Efficacy Of Pharmacotherapy Research Articles

Navigating agitation in neurodevelopmental disorders: A comparative study of pharmacotherapies via network meta-analysis in children and adults with autism spectrum disorder or intellectual disabilities.

Individuals with autism spectrum disorder (ASD) and intellectual disability often experience persistent challenges related to aggressive behaviour and agitation, highlighting the critical need for evidence-based pharmacological interventions among other strategies. Despite previous network meta-analyses (NMAs), the rapidly evolving landscape of treatment options necessitates ongoing and updated assessments. To evaluate the efficacy and tolerability of various pharmacotherapies in managing agitation in children and adults with ASD or intellectual disabilities (ID). Employing a systematic review and network meta-analysis methodology, we conducted an exhaustive search across multiple databases for double-blind, randomized controlled trials focusing on pharmacotherapies targeting agitation in these neurodevelopmental disorders. Adhering to Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines, our assessment of study quality utilized the Cochrane Risk of Bias Tool to ensure methodological rigour and accuracy in data synthesis. Primary outcomes encompassed measures of reduced agitation, as indicated by treatment response on standardized agitation scales, alongside dropout rates, providing a comprehensive overview of treatment efficacy and tolerability. Our analysis included data from 38 eligible trials, involving 2503 participants across both pediatric and adult populations. Key pharmacological interventions, such as arbaclofen, risperidone plus buspirone, omega-3 fatty acids, risperidone plus palmitoylethanolamide, aripiprazole and risperidone, demonstrated significant efficacy in reducing agitation compared to placebo. Importantly, these treatments were generally well-tolerated, with no significant increase in all-cause dropouts compared to placebo, highlighting their suitability for clinical use in managing agitation in individuals with ASD or ID. This study underscores the efficacy and tolerability of several pharmacotherapies in managing agitation among children and adults with ASD or ID. Our findings provide robust evidence that specific treatments, such as arbaclofen, risperidone plus buspirone and omega-3 fatty acids, are both effective and well-tolerated, offering valuable therapeutic options for clinicians. The study emphasizes the need for ongoing research to ensure that treatment strategies remain aligned with the evolving clinical landscape, ultimately improving patient outcomes in this challenging population.

Tracking the journey: Gastrointestinal transit and intraluminal pH dynamics in aging populations using wireless motility capsule.

Gastrointestinal (GI) changes may alter drug absorption, potentially impacting both efficacy and safety of oral pharmacotherapy. However, the GI physiology is rarely studied in the aging population. This study aimed to explore GI transit time and pH in geriatric inpatients and older adults, and compare these findings with those from young volunteers METHODS: A prospective study was performed in geriatric inpatients and community-dwelling adults aged ≥ 75 years. GI transit and intraluminal pH were assessed by using a wireless motility capsule system. Participants' data were pooled with those from a previous study in healthy young volunteers (n = 11). Multivariable linear regression models were developed to identify explanatory variables for GI transit time and pH value. We recruited 30 subjects (median age 80 [interquartile range (IQR) = 77-83] years). When compared to young volunteers (median age 21 [20-33]) years), geriatric inpatients (N = 8) exhibited prolonged gastric emptying times (median = 0.63 h [IQR = 0.32-0.86 h] vs median = 2.98 h [IQR = 1.50-20.35 h], p < 0.01). Community-dwelling older adults (N = 22) did not demonstrate delayed gastric emptying (median = 0.42 h [IQR = 0.36-0.53 h]; p = 0.85. Proton pump inhibitors (PPI) use was associated with increased gastric pH (median pH = 3.75 [IQR = 1.69-4.96] vs. non-PPI median pH = 1.28[IQR = 1.01-1.70]; p < 0.01) in the pooled analysis. The total older cohort had significantly lower small intestine pH compared to young group (median pH = 6.8 vs. 7.2; p < 0.01). Older age did not necessarily alter GI physiology with respect to gastric emptying time and luminal pH values. Only geriatric inpatients exhibited delayed gastric emptying of the motility capsule as compared to young volunteers, while community-dwelling older adults did not. Prevalent PPI use in the aging population led to higher gastric pH levels, with substantial intersubject variability.

