ppi-0903 and Acute-Disease

To develop the 'Stronger Towns Index': a deprivation index that took into account characteristics of areas encompassing towns that may be eligible for redevelopment funding and explore how this index was associated with self-rated health and migration within England between 2001 and 2011.. There were areas in the lowest deciles of Town Strength who did not receive funding. After multiple adjustment, LS members living in areas with higher deciles were significantly more likely (7% to 38%) to report good health than those in the lowest decile in 2001. Remaining in the same decile between 2001 and 2011 was associated with 7% lower odds of good self-rated health in 2011.. It is important to consider health in towns when allocating funding. Areas in the Midlands may have missed out on funding which might help mitigate poor health.. Ferritin levels <30µg/L were associated with unexplained infertility and might be screened in the future. Further studies with a focus on iron deficiency and iron treatment on women with unexplained infertility are warranted.. This EGM provides a valuable resource for researchers, policy-makers and the public to access the available evidence on the determinants of various COVID-19 health-related behaviours. The map can also be used to help guide research commissioning, by evidence synthesis teams and evidence intermediaries to inform policy during the ongoing pandemic and potential future outbreaks of COVID-19 or other respiratory infections. Evidence included in the map will be explored further through a series of systematic reviews examining the strength of the associations between malleable determinants and the uptake and maintenance of individual protective behaviours.. Patients with polymicrobial bloodstream infections are typically critically ill and harbor multidrug-resistant bacteria. Thus, to minimize mortality rate in critically ill patients, changes in infectious flora should be monitored, antibiotics selected reasonably, and invasive procedures reduced.. Altogether, these findings clearly revealed the great potential of the in vitro biological activity of linseed extract as a safe source for combatting multidrug-resistant. In this work, the capture of carbon dioxide using a dense hollow fiber membrane was studied experimentally and theoretically. The factors affecting the flux and recovery of carbon dioxide were studied using a lab-scale system. Experiments were conducted using a mixture of methane and carbon dioxide to simulate natural gas. The effect of changing the CO. Persistent gender and racial disparities in high-impact medical and critical care journals underscore the need to revise policies and strategies to encourage greater diversity in critical care research.. Thirty evaluable patients were enrolled. Median age was 60.5 years. Median follow-up for all patients was 17 months. Ten patients (33%) experienced grade ≥ 3 treatment-related adverse events, the most common being neutropenia and diarrhea; 50% required ≥ 1 dose reduction. The disease control rate was 90% (progressive disease: 10%, partial response: 23%, stable disease: 67%). There was zero treatment-related mortality. Twenty-two patients (73%, 90% CI 57-86; p = 0.008) completed all chemotherapy and surgery. Two patients (9%) who successfully underwent resection had minor postoperative complications. Median length of hospital stay was 4 days. Median RFS was 7.1 months. Median OS for the entire cohort was 24 months and was not reached in patients who underwent surgical resection.. Neoadjuvant treatment with gemcitabine, cisplatin, and nab-paclitaxel is feasible and safe prior to resection of intrahepatic cholangiocarcinoma and does not adversely impact perioperative outcomes.

