Pharmacological Medications Research Articles

Ketamine Treatment for Pediatric Refractory Obsessive: Five Open Label Cases.

Importance: Selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioral therapy are the first-line treatments for pediatric obsessive-compulsive disorder (OCD) populations. Due to their limited effectiveness, additional treatment options are needed. A new potential pharmacological medication treatment avenue for OCD is intravenous (IV) ketamine. Objective: This study aimed to establish the feasibility, acceptability, and preliminary efficacy of an IV ketamine infusion for the treatment of refractory OCD in adolescents. Design: In this clinical pilot trial, every participant received IV ketamine infusion. Symptom severity and side effects were assessed daily for 2 weeks following the infusion. Setting: Study procedures were conducted at the New York State Psychiatric Institute, including a combination of in-person visits and phone calls. Participants: Five adolescents with OCD (age M, SD: 16.6 ± 1.5), who had previously failed trials of first-line treatments were enrolled. Intervention: All participants received an IV infusion of 0.5 mg/kg ketamine hydrochloride. Main Outcomes and Measures: A multimethod approach was applied, including physiological, self-report, and clinician-rated measures. To assess feasibility and acceptability, vital signs, electrocardiogram suicidality, self-reported adverse events, and dissociative symptoms were obtained. Obsessive-compulsive (OC) (Yale-Brown Obsessive Compulsive Challenge Scale, CY-BOCS) and depressive symptom severity, as well as global clinical impression, were assessed to investigate preliminary efficacy. Results: The mean (SD) pre- and 14-day posttreatment CY-BOCS were 29 (5.5) and 26.2 (5.6). There were no incidents of abnormal vital signs, mortality, or suicidal ideation in the 2 weeks following the infusion. All participants experienced mild dissociative symptoms in the 40 minutes after the IV ketamine infusion. Descriptively, OC symptom severity decreased immediately after the infusion but was not maintained over the course of the study. Conclusions and Clinical Significance: Ketamine is well-tolerated in adolescents with OCD and therefore appropriate for further efficacy testing. Trial Registration: ClinicalTrials.gov Identifier: NCT02422290.

Systemic therapy of psoriasis and psoriatic arthritis: assignment algorithms

The article contains a review of modern literature data and the authors' personal long-term experience in treating patients with psoriasis and psoriatic arthritis. The possibilities of prescribing various drugs for systemic therapy based on the clinical situation, issues of monitoring and evaluating the effectiveness of therapy, and the mechanism for switching therapy from one pharmacological medication to another are discussed in detail. Therapy of patients with psoriasis requires solving the complex issue of drug selection, which depends on many factors. The choice of systemic therapy algorithm is an important issue that determines the effectiveness and safety of treatment, influences the prognosis of the disease and the patient's quality of life.

Real‐Time Nail‐Biting Detection on a Smartwatch Using Three CNN Models Pipeline

ABSTRACTNail‐biting (NB) or onychophagia is a compulsive disorder that affects millions of people in both children and adults. It has several health complications and negative social effects. Treatments include surgical interventions, pharmacological medications, or additionally, it can be treated using behavioral modification therapies that utilize positive reinforcement and periodical reminders. Although it is the least invasive, such therapies still depend on manual monitoring and tracking which limits their success. In this work, we propose a novel approach for automatic real‐time NB detection and alert on a smartwatch that does not require surgical intervention, medications, or manual habit monitoring. It addresses two key challenges: First, NB actions generate subtle motion patterns at the wrist that lead to a high false‐positives (FP) rate even when the hand is not on the face. Second, is the challenge to run power‐intensive applications on a power‐constrained edge device like a smartwatch. To overcome these challenges, our proposed approach implements a pipeline of three convolutional neural networks (CNN) models instead of a single model. The first two models are small and efficient, designed to detect face‐touch (FT) actions and hand movement away (MA) from the face. The third model is a larger and deeper CNN model dedicated to classifying hand actions on the face and detecting NB actions. This separation of tasks addresses the key challenges: decreasing FPs by ensuring NB model is activated only when the hand on the face, and optimizing power usage by ensuring the larger NB model runs only for short periods while the efficient FT model runs most of the time. In addition, this separation of tasks gives more freedom to design, configure, and optimize the three models based on each model task. Lastly, for training the main NB model, this work presents further optimizations including developing NB dataset from start through a dedicated data collection application, applying data augmentation, and utilizing several CNN optimization techniques during training. Results show that the model pipeline approach minimizes FPs significantly compared with the single model for NB detection while improving the overall efficiency.

