Obesity Management in Youth with Duchenne Muscular Dystrophy: A Review of Metformin and Alternative Pharmacotherapies.

Background: Individuals with Duchenne muscular dystrophy (DMD) have increased risk of obesity from prolonged glucocorticoid use and progressive muscle weakness. Over 50% have obesity by the teenage years. Objectives: The current study examines literature on obesity management in DMD and describes how obesity pharmacotherapy can be used in this high-risk cohort. Methods: This review was conducted in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist. A Pubmed Database search was conducted from January 2000 to May 2024. Included terms were DMD and topiramate, phentermine, metformin, glucagon-like peptide-1 receptor agonist, semaglutide, and liraglutide. Eligible studies were cataloged to examine obesity pharmacotherapy, side effect profiles, and clinical outcomes. Results: Twenty studies met inclusion criteria, 18 on metformin. Reviewed studies varied in duration from 4 to 24 weeks, ages 6.5-44 years old, with 112 participants total (range: 1-30 participants). Included studies were: eight animal studies, six clinical trials, four reviews, one cohort study, and one case report. Primary outcomes varied among studies: muscular degeneration and function (15 articles), cardiac function (2 articles), weight loss (2 articles), and general endocrine care (1 article). Conclusions: Adjunct obesity pharmacotherapy use in youth with DMD is promising but needs to be confirmed. Large gaps include appropriate agent selection, side effect monitoring, and dose escalation. The overall quality of pediatric-specific evidence for the use of obesity pharmacotherapy in youth with DMD is low. Future research is needed to investigate how to safely utilize these agents.

Pharmacological management of gastro-esophageal reflux disease: state of the art in 2024.

INTRODUCTION: Gastroesophagealreflux disease (GERD) is a chronic disease of the esophagus characterized bythe regurgitation of stomach contents into the esophagus causing troublesomesymptoms and/or complications. Among patients with GERD, around 30% of patientshave visible mucosal damage, while 70% have a normal esophageal mucosa. Accordingly,the optimal pharmacological treatment of GERD should address different diseasemanifestations, including symptoms, the mucosal damage when present, and possiblechronic complications, including strictures, Barrett's esophagus, andesophageal adenocarcinoma. AREASCOVERED: Available medicaltreatments for GERD include proton pump inhibitors (PPIs),potassium-competitive acid blockers (PCABs), histamine receptor antagonists (H2-RAs),prokinetics, and mucosal protectants such as alginates, hyaluronicacid/chondroitin-sulfate, and poliprotect. Each compound has its ownadvantages and disadvantages, and knowledge of expected benefits and tips fortheir use are paramount for the success of treatment. In addition, theappropriateness of indications for initiating treatment is also crucial toachieve positive results when managing GERD patients. EXPERTOPINION: PPIs,PCABs, H2-RAs, prokinetics, and mucosal protectants can all be used in patientswith GERD, but careful assessment of patients' characteristics as well asadvantages and disadvantages of each therapeutic compound is essential toensure successful treatment of GERD.

Comparing Selective Serotonin Reuptake Inhibitors (SSRIs) Alone and in Combination With Beta-Blockers for Treating Panic Disorders: A Prospective Cohort Study.

