Pharmacological Treatment for Atrial Fibrillation—Modalities in Equines and Companion Animals

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.

Comparison of Pharmacological Treatment Versus Acupuncture Treatment for Migraine Without Aura——Analysis of Socio-medical Parameters

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.

Postoperative ileus: Impact of pharmacological treatment,laparoscopic surgery and enhanced recovery pathways

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.

Treatment with neurohormonal inhibitors and prognostic outcome in pulmonary arterial hypertension with risk factors for left heart disease

BACKGROUND Despite major advances in pharmacologic treatment,patients with pulmonary arterial hypertension(PAH)still have a considerably reduced life expectancy.In this context,chronic hyperactivity of the neurohormonal axis has been shown to be detrimental in PAH,thus providing novel insights on the role of neurohormonal blockade as a potential therapeutic target.AIM To evaluate the application and prognostic effect of neurohormonal inhibitors(NEUi)in a single-center sample of patients with idiopathic PAH and risk factors for left heart disease.METHODS We analyzed data retrospectively collected from our register of right heart catheterizations performed consecutively from January 1,2005 to October 31,2018.Patients on beta-blocker,angiotensin-converting enzyme inhibitor,angiotensin receptor blocker or mineralocorticoid receptor antagonist at the time of right heart catheterization were classified as NEUi users and compared to NEUi nonrecipients.RESULTS Complete data were available for 57 PAH subjects:27 of those(47.4%)were taking at least one NEUi at the time of right heart catheterization and were compared with the remaining 36 NEUi non-recipients.NEUi users were older and had a higher cardiovascular risk profile compared to non-recipients.Additionally,NEUi non-users had a higher probability of dying during the course of follow-up than NEUi recipients(56.7%vs 25.9%,log-rank P=0.020).CONCLUSION The above data highlighted a subgroup of patients with PAH and comorbidities for left heart disease in which NEUi use has shown to be associated with improved survival.Future prospective studies are needed to identify the most appropriate therapeutic strategies in this subset population.

Non-alcoholic fatty liver disease: What has changed in the treatment since the beginning?

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.

Pharmacologic treatment of depression in patients with myocardial infarction

Depression is a common medical problem and is more prevalent among patients with coronary artery disease. Whether early detection and treatment of depression will enhance cardiovascular outcome is uncertain. Obviously, the safety and efficacy of the anti-depression drugs is an important link. This article reviews the patho-physiologic and behavioural links between depression and cardiovascular disease progression, the treatment of depression, and the potential benefits of anti-depressants in patients with coronary disease.

Combination strategies for pharmacologic treatment of nonalcoholic steatohepatitis

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.

Management of autoimmune hepatitis:Focus on pharmacologic treatments beyond corticosteroids

In autoimmune hepatitis, patients who are intolerant or with toxicity experience, non-responders, relapsers or refractory are challenging. Non-standard drugs are being tried to preemptively avoid corticosteroid-related side effects. Prognosis and quality of life of life rely on treatment optimization. Recently, emergence of powerful immunosuppressive agents, mainly from liver transplantation, challenged the supremacy of the corticosteroid regime and promise greater immunosuppression than conventional medications, offer site-specific actions and satisfactory patient tolerance. Successes in experimental models of related diseases have primed these molecular interventions. We performed a literature review on alternative treatments. Azatioprine intolerance is the principal indication for mycophenolate use butit can be used as a front-line therapy. Cyclosporine A and tacrolimus have been tested for non-responders or relapsers. Rituximab may be used as salvage therapy. Anti-tumor necrosis factor-alpha agents may be used for incomplete responses or non-responders. Methotrexate is possibly an alternative for induction of remission and maintenance in refractory patients. Cyclophosphamide has been included in the induction regimen with corticosteroids. Ursodeoxycholic acid action is mainly immunomodulatory. Non-standard treatments are coming slowly to the attention, but its use should be cautious performed by experienced centers.

Management of BPH then 2000 and now 2016-From BPH to BPO

The diagnosis and treatment of benign prostatic obstruction(BPO)is based on a number of well-known lower urinary tract symptoms(LUTS)feared by all ageing males with functional testes.The ascent of modern urology turned this disease from lethal into an annoying but treatable health problem in the previous century.We are able to relieve the great majority of patients from their bothersome symptoms to a respectable quality of life by medication or removal of the obstructive part of the enlarged prostate.We can be proud of some progress made in the new millennium to reach a correct diagnosis and subsequent choice of treatment aiming for quality of life and cost-efficiency for public health.Still it remains symptomatic treatment and we expect the new generation of urologists to close some gaps in our knowledge on the regulation of prostatic growth to focus on prevention and elimination of the disease in the foreseeable future.

Anti-obesity drugs currently used and new compounds in clinical development

Obesity is a chronic disease which requires treatment. As lifestyle interventions alone hardly ever result in long-term weight loss, pharmacotherapy is an impor-tant adjunct to lifestyle measures to improve the induc-tion and maintenance of weight loss. Owing to the lim-ited options currently available for the pharmacological treatment of obesity, it is imperative to develop new safe compounds. This study aims to review the current medications approved by European Medicines Agency and United States Food and Drug Administration （FDA） for the treatment of obesity, focusing essentially on their benefits and risks, as well as on the new drugs which are presently under clinical trials. Moreover, it lists the anti-obesity agents that have been recently withdrawn from the market. A revision of the scientifc literature was carried out, through a search on Pubmedfor papers published from January 2010 to January2013. Orlistat （Xenical？） is currently the only long-termpharmacotherapy for obesity available in the Europeanmarket, as rimonabant and sibutramine were with-drawn in 2008 and 2010, respectively, due to serious psychiatric and cardiovascular adverse effects. Lorca-serin （Belviq？） and the association of phentermine and topiramate （QsymiaTM） were recently approved by FDA. Orlistat suppresses appetite inhibiting gastrointestinal lipase, being its adverse effects mostly gastrointestinal. Lorcaserin activates 5-HT2C receptors, phentermine is a norepinephrine releasing drug, and topiramate is an anticonvulsivant drug with weight loss properties.

