Background
Prior economic analysis that compared the 12-gene assay to published patterns of care predicted the assay would improve outcomes while lowering medical costs for stage II, T3, ...mismatch-repair-proficient (MMR-P) colon cancer patients. This study assessed the validity of those findings with real-world adjuvant chemotherapy (aCT) recommendations from the US third-party payer perspective.
Methods
Costs and quality-adjusted life-years (QALYs) were estimated for stage II, T3, MMR-P colon cancer patients using guideline-compliant, state-transition probability estimation methods in a Markov model. A study of 141 patients from 17 sites in the Mayo Clinic Cancer Research Consortium provided aCT recommendations before and after knowledge of the 12-gene assay results. Progression and adverse events data with aCT regimens were based on published literature. Drug and administration costs for aCT were obtained from 2014 Medicare Fee Schedule. Sensitivity analyses evaluated the drivers and robustness of the primary outcomes.
Results
After receiving the 12-gene assay results, physician recommendations in favor of aCT decreased 22 %; fluoropyrimidine monotherapy and FOLFOX recommendations each declined 11 %. Average per-patient drugs, administration, and adverse events costs decreased $US2,339, $US733, and $US3,211, respectively. Average total direct medical costs decreased $US991. Average patient well-being improved by 0.114 QALYs. Savings are expected to persist even if the cost of oxaliplatin drops by >75 % due to generic substitution.
Conclusions
This study provides evidence that real-world changes in aCT recommendations due to the 12-gene assay are likely to reduce direct medical costs and improve well-being for stage II, T3, MMR-P colon cancer patients.
Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are important causes of morbidity and mortality, with mortality rates approaching 62%. HAP and VAP are the second most ...common cause of nosocomial infection overall, but are the most common cause documented in the intensive care unit setting. In addition, HAP and VAP produce the highest mortality associated with nosocomial infection. As a result, evidence-based guidelines were prepared detailing the epidemiology, microbial etiology, risk factors and clinical manifestations of HAP and VAP. Furthermore, an approach based on the available data, expert opinion and current practice for the provision of care within the Canadian health care system was used to determine risk stratification schemas to enable appropriate diagnosis, antimicrobial management and nonantimicrobial management of HAP and VAP. Finally, prevention and risk-reduction strategies to reduce the risk of acquiring these infections were collated. Future initiatives to enhance more rapid diagnosis and to effect better treatment for resistant pathogens are necessary to reduce morbidity and improve survival.
The ACCOMPLISH trial (Avoiding Cardiovascular events through Combination therapy in Patients Living with Systolic Hypertension) was a 3-year multicenter, event-driven trial involving patients with ...high cardiovascular risk who were randomized in a double-blinded manner to benazepril plus either hydrochlorothiazide or amlodipine and titrated in parallel to reach recommended blood pressure goals. Of the 8125 participants in the United States, 1414 were of self-described Black ethnicity. The composite kidney disease end point, defined as a doubling in serum creatinine, end-stage renal disease, or death was not different between Black and non-Black patients, although the Blacks were significantly more likely to develop a greater than 50% increase in serum creatinine to a level above 2.6mg/dl. We found important early differences in the estimated glomerular filtration rate (eGFR) due to acute hemodynamic effects, indicating that benazepril plus amlodipine was more effective in stabilizing eGFR compared to benazepril plus hydrochlorothiazide in non-Blacks. There was no difference in the mean eGFR loss in Blacks between therapies. Thus, benazepril coupled to amlodipine was a more effective antihypertensive treatment than when coupled to hydrochlorothiazide in non-Black patients to reduced kidney disease progression. Blacks have a modestly higher increased risk for more advanced increases in serum creatinine than non-Blacks.
The conversion of soluble prion protein into an insoluble, pathogenic, protease-resistant isoform is a key event in the development of prion diseases. Although the mechanism by which the conversion ...engenders a pathogenic event is unclear, there is increasing evidence to suggest that this may depend on the function of the prion protein in preventing oxidative damage. Therefore, in this study, we assessed the interrelationship between redox-sensitive cysteine, glycosylation, and prion metabolism. Cells were treated with a thioreductant, dithiothreitol, to assess the effect of the cellular oxidation state on the synthesis of the prion protein. This change in redox balance affected the glycosylation of the prion protein, resulting in the sole production of glycosylated forms. The role of the single disulfide bridge in mediating this effect within the prion protein was confirmed by mutating the cysteine residues involved in its formation. These data suggest that conditions that increase the rate of formation of the disulfide bridge favor formation of the unglycosylated prion protein. Thus, since the presence of glycans on the prion protein is protective against its pathogenic conversion, a change in the redox status of the cell would increase the risk of developing a prion disease by favoring the production of the unglycosylated form.
Whilst there is international evidence around the high healthcare resource utilization (HRU) associated with atopic dermatitis (AD), there is a lack of published data from the United Kingdom (UK).
A ...retrospective, descriptive, observational study was conducted to evaluate the burden of moderate-to-severe AD on the National Health Service (NHS) in an adult UK population treated with traditional standard of care prior to the introduction of biologics. Patients (n=59) were recruited from 6 UK NHS Hospital Trusts and observed over three years.