Background Panic disorders are prevalent psychiatric conditions affecting 1.6% to 2.2% of the global population. While selective serotonin reuptake inhibitors (SSRIs) are the first line of treatment, their initial exacerbation of symptoms presents challenges. Beta-blockers have shown promise in managing panic symptoms, but research comparing the efficacy of combined SSRI and beta-blocker therapy to SSRI monotherapy is limited, particularly in Saudi Arabia. Objective To assess the effectiveness of SSRIs combined with beta-blockers vs. SSRI monotherapy in improving panic disorder symptoms severity in patients at King Abdul-Aziz Hospital, Makkah, Saudi Arabia. Methods This prospective cohort study included 62 patients with panic disorder, divided into two groups: SSRI monotherapy (n=29) and SSRIs with beta-blockers (n=33). Panic disorder severity was assessed using the Panic Disorder Severity Scale (PDSS) after three months of treatment. Secondary outcomes included depression and anxiety symptoms, measured by the Patient Health Questionnaire (PHQ-9) and General Anxiety Disorder Scale (GAD-7), respectively. Statistical analysis involved Mann-Whitney U tests for comparing PDSS scores between the groups due to non-parametric distribution and Chi-square tests for categorical variables. Relative risks (RR) were calculated to assess the likelihood of abnormal PDSS, PHQ-9, and GAD-7 scores between the groups. Multivariable linear regression was used to adjust for potential confounding factors. Results No statistically significant difference in PDSS scores was found between SSRI monotherapy (median=6, interquartile range (IQR)=3-9) and combination therapy (median=8, IQR=3-13) groups (p=0.188). The relative risk of abnormal PDSS scores was 1.8 times higher in the combination therapy group (p=0.077). No significant differences in depression (p=0.386) or anxiety (p=0.182) symptoms were observed. Additionally, 66.7% of combination therapy patients had abnormal PDSS scores compared to 33.3% in the SSRI group. The mean PHQ-9 score was 11.08±6.93, and the mean GAD-7 score was 10.69±6.41 for the total sample. Conclusion This study found no significant difference in the effectiveness of SSRIs combined with beta-blockers vs. SSRI monotherapy for treating panic disorders. However, the trend towards higher PDSS scores in the combination therapy group suggests further investigation is needed. Study limitations included small sample size, single-center design, short follow-up period, and lack of randomization. Despite these, the study provided valuable insights into treatment approaches for panic disorders in the Saudi population. Larger, randomized controlled trials with longer follow-up periods and multi-center designs are recommended for future research.

Treatment for Depression in Patients Who Have Suffered from Early Life Stress.

BACKGROUND: People with Major Depressive Disorder (MDD) are far more likely to suffer from Early Life Stress (ELS) than the average population. This typically increases severity of symptoms, and often leads to treatment resistance. This study set out to examine which treatments work best to treat depression in patients who have suffered from ELS, as well as possible interactions between ELS and antidepressant effects in therapies. METHOD: A literature review was conducted in July 2020 using the databases Embase, PsychInfo, and MEDLINE. The search looked for clinical trials treating MDD with psychotherapies and pharmacotherapies with patients who suffered from ELS. Data regarding demographics, comorbidities, measurement tools, and outcomes (generally response rates and remission) were extracted. The data was compared according to treatment types. RESULTS: Cognitive Behavioural Therapy (CBT) had the best evidence for treating MDD in people with ELS. There was some mixed evidence for Interpersonal Therapy, SSRIs, and SNRIs as suitable treatments for MDD. There was also very promising but limited evidence for Cognitive Behavioural Analysis of System Therapy and combination treatments (pharmacotherapy and psychotherapy together). Nefazodone (a SARI) had the weakest evidence. CONCLUSIONS: CBT was the most effective treatment for MDD with ELS. However, more research needs to be conducted to ascertain a proper hierarchy of treatments, particularly with combination treatments.

Efficacy of add-on Cenobamate treatment in refractory epilepsy due to Rasmussen's encephalitis.

OBJECTIVE: To assess antiseizure effects of cenobamate, a new antiseizure medication with at least two mechanisms of action, in the rare, highly pharmacoresistant and progressive epilepsy syndrome related to Rasmussen's encephalitis. METHODS: Three patients from the epilepsy centers in Freiburg, Kork, and Valencia are reported with focal epilepsy which had been pharmacoresistant to more than 10 prior treatment regimens. Assessment included at least 1 year of follow-up after cenobamate introduction and included seizure frequency, seizure severity (in particular status epilepticus) and changes in co-medication. RESULTS: In the three patients, cenobamate add on treatment proved superior to all prior antiseizure and immunomodulatory treatments which had been individually applied. Not only were focal to bilateral tonic-clonic seizure completely controlled, but also focal motor status epilepticus no longer occurred. Co-medication could be reduced in all patients. SIGNIFICANCE: This case series in a rare and highly pharmacoresistant epilepsy syndrome suggests high efficacy of cenobamate add-on treatment for seizure control. This may be a valuable information in epilepsy related to Rasmussen encephalitis and calls for further elucidation of the mechanism involved in superior seizure control also compared to prior treatments including sodium channel blockers and benzodiazepines. PLAIN LANGUAGE SUMMARY: Rasmussen's encephalitis is a rare type of epilepsy that gets worse over time and doesn't respond well to most seizure medications. We describe three patients who tried many treatments without much success, but when they added cenobamate to their treatment, it worked better than the other medications. This also let them lower the overall amount of medication they were taking.

