Epidemiological Trends and Clinicopathological Characteristics of Oral Leukoplakia: A Retrospective Analysis From a Single Institution in Chennai, Tamil Nadu, India.

Background India has a high prevalence of oral potentially malignant disorders and malignant transformation. Cases of oral leukoplakia are not commonly encountered, and only a small cohort of patients undergo biopsies for the same. This study aims to assess the various etiological factors causing leukoplakia, the clinical features, histopathological findings, and treatment received by the patients who were histopathologically diagnosed with oral leukoplakia. Methodology Oral leukoplakia cases were included in this study from total biopsy samples received in the oral pathology department. Details were collected from the Dental Information Archival Software of our institution. The period analyzed was from January 1, 2021, to December 31, 2023. Relevant clinical and histopathological details were retrieved and tabulated. Statistical analysis (chi-square test) was used to assess the association between the clinicopathological parameters using SPSS software version 21.0 (IBM Corp., Armonk, NY, USA) with a significance level set at a p-value <0.05. Results A total of 76 oral leukoplakia cases were retrieved from 2,600 biopsy samples. The prevalence of oral leukoplakia was 3.1% to 3.4% for the three years. Leukoplakia was commonly observed in those aged 51 to 60 years (33%). Overall, 21% of the patients with leukoplakia showed severe epithelial dysplasia, 22% showed mild epithelial dysplasia, and 39% showed moderate epithelial dysplasia. Moreover, 30% of the patients presented with leukoplakia and oral submucous fibrosis and showed varying degrees of epithelial dysplasia. Finally, 45% of the patients were managed conservatively using pharmacotherapy. Conclusions Severe epithelial dysplasia was commonly associated with oral leukoplakia. Oral submucous fibrosis was also found to be associated with leukoplakia and showed epithelial dysplasia. None of our proliferative verrucous leukoplakia cases showed any association with oral submucous fibrosis. Surgical management was the preferred treatment.

Expert opinion on screening, diagnosis and management of diabetic peripheral neuropathy: a multidisciplinary approach.

The proposed expert opinion aimed to address the current knowledge on conceptual, clinical, and therapeutic aspects of diabetic peripheral neuropathy (DPN) and to provide a guidance document to assist clinicians for the best practice in DPN care. The participating experts consider the suspicion of the disease by clinicians as a key factor in early recognition and diagnosis, emphasizing an improved awareness of the disease by the first-admission or referring physicians. The proposed "screening and diagnostic" algorithm involves the consideration of DPN in a patient with prediabetes or diabetes who presents with neuropathic symptoms and/or signs of neuropathy in the presence of DPN risk factors, with careful consideration of laboratory testing to rule out other causes of distal symmetric peripheral neuropathy and referral for a detailed neurological work-up for a confirmative test of either small or large nerve fiber dysfunction in atypical cases. Although, the first-line interventions for DPN are currently represented by optimized glycemic control (mainly for type 1 diabetes) and multifactorial intervention (mainly for type 2 diabetes), there is a need for individualized pathogenesis-directed treatment approaches for DPN. Alpha-lipoic acid (ALA) seems to be an important first-line pathogenesis-directed agent, given that it is a direct and indirect antioxidant that works with a strategy targeted directly against reactive oxygen species and indirectly in favor of endogenous antioxidant capacity for improving DPN conditions. There is still a gap in existing research in the field, necessitating well-designed, robust, multicenter clinical trials with sensitive endpoints and standardized protocols to facilitate the diagnosis of DPN via a simple and effective algorithm and to track progression of disease and treatment response. Identification of biomarkers/predictors that would allow an individualized approach from a potentially disease-modifying perspective may provide opportunities for novel treatments that would be efficacious in early stages of DPN, and may modify the natural course of the disease. This expert opinion document is expected to increase awareness among physicians about conceptual, clinical, and therapeutic aspects of DPN and to assist them in timely recognition of DPN and translating this information into their clinical practice for best practice in the management of patients with DPN.

Optimizing anticoagulation therapy for in-hospital patients on direct oral anticoagulants: a single-centre modified Delphi study.