Topics: Acetogenins; Acute Disease; Acute Kidney Injury; Administration, Intravenous; Aged; Albumins; Alcoholism; Aldehyde Dehydrogenase; Aldehyde Dehydrogenase, Mitochondrial; alpha-Glucosidases; Anemia; Animals; Anthozoa; Anti-Bacterial Agents; Anti-Infective Agents; Antibodies, Bacterial; Antigens, Bacterial; Antihypertensive Agents; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Apoptosis; Ascites; Asthma; Bacteria; beta-Lactamases; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Binding Sites; Biological Availability; Biomass; Borderline Personality Disorder; Brain; Brucella abortus; Brucella melitensis; Brucellosis; Calcium; Carbapenems; Case-Control Studies; Caseins; Cattle; CD8-Positive T-Lymphocytes; Ceftaroline; Cell Line; Cell Line, Tumor; Cell Physiological Phenomena; Cell Proliferation; Cephalosporins; Chemotherapy, Adjuvant; China; Chitin; Chlorella; Chlorophyll; Chlorophyll A; Chlorophyta; Cholangiocarcinoma; Cisplatin; Conotoxins; Contrast Media; Conus Snail; Cross-Sectional Studies; Cytokines; Decapodiformes; Deoxycytidine; Diagnostic and Statistical Manual of Mental Disorders; Dietary Fiber; Diterpenes; DNA Methylation; Dogs; Double-Blind Method; Drug Design; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Drug Screening Assays, Antitumor; Eicosapentaenoic Acid; Enzyme-Linked Immunosorbent Assay; Epidermis; Escherichia coli; Escherichia coli Infections; Extraintestinal Pathogenic Escherichia coli; Fatty Acids; Fatty Acids, Unsaturated; Fatty Acids, Volatile; Feasibility Studies; Feces; Female; Ferritins; Fluorodeoxyglucose F18; Gastrectomy; Gastrointestinal Microbiome; Gemcitabine; Glomerular Filtration Rate; Glucose; Glycerol; Granulocyte-Macrophage Colony-Stimulating Factor; HeLa Cells; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Hypoxia-Inducible Factor-Proline Dioxygenases; Immunoassay; Immunoglobulin G; India; Infant, Newborn; Infertility; Inflammation; Intensive Care Units; Iron; Iron Deficiencies; Kidney; Lacticaseibacillus rhamnosus; Laurencia; Leukocytes; Lipids; Liver Cirrhosis; Long Interspersed Nucleotide Elements; Longitudinal Studies; Male; Mesenchymal Stem Cells; Methicillin-Resistant Staphylococcus aureus; Mice; Microalgae; Microbial Sensitivity Tests; Microscopy; Middle Aged; Minerals; Molecular Conformation; Molecular Docking Simulation; Molecular Structure; Mycobacterium tuberculosis; Myeloid Cells; Myeloid-Derived Suppressor Cells; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Nephropidae; Nicotinic Antagonists; Nitrogen; Obesity; Oxaliplatin; Paclitaxel; Panax; Pancreatic Neoplasms; Pancreatitis; Personality; Personality Disorders; Personality Inventory; Photobioreactors; Plant Extracts; Plasmalogens; Plasmids; Polymorphism, Genetic; Polynesia; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Prebiotics; Predictive Value of Tests; Prognosis; Prolyl-Hydroxylase Inhibitors; Rabbits; Radiopharmaceuticals; Rats; Rats, Wistar; Receptors, Nicotinic; Recombinant Proteins; Retrospective Studies; Rifampin; Risk Factors; RNA, Ribosomal, 16S; Salinity; Seaweed; Sensitivity and Specificity; Sepsis; Sesquiterpenes; Severity of Illness Index; Shock, Septic; Silicones; Single Photon Emission Computed Tomography Computed Tomography; Skin; Snails; Solubility; Solvents; Sputum; Staphylococcal Infections; Stomach Neoplasms; Stramenopiles; Structure-Activity Relationship; Technetium Tc 99m Exametazime; Technology; Terpenes; Tuberculosis; Tuberculosis, Multidrug-Resistant; Urinary Catheters; Urinary Tract Infections; Vascular Endothelial Growth Factor A; Virulence Factors; Water; Wound Healing

Skin infections have traditionally been classified by the US FDA as uncomplicated and complicated. In August 2010, the FDA released a new guidance document for the development of drugs to treat acute bacterial skin and skin structure infections (ABSSSI) and this was updated in 2013. Several new issues were addressed and henceforth skin infections in clinical trials were termed ABSSSI. In the USA, the annual prevalence of methicillin-resistant Staphylococcus aureus-related skin infections have continuously increased from 32.7% in 1998 to 53.8% in 2007. Ceftaroline fosamil is the only cephalosporin approved in the USA for monotherapy treatment of ABSSSI including infections caused by methicillin-resistant S. aureus. The efficacy of ceftaroline fosamil was shown in the CANVAS clinical trials. The CANVAS Day-3 analyses met an earlier, primary efficacy time point requested by the FDA. Ceftaroline has minimal drug-drug interactions, is well tolerated and possesses the safety profile associated with the cephalosporin class.

