Regular Dose Research Articles

In Reply to: An observational case-control study comparing the recovery profile in patients receiving additional dose of anticonvulsant vs. regular dose during supratentorial craniotomy

In Reply to: An observational case-control study comparing the recovery profile in patients receiving additional dose of anticonvulsant vs. regular dose during supratentorial craniotomy

Dietary natural methylxanthines and colorectal cancer: a systematic review and meta-analysis.

Some evidence suggests that caffeine, theophylline, and theobromine, as natural methylxanthines (MTXs), possess anti-cancer effects. We systematically reviewed the animal and human studies investigating the effect of (or association between) dietary natural MTXs on (and) colorectal cancer (CRC) and performed a meta-analysis of epidemiological studies. Relevant studies were identified by searching MEDLINE, Embase, Scopus, and Web of Knowledge through September 2020. The overall relative risk (RR) and confidence interval (CI) were determined using a random-effects model. Eight animal and eight epidemiological investigations met our inclusion criteria. Animal studies indicated detrimental effects of high levels of caffeine intake on the initiation and promotion of CRC, while showing beneficial or non-significant effects at lower doses. The meta-analysis of six epidemiological studies found no association between dietary caffeine intake and the risk of CRC (RR = 0.98 (95% CI = 0.88-1.10)). Subgroup analysis revealed a direct association between caffeine intake and risk of CRC only in the studies with a moderate risk of bias and a lack of adjustment for smoking. The results of the only epidemiological study investigating the association between the serum levels of MTXs and the risk of CRC showed an inverse association. In conclusion, some animal studies underlined the beneficial effects of caffeine, at regular doses consumed by humans, on CRC. However, current epidemiological evidence does not support an association between caffeine intake and the risk of CRC.

Single-shot thoracic epidural analgesia for neonates undergoing thoracotomy.

ABSTRACT Background and Aims: Post-thoracotomy pain in neonates have negative physiological consequences include impaired ventilation and vasoconstriction of both systemic and pulmonary vascular beds leading to compromised organ function. Methods: A randomized, single center, prospective, controlled study was conducted in El-Shatby university hospital, from august 2017 to September 2019 were 40 neonates, weighing 2.5–4 kg belonging to the ASA physical Grade II to IV, posted for a trachea-oesophagal fistula (TOF) repair via thoracotomy. After general anesthesia, in Group A, intra-operatively received fentanyl 2 µg/kg and paracetamol (10 mg/kg/6 h) intravenously and Group B (thoracic epidural single injection with 0.5 ml/kg of 0.25% of the L-Bupivacaine and 2 µg/kg of fentanyl), postoperatively paracetamol (10 mg/kg/6 h) intravenous (IV) or pain score >4. The primary objective was to compare the effect of the single-shot epidural blockade to intravenous fentanyl on post-thoracotomy pain control, the length of stay (LOS), supplemental analgesic requirements, and the incidence of adverse respiratory events were also measured. Results: Group A remained hemodynamically stable in the intraoperative period except for occasional bradycardia below 100 which was successfully managed with anticholinergic, and multiple and regular dosage of IV paracetamol was required to maintain adequate analgesia for about 6 h post-operative. While in Group B, good quality of analgesia for 8 h post-operative with a lesser dose of rescue opioids (fentanyl) required to maintain adequate analgesia which shortened length of hospital stay. Conclusion: Very efficient postoperative analgesia can be achieved via single-shot epidural blockade compared to intravenous fentanyl in neonatal post-thoracotomy pain.

A randomized cross-over study with objective quantification of the performance of an asymmetric triacetate and a polysulfone dialysis membrane using different anticoagulation strategies.