AIMS: The management of patients treated with direct oral anticoagulants (DOACs) during hospitalization is a common challenge in clinical practice. Although bridging is generally not recommended, too often DOACs are switched to parenteral therapy with low molecular weight heparins. Our objectives were to update a local guideline for perioperative DOAC management and to develop a guideline for the anticoagulation management in non-surgical patients regarding temporary DOAC discontinuation. METHODS: We executed a two-step modified Delphi study in a 1000-bed university hospital in Belgium. The Delphi questionnaires were developed based on a literature review and a telephone survey of prescribers. Two expert panels were established: one dedicated to perioperative DOAC management and the other to DOAC management in non-surgical patients. Both panels completed two rounds, commencing with an individual and online round, followed by a face-to-face group session. RESULTS: After the two-round Delphi process, the updated perioperative guideline on DOAC management included reasons for delaying the resumption of DOACs following surgery, such as oral intake not possible, the probability of re-intervention within 3 days, and insufficient haemostasis (e.g. active clinically significant haematoma, haemorrhagic drains or wounds). Furthermore, a guideline for non-surgical hospitalized patients was developed, outlining possible reasons for interrupting DOAC therapy. Both guidelines offer clear anticoagulation therapy strategies corresponding to the identified scenarios. CONCLUSIONS: We have updated and developed guidelines for DOAC management in surgical and non-surgical patients during hospitalization, which aim to support prescribers and to enhance targeted prescription review by hospital pharmacists.

The Surgical Infection Society Guidelines on the Management of Intra-Abdominal Infection: 2024 Update.

Background: The Surgical Infection Society (SIS) published evidence-based guidelines for the management of intra-abdominal infection (IAI) in 1992, 2002, 2010, and 2017. Here, we present the most recent guideline update based on a systematic review of current literature. Methods: The writing group, including current and former members of the SIS Therapeutics and Guidelines Committee and other individuals with content or guideline expertise within the SIS, working with a professional librarian, performed a systematic review using PubMed/Medline, the Cochrane Library, Embase, and Web of Science from 2016 until February 2024. Keyword descriptors combined "surgical site infections" or "intra-abdominal infections" in adults limited to randomized controlled trials, systematic reviews, and meta-analyses. Additional relevant publications not in the initial search but identified during literature review were included. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) system was utilized to evaluate the evidence. The strength of each recommendation was rated strong (1) or weak (2). The quality of the evidence was rated high (A), moderate (B), or weak (C). The guideline contains new recommendations and updates to recommendations from previous IAI guideline versions. Final recommendations were developed by an iterative process. All writing group members voted to accept or reject each recommendation. Results: This updated evidence-based guideline contains recommendations from the SIS for the treatment of adult patients with IAI. Evidence-based recommendations were developed for antimicrobial agent selection, timing, route of administration, duration, and de-escalation; timing of source control; treatment of specific pathogens; treatment of specific intra-abdominal disease processes; and implementation of hospital-based antimicrobial agent stewardship programs. Summary: This document contains the most up-to-date recommendations from the SIS on the prevention and management of IAI in adult patients.

Interventions for increasing medication adherence in heart failure patients: A narrative review.

Heart failure is one of the critical and most costly medical challenges of the 21st century. It is a chronic debilitating condition and adherence to medication, a precondition for successful treatment is often poor. There are various interventions for improving the adherence. Depending on the goal of the intervention, these are roughly patient centric, healthcare provider centric and system centric. We provide an overview of these interventions with a focus on effectiveness and appropriateness in different clinical situations. Their use can lead to improved patient outcomes and reduced economic burden of the disease.

Management of obesity in menopause.