Topics: Acute Disease; Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Drug Approval; Drug Design; Drug Interactions; Humans; Methicillin-Resistant Staphylococcus aureus; Skin Diseases, Bacterial; Staphylococcal Infections; United States; United States Food and Drug Administration

To develop the 'Stronger Towns Index': a deprivation index that took into account characteristics of areas encompassing towns that may be eligible for redevelopment funding and explore how this index was associated with self-rated health and migration within England between 2001 and 2011.. There were areas in the lowest deciles of Town Strength who did not receive funding. After multiple adjustment, LS members living in areas with higher deciles were significantly more likely (7% to 38%) to report good health than those in the lowest decile in 2001. Remaining in the same decile between 2001 and 2011 was associated with 7% lower odds of good self-rated health in 2011.. It is important to consider health in towns when allocating funding. Areas in the Midlands may have missed out on funding which might help mitigate poor health.. Ferritin levels <30µg/L were associated with unexplained infertility and might be screened in the future. Further studies with a focus on iron deficiency and iron treatment on women with unexplained infertility are warranted.. This EGM provides a valuable resource for researchers, policy-makers and the public to access the available evidence on the determinants of various COVID-19 health-related behaviours. The map can also be used to help guide research commissioning, by evidence synthesis teams and evidence intermediaries to inform policy during the ongoing pandemic and potential future outbreaks of COVID-19 or other respiratory infections. Evidence included in the map will be explored further through a series of systematic reviews examining the strength of the associations between malleable determinants and the uptake and maintenance of individual protective behaviours.. Patients with polymicrobial bloodstream infections are typically critically ill and harbor multidrug-resistant bacteria. Thus, to minimize mortality rate in critically ill patients, changes in infectious flora should be monitored, antibiotics selected reasonably, and invasive procedures reduced.. Altogether, these findings clearly revealed the great potential of the in vitro biological activity of linseed extract as a safe source for combatting multidrug-resistant. In this work, the capture of carbon dioxide using a dense hollow fiber membrane was studied experimentally and theoretically. The factors affecting the flux and recovery of carbon dioxide were studied using a lab-scale system. Experiments were conducted using a mixture of methane and carbon dioxide to simulate natural gas. The effect of changing the CO. Persistent gender and racial disparities in high-impact medical and critical care journals underscore the need to revise policies and strategies to encourage greater diversity in critical care research.. Thirty evaluable patients were enrolled. Median age was 60.5 years. Median follow-up for all patients was 17 months. Ten patients (33%) experienced grade ≥ 3 treatment-related adverse events, the most common being neutropenia and diarrhea; 50% required ≥ 1 dose reduction. The disease control rate was 90% (progressive disease: 10%, partial response: 23%, stable disease: 67%). There was zero treatment-related mortality. Twenty-two patients (73%, 90% CI 57-86; p = 0.008) completed all chemotherapy and surgery. Two patients (9%) who successfully underwent resection had minor postoperative complications. Median length of hospital stay was 4 days. Median RFS was 7.1 months. Median OS for the entire cohort was 24 months and was not reached in patients who underwent surgical resection.. Neoadjuvant treatment with gemcitabine, cisplatin, and nab-paclitaxel is feasible and safe prior to resection of intrahepatic cholangiocarcinoma and does not adversely impact perioperative outcomes.

