Laser Therapy Effects on Periodontal Status: A Randomized Study Using Gaussian Network Analysis and Structural Equation Modeling Approach.

Background and Objectives: This paper aims to assess the role of laser therapy in periodontitis through an innovative approach involving computational prediction and advanced modeling performed through network analysis (Gaussian graphical models-GGMs) and structural equations (SEM). Materials and Methods: Forty patients, exhibiting periodontal pockets with a minimum depth of 5 mm, were randomly divided into two groups: a control group and a laser group. Four specific indicators were measured for each tooth, namely periodontal pocket depth (PPD), clinical attachment level (CAL), bleeding on probing (BOP), and plaque index (PI), and the mean of six measured values was recorded at five time markers (baseline, 6 months, 1 year, 2 years, and 4 years). The assessment algorithm included enrollment, measurements, and differential non-surgical periodontal treatment, according to the group allocation. Scaling, root planing, and chlorhexidine 1% were conducted for the control group, and scaling, root planing and erbium, chromium:yttrium-scandium-gallium-garnet (Er,CR:YSGG) laser therapy were conducted for the laser group. Results: The main results highlight that the addition of laser treatment to scaling and root planing led to notable clinical improvements, decreasing the PPD values, reducing the BOP scores, and increasing the CAL. Conclusions: Notable relationships between the specific indicators considered were highlighted by both the GGMs and by SEM, thus confirming their suitability as proxies for the success of periodontal treatment.

Royal Jelly and Fermented Soy Extracts-A Holistic Approach to Menopausal Symptoms That Increase the Quality of Life in Pre- and Post-menopausal Women: An Observational Study.

BACKGROUND: The objective of this study was to determine the effects of royal jelly and fermented soy extracts on menopausal symptoms and on quality of life in pre- and post-menopausal women. MATERIALS AND METHOD: This prospective observational study was carried out in a Clinical Hospital of Brasov, Romania, during June 2020 and December 2021. Eighty pre- and post-menopausal women, aged between 45 and 60 years, were included in two groups. The first group (40 women) received a dietary supplement with fermented soy extract twice a day for eight weeks and the second group (40 women) received the same dietary supplement with fermented soy extracts and 1500 mg of royal jelly capsules for eight weeks. After the treatment, the MENQOL score, DASS-21 score, and the mean number and intensity of daily hot flushes were recorded and compared with baseline values. RESULTS: After eight weeks of treatment, the score of the MENQOL questionnaire and all its domains' scores decreased in comparison with the baseline in both groups (p < 0.001). Also, the DASS-21 score (p < 0.001), depression score (p < 0.001), anxiety score (p < 0.001), and stress score (p < 0.001) improved. The mean number and the intensity of hot flushes decreased in both groups (p < 0.001). Comparing these variables after the treatment in both groups, we observed that the women who received dietary supplements with fermented soy extracts and royal jelly capsules recorded better scores for MENQOL (vasomotor, physical, and psychosocial domains) and a more reduced mean number of daily hot flushes. CONCLUSIONS: This observational study suggests that both dietary fermented soy supplements and royal jelly capsules possess beneficial effects against menopausal symptoms, increase the quality of life in pre- and post-menopausal women, and that the effects might be significantly improved if those dietary supplements are administered in association.

Development of biosensors for detection of fibrinogen: a review.

Fibrinogen as a major inflammation marker and blood coagulation factor has a direct impact on the health of humanity. The variations in fibrinogen content lead to risky conditions such as bleeding and cardiovascular diseases. So, accurate methods for monitoring of this glycoprotein are of high importance. The conventional methods, such as the Clauss method, are time consuming and require highly specialized expert analysts. The development of fast, simple, easy to use, and inexpensive methods is highly desired. In this way, biosensors have gained outstanding attention since they offer means for performing analyses at the points-of-care using self-testing devices, which can be applied outside of clinical laboratories or hospital. This review indicates that different electrochemical and optical sensors have been successfully implemented for the detection of fibrinogen under normal levels of fibrinogen in plasma. The biosensors for the detection of fibrinogen have been designed based on the quartz crystal microbalance, field-effect transistor, electrochemical impedance spectroscopy, amperometry, surface plasmon resonance, localized surface plasmon resonance, and colorimetric techniques. Also, this review demonstrates the utility of the application of nanoparticles in different detection techniques.

