scholarly journals Prospective Evaluation of Local Sustained Release of Celecoxib in Dogs with Low Back Pain

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1178
Author(s):  
Tijn Wiersema ◽  
Anna R. Tellegen ◽  
Martijn Beukers ◽  
Marijn van Stralen ◽  
Erik Wouters ◽  
...  

Back pain affects millions globally and in 40% of the cases is attributed to intervertebral disc degeneration. Oral analgesics are associated with adverse systemic side-effects and insufficient pain relief. Local drug delivery mitigates systemic effects and accomplishes higher local dosing. Clinical efficacy of intradiscally injected celecoxib (CXB)-loaded polyesteramide microspheres (PEAMs) was studied in a randomized prospective double-blinded placebo controlled veterinary study. Client-owned dog patients suffering from back pain were treated with CXB-loaded (n = 20) or unloaded PEAMs (“placebo”) (n = 10) and evaluated by clinical examination, gait analysis, owners’ questionnaires, and MRI at 6 and 12 weeks follow-up. At 6 and 12 weeks, CXB-treated dogs experienced significantly less pain interference with their daily life activities compared to placebo. The risk ratio for treatment success was 1.90 (95% C.I. 1.24–2.91, p = 0.023) at week 6 and 1.95 (95% C.I. 1.10–3.45, p = 0.036) at week 12. The beneficial effects of CXB-PEAMs were more pronounced for the subpopulation of male dogs and those with no Modic changes in MRI at inclusion in the study; disc protrusion did not affect the outcome. It remains to be determined whether intradiscal injection of CXB-PEAMs, in addition to analgesic properties, has the ability to halt the degenerative process in the long term or restore the disc.

2019 ◽  
Vol 10 (1) ◽  
pp. 30-38
Author(s):  
Haider Kareem ◽  
Christian Ulbricht

Study Design: Prospective cohort study. Objective: To evaluate the long-term effectiveness of a posterior dynamic spine stabilization (PDS) System called PercuDyn system as a treatment for low back pain (LBP) in patients with degenerative disc disease who have failed conservative treatment. Methods: Thirty-five patients (21 males, 14 females, mean age 36 years) with chronic LBP due to degenerative disc disease underwent percutaneous facet augmentation with the PercuDyn system. Indications for implanting the PercuDyn device were chronic LBP without sciatica, significant disc degeneration, and who failed conservative treatment. Follow-up after surgery ranged from 4 to 8 years. Patients were clinically evaluated using visual analogue scale (VAS), Oswestry Disability Index (ODI) questionnaire, and the EQ-5D3L. Results: The VAS scale and ODI scores improved at 6 months, 1 year, 2 years, and 4 to 8 years in comparison with the baseline values ( P < .001 and P < .01, respectively). Equally, data from the EQ-5D-3L questionnaire suggested improvements in all domains, including pain and discomfort, over the follow-up period. However, during follow-up, 16 patients (46%) have had unsatisfactory outcome including failure of implant to resolve symptoms (n = 8), developed symptomatic disc protrusion (n = 4), and loosening of the screws (n = 4). Conclusion: Our clinical experience highlights the rather high overall failure rate of this system. Although, some patients show significant improvement in their symptoms, we believe that patients with LBP related to degenerative disc disease are a poor indication for this PDS device.However, large scale studies, with optimised selection criteria are needed to demonstrate the exact role of this device in spinal patients.


2018 ◽  
Vol 5 (3) ◽  
pp. 175-187 ◽  
Author(s):  
O. V. Gorovtsova ◽  
T. L. Ushakova ◽  
V. G. Polyakov

Retinoblastoma is one of highly curable diseases; today the total 5-year survival rate in patients with retinoblastoma exceeds 95%. The article summarizes the current world experience on treatment of patients with intraocular retinoblastoma. The treating skills of intraocular malignant tumor in children are a balance between the patient’s life and the preservation of an eye and its visual functions. The complex and challenging task is the treatment of common intraocular retinoblastoma groups «C», «D», «E» when the large size or localization of the tumor does not allow performing the local (focal) destruction of the tumor. As a rule, in such cases neoadjuvant chemotherapy (CT) is performed at the first stage in order to reduce the size of the tumor for further focal therapy. However, the analysed data on the effectiveness of neoadjuvant CT in combination with focal or radiotherapy demonstrated the limited possibilities of the proposed therapy. Local drug delivery in cancer therapy became a real breakthrough in the organ-preserving treatment of children with large intraocular retinoblastoma. The most widely used current methods of local drug delivery are intravitreal (IVitC) and selective intra-arterial chemotherapy (SIAC) as monotherapy or in combination with neoadjuvant CT and focal therapy which significantly increased the percentage of preserved eyes without radiotherapy administration or damage to the patient survival. The review discusses the different IVitC and SIAC techniques, chemotherapy schemes, dosages of chemotherapy, immediate and long-term complications of treatment.