Anticancer Drug Discovery from Natural Compounds Targeting PI3K/AKT/mTOR Signaling Pathway.

The term cancer is used to describe a complex pathology characterized by the uncontrollable proliferation of cells, which displays a fast metastatic spread, being a disease with difficult treatment. In this context, Phosphatidylinositol 3-kinase (PI3K) represents a promising pathway to be inhibited, aiming to develop anticancer agents, since it performs a pivotal role in regulating essential cellular processes, including cell proliferation, growth, autophagy, and apoptosis. In parallel, natural compounds can effectively represent a therapeutic strategy to fight against malignant cells. Then, compounds derived from various plant sources, such as flavonoids, terpenoids, alkaloids, coumarins, and lignans, have exhibited remarkable in vitro and in vivo anticancer properties. This review focused in the exploration of natural products targeting the PI3K/AKT/m-TOR signaling pathway, demonstrating that these compounds could even further investigated to reveal novel and effective anticancer drugs in the future.

An insight into the updated pharmacotherapy of metabolic-associated fatty liver disease (MAFLD) or metabolic dysfunction-associated steatohepatitis (MASH) in lean individuals: a review.

Metabolic-associated fatty liver disease (MAFLD) or metabolic dysfunction-associated steatohepatitis (MASH) in lean individuals represents a distinctive subset of MASH. Current pharmacotherapies, for MASH as demonstrated in clinical trials, predominantly target obese patients with limited consideration for lean MASH. We aimed to systematically review the literature on the pharmacotherapy of lean MASH. We searched standard medical databases, such as PubMed, Embase, Scopus, Cochrane CENTRAL, and ClinicalTrials.gov to identify eligible studies published in English up to 31 December 2023 regarding the effect of pharmacological interventions in individuals with lean MASH. We have summarized the role of various drug classes including peroxisome proliferator-activated receptor agonists, glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter 2 inhibitors, vitamin E, farnesoid X receptor agonists, selective thyroid hormone receptor-ß agonists, and selective cholesterol absorption inhibitors. Consequently, lifestyle interventions, encompassing dietary modifications, exercise, and weight loss particularly directed at visceral obesity or achieving a reduction in body weight are recommended for all non-obese individuals with MASH. A highlight on the only available treatment recommendation for lean MASH is also presented. The available evidence regarding the efficacy of various drugs for the treatment of lean MASH is limited. Conclusive evidence is warranted from clinical trials exclusively involving lean individuals with MASH.

Treatments with versus without medication for children with behavioural difficulties in clinical practice: an economic evaluation with observational data.

BACKGROUND: Economic evaluations of treatments for children with behavioural difficulties (i.e., characteristics of attention-deficit/hyperactivity disorder (ADHD) and/or oppositional defiant disorder (ODD)) usually rely on data of randomised controlled trials or are model-based. Findings of such studies may not be representative of cost-effectiveness and cost-utility in clinical practice. The current longitudinal study aimed to perform an economic evaluation of treatments for children with hyperactivity, impulsive behaviours, inattention, and/or behavioural difficulties using observational data that were obtained in clinical practice. METHODS: Parents of 209 children (aged 5-12) who were referred to 1 of 10 Dutch youth mental healthcare institutions and who received treatment with (n = 108) or without (n = 101) the use of medication, filled out questionnaires at three timepoints (baseline, and ~ 6 and ~12 months later). Propensity score matching was used to make both groups comparable. Outcomes included quality-adjusted life years (QALYs), ADHD and ODD symptom severity, and impairment. Costs were measured from a societal perspective. Incremental cost-effectiveness ratios (ICERs) were estimated, and cost-effectiveness acceptability curves (CEACs) were derived to show uncertainty around the ICER. RESULTS: Results did not show statistically significant differences in costs and effects between children who were treated with medication (alone or in combination with non-medication treatment) and those who were treated without medication. CEAC suggested that medication treatment has a 55% probability of being cost-effective at the €80,000 threshold and 36% at the €20,000 threshold compared with treatment without medication. CONCLUSIONS: Using observational data, our study did not provide clear evidence of the cost-effectiveness and cost-utility of treatment with medication compared with treatment without medication in clinical practice.

