Therapeutic Adjustments Research Articles

The use of ultrasound to determine volume status and identify sites of edema in patients with heart failure

The management of patients with congestive heart failure requires an accurate working diagnosis and frequent assessment of responses to treatment. In addition, the prediction of short-term and long-term outcomes is important to both the clinician and the patient. The development of pulmonary edema usually represents an acute deterioration of cardiac status and requires immediate attention. The development of peripheral edema usually represents chronic heart failure and warrants evaluation and possibly therapeutic adjustments. Noninvasive tests to identify sites of extravascular fluid formation can help the clinician manage his or her patients. Lung ultrasound can identify B-lines that usually represent pulmonary edema. Ultrasound studies of the inferior vena cava and its dimensions can help determine volume status and make decisions regarding fluid management. This review outlines the use of ultrasound to determine sites of edema formation in patients with heart failure. Key words: ultrasound, inferior vena cava, pulmonary edema, congestive heart failure

Investigation of Teicoplanin Trough Concentrations and Safety Following High-Dose Loading in a Pediatric Population.

Therapeutic drug monitoring-informed teicoplanin dosage adjustments are recommended for safe and effective use. The authors' group previously reported that only half of children reached the recommended blood concentration range at the standard teicoplanin loading dose. It has been suggested that higher loading doses are necessary; however, the usefulness and safety of high-dose loading in pediatric patients in clinical practice are unknown. This retrospective cohort study was conducted between January 2018 and June 2021 using electronic medical records. The analysis included 2- to 16-year-old patients treated with teicoplanin who met the eligibility criteria. We assessed the trough concentration of teicoplanin and its safety after high-dose loading in pediatric patients. Overall, 86 patients received a high-dose loading regimen (15 mg/kg every 12 hours for 3 doses, followed by 10 mg/kg once daily). Notably, 55 of the 86 patients (64%) achieved the target trough concentration (>15 mg/L) at significantly higher rates without increasing the incidence of organ damage compared with the standard loading regimen. Multivariate analysis revealed significant differences in age and renal function as factors that inhibited the attainment of the target trough concentration. Simulation analysis using a nomogram stratified by age and renal function revealed that the predicted teicoplanin trough levels were within the target trough values in 73% of patients. High-dose teicoplanin loading safely increases trough blood concentrations in the pediatric population. For further optimization, the dose selection should be stratified according to age and renal function.

Risk factors and surgical outcomes in pediatric patients with congenital heart disease and ischemic colitis

IntroductionThis study investigates risk factors and surgical outcomes in pediatric patients with congenital heart defects (CHD) who develop ischemic colitis (IC). Previous research indicates a higher IC risk in very low birth weight neonates with CHD.MethodsA retrospective analysis compared an IC-CHD group to a CHD-only group. Key variables included gestational age, birth weight, multiple pregnancies, prematurity, APGAR scores, cardiac and surgical characteristics, Aristotle-Score, and mortality rates. Surgical outcomes such as bowel resection and stoma procedures were also evaluated.ResultsIC-CHD exhibited significantly lower gestational ages and birth weights, with higher rates of multiple pregnancies and prematurity. APGAR scores were notably lower. Cardiac and surgical data showed more frequent ECMO use and shorter cardiopulmonary bypass durations in the IC-CHD group. High rates of bowel resection highlighted severe gastrointestinal involvement. Mortality was significantly higher in IC-CHD with elevated Aristotle scores correlating with poorer outcomes.ConclusionGestational age, birth weight, and initial health status are critical in predicting IC risk and surgical outcomes in pediatric patients with CHD. The significantly higher mortality and complex surgical needs in the IC-CHD group underscore the necessity for vigilant monitoring and tailored interventions. Development of targeted therapeutic strategies adjustment for confounding factors in future studies is needed.

Prediction of lacosamide concentrations to support dose optimization during pregnancy.

