Strengthening pharmacotherapy research for COVID-19-induced pulmonary fibrosis

The global spread of severe acute respiratory syndrome coronavirus 2 has resulted in a significant number of individuals developing pulmonary fibrosis(PF),an irreversible lung injury.This condition can manifest within a short inter-val following the onset of pneumonia symptoms,sometimes even within a few days.While lung transplantation is a potentially lifesaving procedure,its limited availability,high costs,intricate surgeries,and risk of immunological rejection present significant drawbacks.The optimal timing of medication administration for coronavirus disease 2019(COVID-19)-induced PF remains controversial.Despite this,it is crucial to explore pharmacotherapy interventions,involving early and preventative treatment as well as pharmacotherapy options for advanced-stage PF.Additionally,studies have demonstrated disparities in anti-fibrotic treatment based on race and gender factors.Genetic mutations may also impact therapeutic efficacy.Enhancing research efforts on pharmacotherapy interventions,while considering relevant pharmacological factors and optimizing the timing and dosage of medication administration,will lead to enhanced,personalized,and fair treatment for individuals impacted by COVID-19-related PF.These measures are crucial in lessening the burden of the disease on healthcare systems and improving patients'quality of life.

Comparative Efficacy of Lifestyle Modifications versus Pharmacotherapy on Weight Loss and Metabolic Health Outcomes: A Comprehensive Review

Background: Obesity has become a serious global public health challenge, given that it leads to various adverse health outcomes that include cardiovascular illnesses, diabetes, and certain types of cancer. The World Health Organization (WHO) has estimated that, at the end of 2022, 1 out of every 8 individuals were obese, and that the global adult obesity rates have over doubled since 1990, even as the adolescent obesity rates have quadrupled. Thus, as of 2022, nearly 2.5 billion adults, aged 18 years and above, were overweight, with 890 million being obese. Obesity and overweight incidence rate has been gradually increasing over the years, presenting significant challenges to the healthcare systems throughout the globe. In this regard, the objective of this systematic review was to evaluate the effectiveness and safety of lifestyle modifications (diet and physical activity) and pharmacotherapy in promoting weight loss and improving metabolic health in overweight adults. Methodology: To attain the above stated study objective, a systematic evaluation of previous studies was carried out, particularly studies that assessed the effectiveness and safety of lifestyle modifications (diet and physical activity) and pharmacotherapy in promoting weight loss and improving metabolic health in overweight adults. The authors have used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) in the selection of eligible studies for inclusion in the study. Results: The findings indicate that lifestyle interventions resulted in 5% - 10% weight reduction and significant improvements in metabolic indicators, while pharmacotherapy (GLP-1 receptor agonists) achieved up to 15% weight reduction and considerable metabolic health benefits. Further, comparative studies show lifestyle modifications provide overall health benefits, while medication is necessary for non-responders. Conclusion: Individualized treatment strategies are crucial, and further research is needed on long-term consequences and combination therapies.

Pharmacotherapy in autism spectrum disorders,including promising older drugs warranting trials

Available pharmacotherapies for autism spectrum disorders(ASD)are reviewed based on clinical and research experience,highlighting some older drugs with emerging evidence.Several medications show efficacy in ASD,though controlled studies in ASD are largely lacking.Only risperidone and aripiprazole have Federal Drug Administration approval in the United States.Methylphenidate(MPH)studies showed lower efficacy and tolerability for attention deficit hyperactivity disorder(ADHD)than in the typically developing(TD)population;atomoxetine demonstrated lower efficacy but comparable tolerability to TD outcomes.Guanfacine improved hyperactivity in ASD comparably to TD.Dextroamphetamine promises greater efficacy than MPH in ASD.ADHD medications reduce impulsive aggression in youth,and may also be key for this in adults.Controlled trials of the selective serotonin reuptake inhibitors citalopram and fluoxetine demonstrated poor tolerability and lack of efficacy for repetitive behaviors.Trials of antiseizure medications in ASD remain inconclusive,however clinical trials may be warranted in severely disabled individuals showing bizarre behaviors.No identified drugs treat ASD core symptoms;oxytocin lacked efficacy.Amitriptyline and loxapine however,show promise.Loxapine at 5-10 mg daily resembled an atypical antipsychotic in positron emission tomography studies,but may be weight-sparing.Amitriptyline at approximately 1 mg/kg/day used cautiously,shows efficacy for sleep,anxiety,impulsivity and ADHD,repetitive behaviors,and enuresis.Both drugs have promising neurotrophic properties.