Metformin: The Winding Path from Understanding Its Molecular Mechanisms to Proving Therapeutic Benefits in Neurodegenerative Disorders.

Metformin, a widely prescribed medication for type 2 diabetes, has garnered increasing attention for its potential neuroprotective properties due to the growing demand for treatments for Alzheimer's, Parkinson's, and motor neuron diseases. This review synthesizes experimental and clinical studies on metformin's mechanisms of action and potential therapeutic benefits for neurodegenerative disorders. A comprehensive search of electronic databases, including PubMed, MEDLINE, Embase, and Cochrane library, focused on key phrases such as "metformin", "neuroprotection", and "neurodegenerative diseases", with data up to September 2023. Recent research on metformin's glucoregulatory mechanisms reveals new molecular targets, including the activation of the LKB1-AMPK signaling pathway, which is crucial for chronic administration of metformin. The pleiotropic impact may involve other stress kinases that are acutely activated. The precise role of respiratory chain complexes (I and IV), of the mitochondrial targets, or of the lysosomes in metformin effects remains to be established by further research. Research on extrahepatic targets like the gut and microbiota, as well as its antioxidant and immunomodulatory properties, is crucial for understanding neurodegenerative disorders. Experimental data on animal models shows promising results, but clinical studies are inconclusive. Understanding the molecular targets and mechanisms of its effects could help design clinical trials to explore and, hopefully, prove its therapeutic effects in neurodegenerative conditions.

Roflumilast 0.3% Cream: a Phosphodiesterase 4 Inhibitor for the Treatment of Chronic Plaque Psoriasis.

BACKGROUND: Plaque psoriasis is a chronic dermatologic autoimmune disease that affects adults and children. Roflumilast 0.3% cream is currently the only topical phosphodiesterase 4 inhibitor indicated for the treatment of plaque psoriasis in patients 12 years or older. PHARMACODYNAMICS AND PHARMACOKINETICS: Roflumilast inhibits phosphodiesterase 4 inhibitor enzyme leading to the accumulation of cyclic adenosine monophosphate, which suppresses the inflammatory mediators interferon-γ and tumor necrosis factor-α. Roflumilast, applied once daily, reaches steady state by day 15 and has a half life of approximately 4 days in adults. Roflumilast undergoes extensive hepatic metabolism by cytochrome P450 enzymes and conjugation. Roflumilast is 99% bound to plasma proteins. CLINICAL TRIALS: Roflumilast efficacy and safety were evaluated in the DERMIS-1 and DERMIS-2 clinical trials. These identically designed, double-blind, vehicle-controlled phase 3 trials randomized 881 patients to roflumilast 0.3% cream or vehicle, applied once daily for 8 weeks. In DERMIS-1, the Investigator Global Assessment success rate was 42.4% with roflumilast 0.3% cream compared with 6.1% with the vehicle (32.3%-46.9%; P <0.001). Similarly, in DERMIS-2, the Investigator Global Assessment success rate was 37.5% with roflumilast 0.3% cream compared with 6.9% with the vehicle (20.8%-36.9%; P <0.001). Of 881 participants, 1% discontinued treatment with roflumilast cream due to adverse reactions compared with 1.3% treated with vehicle. Urticaria at the application site (0.3%) was the most common adverse reaction that led to discontinuation of roflumilast. THERAPEUTIC ADVANCE: To date, topical corticosteroids are the most commonly used agents to treat mild plaque psoriasis. Sensitive areas are often challenging to treat with existing topical therapy, including corticosteroids. Topical roflumilast has shown to be effective in treating sensitive areas, including skin folds, and may be an alternative to systemic therapy for some patients. The Food and Drug Administration approved topical roflumilast for the treatment of plaque psoriasis, including intertriginous areas, for patients 12 years or older.

Nivolumab/Relatlimab-rmbw: A Novel Dual Combination Therapy to Treat Adult and Pediatric Patients With Unresectable or Metastatic Melanoma.

