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Technical Innovations & Patient Support... Sep 2019Proton Therapy (PR) is an emerging treatment for prostate cancer (Pca) patients. However, limited and conflicting data exists regarding its ability to result in fewer... (Review)
Review
BACKGROUND
Proton Therapy (PR) is an emerging treatment for prostate cancer (Pca) patients. However, limited and conflicting data exists regarding its ability to result in fewer bladder and rectal toxicities compared to Photon Therapy (PT), as well as its cost efficiency and plan robustness.
MATERIALS AND METHODS
An electronic literature search was performed to acquire eligible studies published between 2007 and 2018. Studies comparing bladder and rectal dosimetry or Gastrointestinal (GI) and Genitourinary (GU) toxicities between PR and PT, the plan robustness of PR relative to motion and its cost efficiency for Pca patients were assessed.
RESULTS
28 studies were eligible for inclusion in this review. PR resulted in improved bladder and rectal dosimetry but did not manifest as improved GI/GU toxicities clinically compared to PT. PR plans were considered robust when specific corrections, techniques, positioning or immobilisation devices were applied. PR is not cost effective for intermediate risk Pca patients; however PR may be cost effective for younger or high risk Pca patients.
CONCLUSION
PR offers improved bladder and rectal dosimetry compared to PT but this does not specifically translate to improved GI/GU toxicities clinically. The robustness of PR plans is acceptable under specific conditions. PR is not cost effective for all Pca patients.
PubMed: 32095544
DOI: 10.1016/j.tipsro.2019.08.001 -
Protein Science : a Publication of the... Dec 2023Hirudin from Hirudo medicinalis is a bivalent α-Thrombin (αT) inhibitor, targeting the enzyme active site and exosite-I, and is currently used in anticoagulant therapy...
From haemadin to haemanorm: Synthesis and characterization of full-length haemadin from the leech Haemadipsa sylvestris and of a novel bivalent, highly potent thrombin inhibitor (haemanorm).
Hirudin from Hirudo medicinalis is a bivalent α-Thrombin (αT) inhibitor, targeting the enzyme active site and exosite-I, and is currently used in anticoagulant therapy along with its simplified analogue hirulog. Haemadin, a small protein (57 amino acids) isolated from the land-living leech Haemadipsa sylvestris, selectively inhibits αT with a potency identical to that of recombinant hirudin (K = 0.2 pM), with which it shares a common disulfide topology and overall fold. At variance with hirudin, haemadin targets exosite-II and therefore (besides the free protease) it also blocks thrombomodulin-bound αT without inhibiting the active intermediate meizothrombin, thus offering potential advantages over hirudin. Here, we produced in reasonably high yields and pharmaceutical purity (>98%) wild-type haemadin and the oxidation resistant Met5 → nor-Leucine analogue, both inhibiting αT with a K of 0.2 pM. Thereafter, we used site-directed mutagenesis, spectroscopic, ligand-displacement, and Hydrogen/Deuterium Exchange-Mass Spectrometry techniques to map the αT regions relevant for the interaction with full-length haemadin and with the synthetic N- and C-terminal peptides Haem(1-10) and Haem(45-57). Haem(1-10) competitively binds to/inhibits αT active site (K = 1.9 μM) and its potency was enhanced by 10-fold after Phe3 → β-Naphthylalanine exchange. Conversely to full-length haemadin, haem(45-57) displays intrinsic affinity for exosite-I (K = 1.6 μM). Hence, we synthesized a peptide in which the sequences 1-9 and 45-57 were joined together through a 3-Glycine spacer to yield haemanorm, a highly potent (K = 0.8 nM) inhibitor targeting αT active site and exosite-I. Haemanorm can be regarded as a novel class of hirulog-like αT inhibitors with potential pharmacological applications.
Topics: Hirudins; Thrombin; Amino Acid Sequence; Peptides; Heme
PubMed: 37924304
DOI: 10.1002/pro.4825 -
Plastic Surgery (Oakville, Ont.) Feb 2023Understanding the variables that influence success in digital replant surgery is essential to guide clinical decision-making and to counsel patients. The purpose of...
Understanding the variables that influence success in digital replant surgery is essential to guide clinical decision-making and to counsel patients. The purpose of this study was to determine the replant success rate and identify predictors of success at our tertiary care centre. This was a single centre, retrospective cohort study of consecutive patients who underwent digital replantation from January 2000 to September 2018. Adult patients with flexor zone I to III amputations were included. Patient demographics, comorbidities, injury pattern, operative data, and post-operative care were reviewed. The primary outcome was survival of the replanted digit at discharge. A total of 146 patients met inclusion criteria. Of these, 100 had single-digit replants and 46 underwent multi-digit replants for a total of 220 digits. The success rate was 71%. Predictors of success included sharp mechanism of injury (P < .01), incomplete amputation (P < .01), amputation proximal to zone I flexor level (P = .02), post-operative acetylsalicylic acid use (P < .01), absence of leech use (P = .05), and absence of operative re-exploration (P < .01). Daytime replants had similar outcome compared to nighttime replants despite having increased ischemia time (7.9 ± 3.9 hours vs 6.8 ± 2.6 hours, P = .02). However, daytime operative time (7.8 ± 3.7 hours) was significantly shorter than nighttime replant time (9.6 ± 5.9 hours, P = .01). Sharp amputation, intact venous drainage, proximal amputation, and acetylsalicylic acid use were associated with replant survival and are factors to consider when managing patients for digital replantation. Leech therapy and operative re-exploration were associated with poor outcome. Nighttime replants required significantly longer operative time than daytime replants despite similar survival outcome.
