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Zeitschrift Fur Rheumatologie Mar 2023Conventional synthetic (cs) and targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARD) have potential interactions with a multitude of drugs.... (Review)
Review
Conventional synthetic (cs) and targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARD) have potential interactions with a multitude of drugs. Furthermore, they sometimes have a lower therapeutic index, particularly in cases of limited organ functions. The aim of this work was to establish evidence-based recommendations on the therapeutic use of DMARDs in the context of drug interactions and dosage recommendations. A systematic literature search was carried out on the issue of drug interactions and dosages in cases of patients with limited kidney function and higher age and suffering from rheumatoid arthritis. A total of 2756 scientific publications were screened and 154 selected of which 68 were scrutinized in detail. Furthermore, the respective specialist subject information was also analyzed. A multitude of possible interactions of synthetic DMARDs with different drugs were detected, which were then assessed with respect to the clinical significance and consequences. A consensus process led to making recommendations with which the interactions were classified: A: dangerous combination, B: avoid combination (if possible, pausing DMARD treatment), C: possible combination requiring increased monitoring and potential adjustments in dosage and D: pharmacological interaction without relevance in DMARD standard doses. Apart from that dosage recommendations were established for each csDMARD and tsDMARD depending on kidney function and age. There are 3 primary recommendations and 11 core recommendations on interactions and dosages of csDMARDs and tsDMARDs meant as a practical help for therapeutic decision making and to improve safety in the treatment of rheumatoid arthritis.
Topics: Humans; Consensus; Antirheumatic Agents; Arthritis, Rheumatoid; Drug Therapy, Combination; Drug Interactions; Biological Products
PubMed: 36633662
DOI: 10.1007/s00393-022-01308-z -
CMAJ : Canadian Medical Association... Apr 2019Opioid agonist treatment is considered important in preventing acquisition of hepatitis C virus (HCV) among people who inject drugs; however, the role of dosage in...
BACKGROUND
Opioid agonist treatment is considered important in preventing acquisition of hepatitis C virus (HCV) among people who inject drugs; however, the role of dosage in opioid agonist treatment is unclear. We investigated the joint association of prescribed dosage of opioid agonist treatment and patient-perceived dosage adequacy with risk of HCV infection among people who inject drugs.
METHODS
We followed prospectively people who inject drugs at risk of acquiring HCV infection (who were RNA negative and HCV-antibody negative or positive) in Montréal, Canada (2004-2017). At 6-month, then 3-month intervals, participants were tested for HCV antibodies or RNA, and completed an interviewer-administered behavioural questionnaire, reporting the following: current exposure to opioid agonist treatment (yes/no), prescribed dosage either high (methadone ≥ 60 mg/d or buprenorphine ≥ 16 mg/d) or low, and perceived dosage adequacy (adequate/inadequate). We then assigned participants to 1 of 5 exposure categories: no opioid agonist treatment, high dosage of opioid agonist treatment perceived to be adequate, high dosage perceived to be inadequate, low dosage perceived to be adequate or low dosage perceived to be inadequate. To estimate associations between categories of opioid agonist treatment dosage and incident HCV infection, we conducted Cox regression analyses, adjusting for multiple confounding factors.
RESULTS
Of 513 participants (median age 35.0 yr, 77.6% male), 168 acquired HCV over 1422.6 person-years of follow-up (incidence 11.8/100 person-years, 95% confidence interval [CI] 10.1-13.7). We observed a gradient in the relative risks of HCV infection across categories of opioid agonist treatment dosage. Compared with people who inject drugs not receiving opioid agonist treatment, adjusted hazard ratios were 0.43 (95% CI 0.23-0.84) for those receiving high dosages perceived to be adequate, 0.61 (95% CI 0.25-1.50) for those receiving high dosages perceived to be inadequate, 1.22 (95% CI 0.74-2.00) for those receiving low dosages perceived to be adequate and 1.94 (95% CI 1.11-3.39) for those receiving low dosages perceived to be inadequate.
INTERPRETATION
Risk of HCV infection varies considerably according to dosage of opioid agonist treatment and patient-perceived adequacy, with associations indicating both protective and harmful effects relative to no exposure to opioid agonist treatment.
Topics: Adult; Buprenorphine; Cohort Studies; Disease Transmission, Infectious; Drug Users; Female; Hepatitis C; Humans; Injections, Intravenous; Male; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders
PubMed: 31036608
DOI: 10.1503/cmaj.181506 -
Ecotoxicology and Environmental Safety Feb 2021Fluoride, widely presented in drinking water and tea, may be detrimental or beneficial to the human health, depending on its dosages ingested. However, the relationship...
