Adverse pharmacokinetic interactions between illicit substances and clinical drugs are of a significant health concern. Illicit substances are taken by healthy individuals as well as by patients with ...medical conditions such as mental illnesses, acquired immunodeficiency syndrome, diabetes mellitus and cancer. Many individuals that use illicit substances simultaneously take clinical drugs meant for targeted treatment. This concomitant usage can lead to life-threatening pharmacokinetic interactions between illicit substances and clinical drugs. Optimal levels and activity of drug-metabolizing enzymes and drug-transporters are crucial for metabolism and disposition of illicit substances as well as clinical drugs. However, both illicit substances and clinical drugs can induce changes in the expression and/or activity of drug-metabolizing enzymes and drug-transporters. Consequently, with concomitant usage, illicit substances can adversely influence the therapeutic outcome of coadministered clinical drugs. Likewise, clinical drugs can adversely affect the response of coadministered illicit substances. While the interactions between illicit substances and clinical drugs pose a tremendous health and financial burden, they lack a similar level of attention as drug-drug, food-drug, supplement-drug, herb-drug, disease-drug, or other substance-drug interactions such as alcohol-drug and tobacco-drug interactions. This review highlights the clinical pharmacokinetic interactions between clinical drugs and commonly used illicit substances such as cannabis, cocaine and 3, 4-Methylenedioxymethamphetamine (MDMA). Rigorous efforts are warranted to further understand the underlying mechanisms responsible for these clinical pharmacokinetic interactions. It is also critical to extend the awareness of the life-threatening adverse interactions to both health care professionals and patients.
•A novel CO2/NH3 cascade refrigeration system with subcooling in LTC and HTC is proposed.•The proposed system is compared with conventional HFC-404A and CO2/NH3 cascade refrigeration ...systems.•Mathematical models are based on the actual compressors equations.
CO2/NH3 cascade refrigeration system is an all-natural refrigeration option which can be specifically designed and gainfully operated for low temperature applications in warm ambient conditions. In the present study, a novel CO2/NH3 cascade refrigeration system with subcooling is proposed and evaluated as an alternative to the HFC-404A refrigeration system, which is typically used for blast freezer applications in the seafood processing industry. The performance of the proposed system is also compared with a conventional CO2/NH3 cascade refrigeration system without any subcooling arrangement. Real compressor specific equations were used to simulate the performance of the systems under various conditions. The proposed system yields 26% higher performance ratio (COP) than the conventional HFC-404A system at the design condition. In addition, the proposed subcooling arrangement enhances COP of the conventional CO2/NH3 cascade unit by around 5%. The system performance is investigated theoretically under various condensing temperatures and subcooling degrees. The annual energy demand and total equivalent warming impact (TEWI) of the proposed system are 15% and 48% lower than for the conventional HFC-404A system which results in significant economic and environmental benefits. Overall, the proposed system exhibits superior energy efficiency and offers a climate and environmental friendly alternative to the conventional environmentally harmful systems within the seafood industry. Adoption of such energy efficient all natural and clean refrigerant technology is crucial for the future phase out of hydrofluorocarbon (HFC) fluids, as ratified in accordance with the Kigali Amendment to the Montreal Protocol in India and other tropical countries.
The effect of exercise on disease development in hypertrophic cardiomyopathy (HCM) genotype-positive individuals is unresolved. Our objective was to test the effect of exercise training initiated ...before phenotype development on cardiac fibrosis, morphology, and function in a mouse model of HCM. Genotype-positive
R403Q mice exposed to cyclosporine A (CsA) for induction of HCM (HCM mice) were allocated to high-intensity interval treadmill running or sedentary behavior for 6 wk. CsA was initiated from
of the protocol. Cardiac imaging and exercise testing were performed at
,
, and
. After protocol completion, arrhythmia provocation was performed in isolated hearts, and left ventricles (LVs) were harvested for molecular biology and histology. Exercised HCM mice ran farther and faster and exhibited attenuated left atrial (LA) dilatation compared with sedentary mice. Exercised HCM mice had no difference in fibrosis compared with sedentary HCM mice despite lower expression of key extracellular matrix (ECM) genes collagen 1 and 3, fibronectin, and lysyl oxidase, accompanied by increased activation of Akt, GSK3b, and p38. Exercise did not have negative effects on LV function in HCM mice. Our findings indicate mild beneficial effects of exercise initiated before HCM phenotype development, specifically lower ECM gene expression and LA dilatation, and importantly, no detrimental effects.