Study protocol for a randomized controlled trial evaluating the effectiveness of a mother-child intervention model of neurogenic tremor as an add-on to treatment for emotional disorders in adolescents

BackgroundAdolescents exhibit a high prevalence of mental health disorders, with more than half of all cases emerging before the age of 14 years. Since the advent of the COVID-19 pandemic, there has been a marked upsurge in anxiety and depression among adolescents across several nations. Emotional disorders often lead to severe outcomes, including school absenteeism, self-harm, and suicidal tendencies. The suboptimal efficacy of pharmacotherapy, compounded by limited availability and substantial costs associated with individual psychotherapy, underscores the critical need for identifying simple yet efficacious psychotherapeutic interventions suitable for both individual and group settings. Tension and Trauma Release Exercise (TRE) is a mind-body therapeutic approach that efficiently alleviates symptoms of anxiety and depression. This randomized controlled trial (RCT) aims to evaluate the effectiveness of a mother-child intervention model using TRE in enhancing the clinical management of adolescent patients diagnosed with emotional disorders.Methods This study recruits 140 dyads of adolescents with emotional disorders and their mothers, randomly assigned to intervention or control groups. The intervention arm combines eight weeks of standard pharmacotherapy with an eight-week TRE group therapy, assessing at baseline, post-8-week treatment, and three-month follow-up. Initially, controls receive eight weeks of standard medication with parallel assessments, later transitioning to the same TRE intervention while maintaining continuous evaluation. The study further examines the influence of maternal emotional health on adolescent treatment response and investigates associated neurophysiological and psychological mechanisms.DiscussionThis research endeavors to identify a straightforward and potent body-oriented psychological intervention that could improve the clinical outcomes for adolescent patients with emotional disorders. Such findings would carry profound implications not only for the healthy development of teenagers but also for potentially mitigating the burden on families, educational institutions, and society as a whole.Trial registrationChiCTR2100044553, Registered March 24, 2021.

Efficacy and Safety of Amiodarone and Propranolol in Pediatric Cardiology for Arrhythmia After Cardiac Surgery: A Retrospective Design Study.

Objectives The study evaluated the efficacy of antiarrhythmic pharmacotherapies in managing tachyarrhythmia episodes in pediatric patients with congenital heart diseases post-tricuspid valve repair, assessing reductions in haemodynamic parameters and symptomatic variables, and observing side effects. Methods From January 2020 to January 2024, this study reviewed data from 300 patients, aged up to 18 years, who experienced arrhythmia following cardiac surgery and received treatment with amiodarone, propranolol, or both. The information included demographic and anthropometric measures, haemodynamic parameters, and antiarrhythmic drugs used to treat arrhythmias before and after tricuspid valve repair. The study employed two validated symptomatic assessment scales: the four "A" symptomatic (4ASX) score and the New York Heart Association (NYHA) classification I-IV. We categorised the outcomes into two groups: the unresponsive cohort (Cohort I) and the responsive cohort (Cohort II). The study determined the antiarrhythmic efficacy by observing that the responsiveness group exhibited higher distribution rates in the lower heart rate category and higher decrementing rates in the tracked haemodynamics categories. The negative occurrence of at least one composited side effect of interest identified the safety significance profile for these three adopted antiarrhythmic interventions. The study adopted the threshold of 0.05 as the level of statistical significance. Results This study found that 32.33% exhibited clinical unresponsiveness to antiarrhythmic agents, while 67.67% achieved desired responsiveness. 38% used amiodarone as the choice antiarrhythmic medication, while 32.3% used propranolol. The study found significant distribution rates concerning heart rates, with 56.2% of patients with a heart rate of <100 bpm being responsive, compared to 38.1% in the unresponsive cohort. Symptomatic improvement was noted after transcatheter atrial septal defect closure in the 300 patients undergoing this procedure to address complications related to tricuspid regurgitation. Most of the adopted haemodynamic indices showed statistical significance decrementing rates in the responsiveness cohort compared to the unresponsiveness cohort. Conclusion Using antiarrhythmic pharmacotherapies during tricuspid valve repair had statistically significant responsiveness statuses against procedural arrhythmia, positive outcomes in symptomatic and haemodynamic monitored parameters, and a statistically significant noninferior safety profile regardless of the antiarrhythmic agent used (amiodarone, propranolol, or a combination of both.