Fluoride, widely presented in drinking water and tea, may be detrimental or beneficial to the human health, depending on its dosages ingested. However, the relationship of different dosages of fluoride and gut microbiota is still unclear. In this work, the fermentation model using fecal samples provided by four volunteers was used to evaluate the effects of different dosages of fluoride (1, 2, 10 and 15 mg/L) on the gut microbiota in vitro. The result showed low dosages of fluoride (1 and 2 mg/L) had limited effect on the structure and functional Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of gut microbiota. Furthermore, the low dosage of fluoride could promote the growth of beneficial gut microbiota, including Faecalibacterium and Lactobacillus. Whereas, the high dosage of fluoride (10 and 15 mg/L) significantly changed the composition and functional KEGG pathway of gut microbiota. Moreover, the high dosage of fluoride could also reduce the beneficial gut microbiota, including Faecalibacterium and Phascolarctobacterium, and increase the harmful bacterium including Proteobacteria and Enterobacteriaceae. Both low and high dosages of fluoride showed limited effect on the productions of short-chain fatty acids (SCFAs). Thus, the beneficial or detrimental fluoride to gut microbiota depends on its dosages. The fluoride is expected to serve as a food additive in suitable dosage to improve human health through modulation of the gut microbiota. Moreover, more attention should be paid to toxicity of fluoride with high dosage to gut microbiota.
Topics: Bacteria; Fatty Acids, Volatile; Feces; Fermentation; Fluorides; Gastrointestinal Microbiome; Humans; Lactobacillus; Water Pollutants, Chemical
PubMed: 33373928
DOI: 10.1016/j.ecoenv.2020.111732 -
Contraception Jun 2022To investigate the effect of different oral dosages of levonorgestrel (LNG) on ovarian activity and to identify the lowest dosage at which no ovulation occurred....
OBJECTIVES
To investigate the effect of different oral dosages of levonorgestrel (LNG) on ovarian activity and to identify the lowest dosage at which no ovulation occurred. Secondary objectives were to assess return of ovulation after stopping treatment, bleeding pattern, pharmacokinetic (PK) parameters and safety and tolerability.
STUDY DESIGN
A parallel-group study with adaptive design was performed in 90 healthy women with proven ovulatory cycles. Investigated dosages were LNG 0.095, 0.115 and 0.135 mg per day. Measurements of follicular growth and estradiol (E) and progesterone concentrations were performed every 3 (±1) days during a 56-day treatment and a post-treatment period. Follicle-stimulating hormone and luteinizing hormone concentrations and multiple-dose PK parameters were determined during treatment.
RESULTS
Two normal ovulations occurred in the LNG 0.095 mg group, none in the higher dose groups. Most subjects had active follicle-like structures without ovulation (Hoogland-Skouby scores 4). Ovarian activity was more suppressed in the highest dose group than in the other groups. Mean E concentrations were 241, 219 and 180 pmol/L during treatment with 0.095, 0.115 and 0.135 mg per day, respectively. PK results showed dose-proportionality. Most subjects ovulated during the post-treatment period.
CONCLUSION
LNG 0.115 mg per day was the lowest effective dosage for consistent ovulation inhibition. All investigated dosages were safe and well-tolerated, and mean E concentrations were sufficient for prevention of hypoestrogenic side effects.
IMPLICATIONS
Marketed progestogen-only pills (POP) containing 0.03 mg LNG do not consistently inhibit ovulation. Increasing the dosage to 0.115 mg or 0.135 mg per day, resulting in consistent ovulation inhibition, may improve the contraceptive efficacy of the LNG-POP.
Topics: Estradiol; Female; Follicle Stimulating Hormone; Humans; Levonorgestrel; Luteinizing Hormone; Ovary; Ovulation; Ovulation Inhibition; Progesterone
PubMed: 35123981
DOI: 10.1016/j.contraception.2022.01.018 -
Veterinary Anaesthesia and Analgesia Mar 2022To determine the effect of butorphanol, administered by intravenous (IV) infusion, on the minimum alveolar concentration of isoflurane (MAC) in cats and to examine the...
OBJECTIVE
To determine the effect of butorphanol, administered by intravenous (IV) infusion, on the minimum alveolar concentration of isoflurane (MAC) in cats and to examine the dosage dependence of this effect.
STUDY DESIGN
Randomized, placebo-controlled, crossover experimental study.
ANIMALS
A group of six healthy adult male neutered cats.
METHODS
Cats were anesthetized with isoflurane in oxygen. A venous catheter was placed for fluid and drug administration, and an arterial catheter was placed for measurement of arterial pressure and blood sampling. Four treatments were administered at random with at least 2 week interval between treatments: saline (control), butorphanol low dosage (treatment LD; 0.25 mg kg IV bolus followed by 85 μg kg minute for 20 minutes, then 43 μg kg minute for 40 minutes, then 19 μg kg minute), medium dosage (treatment MD, double the dosages in LD) and high dosage (treatment HD, quadruple the dosages in LD). MAC was determined in duplicate using the bracketing technique and tail clamping. Pulse rate, arterial pressure, hemoglobin oxygen saturation, end-tidal partial pressure of carbon dioxide and arterial blood gas and pH were measured.