Genotype-positive hypertrophic cardiomyopathy (HCM) mice had beneficial effects of exercise initiated before phenotype development. Exercised HCM mice had increased exercise capacity, smaller left atria, no increase in hypertrophy, or reduction of function, and a similar degree of fibrosis despite reduction of central extracellular matrix (ECM) genes, including collagens, compared with sedentary HCM mice.
Context: Nerves or fascia may limit motion in young soccer players, thereby contributing to frequent hamstring injuries. Nerve gliding exercises and self-myofascial release techniques may enhance the ...range of motion. Objective: The aim of this study was to compare the acute effect of foam rolling (FR) and neurodynamic nerve gliding (NDNG) on hamstring flexibility, passive stiffness, viscoelasticity and proprioception during the warm-up of soccer players. Design: Crossover study design. Setting: Research laboratory. Participants: Fifteen male soccer players on the same team (age 18.0 ± 1.4 years, body mass 76.9 ± 7.8 kg, height 183 ± 6 cm). Intervention: FR and NDNG included six sets of 45 s with 15 s rest between each set. Over a two-week period subjects performed NDNG and FR on two separate occasions. Main Outcome Measure(s): Hip flexion angle (SLR), knee extension range of motion (ROM), knee joint position sense (AKJPS), hamstring passive resistance torque (PRT), stiffness (STFmax and STF80%) and viscoelasticity (stress-relaxation test (SRT)). Results: A significant interaction between time and intervention was found for knee ROM (p = 0.017), PRT (p = 0.044), and STFmax (p = 0.042). NDNG induced an increase in ROM (p = 0.011), PRT (p = 0.008), and STFmax (p = 0.030). Both NDNG and FR induced an increase in SLR (p < 0.001). No interaction or main effects was found for SRT and AKJPS. Conclusion: The inclusion of NDNG in the warm-up routine increased the ROM more in comparison with FR and may be of benefit to soccer players.
Abstract
Background
The Swedish Breast Reconstruction Outcome Study (SweBRO) initiative is a nationwide study with the primary aim of assessing long-term outcomes after mastectomy with and without ...breast reconstruction (BR). The current part (SweBRO 2) is designed to evaluate health-related quality of life (HRQoL), with the hypothesis that BR has a positive impact on patient-reported HRQoL in the long-term.
Methods
Women who underwent mastectomy in Sweden in 2000, 2005, or 2010 and were alive at the time of the survey were identified through the National Breast Cancer Registry. Eligible participants received formal invitation letters to take part in a survey evaluating their HRQoL at 5 , 10, or 15 years post-mastectomy. The EORTC QLQ-C30, EORTC QLQ-BR23, and EQ-5D-3L questionnaires were employed.
Results
Of 2904 respondents (50% of 5853 invited), 895 (31%) had received BR. Among them, 516 (58%) were reconstructed with implants and 281 (31%) with autologous tissue. Women with BR scored significantly better in the EORCT QLQ-C30 physical functioning domain (mean 90 versus 81 points), fatigue (mean 21 versus 25), and dyspnoea (mean 16 versus 22) compared to non-reconstructed women. The EORTC QLQ-BR23 revealed that women with BR experienced favourable sexual functioning compared with non-reconstructed women (mean 26 versus 14). The EQ-5D-3L visual analogue scale score was similar between groups.
Conclusion
The current study underscores the benefits of BR for long-term well-being, for example, in terms of physical and sexual functioning. These underline the importance of informing women undergoing mastectomy about BR alternatives and its potential benefits in enhancing long-term well-being.
The Swedish Breast Reconstruction Outcome Study (SweBRO) initiative is a nationwide study with the primary aim of assessing long-term outcomes after mastectomy with and without breast reconstruction (BR). Women who had undergone mastectomy in Sweden in 2000, 2005, or 2010 and were alive at the time of the survey were identified through the National Breast Cancer Registry. The current study underscores the benefits of BR for long-term well-being, for example, in terms of physical and sexual functioning.