Gut-brain axis and brain health: modulating neuroinflammation, cognitive decline, and neurodegeneration.

The microbiota-gut-brain axis is a pivotal medium of crosstalk between the central nervous system (CNS) and the gastrointestinal tract. It is an intricate network of synergistic molecular pathways that exert their effects far beyond their local vicinity and even affect the systemic functioning of the body. The current review explores the involvement of the gut-brain axis (GBA) in the functioning of the nervous system, with a special emphasis on the neurodegeneration, cognitive decline, and neuroinflammation that occur in Alzheimer's disease (AD) and Parkinson's disease (PD). Gut-derived microbial metabolites play an important role in facilitating this interaction. We also highlighted the complex interaction between gut-derived metabolites and CNS processes, demonstrating how microbial dysbiosis might result in clinical disorders. Short-chain fatty acids have neuroprotective properties, whereas branched-chain amino acids, trimethylamine-N-oxide (TMAO), and tryptophan derivatives such as indole have negative effects at high concentrations. Furthermore, we cover pharmaceutical and nonpharmacological approaches for restoring the gut microbial balance and promoting neurological health. We further expanded on nutritional therapies and lifestyle changes, such as the Mediterranean diet and exercise. Next, we focused on food-controlling habits such as caloric restriction and intermittent fasting. Moreover, interventional techniques such as prebiotics, probiotics, and pharmacological medications have also been utilized to modify the GBA. Historical microbiome research from early discoveries to recent studies linking gut health to cognitive and emotional well-being has increased our understanding of the GBA.

The Importance of Stem Cells in the Treatment of Neuropathic Pain.

Many disorders, including heart, bone, cancer, liver, and brain disease, have been treated using stem cell therapy as a viable alternative. The somatosensory system is affected by a lesion, which leads to neuropathic pain (NP), and just a relatively tiny fraction of patients now receive effective care from existing pharmacological medications. There have been studies to show the effectiveness of various stem cells in reducing or treating experimental neurological pain, although these studies are uncommon in number. In this narrative review, we will summarize the preclinical and clinical research that has been conducted on the effectiveness of several stem cell types, such as mesenchymal stem cells, bone-derived stem cells, and neural stem cells, in reducing neurological pain in this study.

Poloxamer®s anchored with TAT enhance blood–brain barrier penetration of carbamazepine for the treatment of epilepsy: an in vivo study

Carbamazepine is a pharmacological medication commonly prescribed to treat epilepsy. Dose adjustments, poor bioavailability, and prolonged side effects present significant challenges associated with its use. Poloxamer micelles have demonstrated exceptional properties as nanocarriers for drug delivery. This research aimed to develop Poloxamer nanomicelles containing carbamazepine and assess their potential to cross the blood–brain barrier.Poloxamer 407 and P-85 micelles, anchored with TAT as a ligand and containing carbamazepine, were prepared. The morphology, entrapment efficiency, drug release, stability, and toxicity of nanomicelles were examined, along with animal studies conducted to evaluate their anticonvulsant effects. The distribution of carbamazepine-Poloxamer in the brain and plasma was assessed.The results indicated the successful formation of spherical nanomicelles with an average size of less than 100 nm, and carbamazepine was effectively incorporated into the micelles. Formulations composed of mixtures of Poloxamer exhibited a high encapsulation efficiency of approximately 92.1% and remained stable for three months. A sustained release of carbamazepine was observed for up to 72 h. The anticonvulsant effect of carbamazepine-loaded nanomicelles in mice was found to be significantly greater than that of those treated with carbamazepine solution, with the effect increasing by approximately tenfold. Compared to free carbamazepine, the carbamazepine-loaded nanomicelles exhibited a 5.5-fold increase in the brain targeting index, with no toxicity observed in mice treated with these nanomicelles. These findings suggest that Poloxamer micelles represent a promising nanoscale, controlled-release delivery system that is free from toxicity and can enhance the penetration of carbamazepine into the brain while improving its anticonvulsant activity.Graphical

Prehabilitative/rehabilitative exercise, nutrition, and psychological support for bladder cancer: A scoping review of randomized clinical trials.