Tranexamic acid may be a useful pharmacotherapy for endoscopically resistant small bowel angiodysplasia

Small bowel angiodysplasia(SBAD)is reported to account for nearly 50%of cases of small bowel bleeding.When SBAD occurs frequently,it is difficult to treat all the angiodysplasias endoscopically,and gastrointestinal bleeding often recurs.Hormone therapy,somatostatin analogs,thalidomide and vascular endothelial growth factor(VEGF)-neutralizing antibodies have been reported to reduce gastrointestinal angiodysplasia(GIAD)bleeding.However,there is no strong evidence to recommend them.Also,there are no guidelines for their use.Hereditary hemorrhagic telangiectasia(HHT)is a hereditary disease caused by abnormalities in VEGF,resulting in multiple GIADs.A treatment guideline has been created for GIAD in HHT,and the use of tranexamic acid,an antifibrinolytic agent,is the first recommendation pharmacotherapy for GIAD with gastrointestinal bleeding that is difficult to treat endoscopically.It has been reported that fibrinolysis is accelerated in GIAD patients who are not HHT,similar to HHT patients.The use of tranexamic acid for gastric antral vascular ectasia in GIAD has been reported to be useful.However,there are very few reports of its use for SBAD.There are concerns with tranexamic acid use regarding the development of thrombosis/embolism,but there are few reports of such side effects.Future clinical trials including tranexamic acid for SBAD are desired.

Pharmacotherapy for the management of achalasia: Current status, challenges and future directions

This article reviews currently available pharmacological options available for the treatment of achalasia, with a special focus on the role of botulinum toxin(BT) injection due to its superior therapeutic effect and side effect profile. The discussion on BT includes the role of different BT serotypes, better pharmacological formulations, improved BT injection techniques, the use of sprouting inhibitors, designer recombinant BT formulations and alternative substances used in endoscopic injections. The large body of ongoing research into achalasia and BT may provide a stronger role for BT injection as a form of minimally invasive, cost effective and efficacious form of therapy for patients with achalasia. The article also explores current issues and future research avenues that may prove beneficial in improving the efficacy of pharmacological treatment approaches in patients with achalasia.

COVID-19 managed with early non-invasive ventilation and a bundle pharmacotherapy: A case report

BACKGROUND The coronavirus disease 2019(COVID-19)pandemic has become an immense public health burden,first in China and subsequently worldwide.Developing effective control measures for COVID-19,especially measures that can halt the worsening of severe cases to a critical status is of urgent importance.CASE SUMMARY A 52-year-old woman presented with a high fever(38.8°C),chills,dizziness,and weakness.Epidemiologically,she had not been to Wuhan where COVID-19 emerged and did not have a family history of a disease cluster.A blood test yielded a white blood cell count of 4.41×109/L(60.6±2.67%neutrophils and 30.4±1.34%lymphocytes).Chest imaging revealed bilateral ground-glass lung changes.Based on a positive nasopharyngeal swab nucleic acid test result and clinical characteristics,the patient was diagnosed with COVID-19.Following treatment with early non-invasive ventilation and a bundle pharmacotherapy,she recovered with a good outcome.CONCLUSION Early non-invasive ventilation with a bundle pharmacotherapy may be an effective treatment regimen for the broader population of patients with COVID-19.

