PURPOSE.This article reviews the pharmacology, clinical utility, adverse effects, and abuse potential of kratom.
SUMMARY.The leaves of Mitragyna speciosa contain the biologically active alkaloids of ...kratom. Kratom exerts opioid and α-2 receptor agonistic effects as well as antiinflammatory and parasympathetic-impeding effects. There are no published human pharmacologic, pharmacokinetic, or drug interaction studies on kratom or mitragynine, making it virtually impossible to fully understand kratomʼs therapeutic potential and risks and the populations most likely to benefit or experience harm from its use. Kratom has been used to ameliorate opioid withdrawal symptoms but also induces withdrawal. Human pharmacologic, pharmacokinetic, and clinical data are of low quality, precluding any firm conclusions regarding safety and efficacy. Respiratory depression has not been commonly reported, but kratom does cause a host of adverse effects without clear guidance for how they should be treated. There are numerous assessments where people have been unable to stop using kratom therapy, and withdrawal signs and symptoms are problematic. Kratom does not appear in normal drug screens and, when taken with other substances of abuse, may not be recognized. Thirty-six deaths have been attributed to kratom, and the Food and Drug Administration issued a public health warning about the substance in November 2017.
CONCLUSION.Kratom exerts opioid and α-2 receptor agonistic effects as well as antiinflammatory and parasympathetic-impeding effects. Human pharmacologic, pharmacokinetic, and clinical data are of low quality, precluding any firm conclusions regarding safety and efficacy.
The Dietary Supplement Health and Education Act led to a flood of poor-quality dietary supplements. The Food and Drug Administration’s (FDA’s) jurisdiction is limited to removing products proven ...unsafe, rather than prospectively assessing them for quality manufacturing. With so many products available, there is very little FDA oversight until reports of patient harm occur. Microbial and heavy metal contamination, adulteration with synthetic drugs (including drugs banned from the United States), substituting herbs, and fraudulently specifying ingredients on the label have all occurred. Clinicians should collectively advocate for legislative change, only recommend products tested by outside laboratories for quality, and educate consumers about the risks of using unverified products.
We measure new estimates for the galaxy stellar mass function and star formation rates for samples of galaxies at z ∼ 4, 5, 6 and 7 using data in the CANDELS GOODS South field. The deep near-infrared ...observations allow us to construct the stellar mass function at z ≥ 6 directly for the first time. We estimate stellar masses for our sample by fitting the observed spectral energy distributions with synthetic stellar populations, including nebular line and continuum emission. The observed UV luminosity functions for the samples are consistent with previous observations; however, we find that the observed M
UV-M
* relation has a shallow slope more consistent with a constant mass-to-light ratio and a normalization which evolves with redshift. Our stellar mass functions have steep low-mass slopes (α ≈ −1.9), steeper than previously observed at these redshifts and closer to that of the UV luminosity function. Integrating our new mass functions, we find the observed stellar mass density evolves from
$\log _{10} \rho _{*} = 6.64^{+0.58}_{-0.89}$
at z ∼ 7 to 7.36 ± 0.06 M⊙ Mpc− 3 at z ∼ 4. Finally, combining the measured UV continuum slopes (β) with their rest-frame UV luminosities, we calculate dust-corrected star formation rates (SFR) for our sample. We find the specific SFR for a fixed stellar mass increases with redshift whilst the global SFR density falls rapidly over this period. Our new SFR density estimates are higher than previously observed at this redshift.
With its two degenerate valleys at the Fermi level, the band structure of graphene provides the opportunity to develop unconventional electronic applications. Herein, we show that electron and hole ...quasiparticles in graphene can be filtered according to which valley they occupy without the need to introduce confinement. The proposed valley filter is based on scattering off a recently observed line defect in graphene. Quantum transport calculations show that the line defect is semitransparent and that quasiparticles arriving at the line defect with a high angle of incidence are transmitted with a valley polarization near 100%.
N-nitrosodimethylamine (NDMA) is a hepatotoxic agent and carcinogen contaminant in commonly used medications such as valsartan, losartan, irbesartan, and ranitidine. NDMA can be produced during ...manufacture, introduced from contaminated ingredients procured elsewhere, or introduced from contaminated solvents and catalysts. The Food and Drug Administration has established a maximum dose of NDMA that is permissible per tablet and guidance for manufacturers. However, many unanswered questions about NDMA contamination need rigorous investigation.
Objective
To develop an evidence‐based guideline on contraception, assisted reproductive technologies (ART), fertility preservation with gonadotoxic therapy, use of menopausal hormone replacement ...therapy (HRT), pregnancy assessment and management, and medication use in patients with rheumatic and musculoskeletal disease (RMD).