The increasing prevalence of obesity imposes significant health challenges, particularly in women undergoing menopause. Effective obesity management is essential to mitigate associated comorbidities and improve quality of life. The pillars of obesity treatment encompass lifestyle modifications, pharmacotherapy and surgical interventions. Pharmacotherapy may be considered for women who do not achieve adequate weight loss through lifestyle changes alone and have obesity or overweight with risk factors. Bariatric surgery is reserved for individuals with severe obesity or those with obesity-related complications. During menopause, hormonal changes contribute to weight gain and fat redistribution, complicating obesity management. Tailored treatment strategies are necessary to address the unique challenges faced by this population. The role of physicians and gynecologists is pivotal in the multidisciplinary approach to obesity management during menopause. Gynecologists are often the primary health-care providers for menopausal women and are in a unique position to offer guidance on weight management. They can provide personalized counseling, coordinate with nutritionists, endocrinologists and bariatric specialists, and monitor the effects of obesity and its treatment on reproductive health. By integrating obesity management into routine gynecological care, gynecologists can significantly impact the overall health and well-being of menopausal women.

Effectiveness of eHealth Interventions in Improving Medication Adherence Among Patients With Cardiovascular Disease: Systematic Review and Meta-Analysis.

BACKGROUND: Nonadherence to medication among patients with cardiovascular diseases undermines the desired therapeutic outcomes. eHealth interventions emerge as promising strategies to effectively tackle this issue. OBJECTIVE: The aim of this study was to conduct a network meta-analysis (NMA) to compare and rank the efficacy of various eHealth interventions in improving medication adherence among patients with cardiovascular diseases (CVDs). METHODS: A systematic search strategy was conducted in PubMed, Embase, Web of Science, Cochrane, China National Knowledge Infrastructure Library (CNKI), China Science and Technology Journal Database (Weipu), and WanFang databases to search for randomized controlled trials (RCTs) published from their inception on January 15, 2024. We carried out a frequentist NMA to compare the efficacy of various eHealth interventions. The quality of the literature was assessed using the risk of bias tool from the Cochrane Handbook (version 2.0), and extracted data were analyzed using Stata16.0 (StataCorp LLC) and RevMan5.4 software (Cochrane Collaboration). The certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. RESULTS: A total of 21 RCTs involving 3904 patients were enrolled. The NMA revealed that combined interventions (standardized mean difference [SMD] 0.89, 95% CI 0.22-1.57), telephone support (SMD 0.68, 95% CI 0.02-1.33), telemonitoring interventions (SMD 0.70, 95% CI 0.02-1.39), and mobile phone app interventions (SMD 0.65, 95% CI 0.01-1.30) were statistically superior to usual care. However, SMS compared to usual care showed no statistical difference. Notably, the combined intervention, with a surface under the cumulative ranking curve of 79.3%, appeared to be the most effective option for patients with CVDs. Regarding systolic blood pressure and diastolic blood pressure outcomes, the combined intervention also had the highest probability of being the best intervention. CONCLUSIONS: The research indicates that the combined intervention (SMS text messaging and telephone support) has the greatest likelihood of being the most effective eHealth intervention to improve medication adherence in patients with CVDs, followed by telemonitoring, telephone support, and app interventions. The results of these network meta-analyses can provide crucial evidence-based support for health care providers to enhance patients' medication adherence. Given the differences in the design and implementation of eHealth interventions, further large-scale, well-designed multicenter trials are needed. TRIAL REGISTRATION: INPLASY 2023120063; https://inplasy.com/inplasy-2023-12-0063/.

Obesity-associated factors in psychiatric outpatients: A multicenter questionnaire survey.

The prevalence of obesity is increasing worldwide, resulting in various health issues such as hypertension, dyslipidemia, diabetes mellitus, heart disease, and a lower life expectancy. Importantly, several psychiatric disorders and the use of psychotropic medications have been linked to obesity, and the possible risk factors need further investigation. This study examined the prevalence of obesity and its associated factors using a self-administered questionnaire. Participants were recruited from three outpatient clinics and individuals who met one or more of the ICD-10 F0-F9, G4 diagnoses were included. In total, 1384 participants completed the questionnaire about their lifestyle. Statistical analysis compared the demographic and clinical characteristics of the individuals who were obese (Body Mass Index: BMI ≥25) and those who were non-obese (BMI <25). The results revealed that the factors associated with obesity in psychiatric outpatients were being male, prolonged treatment duration, eating out frequently, and use of both second- and first-generation antipsychotics. The study emphasized the importance of closely monitoring BMI in individuals with multiple obesity-related factors.