Rehabilitation and pharmacotherapy of neuromyelitis optica spectrum disorder:A case report

BACKGROUND Neuromyelitis optica spectrum disorder(NMOSD)is a demyelinating autoimmune disease that affects the central nervous system.It typically manifests as optic neuritis or extensive longitudinal myelitis,with or without the presence of anti-aquaporin protein 4 autoantibodies(immunoglobulin G).CASE SUMMARY We report the case of a 45-year-old woman with a history of Sjogren's syndrome who was diagnosed with NMOSD accompanied by spinal cord injury and left calf intermuscular vein thrombosis.The patient received hormone shock and gamma globulin therapy in the acute phase and standard rehabilitation treatment during convalescence.Upon discharge,the patient was able to control urination and defecation,stand independently,and walk short distances with the aid of a walker.CONCLUSION This case suggests that pharmacotherapy and standard rehabilitation treatment can improve the prognosis of NMSOD patients.

Pharmacotherapy Cost of Controlled Ovarian Hyperstimulation of <i>in Vitro</i>Fertilization—A Real Life Study

The aim of the current study is to analyze the cost of controlled ovarian hyperstimulation (COH) of in vitro fertilization (IVF) during the period 2009-2013 in a specialized gynecology clinic. It is a prospective, observational study and bottom up cost analysis of the COH pharmacotherapy of IVF. The data was collected for all women admitted to the clinic, therapeutic COH protocols, prescribed medicines and doses, average length of therapy and its cost. Statistical analysis is applied towards the pharmacotherapy and cost data. On average 136 (SD 21.92) women were admitted varying from 105 to 179 for 10.7 (SD 1.47) days. 11% were on long (GnRH agonist containing) therapeutic COH protocol and all other on short (GnRH antagonist containing). Therapeutic protocols include Follitropin-α IU (103 women at average dose of 1171 IU (SD 314.16));Follitropin-β IU (299 women at average dose of 1634 IU (SD 423.5));Urofollitropin 75 IU amp (243 women at average dose of 21.3 IU (SD 7.37));urFSH + urLH 75IU:75IU/amp (354 women at average dose of 23.4 IU (SD 8.8));cetrorelix amp 0.25 mg prescribed at 264 women at average dose of 3.84 IU (SD 1.32);ganirelix amp 0.25 mg for 299 women at average dose of 4.01 mg (SD 1.32);Human chorion gonadotropin for 535 women at average dose of 6752.52 IU (SD 1216.23);Nafarelin mcg/ml for 8 women at dose of 17,700 mcg (SD 10,725);triptorelinacetat 0.1 mg amp - 63 women at doses of 5.5 (SD 3.25) mg at 14 women and average dose of 7.5 mg (SD 2.5);clomiphen citrate and letrozole for 15 women at average dose of 8 mg (SD 2.4). The average cost of COH pharmacotherapy is varying among the years with highest value of 1803.776 (SD - 624.89) BGN in 2009. Controlled ovarian hyperstimulation of in vitro fertilization is cost and resource consuming procedure in regards to pharmacotherapy. Age and reason of infertility influence significantly the cost.

Pharmacotherapy of urethral stricture

Urethral stricture is characterized by the chronic formation of fibrous tissue,leading to the narrowing of the urethral lumen.Despite the availability of various endoscopic treatments,the recurrence of urethral strictures remains a common challenge.Postsurgery pharmacotherapy targeting tissue fibrosis is a promising option for reducing recurrence rates.Although drugs cannot replace surgery,they can be used as adjuvant therapies to improve outcomes.In this regard,many drugs have been proposed based on the mechanisms underlying the pathophysiology of urethral stricture.Ongoing studies have obtained substantial progress in treating urethral strictures,highlighting the potential for improved drug effectiveness through appropriate clinical delivery methods.Therefore,this review summarizes the latest researches on the mechanisms related to the pathophysiology of urethral stricture and the drugs to provide a theoretical basis and new insights for the effective use and future advancements in drug therapy for urethral stricture.