Comparative Short- and Long-Term Effectiveness and Safety of Pramipexole and Aripiprazole Augmentation in Treatment-Resistant Unipolar Depression: An Observational Study.

BACKGROUND: This study compares the short- and long-term effectiveness and safety of pramipexole augmentation (PA) and aripiprazole augmentation (AA) for unipolar treatment-resistant depression (TRD). METHODS: Patients were recruited in a private out-patients clinic specializing in mood disorders. At intake and at each visit, depressive and (hypo)manic symptoms, clinical status, and level of functioning were evaluated with appropriate scales. The trend of outcomes was analyzed using mixed-effect linear regression models. RESULTS: The study includes 81 patients with unipolar TRD treated with PA and 51 with AA. After 12 and 24 weeks of treatment with PA, the predicted response (64.1% and 76.2%) and remission rates (49.7% and 72.7%) were significantly higher than the predicted response (32.2% and 38.0%) and remission rates (18.9% and 28.1%) for AA. The improvement in psychosocial functioning was significantly greater and faster in PA than in AA. PA showed significant superiority over AA as a maintenance strategy (time spent ill and psychosocial functioning) up to 12 months. No difference in safety was found at each time point. CONCLUSIONS: PA could be an alternative option for the short- and long-term treatment of unipolar TRD, more effective than AA and similar in safety. These preliminary results need confirmation from randomized clinical trials.

Pharmacotherapy guideline concordance for major depressive disorder and its link to functioning via symptom change.

Introduction: Alleviation of symptom severity for major depressive disorder (MDD) is known to be associated with a lagged improvement of functioning. Pharmacotherapy guidelines support algorithms for MDD treatment. However, it is currently unclear whether concordance with guidelines influences functional recovery. A guideline concordance algorithm (GCA-8) was used to measure this pathway in a naturalistic clinical setting. Methods: Data from 1403 adults (67% female, 84% non-Hispanic/Latino White, mean age of 43 years) with nonpsychotic MDD from the Penn State Psychiatry Clinical Assessment and Rating Evaluation System registry (visits from 02/01/2015 to 04/13/2021) were evaluated. Multivariable linear regression measured associations between GCA-8 and World Health Organization Disability Assessment Schedule 2.0 (WHODAS) scores. Mediation by MDD symptom severity using the Patient Health Questionnaire depression module (PHQ-9) was also evaluated. Results: This study found a statistically significant improvement in WHODAS scores (functioning) between baseline and final measures (-2 points, P < .001) within one year. A one standard deviation increase in the GCA-8 score was associated with a 0.48-point reduction in mean disability score (total effect; P = .02) with significant mediation by the change in MDD symptom severity (coefficient = -0.51, P < .001) and a nonsignificant natural direct effect of the GCA-8 independent of PHQ-9 change (coefficient = -0.02, P = .92). Conclusions: Higher pharmacotherapy guideline concordance is associated with better functioning for MDD patients; this association likely occurs through improvement in MDD symptom severity rather than directly.

Risk Stratification in Twin Pregnancies Complicated by GDM.

Aims: This study was aimed at assessing the association of oral glucose tolerance test (OGTT) glucose threshold levels and the requirement of insulin therapy in twin pregnancies with gestational diabetes mellitus (GDM). Methods: In this post hoc analysis of a cohort study spanning 18 years, 446 patients with twin pregnancy and GDM (246 managed with lifestyle modification and 200 requiring pharmacotherapy) were included. We collected and evaluated maternal characteristics, as well as fasting, 1-h, and 2-h glucose concentrations from a standardized 75-g OGTT. The assessment methods included logistic regression analysis, positive and negative predictive values, area under the curve (AUC), and random forest analysis. Results: The fasting (p < 0.01, OR: 1.03 [95% CI 1.01-1.05]) and 1-h (p < 0.01; OR: 1.01 [95% CI 1.00-1.02]) glucose levels during the OGTT were significantly associated with the subsequent need for insulin therapy, with thresholds of 95 mg/dL for fasting glucose and 184 mg/dL for the 1-h OGTT. Additionally, indications for insulin therapy were marked by thresholds of 108 mg/dL at G0, 215 mg/dL at G60, and 86 mg/dL at G120. Conclusion: Identifying threshold values for insulin therapy and risk stratification in twin pregnancy are crucial for optimal patient management.