We aimed to quantify and predict lacosamide exposure during pregnancy by developing a pregnancy physiologically-based pharmacokinetic model, allowing the prediction of potential dose increases to support maintaining a patient's preconception lacosamide concentrations. Models for nonpregnant adults and pregnant female patients were constructed using physiochemical and pharmacological parameters identified from literature review. Evaluation of plasma concentration data from human males was digitized from the literature. Concentration data in nonpregnant and pregnant human females were available from the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study, a longitudinal observational study which followed 11 nonpregnant and 16 pregnant women receiving lacosamide. Evaluation was conducted qualitatively with visual overlay (>80% of observed concentrations within 90% confidence interval) and quantitatively with average fold error and absolute average fold error (0.8-1.25 ratio acceptance criteria). Simulations of intensively-sampled dosing regimens at steady-state dosing across multiple gestational ages were conducted in Simcyp to evaluate the potential changes in lacosamide pharmacokinetics during pregnancy. Additional simulations were performed to explore the effects of cytochrome polymorphisms and glomerular filtration rate variability. The model adequately described the evaluation data in nonpregnant adults and pregnant adults between 10 and 40 weeks of gestation. Estimates in patients at 40- weeks of gestation indicated that lacosamide clearance increased by 48.2% compared to nonpregnant patients. Maximum lacosamide concentration (Cmax) during a simulated dosing interval also fell by 30% from preconception to 40 weeks. A simulated dose increase of 50 mg once daily at 10 weeks of gestation supported maintenance of preconception concentration for a typical patient taking the most common dosing regimen of 200 mg, twice daily (BID), preconception. Simulated changes in lacosamide concentration align with the limited data available in observational studies. Our simulations support the use of therapeutic drug monitoring and dose adjustments to maintain the efficacy of lacosamide pharmacotherapy.

From Wristbands to Implants: The Transformative Role of Wearables in Heart Failure Care

Background: Heart failure (HF) management increasingly relies on innovative solutions to enhance monitoring and care. Wearable devices, originally popularized for fitness tracking, show promise in clinical decision-making for HF. This study explores the application and potential for the broader integration of wearable technology in HF management, emphasizing remote monitoring and personalized care. Methods: A comprehensive literature review was performed to assess the role of wearables in HF management, focusing on functionalities like vital sign tracking, patient engagement, and clinical decision support. Clinical outcomes and barriers to adopting wearable technology in HF care were critically analyzed. Results: Wearable devices increasingly track physiological parameters relevant to HF, such as heart rate, physical activity, and sleep. They can identify at-risk patients, promote lifestyle changes, facilitate early diagnosis, and accurately detect arrhythmias that lead to decompensation. Additionally, wearables may assess fluid status, identifying early signs of decompensation to prevent hospitalization and supporting therapeutic adjustments. They also enhance physical activity and optimize cardiac rehabilitation programs, improving patient outcomes. Both wearable and implanted cardiac devices enable continuous, non-invasive monitoring through small devices. However, challenges like data integration, regulatory approval, and reimbursement impede their widespread adoption. Conclusions: Wearable technology can transform HF management through continuous monitoring and early interventions. Collaboration among involved parties is essential to overcome integration challenges and validate most of these devices in clinical practice.

Early detection of OXA-48 producing Klebsiella pneumoniae with the use of rapid antibiotic susceptibility testing.

Rapid antimicrobial susceptibility testing of positive blood cultures can enhance antimicrobial stewardship and patient outcomes. We present a case where OXA-48-producing Klebsiella pneumoniae with low-level carbapenem resistance was suspected 6h after blood-culture positivity, based on ASTar system (Q-Linea, Sweden) results. OXA-48 carbapenemase presence was confirmed by the OXA-48K-SeT lateral flow assay (Coris, Belgium) on a short-term subculture. This led to timely therapeutic adjustments. Following this case, we validated the OXA-48K-SeT and Xpert Carba-R assay (Cepheid, USA) on short-term incubated (6h) subcultures of positive blood cultures, demonstrating that OXA-48K-SeT and Xpert Carba-R respectively accurately identified OXA-48 and various (OXA-48, VIM, NDM, KPC, IMP) carbapenemase-producing Enterobacterales (CPE) types. Both assays prove valuable for rapid CPE detection in clinical settings.

