Davidson and Smolensky

This is a copy of the book, Davidson, P., Smolensky, E., & Leven, C. L. (1964). Aggregate supply and demand analysis. Harper & Row, copied from the Graduate Business Library at NYU

Doxorubicin-conjugated quantum dots to target alveolar macrophages and inflammation

Abstract The ability to provide targeted therapeutic delivery in the lung would be a major advancement in pharmacological treatments for many pulmonary diseases. Critical issues for such successful delivery would require the ability to target specific cell types, minimize toxicity (e.g., inflammatory response), and deliver therapeutic levels of drugs. We report here on the ability of nanoconjugates of CdSe/CdS/ZnS quantum dots (QDs) and doxorubicin (Dox) to target alveolar macrophages (aMØs), cells that play a critical role in the pathogenesis of inflammatory lung injuries. Confocal imaging showed the release of Dox from the QD-Dox nanoconjugate, as was evident by its accumulation in the cell nucleus and induction of apoptosis, implying that the drug retains its bioactivity after coupling to the nanoparticle. Inflammatory injury parameters (albumin leakage, proinflammatory cytokines, and neutrophil infiltration) were recorded after in vivo administration of QD-Dox and Dox, observing no significant effect after QD-Dox treatment compared with Dox. These results demonstrate that nanoparticle platforms can provide targeted macrophage-selective therapy for the treatment of pulmonary disease. From the Clinical Editor: Pulmonary inflammatory diseases still often remain challenging to treat, despite decades of advances and several available agents. In this study, a quantum dot-based alveolar delivery system is presented, targeting macrophages with doxorubicin

A cross Canada surveillance of antimicrobial resistance in respiratory tract pathogens