Prevalence and Impact of Psychological Disorders on Pharmacotherapy of Diabetic Patients in Low Resource Settings: A Prospective Assessment in Primary Healthcare Settings.

Background: Prevalence of psychological disorders among individuals with diabetes is significantly higher as compared to the general population. Aim: This study aimed to assess the prevalence and impact of psychological disorders on pharmacotherapy of diabetes patients. Methodology: This cross-sectional study was conducted at two primary care hospitals in Pakistan from April to June 2023. The nine-item Patient Health Care Questionnaire (PHQ-9) scale was used to assess depression in the study's population, and its effects on pharmacotherapy of diabetes. Chi-square test was used to evaluate relationship between ordinal variables/categorical variables and depression whereas; Student's t-test was used to assess the relationship between numerical variables with depression. Results: A total of 320 patients were assessed, comprising 120 (37.5%) males and 200 (62.5%) females, with a mean age of 52.5 (SD±11.8) years. The average duration of diabetes is 7.0 (SD±5.4). The average PHQ-9 score was 8.3 (SD±5.5). Depression was found to be prevalent in 43.7% of the study population. Gender (female) (p-value 0.002), advanced age (p-value 0.002), lower income (p-value 0.001), education levels (p-value 0.001), longer duration of diabetes (p-value 0.001), poor diabetes control according to BSR value (p-value 0.001), usage of injectable insulin (p-value 0.005), and concomitant diseases (p-value 0.001) were found to be independently linked with depression. Significant association was observed between depression and treatment adherence (p-value 0.0025), number of missed doses (p-value 0.045), and difficulty in diabetes management (p-value 0.0015). Conclusion: Our study highlights significant prevalence of depression in study population and the prevalent depression negatively impacts on treatment adherence. It also revealed that depression complicates diabetes management resulting in poor medication adherence, poor diabetes control and diabetes related complications, making diabetes control more challenging and difficult.

Pharmacologic Treatment of Hypertension in Older Adults.

The authors conducted a review of pharmacologic therapy in older adults with hypertension. They reviewed the evidence supporting their use in older adults, understanding the physiologic changes and potential adverse drug effects associated with aging and antihypertensive medication use, exploring guideline recommendations for antihypertensive use in older adults, and evaluating the associated risks and benefits of specific classes of antihypertensive medications.

The Patient's Journey in Obesity within the United States: An Exercise of Resilience against Disease.

Obesity is often viewed as a result of patient failure to adhere to healthy dietary intake and physical activity; however, this belief undermines the complexity of obesity as a disease. Rates of obesity have doubled for adults and quadrupled for adolescents since the 1990s. Without effective interventions to help combat this disease, patients with obesity are at increased risk for developing type 2 diabetes, heart attack, stroke, liver disease, obstructive sleep apnea, and more. Patients often go through several barriers before they are offered pharmacotherapy or bariatric surgery, even though evidence supports the use of these interventions earlier. This partially stems from the cultural barriers associated with using these therapies, but it is also related to healthcare provider bias and limited knowledge of these therapies. Finally, even when patients are offered treatment for obesity, they often run into insurance barriers that keep them from treatment. There needs to be a cultural shift to accept obesity as a disease and improve access to effective treatments sooner to help decrease the risk of health complications associated with obesity.

Molded Round Window Niche Implant as a Dexamethasone Delivery System in a Cochlear Implant-Trauma Animal Model.

