Methods: In this prospective, double-blin d, non-inferiority phase 3 trial, eligible patients with a clinical diagnosis of CAP supported by radiographic evidence were stratified by Fine Pneumonia Severity Index and randomized to tigecycline or levofloxacin for 7-14 days of therapy. Co-primary efficacy endpoints were clinical response in the clinically evaluable (CE) and clinical modified intent- to-treat (c-mITT) populations at te st-of-cure (Day 10-21 post-therapy). Results: Of the 428 patients who received at least on e dose of study drug, 79% had CAP of mild-moderate severity according to their Fine score. Clinical cure rates for the CE population were 88.9% for tigecycline and 85.3% for levofloxac in. Corresponding c-mITT population rates were 83.7% and 81.5%, respectively. Eradication rates for Streptococcus pneumoniae were 92% for tigecycline and 89% for levofloxac in. Nausea, vomiting, and diarrhoea were the most frequently reported adverse events. Rates of premature disc continuation of study drug or study withdrawal because of any adverse event were similar for both study drugs. Conclusion: These findings suggest that IV tigecycline is non-inferior to IV levofloxacin and is generally well-tolerated in the treatment of hospitalized adults with CAP.

Efficacy and safety of once-daily aclidinium in chronic obstructive pulmonary disease

Background: The long-term efficacy and safety of aclidinium bromide, a novel, long-acting muscarinic antagonist, were investigated in patients with moderate to severe chronic obstructive pulmonary disease (COPD). Methods: In two double-blind, 52-week studies, ACCLAIM/COPD I (n = 843) and II (n = 804), patients were randomised to inhaled aclidinium 200 μg or placebo once-daily. Patients were required to have a postbronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity ratio of ≤70% and FEV1 <80% of the predicted value. The primary endpoint was trough FEV1 at 12 and 28 weeks. Secondary endpoints were health status measured by St George"s Respiratory Questionnaire (SGRQ) and time to first moderate or severe COPD exacerbation. Results: At 12 and 28 weeks, aclidinium improved trough FEV1 versus placebo in ACCLAIM/COPD I (by 61 and 67 mL; both p < 0.001) and ACCLAIM/COPD II (by 63 and 59 mL; both p < 0.001). More patients had a SGRQ improvement ≥4 units at 52 weeks with aclidinium versus placebo in ACCLAIM/COPD I (48.1% versus 39.5%; p = 0.025) and ACCLAIM/COPD II (39.0% versus 32.8%; p = 0.074). The time to first exacerbation was significantly delayed by aclidinium in ACCLAIM/COPD II (hazard ratio [HR] 0.7; 95% confidence interval [CI] 0.55 to 0.92; p = 0.01), but not ACCLAIM/COPD I (HR 1.0; 95% CI 0.72 to 1.33; p = 0.9). Adverse events were minor in both studies. Conclusion: Aclidinium is effective and well tolerated in patients with moderate to severe COPD. Trial registration: ClinicalTrials.gov: NCT00363896 ACCLAIM/COPD I) and NCT00358436 (ACCLAIM/COPD II).

Quality and safety requirements for sustainable phage therapy products.

The worldwide antibiotic crisis has led to a renewed interest in phage therapy. Since time immemorial phages control bacterial populations on Earth. Potent lytic phages against bacterial pathogens can be isolated from the environment or selected from a collection in a matter of days. In addition, phages have the capacity to rapidly overcome bacterial resistances, which will inevitably emerge. To maximally exploit these advantage phages have over conventional drugs such as antibiotics, it is important that sustainable phage products are not submitted to the conventional long medicinal product development and licensing pathway. There is a need for an adapted framework, including realistic production and quality and safety requirements, that allowsa timely supplying of phage therapy products for 'personalized therapy' or for public health or medical emergencies. This paper enumerates all phage therapy product related quality and safety risks known to the authors, as well as the tests that can be performed to minimize these risks, only to the extent needed to protect the patients and to allow and advance responsible phage therapy and research.