Cost-effectiveness analysis of genotype-guided optimization of major depression treatment in Qatar.

Pharmacogenetic testing improves the efficacy and safety of antidepressant pharmacotherapy for moderate-severe major depressive disorder by identifying genetic variations that influence medication metabolism, and adjusting treatment regimens accordingly. This study aims to assess the cost-effectiveness of implementing a pharmacogenetic testing approach to guide the prescription of antidepressants. From the public hospital perspective, we developed a two-stage decision tree diagram of a short-term 6-week follow up, and a lifetime Markov model with 3-month cycles. The analysis compared the current standard of care with the alternative strategy of Pharmacogenetic-guided (multi-gene panel) testing in adult patients with moderate-severe major depressive disorder. Clinical outcomes and utilities were obtained from published studies, while healthcare costs were locally available. The short-term incremental cost-effectiveness ratio was against treatment response without side effects and without relapse, and against treatment response with/without side effects and without relapse. The long-term incremental cost-effectiveness ratio was against the quality-adjusted life year gained and years of life saved. Adopting the pharmacogenetic-guided therapy for adult patients with moderate-severe major depressive disorder in Qatar resulted in cost savings of Qatari Riyal 2,289 (95% confidence interval, -22,654-26,340) for the health system. In the short term, the pharmacogenetic-guided testing was associated with higher response rates without side effects and without relapse (mean difference 0.10, 95% confidence interval 0.09-0.15) and higher response rates with or without side effects and without relapse (mean difference 0.05, 95% confidence interval 0.04-0.06). For long term, the pharmacogenetic-guided testing resulted in 0.13 years of life saved and 0.06 quality-adjusted life year gained, per person, along with cost savings of Qatari Riyal 46,215 (95% confidence interval-15,744-101,758). The sensitivity analyses confirmed the robustness of the model results. Implementing pharmacogenetic testing to guide antidepressant use was found to improve population health outcomes, while also significantly reducing health system costs.

Comparative efficacy of pharmacotherapies on anthropometric measures in overweight and obese children: A systematic review and network meta-analysis

Comparative efficacy of pharmacotherapies on anthropometric measures in overweight and obese children: A systematic review and network meta-analysis

Mechanisms by Which Pharmacotherapy May Impact Cancer Risk among Individuals with Overweight and Obesity.

Diets geared to reduce cancer risk in overweight and obese individuals focus on (1) caloric restriction (every day, some days, or most hours of each day); (2) changes in macronutrient intake; or (3) a combination of the prior two strategies. Diets generally fail because of nonadherence or due to limited sustained weight loss. This is in contrast to a diet supplemented with a weight loss medication, so long as the participant continues the medication or after bariatric surgery, in which adherence tends to be much higher. Among individuals who regain weight after surgery, weight loss medications are proving beneficial in maintaining weight loss. Both maximum and sustained weight loss are essential for all forms of effective metabolic improvement, including cancer risk reduction. The focus of this report is to assess the state of research on the consequence of pharmacotherapy use on weight loss and proposed weight loss-independent effects on subsequent cancer risk reduction, including the potential role of medication use in conjunction with metabolic (bariatric) surgery (MBS). Finally, we present Notices of Funding Opportunities (NOFOs) by the National Cancer Institute (NCI) to better understand the mechanism(s) that are driving the efficacy of pharmacotherapy in cancer risk reduction.