BackgroundDifferent strategies can be used to counteract coagulation of extracorporeal systems. Systemic anticoagulation is most widely used in routine clinical practice, but can be contraindicated in specific settings. The Solacea™ dialyser, containing the asymmetric triacetate membrane, claims improved biocompatibility, which should result in decreased tendency for coagulation. We quantified the performance of the Solacea™ versus the FX800CORDIAX dialyser regarding resistance to fibre blocking as assessed by micro-computed tomography (CT).MethodsThis cross-over study with four arms randomized consecutively 10 maintenance haemodialysis patients to a 4-h post-dilution haemodiafiltration session at midweek, using either Solacea™ 19 H or FX800CORDIAX, with either regular or half dose of anticoagulation (EC2017/1459-NCT03820401). Dialyser fibre blocking was visualized in the dialyser outlet potting using a 3D CT scanning technique on micrometre resolution. Extraction ratios of middle molecules [myoglobin, lambda and kappa free light chains (FLCs)] were determined.ResultsThe relative number of open fibres post-dialysis was lower in FX800CORDIAX versus Solacea™ dialyser, and this was irrespective of the anticoagulation dose used or the threshold for counting open fibres. Extraction ratios of FLCs were not different at regular anticoagulation between Solacea™ and FX800CORDIAX (21% ± 4% for kappa and 32% ± 8% for lambda with Solacea™ versus 23% ± 7% and 38% ± 6% for FX800CORDIAX), but were superior with the Solacea™ (34% ± 12% versus 22% ± 8% with FX800CORDIAX; P = 0.02) for myoglobin in case of halving anticoagulation dose. No clinically relevant albumin loss was detected.ConclusionsThe Solacea™ dialyser seems to be promising for use in conditions where systemic anticoagulation is contraindicated, as even under conditions of low systemic anticoagulation, virtually no signs of fibre blocking could be observed using the sensitive micro-CT scanning technique. This finding is in line with its presumed good performance in terms of biocompatibility.

Some aspects of application of the combination of formoterol and budesonide: what is changed?

The use of a combination of the inhaled glucocorticosteroid budesonide and beta2-selective long-acting adrenergic agonist formoterol is recommended for both bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD), however, indications for their use have changed significantly over the past 20 years. In BA, there was a transition from regular dosing to the tactics of a single drug – regularly and on demand, to the last recommendation – to apply as necessary at all stages of BA treatment. In COPD, this combination was a universal drug for the treatment of severe COPD with frequent exacerbations or in combination with BA, and now not only the severity and frequency of exacerbations, but also the level of blood eosinophilia is taken into account. The combination of budesonide / formoterol, which is important for practical health care, has become more accessible in recent years thanks to the advent of a domestic reconstituted drug with an original capsule powder inhaler. The drug went through comparative studies with the original drug both in clinical efficacy and in the properties of the delivered particles.

A network meta-analysis on comparative efficacy of statins focusing for prevention of contrast-induced acute kidney injury in chronic kidney disease patients undergoing percutaneus coronary intervention

Background: The use of interventional diagnostic and therapeutic procedures required intravascular iodinated contrast are performed in millions of patients worldwide and are steadily increasing the risks of contrast-induced acute kidney injury (CI-AKI). Statins are primarily used in cardiovascular medicine for their lipid-lowering effects but they possess remarkable pleiotropic effects such as improving endothelial function as well as decreasing oxidative stress and inflammation. A network meta-analysis was carried out to evaluate the effect of different statins in prevention of CI-AKI and also to investigate which type and dose of statins maybe the best choice specifically in CKD patients who have higher risk. Methods: We performed a pairwise and network meta analysis of 14 randomized studies (9847 patients) comparing a total of 6 different statins: rosuvastatin high dose, atorvastatin high dose, simvastatin high dose, rosuvastatin regular dose, atorvastatin regular dose, pravastatin regular dose versus each other and versus placebo in CKD patients undergoing PCI with iodinated contrast for prevention of CIAKI. Google Scholar, Pubmed, Science Direct databases were searched up to May 2019. The data were pooled using STATA, and R version statistics calculating odds ratios (ORs) with 95% confidence intervals. Results: Statin loading before contrast administration was associated with a significantly reduced risk of CI-AKI in patients with CKD undergoing cardiac catheterization (pooled OR= 0.51; P=0.0001). Regular dose pravastatin comprised the best effect size for a reduction in CIAKI risk (OR = 0.32, 95% CI 0.14-0.72, p=0.006). Regular dose pravastatin and high dose atorvastatin were ranked as the highest probability to be the best treatment (Pbest) with 44% and 31% respectively for effect on CIAKI prevention.Conclusion: Preloading with statins is associated with significantly reduced risk of CI-AKI in patients with CKD undergoing cardiac catheterization. Regular dose pravastatin and high dose atorvastatin have the highest probability to be the most effective prevention strategy.