Wireless Technologies in e-Business; Services, Security and Management

Uusien mobiilien laitteiden ja palveluiden kehitys ovat herättäneet yritysten mielenkiinnon soveltaa langattomia sovelluksia omassa liiketoiminnassaan. Erilaisten tekniikoiden myötä myös mahdollisuuksien kirjo on laajentumassa, mikä johtaa erilaisten verkkojen ja laitteiden yhtenäiselle hallinnalle asetettavien vaatimusten kasvuun. Yritysten siirtyessä soveltamaan uusia langattomia palveluita ja sovelluksia on myös huomioon otettavaa sovellusten sekä palveluiden vaatima tietoturva ja sen hallittavuus. Tutkimuksessa esitetään langattoman sähköisen liiketoiminnan määritelmä sekä kyseisien teknologioiden käyttöä edistävät tekijät. Tutkimus luo viitekehyksen yrityksen langattomien teknologioiden käytölle ja siihen olennaisesti vaikuttavista tekijöistä. Viitekehystä on käytetty todelliseen esimerkkiin, liikkuva myyntihenkilö, kyseisten teknologioiden, palveluiden, tietoturvan ja hallittavuuden näkökulmasta. Johtopäätöksinä on arvioitu mobiilien ja langattomien teknologioiden sekä palveluiden, tietoturvan ja hallittavuuden tilaa ja analysoimalla niitä tulevaa ajatellen.

Preclinical Pharmacokinetics, Pharmacodynamics and Safety of Sucroferric Oxyhydroxide.

Sucroferric oxyhydroxide (VELPHORO(®)) is a polynuclear iron-based phosphate binder recently approved for the treatment of hyperphosphataemia in patients with chronic kidney disease (CKD). As a number of the available phosphate binders do not provide the optimal combination of good efficacy, adequate tolerability and low pill burden, sucroferric oxyhydroxide constitutes a promising alternative. Among the attributes of an ideal phosphate binder is minimal absorption and, hence, low risk of systemic toxicity. Accordingly, the iron-releasing properties and absorption, distribution, metabolism and excretion (ADME) profile of sucroferric oxyhydroxide, as well as the possibility of iron accumulation and toxicity, were investigated in a series of preclinical studies. The effect of sucroferric oxyhydroxide on the progression of vascular calcification was also investigated. Sucroferric oxyhydroxide exhibited a high phosphate-binding capacity and low iron-releasing properties across the physiological pH range found in the gastrointestinal tract. In the ADME studies, uptake of (59)Fe-radiolabelled sucroferric oxyhydroxide was low in rats and dogs (<1% from a 50 mg Fe/kg bodyweight dose), with the majority of absorbed iron located in red blood cells. Long-term (up to 2 years) administration of sucroferric oxyhydroxide in rats and dogs was associated with modest increases in tissue iron levels and no iron toxicity. Moreoever, in uraemic rats, sucroferric oxyhydroxide was associated with reduced progression of vascular calcification compared with calcium carbonate. In conclusion, sucroferric oxyhydroxide offers a new option for the treatment of hyperphosphataemia, with a high phosphate-binding capacity, minimal iron release, and low potential for iron accumulation and toxicity.

Capturing diagnosis-timing in ICD-coded hospital data: recommendations from the WHO ICD-11 topic advisory group on quality and safety.

PURPOSE: To develop a consensus opinion regarding capturing diagnosis-timing in coded hospital data. METHODS: As part of the World Health Organization International Classification of Diseases-11th Revision initiative, the Quality and Safety Topic Advisory Group is charged with enhancing the capture of quality and patient safety information in morbidity data sets. One such feature is a diagnosis-timing flag. The Group has undertaken a narrative literature review, scanned national experiences focusing on countries currently using timing flags, and held a series of meetings to derive formal recommendations regarding diagnosis-timing reporting. RESULTS: The completeness of diagnosis-timing reporting continues to improve with experience and use; studies indicate that it enhances risk-adjustment and may have a substantial impact on hospital performance estimates, especially for conditions/procedures that involve acutely ill patients. However, studies suggest that its reliability varies, is better for surgical than medical patients (kappa in hip fracture patients of 0.7-1.0 versus kappa in pneumonia of 0.2-0.6) and is dependent on coder training and setting. It may allow simpler and more precise specification of quality indicators. CONCLUSIONS: As the evidence indicates that a diagnosis-timing flag improves the ability of routinely collected, coded hospital data to support outcomes research and the development of quality and safety indicators, the Group recommends that a classification of 'arising after admission' (yes/no), with permitted designations of 'unknown or clinically undetermined', will facilitate coding while providing flexibility when there is uncertainty. Clear coding standards and guidelines with ongoing coder education will be necessary to ensure reliability of the diagnosis-timing flag.

