Cardiac arrhythmias are probably more common in horses than in any other domestic animal species where poor performance and exercise intolerance is the most frequent clinical complaint. Atrial fibrillation is a type o...Cardiac arrhythmias are probably more common in horses than in any other domestic animal species where poor performance and exercise intolerance is the most frequent clinical complaint. Atrial fibrillation is a type of cardiac arrhythmia that appears as a common finding during medical examinations in humans, large breed dogs and horses. Clinical presentations are of a particular value in racehorses in high performing activities. Atrial fibrillation is characterized by an irregular heart rhythm, secondary to a primary disease or without any sign of comorbidity. The generation and maintenance of Atrial Fibrillation requires a substrate. Some breeds have a genetic predisposition to developing Atrial Fibrillation. Most cases of Atrial Fibrillation are of the paroxysmal type and self-regulate within a few hours to days without the need for treatment. The focus of this study is on the arrhythmic agents that are used for the treatment of Atrial Fibrillation, therefore other arrhythmic agents may not be included, or are included to demonstrate their effect on increasing, inhibiting or decreasing efficacy when used together with medications for the treatment of Atrial Fibrillation. The “working horse” for the pharmacological treatment of Atrial Fibrillation is Quinidine.展开更多
Background: Non-invasive facial treatments have the ability to rejuvenate the facial profile when specific pharmacologic agents and modalities are prescribed and used in combination taking into consideration each pati...Background: Non-invasive facial treatments have the ability to rejuvenate the facial profile when specific pharmacologic agents and modalities are prescribed and used in combination taking into consideration each patient’s unique skin type and condition. RATIONALE Epinova is a non-invasive skin treatment that combines the correct concentrations and combinations of topicals and modalities to elicit facial rejuvenation with no down-time or side effects. Purpose: This paper focuses on facial rejuvenation improvements combining the RATIONALE Essential Six skincare system (RATIONALE, Victoria, Australia) to protect and repair the skin with the RATIONALE Epinova facial treatment every 4-6 weeks—which uses non-invasive technologies and professional strength active ingredients to deliver visible changes to skin tone and texture. Methods: Subjects underwent a RATIONALE consultation, including taking a skin history and skin imaging, followed by a data analysis and diagnosis of skin condition and prescription of a customized RATIONALE treatement (Epinova), including appropriate pharmacologic agents and treatment with personalized photo/sono therapeutic devices. Results: Subjects reported increased skin hydration, tactile improvements, skin firmness and visible radiance following the RATIONALE Epinova treatment. Further investigations will be initiated to explore the potential for longer term improvements, including connenctive tissue deposition, reduction of erythema etc. Treatments should be performed every 4-6 weeks for patients under 40 and every 3-4 weeks for patients over 40, to support cell differentiation, migration and desquamation to achieve non-invasive facial rejuvenation. Conclusion: This study demonstrated that the synergy of pharmacologic, LED light therapy and ultrasonic technologies when prescribed and administered by a trained skin therapist, can lead to a visible improvement in the signs of facial ageing and photodamage, restoring the appearance of healthy, radiant skin. .展开更多
Background: Fractures of humeral shaft in adults are common injuries. Humeral shafts non-union either from late presentation after initial treatment by traditional bone setters or failed non-operative orthodox care is...Background: Fractures of humeral shaft in adults are common injuries. Humeral shafts non-union either from late presentation after initial treatment by traditional bone setters or failed non-operative orthodox care is a major problem in this part of the world. This non-union is a major treatment challenge with increased cost of care and morbidity in this part of the world. Humeral shaft non-union can be treated with locked intra-medullary nailing (LIMN) or dynamic compression plating (DCP). Study on comparison of these methods of fixation in this part of the world is scarce in literature search, hence the reason for this study. Objective: The objectives of this study are: (1) to compare early clinical outcome following fixation of humeral shaft fracture nonunion with DCP versus LIMN;(2) to compare the time of radiologic fracture union of DCP with LIMN;(3) to compare complications following fixation of humeral shaft fracture nonunion with DCP versus LIMN. Patients and Methods: This was a randomized control study done for 2 years in which fifty adult patients with humeral shaft non-union were recruited. The patients were grouped into 2 (P = DCP & N = LIMN). Forty five of the patients completed the follow up periods of the study and then analyzed. The P group had ORIF with DCP while the N group had ORIF with LIMN. Both groups had grafting with cancellous bones. Each patient was followed up for a period of 6 months at the time which radiographic union is expected. Any patient without clinical and/or radiographic evidence of union after six months of surgery was diagnosed as having recurrent non-union. The data generated was analyzed using SPSS Version 23. The results were presented in charts and tables. The paired t-test was used while considering p value Result: Forty five patients completed follow up. There was a male preponderance (4:1), right humerus predominated (3:2). Motor vehicular accidents were the commonest cause of the fractures (62%). Most non-union fractures occurred at the level of the middle 3<sup>rd</sup> of the humeral shaft (60%). Failed TBS treatment was the commonest indication for the osteosynthesis (71%). More patients had plating (53%) compared to 47% who had LIMN. Most patients (93.4%) had union between 3 to 6 months irrespective of fixation type with no significant statistical difference between the union rate of DCP and LIMN (p value 0.06) with similar functional outcome and complication rates irrespective of the type of fixation. Conclusion: This study showed that the success rates in term of fracture union, outcome functional grades and complication rates were not directly dependent on the types of the fixation: plating or locked intra-medullary nailing.展开更多
Almost all patients develop postoperative ileus (POI) after abdominal surgery.POI represents the single largest factor influencing length of stay (LOS) after bowel resection,and has great implications for patients and...Almost all patients develop postoperative ileus (POI) after abdominal surgery.POI represents the single largest factor influencing length of stay (LOS) after bowel resection,and has great implications for patients and resource utilization in health care.New methods to treat and decrease the length of POI are therefore of great importance.During the past decade,a substantial amount of research has been performed evaluating POI,and great progress has been made in our understanding and treatment of POI.Laparoscopic procedures,enhanced recovery pathways and pharmacologic treatment have been introduced.Each factor has substantially contributed to decreasing the length of POI and thus LOS after bowel resection.This editorial outlines resource utilization of POI,normal physiology of gut motility and pathogenesis of POI.Pharmacological treatment,fast track protocols and laparoscopic surgery can each have significant impact on pathways causing POI.The optimal integration of these treatment options continues to be assessed in prospective studies.展开更多
The increase in cardiovascular disease prevalence with ageing has been attributed to several age-related changes such as changes in the vascular wall elasticity, the coagulation and haernostatic system and endothelial...The increase in cardiovascular disease prevalence with ageing has been attributed to several age-related changes such as changes in the vascular wall elasticity, the coagulation and haernostatic system and endothelial dysfunction, among other causes. There is a 50% increased mortality risk per 10-year increase in age starting at 65 years old. Here, we aimed to discuss pharmacological treatment in acute coronary syndrome （ACS） without persistent ST segment elevation myocardial infarction in the elderly. The main aim of ACS treatment in elderly people is at preventing ischemia, myocardial damage and complications. A meta-analysis suggests that invasive revascularization therapy is probably most useful in older patients. Dual antiplatelet therapy is currently the standard of care post-ACS. Platelet P2Y12 inhibitors are among the most commonly used medications worldwide, due to their established benefits in the treatment and prevention of arterial throm- bosis. The main recommendation is to tailor antithrombotic treatment, considering body weight, renal function （Class I, level C） and careful evaluation of life expectancy, comorbidities, risk/benefit profile, quality of life and fxailty when invasive strategies are considered （Class IIa, level A） on top of the different recommendations given for a general non ST elevation ACS population. It is obvious that potent P2Y12 in- hibitors will continue to play an important role in pharmacological treatment for elderly ACS patients in the future.展开更多
Non-alcoholic steatohepatitis (NASH) is defined as hepatic steatosis, inflammation,and hepatocyte injury with or without fibrosis. It has emerged as thesecond leading indication for liver transplantation with a rising...Non-alcoholic steatohepatitis (NASH) is defined as hepatic steatosis, inflammation,and hepatocyte injury with or without fibrosis. It has emerged as thesecond leading indication for liver transplantation with a rising death rate in thenon-transplantable population. While there are many drugs in evaluation,currently no approved therapies are on the market for this condition. Given thisimportance, the Food and Drug Administration has provided formal guidanceregarding drug development for stopping or reversing NASH or NASH associatedfibrosis. The complex pathogenesis of NASH and its bidirectional relationshipwith metabolic syndrome has highlighted multiple drugs of interest thataddress metabolic, inflammatory, and fibrotic factors. A few promising liverspecific targets include farnesoid X receptor agonists and peroxisome proliferatoractivatedreceptor agonists. Previously studied drug classes such as glucagon-likepeptide-1 analogs or sodium/glucose transport protein 2 inhibitors have alsodemonstrated ability to improve hepatic steatosis. Here we discuss currentrationale, scientific work, and preliminary data in combining multiple drugs forthe purposes of a multimodal attack on the pathogenesis of NASH. We highlightmultiple Phase 2 and Phase 3 studies that demonstrate the potential to achieve aresponse rate higher than previously assessed monotherapies for this condition.Ultimately, one of these combination strategies may rise above in its safety andefficacy to become a part of a standardized approach to NASH.展开更多
This study was carried out in 120 patients affected by migraine without aura, treated in 4 public health centers and randomly divided into acupuncture group (AG) and conventional drug therapy group (CDTG).