Obesity treatment in adolescents and adults in the era of personalized medicine.

In this multi-professional review, we will provide the in-depth knowledge required to work in the expanding field of obesity treatment. The prevalence of obesity has doubled in adults and quadrupled in children over the last three decades. The most common treatment offered has been lifestyle treatment, which has a modest or little long-term effect. Recently, several new treatment options-leading to improved weight loss-have become available. However, long-term care is not only about weight loss but also aims to improve health and wellbeing overall. In the era of personalized medicine, we have an obligation to tailor the treatment in close dialogue with our patients. The main focus of this review is new pharmacological treatments and modern metabolic surgery, with practical guidance on what to consider when selecting and guiding the patients and what to include in the follow-up care. Furthermore, we discuss common clinical challenges, such as patients with concurrent eating disorder or mental health problems, and treatment in the older adults. We also provide recommendations on how to deal with obesity in a non-stigmatizing way to diminish weight stigma during treatment. Finally, we present six microcases-obesity treatment for persons with neuropsychiatric disorders and/or intellectual disability; obesity treatment in the nonresponsive patient who has "tried everything"; and hypoglycemia, abdominal pain, and weight regain after metabolic surgery-to highlight common problems in weight-loss treatment and provide personalized treatment suggestions.

Effects of Lipoproteins on Metabolic Health.

Lipids are primarily transported in the bloodstream by lipoproteins, which are macromolecules of lipids and conjugated proteins also known as apolipoproteins. The processes of lipoprotein assembly, secretion, transportation, modification, and clearance are crucial components of maintaining a healthy lipid metabolism. Disruption in any of these steps results in pathophysiological abnormalities such as dyslipidemia, obesity, insulin resistance, inflammation, atherosclerosis, peripheral artery disease, and cardiovascular diseases. By studying these genetic mutations, researchers can gain valuable insights into the underlying mechanisms that govern the relationship between protein structure and its physiological role. These lipoproteins, including HDL, LDL, lipoprotein(a), and VLDL, mainly serve the purpose of transporting lipids between tissues and organs. However, studies have provided evidence that apo(a) also possesses protective properties against pathogens. In the future, the field of study will be significantly influenced by the integration of recombinant DNA technology and human site-specific mutagenesis for treating hereditary disorders. Several medications are available for the treatment of dyslipoproteinemia. These include statins, fibrates, ezetimibe, niacin, PCSK9 inhibitors, evinacumab, DPP 4 inhibitors, glucagon-like peptide-1 receptor agonists GLP1RAs, GLP-1, and GIP dual receptor agonists, in addition to SGLT2 inhibitors. This current review article exhibits, for the first time, a comprehensive reflection of the available body of publications concerning the impact of lipoproteins on metabolic well-being across various pathological states.

Efficacy and tolerability of brexpiprazole - a new antipsychotic drug from the group of dopamine D2 receptor partial agonists. / Skutecznosc i tolerancja brekspiprazolu ­ nowego leku przeciwpsychotycznego z grupy czesciowych agonistów receptorów dopaminowych D2.

Brexpiprazole is a new antipsychotic drug from the group of dopamine D2/D3 receptor partial agonists. It represents a development of the second-generation antipsychotics and is an important addition to the pharmacological treatment options for schizophrenia. The purpose of this article is to present, illustrated by the case of brexpiprazole, how advances in the pharmacological properties of new antipsychotics translate into improved results in the treatment of schizophrenia, not only in terms of symptom reduction, but also in terms of functional improvement. The ratio of activation to blocking of the D2/D3 receptor is lower for brexpiprazole than for aripiprazole and cariprazine, which may translate into a lower risk of akathisia. Brexpiprazole has also stronger antihistaminic activity, which is likely to be associated with a stronger sedative effect, a lower risk of akathisia, excessive agitation and insomnia. Brexpiprazole meets the traditional requirements for an antipsychotic drug's efficacy, i.e., compared to placebo, it brings a greater reduction in schizophrenia symptoms in short-term studies and prevents schizophrenia relapses in long-term follow-up. The highest antipsychotic efficacy was found with the highest registered dose (4 mg/day). In addition to reducing positive symptoms, brexpiprazole treatment also leads to a reduction in negative and depressive symptoms, as well as anxiety. It has also a positive effect on patients' social and personal functioning and quality of life. This action of the drug is in line with the expectations of patients and their families regarding effective treatment. It should not only reduce symptoms, but also enable a return to health, i.e., a state that, in addition to optimal health and a sense of psychological well-being, also makes it possible to maintain proper social relations.