RESULTS
Butorphanol reduced MAC in a dosage-dependent manner, by 23 ± 8%, 37 ± 12% and 68 ± 10% (mean ± standard deviation) in treatments LD, MD and HD, respectively. The main cardiopulmonary effect observed was a decrease in pulse rate, significant in treatment HD compared with control.
CONCLUSIONS AND CLINICAL RELEVANCE
Butorphanol caused a dosage-dependent MAC reduction in cats. IV infusion of butorphanol may be of interest for partial IV anesthesia in cats.
Topics: Analgesics, Opioid; Anesthetics, Inhalation; Animals; Blood Pressure; Butorphanol; Cats; Heart Rate; Isoflurane; Male
PubMed: 35033447
DOI: 10.1016/j.vaa.2021.12.004 -
Journal of Ophthalmology 2016Zeaxanthin is a nutritional carotenoid with a considerable amount of safety data based on regulatory studies, which form the basis of its safety evaluation. Subchronic... (Review)
Review
Zeaxanthin is a nutritional carotenoid with a considerable amount of safety data based on regulatory studies, which form the basis of its safety evaluation. Subchronic OECD guideline studies with mice and rats receiving beadlet formulations of high purity synthetic zeaxanthin in the diet at dosages up to 1000 mg/kg body weight (bw)/day, and in dogs at over 400 mg/kg bw/day, produced no adverse effects or histopathological changes. In developmental toxicity studies, there was no evidence of fetal toxicity or teratogenicity in rats or rabbits at dosages up to 1000 or 400 mg/kg bw/day, respectively. Formulated zeaxanthin was not mutagenic or clastogenic in a series of in vitro and in vivo tests for genotoxicity. A 52-week chronic oral study in Cynomolgus monkeys at doses of 0.2 and 20 mg/kg bw/day, mainly designed to assess accumulation and effects in primate eyes, showed no adverse effects. In a rat two-generation study, the NOAEL was 150 mg/kg bw/day. In 2012, this dosage was used by EFSA (NDA Panel), in association with a 200-fold safety factor, to propose an Acceptable Daily Intake equivalent to 53 mg/day for a 70 kg adult. The requested use level of 2 mg/day was ratified by the EU Commission.
PubMed: 26885380
DOI: 10.1155/2016/3690140 -
Frontiers in Microbiology 2023In Taiwan, the pesticides dimethomorph and imidacloprid are recommended for pest control in vineyards. Therefore, tank-mixing of these two pesticides is usually a...
In Taiwan, the pesticides dimethomorph and imidacloprid are recommended for pest control in vineyards. Therefore, tank-mixing of these two pesticides is usually a routine practice before application. This study analyzed the influence of vineyard soil microbial flora under the recommended and high dosages (100 times the recommended dosage) of dimethomorph and imidacloprid. Individual and combined applications of pesticides were also tested through batches of soil incubation experiments. Four treatments-control (C), dimethomorph (DT), imidacloprid (IM), and mixed application of dimethomorph and imidacloprid (ID)-were used in the experimental design. From the soil metabolism, no significant reaction was observed after 2 months in the recommended dosage group, regardless of whether the pesticides were being applied individually or combined. For the high dosage, imidacloprid showed a higher effect than the co-exposure treatments, showing a possible prolonged effect after its repetitive application. From PCoA analysis, pesticide treatments altered the soil ecology after 2 months, and the effect of imidacloprid can be explicitly observed at high dosages. At the phylum level, can indicate pesticide application around the recommended dosage. It was inhibited by ID on day 7 and was augmented by all pesticides on day 63. The effect of the recommended dosage of pesticide mixtures after 2 months of incubation was revealed in the minor families and , while the high dosage treatments affected both the core and the minor families. Our findings verified the changes in the composition of microbial communities upon pesticide application, which would affect carbon, nitrogen, sulfur, phosphorous cycles, and contaminant removal ability within the vineyard.
PubMed: 38029114
DOI: 10.3389/fmicb.2023.1249167 -
Musculoskeletal Science & Practice Apr 2024Evidence supporting type and dosage of joint mobilizations and rationale for selecting joint mobilization dosage for patients with rotator cuff-related shoulder pain are... (Review)
Review
BACKGROUND
Evidence supporting type and dosage of joint mobilizations and rationale for selecting joint mobilization dosage for patients with rotator cuff-related shoulder pain are limited.