2020 ◽  
Vol 70 (suppl 1) ◽  
pp. bjgp20X711581
Author(s):  
Charlotte Greene ◽  
Alice Pearson

BackgroundOpioids are effective analgesics for acute and palliative pain, but there is no evidence base for long-term pain relief. They also carry considerable risks such as overdose and dependence. Despite this, they are increasingly prescribed for chronic pain. In the UK, opioid prescribing more than doubled between 1998 and 2018.AimAn audit at Bangholm GP Practice to understand the scale of high-strength opioid prescribing. The aim of the audit was to find out if indications, length of prescription, discussion, and documentation at initial consultation and review process were consistent with best-practice guidelines.MethodA search on Scottish Therapeutics Utility for patients prescribed an average daily dose of opioid equivalent ≥50 mg morphine between 1 July 2019 and 1 October 2019, excluding methadone, cancer pain, or palliative prescriptions. The Faculty of Pain Medicine’s best-practice guidelines were used.ResultsDemographics: 60 patients (37 females), average age 62, 28% registered with repeat opioid prescription, 38% comorbid depression. Length of prescription: average 6 years, 57% >5 years, 22% >10 years. Opioid: 52% tramadol, 23% on two opioids. Indications: back pain (42%), osteoarthritis (12%), fibromyalgia (10%). Initial consultation: 7% agreed outcomes, 35% follow-up documented. Review: 56% 4-week, 70% past year.ConclusionOpioid prescribing guidelines are not followed. The significant issues are: long-term prescriptions for chronic pain, especially back pain; new patients registering with repeat prescriptions; and no outcomes of treatment agreed, a crucial message is the goal is pain management rather than relief. Changes have been introduced at the practice: a patient information sheet, compulsory 1-month review for new patients on opioids, and in-surgery pain referrals.


2021 ◽  
Vol 13 (11) ◽  
pp. 2131
Author(s):  
Jamon Van Den Hoek ◽  
Alexander C. Smith ◽  
Kaspar Hurni ◽  
Sumeet Saksena ◽  
Jefferson Fox

Accurate remote sensing of mountainous forest cover change is important for myriad social and ecological reasons, but is challenged by topographic and illumination conditions that can affect detection of forests. Several topographic illumination correction (TIC) approaches have been developed to mitigate these effects, but existing research has focused mostly on whether TIC improves forest cover classification accuracy and has usually found only marginal gains. However, the beneficial effects of TIC may go well beyond accuracy since TIC promises to improve detection of low illuminated forest cover and thereby normalize measurements of the amount, geographic distribution, and rate of forest cover change regardless of illumination. To assess the effects of TIC on the extent and geographic distribution of forest cover change, in addition to classification accuracy, we mapped forest cover across mountainous Nepal using a 25-year (1992–2016) gap-filled Landsat time series in two ways—with and without TIC (i.e., nonTIC)—and classified annual forest cover using a Random Forest classifier. We found that TIC modestly increased classifier accuracy and produced more conservative estimates of net forest cover change across Nepal (−5.2% from 1992–2016) TIC. TIC also resulted in a more even distribution of forest cover gain across Nepal with 3–5% more net gain and 4–6% more regenerated forest in the least illuminated regions. These results show that TIC helped to normalize forest cover change across varying illumination conditions with particular benefits for detecting mountainous forest cover gain. We encourage the use of TIC for satellite remote sensing detection of long-term mountainous forest cover change.


2021 ◽  
pp. 112067212110356
Author(s):  
Manpreet Singh ◽  
Aditi Mehta Grewal ◽  
Himanshi Singh ◽  
Manjula Sharma ◽  
Manpreet Kaur ◽  
...  