Impact of previous gestational diabetes management on perinatal outcomes in subsequent pregnancies affected by gestational diabetes mellitus.

OBJECTIVE: To determine the impact of prior gestational diabetes mellitus (GDM) on perinatal outcomes in a subsequent GDM pregnancy. METHODS: This retrospective cohort study included 544 multiparous patients with two consecutive pregnancies between 2012-2019, where the second (index) pregnancy was affected by GDM. The primary exposure was prior GDM diagnosis, categorized into medical and dietary management. The primary outcome was a composite including need for pharmacotherapy, large-for-gestational age, or neonatal hypoglycemia. Adjusted odds ratios (aOR) were calculated using multivariable logistic regression controlling for maternal age, pre-pregnancy body mass index, and gestational age at GDM diagnosis in the index pregnancy. RESULTS: Of the 544 patients, 164 (30.1%) had prior GDM. Prior GDM significantly increased the likelihood of composite outcome compared to no prior GDM (74.4% vs. 57.4%; P < 0.001). After adjusting for confounders, prior GDM remained significantly associated with the composite outcome (aOR 2.03, 95% confidence interval [CI] 1.31-3.15). Stratifying by prior GDM treatment modality, a significant association was found for prior pharmacotherapy-controlled GDM (aOR 3.29, 95% CI 1.64-6.59), but not for prior diet-controlled GDM (aOR = 1.54, 95% CI 0.92-2.60). CONCLUSION: A history of pharmacotherapy-controlled GDM in a previous pregnancy increases odds of adverse perinatal outcomes in a subsequent GDM pregnancy.

High-intensity care for GDMT titration.

Heart failure (HF) is a systemic disease associated with a high risk of morbidity, mortality, increased risk of hospitalizations, and low quality of life. Therefore, effective, systemic treatment strategies are necessary to mitigate these risks. In this manuscript, we emphasize the concept of high-intensity care to optimize guideline-directed medical therapy (GDMT) in HF patients. The document highlights the importance of achieving optimal recommended doses of GDMT medications, including beta-blockers, renin-angiotensin-aldosterone inhibitors, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter inhibitors to improve patient outcomes, achieve effective, sustainable decongestion, and improve patient quality of life. The document also discusses potential obstacles to GDMT optimization, such as clinical inertia, physiological limitations, comorbidities, non-adherence, and frailty. Lastly, it also attempts to provide possible future scenarios of high-intensive care that could improve patient outcomes.

Efficacy and Safety of Modafinil for Treatment of Amphetamine-Type Stimulant Use Disorder: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials: Efficacité et innocuité du modafinil pour le traitement des troubles liés à l'usage de stimulants de type amphétamine : revue systématique et méta-analyse d'essais randomisés contrôlés par placebo.