Implantable Biomaterials for Cancer Immunotherapies

AbstractCancer immunotherapy has revolutionized cancer treatment by leveraging the immune system to target and eliminate tumor cells. Implantable biomaterials, such as hydrogels, sponges, scaffolds, implantable microdevice platforms, and macrobeads, offer localized and sustained release of immunomodulatory agents, improving the delivery of treatments such as immune checkpoint inhibitors, cancer vaccines, and adoptive cell therapies like CAR‐T cells. This review examines the emerging role of these biomaterials in modulating the tumor microenvironment, enhancing immune cell recruitment, and reducing systemic side effects, positioning them as significant tools for treating solid tumors. Recent advances in material engineering are also discussed, including the integration of bioactive molecules and real‐time therapeutic adjustments based on patient‐specific immune responses, which offer new potential in personalized cancer treatments. However, challenges such as biocompatibility, high production costs, variability in patient response, and the necessity of surgical manipulations remain key obstacles. Nonetheless, ongoing research and technological advancements are steadily addressing these issues, paving the way for more effective and accessible cancer immunotherapies. Overall, this review highlights the promise of implantable biomaterials overcoming the current limitations of cancer immunotherapy and expanding the scope of effective, targeted cancer treatments.

Early Alpha-Fetoprotein Response Predicts Sustained Tumor Response Following Immune Checkpoint Inhibitors Combined with Targeted Therapy in Liver Cancer.

Background: Although immune checkpoint inhibitors (ICI) have revolutionized liver cancer treatment, some patients experience early tumor progression after therapy, missing the window for other potential treatments, such as neoadjuvant therapy. Therefore, identifying the predictive factors for early progression is critical for timely therapeutic adjustment and the optimization of patient outcomes. Methods: This retrospective study enrolled patients with liver cancer who received their first ICI combined with targeted therapy at the Fifth Medical Center of the PLA General Hospital between June 2022 and December 2023. Early tumor progression was defined as tumor progression within 6 months of therapy initiation. Multivariate logistic regression analysis was used to identify independent risk factors for early tumor progression, and overall survival (OS) curves were generated using the Kaplan-Meier method. Results: A total of 159 patients were enrolled. Multivariate logistic regression analysis indicated that patients with an early alpha-fetoprotein (AFP) response had a significantly reduced risk of early tumor progression (OR = 0.34, 95% CI: 0.13-0.84, p = 0.019), suggesting that an early AFP response is a protective factor against early progression. The area under curve (AUC) for the predictive model was 0.73 (95% CI: 0.63-0.83, p < 0.001). Stratified survival analysis showed that the median overall survival (mOS) in the early AFP response group was significantly longer than that in the poor response group (17.3 months vs. 6.1 months, HR = 2.11, 95% CI: 1.19-2.74, p = 0.009). Conclusions: Early AFP response is not only an effective biomarker for identifying high-risk patients prone to early tumor progression but is also significantly associated with long-term survival in liver cancer patients treated with ICI combined with targeted therapy. This finding will enable clinicians to make timely therapeutic adjustments and optimize treatment outcomes, thereby improving both progression-free survival and overall survival.

Understanding early maladaptive schemas in autistic and ADHD individuals: exploring the impact, changing the narrative, and schema therapy considerations.

Autistic/ADHD individuals are increasingly recognised as a valid minority group, with consistent research demonstrating a higher prevalence of co-occurring mental health conditions such as PTSD, anxiety, depression, substance use, and eating disorders among other mental health challenges. Due to this, there is increasing focus on the adaptations required for Autistic and ADHD individuals of current therapeutic approaches such as Schema Therapy. Particular emphasis when creating these adaptations needs to include looking at the developmental experiences, social influences, and continued adversity faced by Autistic and ADHD individuals across the lifespan, and how the narrative around Autism and ADHD within psychotherapy in general needs to change. This paper critically examines the role of attachment, unmet needs, and adverse childhood experiences in Autistic and ADHD individuals and the subsequent impact on schema development and maintenance and mental health. This will include an overview of the current literature in this area, reconsideration of understandings of Autism and ADHD, particular therapeutic considerations and adjustments and importantly discussion around the wider societal changes that need to occur to prevent schema development and reinforcement across the lifespan.

Changes in the pharmacokinetics of lurasidone in a pregnant woman with schizophrenia.