BACKGROUND: Immune checkpoint inhibitors control effector mechanisms and work to restore downregulated T-cells in patients with melanoma. Examples of such include programmed death-1 inhibitors and lymphocyte-activating gene 3 inhibitors. The combination of nivolumab, a programmed death-1 inhibitor, and relatlimab-rmbw, a lymphocyte-activating gene 3 inhibitor, has shown antitumor activity and improved progression-free survival in patients with unresectable or metastatic melanoma. MECHANISM OF ACTION PHARMACOKINETICS/PHARMACODYNAMICS: The fixed-dose combination of nivolumab and relatlimab immunotherapy is approved for adults and pediatrics 12 years of age or older with metastatic or unresectable melanoma. Volume of distribution is 6.6 L for relatlimab and nivolumab, and half-life is 27 and 26 days, respectively. Clearance at steady state is 7.6 mL/h for nivolumab and 5.5 mL/h for relatlimab. Sex, age, race, and mild hepatic/renal impairment had no clinical effect on clearance. The exposure-response relationship and pharmacodynamic response for the safety and effectiveness of nivolumab/relatlimab-rmbw have not been fully characterized. Safety concerns include severe and fatal immune-mediated adverse reactions, infusion-related reactions, and complications of allogeneic hematopoietic stem cell transplantation, and fetal toxicity. Dosing is determined by patient's age and weight. Solution is infused over a 30-minute timeframe. CLINICAL TRIALS: In the RELATIVITY-047 trial, patients received nivolumab or nivolumab/relatlimab-rmbw. Results showed superiority of dual therapy over monotherapy with a progression-free survival of 10.1 months (95% CI, 6.4-15.7) compared with 4.6 months (95% CI, 3.4-5.6) and hazard ratio of 0.75 (95% CI, 0.62-0.92); P = 0.006, respectively. No safety concerns were observed compared with monotherapy with treatment-related adverse events occurring in 18.9% of patients on combination therapy compared with 9.7% on nivolumab alone. THERAPEUTIC ADVANCE: The novel mechanism and improvement in progression-free survival compared with standard of care highlight the therapeutic advancement of nivolumab/relatlimab-rmbw in the treatment of unresectable and metastatic melanoma.

Mitapivat: A Quinolone Sulfonamide to Manage Hemolytic Anemia in Adults With Pyruvate Kinase Deficiency.

BACKGROUND: Pyruvate kinase (PK) deficiency is a rare enzyme-linked glycolytic defect resulting in mild-to-severe chronic persistent erythrocyte hemolysis. The disease is an autosomal recessive trait caused by mutations in the PK liver and red blood cell gene characterized by insufficient erythrocyte PK activity. PK deficiency is most diagnosed in persons of northern European descent and managed with packed red blood cell transfusions, chelation, and splenectomy with cholecystectomy. Mitapivat is the first approved therapy indicated for hemolytic anemia in adults with PK deficiency with the potential for delaying splenectomy in mild-moderate disease. MECHANISM OF ACTION, PHARMACODYNAMICS, AND PHARMACOKINETICS: Mitapivat is a PK activator that acts by allosterically binding to the PK tetramer and increases PK activity. The red blood cell form of PK is mutated in PK deficiency, which leads to reduced adenosine triphosphate, shortened red blood cell lifespan, and chronic hemolysis. The half-life of elimination is 3-5 hours, with 73% bioavailability, 98% plasma protein binding, and a median duration of response of 7 months. CLINICAL TRIALS: Mitapivat has been investigated through various clinical trials for different therapeutic indications. Pivotal trials that serve the primary focus throughout this article are ACTIVATE, ACTIVATE-T, and RISE. ACTIVATE is a phase 3, randomized, double-blind, placebo-controlled study that evaluated the efficacy and safety of mitapivat in adult patients who were not receiving regular blood transfusions. Contrarily, ACTIVATE-T explored the safety and efficacy of mitapivat in adults with PK deficiency who received regular blood transfusions. Both trials demonstrated favorable use of mitapivat in PK deficiency. Focusing on another indication, the ongoing RISE trial investigates the optimal dosage of mitapivat in sickle cell disease. THERAPEUTIC ADVANCE: Mitapivat is an appropriate treatment for adults with PK deficiency requiring transfusions and may be considered for patients with symptomatic anemia who do not require transfusions and/or PK deficiency with compensated hemolysis without overt anemia.

Pharmacological Basis for Antispasmodic, Bronchodilator, and Antidiarrheal Potential of Dryopteris ramosa (Hope) C. via In Vitro, In Vivo, and In Silico Studies.