The study of prehabilitation and rehabilitation ([p]rehabilitation) to alleviate the sequelae of bladder cancer and its treatment has generated numerous opportunities to improve the quality of life of bladder cancer survivors. The authors conducted a scoping review of randomized clinical trials (RCTs) to identify knowledge gaps in and research directions for (p)rehabilitative support for those affected by bladder cancer. The authors systematically searched six databases and synthesized key findings from RCTs conducted from January 1, 2004, through March 15, 2022, that enrolled participants with bladder cancer, survivors, or caregivers in outpatient (p)rehabilitative programs (e.g., exercise, nutrition, or psychological support). Outcomes were characterized according to eight prespecified, clinically relevant categories. The search retrieved 10,968 records, 27 of which met the inclusion criteria, and 24 described unique RCTs with 2471 enrolled participants. Of 24 interventions, 17 (71%) yielded statistically significant results for the outcome of interest. Only one RCT included a cost-effectiveness analysis, and only two characterized the efficacy of interventions for caregivers. Of 11 RCTs involving psychological support, eight yielded statistically significant results, as did nine of 11 RCTs with physical exercise interventions, three of four RCTs with educational interventions, three of four RCTs with nutritional support interventions, one of two RCTs with pharmacologic medications, and zero of one RCT with physical therapy. The most promising interventions for inclusion in multimodal, personalized (p)rehabilitation programs included exercise, stress management training, cognitive training, smoking and alcohol cessation counseling, immunonutrition, stoma education, and penile rehabilitation. Further studies of the cost effectiveness and efficacy for caregivers of such interventions are needed. PLAIN LANGUAGE SUMMARY: In a scoping review of all randomized clinical trials involving prehabilitative or rehabilitative diet, exercise, and psychological support interventions for patients with bladder cancer, survivors, and their caregivers, 17 of 24 (71%) interventions yielded statistically significant improvements in the outcome of interest. Clinicians should consider implementing such interventions for those affected by bladder cancer.

Emergency Medical Services and Police Utilization for Pediatric Mental and Behavioral Health Concerns Within a Large Hospital System.

This study aimed to compare emergency medical services (EMS) and police utilization trends, epidemiology, and emergency department (ED) outcomes between pediatric patients with mental or behavioral health (MBH) emergencies and those with non-MBH concerns transported to a large children's hospital system. This was a retrospective cohort study of patients aged 5 to 18 years transported via EMS and police to two EDs affiliated with a children's hospital from January 2012 through December 2020. Data were abstracted from electronic hospital records. Encounters for MBH emergencies were identified using diagnostic codes and chief complaints. Trends of EMS and police transports of patients with MBH emergencies were examined. Patient demographics and ED outcomes were compared between children presenting with MBH emergencies and those with non-MBH concerns. During the 9-year study period, out of 40,663 transports to the EDs, 36,137 (89%) arrived via EMS, and 4,526 (11%) arrived via police. A total of 10,250 (28.4%) EMS transports were for MBH emergencies. The volume of patients transported by EMS for MBH emergencies increased by 1.4% per year (P < 0.01) with no significant change in total EMS patient volumes. Patients with MBH emergencies transported by EMS were more likely to be older, female, of White race, and publicly insured; require restraint in the ED; and be admitted (P < 0.001). Of police transports, 4153 (91.8%) were for MBH emergencies, with no statistical change in the proportion of police transports that were for MBH emergencies. Police-transported MBH patients compared to non-MBH police-transported patients were more likely to be younger, female, and of White race (P < 0.001); 8.7% required mechanical/physical restraints in ED, 6.7% required pharmacologic restraint medications in ED, and 53% were admitted. The proportion of pediatric transports for MBH emergencies by EMS is rising and comprises the majority of police transports. Distinct from non-MBH pediatric patients transported, MBH patients necessitate significant ED resources, including ED-administered restraints and admission, highlighting their unique burden on the prehospital and ED systems.

Patterns, Barriers, and Preferences of Treating Migraine Within the School Setting: A Survey Study of Students.