The population of pregnant women with schizophrenia is increasing. Managing schizophrenia during pregnancy poses unique challenges due to the potential effects of second-generation antipsychotics on maternal mental health and fetal development and changes in drug pharmacokinetics. Evidence on how physiological changes during pregnancy affect the levels of second-generation antipsychotics, particularly lurasidone, is limited. There are no data on effectively managing medications and decreasing side-effects during pregnancy. We presented the case of a 34-year-old pregnant woman with schizophrenia who had a stable condition with lurasidone therapy before conception. However, she exhibited worsening psychiatric symptoms during the third trimester of pregnancy. Serial measurements of serum lurasidone levels were performed during late pregnancy. Despite maintaining the same dosage, her serum lurasidone levels significantly decreased during the third trimester (maximum decrease of ~65% compared with baseline) and rapidly increased during the postpartum period, coinciding with an improvement in psychiatric symptoms. Decreased serum lurasidone levels during pregnancy may increase the risk of symptom worsening in patients with schizophrenia. Hence, clinicians should be knowledgeable about the risk of decreased drug levels and the need for therapeutic monitoring and dosage adjustments during pregnancy to maintain treatment efficacy and maternal and fetal health.

Immune checkpoint inhibitors for glioblastoma: emerging science, clinical advances, and future directions.

Glioblastoma (GBM), the most common and aggressive primary central nervous system (CNS) tumor in adults, continues to have a dismal prognosis. Across hundreds of clinical trials, few novel approaches have translated to clinical practice while survival has improved by only a few months over the past three decades. Randomized controlled trials of immune checkpoint inhibitors (ICIs), which have seen impressive success for advanced or metastatic extracranial solid tumors, have so far failed to demonstrate a clinical benefit for patients with GBM. This has been secondary to GBM heterogeneity, the unique immunosuppressive CNS microenvironment, immune-evasive strategies by cancer cells, and the rapid evolution of tumor on therapy. This review aims to summarize findings from major clinical trials of ICIs for GBM, review historic failures, and describe currently promising avenues of investigation. We explore the biological mechanisms driving ICI responses, focusing on the role of the tumor microenvironment, immune evasion, and molecular biomarkers. Beyond conventional monotherapy approaches targeting PD-1, PD-L1, CTLA-4, we describe emerging approaches for GBM, such as dual-agent ICIs, and combination of ICIs with oncolytic virotherapy, antigenic peptide vaccines, chimeric antigenic receptor (CAR) T-cell therapy, along with nanoparticle-based delivery systems to enhance ICI efficacy. We highlight potential strategies for improving patient selection and treatment personalization, along with real-time, longitudinal monitoring of therapeutic responses through advanced imaging and liquid biopsy techniques. Integrated radiomics, tissue, and plasma-based analyses, may potentially uncover immunotherapeutic response signatures, enabling early, adaptive therapeutic adjustments. By specifically targeting current therapeutic challenges, outcomes for GBM patients may potentially be improved.

Missing appointments in Parkinson´s Disease: A longitudinal study on the pattern of attendance and its effects on motor and non-motor symptoms, quality of life and disability progression

Background and purposeParkinson's Disease (PD) requires regular therapeutic adjustments and ongoing outpatient clinic follow-up. Nevertheless, the impact of appointment non-attendance on PD patients concerning the different symptomatic dimensions of the condition remains uncertain. We compared the level of attendance of PD and Essential Tremor (ET) patients and assessed the value of attendance variables as predictors of progression in cognition, motor dysfunction, affect, disability and health-related quality of life in PD. MethodsThe number of attended, no-shows and cancelled appointments of PD and ET patients were collected over 4 years. PD patients were assessed at baseline and 4 years later with the Non-Motor Symptoms Scale (NMSS), cognition (MoCA), disability (Schwab and England [S&E]), motor dysfunction (UPDRS-III), health-related quality of life measured with EQ-5D and hospital anxiety and depression scale (HADS). Linear regression (univariate) was used to test the correlation between the number of appointments (predictors) and absolute change in the NMSS, MoCA, S&E, UPDRS-III, EQ-5D and HADS. Results62 PD and 35 ET patients were assessed. PD patients attended more appointments (8,08 ± 3,13 vs 5,43 ± 2,09) and had a similar number of no-shows (0,39 ± 0,66 vs 0,46 ± 0,70) and cancelled (0,74 ± 0,88 vs 0,54 ±0,65) appointments than ET patients. In the univariate analysis there was a significant relation between the number of cancelled appointments and change in the S&E score (B=6375; p=0022). ConclusionOur findings suggest the number of cancelled appointments, but not no-shows, could be considered a predictor of disability progression in PD.