Protocol, rationale and design of PEOPLE (Post ExpOsure Prophylaxis for LEprosy in the Comoros and Madagascar): a cluster randomized trial on effectiveness of different modalities of implementation of post-exposure prophylaxis of leprosy contacts

BackgroundLeprosy is an ancient infectious disease with a global annual incidence that has plateaued above 200,000 new cases since over a decade. New strategies are required to overcome this stalemate. Post-exposure prophylaxis (PEP) with a single dose of Rifampicin (SDR) has conditionally been recommended by the World Health Organization (WHO), based on a randomized-controlled-trial in Bangladesh. More evidence is required. The Post ExpOsure Prophylaxis for Leprosy (PEOPLE) trial will assess effectiveness of different modalities of PEP on the Comoros and Madagascar.MethodsPEOPLE is a cluster-randomized trial with villages selected on previous leprosy-incidence and randomly allocated to four arms. Four annual door-to-door surveys will be performed in all arms. All consenting permanent residents will be screened for leprosy. Leprosy patients will be treated according to international guidelines and eligible contacts will be provided with SDR-PEP.Arm-1 is the comparator in which no PEP will be provided. In arms 2, 3 and 4, SDR-PEP will be provided at double the regular dose (20 mg/kg) to eligible contacts aged two years and above. In arm 2 all household-members of incident leprosy patients are eligible. In arm 3 not only household-members but also neighbourhood contacts living within 100-m of an incident case are eligible. In arm 4 such neighbourhood contacts are only eligible if they test positive to anti-PGL-I, a serological marker. Incidence rate ratios calculated between the comparator arm 1 and each of the intervention arms will constitute the primary outcome.DiscussionDifferent trials on PEP have yielded varying results. The pivotal COLEP trial in Bangladesh showed a 57% reduction in incidence over a two-year period post-intervention without any rebound in the following years. A study in a high-incidence setting in Indonesia showed no effect of PEP provided to close contacts but a major effect of PEP provided as a blanket measure to an entire island population. High background incidence could be the reason of the lack of effect of PEP provided to individual contacts. The PEOPLE trial will assess effectiveness of PEP in a high incidence setting and will compare three different approaches, to identify who benefits most from PEP.Trial registrationClinicaltrials.Gov. NCT03662022. Initial Protocol Version 1.2, 27-Aug-2018.

A novel micro-ferrous dosing strategy for enhancing biological phosphorus removal from municipal wastewater

Ferrous salts have been widely used to enhance phosphorus removal in full-scale wastewater treatment plants, with an average dosage of 0.24–0.35 mM. However, such high dosage inevitably caused serious concerns on operation, potential biological toxicity and excessive sludge production. Thus, this study investigated the effect of micro-dosing of ferrous salt at the level of 0.02 mM on enhanced biological phosphorus removal (EBPR) in sequencing batch reactors. Results showed that micro-dosing of ferrous salt enhanced the overall performance, with average COD, TN and TP removal of more than 4.2%, 2.0% and 5.8%, respectively. In addition, the sequencing analysis further revealed that micro-ferrous dosing could significantly improve the diversity and richness of the microbial community (p < 0.05), whereas the regular dosing of ferrous salts (0.25 mM) negatively impacted on the EBPR performance. It was found that the abundances of phosphorus accumulating organisms (PAOs) in R2 (micro-dosing) were nearly 1.5-fold and 2-fold higher than those in R1 (control) and R3 (regular dosing). The contributions of biological and chemical pathways towards the observed phosphorus removal were also determined according to the phosphorus releasing rate. For micro-dosage and regular dosage of ferrous salts, phosphorus removal mainly relied on biological phosphorus removal and chemical phosphorus removal, respectively. It appears from this this study that the micro-ferrous dosing strategy is practically feasible and economically viable for enhanced phosphorus removal from municipal wastewater.

Wogonin ameliorate complete Freund's adjuvant induced rheumatoid arthritis via targeting NF-κB/MAPK signaling pathway.

Rheumatoid arthritis (RA) is a chronic and accelerated autoimmune illness with proliferative and damaging synovitis, resulting in joint death and cartilage and bone erosion. This study focused on the potential therapeutic effect of wogonin on complete Freund's adjuvant (CFA) induced RA in rats and the underlying mechanisms. Arthritis was experimentally caused in rats by subcutaneously injecting 0.1 mL of CFA into the subplantar area of the left hind paw under moderate anesthesia on day zero. The regular oral doses of indomethacin/wogonin began on day zero and proceeded after injection to day 35. Wogonin reduced arthritic score considerably, enhanced body weight, and reduced paw thickness. Wogonin also boosted red blood cell considerably along with hemoglobin and reduced white blood cell count and erythrocyte sedimentation rate. Wogonin substantially improved an altered level of oxidative stress markers, antioxidant proteins, and inflammatory cytokines in a dose-dependent way. Wogonin inhibited p38 phosphorylation triggered by CFA and p65 nuclear translocation.