Background/Objectives: Migraine affects 10% of adolescents and children. Typical school protocols in the USA require pharmacological medications to be administered by school nurses, often resulting in treatment delays or omissions when migraine attacks occur during school hours. The Remote Electrical Neuromodulation (REN) wearable is an FDA-cleared smartphone-controlled device delivering acute and preventive treatment of migraine attacks in patients aged 8 and above, allowing safe, effective, discreet, and independent usage. Methods: This retrospective study (NCT06180577) evaluates treatment patterns, barriers, and preferences among school-age students. REN users < 18 years old were invited to complete an online survey. Participants signed an assent form, and their parents/legal guardians signed an informed consent form. Results: 332 patients aged 7-17 (15.5 ± 2.1) participated (80.4% female). After being prescribed the REN wearable, the percentage of students who treated their headaches at school increased from 78.3% to 89.8%. Most participants (65.4%) treated with either REN standalone (38.0%) or in combination with medications (27.4%). Common barriers to treatment included the need to leave class for the nurse's office (64.2%), concerns about standing out (42.2%), and one barrier unique to REN-permission needed to use a smartphone in class (22.9%). The most common reasons given for preferring REN treatment at school are the ability to avoid going to the nurse's office (42.5%) and to treat discreetly (39.2%). Conclusions: This study underscores the challenges of managing migraine at school while suggesting the importance of the REN wearable as a discreet and independently used first-line treatment for children and adolescents.

An Analysis of Cost Variation Among Drugs Available in the Indian Market for the Treatment of Chronic Bone-Related Ailments.

Treating widely prevalent bone illnesses such as back and neck pain, osteoarthritis, rheumatoid arthritis, gout, and osteoporosis with pharmacological medication can be excessively costly for both the individual and their family. This study aimed to conduct a cost minimization analysis by comparing the prices of Jan Aushadhi (JA) medications with the most expensive and least expensive branded alternatives available in India. The prices of the most costly, least costly branded, and JA medicines were acquired from the relevant websites. The cost difference, cost ratio, and percentage of cost variation were determined based on the guidelines outlined in the cost minimization analysis research. A total of 67 drugs/combinations used to treat various chronic bone ailments were analyzed. With regard to analgesic/anti-inflammatory drugs, the most expensive brand of diclofenac sodium + serratiopeptidase (50mg + 10mg) tablet was 32.5 times more expensive than the cheapest and 10.5 times more costly than the JA brand. Also, the paracetamol 325mg + tramadol 37.5mg combination of the branded tablets was more expensive than JA. Branded cyclosporine was 2.3 times more expensive than JA among immunosuppressants in the disease-modifying antirheumatic drugs (DMARD) group. The most expensive immunomodulator, leflunomide, costs four times more than JA. Hydrocortisone injection, an adjuvant, costs 10.8 times more than the cheapest and 2.1 times more than JA. IL-1 inhibitor + nutraceutical combination costs 4.8 times more than the costliest JA brand. Zoledronic acid was 16.1 and 6.8 times more expensive than the cheapest branded and JA drugs. Xanthine oxidase inhibitor febuxostat, used to treat gout, costs 5.2 and 3.3 times more than JA and the cheapest brands. This cost minimization study, the first to the best of our knowledge in the field of chronic musculoskeletal ailments, indicates the usefulness of JA drugs in reducing the patient's financial costs for most drugs.

Potentially inappropriate prescription of medications to older adults who access a community pharmacy in Peru

Polypharmacy in older adults is associated with a higher incidence of medication-related problems, such as pharmacological interactions, adverse reactions, and medication errors. This study aimed to identify and evaluate potentially inappropriate prescription of medications (PIP) using the screening tool of older persons’ prescriptions/screening tool to alert doctors to right treatment (STOPP/START) criteria in a representative community pharmacy in Trujillo, Peru. The population sample consisted of 158 subjects, with 66.5% between 65 and 69 years old, 53.8% male, and 77.9% receiving between 3 and 4 medications. Medical prescriptions were analyzed using the explicit STOPP/START version 2 criteria, revealing that 93.7% of patients presented STOPP criteria (to stop medication) and 53.8% presented START criteria (to start medication). The most frequently identified STOPP criterion was the gradual withdrawal of benzodiazepines, while the most frequently identified START criterion was the initiation of antihypertensive treatment in patients with systolic blood pressure &amp;gt; 160 mmHg and diastolic blood pressure &amp;gt; 90 mmHg. Principal component analysis showed that the high prevalence of PIP was significantly associated (p &amp;lt; 0.05) with the number of prescribed medications and as age decreases, the number of medical diagnoses also decreases. It is concluded that there is a high prevalence of PIP in the studied population, posing a greater challenge in older adults, highlighting the importance of addressing prescribing practices with greater involvement of community pharmacists.