Sjögren's Syndrome and Ankylosing Spondylitis Association: A Case-Based Review.

Unlike restrictive pulmonary function and apical fibrobullous disease, diffuse interstitial lung disease is scarce in patients with ankylosing spondylitis (AS). We present a systematic review of the association between AS and SS. We also report a new case of SS revealed by interstitial lung disease in AS patients treated with tumor necrosis factor (TNF) inhibitors. The systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline using the MEDLINE and SCOPUS databases and included case reports and case series describing the association between AS and SS. There were sixty-three patients, including our case: 16 males and 47 females. The mean age was 49.2 years. The mean SpA duration was 14.1 years. The mean delay between SpA and SS was 12.8 years (0-27). SS was diagnosed after SpA in 62% of cases (n=39). It preceded SpA in 36.5% (n=23) and was concomitant with SpA in 1 case. All patients had sicca symptoms. MSGB showed focal sialadenitis grade III or grade IV in the Chisholm classification in 20 patients. Anti- nuclear antibody was positive in 75.8% of cases. Among them, anti-SSA and anti-SSB were positive in 44.4% and 35.3% of cases. Except for our patient, no patient had interstitial lung disease. SS extra glandular manifestations were reported in 12 cases. The occurrence of Sjögren's syndrome is uncommon in patients with ankylosing spondylitis. This association has been reported in the literature, suggesting a pathogenetic link between these two diseases. This association should be considered in ankylosing spondylitis patients with diffuse interstitial lung disease. Knowing this association is necessary for therapeutic adjustment. Our study has some limitations. Publication bias was the major bias in our study. Indeed, we only included case reports and case series describing the association between SpA and SS. We did not search for unpublished work. Moreover, the follow-up was not specified in most included articles.

Beyond telehealth in heart failure, how a nurse-led mobile team unit improves management and reduces re-admission in elderly patients living in a rural area

Abstract Introduction Telehealth plays a crucial role in improving access to healthcare for elderly patients with heart failure (HF), particularly those who live in under-resourced geographic areas, have physical disabilities, or have difficulties with transportation. However, extending and improving telehealth faces significant obstacles, primarily due to its inadequacy to fully assess a patient's clinical status. While some components of HF can be measured remotely, others, such as cardiac and lung examinations, require in-person clinical evaluation. This leads to imprecise assessments of HF severity, excessive medical consultations, and inappropriate emergency transfers or hospitalization. We conducted an evaluation of a specialized mobile team unit (MTU) for HF care in a rural area. The team consisted of nurses trained in performing electrocardiograms (ECGs) and point-of-care ultrasound (POCUS) to extend telemonitoring services to elderly patients with HF in the comfort of their homes. This approach offers a direct and optimal evaluation of the patient's condition. Purpose This study aimed to evaluate the added value of an MTU in assessing and optimizing treatment for HF in elderly patients, ultimately leading to decreased hospitalization or medical request rates. Materials and methods This retrospective analysis examined data from elderly patients diagnosed with HF, who participated in a 6-month telemonitoring program, and received MTU visits. MTU was activated by the telemonitoring team, in patients presenting signs of decompensation, with an imprecise assessment of severity based on digital data only. Results During six months, 165 elderly patients were included in the telemonitoring platform after index HF hospitalization. The mobile team traveled over 3,040 kilometers in a rural area with limited cardiological care. They visited 84 patients (50.9%), offering personalized education and physical assessments to all of the patients, 45% received additional imaging (EKG, POCUS). This resulted in 30% therapeutic adjustments, 90% fewer General practitioner (GP) /Cardiologist consultations and 54% avoided readmissions: 20% of hospitalizations were avoided immediately and 34% likely avoided in the near future, demonstrating the intervention's 80% effectiveness. Conclusion Monitoring heart failure (HF) in elderly patients can be challenging, especially in rural areas with limited access to care, few caregivers, cognitive impairments, or difficulty using e-health platforms. This study emphasizes the benefits of a nurse-led mobile team unit in providing a reliable direct assessment of HF severity. This home intervention provides education, strengthens the decision-making capacity of the remote monitoring platform, assists with patient management, and significantly reduces the readmission rate.