Efficacy of Addiction Pharmacotherapy in Alcohol Use Disorder and Their Effects on Liver Health

Both alcohol-associated liver disease(ALD)and metabolic dysfunction-associated steatotic liver disease are leading contributors to chronic liver diseases.These conditions often coexist,exacerbating disease progression.Despite ALD being a leading cause of liver transplantation,many individuals with alcohol use disorder(AUD)do not receive treatment.In this review,we discussed the epidemiology of ALD in AUD,various treatment options for AUD,and their efficacy on liver health.Our critical analysis of current evidence underscores the need for integrated models involving multiple stakeholders to improve ALD management.

Pharmacological interventions targeting the microcirculation following traumatic spinal cord injury

Traumatic spinal cord injury is a devastating disorder chara cterized by sensory,motor,and autonomic dysfunction that seve rely compromises an individual's ability to perform activities of daily living.These adve rse outcomes are closely related to the complex mechanism of spinal cord injury,the limited regenerative capacity of central neurons,and the inhibitory environment fo rmed by traumatic injury.Disruption to the microcirculation is an important pathophysiological mechanism of spinal cord injury.A number of therapeutic agents have been shown to improve the injury environment,mitigate secondary damage,and/or promote regeneration and repair.Among them,the spinal cord microcirculation has become an important target for the treatment of spinal cord injury.Drug inte rventions targeting the microcirculation can improve the microenvironment and promote recovery following spinal cord injury.These drugs target the structure and function of the spinal cord microcirculation and are essential for maintaining the normal function of spinal neuro ns,axons,and glial cells.This review discusses the pathophysiological role of spinal cord microcirculation in spinal cord injury,including its structure and histopathological changes.Further,it summarizes the progress of drug therapies targeting the spinal cord mic rocirc ulation after spinal cord injury.

Pharmacological intervention for chronic phase of spinal cord injury

Spinal cord injury is an intractable traumatic injury. The most common hurdles faced during spinal cord injury are failure of axonal regrowth and reconnection to target sites. These also tend to be the most challenging issues in spinal cord injury. As spinal cord injury progresses to the chronic phase, lost motor and sensory functions are not recovered. Several reasons may be attributed to the failure of recovery from chronic spinal cord injury. These include factors that inhibit axonal growth such as activated astrocytes, chondroitin sulfate proteoglycan, myelin-associated proteins, inflammatory microglia, and fibroblasts that accumulate at lesion sites. Skeletal muscle atrophy due to denervation is another chronic and detrimental spinal cord injury–specific condition. Although several intervention strategies based on multiple outlooks have been attempted for treating spinal cord injury, few approaches have been successful. To treat chronic spinal cord injury, neural cells or tissue substitutes may need to be supplied in the cavity area to enable possible axonal growth. Additionally, stimulating axonal growth activity by extrinsic factors is extremely important and essential for maintaining the remaining host neurons and transplanted neurons. This review focuses on pharmacotherapeutic approaches using small compounds and proteins to enable axonal growth in chronic spinal cord injury. This review presents some of these candidates that have shown promising outcomes in basic research(in vivo animal studies) and clinical trials: AA-NgR(310)ecto-Fc(AXER-204), fasudil, phosphatase and tensin homolog protein antagonist peptide 4, chondroitinase ABC, intracellular sigma peptide,(-)-epigallocatechin gallate, matrine, acteoside, pyrvate kinase M2, diosgenin, granulocyte-colony stimulating factor, and fampridine-sustained release. Although the current situation suggests that drug-based therapies to recover function in chronic spinal cord injury are limited, potential candidates have been identified through basic research, and these candidates may be subjects of clinical studies in the future. Moreover, cocktail therapy comprising drugs with varied underlying mechanisms may be effective in treating the refractory status of chronic spinal cord injury.

Non-pharmacological interventions for diabetic peripheral neuropathy:Are we winning the battle?