OBJECTIVES
This scoping review aimed to systematically map the type and dosage of joint mobilizations used in previous trials for managing patients with rotator cuff-related shoulder pain; and summarize the rationale for adopting a specific joint mobilization dosage.
METHODS
We searched six databases. We included randomised controlled trials using joint mobilization for patients with rotator cuff-related shoulder pain. We extracted data regarding technique, treatment joint mobilization dosages and rationale for a specific dosage.
RESULTS
We included 32 studies. Most studies did not or partially report technique (67%) and within-session dosage (64%) of passive joint mobilization. Overall treatment was fully reported in 95% of studies. The dosage used for passive joint mobilization was heterogeneous (ranging from grade I to grade V). Most studies (85%) did not or partially report technique of mobilization with movement (MWM), whereas within-session and overall treatment dosages were fully reported in more than 85% of studies. Three sets of 10 repetitions were commonly used within-session dosage for MWM. We found very limited information on the rationale for selecting dosage of joint mobilization.
CONCLUSION
We found limited information about the dosage or the rationale for selecting joint mobilization, with a heterogeneous dosage being tested across trials. Our findings highlight the importance of detailed reporting for dosage and rationale for selecting a specific dosage of joint mobilization.
Topics: Humans; Rotator Cuff; Shoulder Pain; Physical Therapy Modalities; Rotator Cuff Injuries
PubMed: 38412572
DOI: 10.1016/j.msksp.2023.102903 -
Clinical and Experimental Pharmacology... Jul 2016Simvastatin is a lipid lowering drug whose beneficial role on bone metabolism was discovered in 1999. Several in vivo studies evaluated its role on osteoporosis and... (Review)
Review
Simvastatin is a lipid lowering drug whose beneficial role on bone metabolism was discovered in 1999. Several in vivo studies evaluated its role on osteoporosis and fracture healing, however, controversial results are seen in the literature. For this reason, Simvastatin has not been the focus of any clinical trials as yet. This systematic review clears the mechanisms of action of Simvastatin on bone metabolism and focuses on in vivo investigations that have evaluated its role on osteoporosis and fracture repair to find out (i) whether Simvastatin is effective on treatment of osteoporosis and fracture repair, and (ii) which of the many available protocols may have the ability to be translated in the clinical setting. Simvastatin induces osteoinduction by increasing osteoblast activity and differentiation and inhibiting their apoptosis. It also reduces osteoclastogenesis by decreasing both the number and activity of osteoclasts and their differentiation. Controversial results between the in vivo studies are mostly due to the differences in the route of administration, dose, dosage and carrier type. Local delivery of Simvastatin through controlled drug delivery systems with much lower doses and dosages than the systemic route seems to be the most valuable option in fracture healing. However, systemic delivery of Simvastatin with much higher doses and dosages than the clinical ones seems to be effective in managing osteoporosis. Simvastatin, in a particular range of doses and dosages, may be beneficial in managing osteoporosis and fracture injuries. This review showed that Simvastatin is effective in the treatment of osteoporosis and fracture healing.
Topics: Animals; Cell Differentiation; Fracture Healing; Fractures, Bone; Humans; Osteoclasts; Osteogenesis; Osteoporosis; Simvastatin
PubMed: 27061579
DOI: 10.1111/1440-1681.12577 -
Expert Opinion on Drug Metabolism &... Apr 2019Hypertension is an important risk factor for developing cardiovascular diseases. It is more prevalent in the elderly population. Recently updated American and European... (Review)
Review
Hypertension is an important risk factor for developing cardiovascular diseases. It is more prevalent in the elderly population. Recently updated American and European guidelines recommend treating every elderly patient with hypertension independent of age, starting with a low dose of antihypertensive drugs. However, little information is available on the optimal dosages of antihypertensive drugs to treat the elderly safely. Areas covered: Comorbidities, co-medication and frailty status can alter the clinical outcome of drug treatment and can cause adverse events in the elderly. Also, due to pharmacokinetic and pharmacodynamic changes the interpatient variability when using antihypertensive drugs is considerable. In this review, an overview is given on the extent to which the previously mentioned parameters are changed in elderly patients and what this means for the exposure to antihypertensive medication. Also, recommendations on the starting dose of the most frequently used antihypertensive drugs are given based on literature data. Expert opinion: We believe that recommendations on starting dosages followed by a stepwise increase of dosages will lead to improved blood pressure control and less adverse drug reactions in the elderly patient. This may improve adherence to antihypertensive therapy.
Topics: Age Factors; Aged; Antihypertensive Agents; Blood Pressure; Dose-Response Relationship, Drug; Frail Elderly; Frailty; Humans; Hypertension; Medication Adherence; Practice Guidelines as Topic; Prevalence; Risk Factors
PubMed: 30880496
DOI: 10.1080/17425255.2019.1588249