Tolerogenic dendritic cell transfer ameliorates systemic lupus erythematosus in mice.

Current treatments for systemic autoimmune diseases partially improve the health of patients displaying low pharmacological efficacy and systemic immunosuppression. Here, the therapeutic potential of transferring tolerogenic dendritic cells (tolDCs) generated with heme-oxygenase inductor cobalt (III) protoporphyrin IX (CoPP), dexamethasone and rosiglitazone for the treatment of systemic autoimmunity was evaluated in two murine models of systemic lupus erythematosus (SLE), MRL-Faslpr and NZM2410 mice. Dendritic cells treated ex vivo with these drugs showed a stable tolerogenic profile after lipopolysaccharide stimulation. Regular doses of tolDCs were administered to anti-nuclear antibody-positive mice throughout 60-70days, andthe clinical score was evaluated. Long-term treatment with these tolDCs was well tolerated and effective to improve the clinical score on MRL-Faslpr lupus-prone mice. Additionally, decreased levels of anti-nuclear antibodies in NZM2410 mice were observed. Although tolDC treatment increased regulatory T cells, no significant reduction of renal damage or glomerulonephritis could be found. In conclusion, these results suggest that the transfer of histone-loaded tolDCs could improve only some SLE symptoms and reduced anti-nuclear antibodies. This is the first study to evaluate antigen-specific tolDC administration to treat SLE. Our report strengthens the clinical relevance of tolDC generation with CoPP, dexamethasone and rosiglitazone and the use of these modified cells as a therapy for systemic autoimmunity.

777 Effect of Ustekinumab Dose Escalation on Recapturing Clinical Response in Patients With Crohn's Disease

INTRODUCTION: Previous studies have shown that ustekinumab (UST) is an effective induction and maintenance therapy for patients with moderate to severe Crohn's Disease (CD). We sought to examine the real-world efficacy and safety of UST and whether UST dose escalation helps to recapture clinical response. METHODS: All patients who received the initial weight-based UST infusion between 4/2017 and 4/2018 were identified through a query of the EMR. Patients were followed from the time they initiated UST through 5/2019 or their date of UST discontinuation, whichever came first. Specifically, patients who lost response to UST 90 mg injection every 8 wk dosing and were then dose escalated to either every 4 or 6 wk dosing were identified. Recaptured clinical response to dose escalation was determined by reviewing clinical documentation and assessing for a reduction of ≥3 in the modified Harvey Bradshaw index (mHBI) after ≥8 wks following dose escalation. RESULTS: We included 27 patients with CD [median age 40 (range 24-61); 56% male; 96% tumor necrosis factor (TNF)-antagonist exposed]. Table 1 compares characteristics and outcomes of patients who underwent dose escalation vs. those who remained on regular dosing. Of the 11 dose escalated patients, 9 were switched to an every 4 wk regimen while the other 2 were switched to an every 6 wk regimen. Patients who underwent dose escalation were more likely to be a smoker (18% vs. 13%), have a history of perianal disease (73% vs. 38%), have previously tried a greater number of biologics (2.7 vs. 1.9), and be exposed to concomitant steroid (55% vs. 25%). Moreover, patients who underwent dose escalation were less likely to achieve steroid discontinuation within the first 8 wks compared to those who remained on regular dosing (9% vs. 50%). The only adverse event in the dose escalation group was one case of pneumonia. Table 2 further examines those patients that underwent dose escalation. The median mHBI improved from 9 to 7 following dose escalation. Recaptured clinical response occurred at a rate of 6/11 (55%) based on clinical documentation and 3/11 (27%) based on mHBI. CONCLUSION: UST dose escalation from 90 mg every 8 wks to either every 4 or 6 wk dosing allowed for recaptured clinical response in ∼25-50% of CD patients. There were minimal adverse events in patients who were dose escalated. Given its safety profile, dose escalation should be considered in patients with moderate to severe CD who have incomplete response to UST.