Topics: Acetogenins; Acute Disease; Acute Kidney Injury; Administration, Intravenous; Aged; Albumins; Alcoholism; Aldehyde Dehydrogenase; Aldehyde Dehydrogenase, Mitochondrial; alpha-Glucosidases; Anemia; Animals; Anthozoa; Anti-Bacterial Agents; Anti-Infective Agents; Antibodies, Bacterial; Antigens, Bacterial; Antihypertensive Agents; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Apoptosis; Ascites; Asthma; Bacteria; beta-Lactamases; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Binding Sites; Biological Availability; Biomass; Borderline Personality Disorder; Brain; Brucella abortus; Brucella melitensis; Brucellosis; Calcium; Carbapenems; Case-Control Studies; Caseins; Cattle; CD8-Positive T-Lymphocytes; Ceftaroline; Cell Line; Cell Line, Tumor; Cell Physiological Phenomena; Cell Proliferation; Cephalosporins; Chemotherapy, Adjuvant; China; Chitin; Chlorella; Chlorophyll; Chlorophyll A; Chlorophyta; Cholangiocarcinoma; Cisplatin; Conotoxins; Contrast Media; Conus Snail; Cross-Sectional Studies; Cytokines; Decapodiformes; Deoxycytidine; Diagnostic and Statistical Manual of Mental Disorders; Dietary Fiber; Diterpenes; DNA Methylation; Dogs; Double-Blind Method; Drug Design; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Drug Screening Assays, Antitumor; Eicosapentaenoic Acid; Enzyme-Linked Immunosorbent Assay; Epidermis; Escherichia coli; Escherichia coli Infections; Extraintestinal Pathogenic Escherichia coli; Fatty Acids; Fatty Acids, Unsaturated; Fatty Acids, Volatile; Feasibility Studies; Feces; Female; Ferritins; Fluorodeoxyglucose F18; Gastrectomy; Gastrointestinal Microbiome; Gemcitabine; Glomerular Filtration Rate; Glucose; Glycerol; Granulocyte-Macrophage Colony-Stimulating Factor; HeLa Cells; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Hypoxia-Inducible Factor-Proline Dioxygenases; Immunoassay; Immunoglobulin G; India; Infant, Newborn; Infertility; Inflammation; Intensive Care Units; Iron; Iron Deficiencies; Kidney; Lacticaseibacillus rhamnosus; Laurencia; Leukocytes; Lipids; Liver Cirrhosis; Long Interspersed Nucleotide Elements; Longitudinal Studies; Male; Mesenchymal Stem Cells; Methicillin-Resistant Staphylococcus aureus; Mice; Microalgae; Microbial Sensitivity Tests; Microscopy; Middle Aged; Minerals; Molecular Conformation; Molecular Docking Simulation; Molecular Structure; Mycobacterium tuberculosis; Myeloid Cells; Myeloid-Derived Suppressor Cells; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Nephropidae; Nicotinic Antagonists; Nitrogen; Obesity; Oxaliplatin; Paclitaxel; Panax; Pancreatic Neoplasms; Pancreatitis; Personality; Personality Disorders; Personality Inventory; Photobioreactors; Plant Extracts; Plasmalogens; Plasmids; Polymorphism, Genetic; Polynesia; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Prebiotics; Predictive Value of Tests; Prognosis; Prolyl-Hydroxylase Inhibitors; Rabbits; Radiopharmaceuticals; Rats; Rats, Wistar; Receptors, Nicotinic; Recombinant Proteins; Retrospective Studies; Rifampin; Risk Factors; RNA, Ribosomal, 16S; Salinity; Seaweed; Sensitivity and Specificity; Sepsis; Sesquiterpenes; Severity of Illness Index; Shock, Septic; Silicones; Single Photon Emission Computed Tomography Computed Tomography; Skin; Snails; Solubility; Solvents; Sputum; Staphylococcal Infections; Stomach Neoplasms; Stramenopiles; Structure-Activity Relationship; Technetium Tc 99m Exametazime; Technology; Terpenes; Tuberculosis; Tuberculosis, Multidrug-Resistant; Urinary Catheters; Urinary Tract Infections; Vascular Endothelial Growth Factor A; Virulence Factors; Water; Wound Healing