Th... This study was carried out in 120 patients affected by migraine without aura, treated in 4 public health centers and randomly divided into acupuncture group (AG) and conventional drug therapy group (CDTG).
The evaluation of clinical results was made 6 and 12 months after the beginning of treatment and was worked out as well according to socio-medical parameters. Acupuncture was applied to the following points: Touwei (ST 8), Xuanlu (GB 5), Fengchi (GB 20), Dazhui (GV 14), Lieque (LU 7), treated with the reducing method. In AG, the figure scoring the entity and frequency of migraine attacks drops from 9,823 before treatment to 1,990 6 months after and 1,590 12 months after; while in CDTG, it drops from 8,405 before treatment to 3,927 6 months after and 3,084 12 months after. In AG, the total absence from work amounted to 1,120 working days/year, with a total cost (private + social costs) of 186,677,000 Italian liras. In CDTG, the absence from work amounted to 1,404 working days/year, with a total cost of 266,614,000 Italian liras.
If we consider that in Italy the patients affected by migraine without aura are around 800,000, and that acupuncture therapy is able to save 1,332,000 Italian liras on the total average cost supported for every single patient, the application of acupuncture in the treatment of migraine without aura would allow a saving of the health expenses in Italy of over 1,000 billion liras.展开更多
Osthole has various pharmacological effects such as anti-cancer,anti-inflammation,prevention and treatment of cardiovascular diseases and neuroprotection.This paper reviews the advances in the research of the pharmaco...Osthole has various pharmacological effects such as anti-cancer,anti-inflammation,prevention and treatment of cardiovascular diseases and neuroprotection.This paper reviews the advances in the research of the pharmacological effects and molecular mechanisms of osthole,in order to provide new ideas for further research and clinical application of osthole.展开更多
In recent years, cognitive difficulties associated with normal aging and dementia have been receiving increased attention from both public and scientific communities. With an increase in overall lifespan, promoting he...In recent years, cognitive difficulties associated with normal aging and dementia have been receiving increased attention from both public and scientific communities. With an increase in overall lifespan, promoting healthy cognition has become a priority and a necessity for minimizing and preventing individual and societal burdens associated with cognitive dysfunctions in the elderly. The general awareness concerning the efficacy of preventive(e.g., lifestyles) and palliative treatment strategies of cognitive impairments, related to either healthy or unhealthy trajectories in cognitive aging, is continuously rising. There are several therapeutic strategies which can be broadly classified as either pharmacological or non-pharmacological/psychosocial. In face of the modest evidence for success of pharmacological treatments, especially for dementia related impairments, psychosocial interventions are progressively considered as a complementary treatment. Despite the relative spread of psychosocial interventions in clinical settings, research in this area is rather scarce with evidence for success of these therapies remaining controversial. In this work we provide an evidence based perspective on cognitive intervention(s) for healthy aging, pre-dementia(mild cognitive impairment), and dementia populations. Current evidence and future directions for improving cognitive functions in the elderly are discussed as well.展开更多
The main treatment of patients with non-alcoholic fatty liver disease(NAFLD) is life style modification including weight reduction and dietary regimen.Majority of patients are safely treated with this management and p...The main treatment of patients with non-alcoholic fatty liver disease(NAFLD) is life style modification including weight reduction and dietary regimen.Majority of patients are safely treated with this management and pharmacologic interventions are not recommended. However, a subgroup of NAFLD patients with non-alcoholic steatohepatitis(NASH) who cannot achieve goals of life style modification may need pharmacological therapy. One major obstacle is measurement of histological outcome by liver biopsy which is an invasive method and is not recommended routinely in these patients. Several medications, mainly targeting baseline mechanism of NAFLD, have been investigated in clinical trials for treatment of NASH with promising results. At present, only pioglitazone acting as insulin sensitizing agent and vitamin E as an antioxidant have been recommended for treatment of NASH by international guidelines. Lipid lowering agents including statins and fibrates, pentoxifylline, angiotensin receptor blockers, ursodeoxycholic acid, probiotics and synbiotics are current agents with beneficial effects for treatment of NASH but have not been approved yet. Several emerging medications are in development for treatment of NASH. Obeticholic acid, liraglutide, elafibranor, cenicriviroc and aramchol have been tested in clinical trials or are completing trials. Here in, current and upcoming medications with promising results in clinical trial for treatment of NAFLD were reviewed.展开更多
Introduction: Sickle cell disease is a real public health problem in the world and particularly in Niger where the prevalence of the S gene is estimated at 25% and that of the homozygous forms at between 1% and 2%. Tr...Introduction: Sickle cell disease is a real public health problem in the world and particularly in Niger where the prevalence of the S gene is estimated at 25% and that of the homozygous forms at between 1% and 2%. Treatment combines quarterly follow-up of patients and management of complications. The objective of this study was to identify the potential explanatory factors of non-adherence to treatment in sickle cell patients followed at the national reference center for sickle cell disease in Niger. Methods: This is a cross-sectional study of sickle cell cases followed at the CNRD in Niger. The population consisted of all sickle cell patients followed in this center in 2021. The data collection techniques were individual interviews and documentary reviews. Non-adherence was assessed with the Girerd test. Descriptive statistical tests and simple and multiple logistic regression models were performed. Results: A total of 368 patients were enrolled. The median age is 7 years (4;10) and the sex ratio is 1.04. Ninety-eight (98) or 26.6% were compliant and 270 (73.4%) were non-compliant. In multivariate analysis, the factors independently and negatively associated with non-adherence to treatment were schooling (adjusted OR [95% CI], p-value), 0.17 [0.10 - 0.30];p Conclusion: The factors influencing treatment compliance identified in this study are all modifiable. To prevent the complications of sickle cell disease, we must fight against ignorance, make care services accessible and make care free.展开更多
Objective:To explore the efficacy of intermittent preventive treatment in pregnancy(IPTp)with sulfadoxine and pyrimethamine(SP)against sensitive parasites.Methods:A pharmacological model was used to investigate the ef...Objective:To explore the efficacy of intermittent preventive treatment in pregnancy(IPTp)with sulfadoxine and pyrimethamine(SP)against sensitive parasites.Methods:A pharmacological model was used to investigate the effectiveness of the previous recommended at least two-dose regimen,currently recommended three-dose regimen and 4,6,8-weekly regimens with specific focus on the impact of various nonadherence patterns in multiple transmission settings.Results:The effectiveness of the recommended three-dose regimen is high in all the transmission intensities,i.e.>99%,98%and 92%in low,moderate and high transmission intensities respectively.The simulated 4 and 6 weekly IPTp-SP regimens were able to prevent new infections with sensitive parasites in almost all women(>99%)regardless of transmission intensity.However,8 weekly interval dose schedules were found to have 71%and 86%protective efficacies in high and moderate transmission areas,respectively.It highlights that patients are particularly vulnerable to acquiring new infections if IPTp-SP doses are missed.Conclusions:The pharmacological model predicts that full adherence to the currently recommended three-dose regimen should provide almost complete protection from malaria infection in moderate and high transmission regions.However,it also highlights that patients are particularly vulnerable to acquiring new infections if IPTp doses are spaced too widely or if doses are missed.Adherence to the recommended IPTp-SP schedules is recommended.展开更多