Chronic Pain and Chronic Bias in Women’s Healthcare

Gender bias against women with respect to the treatment of chronic pain is evident in several ways. Recent studies reveal that women receive poorer pain management care and have less access to such care. Such disparities are further perpetuated in the type of pain management offered to females in the form of psychotherapy as compared to men who typically receive pharmacological medications. The 2023 documentary Below the Belt shows real life journeys of women battling endometriosis, illustrating how the medical system in modern America marginalizes female pain management. Women’s health issues receive less research funding, inspiring the gender biases that are prevalent across all aspects of medical healthcare and healthcare research. In addition, a lack of focus on gender and sex disparities in medical school curricula further perpetuates the problem, as medical practitioners are not educated on the differences in experience between populations. Raising issues of gender awareness and differences in care for males and females at the start of the medical journey enables the issue of gender bias in medical care to be dealt with at the root of the system. This paper aims to highlight the impact of gender bias in women’s healthcare for chronic pain within every step of the medical process.

Diabetic Patients with Chronic Pain After Lumbar Surgery Experienced Fewer Analgesic Effects of Laser Therapy

Background: Recent studies indicate that several factors are associated with different responses to pain relief and alteration in reactions to non-pharmacological modalities and pharmacological medications. Biological processes appear to be contributory factors to these outcomes. Objectives: The purpose of this study is to examine how laser therapy can help as a conservative approach for chronic pain after back surgery in patients with diabetes mellitus (DM). Methods: This research included 22 diabetic patients and 26 non-diabetic patients with chronic pain after back surgery. Points of laser irradiation were determined by an ultrasound examination, specifically targeting bilateral sacroiliac joints, L2 - L3 through L5 - S1 facet joints, and the area of cluneal nerves. The duration of laser therapy was three weeks, with treatment sessions using an 808 nm diode laser at a power of 0.5W, performed every other day. Individuals were evaluated using the Oswestry Disability Index (ODI) and Numeric Rating Scale (NRS) before and after treatment, and again six months later. Results: Oswestry Disability Index and Numeric Rating Scale scores decreased significantly after treatment and six months later. Furthermore, analysis of the data showed that diabetic patients experienced less therapeutic effect during and after laser therapy sessions. Conclusions: Although laser therapy can reduce pain, diabetic patients reported a lower level of effectiveness compared to non-diabetic patients.

From chaos to kaleidoscope: Exploring factors in psychedelic self-treatment for mental health conditions.

This study explores how individuals self-treat psychiatric conditions with psychedelics outside medical guidance bridging the gap in understanding unregulated therapeutic use. The primary objective was to extract specific factors underlying the effects of psychedelics, exploring their relationship with the need for medication, particularly for mental health conditions like depression and anxiety. Additionally, we aimed to understand how the likelihood of being prescribed pharmacological medication varies based on mental health diagnoses and demographic factors. This research utilised the Global Drug Survey 2020, an annual online survey focused on substance use patterns and demographics, incorporating modules addressing mental health and psychedelic use. The study employed Exploratory Factor Analysis to discern latent factors underlying the self-reported effects of psychedelics. Bivariable and multivariable logistic regressions were conducted to investigate the association between identified factors and the likelihood of current prescribed medication usage. In all, 2552 respondents reported using psychedelics for self-treatment of mental health conditions. Three significant factors were identified: Improved Mental Health, Improved Self-Awareness and Neuro-Sensory Changes. The majority of the sample reported a history of depression (80%) or anxiety (65.6%), with a significant association observed between reported factors of psychedelics' effects and current medication usage for mental health, especially notable in cases of depression or comorbid depression and anxiety. Perceived symptom improvement following psychedelic self-treatment may reduce the need for medically supervised pharmacological interventions. These findings highlight the potential of psychedelics to positively influence mental health and self-awareness, paving the way for further research into their therapeutic application.

Assessing Decision Fatigue in General Practitioners' Prescribing Decisions Using the Australian BEACH Data Set.