OBJECTIVE: To determine the prevalence of antimicrobial resistance in clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis from medical centres across Canada. METHODS: Fifty laboratories from across Canada were asked to collect up to 25 consecutive clinical isolates of S pneumoniae, H influenzae and M catarrhalis at some time between September 1994 and May 1995, and then again between September and December of 1996. A total of 2364 S pneumoniae, 575 H influenzae and 200 M catarrhalis samples were collected. H influenzae and M catarrhalis isolates were tested for the production of beta-lactamase. S pneumoniae isolates were characterized as penicillin susceptible, intermediately resistant or high level penicillin-resistant. Minimal inhibitory concentrations (MICs) were determined using a microbroth dilution technique described by the National Committee of Clinical Laboratory Standards. RESULTS: Between the two collection periods, there was a significant increase in highly penicillin-resistant S pneumoniae from 2.1% to 4.4% (P<0.05) and an increase in intermediately penicillin-resistant strains from 6.4% to 8.9% (P<0.05). A significant increase in high level penicillin-resistant S pneumoniae was noted among paediatric isolates. No significant difference in the susceptibilities of comparator agents was detected. A significant increase in the number of beta-lactamase producing H influenzae, 34% to 43% (P<0.05) was observed. Ninety-five per cent of M catarrhalis isolates were beta-lactamase producers in both time periods. see next page S treptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis are the most common bacterial pathogens associated with upper respiratory tract infections in both children and adults (1,2). These pathogens are frequently the causative agents in community-acquired pneumonia, acute sinusitis, acute exacerbation of chronic bronchitis, otitis media and meningitis. Worldwide increases in antimicrobial resistance and the changing epidemiology of pathogenic strains have required a change in the approach to treatment of infections due to these organisms. Because rapid, sensitive and specific diagnostic tests are not available for the common respiratory bacterial pathogens, choice of antimicrobial therapy is nearly always empirical. Thus, it is essential to monitor rates of resistance to such pathogens so that the most efficacious agent can be used. The present study was performed to determine the rates of antimicrobial resistance to three respiratory tract pathogens from across Canada. Centres that had previously provided isolates to determine resistance rates in various pathogens were asked to participate in the present study. Specifically, the rates of penicillin susceptibility in S pneumoniae and betalactamase production in H influenzae and M catarrhalis were determined. As well, the in vitro activities of selected antimicrobial agents were determined against all three pathogens. METHODS Fifty laboratories from across Canada were asked to collect up to 25 consecutive clinical isolates of S pneumoniae, H influenzae and M catarrhalis at some time between September 1994 and May 1995, and then again between September and December of 1996. A total of 2364 S pneumoniae, 575 H influenzae and 200 M catarrhalis samples were collected. Almost all centres were tertiary care centres that served urban areas. All isolates were sent to Mount Sinai Hospital (Toronto, Ontario) microbiology laboratory for analysis. All isolates were nonsterile respiratory tract specimens that were predominately sputum cultures (greater than 90%). Only single isolates from different patients were included in the study. Study sites were asked to provide information on the patient's age and site of isolation. Isolates were identified using standard criteria (3). H influenzae were serotyped to determine whether they were type b using a commercial latex agglutination serotyping kit (Difco Laboratories, Michigan). H influenzae and M catarrhalis isolates were tested for the production of beta-lactamase by the cefinase disk method (Becton Dickinson Microbiology Systems, Maryland) (4). Minimal inhibitory concentrations (MICs) were determined using a microbroth dilution technique described by the National Committee of Clinical Laboratory Standards (NCCLS) (Villanova, Pennsylvania) (5). The susceptible, intermediate and resistant breakpoints for determining penicillin susceptibility of S pneumoniae were: susceptible 0.06 mg/L or less, intermediate 0.12 to 1 mg/L and resistant 2.0 mg/L or greater. The following antimicrobials were evaluated: cefprozil (Cefzil, Bristol-Myers Squibb Canada Inc), cefaclor (Ceclor, Eli Lilly Canada Inc), cefixime (Suprax, Rhône-Poulenc Rorer Canada Inc), cephalexin (Keflex, Eli Lilly Canada Inc), cefuroxime (Zinacef, Glaxo Wellcome Canada Inc), ampicillin, clarithromycin (Biaxin, Abbott), azithromycin (Zithromax, Pfizer Canada), erythromycin and ciprofloxacin (Cipro, Bayer Inc). Erythromy- Can J Infect Dis Vol 10 No 2 March/April 1999 129 Antimicrobial resistance in respiratory pathogens CONCLUSIONS: During the course of this study, the incidence of penicillin resistance in S pneumoniae doubled. As a result of this increase, infections due to this organism in sites where poor penetration of beta-lactam antibiotics occur may become increasingly difficult to manage. RÉSULTATS : Entre les deux périodes de cueillette, on a noté une augmentation significative du nombre de souches de S. pneumoniae très résistantes à la pénicilline, qui est passée de 2,1 % à 4,4 % (p < 0,05) et une augmentation de 6,4 % à 8,9 % (p < 0,05) des souches moyennement résistantes à la pénicilline. Une augmentation significative des souches de S. pneumoniae très résistantes à la pénicilline a été notée parmi les spécimens pédiatriques. Aucune différence significative n'a été notée entre les agents de comparaison. Une augmentation significative du nombre de souches de H. influenzae productrices de bêta-lactamases a été observée, soit de 34 % à 43 % (p < 0,05). Quatre-vingt-quinze pour cent des isolats de M. catarrhalis étaient producteurs de bêta-lactamases pendant les deux périodes en question. CONCLUSION : Durant l'étude, l'incidence de la résistance de S. pneumoniae à la pénicilline a doublé. Par conséquent, les infections attribuables à cet organisme, là où la pénétration des bêta-lactamines est faible, pourraient devenir plus difficiles à traiter. cin, ampicillin, clindamycin, tetracycline, chloramphenicol, and trimethoprim/sulphamethoxazole (TMP/SMX) were obtained from Sigma Chemical Company (Michigan). RESULTS Of 3139 clinical isolates, S pneumoniae accounted for 75% (2364) of the isolates, 18.5% (575) were H influenzae, and the remaining 6.5% (or should be 6%) (200) were M catarrhalis. More than 90% of specimens were isolated from sputum samples. Overall, approximately 40% of the S pneumoniae isolates were from a paediatric (age birth to 16 years) population, and 60% originated from adults during both time periods. In 1994-95, 91.4% of S pneumoniae strains were penicillin susceptible, 6.4% were intermediately resistant and 2.1% were highly resistant to penicillin All agents tested had excellent activity against penicillinsusceptible strains. Among intermediately resistant strains, high rates of resistance were observed for erythromycin (12.9%), TMP/SMX (65.6%), cefuroxime (42.4%) and tetracy- Beta-lactamase was detected in 34% of H influenzae strains in 1994-95 and 43% in 1996. Of the 575 isolates that were collected, only three strains were serotype b. Two of these were isolated from adults and one from a child. Forty-four per cent of the H influenzae isolates were from a paediatric population, the remaining 56% were from adults. For beta-lactamase negative H influenzae, all agents had good activity. Ninety-six per cent of beta-lactamase producing H influenzae were resistant to ampicillin, and 13.7% were resistant to TMP/SMX Beta-lactamase production was detected in 95% of the M catarrhalis isolate

An Examination of ESI Triage Scoring Accuracy in Relationship to ED Nursing Attitudes and Experience.

INTRODUCTION: This research was designed to examine if there is a difference in nurse attitudes and experience for those who assign Emergency Severity Index (ESI) scores accurately and those who do not assign ESI scores accurately. Studies that have used ESI scoring discussed the role of experience, but have not specifically addressed how the amount of experience and attitude towards patients in triage affect the triage nurse\u27s decision-making capabilities. METHODS: A descriptive, exploratory study design was used. Data from 64 nurses and 1,644 triage events at 3 emergency departments was collected. Participants completed demographic data, attitude (Caring Nurse Patient Interaction, CNPI-23) survey, and triage data collection tools during the continuous 8-hour triage shift. Clinical nurse expert raters retrospectively reviewed the charts and assigned an ESI score to be compared with the nurse. Descriptive statistics were used to describe the nurse and Pearson\u27s correlation was used to examine the relationship between experience and attitude. RESULTS: In this study of 64 nurse participants, the ESI score assigned by nurse participants did not differ significantly based on years of experience or CNPI mean score. The Kappa statistic ranged from a high of 0.63 in the nurse participant with 1.00 to 1.99 years of experience to a low of 0.51 in the nurse participant with 15 to 19 years of experience. The nurse participants with an overall mean CNPI-23 score of 106 to 115 achieved the highest agreement compared with a single participant with a CNPI-23 overall mean score of less than 77 who had a Kappa agreement of 0.50. The nurse participants with a CNPI-23 overall mean score between 81 and 92 demonstrated agreement of 0.54 to 0.60. DISCUSSION: Based on the high level of liability the triage area presents, special consideration needs to be made when deciding which nurse should be assigned to that area. The evidence produced from this study should provide some reassurance to ED managers and nurses alike that nurses with minimal ED experience and a working understanding of the ESI 5-level triage algorithm possess the knowledge and the capacity to safely and appropriately triage patients in the emergency department