Ceftaroline has in vitro activity against bacterial isolates, including methicillin-resistant Staphylococcus aureus. This is the first study to investigate ceftaroline fosamil in pediatric patients with acute bacterial skin and skin structure infections (ABSSSIs).. A multicenter, observer-blinded study (NCT01400867) in pediatric patients (2 months-17 years of age) with ABSSSIs. Patients were randomized 2:1 to receive intravenous (IV) ceftaroline fosamil or IV comparator (vancomycin or cefazolin, plus optional aztreonam) with optional switch to oral antibacterials from Day 4. Safety and clinical outcomes were assessed.. Of 163 enrolled patients, 159 received treatment. Treatment groups were comparable for baseline characteristics. Rates of study drug-related treatment-emergent adverse events were similar for ceftaroline fosamil [22% (23/106)] and comparator [23% (12/53)]. One serious adverse event, considered to be related to IV study drug, occurred in the ceftaroline fosamil group (hypersensitivity). In both the treatment groups, 85% (ceftaroline fosamil, 91/107 and comparator, 44/52) of the modified intent-to-treat population achieved early clinical response (≥20% reduction in infection area from baseline). Clinical cure rates at test-of-cure were high [ceftaroline fosamil, 94% (101/107) and comparator, 87% (45/52)]. For patients evaluated 8 to 15 days after the last dose of any antibiotic (IV or oral), from whom methicillin-resistant Staphylococcus aureus was initially isolated, a favorable microbiologic response (reflecting the efficacy of oral/IV therapy and capturing a relapse or reinfection) was achieved with ceftaroline fosamil [89% (16/18)] and comparator [57% (4/7)].. Ceftaroline fosamil, with optional oral switch, was as well-tolerated and effective in pediatric patients with ABSSSIs as comparator therapy.

Topics: Acute Disease; Adolescent; Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Child; Child, Preschool; Female; Humans; Infant; Male; Microbial Sensitivity Tests; Skin Diseases, Bacterial; Staphylococcus aureus; Streptococcus pyogenes; Treatment Outcome

Scientific and regulatory interest in assessing clinical endpoints after 48 to 72 h of treatment for acute bacterial skin and skin structure infections (ABSSSI) has increased. Historical, pre-antibiotic-era data suggest that a treatment effect relative to untreated controls can be discerned in this time interval. Ceftaroline fosamil, a broad-spectrum bactericidal cephalosporin with activity against Gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA), and Gram-negative organisms was efficacious in two phase 3 trials of complicated skin infections (CANVAS 1 and 2) using clinical cure rates at the test-of-cure visit. To assess an early clinical response in the CANVAS trials, a retrospective analysis using a day 3 clinical endpoint was conducted. Adults with ABSSSI received intravenous ceftaroline fosamil at 600 mg every 12 h (q12h) or vancomycin at 1 g plus aztreonam at 1 g (V/A) q12h for 5 to 14 days. Clinical response at day 3, defined as cessation of infection spread and absence of fever, was analyzed in patients with a lesion size of ≥ 75 cm(2) and either deep and/or extensive cellulitis, major abscess, or an infected wound. Day 3 integrated CANVAS clinical response rates were 74.0% (296/400) for ceftaroline and 66.2% (263/397) for V/A (difference, 7.8%; 95% confidence interval [CI], 1.3% to 14.0%). In the individual studies, absolute treatment differences of 9.4% (CANVAS 1) and 5.9% (CANVAS 2) favoring ceftaroline were observed. For ABSSSI due to MRSA, response rates were 81.7% and 77.4% in the ceftaroline and V/A groups, respectively. In this retrospective analysis, ceftaroline fosamil monotherapy had a numerically higher clinical response than V/A at day 3 in the treatment of ABSSSI.