PubMed: 36755824
DOI: 10.1177/22925503211024767 -
Physical Therapy Aug 2022
PubMed: 35713528
DOI: 10.1093/ptj/pzac084 -
JAMA Cardiology May 2023Ultrasound renal denervation (uRDN) was shown to lower blood pressure (BP) in patients with uncontrolled hypertension (HTN). Establishing the magnitude and consistency...
IMPORTANCE
Ultrasound renal denervation (uRDN) was shown to lower blood pressure (BP) in patients with uncontrolled hypertension (HTN). Establishing the magnitude and consistency of the uRDN effect across the HTN spectrum is clinically important.
OBJECTIVE
To characterize the effectiveness and safety of uRDN vs a sham procedure from individual patient-level pooled data across uRDN trials including either patients with mild to moderate HTN on a background of no medications or with HTN resistant to standardized triple-combination therapy.
DATA SOURCES
A Study of the ReCor Medical Paradise System in Clinical Hypertension (RADIANCE-HTN SOLO and TRIO) and A Study of the ReCor Medical Paradise System in Stage II Hypertension (RADIANCE II) trials.
STUDY SELECTION
Trials with similar designs, standardized operational implementation (medication standardization and blinding of both patients and physicians to treatment assignment), and follow-up.
DATA EXTRACTION AND SYNTHESIS
Pooled analysis using individual patient-level data using linear regression models to compare uRDN with sham across the trials.
MAIN OUTCOMES AND MEASURES
The primary outcome was baseline-adjusted change in 2-month daytime ambulatory systolic BP (dASBP) between groups.
RESULTS
A total of 506 patients were randomized in the 3 studies (uRDN, 293; sham, 213; mean [SD] age, 54.1 [9.3]; 354 male [70.0%]). After a 1-month medication stabilization period, dASBP was similar between the groups (mean [SD], uRDN, 150.3 [9.2] mm Hg; sham, 150.8 [10.5] mm Hg). At 2 months, dASBP decreased by 8.5 mm Hg to mean (SD) 141.8 (13.8) mm Hg among patients treated with uRDN and by 2.9 mm Hg to 147.9 (14.6) mm Hg among patients treated with a sham procedure (mean difference, -5.9; 95% CI, -8.1 to -3.8 mm Hg; P < .001 in favor of uRDN). BP decreases from baseline with uRDN vs sham were consistent across trials and across BP parameters (office SBP: -10.4 mm Hg vs -3.4 mm Hg; mean difference, -6.4 mm Hg; 95% CI, -9.1 to -3.6 mm Hg; home SBP: -8.4 mm Hg vs -1.4 mm Hg; mean difference, -6.8 mm Hg; 95% CI, -8.7 to -4.9 mm Hg, respectively). The BP reductions with uRDN vs sham were consistent across prespecified subgroups. Independent predictors of a larger BP response to uRDN were higher baseline BP and heart rate and the presence of orthostatic hypertension. No differences in early safety end points were observed between groups.
CONCLUSIONS AND RELEVANCE
Results of this patient-level pooled analysis suggest that BP reductions with uRDN were consistent across HTN severity in sham-controlled trials designed with a 2-month primary end point to standardize medications across randomized groups.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02649426 and NCT03614260.
Topics: Humans; Male; Middle Aged; Antihypertensive Agents; Sympathectomy; Treatment Outcome; Hypertension; Kidney; Hypotension
PubMed: 36853627
DOI: 10.1001/jamacardio.2023.0338 -
Molecular Oncology Jul 2020The decision as to whether or not a patient should receive radiation therapy as part of their cancer treatment is based on evidence-based practice and on recommended... (Review)
Review
The decision as to whether or not a patient should receive radiation therapy as part of their cancer treatment is based on evidence-based practice and on recommended international consensus treatment guidelines. However, the merit of involving the patients' individual preferences and values in the treatment decision is frequently overlooked. Here, we review the current literature pertaining to shared decision-making (SDM) in the field of radiation oncology, including discussion of the patient's perception of radiation therapy as a treatment option and patient involvement in clinical trials. The merit of decision aids during the SDM process in radiation oncology is considered, as are patient preferences for active or passive involvement in decisions about their treatment. Clarity of terminology, a better understanding of effective strategies and increased resources will be needed to ensure SDM in radiation oncology becomes a reality.