INTRODUCTION: Amphetamine-type stimulants (ATSs) are related to significant harm worldwide, with limited effective pharmacological treatments for ATS use disorder (ATSUD). Modafinil has been explored as a potential treatment for ATSUD. This systematic review and meta-analysis (PROSPERO ID: CRD42023388487) aimed to evaluate the efficacy and safety of modafinil for the treatment of ATSUD. METHODS: A comprehensive search of major indexing sources and trial registries, from inception to search date, was conducted on February 15, 2023, and updated on October 31, 2023. Eligible studies were randomized placebo-controlled trials (RCTs) of modafinil in individuals meeting the criteria for the Diagnostic and Statistical Manual of Mental Disorders, fourth and fifth editions, diagnoses of ATSUD. Eligible studies were assessed for risk of bias, using the Cochrane Risk of Bias tool. The primary outcome included the effect of modafinil on ATS use. Secondary outcomes included retention in treatment, ATS craving, treatment discontinuation due to adverse events (AEs), and serious AEs. Subgroup analysis by modafinil dose was conducted where appropriate. Risk ratio (RR) or Peto's odds ratio (OR) was calculated for the meta-analysis of dichotomous variables and standardized mean difference (SMD) was calculated for the random-effect meta-analysis of continuous variables. RESULTS: Five RCTs (N = 451 participants) were included. Modafinil did not significantly impact ATS use (RR = 0.99; 95% CI, 0.97 to 1.02; p = 0.655), retention in treatment (RR = 1.02; 95% CI, 0.91 to 1.14; p = 0.799), ATS craving (SMD = -0.36; 95% CI, -1.19 to 0.47; p = 0.398), or treatment discontinuation due to AEs (Peto's OR = 0.48; 95% CI, 0.20 to 1.14; p = 0.100). These results were consistent across subgroup analyses. More episodes of serious AEs were reported in the modafinil group than in the placebo group, at higher doses (Peto's OR = 4.80; 95% CI, 1.18 to 19.56, p = 0.029). CONCLUSION: There is currently no evidence suggesting that modafinil has a statistically significant effect on efficacy outcomes in populations with ATSUD. Continued research into effective treatments and harm reduction strategies for ATSUD is essential.

Possible pathophysiologic roles of neurotransmitter systems in men with lifelong premature ejaculation: a scoping review.

INTRODUCTION: Lifelong premature ejaculation (LPE) is a subtype of premature ejaculation. Genetic research on LPE has primarily focused on neurotransmitters such as serotonin, dopamine, and norepinephrine, whereas LPE treatment studies have focused on drugs such as selective serotonin reuptake inhibitors. However, findings from genetic association and pharmacotherapeutic studies have been inconsistent. OBJECTIVES: To provide a quality overview of neurobiological targets that are potentially associated with LPE by investigating genetic association and pharmacotherapeutic studies. METHODS: This scoping review was conducted per the PRISMA-ScR tool (Preferred Reporting Items for Systematic Reviews and Meta-analyses Extension for Scoping Reviews). Five databases were searched in March 2023 without timeline- or language-related restrictions. RESULTS: After deduplication, 3949 records were obtained for review. Following screening and full-text review with citation tracking, 52 studies were included: 18 genetic and 34 pharmacotherapy studies. Serotonergic targets, such as the serotonin transporter and pre- and postsynaptic serotonergic receptors, were most often associated with LPE in genetic and pharmacotherapeutic studies. Mixed results were found among polymorphisms within genetic studies. This mechanism is in accordance with pharmacotherapeutic studies, as the highest efficacy was found for potent serotonergic antidepressants. Successful treatment was also observed with medication acting on phosphodiesterase-5 enzyme, such as tadalafil and vardenafil. Analyses of other genetic association studies did not yield any further evidence for associated targets. CONCLUSIONS: This review is the first comprehensive scoping review on LPE. We found that serotonergic targets are most often associated with LPE, suggesting that the serotonergic pathway is a predisposing factor in LPE. Furthermore, there is some evidence for phosphodiesterase 5 inhibitors, which should be investigated. Other previously investigated neurobiological targets appear less likely to contribute to LPE. Future studies should focus on multiple targets, ideally in a genome-wide association study design.This review has been registered with the Open Science Framework (doi:10.17605/OSF.IO/JUQSD).

A Nationwide Target Trial Emulation Assessing the Risk of Antidepressant-Induced Mania Among Patients With Bipolar Depression.