Background:Dryopteris ramosa is used as an old treatment for several diseases. D. ramose fronds are eaten to treat gastrointestinal (GIT) issues and as an antibiotic. However, there is a dearth of literature justifying its traditional use. Aims and objectives: the current work used biological and molecular docking studies to support traditional usage and elucidate D. ramosa's multitarget mechanism. Materials and methods: Bioactive compounds were docked in silico. Force displacement transducers coupled with a power lab data gathering system examined the effects of compounds on rabbit jejunum, trachea, and aorta tissues. Albino mice and rats were used for in vivo studies. Results: Bioactive compounds interacted with inflammation, asthma, and diarrhea genes, according to in silico studies. D. ramosa crude extract (Dr.Cr) calmed impulsive contractions and K+ (80 mM)-provoked contractions in the jejunum and tracheal tissue dose-dependently, showing the presence of the Ca++ channel-blocking (CCB) effect, further verified by the rightward parallel shift of CRCs equivalent to verapamil. Polarity-based fractionation showed spasmolytic activity in Dr.DCM and muscarinic receptors mediated spasmogenic activity in the Dr.Aq fraction. Dr.Cr vasoconstricted the aortic preparation, which was totally blocked by an angiotensin II receptor antagonist. This suggests that Dr. Cr's contractile effect is mediated through angiotensin receptors. In rats and mice, it showed anti-inflammatory and antidiarrheal action. Conclusion: This study supports the traditional medicinal uses of D. ramosa against GIT disorders and may be an important therapeutic agent in the future.

Daridorexant, an Orexin Receptor Antagonist for the Management of Insomnia.

BACKGROUND: Insomnia is a common sleep disorder that is diagnosed primarily by patients' subjective reported symptoms. Daridorexant is a new dual orexin receptor antagonist that was recently approved by Food and Drug Administration for insomnia characterized by difficulty falling asleep and/or maintaining sleep. MECHANISM OF ACTION, PHARMACODYNAMICS, AND PHARMACOKINETICS: The orexin neuropeptide signaling system plays a role in wakefulness, and blocking the wake-promoting neuropeptides results in diminished wake signaling, thus exerting a sedative effect using an entirely different mechanism of action than the classical sleep promoting agents. The drug has quick onset of action, high volume of distribution, and high protein binding. Pharmacokinetics and pharmacodynamic parameters were similar in patients of different sex and age and were not significantly affected by race, body size, or mild-to-moderate kidney impairment. Dose limitation to 25 mg in moderate liver impairment and no use in severe liver impairment are recommended. The drug undergoes hepatic CYP3A4 metabolism; thus, caution with strong CYP3A4 inhibitors and inducers is warranted. CLINICAL TRIALS: The drug was approved based on phase 3 trials involving study 1 and study 2. Study 1 noted daridorexant at doses of 25 and 50 mg demonstrated a statistically significant improvement in wake time after sleep onset, latency to persistent sleep, and self-reported total sleep time against placebo at months 1 and 3. Similarly in study 2, compared with placebo, the 25 mg dose demonstrated statistically significant improvement in wake time after sleep onset, latency to persistent sleep, and self-reported total sleep time at months 1 and 3. Treatment-emergent adverse events were similar for daridorexant and placebo, with nasopharyngitis and headache most frequently reported. THERAPEUTIC ADVANCE: Daridorexant is a novel agent with demonstrated efficacy in sleep onset and maintenance and decrease in daytime sedation. Preliminary results from a 1-year extension study note similar incidences of mild-to-moderate side effects as noted in previous trials. Further studies are needed to establish its place in the pharmacological treatment of insomnia.

Abrocitinib for the Treatment of Moderate-to-Severe Atopic Dermatitis.