Topics: Clinical Decision-Making; Clinical Trials as Topic; Humans; Outcome Assessment, Health Care; Patient Participation; Radiation Oncology
PubMed: 32198967
DOI: 10.1002/1878-0261.12675 -
Case Reports in Infectious Diseases 2022The allergic reaction due to leech bites is frequently reported due to complications of leech therapy and also unwanted leech infestation. Regularly, the urticarial...
The allergic reaction due to leech bites is frequently reported due to complications of leech therapy and also unwanted leech infestation. Regularly, the urticarial papules are common, and itching lasts less than 24 h. In the case of leech biting, dermal infection could be caused by leech gut bacterial flora such as Aeromonas spp and histamine from leech saliva. In this case report, a 30-year-old diabetic woman, who works in the field of leech breeding, was bitten by during breeding. Her clinical signs were inflammation, swelling, pain, and redness in the back of her left hand. A microbiological examination revealed that the isolated leech was infected with . The risk of death due to anaphylactic shock and sepsis is high in some cases of underlying diabetes and immunocompromised individuals. The study pointed out the hazards of leech bites and proposed preventative measures such as using gloves and boots for farm workers.
PubMed: 36317193
DOI: 10.1155/2022/5493057 -
Value in Health : the Journal of the... Jul 2021
Topics: Cost-Benefit Analysis; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Protein Kinase Inhibitors
PubMed: 34243833
DOI: 10.1016/j.jval.2020.12.025 -
Therapeutic Advances in Cardiovascular... 2024Vasospastic angina (VSA) refers to chest pain experienced as a consequence of myocardial ischaemia caused by epicardial coronary spasm, a sudden narrowing of the vessels... (Review)
Review
Vasospastic angina (VSA) refers to chest pain experienced as a consequence of myocardial ischaemia caused by epicardial coronary spasm, a sudden narrowing of the vessels responsible for an inadequate supply of blood and oxygen. Coronary artery spasm is a heterogeneous phenomenon that can occur in patients with non-obstructive coronary arteries and obstructive coronary artery disease, with transient spasm causing chest pain and persistent spasm potentially leading to acute myocardial infarction (MI). VSA was originally described as Prinzmetal angina or variant angina, classically presenting at rest, unlike most cases of angina (though in some patients, vasospasm may be triggered by exertion, emotional, mental or physical stress), and associated with transient electrocardiographic changes (transient ST-segment elevation, depression and/or T-wave changes). Ischaemia with non-obstructive coronary arteries (INOCA) is not a benign condition, as patients are at elevated risk of cardiovascular events including acute coronary syndrome, hospitalization due to heart failure, stroke and repeat cardiovascular procedures. INOCA patients also experience impaired quality of life and associated increased healthcare costs. VSA, an endotype of INOCA, is associated with major adverse events, including sudden cardiac death, acute MI and syncope, necessitating the study of the most effective treatment options currently available. The present literature review aims to summarize current data relating to the diagnosis and management of VSA and provide details on the sequence that treatment should follow.
Topics: Humans; Angina Pectoris, Variant; Coronary Vasospasm; Quality of Life; Coronary Angiography; Coronary Artery Disease; Myocardial Infarction; Chest Pain; Spasm
PubMed: 38343041
DOI: 10.1177/17539447241230400 -
The Journal of Manual & Manipulative... Jun 2023Neck pain is a leading cause of disability, and manual therapy (MT) is a common intervention used across disciplines and settings to treat it. While there is consistent... (Review)
Review
Incomplete reporting of manual therapy interventions and a lack of clinician and setting diversity in clinical trials for neck pain limits replication and real-world translation. A scoping review.
INTRODUCTION
Neck pain is a leading cause of disability, and manual therapy (MT) is a common intervention used across disciplines and settings to treat it. While there is consistent support for MT in managing neck pain, questions remain about the feasibility of incorporating MT from research into clinical practice. The purpose of this scoping review was to assess the adequacy of MT intervention descriptions and the variability in clinician and setting for MT delivery in trials for neck pain.
METHODS
Medline (via PubMed), CINAHL, PEDRo, and the Cochrane Central Registry for Controlled Trials were searched for clinical trials published from January 2010 to November 2021. A 11-item tool modified from the Consensus on Exercise Reporting Template was used to assess appropriateness of intervention reporting. Clinicians, subclassifications of neck pain, and clinical settings were also extracted.
RESULTS
113 trials were included. A low percentage of studies provided the recommended level of detail in the description of how MT was delivered (4.4%), while 39.0% included no description at all. Just over half of trials included clinician's qualifications (58.4%), dose of MT (59.3%), and occurrence of adverse events (55.8%). The proportion of trials with clinicians delivering MT were physical therapists (77.9%), chiropractors (10.6%), and osteopaths (2.7%).
DISCUSSION/CONCLUSION
These results reveal incomplete reporting of essential treatment parameters, and a lack of clinician diversity. To foster reproducibility, researchers should report detailed descriptions of MT interventions. Future research should incorporate a variety of MT practitioners to improve generalizability.
Topics: Humans; Neck Pain; Reproducibility of Results; Musculoskeletal Manipulations; Neck; Exercise Therapy
PubMed: 36047903
DOI: 10.1080/10669817.2022.2113295