Detection of inhomogeneities in biological tissues using radio wave tomography

The paper shows the method for detecting and mapping inhomogeneities in biological tissues with using the radio-wave tomosynthesis. The method of radio-wave tomosynthesis allows calculating a three-dimensional distribution of permittivity in a studying space. The distribution gives the opportunity to determine tissue inhomogeneities, also their location and size. This method is suitable for dynamic observation of changes in education size due to harmlessness to humans. Unlike X-ray methods, for which regular doses of ionizing radiation contraindicated. Therefore, the development of non-invasive methods for the search for inhomogeneities in biological media based on radio-wave sounding is very relevant.

Self-Rated Effectiveness of Microdosing With Psychedelics for Mental and Physical Health Problems Among Microdosers.

Background: There is a growing interest in the use of psychedelic substances for health related purposes, including symptom relief for disorders like anxiety, depression, and pain. Although the focus of recent clinical trials has been on high doses of these substances, anecdotal evidence suggests that low (micro) doses are also effective, and may be more suitable for certain conditions. Nonetheless, empirical evidence regarding the efficacy of microdosing with psychedelics for symptomatic relief is lacking. The present study aimed to investigate, by means of an online questionnaire, the self-rated effectiveness (SRE) of microdosing with psychedelics (MDP) for mental and physiological disorders compared to the conventional prescribed treatment and to regular doses of psychedelics. Methods: An online questionnaire was launched on several websites and fora between March and July 2018. Respondents who had consented, were 18 years of age or older, had experience with microdosing and were diagnosed with at least one mental or physiological disorder by a medical doctor or therapist (N = 410; 7.2%) were included in the analyses. Odds ratio were calculated to compare the SRE of MDP with conventional treatment, and regular psychedelic doses for mental and physiological diagnoses for each of the three effectiveness questions (“Did it work,” “Symptom disappear,” “Quality of life improved”). Results: Odds ratio showed that SRE of MDP was significantly higher compared to that of conventional treatments for both mental and physiological diagnoses; and that these effects were specific for ADHD/ADD and anxiety disorders. In contrast, SRE of MDP was lower compared to that of higher, regular psychedelic doses for mental disorders such as anxiety and depression, while for physiological disorders no difference was shown. Conclusion: This study demonstrates that SRE of MDP to alleviate symptoms of a range of mental or physiological diagnoses is higher compared to conventionally offered treatment options, and lower than regular (‘full’) psychedelic doses. Future RCTs in patient populations should objectively assess the effectivity claims of psychedelics, and whether these are dose related, disorder specific, and superior to conventional treatments.

DIAGNOSIS DAN TATALAKSANA KOMPREHENSIF OSTEOARTRITIS

DIAGNOSIS DAN TATALAKSANA KOMPREHENSIF OSTEOARTRITIS

Postoperative Pain Responses in Dental Patients on Chronic Opioid Therapy

It is estimated that 5 to 8 million Americans use opioids daily for the management of chronic pain. Yet, opioid therapy for chronic pain is not an evidence-based intervention, and it is increasingly apparent that outcomes are poorer for patients taking opioids (pain severity, functionality, quality of life) (1). A theorized explanation for these poor outcomes is the phenomenon of opioid-induced hyperalgesia (OIH) (2), defined as increased sensitivity to pain related to chronic opioid use, and which may interfere with desired pain relief in the chronic pain patient. This study was designed to compare pain responses and analgesic need in a sample of dental patients on chronic opioid therapy vs. not on opioid therapy, the first study of its kind. A total of 40 adult dental surgical patients are being enrolled in the study, 20 of whom are on opioid therapy for chronic pain, all undergoing a dental surgical procedure with a similar expected trauma rating, and standardized postoperative non-opioid pain management. Those in the opioid group are taking a regular daily dose of opioids ≥ 50mg morphine equivalents/day for ≥ 3 months and those in the control group have not taken an opioid medication within 3 months. Exclusion criteria include active substance use disorder; severe psychiatric disorder; neurological or psychiatric illness that would affect pain responses; history of GI ulcers; NSAID allergy; poor liver or kidney function; or pregnancy. Prior to the surgical procedure, pain perception is measured using 2 standardized experimental pain assays (cold-pressor testing; quantitative sensory testing) to detect OIH. To determine how OIH may affect postoperative pain responses, patient-reported pain severity and documentation of all analgesic consumption for the first 72 hours are collected. If preoperative opioid use is found to result in increased postoperative pain severity, clinical implications may include anticipation of increased analgesic need or preoperative opioid taper.