Efficacy and safety of pharmacotherapy for cancer cachexia: A systematic review and network meta-analysis.

Cancer cachexia affects more than half of all cancer patients, reducing survival rates. Evidence-based approaches are urgently needed to optimize treatment. A systematic review and network meta-analysis were conducted to assess the effectiveness and safety of different pharmacotherapies for cancer cachexia. Three databases (PubMed, Cochrane Library, and Web of Science) were searched for the period from January 1, 2000, to March 20, 2024. The netmeta package in R software was used to calculate the pooled effect, employing a random effects model. Seven placebo-controlled randomized trials involving 1421 patients were analyzed. Pairwise analysis showed that body weight increases were 4.6 kg (95% confidence interval [CI] 0.83-8.37 kg) for olanzapine, 3.82 kg (95% CI 0.73-6.91 kg) for espindolol (20 mg), 2.36 kg (95% CI 1.84-2.89 kg) for anamorelin (100 mg), and 1.31 kg (95% CI 0.42-2.19 kg) for anamorelin (50 mg). In terms of safety profiles, olanzapine demonstrated the lowest odds ratio when compared to placebo, at 0.26 (95% CI 0.07-0.94), followed by anamorelin (50 mg) at 0.86 (95% CI 0.30-2.48), and anamorelin (100 mg) at 0.89 (95% CI 0.42-1.88). However, network meta-analysis could not confirm the superiority of olanzapine over anamorelin in terms of efficacy and safety. Both olanzapine and anamorelin are useful in improving body weight in patients with cancer cachexia. Personalization may be helpful for different patients.

Comparative efficacy, safety, and tolerability of pharmacotherapies for acute mania in adults: a systematic review and network meta-analysis of randomized controlled trials.

The aim of this study was to provide evidence-based recommendations regarding the efficacy, safety, and tolerability of currently used pharmacological treatments for adults with acute bipolar mania. To achieve this, we conducted a systematic review and network meta-analysis (NMA) using R software and related packages. We searched primary clinical databases until February 2023 for reports of randomized controlled trials of drug treatments and adjunctive therapies for adults with acute bipolar mania, with outcomes including efficacy (mean change from baseline to endpoint in mania rating scores), safety (clinically significant adverse events from baseline to end of treatment), and tolerability (the proportion of patients who completed the whole trial to the planned endpoint). A total of 113 studies were included in our analysis, in which 23,491 participants (50.38% males; mean age = 38.6 years; mean study duration = 3.39 weeks; mean manic baseline score = 29.37) were randomly allocated to one of 51 monotherapies, adjunctive treatments, or placebo. Our results showed that tamoxifen (mean difference, -22.31 [-25.97, -18.63], N = 2, n1 = 43, n2 = 39) and tamoxifen+ lithium or valproate (LIT/VAL) (-16.37 [-22.55, -10.25], N = 1, n1 = 20, n2 = 20) had the best and second-best clinical efficacy in adults with acute bipolar mania over the placebo. Furthermore, olanzapine, paliperidone, quetiapine, ziprasidone, risperidone, divalproex, and haloperidol were significantly better tolerated than placebo. Combination therapies of antipsychotics and LIT/VAL appeared to be more effective than their corresponding monotherapies. While pharmacotherapies were associated with specific common adverse events, we found no evidence of increased incidence of headache or depression events compared to the placebo. Overall, our NMAs provided important insights into the effectiveness, safety, and tolerability of pharmacological treatments for acute bipolar mania and can help guide treatment decisions for clinicians.

The Efficacy of Pharmacotherapy in the Treatment of Obesity in Patients With Type 2 Diabetes: A Systematic Review.