Objective:To analyse the key compounds,targets and pathways of the treatment of non‑alcoholic fatty liver disease(NAFLD)by Jianwei Gexia Zhuyu Decoction based on network pharmacology,in order to explore the molecular ...Objective:To analyse the key compounds,targets and pathways of the treatment of non‑alcoholic fatty liver disease(NAFLD)by Jianwei Gexia Zhuyu Decoction based on network pharmacology,in order to explore the molecular mechanism of its therapeutic effects.Methods:The differential genes between sick and normal conditions were screened by GEO‑Datasets,and the heat map and volcano map were drawn.The active compounds in Jianwei Gexia Zhuyu Decoction were searched by TCMSP platform and Drugbank database.OB≥30%and DL≥0.18 were set as thresholds to screen potential active compounds and action targets.The molecular target maps of Jianwei Gexia Zhuyu Decoction and NAFLD differential genes were constructed,and the PPI network and network topology parameters were obtained by STRING database.The PPI network and network topology parameters were visually analyzed by Cytoscape,and the core regulatory genes were screened.At the same time,the SwissDock platform was used to dock the main active components with the target.The main pathways were determined by GO biological function enrichment analysis and KEGG metabolic pathway enrichment analysis by DAVID.Results:After screening,377 differential genes(127 up‑regulated genes and 250 down‑regulated genes),225 active compounds of Jianwei Gexia Zhuyu Decoction,308 corresponding targets were obtained;14 key targets were screened,corresponding to 168 compounds,and the key targets involved MYC,FOSL2,FOS,etc.The results of GO functional enrichment analysis showed that Jianwei Gexia Zhuyu Decoction mainly regulated the activity expression of DNA binding transcriptional activator and the specific transcription of RNA polymeraseⅡ;The results of molecular docking showed that the main active components quercetin and baicalein had good binding activity with VCAM1,HSPB1,MYC,JUN and so on;The results of KEGG enrichment analysis showed that it was mainly involved in IL‑17 signal pathway,Wnt receptor signal pathway,NF‑κB signal pathway,TNF signal pathway and AGE‑RAGE signal pathway in diabetic complications.Conclusion:Through the interaction of multi‑components and multi‑targets,Jianwei Gexia Zhuyu Decoction has achieved the goal of overall treatment of NAFLD from many ways.The application of network pharmacology provides a new research approach and scientific basis for further study on the mechanism of Jianwei Gexia Zhuyu Decoction in the treatment of NAFLD.展开更多
Posterior cortical atrophy(PCA) is a rare neurodegene-rative condition characterized by progressive visual-perceptual deficits. Although the neurocognitive profile of PCA is a growing and relatively well-established f...Posterior cortical atrophy(PCA) is a rare neurodegene-rative condition characterized by progressive visual-perceptual deficits. Although the neurocognitive profile of PCA is a growing and relatively well-established field, non-pharmacological care remains understudied and to be widely established in clinical practice. In the present work we review the available literature on non-pharmacological approaches for PCA, such as cognitive rehabilitation including individual cognitive exercises and compensatory techniques to improve autonomy in daily life, and psycho-education aiming to inform people with PCA about the nature of their visual deficits and limits of cognitive rehabilitation. The reviewed studies represented a total of 7 patients. There is a scarcity of the number of studies, and mostly consisting of case studies. Results suggest non-pharmacological intervention to be a potentially beneficial approach for the partial compensation of deficits, improvement of daily functionality and improvement of quality of life. Clinical implications and future directions are also highlighted for the advancement of the field, in order to clarify the possible role of non-pharmacological interventions, and its extent, in PCA.展开更多
Purpose: The purpose of this review is to systematically assess the potential effectiveness of targeted educational and other non-pharmacological interventions on diabetes control in populations of African descent in ...Purpose: The purpose of this review is to systematically assess the potential effectiveness of targeted educational and other non-pharmacological interventions on diabetes control in populations of African descent in developed countries. Such information can inform intervention strategies and highlight evidence-based approaches to deal with this significant problem in this population. Methods: A systematic review and a meta-analysis of random controlled trials and cohort studies evaluating the influence of education and other non-pharmacological interventions on HbA1Cconcentrations in patients of African descent with diabetes. A comprehensive search of PubMed, EMBASE, CINAHL, ZETOC, SIGLE databases was carried out. Results: Although nine studies (8 randomised controlled trials and 1 cohort study) met the inclusion criteria, relevant HbA1Cdata were available for 6 of the studies for the subsequent meta-analysis. Heterogeneity of meta-analysis was high (I2 = 92%), the random effects pooled standard mean difference favoured the intervention -0.66 (-1.15, -0.17), p = 0.009. After sensitivity analysis, I2 remained moderate to high at 69%. The random effects pooled standard mean difference continued to favour the intervention -0.48 (-0.81, -0.16), p = 0.009. Conclusion: There is evidence supporting the efficacy of educational and other non-pharmacological interventions in diabetes control in populations of African descent in English speaking developed countries. This conclusion is tempered by the significant heterogeneity of selected interventions and paucity of high quality research in the target population.展开更多
Objective:Based on network pharmacology and molecular docking to explore the mechanism of Wumei Pill in the treatment of non-erosive reflux disease(NERD).Method:We collected the active ingredients and targets of Wumei...Objective:Based on network pharmacology and molecular docking to explore the mechanism of Wumei Pill in the treatment of non-erosive reflux disease(NERD).Method:We collected the active ingredients and targets of Wumei Pill by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and collected NERD related targets through Genecards,PharmGKB,Drugbank,DisGeNET,OMIM,CTD and TTD databases.Intersection targets of Wumei Pill targets and NERD related targets were the potential targets of Wumei Pill in the treatment of NERD.We imported the intersection targets into the STRING database to obtain the PPI network,and obtained the hub targets.The network diagram of"Drugs-Potential active ingredients-Potential targets"was constructed by Cytoscape 3.7.2 software.We used R software to perform Gene Ontology function enrichment analysis(GO)and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis(KEGG)on hub targets,and then performed molecular docking verification.Results:There were 129 active ingredients and 213 drug targets of Wumei Pill of which 114 were the intersection targets.1587 GO enrichment items were identified(P<0.05),including 1,491 biological processes,11 cell components,and 85 molecular functions.143 KEGG pathways(P<0.05),mainly related to Kaposi sarcoma-associated herpesvirus infection,IL-17 signaling pathway,the TNF signaling pathway,MAPK signaling pathway.Results of molecular docking showed that the potential active ingredients in Wumei Pill had relatively stable binding activity to the key targets.Conclusion:Wumei pill for the treatment of non-erosive reflux disease are main active ingredients quercetin,kaempferol,beta sitosterol,Isocorypalmine,Stigmasterol,rutaecarpine,etc,the main targets is JUN,TP53,AKT1,may inhibit excessive inflammation,antioxidant therapy effect into full play.This provided a certain theoretical basis for clinical application.展开更多