Freezing of gait in Parkinson’s disease: pathophysiology, risk factors and treatments

Background Freezing of gait(FOG)is a common,disabling symptom of Parkinson’s disease(PD),but the mechanisms and treatments of FOG remain great challenges for clinicians and researchers.The main focus of this review is to summarize the possible mechanisms underlying FOG,the risk factors for screening and predicting the onset of FOG,and the clinical trials involving various therapeutic strategies.In addition,the limitations and recommendations for future research design are also discussed.Main body In the mechanism section,we briefly introduced the physiological process of gait control and hypotheses about the mechanism of FOG.In the risk factor section,gait disorders,PIGD phenotype,lower striatal DAT uptake were found to be independent risk factors of FOG with consistent evidence.In the treatment section,we summarized the clinical trials of pharmacological and non-pharmacological treatments.Despite the limited effectiveness of current medications for FOG,especially levodopa resistant FOG,there were some drugs that showed promise such as istradefylline and rasagiline.Non-pharmacological treatments encompass invasive brain and spinal cord stimulation,noninvasive repetitive transcranial magnetic stimulation(rTMS)or transcranial direct current stimulation(tDCS)and vagus nerve stimulation(VNS),and physiotherapeutic approaches including cues and other training strategies.Several novel therapeutic strategies seem to be effective,such as rTMS over supplementary motor area(SMA),dual-site DBS,spinal cord stimulation(SCS)and VNS.Of physiotherapy,wearable cueing devices seem to be generally effective and promising.Conclusion FOG model hypotheses are helpful for better understanding and characterizing FOG and they provide clues for further research exploration.Several risk factors of FOG have been identified,but need combinatorial optimization for predicting FOG more precisely.Although firm conclusions cannot be drawn on therapeutic efficacy,the literature suggested that some therapeutic strategies showed promise.

2022 Chinese national clinical practice guideline on Helicobacter pylori eradication treatment

Background:Helicobacter pylori(H.pylori)infection is an infectious disease with a prevalence rate of up to 50%worldwide.It can cause indigestion,gastritis,peptic ulcer,and gastric cancer.H.pylori eradication treatment can effectively control disease progression and reduce the risk of the above conditions.However,the escalating trend of antibiotic resistance presents a global challenge for H.pylori eradication.We aim to provide guidance on pharmacological treatment of H.pylori infection.Methods:This clinical practice guideline is developed following the World Health Organization’s recommended process,adopting Grading of Recommendations Assessment,Development and Evaluation in assessing evidence quality,and utilizing Evidence to Decision framework to formulate clinical recommendations,minimizing bias and increasing transparency of the clinical practice guideline development process.We used the Reporting Items for practice Guidelines in HealThcare(RIGHT)statement and The Appraisal of Guidelines for Research and Evaluation Ⅱ(AGREE Ⅱ)as reporting and conduct guides to ensure the guideline’s completeness and transparency.Results:Though decreasing in developed countries,the prevalence of H.pylori remains high in developing countries,causing a major public health burden.This clinical practice guideline contains 12 recommendations concerning pharmacological treatment for H.pylori eradication.Among them,it is worth highlighting that bismuth preparations are inexpensive,safe,and effective,consequently making bismuth quadruple therapy a preferred choice for initial and rescue treatment.In empirical treatment,high-dose dual therapy is equally effective compared with bismuth quadruple therapy.Conclusions:The 12 recommendations in this clinical practice guideline are formed with consideration for stakeholders’values and preferences,resource use,feasibility,and acceptability.Recommendations are generalizable to resource limited settings with similar antibiotic resistance pattern as China,and lower middle-income countries facing comparable sociological and technical challenges.Registration:Guidelines International Network(GIN)website,https://guidelines.ebmportal.com/node/69996.

Pharmacological Therapeutics:Current Trends for Metabolic Dysfunction-associated Fatty Liver Disease(MAFLD)

Metabolic dysfunction-associated fatty liver disease(MAFLD)is a new term from nonalcoholic fatty liver disease(NAFLD)and is a positive diagnosis based on histopathology,imaging,or blood biomarkers.MAFLD is one of the common causes of liver dysfunction worldwide,likely due to the increase in metabolic syndrome as well as the high burden of disease and its relationship to other extrahepatic conditions.However,effective pharmacological therapeutic agents are still lacking;current management largely focuses on weight reduction and lifestyle modification.The purpose of this review was to summarize the updated evidence of novel therapies targeting different pathogenetic pathways in MAFLD.

Current strategies for the treatment of inborn errors of metabolism

Inborn errors of metabolism（IEMs） are a large group of inherited disorders characterized by disruption of metabolic pathways due to deficient enzymes, cofactors, or transporters. The rapid advances in the understanding of the molecular pathophysiology of many IEMs, have led to significant progress in the development of many new treatments. The institution and continued expansion of newborn screening provide the opportunity for early treatment, leading to reduced morbidity and mortality. This review provides an overview of the diverse therapeutic approaches and recent advances in the treatment of IEMs that focus on the basic principles of reducing substrate accumulation, replacing or enhancing absent or reduced enzyme or cofactor, and supplementing product deficiency. In addition, the challenges and obstacles of current treatment modalities and future treatment perspectives are reviewed and discussed.