Security and Privacy in a Ubiquitous Information Screen

We expose the ubiquitous interaction between an information screen and its’ viewers mobile devices, highlights the communication vulnerabilities, suggest mitigation strategies and finally implement these strategies to secure the communication. The screen infers information preferences’ of viewers within its vicinity transparently from their mobile devices over Bluetooth. Backend processing then retrieves up-to-date versions of preferred information from content providers. Retrieved content such as sporting news, weather forecasts, advertisements, stock markets and aviation schedules, are systematically displayed on the screen. To maximise users’ benefit, experience and acceptance, the service is provided with no user interaction at the screen and securely upholding preferences privacy and viewers anonymity. Compelled by the personal nature of mobile devices, their contents privacy, preferences confidentiality, and vulnerabilities imposed by screen, the service’s security is fortified. Fortification is predominantly through efficient cryptographic algorithms inspired by elliptic curves cryptosystems, access control and anonymity mechanisms. These mechanisms are demonstrated to attain set objectives within reasonable performance.

Probiotic interventions in infancy: Benefit and Safety Assessment of Extended Applications

Immaturity of the gut barrier system in the newborn has been seen to underlie a number of chronic diseases originating in infancy and manifesting later in life. The gut microbiota and breast milk provide the most important maturing signals for the gut-related immune system and reinforcement of the gut mucosal barrier function. Recently, the composition of the gut microbiota has been proposed to be instrumental in control of host body weight and metabolism as well as the inflammatory state characterizing overweight and obesity. On this basis, inflammatory Western lifestyle diseases, including overweight development, may represent a potential target for probiotic interventions beyond the well documented clinical applications. The purpose of the present undertaking was to study the efficacy and safety of perinatal probiotic intervention. The material comprised two ongoing, prospective, double-blind NAMI (Nutrition, Allergy, Mucosal immunology and Intestinal microbiota) probiotic interventions. In the mother-infant nutrition and probiotic study altogether 256 women were randomized at their first trimester of pregnancy into a dietary intervention and a control group. The intervention group received intensive dietary counselling provided by a nutritionist, and were further randomized at baseline, double-blind, to receive probiotics (Lactobacillus rhamnosus GG and Bifidobacterium lactis) or placebo. The intervention period extended from the first trimester of pregnancy to the end of exclusive breastfeeding. In the allergy prevention study altogether 159 women were randomized, double-blind, to receive probiotics (Lactobacillus rhamnosus GG) or placebo 4 weeks before expected delivery, the intervention extending for 6 months postnatally. Additionally, patient data on all premature infants with very low birth weight (VLBW) treated in the Department of Paediatrics, Turku University Hospital, during the years 1997 - 2008 were utilized. The perinatal probiotic intervention reduced the risk of gestational diabetes mellitus (GDM) in the mothers and perinatal dietary counselling reduced that of fetal overgrowth in GDM-affected pregnancies. Early gut microbiota modulation with probiotics modified the growth pattern of the child by restraining excessive weight gain during the first years of life. The colostrum adiponectin concentration was demonstrated to be dependent on maternal diet and nutritional status during pregnancy. It was also higher in the colostrum received by normal-weight compared to overweight children at the age of 10 years. The early perinatal probiotic intervention and the postnatal probiotic intervention in VLBW infants were shown to be safe. To conclude, the findings in this study provided clinical evidence supporting the involvement of the initial microbial and nutritional environment in metabolic programming of the child. The manipulation of early gut microbial communities with probiotics might offer an applicable strategy to impact individual energy homeostasis and thus to prevent excessive body-weight gain. The results add weight to the hypothesis that interventions aiming to prevent obesity and its metabolic consequences later in life should be initiated as early as during the perinatal period.