Abstract
Objective: To estimate time trends in prevalence of symptoms and reported diagnosis related to asthma, allergic rhinitis/conjunctivitis and eczema among school children in the north-west ...coastal part of Croatia. Methods: Results of two identical cross-sectional surveys conducted on the same area 8 years apart (school years 2001/02 versus 2009/10) in complete adherence to the protocol of the International Study of Asthma and Allergies in Childhood were compared. Surveyed population comprised two age groups: 6-7 years (n = 1634 versus n = 1052) and 13-14 years (n = 2194 versus 1181). Results: Significant (p < 0.001) increases in prevalence (%) of symptoms related to asthma (8.4 versus 14.0), allergic rhinitis (17.5 versus 25.6), allergic rhinoconjunctivitis (6.7 versus 15.3) and eczema (3.4 versus 5.9) were observed in the 13-14-year-olds. In the 6-7-year-olds there were observed significant (p < 0.001) increases in prevalence of symptoms of eczema (5.4 versus 8.7) and allergic rhinitis (16.9 versus 22.1) whereas prevalence of symptoms related to asthma (9.7 versus 9.4; p = 0.398) and allergic rhinoconjunctivitis (5.6 versus 6.8; p = 0.102) showed to be stable. Significant increases in prevalence of reported diagnosis were observed for asthma (5.2 versus 6.9; p = 0.02) and hay fever (10.5 versus 14.6; p < 0.001) in the older, and for eczema (10.6 versus 14.1; p < 0.001) in the younger age group. Conclusion: Prevalence of asthma and allergic diseases among the school children living on the surveyed area showed a rising trend.
Abstract
The aim of the study was to investigate self-experienced nasal symptoms among adults treated for UCLP and the association to clinical findings, and to evaluate whether palate closure in ...one-stage or two-stages affected the symptoms or clinical findings. All people with UCLP born between 1960-1987, treated at Uppsala University Hospital, were considered for participation in this cross-sectional population study with long-term follow-up. Eighty-three patients (76% participation rate) participated, a mean of 37 years after the first operation. Fifty-two patients were treated with one-stage palate closure and 31 with two-stage palate closure. An age-matched group of 67 non-cleft controls completed the same study protocol, which included a questionnaire regarding nasal symptoms, nasal inspection, anterior rhinoscopy, and nasal endoscopy. Patients reported a higher frequency of nasal symptoms compared with the control group, e.g., nasal obstruction (81% compared with 60%) and mouth breathing (20% compared with 5%). Patients also rated their nasal symptoms as having a more negative impact on their daily life and physical activities than controls. Nasal examination revealed higher frequencies of nasal deformities among patients. No positive correlation was found between nasal symptoms and severity of findings at nasal examination. No differences were identified between patients treated with one-stage and two-stage palate closure regarding symptoms or nasal findings. Adult patients treated for UCLP suffer from more nasal symptoms than controls. However, symptoms are not associated with findings at clinical nasal examination or method of palate closure.
The multiple sclerosis (MS) treatment landscape in the United States has changed dramatically over the past decade. While many disease-modifying therapies (DMTs) have been approved by the US Food and ...Drug Administration (FDA) for the treatment of relapsing forms of MS, DMT costs continue to rise. The availability of generics and biosimilars in the MS-treatment landscape is unlikely to have a major impact on clinical benefit. However, their availability will provide alternative treatment options and potentially lower costs through competition, thus increasing the affordability of and access to these drugs. In April 2015, the first generic version of the complex drug glatiramer acetate (Glatopa® 20 mg/mL) injection was approved in the United States as a fully substitutable generic for all approved indications of the 20 mg/mL branded glatiramer acetate (Copaxone®) dosage form. Despite glatiramer acetate’s complex nature—being a chemically synthesized (ie, nonbiologic) mixture of peptides—the approval occurred without conducting any clinical trials. Rather, extensive structural and functional characterization was performed to demonstrate therapeutic equivalence to the innovator drug. The approval of Glatopa signifies an important milestone in the US MS-treatment landscape, with the hope that the introduction of generic DMTs and eventually biosimilar DMTs will lead to future improvements in the affordability and access of these much-needed treatments for MS.
PDF
