Refinement and reduction through application of a quantitative score system for estimation of TB-induced disease burden using computed tomography

2018 ◽  
Vol 52 (6) ◽  
pp. 599-610 ◽  
Author(s):  
Sally A Sharpe ◽  
Donna Smyth ◽  
Anthony McIntyre ◽  
Fergus Gleeson ◽  
Mike J Dennis
Keyword(s):  
Computed Tomography ◽  
Disease Burden ◽  
Test Model ◽  
Score System ◽  
Global Epidemic ◽  
Treatment Groups ◽  
Additional Tool ◽  
Treatment Regimens ◽  
Improved Outcomes ◽  
Quantitative Score

Until validated correlates of protection are identified, animal models remain the only way to test the efficacy of the new vaccines and drugs urgently needed to fight the global epidemic caused by infection with Mycobacterium tuberculosis. Non-human primates (NHP) offer the most relevant models of human tuberculosis (TB) and are central to the development process for new interventions. Efficacy evaluations are dependent on the capability of the test model to discriminate improved outcomes between treated groups after experimental exposure to M. tuberculosis and therefore the ability to measure TB-induced disease burden is central to the process. We have developed a score system that allows us to quantify the disease burden induced in macaques by infection with M. tuberculosis, based on the extent and features of disease visible on computed tomography (CT) images. The CT determined disease burden was then verified against that obtained using an established pathology-based approach. Trials of the system as a tool to measure disease burden have shown the approach capable of revealing differences between treatment groups in order to: (a) characterise outcome of infection and enable model refinement; (b) demonstrate the efficacy of drug treatment regimens by showing differences in outcome between test groups. Initial trials suggest that the imaging-based score system provides a valuable additional tool for the measurement of TB-induced disease burden that offers the opportunity to apply both refinement and reduction within studies.

scholarly journals Comparative study utilizing different post-breeding treatment regimens in cyclic Arabian mares

2021 ◽  
pp. 2863-2868
Author(s):  
Khalid Mohammed Karam ◽  
Ahmed Saed Alebady ◽  
Haitham O. Alhilfi ◽  
Dhia Hussain Al-Delemi
Keyword(s):  
Treatment Regimen ◽  
Normal Saline ◽  
Prophylactic Treatment ◽  
Treatment Protocols ◽  
Treatment Groups ◽  
Treatment Regimens ◽  
Reproductive Management ◽  
Natural Breeding ◽  
Uterine Lavage ◽  
Age Category

Background and Aim: Post-breeding treatment is the most common practice in the reproductive management of mares. Oxytocin, uterine lavage, and intrauterine (I/U) antibiotic are usually used as prophylactic therapy. This study aimed to determine the most efficient prophylactic treatment regimen among six treatment protocols applied during natural breeding of cyclic Arabian mares. Materials and Methods: The current study was conducted on cyclic Arabian mares that were subdivided into three age categories (n=968): Category I (5-10 years, n=380), Category II (11-15 years, n=361), and Category III (≥16 years, n=227). Six prophylactic treatments were applied after 4 h of breeding. According to the treatment regimen, treated mares (n=483) were divided into six treatment groups: A (n=80), treated with I/U antibiotic (1 g gentamicin); B (n=81), I/U lavage (normal saline 500 mL); C (n=83), intramuscular (I/M) oxytocin (10 IU); D (n=82), I/U antibiotic and I/M oxytocin; E (n=78), I/U lavage and I/M oxytocin; and F (n=79), I/U lavage with I/U antibiotic and I/M oxytocin. Non-treated mares were classified as controls (n=485). Ultrasonography was performed to monitor pregnant mares 30 and 60 days after mating, and mares were followed until foaling. Results: Pregnancy and foaling results reveals that in age Category I, treatment with oxytocin alone or oxytocin with I/U lavage showed the highest pregnancy and foaling rates (p<0.01). In age Category II, the highest pregnancy and foaling rates were observed in lavage treatment (p<0.01), whereas, in age Category III, the good pregnancy and foaling rates were monitored in treatment with oxytocin and I/U lavage (p<0.01). Conclusion: Treatment with systemic I/M oxytocin is ideal in early age group mares (5-10 years of age). However, irrespective of the age categories, all mares exhibited high pregnancy and foaling rates after treatment with systemic I/M oxytocin and I/U lavage with normal saline (0.9%) 4 h post-breeding.