Despite the advent of relatively reliable modalities of diagnosing diabetic peripheral neuropathy(DPN),such as nerve conduction studies,there is still a knowledge gap about the pathophysiology,and thus limited available in-terventions for symptom control and curtailing disease progression.The pharma-cologic aspect of management is mainly centred on pain control,however,there are several important aspects of DPN such as loss of vibration sense,pressure sense,and proprioception which are associated with risks to lower limb health,which pharmacotherapy does not address.Furthermore,published evidence suggests non-pharmacologic interventions such as glycaemic control through dietary modification and exercise need to be combined with other measures such as psychotherapy,to reach a desired,however modest effect.Acupuncture is emerging as an important treatment modality for several chronic medical conditions including neuropathic and other pain syndromes.In their study published in the World Journal of Diabetes on the potential of acupuncture to reduce DPN symptoms and enhance nerve conduction parameters,Hoerder et al have been able to demonstrate that acupuncture improves sensory function and that this effect is likely sustained two months after treatment cessation.Although previous studies also support these findings,larger multi-center randomized control trials including a sham-controlled arm accounting for a placebo effect are required.Overall,given the satisfactory safety profile and the positive results found in these studies,it is likely that acupuncture may become an important aspect of the repertoire of effective DPN management.

Rising tide: The global surge of type 2 diabetes in children and adolescents demands action now

Childhood-onset obesity has emerged as a major public healthcare challenge across the globe,fueled by an obesogenic environment and influenced by both genetic and epigenetic predispositions.This has led to an exponential rise in the incidence of type 2 diabetes mellitus in children and adolescents.The looming wave of diabetes-related complications in early adulthood is anticipated to strain the healthcare budgets in most countries.Unless there is a collective global effort to curb the devastation caused by the situation,the impact is poised to be pro-found.A multifaceted research effort,governmental legislation,and effective social action are crucial in attaining this goal.This article delves into the current epidemiological landscape,explores evidence concerning potential risks and consequences,delves into the pathobiology of childhood obesity,and discusses the latest evidence-based management strategies for diabesity.

Evaluating Pharmacological and Rehabilitation Strategies for Effective Management of Bipolar Disorder: A Comprehensive Clinical Study

Bipolar disorder presents significant challenges in clinical management, characterized by recurrent episodes of depression and mania often accompanied by impairment in functioning. This study investigates the efficacy of pharmacological interventions and rehabilitation strategies to improve patient outcomes and quality of life. Utilizing a randomized controlled trial with multiple treatment arms, participants will receive pharmacotherapy, polypharmacotherapy, rehabilitation interventions, or combination treatments. Outcome measures will be assessed using standardized scales, including the Hamilton Depression Scale, Yale-Brown Obsessive Compulsive Scale (Y-BOCS), and Mania Scale. Preliminary data suggest improvements in symptom severity and functional outcomes with combination treatments. This research aims to inform clinical practice, guide treatment decisions, and ultimately enhance the quality of care for individuals living with bipolar disorder. Findings will be disseminated through peer-reviewed journals and scientific conferences to advance knowledge in this field.

MAFLD vs.NAFLD:shared features and potential changes in epidemiology,pathophysiology,diagnosis,and pharmacotherapy

Nonalcoholic fatty liver disease(NAFLD)is the most common chronic liver disease worldwide,placing an increasing burden on human health.NAFLD is a complex multifactorial disease involving genetic,metabolic,and environmental factors.It is closely associated with metabolic syndrome,obesity,and type 2 diabetes,of which insulin resistance is the main pathophysiological mechanism.Over the past few decades,investigation of the pathogenesis,diagnosis,and treatments has revealed different aspects of NAFLD,challenging the accuracy of definition and therapeutic strategy for the clinical practice.Recently,experts reach a consensus that NAFLD does not reflect the current knowledge,and metabolic(dysfunction)associated fatty liver disease(MAFLD)is suggested as a more appropriate term.The new definition puts increased emphasis on the important role of metabolic dysfunction in it.Herein,the shared features and potential changes in epidemiology,pathophysiology,diagnosis,and pharmacotherapy of the newly defined MAFLD,as compared with the formerly defined NAFLD,are reviewed for updating our understanding.