BACKGROUND: Atopic dermatitis (AD) is ranked as the third most prevalent skin condition with a worldwide prevalence of 2.4%. Atopic dermatitis is a common form of eczema. It develops in infancy or childhood and continues into adulthood with symptoms ranging from mild to severe. Pruritis and inflammation are the hallmark symptoms of AD. MECHANISM OF ACTION, PHARMACODYNAMICS, AND PHARMACOKINETICS: Abrocitinib is a JAK1 selective inhibitor; inhibition results in a decreased interleukin (IL) 4 activation and decreased pruritis in a patient with AD. Abrocitinib is hepatically metabolized by multiple cytochrome P450 enzymes, and dose modification may be required when administered with concurrent medications. CLINICAL TRIALS: At least 6 JAK1 Atopic Dermatitis Efficacy and Safety (JADE) trials were conducted evaluating Investigator's Global Assessment and Eczema Area and Severity Index score for efficacy. All JADE trials showed abrocitinib 100 mg and 200 mg doses efficacious when compared with placebo. Common adverse reactions were related to gastrointestinal disturbances, headache, and acne. Serious adverse reactions to assess risk for include serious infections, malignancy, major adverse cardiovascular events, and venous thromboembolisms. THERAPEUTIC ADVANCE: Abrocitinib provides a valuable treatment option for patients with moderate-to-severe AD unresponsive to other therapies for those candidates without a high risk for significant adverse reaction associated with its use.

Anakinra-An Interleukin-1 Receptor Antagonist for COVID-19.

BACKGROUND: Coronavirus disease (COVID-19) caused by SARS-CoV-2 virus caused a global pandemic in 2019. There are limited pharmacologic options available. The Food and Drug Administration initiated an emergency use authorization process to expedite pharmacologic agents to treat COVID-19. There are several agents available through the emergency use authorization process, ritonavir-boosted nirmatrelvir, remdesivir, and baricitinib. Anakinra is an interleukin (IL)-1 receptor antagonist that exhibits properties in fighting against COVID-19. MECHANISM OF ACTION, PHARMACODYNAMICS, AND PHARMACOKINETICS: Anakinra is a recombinant IL-1 receptor antagonist. The epithelial cell damage that may occur with COVID-19 enhances the release of IL-1, which plays a central role in severe cases. Thus, drugs that inhibit the IL-1 receptor may be beneficial in the management of COVID-19. Anakinra has good bioavailability after subcutaneous injection and a half-life of up to 6 hours. CLINICAL TRIALS: The SAVE-MORE, double-blind, randomized controlled trial, phase 3 evaluated the efficacy and safety of anakinra. Anakinra 100 mg was given subcutaneously daily for up to 10 days in patients with moderate and severe COVID-19 and plasma suPAR ≥6 ng/mL. Anakinra group had a 50.4% fully recovered with no viral RNA detected on day 28 versus 26.5% for placebo, and more than 50% of relative decrease in mortality. A significantly decreased risk of worse clinical outcome was observed. THERAPEUTIC ADVANCE: COVID-19 causes global pandemic and a serious viral disease. There are limited therapy options to combat this deadly disease. Anakinra is an IL-1 receptor antagonist and shown to be effective for the treatment of COVID-19 in some trials but not others. Anakinra, the first in this class, seems to have a mix result for the treatment of COVID-19.

Tirzepatide: A Dual Glucose-dependent Insulinotropic Polypeptide and Glucagon-Like Peptide-1 Agonist for the Management of Type 2 Diabetes Mellitus.

BACKGROUND: Diabetes is a chronic disease that can lead to many complications, and controlling glucose balance is essential. Incretin hormones are produced in the gut and are essential to maintaining glucose homeostasis. Their effects range from increasing insulin synthesis, insulin secretion, and glucose sensing and decreasing glucagon secretion to promote satiety and suppressing appetite. Tirzepatide is a first in class dual glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide (GIP) analog approved for the management of adult patients with type 2 diabetes mellitus as an adjunct to diet and exercise. PHARMACODYNAMICS AND PHARMACOKINETICS: Tirzepatide is a synthetic chemical structure based on the GIP sequence and consists of 39 amino acid peptides. Tirzepatide increases insulin secretion, reduces glucagon release in a glucose-dependent manner, decreases fasting and postprandial glucose levels, promotes satiety, decreases body weight, and delays gastric emptying. Pharmacodynamics and pharmacokinetics properties of tirzepatide were similar in patients with kidney and hepatic impairment, and its metabolites are excreting through urine and feces. CLINICAL TRIALS: The SURPASS trials are pivotal phase 3 trials assessing the efficacy and safety of tirzepatide as monotherapy and as an add-on to different antihyperglycemic drugs for the management of T2DM. Tirzepatide consistently showed reductions in HbA1c, as well as benefits with weight loss, with common adverse events reported related to gastrointestinal issues. THERAPEUTIC ADVANCE: Tirzepatide is a novel first in class dual GIP and glucagon-like peptide-1 agonist that improves overall glycemic control as an adjunct to diet and exercise. It has the potential benefits in other therapeutic areas such as obesity.