Topics: Acute Disease; Aged; Aged, 80 and over; Anti-Bacterial Agents; Aztreonam; Biomarkers; Ceftaroline; Cephalosporins; Drug Administration Schedule; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Injections, Intravenous; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Retrospective Studies; Skin Diseases, Bacterial; Treatment Outcome; Vancomycin

The objective of this study was to determine if real-world ceftaroline treatment in adults hospitalized for acute bacterial skin and skin structure infections (ABSSSI) is associated with decreased infection-related length of stay (LOS

Topics: Acute Disease; Adult; Aged; Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Female; Humans; Male; Middle Aged; Retrospective Studies; Skin; Skin Diseases, Bacterial; Treatment Outcome; Vancomycin

Ceftaroline, the active form of the prodrug ceftaroline fosamil, is approved for use in adults with community-acquired bacterial pneumonia (CABP) or acute bacterial skin and skin structure infections (ABSSSI) in the United States and for similar indications in Europe. Pharmacokinetic (PK) data from 5 pediatric (birth to <18 years) studies of ceftaroline fosamil were combined with PK data from adults to update a population PK model for ceftaroline and ceftaroline fosamil. This model, based on a data set including 305 children, was used to conduct simulations to estimate ceftaroline exposures and percentage of time that free drug concentrations were above the minimum inhibitory concentration (%fT>MIC) for pediatric dose regimens. With dose regimens of 8 mg/kg every 8 hours (q8h) in children aged 2 months to <2 years and 12 mg/kg (up to a maximum of 400 mg) q8h in children aged 2 years to <18 years or 600 mg q12h in children aged 12 to <18 years, >90% of children were predicted to achieve a target of 36% fT>MIC at an MIC of 2 mg/L, and >97% were predicted to achieve 44% fT>MIC at an MIC of 1 mg/L. Thus, high PK/pharmacodynamic target attainment would be maintained in children for targets associated with 1-log kill of Staphylococcus aureus and Streptococcus pneumoniae. The predicted ceftaroline exposures for these dose regimens were similar to those in adults given 600 mg q12h ceftaroline fosamil. This work contributed to the approval of dose regimens for children aged 2 months to <18 years by the FDA and EMA, which are presented.

Topics: Acute Disease; Adolescent; Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Child; Child, Preschool; Clinical Trials as Topic; Community-Acquired Infections; Computer Simulation; Female; Humans; Infant; Male; Microbial Sensitivity Tests; Models, Biological; Pneumonia, Bacterial; Skin Diseases, Bacterial; Staphylococcus aureus; Streptococcus pneumoniae

The budgetary impact of adding ceftaroline fosamil to a hospital formulary for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) was evaluated.. A three-year hospital budget impact model was constructed with three initial treatment options for ABSSSIs: ceftaroline fosamil, vancomycin plus aztreonam, and other vancomycin-containing regimens. The target population was hospitalized adult patients with an ABSSSI. Clinical cure rates with initial treatment were assumed to be similar to those from ceftaroline fosamil clinical trials. Patients who did not respond to initial treatment were assumed to be treated successfully with second-line antimicrobial therapy. Length of stay and cost per hospital day (by success or failure with initial treatment) were estimated based on a large database from more than 100 U.S. hospitals. Other model inputs included the annual number of ABSSSI admissions, projected annual case growth rate, proportion of ABSSSI target population receiving vancomycin-containing regimen, expected proportion of ABSSSI target population to be treated with ceftaroline fosamil, drug acquisition cost, cost of antibiotic administration, and cost of vancomycin monitoring. Sensitivity analysis using 95% confidence limits of clinical cure rates was also performed.. The estimated total cost of care for treating a patient with an ABSSSI was $395 lower with ceftaroline fosamil ($15,087 versus $15,482) compared with vancomycin plus aztreonam and $72 lower ($15,087 versus $15,159) compared with other vancomycin-containing regimens.. Model estimates indicated that adding ceftaroline fosamil to the hospital formulary would not have a negative effect on a hospital's budget for ABSSSI treatment.

Topics: Acute Disease; Adult; Anti-Bacterial Agents; Aztreonam; Ceftaroline; Cephalosporins; Costs and Cost Analysis; Drug Therapy, Combination; Economics, Hospital; Formularies, Hospital as Topic; Humans; Length of Stay; Models, Economic; Skin Diseases, Bacterial; Vancomycin