Obesity is a global public health challenge that poses a significant threat to the effective control and management of type 2 diabetes mellitus (T2DM). Being overweight/obese with T2DM is associated with a wide range of comorbidities, including cardiovascular, cerebrovascular, and renal diseases. This systematic review aimed to investigate the drug therapy used globally among this type of patients in the period between 2014 and 2024. Four databases (PubMed, Web of Science, Scopus, and Cochrane) were searched using the keywords "(Drug Therapy OR Pharmaceutical Preparations OR Pharmacotherapy) AND (Diabetes Mellitus, Type 2) AND (Obesity OR Overweight OR Weight Loss OR Weight reduction) in the title and abstract. All papers assessing the efficacy of any drug class on blood sugar and body weight (BW) were included in the systematic review. Out of 5,206 papers extracted through the database search, 25 randomized clinical trials (RCTs) were considered suitable for the systematic review. The articles included 8,208 participants who tested different drug classes, e.g., glucagon-like peptide-1 (GLP-1) and sodium-glucose co-transporter-2 (SGLT2), with or without metformin. All the reviewed drugs showed significant weight loss over 12-52 weeks. However, the magnitude of weight loss was modest, and the long-term health benefits and safety remain unclear. Interventions that combine pharmacologic therapy with lifestyle modifications may be more effective but need additional research. Continued development of new treatment options for obesity in T2DM is crucial to reduce morbidity and mortality among these patients.

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.

Endpointsfor Pharmacotherapy Trials for AlcoholUse Disorder.

Alcoholuse disorder (AUD) is a debilitating disorder, yet currently approved pharmacotherapies to treat AUD are under-utilized. The three medications approved by the US Food and Drug Administration (FDA) for the indication of AUD are disulfiram, acamprosate, and naltrexone. The current landscape of pharmacotherapies for AUD suggests opportunities for improvement. Clinical trials investigating novel pharmacotherapies for AUD traditionally use abstinence-based drinking outcomes or no heavy drinking days as trial endpoints to determine the efficacy of pharmacotherapies. These outcomes are typically measured through patient self-report endorsements of their drinking. Apart from these traditional outcomes, there have been recent developments in novel endpoints for AUD pharmacotherapies. These novel endpoints include utilizing the World Health Organization (WHO) riskdrinking level reductions to promote a harm-reduction endpoint rather than an abstinence-based endpoint. Additionally, in contrast to patient self-report measurements, biological markers of alcohol use may serve as objective endpoints in AUD pharmacotherapy trials. Lastly, the National Institute on Alcohol Abuse and Alcoholism (NIAAA) definition of recovery from AUD and patient-oriented outcomes offer new frameworks to consider endpoints associated with more than alcohol consumption itself, such as the provider-patient experiences with novel pharmacotherapies. These recent developments in new endpoints for AUD pharmacotherapies offer promising future opportunities for pharmacotherapy development, so long as validity and reliability measures are demonstrated for the endpoints. A greater breadth of endpoint utilization may better capture the complexity of AUD symptomatology.

Omega-3 polyunsaturated fatty acids and pulmonary arterial hypertension: Insights and perspectives.

Pulmonary arterial hypertension (PAH) is a rare and progressive disorder that affects the pulmonary vasculature. Although recent developments in pharmacotherapy have extended the life expectancy of PAH patients, their 5-year survival remains unacceptably low, underscoring the need for multitarget and more comprehensive approaches to managing the disease. This should incorporate not only medical, but also lifestyle interventions, including dietary changes and the use of nutraceutical support. Among these strategies, n-3 polyunsaturated fatty acids (n-3 PUFAs) are emerging as promising agents able to counteract the inflammatory component of PAH. In this narrative review, we aim at analysing the preclinical evidence for the impact of n-3 PUFAs on the pathogenesis and the course of PAH. Although evidence for the role of n-3 PUFAs deficiencies in the development and progression of PAH in humans is limited, preclinical studies suggest that these dietary components may influence several aspects of the pathobiology of PAH. Further clinical research should test the efficacy of n-3 PUFAs on top of approved clinical management. These studies will provide evidence on whether n-3 PUFAs can genuinely serve as a valuable tool to enhance the efficacy of pharmacotherapy in the treatment of PAH.