AIM: To review evidence supporting pharmacological treatments for treatment-resistant depression(TRD) and to discuss them according to personal clinical experience.METHODS: Original studies, clinical trials, systemati...AIM: To review evidence supporting pharmacological treatments for treatment-resistant depression(TRD) and to discuss them according to personal clinical experience.METHODS: Original studies, clinical trials, systematic reviews, and meta-analyses addressing pharmacological treatment for TRD in adult patients published from 1990 to 2013 were identified by data base queries(Pub Med, Google Scholar e Quertle Searches) using terms: "treatment resistant depression", "treatment refractory depression", "partial response depression", "non responder depression", "optimization strategy", "switching strategy", "combination strategy", "augmentation strategy", selective serotonin reuptake inhibitors antidepressants(SSRI), tricyclic antidepressants(TCA), serotonin norepinephrine reuptake inhibitors antidepressants, mirtazapine, mianserine, bupropione, monoamine oxidase inhibitor antidepressant(MAOI), lithium, thyroid hormones, second generation antipsychotics(SGA), dopamine agonists, lamotrigine, psychostimulants, dextromethorphan, dextrorphan, ketamine, omega-3 fatty acids, S-adenosil-L-metionine, methylfolat, pindolol, sex steroids, glucocorticoid agents. Other citations of interest were further identified from references reported in the accessed articles. Selected publications were grouped by treatment strategy:(1) switching from an ineffective antidepressant(AD) to a new AD from a similar or different class;(2) combining the current AD regimen with a second AD from a different class; and(3) augmenting the current AD regimen with a second agent not thought to be an antidepressant itself.RESULTS: Switching from a TCA to another TCA provides only a modest advantage(response rate 9%-27%), while switching from a SSRI to another SSRI is more advantageous(response rate up to 75%). Evidence supports the usefulness of switching from SSRI to venlafaxine(5 positive trials out 6), TCA(2 positive trials out 3), and MAOI(2 positive trials out 2) but not from SSRI to bupropione, duloxetine and mirtazapine. Three reviews demonstrated that the benefits of intraand cross-class switch do not significantly differ. Data on combination strategy are controversial regarding TCA-SSRI combination(positive results in old studies, negative in more recent study) and bupropion-SSRI combination(three open series studies but not three controlled trails support the useful of this combination) and positive regard mirtazapine(or its analogue mianserine) combination with ADs of different classes. As regards the augmentation strategy, available evidences supported the efficacy of TCA augmentation with lithium salts and thyroid hormone(T3), but are conflicting regard the SSRI augmentation with these two drugs(1 positive trial out of 4 for lithium and 3 out of 5 for thyroid hormone). Double-blind controlled studies showed the efficacy of AD augmentation with aripiprazole(5 positive trials out 5), quetiapine(3 positive trials out 3) and, at less extent, of fluoxetine augmentation with olanzapine(3 positive trials out 6), so these drugs received the FDA indication for the acute treatment of TRD. Results on AD augmentation with risperidone are conflicting(2 short term positive trials, 1 short-term and 1 long-term negative trials). Case series and open-label trials showed that AD augmentation with pramipexole or ropinirole, two dopamine agonists, could be an effective treatment for TRD(response rate to pramipexole 48%-74%, to ropinirole 40%-44%) although one recent double-blind placebo-controlled study does not support the superiority of pramipexole over placebo. Evidences do not justify the use of psychostimulants, omega-3 fatty acids, S-adenosil-Lmetionine, methylfolate, pindolol, lamotrigine, and sex hormone as AD augmentation for TRD. Combining the available evidences with our experience we suggest treating non-responders to one SSRI bupropion or mirtazapine trial by switching to venlafaxine, and nonresponders to one venlafaxine trial by switching to a TCA or, if TCA are not tolerated, combining mirtazapine with SSRI or venlafaxine. In non-responders to two or more ADs(including at least one TCA if tolerated) current AD regimen could be augmented with lithium salts(mainly in patients with bipolar depression or suicidality), SGAs(mostly aripiprazole) or DA-agonists(mostly pramipexole). In patients with severe TRD, i.e., non-responders to combination and augmentation strategies as well as to electroconvulsive therapy if workable, we suggest to try a combination plus augmentation strategy.CONCLUSION: Our study identifies alternative effective treatment strategies for TRD. Further studies are needed to compare the efficacy of different strategies in more homogeneous subpopulations.展开更多
Non-alcoholic fatty liver disease(NAFLD) is an umbrella term to describe the entire spectrum of this common liver disease. In patients with NAFLD, especially those with non-alcoholic steatohepatitis(NASH), most often ...Non-alcoholic fatty liver disease(NAFLD) is an umbrella term to describe the entire spectrum of this common liver disease. In patients with NAFLD, especially those with non-alcoholic steatohepatitis(NASH), most often have one or more components of the metabolic syndrome, but this is not universal. Although most patients with NAFLD share many clinical features, only a subset of patients develops significant liver inflammation and progressive fibrosis. On the other hand, not all patients with NASH exhibit insulin resistance. NASH can be seen in patients who are lean and have no identifiable risk factors. Many clinical studies have tried numerous drugs and alternative medicine, however, investigators have failed to identify a safe and effective therapy for patients with NASH. As summarized, the heterogeneity of pathogenic pathways in individual patients with NASH may warrant the development of an individualized treatment according to the underlying pathogenic pathway. The differentiation of pathogenetic targets may require the development of diagnostic and prognostic biomarkers, and the identification of genetic susceptibilities. At present, evidence-based medicine provides only a few options including life-style modifications targeting weight loss, pioglitazone and vitamin E in non-diabetic patients with biopsy-proven NASH.展开更多
Drug absorption in patients with chronic pancreatitis might be affected by the pathophysiology of the disease.The exocrine pancreatic insufficiency is associated with changes in gastrointestinal intraluminal pH,motili...Drug absorption in patients with chronic pancreatitis might be affected by the pathophysiology of the disease.The exocrine pancreatic insufficiency is associated with changes in gastrointestinal intraluminal pH,motility disorder,bacterial overgrowth and changed pancreatic gland secretion.Together these factors can result in malabsorption and may also affect the efficacy of pharmacological intervention.The lifestyle of chronic pancreatitis patients may also contribute to gastrointestinal changes.Many patients limit their food intake because of the pain caused by eating and in some cases food intake is more or less substituted with alcohol,tobacco and coffee.Alcohol and drug interaction are known to influence the pharmacokinetics by altering either drug absorption or by affecting liver metabolism.Since patients suffering from chronic pancreatitis experience severe pain,opioids are often prescribed as pain treatment.Opioids have intrinsic effects on gastrointestinal motility and hence can modify the absorption of other drugs taken at the same time.Furthermore,the increased fluid absorption caused by opioids will decrease water available for drug dissolution and may hereby affect absorption of the drug.As stated above many factors can influence drug absorption and metabolism in patients with chronic pancreatitis.The factors may not have clinical relevance,but may explain inter-individual variations in responses to a given drug,in patients with chronic pancreatitis.展开更多