A Clinical Pharmacology and Therapeutics Teacher's Guide to Race-Based Medicine, Inclusivity, and Diversity.

The relationship between race and biology is complex. In contemporary medical science, race is a social construct that is measured via self-identification of study participants. But even though race has no biological essence, it is often used as variable in medical guidelines (e.g., treatment recommendations specific for Black people with hypertension). Such recommendations are based on clinical trials in which there was a significant correlation between self-identified race and actual, but often unmeasured, health-related factors such as (pharmaco)genetics, diet, sun exposure, etc. Many teachers are insufficiently aware of this complexity. In their classes, they (unintentionally) portray self-reported race as having a biological essence. This may cause students to see people of shared race as biologically or genetically homogeneous, and believe that race-based recommendations are true for all individuals (rather than reflecting the average of a heterogeneous group). This medicalizes race and reinforces already existing healthcare disparities. Moreover, students may fail to learn that the relation between race and health is easily biased by factors such as socioeconomic status, racism, ancestry, and environment and that this limits the generalizability of race-based recommendations. We observed that the clinical case vignettes that we use in our teaching contain many stereotypes and biases, and do not generally reflect the diversity of actual patients. This guide, written by clinical pharmacology and therapeutics teachers, aims to help our colleagues and teachers in other health professions to reflect on and improve our teaching on race-based medical guidelines and to make our clinical case vignettes more inclusive and diverse.

Drug-drug interactions involving combinations of antipsychotic agents with antidiabetic, lipid-lowering, and weight loss drugs.

INTRODUCTION: Patients with severe mental illness (SMI) have a high risk for diabetes, dyslipidemia, and other components of metabolic syndrome. Patients with these metabolic comorbidities and cardiac risk factors should receive not only antipsychotics but also medications aiming to reduce cardiovascular risk. Therefore, many patients may be exposed to clinically relevant drug-drug interactions. AREAS COVERED: This narrative review summarizes data regarding the known or potential drug-drug interactions between antipsychotics and medications treating metabolic syndrome components, except for hypertension, which has been summarized elsewhere. A literature search in PubMed and Scopus up to 7/31/2021 was performed regarding interactions between antipsychotics and drugs used to treat metabolic syndrome components, aiming to inform clinicians' choice of medication for patients with SMI and cardiometabolic risk factors in need of pharmacologic interventions. EXPERT OPINION: The cytochrome P450 system and, to a lesser extent, the P-glycoprotein transporter is involved in the pharmacokinetic interactions between antipsychotics and some statins or saxagliptin. Regarding pharmacodynamic interactions, the available information is based mostly on small studies, and for newer classes, like PCSK9 inhibitors or SGLT2 inhibitors, data are still lacking. However, there is sufficient information to guide clinicians in the process of selecting safer antipsychotic-cardiometabolic risk reduction drug combinations.

Teaching resources for the European Open Platform for Prescribing Education (EurOP2E)-a nominal group technique study.

The European Open Platform for Prescribing Education (EurOP2E) seeks to improve and harmonize European clinical pharmacology and therapeutics (CPT) education by facilitating international collaboration and sharing problem-based, online, open educational resources. The COVID-19 pandemic forced teachers to switch to virtual modalities, highlighting the need for high-quality online teaching materials. The goal of this study was to establish the online problem-based teaching resources needed to sustain prescribing education during the pandemic and thereafter. A nominal group technique study was conducted with prescribing teachers from 15 European countries. Results were analyzed through thematic analysis. In four meetings, 20 teachers from 15 countries proposed and ranked 35 teaching materials. According to the participants, the most necessary problem-based-online teaching materials related to three overarching themes. Related to learning outcomes for CPT, participants proposed creating prescription scenarios, including materials focusing on background knowledge and resources on personalized medicine and topical/ethical issues such as the prescription's impact on planetary health. Second, related to teaching, they proposed online case discussions, gamification and decision support systems. Finally, in relation to faculty development, they recommend teacher courses, a repository of reusable exam questions and harmonized formularies. Future work will aim to collaboratively produce such materials.