scholarly journals 509. Clinical Characteristics and Outcomes in Patients Infected with SARS-CoV-2 Treated with Remdesivir, Tocilizumab, and/or Dexamethasone at a Mid-Atlantic Hospital Consortium

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S356-S357
Author(s):  
Nellie Darling ◽  
Kristen R Kent ◽  
Gavin Clark ◽  
Xue Geng ◽  
Marybeth Kazanas ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Length Of Stay ◽  
Ventilatory Support ◽  
Combination Group ◽  
Delivery Device ◽  
Research Support ◽  
Material Support ◽  
Treatment Groups ◽  
Treatment Regimens ◽  
All Treatment

Abstract Background Treatment strategies for COVID-19 have evolved based on clinical trials. We performed a retrospective analysis to determine treatment outcomes for Remdesivir (RDV), Tocilizumab (TOCI), and/or Dexamethasone (DEX) in a representative population from the Mid-Atlantic region. Methods A retrospective chart review was performed for patients admitted to MedStar hospitals within the D.C./Baltimore corridor from 03/01/2020 to 12/31/2020, and diagnosed with COVID-19 using a NP SARS-CoV-2 RT PCR assay. The MedStar Pharmacy Database was utilized to stratify based on any combination of RDV, TOCI, DEX treatment. Our primary endpoints included O2 delivery device, length of stay (LOS), and mortality. Results A total of 2488 patients were included. Overall, the average age of patients was 62yrs, 53% male, and the majority of patients were of Black (54%) or White (27%) race. The average length of stay was 11 days (SD = 12) with a mortality of 14%. Using univariate analyses, all combinations of RDV, TOCI, and DEX treatment regimens were evaluated. Patients who received DEX required the most ventilatory support on Day 1 (5%, p&lt; 0.001) compared to all other groups. These same patients, however, did not go on to have higher ventilatory needs (17%, p&lt; 0.001) compared to the group which ultimately required the most ventilatory support, TOCI plus DEX (94%, p&lt; 0.001) at Day 28 of treatment. TOCI use alone was associated with a 4% to 63% (p&lt; 0.001) increase in need for ventilatory support over the course of 28 days (Figure 1). The shortest LOS was seen in those treated with DEX alone (9.5 days, p&lt; 0.001). Longer LOS outcomes were associated with all treatment groups which included TOCI use (19 to 22 days, p&lt; 0.001, Figure 2). Mortality was similarly higher among all treatment groups which contained TOCI (30% to 62.5%, p&lt; 0.001, Figure 3) when compared to those with RDV and/or DEX use alone (10% to 14%, p&lt; 0.001). Barplot of Oxygen Delivery Device at Admission and within 28 Days among Treatments Figure 1. Largest increase in ventilatory support from Day 1 of treatment (left) to Day 28 of treatment (right) was seen among TOCI and DEX (0% to 93.8%), RDV and TOCI (0% to 72.2%) and TOCI alone (3.7% to 63.4%). Figure 2. LOS was higher among all treatments containing TOCI (p&lt;0.001), with the highest being the combination group of RDV, TOCI, and DEX (22.4 days, p&lt;0.001). Figure 3. Treatment regimens containing TOCI accounted for the highest mortality rates as seen in TOCI and DEX use (62.5%), RDV and TOCI (44.4%), and TOCI use alone (30.4%). Conclusion Our study demonstrates that “real-world” clinical outcomes for patients with COVID-19 treated with Remdesivir, Tocilizumab, and Dexamethasone are consistent with what has been reported in clinical trials. The higher mortality associated with Tocilizumab treatment may reflect the use of this agent in critically ill patients with COVID-19. Disclosures Princy N. Kumar, MD, AMGEN (Other Financial or Material Support, Honoraria)Eli Lilly (Grant/Research Support)Gilead (Grant/Research Support, Shareholder, Other Financial or Material Support, Honoraria)GSK (Grant/Research Support, Shareholder, Other Financial or Material Support, Honoraria)Merck & Co., Inc. (Grant/Research Support, Shareholder, Other Financial or Material Support, Honoraria)