Sex-Gender Differences Are Completely Neglected in Treatments for Neuropathic Pain.

As sex-gender differences have been described in the responses of patients to certain medications, we hypothesized that the responses to medications recommended for neuropathic pain may differ between men and women. We conducted a literature review to identify articles reporting potential sex-gender differences in the efficacy and safety of these medications. Only a limited number of studies investigated potential sex-gender differences. Our results show that women seem to achieve higher blood concentrations than men during treatment with amitriptyline, nortriptyline, duloxetine, venlafaxine, and pregabalin. Compared to men, higher rates of women develop side effects during treatment with gabapentin, lidocaine, and tramadol. Globally, the sex-gender differences would suggest initially administering smaller doses of these medications to women with neuropathic pain compared to those administered to men. However, most of these differences have been revealed by studies focused on the treatment of other diseases (e.g., depression). Studies focused on neuropathic pain have overlooked potential sex-gender differences in patient responses to medications. Despite the fact that up to 60% of patients with neuropathic pain fail to achieve an adequate response to medications, the potential role of sex-gender differences in the efficacy and safety of pharmacotherapy has not adequately been investigated. Targeted studies should be implemented to facilitate personalized treatments for neuropathic pain.

Potential drug-drug interactions analysis in Polish pediatric pneumonology units, including cystic fibrosis patients.

The lack of data on drug-drug interactions in pediatrics represents a relevant problem in making appropriate therapeutic decisions. Our study aimed to investigate the incidence and risk factors for potential drug-drug interactions (pDDIs) in pediatric pneumonology units, including cystic fibrosis patients. We performed a 6-month prospective observational study during which clinical pharmacists, using the Lexicomp Drug Interactions checker, screened medical records to identify pDDIs. Spearman's rank coefficient, logistic regression, and the Mann-Whitney U test were used to identify correlations, analyze risk factors for pDDIs, and compare cystic fibrosis patients with the rest, respectively. Recommendations were provided for the D and X pDDIs categories. Within the 218 patients, 428 pDDIs were identified, out of which 237 were classified as clinically significant. Almost 60% of patients were exposed to at least one relevant interaction. The number of pDDIs correlated with the number of; drugs (rs = 0.53, P < .001), hospitalization length (rs = 0.20, P < .01), and off-label medicines (rs = 0.25, P < .001). According to the multivariate analysis, at least 6 administered medications (OR = 4.15; 95% CI = 2.21-7.78), 4 days of hospitalization (OR = 6.41; 95% CI = 2.29-17.97), and off-label therapy (OR = 3.37; 95% CI = 1.69-6.70) were the risk factor for pDDIs. Despite significant differences in the number of medications taken, comorbidities, and off-label drugs, cystic fibrosis patients were not more exposed to pDDI. Given the lack of data on pDDIs in the pediatric population, the need for close cooperation between clinicians and clinical pharmacists to improve the safety and efficacy of pharmacotherapy is highlighted.

Efficacy and acceptability of different probiotic products plus laxatives for pediatric functional constipation: a network meta-analysis of randomized controlled trials