BACKGROUND: Preserving residual hearing after cochlear implant (CI) surgery remains a crucial challenge. The application of dexamethasone (DEX) has been proven to positively affect residual hearing. To deliver DEX in a localized and controlled way, a round window niche implant (RNI), allowing drug diffusion via the round window membrane into the cochlea, may be used. To prove this concept, an RNI for guinea pigs as a CI-trauma model was manufactured by molding and tested for its drug release in vitro and biological effects in vivo. METHODS: The RNIs were molded using silicone containing 10% DEX. Release was analyzed over time using high-performance liquid chromatography (HPLC). Fourteen adult guinea pigs were randomly assigned to two groups (CI or CI + RNI group). All animals received a unilateral CI electrode insertion trauma followed by CI insertion. The CI + RNI group was additionally implanted with an RNI containing 10% DEX. Animals were followed up for 4 weeks. Acoustically evoked auditory brainstem response and impedance measurement, micro-computed tomography (µCT) imaging, and histology were performed for evaluation. RESULTS: DEX was released for more than 250 days in vitro, with an initial burst followed by a slower release over time. Comparing the hearing threshold shift (from day 0 to day 28) of the CI and CI + RNI groups, significant differences were observed at 32 and 40 kHz. The impedance shift at basal contacts was lower in the CI + RNI group than in the CI group. Moreover, the fibrosis in the lower basal turn was reduced in the CI + RNI group in contrast to the CI group. CONCLUSIONS: The RNI containing 10% DEX has anti-inflammatory potential concerning fibrosis inhibition and has beneficial effects on hearing preservation at high frequencies.

Physiology, Pathophysiology and Clinical Relevance of D-Amino Acids Dynamics: From Neurochemistry to Pharmacotherapy.

Over three decades ago, two independent groups of investigators identified free D-aspartic and later D-serine in specific brain nuclei and endocrine glands. This finding revealed a novel, non-proteinogenic role of these molecules. Moreover, the finding that aged proteins from the human eye crystallin, teeth, bone, blood vessels or the brain incorporate D-aspartic acids to specific primary protein sequences fostered the hypothesis that aging might be related to D-amino acid isomerization of body proteins. The experimental confirmation that schizophrenia and neurodegenerative diseases modify plasma free D-amino acids or tissue levelsnurtured the opportunity of using D-amino acids as therapeutic agents for several disease treatments, a strategy that prompted the successful current application of D-amino acids to human medicine.

Efficacy and Safety of a Novel Low-Dose Triple Single-Pill Combination Compared With Placebo for Initial Treatment of Hypertension.

BACKGROUND: Single-pill combinations of 3 or more low-dose blood pressure (BP)-lowering drugs hold promise for initial or early treatment of hypertension. OBJECTIVES: We conducted a placebo-controlled trial of a new single-pill combination containing low doses of telmisartan, amlodipine, and indapamide in 2 dose options to assess efficacy and safety. METHODS: This international, randomized, double-blind, placebo-controlled, parallel-group trial enrolled adults with hypertension receiving 0 to 1 BP-lowering drugs. After a 2-week placebo run-in during which any BP-lowering medication was stopped, participants were eligible if home systolic BP (SBP) was 130 to 154 mm Hg. Participants were randomized in a 2:2:1 ratio to GMRx2 » dose (telmisartan 10 mg/amlodipine 1.25 mg/indapamide 0.625 mg), GMRx2 ½ dose (telmisartan 20 mg/amlodipine 2.5 mg/indapamide 1.25 mg), or placebo. The primary efficacy outcome was difference in change in home SBP from randomization to week 4, and primary safety outcome was treatment discontinuation due to an adverse event. RESULTS: From June 14, 2021 to October 18, 2023, a total of 295 participants (mean age: 51 years; 56% female) were randomized and 96% completed the trial. Baseline mean home BP was 139/86 mm Hg and clinic BP was 138/86 mm Hg after placebo run-in. The placebo-corrected least square mean differences in home SBP at Week 4 were -7.3 mm Hg (95% CI: -4.5 to -10.2) for GMRx2 » dose and -8.2 mm Hg (95% CI: -5.2 to -11.3) for GMRx2 ½ dose; reductions for clinic BP were 8.0/4.0 and 9.5/4.9 mm Hg. At Week 4, clinic BP control (<140/90 mm Hg) was 37%, 65%, and 70% for placebo, GMRx2 » dose, and GMRx2 ½ dose, respectively (both doses P < 0.001 vs placebo). Placebo, GMRx2-triple », and GMRx2 ½ treatment discontinuation due to an adverse event occurred in 1 (1.6%), 0, and 6 (5.1%), respectively; out of normal range serum sodium or potassium was observed in 4 (6.3%), 12 (10.6%), and 12 (10.1%), respectively, but no participant had a serum sodium <130/>150 mmol/L or potassium <3.0/>6.0 mmol/L. Serious adverse events were reported by 2 participants in the placebo and GMRx2 ½ groups and none in the GMRx2 » group. CONCLUSIONS: In a population with mild-to-moderate BP elevation, both dose versions of the novel low-dose triple single-pill combination showed good tolerability and clinically relevant BP reductions compared with placebo. (Efficacy and Safety of GRMx2 Compared to Placebo for the Treatment of Hypertension: NCT04518306).