General practitioners (GPs) make numerous care decisions throughout their workdays. Extended periods of decision making can result in decision fatigue, a gradual shift toward decisions that are less cognitively effortful. This study examines whether observed patterns in GPs' prescribing decisions are consistent with the decision fatigue phenomenon. We hypothesized that the likelihood of prescribing frequently overprescribed medications (antibiotics, benzodiazepines, opioids; less effortful to prescribe) will increase and the likelihood of prescribing frequently underprescribed medications (statins, osteoporosis medications; more effortful to prescribe) will decrease over the workday. This study used nationally representative primary care data on GP-patient encounters from the Bettering the Evaluation and Care of Health program from Australia. The association between prescribing decisions and order of patient encounters over a GP's workday was assessed with generalized linear mixed models accounting for clustering and adjusting for patient, provider, and encounter characteristics. Among 262,456 encounters recorded by 2,909 GPs, the odds of prescribing antibiotics significantly increased by 8.7% with 15 additional patient encounters (odds ratio [OR] = 1.087; confidence interval [CI] = 1.059-1.116). The odds of prescribing decreased significantly with 15 additional patient encounters by 6.3% for benzodiazepines (OR = 0.937; CI = 0.893-0.983), 21.9% for statins (OR = 0.791; CI = 0.753-0.831), and 25.0% for osteoporosis medications (OR = 0.750; CI = 0.690-0.814). No significant effects were observed for opioids. All findings were replicated in confirmatory analyses except the effect of benzodiazepines. GPs were increasingly likely to prescribe antibiotics and were less likely to prescribe statins and osteoporosis medications as the workday wore on, which was consistent with decision fatigue. There was no convincing evidence of decision fatigue effects in the prescribing of opioids or benzodiazepines. These findings establish decision fatigue as a promising target for optimizing prescribing behavior. We found that as general practitioners progress through their workday, they become more likely to prescribe antibiotics that are reportedly overprescribed and less likely to prescribe statins and osteoporosis medications that are reportedly underprescribed.This change in decision making over time is consistent with the decision fatigue phenomenon. Decision fatigue occurs when we make many decisions without taking a rest break. As we make those decisions, we become gradually more likely to make decisions that are less difficult.The findings of this study show that decision fatigue is a possible target for improving guideline-compliant prescribing of pharmacologic medications.

Construct Validation and Reliability Assessment of Tamil Translated Hill-Bone-Compliance to High Blood Pressure Therapy Scale Among Hypertensive Patients in Rural Puducherry, South India.

Pharmacological drugs and medications are being widely used for the control of non-communicable diseases like hypertension. Hill-Bone-Compliance to High Blood Pressure Therapy Scale (HB-HBP) is a newly developed specific questionnaire for assessing the anti-hypertensive medication adherence. Hence, this study was done to translate the HB-HBP in Tamil and to assess the construct validity and reliability of the Tamil version. Translation of HB-HBP to native language, Tamil was done by experts and piloted with subsample of hypertensive patients from rural Puducherry. Final Tamil-translated HB-HBP was administered among 328 Tamil-speaking hypertensive patients in the selected villages of rural Puducherry (union territory in South India). Construct validity was assessed by exploratory factor analysis (EFA) through the principal component method. Based on the minimum average partial and parallel analysis, three-factor model was distinguished. Confirmatory factor analysis was done to obtain the goodness-of-fit. Reliability of questionnaire was assessed through Cronbach's alpha coefficient. Three factor structures were obtained with eigenvalues of 6.5045, 2.8165, and 1.2261, respectively, which accounted for 75.34% of variance. Three-factor model assessed by the confirmatory factor method found Chi-square value of 1055.048 (P value <0.001). Goodness of fit revealed acceptable comparative fit index (0.773), Tucker-Lewis index (0721), standardized root mean square residual (0.077), and root mean square error of approximation (0.201). The reliability coefficient (Cronbach's alpha) for the scale was 0.9020. Our study concludes that the HB-HBP questionnaire is internally valid and consistent with a good reliability coefficient for application in Tamil-speaking patients with hypertension.

In Silico TRials guide optimal stratification of ATrIal FIbrillation patients to Catheter Ablation and pharmacological medicaTION: the i-STRATIFICATION study.