Comprehensive Targeted Treatment for Neuropathic and Nociceptive Pain in Palliative Care Patients.

BACKGROUND: Pain is a common symptom in patients with advanced, metastatic, or terminal cancer. Neuropathic pain and psycho-emotional suffering are factors that increase the difficulty of pain management. Pain control in patients with cancer remains a challenge for medical professionals. STUDY QUESTION: What is the evolution of neuropathic/mixed pain compared with nociceptive pain under standardized treatment in patients with cancer? STUDY DESIGN: A prospective, longitudinal, open-label, nonrandomized study was conducted on patients with cancer pain. MEASURES AND OUTCOMES: Pain type was assessed at admission using the modified Brief Pain Inventory, and pain intensity was assessed daily using the Numerical Rating Scale for 14 days and on days 21 and 28. Screening of depression was performed on days 1, 7, 14, 21, and 28 using the Hamilton Depression Rating Scale. Patients with pain and depression received analgesics with antidepressants, while patients without depression received analgesics or analgesics with an anticonvulsant depending on the pain subtype. RESULTS: Of 72 patients, 23 had nociceptive pain and 49 had neuropathic/mixed pain. At admission, pain intensity was higher for patients with neuropathic/mixed pain compared with nociceptive pain (mean values: 7.06 vs. 5.82) with statistical significance ( P = 0.001) and remained as such at the end of this study (mean values: 3.77 vs. 2.73). A decrease in the mean pain intensity was observed in all types of pain, but without statistical significance regardless of pain type and treatment protocol used ( P = 0.77). If depression was present, antidepressants combined with analgesics decreased pain and depression scores significantly ( P = 0.001). CONCLUSIONS: Patients with neuropathic/mixed pain have higher levels of pain and lower response to treatment. Identifying psycho-emotional suffering can improve pain control by intervening in the physical and psycho-emotional components of pain.

Drug-drug interactions involving antipsychotics and antihypertensives.

INTRODUCTION: Antipsychotics represent the mainstay in the treatment of patients diagnosed with major psychiatric disorders. Hypertension, among other components of metabolic syndrome, is a common finding in these patients. For their psychiatric and physical morbidity, many patients receive polypharmacy, exposing them to the risk of clinically relevant drug-drug interactions. AREAS COVERED: This review summarizes the knowledge regarding the known or potential drug-drug interactions between antipsychotics and the main drug classes used in the treatment of hypertension. We aimed to provide the clinician an insight into the pharmacokinetic and pharmacodynamic interactions between these drugs for a better choice of combinations of drugs to treat both the mental illness and cardiovascular risk factors. For this, we performed a literature search in PubMed and Scopus databases, up to 31 July 2021. EXPERT OPINION: The main pharmacokinetic interactions between antipsychotics and antihypertensive drugs involve mainly the cytochrome P450 system. The pharmacodynamic interactions are produced by multiple mechanisms, leading to concurrent binding to the same receptors. The data available regarding drug-drug interactions is mostly based on case reports and small studies and therefore should be interpreted with caution. The current knowledge is sufficiently strong to guide clinicians in selecting safer drug combinations as summarized here.

WHODAS Assessment Feasibility and Mental Health Impact on Functional Disability in Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE), besides rheumatological dysfunction, manifests in neuropsychiatric disorders like depression and anxiety. Mental health illnesses in SLE patients have a high prevalence and a profound impact on quality of life, generating an increased disability and premature mortality. This study aimed to establish the degree of disability in patients with SLE and the impact of depression and anxiety on patients' functioning. Additionally, the study aimed to verify whether World Health Organization-Disability Assessment Schedule (WHODAS) 2.0 is suitable for the evaluation of patients with SLE associating depression and/or anxiety symptoms. Cross-sectional research was performed, including adult patients, diagnosed with SLE. To evaluate depression, anxiety, and functioning, approved questionnaires Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale, and, World Health Organization-Disability Assessment Schedule (WHODAS) were applied. Confirmatory factor analysis was performed on WHODAS subscales. Sixty-two patients were included in the research, with a mean of SLE diagnosis of 12.48 years; 53 patients (85%) had depression (p < 0.001). Anxiety was found in 38 patients (61.29%, p < 0.05). WHODAS assessment results depicted that 39 patients (62.90%, p < 0.05) manifested disability, from which 26 (66.66%, p < 0.05) presented moderate and severe disability. A strong correlation between the severity of anxiety and the degree of disability (r > 0.6, p < 0.001) was found. The WHODAS scale assessment proved to be a valuable tool for SLE patient's functioning assessment. This study suggests that depression and anxiety negatively impact WHODAS disability scores, decreasing the quality of life in SLE patients.