An Examination of ESI Triage Scoring Accuracy in Relationship to ED Nursing Attitudes and Experience.

INTRODUCTION: This research was designed to examine if there is a difference in nurse attitudes and experience for those who assign Emergency Severity Index (ESI) scores accurately and those who do not assign ESI scores accurately. Studies that have used ESI scoring discussed the role of experience, but have not specifically addressed how the amount of experience and attitude towards patients in triage affect the triage nurse\u27s decision-making capabilities. METHODS: A descriptive, exploratory study design was used. Data from 64 nurses and 1,644 triage events at 3 emergency departments was collected. Participants completed demographic data, attitude (Caring Nurse Patient Interaction, CNPI-23) survey, and triage data collection tools during the continuous 8-hour triage shift. Clinical nurse expert raters retrospectively reviewed the charts and assigned an ESI score to be compared with the nurse. Descriptive statistics were used to describe the nurse and Pearson\u27s correlation was used to examine the relationship between experience and attitude. RESULTS: In this study of 64 nurse participants, the ESI score assigned by nurse participants did not differ significantly based on years of experience or CNPI mean score. The Kappa statistic ranged from a high of 0.63 in the nurse participant with 1.00 to 1.99 years of experience to a low of 0.51 in the nurse participant with 15 to 19 years of experience. The nurse participants with an overall mean CNPI-23 score of 106 to 115 achieved the highest agreement compared with a single participant with a CNPI-23 overall mean score of less than 77 who had a Kappa agreement of 0.50. The nurse participants with a CNPI-23 overall mean score between 81 and 92 demonstrated agreement of 0.54 to 0.60. DISCUSSION: Based on the high level of liability the triage area presents, special consideration needs to be made when deciding which nurse should be assigned to that area. The evidence produced from this study should provide some reassurance to ED managers and nurses alike that nurses with minimal ED experience and a working understanding of the ESI 5-level triage algorithm possess the knowledge and the capacity to safely and appropriately triage patients in the emergency department

Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active-controlled clinical trial

Background: Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin and angiotensin receptor antagonist being examined in an ongoing phase 3 trial in adults with IgA nephropathy. We report the prespecified interim analysis of the primary proteinuria efficacy endpoint, and safety. Methods: PROTECT is an international, randomised, double-blind, active-controlled study, being conducted in 134 clinical practice sites in 18 countries. The study examines sparsentan versus irbesartan in adults (aged ≥18 years) with biopsy-proven IgA nephropathy and proteinuria of 1·0 g/day or higher despite maximised renin-angiotensin system inhibitor treatment for at least 12 weeks. Participants were randomly assigned in a 1:1 ratio to receive sparsentan 400 mg once daily or irbesartan 300 mg once daily, stratified by estimated glomerular filtration rate at screening (30 to 1·75 g/day). The primary efficacy endpoint was change from baseline to week 36 in urine protein-creatinine ratio based on a 24-h urine sample, assessed using mixed model repeated measures. Treatment-emergent adverse events (TEAEs) were safety endpoints. All endpoints were examined in all participants who received at least one dose of randomised treatment. The study is ongoing and is registered with ClinicalTrials.gov, NCT03762850. Findings: Between Dec 20, 2018, and May 26, 2021, 404 participants were randomly assigned to sparsentan (n=202) or irbesartan (n=202) and received treatment. At week 36, the geometric least squares mean percent change from baseline in urine protein-creatinine ratio was statistically significantly greater in the sparsentan group (-49·8%) than the irbesartan group (-15·1%), resulting in a between-group relative reduction of 41% (least squares mean ratio=0·59; 95% CI 0·51-0·69; p<0·0001). TEAEs with sparsentan were similar to irbesartan. There were no cases of severe oedema, heart failure, hepatotoxicity, or oedema-related discontinuations. Bodyweight changes from baseline were not different between the sparsentan and irbesartan groups. Interpretation: Once-daily treatment with sparsentan produced meaningful reduction in proteinuria compared with irbesartan in adults with IgA nephropathy. Safety of sparsentan was similar to irbesartan. Future analyses after completion of the 2-year double-blind period will show whether these beneficial effects translate into a long-term nephroprotective potential of sparsentan. Funding: Travere Therapeutics