Patients with persistent atrial fibrillation (AF) experience 50% recurrence despite pulmonary vein isolation (PVI), and no consensus is established for secondary treatments. The aim of our i-STRATIFICATION study is to provide evidence for stratifying patients with AF recurrence after PVI to optimal pharmacological and ablation therapies, through in silico trials. A cohort of 800 virtual patients, with variability in atrial anatomy, electrophysiology, and tissue structure (low-voltage areas, LVAs), was developed and validated against clinical data from ionic currents to electrocardiogram. Virtual patients presenting AF post-PVI underwent 12 secondary treatments. Sustained AF developed in 522 virtual patients after PVI. Second ablation procedures involving left atrial ablation alone showed 55% efficacy, only succeeding in the small right atria (<60 mL). When additional cavo-tricuspid isthmus ablation was considered, Marshall-PLAN sufficed (66% efficacy) for the small left atria (<90 mL). For the bigger left atria, a more aggressive ablation approach was required, such as anterior mitral line (75% efficacy) or posterior wall isolation plus mitral isthmus ablation (77% efficacy). Virtual patients with LVAs greatly benefited from LVA ablation in the left and right atria (100% efficacy). Conversely, in the absence of LVAs, synergistic ablation and pharmacotherapy could terminate AF. In the absence of ablation, the patient's ionic current substrate modulated the response to antiarrhythmic drugs, being the inward currents critical for optimal stratification to amiodarone or vernakalant. In silico trials identify optimal strategies for AF treatment based on virtual patient characteristics, evidencing the power of human modelling and simulation as a clinical assisting tool.

Nutraceuticals: New Perspective and Approach to Prevent Dysmenorrhea

Background: The words "nutrition" and "pharmaceutical" are combined to form the phrase "nutraceutical." Nutraceuticals are foods or dietary components that have an important role in regulating and sustaining normal physiological function in humans. For the treatment of dysmenorrhoea, a variety of pharmacological medications are available, however, they all have significant side effects. Dietary supplements and lifestyle management, on the other hand, were found to have a major influence on the occurrence and control of dysmenorrhea. Objective: The objective of this paper is to study a comprehensive review of the dietary and nutritional supplements with special emphasis on dysmenorrhea. This paper focuses on understanding and interpreting the details of menstrual pain and its effective nutritional diet that can be used as a treatment for avoiding menstrual discomfort. Methods: The selection of data has been done by studying a combination of various research and review papers from different databases like PubMed, NCBI, Science Direct, WHO, Cochrane Library, and Web of Science from the year 2000-2022. Results: Based on various papers and literature reviews, we have concluded about various dietary supplements and herbs that can be used to avoid pain during mensuration followed by its all-daily requirement of nutrition on different age groups and efficacy of treatments. Conclusion: According to current evidence, young women should be instructed in the proper use of dietary supplements, nutrition, and vitamins, as well as the inclusion of effective diet and lifestyle changes such as exercise and a well-balanced diet with adequate nutrition, as these are likely to reduce the negative effects of dysmenorrhea.

Malus pumila Mill. cv Annurca apple extract might be therapeutically useful against oxidative stress and patterned hair loss.

Patterned hair loss (PHL) or androgenetic alopecia is a condition affecting about 50% of people worldwide. Several pharmacological medications have been developed over the years, but few studies have investigated their effectiveness. Therefore, new, safer and more effective strategies are required. Recent investigations showed that Annurca apple extract application could induce keratin production and promote hair growth thanks to the high amount of procyanidin B2 contained in. Hence, this study aimed to investigate the role of an Annurca apple extract in preventing PHL by testing it on human follicle dermal papilla cells (HFDPCs) for the first time. Treatment of HFDPCs with Annurca apple extract counteracted intracellular reactive oxygen species accumulation by increasing the activity of antioxidant enzymes such as superoxide dismutase 2 and catalase. Furthermore, treatment with Annurca apple extract increased β-catenin and fibroblast growth factor 2, which are involved in hair growth stimulation. These data suggest that Annurca apple extract may be a potential therapeutically useful nutraceutical product for preventing or treating hair loss by reducing oxidative stress and inducing the expression of hair growth-related factors.

An algorithm for pharmacological treatment of mania during hospitalisation.

Current evidence for pharmacological treatment of mania during hospitalisation is insufficient as there are no larger well-designed randomised trials of comparative medical treatments of mania during inpatient stays. Moreover, there is considerable variation in pharmacological medication in clinical practice during hospitalisation for mania. Based on a hospital data overview, a systematic search of the literature and a three-day consensus meeting, this narrative review proposed an algorithm for optimised pharmacological treatment of mania during hospitalisation and its subsequent scientific evaluation.