Prospective Randomized Trial of the Treatment of Patients With Metastatic Melanoma Using Chemotherapy With Cisplatin, Dacarbazine, and Tamoxifen Alone or in Combination With Interleukin-2 and Interferon Alfa-2b

1999 ◽  
Vol 17 (3) ◽  
pp. 968-968 ◽  
Author(s):  
Steven A. Rosenberg ◽  
James C. Yang ◽  
Douglas J. Schwartzentruber ◽  
Patrick Hwu ◽  
Francesco M. Marincola ◽  
...  
Keyword(s):  
Randomized Trial ◽  
Metastatic Melanoma ◽  
Interleukin 2 ◽  
Interferon Alfa ◽  
Prospective Randomized Trial ◽  
Treatment Groups ◽  
Treatment Regimens ◽  
Randomized Protocols ◽  
To Receive

PURPOSE: The combination of chemotherapy with immunotherapeutic agents such as interleukin-2 and interferon alfa-2b has been reported to provide improved treatment results in patients with metastatic melanoma, compared with the use of chemotherapy alone. We have performed a prospective randomized trial in patients with metastatic melanoma, comparing treatment with chemotherapy to treatment with chemoimmunotherapy. PATIENTS AND METHODS: One hundred two patients with metastatic melanoma were prospectively randomized to receive chemotherapy composed of tamoxifen, cisplatin, and dacarbazine or this same chemotherapy followed by interferon alfa-2b and interleukin-2. Objective responses, survival, and toxicity in the two groups were evaluated at a median potential follow-up of 42 months. RESULTS: In 52 patients randomized to receive chemotherapy, there were 14 objective responses (27%), including four complete responses. In 50 patients randomized to receive chemoimmunotherapy, there were 22 objective responses (44%) (P2 = .071), including three complete responses. In both treatment groups, the duration of partial responses was often short, and there was a trend toward a survival advantage for patients receiving chemotherapy alone (P2 = .052; median survival of 15.8 months compared with 10.7 months). Treatment-related toxicities were greater in patients receiving chemoimmunotherapy. CONCLUSION: With the treatment regimens used in this study, the addition of immunotherapy to combination chemotherapy increased toxicity but did not increase survival. The use of combination chemoimmunotherapy regimens is not recommended in the absence of well-designed, prospective, randomized protocols showing the benefit of this treatment strategy.

Role of Radiation Therapy and Fluoropyrimidines in the Treatment of Gastrointestinal Malignancies

1996 ◽  
Vol 3 (4) ◽  
pp. 319-328
Author(s):  
William W. Wong ◽  
Steven E. Schild ◽  
James A. Martenson
Keyword(s):  
Clinical Trial ◽  
Clinical Trial Data ◽  
Trial Data ◽  
Combined Chemotherapy ◽  
Gastrointestinal Malignancies ◽  
Treatment Regimens ◽  
Improved Outcomes ◽  
Clinical Benefits ◽  
Positive Results

Background The use of combined chemotherapy and radiation for gastrointestinal malignancies has several theoretical advantages, and clinical trials to determine the type and extent of clinical benefits have been performed. Methods The basic science and clinical trial data evaluating such combinations are reviewed, with an emphasis on the interactions between fluoropyrimidines and radiation. Results Improved outcomes from chemoradiotherapy have been demonstrated in patients with selected stages of anal, esophageal, rectal, and pancreatic cancer. Conclusion Despite these positive results, further work is needed to demonstrate even more effective and less toxic treatment regimens.