Intense abdominal pain is a prominent feature of chronic pancreatitis and its treatment remains a major clinical challenge.Basic studies of pancreatic nerves and experimental human pain research have provided evidence...Intense abdominal pain is a prominent feature of chronic pancreatitis and its treatment remains a major clinical challenge.Basic studies of pancreatic nerves and experimental human pain research have provided evidence that pain processing is abnormal in these patients and in many cases resembles that seen in neuropathic and chronic pain disorders.An important ultimate outcome of such aberrant pain processing is that once the disease has advanced and the pathophysiological processes are firmly established,the generation of pain can become self-perpetuating and independent of the initial peripheral nociceptive drive.Consequently,the management of pain by traditional methods based on nociceptive deafferentation(e.g.,surgery and visceral nerve blockade)becomes difficult and often ineffective.This novel and improved understanding of pain aetiology requires a paradigm shift in pain management of chronic pancreatitis.Modern mechanism based pain treatments taking into account altered pain processing are likely to increasingly replace invasive therapies targeting the nociceptive source,which should be reserved for special and carefully selected cases.In this review,we offer an overview of the current available pharmacological options for pain management in chronic pancreatitis.In addition,future options for pain management are discussed with special emphasis on personalized pain medicine and multidisciplinarity.展开更多
文摘Cardiac arrhythmias are probably more common in horses than in any other domestic animal species where poor performance and exercise intolerance is the most frequent clinical complaint. Atrial fibrillation is a type of cardiac arrhythmia that appears as a common finding during medical examinations in humans, large breed dogs and horses. Clinical presentations are of a particular value in racehorses in high performing activities. Atrial fibrillation is characterized by an irregular heart rhythm, secondary to a primary disease or without any sign of comorbidity. The generation and maintenance of Atrial Fibrillation requires a substrate. Some breeds have a genetic predisposition to developing Atrial Fibrillation. Most cases of Atrial Fibrillation are of the paroxysmal type and self-regulate within a few hours to days without the need for treatment. The focus of this study is on the arrhythmic agents that are used for the treatment of Atrial Fibrillation, therefore other arrhythmic agents may not be included, or are included to demonstrate their effect on increasing, inhibiting or decreasing efficacy when used together with medications for the treatment of Atrial Fibrillation. The “working horse” for the pharmacological treatment of Atrial Fibrillation is Quinidine.
文摘Background: Non-invasive facial treatments have the ability to rejuvenate the facial profile when specific pharmacologic agents and modalities are prescribed and used in combination taking into consideration each patient’s unique skin type and condition. RATIONALE Epinova is a non-invasive skin treatment that combines the correct concentrations and combinations of topicals and modalities to elicit facial rejuvenation with no down-time or side effects. Purpose: This paper focuses on facial rejuvenation improvements combining the RATIONALE Essential Six skincare system (RATIONALE, Victoria, Australia) to protect and repair the skin with the RATIONALE Epinova facial treatment every 4-6 weeks—which uses non-invasive technologies and professional strength active ingredients to deliver visible changes to skin tone and texture. Methods: Subjects underwent a RATIONALE consultation, including taking a skin history and skin imaging, followed by a data analysis and diagnosis of skin condition and prescription of a customized RATIONALE treatement (Epinova), including appropriate pharmacologic agents and treatment with personalized photo/sono therapeutic devices. Results: Subjects reported increased skin hydration, tactile improvements, skin firmness and visible radiance following the RATIONALE Epinova treatment. Further investigations will be initiated to explore the potential for longer term improvements, including connenctive tissue deposition, reduction of erythema etc. Treatments should be performed every 4-6 weeks for patients under 40 and every 3-4 weeks for patients over 40, to support cell differentiation, migration and desquamation to achieve non-invasive facial rejuvenation. Conclusion: This study demonstrated that the synergy of pharmacologic, LED light therapy and ultrasonic technologies when prescribed and administered by a trained skin therapist, can lead to a visible improvement in the signs of facial ageing and photodamage, restoring the appearance of healthy, radiant skin. .
文摘Background: Fractures of humeral shaft in adults are common injuries. Humeral shafts non-union either from late presentation after initial treatment by traditional bone setters or failed non-operative orthodox care is a major problem in this part of the world. This non-union is a major treatment challenge with increased cost of care and morbidity in this part of the world. Humeral shaft non-union can be treated with locked intra-medullary nailing (LIMN) or dynamic compression plating (DCP). Study on comparison of these methods of fixation in this part of the world is scarce in literature search, hence the reason for this study. Objective: The objectives of this study are: (1) to compare early clinical outcome following fixation of humeral shaft fracture nonunion with DCP versus LIMN;(2) to compare the time of radiologic fracture union of DCP with LIMN;(3) to compare complications following fixation of humeral shaft fracture nonunion with DCP versus LIMN. Patients and Methods: This was a randomized control study done for 2 years in which fifty adult patients with humeral shaft non-union were recruited. The patients were grouped into 2 (P = DCP & N = LIMN). Forty five of the patients completed the follow up periods of the study and then analyzed. The P group had ORIF with DCP while the N group had ORIF with LIMN. Both groups had grafting with cancellous bones. Each patient was followed up for a period of 6 months at the time which radiographic union is expected. Any patient without clinical and/or radiographic evidence of union after six months of surgery was diagnosed as having recurrent non-union. The data generated was analyzed using SPSS Version 23. The results were presented in charts and tables. The paired t-test was used while considering p value Result: Forty five patients completed follow up. There was a male preponderance (4:1), right humerus predominated (3:2). Motor vehicular accidents were the commonest cause of the fractures (62%). Most non-union fractures occurred at the level of the middle 3<sup>rd</sup> of the humeral shaft (60%). Failed TBS treatment was the commonest indication for the osteosynthesis (71%). More patients had plating (53%) compared to 47% who had LIMN. Most patients (93.4%) had union between 3 to 6 months irrespective of fixation type with no significant statistical difference between the union rate of DCP and LIMN (p value 0.06) with similar functional outcome and complication rates irrespective of the type of fixation. Conclusion: This study showed that the success rates in term of fracture union, outcome functional grades and complication rates were not directly dependent on the types of the fixation: plating or locked intra-medullary nailing.
基金Supported by North Norwegian Health Authorities Research Fund
文摘Almost all patients develop postoperative ileus (POI) after abdominal surgery.POI represents the single largest factor influencing length of stay (LOS) after bowel resection,and has great implications for patients and resource utilization in health care.New methods to treat and decrease the length of POI are therefore of great importance.During the past decade,a substantial amount of research has been performed evaluating POI,and great progress has been made in our understanding and treatment of POI.Laparoscopic procedures,enhanced recovery pathways and pharmacologic treatment have been introduced.Each factor has substantially contributed to decreasing the length of POI and thus LOS after bowel resection.This editorial outlines resource utilization of POI,normal physiology of gut motility and pathogenesis of POI.Pharmacological treatment,fast track protocols and laparoscopic surgery can each have significant impact on pathways causing POI.The optimal integration of these treatment options continues to be assessed in prospective studies.