Establishment of a health and safety management system according to the OHSAS 18001 standard

The thesis develops guidelines for the implementation of the health and safety management system according to the OHSAS 18001 standard, as well as the feasible threat analysis, project proposal schedule, future system quality improvements and organizational change evaluation. The theoretical part clarifies determination of occupational health and safety, its management system, the OHSAS 18001 standard and integrated management system compounded of triple ISO 14001, ISO 9001 and OHSAS 18001 standards. The literature includes such important aspects as human factor, organizational policies, possible benefits, threats, organizational safety culture, Deming’s quality improvement cycle, system implementation, maintenance and cost matters. The empirical part demonstrates real-life situation by using Andritz Pulp & Paper Oy as a case study. Prior the thesis proposal, Andritz Group is analysed including separate business areas, acquisition and integration strategies, current status of the health and safety management and parallel experiences of the largest business area Andritz Hydro. The proposal is aimed at improving the current health and safety system for the permanent and sub-contracted employees at Andritz Pulp & Paper both in Finland and in various projects globally.

Efficacy and safety of combined piroxicam, dexamethasone, orphenadrine, and cyanocobalamin treatment in mandibular molar surgery

Third molar extraction is a common procedure frequently accompanied by moderate or severe pain, and involves sufficient numbers of patients to make studies relatively easy to perform. The aim of the present study was to determine the efficacy and safety of the therapeutic combination of 10 mg piroxicam, 1 mg dexamethasone, 35 mg orphenadrine citrate, and 2.5 mg cyanocobalamin (Rheumazin®) when compared with 20 mg piroxicam alone (Feldene®) in mandibular third molar surgery. Eighty patients scheduled for removal of the third molar were included in this randomized and double-blind study. They received (vo) Rheumazin or Feldene 30 min after tooth extraction and once daily for 4 consecutive days. Pain was determined by a visual analogue scale and by the need for escape analgesia (paracetamol). Facial swelling was evaluated with a measuring tape and adverse effects and patient satisfaction were recorded. There was no statistically significant difference in facial swelling between Rheumazin and Feldene (control group). Both drugs were equally effective in the control of pain, with Rheumazin displaying less adverse effects than Feldene. Therefore, Rheumazin appears to provide a better risk/benefit ratio in the mandibular molar surgery. Since the side effects resulting from nonsteroidal anti-inflammatory drug administration are a severe limitation to the routine use of these drugs in clinical practice, our results suggest that Rheumazin can be a good choice for third molar removal treatment.

Comparative efficacy and safety of the left versus right radial approach for percutaneous coronary procedures: a meta-analysis including 6870 patients

The radial approach is widely used in the treatment of patients with coronary artery disease. We conducted a meta-analysis of published results on the efficacy and safety of the left and right radial approaches in patients undergoing percutaneous coronary procedures. A systematic search of reference databases was conducted, and data from 14 randomized controlled trials involving 6870 participants were analyzed. The left radial approach was associated with significant reductions in fluoroscopy time [standardized mean difference (SMD)=-0.14, 95% confidence interval (CI)=-0.19 to -0.09; P<0.00001] and contrast volume (SMD=-0.07, 95%CI=-0.12 to -0.02; P=0.009). There were no significant differences in rate of procedural failure of the left and the right radial approaches [risk ratios (RR)=0.98; 95%CI=0.77-1.25; P=0.88] or procedural time (SMD=-0.05, 95%CI=0.17-0.06; P=0.38). Tortuosity of the subclavian artery (RR=0.27, 95%CI=0.14-0.50; P<0.0001) was reported more frequently with the right radial approach. A greater number of catheters were used with the left than with the right radial approach (SMD=0.25, 95%CI=0.04-0.46; P=0.02). We conclude that the left radial approach is as safe as the right radial approach, and that the left radial approach should be recommended for use in percutaneous coronary procedures, especially in percutaneous coronary angiograms.