The prevalence of pediatric constipation ranges from 0.7 to 29.6% across different countries. Functional constipation accounts for 95% of pediatric constipation, and the efficacy of pharmacotherapy is limited, with a success rate of 60%. Several randomized controlled trials (RCTs) have shown the benefits of probiotic supplements in treating this condition. However, the reported strains of probiotics varied among the RCTs. We aimed to compare the efficacy and acceptability of different probiotic supplements for pediatric functional constipation. The current frequentist model–based network meta-analysis (NMA) included RCTs of probiotic supplements for functional constipation in children. The primary outcome was changes in bowel movement or stool frequency; acceptability outcome was all-cause discontinuation. Nine RCTs were included (N = 710; mean age = 5.5 years; 49.4% girls). Most probiotic products, used either alone or combined with laxatives, were associated with significantly better improvement in bowel movement or stool frequency than placebo/control. Protexin plus laxatives (standardized mean difference (SMD) = 1.87, 95% confidence interval (95% CI) = 0.85 to 2.90) were associated with the greatest improvement in bowel movement or stool frequency among all the investigated probiotic products. For the single probiotic interventions, only Lactobacillus casei rhamnosus Lcr35 was associated with significant efficacy compared to placebo/control treatments (SMD = 1.37, 95% CI: 0.32 to 2.43). All the investigated probiotic products had fecal incontinence and patient drop-out rates similar to those of placebo/control treatments. Conclusion: The results of our NMA support the application of an advanced combination of probiotics and laxatives for pediatric functional constipation if there is no concurrent contraindication. Registration: PROSPERO (CRD42022298724).What is Known:• Despite of the high prevalence of pediatric constipation, which ranges from 0.7% to 29.6%, the efficacy of pharmacotherapy is limited, with a success rate of 60%. Several randomized controlled trials (RCTs) have shown the benefits of probiotic supplements in treating this condition. However, the reported strains of probiotics varied among the RCTs. The widely heterogeneous strains of probiotics let the traditional meta-analysis, which pooled all different strains into one group, be nonsense and insignificant.What is New:• By conducting a comprehensive network meta-analysis, we aimed to compare the efficacy and acceptability of different strains of probiotic supplements for pediatric functional constipation. Network meta-analysis of nine randomized controlled trials revealed that the most probiotic products, used either alone or combined with laxatives, were associated with significantly better improvement in bowel movement or stool frequency than placebo/control. Protexin plus laxatives was associated with the greatest improvement in bowel movement or stool frequency among all the investigated probiotic products. For the single probiotic interventions, only Lactobacillus casei rhamnosus Lcr35 was associated with significant efficacy compared to placebo/control treatments. All the investigated probiotic products had fecal incontinence and patient drop-out rates similar to those of placebo/control treatments.

Assessment of pharmacotherapy efficacy for the treatment of exacerbations of chronic obstructive pulmonary disease associated with viral infection

Justification. Knowledge of the differences in response to therapy between phenotypes of exacerbations of chronic obstructive pulmonary disease (COPD) is necessary to improve treatment outcomes. Objective: to determine the most effective additional pharmacological methods for virus-associated exacerbations of COPD. Material and methods. The study included patients hospitalized with exacerbations of COPD with viral (n = 60) and viral-bacterial (n = 60) infections, and a comparison group with exacerbations of COPD with bacterial infection (n = 60). The diagnosis of COPD was based on spirometric criteria, viral infection — according to the results of PCR-RV of sputum for RNA of respiratory viruses. Treatment was carried out in real clinical practice. The groups were comparable in the use of systemic glucocorticoids, short-acting bronchodilators. Dyspnea was assessed using the TDI index (primary endpoint), lung function (spirometry, diffusion capacity for carbon monoxide), exercise tolerance (6-minute walk test), length of hospital stay (secondary endpoints). The сorrelations were determined with the use of Cox proportional hazards model. Results. In the groups with virus-associated and viral-bacterial exacerbations, unlike bacterial exacerbations, the following types of treatment were associated with achieving TDI +1 (odds ratio — OR, 95 % confidence interval — CI): fixed triple combination (OR 2.69; 95 % CI 1.48–4.90; p = 0.010 and OR 2.74; 95 % CI 1.29–3.80; p = 0.031), inhalation of 3 % sodium chloride solution (OR 3.64; 95 % CI 1.45–5.42; p = 0.001 and OR 3.23; 95 % CI 2.15–5.43;\ p = 0.042), antiviral drugs (OR 2.91; 95 % CI 1.15–3.62; p = 0.009 and OR 2.76; 95 % CI 1.31–3.90; p = 0.008). As a result of treatment, an increase in DLco/Va, SpO2 after a 6-minute walk, and a decrease in the length of hospital stay were observed. Conclusion. Detection of virus-associated infections is a promising marker for determining indications for prescribing long-acting anticholinergic drugs and beta-adrenomimetics, inhaled corticosteroids, inhalations of hypertonic sodium chloride solution, and antiviral drugs for exacerbations of COPD.