Switch from Olanzapine Long-Acting Injectable to its Oral Equivalent during COVID-19 Pandemic: a Real World Observational Study.

Schizophrenia is a psychiatric condition with chronic evolution, one of the most disabling diseases. The main cause for the disease's progression is considered to be the lack of compliance with the treatment. Long-acting injectable antipsychotics (LAIs) are an important treatment option for patients with schizophrenia. Olanzapine long-acting injection (OLZ-LAI) is a pamoate monohydrate salt of olanzapine that is administered by deep intramuscular gluteal injection. The aim of this paper is to report the effects of a sudden and unplanned switch from olanzapine long-acting injectable to oral olanzapine in remitted patients with schizophrenia due to restrictions caused by the COVID-19 pandemic. An observational study conducted in the Clinical Hospital of Psychiatry and Neurology of Brasov, Romania between April 2020 and March 2021. 27 patients with OLZ-LAI were entered into the study. Of 27 cases, 21 patients preferred to be switched to oral olanzapine (77.77%). Only 6 patients continued with the long-acting formulation. The main reason for the initiation of olanzapine pamoate in all the patients was non-adherence to oral medication (80.95%), and the mean age of starting LAI olanzapine was 36.42 years (SD ± 10.09). Within the following 12 months after switching from olanzapine LAI to OA, 15 patients (71.42%) relapsed, and 12 were admitted to the emergency psychiatric unit. The COVID-19 pandemic has brought multiple disservices to current medical practice. Sudden and unplanned switch from olanzapine long-acting formulation to oral olanzapine was followed by the high rate of relapse in remitted schizophrenia.

Trimetazidine Therapy in Coronary Artery Disease: The Impact on Oxidative Stress, Inflammation, Endothelial Dysfunction, and Long-Term Prognosis.

BACKGROUND: In coronary artery disease (CAD), reduction of perfusion in coronary arteries is followed by increases of oxidative stress and decreases of adenosine triphosphate reserve. In this condition, trimetazidine (TMZ), a metabolic anti-ischemic agent, seems to be an ideal therapeutic agent because it increases mitochondrial adenosine triphosphate production. STUDY QUESTION: To evaluate the impact of TMZ on oxidative stress, inflammation, endothelial dysfunction, and long-term prognosis in CAD. STUDY DESIGN: Patients with CAD with symptoms not adequately controlled were enrolled consecutively for a period of 18 months. MEASURES AND OUTCOMES: Five hundred seventy patients with CAD were enrolled in a prospective study and divided into 4 groups in relation with the type of CAD and the addition of TMZ to optimal medical therapy (OMT). The impact of TMZ added to OMT on oxidative stress (total antioxidant status, antioxidized low-density lipoprotein antibodies, and antimyeloperoxidase antibodies), endothelial dysfunction (flow-mediated dilatation and von Willebrand factor activity), and inflammation (C-reactive protein and fibrinogen) at 6 months and on long-term prognosis in CAD in comparison with OMT at 5 years of follow-up was evaluated. RESULTS: At 6 months, TMZ added to OMT significantly decreased the incidence of oxidative stress in CAD (P < 0.03) and reduced endothelial dysfunction and inflammation only in non-ST-elevation acute coronary syndrome (NSTE-ACS, P < 0.04). TMZ added to OMT with or without interventional/surgical vascularization led to decreased readmission for NSTE-ACS and heart failure (P < 0.05) in all patients with CAD and a significantly reduced incidence of cardiovascular death, acute myocardial infarction, and stroke (P < 0.05) in patients with NSTE-ACS at 5 years of follow-up. CONCLUSIONS: In patients with NSTE-ACS, TMZ added to OMT with or without interventional and/or surgical reperfusion reduced oxidative stress, endothelial dysfunction, inflammation, and major acute cardiovascular events, whereas in patients with chronic coronary syndrome, TMZ decreased oxidative stress and readmission for ACS and heart failure.