Biologically informed deep neural networks provide quantitative assessment of intratumoral heterogeneity in post treatment glioblastoma.

Intratumoral heterogeneity poses a significant challenge to the diagnosis and treatment of recurrent glioblastoma. This study addresses the need for non-invasive approaches to map heterogeneous landscape of histopathological alterations throughout the entire lesion for each patient. We developed BioNet, a biologically-informed neural network, to predict regional distributions of two primary tissue-specific gene modules: proliferating tumor (Pro) and reactive/inflammatory cells (Inf). BioNet significantly outperforms existing methods (p < 2e-26). In cross-validation, BioNet achieved AUCs of 0.80 (Pro) and 0.81 (Inf), with accuracies of 80% and 75%, respectively. In blind tests, BioNet achieved AUCs of 0.80 (Pro) and 0.76 (Inf), with accuracies of 81% and 74%. Competing methods had AUCs lower or around 0.6 and accuracies lower or around 70%. BioNet's voxel-level prediction maps reveal intratumoral heterogeneity, potentially improving biopsy targeting and treatment evaluation. This non-invasive approach facilitates regular monitoring and timely therapeutic adjustments, highlighting the role of ML in precision medicine.

Concurrent EGFR mutation and SMARCA4 deficiency in non-small cell lung cancer: A case report and literature review.

SMARCA4-deficient non-small cell lung cancer (NSCLC) represents a highly aggressive subtype with poor prognosis. While clinical studies have identified common co-mutations in TP53, LRP1B, STK11, KEAP1, and KRAS, actionable driver mutations such as EGFR or ALK are rarely reported in conjunction with SMARCA4 deficiency. This case presents a rare instance of NSCLC featuring both an EGFR exon 21 L858R mutation and SMARCA4 deficiency, highlighting the challenges in treatment and the need for novel therapeutic strategies. A 79-year-old female patient presented with concerns of a lung mass, suspected to be peripheral lung cancer based on diagnostic imaging. Histopathological evaluation confirmed SMARCA4-deficient NSCLC. Molecular genetic analysis further revealed an EGFR exon 21 L858R mutation. The patient was initially treated with osimertinib, an EGFR tyrosine kinase inhibitor. Upon disease progression, treatment was adjusted to include anlotinib in combination with ongoing osimertinib. The initial treatment with osimertinib led to partial remission. However, disease progression necessitated a change in therapy. The combination treatment stabilized the disease temporarily, achieving a stable disease status. This case underscores the transient efficacy of targeted therapy in SMARCA4-deficient NSCLC with concurrent EGFR mutations. It highlights the need for continuous therapeutic adjustments and emphasizes the importance of further research into effective strategies for treating this complex and challenging subset of NSCLC, as current modalities have limitations in sustained efficacy.

Clinical characteristics and treatment during preconception and perinatal period of infertile women with non-classical 21-hydroxylase deficiency

ObjectiveA single-center observational study to determine the clinical characteristics and therapeutic dose adjustments in women of reproductive age with infertility and non-classical 21-hydroxylase deficiency (NC-21OHD).DesignA retrospective analysis of 20 women of reproductive age who were diagnosed with NC-21OHD during an infertility evaluation at Shengjing Hospital of China Medical University from January 2013 to May 2024 was performed. The clinical manifestations, auxiliary examinations, adjustment of glucocorticoid (GC) treatment during preconception and perinatal period, and pregnancy outcomes were analyzed.Results14 of 16 patients (87.5%) had inappropriately elevated progesterone levels during the follicular phase. The average levels of 17α-hydroxyprogesterone, testosterone, androstenedione, and dehydroepiandrosterone sulfate in the follicular phase were also significantly increased. All 20 infertile patients received GC treatment before preparing for pregnancy. During the follow-up, six of 20 patients had seven conceptions. three patients had spontaneous abortions in the first trimester and four patients delivered babies (4/20). Three patients had a GC dose that was maintained throughout pregnancy and one had an increase in the GC dose starting in the second trimester. Of the remaining 16 patients, seven are still trying to conceive and nine had discontinued treatment.ConclusionsAn abnormal increase in the follicular phase progesterone level is the most common serologic marker for NC-21OHD among infertile women. Ovulation can be restored after GC treatment, but the proportion of successful conceptions remains low. The dose of GCs in most pregnant women remained unchanged throughout pregnancy.