文摘The increase in cardiovascular disease prevalence with ageing has been attributed to several age-related changes such as changes in the vascular wall elasticity, the coagulation and haernostatic system and endothelial dysfunction, among other causes. There is a 50% increased mortality risk per 10-year increase in age starting at 65 years old. Here, we aimed to discuss pharmacological treatment in acute coronary syndrome （ACS） without persistent ST segment elevation myocardial infarction in the elderly. The main aim of ACS treatment in elderly people is at preventing ischemia, myocardial damage and complications. A meta-analysis suggests that invasive revascularization therapy is probably most useful in older patients. Dual antiplatelet therapy is currently the standard of care post-ACS. Platelet P2Y12 inhibitors are among the most commonly used medications worldwide, due to their established benefits in the treatment and prevention of arterial throm- bosis. The main recommendation is to tailor antithrombotic treatment, considering body weight, renal function （Class I, level C） and careful evaluation of life expectancy, comorbidities, risk/benefit profile, quality of life and fxailty when invasive strategies are considered （Class IIa, level A） on top of the different recommendations given for a general non ST elevation ACS population. It is obvious that potent P2Y12 in- hibitors will continue to play an important role in pharmacological treatment for elderly ACS patients in the future.
文摘Non-alcoholic steatohepatitis (NASH) is defined as hepatic steatosis, inflammation,and hepatocyte injury with or without fibrosis. It has emerged as thesecond leading indication for liver transplantation with a rising death rate in thenon-transplantable population. While there are many drugs in evaluation,currently no approved therapies are on the market for this condition. Given thisimportance, the Food and Drug Administration has provided formal guidanceregarding drug development for stopping or reversing NASH or NASH associatedfibrosis. The complex pathogenesis of NASH and its bidirectional relationshipwith metabolic syndrome has highlighted multiple drugs of interest thataddress metabolic, inflammatory, and fibrotic factors. A few promising liverspecific targets include farnesoid X receptor agonists and peroxisome proliferatoractivatedreceptor agonists. Previously studied drug classes such as glucagon-likepeptide-1 analogs or sodium/glucose transport protein 2 inhibitors have alsodemonstrated ability to improve hepatic steatosis. Here we discuss currentrationale, scientific work, and preliminary data in combining multiple drugs forthe purposes of a multimodal attack on the pathogenesis of NASH. We highlightmultiple Phase 2 and Phase 3 studies that demonstrate the potential to achieve aresponse rate higher than previously assessed monotherapies for this condition.Ultimately, one of these combination strategies may rise above in its safety andefficacy to become a part of a standardized approach to NASH.
文摘 This study was carried out in 120 patients affected by migraine without aura, treated in 4 public health centers and randomly divided into acupuncture group (AG) and conventional drug therapy group (CDTG).
The evaluation of clinical results was made 6 and 12 months after the beginning of treatment and was worked out as well according to socio-medical parameters. Acupuncture was applied to the following points: Touwei (ST 8), Xuanlu (GB 5), Fengchi (GB 20), Dazhui (GV 14), Lieque (LU 7), treated with the reducing method. In AG, the figure scoring the entity and frequency of migraine attacks drops from 9,823 before treatment to 1,990 6 months after and 1,590 12 months after; while in CDTG, it drops from 8,405 before treatment to 3,927 6 months after and 3,084 12 months after. In AG, the total absence from work amounted to 1,120 working days/year, with a total cost (private + social costs) of 186,677,000 Italian liras. In CDTG, the absence from work amounted to 1,404 working days/year, with a total cost of 266,614,000 Italian liras.
If we consider that in Italy the patients affected by migraine without aura are around 800,000, and that acupuncture therapy is able to save 1,332,000 Italian liras on the total average cost supported for every single patient, the application of acupuncture in the treatment of migraine without aura would allow a saving of the health expenses in Italy of over 1,000 billion liras.
基金Supported by the Talent Training Program for the Reform and Development of Local Colleges and University of the Central Government(2020GSP16)Postgraduate Innovative Research Project of Heilongjiang Bayi Agricultural University(YJSCX2022-Y59)。
文摘Osthole has various pharmacological effects such as anti-cancer,anti-inflammation,prevention and treatment of cardiovascular diseases and neuroprotection.This paper reviews the advances in the research of the pharmacological effects and molecular mechanisms of osthole,in order to provide new ideas for further research and clinical application of osthole.
基金Supported by The Foundation for Science and Technology,FCT(SFRH/BD/64457/2009 and SFRH/BD/65213/2009,co-funded by FSE/POPH)project PIC/IC/83290/2007,which is supported by FEDER(POFC-COMPETE) and FCT
文摘In recent years, cognitive difficulties associated with normal aging and dementia have been receiving increased attention from both public and scientific communities. With an increase in overall lifespan, promoting healthy cognition has become a priority and a necessity for minimizing and preventing individual and societal burdens associated with cognitive dysfunctions in the elderly. The general awareness concerning the efficacy of preventive(e.g., lifestyles) and palliative treatment strategies of cognitive impairments, related to either healthy or unhealthy trajectories in cognitive aging, is continuously rising. There are several therapeutic strategies which can be broadly classified as either pharmacological or non-pharmacological/psychosocial. In face of the modest evidence for success of pharmacological treatments, especially for dementia related impairments, psychosocial interventions are progressively considered as a complementary treatment. Despite the relative spread of psychosocial interventions in clinical settings, research in this area is rather scarce with evidence for success of these therapies remaining controversial. In this work we provide an evidence based perspective on cognitive intervention(s) for healthy aging, pre-dementia(mild cognitive impairment), and dementia populations. Current evidence and future directions for improving cognitive functions in the elderly are discussed as well.
文摘The main treatment of patients with non-alcoholic fatty liver disease(NAFLD) is life style modification including weight reduction and dietary regimen.Majority of patients are safely treated with this management and pharmacologic interventions are not recommended. However, a subgroup of NAFLD patients with non-alcoholic steatohepatitis(NASH) who cannot achieve goals of life style modification may need pharmacological therapy. One major obstacle is measurement of histological outcome by liver biopsy which is an invasive method and is not recommended routinely in these patients. Several medications, mainly targeting baseline mechanism of NAFLD, have been investigated in clinical trials for treatment of NASH with promising results. At present, only pioglitazone acting as insulin sensitizing agent and vitamin E as an antioxidant have been recommended for treatment of NASH by international guidelines. Lipid lowering agents including statins and fibrates, pentoxifylline, angiotensin receptor blockers, ursodeoxycholic acid, probiotics and synbiotics are current agents with beneficial effects for treatment of NASH but have not been approved yet. Several emerging medications are in development for treatment of NASH. Obeticholic acid, liraglutide, elafibranor, cenicriviroc and aramchol have been tested in clinical trials or are completing trials. Here in, current and upcoming medications with promising results in clinical trial for treatment of NAFLD were reviewed.
文摘Introduction: Sickle cell disease is a real public health problem in the world and particularly in Niger where the prevalence of the S gene is estimated at 25% and that of the homozygous forms at between 1% and 2%. Treatment combines quarterly follow-up of patients and management of complications. The objective of this study was to identify the potential explanatory factors of non-adherence to treatment in sickle cell patients followed at the national reference center for sickle cell disease in Niger. Methods: This is a cross-sectional study of sickle cell cases followed at the CNRD in Niger. The population consisted of all sickle cell patients followed in this center in 2021. The data collection techniques were individual interviews and documentary reviews. Non-adherence was assessed with the Girerd test. Descriptive statistical tests and simple and multiple logistic regression models were performed. Results: A total of 368 patients were enrolled. The median age is 7 years (4;10) and the sex ratio is 1.04. Ninety-eight (98) or 26.6% were compliant and 270 (73.4%) were non-compliant. In multivariate analysis, the factors independently and negatively associated with non-adherence to treatment were schooling (adjusted OR [95% CI], p-value), 0.17 [0.10 - 0.30];p Conclusion: The factors influencing treatment compliance identified in this study are all modifiable. To prevent the complications of sickle cell disease, we must fight against ignorance, make care services accessible and make care free.