Target lipidomics approach to reveal the resolution of inflammation induced by Chinese medicine combination in Liu-Shen-Wan against realgar overexposure to rats.

Liu-Shen-Wan (LSW) is one of the popular over-the-counter drugs in Asia, which contains realgar (As4S4), used for the treatment of upper respiratory tract inflammation and skin infections. However, the safety and potential risk of this arsenic remain unknown. The aim of this study was to determine total arsenic in tissue and investigate effects of regular dose and overdose LSW exposure on rat liver. We used a target lipidomics approach to quantify inflammatory eicosanoids and employed ICP-MS to determine total arsenic in tissue. The results showed that oral administration of 8 and 40 mg/kg LSW (1 and 5 fold human-equivalent dose) induced light changes of liver lipidomic profile in rats, which was associated with anti-inflammatory function of LSW. In our recent report, we observed that 41 and 134 mg/kg realgar (40 and 132 fold human-equivalent dose) stimulated rat liver inflammation through up-regulation of pro-inflammatory LOX-derived, CYP-derived HETEs and COX-derived PGs. However, we found that LSW in the form of drug combination, containing 41 and 134 mg/kg realger, could not stimulate these similar inflammatory responses in rats, although the liver total arsenic levels of the realger and LSW groups were same. The downregulation of pro-inflammatory response showed that the LSW containing realger is safer than realger alone administrated to rats. These results suggested that Chinese medicines combination could reduce realgar-derived arsenic toxicity in rats.

Combination of oxymatrine and diammonium glycyrrhizinate significantly mitigates mice allergic contact dermatitis induced by dinitrofluorobenzene.

This study investigated the safety and effect of oxymatrine (OMT) and/or diammonium glycyrrhizinate (DG) on allergic contact dermatitis (ACD) induced by 1-fluoro-2,4-dinitrofluorobenzene (DNFB) in ICR mice. Mice were topically smeared with vehicle (control) or DNFB on their ear and skin to induce ACD. The mice were randomized and injected with saline as the model, treated intraperitoneally with dexamethasone (DEX), 45 or 90 mg·kg−1 OMT and/or DG daily beginning one day post the first smearing for two weeks. The body weights, the severity of ear and skin inflammation, the levels of serum IgE, IL-4, and IFNγ, creatinine and urea as well as plasma sodium and potassium in individual mice were measured. In comparison with the control group, the model group did not change the body weights, but developed severe skin and ear inflammation with increased ear thickness, accompanied by many inflammatory infiltrates in the lesions and high levels of serum IgE, IL-4, and IFNγ. Combination of OMT and DG prevented the OMT- or DG-altered body weights in mice. While treatment with either OMT or DG moderately reduced the skin and ear inflammation, their thickness and inflammatory infiltrates, combination of OMT and DG further significantly increased their anti-inflammatory effects in mice. A similar pattern of inhibitory effect on the levels of serum IgE, IL-4, and IFNγ was observed in the different groups of mice. Combination of OMT and DG also prevented the OMT-, DG-, or DEX-altered plasma sodium or potassium levels in mice. Therefore, combination of OMT and DG significantly increased anti-inflammatory effects on ACD induced by DNFB in mice and attenuated DG- or OMT-related adverse effects. Impact statement Diammonium glycyrrhizinate (DG) and oxymatrine (OMT) have similar anti-inflammatory, anti-allergic, anti-tumor, immunomodulatory, and other pharmacological properties. Our previous study has shown that when DG and OMT are combined, DG can attenuate both high-dose (347.44 mg·kg−1) and regular-dose (90 mg·kg−1) OMT-induced mortality and adverse effects (such as body weight loss and hyponatremia). Furthermore, OMT can similarly attenuate the adverse effects (such as body weight gain, hypernatremia, and hypokalemia) induced by regular dose (90 mg·kg−1) of DG. Accordingly, we tested whether combination of OMT and DG would increase anti-inflammatory activities and reduce their adverse effect in a mouse model of allergic contact dermatitis (ACD) induced by 1-fluoro-2,4-dinitrofluorobenzene (DNFB). Our findings indicated that combination of OMT and DG significantly increased anti-inflammatory effects on ACD induced by DNFB in ICR mice and attenuated adverse effects of DG or OMT alone.