OBJECTIVE: Antidepressants are commonly used to treat bipolar depression but may increase the risk of mania. The evidence from randomized controlled trials, however, is limited by short treatment durations, providing little evidence for the long-term risk of antidepressant-induced mania. The authors performed a target trial emulation to compare the risk of mania among individuals with bipolar depression treated or not treated with antidepressants over a 1-year period. METHODS: The authors emulated a target trial using observational data from nationwide Danish health registers. The study included 979 individuals with bipolar depression recently discharged from a psychiatric ward. Of these, 358 individuals received antidepressant treatment, and 621 did not. The occurrence of mania and bipolar depression over the following year was ascertained, and the intention-to-treat effect of antidepressants was analyzed by using Cox proportional hazards regression with adjustment for baseline covariates to emulate randomized open-label treatment allocation. RESULTS: The fully adjusted analyses revealed no statistically significant associations between treatment with an antidepressant and the risk of mania in the full sample (hazard rate ratio=1.08, 95% CI=0.72-1.61), in the subsample concomitantly treated with a mood-stabilizing agent (hazard rate ratio=1.16, 95% CI=0.63-2.13), and in the subsample not treated with a mood-stabilizing agent (hazard rate ratio=1.16, 95% CI=0.65-2.07). Secondary analyses revealed no statistically significant association between treatment with an antidepressant and bipolar depression recurrence. CONCLUSIONS: These findings suggest that the risk of antidepressant-induced mania is negligible and call for further studies to optimize treatment strategies for individuals with bipolar depression.

Investigation of setmelanotide, an MC4R agonist, for obesity in individuals with Smith-Magenis syndrome.

BACKGROUND: Smith Magenis Syndrome (SMS) is a rare genetic disorder caused by RAI1 haploinsufficiency. Obesity in people with SMS is believed partially due to dysfunction of the proximal melanocortin 4 receptor (MC4R) pathway. We therefore studied effects of treatment with the MC4R agonist setmelanotide on obesity and hunger, as well as metabolic, cardiac and safety, in individuals with SMS. METHODS: People with SMS received once-daily setmelanotide injections, with the dose titrated bi-weekly to a maximum of 3 mg over ∼1 month; and a full-dose treatment duration of 3mo. The primary outcome was percent change in body weight. Secondary outcomes included hunger, waist circumference, body composition, and safety. RESULTS: 12 individuals, ages 11-39 y, enrolled and 10 completed the full-dose treatment phase. Mean percent change in body weight at end-treatment was - 0.28 % [(95 % CI, -2.1 % to 1.5 %; n = 12; P = 0.66]. Participants experienced a significant decrease in total cholesterol associated with a significant decrease in HDL-cholesterol and a trend for lower LDL-cholesterol. Self-reported hunger was reduced at end-treatment (p = 0.011). All participants reported adverse events (AEs), most commonly injection-site reactions and skin hyperpigmentation. No AEs led to withdrawal or death. CONCLUSIONS: In this trial, setmelanotide did not significantly reduce body weight in participants with SMS. Participants reported significant differences in hunger, but such self-reports are difficult to interpret without a placebo-treated group. The changes in lipid profiles require further investigation. Results of this study do not suggest that dysfunction of the proximal MC4R pathway is the main etiology for obesity in people with SMS.

A consensus statement from the Japan Diabetes Society: A proposed algorithm for pharmacotherapy in people with type 2 diabetes - 2nd edition (English version).

This algorithm was issued for the appropriate use of drugs for the treatment of type 2 diabetes mellitus in Japan. The revisions include safety considerations, fatty liver disease as a comorbidity to be taken into account and the position of tirzepatide.

Pharmacology Progresses and Applications of Chloroquine in Cancer Therapy.

Chloroquine is a common antimalarial drug and is listed in the World Health Organization Standard List of Essential Medicines because of its safety, low cost and ease of use. Besides its antimalarial property, chloroquine also was used in anti-inflammatory and antivirus, especially in antitumor therapy. A mount of data showed that chloroquine mainly relied on autophagy inhibition to exert its antitumor effects. However, recently, more and more researches have revealed that chloroquine acts through other mechanisms that are autophagy-independent. Nevertheless, the current reviews lacked a comprehensive summary of the antitumor mechanism and combined pharmacotherapy of chloroquine. So here we focused on the antitumor properties of chloroquine, summarized the pharmacological mechanisms of antitumor progression of chloroquine dependent or independent of autophagy inhibition. Moreover, we also discussed the side effects and possible application developments of chloroquine. This review provided a more systematic and cutting-edge knowledge involved in the anti-tumor mechanisms and combined pharmacotherapy of chloroquine in hope of carrying out more in-depth exploration of chloroquine and obtaining more clinical applications.