707 dermatology clinic visits were recorded over the observation period, amounting to 6.6 visits per patient-year, most commonly for routine check-ups most of which involved dermatology consultants (n=469, 66%). Physicians were the most consulted healthcare professional (n=652, 92%); emollients were the most common treatment (n=80 courses). 174 flares requiring additional medical advice were recorded in total (1.6 per patient-year).
Complex treatment pathways for adult patients in the UK with moderate-to-severe AD incur considerable HRU, particularly for those patients non-responsive to systemic therapies with broad immunosuppressant action. Recent advances in biologics-based AD management could possibly have a significant positive impact on HRU through significant reduction in the number of NHS touch points identified in this study.
The growing need for valid assessment procedures of the outdoor thermal environment in the fields of public weather services, public health systems, urban planning, tourism & recreation and climate ...impact research raised the idea to develop the Universal Thermal Climate Index UTCI based on the most recent scientific progress both in thermo-physiology and in heat exchange theory. Following extensive validation of accessible models of human thermoregulation, the advanced multi-node ‘Fiala’ model was selected to form the basis of UTCI. This model was coupled with an adaptive clothing model which considers clothing habits by the general urban population and behavioral changes in clothing insulation related to actual environmental temperature. UTCI was developed conceptually as an equivalent temperature. Thus, for any combination of air temperature, wind, radiation, and humidity, UTCI is defined as the air temperature in the reference condition which would elicit the same dynamic response of the physiological model. This review analyses the sensitivity of UTCI to humidity and radiation in the heat and to wind in the cold and compares the results with observational studies and internationally standardized assessment procedures. The capabilities, restrictions and potential future extensions of UTCI are discussed.
We use weak gravitational lensing to measure the masses of five galaxy clusters selected from the South Pole Telescope (SPT) survey, with the primary goal of comparing these with the SPT ...Sunyaev-Zel'dovich (SZ) and X-ray-based mass estimates. The clusters span redshifts 0.28 < z < 0.43 and have masses M sub(500) > 2 x 10 super(14) h super(-1) M sub(middot in circle), and three of the five clusters were discovered by the SPT survey. We observed the clusters in the g'r'i' passbands with the Megacam imager on the Magellan Clay 6.5 m telescope. We measure a mean ratio of weak-lensing (WL) aperture masses to inferred aperture masses from the SZ data, both within an aperture of R sub(500,SZ) derived from the SZ mass, of 1.04 + or - 0.18. We measure a mean ratio of spherical WL masses evaluated at R sub(500,SZ) to spherical SZ masses of 1.07 + or - 0.18, and a mean ratio of spherical WL masses evaluated at R sub(500,WL) to spherical SZ masses of 1.10 + or - 0.24. We explore potential sources of systematic error in the mass comparisons and conclude that all are subdominant to the statistical uncertainty, with dominant terms being cluster concentration uncertainty and N-body simulation calibration bias. Expanding the sample of SPT clusters with WL observations has the potential to significantly improve the SPT cluster mass calibration and the resulting cosmological constraints from the SPT cluster survey. These are the first WL detections using Megacam on the Magellan Clay telescope.
Purpose
Acute pain after open abdominal hysterectomy limits the function of patients in the postoperative period, but data regarding the analgesic efficacy of a low dose of pregabalin (75 or 150 mg) ...have been conflicting. This study was performed to determine if a low dose of pregabalin could decrease postoperative opioid use following abdominal hysterectomy when compared with placebo.
Methods
American Society of Anesthesiologists I-II patients older than 18 yr and scheduled for open elective abdominal hysterectomy were recruited for participation and randomized to one of three groups: pregabalin 75 mg (P75), pregabalin 150 mg (P150), or placebo. The study drug was administered two hours prior to surgery and 12 hr following the initial dose. Anesthetic technique and postoperative analgesia were standardized. Postoperative pain was managed using patient-controlled analgesia with morphine. Pain at rest and movement as well as nausea were assessed with an 11-point numeric rating scale.
Results
One hundred and one patients were recruited, and 89 patients completed the study. Mean (SD) cumulative morphine consumption at 24 hr postoperatively was 54.0 (26.2) mg for the placebo group, 53.1 (22.7) mg for the P75 group, and 44.3 (20.9) mg for the P150 group. Independent Student’s
t
tests indicated no difference between the placebo group and either the P75 group (95% confidence interval CI: −11.75 to 13.44;
P
= 0.8937) or the P150 group (95% CI: −2.74 to 22.15;
P
= 0.1238).
Conclusions
At the doses used in this study, pregabalin treatment may not be effective in reducing opioid use up to 24 hr postoperatively following abdominal hysterectomy. This trial was registered at
www.ClinicalTrials.gov
: NCT00781131.
Starpharma focuses on the use of dendrimers as drugs in their own right, in contrast to dendrimers as drug delivery vehicles or diagnostics. This contextual review describes how dendrimers offer a ...unique platform for exploring chemical diversity on the nanoscale and how the production of dendrimer libraries covering a diverse array of macromolecular structures can be used in drug discovery and development. Using Starpharma's work on the prevention of HIV and sexually transmitted infections (STIs) through the development of microbicide candidates as an example, the process from which SPL7013 emerged as a development candidate is described. Following a range of preclinical studies, Starpharma submitted an investigational new drug application (IND) for SPL7013 gel (VivaGel) to the United States Food and Drug Administration (FDA) in June 2003, the first such submission for a dendrimer-based drug. The first clinical trial under this IND was completed in 2004.
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