Evaluation of Different Dialyzers and the Impact of Predialysis Albumin Priming in Intermittent Hemodialysis With Reduced Anticoagulation

IntroductionSystemic anticoagulation is widely used in routine clinical hemodialysis, but can be contraindicated in specific settings. Anticoagulant-free treatment regimens are prone to failure even in chronic intermittent hemodialysis. We quantified fiber blocking in settings of reduced anticoagulation to assess performance of different dialyzers and the potential benefit of albumin priming.MethodsThis crossover study included 10 patients performing 4 hours of hemodialysis at midweek in 7 different settings: that is, using Solacea 19H and FX800, both with regular and half dose of anticoagulation, Evodial 1.3 without systemic anticoagulation, and FX800 (half dose) and Evodial (no anticoagulation) when primed with a human albumin solution. Dialyzer fiber blocking was visualized in the dialyzer outlet potting using a 3-dimensional computed tomography (CT) scanning technique on micrometer resolution.ResultsNo sessions had to be prematurely interrupted because of circuit clotting. The relative number of open fibers post dialysis was not influenced by the reduction of anticoagulation in the Solacea making this dialyzer superior in fiber patency in this setting above both the FX800 with reduced anticoagulation and the Evodial with no anticoagulation. Furthermore, no differences in relative number of open fibers were found in the FX800 and Evodial dialyzers with versus without albumin priming.ConclusionIn situations in which reduced anticoagulation is indicated, the asymmetric triacetate ATA Solacea dialyzer outperforms a dialyzer with a conventional polysulfone membrane (FX800) or with the heparin-coated polyacrylonitrile membrane (Evodial). The use of human albumin to prime the dialysis circuit did not improve dialyzer patency.

Iterative image reconstruction for sparse-view CT via total variation regularization and dictionary learning.

Recently, low-dose computed tomography (CT) has become highly desirable due to the increasing attention paid to the potential risks of excessive radiation of the regular dose CT. However, ensuring image quality while reducing the radiation dose in the low-dose CT imaging is a major challenge. Compared to classical filtered back-projection (FBP) algorithms, statistical iterative reconstruction (SIR) methods for modeling measurement statistics and imaging geometry can significantly reduce the radiation dose, while maintaining the image quality in a variety of CT applications. To facilitate low-dose CT imaging, we in this study proposed an improved statistical iterative reconstruction scheme based on the penalized weighted least squares (PWLS) standard combined with total variation (TV) minimization and sparse dictionary learning (DL), which is named as a method of PWLS-TV-DL. To evaluate this PWLS-TV-DL method, we performed experiments on digital phantoms and physical phantoms, and analyzed the results in terms of image quality and calculation. The results show that the proposed method is better than the comparison methods, which indicates the potential of applying this PWLS-TV-DL method to reconstruct low-dose CT images.

Pharmacy-based interdisciplinary intervention for patients with chronic heart failure: results of the PHARM-CHF randomized controlled trial.

Medication non-adherence is frequent and is associated with high morbidity and mortality in patients with chronic heart failure (CHF). We investigated whether an interdisciplinary intervention improves adherence in elderly CHF patients. The study population (mean age 74 years, 62% male, mean left ventricular ejection fraction 47%, 52% in New York Heart Association class III) consisted of 110 patients randomized into the pharmacy care and 127 into the usual care group. The median follow-up was 2.0years (interquartile range 1.2-2.7). The pharmacy care group received a medication review followed by regular dose dispensing and counselling. Control patients received usual care. The primary endpoint was medication adherence as proportion of days covered (PDC) within 365 days for three classes of heart failure medications (beta-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and mineralocorticoid receptor antagonists). The main secondary outcome was the proportion of adherent patients (PDC ≥ 80%). The primary safety endpoint was days lost due to unplanned cardiovascular hospitalizations (blindly adjudicated) or death. Pharmacy care compared with usual care resulted in an absolute increase in mean adherence to three heart failure medications for 365 days [adjusted difference 5.7%, 95% confidence interval (CI) 1.6-9.8, P=0.007]. The proportion of patients classified as adherent increased (odds ratio 2.9, 95% CI 1.4-5.9, P=0.005). Pharmacy care improved quality of life after 2years (adjusted difference in Minnesota Living with Heart Failure Questionnaire scores -7.8 points (-14.5 to -1.1; P=0.02), compared to usual care. Pharmacy care did not affect the safety endpoints of hospitalizations or deaths. Pharmacy care safely improved adherence to heart failure medications and quality of life.