Shifting Treatment Patterns and Clinical Outcomes in Veterans Diagnosed with Waldenstrom Macroglobulinemia from 2006 to 2018

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 12-12
Author(s):  
Hsu-Chih Chien ◽  
Deborah Kay Morreall ◽  
Vikas Patil ◽  
Kelli M Rasmussen ◽  
Christina Yong ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Outcomes ◽  
Real World ◽  
Research Funding ◽  
Practice Patterns ◽  
Treatment Patterns ◽  
Clinical Settings ◽  
Treatment Groups ◽  
Treatment Regimens

Background Waldenström's Macroglobulinemia (WM) is a rare indolent lymphoma with an estimated 1,500 new cases diagnosed each year in the United States (US). Over the last decade, several treatments have been introduced into the WM therapeutics landscape including, bendamustine, bortezomib, and most recently oral Bruton's kinase inhibitor (ibrutinib). There is limited information in the adoption of these WM treatments in real-world clinical settings in the US. We describe the practice patterns and clinical outcomes of first-line (1L) treatment of WM in a nationwide cohort of Veterans. Methods Using Veteran Affairs electronic health records (EHR) data, we identified Veterans who were diagnosed and received 1L treatment for WM between January 2006 and December 2018 in the Veterans Health Administration (VHA). Human annotation of EHR clinical records confirmed the diagnosis and 1L treatment regimens. Patients with another cancer diagnosis or patients with documentation that 1L treatment was received outside the VHA were excluded. Eligible patients were followed until loss to follow-up, death, or the end of the study period (June 30, 2019). Patient demographics, disease characteristics, and treatment patterns were identified. Local polynomial regression model curves were generated to demonstrate treatment changes over time. Unadjusted progression-free survival (PFS) and the unadjusted overall survival (OS) are also provided. Results We identified 505 patients diagnosed with WM in VHA between January 2006 thru December 2018. Of these, 318 patients received 1L treatment, with a median time from diagnosis to 1L treatment of 1.2 months (95% confidence interval [CI]: 0.5-5 months). The median age of WM patients was 69.9 years (standard deviation [SD]: 9.4 years), with approximately 73% of WM patients ≥65 years old. Prior to 1L treatment, the median hemoglobin and platelets observed were similar across all treatment groups, regardless of first 1L treatment. However, the median immunoglobulin M (IgM) was substantially lower in patient's treated with ibrutinib (2,570 mg/dL [range: 422-9,001 mg/dL]) and single-agent rituximab (R), 2,855 mg/dL (range: 84-7,880 mg/dL) when compared to those treated with chlorambucil +/- rituximab (4,416 mg/dL [range: (9-8,130 mg/dL]) and bortezomib/dexamethasone +/- rituximab (BDR), 4,086 mg/dL (range: 16-9,944 mg/dL). MYD88 testing occurred in 40 (13%) of patients, with testing most frequently occurring in patients treated with bendamustine +/- rituximab (BR), ibrutinib, and BDR- likely reflecting increased adoption in later periods. Hepatitis C testing occurred in 61 (19%) of patients, with testing most frequently occurring in patients treated with dexamethasone, rituximab, and cyclophosphamide (DRC), BDR, and BR. Over the study observation period, 1L practice patterns shift significantly with increased adoption of BR, BDR and ibrutinib and de-adoption of chemotherapy (Figure 1). The median follow-up time for all patients was 44 months (range: 1-147 months), although a shorter median follow-up time was observed in patients treated with therapeutics in recent years, such as ibrutinib (18 months [range: 2-53 months]) and BR (23 months [range: 4-86 months]). The median unadjusted PFS for all WM patients was 44 months (95% CI: 37-58 months) and the median unadjusted overall survival (OS) was 94 months (95% CI: 82-117 months). Conclusions The introduction of numerous therapeutic options throughout the past decade has profoundly altered the treatment landscape for WM, suggesting a shift in 1L practices from chlorambucil to BDR, BR, and most recently ibrutinib which has been increasingly adopted, since its approval in 2015, especially in older patients, suggesting that it may provide an effective therapeutic option for patients who may not be able to tolerate more aggressive treatment regimens. Limitations of this study include the differences observed in follow-up time as well as the limited number of patients in some 1L treatment groups. Further research is required to establish the long-term benefits and potential treatment-related toxicities of WM treatments in real-world clinical settings. Disclosures Sauer: Roche: Research Funding; Genentech, Inc.: Research Funding; Pharmacyclics: Research Funding; AbbVie: Research Funding. Halwani:AbbVie: Research Funding; Takeda: Research Funding; Roche: Research Funding; Genentech, Inc.: Research Funding; Miragen: Research Funding; Immunedesign: Research Funding; Kyowa Hakko Kirin: Research Funding; Seattle Genetics: Research Funding; Amgen: Research Funding; Pharmacyclics: Research Funding; Bristol Myers Squibb: Research Funding.