Treatment of insomnia associated with alcohol and opioid use: a narrative review.

Substance use disorders (SUDs) are associated with profound sleep disturbances, including insomnia, sleep fragmentation, and circadian rhythm dysfunction resulting in serious mental and physical consequences. This minireview presents an overview of the neurocircuitry underlying sleep disturbances in SUDs and elaborates on treatment options with emphasis on alcohol use disorder (AUD) and opioid use disorder (OUD). A PubMed, Embase, CINAHL Plus, Cochrane, and Scopus search were conducted using sleep- and AUD/OUD related keywords from January 1st, 2000, to January 31st, 2023, with preferences for recent publications and randomized-controlled trials. A bidirectional relationship exists between insomnia and addiction with the status of each condition impacting the other in dictating clinical outcome. Existing evidence points to a resurgence of insomnia during detoxification, and unless treated satisfactorily, insomnia may lead to relapse. The discussion summarizes the strengths and limitations of cognitive behavioral therapy and pharmacological treatment for insomnia in SUDs covering evidence from both animal and clinical studies. The assumption of reestablishing normal sleep patterns by attaining and maintaining sobriety is misguided. Comorbid insomnia in patients with SUDs should be approached as an independent condition that requires its own treatment. Future clinical trials are needed with the aim of providing a resource for guiding clinical management of the many patients with insomnia and SUD.

The use of naltrexone in the treatment of chronic pain: a systematic review.

This study aims to assess the efficacy of low-dose naltrexone (LDN) in treating chronic pain. We conducted a systematic review using the PICO strategy: (P) Patients with chronic pain, (I) Use of oral naltrexone, (C) Placebo or active drug and (O) Pain relief and quality of life. We included articles from PubMed, Scopus, Cochrane CENTRAL and EMBASE databases. Seven randomized clinical trials involving 406 patients were analyzed. The doses ranging from 2 to 4.5 mg once daily across all studies. Various chronic pain conditions were evaluated. The results suggest that low-dose naltrexone is not effective in managing chronic pain and improving the quality of life in patients with diverse chronic pain conditions. However, further research with larger sample sizes and standardized methodologies is necessary.

This study looks at how well low-dose naltrexone (LDN) works for treating long-lasting pain. We reviewed research where patients with chronic pain were given either LDN or a placebo (a fake treatment). We found eight studies that included a total of 421 patients. The LDN doses used ranged from very small amounts 2­4.5 mg, taken once a day. These studies looked at different types of chronic pain. Our results suggest that LDN cannot help to reduce pain and improve the quality of life for people with chronic pain. However, more research with larger groups of people and consistent methods is needed to confirm these findings.

Weight Loss Pharmacotherapy: Current and Future Therapies.

The rising prevalence of obesity is of major concern. There are currently 5 Food and Drug Administration-approved medications for the treatment of obesity: orlistat, phentermine/topiramate, naltrexone/bupropion, liraglutide 3.0 mg, and semaglutide 2.4 mg. Surgical options such as bariatric surgery and endoscopic surgery induce more durable weight loss than pharmacotherapy or lifestyle interventions alone. However, patients often experience weight regain and weight loss plateau after surgery. The addition of multimodal or multihormonal pharmacotherapy is a promising tool to address these challenges. The optimal timing of obesity pharmacotherapy with surgical and endoscopic interventions requires further investigation.