Future Pharmacotherapy for Non-alcoholic Steatohepatitis (NASH): Review of Phase 2 and 3 Trials

Non-alcoholic steatohepatitis(NASH)results from inflammation and hepatocyte injury in the setting of hepatic steatosis.Non-alcoholic steatohepatitis increases the risk of progression to liver fibrosis and cirrhosis,and is the most rapidly growing etiology for liver failure and indication for liver transplantation in the USA.Weight loss and lifestyle modification remain the standard first-line treatment,as no USA Food and Drug Administration-approved pharmacotherapy currently exists.The past decade has seen an explosion of interest in drug development targeting pathologic pathways in non-alcoholic steatohepatitis,with numerous phase 2 and 3 trials currently in progress.Here,we concisely review the major targets and mechanisms of action by class,summarize results from com-pleted pivotal phase 2 studies,and provide a detailed outline of key active studies with trial data for drugs in development,including obeticholic acid,elafibranor,cenicriviroc and selonsertib.

Hepatic Antifibrotic Pharmacotherapy:Are We Approaching Success?

The incidence rate and mortality of liver fibrosis caused by various etiologies are high throughout the world. Liver fibrosis, the subsequent cirrhosis and other serious related complications threaten the health of patients and represent a serious medical burden;yet, there is still a lack of approved methods to prevent or reverse liver fibrosis. Therefore, effective hepatic antifibrotic drugs are urgently needed. The activation and proliferation of hepatic stellate cells are still the mechanisms of fibrosis that remain the focus of therapeutic research. In recent years, significant progress has been made in the development and applicability of antifibrosis drugs. In this review, we summarize the effectiveness and safety of available antifibrosis drugs utilizing different targets. In addition, some characteristics of antifibrosis drugs in phase II and III trials are introduced in detail.

Pharmacotherapy for Adult Patients with Acute Respiratory Distress Syndrome

Acute respiratory distress syndrome （ARDS） is one of the leading death reasons in Intensive Care Unit （ICU）. It is frustrating that there is no pharmacotherapy effective enough to reduce the mortality of ARDS. The most important treatment of ARDS nowadays is supportive treatment, including mechanical ventilation （MV）, fluid management, and sedation. Successful trials of ARDS treatments usually aim to avoid further lung injury of ARDS patients, such as low tidal volume of MV and conservative fluid strategy. These strategies can only maintain the mortality around 40%.

Successful management of seven cases of critical COVID-19 with early noninvasive-invasive sequential ventilation algorithm and bundle pharmacotherapy

We report the clinical and laboratory findings and successful management of seven patients with critical coronavirus disease 2019(COVID-19)requiring mechanical ventilation(MV).The patients were diagnosed based on epidemiological history,clinical manifestations,and nucleic acid testing.Upon diagnosis with COVID-19 of critical severity,the patients were admitted to the intensive care unit,where they received early noninvasive-invasive sequential ventilation,early prone positioning,and bundle pharmacotherapy regimen,which consists of antiviral,anti-inflammation,immune-enhancing,and complication-prophylaxis medicines.The patients presented fever(n=7,100%),dry cough(n=3,42.9%),weakness(n=2,28.6%),chest tightness(n=1,14.3%),and/or muscle pain(n=1,14.3%).All patients had normal or lower than normal white blood cell count/lymphocyte count,and chest computed tomography scans showed bilateral patchy shadows or ground glass opacity in the lungs.Nucleic acid testing confirmed COVID-19 in all seven patients.The median MV duration and intensive care unit stay were 9.9 days(interquartile range,6.5-14.6 days;range,5-17 days)and 12.9 days(interquartile range,9.7-17.6 days;range,7-19 days),respectively.All seven patients were extubated,weaned off MV,transferred to the common ward,and discharged as of the writing of this report.Thus,we concluded that good outcomes for patients with critical COVID-19 can be achieved with early noninvasive-invasive sequential ventilation and bundle pharmacotherapy.