Assessing and mitigating post-operative castration pain in Bos indicus cattle

2018 ◽  
Vol 58 (5) ◽  
pp. 909 ◽  
Author(s):  
M. Laurence ◽  
A. Barnes ◽  
T. Collins ◽  
T. Hyndman ◽  
G. C. Musk
Keyword(s):  
Cost Efficiency ◽  
Bos Indicus ◽  
Cost Effective ◽  
Technical Skill ◽  
Test Model ◽  
Not Given ◽  
Random Assignment ◽  
Northern Australia ◽  
Treatment Groups ◽  
Mixed Modelling

Cattle on pastoral land are subject to potentially painful husbandry procedures. In northern Australia, these practices generally occur once a year after the muster and the procedures are usually performed on animals older than 6 months of age. It is seldom that any pain mitigating medications are administered at this time and there is increasing concern that this perceived impost on the animal’s welfare will become more significant at both an economic and cultural level. There is a need to investigate the possibility of using simple, cost-effective, readily available medications, administered using relatively quick and easily taught techniques to increase the chance of industry adoption. This research used castration of 6–8-month-old Bos indicus calves as the test model because it is arguably one of the most common and most painful procedures endured by the animals. Forty-eight, 6–8-month-old Brahman bulls were surgically castrated after random assignment to six different treatment groups (n = 8): no castration Control (NC); castration (C); castration with post-operative meloxicam (CMpost-op); castration with lignocaine (CL); castration with lignocaine and post-operative meloxicam (CLMpost-op); castration with pre-operative meloxicam (CMpre-op). Serial measures of weight, blood cortisol concentrations, balk score, crush score, and daily activity (steps taken, number and duration of rest bouts) were taken. Linear mixed modelling was used to compare experimental groups. Bulls that were castrated and did not receive post-operative meloxicam (C and CL) had significantly lower average weights at all time points (Days 0–13, P < 0.001) of 170.9 kg and 168.6 kg, respectively, than those that did (CMpost-op and CLMpost-op) at 174.7 kg and 173.7 kg, respectively. When lignocaine was not administered before castration, Day 1 post-operative cortisol concentrations were significantly lower when post-operative meloxicam was provided than when it was not (CMpost-op: 47.2 nmol/L vs C: 65.5 nmol/L). When post-operative meloxicam was not given, animals that were given lignocaine before castration had significantly lower cortisol concentrations than those that received no lignocaine (CL: 52.7 nmol/L vs C: 65.5 nmol/L). Animals that were given pre-operative meloxicam had, on average, significantly lower Day 1 post-operative cortisol concentrations than animals that received no lignocaine or meloxicam (CMpre-op: 44.8 nmol/L vs C: 65.5 nmol/L). Analysis of Day 1 (the day following castration) data showed that animals that were given pre-operative meloxicam (CMpre-op) were significantly more active than animals in all other treatment groups (P = 0.038). It was concluded that 6–8-month old, Bos indicus bulls benefit from the administration of both lignocaine before surgery and peri-operative meloxicam. The analgesic methods used are readily adoptable by industry with respect to cost, efficiency and degree of technical skill required.

Sign in / Sign up

Export Citation Format

Share Document