Renal Impairment and Dose Adjustment of Long-Acting Injectable Antipsychotics: Are We Getting It Right? A Case Report.

Renal impairment is defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 with or without kidney damage. Creatinine, which is found in serum and urine, is a common biomarker to estimate renal function and is used in most eGFR equations. Renal impairment can decrease or increase drug effects, necessitating therapeutic adjustments. Increased effect is related to drug accumulation that leads to increased elimination time and potential toxicity. eGFR plays a crucial role in drug dosing, particularly for renally excreted medications. However, the lack of recognition of pre-existing renal impairment and the incorrect interpretation of eGFR equations remain challenges. This case report explores the significance of eGFR in patients with psychiatric conditions, especially in the context of long-acting antipsychotic drug dosing.

Pharmacogenetic Considerations in Beta-Blocker Therapy

Pharmacogenetic testing offers a promising approach to personalizing beta-blocker therapy which is used for a variety of diseases, such as heart failure, myocardial infarction and migraine prophylaxis. The genetic variability in the metabolism and response to beta-blockers such as metoprolol can significantly influence treatment outcomes. Understanding these genetic differences can help optimize therapy and minimize adverse effects. A brief summary of the current guideline and recommendations: Approximately 0.3-6.5% (depending on their ancestry) of patients are CYP2D6 poor metabolizers. CYP2D6 Poor Metabolizers have significantly decreased metabolism of metoprolol, leading to increased drug concentration and a higher risk of adverse effects. The highest dose of metoprolol that patients can tolerate may be lower in CYP2D6 poor metabolizers compared to those that are non-poor CYP2D6 metabolizers. Current evidence is insufficient to support routine clinical testing or therapeutic adjustments for other genes affecting beta-blocker pharmacodynamics, such as ADRB1, ADRB2, ADRA2C, and GRK5. Future research should consider the combined effects of multiple genetic variants (e.g., polygenic risk scores) rather than focusing solely on single-gene associations.

Comparative analysis of surgical prognostic between HIC and NHIC patients after cystoscopy with hydrodistention.

This study aims to clarify the pathogenic mechanism of interstitial cystitis (IC), which has led to uncertainty in its diagnosis and treatment. We examined data from 18 interstitial cystitis with Hunner lesions (HIC) and 18 interstitial cystitis without Hunner lesions (NHIC) patients, including their clinical information, urodynamic test results, and maximum bladder capacity. A 1-year follow-up tracked disease progression. Postoperative recovery showed that HIC patients experienced significantly greater improvements in Visual Analog Scale pain scores compared to NHIC patients (P = .0049). This trend continued at the 6-month mark (P = .0056). Over the 1-year follow-up, NHIC patients exhibited a statistically significant improvement in Pain and Urgency/Frequency scores, while HIC patients had a gradual overall score increase from preoperative to postoperative stages. However, no significant differences were observed in either group at 1 year postoperatively compared to preoperative scores. This study revealed distinct differences between HIC and NHIC patients, including reduced bladder volumes and more severe nociceptive pain in HIC patients. Early analgesic interventions effectively alleviated discomfort in HIC patients. The combination of cystoscopic hydrodistention and water dilatation was highly effective in relieving pain symptoms in HIC patients but increased the risk of recurrence, necessitating recurrent bladder infusion and timely therapeutic adjustments. In contradiction to prior paradigms, the surgical intervention of cystoscopic water hydrodistention also yielded favorable outcomes among NHIC patients.