基金funded by the Bill and Melinda Gates Foundation(grant No.37999.01)the Medical Research Council(grant No.G110052)supported by the Liverpool School of Tropical Medicine
文摘Objective:To explore the efficacy of intermittent preventive treatment in pregnancy(IPTp)with sulfadoxine and pyrimethamine(SP)against sensitive parasites.Methods:A pharmacological model was used to investigate the effectiveness of the previous recommended at least two-dose regimen,currently recommended three-dose regimen and 4,6,8-weekly regimens with specific focus on the impact of various nonadherence patterns in multiple transmission settings.Results:The effectiveness of the recommended three-dose regimen is high in all the transmission intensities,i.e.>99%,98%and 92%in low,moderate and high transmission intensities respectively.The simulated 4 and 6 weekly IPTp-SP regimens were able to prevent new infections with sensitive parasites in almost all women(>99%)regardless of transmission intensity.However,8 weekly interval dose schedules were found to have 71%and 86%protective efficacies in high and moderate transmission areas,respectively.It highlights that patients are particularly vulnerable to acquiring new infections if IPTp-SP doses are missed.Conclusions:The pharmacological model predicts that full adherence to the currently recommended three-dose regimen should provide almost complete protection from malaria infection in moderate and high transmission regions.However,it also highlights that patients are particularly vulnerable to acquiring new infections if IPTp doses are spaced too widely or if doses are missed.Adherence to the recommended IPTp-SP schedules is recommended.
基金National Natural Science Foundation of China(NO.81603418)。
文摘Objective:To analyse the key compounds,targets and pathways of the treatment of non‑alcoholic fatty liver disease(NAFLD)by Jianwei Gexia Zhuyu Decoction based on network pharmacology,in order to explore the molecular mechanism of its therapeutic effects.Methods:The differential genes between sick and normal conditions were screened by GEO‑Datasets,and the heat map and volcano map were drawn.The active compounds in Jianwei Gexia Zhuyu Decoction were searched by TCMSP platform and Drugbank database.OB≥30%and DL≥0.18 were set as thresholds to screen potential active compounds and action targets.The molecular target maps of Jianwei Gexia Zhuyu Decoction and NAFLD differential genes were constructed,and the PPI network and network topology parameters were obtained by STRING database.The PPI network and network topology parameters were visually analyzed by Cytoscape,and the core regulatory genes were screened.At the same time,the SwissDock platform was used to dock the main active components with the target.The main pathways were determined by GO biological function enrichment analysis and KEGG metabolic pathway enrichment analysis by DAVID.Results:After screening,377 differential genes(127 up‑regulated genes and 250 down‑regulated genes),225 active compounds of Jianwei Gexia Zhuyu Decoction,308 corresponding targets were obtained;14 key targets were screened,corresponding to 168 compounds,and the key targets involved MYC,FOSL2,FOS,etc.The results of GO functional enrichment analysis showed that Jianwei Gexia Zhuyu Decoction mainly regulated the activity expression of DNA binding transcriptional activator and the specific transcription of RNA polymeraseⅡ;The results of molecular docking showed that the main active components quercetin and baicalein had good binding activity with VCAM1,HSPB1,MYC,JUN and so on;The results of KEGG enrichment analysis showed that it was mainly involved in IL‑17 signal pathway,Wnt receptor signal pathway,NF‑κB signal pathway,TNF signal pathway and AGE‑RAGE signal pathway in diabetic complications.Conclusion:Through the interaction of multi‑components and multi‑targets,Jianwei Gexia Zhuyu Decoction has achieved the goal of overall treatment of NAFLD from many ways.The application of network pharmacology provides a new research approach and scientific basis for further study on the mechanism of Jianwei Gexia Zhuyu Decoction in the treatment of NAFLD.
文摘Posterior cortical atrophy(PCA) is a rare neurodegene-rative condition characterized by progressive visual-perceptual deficits. Although the neurocognitive profile of PCA is a growing and relatively well-established field, non-pharmacological care remains understudied and to be widely established in clinical practice. In the present work we review the available literature on non-pharmacological approaches for PCA, such as cognitive rehabilitation including individual cognitive exercises and compensatory techniques to improve autonomy in daily life, and psycho-education aiming to inform people with PCA about the nature of their visual deficits and limits of cognitive rehabilitation. The reviewed studies represented a total of 7 patients. There is a scarcity of the number of studies, and mostly consisting of case studies. Results suggest non-pharmacological intervention to be a potentially beneficial approach for the partial compensation of deficits, improvement of daily functionality and improvement of quality of life. Clinical implications and future directions are also highlighted for the advancement of the field, in order to clarify the possible role of non-pharmacological interventions, and its extent, in PCA.
文摘Purpose: The purpose of this review is to systematically assess the potential effectiveness of targeted educational and other non-pharmacological interventions on diabetes control in populations of African descent in developed countries. Such information can inform intervention strategies and highlight evidence-based approaches to deal with this significant problem in this population. Methods: A systematic review and a meta-analysis of random controlled trials and cohort studies evaluating the influence of education and other non-pharmacological interventions on HbA1Cconcentrations in patients of African descent with diabetes. A comprehensive search of PubMed, EMBASE, CINAHL, ZETOC, SIGLE databases was carried out. Results: Although nine studies (8 randomised controlled trials and 1 cohort study) met the inclusion criteria, relevant HbA1Cdata were available for 6 of the studies for the subsequent meta-analysis. Heterogeneity of meta-analysis was high (I2 = 92%), the random effects pooled standard mean difference favoured the intervention -0.66 (-1.15, -0.17), p = 0.009. After sensitivity analysis, I2 remained moderate to high at 69%. The random effects pooled standard mean difference continued to favour the intervention -0.48 (-0.81, -0.16), p = 0.009. Conclusion: There is evidence supporting the efficacy of educational and other non-pharmacological interventions in diabetes control in populations of African descent in English speaking developed countries. This conclusion is tempered by the significant heterogeneity of selected interventions and paucity of high quality research in the target population.
文摘Objective:Based on network pharmacology and molecular docking to explore the mechanism of Wumei Pill in the treatment of non-erosive reflux disease(NERD).Method:We collected the active ingredients and targets of Wumei Pill by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and collected NERD related targets through Genecards,PharmGKB,Drugbank,DisGeNET,OMIM,CTD and TTD databases.Intersection targets of Wumei Pill targets and NERD related targets were the potential targets of Wumei Pill in the treatment of NERD.We imported the intersection targets into the STRING database to obtain the PPI network,and obtained the hub targets.The network diagram of"Drugs-Potential active ingredients-Potential targets"was constructed by Cytoscape 3.7.2 software.We used R software to perform Gene Ontology function enrichment analysis(GO)and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis(KEGG)on hub targets,and then performed molecular docking verification.Results:There were 129 active ingredients and 213 drug targets of Wumei Pill of which 114 were the intersection targets.1587 GO enrichment items were identified(P<0.05),including 1,491 biological processes,11 cell components,and 85 molecular functions.143 KEGG pathways(P<0.05),mainly related to Kaposi sarcoma-associated herpesvirus infection,IL-17 signaling pathway,the TNF signaling pathway,MAPK signaling pathway.Results of molecular docking showed that the potential active ingredients in Wumei Pill had relatively stable binding activity to the key targets.Conclusion:Wumei pill for the treatment of non-erosive reflux disease are main active ingredients quercetin,kaempferol,beta sitosterol,Isocorypalmine,Stigmasterol,rutaecarpine,etc,the main targets is JUN,TP53,AKT1,may inhibit excessive inflammation,antioxidant therapy effect into full play.This provided a certain theoretical basis for clinical application.