Vaccines as Immunotherapies for Substance Use Disorders.

Substance use disorders (SUD) present a worldwide challenge with few effective therapies except for the relative efficacy of opioid pharmacotherapies, despite limited treatment access. However, the proliferation of illicit fentanyl use initiated a dramatic and cascading epidemic of lethal overdoses. This rise in fentanyl overdoses regenerated an interest in vaccine immunotherapy, which, despite an optimistic start in animal models over the past 50 years, yielded disappointing results in human clinical trials of vaccines against nicotine, stimulants (cocaine and methamphetamine), and opioids. After a brief review of clinical and selected preclinical vaccine studies, the "lessons learned" from the previous vaccine clinical trials are summarized, and then the newest challenge of a vaccine against fentanyl and its analogs is explored. Animal studies have made significant advances in vaccine technology for SUD treatment over the past 50 years, and the resulting anti-fentanyl vaccines show remarkable promise for ending this epidemic of fentanyl deaths.

Potential applications of nanomedicine in the treatment of Parkinson's disease

Parkinson's disease (PD) is the second most common neurodegenerative disease and leads to severe disability and even death in patients, causing a heavy social burden worldwide. Among the therapeutics for PD, pharmacotherapy is usually the first-line therapy and is typically the basic treatment for other therapeutics, such as surgery, exercise therapy and psychological intervention. Unfortunately, the existing PD therapeutic agents fail to cure the disease due to their low efficacy, cytotoxicity, severe side effects and poor cell targeting. With the development of nanotechnology and the emergence of nanomedicine, the application of nanomaterials has helped improve the efficacy of pharmacotherapy for PD. In the following review, the current pharmacotherapy for PD and its pros and cons are described. A summary of the nanomaterial types commonly used in nanomedicine and their applications in PD treatment is provided. Additionally, challenges related to using nanomaterials for PD pharmacotherapy are discussed.

Melanin Biopolymers in Pharmacology and Medicine-Skin Pigmentation Disorders, Implications for Drug Action, Adverse Effects and Therapy.

Melanins are biopolymeric pigments formed by a multi-step oxidation process of tyrosine in highly specialized cells called melanocytes. Melanin pigments are mainly found in the skin, iris, hair follicles, and inner ear. The photoprotective properties of melanin biopolymers have been linked to their perinuclear localization to protect DNA, but their ability to scavenge metal ions and antioxidant properties has also been noted. Interactions between drugs and melanins are of clinical relevance. The formation of drug-melanin complexes can affect both the efficacy of pharmacotherapy and the occurrence of adverse effects such as phototoxic reactions and discoloration. Because the amount and type of melanin synthesized in the body is subject to multifactorial regulation-determined by both internal factors such as genetic predisposition, inflammation, and hormonal balance and external factors such as contact with allergens or exposure to UV radiation-different effects on the melanogenesis process can be observed. These factors can directly influence skin pigmentation disorders, resulting in hypopigmentation or hyperpigmentation of a genetic or acquired nature. In this review, we will present information on melanocyte biology, melanogenesis, and the multifactorial influence of melanin on pharmacological parameters during pharmacotherapy. In addition, the types of skin color disorders, with special emphasis on the process of their development, symptoms, and methods of treatment, are presented in this article.