Methods
We conducted a systematic review of evidence relating to contraception, ART, fertility preservation, HRT, pregnancy and lactation, and medication use in RMD populations, using Grading of Recommendations Assessment, Development and Evaluation methodology to rate the quality of evidence and a group consensus process to determine final recommendations and grade their strength (conditional or strong). Good practice statements were agreed upon when indirect evidence was sufficiently compelling that a formal vote was unnecessary.
Results
This American College of Rheumatology guideline provides 12 ungraded good practice statements and 131 graded recommendations for reproductive health care in RMD patients. These recommendations are intended to guide care for all patients with RMD, except where indicated as being specific for patients with systemic lupus erythematosus, those positive for antiphospholipid antibody, and/or those positive for anti‐Ro/SSA and/or anti‐La/SSB antibodies. Recommendations and good practice statements support several guiding principles: use of safe and effective contraception to prevent unplanned pregnancy, pre‐pregnancy counseling to encourage conception during periods of disease quiescence and while receiving pregnancy‐compatible medications, and ongoing physician‐patient discussion with obstetrics/gynecology collaboration for all reproductive health issues, given the overall low level of available evidence that relates specifically to RMD.
Conclusion
This guideline provides evidence‐based recommendations developed and reviewed by panels of experts and RMD patients. Many recommendations are conditional, reflecting a lack of data or low‐level data. We intend that this guideline be used to inform a shared decision‐making process between patients and their physicians on issues related to reproductive health that incorporates patients’ values, preferences, and comorbidities.
Efficacy and safety of treatments for hospitalized COVID-19 are uncertain. We systematically reviewed efficacy and safety of remdesivir for the treatment of COVID-19.
Studies evaluating remdesivir in ...adults with hospitalized COVID-19 were searched in several engines until August 21, 2020. Primary outcomes included all-cause mortality, clinical improvement or recovery, need for invasive ventilation, and serious adverse events (SAEs). Inverse variance random effects meta-analyses were performed.
We included four randomized controlled trials (RCTs) (n = 2296) two vs. placebo (n = 1299) and two comparing 5-day vs. 10-day regimens (n = 997), and two case series (n = 88). Studies used intravenous remdesivir 200mg the first day and 100mg for four or nine more days. One RCT (n = 236) was stopped early due to AEs; the other three RCTs reported outcomes between 11 and 15 days. Time to recovery was decreased by 4 days with remdesivir vs. placebo in one RCT (n = 1063), and by 0.8 days with 5-days vs. 10-days of therapy in another RCT (n = 397). Clinical improvement was better for 5-days regimen vs. standard of care in one RCT (n = 600). Remdesivir did not decrease all-cause mortality (RR 0.71, 95%CI 0.39 to 1.28, I2 = 43%) and need for invasive ventilation (RR 0.57, 95%CI 0.23 to 1.42, I2 = 60%) vs. placebo at 14 days but had fewer SAEs; 5-day decreased need for invasive ventilation and SAEs vs. 10-day in one RCT (n = 397). No differences in all-cause mortality or SAEs were seen among 5-day, 10-day and standard of care. There were some concerns of bias to high risk of bias in RCTs. Heterogeneity between studies could be due to different severities of disease, days of therapy before outcome determination, and how ordinal data was analyzed.
There is paucity of adequately powered and fully reported RCTs evaluating effects of remdesivir in hospitalized COVID-19 patients. Until stronger evidence emerges, we cannot conclude that remdesivir is efficacious for treating COVID-19.
Effect of statins on skeletal muscle function Parker, Beth A; Capizzi, Jeffrey A; Grimaldi, Adam S ...
Circulation (New York, N.Y.),
01/2013, Letnik:
127, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Many clinicians believe that statins cause muscle pain, but this has not been observed in clinical trials, and the effect of statins on muscle performance has not been carefully studied.
The Effect ...of Statins on Skeletal Muscle Function and Performance (STOMP) study assessed symptoms and measured creatine kinase, exercise capacity, and muscle strength before and after atorvastatin 80 mg or placebo was administered for 6 months to 420 healthy, statin-naive subjects. No individual creatine kinase value exceeded 10 times normal, but average creatine kinase increased 20.8±141.1 U/L (P<0.0001) with atorvastatin. There were no significant changes in several measures of muscle strength or exercise capacity with atorvastatin, but more atorvastatin than placebo subjects developed myalgia (19 versus 10; P=0.05). Myalgic subjects on atorvastatin or placebo had decreased muscle strength in 5 of 14 and 4 of 14 variables, respectively (P=0.69).
These results indicate that high-dose atorvastatin for 6 months does not decrease average muscle strength or exercise performance in healthy, previously untreated subjects. Nevertheless, this blinded, controlled trial confirms the undocumented impression that statins increase muscle complaints. Atorvastatin also increased average creatine kinase, suggesting that statins produce mild muscle injury even among asymptomatic subjects. This increase in creatine kinase should prompt studies examining the effects of more prolonged, high-dose statin treatment on muscular performance.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00609063.
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