Purpose: To study the long-term efficacy and safety of local application of imiquimod 5% and fluorouracil 1% creams in complex eyelid basal cell carcinomas (BCCs). Methods: A retrospective, non-comparative study in biopsy-proven, complex (involving canthi or >50% of eyelid length) eyelid BCC patients who were medically unfit for surgical procedures. All patients were medically treated with either of the creams using fixed-dose regimens for a minimum of 3 months. All received oral vitamin C 500 mg QID for 3 months as an adjunct for collagen healing. A minimum of “post-treatment” follow-up of 12 months was observed. Results: Of total 30 patients, imiquimod 5% and fluorouracil 1% were used in 16 and 14 patients, respectively. The mean age of our patients was 70.5 years. The co-morbidities included – severe coronary artery disease using blood-thinners ( n = 19), poorly controlled diabetes ( n = 12), poorly controlled hypertension ( n = 6), on nebulization ( n = 3), and tuberculosis with pulmonary fibrosis ( n = 2). Complete clinical tumor resolution was noted in 10 and 8 patients over 12 and 16.5 weeks, respectively, in imiquimod and fluorouracil groups. Periocular skin erythema, chemical conjunctivitis, and skin depigmentation were seen in all the patients of imiquimod group. On the other hand, the local side-effect profile in fluorouracil patients was limited. Conclusion: The medical treatment of complex eyelid BCC is a useful alternative to surgery in the elderly with significant co-morbidities. It provides a promising long-term relief with a tolerable side-effect profile. A prospective, randomized, double-blinded trial would provide stronger evidence for the efficacy of these drugs.


Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 985
Author(s):  
Luisa Müller ◽  
Nicole Power Guerra ◽  
Jan Stenzel ◽  
Claire Rühlmann ◽  
Tobias Lindner ◽  
...  

Caloric restriction (CR) slows the aging process, extends lifespan, and exerts neuroprotective effects. It is widely accepted that CR attenuates β-amyloid (Aβ) neuropathology in models of Alzheimer’s disease (AD) by so-far unknown mechanisms. One promising process induced by CR is autophagy, which is known to degrade aggregated proteins such as amyloids. In addition, autophagy positively regulates glucose uptake and may improve cerebral hypometabolism—a hallmark of AD—and, consequently, neural activity. To evaluate this hypothesis, APPswe/PS1delta9 (tg) mice and their littermates (wild-type, wt) underwent CR for either 16 or 68 weeks. Whereas short-term CR for 16 weeks revealed no noteworthy changes of AD phenotype in tg mice, long-term CR for 68 weeks showed beneficial effects. Thus, cerebral glucose metabolism and neuronal integrity were markedly increased upon 68 weeks CR in tg mice, indicated by an elevated hippocampal fluorodeoxyglucose [18F] ([18F]FDG) uptake and increased N-acetylaspartate-to-creatine ratio using positron emission tomography/computer tomography (PET/CT) imaging and magnet resonance spectroscopy (MRS). Improved neuronal activity and integrity resulted in a better cognitive performance within the Morris Water Maze. Moreover, CR for 68 weeks caused a significant increase of LC3BII and p62 protein expression, showing enhanced autophagy. Additionally, a significant decrease of Aβ plaques in tg mice in the hippocampus was observed, accompanied by reduced microgliosis as indicated by significantly decreased numbers of iba1-positive cells. In summary, long-term CR revealed an overall neuroprotective effect in tg mice. Further, this study shows, for the first time, that CR-induced autophagy in tg mice accompanies the observed attenuation of Aβ pathology.


1989 ◽  
Vol 40 (2) ◽  
pp. 255 ◽  
Author(s):  
ICR Holford

Long-term yields, nitrogen uptake and responsiveness of grain sorghum following three lucerne rotations, an annual legume rotation, long fallowing, and continuous wheat growing were measured on a black earth and red clay in northern New South Wales. The three lucerne rotations compared two methods of lucerne establishment (with or without a cover crop) and two methods of grazing management (short or extended grazing).There were large beneficial effects of lucerne leys on the first grain sorghum crop, whether they were measured as grain yield, nitrogen content of the foliage and grain, or nitrogen uptake. The effect was much smaller in the second year but it increased in the third and fourth years, in direct relation to the rainfall during the sorghum flowering period. The effect was larger on the black earth than on the red clay, reflecting the much higher lucerne yields on the former soil. Evidence indicated that the nitrogen contribution from lucerne after the first year was no greater than the nitrogen accumulated by long fallowing, and this was attributed to very low rainfall and lucerne yields during the four year ley period.The annual legume rotation suffered from drought and insect damage in most years, and following sorghum yields tended to be lower than those achieved by long fallowing.Differences in the effects of establishment method and grazing management on total lucerne yields were reflected in the differences in subsequent grain sorghum yields. Largest differences were on the black earth where extended grazing lowered the total yields of lucerne and subsequent grain sorghum. Sowing lucerne under wheat had little effect on total yields of lucerne or sorghum.


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