文摘AIM: To review evidence supporting pharmacological treatments for treatment-resistant depression(TRD) and to discuss them according to personal clinical experience.METHODS: Original studies, clinical trials, systematic reviews, and meta-analyses addressing pharmacological treatment for TRD in adult patients published from 1990 to 2013 were identified by data base queries(Pub Med, Google Scholar e Quertle Searches) using terms: "treatment resistant depression", "treatment refractory depression", "partial response depression", "non responder depression", "optimization strategy", "switching strategy", "combination strategy", "augmentation strategy", selective serotonin reuptake inhibitors antidepressants(SSRI), tricyclic antidepressants(TCA), serotonin norepinephrine reuptake inhibitors antidepressants, mirtazapine, mianserine, bupropione, monoamine oxidase inhibitor antidepressant(MAOI), lithium, thyroid hormones, second generation antipsychotics(SGA), dopamine agonists, lamotrigine, psychostimulants, dextromethorphan, dextrorphan, ketamine, omega-3 fatty acids, S-adenosil-L-metionine, methylfolat, pindolol, sex steroids, glucocorticoid agents. Other citations of interest were further identified from references reported in the accessed articles. Selected publications were grouped by treatment strategy:(1) switching from an ineffective antidepressant(AD) to a new AD from a similar or different class;(2) combining the current AD regimen with a second AD from a different class; and(3) augmenting the current AD regimen with a second agent not thought to be an antidepressant itself.RESULTS: Switching from a TCA to another TCA provides only a modest advantage(response rate 9%-27%), while switching from a SSRI to another SSRI is more advantageous(response rate up to 75%). Evidence supports the usefulness of switching from SSRI to venlafaxine(5 positive trials out 6), TCA(2 positive trials out 3), and MAOI(2 positive trials out 2) but not from SSRI to bupropione, duloxetine and mirtazapine. Three reviews demonstrated that the benefits of intraand cross-class switch do not significantly differ. Data on combination strategy are controversial regarding TCA-SSRI combination(positive results in old studies, negative in more recent study) and bupropion-SSRI combination(three open series studies but not three controlled trails support the useful of this combination) and positive regard mirtazapine(or its analogue mianserine) combination with ADs of different classes. As regards the augmentation strategy, available evidences supported the efficacy of TCA augmentation with lithium salts and thyroid hormone(T3), but are conflicting regard the SSRI augmentation with these two drugs(1 positive trial out of 4 for lithium and 3 out of 5 for thyroid hormone). Double-blind controlled studies showed the efficacy of AD augmentation with aripiprazole(5 positive trials out 5), quetiapine(3 positive trials out 3) and, at less extent, of fluoxetine augmentation with olanzapine(3 positive trials out 6), so these drugs received the FDA indication for the acute treatment of TRD. Results on AD augmentation with risperidone are conflicting(2 short term positive trials, 1 short-term and 1 long-term negative trials). Case series and open-label trials showed that AD augmentation with pramipexole or ropinirole, two dopamine agonists, could be an effective treatment for TRD(response rate to pramipexole 48%-74%, to ropinirole 40%-44%) although one recent double-blind placebo-controlled study does not support the superiority of pramipexole over placebo. Evidences do not justify the use of psychostimulants, omega-3 fatty acids, S-adenosil-Lmetionine, methylfolate, pindolol, lamotrigine, and sex hormone as AD augmentation for TRD. Combining the available evidences with our experience we suggest treating non-responders to one SSRI bupropion or mirtazapine trial by switching to venlafaxine, and nonresponders to one venlafaxine trial by switching to a TCA or, if TCA are not tolerated, combining mirtazapine with SSRI or venlafaxine. In non-responders to two or more ADs(including at least one TCA if tolerated) current AD regimen could be augmented with lithium salts(mainly in patients with bipolar depression or suicidality), SGAs(mostly aripiprazole) or DA-agonists(mostly pramipexole). In patients with severe TRD, i.e., non-responders to combination and augmentation strategies as well as to electroconvulsive therapy if workable, we suggest to try a combination plus augmentation strategy.CONCLUSION: Our study identifies alternative effective treatment strategies for TRD. Further studies are needed to compare the efficacy of different strategies in more homogeneous subpopulations.
文摘Non-alcoholic fatty liver disease(NAFLD) is an umbrella term to describe the entire spectrum of this common liver disease. In patients with NAFLD, especially those with non-alcoholic steatohepatitis(NASH), most often have one or more components of the metabolic syndrome, but this is not universal. Although most patients with NAFLD share many clinical features, only a subset of patients develops significant liver inflammation and progressive fibrosis. On the other hand, not all patients with NASH exhibit insulin resistance. NASH can be seen in patients who are lean and have no identifiable risk factors. Many clinical studies have tried numerous drugs and alternative medicine, however, investigators have failed to identify a safe and effective therapy for patients with NASH. As summarized, the heterogeneity of pathogenic pathways in individual patients with NASH may warrant the development of an individualized treatment according to the underlying pathogenic pathway. The differentiation of pathogenetic targets may require the development of diagnostic and prognostic biomarkers, and the identification of genetic susceptibilities. At present, evidence-based medicine provides only a few options including life-style modifications targeting weight loss, pioglitazone and vitamin E in non-diabetic patients with biopsy-proven NASH.
基金Supported by The Danish Council for Strategic Research
文摘Drug absorption in patients with chronic pancreatitis might be affected by the pathophysiology of the disease.The exocrine pancreatic insufficiency is associated with changes in gastrointestinal intraluminal pH,motility disorder,bacterial overgrowth and changed pancreatic gland secretion.Together these factors can result in malabsorption and may also affect the efficacy of pharmacological intervention.The lifestyle of chronic pancreatitis patients may also contribute to gastrointestinal changes.Many patients limit their food intake because of the pain caused by eating and in some cases food intake is more or less substituted with alcohol,tobacco and coffee.Alcohol and drug interaction are known to influence the pharmacokinetics by altering either drug absorption or by affecting liver metabolism.Since patients suffering from chronic pancreatitis experience severe pain,opioids are often prescribed as pain treatment.Opioids have intrinsic effects on gastrointestinal motility and hence can modify the absorption of other drugs taken at the same time.Furthermore,the increased fluid absorption caused by opioids will decrease water available for drug dissolution and may hereby affect absorption of the drug.As stated above many factors can influence drug absorption and metabolism in patients with chronic pancreatitis.The factors may not have clinical relevance,but may explain inter-individual variations in responses to a given drug,in patients with chronic pancreatitis.
基金Supported by Karen Elise Jensen`s Foundation and Danish Council for Strategic research,The Danish Agency for Science,Technology and Innovation
文摘Intense abdominal pain is a prominent feature of chronic pancreatitis and its treatment remains a major clinical challenge.Basic studies of pancreatic nerves and experimental human pain research have provided evidence that pain processing is abnormal in these patients and in many cases resembles that seen in neuropathic and chronic pain disorders.An important ultimate outcome of such aberrant pain processing is that once the disease has advanced and the pathophysiological processes are firmly established,the generation of pain can become self-perpetuating and independent of the initial peripheral nociceptive drive.Consequently,the management of pain by traditional methods based on nociceptive deafferentation(e.g.,surgery and visceral nerve blockade)becomes difficult and often ineffective.This novel and improved understanding of pain aetiology requires a paradigm shift in pain management of chronic pancreatitis.Modern mechanism based pain treatments taking into account altered pain processing are likely to increasingly replace invasive therapies targeting the nociceptive source,which should be reserved for special and carefully selected cases.In this review,we offer an overview of the current available pharmacological options for pain management in chronic pancreatitis.In addition,future options for pain management are discussed with special emphasis on personalized pain medicine and multidisciplinarity.
